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["Retinoid and heart",null,null,null,null,null,"PubMed query used: \n(retinoid OR retinoic OR Vitamin A) AND (cardiovascular system[mh] OR Heart Diseases[mh] OR heart OR cardiovascular OR vasculature OR vein OR veins OR arteries) AND (review[pt] OR review[tiab])"]
[null,"Your search terms"]
["PMID","heart","rarg","retin","Total","Pub Yr","Title","Fauthor","LinkPMID","tiab"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I4,I4)","v":20507802},{"$f":"(LEN($J4) - LEN(SUBSTITUTE(LOWER($J4),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J4) - LEN(SUBSTITUTE(LOWER($J4),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J4) - LEN(SUBSTITUTE(LOWER($J4),LOWER(D$3),\"\")))/LEN(D$3)","v":18},{"$f":"SUM(B4:D4)","v":18},2010,"Alitretinoin for the treatment of severe chronic hand eczema.","Paulden",20507802,"Alitretinoin for the treatment of severe chronic hand eczema.    Abstract:   This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of alitretinoin for the treatment of adults with severe chronic hand eczema refractory to topical steroid treatment in accordance with the licensed indication, based upon the evidence submission from Basilea Pharmaceuticals Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The clinical evidence came from a single placebo-controlled randomised controlled trial of daily treatment with alitretinoin for 12-24 weeks, with follow-up for a further 24 weeks, in patients with severe chronic hand eczema (CHE) unresponsive to topical steroids. A statistically significantly greater proportion of patients using alitretinoin achieved the primary end point of clear or almost clear hands by week 24 than did those with placebo. Dose-dependent headache was the most commonly reported adverse event in patients treated with alitretinoin. Serious adverse events were rare, but alitretinoin was associated with increases in both total cholesterol and triglycerides, which has implications for risks of future cardiovascular events. The manufacturer submitted a de novo decision analytic model to estimate, over a time horizon of 3 years, the cost-effectiveness of alitretinoin versus the other relevant comparators identified by NICE. In response to the points of clarification put to it by the ERG regarding the initial submission, the manufacturer provided additional evidence and a revised decision analytic model with a placebo arm. In the manufacturers original submission to NICE, the base-case incremental cost-effectiveness ratios (ICERs) reported for alitretinoin were 8614 pounds per quality-adjusted life-year (QALY) versus ciclosporin, -469 pounds per QALY versus psoralen + UVA (with alitretinoin dominant) and 10,612 pounds per QALY versus azathioprine. These ICERs decreased as the time horizon was extended in sensitivity analyses. In patients with hyperkeratotic CHE and in women of child-bearing potential, the ICER remained below 20,000. pounds When the health-related quality of life (HRQoL) values used in the model were replaced with those derived from an alternative study, these ICERs increased significantly (to 22,312 pounds per QALY for alitretinoin versus azathioprine). In the revised model, alitretinoin was reported to have an ICER of 12,931 pounds per QALY gained versus supportive care (placebo). However, the model underestimates the costs of treatment associated with alitretinoin. The manufacturer assumed that patients receiving alitretinoin visited the dermatologist every 4 weeks and ceased treatment as soon as they responded to it. If, in practice, patients would receive treatment for longer than this, then the manufacturers model will have significantly underestimated the costs to the NHS. Additional analyses undertaken by the ERG produced ICERs close to 30,000 pounds per QALY gained for alitretinoin versus supportive care. This was largely due to uncertainty surrounding the impact of alitretinoin on HRQoL. The placebo-controlled trials conducted to date have established that alitretinoin can be efficacious for the treatment of severe CHE refractory to topical steroids, but longer term follow-up of trials or the implementation of registries is required to better establish the longer term efficacy or safety of alitretinoin. NICE recommended the use of alitretinoin for patients with severe CHE and a Dermatology Life Quality Index (DLQI) score of at least 15. Treatment was recommended to be stopped as soon as an adequate response was observed, or if CHE remained severe at 12 weeks, or if response was inadequate at 24 weeks."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I5,I5)","v":22521611},{"$f":"(LEN($J5) - LEN(SUBSTITUTE(LOWER($J5),LOWER(B$3),\"\")))/LEN(B$3)","v":14},{"$f":"(LEN($J5) - LEN(SUBSTITUTE(LOWER($J5),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J5) - LEN(SUBSTITUTE(LOWER($J5),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B5:D5)","v":15},2012,"New developments in the second heart field.","Zaffran",22521611,"New developments in the second heart field.    Abstract:   During cardiac looping the heart tube elongates by addition of progenitor cells from adjacent pharyngeal mesoderm to the arterial and venous poles. This cell population, termed the second heart field, was first identified ten years ago and many studies in the intervening decade have refined our understanding of how heart tube elongation takes place and identified signaling pathways that regulate proliferation and differentiation during progressive contribution of second heart field cells to the embryonic heart. It has also become apparent that defective second heart field development results in common congenital heart anomalies affecting both the conotruncal region and venous pole of the heart, including atrial and atrioventricular septal defects. In this review we focus on a series of recent papers that have identified new regulators of second heart field development, in particular the retinoic acid signaling pathway and HOX, SIX and EYA transcription factors. We also discuss new findings concerning the regulation of fibroblast growth factor signaling during second heart field deployment and studies that have implicated FGF10 and FGF3 in outflow tract development in addition to FGF8. Second heart field derived parts of the heart share common progenitor cells in pharyngeal mesoderm with craniofacial skeletal muscles and recent findings from xenopus, zebrafish and the protochordate Ciona intestinalis provide insights into the evolution of the second heart field during vertebrate radiation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I6,I6)","v":21350678},{"$f":"(LEN($J6) - LEN(SUBSTITUTE(LOWER($J6),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J6) - LEN(SUBSTITUTE(LOWER($J6),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J6) - LEN(SUBSTITUTE(LOWER($J6),LOWER(D$3),\"\")))/LEN(D$3)","v":15},{"$f":"SUM(B6:D6)","v":15},2011,"Vitamin A metabolism: an update.","DAmbrosio",21350678,"Vitamin A metabolism: an update.    Abstract:   Retinoids are required for maintaining many essential physiological processes in the body, including normal growth and development, normal vision, a healthy immune system, normal reproduction, and healthy skin and barrier functions. In excess of 500 genes are thought to be regulated by retinoic acid. 11-cis-retinal serves as the visual chromophore in vision. The body must acquire retinoid from the diet in order to maintain these essential physiological processes. Retinoid metabolism is complex and involves many different retinoid forms, including retinyl esters, retinol, retinal, retinoic acid and oxidized and conjugated metabolites of both retinol and retinoic acid. In addition, retinoid metabolism involves many carrier proteins and enzymes that are specific to retinoid metabolism, as well as other proteins which may be involved in mediating also triglyceride and/or cholesterol metabolism. This review will focus on recent advances for understanding retinoid metabolism that have taken place in the last ten to fifteen years."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I7,I7)","v":25069047},{"$f":"(LEN($J7) - LEN(SUBSTITUTE(LOWER($J7),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J7) - LEN(SUBSTITUTE(LOWER($J7),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J7) - LEN(SUBSTITUTE(LOWER($J7),LOWER(D$3),\"\")))/LEN(D$3)","v":14},{"$f":"SUM(B7:D7)","v":14},2014,"The mechanisms of Fenretinide-mediated anti-cancer activity and prevention of obesity and type-2 diabetes.","Mody",25069047,"The mechanisms of Fenretinide-mediated anti-cancer activity and prevention of obesity and type-2 diabetes.    Abstract:   Fenretinide remains the most investigated retinoid compound for the prevention of cancer. Its clinical use remains a genuine possibility due to a favourable toxicological profile and accumulation in fatty tissues. Like other well-characterised pharmacological therapies, Fenretinide has been shown to affect multiple signalling pathways. Recent findings have discovered additional beneficial properties the synthetic retinoid was not intentionally designed for, including the prevention of high-fat diet-induced obesity and insulin resistance. These preclinical findings in rodents are timely since obesity has reached pandemic proportions and safe effective therapeutics are severely lacking. Recent investigations have proposed various mechanisms of action for the beneficial effects of Fenretinide. This review covers the current knowledge about Fenretinides use as a therapy for cancer and potential to treat obesity, insulin resistance and glucose intolerance. An overview of the signalling pathways manipulated by Fenretinide including retinoid homeostasis, reactive oxygen species generation and inhibition of ceramide synthesis will be presented and insights into apoptosis and/or autophagy induction by Fenretinide will also be discussed. The largely unexplored area of Fenretinide metabolites as alternative therapeutic options and how these may be relevant will also be presented. Fenretinide shows great promise, but unfortunately evidence is lacking from clinical trials on Fenretinides effectiveness in humans. Finally we identify what action can be taken to further progress the investigation of this extremely important retinoid."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I8,I8)","v":12769644},{"$f":"(LEN($J8) - LEN(SUBSTITUTE(LOWER($J8),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J8) - LEN(SUBSTITUTE(LOWER($J8),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J8) - LEN(SUBSTITUTE(LOWER($J8),LOWER(D$3),\"\")))/LEN(D$3)","v":14},{"$f":"SUM(B8:D8)","v":14},2003,"Retinoids: pleiotropic agents of therapy for vascular diseases?","Streb",12769644,"Retinoids: pleiotropic agents of therapy for vascular diseases?    Abstract:   Retinoids, the natural and synthetic derivatives of vitamin A, exert broad biological effects and have been used clinically to treat a variety of dermatological and neoplastic diseases. The principal mode of action of many retinoids is through the binding and activation of a family of nuclear receptors that modulate gene transcription. Recent evidence demonstrates that retinoids effectively attenuate experimental vessel wall narrowing due to atherosclerosis, post-balloon injury stenosis, and bypass graft failure. Moreover, retinoids promote a differentiated phenotype in smooth muscle cells (SMC) which, unlike other muscle types, is not fixed and is subject to considerable modulation in disease states. A growing number of in vitro studies have reported desirable effects of retinoids on cell migration, proliferation, apoptosis, matrix remodeling, fibrinolysis, coagulation, and inflammation, all of which impinge on vascular disease. Since vascular SMC and endothelial cells (EC) express most retinoid receptors, the mechanisms underlying retinoid-mediated events in these cells and the vessel wall likely relate to an altered transcriptome. In fact, there is a growing list of retinoid-response genes encoding proteins that likely mediate the actions of retinoids. Retinoid-response genes, therefore, represent promising targets of therapy for the refined treatment of vascular diseases. The purpose of this review is to summarize the emerging importance of retinoids in the control of vascular cell responses with special emphasis on potential mechanisms underlying retinoid-induced changes in the vessel wall following injury. Given the similarities in the pathogenesis of neoplasia and vascular disease, it is reasonable to consider testing the efficacy of retinoids for the treatment of human vascular disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I9,I9)","v":22134996},{"$f":"(LEN($J9) - LEN(SUBSTITUTE(LOWER($J9),LOWER(B$3),\"\")))/LEN(B$3)","v":12},{"$f":"(LEN($J9) - LEN(SUBSTITUTE(LOWER($J9),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J9) - LEN(SUBSTITUTE(LOWER($J9),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B9:D9)","v":13},2010,"[Relationship between heart development and pathogenesis of congenital heart defects in current literature].","Ratajska",22134996,"[Relationship between heart development and pathogenesis of congenital heart defects in current literature].    Abstract:   This work presents current ideas on embryonic heart development and is an attempt to elucidate pathogenesis of congenital heart defects. The heart develops from 2 areas, the so-called quot;heart fieldsquot;, which differ in the expression of various genes and in sensitivity to certain substances (for example retinoid acid). Heart fields are the source of cardiomyocytes and endocardial endothelial cells for the developing heart tube. Neural crest cells attaining the heart take part in the formation of tunica media of great vessels and the aorto-pulmonary septum. An interaction between the cells of the secondary heart field and neural crest cells migrating to the heart plays a significant role in heart development. This interaction is accomplished by various mediators released into the cell environment (e.g. activation of Notch, which induces secretion of growth factors such as Fgf8). Disturbances in signaling between these cellular populations lead to malformations of the cardiac outflow tract. The sinus venosus is the source of endothelial cells of the coronary vasculature, whereas the proepicardium provides cells for the epicardium, smooth muscle cells and fibroblasts."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I10,I10)","v":17609502},{"$f":"(LEN($J10) - LEN(SUBSTITUTE(LOWER($J10),LOWER(B$3),\"\")))/LEN(B$3)","v":11},{"$f":"(LEN($J10) - LEN(SUBSTITUTE(LOWER($J10),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J10) - LEN(SUBSTITUTE(LOWER($J10),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B10:D10)","v":13},2007,"Signal transduction in early heart development (II): ventricular chamber specification, trabeculation, and heart valve formation.","Wagner",17609502,"Signal transduction in early heart development (II): ventricular chamber specification, trabeculation, and heart valve formation.    Abstract:   The formation of a four-chambered heart with ventricular chambers aligned in a left-right orientation begins with the rightward looping of the linear heart tube in accordance with the left-right embryonic axis. The functional specification of the ventricular chambers in the looped heart occurs with the formation of a trabeculated myocardium along the outer curvature of the realigned heart tube. Two major signal transduction pathways are involved in this process, the retinoic acid and neuregulin signaling pathways, with the retinoic acid pathway also participating in rightward heart tube looping. With the establishment of the atrial and ventricular chambers, maintenance of a unidirectional flow of blood between the two chambers must be ensured. To achieve this, heart valves develop at the atrioventricular juncture. This process begins with formation of endocardial cushions, the primordia of heart valves, and ends with formation of heart valve leaflets. Underlying this process is a complex network of signal transduction pathways that mediate communication between the endocardial and myocardial cell layers to form the endocardial cushions and nascent heart valve. Some of the signaling molecules involved are vascular endothelial growth factor, Wnts, bone morphogenetic proteins, epidermal growth factor, hyaluronic acid, neurofibromin, and calcium."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I11,I11)","v":9478050},{"$f":"(LEN($J11) - LEN(SUBSTITUTE(LOWER($J11),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J11) - LEN(SUBSTITUTE(LOWER($J11),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J11) - LEN(SUBSTITUTE(LOWER($J11),LOWER(D$3),\"\")))/LEN(D$3)","v":11},{"$f":"SUM(B11:D11)","v":13},1998,"Retinoids and their receptors in vertebrate embryogenesis.","Smith",9478050,"Retinoids and their receptors in vertebrate embryogenesis.    Abstract:   Vitamin A and its derivatives, the retinoids, participate in formation of diverse embryonic structures, including face, heart, eye, limb and nervous system. Studies of retinoid-deficient and -treated embryos, and of receptor null mutants, provide evidence that this participation involves interactions between retinoids and their receptors. Targeted retinoid application and retinoid deficiency, using in ovo avian embryos, has identified early cardiogenic contributions, including cardiocyte gene expression and differentiation, heart tube fusion and laterality, and segmental identity. Also useful is a mammalian model, which targets retinoid deficiency to distinct gestational windows, circumventing limitations of traditional deficiency studies and current null mutant technologies. Rat embryos made deficient in retinoids during gestational d 11.5-13.5 exhibit specific cardiac, limb, ocular and nervous system deficits. That many of the anomalies previously reported in retinoid receptor null mutants are observed in deficiency confirms that ligand-receptor interactions are essential for embryonic development. Other defects are novel, reemphasizing the functional redundancy of retinoid receptors and that retinoid receptors have multiple and overlapping contributions to morphogenesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I12,I12)","v":3054426},{"$f":"(LEN($J12) - LEN(SUBSTITUTE(LOWER($J12),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J12) - LEN(SUBSTITUTE(LOWER($J12),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J12) - LEN(SUBSTITUTE(LOWER($J12),LOWER(D$3),\"\")))/LEN(D$3)","v":12},{"$f":"SUM(B12:D12)","v":13},1988,"Adverse effects of retinoids.","David",3054426,"Adverse effects of retinoids.    Abstract:   Oral retinoids, synthetic derivatives of vitamin A, have been used in the treatment of various dermatoses over the last decade. The most useful drugs have been isotretinoin (13-cis-retinoic acid) for nodulocystic acne and etretinate for psoriasis vulgaris. Retinoids are also effective in the treatment of papulosquamous dermatoses other than psoriasis (i.e. inherited disorders of keratinisation), cutaneous T-cell lymphoma and in chemotherapy and chemoprevention of cancer. However, systemic administration of these compounds is frequently associated with mucocutaneous side effects, liver toxicity and abnormalities of serum lipid profiles, which might be related to an increased risk of coronary heart disease. Of particular concern is the teratogenic effect of all retinoids, which limits their use in women of child-bearing potential. Chronic toxicities from long term therapy with retinoids may result in skeletal abnormalities, usually mimicking diffuse idiopathic hyperostosis syndrome. Furthermore, the chronic use of retinoids in children may inhibit their growth due to premature epiphyseal closure. In contrast to other side effects of retinoids which are dose dependent and reversible upon withdrawal of the drug, it seems unlikely that bone abnormalities will resolve after discontinuation of the medication. In view of the wide spectrum of toxicities, treatment with retinoids requires appropriate selection of patients, careful consideration of the benefit to risk ratio for each individual, periodic monitoring of clinical response and laboratory tests. Clinicians should use special management techniques in order to prevent or minimize slide effects. Extensive investigations are currently being conducted in an attempt to develop new retinoids which will improve the therapeutic efficacy and reduce unwanted reactions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I13,I13)","v":21855651},{"$f":"(LEN($J13) - LEN(SUBSTITUTE(LOWER($J13),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J13) - LEN(SUBSTITUTE(LOWER($J13),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J13) - LEN(SUBSTITUTE(LOWER($J13),LOWER(D$3),\"\")))/LEN(D$3)","v":11},{"$f":"SUM(B13:D13)","v":12},2012,"Emerging roles for retinoids in regeneration and differentiation in normal and disease states.","Gudas",21855651,"Emerging roles for retinoids in regeneration and differentiation in normal and disease states.    Abstract:   The vitamin A (retinol) metabolite, all-trans retinoic acid (RA), is a signaling molecule that plays key roles in the development of the body plan and induces the differentiation of many types of cells. In this review the physiological and pathophysiological roles of retinoids (retinol and related metabolites) in mature animals are discussed. Both in the developing embryo and in the adult, RA signaling via combinatorial Hox gene expression is important for cell positional memory. The genes that require RA for the maturation/differentiation of T cells are only beginning to be cataloged, but it is clear that retinoids play a major role in expression of key genes in the immune system. An exciting, recent publication in regeneration research shows that ALDH1a2 (RALDH2), which is the rate-limiting enzyme in the production of RA from retinaldehyde, is highly induced shortly after amputation in the regenerating heart, adult fin, and larval fin in zebrafish. Thus, local generation of RA presumably plays a key role in fin formation during both embryogenesis and in fin regeneration. HIV transgenic mice and human patients with HIV-associated kidney disease exhibit a profound reduction in the level of RARβ protein in the glomeruli, and HIV transgenic mice show reduced retinol dehydrogenase levels, concomitant with a greater than 3-fold reduction in endogenous RA levels in the glomeruli. Levels of endogenous retinoids (those synthesized from retinol within cells) are altered in many different diseases in the lung, kidney, and central nervous system, contributing to pathophysiology. This article is part of a Special Issue entitled Retinoid and Lipid Metabolism."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I14,I14)","v":22568170},{"$f":"(LEN($J14) - LEN(SUBSTITUTE(LOWER($J14),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J14) - LEN(SUBSTITUTE(LOWER($J14),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J14) - LEN(SUBSTITUTE(LOWER($J14),LOWER(D$3),\"\")))/LEN(D$3)","v":7},{"$f":"SUM(B14:D14)","v":12},2011,"[Retinoids--their metabolites, action, and role in heart development].","Stachurska",22568170,"[Retinoids--their metabolites, action, and role in heart development].    Abstract:   Retinoids constitute a group of active compounds known as vitamin A. Apart from an unquestionable function in adults, retinoids also play a profound role in many events during embryonic development for instancje in axial patterning and organogenesis. Retinoic acid is the most active biological form of vitamin A. Its signaling both in adults and during embryonic development occurs at different levels through interaction with specific proteins and nuclear receptors. Retinoic acid signaling in heart development occurs mostly via interaction with secondary heart field cells by restricting their spatial expansion and controlling proper addition of these cells to the cardiac tube. This signal requires precise level of local retinoic acid, excess or insufficiency of which causes various malformations of the embryo and embryonic heart. Although retinoid signaling in the developing heart is a highly significant developmental factor, it is not yet fully understood. The following review summarises recent developments regarding this subject."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I15,I15)","v":15229353},{"$f":"(LEN($J15) - LEN(SUBSTITUTE(LOWER($J15),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J15) - LEN(SUBSTITUTE(LOWER($J15),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J15) - LEN(SUBSTITUTE(LOWER($J15),LOWER(D$3),\"\")))/LEN(D$3)","v":7},{"$f":"SUM(B15:D15)","v":12},2004,"Vitamin a requirement for early cardiovascular morphogenesis specification in the vertebrate embryo: insights from the avian embryo.","Zile",15229353,"Vitamin a requirement for early cardiovascular morphogenesis specification in the vertebrate embryo: insights from the avian embryo.    Abstract:   Vitamin A is required throughout the life cycle, including crucial stages of embryonic and fetal development. With the identification of retinoic acid-specific nuclear transcription factors, the retinoid receptors, considerable advances have been made in understanding the molecular function of vitamin A. The requirement for vitamin A during early embryogenesis has successfully been examined in the vitamin A-deficient avian embryo during neurulation, when in the vertebrates crucial developmental decisions take place. These studies revealed that retinoic acid is essential during these early stages of embryogenesis for the initiation of organogenesis (i.e., formation of the heart). If retinoic acid is not present at this time, abnormal development ensues, leading to early embryonic death. Though the initial insult of the absence of vitamin A appears to be on the specification of cardiovascular tissues, subsequently all development is adversely affected and the embryo dies. Molecular and functional studies revealed that retinoic acid regulates the expression of the cardiogenic transcription factor GATA-4 and several heart asymmetry genes, which explains why the heart position is random in vitamin A-deficient quail embryos. During the crucial retinoic acid-requiring developmental window, retinoic acid transduces its signals to genes for heart morphogenesis via the receptors RARalpha2, RARgamma, and RXRalpha. Elucidation of the function of vitamin A during early embryonic development may lead to a better understanding of the cardiovascular birth defects prevalent in the Western world."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I16,I16)","v":21810483},{"$f":"(LEN($J16) - LEN(SUBSTITUTE(LOWER($J16),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J16) - LEN(SUBSTITUTE(LOWER($J16),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J16) - LEN(SUBSTITUTE(LOWER($J16),LOWER(D$3),\"\")))/LEN(D$3)","v":11},{"$f":"SUM(B16:D16)","v":11},2012,"Retinoid metabolism and its effects on the vasculature.","Rhee",21810483,"Retinoid metabolism and its effects on the vasculature.    Abstract:   Retinoids, the metabolically-active structural derivatives of vitamin A, are critical signaling molecules in many fundamental biological processes including cell survival, proliferation and differentiation. Emerging evidence, both clinical and molecular, implicates retinoids in atherosclerosis and other vasculoproliferative disorders such as restenosis. Although the data from clinical trials examining effect of vitamin A and vitamin precursors on cardiac events have been contradictory, this data does suggest that retinoids do influence fundamental processes relevant to atherosclerosis. Preclinical animal model and cellular studies support these concepts. Retinoids exhibit complex effects on proliferation, growth, differentiation and migration of vascular smooth muscle cells (VSMC), including responses to injury and atherosclerosis. Retinoids also appear to exert important inhibitory effects on thrombosis and inflammatory responses relevant to atherogenesis. Recent studies suggest retinoids may also be involved in vascular calcification and endothelial function, for example, by modulating nitric oxide pathways. In addition, established retinoid effects on lipid metabolism and adipogenesis may indirectly influence inflammation and atherosclerosis. Collectively, these observations underscore the scope and complexity of retinoid effects relevant to vascular disease. Additional studies are needed to elucidate how context and metabolite-specific retinoid effects affect atherosclerosis. This article is part of a Special Issue entitled: Retinoid and Lipid Metabolism."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I17,I17)","v":21591244},{"$f":"(LEN($J17) - LEN(SUBSTITUTE(LOWER($J17),LOWER(B$3),\"\")))/LEN(B$3)","v":10},{"$f":"(LEN($J17) - LEN(SUBSTITUTE(LOWER($J17),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J17) - LEN(SUBSTITUTE(LOWER($J17),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B17:D17)","v":11},2011,"Tbx1, subpulmonary myocardium and conotruncal congenital heart defects.","Parisot",21591244,"Tbx1, subpulmonary myocardium and conotruncal congenital heart defects.    Abstract:   Conotruncal congenital heart defects, including defects in septation and alignment of the ventricular outlets, account for approximately a third of all congenital heart defects. Failure of the left ventricle to obtain an independent outlet results in incomplete separation of systemic and pulmonary circulation at birth. The embryonic outflow tract, a transient cylinder of myocardium connecting the embryonic ventricles to the aortic sac, plays a critical role in this process during normal development. The outflow tract (OFT) is derived from a population of cardiac progenitor cells called the second heart field that contributes to the arterial pole of the heart tube during cardiac looping. During septation, the OFT is remodeled to form the base of the ascending aorta and pulmonary trunk. Tbx1, the major candidate gene for DiGeorge syndrome, is a critical transcriptional regulator of second heart field development. DiGeorge syndrome patients are haploinsufficient for Tbx1 and present a spectrum of conotruncal anomalies including tetralogy of Fallot, pulmonary atresia, and common arterial trunk. In this review, we focus on the role of Tbx1 in the regulation of second heart field deployment and, in particular, in the development of a specific population of myocardial cells at the base of the pulmonary trunk. Recent data characterizing additional properties and regulators of development of this region of the heart, including the retinoic acid, hedgehog, and semaphorin signaling pathways, are discussed. These findings identify future subpulmonary myocardium as the clinically relevant component of the second heart field and provide new mechanistic insight into a spectrum of common conotruncal congenital heart defects."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I18,I18)","v":20182540},{"$f":"(LEN($J18) - LEN(SUBSTITUTE(LOWER($J18),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J18) - LEN(SUBSTITUTE(LOWER($J18),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J18) - LEN(SUBSTITUTE(LOWER($J18),LOWER(D$3),\"\")))/LEN(D$3)","v":11},{"$f":"SUM(B18:D18)","v":11},2010,"The retinal pigment epithelium: something more than a constituent of the blood-retinal barrier--implications for the pathogenesis of diabetic retinopathy.","Simó",20182540,"The retinal pigment epithelium: something more than a constituent of the blood-retinal barrier--implications for the pathogenesis of diabetic retinopathy.    Abstract:   The retinal pigment epithelium (RPE) is an specialized epithelium lying in the interface between the neural retina and the choriocapillaris where it forms the outer blood-retinal barrier (BRB). The main functions of the RPE are the following: (1) transport of nutrients, ions, and water, (2) absorption of light and protection against photooxidation, (3) reisomerization of all-trans-retinal into 11-cis-retinal, which is crucial for the visual cycle, (4) phagocytosis of shed photoreceptor membranes, and (5) secretion of essential factors for the structural integrity of the retina. An overview of these functions will be given. Most of the research on the physiopathology of diabetic retinopathy has been focused on the impairment of the neuroretina and the breakdown of the inner BRB. By contrast, the effects of diabetes on the RPE and in particular on its secretory activity have received less attention. In this regard, new therapeutic strategies addressed to modulating RPE impairment are warranted."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I19,I19)","v":9478047},{"$f":"(LEN($J19) - LEN(SUBSTITUTE(LOWER($J19),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J19) - LEN(SUBSTITUTE(LOWER($J19),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J19) - LEN(SUBSTITUTE(LOWER($J19),LOWER(D$3),\"\")))/LEN(D$3)","v":9},{"$f":"SUM(B19:D19)","v":11},1998,"Vitamin A and embryonic development: an overview.","Zile",9478047,"Vitamin A and embryonic development: an overview.    Abstract:   Vitamin A is an essential micronutrient throughout the life cycle. Its active form, retinoic acid via retinoid receptors, is involved in signal transduction pathways regulating development. Both the lack and excess of vitamin A during embryonic development result in congenital malformations. Approaches to examine the function of vitamin A in embryonic development have included treatment with excess retinoids and the use of retinoid receptor knock-out mice, which have provided important insights into the complexity of the retinoid signaling system. A recently explored model is the retinoid ligand knock-out, i.e., the vitamin A-deficient embryo. Early development can be successfully examined in the vitamin A-deficient avian embryo, in which bioactive retinoids can rescue the deficient genotype as well as phenotype. In this model it has been possible to unequivocally link the physiological function of vitamin A to development of heart, embryonal circulatory and central nervous systems and the regulation of heart asymmetry. Several developmental genes regulated by endogenous vitamin A during early embryogenesis have been identified. Retinoid receptors and their endogenous ligands, the vitamin A-active forms, are present in the early embryo. It is the developmentally regulated biogeneration of the vitamin A-active forms via distinct spatio-temporal metabolic pathways that is critically linked to the initiation of retinoid signal transduction during embryonic development."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I20,I20)","v":9345570},{"$f":"(LEN($J20) - LEN(SUBSTITUTE(LOWER($J20),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J20) - LEN(SUBSTITUTE(LOWER($J20),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J20) - LEN(SUBSTITUTE(LOWER($J20),LOWER(D$3),\"\")))/LEN(D$3)","v":10},{"$f":"SUM(B20:D20)","v":11},1997,"[Teratogenic effects of vitamin A and its derivates].","Guillonneau",9345570,"[Teratogenic effects of vitamin A and its derivates].    Abstract:   Retinoids, the synthetic derivates of vitamin A, have a key role on cellular differentiation and developmental tissue specificity. Their effects are mediated by nuclear receptors which transactivate homeobox genes. They are teratogenic to animals and they all induce similar malformations dependent on the dose and the duration of exposure. This is a review of the teratogenic effects of vitamin A and its synthetic derivates--isotretinoin, acitretine and topical retinoids--in humans. High dose vitamin A have a potent teratogenic effect and are therefore contra-indicated during pregnancy. Isotretinoin is responsible for a syndrome including malformations of the central nervous system, heart and thymus, together with craniofacial defects. The incidence rate is high and comparable to thalidomide (ie, 25%). This high teratogenic potency justifies a strict limitation of such a prescription in women susceptible to become pregnant. Acitretine, which replaces etretinate because of its long half life of 120 days, might also be teratogenic in humans. In addition, it may be back transformed into etretinate, thus contraindicating pregnancy for 2 years after withdrawal. Finally, despite a low percutaneous resorption, available data on the use of retinoids as topicals are limited and their use during pregnancy is therefore not recommended. Although they are efficient in skin diseases, the use of retinoids in women of the child bearing age is very limited because of their potent teratogenic effect."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I21,I21)","v":17495601},{"$f":"(LEN($J21) - LEN(SUBSTITUTE(LOWER($J21),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J21) - LEN(SUBSTITUTE(LOWER($J21),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J21) - LEN(SUBSTITUTE(LOWER($J21),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B21:D21)","v":10},2007,"Lipids in the heart: a source of fuel and a source of toxins.","Park",17495601,"Lipids in the heart: a source of fuel and a source of toxins.    Abstract:    PURPOSE OF REVIEW : How do lipids arrive in the heart and other tissues? This review focuses on new information on pathways of lipid uptake into the heart.  RECENT FINDINGS : Fatty acids, the major cardiac fuel, are obtained from either lipoproteins or free fatty acids associated with albumin. The heart is the tissue with the most robust expression of lipoprotein lipase, and recent data attest to the importance of this enzyme in supplying optimal amounts of fatty acids for the heart. Genetic deletion of CD36 also shows that this transporter is important for cardiac uptake of lipids. Retinoid acquisition by the heart involves pathways parallel to those used for fatty acid uptake: a pathway for acquisition of core lipoprotein retinyl ester and another for nonlipoprotein retinol. Dilated lipotoxic cardiomyopathy is the consequence of excess lipid uptake.  SUMMARY : Genetic modifications that affect lipid uptake, oxidation, and storage are being exploited to elucidate the pathophysiology of cardiomyopathies and to discover how lipids relate to heart failure in humans with obesity and diabetes mellitus. This information is likely to lead to new diagnostic categories of cardiomyopathy and more pathophysiologically appropriate treatments."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I22,I22)","v":12189278},{"$f":"(LEN($J22) - LEN(SUBSTITUTE(LOWER($J22),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J22) - LEN(SUBSTITUTE(LOWER($J22),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J22) - LEN(SUBSTITUTE(LOWER($J22),LOWER(D$3),\"\")))/LEN(D$3)","v":7},{"$f":"SUM(B22:D22)","v":10},2002,"Retinoids and cardiovascular developmental defects.","Colbert",12189278,"Retinoids and cardiovascular developmental defects.    Abstract:   Vitamin A and related retinoids are critical regulators of normal cardiovascular development. Extreme variations in retinoid levels, too little or too much, dramatically alter embryonic morphogenesis that has teratogenic consequences, including effects on the heart and great vessels. Specific cardiovascular targets of retinoid action include effects on the anteroposterior patterning of the early heart, left-right decisions and cardiac situs, endocardial cushion formation, and, in particular, the neural crest. The cardiovascular defects produced are remarkably similar in deficiency and excess, suggesting modulation of common developmental or cellular processes by different levels of retinoids. The isolation of nuclear receptors that mediate retinoid action has led to the identification of some genes directly involved in the regulation of these processes and other gene products that may be affected more indirectly. This review will examine the mechanism of retinoid action, the requirements for vitamin A during normal heart development, and the consequences of nonphysiologic or teratogenic exposure."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I23,I23)","v":9811123},{"$f":"(LEN($J23) - LEN(SUBSTITUTE(LOWER($J23),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J23) - LEN(SUBSTITUTE(LOWER($J23),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J23) - LEN(SUBSTITUTE(LOWER($J23),LOWER(D$3),\"\")))/LEN(D$3)","v":6},{"$f":"SUM(B23:D23)","v":10},1998,"Role of vitamin A in the formation of congenital heart defects.","Sinning",9811123,"Role of vitamin A in the formation of congenital heart defects.    Abstract:   Retinoic acid, the biologically active form of vitamin A, is a critical player in normal development. The concentration of retinoic acid is highly regulated by the embryo to prevent either a deficit or an excess of this molecule, conditions that have been shown to produce cardiac defects that vary depending on the severity and the timing of the insult. The vast majority of these defects are associated with the valves or the membranous septa of the heart, suggesting a problem with the formation of the cardiac mesenchyme from both within and outside the heart. While the exact role of retinoic acid in cardiac development is not known, it is believed that retinoic acid influences development by up- or down-regulating cardiac specific genes. This review briefly discusses the role of cardiac mesenchyme and cardiac neural crest in septation of the heart. This is followed by a discussion of vitamin A metabolism and the cardiac defects associated with abnormal levels of retinoic acid. Finally, a mechanism is proposed concerning the ways abnormal levels of retinoic acid lead to similar cardiac defects by disrupting the production of the extracellular matrix."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I24,I24)","v":21235904},{"$f":"(LEN($J24) - LEN(SUBSTITUTE(LOWER($J24),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J24) - LEN(SUBSTITUTE(LOWER($J24),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J24) - LEN(SUBSTITUTE(LOWER($J24),LOWER(D$3),\"\")))/LEN(D$3)","v":7},{"$f":"SUM(B24:D24)","v":10},1997,"New insights into retinoid signaling in cardiac development and physiology.","Smith",21235904,"New insights into retinoid signaling in cardiac development and physiology.    Abstract:   Retinoic acid (RA) and the retinoids are potent hormones derived from the nutrient vitamin A; they bind members of the nuclear steroid receptor family (RAR, RXR), which are ligand-dependent trans-activators of target gene transcription. Although classic nutrition studies largely ignored heart as a retinoid target, recent interest in this subject stems from RAs potent cardiac teratogenicity, the identification of retinoid receptors in the heart, and the cardiac malformations observed in retinoid receptor null mutant mice. This review summarizes recent research into retinoid contributions predominantly in the embryonic heart. (Trends Cardiovasc Med 1997;7:324-329). © 1997, Elsevier Science Inc."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I25,I25)","v":22709814},{"$f":"(LEN($J25) - LEN(SUBSTITUTE(LOWER($J25),LOWER(B$3),\"\")))/LEN(B$3)","v":9},{"$f":"(LEN($J25) - LEN(SUBSTITUTE(LOWER($J25),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J25) - LEN(SUBSTITUTE(LOWER($J25),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B25:D25)","v":9},2012,"The role of micronutrients in heart failure.","McKeag",22709814,"The role of micronutrients in heart failure.    Abstract:   Heart failure is a common condition in the Western world, particularly among elderly persons and with an ever-aging population, the incidence is expected to increase. Diet in the setting of heart failure is important--patients with this condition are advised to consume a low-salt diet and monitor their weight closely. Nutritional status of patients with heart failure also is important--those with poor nutritional status tend to have a poor long-term prognosis. A growing body of evidence suggests an association between heart failure and micronutrient status. Reversible heart failure has been described as a consequence of severe thiamine and selenium deficiency. However, contemporary studies suggest that a more subtle relationship may exist between micronutrients and heart failure. This article reviews the existing literature linking heart failure and micronutrients, examining studies that investigated micronutrient intake, micronutrient status, and the effect of micronutrient supplementation in patients with heart failure, and focusing particularly on vitamin A, vitamin C, vitamin E, thiamine, other B vitamins, vitamin D, selenium, zinc, and copper."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I26,I26)","v":20090511},{"$f":"(LEN($J26) - LEN(SUBSTITUTE(LOWER($J26),LOWER(B$3),\"\")))/LEN(B$3)","v":8},{"$f":"(LEN($J26) - LEN(SUBSTITUTE(LOWER($J26),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J26) - LEN(SUBSTITUTE(LOWER($J26),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B26:D26)","v":9},2010,"Unicuspid aortic valve, hand anomalies: a heart-hand syndrome.","Nanda",20090511,"Unicuspid aortic valve, hand anomalies: a heart-hand syndrome.    Abstract:   Embryonic heart and limb development are closely related with gt;100 known inherited disorders affecting both. Common limb defects include duplication, deficiencies, and hypoplasia. Ventricular septal defects and atrial septal defects are the commonest associated cardiac conditions. A positive association exists between heart defects and limb disorders when these disorders are analyzed separately. Closer associations exist between heart defects and upper limb defects compared with lower limb defects. The majority of limb defects occur in the more distal parts of the affected limb. Genes expressed in both the heart and limb development include TGF-beta, BMP4, Msx transcription factor, HAND gene, retinoic acid receptor, and sonic hedgehog gene. Radial ray-heart syndromes are better described than ulnar ray-hand syndromes. There is significant variability of malformations. Partial phenocopies that are not genetically linked are well documented. An appreciation of ulnar anomalies should always provoke an evaluation of the heart for potential abnormalities. Although heart-hand syndromes are rare, valvular abnormalities and aortic aneurysms can lead to significant complications unless identified in time. The presence of radial or ulnar ray anomalies merit a detailed cardiac examination and a low threshold for cardiac imaging."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I27,I27)","v":19390062},{"$f":"(LEN($J27) - LEN(SUBSTITUTE(LOWER($J27),LOWER(B$3),\"\")))/LEN(B$3)","v":8},{"$f":"(LEN($J27) - LEN(SUBSTITUTE(LOWER($J27),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J27) - LEN(SUBSTITUTE(LOWER($J27),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B27:D27)","v":9},2009,"Signaling pathways controlling second heart field development.","Rochais",19390062,"Signaling pathways controlling second heart field development.    Abstract:   Insight into the mechanisms underlying congenital heart defects and the use of stem cells for cardiac repair are major research goals in cardiovascular biology. In the early embryo, progenitor cells in pharyngeal mesoderm contribute to the rapid growth of the heart tube during looping morphogenesis. These progenitor cells constitute the second heart field (SHF) and were first identified in 2001. Direct or indirect perturbation of SHF addition to the heart results in congenital heart defects, including arterial pole alignment defects. Over the last 3 years, a number of studies have identified key intercellular signaling pathways that control the proliferation and deployment of SHF progenitor cells. Here, we review data concerning Wnt, fibroblast growth factor, bone morphogenetic protein, Hedgehog, and retinoic acid signaling that have begun to identify the ligand sources and responding cell types controlling SHF development. These studies have revealed the importance of signals from pharyngeal mesoderm itself, as well as critical inputs from adjacent pharyngeal epithelia and neural crest cells. Proliferation is emerging as a central checkpoint in the regulation of SHF development. Together, these studies contribute to defining the niche of cardiac progenitor cells in the early embryo, and we discuss the implications of these findings for the regulation of resident stem cell populations in the fetal and postnatal heart. Characterization of signals that maintain, expand, and regulate the differentiation of cardiac progenitor cells is essential for understanding both the etiology of congenital heart defects and the biomedical application of stem cell populations for cardiac repair."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I28,I28)","v":19063930},{"$f":"(LEN($J28) - LEN(SUBSTITUTE(LOWER($J28),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J28) - LEN(SUBSTITUTE(LOWER($J28),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J28) - LEN(SUBSTITUTE(LOWER($J28),LOWER(D$3),\"\")))/LEN(D$3)","v":5},{"$f":"SUM(B28:D28)","v":9},2009,"On the association between low resting heart rate and chronic aggression: retinoid toxicity hypothesis.","Mawson",19063930,"On the association between low resting heart rate and chronic aggression: retinoid toxicity hypothesis.    Abstract:   Low resting heart rate is a strong and consistent predictor of conduct disorder and chronic aggression. Explanations such as fearlessness and low arousal-induced stimulus-seeking have been offered, assuming a causal association between the phenomena, but the origin of low heart rate and its significance for understanding aggression and violence remain obscure. Retinoids (vitamin A and its congeners) play important roles in embryogenesis and neural development. Several lines of evidence also suggest a causal role of retinoids in aggression as well as cognitive and mood disorders. The hypothesis is proposed that retinoid overexpression in utero induces, via a noradrenergic-to-cholinergic switch, alterations in cardiac functioning and hemodynamics resulting in low resting heart rate, brain structural and functional changes, minor physical anomalies, and persistent aggression. Retinoid toxicity occurring early in pregnancy could represent a final common pathway by which various prenatal challenges result in conduct disorder and chronic aggression (e.g., maternal cigarette smoking, alcohol consumption, drug use, exposure to environmental chemicals, stress, trauma or infection). Implications of the model for understanding related aspects of chronic aggression are discussed, as well as strategies for prevention and treatment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I29,I29)","v":11238746},{"$f":"(LEN($J29) - LEN(SUBSTITUTE(LOWER($J29),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J29) - LEN(SUBSTITUTE(LOWER($J29),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J29) - LEN(SUBSTITUTE(LOWER($J29),LOWER(D$3),\"\")))/LEN(D$3)","v":7},{"$f":"SUM(B29:D29)","v":9},2001,"Function of vitamin A in vertebrate embryonic development.","Zile",11238746,"Function of vitamin A in vertebrate embryonic development.    Abstract:   Advances in molecular biology and retinoic acid receptor research have significantly contributed to the understanding of the role of vitamin A during vertebrate development. Examination of the function of this vitamin during very early developmental stages using the completely vitamin A-depleted avian embryo has revealed that the vitamin A requirement begins at the time of formation of the primitive heart, circulation and specification of hindbrain. The lack of vitamin A at this critical time results in gross abnormalities and early embryonic death. In rodent models, vitamin A deficiency can be targeted to later gestational windows and documents the need for vitamin A for more advanced stages of development. Major target tissues of vitamin A deficiency include the heart, central nervous system and structures derived from it, the circulatory, urogenital and respiratory systems, and the development of skull, skeleton and limbs. These abnormalities are also evident in mice mutants from retinoid receptor knockouts; they have revealed both morphological and molecular aspects of vitamin A function during development. Retinoic acid receptors (RAR) in partnership with retinoid X receptor (RXR)alpha appear to be the important retinoid receptor transcription factors regulating vitamin A function at the gene level during development via the physiologic ligand all-trans-retinoic acid. Homeostasis of retinoic acid is maintained by developmentally regulated vitamin A metabolism enzyme systems. Inadequate vitamin A nutrition during early pregnancy may account for some pediatric congenital abnormalities."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I30,I30)","v":10466190},{"$f":"(LEN($J30) - LEN(SUBSTITUTE(LOWER($J30),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J30) - LEN(SUBSTITUTE(LOWER($J30),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J30) - LEN(SUBSTITUTE(LOWER($J30),LOWER(D$3),\"\")))/LEN(D$3)","v":8},{"$f":"SUM(B30:D30)","v":9},1999,"Optimal nutrition: vitamin A and the carotenoids.","Thurnham",10466190,"Optimal nutrition: vitamin A and the carotenoids.    Abstract:   There are two major dietary sources of vitamin A: easily absorbed retinyl palmitate in foods of animal origin, and poorly bioavailable carotenoids from plant foods. Plasma retinol is tightly controlled, probably by regulation of retinol-binding protein (RBP) formation in the liver, and only hormonal factors (e.g. oral contraceptives) and infection will alter the homeostasis. Delivery of retinol to the tissues is facilitated by the RBP-retinol complex; however, there is evidence that this mechanism can be bypassed when very high doses of vitamin A are given. Some retinyl ester may be released to tissues from chylomicrons when the latter bind to tissue lipoprotein receptors during their passage from the gut to the liver following a meal. High-dose vitamin A therapy is a means of rapidly improving vitamin A status in persons with sub-optimal vitamin A nutrition but there are dangers of toxic symptoms (e.g. teratogenicity) from excess vitamin A usage. Evidence is presented to suggest that the plasma retinol: RBP may be a guide to optimal vitamin A status, since values less than one frequently occur in less-developed countries and during infection. In contrast to plasma retinol, plasma carotenoids reflect the dietary intake of plant foods. However, absorption is limited by poor bioavailability and a saturable uptake mechanism in competition with other phytochemicals. Recent work on bioavailability suggests that the calculation of plant food vitamin A activity should be re-examined. Illness has little influence on plasma levels except by suppressing appetite. Carotenoids are generally regarded as non-toxic yet intervention studies with beta-carotene in smokers have been associated with increased lung cancer and heart disease. Some carotenoids are important as vitamin A precursors, but the physiological importance of their antioxidant properties is not known and consequently the amount needed for optimal nutrition is uncertain."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I31,I31)","v":10357725},{"$f":"(LEN($J31) - LEN(SUBSTITUTE(LOWER($J31),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J31) - LEN(SUBSTITUTE(LOWER($J31),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J31) - LEN(SUBSTITUTE(LOWER($J31),LOWER(D$3),\"\")))/LEN(D$3)","v":9},{"$f":"SUM(B31:D31)","v":9},1999,"Alcohol, vitamin A, and beta-carotene: adverse interactions, including hepatotoxicity and carcinogenicity.","Leo",10357725,"Alcohol, vitamin A, and beta-carotene: adverse interactions, including hepatotoxicity and carcinogenicity.    Abstract:   Isozymes of alcohol and other dehydrogenases convert ethanol and retinol to their corresponding aldehydes in vitro. In addition, new pathways of retinol metabolism have been described in hepatic microsomes that involve, in part, cytochrome P450s, which can also metabolize various drugs. In view of these overlapping metabolic pathways, it is not surprising that multiple interactions between retinol, ethanol, and other drugs occur. Accordingly, prolonged use of alcohol, drugs, or both, results not only in decreased dietary intake of retinoids and carotenoids, but also accelerates the breakdown of retinol through cross-induction of degradative enzymes. There is also competition between ethanol and retinoic acid precursors. Depletion ensues, with associated hepatic and extrahepatic pathology, including carcinogenesis and contribution to fetal defects. Correction of deficiency through vitamin A supplementation has been advocated. It is, however, complicated by the intrinsic hepatotoxicity of retinol, which is potentiated by concomitant alcohol consumption. By contrast, beta-carotene, a precursor of vitamin A, was considered innocuous until recently, when it was found to also interact with ethanol, which interferes with its conversion to retinol. Furthermore, the combination of beta-carotene with ethanol results in hepatotoxicity. Moreover, in smokers who also consume alcohol, beta-carotene supplementation promotes pulmonary cancer and, possibly, cardiovascular complications. Experimentally, beta-carotene toxicity was exacerbated when administered as part of beadlets. Thus ethanol, while promoting a deficiency of vitamin A also enhances its toxicity as well as that of beta-carotene. This narrowing of the therapeutic window for retinol and beta-carotene must be taken into account when formulating treatments aimed at correcting vitamin A deficiency, especially in drinking populations."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I32,I32)","v":10208011},{"$f":"(LEN($J32) - LEN(SUBSTITUTE(LOWER($J32),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J32) - LEN(SUBSTITUTE(LOWER($J32),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J32) - LEN(SUBSTITUTE(LOWER($J32),LOWER(D$3),\"\")))/LEN(D$3)","v":8},{"$f":"SUM(B32:D32)","v":9},1999,"Retinoids and mammalian development.","Morriss-Kay",10208011,"Retinoids and mammalian development.    Abstract:   All vertebrate embryos require retinoic acid (RA) for fulfilment of the developmental program encoded in the genome. In mammals, maternal homeostatic mechanisms minimize variation of retinoid levels reaching the embryo. Retinol is transported as a complex with retinol-binding protein (RBP): transplacental transfer of retinol and its uptake by the embryonic tissues involves binding to an RBP receptor at the cell surface. Embryonic tissues in which this receptor is present also contain the retinol-binding protein CRBP I and the enzymes involved in RA synthesis; the same tissues are particularly vulnerable to vitamin A deficiency. In the nucleus, the RA signal is transduced by binding to a heterodimeric pair of retinoid receptors (RAR/RXR). In general, the receptors show functional plasticity, disruption of one RAR or RXR gene having minor or no effects on embryogenesis. However, genetic studies indicate that RXR alpha is essential for normal development of the heart and eye. Excess RA causes abnormalities of many systems; altered susceptibility to RA excess in mice lacking RAR gamma or RXR alpha suggests that the teratogenic signal is transduced through different receptors compared with physiological RA function in the same tissue."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I33,I33)","v":9565738},{"$f":"(LEN($J33) - LEN(SUBSTITUTE(LOWER($J33),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J33) - LEN(SUBSTITUTE(LOWER($J33),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J33) - LEN(SUBSTITUTE(LOWER($J33),LOWER(D$3),\"\")))/LEN(D$3)","v":9},{"$f":"SUM(B33:D33)","v":9},1998,"Retinoic acid syndrome. Recognition, prevention and management.","Fenaux",9565738,"Retinoic acid syndrome. Recognition, prevention and management.    Abstract:   The introduction of treatment with tretinoin (all-trans retinoic acid) and its combination with antineoplastic therapy has improved the outcome of acute promyelocytic leukaemia (APL). Retinoic acid syndrome is the major adverse effect of tretinoin and it occurs in about 25% of treated APL patients in the absence of prophylactic measures and is often fatal. Generally, the retinoic acid syndrome is associated with increasing leucocyte counts and is probably caused by the release of several cytokines by maturing blast cells. The retinoic acid syndrome gives a clinical picture of bodyweight gain, respiratory distress, serous effusions and cardiac and renal failure. Adequate prophylaxis, based on the addition to tretinoin of dexamethasone and also, according to most authors, antineoplastic therapy (in case of rapidly increasing leucocyte counts) has decreased the incidence of retinoic acid syndrome to about 15%. Most importantly, these measures have reduced its mortality to about 1% of all treated patients."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I34,I34)","v":7788867},{"$f":"(LEN($J34) - LEN(SUBSTITUTE(LOWER($J34),LOWER(B$3),\"\")))/LEN(B$3)","v":8},{"$f":"(LEN($J34) - LEN(SUBSTITUTE(LOWER($J34),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J34) - LEN(SUBSTITUTE(LOWER($J34),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B34:D34)","v":9},1995,"Molecular regulation of atrioventricular valvuloseptal morphogenesis.","Eisenberg",7788867,"Molecular regulation of atrioventricular valvuloseptal morphogenesis.    Abstract:   The majority of congenital heart defects arise from abnormal development of valvuloseptal tissue. The primordia of the valve leaflets and membranous septa of the heart are the cardiac cushions. Remodeling of the cushions is associated with a transitional extracellular matrix that includes sulfated proteoglycans and the microfibrillar proteins fibulin and fibrillin. Cushion formation is restricted to the AV canal and ventricular outflow tract regions of the primary heart tube. The proper placement of the cushions may be the result of the development of the primary heart tube as a segmented organ, as well as the subsequent looping of the heart. Segmentation of the heart tube may be demonstrated by the alternating molecular expression pattern along the longitudinal axis. In support of this hypothesis is the restricted expression of BMP-4 and msx-2 to the AV canal and ventricular outflow tract. The importance of looping for cushion positioning may imply that the iv and inv genes and retinoic acid are important for the proper patterning of the heart. The cells of the cushions evolve from endocardial cells that undergo an epithelial-to-mesenchymal transformation. This developmental event is regulated by the myocardium and is probably due to the production of protein complexes, present within the cardiac jelly of the cushion-forming regions, that consist of fibronectin and the ES proteins. Both the cushion mesenchyme and its endocardial cell antecedents express JB3, an ECM protein. JB3 expression is also featured within the heart-forming fields of the primary mesoderm, from which the endocardial progenitors of the cushion cells originate.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I35,I35)","v":25134739},{"$f":"(LEN($J35) - LEN(SUBSTITUTE(LOWER($J35),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J35) - LEN(SUBSTITUTE(LOWER($J35),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J35) - LEN(SUBSTITUTE(LOWER($J35),LOWER(D$3),\"\")))/LEN(D$3)","v":6},{"$f":"SUM(B35:D35)","v":8},2015,"Signaling through retinoic acid receptors in cardiac development: Doing the right things at the right times.","Xavier-Neto",25134739,"Signaling through retinoic acid receptors in cardiac development: Doing the right things at the right times.    Abstract:   Retinoic acid (RA) is a terpenoid that is synthesized from vitamin A/retinol (ROL) and binds to the nuclear receptors retinoic acid receptor (RAR)/retinoid X receptor (RXR) to control multiple developmental processes in vertebrates. The available clinical and experimental data provide uncontested evidence for the pleiotropic roles of RA signaling in development of multiple embryonic structures and organs such eyes, central nervous system, gonads, lungs and heart. The development of any of these above-mentioned embryonic organ systems can be effectively utilized to showcase the many strategies utilized by RA signaling. However, it is very likely that the strategies employed to transfer RA signals during cardiac development comprise the majority of the relevant and sophisticated ways through which retinoid signals can be conveyed in a complex biological system. Here, we provide the reader with arguments indicating that RA signaling is exquisitely regulated according to specific phases of cardiac development and that RA signaling itself is one of the major regulators of the timing of cardiac morphogenesis and differentiation. We will focus on the role of signaling by RA receptors (RARs) in early phases of heart development. This article is part of a Special Issue entitled: Nuclear receptors in animal development."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I36,I36)","v":22254040},{"$f":"(LEN($J36) - LEN(SUBSTITUTE(LOWER($J36),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J36) - LEN(SUBSTITUTE(LOWER($J36),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J36) - LEN(SUBSTITUTE(LOWER($J36),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B36:D36)","v":8},2010,"Vitamin A-not for your eyes only: requirement for heart formation begins early in embryogenesis.","Zile",22254040,"Vitamin A-not for your eyes only: requirement for heart formation begins early in embryogenesis.    Abstract:   Vitamin A insufficiency has profound adverse effects on embryonic development. Major advances in understanding the role of vitamin A in vertebrate heart formation have been made since the discovery that the vitamin A active form, all-trans-retinoic acid, regulates many genes, including developmental genes. Among the experimental models used, the vitamin A-deficient avian embryo has been an important tool to study the function of vitamin A during early heart formation. A cluster of retinoic acid-regulated developmental genes have been identified that participate in building the heart. In the absence of retinoic acid the embryonic heart develops abnormally leading to embryolethality."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I37,I37)","v":18661045},{"$f":"(LEN($J37) - LEN(SUBSTITUTE(LOWER($J37),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J37) - LEN(SUBSTITUTE(LOWER($J37),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J37) - LEN(SUBSTITUTE(LOWER($J37),LOWER(D$3),\"\")))/LEN(D$3)","v":5},{"$f":"SUM(B37:D37)","v":8},2008,"The expanding role for retinoid signaling in heart development.","Hoover",18661045,"The expanding role for retinoid signaling in heart development.    Abstract:   The importance of retinoid signaling during cardiac development has long been appreciated, but recently has become a rapidly expanding field of research. Experiments performed over 50 years ago showed that too much or too little maternal intake of vitamin A proved detrimental for embryos, resulting in a cadre of predictable cardiac developmental defects. Germline and conditional knockout mice have revealed which molecular players in the vitamin A signaling cascade are potentially responsible for regulating specific developmental events, and many of these molecules have been temporally and spatially characterized. It is evident that intact and controlled retinoid signaling is necessary for each stage of cardiac development to proceed normally, including cardiac lineage determination, heart tube formation, looping, epicardium formation, ventricular maturation, chamber and outflow tract septation, and coronary arteriogenesis. This review summarizes many of the significant milestones in this field and particular attention is given to recently uncovered cross-talk between retinoid signaling and other developmentally significant pathways. It is our hope that this review of the role of retinoid signaling during formation, remodeling, and maturation of the developing heart will serve as a tool for future discoveries."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I38,I38)","v":17368319},{"$f":"(LEN($J38) - LEN(SUBSTITUTE(LOWER($J38),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J38) - LEN(SUBSTITUTE(LOWER($J38),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J38) - LEN(SUBSTITUTE(LOWER($J38),LOWER(D$3),\"\")))/LEN(D$3)","v":5},{"$f":"SUM(B38:D38)","v":8},2007,"Retinoic acid and the heart.","Pan",17368319,"Retinoic acid and the heart.    Abstract:   Retinoic acid (RA), the active derivative of vitamin A, by acting through retinoid receptors, is involved in signal transduction pathways regulating embryonic development, tissue homeostasis, and cellular differentiation and proliferation. RA is important for the development of the heart. The requirement of RA during early cardiovascular morphogenesis has been studied in targeted gene deletion of retinoic acid receptors and in the vitamin A-deficient avian embryo. The teratogenic effects of high doses of RA on cardiovascular morphogenesis have also been demonstrated in different animal models. Specific cardiovascular targets of retinoid action include effects on the specification of cardiovascular tissues during early development, anteroposterior patterning of the early heart, left/right decisions and cardiac situs, endocardial cushion formation, and in particular, the neural crest. In the postdevelopment period, RA has antigrowth activity in fully differentiated neonatal cardiomyocytes and cardiac fibroblasts. Recent studies have shown that RA has an important role in the cardiac remodeling process in rats with hypertension and following myocardial infarction. This chapter will focus on the role of RA in regulating cardiomyocyte growth and differentiation during embryonic and the postdevelopment period."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I39,I39)","v":14754643},{"$f":"(LEN($J39) - LEN(SUBSTITUTE(LOWER($J39),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J39) - LEN(SUBSTITUTE(LOWER($J39),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J39) - LEN(SUBSTITUTE(LOWER($J39),LOWER(D$3),\"\")))/LEN(D$3)","v":7},{"$f":"SUM(B39:D39)","v":8},2004,"Single-center retrospective study of long-term use of low-dose acitretin (Soriatane) for psoriasis.","Lee",14754643,"Single-center retrospective study of long-term use of low-dose acitretin (Soriatane) for psoriasis.    Abstract:    BACKGROUND : Indicated as monotherapy for severe psoriasis in adults, acitretin (Soriatane) can be used in combination therapy or as a disease-stabilizing, maintenance agent. While its efficacy for psoriasis and other disorders of keratinization is well established, its safety is often a concern for many dermatologists. The possible side effects associated with short-term treatment of oral retinoids include mucocutaneous effects, elevation in serum lipid chemistries and liver enzymes, and teratogenicity. However, the only possible long-term, cumulative side effect is skeletal and ligamentous calcification such as hyperostosis. There is a specific syndrome of hyperostosis associated with oral retinoids called DISH (diffuse idiopathic skeletal hyperostosis).  OBJECTIVE : To examine the incidence of DISH syndrome in long-term acitretin use for psoriasis and to quantify the incidence of other side effects.  METHODS : All patients seen at the UCSF Psoriasis and Skin Treatment Center who had been on acitretin for more than 1 year were identified.  RESULTS : A chart review of these patients revealed no X-ray-confirmed cases of DISH syndrome, minimal changes in coronary heart disease risk indicators, and extremely rare significant elevation of liver enzymes.  CONCLUSION : Acitretin does not appear to cause significant long-term side effects at low doses; the implications for thousands of patients are that use of this medication can be continued for long periods of time with routine monitoring."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I40,I40)","v":11606948},{"$f":"(LEN($J40) - LEN(SUBSTITUTE(LOWER($J40),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J40) - LEN(SUBSTITUTE(LOWER($J40),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J40) - LEN(SUBSTITUTE(LOWER($J40),LOWER(D$3),\"\")))/LEN(D$3)","v":8},{"$f":"SUM(B40:D40)","v":8},2001,"Regulation of lipid and lipoprotein metabolism by retinoids.","Staels",11606948,"Regulation of lipid and lipoprotein metabolism by retinoids.    Abstract:   Retinoids are small vitamin A-derived lipophilic compounds that influence a wide variety of developmental and metabolic processes. Retinoids exert their action by activating transcription factors belonging to the retinoic acid receptor (RAR) and retinoid X receptor (RXR) subfamilies of nuclear receptors. Therapeutically, retinoids are used for the treatment of dermatological disorders and certain cancers. Dyslipidemia is a common side-effect of therapy with the currently available retinoids. This review summarizes our current understanding of the molecular mechanisms of regulation of lipid and lipoprotein metabolism by retinoids."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I41,I41)","v":8801178},{"$f":"(LEN($J41) - LEN(SUBSTITUTE(LOWER($J41),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J41) - LEN(SUBSTITUTE(LOWER($J41),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J41) - LEN(SUBSTITUTE(LOWER($J41),LOWER(D$3),\"\")))/LEN(D$3)","v":7},{"$f":"SUM(B41:D41)","v":8},1996,"Embryonic development and pattern formation.","Morriss-Kay",8801178,"Embryonic development and pattern formation.    Abstract:   During embryogenesis, information encoded in the genome is translated into cell proliferation, morphogenesis, and early stages of differentiation. Embryonic pattern arises from the spatial and temporal regulation and coordination of these events. The vitamin A (retinol) derivative retinoic acid (RA) is essential for normal development. Mammalian embryos are protected against vitamin A deficiency by maternal retinoid homeostasis until stored retinoids fall to very low levels. Retinol binding protein, which is synthesized in the yolk sac placenta of rodent embryos and in the syncytiotrophoblast of the human placenta, is essential for access of retinol to the embryo. Synthesis and metabolism of RA may involve cytoplasmic binding proteins, but the observation that mutants lacking these proteins are normal or near-normal suggests that they are not essential. Severe congenital vitamin A deficiency results in a spectrum of malformations including defects of the eye, lungs, cardiovascular system, and urogenital system. Extreme deficiency results as well in forelimb abnormalities and cleft face, but the embryos are not viable. Similar abnormalities are observed in embryos lacking two retinoid receptors, but loss of one receptor results in either normal development or mild abnormalities. Two single-receptor null mutants, RARgamma-/- and RXRalpha-/-, show regional pattern-specific resistance to teratogenic levels of RA. Mutations leading to abnormality of the structure or regulation of RA signaling pathway genes may be an important cause of human congenital abnormality."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I42,I42)","v":1460122},{"$f":"(LEN($J42) - LEN(SUBSTITUTE(LOWER($J42),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J42) - LEN(SUBSTITUTE(LOWER($J42),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J42) - LEN(SUBSTITUTE(LOWER($J42),LOWER(D$3),\"\")))/LEN(D$3)","v":8},{"$f":"SUM(B42:D42)","v":8},1992,"Long-term safety of retinoid therapy.","Vahlquist",1460122,"Long-term safety of retinoid therapy.    Abstract:   The concern about long-term toxicity of oral synthetic retinoids has developed because many patients, especially those with genodermatoses, require lifelong therapy. Several organ systems are at risk, especially the hepatic, skeletal, and cardiovascular systems. Although acute hepatotoxicity is a rare side effect of etretinate and acitretin therapy, prospective studies have not demonstrated chronic liver toxicity. The frequency of bone changes induced by retinoids is difficult to estimate, because this adverse effect is usually asymptomatic and requires x-ray or scintigraphic examination for detection. Atherosclerosis develops in many patients who receive long-term retinoid therapy, but the extent to which the process is aggravated by drug-induced hyperlipidemia is not known. Many patients have now been treated with either etretinate or isotretinoin continuously for as many as 15 years and have not developed any signs of severe chronic toxicity. However, continued intense surveillance is recommended for patients expected to require lifelong therapy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I43,I43)","v":1667403},{"$f":"(LEN($J43) - LEN(SUBSTITUTE(LOWER($J43),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J43) - LEN(SUBSTITUTE(LOWER($J43),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J43) - LEN(SUBSTITUTE(LOWER($J43),LOWER(D$3),\"\")))/LEN(D$3)","v":7},{"$f":"SUM(B43:D43)","v":8},1991,"Retinoid-binding proteins in craniofacial development.","Dencker",1667403,"Retinoid-binding proteins in craniofacial development.    Abstract:   Cephalic neural crest cells are known to form the frontonasal mesenchyme and contribute to the mesenchyme of the visceral arches. Retinoids affect neural crest cells and their derivatives during development, and thus cause craniofacial, thymus, and conotruncal heart malformations. In addition, retinoids induce malformations of the central nervous system (CNS). Retinoic acid (RA) and its congeners accumulate in a saturable manner in neural crest and neural crest-derived cells, in the hindbrain, and the spinal cord of mouse embryos. Cellular retinoic acid-binding protein (CRABP) was localized by immunohistochemistry in the same areas as were the labelled RA congeners. Thus, CRABP and RA congeners were found in the transitional zone between surface ectoderm and neuropeithelium, from where neural crest cells are known to emanate (day 8 1/2). Later, specific labelling was found in the frontonasal mesenchyme and in the visceral arches. Also in the trunk, neural crest cells were labelled. In CNS, strong staining was seen in the rhombomeres (especially numbers 4-6) of the hindbrain and in the spinal cord. Retinol and cellular retinol-binding protein (CRBP) were more evenly distributed, with exception of surface ectoderm, epithelium of gut, and myocardium, where CRBP was specifically expressed. These findings are discussed in relation to the differential expression of nuclear RA receptors and homeobox genes in the craniofacial region and in the hindbrain. It is possible that RA is important for the normal pattern formation in these regions and acts as a morphogen as previously proposed in limb development."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I44,I44)","v":337808},{"$f":"(LEN($J44) - LEN(SUBSTITUTE(LOWER($J44),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J44) - LEN(SUBSTITUTE(LOWER($J44),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J44) - LEN(SUBSTITUTE(LOWER($J44),LOWER(D$3),\"\")))/LEN(D$3)","v":8},{"$f":"SUM(B44:D44)","v":8},1977,"Diseases of the retina: 1975-76 review.","Cohen",337808,"Diseases of the retina: 1975-76 review.    Abstract:   Articles on the retina which appeared in the American Journal of Ophthalmology, Archives of Ophthalmology, and British Journal of Ophthalmology from July 1975 to June 1976 are summarized. Topics include a specific receptor for retinol-binding protein, retinal pigment epithelium, retinitis pigmentosa, diabetic retinopathy, infections, degenerations, maculopathy, sickle hemoglobinopathy, retinoblastoma and retrolent fibroplasia, and macular hole and retinal detachment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I45,I45)","v":23891453},{"$f":"(LEN($J45) - LEN(SUBSTITUTE(LOWER($J45),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J45) - LEN(SUBSTITUTE(LOWER($J45),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J45) - LEN(SUBSTITUTE(LOWER($J45),LOWER(D$3),\"\")))/LEN(D$3)","v":7},{"$f":"SUM(B45:D45)","v":7},2013,"Guidelines for the use of acitretin in psoriasis. Psoriasis Group of the Spanish Academy of Dermatology and Venereology.","Carretero",23891453,"Guidelines for the use of acitretin in psoriasis. Psoriasis Group of the Spanish Academy of Dermatology and Venereology.    Abstract:   Phototherapy, classic systemic treatments (methotrexate, acitretin, and ciclosporin), and biologic agents (etanercept, infliximab, adalimumab, and ustekinumab) constitute a broad therapeutic arsenal that increases the likelihood of achieving control of severe and extensive disease in patients with psoriasis. Acitretin continues to be a very valuable tool in both monotherapy, in which it is combined with other systemic treatments (classic or biologic), and in sequential therapy. Thanks to its lack of a direct immunosuppressive effect and its ability to achieve a long-term response, acitretin has an important role in the treatment of psoriasis, although this has not always been acknowledged in relevant treatment guidelines. We present consensus guidelines for the use of acitretin in psoriasis drawn up by the Psoriasis Group of the Spanish Academy of Dermatology and Venereology. These guidelines provide a detailed account of acitretin, including pharmacological properties, indications and contraindications, adverse effects, and factors that should be taken into account to enhance the safe use of this drug. They also propose treatment strategies for use in routine clinical practice. The overall aim of these guidelines is to define the criteria for the use and management of acetretin in psoriasis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I46,I46)","v":23479131},{"$f":"(LEN($J46) - LEN(SUBSTITUTE(LOWER($J46),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J46) - LEN(SUBSTITUTE(LOWER($J46),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J46) - LEN(SUBSTITUTE(LOWER($J46),LOWER(D$3),\"\")))/LEN(D$3)","v":7},{"$f":"SUM(B46:D46)","v":7},2013,"The roles of endogenous retinoid signaling in organ and appendage regeneration.","Blum",23479131,"The roles of endogenous retinoid signaling in organ and appendage regeneration.    Abstract:   The ability to regenerate injured or lost body parts has been an age-old ambition of medical science. In contrast to humans, teleost fish and urodele amphibians can regrow almost any part of the body with seeming effortlessness. Retinoic acid is a molecule that has long been associated with these impressive regenerative capacities. The discovery 30 years ago that addition of retinoic acid to regenerating amphibian limbs causes quot;super-regenerationquot; initiated investigations into the presumptive roles of retinoic acid in regeneration of appendages and other organs. However, the evidence favoring or dismissing a role for endogenous retinoids in regeneration processes remained sparse and ambiguous. Now, the availability of genetic tools to manipulate and visualize the retinoic acid signaling pathway has opened up new routes to dissect its roles in regeneration. Here, we review the current understanding on endogenous functions of retinoic acid in regeneration and discuss key questions to be addressed in future research."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I47,I47)","v":22427324},{"$f":"(LEN($J47) - LEN(SUBSTITUTE(LOWER($J47),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J47) - LEN(SUBSTITUTE(LOWER($J47),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J47) - LEN(SUBSTITUTE(LOWER($J47),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B47:D47)","v":7},2012,"Zebrafish in the study of early cardiac development.","Liu",22427324,"Zebrafish in the study of early cardiac development.    Abstract:   Heart development is a complex process that involves cell specification and differentiation, as well as elaborate tissue morphogenesis and remodeling, to generate a functional organ. The zebrafish has emerged as a powerful model system to unravel the basic genetic, molecular, and cellular mechanisms of cardiac development and function. We summarize and discuss recent discoveries on early cardiac specification and the identification of the second heart field in zebrafish. In addition to the inductive signals regulating cardiac specification, these studies have shown that heart development also requires a repressive mechanism imposed by retinoic acid signaling to select cardiac progenitors from a multipotent population. Another recent advance in the study of early zebrafish cardiac development is the identification of the second heart field. These studies suggest that the molecular mechanisms that regulate the second heart field development are conserved between zebrafish and other vertebrates including mammals and provide insight into the evolution of the second heart field and its derivatives."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I48,I48)","v":17203669},{"$f":"(LEN($J48) - LEN(SUBSTITUTE(LOWER($J48),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J48) - LEN(SUBSTITUTE(LOWER($J48),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J48) - LEN(SUBSTITUTE(LOWER($J48),LOWER(D$3),\"\")))/LEN(D$3)","v":7},{"$f":"SUM(B48:D48)","v":7},2007,"Contribution of targeted conditional somatic mutagenesis to deciphering retinoid X receptor functions and to generating mouse models of human diseases.","Metzger",17203669,"Contribution of targeted conditional somatic mutagenesis to deciphering retinoid X receptor functions and to generating mouse models of human diseases.    Abstract:   The last decade has witnessed an enormous rise in the interest for retinoid signalling and its cognate receptors, because of their central role in the coordination of development and homeostasis, through their ability to orchestrate the expression of numerous target genes. These receptors include six nuclear receptor (NR) family members, the retinoic acid receptor (RAR) alpha, beta and gamma, and the retinoid X receptor (RXR) alpha, beta and gamma, which are expressed in many cell types in mammals. Analysis of the development of mouse embryos bearing retinoid receptor null mutations demonstrated that these receptors transduce the effects of retinoic acid (RA, the active derivative of vitamin A) in vivo, and revealed impressive complexity. However, frequent redundancy in receptor functions and lethality of compound RAR-null mutants, as well as of RXRalpha-null mutants, precluded the characterisation of the functions of these receptors during late development and postnatally. We illustrate here how recent developments of conditional targeted somatic mutagenesis have opened new avenues in analysing the physiological functions of retinoid X receptor signalling in a variety of tissues and cell types, as well as in exploring the pathophysiological consequences of their alteration that led to novel mouse models of human diseases."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I49,I49)","v":10218665},{"$f":"(LEN($J49) - LEN(SUBSTITUTE(LOWER($J49),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J49) - LEN(SUBSTITUTE(LOWER($J49),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J49) - LEN(SUBSTITUTE(LOWER($J49),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B49:D49)","v":7},1999,"Antioxidant potentials of vitamin A and carotenoids and their relevance to heart disease.","Palace",10218665,"Antioxidant potentials of vitamin A and carotenoids and their relevance to heart disease.    Abstract:   Despite being one of the first vitamins to be discovered, the full range of biological activities for vitamin A remains to be defined. Structurally similar to vitamin A, carotenoids are a group of nearly 600 compounds. Only about 50 of these have provitamin A activity. Recent evidence has shown vitamin A, carotenoids and provitamin A carotenoids can be effective antioxidants for inhibiting the development of heart disease. Vitamin A must be obtained from the diet: green and yellow vegetables, dairy products, fruits and organ meats are some of the richest sources. Within the body, vitamin A can be found as retinol, retinal and retinoic acid. Because all of these forms are toxic at high concentrations, they are bound to proteins in the extracellular fluids and inside cells. Vitamin A is stored primarily as long chain fatty esters and as provitamin carotenoids in the liver, kidney and adipose tissue. The antioxidant activity of vitamin A and carotenoids is conferred by the hydrophobic chain of polyene units that can quench singlet oxygen , neutralize thiyl radicals and combine with and stabilize peroxyl radicals. In general, the longer the polyene chain, the greater the peroxyl radical stabilizing ability. Because of their structures, vitamin A and carotenoids can autoxidize when O2 tension increases, and thus are most effective antioxidants at low oxygen tensions that are typical of physiological levels found in tissues. Overall, the epidemiological evidence suggests that vitamin A and carotenoids are important dietary factors for reducing the incidence of heart disease. Although there is considerable discrepancy in the results from studies in humans regarding this relationship, carefully controlled experimental studies continue to indicate that these compounds are effective for mitigating and defending against many forms of cardiovascular disease. More work, especially concerning the relevance of how tissue concentrations, rather than plasma levels, relate to the progression of tissue damage in heart disease is required. This review assembles information regarding the basic structure and metabolism of vitamin A and carotenoids as related to their antioxidant activities. Epidemiological, intervention trials and experimental evidence about the effectiveness of vitamin A and carotenoids for reducing cardiovascular disease is also reviewed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I50,I50)","v":2049060},{"$f":"(LEN($J50) - LEN(SUBSTITUTE(LOWER($J50),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J50) - LEN(SUBSTITUTE(LOWER($J50),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J50) - LEN(SUBSTITUTE(LOWER($J50),LOWER(D$3),\"\")))/LEN(D$3)","v":7},{"$f":"SUM(B50:D50)","v":7},1991,"[Individual differences in the vitamin A metabolism of the order Carnivora--a review].","Schweigert",2049060,"[Individual differences in the vitamin A metabolism of the order Carnivora--a review].    Abstract:   Vitamin A transport in blood of most species in the order carnivora is fundamentally different from other animals and man. Very high levels of vitamin A in blood plasma of canines and mustelides are due to a high percentage of retinyl esters. These esters (basically retinyl palmitate and stearate) are transported nonspecifically bound to lipoproteins with very-low and low density lipoproteins representing the major fractions (about 70% of total vitamin A esters). A high percentage of retinyl esters could also be found in the families Ursidae, Procyonidae, Viverridae and Felidae in which total vitamin A in blood was low. In man and rat severe signs of vitamin A intoxication can be observed due to a similarly high percentage of nonspecifically bound vitamin A esters. No clinical or clinical-chemical signs of vitamin A intoxication were observed in the animals investigated. Because vitamin A esters are transported by lipoproteins, their blood levels are readily affected by dietary vitamin A supply as it is known to be the case for vitamin E. Furthermore, canines seem to be the only ones that excrete vitamin A as retinol and retinyl esters (basically retinyl palmitate) under physiological conditions with the urine. These fat-soluble metabolites of vitamin A are bound to a protein with a molecular weight between 50,000 and 125,000 Da which shows characteristics of a lipoprotein when subjected to ultracentrifugation or selective precipitation. Higher levels of vitamin A in organs and tissues, as well as the excretion of vitamin A with the urine, might be a consequence of the nonspecific binding of large amounts of retinyl esters to lipoproteins in blood.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I51,I51)","v":26237391},{"$f":"(LEN($J51) - LEN(SUBSTITUTE(LOWER($J51),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J51) - LEN(SUBSTITUTE(LOWER($J51),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J51) - LEN(SUBSTITUTE(LOWER($J51),LOWER(D$3),\"\")))/LEN(D$3)","v":5},{"$f":"SUM(B51:D51)","v":6},2014,"Molecular Mechanisms of Retinoid Receptors in Diabetes-Induced Cardiac Remodeling.","Pan",26237391,"Molecular Mechanisms of Retinoid Receptors in Diabetes-Induced Cardiac Remodeling.    Abstract:   Diabetic cardiomyopathy (DCM), a significant contributor to morbidity and mortality in diabetic patients, is characterized by ventricular dysfunction, in the absence of coronary atherosclerosis and hypertension. There is no specific therapeutic strategy to effectively treat patients with DCM, due to a lack of a mechanistic understanding of the disease process. Retinoic acid, the active metabolite of vitamin A, is involved in a wide range of biological processes, through binding and activation of nuclear receptors: retinoic acid receptors (RAR) and retinoid X receptors (RXR). RAR/RXR-mediated signaling has been implicated in the regulation of glucose and lipid metabolism. Recently, it has been reported that activation of RAR/RXR has an important role in preventing the development of diabetic cardiomyopathy, through improving cardiac insulin resistance, inhibition of intracellular oxidative stress, NF-κB-mediated inflammatory responses and the renin-angiotensin system. Moreover, downregulated RAR/RXR signaling has been demonstrated in diabetic myocardium, suggesting that impaired RAR/RXR signaling may be a trigger to accelerate diabetes-induced development of DCM. Understanding the molecular mechanisms of retinoid receptors in the regulation of cardiac metabolism and remodeling under diabetic conditions is important in providing the impetus for generating novel therapeutic approaches for the prevention and treatment of diabetes-induced cardiac complications and heart failure."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I52,I52)","v":23932046},{"$f":"(LEN($J52) - LEN(SUBSTITUTE(LOWER($J52),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J52) - LEN(SUBSTITUTE(LOWER($J52),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J52) - LEN(SUBSTITUTE(LOWER($J52),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B52:D52)","v":6},2013,"An overview of the crosstalk between inflammatory processes and metabolic dysregulation during diabetic cardiomyopathy.","Palomer",23932046,"An overview of the crosstalk between inflammatory processes and metabolic dysregulation during diabetic cardiomyopathy.    Abstract:   Metabolic disorders such as obesity, insulin resistance and type 2 diabetes mellitus are all linked to cardiovascular diseases such as cardiac hypertrophy and heart failure. Diabetic cardiomyopathy in particular, is characterized by structural and functional alterations in the heart muscle of people with diabetes that finally lead to heart failure, and which is not directly attributable to coronary artery disease or hypertension. Several mechanisms have been involved in the pathogenesis of diabetic cardiomyopathy, such as alterations in myocardial energy metabolism and calcium signaling. Metabolic disturbances during diabetic cardiomyopathy are characterized by increased lipid oxidation, intramyocardial triglyceride accumulation, and reduced glucose utilization. Overall changes result in enhanced oxidative stress, mitochondrial dysfunction and apoptosis of the cardiomyocytes. On the other hand, the progression of heart failure and cardiac hypertrophy usually entails a local rise in cytokines in cardiac cells and the activation of the proinflammatory transcription factor nuclear factor (NF)-κB. Interestingly, increasing evidences are arising in the recent years that point to a potential link between chronic low-grade inflammation in the heart and metabolic dysregulation. Therefore, in this review we summarize recent new insights into the crosstalk between inflammatory processes and metabolic dysregulation in the failing heart during diabetes, paying special attention to the role of NF-κB and peroxisome proliferator activated receptors (PPARs). In addition, we briefly describe the role of the AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1) and other pathways regulating cardiac energy metabolism, as well as their relationship with diabetic cardiomyopathy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I53,I53)","v":23720419},{"$f":"(LEN($J53) - LEN(SUBSTITUTE(LOWER($J53),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J53) - LEN(SUBSTITUTE(LOWER($J53),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J53) - LEN(SUBSTITUTE(LOWER($J53),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B53:D53)","v":6},2013,"Embryonic cardiac chamber maturation: Trabeculation, conduction, and cardiomyocyte proliferation.","Samsa",23720419,"Embryonic cardiac chamber maturation: Trabeculation, conduction, and cardiomyocyte proliferation.    Abstract:   Congenital heart diseases are some of the most common human birth defects. Though some congenital heart defects can be surgically corrected, treatment options for other congenital heart diseases are very limited. In many congenital heart diseases, genetic defects lead to impaired embryonic heart development or growth. One of the key development processes in cardiac development is chamber maturation, and alterations in this maturation process can manifest as a variety of congenital defects including non-compaction, systolic dysfunction, diastolic dysfunction, and arrhythmia. During development, to meet the increasing metabolic demands of the developing embryo, the myocardial wall undergoes extensive remodeling characterized by the formation of muscular luminal protrusions called cardiac trabeculae, increased cardiomyocyte mass, and development of the ventricular conduction system. Though the basic morphological and cytological changes involved in early heart development are clear, much remains unknown about the complex biomolecular mechanisms governing chamber maturation. In this review, we highlight evidence suggesting that a wide variety of basic signaling pathways and biomechanical forces are involved in cardiac wall maturation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I54,I54)","v":19876792},{"$f":"(LEN($J54) - LEN(SUBSTITUTE(LOWER($J54),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J54) - LEN(SUBSTITUTE(LOWER($J54),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J54) - LEN(SUBSTITUTE(LOWER($J54),LOWER(D$3),\"\")))/LEN(D$3)","v":6},{"$f":"SUM(B54:D54)","v":6},2009,"Palovarotene, a novel retinoic acid receptor gamma agonist for the treatment of emphysema.","Hind",19876792,"Palovarotene, a novel retinoic acid receptor gamma agonist for the treatment of emphysema.    Abstract:   Emphysema is characterized by the destruction of alveoli and alveolar ducts within the lungs. Retinoid signaling is believed to play a role in alveologenesis, with the retinoic acid receptor gamma thought to be required for alveolar formation. Based on this hypothesis, Roche Holding AG is developing palovarotene (R-667, RO-3300074), a selective retinoic acid receptor gamma agonist for the treatment of emphysema. In small animal studies, palovarotene was claimed to reverse the structural, functional and inflammatory features of cigarette smoke-induced emphysema. Phase I clinical trials of palovarotene in patients with emphysema demonstrated that the drug is well tolerated, with improvements observed in markers of emphysema progression. Unlike all-trans retinoic acid, the pharmacokinetic profile of palovarotene appears to be dose-proportional. At the time of publication, a phase II, placebo-controlled trial was ongoing, and was expected to report prospective measurements of exercise, gas transfer and lung densitometry endpoints. The development of a selective retinoic acid receptor gamma agonist for the treatment of emphysema represents the first of a new class of small-molecule regenerative therapies that may prove useful for the treatment of destructive or age-related lung disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I55,I55)","v":19239019},{"$f":"(LEN($J55) - LEN(SUBSTITUTE(LOWER($J55),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J55) - LEN(SUBSTITUTE(LOWER($J55),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J55) - LEN(SUBSTITUTE(LOWER($J55),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B55:D55)","v":6},2008,"[Advance of study on vitamin A deficiency and excess associatied with congenital heart disease].","Xing",19239019,"[Advance of study on vitamin A deficiency and excess associatied with congenital heart disease].    Abstract:   It was demonstrated that Vitamin A may be crucial for heart morphogenesis during pregnancy. Both deficiency and excess of Vitamin A could induce certain congenital heart disease. In the gastrula stage, vitamin A could play a specific role in the process of heart development because of activating many gene regulations, in order to promote heart development. In this article, the advance of mechanism study on vitamin A associated with congenital heart disease were reviewed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I56,I56)","v":15981190},{"$f":"(LEN($J56) - LEN(SUBSTITUTE(LOWER($J56),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J56) - LEN(SUBSTITUTE(LOWER($J56),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J56) - LEN(SUBSTITUTE(LOWER($J56),LOWER(D$3),\"\")))/LEN(D$3)","v":6},{"$f":"SUM(B56:D56)","v":6},2005,"Congenital diaphragmatic hernia: a retinoid-signaling pathway disruption during lung development?","Gallot",15981190,"Congenital diaphragmatic hernia: a retinoid-signaling pathway disruption during lung development?    Abstract:   Congenital diaphragmatic hernia (CDH) usually occurs sporadically. The prognosis remains poor, with a 50% perinatal mortality rate. Most deaths result from hypoxemia due to lung hypoplasia and abnormal development of pulmonary vasculature that results in persistent pulmonary hypertension. Our current understanding of the pathogenesis of CDH is based on an assumption linking herniation of abdominal viscera into the thorax with compression of the developing lung. Pulmonary hypoplasia, however, can also result from reduced distension of the developing lung secondary to impaired fetal breathing movements. Moreover, a nitrofen-induced CDH model shows that lung hypoplasia precedes the diaphragmatic defect, leading to a quot;dual-hit hypothesis.quot; Recent data reveal the role of a retinoid-signaling pathway disruption in the pathogenesis of CDH. We describe the clinical and epidemiological aspects of human CDH, the metabolic and molecular aspects of the retinoid-signaling pathway, and the implications of retinoids in the development of the diaphragm and the lung. Finally, we highlight the existing links between CDH and disruption of the retinoid-signaling pathway, which may suggest an eventual use of retinoids in the treatment of CDH."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I57,I57)","v":15572135},{"$f":"(LEN($J57) - LEN(SUBSTITUTE(LOWER($J57),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J57) - LEN(SUBSTITUTE(LOWER($J57),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J57) - LEN(SUBSTITUTE(LOWER($J57),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B57:D57)","v":6},2005,"The evolutionary origin of cardiac chambers.","Simões-Costa",15572135,"The evolutionary origin of cardiac chambers.    Abstract:   Identification of cardiac mechanisms of retinoic acid (RA) signaling, description of homologous genetic circuits in Ciona intestinalis and consolidation of views on the secondary heart field have fundamental, but still unrecognized implications for vertebrate heart evolution. Utilizing concepts from evolution, development, zoology, and circulatory physiology, we evaluate the strengths of animal models and scenarios for the origin of vertebrate hearts. Analyzing chordates, lower and higher vertebrates, we propose a paradigm picturing vertebrate hearts as advanced circulatory pumps formed by segments, chambered or not, devoted to inflow or outflow. We suggest that chambers arose not as single units, but as components of a peristaltic pump divided by patterning events, contrasting with scenarios assuming that chambers developed one at a time. Recognizing RA signaling as a potential mechanism patterning cardiac segments, we propose to use it as a tool to scrutinize the phylogenetic origins of cardiac chambers within chordates. Finally, we integrate recent ideas on cardiac development such as the ballooning and secondary/anterior heart field paradigms, showing how inflow/outflow patterning may interact with developmental mechanisms suggested by these models."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I58,I58)","v":10573178},{"$f":"(LEN($J58) - LEN(SUBSTITUTE(LOWER($J58),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J58) - LEN(SUBSTITUTE(LOWER($J58),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J58) - LEN(SUBSTITUTE(LOWER($J58),LOWER(D$3),\"\")))/LEN(D$3)","v":5},{"$f":"SUM(B58:D58)","v":6},1999,"Retinoids and cell growth in the cardiovascular system.","Gardner",10573178,"Retinoids and cell growth in the cardiovascular system.    Abstract:   Deficiency of vitamin A and its retinoid metabolites has been associated with a number of developmental abnormalities in the cardiovascular system. Many of these effects are mimicked by targeted deletion of retinoic acid receptors in the embryo. Retinoids also display anti-growth activity in fully differentiated cardiac and vascular cells. These activities together with favorable effects on the clotting mechanism suggest that retinoids may prove useful in the management of hypertrophic/hyperproliferative disorders of the heart and vascular wall."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I59,I59)","v":9606738},{"$f":"(LEN($J59) - LEN(SUBSTITUTE(LOWER($J59),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J59) - LEN(SUBSTITUTE(LOWER($J59),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J59) - LEN(SUBSTITUTE(LOWER($J59),LOWER(D$3),\"\")))/LEN(D$3)","v":6},{"$f":"SUM(B59:D59)","v":6},1998,"Retinol and alpha-tocopherol in hemodialysis patients.","Zima",9606738,"Retinol and alpha-tocopherol in hemodialysis patients.    Abstract:   The biological effects of reactive oxygen species and other radicals controlled by antioxidant mechanisms are modified by various enzymes and other substrates. Antioxidant substrates are divided into those with lipophilic and hydrophilic groups. Retinol and tocopherol are the main representations of lipophilic antioxidants. The aim of the present study was to describe the changes of retinol and alpha-tocopherol which occurred in hemodialysis (HD) patients in respect to the influence of antioxidant systems. The experimental group consisted of 14 patients on regular HD treatment. The control group consisted of 14 healthy blood donors. HPLC was used to measure retinol and alpha-tocopherol in serum. We found that the retinol concentration was significantly higher in HD patients compared to controls (2.35 +/- 0.95 versus 0.90 +/- 0.23 mg/L, p lt; 0.0001). The concentration of alpha-tocopherol in serum was not different in both study groups (7.32 +/- 3.01 versus. 8.94 +/- 3.57 mg/L). A review of the MEDLINE database since 1985 found a few references concerning these important antioxidant vitamins in HD patients and these contained contrasting results. It has been suggested that some of the complications related to HD including cardiovascular complications, anemia and atherosclerosis may be due to ineffective antioxidant systems and/or to increased free oxygen radical production. The question about supplementation of antioxidants in HD patients is open although there are some positive data regarding the use of moderate and safe selenium supplementation in HD patients. HD patients treated by erythropoietin had increased plasma concentration of retinol and normal level of alpha-tocopherol compared to healthy group. However, this positive finding did not affect lipid peroxidation, which is increased in HD patients and leads to some complications during HD treatment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I60,I60)","v":9545093},{"$f":"(LEN($J60) - LEN(SUBSTITUTE(LOWER($J60),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J60) - LEN(SUBSTITUTE(LOWER($J60),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J60) - LEN(SUBSTITUTE(LOWER($J60),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B60:D60)","v":6},1998,"Correlated heart/limb anomalies in Mendelian syndromes provide evidence for a cardiomelic developmental field.","Wilson",9545093,"Correlated heart/limb anomalies in Mendelian syndromes provide evidence for a cardiomelic developmental field.    Abstract:   Coordinated development of heart and limbs is suggested by a review of human abortus, chromosomal, and teratogenic syndromes, and characterized by an analysis of Mendelian disorders that affect the limbs, heart, or both (672, 202, or 107, respectively). Mendelian syndromes with altered limb patterns often include cardiac anomalies, as shown by limb duplications (34%), deficiencies (30%), hypoplasias (23%), or dysplasias (9.3%). Syndromes with particular cardiac anomalies, illustrated by VSD (85%) or ASD (90%), frequently include limb defects. Positional correlations of anterior (preaxial/conotruncal), posterior (postaxial/atrial), or lateral (mirror hand/atrial isometry) heart/limb anomalies are consistent with the existence of a cardiomelic developmental field. Vertebrate comparisons suggest an early D-V limb-heart gradient, influenced by the neural crest, with distal limb segments (80% of syndromic defects) at its dorsal extreme. The proposed cardiomelic field relates the genetic heterogeneity of disorders such as Holt-Oram syndrome to a cascade of molecules, including the brachyury, sonic hedgehog, bone morphogenetic protein, retinoic acid receptor, and transforming growth factor-beta families."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I61,I61)","v":8901853},{"$f":"(LEN($J61) - LEN(SUBSTITUTE(LOWER($J61),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J61) - LEN(SUBSTITUTE(LOWER($J61),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J61) - LEN(SUBSTITUTE(LOWER($J61),LOWER(D$3),\"\")))/LEN(D$3)","v":5},{"$f":"SUM(B61:D61)","v":6},1996,"Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial.","Omenn",8901853,"Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial.    Abstract:    BACKGROUND : Evidence has accumulated from observational studies that people eating more fruits and vegetables, which are rich in beta-carotene (a violet to yellow plant pigment that acts as an antioxidant and can be converted to vitamin A by enzymes in the intestinal wall and liver) and retinol (an alcohol chemical form of vitamin A), and people having higher serum beta-carotene concentrations had lower rates of lung cancer. The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate (vitamin A) taken daily against placebo in 18314 men and women at high risk of developing lung cancer. The CARET intervention was stopped 21 months early because of clear evidence of no benefit and substantial evidence of possible harm; there were 28% more lung cancers and 17% more deaths in the active intervention group (active = the daily combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate). Promptly after the January 18, 1996, announcement that the CARET active intervention had been stopped, we published preliminary findings from CARET regarding cancer, heart disease, and total mortality.  PURPOSE : We present for the first time results based on the pre-specified analytic method, details about risk factors for lung cancer, and analyses of subgroups and of factors that possibly influence response to the intervention.  METHODS : CARET was a randomized, double-blinded, placebo-controlled chemoprevention trial, initiated with a pilot phase and then expanded 10-fold at six study centers. Cigarette smoking history and status and alcohol intake were assessed through participant self-report. Serum was collected from the participants at base line and periodically after randomization and was analyzed for beta-carotene concentration. An Endpoints Review Committee evaluated endpoint reports, including pathologic review of tissue specimens. The primary analysis is a stratified logrank test for intervention arm differences in lung cancer incidence, with weighting linearly to hypothesized full effect at 24 months after randomization. Relative risks (RRs) were estimated by use of Cox regression models; tests were performed for quantitative and qualitative interactions between the intervention and smoking status or alcohol intake. OBrien-Fleming boundaries were used for stopping criteria at interim analyses. Statistical significance was set at the .05 alpha value, and all P values were derived from two-sided statistical tests.  RESULTS : According to CARETs pre-specified analysis, there was an RR of 1.36 (95% confidence interval [CI] = 1.07-1.73; P = .01) for weighted lung cancer incidence for the active intervention group compared with the placebo group, and RR = 1.59 (95% CI = 1.13-2.23; P = .01) for weighted lung cancer mortality. All subgroups, except former smokers, had a point estimate of RR of 1.10 or greater for lung cancer. There are suggestions of associations of the excess lung cancer incidence with the highest quartile of alcohol intake (RR = 1.99; 95% CI = 1.28-3.09; test for heterogeneity of RR among quartiles of alcohol intake has P = .01, unadjusted for multiple comparisons) and with large-cell histology (RR = 1.89; 95% CI = 1.09-3.26; test for heterogeneity among histologic categories has P = .35), but not with base-line serum beta-carotene concentrations.  CONCLUSIONS : CARET participants receiving the combination of beta-carotene and vitamin A had no chemopreventive benefit and had excess lung cancer incidence and mortality. The results are highly consistent with those found for beta-carotene in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study in 29133 male smokers in Finland."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I62,I62)","v":8297038},{"$f":"(LEN($J62) - LEN(SUBSTITUTE(LOWER($J62),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J62) - LEN(SUBSTITUTE(LOWER($J62),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J62) - LEN(SUBSTITUTE(LOWER($J62),LOWER(D$3),\"\")))/LEN(D$3)","v":4},{"$f":"SUM(B62:D62)","v":6},1993,"Mammalian neural crest and neural crest derivatives.","Morriss-Kay",8297038,"Mammalian neural crest and neural crest derivatives.    Abstract:   In the mammalian embryonic trunk, neural crest cells emigrate from the closed neural tube in a cranio-caudal sequences and appear to have similar migration pathways and derivatives to those of avian embryos. In the cranial region, however, there are mammalian-specific features, which are related to the mammalian-specific pattern of cranial neurulation. Midbrain and rostral hindbrain neural crest cells emigrate from widely open neural folds; caudal hindbrain crest emigrates in a caudo-rostral sequence, following the sequence of neural tube closure in this region. The forebrain is also a source of neural crest cells at early stages of neurulation; both forebrain and midbrain crest cells contribute to the frontonasal mesenchyme, although their relative contributions have not been analysed. Few studies have provided direct information about mammalian neural crest cell derivatives. Studies on the effects of retinoid excess on craniofacial development provide indirect evidence that mammalian cranial neural crest, like that of avian embryos, includes two populations whose differentiated phenotype and morphological tissue structure are determined prior to emigration. Retinoid-induced shortening of the preotic hindbrain leads to abnormal migration pathways of the neural crest cells that normally migrate into the mandibular arch to form Meckels cartilage, so that an ectopic Meckels cartilage-like structure forms in the maxillary region of the face. Slow descent of the heart in retinoid-exposed embryos enables the quot;wrongquot; crest cell population to populate the wall of the truncus arteriosus. These observations correlate well with observations of retinoid-induced craniofacial and heart abnormalities in human infants."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I63,I63)","v":8463566},{"$f":"(LEN($J63) - LEN(SUBSTITUTE(LOWER($J63),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J63) - LEN(SUBSTITUTE(LOWER($J63),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J63) - LEN(SUBSTITUTE(LOWER($J63),LOWER(D$3),\"\")))/LEN(D$3)","v":5},{"$f":"SUM(B63:D63)","v":6},1993,"[Teratogenicity of retinoids. A case and review of the literature].","Heckel",8463566,"[Teratogenicity of retinoids. A case and review of the literature].    Abstract:   Retinoids are vitamin A derivatives used in dermatology. One of them, isotretinoin, is frequently prescribed for refractory juvenile acne. The teratogenetic power of this drug is substantial, being estimated at 15 to 45% of exposures in utero. The risk is maximum in the first trimester of pregnancy and persists up to one month after treatment has been discontinued. The most frequently described multiple malformation syndrome involves the face, the central nervous system and the heart. There is also a 20 to 30% rate of spontaneous abortion. The authors report a case where exposure during the first trimester did not result in foetal malformation. From a full review of the literature the various malformations observed, the presumed mechanisms of teratogenesis and the strict rules of prescription and surveillance in women child-bearing age are presented. The problem of the measures to be taken in case of retinoid treatment during pregnancy is discussed. The teratogenic risk from other retinoids is dealt with."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I64,I64)","v":26310145},{"$f":"(LEN($J64) - LEN(SUBSTITUTE(LOWER($J64),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J64) - LEN(SUBSTITUTE(LOWER($J64),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J64) - LEN(SUBSTITUTE(LOWER($J64),LOWER(D$3),\"\")))/LEN(D$3)","v":5},{"$f":"SUM(B64:D64)","v":5},2015,"Overview of the Visual System.","Hejtmancik",26310145,"Overview of the Visual System.    Abstract:   This introduction provides an overview of the retina, in which we survey the fundus, layers of the retina, retinal cell types, visual transduction cascade, vitamin A cycle, neuronal wiring of the retina, and blood supply of the retina."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I65,I65)","v":24088538},{"$f":"(LEN($J65) - LEN(SUBSTITUTE(LOWER($J65),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J65) - LEN(SUBSTITUTE(LOWER($J65),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J65) - LEN(SUBSTITUTE(LOWER($J65),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B65:D65)","v":5},2013,"[Morphological and molecular bases of cardiac development].","Kobylińska",24088538,"[Morphological and molecular bases of cardiac development].    Abstract:   The heart is a mesoderm-derived organ, whose formation is regulated by various genes. Initially, the most important is expression of Nkx2.5, CR1, pitx2, anf and mhc2a, which are responsible for differentiation of cardiomyocytes. In a later phase activation of mhc2b, pitx2c, mesp1, pcmf1, vmhc, xin, mcl2v, mlc2a, mlc2a, mef2, hand1 and hand2 was revealed. Their expression is regulated by various molecules, including transcription (XIN, GATA, MEF, Tbx5, Baf60c, PECAM, tie-2, MEF2) and growth (VEGF, FGF, PDGF) factors, as well as proteins (i.e., dickkopf-1, cerberus, cytotactin, fibrillin, nodal, thrombomodulin, Wnt, bone morphometric ones - BMP2, BMP 4, BMP5, BMP7) and other substances, such as retinoid and folic acid. Crucial steps in cardiac organogenesis are development of the ventricle and atrial formation, as well as septation and valve formation. Any disturbances of such processes may lead to various congenital heart diseases and defects that could be initiated by various genetic, epigenetic or environmental factors. The most common heart malformations are: stenosis (coarctation) of the aorta and pulmonary trunk, bicuspid aortic valve, atrial and/or ventricular septal defect, persistent truncus arteriosus (Botallo duct), transposition of the great vessels, tricuspid atresia, hypoplastic left and right heart, as well as syndrome of Lutembachera, Cantrell, Ebstein, Eisenmenger and Shone and trilogy, tetralogy, pentalogy of Fallot."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I66,I66)","v":24056119},{"$f":"(LEN($J66) - LEN(SUBSTITUTE(LOWER($J66),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J66) - LEN(SUBSTITUTE(LOWER($J66),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J66) - LEN(SUBSTITUTE(LOWER($J66),LOWER(D$3),\"\")))/LEN(D$3)","v":5},{"$f":"SUM(B66:D66)","v":5},2014,"Retinoid signaling in pathological remodeling related to cardiovascular disease.","Kotake",24056119,"Retinoid signaling in pathological remodeling related to cardiovascular disease.    Abstract:   Retinoids, the active derivatives of vitamin A, are critical signaling molecules in crucial biological processes such as embryonic development, the maintenance of immune function, and cellular differentiation and proliferation. Preclinical studies have shown that retinoids also regulate morphological changes during the progression of cardiovascular disease (CVD). CVD is complexly formed in a mutual chain reaction of various modern lifestyle-related risk factors such as dyslipidemia, hypertension, diabetes, and obesity. These factors induce the pathological remodeling of adipose tissue, the vasculature, and the ventricles, which are a potential target for retinoid signaling. This perspective highlights emerging topics and future prospectives on the relationship between CVD and retinoid signaling."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I67,I67)","v":22393824},{"$f":"(LEN($J67) - LEN(SUBSTITUTE(LOWER($J67),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J67) - LEN(SUBSTITUTE(LOWER($J67),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J67) - LEN(SUBSTITUTE(LOWER($J67),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B67:D67)","v":5},2012,"Forskolin and derivatives as tools for studying the role of cAMP.","Alasbahi",22393824,"Forskolin and derivatives as tools for studying the role of cAMP.    Abstract:   Forskolin (7beta-acetoxy-1alpha,6beta,9alpha-trihydroxy-8,13-epoxy-labd-14-en-11-one) is the first main labdane diterpenoid isolated from the roots of the Indian Plectranthus barbatus ANDREWS and one of the most extensively studied constituents of this plant. The unique character of forskolin as a general direct, rapid and reversible activator of adenylyl cyclase not only underlies its wide range of pharmacological effects but also renders it as a valuable tool in the study of the role of cAMP. The purpose of this review is to provide data presenting the utility of forskolin--as a cAMP activator--for studying the function of cAMP from different biological viewpoints as follows: 1) Investigation on the role of cAMP in various cellular processes in different organs such as gastrointestinal tract, respiratory tract, reproductive organs, endocrine system, urinary system, olfactory system, nervous system, platelet aggregating system, skin, bones, eyes, and smooth muscles. 2) Studies on the role of cAMP activation and inhibition to understand the pathogenesis (e.g. thyroid autoimmune disorders, leukocyte signal transduction defect in depression, acute malaria infection, secretory dysfunction in inflammatory diseases) as well as its possibly beneficial role for curing diseases such as the regulation of coronary microvascular NO production after heart failure, the attenuation of the development or progression of fibrosis in the heart and lungs, the augmentation of myo-protective effects of ischemic preconditioning especially in the failing hearts after myocardial infarction, the stimulation of the regeneration of injured retinal ganglion cells, the curing of glaucoma and inflammatory diseases, the reducing of cyst formation early in the polycystic kidney disease, and the management of autoimmune disorders by enhancing Fas-mediated apoptosis. 3) Studies on the role of cAMP in the mechanism of actions of a number of drugs and substances such as the effect of the protoberberine alkaloid palmatine on the active ion transport across rat colonic epithelium, the inhibitory effect of retinoic acid on HIV-1-induced podocyte proliferation, the whitening activity of luteolin, the effect of cilostazol on nitric oxide production, an effect that is involved in capillary-like tube formation in human aortic endothelial cells, the apoptotic effect of bullatacin, the effects of paraoxon and chlorpyrifos oxon on nervous system. Moreover, cAMP was found to play a role in acute and chronic exposure to ethanol, in morphine dependence and withdrawal and in behavioral sensitization to cocaine as well as in the protection against cisplatin-induced oxidative injuries."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I68,I68)","v":19903021},{"$f":"(LEN($J68) - LEN(SUBSTITUTE(LOWER($J68),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J68) - LEN(SUBSTITUTE(LOWER($J68),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J68) - LEN(SUBSTITUTE(LOWER($J68),LOWER(D$3),\"\")))/LEN(D$3)","v":5},{"$f":"SUM(B68:D68)","v":5},2009,"All-trans retinoic acid as a novel therapeutic strategy for Alzheimers disease.","Lee",19903021,"All-trans retinoic acid as a novel therapeutic strategy for Alzheimers disease.    Abstract:   Retinoic acid, an essential factor derived from vitamin A, has been shown to have a variety of functions including roles as an antioxidant and in cellular differentiation. Since oxidative stress and dedifferentiation of neurons appear to be common pathological elements of a number of neurodegenerative disorders, we speculated that retinoic acid may offer therapeutic promise. In this vein, recent compelling evidence indicates a role of retinoic acid in cognitive activities and anti-amyloidogenic properties. Here, we review the actions of retinoic acid that indicate that it may have therapeutic properties ideally served for the treatment of neurodegenerative diseases such as Alzheimers disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I69,I69)","v":19401491},{"$f":"(LEN($J69) - LEN(SUBSTITUTE(LOWER($J69),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J69) - LEN(SUBSTITUTE(LOWER($J69),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J69) - LEN(SUBSTITUTE(LOWER($J69),LOWER(D$3),\"\")))/LEN(D$3)","v":5},{"$f":"SUM(B69:D69)","v":5},2009,"Retinoid induction of alveolar regeneration: from mice to man?","Hind",19401491,"Retinoid induction of alveolar regeneration: from mice to man?    Abstract:   The use of retinoids to induce human lung regeneration is under investigation in a number of studies in patients with chronic obstructive pulmonary disease (COPD). Retinoic acid (RA) has complex pleiotropic functions during vertebrate patterning and development and can induce regeneration in a number of different organ systems. Studies of retinoid signalling during lung development might provide a molecular basis to explain pharmacological induction of alveolar regeneration in adult models of lung disease. In this review the role of endogenous RA signalling during alveologenesis is explored and data suggesting that a number of exogenous retinoids can induce regeneration in the adult lung are discussed. Current controversies in this area are highlighted and a hypothesis of lung regeneration is put forward. Understanding the cellular and molecular mechanisms of induction of regeneration will be central for effective translation into patients with lung disease and may reveal novel insights into the pathogenesis of alveolar disease and senescence."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I70,I70)","v":10893067},{"$f":"(LEN($J70) - LEN(SUBSTITUTE(LOWER($J70),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J70) - LEN(SUBSTITUTE(LOWER($J70),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J70) - LEN(SUBSTITUTE(LOWER($J70),LOWER(D$3),\"\")))/LEN(D$3)","v":5},{"$f":"SUM(B70:D70)","v":5},2000,"Tapetoretinal degenerations: experiences, experiments and expectations.","Ehinger",10893067,"Tapetoretinal degenerations: experiences, experiments and expectations.    Abstract:   Tapetoretinal degenerations are a common cause for vision problems, but have until recently not been amenable to rational treatment. With rapidly increasing insights into basic neurobiology and pathobiology this has now begun to change. From having been a relatively small group of largely unknown yet fairly prevalent disorders, they are rapidly forming a large set of well defined diseases, and it is easy to predict that our knowledge about them will continue to increase for many years to come. Vitamin A (15,000 IU daily) is currently the only rational treatment available. However, in experimental animals, therapy strategies are now actively being developed along several different lines. Apoptotic photoreceptor cell death can be delayed with different drugs, and at least one of them, diltiazem, is approved for human use in cardiovascular diseases. It remains to be seen if it has any clinically significant effect in human tapetoretinal degenerations. Other strategies aim at counteracting the production of harmful protein variants, acting either on DNA or mRNA levels. Transgenes can also be used to induce the production of important but missing metabolic components. Finally, cells or retina sheets can be transplanted, either to replace failing cells or as a source for missing trophic factors. Neither of these strategies has yet been transferred to humans, but trials are under way. With the high increase in the flow of new information on tapetoretinal disorders, much more precise diagnoses and much improved treatments are soon to be expected, augmenting considerably the possibilities for ophthalmologists to help patients with such diseases. It is not likely that there will be a single treatment for all the many varieties. Instead, we are most likely going to see pharmacological treatments for some of them, DNA transfers for some, and transplantations for others."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I71,I71)","v":8971347},{"$f":"(LEN($J71) - LEN(SUBSTITUTE(LOWER($J71),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J71) - LEN(SUBSTITUTE(LOWER($J71),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J71) - LEN(SUBSTITUTE(LOWER($J71),LOWER(D$3),\"\")))/LEN(D$3)","v":5},{"$f":"SUM(B71:D71)","v":5},1996,"The molecular genetics of retinoic acid receptors: cardiovascular and limb development.","Sucov",8971347,"The molecular genetics of retinoic acid receptors: cardiovascular and limb development.    Abstract:   The vitamin A metabolite retinoic acid (RA) is utilized as a signalling molecule in wide variety of developmental processes, defined by defects which occur after nutritional vitamin A deficiency or after exposure to excess vitamin A. We have initiated a genetic analysis of RA function through the establishment of lines of mice which carry germline mutations in the genes which encode retinoid receptors. Defects which result from developmental RA deficiency or excess have been recovered in embryos which are deficient in various combinations of retinoid receptors. In this chapter, our current understanding of the role of RA and retinoid receptors in cardiovascular and limb development are described, as for these our level of understanding is most advanced."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I72,I72)","v":7499738},{"$f":"(LEN($J72) - LEN(SUBSTITUTE(LOWER($J72),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J72) - LEN(SUBSTITUTE(LOWER($J72),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J72) - LEN(SUBSTITUTE(LOWER($J72),LOWER(D$3),\"\")))/LEN(D$3)","v":4},{"$f":"SUM(B72:D72)","v":5},1995,"[Isotretinoin (RoAccutane) embryopathy. A case report].","Pilorget",7499738,"[Isotretinoin (RoAccutane) embryopathy. A case report].    Abstract:   Retinoids are synthetic vitamin A derivatives, particularly used in dermatology. Their prescription in women of childbearing age can cause, if pregnancy occurs, a serious malformative embryopathy, mainly involving external ear, brain and heart. A neonatal case caused by isotretinoin (RoAccutane) emphasizes the clinical and epidemiological data concerning this embryopathy. The aetiopathological hypothesis of an interaction between isotretinoin and Hox genes is advanced. Prophylactic measures are difficult since neonatal reported cases are uncommon, but antenatal exposition to this strong teratogenic agent results in multiple spontaneous abortions or pregnancy interruptions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I73,I73)","v":7621297},{"$f":"(LEN($J73) - LEN(SUBSTITUTE(LOWER($J73),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J73) - LEN(SUBSTITUTE(LOWER($J73),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J73) - LEN(SUBSTITUTE(LOWER($J73),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B73:D73)","v":5},1994,"Postprandial lipoproteins and coronary heart disease.","Clifton",7621297,"Postprandial lipoproteins and coronary heart disease.    Abstract:   Postprandial lipaemia, whether measured using levels of triglyceride of retinyl palmitate, is more severe in patients with coronary heart disease; however, little improvement in the discrimination between individuals with and without coronary heart disease can be made using postprandial measurements rather than measuring levels of high-density-lipoprotein2 cholesterol of apolipoproteins B. Retinyl palmitate levels occasionally reveal differences not apparent from triglyceride measurements. Elevated fasting and postprandial triglyceride levels may produce clinical disease partly by enhancing coagulation and by interfering with fibrinolysis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I74,I74)","v":6233342},{"$f":"(LEN($J74) - LEN(SUBSTITUTE(LOWER($J74),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J74) - LEN(SUBSTITUTE(LOWER($J74),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J74) - LEN(SUBSTITUTE(LOWER($J74),LOWER(D$3),\"\")))/LEN(D$3)","v":5},{"$f":"SUM(B74:D74)","v":5},1984,"Isotretinoin and pregnancy.","Stern",6233342,"Isotretinoin and pregnancy.    Abstract:   Approximately 120,000 women of childbearing age used isotretinoin in the first 16 months after its release for the treatment of cystic acne. In September, 1983, the American Academy of Dermatology requested its members to relate the outcome of pregnancies of women inadvertently exposed to isotretinoin ( Accutane ) during pregnancy to its Adverse Drug Reaction Reporting System ( ADRRS ). Of nine pregnancies reported, seven ended in spontaneous abortion or the birth of an infant with birth defects. Of thirty-five pregnancies with isotretinoin exposure reported to the ADRRS or the U.S. Food and Drug Administration, twenty-nine (83%) resulted in spontaneous abortion or infants with birth defects. The most frequently reported severe birth defects involved the central nervous system (microcephaly or hydrocephalus) and the cardiovascular system (anomalies of the great vessels). Microtia or absence of external ears were also noted in a majority of cases. These findings illustrate the usefulness of specialty-based reporting of adverse drug effects and emphasize the teratogenic risk of isotretinoin in humans. Physicians need to fully and carefully inform women of childbearing age of these risks."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I75,I75)","v":27351724},{"$f":"(LEN($J75) - LEN(SUBSTITUTE(LOWER($J75),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J75) - LEN(SUBSTITUTE(LOWER($J75),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J75) - LEN(SUBSTITUTE(LOWER($J75),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B75:D75)","v":4},2016,"Zebrafish fin and heart: whats special about regeneration?","Sehring",27351724,"Zebrafish fin and heart: whats special about regeneration?    Abstract:    NlmCategory=UNASSIGNEDMany organs regenerate well in adult zebrafish, but most research has been directed toward fin and heart regeneration. Cells have been found to remain generally lineage-restricted during regeneration, and proliferative regenerative progenitors can be formed by dedifferentiation from differentiated cells. Recent studies begin to shed light on the molecular underpinnings of differences between development and regeneration. Retinoic acid, BMP and NF-κB signaling are emerging as regulators of cellular dedifferentiation. Reactive oxygen species promote regeneration, and the dynamics of ROS signaling might help explain differences between wound healing and regeneration. Finally, the heart has been added to those organs that require a nerve supply to regenerate, and a trade-off between regeneration and tumor suppression has been proposed to help explain why mammals regenerate poorly."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I76,I76)","v":25418431},{"$f":"(LEN($J76) - LEN(SUBSTITUTE(LOWER($J76),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J76) - LEN(SUBSTITUTE(LOWER($J76),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J76) - LEN(SUBSTITUTE(LOWER($J76),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B76:D76)","v":4},2015,"Input overload: Contributions of retinoic acid signaling feedback mechanisms to heart development and teratogenesis.","DAniello",25418431,"Input overload: Contributions of retinoic acid signaling feedback mechanisms to heart development and teratogenesis.    Abstract:   Appropriate levels of retinoic acid (RA) signaling are critical for normal heart development in vertebrates. A fascinating property of RA signaling is the thoroughness by which positive and negative feedback are employed to promote proper embryonic RA levels. In the present short review, we first cover the advancement of hypotheses regarding the impact of RA signaling on cardiac specification. We then discuss our current understanding of RA signaling feedback mechanisms and the implications of recent studies, which have indicated improperly maintained RA signaling feedback can be a contributing factor to developmental malformations."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I77,I77)","v":24928143},{"$f":"(LEN($J77) - LEN(SUBSTITUTE(LOWER($J77),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J77) - LEN(SUBSTITUTE(LOWER($J77),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J77) - LEN(SUBSTITUTE(LOWER($J77),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B77:D77)","v":4},2015,"ZebRA: An overview of retinoic acid signaling during zebrafish development.","Samarut",24928143,"ZebRA: An overview of retinoic acid signaling during zebrafish development.    Abstract:   Retinoic acid (RA), the main active vitamin A derivative, is crucial for embryo development, regulating cellular processes, embryo patterning and organogenesis. Many studies performed in mammalian or avian models have successfully undertaken the investigation of the role played by RA during embryogenesis. Since the early 1980s, the zebraﬁsh (Danio rerio) has emerged as a powerful developmental model to study the in vivo role of RA during embryogenesis. Unlike mammalian models, zebraﬁsh embryogenesis is external, not only allowing the observation of the translucent embryo from the earliest steps but also providing an easily accessible system for pharmacological treatment or genetic approaches. Therefore, zebraﬁsh research largely participates in deciphering the role of RA during development. This review aims at illustrating different concepts of RA signaling based on the research performed on zebraﬁsh. Indeed, RA action relies on a multitude of cross-talk with other signaling pathways and requires a coordinated, dynamic and ﬁne-regulation of its level and activity in both temporal and spatial dimensions. This review also highlights major advances that have been discovered using zebraﬁsh such as the observation of the RA gradient in vivo for the ﬁrst time, the effects of RA signaling in brain patterning, its role in establishing left-right asymmetry and its effects on the development of a variety of organs and tissues including the heart, blood, bone and fat. This review demonstrates that the zebraﬁsh is a convenient and powerful model to study retinoic acid signaling during vertebrate embryogenesis. This article is part of a Special Issue entitled: Nuclear receptors in animal development."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I78,I78)","v":24400257},{"$f":"(LEN($J78) - LEN(SUBSTITUTE(LOWER($J78),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J78) - LEN(SUBSTITUTE(LOWER($J78),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J78) - LEN(SUBSTITUTE(LOWER($J78),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B78:D78)","v":4},2013,"Transposition of great arteries: new insights into the pathogenesis.","Unolt",24400257,"Transposition of great arteries: new insights into the pathogenesis.    Abstract:   Transposition of great arteries (TGA) is one of the most common and severe congenital heart diseases (CHD). It is also one of the most mysterious CHD because it has no precedent in phylogenetic and ontogenetic development, it does not represent an alternative physiological model of blood circulation and its etiology and morphogenesis are still largely unknown. However, recent epidemiologic, experimental, and genetic data suggest new insights into the pathogenesis. TGA is very rarely associated with the most frequent genetic syndromes, such as Turner, Noonan, Williams or Marfan syndromes, and in Down syndrome, it is virtually absent. The only genetic syndrome with a strong relation with TGA is Heterotaxy. In lateralization defects TGA is frequently associated with asplenia syndrome. Moreover, TGA is rather frequent in cases of isolated dextrocardia with situs solitus, showing link with defect of visceral situs. Nowadays, the most reliable method to induce TGA consists in treating pregnant mice with retinoic acid or with retinoic acid inhibitors. Following such treatment not only cases of TGA with d-ventricular loop have been registered, but also some cases of congenitally corrected transposition of great arteries (CCTGA). In another experiment, the embryos of mice treated with retinoic acid in day 6.5 presented Heterotaxy, suggesting a relationship among these morphologically different CHD. In humans, some families, beside TGA cases, present first-degree relatives with CCTGA. This data suggest that monogenic inheritance with a variable phenotypic expression could explain the familial aggregation of TGA and CCTGA. In some of these families we previously found multiple mutations in laterality genes including Nodal and ZIC3, confirming a pathogenetic relation between TGA and Heterotaxy. These overall data suggest to include TGA in the pathogenetic group of laterality defects instead of conotruncal abnormalities due to ectomesenchymal tissue migration."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I79,I79)","v":24099071},{"$f":"(LEN($J79) - LEN(SUBSTITUTE(LOWER($J79),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J79) - LEN(SUBSTITUTE(LOWER($J79),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J79) - LEN(SUBSTITUTE(LOWER($J79),LOWER(D$3),\"\")))/LEN(D$3)","v":4},{"$f":"SUM(B79:D79)","v":4},2013,"Oral retinoids and plasma lipids.","Lilley",24099071,"Oral retinoids and plasma lipids.    Abstract:   Retinoids and rexinoids are prescribed for conditions ranging from acne vulgaris to hyperkeratosis to cutaneous T cell lymphoma. Dyslipidemia is a frequent consequence of the use of these drugs, with more than one-third of patients manifesting aberrations in triglyceride (TG) levels. The efficacy of retinoic acid derivatives is linked to their influence on lipid metabolism in the skin, which can impair systemic lipid trafficking and metabolism in some patients. Thus, baseline screening for preexisting dyslipidemia and regular follow-up lipid panels are mandated, especially when powerful agents such as bexarotene are used. Dietary modification, increased physical activity, and weight management are the cornerstones of initial management for mild hypertriglyceridemia, which is a contributor to cardiovascular risk. More severe impairments (fasting TG gt; 500 mg/dL) warrant pharmacologic interventions early on to reduce the risk of pancreatitis. Retinoic acid derivative action, lipid metabolism, and treatment of incident dyslipidemias are reviewed to empower prescribers in management of adverse lipid effects."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I80,I80)","v":23847917},{"$f":"(LEN($J80) - LEN(SUBSTITUTE(LOWER($J80),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J80) - LEN(SUBSTITUTE(LOWER($J80),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J80) - LEN(SUBSTITUTE(LOWER($J80),LOWER(D$3),\"\")))/LEN(D$3)","v":4},{"$f":"SUM(B80:D80)","v":4},2013,"[The pathophysiological roles and regulatory mechanism of retinoic acid receptor-related orphan receptors].","Chai",23847917,"[The pathophysiological roles and regulatory mechanism of retinoic acid receptor-related orphan receptors].    Abstract:   Nuclear receptors are a large superfamily of transcription factors that regulate genes important to physiological functions. Retinoid-related orphan receptors (RORs), also known as NF1R, are so named because its gene sequence is similar to retinoid acid receptor and retinoid X receptor. RORs subfamily consists of three members: RORalpha, RORbeta, and RORgamma. Previous studies have established key roles for the RORs in physiological development, cytogenesis and differentiation of immune cells, circadian rhythm, and metabolism, through the regulation of gene expression. Besides, RORs also involve in many pathological process. Recent studies indicated that the abnormal expression of RORs is related to the development of tumor, immune inflammatory diseases, and cardiovascular diseases. thought to be the one of the key transcription factors which regulate the gene expression of these diseases. This review discusses the biological characteristics and pathophysiological roles of RORs subfamily."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I81,I81)","v":23445813},{"$f":"(LEN($J81) - LEN(SUBSTITUTE(LOWER($J81),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J81) - LEN(SUBSTITUTE(LOWER($J81),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J81) - LEN(SUBSTITUTE(LOWER($J81),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B81:D81)","v":4},2013,"New insights into the developmental mechanisms of coronary vessels and epicardium.","Nakajima",23445813,"New insights into the developmental mechanisms of coronary vessels and epicardium.    Abstract:   During heart development, the epicardium, which originates from the proepicardial organ (PE), is a source of coronary vessels. The PE develops from the posterior visceral mesoderm of the pericardial coelom after stimulation with a combination of weak bone morphogenetic protein and strong fibroblast growth factor (FGF) signaling. PE-derived cells migrate across the heart surface to form the epicardial sheet, which subsequently seeds multipotent subepicardial mesenchymal cells via epithelial-mesenchymal transition, which is regulated by several signaling pathways including retinoic acid, FGF, sonic hedgehog, Wnt, transforming growth factor-β, and platelet-derived growth factor. Subepicardial endothelial progenitors eventually generate the coronary vascular plexus, which acquires an arterial or venous phenotype, connects with the sinus venosus and aortic sinuses, and then matures through the recruitment of vascular smooth muscle cells under the regulation of complex growth factor signaling pathways. These developmental programs might be activated in the adult heart after injury and play a role in the regeneration/repair of the myocardium."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I82,I82)","v":22727981},{"$f":"(LEN($J82) - LEN(SUBSTITUTE(LOWER($J82),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J82) - LEN(SUBSTITUTE(LOWER($J82),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J82) - LEN(SUBSTITUTE(LOWER($J82),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B82:D82)","v":4},2013,"[Cardiotoxicity of chemotherapies].","Castel",22727981,"[Cardiotoxicity of chemotherapies].    Abstract:   The spectrum of chemotherapys cardiac side effect of chemotherapy has expanded with the new combinations of cytotoxic and targeted therapies over the past 10 years. Moreover, cancer therapy administrated to quot;newquot; populations, especially elderly patients or patients with cardiovascular disease and/or coronary artery disease history, has increased considerably. According to the American College of Cardiology and American Heart Association (ACC/AHA), patients receiving chemotherapy can be considered in the A group of heart failure. Many cardiovascular adverse effects appear with cancer therapy and suspend treatment purchase, or leading to an alteration of quality of life, and increasing mortality risks. The most clinically evident cardiotoxicity and best known is the anthracyclines adverse effect. Other cytotoxic are associated with a significant risk of cardiovascular complications include alkylating agents such as 5-fluorouracil and paclitaxel. Cardiovascular adverse effects are associated with the use of targeted therapies such as tyrosine kinase inhibitors: trastuzumab, bevacizumab. At the same time, drugs used to hematological malignancies, as acid all-trans-retinoic acid and arsenic trioxide are cardiotoxics. The most serious cardiac complications of cancer therapies is heart congestive failure, mainly due to the use of anthracyclines, cyclophosphamide and trastuzumab, usually at high doses. Myocardial ischemia is mainly caused by interferon and antimetabolites. Other side effects may occur such as hypotension, hypertension, arrhythmias and conduction disturbances, pericarditis, and thromboembolic complications."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I83,I83)","v":22461366},{"$f":"(LEN($J83) - LEN(SUBSTITUTE(LOWER($J83),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J83) - LEN(SUBSTITUTE(LOWER($J83),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J83) - LEN(SUBSTITUTE(LOWER($J83),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B83:D83)","v":4},2012,"Importance of myocyte-nonmyocyte interactions in cardiac development and disease.","Tian",22461366,"Importance of myocyte-nonmyocyte interactions in cardiac development and disease.    Abstract:   Emerging data in the field of cardiac development as well as repair and regeneration indicate a complex and important interplay between endocardial, epicardial, and myofibroblast populations that is critical for cardiomyocyte differentiation and postnatal function. For example, epicardial cells have been shown to generate cardiac myofibroblasts and may be one of the primary sources for this cell lineage during development. Moreover, paracrine signaling from the epicardium and endocardium is critical for proper development of the heart and pathways such as Wnt, fibroblast growth factor, and retinoic acid signaling have been shown to be key players in this process. Despite this progress, interactions between nonmyocyte cells and cardiomyocytes in the heart are still poorly understood. We review the various nonmyocyte-myocyte interactions that occur in the heart and how these interactions, primarily through signaling networks, help direct cardiomyocyte differentiation and regulate postnatal cardiac function."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I84,I84)","v":21482409},{"$f":"(LEN($J84) - LEN(SUBSTITUTE(LOWER($J84),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J84) - LEN(SUBSTITUTE(LOWER($J84),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J84) - LEN(SUBSTITUTE(LOWER($J84),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B84:D84)","v":4},2011,"The membrane receptor for plasma retinol-binding protein, a new type of cell-surface receptor.","Sun",21482409,"The membrane receptor for plasma retinol-binding protein, a new type of cell-surface receptor.    Abstract:   Vitamin A is essential for diverse aspects of life ranging from embryogenesis to the proper functioning of most adult organs. Its derivatives (retinoids) have potent biological activities such as regulating cell growth and differentiation. Plasma retinol-binding protein (RBP) is the specific vitamin A carrier protein in the blood that binds to vitamin A with high affinity and delivers it to target organs. A large amount of evidence has accumulated over the past decades supporting the existence of a cell-surface receptor for RBP that mediates cellular vitamin A uptake. Using an unbiased strategy, this specific cell-surface RBP receptor has been identified as STRA6, a multitransmembrane domain protein with previously unknown function. STRA6 is not homologous to any protein of known function and represents a new type of cell-surface receptor. Consistent with the diverse functions of vitamin A, STRA6 is widely expressed in embryonic development and in adult organ systems. Mutations in human STRA6 are associated with severe pathological phenotypes in many organs such as the eye, brain, heart, and lung. STRA6 binds to RBP with high affinity and mediates vitamin A uptake into cells. This review summarizes the history of the RBP receptor research, its expression in the context of known functions of vitamin A in distinct human organs, structure/function analysis of this new type of membrane receptor, pertinent questions regarding its very existence, and its potential implication in treating human diseases."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I85,I85)","v":18516775},{"$f":"(LEN($J85) - LEN(SUBSTITUTE(LOWER($J85),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J85) - LEN(SUBSTITUTE(LOWER($J85),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J85) - LEN(SUBSTITUTE(LOWER($J85),LOWER(D$3),\"\")))/LEN(D$3)","v":4},{"$f":"SUM(B85:D85)","v":4},2008,"[Pathomechanisms for aging of retinal pigment epithelium (RPE) and prophylactic therapy options in regard to AMD].","Schütt",18516775,"[Pathomechanisms for aging of retinal pigment epithelium (RPE) and prophylactic therapy options in regard to AMD].    Abstract:   An intact retinal pigment epithelium (RPE) represents an essential condition for the visual process. This post-mitotic RPE monolayer combines different functions such as degradation of photoreceptor outer segments, vitamin A cycle, support of retinal metabolism and maintenance of the outer blood-retina barrier. As a consequence of excessive metabolism, high oxygen levels, exposition to light of short wave length and ensuing radical formation, the RPE is highly dependent on protective systems. In spite of differentiated defence mechanisms, aging processes cause cumulative RPE damage, representing a major component of age-related macular degeneration (AMD), the leading cause of irreversible severe vision loss in people over 50 years old. A better understanding of the underlying pathophysiology will help to develop new prophylactic options which is becoming more and more important with increasing life expectancy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I86,I86)","v":18456715},{"$f":"(LEN($J86) - LEN(SUBSTITUTE(LOWER($J86),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J86) - LEN(SUBSTITUTE(LOWER($J86),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J86) - LEN(SUBSTITUTE(LOWER($J86),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B86:D86)","v":4},2008,"Double outlet right ventricle: aetiologies and associations.","Obler",18456715,"Double outlet right ventricle: aetiologies and associations.    Abstract:    BACKGROUND : Double outlet right ventricle (DORV), a clinically significant congenital heart defect, occurs in 1-3% of individuals with congenital heart defects. In contrast to other major congenital heart defects, there are no systematic or comprehensive data regarding associations, aetiologies, and pathogenesis of DORV. We analysed reported cases in the medical literature to address these issues.  METHODS : We queried the PubMed database using key words quot;double outlet right ventriclequot; and quot;DORVquot; for case reports, epidemiologic analyses and animal studies with this cardiac anomaly. The anatomic subtype of DORV was classified according to criteria of Van Praagh.  RESULTS : Chromosomal abnormalities were present in 61 of the 149 cases of DORV. Trisomies 13 and 18, and del 22q11 were the most commonly associated cytogenetic lesions; different anatomic subtypes of DORV were noted in trisomies 13 and 18 versus del 22q11. DORV was reported in many uncommon or rare non-chromosomal syndromes. Mutations and non-synonymous sequence variants in the CFC1 and CSX genes were the most commonly reported monogenic loci associated with DORV in humans; numerous genes are reported in murine models of DORV. Animal studies implicate maternal diabetes and prenatal exposure to ethanol, retinoids, theophylline, and valproate in DORV teratogenesis.  CONCLUSIONS : The large number of genes associated with DORV in both humans and animal models and the different anatomic subtypes seen in specific aetiologies indicate the likelihood of several distinct pathogenetic mechanisms for DORV, including impairment of neural crest derivative migration and impairment of normal cardiac situs and looping."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I87,I87)","v":17519397},{"$f":"(LEN($J87) - LEN(SUBSTITUTE(LOWER($J87),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J87) - LEN(SUBSTITUTE(LOWER($J87),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J87) - LEN(SUBSTITUTE(LOWER($J87),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B87:D87)","v":4},2007,"Noninherited risk factors and congenital cardiovascular defects: current knowledge: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics.","Jenkins",17519397,"Noninherited risk factors and congenital cardiovascular defects: current knowledge: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics.    Abstract:   Prevention of congenital cardiovascular defects has been hampered by a lack of information about modifiable risk factors for abnormalities in cardiac development. Over the past decade, there have been major breakthroughs in the understanding of inherited causes of congenital heart disease, including the identification of specific genetic abnormalities for some types of malformations. Although relatively less information has been available on noninherited modifiable factors that may have an adverse effect on the fetal heart, there is a growing body of epidemiological literature on this topic. This statement summarizes the currently available literature on potential fetal exposures that might alter risk for cardiovascular defects. Information is summarized for periconceptional multivitamin or folic acid intake, which may reduce the risk of cardiac disease in the fetus, and for additional types of potential exposures that may increase the risk, including maternal illnesses, maternal therapeutic and nontherapeutic drug exposures, environmental exposures, and paternal exposures. Information is highlighted regarding definitive risk factors such as maternal rubella; phenylketonuria; pregestational diabetes; exposure to thalidomide, vitamin A cogeners, or retinoids; and indomethacin tocolysis. Caveats regarding interpretation of possible exposure-outcome relationships from case-control studies are given because this type of study has provided most of the available information. Guidelines for prospective parents that could reduce the likelihood that their child will have a major cardiac malformation are given. Issues related to pregnancy monitoring are discussed. Knowledge gaps and future sources of new information on risk factors are described."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I88,I88)","v":16713393},{"$f":"(LEN($J88) - LEN(SUBSTITUTE(LOWER($J88),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J88) - LEN(SUBSTITUTE(LOWER($J88),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J88) - LEN(SUBSTITUTE(LOWER($J88),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B88:D88)","v":4},2006,"Trans fatty acids - effects on systemic inflammation and endothelial function.","Mozaffarian",16713393,"Trans fatty acids - effects on systemic inflammation and endothelial function.    Abstract:   Consumption of trans fatty acids (TFA) predicts higher risk of coronary heart disease, sudden death, and possibly diabetes mellitus. These associations are greater than would be predicted by effects of TFA on serum lipoproteins alone. Systemic inflammation and endothelial dysfunction may be involved in the pathogenesis of atherosclerosis, acute coronary syndromes, sudden death, insulin resistance, dyslipidemia, and heart failure. Evidence from both observational and experimental studies indicates that TFA are pro-inflammatory. Limited evidence suggests that pro-inflammatory effects may be stronger for trans isomers of linoleic acid (trans-C18:2) and oleic acid (trans-C18:1), rather than of palmitoleic acid (trans-C16:1), but further study of potential isomer-specific effects is needed. TFA also appear to induce endothelial dysfunction. The mechanisms underlying these effects are not well-established, but may involve TFA incorporation into endothelial cell, monocyte/macrophage, or adipocyte cell membranes (affecting membrane signaling pathway relating to inflammation) or ligand-dependent effects on peroxisome proliferator-activated receptor (PPAR) or retinoid X receptor (RXR) pathways. Activation of inflammatory responses and endothelial dysfunction may represent important mediating pathways between TFA consumption and risk of coronary heart disease, sudden death, and diabetes. Further study is indicated to define these effects of TFA and the implications of such effects for cardiovascular health."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I89,I89)","v":16293002},{"$f":"(LEN($J89) - LEN(SUBSTITUTE(LOWER($J89),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J89) - LEN(SUBSTITUTE(LOWER($J89),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J89) - LEN(SUBSTITUTE(LOWER($J89),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B89:D89)","v":4},2005,"Genetic and environmental influences on malformations of the cardiac outflow tract.","Kuehl",16293002,"Genetic and environmental influences on malformations of the cardiac outflow tract.    Abstract:   Congenital cardiovascular malformations are the most common form of birth defect recorded. Specific malformations of the outflow portions of the heart are termed conotruncal malformations and arise from the septation of the common conotruncus of the heart. There are multiple lines of evidence that point towards genetic-environmental interactions in the genesis of conotruncal congenital cardiovascular malformations. In particular, environmental exposures that involve vitamin A, retinol, folic acid or retinol receptors are identified as cardiac teratogens. Other environmental agents for which there is evidence of cardiac teratogenicity for outflow tract malformations include nitrofen, ambient air pollution, chlorinated hydrocarbons and pesticides. Genetic polymorphisms of xenobiotic metabolism are clearly differentiating in the effect of potential teratogens. Work in this field is at a new cusp, with the ability to measure xenobiotic exposure, document xenobiotic metabolizing genetic polymorphisms and integrate these data into models of cardiac teratogenesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I90,I90)","v":16140154},{"$f":"(LEN($J90) - LEN(SUBSTITUTE(LOWER($J90),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J90) - LEN(SUBSTITUTE(LOWER($J90),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J90) - LEN(SUBSTITUTE(LOWER($J90),LOWER(D$3),\"\")))/LEN(D$3)","v":4},{"$f":"SUM(B90:D90)","v":4},2005,"Regulation of hematopoiesis by retinoid signaling.","Evans",16140154,"Regulation of hematopoiesis by retinoid signaling.    Abstract:   The discovery that retinoic acid efficiently stimulates the terminal differentiation of granulocytic leukemia cells had a major impact on clinical hematology, but has also inspired research into the normal function of the retinoid signaling pathway during hematopoiesis. New animal models and loss-of-function approaches have successfully revealed requirements for the pathway at defined embryonic stages that are relevant for distinct hematopoietic cell populations. For example, novel insight has been gained regarding the function of retinoids in yolk sac hematovascular development, fetal erythropoiesis, T-cell homing, and hematopoietic stem and progenitor cell biology. The lessons learned so far indicate that future development of sophisticated animal models will be needed to fully understand the intricacy and specificity of this complex signaling pathway, but that this effort will be productive and continue to inform both basic and clinical research on many fronts."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I91,I91)","v":15526929},{"$f":"(LEN($J91) - LEN(SUBSTITUTE(LOWER($J91),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J91) - LEN(SUBSTITUTE(LOWER($J91),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J91) - LEN(SUBSTITUTE(LOWER($J91),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B91:D91)","v":4},2004,"Heart defects and other malformations in the Inuit in Canada: a baseline study.","Arbour",15526929,"Heart defects and other malformations in the Inuit in Canada: a baseline study.    Abstract:    OBJECTIVES : Birth defects occur in all ethnic groups, remaining an important world-wide cause of perinatal and infant morbidity. This contributes greatly to an excess of health care dollars allocated to the care and repair of those affected. This is especially true when those affected live in remote geographical locations.  STUDY DESIGN : A chart review of 2567 live births of children of Inuit parents residing in Arctic Quebec (Nunavik) and on Baffin Island (Nunavut) between 1989 and 1994 (five years) was carried out compared to rates of anomalies of the Alberta Congenital Anomalies Surveillance System (ACASS).  RESULTS : Birth defects were higher in the Inuit sample in nearly every major ICD-9 category with the exception of neural tube defects, eye anomalies and chromosome abnormalities. (Total: 99.7/1000 Vs 51.5/1000; OR 1.93 95% CI 1.7-2.3). Congenital heart defects were significantly increased 22.9/1000 Vs 5.6/1000, with an OR of 4.18 (95% CI 3.2-5.4) in the ICD-9 category 745. In particular, ventricular septal defects (VSDs) and atrial septal defects (ASDs) (OR 4.9 CI 3.5-6.9 and 4.6 CI 2.9-7.2) were frequent.  CONCLUSIONS : A high rate of heart defects was an important contributor to the nearly two times rate of total birth defects in the Inuit compared to the ACASS. Further study should be carried out to determine the contributing factors. Genetic predisposition to specific heart defects, and a diet low in folate and vitamin A are considerations. The use of alcohol may exacerbate vitamin status in pregnancy. Optimizing vitamin status in the periconceptional period may reduce the rate of birth defects."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I92,I92)","v":15485588},{"$f":"(LEN($J92) - LEN(SUBSTITUTE(LOWER($J92),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J92) - LEN(SUBSTITUTE(LOWER($J92),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J92) - LEN(SUBSTITUTE(LOWER($J92),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B92:D92)","v":4},2004,"Diet, fatty acids, and regulation of genes important for heart disease.","Vanden Heuvel",15485588,"Diet, fatty acids, and regulation of genes important for heart disease.    Abstract:   Diets rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs), such as alpha-linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid, are associated with decreased incidence and severity of coronary heart disease. Similarly, conjugated linoleic acids (CLAs), which are found in meat and dairy products, have beneficial effects against atherosclerosis, diabetes, and obesity. The effects of n3-PUFAs and CLAs are in contrast to fatty acids with virtually identical structures, such as linoleic acid and arachidonic acid (ie, n-6 PUFAs). This article discusses the possibility that cognate receptors exist for fatty acids or their metabolites that are able to regulate gene expression and coordinately affect metabolic or signaling pathways associated with coronary heart disease. Three nuclear receptors are emphasized as fatty acid receptors that respond to dietary and endogenous ligands: peroxisome proliferator activated receptors, retinoid X receptors, and liver X receptors."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I93,I93)","v":15374828},{"$f":"(LEN($J93) - LEN(SUBSTITUTE(LOWER($J93),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J93) - LEN(SUBSTITUTE(LOWER($J93),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J93) - LEN(SUBSTITUTE(LOWER($J93),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B93:D93)","v":4},2005,"Peroxisome proliferator-activated receptors and cardiovascular remodeling.","Schiffrin",15374828,"Peroxisome proliferator-activated receptors and cardiovascular remodeling.    Abstract:   Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that heterodimerize with the retinoid X receptor and then modulate the function of many target genes. Three PPARs are known: alpha, beta/delta, and gamma. The better known are PPAR-alpha and PPAR-gamma, which may be activated by different synthetic agonists, although the endogenous ligands are unknown. PPAR-alpha is involved in fatty acid oxidation and expressed in the liver, kidney, and skeletal muscle, whereas PPAR-gamma is involved in fat cell differentiation, lipid storage, and insulin sensitivity. However, both have been shown to be present in variable amounts in cardiovascular tissues, including endothelium, smooth muscle cells, macrophages, and the heart. The activators of PPAR-alpha (fibrates) and PPAR-gamma (thiazolidinediones or glitazones) antagonized the actions of angiotensin II in vivo and in vitro and exerted cardiovascular antioxidant and anti-inflammatory effects. PPAR activators lowered blood pressure, induced favorable effects on the heart, and corrected vascular structure and endothelial dysfunction in several rodent models of hypertension. Activators of PPARs may become therapeutic agents useful in the prevention of cardiovascular disease beyond their effects on carbohydrate and lipid metabolism. Some side effects, such as weight gain, as well as documented aggravation of advanced heart failure through fluid retention by glitazones, may, however, limit their therapeutic application in prevention of cardiovascular disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I94,I94)","v":11747199},{"$f":"(LEN($J94) - LEN(SUBSTITUTE(LOWER($J94),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J94) - LEN(SUBSTITUTE(LOWER($J94),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J94) - LEN(SUBSTITUTE(LOWER($J94),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B94:D94)","v":4},2001,"Retinoid signaling and cardiac anteroposterior segmentation.","Xavier-Neto",11747199,"Retinoid signaling and cardiac anteroposterior segmentation.    Abstract:   Establishment of anterior-posterior polarity is one of the earliest decisions in cardiogenesis. Specification of anterior (outflow) and posterior (inflow) structures ensures proper connections between venous system and inflow tract and between arterial tree and outflow tract. The last few years have witnessed remarkable progress in our understanding of cardiac anteroposterior patterning. Molecular cloning and subsequent studies on RALDH2, the key embryonic retinaldehyde dehydrogenase in retinoic acid (RA) synthesis, provided the missing link between teratogenic studies on RA deficiency and excess and normal chamber morphogenesis. We discuss work establishing the foundations of our current understanding of the mechanisms of cardiac anteroposterior segmentation, the reasons why early evidence pointing to the role of RA in anteroposterior segmentation was overlooked, and the key experiments unraveling the role of RA in cardiac anteroposterior segmentation. We have also integrated recent experiments in a model of cardiac anteroposterior patterning in which RALDH2 expression determines anteroposterior boundaries in the heart field."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I95,I95)","v":11063942},{"$f":"(LEN($J95) - LEN(SUBSTITUTE(LOWER($J95),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J95) - LEN(SUBSTITUTE(LOWER($J95),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J95) - LEN(SUBSTITUTE(LOWER($J95),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B95:D95)","v":4},2000,"From the bottom of the heart: anteroposterior decisions in cardiac muscle differentiation.","Rosenthal",11063942,"From the bottom of the heart: anteroposterior decisions in cardiac muscle differentiation.    Abstract:   Recently, studies on specification of axes in the developing embryo have focused on the heart, which is the first functional organ to form and probably responds to common cues controlling positional information in surrounding tissues. The early differentiation of heart cells affords an opportunity to link the acquisition of regional identity with the signals underlying terminal differentiation. In the past year, a wealth of information on these signals has emerged, elucidating the general pathways controlling body axes in the context of the developing heart."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I96,I96)","v":10394471},{"$f":"(LEN($J96) - LEN(SUBSTITUTE(LOWER($J96),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J96) - LEN(SUBSTITUTE(LOWER($J96),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J96) - LEN(SUBSTITUTE(LOWER($J96),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B96:D96)","v":4},1999,"Forebrain induction, retinoic acid, and vulnerability to schizophrenia: insights from molecular and genetic analysis in developing mice.","LaMantia",10394471,"Forebrain induction, retinoic acid, and vulnerability to schizophrenia: insights from molecular and genetic analysis in developing mice.    Abstract:   Schizophrenia is thought to be a disease of early development that ultimately affects forebrain neurons and circuits. There may be a relationship between disrupted forebrain development; malformations of the limb, face, and heart; and signaling via the steroid-like hormone retinoic acid (RA) in some schizophrenic patients. The limbs, face, heart, and forebrain all develop from sites where neural crest-derived, RA-producing mesenchyme contributes to induction and differentiation of adjacent epithelia. Induction between neural crest-derived, RA-producing mesenchyme, the anterior neural tube, and the anterior surface epithelium of the embryo guides regional differentiation and pathway formation during forebrain development. Furthermore, there are at least two mouse mutations--in the Pax-6 and Gli-3 genes--that cause peripheral malformations and specifically disrupt neural crest mediated, RA-dependent induction and differentiation in the forebrain. These observations suggest that induction might provide a common target for genes that alter morphogenesis of peripheral structures, disrupt RA-signaling, and compromise forebrain development. In the forebrain, some of these disruptions might influence the numbers or cellular properties of neurons and circuits. Such changes might be reflected in the aberrant forebrain function that characterizes schizophrenia."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I97,I97)","v":10193589},{"$f":"(LEN($J97) - LEN(SUBSTITUTE(LOWER($J97),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J97) - LEN(SUBSTITUTE(LOWER($J97),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J97) - LEN(SUBSTITUTE(LOWER($J97),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B97:D97)","v":4},1999,"Primary prevention of CHD: nine ways to reduce risk.","Havranek",10193589,"Primary prevention of CHD: nine ways to reduce risk.    Abstract:   Lowering cholesterol can reduce the incidence of coronary heart disease. Treating hypertension reduces overall mortality and is most effective in reducing the risk of coronary heart disease in older patients. Smoking cessation reduces the level of risk to that of nonsmokers within about three years of cessation. Aspirin is likely to be an effective means of primary prevention, but a group in whom treatment is appropriate has yet to be defined. Evidence that supplementation with vitamin A or C reduces the risk of coronary heart disease is inadequate; the data for use of vitamin E are inconclusive. Epidemiologic evidence is sufficient to recommend that most persons increase their levels of physical activity. Lowering homocysteine levels through increased folate intake is a promising but unproven primary prevention strategy. Hormone replacement therapy was associated with reduced incidence of coronary heart disease in epidemiologic studies but was not effective in a secondary prevention trial."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I98,I98)","v":9457009},{"$f":"(LEN($J98) - LEN(SUBSTITUTE(LOWER($J98),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J98) - LEN(SUBSTITUTE(LOWER($J98),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J98) - LEN(SUBSTITUTE(LOWER($J98),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B98:D98)","v":4},1998,"Prospective association between lipid soluble antioxidants and coronary heart disease in men. The Multiple Risk Factor Intervention Trial.","Evans",9457009,"Prospective association between lipid soluble antioxidants and coronary heart disease in men. The Multiple Risk Factor Intervention Trial.    Abstract:   A nested case-control study was performed using participants enrolled in the Multiple Risk Factor Intervention Trial (MRFIT). The cases involved nonfatal myocardial infarction or death from coronary heart disease. Serum samples (n = 734) obtained at baseline and frozen for approximately 20 years were analyzed for the antioxidants, carotenoids, retinol, and alpha-, gamma-, and total tocopherol. The concentrations of antioxidants were in the expected range and their association with low density lipoprotein (LDL) cholesterol reflected their absorption and transport mechanisms. Among nonsmokers, the odds ratios (95% confidence intervals (CI)) for quartile IV versus quartile I were 1.40 (0.40-4.89), 0.77 (0.20-2.96), 1.45 (0.38-5.56), 2.34 (0.56-9.81), and 2.40 (0.52-11.07) for retinol, total carotenoids, and alpha-, gamma-, and total tocopherol, respectively. The equivalent odds ratios (95% CI) for smokers were 0.90 (0.34-2.41), 0.66 (0.23-1.84), 0.67 (0.21-2.13), 2.04 (0.88-4.73), and 0.52 (0.16-1.67), respectively. This analysis of antioxidant concentrations by quartiles indicated no significant association of antioxidant levels with the risk of coronary disease death or nonfatal myocardial infarction."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I99,I99)","v":8977705},{"$f":"(LEN($J99) - LEN(SUBSTITUTE(LOWER($J99),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J99) - LEN(SUBSTITUTE(LOWER($J99),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J99) - LEN(SUBSTITUTE(LOWER($J99),LOWER(D$3),\"\")))/LEN(D$3)","v":4},{"$f":"SUM(B99:D99)","v":4},1996,"A review of skin ageing and its medical therapy.","Gilchrest",8977705,"A review of skin ageing and its medical therapy.    Abstract:   Intrinsic (chronological) skin ageing is characterized by atrophy of the skin with loss of elasticity and slowed metabolic activity. The superposition of environmental damage, particularly exposure to ultraviolet radiation (photodamage), on the intrinsic ageing process results, at least initially, in a hypertrophic repair response, with a thickened epidermis and increased melanogenesis. Even more striking changes occur in the dermis: massive elastosis (deposition of abnormal elastic fibres), collagen degeneration, and twisted, dilated microvasculature. Regular use of a sunscreen alone appears to allow some repair as well as protection from further photodamage. Topical tretinoin has been shown to partially reverse the clinical and histological changes induced by the combination of sunlight exposure and chronological ageing. A formulation of tretinoin in an emollient cream (Retinova, Renova), developed specifically for the treatment of photodamaged skin, has been extensively investigated in multicentre, double-blind trials and has been shown to produce significant improvement within 4-6 months of daily use, compared with vehicle alone, as part of a regimen including sun protection and moisturizer use. Histological changes in the epidermis and dermis noted after 12 months suggest tretinoin repairs photodamage by reconstitution of the rete pegs, repair of keratinocyte ultrastructural damage, more even distribution of melanocytes and melanin pigment, deposition of new papillary dermal collagen, and improvements in vasculature. Alpha-hydroxy acids (AHAs) have also been widely used for therapy of photodamaged skin, and these compounds have been reported to normalize hyperkeratinization and increase viable epidermal thickness and dermal glycosaminoglycans content. The single randomized controlled study now available appears to substantiate AHA efficacy and safety. In summary, recent work has substantially elucidated the ageing processes that affect the skin and has demonstrated that many of the unwanted changes can be improved by topical therapy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I100,I100)","v":1463588},{"$f":"(LEN($J100) - LEN(SUBSTITUTE(LOWER($J100),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J100) - LEN(SUBSTITUTE(LOWER($J100),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J100) - LEN(SUBSTITUTE(LOWER($J100),LOWER(D$3),\"\")))/LEN(D$3)","v":4},{"$f":"SUM(B100:D100)","v":4},1992,"Vitamin neurotoxicity.","Snodgrass",1463588,"Vitamin neurotoxicity.    Abstract:   Vitamins contain reactive functional groups necessary to their established roles as coenzymes and reducing agents. Their reactive potential may produce injury if vitamin concentration, distribution, or metabolism is altered. However, identification of vitamin toxicity has been difficult. The only well-established human vitamin neurotoxic effects are those due to hypervitaminosis A (pseudotumor cerebri) and pyridoxine (sensory neuropathy). In each case, the neurological effects of vitamin deficiency and vitamin excess are similar. Closely related to the neurological symptoms of hypervitaminosis A are symptoms including headache, pseudotumor cerebri, and embryotoxic effects reported in patients given vitamin A analogs or retinoids. Most tissues contain retinoic acid (RA) and vitamin D receptors, members of a steroid receptor superfamily known to regulate development and gene expression. Vitamin D3 effects on central nervous system (CNS) gene expression are predictable, in addition to the indirect effects owing to its influence on calcium and phosphorus homeostasis. Folates and thiamine cause seizures and excitation when administered in high dosage directly into the brain or cerebrospinal fluid (CSF) of experimental animals but have rarely been reported to cause human neurotoxicity, although fatal reactions to i.v. thiamine are well known. Ascorbic acid influences CNS function after peripheral administration and influences brain cell differentiation and 2-deoxyglucose accumulation by cultured glial cells. Biotin influences gene expression in animals that are not vitamin-deficient and alters astrocyte glucose utilization. The multiple enzymes and binding proteins involved in regeneration of retinal vitamin A illustrate the complexity of vitamin processing in the body. Vitamin A toxicity is also a good general model of vitamin neurotoxicity, because it shows the importance of the ratio of vitamin and vitamin-binding proteins in producing vitamin toxicity and of CNS permeability barriers. Because vitamin A and analogs enter the CNS better than most vitamins, and because retinoids have many effects on enzyme activity and gene expression, Vitamin A neurotoxicity is more likely than that of most, perhaps all other vitamins. Megadose vitamin therapy may cause injury that is confused with disease symptoms. High vitamin intake is more hazardous to peripheral organs than to the nervous system, because CNS vitamin entry is restricted. Vitamin administration into the brain or CSF, recommended in certain disease states, is hazardous and best avoided. The lack of controlled trials prevents us from defining the lowest human neurotoxic dose of any vitamin. Large differences in individual susceptibility to vitamin neurotoxicity probably exist, and ordinary vitamin doses may harm occasional patients with genetic disorders.(ABSTRACT TRUNCATED AT 400 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I101,I101)","v":26768185},{"$f":"(LEN($J101) - LEN(SUBSTITUTE(LOWER($J101),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J101) - LEN(SUBSTITUTE(LOWER($J101),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J101) - LEN(SUBSTITUTE(LOWER($J101),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B101:D101)","v":3},2015,"De novo 9q gain in an infant with tetralogy of Fallot with absent pulmonary valve: Patient report and review of congenital heart disease in 9q duplication syndrome.","Amarillo",26768185,"De novo 9q gain in an infant with tetralogy of Fallot with absent pulmonary valve: Patient report and review of congenital heart disease in 9q duplication syndrome.    Abstract:   Genomic disruptions, altered epigenetic mechanisms, and environmental factors contribute to the heterogeneity of congenital heart defects (CHD). In recent years, chromosomal microarray analysis (CMA) has led to the identification of numerous copy number variations (CNV) in patients with CHD. Genes disrupted by and within these CNVs thus represent excellent candidate genes for CHD. Microduplications of 9q (9q+) have been described in patients with CHD, however, the critical gene locus remains undetermined. Here we discuss an infant with tetralogy of Fallot with absent pulmonary valve, fetal hydrops, and a 3.76 Mb de novo contiguous gain of 9q34.2-q34.3 detected by CMA, and confirmed by karyotype and FISH studies. This duplicated interval disrupted RXRA (retinoid X receptor alpha; OMIM #180245) at intron 1. We also review CHD findings among previously reported patients with 9q (9q+) duplication syndrome. This is the first report implicating RXRA in CHD with 9q duplication, providing additional data in understanding the genetic etiology of tetralogy of Fallot, CHD, and disorders linked to 9q microduplication syndrome. This report also highlights the significance of CMA in the clinical diagnosis and genetic counseling of patients and families with complex CHD."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I102,I102)","v":25392110},{"$f":"(LEN($J102) - LEN(SUBSTITUTE(LOWER($J102),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J102) - LEN(SUBSTITUTE(LOWER($J102),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J102) - LEN(SUBSTITUTE(LOWER($J102),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B102:D102)","v":3},2014,"Cardiovascular diseases: oxidative damage and antioxidant protection.","Zhang",25392110,"Cardiovascular diseases: oxidative damage and antioxidant protection.    Abstract:   Atherosclerosis, the hardening of arteries under oxidative stress is related to oxidative changes of low density lipoproteins (LDL). The antioxidants prevent the formation of oxidized LDL during atherogenesis. Perhaps more than one mechanism is involved in the atherosclerosis disease where LDL is oxidized in all the cells of arterial wall during the development of this disease. The oxidation of LDL produces lipid peroxidation products such as isoprostans from arachidonic, eicosapentaenoic and docosahexaenoic acids, oxysterols from cholesterol, hydroxyl fatty acids, lipid peroxides and aldehydes. The lipid peroxidation bioassay can serve as a marker for the risk of cardiovascular. An in vivo test of levels of oxidative lipid damage is an early prediction of development of cardiovascular disease (CVD). Serum paraoxonase (PON) activity is correlated to severity of the coronary artery disease. The antioxidants level in the serum and serum paraoxonase activity provides information for the risk of CVD. The antioxidant enzyme superoxide dismutase is responsible for dismutation of superoxide, a free radical chain initiator. The subcellular changes in the equilibrium in favor of free radicals can cause increase in the oxidative stress which leads to cardiomyopathy, heart attack or cardiac dysfunction. The oxidative damage and defense of heart disease has been reported where dietary antioxidants protect the free radical damage to DNA, proteins and lipids. The ascorbic acid, vitamin C is an effective antioxidant and high vitamin E intake can reduce the risk of coronary heart disease (CHD) by inhibition of atherogenic forms of oxidized LDL. The vitamin A and beta-carotene protect lipid peroxidation and provitamin-A activity. It has been recently suggested that the protection of oxidative damage and related CVD is best served by antioxidants found in the fruits and vegetables. The oxidative damage and antioxidant protection of CVD have been described here."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I103,I103)","v":23973941},{"$f":"(LEN($J103) - LEN(SUBSTITUTE(LOWER($J103),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J103) - LEN(SUBSTITUTE(LOWER($J103),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J103) - LEN(SUBSTITUTE(LOWER($J103),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B103:D103)","v":3},2013,"Retinoid signaling in control of progenitor cell differentiation during mouse development.","Duester",23973941,"Retinoid signaling in control of progenitor cell differentiation during mouse development.    Abstract:   The vitamin A metabolite retinoic acid (RA) serves as a ligand for nuclear RA receptors that control differentiation of progenitor cells important for vertebrate development. Genetic studies in mouse embryos deficient for RA-generating enzymes have been invaluable for deciphering RA function. RA first begins to act during early organogenesis when RA generated in trunk mesoderm begins to function as a diffusible signal controlling progenitor cell differentiation. In neuroectoderm, RA functions as an instructive signal to stimulate neuronal differentiation of progenitor cells in the hindbrain and spinal cord. RA is not required for early neuronal differentiation of the forebrain, but at later stages RA stimulates neuronal differentiation in forebrain basal ganglia. RA also acts as a permissive signal for differentiation by repressing fibroblast growth factor (FGF) signaling in differentiated cells as they emerge from progenitor populations in the caudal progenitor zone and second heart field. In addition, RA signaling stimulates differentiation of spermatogonial germ cells and induces meiosis in male but not female gonads. A more complete understanding of the normal functions of RA signaling during development will guide efforts to use RA as a differentiation agent for therapeutic purposes."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I104,I104)","v":22595346},{"$f":"(LEN($J104) - LEN(SUBSTITUTE(LOWER($J104),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J104) - LEN(SUBSTITUTE(LOWER($J104),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J104) - LEN(SUBSTITUTE(LOWER($J104),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B104:D104)","v":3},2012,"The neural crest in cardiac congenital anomalies.","Keyte",22595346,"The neural crest in cardiac congenital anomalies.    Abstract:   This review discusses the function of neural crest as they relate to cardiovascular defects. The cardiac neural crest cells are a subpopulation of cranial neural crest discovered nearly 30 years ago by ablation of premigratory neural crest. The cardiac neural crest cells are necessary for normal cardiovascular development. We begin with a description of the crest cells in normal development, including their function in remodeling the pharyngeal arch arteries, outflow tract septation, valvulogenesis, and development of the cardiac conduction system. The cells are also responsible for modulating signaling in the caudal pharynx, including the second heart field. Many of the molecular pathways that are known to influence specification, migration, patterning and final targeting of the cardiac neural crest cells are reviewed. The cardiac neural crest cells play a critical role in the pathogenesis of various human cardiocraniofacial syndromes such as DiGeorge, Velocardiofacial, CHARGE, Fetal Alcohol, Alagille, LEOPARD, and Noonan syndromes, as well as Retinoic Acid Embryopathy. The loss of neural crest cells or their dysfunction may not always directly cause abnormal cardiovascular development, but are involved secondarily because crest cells represent a major component in the complex tissue interactions in the head, pharynx and outflow tract. Thus many of the human syndromes linking defects in the heart, face and brain can be better understood when considered within the context of a single cardiocraniofacial developmental module with the neural crest being a key cell type that interconnects the regions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I105,I105)","v":21293221},{"$f":"(LEN($J105) - LEN(SUBSTITUTE(LOWER($J105),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J105) - LEN(SUBSTITUTE(LOWER($J105),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J105) - LEN(SUBSTITUTE(LOWER($J105),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B105:D105)","v":3},2011,"A case of lower extremity venous thrombosis in the pediatric emergency department: associations with May-Thurner syndrome and isotretinoin use.","Whitman",21293221,"A case of lower extremity venous thrombosis in the pediatric emergency department: associations with May-Thurner syndrome and isotretinoin use.    Abstract:   Unilateral calf swelling and pain is not a common complaint in the pediatric emergency department. We present a case of a 17-year-old adolescent boy with no past medical history who presented with left leg swelling and pain while taking prednisone and isotretinoin. He was found to have an extensive occlusive thrombus throughout the deep venous system in his left leg. He was later diagnosed with May-Thurner syndrome, an anatomic variant in which the right iliac artery compresses the left iliac vein. We review the differential diagnosis, diagnostic workup, and initial ED management of deep venous thrombosis and provide a brief discussion of May-Thurner syndrome and the association of isotretinoin and vascular thrombi."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I106,I106)","v":20026355},{"$f":"(LEN($J106) - LEN(SUBSTITUTE(LOWER($J106),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J106) - LEN(SUBSTITUTE(LOWER($J106),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J106) - LEN(SUBSTITUTE(LOWER($J106),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B106:D106)","v":3},2010,"Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) acts as regulator of metabolism linked to multiple cellular functions.","Wagner",20026355,"Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) acts as regulator of metabolism linked to multiple cellular functions.    Abstract:   Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors. They function as ligand activated transcription factors. They exist in three isoforms, PPARalpha, PPARbeta (formerly PPARdelta), and PPARgamma. For all PPARs lipids are endogenous ligands, linking them directly to metabolism. PPARs form heterodimers with retinoic X receptors, and, upon ligand binding, modulate gene expression of downstream target genes dependent on the presence of co-repressors or co-activators. This results in cell-type specific complex regulations of proliferation, differentiation and cell survival. Specific synthetic agonists for all PPARs are available. PPARalpha and PPARgamma agonists are already in clinical use for the treatment of hyperlipidemia and type 2 diabetes, respectively. More recently, PPARbeta activation came into focus as an interesting novel approach for the treatment of metabolic syndrome and associated cardiovascular diseases. Although the initial notion was that PPARbeta is expressed ubiquitously, more recently extensive investigations have been performed demonstrating high PPARbeta expression in a variety of tissues, e.g. skin, skeletal muscle, adipose tissue, inflammatory cells, heart, and various types of cancer. In addition, in vitro and in vivo studies using specific PPARbeta agonists, tissue-specific over-expression or knockout mouse models have demonstrated a variety of functions of PPARbeta in adipose tissue, muscle, skin, inflammation, and cancer. We will focus here on functions of PPARbeta in adipose tissue, skeletal muscle, heart, angiogenesis and cancer related to modifications in metabolism and the identified underlying molecular mechanisms."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I107,I107)","v":19213559},{"$f":"(LEN($J107) - LEN(SUBSTITUTE(LOWER($J107),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J107) - LEN(SUBSTITUTE(LOWER($J107),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J107) - LEN(SUBSTITUTE(LOWER($J107),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B107:D107)","v":3},2009,"Anti-angiogenic properties of chemopreventive drugs: fenretinide as a prototype.","Sogno",19213559,"Anti-angiogenic properties of chemopreventive drugs: fenretinide as a prototype.    Abstract:   Several cancer chemopreventive agents have been demonstrated to exert antiangiogenic effects. Blocking tumor angiogenesis, a process critical for tumor mass expansion and metastasis, represents an intriguing approach not only to cancer therapy, but also to cancer chemoprevention. We found that angiogenesis is a common and key target of many chemopreventive molecules, where they most likely suppress the angiogenic switch in premalignant tumors, a concept we termed quot;angioprevention.quot; In this manuscript we use as an example the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4HPR), a molecule with confirmed clinical applications in breast cancer adjuvant therapy to prevent cancer recurrence and under evaluation in neuroblastoma and glioblastoma treatment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I108,I108)","v":18220722},{"$f":"(LEN($J108) - LEN(SUBSTITUTE(LOWER($J108),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J108) - LEN(SUBSTITUTE(LOWER($J108),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J108) - LEN(SUBSTITUTE(LOWER($J108),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B108:D108)","v":3},2008,"Stem cells and cardiovascular repair: a role for natural and synthetic molecules harboring differentiating and paracrine logics.","Ventura",18220722,"Stem cells and cardiovascular repair: a role for natural and synthetic molecules harboring differentiating and paracrine logics.    Abstract:   Stem cells hold considerable promise for cardiovascular rescue in patients with heart failure due to myocardial infarction or hereditary cardiomyopathies. However, cardiogenesis, one of the earliest and most complex morphogenetic events in the embryo, is only partially exploited at molecular level. The yield of myocardial cells spontaneously derived from human embryonic or adult stem cells is extremely low (usually less than 0.1%). Moreover, it is now evident that secretion of specific growth factors from transplanted stem cells may activate angiogenic, antiapoptotic and antifibrotic paracrine patterning within the recipient heart, playing a major role in tissue repair. Within this context, targeting stem cell fate at the level of gene expression represents a potentially powerful therapeutic approach to afford a high-throughput of cardiovascular lineage commitment and paracrine secretion of quot;trophic factorsquot;. Cell-based phenotypic- and pathway-specific screens of natural and synthetic compounds have provided a number of molecules achieving selective control of stem cell growth and differentiation. Novel hyaluronan mixed esters of butyric and retinoic acids have been recently synthesized, emerging as new tools for manipulation of cardio/vasculogenic gene expression through the modulation of targeted signaling pathways and chromatin-remodeling enzymes. These molecules have coaxed both murine embryonic and human mesenchymal stem cells towards cardiovascular decision and paracrine secretion of bioactive factors, remarkably enhancing the rescuing potential of human stem cells in in vivo animal models of myocardial infarction. These molecules may ultimately provide new insights in stem cell biology and pave the way to novel approaches in tissue engineering and cardiovascular repair."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I109,I109)","v":18047466},{"$f":"(LEN($J109) - LEN(SUBSTITUTE(LOWER($J109),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J109) - LEN(SUBSTITUTE(LOWER($J109),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J109) - LEN(SUBSTITUTE(LOWER($J109),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B109:D109)","v":3},2008,"Vitamin A: a drug for prevention of restenosis/reocclusion after percutaneous coronary intervention?","Gidlöf",18047466,"Vitamin A: a drug for prevention of restenosis/reocclusion after percutaneous coronary intervention?    Abstract:   The re-establishment of adequate blood flow in a vessel with a reduced lumen due to an atherosclerotic plaque by percutaneous vascular intervention is a well established procedure. However, the long-term outcome of such interventions is negatively influenced by the development of intimal hyperplasia/restenosis. Although extensively researched, this still represents a significant clinical problem. Retinoids, i.e. natural and synthetic derivates of vitamin A, represent a potential therapeutic compound, since they have been shown to influence the vast majority of processes that ultimately lead to reocclusion of the injured vessel. Retinoids exert their effects at the transcriptional level through their nuclear receptors. Targeting multiple processes, i.e. proliferation, migration, extracellular matrix composition and cell differentiation, as well as coagulation/fibrinolysis, should increase their future role in the prevention of restenosis. The purpose of this review is to summarize the diverse effects of retinoids on pathobiological and biological processes activated at sites of vascular injury with particular emphasis on intimal hyperplasia/restenosis after endovascular interventions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I110,I110)","v":17924560},{"$f":"(LEN($J110) - LEN(SUBSTITUTE(LOWER($J110),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J110) - LEN(SUBSTITUTE(LOWER($J110),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J110) - LEN(SUBSTITUTE(LOWER($J110),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B110:D110)","v":3},2008,"Homing imprinting and immunomodulation in the gut: role of dendritic cells and retinoids.","Mora",17924560,"Homing imprinting and immunomodulation in the gut: role of dendritic cells and retinoids.    Abstract:   Lymphocyte migration is at the heart of chronic inflammatory ailments, including inflammatory bowel disease (IBD). Whereas naïve lymphocytes migrate to all secondary lymphoid organs, they are mostly excluded from nonlymphoid peripheral tissues. Upon activation, lymphocytes change their pattern of adhesion receptors and acquire the capacity to migrate to extralymphoid tissues. Antigen-experienced T cells are subdivided into different subsets based on their expression of homing receptors that favor their accumulation in specific tissues, such as the skin and the gut mucosa. B cells and antibody-secreting cells (ASC) also show tissue-tropism, which is somewhat correlated with the class of immunoglobulin that they produce. In fact, IgA-ASC are located in mucosal tissues, where they produce IgA, the main class of antibodies found in secretions. Although IgA-ASC are usually considered as a homogeneous pool of cells, those located in the small bowel have some unique migratory characteristics, suggesting that they are generated under different conditions as compared to IgA-ASC in other mucosal compartments. Foxp3(+) regulatory T cells (T(REG)) can also exhibit tissue-specific migratory potential and recent evidence suggests that T(REG) can be imprinted with gut-specific homing. Moreover, foxp3(+) T(REG) are enriched in the small bowel lamina propria, where they can be generated locally. The present review addresses our current understanding of how tissue-specific homing is acquired and modulated on T cells, B cells, and ASC, with a special emphasis on the intestinal mucosa. Harnessing these mechanisms could offer novel, effective, and more specific therapeutic strategies in IBD."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I111,I111)","v":17600781},{"$f":"(LEN($J111) - LEN(SUBSTITUTE(LOWER($J111),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J111) - LEN(SUBSTITUTE(LOWER($J111),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J111) - LEN(SUBSTITUTE(LOWER($J111),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B111:D111)","v":3},2007,"Retinoic acid regulation of the somitogenesis clock.","Duester",17600781,"Retinoic acid regulation of the somitogenesis clock.    Abstract:   Retinoic acid (RA) is a signaling molecule synthesized from vitamin A that controls gene expression at the transcriptional level by functioning as a ligand for nuclear RA receptors. RA plays an essential role during embryonic development in higher animals by regulating key genes involved in pattern formation. RA is required for induction of several Hox genes involved in patterning of the hindbrain and spinal cord as neuroectoderm emerges from the primitive streak. Recent findings indicate that RA is also required to ensure bilaterally symmetrical generation of left and right somites as presomitic mesoderm emerges from the primitive streak. RA may control somitogenesis through its ability to repress posterior ectodermal expression of fibroblast growth factor-8 (Fgf8) for a short period of time during the late primitive streak stage when the somitogenesis clock initiates. During this tight temporal window, RA is required to limit Fgf8 expression to the most posterior ectoderm (epiblast), thus preventing ectopic Fgf8 expression in more anterior ectoderm including the node ectoderm and neuroectoderm. Although Fgf8 is required for the node to impart left-right asymmetry on specific tissues (heart, visceral organs, etc.), excess Fgf8 signaling following a loss of RA may stimulate the node to generate asymmetry also in presomitic mesoderm, leading to left-right asymmetry in the somitogenesis clock. These findings suggest that human vertebral birth defects such as scoliosis, an abnormal left-right bending of the vertebral column, may be caused by a defect in RA signaling during somitogenesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I112,I112)","v":17415088},{"$f":"(LEN($J112) - LEN(SUBSTITUTE(LOWER($J112),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J112) - LEN(SUBSTITUTE(LOWER($J112),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J112) - LEN(SUBSTITUTE(LOWER($J112),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B112:D112)","v":3},2007,"Chemoprevention of lung cancers: lessons from CARET, the beta-carotene and retinol efficacy trial, and prospects for the future.","Omenn",17415088,"Chemoprevention of lung cancers: lessons from CARET, the beta-carotene and retinol efficacy trial, and prospects for the future.    Abstract:   The objective of this paper was to review the strategies for lung cancer chemoprevention. A retrospective assessment of the major findings from the most informative lung cancer chemoprevention clinical trials [alpha-tocopherol (vitamin E), beta-carotene trial and beta-carotene and retinol efficacy trial] was employed. Both trials and many others showed no benefit from what was once the prime candidate for lung cancer chemoprevention, beta-carotene. Furthermore, both trials found that beta-carotene, alone or in combination with vitamin E or retinyl palmitate, increased the incidence of lung cancers and the total and cardiovascular mortality rates. In conclusion, design, conduct, documentation, relationships with participants, and preparedness for unexpected findings are all important for chemoprevention research. Trials are necessary to test inferences from observational epidemiology and animal models. Multiple classes of promising agents are available for evaluation and for eventual randomized trials."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I113,I113)","v":17148746},{"$f":"(LEN($J113) - LEN(SUBSTITUTE(LOWER($J113),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J113) - LEN(SUBSTITUTE(LOWER($J113),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J113) - LEN(SUBSTITUTE(LOWER($J113),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B113:D113)","v":3},2006,"Targeting components of the stress system as potential therapies for the metabolic syndrome: the peroxisome-proliferator-activated receptors.","Yumuk",17148746,"Targeting components of the stress system as potential therapies for the metabolic syndrome: the peroxisome-proliferator-activated receptors.    Abstract:   The three peroxisome-proliferator-activated receptor (PPAR) subtypes PPAR-alpha, PPAR-gamma, and PPAR-delta are ligand-activated transcription factors of the nuclear receptor family. PPARs form obligate heterodimers with the retinoid X receptor, which bind to peroxisome-proliferator-response elements (PPREs). PPAR-alpha is expressed mainly in liver, brown fat, kidney, heart, and skeletal muscle; PPAR-gamma in intestine and adipose tissue; PPAR-alpha and PPAR-gamma are both expressed in vascular endothelium, smooth muscle cells, macrophages, and foam cells; PPAR-delta in skeletal muscle, human embryonic kidney, intestine, heart, adipose tissue, developing brain, and keratinocytes. Intense interest in the development of drugs with new mechanisms of action for the metabolic syndrome has focused attention on nuclear receptors, such as PPARs that function as regulators of energy homeostasis. Agonists of PPAR-alpha and PPAR-gamma are currently used to treat diabetic dyslipidemia and type 2 diabetes. Dual PPAR-alpha/gamma agonists and PPAR-alpha/gamma/delta pan-agonists are under investigation for treatment of cardiovascular disease and the metabolic syndrome. Selective PPAR modulators (SPPARMs) are PPAR ligands that possess desirable efficacy and improved tolerance. Efforts are being made to identify novel partial agonists or antagonists for PPAR-gamma in order to combine their antidiabetic and antiobesity effects. Glucocorticoids are major mediators of the stress response and could be the link between stress and PPAR activator signaling and thus may affect the downstream metabolic pathways involved in fuel homeostasis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I114,I114)","v":16454534},{"$f":"(LEN($J114) - LEN(SUBSTITUTE(LOWER($J114),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J114) - LEN(SUBSTITUTE(LOWER($J114),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J114) - LEN(SUBSTITUTE(LOWER($J114),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B114:D114)","v":3},2006,"Fulfilling an unmet need in psoriasis : do biologicals hold the key to improved tolerability?","Shear",16454534,"Fulfilling an unmet need in psoriasis : do biologicals hold the key to improved tolerability?    Abstract:   Psoriasis is a chronic inflammatory disease of the skin affecting approximately 2% of the worlds population. Traditional systemic treatments, including methotrexate, ciclosporin, psoralen plus UVA (PUVA), oral retinoids and fumaric acid esters, are widely used for severe disease and are effective in the short term. Severe psoriasis is a chronic disease and patients and physicians have expressed concerns about possible harm from organ toxicity, such as skin cancer (PUVA), hyperlipidaemia (retinoids), renal (ciclosporin) or hepatotoxicity (methotrexate). Long-term monitoring is required and may not detect early organ damage. The pathophysiology of psoriasis remains to be clarified, but advances toward the understanding of the immunological basis of psoriasis have uncovered the involvement of immunological pathways; for example, the role of tumour necrosis factor (TNF)-alpha, T cell proliferation and T cell activation, and migration to the epidermis. This advancement in knowledge combined with developments in recombinant technologies has led to the development of target-specific therapies. Biological agents are defined as proteins that can be extracted from animal tissue or produced via recombinant DNA technologies and possess pharmacological activity. Adalimumab, alefacept, infliximab, efalizumab and etanercept are examples of biological agents currently used for the treatment of psoriasis. Some of these are also therapy for other autoimmune conditions, such as rheumatoid arthritis and Crohns disease. These biological agents are effective in psoriasis but raise new safety concerns. Information on the safety of biological agents in conditions such as rheumatoid arthritis and Crohns disease can not be directly extrapolated to psoriasis. An increased incidence of lymphomas has been postulated to be associated with etanercept, infliximab and adalimumab; serious infections, such as tuberculosis, have also been reported with these three biologicals, all of which target TNF-alpha. Demyelinating disorders, such as multiple sclerosis, have been reported with some biologicals as has congestive heart failure. Alefacept, because of its mechanism of action of lowering the number of active T cells, is associated with low T cell counts. Efalizumab has been associated with thrombocytopenia and haemolytic anaemia. Data on the safety of gt;2.5 years continuous treatment with efalizumab are reassuring and a valuable beginning to understanding the role and risk of harm of long-term therapy for a chronic disease. Longer follow-up studies and safety databases, for each of the biologicals used in psoriasis, are needed to ensure both prolonged efficacy and minimal risk of harm."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I115,I115)","v":14561188},{"$f":"(LEN($J115) - LEN(SUBSTITUTE(LOWER($J115),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J115) - LEN(SUBSTITUTE(LOWER($J115),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J115) - LEN(SUBSTITUTE(LOWER($J115),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B115:D115)","v":3},2002,"Peroxisome proliferator-activated receptors and the control of inflammation.","Cabrero",14561188,"Peroxisome proliferator-activated receptors and the control of inflammation.    Abstract:   Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors which form a subfamily of the nuclear receptor gene family. This subfamily consists of three isotypes, alpha (NR1C1), gamma (NR1C3), and beta/delta (NRC1C2) with a differential tissue distribution. PPARalpha is expressed primarily in tissues with a high level of fatty acid catabolism such as liver, brown fat, kidney, heart and skeletal muscle. PPARbeta is ubiquitously expressed, and PPARgamma has a restricted pattern of expression, mainly in white and brown adipose tissues, whereas other tissues such as skeletal muscle and heart contain limited amounts. Furthermore, PPARalpha and gamma isotypes are expressed in vascular cells including endothelial and smooth muscle cells and macrophages/foam cells. PPARs are activated by ligands, such as naturally occurring fatty acids, which are activators of all three PPAR isotypes. In addition to fatty acids, several synthetic compounds, such as fibrates and thiazolidinediones, bind and activate PPARalpha and PPARgamma, respectively. In order to be transcriptionally active, PPARs need to heterodimerize with the retinoid-X-receptor (RXR). Upon activation, PPAR-RXR heterodimers bind to DNA specific sequences called peroxisome proliferator-response elements (PPRE) and stimulate transcription of target genes. PPARs play a critical role in lipid and glucose homeostasis, but lately they have been implicated as regulators of inflammatory responses. The first evidence of the involvement of PPARs in the control of inflammation came from the PPARalpha null mice, which showed a prolonged inflammatory response. PPARalpha activation results in the repression of NF-kappaB signaling and inflammatory cytokine production in different cell-types. A role for PPARgamma in inflammation has also been reported in monocyte/macrophages, where ligands of this receptor inhibited the activation of macrophages and the production of inflammatory cytokines (TNFalpha, interleukin 6 and 1beta), although part of the anti-inflammatory effects of these ligands seems to be mediated by a mechanism not involving PPARgamma. All these findings suggest a role of PPARs in the control of the inflammatory response with potential therapeutic applications in inflammation-related diseases."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I116,I116)","v":11411341},{"$f":"(LEN($J116) - LEN(SUBSTITUTE(LOWER($J116),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J116) - LEN(SUBSTITUTE(LOWER($J116),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J116) - LEN(SUBSTITUTE(LOWER($J116),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B116:D116)","v":3},2001,"[Physiological and pharmacological function of PPARs].","Takahashi",11411341,"[Physiological and pharmacological function of PPARs].    Abstract:   The finding of nuclear receptors has greatly enhanced our understanding of gene regulation by lipophilic hormones such as steroids, thyroxine, vitamin D and retinoids. These receptors comprise a superfamily of transcription factors containing highly related DNA-binding domains. In mammals, the peroxisome proliferator-activated receptor (PPAR) family of nuclear hormone receptors consists of three subtypes by separate genes: PPAR alpha, PPAR delta (also referred to as hNUC1 or PPAR beta), and PPAR gamma. PPARs have been associated with several distinct biological programs. PPARs function as a heterodimer with the retinoid X receptor. This complex binds to sequences termed direct repeat-1 response element in enhancer sites of regulated genes and activates transcription upon ligand and coactivator binding. Three different PPAR subtypes have specific roles in different organs. PPAR alpha, mainly expressed in liver, plays an important role in fatty acid metabolism. PPAR gamma predominantly is expressed in adipose cells. PPAR delta displays a high level of expression in lipid-metabolizing organs such as small intestine, heart and adipose tissue. Naturally occurring and synthetic molecules (anti-hyperlipidemia and diabetic drugs) that are ligands for these nuclear receptors control transcriptional activity of PPARs. We believe that the pharmacological and genomic researches on PPAR will develop powerful tools for prevention and medical care against common diseases."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I117,I117)","v":11058767},{"$f":"(LEN($J117) - LEN(SUBSTITUTE(LOWER($J117),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J117) - LEN(SUBSTITUTE(LOWER($J117),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J117) - LEN(SUBSTITUTE(LOWER($J117),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B117:D117)","v":3},2000,"Biochemical, structural, genetic, physiological, and pathophysiological features of lipocalin-type prostaglandin D synthase.","Urade",11058767,"Biochemical, structural, genetic, physiological, and pathophysiological features of lipocalin-type prostaglandin D synthase.    Abstract:   Lipocalin-type prostaglandin (PG) D synthase (PGDS) catalyzes the isomerization of PGH(2), a common precursor of various prostanoids, to produce PGD(2), a potent endogenous somnogen and nociceptive modulator, in the presence of sulfhydryl compounds. PGDS is an N-glycosylated monomeric protein with an M(r) of 20000-31000 depending on the size of the glycosyl moiety. PGDS is localized in the central nervous system and male genital organs of various mammals and in the human heart and is secreted into the cerebrospinal fluid, seminal plasma, and plasma, respectively, as beta-trace. The PGDS concentrations in these body fluids are useful for the diagnosis of several neurological disorders, dysfunction of sperm formation, and cardiovascular and renal diseases. The cDNA and gene for PGDS have been isolated from several animal species, and the tissue distribution and cellular localization have also been determined. This enzyme is considered to be a dual functional protein; i.e. it acts as a PGD(2)-producing enzyme and also as a lipophilic ligand-binding protein, because the enzyme binds biliverdin, bilirubin (K(d)=30 nM), retinaldehyde, retinoic acid (K(d)=80 nM) with high affinities. X-ray crystallographic analyses revealed that PGDS possesses a beta-barrel structure with a hydrophobic pocket in which an active thiol, Cys(65), the active center for the catalytic reaction, was located facing to the inside of the pocket. Gene-knockout and transgenic mice for PGDS were generated and found to have abnormalities in the regulation of nociception and sleep."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I118,I118)","v":10874164},{"$f":"(LEN($J118) - LEN(SUBSTITUTE(LOWER($J118),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J118) - LEN(SUBSTITUTE(LOWER($J118),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J118) - LEN(SUBSTITUTE(LOWER($J118),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B118:D118)","v":3},2000,"In vitro control of organogenesis and body patterning by activin during early amphibian development.","Asashima",10874164,"In vitro control of organogenesis and body patterning by activin during early amphibian development.    Abstract:   In the process of amphibian development, an embryonic body plan is established through cell division, sequential gene expression, morphogenesis and cell differentiation. The mechanism of body patterning is complex and includes multiple induction events. Activin, a TGF-beta family protein, can induce several kinds of mesodermal and endodermal tissues in animal cap explants in a dose-dependent manner. In a recent study of the role of activin in organogenesis, we succeeded in raising a beating heart by treating animal caps with a high concentration of activin. Activin also participates in kidney organogenesis in combination with retinoic acid. An embryonic kidney induced by activin and retinoic acid in vitro can function in vivo when it is transplanted into a larva in which pronephros rudiments have already been removed. Further, the activin-treated animal caps clearly show organizer actions that are closely related to body patterning along the anteroposterior axis. These experiments will help to serve as a model system for understanding organogenesis and body patterning at the cellular and molecular levels."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I119,I119)","v":10194513},{"$f":"(LEN($J119) - LEN(SUBSTITUTE(LOWER($J119),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J119) - LEN(SUBSTITUTE(LOWER($J119),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J119) - LEN(SUBSTITUTE(LOWER($J119),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B119:D119)","v":3},1999,"Hormonal regulation of apolipoprotein AI.","Hargrove",10194513,"Hormonal regulation of apolipoprotein AI.    Abstract:   Apolipoprotein AI (apo AI) is the major protein component of the serum high-density lipoprotein (HDL) particles. The antiatherogenic properties of apo AI alone or as part of HDL and their inverse correlation with the incidence of coronary heart disease underlie the clinical importance of the protein. A detailed understanding of the mechanisms by which apo AI is regulated will help us develop new and better ways to manipulate expression of the protein. Although there are many factors that influence apo AI expression, endogenous hormones are attractive because simple changes in abundance of these compounds will alter gene activity. Hormones belonging to the thyroid/steroid family that influence activity of the gene include thyroid hormone, glucocorticoids, gender-specific steroids and retinoic acid. Whereas thyroid, glucocorticoid and estradiol enhance activity of the gene, retinoic acid and androgens decrease it. The mechanisms that mediate the effects of the hormones include direct effects of the ligand and nuclear receptor complex on gene activity. However, indirect means involving the participation of transcription factors other than the hormone receptors are also possible. In summary, members of the same hormone family may have different mechanisms that mediate their activities on apo AI gene activity."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I120,I120)","v":9929823},{"$f":"(LEN($J120) - LEN(SUBSTITUTE(LOWER($J120),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J120) - LEN(SUBSTITUTE(LOWER($J120),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J120) - LEN(SUBSTITUTE(LOWER($J120),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B120:D120)","v":3},1998,"[Current concepts of the structure and functions of retinoid receptors].","Uteshev",9929823,"[Current concepts of the structure and functions of retinoid receptors].    Abstract:   The article discusses the principal structure of nuclear receptors. The structure and function of retinoid receptors, their main ligands and inhibitors are analysed. Data (experimental and clinical) concerning the immunotropic antineoplastic and cardiovascular activity of the main retinoids are given."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I121,I121)","v":9243347},{"$f":"(LEN($J121) - LEN(SUBSTITUTE(LOWER($J121),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J121) - LEN(SUBSTITUTE(LOWER($J121),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J121) - LEN(SUBSTITUTE(LOWER($J121),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B121:D121)","v":3},1997,"Carotenoids and retinoids: a review of research, clinical, and public health applications.","Hinds",9243347,"Carotenoids and retinoids: a review of research, clinical, and public health applications.    Abstract:   Traditionally, the carotenoids and retinoids have been regarded as dietary sources of vitamin A and have been evaluated regarding their respective physiologic roles in vision, growth, immune system integrity, and prevention of vitamin A deficiency. In the 1990s, however, vitamin A deficiency is no longer widespread in Western countries. Therefore, the role of carotenoids and retinoids is evolving to encompass treatment and prevention of conditions such as cancer and cardiovascular disease, which are prevalent in Western societies. This review summarizes current research concerning the therapeutic utility of vitamin A and its analogues and their roles in the prevention of cancer and cardiovascular disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I122,I122)","v":8981600},{"$f":"(LEN($J122) - LEN(SUBSTITUTE(LOWER($J122),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J122) - LEN(SUBSTITUTE(LOWER($J122),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J122) - LEN(SUBSTITUTE(LOWER($J122),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B122:D122)","v":3},1996,"Similarities in genetic mental retardation and neuroteratogenic syndromes.","Adams",8981600,"Similarities in genetic mental retardation and neuroteratogenic syndromes.    Abstract:   Principles and mechanisms of neurobehavioral teratogenesis are used to show commonalities between manifestations of abnormal development consequent to genetic abnormality or teratogenic exposure. A comparison and contrast of both the neuropathological and neuropsychological characteristics of children with early embryonic exposure to isotretinoin (Accutane) or with selected mental retardation syndromes is presented. Putative mechanisms of retinoid teratogenesis through the disruption of normal retinoid-triggered embryogenesis and the alteration of homeobox gene expression are discussed. Interference with homeobox gene expression as an avenue to the perturbation of early developmental processes and the production of hindbrain and craniofacial abnormalities is then proposed as a common basis for the translation and expression of several genetic mental retardation syndromes. Finally, dose-response effects and other modulators of vulnerability to abnormal development are used to provide a conceptual framework for the understanding of variability in the expression of genetically caused abnormalities."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I123,I123)","v":18406732},{"$f":"(LEN($J123) - LEN(SUBSTITUTE(LOWER($J123),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J123) - LEN(SUBSTITUTE(LOWER($J123),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J123) - LEN(SUBSTITUTE(LOWER($J123),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B123:D123)","v":3},1996,"The thyrotropin-releasing hormone gene: differential regulation, expression, and function in hypothalamus and two unexpected extrahypothalamic loci, the heart and testis.","Wilber",18406732,"The thyrotropin-releasing hormone gene: differential regulation, expression, and function in hypothalamus and two unexpected extrahypothalamic loci, the heart and testis.    Abstract:   Thyrotropin-releasing hormone (TRH) is the key regulator of the synthesis and secretion of TSH in animals and humans (Wilber and Yamada 1990). The biological implications of this peptide, the first releasing hormone to be characterized, has generated a large literature regarding both pituitary TSH and extrapituitary roles of TRH as a neurotransmitter and/or neuro-modulator in the central nervous system (OLeary and OConnor 1995, Morley 1981). In this review, new areas of TRH biology are explored, focused on the differential regulation of the TRH gene by triiodothyronine (T(3)) and other substances in the hypothalamus and two unexpected extrahypothalamic loci, the heart and testis. These new directions should enlarge our understanding concerning how hormones like T(3) regulate genes negatively and selectively with the identical receptors and DNA elements required for positive gene stimulation. In addition, regulatory studies of the TRH gene by T(3) should be relevant to other hormone receptor interactions with DNA sequences in general, as glucocorticoids, mineralocorticoids, sex steroids, vitamin D, and retinoic acid are ligands for homologous receptor proteins in the nuclear receptor superfamily."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I124,I124)","v":9026350},{"$f":"(LEN($J124) - LEN(SUBSTITUTE(LOWER($J124),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J124) - LEN(SUBSTITUTE(LOWER($J124),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J124) - LEN(SUBSTITUTE(LOWER($J124),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B124:D124)","v":3},1996,"Transcription factors and the cardiac gene programme.","Doevendans",9026350,"Transcription factors and the cardiac gene programme.    Abstract:   During the past decade, major advances have been made in uncovering the mechanisms that switch genes on and off. Gene methylation and histones play an important role in gene (in)activation. Following gene activation, the initiation of transcription by RNA polymerase requires the assembly of multiple protein complexes on the promoter region of a gene. How a cell type-specific gene expression pattern can be induced is a key question in cardiovascular biology today. Members of the helix-loop-helix-family of the transcription factors play a dominant role in skeletal muscle formation. In cardiac muscle the situation is less obvious. Recent studies identified muscle transcription factors like MEF-2, TEF-1 and MNF, which are common to both the skeletal and cardiac muscle lineages. A few transcription factors, among which Nkx 2.5 and GATA-4, are expressed predominantly in the heart. The absence of master regulators in the heart points to the importance of interaction between ubiquitous factors and tissue restricted factors to initiate the cardiac gene programme and to lock these cells in their differentiated state. The recent development of murine transgenic and gene-targeting technology provides tools to study the role of mammalian transcription factors in vivo. Interesting cardiac phenotypes are found in gene targeted mice, indicating a crucial role for retinoic acid and homeobox genes in murine cardiogenesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I125,I125)","v":8923025},{"$f":"(LEN($J125) - LEN(SUBSTITUTE(LOWER($J125),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J125) - LEN(SUBSTITUTE(LOWER($J125),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J125) - LEN(SUBSTITUTE(LOWER($J125),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B125:D125)","v":3},1996,"Adverse effects of preventive therapy in humans.","La Vecchia",8923025,"Adverse effects of preventive therapy in humans.    Abstract:   The main adverse effects of tamoxifen, aspirin, oral contraceptives (OCs) and retinoids used as chemopreventive agents in humans are reviewed and quantified here. With regard to tamoxifen, there are suggestions of some excess risk of liver, and perhaps gastrointestinal, cancers. The public health impact of such associations, if any, is still unclear. Tamoxifen use is associated with endometrial and myometrial hyperplasia. Data from five studies based on 174 cases indicate that the overall relative risk (RR) of endometrial cancer in ever tamoxifen users is 1.73 (95% confidence interval = 1.1-2.6). However, there is a significant difference between the results of American and European studies, so the relationship between tamoxifen and endometrial cancer remains open to debate. The major side-effect of aspirin is gastrointestinal lesions; the risk of these is increased two- to tenfold, depending on the dose. Aspirin is also associated with an increased risk of haemorrhagic stroke, although its protection against other types of stroke and against myocardial infarction leads to a favourable pattern of risk for all cardiovascular conditions. Short-term side-effects of OCs include vascular diseases and a moderately increased risk of breast cancer. The RR of cervical cancer and hepatocellular carcinoma are also increased in OC users, although the public health impact of such associations is small. Toxicity associated with retinoid treatment is rarely serious as most effects observed are reversible on stopping use. Side-effects include changes in the skin and mucous membranes (dry skin, hair loss, dry nose, conjunctivitis), musculoskeletal symptoms, ophthalmological effects, changes in transaminase activity, changes in clinical chemistry markers (increase in serum triglycerides and decrease in high-density lipoproteins) and, rarely, central nervous system effects. A serious toxicological aspect of retinoid treatment is teratogenesis; its use should therefore be avoided in women with childbearing potential, and, in cases of use, conception should be delayed for a long time after stopping treatment. Thus, when considering side-effects of chemoprevention, the major issues of concern are the rare long-term effects (chiefly neoplasms), and the need for more precise overall risk-and cost-benefit assessment, particularly for healthy people."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I126,I126)","v":8145203},{"$f":"(LEN($J126) - LEN(SUBSTITUTE(LOWER($J126),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J126) - LEN(SUBSTITUTE(LOWER($J126),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J126) - LEN(SUBSTITUTE(LOWER($J126),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B126:D126)","v":3},1993,"Embryo-uterine interactions in pigs during week 2 of pregnancy.","Roberts",8145203,"Embryo-uterine interactions in pigs during week 2 of pregnancy.    Abstract:   The second week of pregnancy is a particularly critical period for embryonic survival in pigs. Within that time, conceptus oestrogen synthesis is initiated, spacing and final placement of conceptuses is completed, and the signal for extending the functional lifespan of the corpora lutea is received by the mother. There is also a marked increase in blood flow to the uterus and the uterine endometrium produces and secretes nutrient histotrophe. Conceptus-derived oestrogen has been implicated in many of these events. It is also during this period that the trophoblast elongates dramatically and the inner cell mass starts to differentiate into the embryo proper. Here, we critically review the evidence that oestrogen is the sole factor initiating long-term corpus luteum maintenance in pigs. We also review the functions and general properties of the major secretory proteins in histotrophe and the role of oestrogen in controlling their expression. It is now generally accepted that asynchrony within a litter underlies much of the losses of conceptuses that are otherwise genetically normal, but which are lagging in their development; however, the underlying mechanisms remain unclear. Here we hypothesize that oestrogenic compounds derived from more advanced conceptuses or provided prematurely, either by injection or in the diet, trigger a massive increase in uterine expression and secretion of retinol-binding protein laden with retinol. We propose that less developed, smaller conceptuses are least able to contend with the sudden exposure to this potential teratogen at a time when they are particularly susceptible to imbalance in retinol supply. Hence, even though their growth proceeds for a few days, their developmental potential is irrevocably compromised."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I127,I127)","v":1390188},{"$f":"(LEN($J127) - LEN(SUBSTITUTE(LOWER($J127),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J127) - LEN(SUBSTITUTE(LOWER($J127),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J127) - LEN(SUBSTITUTE(LOWER($J127),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B127:D127)","v":3},1992,"The measurement of photodamage.","Marks",1390188,"The measurement of photodamage.    Abstract:   The use of non-invasive and invasive techniques for the assessment of human photodamaged skin is reviewed. Physical changes during photodamage and its treatment are best scored using a visual analogue scale rather than a short, non-equal interval scale. Epidermal thickness can be measured by histometric methods but dermal thickness can be measured non-invasively using pulsed A-scan and B-scan ultrasound techniques. These approaches are not effective in detecting any changes due to photodamage. Mechanical properties of the dermis can be determined using either a static or a dynamic test mode. The authors have used extensometry to provide a measure of the laxity of skin. Replicas of the crows foot areas have been taken before and after tretinoin treatment, and the replicas have been inspected by optical profilometry. Reductions of blood flow in photodamaged skin have been established using laser Doppler measurements, the effect being reversed by topical tretinoin. Invasive biochemical techniques have the disadvantage that they generally require large amounts of tissue. Cytochemical techniques, however, have shown increased glucose-6-phosphate dehydrogenase activity in the granular cell layer of patients with non-melanoma skin cancer, premalignant epidermal lesions, sun-damaged epidermis and artificially irradiated skin. This technique may provide an important model for the study of photodamage. It is concluded that there is no single method available to quantify the degenerative changes associated with photodamage and the effects of tretinoin."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I128,I128)","v":1812129},{"$f":"(LEN($J128) - LEN(SUBSTITUTE(LOWER($J128),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J128) - LEN(SUBSTITUTE(LOWER($J128),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J128) - LEN(SUBSTITUTE(LOWER($J128),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B128:D128)","v":3},1991,"Animal models for human craniofacial malformations.","Johnston",1812129,"Animal models for human craniofacial malformations.    Abstract:   Holoprosencephaly malformations, of which the fetal alcohol syndrome appears to be a mild form, can result from medial anterior neural plate deficiencies as demonstrated in an ethanol treated animal model. These malformations are associated with more medial positioning of the nasal placodes and resulting underdevelopment or absence of the medial nasal prominences (MNPs) and their derivatives. Malformations seen in the human retinoic acid syndrome (RAS) can be produced by administration of the drug 13-cis-retinoic acid in animals. Primary effects on neural crest cells account for most of these RAS malformations. Many of the malformations seen in the RAS are similar to those of hemifacial microsomia, suggesting similar neural crest involvement. Excessive cell death, apparently limited to trigeminal ganglion neuroblasts of placodal origin, follows 13-cis retinoic acid administration at the time of ganglion formation and leads to malformations virtually identical to those of the Treacher Collins syndrome (TCS). Secondary effects on neural crest cells in the area of the ganglion appear to be responsible for the TCS malformations. Malformations of the DiGeorge Syndrome are similar to those of the RAS and can be produced in mice by ethanol administration or by quot;knocking outquot; a homeobox gene (box 1.5). Human and animal studies indicate that cleft lips of multifactorial etiology may be generically susceptible because of small MNP)s or other MNP developmental alterations, such as those found in A/J mice, that make prominence contact more difficult. Experimental maternal hypoxia in mice indicates that cigarette smoking may increase the incidence of cleft lip by interfering with morphogenetic movements. Other human cleft lips may result from the action of a single major gene coding for TGF-alpha variants. A study with mouse palatal shelves in culture and other information suggest that a fusion problem may be involved."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I129,I129)","v":6315467},{"$f":"(LEN($J129) - LEN(SUBSTITUTE(LOWER($J129),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J129) - LEN(SUBSTITUTE(LOWER($J129),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J129) - LEN(SUBSTITUTE(LOWER($J129),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B129:D129)","v":3},1983,"Toward a dietary prevention of cancer.","Graham",6315467,"Toward a dietary prevention of cancer.    Abstract:   I have attempted to address in brief fashion the question as to whether we can recommend a dietary prevention of cancer. This same question was explored in hundreds of pages recently by the large number of advisors assembled by the National Academy of Sciences to assess the animal, cell culture, and human data with regard to diet and cancer (52). My brief assessment has resulted in recommendations to the scientific community not unlike those of the National Academy, but without their clear-cut recommendation against dietary fat. It is obvious that we need a great deal more research on the factors evaluated here, that is, fiber, ascorbic acid, retinoids, the cruciferae, nitrates, alcohol, coffee, saccharine, alpha-tocopherol, aflatoxins, selenium, and saturated and polyunsaturated fats. These factors need assessment not only as they might affect the incidence of any single cancer, but also in relationship to at least the incidence of the cancers that frequently occur in humans. The human epidemiologic inquires have barely begun. We have a few studies of cancer of the colon and of cancer of the lung, and only one or two studies of such important sites as cancer of the larynx, oropharynx, stomach, and breast. Not only have the studies of specific sites been lamentably too few, but only a small number of nutrients have been evaluated. To make matters worse, we have little notion as to the competing risk of different cancers and of other diseases associated with various nutrients. There may be factors that enhance the risk of some diseases at the same time they reduce the risk of others. It is not outside the realm of possibility that the relationship discovered to date with regard to serum cholesterol, heart disease, and cancer may continue to be replicated and may be found related to ingestion of dietary fats. If such should be the case, and the potential is there, we would need to weigh the risks associated with reducing dietary fats for cancer as well as for coronary disease. Questions will need to be answered. For example, what is the optimum level of serum cholesterol to lower the risk of heart disease and at the same time not to enhance the risk of cancer. The same may be said for the association of alcohol with the risk of coronary disease compared to the risk of cancer of the upper alimentary tract.(ABSTRACT TRUNCATED AT 400 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I130,I130)","v":27638711},{"$f":"(LEN($J130) - LEN(SUBSTITUTE(LOWER($J130),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J130) - LEN(SUBSTITUTE(LOWER($J130),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J130) - LEN(SUBSTITUTE(LOWER($J130),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B130:D130)","v":2},2016,"Carotenoids: biochemistry, pharmacology and treatment.","Milani",27638711,"Carotenoids: biochemistry, pharmacology and treatment.    Abstract:    NlmCategory=UNASSIGNEDCarotenoids and retinoids have several similar biological activities such as antioxidant properties, the inhibition of malignant tumour growth and the induction of apoptosis. Supplementation with carotenoids can affect cell growth and modulate gene expression and immune responses. Epidemiological studies have shown a correlation between a high carotenoid intake in the diet with a reduced risk of breast, cervical, ovarian, colorectal cancers, and cardiovascular and eye diseases. Cancer chemoprevention by dietary carotenoids involves several mechanisms, including effects on gap junctional intercellular communication, growth factor signalling, cell cycle progression, differentiation-related proteins, retinoid-like receptors, antioxidant response element, nuclear receptors, AP-1 transcriptional complex, the Wnt/β-catenin pathway and inflammatory cytokines. Moreover, carotenoids can stimulate the proliferation of B- and T-lymphocytes, the activity of macrophages and cytotoxic T-cells, effector T-cell function and the production of cytokines. Recently, the beneficial effects of carotenoid-rich vegetables and fruits in health and in decreasing the risk of certain diseases has been attributed to the major carotenoids, β-carotene, lycopene, lutein, zeaxanthin, crocin (/crocetin) and curcumin, due to their antioxidant effects. It is thought that carotenoids act in a time- and dose-dependent manner. In this review, we briefly describe the biological and immunological activities of the main carotenoids used for the treatment of various diseases and their possible mechanisms of action."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I131,I131)","v":27599465},{"$f":"(LEN($J131) - LEN(SUBSTITUTE(LOWER($J131),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J131) - LEN(SUBSTITUTE(LOWER($J131),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J131) - LEN(SUBSTITUTE(LOWER($J131),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B131:D131)","v":2},2016,"On-site remodeling at chromatin: How multiprotein complexes are rebuilt during DNA repair and transcriptional activation.","Papadopoulou",27599465,"On-site remodeling at chromatin: How multiprotein complexes are rebuilt during DNA repair and transcriptional activation.    Abstract:    NlmCategory=UNASSIGNEDIn this review, we discuss a novel on-site remodeling function that is mediated by the H2A-ubiquitin binding protein ZRF1. ZRF1 facilitates the remodeling of multiprotein complexes at chromatin and lies at the heart of signaling processes that occur at DNA damage sites and during transcriptional activation. In nucleotide excision repair ZRF1 remodels E3 ubiquitin ligase complexes at the damage site. During embryonic stem cell differentiation, it contributes to retinoic acid-mediated gene activation by altering the subunit composition of the Mediator complex. We postulate that ZRF1 operates in conjunction with cellular remodeling machines and suggest that on-site remodeling might be a hallmark of many chromatin-associated signaling pathways. We discuss yet unexplored functions of ZRF1-mediated remodeling in replication and double strand break repair. In conclusion, we postulate that on-site remodeling of multiprotein complexes is essential for the timing of chromatin signaling processes."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I132,I132)","v":27178440},{"$f":"(LEN($J132) - LEN(SUBSTITUTE(LOWER($J132),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J132) - LEN(SUBSTITUTE(LOWER($J132),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J132) - LEN(SUBSTITUTE(LOWER($J132),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B132:D132)","v":2},2016,"Olfactomedin 4 expression and functions in innate immunity, inflammation, and cancer.","Liu",27178440,"Olfactomedin 4 expression and functions in innate immunity, inflammation, and cancer.    Abstract:   Olfactomedin 4 (OLFM4) is an olfactomedin domain-containing glycoprotein. Multiple signaling pathways and factors, including NF-κB, Wnt, Notch, PU.1, retinoic acids, estrogen receptor, and miR-486, regulate its expression. OLFM4 interacts with several other proteins, such as gene associated with retinoic-interferon-induced mortality 19 (GRIM-19), cadherins, lectins, nucleotide oligomerization domain-1 (NOD1) and nucleotide oligomerization domain-2 (NOD2), and cathepsins C and D, known to regulate important cellular functions. Recent investigations using Olfm4-deficient mouse models have provided important clues about its in vivo biological functions. Olfm4 inhibited Helicobacter pylori-induced NF-κB pathway activity and inflammation and facilitated H. pylori colonization in the mouse stomach. Olfm4-deficient mice exhibited enhanced immunity against Escherichia coli and Staphylococcus aureus infection. Olfm4 deletion in a chronic granulomatous disease mouse model rescued them from S. aureus infection. Olfm4 deletion in mice treated with azoxymethane/dextran sodium sulfate led to robust intestinal inflammation and intestinal crypt hyperplasia. Olfm4 deletion in Apc (Min/+) mice promoted intestinal polyp formation as well as adenocarcinoma development in the distal colon. Further, Olfm4-deficient mice spontaneously developed prostatic epithelial lesions as they age. OLFM4 expression is correlated with cancer differentiation, stage, metastasis, and prognosis in a variety of cancers, suggesting its potential clinical value as an early-stage cancer marker or a therapeutic target. Collectively, these data suggest that OLFM4 plays important roles in innate immunity against bacterial infection, gastrointestinal inflammation, and cancer. In this review, we have summarized OLFM4s initial characterization, expression, regulation, protein interactions, and biological functions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I133,I133)","v":26981297},{"$f":"(LEN($J133) - LEN(SUBSTITUTE(LOWER($J133),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J133) - LEN(SUBSTITUTE(LOWER($J133),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J133) - LEN(SUBSTITUTE(LOWER($J133),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B133:D133)","v":2},2016,"Acute Coronary Syndrome Manifesting as an Adverse Effect of All-trans-Retinoic Acid in Acute Promyelocytic Leukemia: A Case Report with Review of the Literature and a Spotlight on Management.","Govind Babu",26981297,"Acute Coronary Syndrome Manifesting as an Adverse Effect of All-trans-Retinoic Acid in Acute Promyelocytic Leukemia: A Case Report with Review of the Literature and a Spotlight on Management.    Abstract:   Background. Acute promyelocytic leukemia is characterized by t(15;17). This leads to the formation of PML/RARα which blocks the differentiation of blasts at the stage of promyelocytes. This is reversed by all-trans-retinoic acid (ATRA), a vitamin A derivative. Acute myocardial ischemia is a rare side effect of ATRA. Case Report. We report a case of acute coronary syndrome manifesting as an adverse effect of ATRA in a lady with APL who had no other risk factors for cardiovascular disease. Conclusions. We emphasize the need for high index of suspicion for the diagnosis of this entity. In the light of this case, the rare instances of ATRA associated acute myocardial ischemia recorded in the literature and the options available for treatment of acute promyelocytic leukemia sans ATRA have been reviewed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I134,I134)","v":26572245},{"$f":"(LEN($J134) - LEN(SUBSTITUTE(LOWER($J134),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J134) - LEN(SUBSTITUTE(LOWER($J134),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J134) - LEN(SUBSTITUTE(LOWER($J134),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B134:D134)","v":2},2016,"Complementing the inflammasome.","Triantafilou",26572245,"Complementing the inflammasome.    Abstract:   The innate immune system is an ancient surveillance system able to sense microbial invaders as well as aberrations in normal cell function. No longer viewed as a static and non-specific part of immunity, the innate immune system employs a plethora of specialized pattern recognition sensors to monitor and achieve homeostasis; these include the Toll-like receptors, the retinoic acid-inducible gene-like receptors, the nucleotide-binding oligomerization domain receptors (NLRs), the C-type lectins and the complement system. In order to increase specificity and diversity, innate immunity uses homotypic and heterotypic associations among these different components. Multi-molecular assemblies are formed both on the cell surface and in the cytosol to respond to pathogen and danger signals. Diverse, but tailored, responses to a changing environment are orchestrated depending on the the nature of the challenge and the repertoire of interacting receptors and components available in the sensing cell. It is now emerging that innate immunity operates a system of checks and balances where interaction among the sensors is key in maintaining normal cell function. Complement sits at the heart of this alarm system and it is becoming apparent that it is capable of interacting with all the other pathways to effect a tailored immune response. In this review, we will focus on complement interactions with NLRs, the so-called inflammasomes, describing the molecular mechanisms that have been revealed so far and discussing the circumstantial evidence that exists for these interactions in disease states."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I135,I135)","v":26373900},{"$f":"(LEN($J135) - LEN(SUBSTITUTE(LOWER($J135),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J135) - LEN(SUBSTITUTE(LOWER($J135),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J135) - LEN(SUBSTITUTE(LOWER($J135),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B135:D135)","v":2},2016,"A novel mutation in two Hmong families broadens the range of STRA6-related malformations to include contractures and camptodactyly.","Marcadier",26373900,"A novel mutation in two Hmong families broadens the range of STRA6-related malformations to include contractures and camptodactyly.    Abstract:   PDAC (also termed Matthew Wood) syndrome is a rare, autosomal recessive disorder characterized by pulmonary hypoplasia/aplasia, diaphragmatic defects, bilateral anophthalmia, and cardiac malformations. The disorder is caused by mutations in STRA6, an important regulator of vitamin A and retinoic acid metabolism. We describe six cases from four families of Hmong ancestry, seen over a 30 years period in California. These include: (i) consanguineous siblings with a combination of bilateral anophthalmia, diaphragmatic abnormalities, truncus arteriosus, and/or pulmonary agenesis/hypoplasia; (ii) a singleton fetus with bilateral anophthalmia, pulmonary agenesis, cardiac malformation, and renal hypoplasia; (iii) a sibling pair with a combination of antenatal contractures, camptodactyly, fused palpebral fissures, pulmonary agenesis, and/or truncus arteriosus; (iv) a fetus with bilateral anophthalmia, bushy eyebrows, pulmonary agenesis, heart malformation, and abnormal hand positioning. The phenotypic spectrum of PDAC syndrome has until now not included contractures or camptodactyly. Sequencing of STRA6 in unrelated members of families three and four identified a novel, shared homozygous splice site alteration (c.113 + 3_4delAA) that is predicted to be pathogenic. We hypothesize this may represent a unique disease allele in the Hmong. We also provide a focused review of all published PDAC syndrome cases with confirmed or inferred STRA6 mutations, illustrating the phenotypic and molecular variability that characterizes this disorder."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I136,I136)","v":25963488},{"$f":"(LEN($J136) - LEN(SUBSTITUTE(LOWER($J136),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J136) - LEN(SUBSTITUTE(LOWER($J136),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J136) - LEN(SUBSTITUTE(LOWER($J136),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B136:D136)","v":2},2015,"Vitamin A as a key regulator of obesity amp; its associated disorders: Evidences from an obese rat model.","Jeyakumar",25963488,"Vitamin A as a key regulator of obesity amp; its associated disorders: Evidences from an obese rat model.    Abstract:   During the last century, vitamin A has evolved from its classical role as a fat-soluble vitamin and attained the status of para-/autocrine hormone. Besides its well-established role in embryogenesis, growth and development, reproduction and vision, vitamin A has also been implicated in several other physiological processes. Emerging experimental evidences emphasize adipose tissue as an active endocrine organ with great propensity to continuous growth (throughout life). Due to various genetic and lifestyle factors, excess energy accumulates in adipose tissue as fat, resulting in obesity and other complications such as type 2 diabetes, hypertension, and cardiovascular disease. Recent in vitro and in vivo studies have shed light on vitamin A metabolites; retinaldehyde and retinoic acid and participation of their pathway proteins in the regulation of adipose tissue metabolism and thus, obesity. In this context, we discuss here some of our important findings, which establish the role of vitamin A (supplementation) in obesity and its associated disorders by employing an obese rat model; WNIN/Ob strain."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I137,I137)","v":25721497},{"$f":"(LEN($J137) - LEN(SUBSTITUTE(LOWER($J137),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J137) - LEN(SUBSTITUTE(LOWER($J137),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J137) - LEN(SUBSTITUTE(LOWER($J137),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B137:D137)","v":2},2015,"Carotenoids and their conversion products in the control of adipocyte function, adiposity and obesity.","Bonet",25721497,"Carotenoids and their conversion products in the control of adipocyte function, adiposity and obesity.    Abstract:   A novel perspective of the function of carotenoids and carotenoid-derived products - including, but not restricted to, the retinoids - is emerging in recent years which connects these compounds to the control of adipocyte biology and body fat accumulation, with implications for the management of obesity, diabetes and cardiovascular disease. Cell and animal studies indicate that carotenoids and carotenoids derivatives can reduce adiposity and impact key aspects of adipose tissue biology including adipocyte differentiation, hypertrophy, capacity for fatty acid oxidation and thermogenesis (including browning of white adipose tissue) and secretory function. Epidemiological studies in humans associate higher dietary intakes and serum levels of carotenoids with decreased adiposity. Specifically designed human intervention studies, though still sparse, indicate a beneficial effect of carotenoid supplementation in the accrual of abdominal adiposity. The objective of this review is to summarize recent findings in this area, place them in physiological contexts, and provide likely regulatory schemes whenever possible. The focus will be on the effects of carotenoids as nutritional regulators of adipose tissue biology and both animal and human studies, which support a role of carotenoids and retinoids in the prevention of abdominal adiposity."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I138,I138)","v":24618374},{"$f":"(LEN($J138) - LEN(SUBSTITUTE(LOWER($J138),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J138) - LEN(SUBSTITUTE(LOWER($J138),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J138) - LEN(SUBSTITUTE(LOWER($J138),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B138:D138)","v":2},2014,"The failure of cancer chemoprevention.","Potter",24618374,"The failure of cancer chemoprevention.    Abstract:   Chemoprevention is proposed as a clinical analogue of population prevention, aimed at reducing likelihood of disease progression, not across the population, but in identified high-risk individuals and not by behavioral or lifestyle modification, but by the use of pharmaceutical agents. Cardiovascular chemoprevention is successful via control of hyperlipidemias and hypertension. However, chemoprevention of cancer is an almost universal failure: not only are some results null; even more frequently, there is an excess of disease, including disease that the agents were chosen specifically to reduce. A brief introduction is followed by the evidence for a wide variety of agents and their largely deleterious, sometimes null, and in one case, largely beneficial, consequences as possible chemopreventives. The agents include (i) those that are food derived and their synthetic analogues: β-carotene, folic acid, retinol and retinoids, vitamin E, multivitamin supplements, vitamin C, calcium and selenium and (ii) agents targeted at metabolic and hormonal pathways: statins, estrogen and antagonists, 5α-reductase inhibitors. There are two agents for which there is good evidence of benefit when the strategy is focused on those at defined high risk but where wider application is much more problematic: aspirin and tamoxifen. The major problems with cancer chemoprevention are presented. This is followed by a hypothesis to explain the failure of cancer chemoprevention as an enterprise, arguing that the central tenets that underpin it are flawed and showing why, far from doing good, cancer chemoprevention causes harm."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I139,I139)","v":24527318},{"$f":"(LEN($J139) - LEN(SUBSTITUTE(LOWER($J139),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J139) - LEN(SUBSTITUTE(LOWER($J139),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J139) - LEN(SUBSTITUTE(LOWER($J139),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B139:D139)","v":2},2013,"Age-Related Tissue Stiffening: Cause and Effect.","Sherratt",24527318,"Age-Related Tissue Stiffening: Cause and Effect.    Abstract:    SIGNIFICANCE : Tissue elasticity is severely compromised in aging skin, lungs, and blood vessels. In the vascular and pulmonary systems, respectively, loss of mechanical function is linked to hypertension, which in turn is a risk factor for heart and renal failure, stroke, and aortic aneurysms, and to an increased risk of mortality as a result of acute lung infections.  RECENT ADVANCES NlmCategory=UNASSIGNEDAlthough cellular mechanisms were thought to play an important role in mediating tissue aging, the reason for the apparent sensitivity of elastic fibers to age-related degradation remained unclear. We have recently demonstrated that compared with type I collagen, a key component of the elastic fiber system, the cysteine-rich fibrillin microfibril is highly susceptible to direct UV exposure in a cell-free environment. We hypothesized therefore that, as a consequence of both their remarkable longevity and cysteine-rich composition, many elastic fiber-associated components will be susceptible to the accumulation of damage by both direct UV radiation and reactive oxygen species-mediated oxidation.  CRITICAL ISSUES : Although elastic fiber remodeling is a common feature of aging dynamic tissues, the inaccessibility of most human tissues has hampered attempts to define the molecular causes.  CLINICAL CARE RELEVANCE NlmCategory=UNASSIGNEDAlthough, currently, the localized repair of damaged elastic fibers may be effected by the topical application of retinoids and some cosmetic products, future studies may extend the application of systemic transforming growth factor β antagonists, which can prevent cardiovascular remodeling in murine Marfan syndrome, to aging humans. Acellular mechanisms may be key mediators of elastic fiber remodeling and hence age-related tissue stiffening."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I140,I140)","v":24269582},{"$f":"(LEN($J140) - LEN(SUBSTITUTE(LOWER($J140),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J140) - LEN(SUBSTITUTE(LOWER($J140),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J140) - LEN(SUBSTITUTE(LOWER($J140),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B140:D140)","v":2},2014,"Saffron and natural carotenoids: Biochemical activities and anti-tumor effects.","Bolhassani",24269582,"Saffron and natural carotenoids: Biochemical activities and anti-tumor effects.    Abstract:   Saffron, a spice derived from the flower of Crocus sativus, is rich in carotenoids. Two main natural carotenoids of saffron, crocin and crocetin, are responsible for its color. Preclinical studies have shown that dietary intake of some carotenoids have potent anti-tumor effects both in vitro and in vivo, suggesting their potential preventive and/or therapeutic roles in several tissues. The reports represent that the use of carotenoids without the potential for conversion to vitamin A may provide further protection and avoid toxicity. The mechanisms underlying cancer chemo-preventive activities of carotenoids include modulation of carcinogen metabolism, regulation of cell growth and cell cycle progression, inhibition of cell proliferation, anti-oxidant activity, immune modulation, enhancement of cell differentiation, stimulation of cell-to-cell gap junction communication, apoptosis and retinoid-dependent signaling. Taken together, different hypotheses for the antitumor actions of saffron and its components have been proposed such as a) the inhibitory effect on cellular DNA and RNA synthesis, but not on protein synthesis; b) the inhibitory effect on free radical chain reactions; c) the metabolic conversion of naturally occurring carotenoids to retinoids; d) the interaction of carotenoids with topoisomerase II, an enzyme involved in cellular DNA-protein interaction. Furthermore, the immunomodulatory activity of saffron was studied on driving toward Th1 and Th2 limbs of the immune system. In this mini-review, we briefly describe biochemical and immunological activities and chemo-preventive properties of saffron and natural carotenoids as an anticancer drug."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I141,I141)","v":23845149},{"$f":"(LEN($J141) - LEN(SUBSTITUTE(LOWER($J141),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J141) - LEN(SUBSTITUTE(LOWER($J141),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J141) - LEN(SUBSTITUTE(LOWER($J141),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B141:D141)","v":2},2013,"Cardiovascular morbidity and mortality in psoriasis and psoriatic arthritis: a systematic literature review.","Horreau",23845149,"Cardiovascular morbidity and mortality in psoriasis and psoriatic arthritis: a systematic literature review.    Abstract:    UNLABELLEDPrevious epidemiological studies have demonstrated a high prevalence of cardiovascular (CV) risk factors in psoriasis patients, including metabolic syndrome, cigarette smoking, obesity, hypertension, diabetes mellitus, insulin resistance and dyslipidaemia. An increase in CV morbidity and mortality attributable to psoriasis is still under question.  PRIMARY OBJECTIVE : to assess CV morbidity and mortality in psoriasis and psoriatic arthritis (PsA) including stroke, coronary artery disease, myocardial infarction (MI) and peripheral artery disease.  SECONDARY OBJECTIVES : to assess if psoriasis per se is an independent CV risk factor and if psoriasis severity is a predictor of CV risk. We also evaluated the effect of conventional systemic treatments for psoriasis on CV mortality. A systematic literature search was carried out from 1980 to December 2011, in the Embase, Medline and Cochrane Library databases, in English and French using a combination of keywords including (Psoriasis) OR (Psoriatic arthritis) AND (Myocardial infarction) OR (Coronaropathy) OR (Stroke) OR (Cardiovascular) AND (Methotrexate) AND (Ciclosporin) AND (Retinoids). Of the 929 identified references, 33 observational studies evaluating the rates of cardiovascular events (CVE) in patients with psoriasis and PsA compared with controls were selected. Meta-analysis of both cohort and cross-sectional studies showed an increased risk of MI with Odds Ratio (OR) of 1.25 (95% CI 1.03-1.52) and 1.57 (95% CI 1.08-2.27) in psoriasis and PsA, respectively, compared with the general population. The risk of MI was more pronounced for patients having severe psoriasis and for patients with psoriasis of early onset. It remained significantly elevated after controlling for major CV risk factors. The meta-analysis identified a small, but significant association between psoriasis, PsA and coronary artery disease with an OR between 1.19 (95% CI 1.14-1.24) for cross-sectional studies, 1.20 (95% CI 1.13-1.27) for cohort studies and 1.84 (95% CI 1.09-3.09) for case-control studies. The risk of coronary artery disease seemed to be more pronounced in patients with severe psoriasis and in patients with psoriasis of early onset. The meta-analysis assessing the risk of stroke gave inconclusive results: analysis of cross-sectional studies suggested that psoriasis patients had a slightly higher risk of stroke with an OR of 1.14 (95% CI 1.08-1.99), whereas the meta-analysis of cohort studies failed to show an association. There was also an increased risk of peripheral artery disease in psoriasis. No significant increased risk of CV mortality could be shown for both psoriasis and PsA patients. The use of methotrexate was associated with a reduced incidence of cardiovascular disease in two studies. The use of etretinate was associated with a reduction of CV mortality in one study. Potential selection bias such as the healthy user effect prevents from drawing definite conclusions. There may be a small, but significant increased risk of CVE, but not of CV mortality in psoriasis and PsA patients. The psoriasis attributable risk remains difficult to assess due to confounding factors. The moderate quality of CV risk factors reporting in studies should be acknowledged. In addition, heterogeneity in study design, outcome definition and assessment represent major limitations. Nevertheless, screening and management of CV risk factors are important in psoriasis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I142,I142)","v":23701753},{"$f":"(LEN($J142) - LEN(SUBSTITUTE(LOWER($J142),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J142) - LEN(SUBSTITUTE(LOWER($J142),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J142) - LEN(SUBSTITUTE(LOWER($J142),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B142:D142)","v":2},2013,"Retinoid X receptors in macrophage biology.","Rőszer",23701753,"Retinoid X receptors in macrophage biology.    Abstract:   Retinoid X receptors (RXRs) form a distinct and unique subclass within the nuclear receptor (NR) superfamily of ligand-dependent transcription factors. RXRs regulate a plethora of genetic programs, including cell differentiation, the immune response, and lipid and glucose metabolism. Recent advances reveal that RXRs are important regulators of macrophages, key players in inflammatory and metabolic disorders. This review outlines the versatility of RXR action in the control of macrophage gene transcription through its heterodimerization with other NRs or through RXR homodimerization. We also highlight the potential of RXR-controlled transcriptional programs as targets for the treatment of pathologies associated with altered macrophage function, such as atherosclerosis, insulin resistance, autoimmunity, and neurodegeneration."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I143,I143)","v":22037188},{"$f":"(LEN($J143) - LEN(SUBSTITUTE(LOWER($J143),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J143) - LEN(SUBSTITUTE(LOWER($J143),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J143) - LEN(SUBSTITUTE(LOWER($J143),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B143:D143)","v":2},2012,"The story so far: post-translational regulation of peroxisome proliferator-activated receptors by ubiquitination and SUMOylation.","Wadosky",22037188,"The story so far: post-translational regulation of peroxisome proliferator-activated receptors by ubiquitination and SUMOylation.    Abstract:   Many studies have implicated the peroxisome proliferator-activated receptor (PPAR) family of nuclear receptor transcription factors in regulating cardiac substrate metabolism and ATP generation. Recently, evidence from a variety of cell culture and organ systems has implicated ubiquitin and small ubiquitin-like modifier (SUMO) conjugation as post-translational modifications that regulate the activity of PPAR transcription factors and their coreceptors/coactivators. Here we introduce the ubiquitin and SUMO conjugation systems and extensively review how they have been shown to regulate all three PPAR isoforms (PPARα, PPARβ/δ, and PPARγ) in addition to the retinoid X receptor and PPARγ coactivator-1α subunits of the larger PPAR transcription factor complex. We then present how the specific ubiquitin (E3) ligases have been implicated and review emerging evidence that post-translational modifications of PPARs with ubiquitin and/or SUMO may play a role in cardiac disease. Because PPAR activity is perturbed in a variety of forms of heart disease and specific proteins regulate this process (E3 ligases), this may be a fruitful area of investigation with respect to finding new therapeutic targets."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I144,I144)","v":21493923},{"$f":"(LEN($J144) - LEN(SUBSTITUTE(LOWER($J144),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J144) - LEN(SUBSTITUTE(LOWER($J144),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J144) - LEN(SUBSTITUTE(LOWER($J144),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B144:D144)","v":2},2011,"The PPAR-RXR transcriptional complex in the vasculature: energy in the balance.","Plutzky",21493923,"The PPAR-RXR transcriptional complex in the vasculature: energy in the balance.    Abstract:   The peroxisome proliferator-activated receptors (PPARs) and the retinoid X receptors (RXRs) are ligand-activated transcription factors that coordinately regulate gene expression. This PPAR-RXR transcriptional complex plays a critical role in energy balance, including triglyceride metabolism, fatty acid handling and storage, and glucose homeostasis: processes whose dysregulation characterize obesity, diabetes, and atherosclerosis. PPARs and RXRs are also involved directly in inflammatory and vascular responses in endothelial and vascular smooth muscle cells. New insights into fundamental aspects of PPAR and RXR biology, and their actions in the vasculature, continue to appear. Although RXRs are obligate heterodimeric partners for PPAR action, the part that RXRs, and their endogenous retinoid mediators, exert in the vessel wall is less well understood. Biological insights into PPAR-RXRs may help inform interpretation of clinical trials with synthetic PPAR agonists and prospects for future PPAR therapeutics. Importantly, the extensive data establishing a key role for PPARs and RXRs in energy balance, inflammation, and vascular biology stands separately from the clinical experience with any given synthetic PPAR agonist. Both the basic science data and the clinical experience with PPAR agonists identify the need to better understand these important transcriptional regulators."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I145,I145)","v":21265829},{"$f":"(LEN($J145) - LEN(SUBSTITUTE(LOWER($J145),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J145) - LEN(SUBSTITUTE(LOWER($J145),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J145) - LEN(SUBSTITUTE(LOWER($J145),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B145:D145)","v":2},2011,"Is a regenerative approach viable for the treatment of COPD?","Hind",21265829,"Is a regenerative approach viable for the treatment of COPD?    Abstract:   Degenerative lung diseases such as chronic obstructive pulmonary disease (COPD) are common with huge worldwide morbidity. Anti-inflammatory drug development strategies have proved disappointing and current treatment is aimed at symptomatic relief. Only lung transplantation with all its attendant difficulties offers hope of cure and the outlook for affected patients is bleak. Lung regeneration therapies aim to reverse the structural and functional deficits in COPD either by delivery of exogenous lung cells to replace lost tissue, delivery of exogenous stem cells to induce a local paracrine effect probably through an anti-inflammatory action or by the administration of small molecules to stimulate the endogenous regenerative ability of lung cells. In animal models of emphysema and disrupted alveolar development each of these strategies has shown some success but there are potential tumour-inducing dangers with a cellular approach. Small molecules such as all-trans retinoic acid have been successful in animal models although the mechanism is not completely understood. There are currently two Pharma-sponsored trials in progress concerning patients with COPD, one of a specific retinoic acid receptor gamma agonist and another using mesenchymal stem cells."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I146,I146)","v":21189687},{"$f":"(LEN($J146) - LEN(SUBSTITUTE(LOWER($J146),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J146) - LEN(SUBSTITUTE(LOWER($J146),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J146) - LEN(SUBSTITUTE(LOWER($J146),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B146:D146)","v":2},2010,"The role of quaking in mammalian embryonic development.","Justice",21189687,"The role of quaking in mammalian embryonic development.    Abstract:   Functional studies of the mouse quaking gene (Qk) have focused on its role in the postnatal central nervous system during myelination. However, the death of the majority of homozygous mouse quaking alleles revealed that quaking has a critical role in embryonic development prior to the start of myelination. Surprisingly, the lethal alleles revealed that quaking has a function in embryonic blood vessel formation and remodeling. Further studies ofthe extraembryonic yolk sac showed that Qk regulates visceral endoderm differentiated function at the cellular level, including the local synthesis of retinoic acid (RA), which then exerts paracrine control of endothelial cells within adjacent mesoderm. Endoderm-derived RA regulates proliferation of endothelial cells and extracellular matrix (ECM) production, which in a reciprocal manner, modulates visceral endoderm survival and function. Although exogenous RA can rescue endothelial cell growth control and ECM production in mutants carrying a lethal mutation, which lack functional Qk, neither visceral endoderm function nor vascular remodeling is restored. Thus, Qk also regulates cell autonomous functions of visceral endoderm that are critical for vascular remodeling. Interestingly, quaking is highly expressed during normal cardiac development, particularly in the outflow tract, suggesting potentially unique functions in the developing heart. Together, the work on Qk in mammalian embryos reveals an essential, yet under appreciated, role in cardiovascular development. This suggests that certain functions may remain conserved in the early embryo throughout the evolution of nonvertebrate and vertebrate organisms and that additional roles for quaking remain to be discovered."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I147,I147)","v":21126826},{"$f":"(LEN($J147) - LEN(SUBSTITUTE(LOWER($J147),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J147) - LEN(SUBSTITUTE(LOWER($J147),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J147) - LEN(SUBSTITUTE(LOWER($J147),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B147:D147)","v":2},2011,"Cardiovascular effects of systemic cancer treatment.","Senkus",21126826,"Cardiovascular effects of systemic cancer treatment.    Abstract:   Many methods of systemic anticancer treatment have detrimental effects on the cardiovascular system, thus limiting the possibility of further therapy, worsening patients quality of life and increasing mortality. The best recognized and most clinically relevant is the cardiotoxicity of anthracyclines. Other cytotoxic drugs associated with significant risk of cardiovascular complications include alkylating agents, 5-fluorouracil and paclitaxel. Cardiovascular adverse effects are also associated with the use of targeted therapies, such as trastuzumab, bevacizumab and tyrosine kinase inhibitors, and some of the drugs used in the treatment of hematological malignancies, such as all-trans-retinoic acid and arsenic trioxide. The most serious cardiac complication of anticancer therapy is congestive heart failure, associated predominantly with the use of anthracyclines, trastuzumab and high-dose cyclophosphamide. Myocardial ischemia is mainly caused by antimetabolite and interferon alpha treatment. Other adverse effects may include hypotension, hypertension, arrhythmias and conduction disorders, edema, pericarditis and thrombo-embolic complications. The aim of this review is to summarize and critically analyze the available evidence on the cardiovascular toxicity of systemic anticancer therapies, with particular attention to the recently recognized adverse effects of targeted therapies."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I148,I148)","v":19906796},{"$f":"(LEN($J148) - LEN(SUBSTITUTE(LOWER($J148),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J148) - LEN(SUBSTITUTE(LOWER($J148),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J148) - LEN(SUBSTITUTE(LOWER($J148),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B148:D148)","v":2},2010,"Selective peroxisome proliferator-activated receptor gamma (PPARgamma) modulation as a strategy for safer therapeutic PPARgamma activation.","Higgins",19906796,"Selective peroxisome proliferator-activated receptor gamma (PPARgamma) modulation as a strategy for safer therapeutic PPARgamma activation.    Abstract:   Peroxisome proliferator-activated receptor gamma (PPARgamma) is a clinically validated target for treatment of insulin resistance. PPARgamma activation by full agonists such as thiazolidinediones has shown potent and durable glucose-lowering activity in patients with type 2 diabetes without the concern for hypoglycemia or gastrointestinal toxicities associated with some other medications used to treat this disease. However, thiazolidinediones are linked to safety and tolerability issues such as weight gain, fluid retention, edema, congestive heart failure, and bone fracture. Distinctive properties of PPARgamma provide the opportunity for selective modulation of the receptor such that desirable therapeutic effects may be attained without the unwanted effects of full activation. PPARgamma is a nuclear receptor that forms a complex with coreceptor RXR and a cell type- and cell state-specific array of coregulators to control gene transcription. PPARgamma affinity for these components, and hence transcriptional response, is determined by the conformational changes induced by ligand binding within a complex pocket with multiple interaction points. This molecular mechanism thereby offers the opportunity for selective modulation. A desirable selective PPARgamma modulator profile would include high-affinity interaction with the PPARgamma-binding pocket in a manner that leads to retention of the insulin-sensitizing activity that is characteristic of full agonists as well as mitigation of the effects leading to increased adiposity, fluid retention, congestive heart failure, and bone fracture. Examples of endogenous and synthetic selective PPARgamma modulator (SPPARM) ligands have been identified. SPPARM drug candidates are being tested clinically and provide support for this strategy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I149,I149)","v":19760653},{"$f":"(LEN($J149) - LEN(SUBSTITUTE(LOWER($J149),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J149) - LEN(SUBSTITUTE(LOWER($J149),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J149) - LEN(SUBSTITUTE(LOWER($J149),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B149:D149)","v":2},2009,"Vitamin A deficiency in an infant with PAGOD syndrome.","Gavrilova",19760653,"Vitamin A deficiency in an infant with PAGOD syndrome.    Abstract:   PAGOD syndrome is a rare condition characterized by multiple congenital anomalies including pulmonary artery and lung hypoplasia, agonadism, diaphragmatic abnormalities, cardiac defects, omphalocele, and various genital anomalies. The etiology of this condition is unknown but the spectrum of birth defects is similar to the developmental anomalies observed in vitamin A deficiency animal models. We describe an infant with PAGOD syndrome phenotype. The patient had a normal male karyotype and no copy number changes were seen on chromosome genomic hybridization (CGH) microarray. Endocrine evaluation was consistent with primary hypogonadism. The testes and Müllerian structures were absent by imaging studies, raising the possibility of arrest of early gonadogenesis. The plasma free vitamin A was low, consistent with moderate to severe vitamin A deficiency; the maternal plasma vitamin A level was normal. During pregnancy maternal vitamin A is taken up by retinol binding protein 4 (RBP4) which is expressed in the embryonic visceral endoderm from pregastrulational stages. This transport is mediated via the specific membrane receptor for RBP, stimulated by retinoic acid 6 (STRA6). STRA6 is widely expressed in human organ systems including the placenta during embryonic development. Mutations in the STRA6 gene result in Matthew-Wood syndrome, which demonstrates significant phenotypic overlap with PAGOD syndrome. Sequencing of STRA6 coding regions in our patient, revealed no mutations. We present a case of PAGOD syndrome with a review of the literature, posing the hypothesis that a vitamin A metabolic defect, other than transport mediated by STRA6 receptor, might have an etiological role in the development of this multiple congenital anomalies syndrome."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I150,I150)","v":19672026},{"$f":"(LEN($J150) - LEN(SUBSTITUTE(LOWER($J150),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J150) - LEN(SUBSTITUTE(LOWER($J150),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J150) - LEN(SUBSTITUTE(LOWER($J150),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B150:D150)","v":2},2009,"Retinoid X receptor heterodimer variants and cardiovascular risk factors.","Nohara",19672026,"Retinoid X receptor heterodimer variants and cardiovascular risk factors.    Abstract:   Nuclear receptors are transcription factors that can be activated by specific ligands. Recent progress has shown that retinoid X receptor (RXR) and its heterodimerization partners, including peroxisome proliferator-activated receptors, regulate many important genes involved in energy homeostasis and atherosclerosis, and should be promising therapeutic targets of metabolic syndrome. RXR heterodimers regulate a number of complex cellular processes, and genetic studies of RXR heterodimers have provided important clinical information in addition to knowledge gained from basic research. Genetic variants of RXR heterodimers were screened and investigated, and some variants were shown to have a considerable impact on metabolic disorders, including phenotypic components of familial combined hyperlipidemia. The combined efforts of basic and clinical science regarding nuclear receptors have achieved significant progress in unraveling the inextricably linked control system of energy expenditure, lipid and glucose homeostasis, inflammation, and atherosclerosis.This review summarizes the current understanding regarding RXR heterodimers based on their human genetic variants, which will provide new clues to uncover the background of multifactorial disease, such as metabolic syndrome or familial combined hyperlipidemia."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I151,I151)","v":19448538},{"$f":"(LEN($J151) - LEN(SUBSTITUTE(LOWER($J151),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J151) - LEN(SUBSTITUTE(LOWER($J151),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J151) - LEN(SUBSTITUTE(LOWER($J151),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B151:D151)","v":2},2009,"The T helper 17-regulatory T cell axis in transplant rejection and tolerance.","Mitchell",19448538,"The T helper 17-regulatory T cell axis in transplant rejection and tolerance.    Abstract:    PURPOSE OF REVIEW : Regulatory T cells (Tregs) are potential therapeutic tools in averting transplant rejection and promoting lifelong tolerance. However, Tregs can be subverted by inflammatory conditions, resulting in a T helper 17 (Th17) cell response. This review looks at the relationship between Tregs and Th17 cells.  RECENT FINDINGS : Both naturally occurring and transforming growth factor-beta-induced Tregs can be converted into Th17 cells in the presence of inflammatory cytokines. Transforming growth factor-beta upregulates the Treg transcription factor, forkhead box P3, as well as the Th17 transcription factor, retinoic acid receptor-related orphan receptor gamma. However, forkhead box P3 binds to retinoic acid receptor-related orphan receptor gamma, inhibiting its promotion of IL-17 gene transcription. Inflammatory cytokines can disrupt this interaction through the inhibition of forkhead box P3 expression by signal transducer and activator of transcription 3.  SUMMARY : The plasticity of the Treg population during inflammation presents a challenge to the use of Tregs as a therapeutic tool in solid organ transplantation. Investigations into the Th17-Treg axis have identified a number of potential pharmacological targets to avoid the risk of conversion to Th17 cells, but further work must be done before we can separate the benefits of Treg therapy from the hazards of the Th17 response."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I152,I152)","v":19153651},{"$f":"(LEN($J152) - LEN(SUBSTITUTE(LOWER($J152),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J152) - LEN(SUBSTITUTE(LOWER($J152),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J152) - LEN(SUBSTITUTE(LOWER($J152),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B152:D152)","v":2},2009,"Apolipoprotein M affecting lipid metabolism or just catching a ride with lipoproteins in the circulation?","Dahlbäck",19153651,"Apolipoprotein M affecting lipid metabolism or just catching a ride with lipoproteins in the circulation?    Abstract:   Apolipoprotein M (apoM) is a novel apolipoprotein found mainly in high-density lipoproteins (HDL). Its function is yet to be defined. ApoM (25 kDa) has a typical lipocalin ss-barrel fold and a hydrophobic pocket. Retinoids bind apoM but with low affinity and may not be the natural ligands. ApoM retains its signal peptide, which serves as a hydrophobic anchor to the lipoproteins. This prevents apoM from being lost in the urine. Approximately 5% of HDL carries an apoM molecule. ApoM in plasma (1 microM) correlates strongly with both low-density lipoprotein (LDL) and HDL cholesterol, suggesting a link to cholesterol metabolism. However, in casecontrol studies, apoM levels in patients with coronary heart disease (CHD) and controls were similar, suggesting apoM levels not to affect the risk for CHD in humans. Experiments in transgenic mice suggested apoM to have antiatherogenic properties; possible mechanisms include increased formation of pre-ss HDL, enhanced cholesterol mobilization from foam cells, and increased antioxidant properties."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I153,I153)","v":19144126},{"$f":"(LEN($J153) - LEN(SUBSTITUTE(LOWER($J153),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J153) - LEN(SUBSTITUTE(LOWER($J153),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J153) - LEN(SUBSTITUTE(LOWER($J153),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B153:D153)","v":2},2009,"Tetralogy of Fallot.","Bailliard",19144126,"Tetralogy of Fallot.    Abstract:   Tetralogy of Fallot is a congenital cardiac malformation that consists of an interventricular communication, also known as a ventricular septal defect, obstruction of the right ventricular outflow tract, override of the ventricular septum by the aortic root, and right ventricular hypertrophy. This combination of lesions occurs in 3 of every 10,000 live births, and accounts for 7-10% of all congenital cardiac malformations. Patients nowadays usually present as neonates, with cyanosis of varying intensity based on the degree of obstruction to flow of blood to the lungs. The aetiology is multifactorial, but reported associations include untreated maternal diabetes, phenylketonuria, and intake of retinoic acid. Associated chromosomal anomalies can include trisomies 21, 18, and 13, but recent experience points to the much more frequent association of microdeletions of chromosome 22. The risk of recurrence in families is 3%. Useful diagnostic tests are the chest radiograph, electrocardiogram, and echocardiogram. The echocardiogram establishes the definitive diagnosis, and usually provides sufficient information for planning of treatment, which is surgical. Approximately half of patients are now diagnosed antenatally. Differential diagnosis includes primary pulmonary causes of cyanosis, along with other cyanotic heart lesions, such as critical pulmonary stenosis and transposed arterial trunks. Neonates who present with ductal-dependent flow to the lungs will receive prostaglandins to maintain ductal patency until surgical intervention is performed. Initial intervention may be palliative, such as surgical creation of a systemic-to-pulmonary arterial shunt, but the trend in centres of excellence is increasingly towards neonatal complete repair. Centres that undertake neonatal palliation will perform the complete repair at the age of 4 to 6 months. Follow-up in patients born 30 years ago shows a rate of survival greater than 85%. Chronic issues that now face such adults include pulmonary regurgitation, recurrence of pulmonary stenosis, and ventricular arrhythmias. As the strategies for surgical and medical management have progressed, the morbidity and mortality of those born with tetralogy of Fallot in the current era is expected to be significantly improved."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I154,I154)","v":18850203},{"$f":"(LEN($J154) - LEN(SUBSTITUTE(LOWER($J154),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J154) - LEN(SUBSTITUTE(LOWER($J154),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J154) - LEN(SUBSTITUTE(LOWER($J154),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B154:D154)","v":2},2006,"Polyunsaturated fatty acids: From diet to binding to ppars and other nuclear receptors.","Bordoni",18850203,"Polyunsaturated fatty acids: From diet to binding to ppars and other nuclear receptors.    Abstract:   Dietary polyunsaturated fatty acids (PUFAs) function not only by altering membrane lipid composition, cellular metabolism, signal transduction, but possess also effects on gene expression by regulating the activity/abundance of different nuclear transcription factors: peroxisome proliferator activated receptors, retinoid X receptors, liver X receptors, hepatic nuclear factors-4a, and sterol regulatory binding proteins 1 and 2. PUFAs regulate the expression of genes in various tissues, including the liver, heart, adipose tissue, and brain, playing a major role in carbohydrate, fatty acid, triglyceride, and cholesterol metabolism. Before binding to transcription factors, PUFAs must be absorbed in the intestine and delivered to cells, and then they must enter the cell and the nucleus. PUFA concentration within the cell depends on many different factors, and regulate their possibility to act as transcription modulators. The aim of this review is to summarize recent knowledge about PUFAs destiny from dietto nuclear factors binding, examining the different variables which can modulate their interaction with nuclear factors themselves and therefore their effect on gene expression."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I155,I155)","v":17882463},{"$f":"(LEN($J155) - LEN(SUBSTITUTE(LOWER($J155),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J155) - LEN(SUBSTITUTE(LOWER($J155),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J155) - LEN(SUBSTITUTE(LOWER($J155),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B155:D155)","v":2},2008,"Role of fatty acid binding proteins and long chain fatty acids in modulating nuclear receptors and gene transcription.","Schroeder",17882463,"Role of fatty acid binding proteins and long chain fatty acids in modulating nuclear receptors and gene transcription.    Abstract:   Abnormal energy regulation may significantly contribute to the pathogenesis of obesity, diabetes mellitus, cardiovascular disease, and cancer. For rapid control of energy homeostasis, allosteric and posttranslational events activate or alter activity of key metabolic enzymes. For longer impact, transcriptional regulation is more effective, especially in response to nutrients such as long chain fatty acids (LCFA). Recent advances provide insights into how poorly water-soluble lipid nutrients [LCFA; retinoic acid (RA)] and their metabolites (long chain fatty acyl Coenzyme A, LCFA-CoA) reach nuclei, bind their cognate ligand-activated receptors, and regulate transcription for signaling lipid and glucose catabolism or storage: (i) while serum and cytoplasmic LCFA levels are in the 200 mircroM-mM range, real-time imaging recently revealed that LCFA and LCFA-CoA are also located within nuclei (nM range); (ii) sensitive fluorescence binding assays show that LCFA-activated nuclear receptors [peroxisome proliferator-activated receptor-alpha (PPARalpha) and hepatocyte nuclear factor 4alpha (HNF4alpha)] exhibit high affinity (low nM KdS) for LCFA (PPARalpha) and/or LCFA-CoA (PPARalpha, HNF4alpha)-in the same range as nuclear levels of these ligands; (iii) live and fixed cell immunolabeling and imaging revealed that some cytoplasmic lipid binding proteins [liver fatty acid binding protein (L-FABP), acyl CoA binding protein (ACBP), cellular retinoic acid binding protein-2 (CRABP-2)] enter nuclei, bind nuclear receptors (PPARalpha, HNF4alpha, CRABP-2), and activate transcription of genes in fatty acid and glucose metabolism; and (iv) studies with gene ablated mice provided physiological relevance of LCFA and LCFA-CoA binding proteins in nuclear signaling. This led to the hypothesis that cytoplasmic lipid binding proteins transfer and channel lipidic ligands into nuclei for initiating nuclear receptor transcriptional activity to provide new lipid nutrient signaling pathways that affect lipid and glucose catabolism and storage."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I156,I156)","v":17560195},{"$f":"(LEN($J156) - LEN(SUBSTITUTE(LOWER($J156),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J156) - LEN(SUBSTITUTE(LOWER($J156),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J156) - LEN(SUBSTITUTE(LOWER($J156),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B156:D156)","v":2},2007,"Stephen L. Gans Distinguished Overseas Lecture. The neural crest in pediatric surgery.","Tovar",17560195,"Stephen L. Gans Distinguished Overseas Lecture. The neural crest in pediatric surgery.    Abstract:    AIM : This review highlights the relevance of the neural crest (NC) as a developmental control mechanism involved in several pediatric surgical conditions and the investigative interest of following some of its known signaling pathways.  METHODS : The participation of the NC in facial clefts, ear defects, branchial fistulae and cysts, heart outflow tract and aortic arch anomalies, pigmentary disorders, abnormal enteric innervation, neural tumors, hemangiomas, and vascular anomalies is briefly reviewed. Then, the literature on clinical and experimental esophageal atresia-tracheoesophageal fistula (EA-TEF) and congenital diaphragmatic hernia (CDH) is reviewed for the presence of associated NC defects. Finally, some of the molecular signaling pathways involved in both conditions (sonic hedgehog, Hox genes, and retinoids) are summarized.  RESULTS : The association of facial, cardiovascular, thymic, parathyroid, and C-cell defects together with anomalies of extrinsic and intrinsic esophageal innervation in babies and/or animals with both EA-TEF and CDH strongly supports the hypothesis that NC is involved in the pathogenesis of these malformative clusters. On the other hand, both EA-TEF and CDH are observed in mice mutant for genes involved in the previously mentioned signaling pathways.  CONCLUSIONS : The investigation of NC-related molecular pathogenic pathways involved in malformative associations like EA-TEF and CDH that are induced by chromosomal anomalies, chemical teratogens, and engineered mutations is a promising way of clarifying why and how some pediatric surgical conditions occur. Pediatric surgeons should be actively involved in these investigations."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I157,I157)","v":17267246},{"$f":"(LEN($J157) - LEN(SUBSTITUTE(LOWER($J157),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J157) - LEN(SUBSTITUTE(LOWER($J157),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J157) - LEN(SUBSTITUTE(LOWER($J157),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B157:D157)","v":2},2007,"Signals from both sides: Control of cardiac development by the endocardium and epicardium.","Smith",17267246,"Signals from both sides: Control of cardiac development by the endocardium and epicardium.    Abstract:   It is readily apparent that the process of heart development is an intricate one, in which cells derived from many embryonic sources coalesce and coordinate their behaviors and development, resulting in the mature heart. The behaviors and mechanisms of this process are complex, and still incompletely understood. However, it is readily apparent that communication between diverse cell types must be involved in this process. The signaling that emanates from epicardial and endocardial sources is the focus of this review."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I158,I158)","v":17033682},{"$f":"(LEN($J158) - LEN(SUBSTITUTE(LOWER($J158),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J158) - LEN(SUBSTITUTE(LOWER($J158),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J158) - LEN(SUBSTITUTE(LOWER($J158),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B158:D158)","v":2},2006,"Macular degeneration: recent advances and therapeutic opportunities.","Rattner",17033682,"Macular degeneration: recent advances and therapeutic opportunities.    Abstract:   The central retina mediates high acuity vision, and its progressive dysfunction due to macular degeneration is the leading cause of visual disability among adults in industrialized societies. Here, we summarize recent progress in understanding the pathophysiology of macular degeneration and the implications of this new knowledge for treatment and prevention. The past decade has witnessed remarkable advances in this field, including the development of new, non-invasive retinal imaging technologies, the development of animal models for macular disease, and the isolation of many of the genes responsible for both early- and late-onset macular diseases. These advances have set the stage for the development of effective mechanism-based therapies."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I159,I159)","v":17017903},{"$f":"(LEN($J159) - LEN(SUBSTITUTE(LOWER($J159),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J159) - LEN(SUBSTITUTE(LOWER($J159),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J159) - LEN(SUBSTITUTE(LOWER($J159),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B159:D159)","v":2},2006,"Novel agents to manage dyslipidemias and impact atherosclerosis.","Nachimuthu",17017903,"Novel agents to manage dyslipidemias and impact atherosclerosis.    Abstract:   Strong epidemiological evidence linked elevated levels of low-density lipoprotein cholesterol (LDL-C) to risk of atherosclerotic heart disease. As a consequence, LDL-C lowering has been the main goal of therapy to reduce cardiovascular risk for the past few decades and hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have become some of the most commonly prescribed drugs. In spite of the proven efficacy of these drugs, statins reduce cardiovascular events by only 30-40%. Epidemiological analyses clearly indicate that a significant portion of risk is linked to other particles such as low high-density lipoprotein cholesterol (HDL-C), high triglycerides and others. Furthermore, several quantitative coronary angiography studies showing regression of atherosclerosis and reduction in subsequent events utilized a combination of drugs effective on LDL-C as well as other lipoproteins. Hence, several new drugs are being investigated that affect more than the traditional LDL-C pathways. In this article, we review lipoprotein-modifying agents that have either been recently released, or are still in various phases of development. They include agents that reduce LDL-C levels by mechanisms other than HMG-CoA inhibition (such as cholesterol absorption inhibitors, Acyl-CoA cholesterol acyl transferase inhibitors, sterol-regulating binding protein cleavage activating protein ligands, microsomal triglyceride transfer protein inhibitors, LDL-C receptor activators and farnesoid X receptor antagonists) and agents that raise HDL-C cholesterol or improve cholesterol efflux (such as cholesterol ester transfer protein inhibitors, retinoid X receptor selective agonists, specific peroxisome proliferator-activated receptor (PPAR) agonists and estrogen like compounds)."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I160,I160)","v":16628264},{"$f":"(LEN($J160) - LEN(SUBSTITUTE(LOWER($J160),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J160) - LEN(SUBSTITUTE(LOWER($J160),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J160) - LEN(SUBSTITUTE(LOWER($J160),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B160:D160)","v":2},2006,"Retinoic acid receptor-related orphan receptor alpha as a therapeutic target in the treatment of dyslipidemia and atherosclerosis.","Jakel",16628264,"Retinoic acid receptor-related orphan receptor alpha as a therapeutic target in the treatment of dyslipidemia and atherosclerosis.    Abstract:   Retinoic acid receptor-related orphan receptor alpha (RORalpha) is a member of the nuclear receptor family. Recently, cholesterol (derivatives) has been identified as an RORalpha ligand and deorphanized this receptor. RORalpha is expressed in many tissues and is therefore a regulator of multiple biological processes. Studies of staggerer mice and in vitro assays indicate a beneficial modulatory role of RORalpha in the pathogenesis of dyslipidemia, inflammation and atherosclerosis. This paper provides an overview on the role of RORalpha in lipid metabolism and discusses its potential therapeutic option for treating lipid and inflammatory disorders leading to atherosclerosis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I161,I161)","v":16424607},{"$f":"(LEN($J161) - LEN(SUBSTITUTE(LOWER($J161),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J161) - LEN(SUBSTITUTE(LOWER($J161),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J161) - LEN(SUBSTITUTE(LOWER($J161),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B161:D161)","v":2},2006,"The multigene family of fatty acid-binding proteins (FABPs): function, structure and polymorphism.","Chmurzyńska",16424607,"The multigene family of fatty acid-binding proteins (FABPs): function, structure and polymorphism.    Abstract:   Fatty acid-binding proteins (FABPs) are members of the superfamily of lipid-binding proteins (LBP). So far 9 different FABPs, with tissue-specific distribution, have been identified: L (liver), I (intestinal), H (muscle and heart), A (adipocyte), E (epidermal), Il (ileal), B (brain), M (myelin) and T (testis). The primary role of all the FABP family members is regulation of fatty acid uptake and intracellular transport. The structure of all FABPs is similar - the basic motif characterizing these proteins is beta-barrel, and a single ligand (e.g. a fatty acid, cholesterol, or retinoid) is bound in its internal water-filled cavity. Despite the wide variance in the protein sequence, the gene structure is identical. The FABP genes consist of 4 exons and 3 introns and a few of them are located in the same chromosomal region. For example, A-FABP, E-FABP and M-FABP create a gene cluster. Because of their physiological properties some FABP genes were tested in order to identify mutations altering lipid metabolism. Furthermore, the porcine A-FABP and H-FABP were studied as candidate genes with major effect on fatness traits."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I162,I162)","v":16370327},{"$f":"(LEN($J162) - LEN(SUBSTITUTE(LOWER($J162),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J162) - LEN(SUBSTITUTE(LOWER($J162),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J162) - LEN(SUBSTITUTE(LOWER($J162),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B162:D162)","v":2},2006,"Autocrine and intracrine signaling for cardiogenesis in embryonic stem cells: a clue for the development of novel differentiating agents.","Ventura",16370327,"Autocrine and intracrine signaling for cardiogenesis in embryonic stem cells: a clue for the development of novel differentiating agents.    Abstract:   Cardiogenesis, one of the earliest and most complex morphogenetic events in the embryo, is not fully understood at the molecular level and is typically a low-yield process. Affording a high throughput of cardiogenesis from a suitable population of pluripotent cells is therefore a major assignment in the perspective of a stem cell therapy for heart failure. Analysis of cardiac lineage commitment in mouse embryonic stem cells and in vivo models of cardiac differentiation revealed that a number of crucial growth factors are released from precursor cells, acting in an autocrine fashion on specific plasma membrane receptors to prime a cardiogenic decision. Nevertheless, it is increasingly becoming evident that cell nuclei harbor the potential for intrinsic signal transduction pathways. The term quot;intracrinequot; has been proposed for growth regulatory peptides that have been shown to act within their cell of synthesis at the level of the nuclear envelope, chromatin, or other subnuclear components. Considerable evidence links known intracrines with transcriptional responses and self-sustaining loops that behave as long-lived signals and impart features characteristic of differentiation, growth regulation and cell memory. This review focuses on a number of autocrine and intracrine systems within the context of cardiac differentiation and emphasizes the identification of cardiogenic mechanisms as a clue for the development of unprecedented differentiating strategies. In this regard, recently synthesized mixed esters of hyaluronan with butyric and retinoic acid primed the expression of cardiogenic genes and elicited a remarkable increase in cardiomyocyte yield in mouse embryonic stem cells. This demonstrates the potential for chemically modifying the gene program of cardiac differentiation without the aid of gene transfer technologies and sets the basis for the design of a novel generation of chemicals suited for the organization of targeted lineage patterning in stem cells."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I163,I163)","v":16102021},{"$f":"(LEN($J163) - LEN(SUBSTITUTE(LOWER($J163),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J163) - LEN(SUBSTITUTE(LOWER($J163),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J163) - LEN(SUBSTITUTE(LOWER($J163),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B163:D163)","v":2},2005,"Significance of the transcription factor KLF5 in cardiovascular remodeling.","Nagai",16102021,"Significance of the transcription factor KLF5 in cardiovascular remodeling.    Abstract:   Structural remodeling of the heart and blood vessels is an important pathologic process in the development of many cardiovascular diseases. However, transcriptional regulation of altered gene expression during cardiovascular remodeling is not well understood. We previously isolated KLF5/basic transcription element-binding (BTEB)2, a Krüppel-like factor, as a transcription factor that binds the promoter of the embryonic smooth muscle myosin heavy chain gene (SMemb). KLF5 activates many genes inducible during cardiovascular remodeling, such as platelet-derived growth factor (PDGF)-A/B, Egr-1, plasminogen activator inhibitor-1 (PAI-1), inducible nitric oxide synthase (iNOS), and vascular endothelial growth factor (VEGF) receptors. KLF5 is abundantly expressed in embryonic smooth muscles and is down-regulated with vascular development, but reinduced in proliferative neointimal smooth muscles in response to vascular injury. In KLF5 gene-targeted mice, homozygotes die at an early embryonic stage whereas heterozygotes are apparently normal. However, in response to external stress, arteries of heterozygotes exhibit diminished levels of smooth muscle and adventitial cell activation. Furthermore, angiotensin II-induced cardiac hypertrophy and fibrosis are attenuated in heterozygotes. KLF5 activities are regulated by many transcriptional regulators and nuclear receptors, such as retinoic acid receptor-alpha (RAR alpha), NF-kappaB, PPAR gamma, p300, and SET. Interestingly, RAR alpha agonist suppresses KLF5 and cardiovascular remodeling, whereas RAR alpha antagonist activates KLF5 and induces angiogenesis. These results indicate that KLF5 is an essential transcription factor in cardiovascular remodeling and a potential therapeutic target for cardiovascular disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I164,I164)","v":15721857},{"$f":"(LEN($J164) - LEN(SUBSTITUTE(LOWER($J164),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J164) - LEN(SUBSTITUTE(LOWER($J164),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J164) - LEN(SUBSTITUTE(LOWER($J164),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B164:D164)","v":2},2005,"Beneficial effects of PPAR-gamma ligands in ischemia-reperfusion injury, inflammation and shock.","Abdelrahman",15721857,"Beneficial effects of PPAR-gamma ligands in ischemia-reperfusion injury, inflammation and shock.    Abstract:   Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily. PPAR-gamma regulates gene expression by forming a heterodimer with the retinoid X receptor (RXR) before binding to sequence-specific PPAR response elements (PPREs) in the promoter region of target genes, thereby regulating several metabolic pathways, including lipid biosynthesis and glucose metabolism. Thiazolidinediones (TZDs, i.e. rosiglitazone, pioglitazone), which are synthetic PPAR-gamma agonists, act as insulin sensitizers and are used in the treatment of type 2 diabetes. In the last few years, it has, however, become evident that the therapeutic effects of PPAR-gamma ligands reach far beyond their use as insulin sensitizers. Recently, PPAR-gamma has been implicated as a regulator of cellular inflammatory and ischemic responses. PPAR-gamma agonists may exert their anti-inflammatory effects by negatively regulating the expression of pro-inflammatory genes induced during macrophage differentiation and activation, by either PPAR-gamma-dependent or -independent mechanisms. Several lines of evidence suggest that TZDs protect the heart and other organs against the tissue injury caused by ischemia/reperfusion (I/R) injury and shock. This review discusses the anti-inflammatory signalling pathways activated by PPAR-gamma, as well as the potential therapeutic effects of PPAR-gamma agonists in animal models of ischemia/reperfusion, inflammation and shock."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I165,I165)","v":15380252},{"$f":"(LEN($J165) - LEN(SUBSTITUTE(LOWER($J165),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J165) - LEN(SUBSTITUTE(LOWER($J165),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J165) - LEN(SUBSTITUTE(LOWER($J165),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B165:D165)","v":2},2004,"Retinoic acid signalling in the development of branchial arches.","Mark",15380252,"Retinoic acid signalling in the development of branchial arches.    Abstract:   Branchial arches develop through a complex sequence of interactions between migrating cells, derived from neural crest and mesoderm, and epithelia of ectodermal and endodermal origin, to yield a variety of derivatives, notably skeletal elements, arteries and glands. In all vertebrate species, dramatic malformations generated by experimental blocks or activations of retinoic acid signalling highlight key roles for this molecule in the endoderm for branchial arch formation and morphogenesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I166,I166)","v":15320743},{"$f":"(LEN($J166) - LEN(SUBSTITUTE(LOWER($J166),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J166) - LEN(SUBSTITUTE(LOWER($J166),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J166) - LEN(SUBSTITUTE(LOWER($J166),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B166:D166)","v":2},2004,"Pleiotropic actions of PPAR gamma activators thiazolidinediones in cardiovascular diseases.","Takano",15320743,"Pleiotropic actions of PPAR gamma activators thiazolidinediones in cardiovascular diseases.    Abstract:   Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily and form heterodimers with retinoid X receptor. To date, three PPARs isoforms have been isolated and termed alpha, beta (or delta), and gamma. Although PPAR gamma is expressed predominantly in adipose tissue and associated with adipocyte differentiation and glucose homeostasis, it has been recently demonstrated that PPAR gamma is present in a variety of cell types. Synthetic antidiabetic thiazolidinediones (TZDs) and natural prostaglandin D(2) (PGD(2)) metabolite, 15-deoxy-Delta(12, 14)-prostaglandin J(2) (15d-PGJ(2)), are well-known as ligands for PPAR gamma. After it has been reported that activation of PPAR gamma suppresses production of proinflammatory cytokines in activated macrophages, medical interest in PPAR gamma have grown and a huge research effort has been concentrated. PPAR gamma, is currently known to be implicated in various human chronic diseases such as diabetes mellitus, atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, and Alzheimers disease. Moreover, PPAR gamma ligands have potent tumor modulatory effects against colorectal, prostate, and breast cancers. Recent studies suggest that TZDs not only ameliorate insulin sensitivity but also have pleiotropic effects on many tissues and cell types. Although activation of PPAR gamma seems to have beneficial effects on atherosclerosis and heart failure, the mechanisms by which PPAR gamma ligands prevent the development of cardiovascular diseases are not fully understood. This review will focus on the latest developments in the PPAR gamma field and the roles of PPAR gamma-dependent pathway in cardiovascular diseases."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I167,I167)","v":15225593},{"$f":"(LEN($J167) - LEN(SUBSTITUTE(LOWER($J167),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J167) - LEN(SUBSTITUTE(LOWER($J167),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J167) - LEN(SUBSTITUTE(LOWER($J167),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B167:D167)","v":2},2004,"Molecular imaging of the transcription factor NF-kappaB, a primary regulator of stress response.","Carlsen",15225593,"Molecular imaging of the transcription factor NF-kappaB, a primary regulator of stress response.    Abstract:   A wide range of environmental stress and human disorders involves inappropriate regulation of NF-kappaB, including cancers and numerous inflammatory conditions. We have developed transgenic mice that express luciferase under the control of NF-kappaB, enabling real-time non-invasive imaging of NF-kappaB activity in intact animals. We show that, in the absence of stimulation, strong, intrinsic luminescence is evident in lymph nodes in the neck region, thymus, and Peyers patches. Treating mice with stressors, such as TNF-alpha, IL-1alpha, or lipopolysaccharide (LPS) increases the luminescence in a tissue-specific manner, with the strongest activity observable in the skin, lungs, spleen, Peyers patches, and the wall of the small intestine. Liver, kidney, heart, muscle, and adipose tissue exhibit less intense activities. Exposure of the skin to a low dose of UV-B radiation increases luminescence in the exposed areas. In ocular experiments, LPS- and TNF-alpha injected NF-kappaB-luciferase transgenic mice exhibit a 20-40-fold increase in lens NF-kappaB activity, similar to other LPS- and TNF-alpha-responsive organs. Peak NF-kappaB activity occurs 6h after injection of TNF-alpha and 12h after injection of LPS. Peak activities occur, respectively, 3 and 6h later than that in other tissues. Mice exposed to 360J/m(2) of UV-B exhibit a 16-fold increase in NF-kappaB activity 6h after exposure, characteristically similar to TNF-alpha-exposed mice. Thus, in NF-kappaB-luciferase transgenic mice, NF-kappaB activity also occurs in lens epithelial tissue and is activated when the intact mouse is exposed to classical stressors. Furthermore, as revealed by real-time non-invasive imaging, induction of chronic inflammation resembling rheumatoid arthritis produces strong NF-kappaB activity in the affected joints. Finally, we have used the model to demonstrate NF-kappaB regulation by manipulating the Vitamin A status in mice. NF-kappaB activity is elevated in mice fed a Vitamin A deficient (VAD) diet, and suppressed by surplus doses of retinoic acid (RA). We thus demonstrate the development and use of a versatile model for monitoring NF-kappaB activation both in tissue homogenates and in intact animals after the use of classical activators, during disease progression and after dietary intervention."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I168,I168)","v":15067580},{"$f":"(LEN($J168) - LEN(SUBSTITUTE(LOWER($J168),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J168) - LEN(SUBSTITUTE(LOWER($J168),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J168) - LEN(SUBSTITUTE(LOWER($J168),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B168:D168)","v":2},2004,"[What is the role of endothelin system?].","Pinet",15067580,"[What is the role of endothelin system?].    Abstract:   Endothelins are a family of three peptides of 21 amino acids with strong vasoconstrictor effects. The three peptides are encoded by three different genes and derived from precursors (quot; big endothelinsquot;) which are cleaved by metalloproteases, named endothelin-converting enzyme. Two receptors have been cloned, ET-A and ET-B which bind the three endothelins with various affinities. The diverse expression pattern of the endothelin system (ET) components is associated with a complex pharmacology and its counteracting physiological actions. New modulators of the ET system have been described : retinoic acid, leptin, prostaglandins, hypoxia. Endothelins can be considered as regulators working in paracrine and autocrine fashion in a variety of organs in different cellular types. The ET system has beneficial and detrimental roles in mammals. The different components have been shown to be essential for a normal embryonic and neonatal development, for renal homeostasis and maintenance of basal vascular tone. They are involved in physiological and tumoral angiogenesis. They affect the physiology and pathophysiology of the liver, muscle, skin, adipose tissue and reproductive tract. The endothelin system participates in the development of atherosclerosis as well as pulmonary hypertension, and mediates cardiac remodeling in heart failure. Elaboration of new animal models (knock-out, pathophysiological models em leader ) will allow the clear genetic dissection of physiological and pathophysiological roles of the endothelin system."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I169,I169)","v":15062601},{"$f":"(LEN($J169) - LEN(SUBSTITUTE(LOWER($J169),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J169) - LEN(SUBSTITUTE(LOWER($J169),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J169) - LEN(SUBSTITUTE(LOWER($J169),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B169:D169)","v":2},2004,"Drug-induced pulmonary edema and acute respiratory distress syndrome.","Lee-Chiong",15062601,"Drug-induced pulmonary edema and acute respiratory distress syndrome.    Abstract:   Noncardiogenic pulmonary edema, and, to a lesser extent, acute respiratory distress syndrome (ARDS), are common clinical manifestations of drug-induced lung diseases. Clinical features and radiographic appearances are generally indistinguishable from other causes of pulmonary edema and ARDS. Typical manifestations include dyspnea, chest discomfort, tachypnea, and hypoxemia. Chest radiographs commonly reveal interstitial and alveolar filling infiltrates. Unlike pulmonary edema that is due to congestive heart failure, cardiomegaly and pulmonary vascular redistribution are generally absent in cases that are drug-related. Rare cases of drug-induced myocarditis with heart failure and pulmonary edema have been described. Results from laboratory evaluation and respiratory function tests are nonspecific."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I170,I170)","v":14749265},{"$f":"(LEN($J170) - LEN(SUBSTITUTE(LOWER($J170),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J170) - LEN(SUBSTITUTE(LOWER($J170),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J170) - LEN(SUBSTITUTE(LOWER($J170),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B170:D170)","v":2},2004,"The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity.","Ferré",14749265,"The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity.    Abstract:   Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the superfamily of nuclear receptors. Three isoforms (alpha, delta, and gamma) have been described. They act on DNA response elements as heterodimers with the nuclear retinoic acid receptor. Their natural activating ligands are fatty acids and lipid-derived substrates. PPAR-alpha is present in liver, heart, and, to a lesser extent, skeletal muscle. When activated, it promotes fatty acid oxidation, ketone body synthesis, and glucose sparing. Fibrates, which are used as hypolipidemic drugs, are ligands of PPAR-alpha. PPAR-delta is ubiquitous and could also favor fatty acid oxidation in tissues in which PPAR-alpha is absent or less expressed. PPAR-gamma is expressed in adipose tissue, lower intestine, and cells involved in immunity. Activation of PPAR-gamma induces the differentiation of preadipocytes into adipocytes and stimulates triglyceride storage. Thiazolidinediones are compounds used as hypoglycemic, muscle insulin-sensitizing agents in type 2 diabetes. Unexpectedly, they are activators of PPAR-gamma. Their action on muscle insulin sensitivity may be secondary to the lowering of circulating lipids on PPAR-gamma activation and to the secretion by adipocytes of insulin-sensitizing hormones such as adiponectin, all promoting glucose utilization. The PPARs are thus major regulators of lipid and glucose metabolism, allowing adaptation to the prevailing nutritional environment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I171,I171)","v":12962514},{"$f":"(LEN($J171) - LEN(SUBSTITUTE(LOWER($J171),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J171) - LEN(SUBSTITUTE(LOWER($J171),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J171) - LEN(SUBSTITUTE(LOWER($J171),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B171:D171)","v":2},2003,"Therapy for chronic obstructive pulmonary disease in the 21st century.","Donnelly",12962514,"Therapy for chronic obstructive pulmonary disease in the 21st century.    Abstract:   Chronic obstructive pulmonary disease (COPD) is a common, smoking-related, severe respiratory condition characterised by progressive, irreversible airflow limitation. Current treatment of COPD is symptomatic, with no drugs capable of halting the relentless progression of airflow obstruction. Better understanding of the airway inflammation, oxidative stress and alveolar destruction that characterise COPD has delineated new disease targets, with consequent identification of novel compounds with therapeutic potential. These new drugs include aids to smoking cessation (e.g. bupropion) and improvements to existing therapies, for example long-acting rather than short-acting bronchodilators, as well as combination therapy. New antiproteases include acyl-enzyme and transition state inhibitors of neutrophil elastase (e.g. sivelestat and ONO-6818), matrix metalloprotease inhibitors (e.g. batimastat), cathepsin inhibitors and peptide protease inhibitors (e.g. DX-890 [EPI-HNE-4] and trappin-2). New antioxidants include superoxide dismutase mimetics (e.g. AEOL-10113) and spin trap compounds (e.g. N-tert-butyl-alpha-phenylnitrone). New anti-inflammatory interventions include phosphodiesterase-4 inhibitors (e.g. cilomilast), inhibitors of tumour necrosis factor-alpha (e.g. humanised monoclonal antibodies), adenosine A(2a) receptor agonists (e.g. CGS-21680), adhesion molecule inhibitors (e.g. bimosiamose [TBC1269]), inhibitors of nuclear factor-kappaB (e.g. the naturally occurring compounds hypoestoxide and (-)-epigallocatechin-3-gallate) and activators of histone deacetylase (e.g. theophylline). There are also selective inhibitors of specific extracellular mediators such as chemokines (e.g. CXCR2 and CCR2 antagonists) and leukotriene B(4) (e.g. SB201146), and of intracellular signal transduction molecules such as p38 mitogen activated protein kinase (e.g. RWJ67657) and phosphoinositide 3-kinase. Retinoids may be one of the few potential treatments capable of reversing alveolar destruction in COPD, and a number of compounds are in clinical trial (e.g. all-trans-retinoic acid). Talniflumate (MSI-1995), an inhibitor of human calcium-activated chloride channels, has been developed to treat mucous hypersecretion. In addition, the purinoceptor P2Y(2) receptor agonist diquafosol (INS365) is undergoing clinical trials to increase mucus clearance. The challenge to transferral of these new compounds from preclinical research to disease management is the design of effective clinical trials. The current scarcity of well characterised surrogate markers predicts that long-term studies in large numbers of patients will be needed to monitor changes in disease progression."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I172,I172)","v":12952241},{"$f":"(LEN($J172) - LEN(SUBSTITUTE(LOWER($J172),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J172) - LEN(SUBSTITUTE(LOWER($J172),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J172) - LEN(SUBSTITUTE(LOWER($J172),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B172:D172)","v":2},2003,"Extensive splenic infarction, deep vein thrombosis and pulmonary emboli complicating induction therapy with all-trans-retinoic acid (ATRA) for acute promyelocytic leukemia.","Goldschmidt",12952241,"Extensive splenic infarction, deep vein thrombosis and pulmonary emboli complicating induction therapy with all-trans-retinoic acid (ATRA) for acute promyelocytic leukemia.    Abstract:   Bleeding is a common complication during initial induction treatment for acute promyelocytic leukemia (APL). Administration of all-trans-retinoic acid (ATRA), which is in routine use for APL in the past decade improves the bleeding tendency dramatically. Nevertheless, thrombotic events have still been reported in a small proportion of APL patients treated with ATRA. Here we describe a case of splenic infarction and life threatening thrombosis in a young patient with APL treated with ATRA. We review the relevant literature and discuss the pathophysiology, risk factors and treatment of this complication occurring during therapy, for APL."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I173,I173)","v":12880979},{"$f":"(LEN($J173) - LEN(SUBSTITUTE(LOWER($J173),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J173) - LEN(SUBSTITUTE(LOWER($J173),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J173) - LEN(SUBSTITUTE(LOWER($J173),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B173:D173)","v":2},2003,"Fenretinide as an anti-angiogenic agent in neuroblastoma.","Ribatti",12880979,"Fenretinide as an anti-angiogenic agent in neuroblastoma.    Abstract:   Angiogenesis is a critical event in the progression of human neuroblastoma. This mini-review summarizes our literature and experimental data concerning the use of anti-angiogenic molecules, such as TNP-470 and fenretinide, in neuroblastoma treatment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I174,I174)","v":12848275},{"$f":"(LEN($J174) - LEN(SUBSTITUTE(LOWER($J174),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J174) - LEN(SUBSTITUTE(LOWER($J174),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J174) - LEN(SUBSTITUTE(LOWER($J174),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B174:D174)","v":2},2003,"The potential role for arachidonic and docosahexaenoic acids in protection against some central nervous system injuries in preterm infants.","Crawford",12848275,"The potential role for arachidonic and docosahexaenoic acids in protection against some central nervous system injuries in preterm infants.    Abstract:   The risk of central nervous, visual, and auditory damage increases from 2/1000 live births in the normal birthweight to gt; 200/1000 as birthweight falls below 1500 g. Such babies are most likely to be born preterm. Advances in infant care have led to increasing numbers of very-low-birthweight, preterm infants surviving to school age with moderate to severe brain damage. Steroids are one of the current treatments, but they cause significant, long-term problems. The evidence reported here suggests an additional approach to protecting the very preterm infant by supporting neurovascular membrane integrity. The complications of preterm, very-low-birthweight babies include bronchopulmonary dysplasia, retinopathy of prematurity, intraventricular hemorrhage, periventricular leukomalacia, and necrotizing enterocolitis, all of which have a vascular component. Arachidonic acid (AA) and DHA are essential, structural, and functional constituents of cell membranes. They are especially required for the growth and function of the brain and vascular systems, which are the primary biofocus of human fetal growth. Molecular dynamics and experimental evidence suggest that DHA could be the ligand for the retinoid X receptor (RXR) in neural tissue. RXR activation is an obligatory step in signaling to the nucleus and in the regulation of gene expression. Very preterm babies are born with minimal fat stores and suboptimal circulating levels of these nutrients. Postnatally, they lose the biomagnification of the proportions of AA and DHA by the placenta for the fetus. No current nutritional management repairs these deficits. The placental biomagnification profile highlights AA rather than DHA. The resultant fetal FA profile closely resembles that of the vascular endothelium and not the brain. Without this nourishment, cell membrane abnormalities would be predicted. We present a scientific rationale for a common pathogenic process in the complications of prematurity."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I175,I175)","v":12743459},{"$f":"(LEN($J175) - LEN(SUBSTITUTE(LOWER($J175),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J175) - LEN(SUBSTITUTE(LOWER($J175),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J175) - LEN(SUBSTITUTE(LOWER($J175),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B175:D175)","v":2},2003,"Biological relevance of terpenoids. Overview focusing on mono-, di- and tetraterpenes.","Wagner",12743459,"Biological relevance of terpenoids. Overview focusing on mono-, di- and tetraterpenes.    Abstract:   The role of fruit and vegetables in human nutrition and public health are taken into account in most nutritional recommendations. Fruit and vegetables contain an abundance of phenolic substances, terpenoids and other natural antioxidants that have been associated with protection from and treatment of chronic diseases such as heart disease or cancer. Terpenoids are a group of substances which occur in nearly every natural food. Their main subclasses discussed as beneficial to maintain and improve health are monoterpenes (like limonene, carvone or carveol), diterpenes (including the retinoids), and tetraterpenes (which include all different carotenoids like alpha- and beta-carotene, lutein, lycopene, zeaxanthine and cryptoxanthine). To be discussed as health promoting or biofunctional, the significant impact of a substance either on human metabolism or on well-defined and appropriate biomarkers must be shown. Based on the latter point, this paper reviews the literature on mono-, di- and tetraterpenes, with special focus on their impact on human health to answer the question of their biofunctionality. Special emphasis will be placed on their different mode of action, e.g. to affect oxidative stress, carcinogenesis and cardiovascular diseases."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I176,I176)","v":12570784},{"$f":"(LEN($J176) - LEN(SUBSTITUTE(LOWER($J176),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J176) - LEN(SUBSTITUTE(LOWER($J176),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J176) - LEN(SUBSTITUTE(LOWER($J176),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B176:D176)","v":2},2003,"Hormonal control of the neuropeptide Y system.","Magni",12570784,"Hormonal control of the neuropeptide Y system.    Abstract:   Neuropeptide Y (NPY) and the related receptors represent a widely diffused system that is involved in the regulation of multiple biological functions. NPY, a 36-aminoacid peptide expressed in several areas of the nervous system, is a pleiotropic factor participating to the control of some physiological processes, such as cognitive functions, eating behavior, circadian rhythms, neuroendocrine mechanisms, reproductive and cardiovascular functions. NPY acts through a series of G-protein-associated membrane receptors (NPY-Rs), characterized by different tissue distribution and affinity for the ligand. The expression and secretion of NPY and the expression of NPY-R isoforms are controlled by a very wide range of agents, acting in an endocrine and/or paracrine fashion. NPY and NPY-Rs appear to be strongly involved in the control of eating behavior; their expression is modulated by changes of food intake and energy balance and is disrupted in several animal models of obesity and diabetes. Moreover, the hypothalamic NPY system appears to integrate signals of energy balance in the modulation of the reproductive axis. Agents that stimulate their expression include activators of intracellular signalling pathways (protein kinase A and C), classical neurotransmitters, steroid and peptide hormones and growth factors, while other agents (leptin, insulin and retinoic acid) have been shown to be inhibitory. Interestingly, some agents, like retinoic acid, have been shown to modulate the expression of both NPY and NPY-Rs in the same direction, thus providing a fine mechanism for the tuning of the system. The regulation of NPY/NPY-R expression and function appears to be part of a complex system controlling multiple physiological functions, and its disruption might be relevant in the pathophysiology of disease states such as obesity."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I177,I177)","v":12479567},{"$f":"(LEN($J177) - LEN(SUBSTITUTE(LOWER($J177),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J177) - LEN(SUBSTITUTE(LOWER($J177),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J177) - LEN(SUBSTITUTE(LOWER($J177),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B177:D177)","v":2},2002,"Insights into binding of fatty acids by fatty acid binding proteins.","Hanhoff",12479567,"Insights into binding of fatty acids by fatty acid binding proteins.    Abstract:   Members of the phylogenetically related intracellular lipid binding protein (iLBP) are characterized by a highly conserved tertiary structure, but reveal distinct binding preferences with regard to ligand structure and conformation, when binding is assessed by the Lipidex method (removal of unbound ligand by hydrophobic polymer) or by isothermal titration calorimetry, a true equilibrium method. Subfamily proteins bind retinoids, subfamily II proteins bind bulky ligands, examples are intestinal bile acid binding protein (I-BABP) and liver fatty acid binding protein (L-FABP) which binds 2 ligand molecules, preferably monounsaturated and n-3 fatty acids. Subfamily III intestinal fatty acid binding protein (I-FABP) binds fatty acid in a bent conformation. The fatty acid bound by subfamily IV FABPs has a U-shaped conformation; here heart (H-) FABP preferably binds n-6, brain (B-) FABP n-3 fatty acids. The ADIFAB-method is a fluorescent test for fatty acid in equilibrium with iLBP and reveals some correlation of binding affinity to fatty acid solubility in the aqueous phase; these data are often at variance with those obtained by the other methods. Thus, in this review published binding data are critically discussed, taking into account on the one hand binding increments calculated for fatty acid double bonds on the basis of the solubility hypothesis, on the other hand the interpretation of calorimetric data on the basis of crystallographic and solution structures of iLBPs."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I178,I178)","v":12069675},{"$f":"(LEN($J178) - LEN(SUBSTITUTE(LOWER($J178),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J178) - LEN(SUBSTITUTE(LOWER($J178),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J178) - LEN(SUBSTITUTE(LOWER($J178),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B178:D178)","v":2},2002,"Vitamins for chronic disease prevention in adults: scientific review.","Fairfield",12069675,"Vitamins for chronic disease prevention in adults: scientific review.    Abstract:    CONTEXT : Although vitamin deficiency is encountered infrequently in developed countries, inadequate intake of several vitamins is associated with chronic disease.  OBJECTIVE : To review the clinically important vitamins with regard to their biological effects, food sources, deficiency syndromes, potential for toxicity, and relationship to chronic disease.  DATA SOURCES AND STUDY SELECTION : We searched MEDLINE for English-language articles about vitamins in relation to chronic diseases and their references published from 1966 through January 11, 2002.  DATA EXTRACTION : We reviewed articles jointly for the most clinically important information, emphasizing randomized trials where available.  DATA SYNTHESIS : Our review of 9 vitamins showed that elderly people, vegans, alcohol-dependent individuals, and patients with malabsorption are at higher risk of inadequate intake or absorption of several vitamins. Excessive doses of vitamin A during early pregnancy and fat-soluble vitamins taken anytime may result in adverse outcomes. Inadequate folate status is associated with neural tube defect and some cancers. Folate and vitamins B(6) and B(12) are required for homocysteine metabolism and are associated with coronary heart disease risk. Vitamin E and lycopene may decrease the risk of prostate cancer. Vitamin D is associated with decreased occurrence of fractures when taken with calcium.  CONCLUSIONS : Some groups of patients are at higher risk for vitamin deficiency and suboptimal vitamin status. Many physicians may be unaware of common food sources of vitamins or unsure which vitamins they should recommend for their patients. Vitamin excess is possible with supplementation, particularly for fat-soluble vitamins. Inadequate intake of several vitamins has been linked to chronic diseases, including coronary heart disease, cancer, and osteoporosis"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I179,I179)","v":11926021},{"$f":"(LEN($J179) - LEN(SUBSTITUTE(LOWER($J179),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J179) - LEN(SUBSTITUTE(LOWER($J179),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J179) - LEN(SUBSTITUTE(LOWER($J179),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B179:D179)","v":2},2002,"[Transposition of great arteries. Understanding its pathogenesis].","Marino",11926021,"[Transposition of great arteries. Understanding its pathogenesis].    Abstract:   Transposition of the great arteries (TGA) is a frequent and severe cardiac defect. In patients with this malformation, diagnostic and surgical results and the long-term prognosis significantly improved in the last years. From the embryological point of view there are two main theories: 1) the anomalous infundibular rotation, and 2) the anomaly of the aortico-pulmonary septum. Both of them still present important limits. Moreover, TGA is difficult to reproduce by animal experiments, but interesting data, using retinoid acid in pregnant rats, are nowadays available, as well as there are interesting data from the epidemiologic studies on human teratologic agents. TGA is rarely associated with genetic syndromes and with additional extracardiac anomalies. A few cases are in relation with DiGeorge syndrome with deletion of chromosome 22q11. On the contrary TGA is significantly prevalent, in association with other cardiac and extracardiac anomalies, in children with lateralization defects, heterotaxy and asplenia syndrome (right isomerism). However in patients with heterotaxy and polysplenia syndrome (left isomerism) TGA is significantly more rare. In mice with mutation of Smad2 and NODAL, two genes involved in the lateralization process, some cases of TGA, with or without right isomerism of the lungs, were reported. Moreover, in families with heterotaxy some cases with congenitally corrected TGA were reported and a new gene associated with heterotaxy, CRYPTIC, can present mutations in patients with quot;isolatedquot; TGA. A recent study on familiar recurrence of TGA shows in the same family some cases of TGA and of corrected TGA so that a monogenic inheritance (autosomic dominant or recessive) with variable phenotypic expression can be suggested. The normal righthand spiralization of the heart is genetically determined in cases of situs solitus and d-loop of the ventricles. This pattern is not present in cases of TGA presenting a parallel position of the great arteries. On the basis of these observations and according to new epidemiologic and genetic data some cases of TGA should be classified in the group of the anomalies of lateralization and ventricular loop. The mystery is still present but perhaps some gleams of light are appearing."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I180,I180)","v":11891692},{"$f":"(LEN($J180) - LEN(SUBSTITUTE(LOWER($J180),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J180) - LEN(SUBSTITUTE(LOWER($J180),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J180) - LEN(SUBSTITUTE(LOWER($J180),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B180:D180)","v":2},2002,"PAGOD syndrome: eighth case and comparison to animal models of congenital vitamin A deficiency.","Macayran",11891692,"PAGOD syndrome: eighth case and comparison to animal models of congenital vitamin A deficiency.    Abstract:   We observed a 46, XY infant with atrophy of the optic nerve, complex congenital heart disease including a double outlet right ventricle, hypoplasia of the right pulmonary artery and lung, eventration of the diaphragm, and ambiguous genitalia. The baby died of cardiac arrhythmias at 204 days. The pattern of malformations was compatible with pulmonary tract and pulmonary artery, agonadism, omphalocele, diaphragmatic defect, and dextrocardia (PAGOD) syndrome. The condition may resemble the malformation complex associated with developmental deficiency of vitamin A or retinoic acid, as described in animal models."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I181,I181)","v":11772294},{"$f":"(LEN($J181) - LEN(SUBSTITUTE(LOWER($J181),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J181) - LEN(SUBSTITUTE(LOWER($J181),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J181) - LEN(SUBSTITUTE(LOWER($J181),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B181:D181)","v":2},2001,"Novel agents for managing dyslipidaemia.","Best",11772294,"Novel agents for managing dyslipidaemia.    Abstract:   An elevated low-density lipoprotein (LDL) cholesterol level is a strong predictor of coronary heart disease (CHD) risk. Over the past seven years, equally strong evidence has accumulated that lowering LDL cholesterol with HMG-CoA reductase inhibitors or statins reduces CHD risk and there is now widespread use of these agents for the primary and secondary prevention of CHD. Treatment issues remain regarding the appropriate degree of LDL cholesterol reduction and whether, in people with very high levels, it would be preferable to achieve the LDL cholesterol goal with a powerful statin alone or combined with an agent that lowers LDL cholesterol by a different mechanism. The main focus in the development of novel agents is the patient with low high-density lipoprotein (HDL) cholesterol, usually associated with hypertriglyceridaemia. Already prevalent as a risk factor for CHD, this abnormality has been linked with insulin resistance, which is likely to increase greatly over the next decade, along with increasing obesity and diabetes. Agents that have potent HDL cholesterol raising capacity include cholesteryl ester transfer protein (CETP) inhibitors, retinoid X receptor (RXR) selective agonists, specific peroxisome proliferator-activated receptor (PPAR) agonists and oestrogen-like compounds. Another area of development involves agents that will lower both cholesterol and triglyceride levels, such as partial inhibitors of microsomal triglyceride transfer protein (MTP) and perhaps squalene synthase inhibitors and agonists of AMP kinase. Future emphasis will be on correcting all lipid abnormalities for the prevention of CHD, not just lowering LDL cholesterol."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I182,I182)","v":11754790},{"$f":"(LEN($J182) - LEN(SUBSTITUTE(LOWER($J182),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J182) - LEN(SUBSTITUTE(LOWER($J182),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J182) - LEN(SUBSTITUTE(LOWER($J182),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B182:D182)","v":2},2001,"[Developmental genes and heart disease].","Ruiz-Lozano",11754790,"[Developmental genes and heart disease].    Abstract:   The past three years can be considered in cardiology as critical for understanding the relevance of developmental genes in the adult cardiac physiology. Also, for the first time, endogenous control of programmed cell death has been demonstrated to mark the transition between normal adaptation and cardiac hypertrophy. Most of this work has been based on previous analysis using molecular markers of cardiac determination and differentiation, work that has served a double aim: First, the determination of the cellular process that contribute to the specification of the working heart and secondly, the characterization of key regulatory factors in cardiogenesis. These studies in conjunction with the recent availability of single gene mutation in transgenic mice have furnished a new perspective in the nature of cardiac defects either in shape or function. Here we review some of the key factors in cardiac morphogenesis from the perspective of the analysis of gene mutation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I183,I183)","v":11697231},{"$f":"(LEN($J183) - LEN(SUBSTITUTE(LOWER($J183),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J183) - LEN(SUBSTITUTE(LOWER($J183),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J183) - LEN(SUBSTITUTE(LOWER($J183),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B183:D183)","v":2},2001,"PPAR gamma/RXR as a molecular target for diabetes.","Lenhard",11697231,"PPAR gamma/RXR as a molecular target for diabetes.    Abstract:   Type 2 diabetes is associated with insulin resistance in peripheral tissues, such as muscle and fat. Novel therapies that improve insulin action include ligands that bind and activate the nuclear receptors peroxisome proliferator activating receptor gamma (PPAR gamma) and retinoid X receptor (RXR). PPAR gamma/RXR form heterodimers that regulate transcription of genes involved in insulin action, adipocyte differentiation, lipid metabolism and inflammation. PPAR gamma activators include prostanoids, fatty acids, thiazolidinediones and N-(2-benzoylphenyl)tyrosine analogues. RXR ligands include naturally occurring retinoic acid and synthetic rexinoids. Selective ligands for these receptors improve metabolic abnormalities associated with type 2 diabetes, such as hyperglycemia, hyperlipidemia, insulin resistance and other cardiovascular risk factors. Although adipose tissue mediates some of the effects of PPAR gamma/RXR ligands, other tissues also regulate the effects of these receptors. The activity of the PPAR gamma/RXR heterodimer is influenced by posttranslational modifications, receptor turnover, polymorphisms, splice variants, coactivators and corepressors. This article reviews recent developments in research on these receptors, with particular emphasis on metabolic effects, ligand selectivity, structure and regulation of the PPAR gamma/RXR heterodimer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I184,I184)","v":11586463},{"$f":"(LEN($J184) - LEN(SUBSTITUTE(LOWER($J184),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J184) - LEN(SUBSTITUTE(LOWER($J184),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J184) - LEN(SUBSTITUTE(LOWER($J184),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B184:D184)","v":2},2001,"History, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells.","Geerts",11586463,"History, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells.    Abstract:   In 1876, von Kupffer described liver Sternzellen (star-shaped cells). The functions of these cells remained enigmatic for 75 years until Ito observed lipid-containing perisinusoidal cells in human liver. In 1971, Wake demonstrated that the Sternzellen of von Kupffer and the fat-storing cells described by Ito were identical. Wake also established that these cells were important sites of vitamin A storage. Soon thereafter, Kent and Popper demonstrated that the stellate cells were intimately linked to the pathogenesis of hepatic fibrosis. Since then, these cells have been studied in detail. Quiescent stellate cells represent 5-8% of the total number of liver cells. They play a cardinal role in storage and controlled release of retinoids. They control extracellular matrix (ECM) turnover in the space of Disse by secreting the correct amounts of a limited number of ECM molecules, and by releasing matrix metalloproteinases and their inhibitors. By virtue of their long cytoplasmic processes, quiescent stellate cells presumably contribute to the control of blood flow through the sinusoidal capillaries. They are important sources of paracrine, autocrine, juxtacrine, and chemoattractant factors that maintain homeostasis in the microenvironment of the hepatic sinusoid."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I185,I185)","v":11478382},{"$f":"(LEN($J185) - LEN(SUBSTITUTE(LOWER($J185),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J185) - LEN(SUBSTITUTE(LOWER($J185),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J185) - LEN(SUBSTITUTE(LOWER($J185),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B185:D185)","v":2},2001,"Polyunsaturated fatty acid regulation of gene expression.","Ntambi",11478382,"Polyunsaturated fatty acid regulation of gene expression.    Abstract:   Polyunsaturated fatty acids (PUFAs), specifically the n-3 and n-6 series, play a key role in the progression or prevention of human diseases such as obesity, diabetes, cancer, neurological and heart disease, mainly by affecting cellular membrane lipid composition, metabolism, signal-transduction pathways, and by direct control of gene expression. PUFAs show regulation of gene expression in several tissues, including brain, liver, heart, and adipose. Most recently, research has focused on identifying the mechanisms by which PUFAs regulate lipogenic gene expression. Research to date indicates that PUFA-mediated regulation of the genetic expression and proteolytic maturation of a group of transcription factors termed sterol regulatory element binding proteins (SREBPs) accounts for the suppression of hepatic lipogenic gene expression. However, our recent studies on the transcriptional regulation of the stearoyl-coenzyme A (CoA) desaturase gene, encoding a key enzyme in the cellular synthesis of monounsaturated fatty acids from saturated fatty acids indicates that PUFA can suppress gene transcription by a mechanism independent of SREBP maturation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I186,I186)","v":11441326},{"$f":"(LEN($J186) - LEN(SUBSTITUTE(LOWER($J186),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J186) - LEN(SUBSTITUTE(LOWER($J186),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J186) - LEN(SUBSTITUTE(LOWER($J186),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B186:D186)","v":2},2001,"Oral nutritional supplements and heart disease: a review.","Gaytan",11441326,"Oral nutritional supplements and heart disease: a review.    Abstract:   The use of nutritional supplements in the treatment of cardiovascular disease is rapidly growing in the United States. Many substances are marketed with anecdotal claims of efficacy. Most have not been scientifically studied. Excitement exists in the lay press about the homocysteine hypothesis of coronary artery disease and vitamin cures. A MEDLINE search and review of papers covering the study of popular nutritional supplements were undertaken. The papers were limited to peer-review journals using patient series reports, double-blinded prospective studies, and population studies. A compendium of the available data was obtained and an analysis of each papers methodology was done. A review of the most popular and most studied oral nutritional supplements for the treatment of heart disease demonstrated relatively few well-founded indications for the widespread application of substances with the exception of the bioflavonoids. Some modest effects for endothelial dysfunction were noted for vitamins C and E. Red wines and beers were also noted to be beneficial. The majority of substances either had no effect or were deleterious."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I187,I187)","v":11306727},{"$f":"(LEN($J187) - LEN(SUBSTITUTE(LOWER($J187),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J187) - LEN(SUBSTITUTE(LOWER($J187),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J187) - LEN(SUBSTITUTE(LOWER($J187),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B187:D187)","v":2},2001,"Noncardiogenic pulmonary edema: an unusual and serious complication of anticancer therapy.","Briasoulis",11306727,"Noncardiogenic pulmonary edema: an unusual and serious complication of anticancer therapy.    Abstract:   Noncardiogenic pulmonary edema (NCPE) is a rare and less well-recognizable pulmonotoxic syndrome of anticancer therapy than pneumonitis/fibrosis. NCPE is a clinical syndrome characterized by simultaneous presence of severe hypoxemia, bilateral alveolar infiltrates on chest radiograph, and no evidence of left atrial hypertension/congestive heart failure. The diagnosis of drug-related NCPE relies upon documented exclusion of any infectious, metabolic, or cancer-related causes. The time proximity to therapy with drugs that are known to precipitate NCPE, any preceding episodes of flu-like symptoms during previous chemotherapy courses and possible response to corticosteroids may further support such a diagnosis. Cancer therapeutic agents clearly associated with NCPE are cytarabine, gemcitabine, and interleukin-2, as well as all-trans retinoic acid in acute promyelocytic leukemia patients, while a few other compounds have rarely or occasionally been implicated. The pathophysiology of lung injury in drug-induced NCPE remains unclear. There are indications suggesting that both a direct cytotoxic insult to the lung epithelial cells and induction of a cytokine-triggered inflammatory response may be involved in its pathogenesis. By distinction to drug-induced pulmonary pneumonitis that may lead to permanent pulmonary fibrosis, NCPE if not fatal, can be reversed upon prompt recognition, following immediate discontinuation of the offensive drug and start of intensive supportive treatment and intravenous corticosteroids."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I188,I188)","v":11291857},{"$f":"(LEN($J188) - LEN(SUBSTITUTE(LOWER($J188),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J188) - LEN(SUBSTITUTE(LOWER($J188),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J188) - LEN(SUBSTITUTE(LOWER($J188),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B188:D188)","v":2},2001,"In vitro induction systems for analyses of amphibian organogenesis and body patterning.","Ariizumi",11291857,"In vitro induction systems for analyses of amphibian organogenesis and body patterning.    Abstract:   The discovery that some well-known growth factors have inducing activity in embryogenesis has accelerated our understanding of embryonic induction. Relevant receptors, signal transduction pathways and patterns of gene expression have been characterized over the past decade. Amphibian embryos have provided an excellent model for analysis of embryonic induction because they are easily surgically manipulated and cultured in vitro, and with the addition of treatment with various inducing factors we have been able to control organogenesis and body patterning during early development in vitro. Activin A, a TGF-beta family protein, has a potent mesoderm-inducing activity on the isolated ectoderm called the animal cap. Activin induces animal caps to differentiate into various mesodermal and endodermal tissues, including beating hearts, in a dose-dependent fashion. Activin, in combination with retinoic acid, also induces the formation of the pronephros, a primitive embryonic kidney. The in vitro induced kidney was confirmed to function in vivo in a transplantation experiment. Furthermore, the activin-induced animal caps organize heads or trunk-and-tails in exactly the same manner as the organizer. The potential use of in vitro induction systems to further our understanding of vertebrate organogenesis and body patterning will be discussed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I189,I189)","v":10668396},{"$f":"(LEN($J189) - LEN(SUBSTITUTE(LOWER($J189),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J189) - LEN(SUBSTITUTE(LOWER($J189),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J189) - LEN(SUBSTITUTE(LOWER($J189),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B189:D189)","v":2},2000,"Prostaglandin D synthase: structure and function.","Urade",10668396,"Prostaglandin D synthase: structure and function.    Abstract:   Prostaglandin (PG) D synthase catalyzes the isomerization of PGH2, a common precursor of various prostanoids, to produce PGD2 in the presence of sulfhydryl compounds. PGD2 induces sleep, regulates nociception, inhibits platelet aggregation, acts as an allergic mediator, and is further converted to 9 alpha, 11 beta-PGF2 or the J series of prostanoids, such as PGJ2, delta 12-PGJ2, and 15-deoxy-delta 12,14-PGJ2. We have purified two distinct types of PGD synthase; one is the lipocalin-type enzyme and the other is the hematopoietic enzyme. We isolated the cDNA and the gene for each enzyme and determined the tissue distribution profile and the cellular localization in several animal species. Lipocalin-type PGD synthase is localized in the central nervous system and male genital organs of various mammals and the human heart and is secreted into cerebrospinal fluid, seminal plasma, and plasma, respectively. The human enzyme was identified as beta-trace, which is a major protein in human cerebrospinal fluid. This enzyme is considered to be a dual-function protein; it acts as a PGD2-producing enzyme and also as a lipophilic ligand-binding protein, because the enzyme binds retinoids, thyroids, and bile pigments, with high affinities. Hematopoietic PGD synthase is widely distributed in the peripheral tissues and localized in the antigen-presenting cells, mast cells, and megakaryocytes. The hematopoietic enzyme is the first recognized vertebrate homolog of the sigma class of glutathione S-transferase. X-ray crystallographic analyses and generation of gene-knockout and transgenic mice for each enzyme have been performed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I190,I190)","v":10517280},{"$f":"(LEN($J190) - LEN(SUBSTITUTE(LOWER($J190),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J190) - LEN(SUBSTITUTE(LOWER($J190),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J190) - LEN(SUBSTITUTE(LOWER($J190),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B190:D190)","v":2},1999,"Influence of palm oil (Elaesis guineensis) on health.","Ebong",10517280,"Influence of palm oil (Elaesis guineensis) on health.    Abstract:   In recent times there has been a growing research interest in palm oil, one of the major edible plant oils in the tropical countries, because of the link between dietary fats and coronary heart disease. Obtained from a tropical plant, Elaesis guineensis, it has a polyunsaturated fatty acid/saturated fatty acid ratio close to unity and a high amount of antioxidant vitamin A precursors and vitamin E. Palm oil is consumed in the fresh state and/or at various levels of oxidation. Feeding experiments in various animal species and humans have highlighted the beneficial role of fresh palm oil to health. These benefits include reduction in the risk of arterial thrombosis and atherosclerosis, inhibition of cholesterol biosynthesis and platelet aggregation, and reduction in blood pressure. However, a considerable amount of the commonly used palm oil is in the oxidized state which possesses potential dangers to the physiological and biochemical functions of the body. Oxidation is as a result of processing the oil for various culinary purposes. Studies have revealed that relative to fresh palm oil, oxidized palm oil induces an adverse plasma lipid profile, free fatty acids, phospholipids and cerebrosides. Additionally, oxidized palm oil induces reproductive toxicity and organotoxicity particularly of the kidneys, lungs, liver and heart. Available evidence suggests that at least part of the oxidized oil impact on health reflects generation of toxicants due to oxidation. The reduction of the dietary level of oxidized oil and/or the level of oxidation may reduce the health risk associated with consumption of oxidized fats."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I191,I191)","v":9740599},{"$f":"(LEN($J191) - LEN(SUBSTITUTE(LOWER($J191),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J191) - LEN(SUBSTITUTE(LOWER($J191),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J191) - LEN(SUBSTITUTE(LOWER($J191),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B191:D191)","v":2},1998,"Transcription-modulating drugs: a new frontier in the treatment of essential hypertension.","Kurtz",9740599,"Transcription-modulating drugs: a new frontier in the treatment of essential hypertension.    Abstract:   While the promises of gene therapy may be years away from realization, the therapeutic use of drugs that act by modifying gene transcription is a well-established practice in clinical medicine. Although transcription-modulating drugs are frequently used in many different specialties, the deliberate development and use of these agents in cardiovascular medicine has been comparatively limited. However, research advances in the area of gene transcription and in the molecular genetic regulation of blood pressure, insulin resistance, lipid metabolism, and cell growth are providing new opportunities for controlling the expression of genes that are relevant to the pathogenesis of cardiovascular disease and essential hypertension. These research advances are beginning to converge in the development of transcription-modulating drugs with the potential to attack genetically determined risk factors that often cluster in patients with essential hypertension. Ligand-activated transcription factors that serve as receptors for small lipophilic compounds such as the thiazolidinediones and retinoids represent examples of potential therapeutic targets with direct effects on the expression of genes relevant to the pathogenesis of essential hypertension and its complications. Mounting evidence suggesting that the superior cardiorenal protective properties of converting enzyme inhibitors are related in part to their ability to indirectly modify the expression of genes in the heart and vasculature provides provisional support for the clinical value of this therapeutic approach. Given the success of transcription-modulating drugs in the treatment of type II diabetes and many other clinical disorders, it is anticipated that these agents will be developed as tools for the prevention and treatment of hypertension and cardiovascular disease in the not too distant future."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I192,I192)","v":9629233},{"$f":"(LEN($J192) - LEN(SUBSTITUTE(LOWER($J192),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J192) - LEN(SUBSTITUTE(LOWER($J192),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J192) - LEN(SUBSTITUTE(LOWER($J192),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B192:D192)","v":2},1998,"Corticotropin-releasing hormone and inflammation.","Webster",9629233,"Corticotropin-releasing hormone and inflammation.    Abstract:   Corticotropin-releasing hormone (CRH) is a major regulator of the hypothalamic-pituitary-adrenal axis (HPA) and principal coordinator of the stress response. As in stress, intracerebroventricular administration of CRH suppresses the immune system indirectly, via glucocorticoid and/or sympathetic system-mediated mechanisms. Also, during inflammatory stress, the cytokines TNF alpha, IL-1, and IL-6 stimulate hypothalamic CRH and/or vasopressin secretion as a way of preventing the inflammatory reaction from overreacting. Recently, CRH receptors were described in peripheral sites of the immune system, and CRH was found to promote several immune functions in vitro. We demonstrated a direct role of CRH in the inflammatory immune process in vivo, by first studying the effect of systemic CRH immunoneutralization in an experimental model of carrageenin-induced aseptic inflammation in Spague-Dawley rats. We extended these observations to other forms of experimental inflammation, including streptococcal cell wall polysaccharide- and adjuvant-induced arthritides and peptide R16 (epitope of the interphotoreceptor retinoid-binding protein)-induced uveitis in Lewis rats. We also studied human disease states, including rheumatoid arthritis, Hashimoto thyroiditis, and ulcerative colitis. Inflamed tissues contained large amounts of IR CRH, reaching levels similar to those observed in the hypophyseal portal system. We also demonstrated the presence of CRH mRNA and CRH receptors in inflammatory cells and identified the mast cells as a major immune target for CRH. In addition to production by immune cells, the peripheral nervous system, including the postganglionic sympathetic neurons and the sensory fibers type C, appears to contribute to IR CRH production in inflammatory sites. The production of CRH from the postganglionic sympathetic neurons may be responsible for the stress-induced activation of allergic/autoimmune phenomena, such as asthma and eczema, via mast cell degranulation. Antalarmin, a novel nonpeptide CRH receptor antagonist, displaced 125I-labeled ovine CRH binding in rat pituitary, frontal cortex, and cerebellum, but not heart, consistent with antagonism at the CRHR1 receptor. In vivo antalarmin significantly inhibited CRH-stimulated ACTH release and carrageenin-induced subcutaneous inflammation in rats. Thus, antalarmin and other related compounds that antagonize CRH at the level of its own receptor have therapeutic potential in some forms of inflammation directly mediated by type 1 CRH receptors and promise to enhance our understanding of the many roles of CRH in immune/inflammatory reactions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I193,I193)","v":9433514},{"$f":"(LEN($J193) - LEN(SUBSTITUTE(LOWER($J193),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J193) - LEN(SUBSTITUTE(LOWER($J193),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J193) - LEN(SUBSTITUTE(LOWER($J193),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B193:D193)","v":2},1997,"Modulation of cardiac hypertrophy by estrogens.","Pelzer",9433514,"Modulation of cardiac hypertrophy by estrogens.    Abstract:   Gender-specific differences in heart disease have long been known but it has only been since the advent of molecular biology that it has become possible to investigate the molecular mechanisms. Most biochemical work in the last 50 years has focused on the characterization of the steroid hormones involved in gender specificity. More recently, the cloning of the steroid receptors and characterization of the signaling pathways through these proteins has given new insights into the mechanisms underlying the mode of action of steroid hormones. It has also become clear that the steroid receptors can be classified into families (receptors for thyroid hormone, glucocorticoids, estrogens, androgens, retinoic acid, and so called orphan receptors of mostly unknown function). The structures of these receptors show very close resemblance and all are DNA-binding proteins acting as transcription factors. Some (if not all) act as repressors of transcription of some genes in the native state and are converted to activators (or perhaps repressors of other genes) upon binding of the cognate hormone. Naturally, classical target tissues for estrogens and androgens have been studied first and only in very recent years has it been recognized that estrogens and androgens act on a much wider spectrum of tissues. In the cardiovascular field, the beneficial effect of estrogen replacement therapy in postmenopausal women which reduces the incidence of cardiovascular disease by some 40% and the lower incidence of cardiovascular disease in premenopausal women have mostly been explained by the beneficial action of estrogens on the lipid profile (increase in HDL and decrease in LDL cholesterol). Recently, functional estrogen receptors have also been shown in vascular smooth muscle cells and in the endothelium. Our own group has characterized the presence of estrogen receptors in the myocardium and in cardiac fibroblasts. We have also shown that these receptors are transcriptionally active because they are able to drive a minigene composed of a triple estrogen responsive DNA regulatory element (promoter) coupled to the firefly luciferase gene which serves as a reporter by way of its ability to drive a light-emitting reaction. We are in the process of characterizing the target genes for estrogen in the myocardium. A specific series of immediate-early genes is induced by estradiol (the major premenopausal estrogen) and we have also characterized a number of tissue-specific genes whose expression is driven by estrogens in the myocardium. The ultimate goal of these investigations is to explore the use of estrogens in the treatment of cardiac hypertrophy (and failure) by way of their properties to counteract (at least some of) the pathological switches in gene expression in these disease entities."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I194,I194)","v":9350470},{"$f":"(LEN($J194) - LEN(SUBSTITUTE(LOWER($J194),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J194) - LEN(SUBSTITUTE(LOWER($J194),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J194) - LEN(SUBSTITUTE(LOWER($J194),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B194:D194)","v":2},1997,"Antioxidative vitamins in prevention of ischemia/reperfusion injury.","Nagel",9350470,"Antioxidative vitamins in prevention of ischemia/reperfusion injury.    Abstract:   Involvement of oxygen free radicals in ischemia-/reperfusion injury is based on measurement of increased products of lipid peroxidation after organ ischemia and restoration of blood flow during surgical operations and reperfusion of organ transplants. In cardiology inverse epidemiological correlations between plasma vitamin E levels and mortality due to ischemic heart disease, as well as beneficial effects of vitamin E on experimentally induced oxidative damage to the heart support the hypothesis, that vitamin E might have a protective role against myocardial ischemia-/reperfusion injury. In abdominal surgery efficiency of free radical scavengers has been intensively studied on animal models of hepatic ischemia and reperfusion. Examination of free radical scavengers and adenosine metabolites in liver tissue during hepatic ischemia revealed that vitamin E and glutathione levels as well as hepatic adenosine triphosphate levels are decreased during hepatic ischemia and reperfusion. The beneficial effects of alpha-tocopherol on hepatic viability and survival rate after ischemia and reperfusion demonstrated in these studies will be of great importance concerning further studies in organ preservation. In clinical kidney transplantation prevention of lipid peroxidation and improvement in kidney viability and function was demonstrated after infusion of a multivitamin cocktail in a prospective randomised study."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I195,I195)","v":9216791},{"$f":"(LEN($J195) - LEN(SUBSTITUTE(LOWER($J195),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J195) - LEN(SUBSTITUTE(LOWER($J195),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J195) - LEN(SUBSTITUTE(LOWER($J195),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B195:D195)","v":2},1996,"Carotenoids in cancer, mastalgia, and AIDS: prevention and treatment--an overview.","Santamaria",9216791,"Carotenoids in cancer, mastalgia, and AIDS: prevention and treatment--an overview.    Abstract:   In 1980, two carotenoids, beta-carotene (BC) and canthaxanthine (CX) with and without pro-vitamin A activity, respectively, were orally administered to female Swiss albino mice and were found to substantially prevent skin carcinogenesis induced by benzo(a)pyrene (BP). This preventive effect was observed in darkness by means of photocarcinogenic enhancement (PCE) following UV (300 to 400 nm) irradiation. In 1984, the same experiment produced antitumorigenic activity when applied to breast carcinogenesis induced in mice by 8-methoxypsoralen (8-MOP) plus UV-A light and, in 1985, when directed toward gastric carcinogenesis induced in rats by N-methyl-N-nitro-N-nitrosoguanidine (MNNG). These data suggested a rationale for human intervention to prevent, by carotenoid supplementation, a second primary malignancy after the primary malignancy has been radically excised. In the 1980s, a pilot clinical study (15 cases) showed a longer than expected disease-free interval in all surviving patients. It was also subsequently found that, if treated daily with 20 mg of BC and intermittently with retinol 150 to 300,000 IU daily for seven days just prior to menses, women suffering from cyclical mastalgia were relieved from pain, without any toxic side effects. When BC was given in high daily doses (60 mg) to 60 drug addicts suffering from AIDS-related complex (ARC), they recovered from their objective and subjective symptoms (but not from lymphadenopathy) with improvement in their general health and increased performance status. At higher doses, BC (with or without hyperthermia) was effective even in patients in advanced stages of AIDS. A debate has arisen concerning a recent statement by the U.S. Government that quot;beta-carotene supplements do not protect Americans against cancer or heart disease, and may actually increase the risk of deadly lung tumors in smokersquot;."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I196,I196)","v":7522288},{"$f":"(LEN($J196) - LEN(SUBSTITUTE(LOWER($J196),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J196) - LEN(SUBSTITUTE(LOWER($J196),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J196) - LEN(SUBSTITUTE(LOWER($J196),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B196:D196)","v":2},1994,"Cancer combination chemotherapy with retinoids: experimental rationale.","Bollag",7522288,"Cancer combination chemotherapy with retinoids: experimental rationale.    Abstract:   Retinoids, cytokines as well as 1,25-dihydroxyvitamin D3 and its analogs are all classes of compounds with pleiotropic actions. They inhibit proliferation in human transformed epithelial cell lines and induce differentiation in human transformed hemopoietic cell lines. In a murine model of tumor cell-induced angiogenesis all three classes of compounds inhibit the formation of new blood vessels, necessary for supplying the growing tumor with oxygen and nutrients. Combinations of compounds from the three different classes lead to higher efficacy than the compounds administered as single agents. The effects of combinations vary depending on the individual representatives of the three classes and on the particular test models used. Additive, synergistic and potentiating effects have been observed. The results obtained in experimental systems raise hope that combination therapy might be useful in the treatment of certain human neoplastic diseases."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I197,I197)","v":8242570},{"$f":"(LEN($J197) - LEN(SUBSTITUTE(LOWER($J197),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J197) - LEN(SUBSTITUTE(LOWER($J197),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J197) - LEN(SUBSTITUTE(LOWER($J197),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B197:D197)","v":2},1993,"Cancer chemoprevention.","Itri",8242570,"Cancer chemoprevention.    Abstract:   Encouraging results from several recent trials have increased interest in the potential of chemoprevention in reducing the incidence of cancer. Treatment with 13-cis-retinoic acid has reversed oral leukoplakia, a premalignant lesion, and prevented the development of second primary carcinomas of the head and neck. Tamoxifen has proven effective in preventing both the recurrence of breast cancer and the development of new tumors in the contralateral breast, and is being tested in high-risk patients who have not yet developed disease. The results of the Physicians Health Study, which demonstrated the effectiveness of aspirin in reducing heart attacks, already have been incorporated into health care practice, while the component investigating the effect of beta carotene on the incidence of cancer still is underway. These studies demonstrate the importance of careful design if chemoprevention trials are to yield convincing data."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I198,I198)","v":7693404},{"$f":"(LEN($J198) - LEN(SUBSTITUTE(LOWER($J198),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J198) - LEN(SUBSTITUTE(LOWER($J198),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J198) - LEN(SUBSTITUTE(LOWER($J198),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B198:D198)","v":2},1993,"Food quality and human nutrition.","James",7693404,"Food quality and human nutrition.    Abstract:   New nutritional analyses suggest that current trends in the production of food are inappropriate for the health of most of the worlds populations. Four deficiency problems now dominate analyses of the nutritional disorders of developing countries: the risks from iodine, vitamin A and iron deficiencies and protein energy malnutrition now affect over two billion children and adults. Chronic energy deficiency affects half of Indian adults, with similar rates in Pakistan and Ethiopia. India will need to increase food production two- to three-fold by 2020 to cope with the predicted population explosion and desirable increases in food consumption. As erosion, salination and environmental degradation further limit land availability, current problems will overwhelm agricultural demand. Societies increase their meat, milk and fat consumption as they become affluent, and suffer from heart disease, diabetes, obesity, cancers and a variety of other Western public health problems. Agricultural production is then regeared inappropriately. The Second World has an agriculture system geared to 1940s Western concepts of high animal production. Russia now vies with Scotland and Northern Ireland for the highest heart disease rates in the world and has the fattest adults in Europe. Most major non-infective public health issues throughout the world are nutritionally related. Global warming will exacerbate these problems, but effective dietary change with less animal production could release land which could be used more efficiently."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I199,I199)","v":2088799},{"$f":"(LEN($J199) - LEN(SUBSTITUTE(LOWER($J199),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J199) - LEN(SUBSTITUTE(LOWER($J199),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J199) - LEN(SUBSTITUTE(LOWER($J199),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B199:D199)","v":2},1990,"The antioxidant hypothesis of cardiovascular disease: epidemiology and mechanisms.","Gey",2088799,"The antioxidant hypothesis of cardiovascular disease: epidemiology and mechanisms.    Abstract:   Plasma levels of major essential antioxidants were determined in representative random samples of middle-aged men from 16 European study populations which differed up to 6-fold in age-specific mortality from ischaemic heart disease (IHD). In 12 study populations having total plasma cholesterol in the medium range (5.7-6.2 mmol/l) and usual blood pressure, both these classical risk factors lacked a significant correlation to IHD mortality, whereas the absolute level of vitamin E (alpha-tocopherol) showed a strong inverse correlation (r2 = 0.63, P = 0.002). On evaluation of all study populations, cholesterol and diastolic blood pressure had a moderate direct association with IHD, but their importance still remained inferior to that of vitamin E as an inversely associated, presumably protective factor. In stepwise regression and multiple regression analysis, the IHD mortality of the study populations was predictable to 62% by lipid-standardized vitamin E, to 79% by vitamin E and total cholesterol, to 83% after inclusion of lipid-standardized vitamin A (retinol) and to 87% by all the above parameters plus diastolic blood pressure. In conclusion, in the present study the plasma status of vitamin E is the most important factor to explain cross-cultural differences of IHD mortality. This finding is consistent with the hypothesis of the prevention of arteriosclerosis by antioxidant protection against peroxidative lipoprotein modification, but does not exclude additional effects of antioxidant vitamins, e.g. on the cellular or immunological level."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I200,I200)","v":2195481},{"$f":"(LEN($J200) - LEN(SUBSTITUTE(LOWER($J200),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J200) - LEN(SUBSTITUTE(LOWER($J200),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J200) - LEN(SUBSTITUTE(LOWER($J200),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B200:D200)","v":2},1990,"Facial wrinkles. Prevention and nonsurgical correction.","Burke",2195481,"Facial wrinkles. Prevention and nonsurgical correction.    Abstract:   There is no way to age without getting wrinkles. However, patients can be taught how to retard the onset of wrinkles by avoiding unprotected sun exposure, unnecessary facial movements, and certain sleeping positions. Relatively simple non-surgical techniques are available for correction of wrinkles. Small wrinkles can be treated with exfoliation, topical tretinoin (Retin-A), or topical alpha hydroxy acids. Large wrinkles can be improved with implantation of bovine collagen, silicone, or fat extracted from the abdomen or thigh of the patient. Each method is effective when used for the correct indications."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I201,I201)","v":2198038},{"$f":"(LEN($J201) - LEN(SUBSTITUTE(LOWER($J201),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J201) - LEN(SUBSTITUTE(LOWER($J201),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J201) - LEN(SUBSTITUTE(LOWER($J201),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B201:D201)","v":2},1990,"Ethanol-induced lipid peroxidation and oxidative stress in extrahepatic tissues.","Nordmann",2198038,"Ethanol-induced lipid peroxidation and oxidative stress in extrahepatic tissues.    Abstract:   An ethanol-induced oxidative stress is not restricted to the liver, where ethanol is actively oxidized, but can affect various extrahepatic tissues as shown by experimental data obtained in the rat during acute or chronic ethanol intoxication. Most of these data concern the central nervous system, the heart and the testes. An acute ethanol load has been reported to enhance lipid peroxidation in the cerebellum. This is accompanied by an increase in the cytosolic concentration of low-molecular-weight iron derivatives which may contribute to the generation of aggressive free radicals. The ethanol-induced decrease in the main antioxidant systems (superoxide dismutase, alpha-tocopherol, ascorbate and selenium) is a likely contributor to the cerebellar oxidative stress. Most of these disturbances can be prevented by allopurinol administration. Some experimental data support also the occurrence of pro- and anti-oxidant disturbances in the cerebellum and in other regions of the central nervous system after chronic ethanol administration. Chronic ethanol administration enhances lipid peroxidation in the heart. The increased conversion of xanthine dehydrogenase into xanthine oxidase as well as the activation of peroxisomal acyl CoA-oxidase linked to ethanol administration could contribute to the oxidative stress. Chronic ethanol administration elicits in the testes an enhancement in mitochondrial lipid peroxidation and a decrease in the glutathione level, which appear to be correlated to the gross testicular atrophy observed. Vitamin A supplementation attenuates the changes in lipid peroxidation, glutathione and testicular morphology. Whether the reported disturbances are involved in the pathogenesis of the tissue disorders observed in alcoholic patients remains unanswered.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I202,I202)","v":3547011},{"$f":"(LEN($J202) - LEN(SUBSTITUTE(LOWER($J202),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J202) - LEN(SUBSTITUTE(LOWER($J202),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J202) - LEN(SUBSTITUTE(LOWER($J202),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B202:D202)","v":2},1987,"Nevoid basal-cell carcinoma syndrome.","Gorlin",3547011,"Nevoid basal-cell carcinoma syndrome.    Abstract:   The nevoid basal-cell carcinoma syndrome is characterized by major manifestations, such as multiple basal-cell carcinomata, cysts of the jaws, and skeletal--specifically, rib--abnormalities. Findings in 53 patients and a review of the literature document both major and lesser-known manifestations of the disorder. The odontogenic keratocyst, which usually appears during adolescence, has a marked tendency to recur. In addition to the skin tumors, milia, epidermoid cysts, chalazia, comedones, and palmar and plantar pits are frequent. The skin tumors, originally thought to be independent of sun exposure, are more common in sun-exposed areas and are far less frequent and occur at a much later age in blacks than in whites. There is some evidence that radiation of the skin promotes the appearance of skin cancers in this disorder. Unilateral linear nevoid basal-cell carcinomas with comedones may represent postzygotic somatic mutation. A proclivity to other forms of neoplasia exists. Patients with this syndrome have had medulloblastoma, meningioma, ovarian fibroma, ovarian fibrosarcoma, fibrosarcoma of the jaws, cardiac fibroma, fetal rhabdomyoma, and lymphatic or chylous cysts of the mesentery. In addition to the usual modalities of treatment, topical immunotherapy and topical 5-fluorouracil have been used with success. Oral synthetic retinoids, such as 13-cis-retinoic acid, have been used to prevent new lesions from appearing and to arrest the growth of older lesions by inducing differentiation. The independent observations of increased prostaglandin levels associated both with odontogenic keratocyst expansion and aggression of basal cell cancers merit further investigation both as a fundamental cellular mechanism and as a possible basis for treatment (e.g., with antiprostaglandins). The key to pre- and early postnatal diagnosis of the disorder--as well as to an understanding of the basic abnormality--lies in molecular genetics. Prime attention should be given to finding the site of the gene through the use of DNA and other markers."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I203,I203)","v":3516195},{"$f":"(LEN($J203) - LEN(SUBSTITUTE(LOWER($J203),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J203) - LEN(SUBSTITUTE(LOWER($J203),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J203) - LEN(SUBSTITUTE(LOWER($J203),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B203:D203)","v":2},1986,"Hyperlipidaemia due to isotretinoin and etretinate: possible mechanisms and consequences.","Marsden",3516195,"Hyperlipidaemia due to isotretinoin and etretinate: possible mechanisms and consequences.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I204,I204)","v":2871933},{"$f":"(LEN($J204) - LEN(SUBSTITUTE(LOWER($J204),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J204) - LEN(SUBSTITUTE(LOWER($J204),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J204) - LEN(SUBSTITUTE(LOWER($J204),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B204:D204)","v":2},1986,"Risks for hyperlipidemia.","Nestruck",2871933,"Risks for hyperlipidemia.    Abstract:   The predisposition for the development of hyperlipidemia rests almost equally on genetic and environmental factors and their interplay. Because one of the least understood factors is the duration of exposure to risk, the authors have chosen to review here some of the genetic factors and some of the relatively long-term environmental factors, such as diet and drug therapies, that are known to increase the risk of hyperlipidemia and likely the predisposition to cardiovascular disease. Some of the genetic factors and environmental factors such as diet and drug therapies that are known to increase the risk of hyperlipidemia and possibly the predisposition to cardiovascular disease are reviewed. The cholesterol associated with the low-density lipoproteins (LDL), accounting for 60-75% of the plasma levels, is responsible for the powerful and direct relationship which exists between plasma cholesterol and coronary heart disease. Also, the cholesterol that accumulates in atheromatous lesions is derived primarily from plasma LDL. Hyperlipidemia is defined by elevated levels of the plasma levels; the risk for atherosclerosis is associated with the classification types IIa, IIb, III, and possibly IV, a classification system based on phenotypic manifestations of increased lipoprotein fractions. The Lipid Research Clinics Program reports data on plasma lipid and lipoprotein cholesterol distributions of a large-scale screening of white men and women (both with and without sex hormone usage) aged 20-59 years in the US. They found age-related trends for rising triglycerides and cholesterol with differences between the sexes clearly demonstrated. It has been established that normolipemic individuals are not immune to the development of atherosclerosis. The recent focus on the apolipoprotein moieties has revealed a number of normolipemic dyslipoproteinemias associated with tissue lipid infiltration. Multifactorial population studies provide a strong case for the powerful role of the environment, i.e., predominantly dietary intake of total fat, saturated fat, saturated fats, and calories, in hyperlipidemia. According to the Seven Countries Study, populations with higher levels of cholesterol and LDL cholesterol (and increased atherosclerosis) have saturated fat intakes of 10% or more of calories. Migration studies of Japanese populations in Japan and in the US also show the influence of diet. As was shown early on, oral contraceptive (OC) use predisposes to the development of hyperlipidemia. OCs also predispose to other cardiovascular risk factors that, when combined with smoking, bring about a greatly magnified risk for myocardial infarction. Also reviewed in terms of their effect on the lipoprotein profile are antihypertensive therapies, retinoids, and hypolipidemic agents. Regarding genetic predisposition, single-gene mutations in apoproteins, lipoproteins, and some of the enzymes involved in lipoprotein may underlie disorders of hyperlipoproteinemia or hypolipoproteinemia."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I205,I205)","v":27617127},{"$f":"(LEN($J205) - LEN(SUBSTITUTE(LOWER($J205),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J205) - LEN(SUBSTITUTE(LOWER($J205),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J205) - LEN(SUBSTITUTE(LOWER($J205),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B205:D205)","v":1},2015,"Neurodevelopmental Disorders Associated with Abnormal Gene Dosage: Smith-Magenis and Potocki-Lupski Syndromes.","Neira-Fresneda",27617127,"Neurodevelopmental Disorders Associated with Abnormal Gene Dosage: Smith-Magenis and Potocki-Lupski Syndromes.    Abstract:   Smith-Magenis syndrome (SMS) and Potocki-Lupski syndrome (PTLS) are reciprocal contiguous gene syndromes within the well-characterized 17p11.2 region. Approximately 3.6 Mb microduplication of 17p11.2, known as PTLS, represents the mechanistically predicted homologous recombination reciprocal of the SMS microdeletion, both resulting in multiple congenital anomalies. Mouse model studies have revealed that the retinoic acid-inducible 1 gene (RAI1) within the SMS and PTLS critical genomic interval is the dosage-sensitive gene responsible for the major phenotypic features in these disorders. Even though PTLS and SMS share the same genomic region, clinical manifestations and behavioral issues are distinct and in fact some mirror traits may be on opposite ends of a given phenotypic spectrum. We describe the neurobehavioral phenotypes of SMS and PTLS patients during different life phases as well as clinical guidelines for diagnosis and a multidisciplinary approach once diagnosis is confirmed by array comparative genomic hybridization or RAI1 gene sequencing. The main goal is to increase awareness of these rare disorders because an earlier diagnosis will lead to more timely developmental intervention and medical management which will improve clinical outcome."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I206,I206)","v":27390265},{"$f":"(LEN($J206) - LEN(SUBSTITUTE(LOWER($J206),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J206) - LEN(SUBSTITUTE(LOWER($J206),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J206) - LEN(SUBSTITUTE(LOWER($J206),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B206:D206)","v":1},2016,"Molecular aspects of β, β-carotene-9, 10-oxygenase 2 in carotenoid metabolism and diseases.","Wu",27390265,"Molecular aspects of β, β-carotene-9, 10-oxygenase 2 in carotenoid metabolism and diseases.    Abstract:    NlmCategory=UNASSIGNEDCarotenoids, the carotenes and xanthophylls, are essential components in human nutrition. β, β-carotene-9, 10-oxygenase 2 (BCO2), also named as β, β-carotene-9, 10-dioxygenase 2 (BCDO2) catalyzes the asymmetrical cleavage of carotenoids, whereas β, β-carotene-15, 15-monooxygenase (BCMO1) conducts the symmetrical cleavage of pro-vitamin A carotenoids into retinoid. Unlike BCMO1, BCO2 has a broader substrate specificity and has been considered an alternative way to produce vitamin A. In contrast to BCMO1, a cytoplasmic protein, BCO2 is located in the inner mitochondrial membrane. The difference in cellular compartmentalization may reflect the different substrate specificity and physiological functions with respect to BCMO1 and BCO2. The BCO2 gene mutations are proven to be associated with yellow color of skin and fat tissue and milk in livestock. Mutation in intron 2 of BCO2 gene is also supposed to be related to the expression of IL-18, a pro-inflammatory cytokine associated with obesity, cardiovascular diseases, and type 2 diabetes. Further, BCO2 is associated with the development of mitochondrial oxidative stress, macular degeneration, anemia, and hepatic steatosis. This review of the literature will mostly address recent updates regarding the role of BCO2 in carotenoid metabolism, and discuss the potential impacts of BCO2 protein and the mutations in mammalian diseases."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I207,I207)","v":27353840},{"$f":"(LEN($J207) - LEN(SUBSTITUTE(LOWER($J207),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J207) - LEN(SUBSTITUTE(LOWER($J207),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J207) - LEN(SUBSTITUTE(LOWER($J207),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B207:D207)","v":1},2016,"Regulation of the blood-testis barrier.","Stanton",27353840,"Regulation of the blood-testis barrier.    Abstract:    NlmCategory=UNASSIGNEDThe purpose of this review is to describe the endocrine and local testicular factors that contribute to the regulation of the blood-testis barrier (BTB), using information gained from in vivo and in vitro models of BTB formation during/after puberty, and from the maintenance of BTB function during adulthood. In vivo the BTB, in part comprised of tight junctions between adjacent somatic Sertoli cells, compartmentalizes meiotic spermatocytes and post-meiotic spermatids away from the vasculature, and therefore prevents autoantibody production by the immune system against these immunogenic germ cells. This adluminal compartment also features a unique biochemical milieu required for the completion of germ cell development. During the normal process of spermatogenesis, earlier germ cells continually cross into the adluminal compartment, but the regulatory mechanisms and changes in junctional proteins that allow this translocation step without causing a leak remain poorly understood. Recent data describing the roles of FSH and androgen on the regulation of Sertoli cell tight junctions and tight junction proteins will be discussed, followed by an examination of the role of paracrine factors, including members of the TGFβ superfamily (TGFβ3, activin A) and retinoid signalling, as potential mediators of junction assembly and disassembly during the translocation process."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I208,I208)","v":27282881},{"$f":"(LEN($J208) - LEN(SUBSTITUTE(LOWER($J208),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J208) - LEN(SUBSTITUTE(LOWER($J208),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J208) - LEN(SUBSTITUTE(LOWER($J208),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B208:D208)","v":1},2016,"Steroid receptor RNA activator: Biologic function and role in disease.","Liu",27282881,"Steroid receptor RNA activator: Biologic function and role in disease.    Abstract:   Steroid receptor RNA activator (SRA) is a type of long noncoding RNA (lncRNA) which coordinates the functions of various transcription factors, enhances steroid receptor-dependent gene expression, and also serves as a distinct scaffold. The novel, profound and expanded roles of SRA are emerging in critical aspects of coactivation of nuclear receptors (NRs). As a nuclear receptor coactivator, SRA can coactivate androgen receptor (AR), estrogen receptor α (ERα), ERβ, progesterone receptor (PR), glucocorticoid receptor (GR), thyroid hormone receptor and retinoic acid receptor (RAR). Although SRA is one of the least well-understood molecules, increasing studies have revealed that SRA plays a key role in both biological processes, such as myogenesis and steroidogenesis, and pathological changes, including obesity, cardiomyopathy, and tumorigenesis. Furthermore, the SRA-related signaling pathways, such as the mitogen-activated protein kinase (p38 MAPK), Notch and tumor necrosis factor α (TNFα) pathways, play critical roles in the pathogenesis of estrogen-dependent breast cancers. In addition, the most recent data demonstrates that SRA expression may serve as a new prognostic marker in patients with ER-positive breast cancer. Thus, elucidating the molecular mechanisms underlying SRA-mediated functions is important to develop proper novel strategies to target SRA in the diagnosis and treatment of human diseases."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I209,I209)","v":26846756},{"$f":"(LEN($J209) - LEN(SUBSTITUTE(LOWER($J209),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J209) - LEN(SUBSTITUTE(LOWER($J209),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J209) - LEN(SUBSTITUTE(LOWER($J209),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B209:D209)","v":1},2016,"The Pathophysiology of Moyamoya Disease: An Update.","Bang",26846756,"The Pathophysiology of Moyamoya Disease: An Update.    Abstract:   Moyamoya disease (MMD) is a unique cerebrovascular disease characterized by the progressive stenosis of large intracranial arteries and a hazy network of basal collaterals called moyamoya vessels. Because the etiology of MMD is unknown, its diagnosis is based on characteristic angiographic findings. Re-vascularization techniques (e.g., bypass surgery) are used to restore perfusion, and are the primary treatment for MMD. There is no specific treatment to prevent MMD progression. This review summarizes the recent advances in MMD pathophysiology, including the genetic and circulating factors related to disease development. Genetic and environmental factors may play important roles in the development of the vascular stenosis and aberrant angiogenesis in complex ways. These factors include the related changes in circulating endothelial/smooth muscle progenitor cells, cytokines related to vascular remodeling and angiogenesis, and endothelium, such as caveolin which is a plasma membrane protein. With a better understanding of MMD pathophysiology, nonsurgical approaches targeting MMD pathogenesis may be available to stop or slow the progression of this disease. The possible strategies include targeting growth factors, retinoic acid, caveolin-1, and stem cells."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I210,I210)","v":26769782},{"$f":"(LEN($J210) - LEN(SUBSTITUTE(LOWER($J210),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J210) - LEN(SUBSTITUTE(LOWER($J210),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J210) - LEN(SUBSTITUTE(LOWER($J210),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B210:D210)","v":1},2016,"Non-psychotropic medication and risk of suicide or attempted suicide: a systematic review.","Gorton",26769782,"Non-psychotropic medication and risk of suicide or attempted suicide: a systematic review.    Abstract:    OBJECTIVES : To establish which non-psychotropic medications have been assessed in relation to risk of suicide or attempted suicide in observational studies, document reported associations and consider study strengths and limitations.  DESIGN : Systematic review.  METHODS : Four databases (Embase, Medline, PsycINFO and International Pharmaceutical Abstracts) were searched from 1990 to June 2014, and reference lists of included articles were hand-searched. Case-control, cohort and case only studies which reported suicide or attempted suicide in association with any non-psychotropic medication were included.  OUTCOME MEASURES : The outcomes eligible for inclusion were suicide and attempted suicide, as defined by the authors of the included study.  RESULTS : Of 11,792 retrieved articles, 19 were eligible for inclusion. Five studies considered cardiovascular medication and antiepileptics; two considered leukotriene receptor antagonists, isotretinoin and corticosteroids; one assessed antibiotics and another assessed varenicline. An additional study compared multiple medications prescribed to suicide cases versus controls. There was marked heterogeneity in study design, outcome and exposure classification, and control for confounding factors; particularly comorbid mental and physical illness. No increased risk was associated with cardiovascular medications, but associations with other medications remained inconclusive and meta-analysis was inappropriate due to study heterogeneity.  CONCLUSIONS : Whether non-psychotropic medications are associated with increased risk of suicide or attempted suicide remains largely unknown. Robust identification of suicide outcomes and control of comorbidities could improve quantification of risk associated with non-psychotropic medication, beyond that conferred by underlying physical and mental illnesses."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I211,I211)","v":26688184},{"$f":"(LEN($J211) - LEN(SUBSTITUTE(LOWER($J211),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J211) - LEN(SUBSTITUTE(LOWER($J211),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J211) - LEN(SUBSTITUTE(LOWER($J211),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B211:D211)","v":1},2016,"[Thyroid and lipidic dysfunction associated with bexarotene in cutaneous T-cell lymphoma].","Rodriguez Suarez",26688184,"[Thyroid and lipidic dysfunction associated with bexarotene in cutaneous T-cell lymphoma].    Abstract:    BACKGROUND AND OBJECTIVE : Bexarotene is a synthetic selective X receptor rexinoide approved for the systemic treatment of cutaneous T-cell lymphoma. During treatment is very frequent the occurrence of hypothyroidism and severe mixed hyperlipidemia, both are reversibles and dose-dependent adverse events. Increase of triglycerides and LDL-cholesterol level (up to even higher levels have been associated with pancreatitis in some cases) is widely described (as is the case with other retinoids) but decrease in HDL-cholesterol is poored know. We review our experience with the use of bexarotene.  MATERIAL AND METHODS : We present a serie of 3 clinical report of patients treated with bexarotene in whose, in addition to these well-known adverse event, a serious lowering of HDL-cholesterol was observed.  RESULTS : The 3 patients studied had metabolic complications like central hypothyroidism and severe mixed hyperlipidemia; with special emphasis on the sharp fall (mean decreasegt;83%) in the HDL-cholesterol level. Cholesterol lowering medication and substitutive hormonal replacement with levotiroxine resulted in an improvement of the biochimical parameters without reaching the correct goals.  CONCLUSIONS : Bexarotene produce as predictable side effects severe mixed hyperlipidemia with marked decrease in HDL-cholesterol levels and central hypothyroidism, being the both reversible and dose-dependent. A reflection on the possible aetiological mechanisms and implications of this phenomenon are included."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I212,I212)","v":26681795},{"$f":"(LEN($J212) - LEN(SUBSTITUTE(LOWER($J212),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J212) - LEN(SUBSTITUTE(LOWER($J212),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J212) - LEN(SUBSTITUTE(LOWER($J212),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B212:D212)","v":1},2016,"Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects.","Christakos",26681795,"Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects.    Abstract:   1,25-Dihydroxvitamin D3 [1,25(OH)2D3] is the hormonally active form of vitamin D. The genomic mechanism of 1,25(OH)2D3 action involves the direct binding of the 1,25(OH)2D3 activated vitamin D receptor/retinoic X receptor (VDR/RXR) heterodimeric complex to specific DNA sequences. Numerous VDR co-regulatory proteins have been identified, and genome-wide studies have shown that the actions of 1,25(OH)2D3 involve regulation of gene activity at a range of locations many kilobases from the transcription start site. The structure of the liganded VDR/RXR complex was recently characterized using cryoelectron microscopy, X-ray scattering, and hydrogen deuterium exchange. These recent technological advances will result in a more complete understanding of VDR coactivator interactions, thus facilitating cell and gene specific clinical applications. Although the identification of mechanisms mediating VDR-regulated transcription has been one focus of recent research in the field, other topics of fundamental importance include the identification and functional significance of proteins involved in the metabolism of vitamin D. CYP2R1 has been identified as the most important 25-hydroxylase, and a critical role for CYP24A1 in humans was noted in studies showing that inactivating mutations in CYP24A1 are a probable cause of idiopathic infantile hypercalcemia. In addition, studies using knockout and transgenic mice have provided new insight on the physiological role of vitamin D in classical target tissues as well as evidence of extraskeletal effects of 1,25(OH)2D3 including inhibition of cancer progression, effects on the cardiovascular system, and immunomodulatory effects in certain autoimmune diseases. Some of the mechanistic findings in mouse models have also been observed in humans. The identification of similar pathways in humans could lead to the development of new therapies to prevent and treat disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I213,I213)","v":26416507},{"$f":"(LEN($J213) - LEN(SUBSTITUTE(LOWER($J213),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J213) - LEN(SUBSTITUTE(LOWER($J213),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J213) - LEN(SUBSTITUTE(LOWER($J213),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B213:D213)","v":1},2015,"Mitochondrial regulation of macrophage cholesterol homeostasis.","Graham",26416507,"Mitochondrial regulation of macrophage cholesterol homeostasis.    Abstract:   This review explores the relationship between mitochondrial structure and function in the regulation of macrophage cholesterol metabolism and proposes that mitochondrial dysfunction contributes to loss of the elegant homeostatic mechanisms which normally maintain cellular sterol levels within defined limits. Mitochondrial sterol 27-hydroxylase (CYP27A1) can generate oxysterol activators of liver X receptors which heterodimerise with retinoid X receptors, enhancing the transcription of ATP binding cassette transporters (ABCA1, ABCG1, and ABCG4), that can remove excess cholesterol via efflux to apolipoproteins A-1, E, and high density lipoprotein, and inhibit inflammation. The activity of CYP27A1 is regulated by the rate of supply of cholesterol substrate to the inner mitochondrial membrane, mediated by a complex of proteins. The precise identity of this dynamic complex remains controversial, even in steroidogenic tissues, but may include steroidogenic acute regulatory protein and the 18 kDa translocator protein, together with voltage-dependent anion channels, ATPase AAA domain containing protein 3A, and optic atrophy type 1 proteins. Certainly, overexpression of StAR and TSPO proteins can enhance macrophage cholesterol efflux to apoA-I and/or HDL, while perturbations in mitochondrial function, or changes in the expression of mitochondrial fusion proteins, alter the efficiency of cholesterol efflux. Molecules which can sustain or improve mitochondrial function or increase the activity of the protein complex involved in cholesterol transfer may have utility in resolving the problem of dysregulated macrophage cholesterol homeostasis, a condition which may contribute to inflammation, atherosclerosis, nonalcoholic steatohepatitis, osteoblastic bone resorption, and some disorders of the central nervous system."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I214,I214)","v":26411415},{"$f":"(LEN($J214) - LEN(SUBSTITUTE(LOWER($J214),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J214) - LEN(SUBSTITUTE(LOWER($J214),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J214) - LEN(SUBSTITUTE(LOWER($J214),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B214:D214)","v":1},2015,"Peroxisome Proliferator-Activated Receptor α in Lipid Metabolism and Atherosclerosis.","Yu",26411415,"Peroxisome Proliferator-Activated Receptor α in Lipid Metabolism and Atherosclerosis.    Abstract:   Atherosclerosis is a chronic inflammatory disease with deposition of excessive cholesterol in the arterial intima. Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor that can activate or inhibit the expression of many target genes by forming a heterodimer complex with the retinoid X receptor. Activation of PPARα plays an important role in the metabolism of multiple lipids, including high-density lipoprotein, cholesterol, low-density lipoprotein, triglyceride, phospholipid, bile acids, and fatty acids. Increased PPARα activity also mitigates atherosclerosis by blocking macrophage foam cell formation, vascular inflammation, vascular smooth muscle cell proliferation and migration, plaque instability, and thrombogenicity. Clinical use of synthetic PPARα agonist fibrate improved dyslipidemia and attenuated atherosclerosis-related disease risk. This review summarizes PPARα in lipid and lipoprotein metabolism and atherosclerosis, and also highlights its potential therapeutic benefits."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I215,I215)","v":26168011},{"$f":"(LEN($J215) - LEN(SUBSTITUTE(LOWER($J215),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J215) - LEN(SUBSTITUTE(LOWER($J215),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J215) - LEN(SUBSTITUTE(LOWER($J215),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B215:D215)","v":1},2015,"A Review on Factors Influencing Bioaccessibility and Bioefficacy of Carotenoids.","Priyadarshani",26168011,"A Review on Factors Influencing Bioaccessibility and Bioefficacy of Carotenoids.    Abstract:    NlmCategory=UNASSIGNEDVitamin A deficiency is one of the most prevalent deficiency disorders in the world. As shown by many studies plant food based approaches have a real potential on prevention of vitamin A deficiency in a sustainable way. Carotenoids are important as precursors of vitamin A as well as for prevention of cancers, coronary heart diseases, age-related macular degeneration, cataract etc. Bioaccessibility and bioefficacy of carotenoids are known to be influenced by numerous factors including dietary factors such as fat, fiber, dosage of carotenoid, location of carotenoid in the plant tissue, heat treatment, particle size of food, carotenoid species, interactions among carotenoids, isomeric form and molecular linkage and subject characteristics. Therefore even when carotenoids are found in high quantities in plant foods their utilization may be unsatisfactory because some factors are known to interfere as negative effectors."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I216,I216)","v":25858547},{"$f":"(LEN($J216) - LEN(SUBSTITUTE(LOWER($J216),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J216) - LEN(SUBSTITUTE(LOWER($J216),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J216) - LEN(SUBSTITUTE(LOWER($J216),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B216:D216)","v":1},2015,"Apolipoprotein M.","Ren",25858547,"Apolipoprotein M.    Abstract:   Apolipoprotein M (ApoM) is a novel apolipoprotein that was discovered in 1999 and is bound primarily to high-density lipoproteins (HDLs) in the plasma. Multiple factors may influence its expression at both the post-transcriptional and the transcriptional levels both in vivo and ex vivo as follows: hepatocyte nuclear factor-1α, 4α (HNF-1α, 4α), liver receptor homolog-1 (LRH-1), forkhead box A2 (Foxa2) and platelet activating factor (PAF) upregulate its expression; liver X receptor (LXR), retinoid X receptor (RXR), farnesoid X receptor (FXR), small heterodimer partner (SHP) and the majority of cytokines downregulate its expression. However, mechanisms underlying these processes remain unknown. Structurally, there exists a characterized hydrophobic binding pocket within the apoM protein, which enables it to bind functional lipids such as Sphingosine-1-Phosphate (S1P). Functionally, it facilitates the formation of preβ-HDL and enhances an avalanche of atheroprotective effects exerted by HDL. Moreover, in patients with diabetes, the levels of plasma apoM may decrease, whereas the augmentation of apoM decreases plasma glucose levels and magnifies the secretion of insulin. This article offers a panorama of the progress made in the research regarding the characteristics of apoM, particularly the regulation of its expression and its functions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I217,I217)","v":25722444},{"$f":"(LEN($J217) - LEN(SUBSTITUTE(LOWER($J217),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J217) - LEN(SUBSTITUTE(LOWER($J217),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J217) - LEN(SUBSTITUTE(LOWER($J217),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B217:D217)","v":1},2015,"Are there genetic paths common to obesity, cardiovascular disease outcomes, and cardiovascular risk factors?","Rankinen",25722444,"Are there genetic paths common to obesity, cardiovascular disease outcomes, and cardiovascular risk factors?    Abstract:   Clustering of obesity, coronary artery disease, and cardiovascular disease risk factors is observed in epidemiological studies and clinical settings. Twin and family studies have provided some supporting evidence for the clustering hypothesis. Loci nearest a lead single nucleotide polymorphism (SNP) showing genome-wide significant associations with coronary artery disease, body mass index, C-reactive protein, blood pressure, lipids, and type 2 diabetes mellitus were selected for pathway and network analyses. Eighty-seven autosomal regions (181 SNPs), mapping to 56 genes, were found to be pleiotropic. Most pleiotropic regions contained genes associated with coronary artery disease and plasma lipids, whereas some exhibited coaggregation between obesity and cardiovascular disease risk factors. We observed enrichment for liver X receptor (LXR)/retinoid X receptor (RXR) and farnesoid X receptor/RXR nuclear receptor signaling among pleiotropic genes and for signatures of coronary artery disease and hepatic steatosis. In the search for functionally interacting networks, we found that 43 pleiotropic genes were interacting in a network with an additional 24 linker genes. ENCODE (Encyclopedia of DNA Elements) data were queried for distribution of pleiotropic SNPs among regulatory elements and coding sequence variations. Of the 181 SNPs, 136 were annotated to ≥ 1 regulatory feature. An enrichment analysis found over-representation of enhancers and DNAse hypersensitive regions when compared against all SNPs of the 1000 Genomes pilot project. In summary, there are genomic regions exerting pleiotropic effects on cardiovascular disease risk factors, although only a few included obesity. Further studies are needed to resolve the clustering in terms of DNA variants, genes, pathways, and actionable targets."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I218,I218)","v":25563353},{"$f":"(LEN($J218) - LEN(SUBSTITUTE(LOWER($J218),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J218) - LEN(SUBSTITUTE(LOWER($J218),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J218) - LEN(SUBSTITUTE(LOWER($J218),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B218:D218)","v":1},2015,"Androgen receptor in human endothelial cells.","Torres-Estay",25563353,"Androgen receptor in human endothelial cells.    Abstract:   Androgen receptor (AR) is a ligand-inducible transcription factor, and a member of the steroid-thyroid-retinoid receptor superfamily, that mediates the biological effects of androgens in a wide range of physiological and pathological processes. AR expression was identified in vascular cells nearly 20 years ago, and recent research has shown that AR mediates a variety of actions of androgens in endothelial and vascular smooth muscle cells. In this mini-review, we review evidence indicating the importance of AR in human endothelial cell (HUVEC) homeostatic and pathogenic processes. Although a role for AR in the modulation of HUVEC biology is evident, the molecular mechanisms by which AR regulates HUVEC homeostasis and disease processes are not fully understood. Understanding these mechanisms could provide critical insights into the processes of pathogenesis of diseases ranging from cardiovascular disease to cancer that are major causes of human morbidity and mortality."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I219,I219)","v":24863141},{"$f":"(LEN($J219) - LEN(SUBSTITUTE(LOWER($J219),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J219) - LEN(SUBSTITUTE(LOWER($J219),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J219) - LEN(SUBSTITUTE(LOWER($J219),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B219:D219)","v":1},2014,"The role of vitamin supplementation in the prevention of cardiovascular disease events.","Desai",24863141,"The role of vitamin supplementation in the prevention of cardiovascular disease events.    Abstract:   The production, sale, and consumption of multiple vitamins is a multibillion-dollar industry. Most Americans take some form of supplement ostensibly for prevention of cardiovascular disease. It has been claimed that vitamin A retards atherogenesis. Vitamin C is an antioxidant and is thought to possibly decrease free radical-induced endothelial injury, which can lead to atherosclerotic plaque formation. Vitamin E has been extensively studied for its possible effects on platelet function as well as inhibition of foam-cell formation. Low levels of vitamin D have been thought to negatively impact myocardial structure and increase the risk for cardiovascular events. Increased intake of vitamin B6, B12, and folate has been associated with reduction of homocysteine levels; elevated homocysteine blood levels have been associated with the occurrence of stroke, heart attack, and cardiovascular death. The purpose of this study was to review the currently available literature for vitamin supplementation with respect to prevention of cardiovascular disease. Unfortunately, the current evidence suggests no benefit exists with vitamin supplementation in the general US population. Further research is needed to evaluate whether there are specific populations that might benefit from vitamin supplementation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I220,I220)","v":24844148},{"$f":"(LEN($J220) - LEN(SUBSTITUTE(LOWER($J220),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J220) - LEN(SUBSTITUTE(LOWER($J220),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J220) - LEN(SUBSTITUTE(LOWER($J220),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B220:D220)","v":1},2014,"ATP-binding cassette transporter A1: from metabolism to neurodegeneration.","Koldamova",24844148,"ATP-binding cassette transporter A1: from metabolism to neurodegeneration.    Abstract:   ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol efflux to lipid-free apolipoprotein A-I (apoA-I) and apolipoprotein E (apoE). ABCA1 is an essential regulator of high density lipoproteins (HDL) and reverse cholesterol transport - a role that determines its importance for atherosclerosis. Over the last 10 years studies have provided convincing evidence that ABCA1, via its control of apoE lipidation, also has a role in Alzheimers disease (AD). A series of reports have revealed a significant impact of ABCA1 on Aβ deposition and clearance in AD model mice, as well as an association of common and rare ABCA1 gene variants with the risk for AD. Since APOE is the major genetic risk factor for late onset AD, the regulation of apoE level or its functionality by ABCA1 may prove significant for AD pathogenesis. ABCA1 is transcriptionally regulated by Liver X Receptors (LXR) and Retinoic X Receptors (RXR) which provides a starting point for drug discovery and development of synthetic LXR and RXR agonists for treatment of metabolic and neurodegenerative disorders. This review summarizes the recent results of research on ABCA1, particularly relevant to atherosclerosis and AD."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I221,I221)","v":24695022},{"$f":"(LEN($J221) - LEN(SUBSTITUTE(LOWER($J221),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J221) - LEN(SUBSTITUTE(LOWER($J221),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J221) - LEN(SUBSTITUTE(LOWER($J221),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B221:D221)","v":1},2014,"Liver X receptor: a cardinal target for atherosclerosis and beyond.","Parikh",24695022,"Liver X receptor: a cardinal target for atherosclerosis and beyond.    Abstract:   The nuclear receptor liver X receptor [LXR] is activated by endogenous oxidized derivatives of cholesterol. It constitutes a critical receptor in the regulation of various physiological functions related to the development of metabolic and cardiovascular diseases, such as atherosclerosis and diabetes, as well as various other disorders. Both isoforms of LXR, LXRα [NR1H3] and LXRβ [NR1H2], form heterodimers with the isoforms of the retinoid X receptor [RXR], which then regulate the gene expression by binding to DNA sequences associated with target genes. LXR acts as a cholesterol sensor in response to an increased concentration of cholesterol in cells and induces the transcription of genes that protect cells from cholesterol overload. LXRs play numerous roles in controlling cholesterol homeostasis via their actions on bile acid synthesis and metabolism/excretion, reverse cholesterol transport and cholesterol absorption/excretion in the intestines. Therefore, these receptors show great potential as pharmacological targets for anti-atherosclerotic activities. Recent discoveries have also emphasized the important involvement of LXRs in the pathogenesis of diabetes, Alzheimers disease, inflammation, adrenal steroid synthesis, skin aging and male fertility. However, LXR activation has also been shown to stimulate lipogenesis via sterol regulatory element binding protein-1c, leading to liver steatosis and hypertriglyceridemia. This review summarizes recent scientific discoveries and the biological actions of LXR with a special focus on the involvement of this type of receptor in important diseases and conditions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I222,I222)","v":24664180},{"$f":"(LEN($J222) - LEN(SUBSTITUTE(LOWER($J222),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J222) - LEN(SUBSTITUTE(LOWER($J222),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J222) - LEN(SUBSTITUTE(LOWER($J222),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B222:D222)","v":1},2014,"Brain metabolite clearance: impact on Alzheimers disease.","Zolezzi",24664180,"Brain metabolite clearance: impact on Alzheimers disease.    Abstract:   Alzheimers Disease (AD) is a complex neurodegenerative disorder often associated with aging and characterized by several critical molecular changes that take place in the brain. Among the molecular hallmarks of AD, increased levels of amyloid β-peptide (Aβ) and the subsequent Aβ-derived damage are the most well-studied factors; however, despite the large amounts of effort and resources devoted to the study of AD and AD pathophysiology, the scientific community still awaits therapeutic alternatives capable of ensuring a better outcome for AD patients. In 2012, Cramer et al. (Science 335:1503-1506 2012) astonished the scientific community by rescuing behavioral and cognitive impairments in AD mouse models via oral administration of bexarotene, a drug used to treat some types of skin cancer. Moreover, these authors demonstrated that bexarotene, a retinoid X receptor (RXR) agonist, exerts major effects on Aβ levels, mainly through increased apolipoprotein E (ApoE) expression. Apart from the valid questions addressed in Cramers work, only a few attempts have been made to explain the effects of bexarotene. Most of these explanations have been solely based on the ability of bexarotene to reduce Aβ levels and not on the mechanisms that lead to such a reduction. Although it is well known that an imbalance in the Aβ production/excretion rate is the basis of increased Aβ levels in AD, no further explanations have been proposed to address the potential involvement of the blood-brain barrier (BBB), a critical Aβ-clearance structure, in the bexarotene-mediated effects. Moreover, no attempt has been made to explain how the different effects observed after bexarotene administration are connected to each other. Based on current information and on our own experience with nuclear receptors (NR), we offer new perspectives on the mechanisms of bexarotene action, which should help to improve our knowledge of NRs."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I223,I223)","v":24568879},{"$f":"(LEN($J223) - LEN(SUBSTITUTE(LOWER($J223),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J223) - LEN(SUBSTITUTE(LOWER($J223),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J223) - LEN(SUBSTITUTE(LOWER($J223),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B223:D223)","v":1},2014,"Innate immune recognition of respiratory syncytial virus infection.","Kim",24568879,"Innate immune recognition of respiratory syncytial virus infection.    Abstract:   Respiratory syncytial virus (RSV) is the leading cause of respiratory infection in infants and young children. Severe clinical manifestation of RSV infection is a bronchiolitis, which is common in infants under six months of age. Recently, RSV has been recognized as an important cause of respiratory infection in older populations with cardiovascular morbidity or immunocompromised patients. However, neither a vaccine nor an effective antiviral therapy is currently available. Moreover, the interaction between the host immune system and the RSV pathogen during an infection is not well understood. The innate immune system recognizes RSV through multiple mechanisms. The first innate immune RSV detectors are the pattern recognition receptors (PRRs), including toll-like receptors (TLRs), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), and nucleotide-biding oligomerization domain (NOD)-like receptors (NLRs). The following is a review of studies associated with various PRRs that are responsible for RSV virion recognition and subsequent induction of the antiviral immune response during RSV infection."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I224,I224)","v":24507848},{"$f":"(LEN($J224) - LEN(SUBSTITUTE(LOWER($J224),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J224) - LEN(SUBSTITUTE(LOWER($J224),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J224) - LEN(SUBSTITUTE(LOWER($J224),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B224:D224)","v":1},2014,"New drug therapies for COPD.","Ross",24507848,"New drug therapies for COPD.    Abstract:   Clinical trials with new drugs for chronic obstructive pulmonary disease (COPD) have been performed. Viruses exacerbate COPD and bacteria may play a part in severe COPD; therefore, antibiotic and antiviral approaches have a sound rationale. Antiinflammatory approaches have been studied. Advances in understanding the molecular basis of other processes have resulted in novel drugs to target reactive oxidant species, mucus, proteases, fibrosis, cachexia, and muscle wasting, and accelerated aging. Studies with monoclonal antibodies have been disappointing, highlighting the tendency for infections and malignancies during treatment. Promising future directions are lung regeneration with retinoids and stem cells."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I225,I225)","v":26237385},{"$f":"(LEN($J225) - LEN(SUBSTITUTE(LOWER($J225),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J225) - LEN(SUBSTITUTE(LOWER($J225),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J225) - LEN(SUBSTITUTE(LOWER($J225),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B225:D225)","v":1},2014,"The Roles of Vitamin A in the Regulation of Carbohydrate, Lipid, and Protein Metabolism.","Chen",26237385,"The Roles of Vitamin A in the Regulation of Carbohydrate, Lipid, and Protein Metabolism.    Abstract:   Currently, two-thirds of American adults are overweight or obese. This high prevalence of overweight/obesity negatively affects the health of the population, as obese individuals tend to develop several chronic diseases, such as type 2 diabetes and cardiovascular diseases. Due to obesitys impact on health, medical costs, and longevity, the rise in the number of obese people has become a public health concern. Both genetic and environmental/dietary factors play a role in the development of metabolic diseases. Intuitively, it seems to be obvious to link over-nutrition to the development of obesity and other metabolic diseases. However, the underlying mechanisms are still unclear. Dietary nutrients not only provide energy derived from macronutrients, but also factors such as micronutrients with regulatory roles. How micronutrients, such as vitamin A (VA; retinol), regulate macronutrient homeostasis is still an ongoing research topic. As an essential micronutrient, VA plays a key role in the general health of an individual. This review summarizes recent research progress regarding VAs role in carbohydrate, lipid, and protein metabolism. Due to the large amount of information regarding VA functions, this review focusses on metabolism in metabolic active organs and tissues. Additionally, some perspectives for future studies will be provided."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I226,I226)","v":24350319},{"$f":"(LEN($J226) - LEN(SUBSTITUTE(LOWER($J226),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J226) - LEN(SUBSTITUTE(LOWER($J226),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J226) - LEN(SUBSTITUTE(LOWER($J226),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B226:D226)","v":1},2013,"Psoriasis.","Burfield",24350319,"Psoriasis.    Abstract:   Psoriasis is a chronic, immune-mediated inflammatory skin disease affecting 1.3-2.2% of the UK population.1 Most commonly, psoriasis is characterised by well-demarcated, red plaques with adherent scale with a predilection for the scalp and extensor surfaces of the limbs. However, the effects of psoriasis go far beyond a patients skin and may result in a degree of disability and impaired quality of life similar to that of other major medical conditions, such as cancer and heart disease. First-line therapies for most patients are topical treatments such as topical corticosteroids and vitamin D analogues. For those with more severe or treatment-resistant disease, second- or third-line therapies include phototherapy, systemic therapies such as methotrexate and more recently biologic therapies such as tumour necrosis factor (TNF) inhibitors. These therapeutic modalities are proven to be highly effective; however, the potential for long-term toxicity needs to be considered. Aside from the visible skin disease, psoriasis is also increasingly recognised to have important systemic manifestations. Psoriatic arthritis has long been established as an associated condition and, more recently, it has emerged that psoriasis is also associated with an increased risk of inflammatory bowel disease, cardiovascular disease and the metabolic syndrome. Both National Institute for Health and Care Excellence (NICE)2 and Scottish Intercollegiate Guidelines Network (SIGN)3 have recently published guidelines for the assessment and management of psoriasis which highlight the need for regular assessment in order to detect the development of arthritis and the presence of other co-morbidities such as obesity, diabetes, dyslipidaemia and hypertension."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I227,I227)","v":24184141},{"$f":"(LEN($J227) - LEN(SUBSTITUTE(LOWER($J227),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J227) - LEN(SUBSTITUTE(LOWER($J227),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J227) - LEN(SUBSTITUTE(LOWER($J227),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B227:D227)","v":1},2014,"From the Medical Board of the National Psoriasis Foundation: The risk of cardiovascular disease in individuals with psoriasis and the potential impact of current therapies.","Hugh",24184141,"From the Medical Board of the National Psoriasis Foundation: The risk of cardiovascular disease in individuals with psoriasis and the potential impact of current therapies.    Abstract:    BACKGROUND : Many studies have identified cardiovascular risk factors in patients with psoriasis. Some psoriasis therapies may increase cardiovascular disease (CVD) and others may decrease CVD.  OBJECTIVE : We reviewed the literature to define the impact of common psoriasis therapies on cardiovascular measures and outcomes.  RESULTS : Phototherapy has no major cardiovascular impact and may reduce levels of proinflammatory cytokines. Acitretin increases serum lipids and triglycerides, but has not been shown to increase cardiovascular risk. Cyclosporine A increases blood pressure, serum triglycerides, and total cholesterol. Methotrexate is associated with a decreased risk of CVD morbidity and mortality. Among the biologics, data for tumor necrosis factor inhibitors suggest an overall reduction in cardiovascular events. Most data on short-term ustekinumab use suggest no effect on major adverse cardiovascular events, however some authorities remain concerned. Nevertheless, ustekinumab use over a 4-year period shows a decrease in major adverse cardiovascular events when compared both with the general US population and with psoriatics in Great Britain.  LIMITATIONS : Most studies lack the power and randomization of large clinical trials and long-term follow-up periods. In addition, the increased risk of CVD associated with psoriasis itself is a confounding factor.  CONCLUSION : Some therapies for moderate to severe psoriasis, including methotrexate and tumor necrosis factor inhibitors, may reduce cardiovascular events in psoriatic patients. Ustekinumab appears to be neutral but there may be a long-term benefit. Appropriate patient counseling and selection and clinical follow-up are necessary to maximize safety with these agents. Further long-term study is necessary to quantify the benefits and risks associated with biologic therapies."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I228,I228)","v":23965907},{"$f":"(LEN($J228) - LEN(SUBSTITUTE(LOWER($J228),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J228) - LEN(SUBSTITUTE(LOWER($J228),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J228) - LEN(SUBSTITUTE(LOWER($J228),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B228:D228)","v":1},2014,"Effect of the vegetarian diet on non-communicable diseases.","Li",23965907,"Effect of the vegetarian diet on non-communicable diseases.    Abstract:   A vegetarian diet generally includes plenty of vegetables and fruits, which are rich in phytochemicals, antioxidants, fiber, magnesium, vitamins C and E, Fe³⁺, folic acid and n-6 polyunsaturated fatty acid (PUFA), and is low in cholesterol, total fat and saturated fatty acid, sodium, Fe²⁺, zinc, vitamin A, B₁₂ and D, and especially n-3 PUFA. Mortality from all-cause, ischemic heart disease, and circulatory and cerebrovascular diseases was significantly lower in vegetarians than in omnivorous populations. Compared with omnivores, the incidence of cancer and type 2 diabetes was also significantly lower in vegetarians. However, vegetarians have a number of increased risk factors for non-communicable diseases such as increased plasma homocysteine, mean platelet volume and platelet aggregability compared with omnivores, which are associated with low intake of vitamin B₁₂ and n-3 PUFA. Based on the present data, it would seem appropriate for vegetarians to carefully design their diet, specifically focusing on increasing their intake of vitamin B₁₂ and n-3 PUFA to further reduce already low mortality and morbidity from non-communicable diseases."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I229,I229)","v":23851159},{"$f":"(LEN($J229) - LEN(SUBSTITUTE(LOWER($J229),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J229) - LEN(SUBSTITUTE(LOWER($J229),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J229) - LEN(SUBSTITUTE(LOWER($J229),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B229:D229)","v":1},2013,"Impairment of autophagy: from hereditary disorder to drug intoxication.","Aki",23851159,"Impairment of autophagy: from hereditary disorder to drug intoxication.    Abstract:   At first, the molecular mechanism of autophagy was unveiled in a unicellular organism Saccharomyces cerevisiae (budding yeast), followed by the discovery that the basic mechanism of autophagy is conserved in multicellular organisms including mammals. Although autophagy was considered to be a non-selective bulk protein degradation system to recycle amino acids during periods of nutrient starvation, it is also believed to be an essential mechanism for the selective elimination of proteins/organelles that are damaged under pathological conditions. Research advances made using autophagy-deficient animals have revealed that impairments of autophagy often underlie the pathogenesis of hereditary disorders such as Danon, Parkinsons, Alzheimers, and Huntingtons diseases, and amyotrophic lateral sclerosis. On the other hand, there are many reports that drugs and toxicants, including arsenic, cadmium, paraquat, methamphetamine, and ethanol, induce autophagy during the development of their toxicity on many organs including heart, brain, lung, kidney, and liver. Although the question as to whether autophagic machinery is involved in the execution of cell death or not remains controversial, the current view of the role of autophagy during cell/tissue injury is that it is an important, often essential, cytoprotective reaction; disturbances in cytoprotective autophagy aggravate cell/tissue injuries. The purpose of this review is to provide (1) a gross summarization of autophagy processes, which are becoming more important in the field of toxicology, and (2) examples of important studies reporting the involvement of perturbations in autophagy in cell/tissue injuries caused by acute as well as chronic intoxication."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I230,I230)","v":23363754},{"$f":"(LEN($J230) - LEN(SUBSTITUTE(LOWER($J230),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J230) - LEN(SUBSTITUTE(LOWER($J230),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J230) - LEN(SUBSTITUTE(LOWER($J230),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B230:D230)","v":1},2012,"[Thrombosis of the cerebral veins and sinuses in acute promyelocytic leukemia after all-trans retinoic acid treatment: a case report and literature review].","Song",23363754,"[Thrombosis of the cerebral veins and sinuses in acute promyelocytic leukemia after all-trans retinoic acid treatment: a case report and literature review].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I231,I231)","v":23325835},{"$f":"(LEN($J231) - LEN(SUBSTITUTE(LOWER($J231),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J231) - LEN(SUBSTITUTE(LOWER($J231),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J231) - LEN(SUBSTITUTE(LOWER($J231),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B231:D231)","v":1},2013,"Essentials of Th17 cell commitment and plasticity.","Muranski",23325835,"Essentials of Th17 cell commitment and plasticity.    Abstract:   CD4(+) T helper (Th) cells exist in a variety of epigenetic states that determine their function, phenotype, and capacity for persistence. These polarization states include Th1, Th2, Th17, and Foxp3(+) T regulatory cells, as well as the more recently described T follicular helper, Th9, and Th22 cells. Th17 cells express the master transcriptional regulator retinoic acid-related orphan receptor γ thymus and produce canonical interleukin (IL)-17A and IL-17F cytokines. Th17 cells display a great degree of context-dependent plasticity, as they are capable of acquiring functional characteristics of Th1 cells. This late plasticity may contribute to the protection against microbes, plays a role in the development of autoimmunity, and is necessary for antitumor activity of Th17 cells in adoptive cell transfer therapy models. Moreover, plasticity of this subset is associated with higher in vivo survival and self-renewal capacity and less senescence than Th1 polarized cells, which have less plasticity and more phenotypic stability. New findings indicate that subset polarization of CD4(+) T cells not only induces characteristic patterns of surface markers and cytokine production but also has a maturational aspect that affects a cells ability to survive, respond to secondary stimulation, and form long-term immune memory."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I232,I232)","v":23266518},{"$f":"(LEN($J232) - LEN(SUBSTITUTE(LOWER($J232),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J232) - LEN(SUBSTITUTE(LOWER($J232),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J232) - LEN(SUBSTITUTE(LOWER($J232),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B232:D232)","v":1},2013,"Thrombosis in acute promyelocytic leukemia.","Rashidi",23266518,"Thrombosis in acute promyelocytic leukemia.    Abstract:    INTRODUCTION : Compared to bleeding, major thromboses are a less commonly encountered problem in acute promyelocytic leukemia (APL), and our knowledge about the epidemiology of major thromboses in APL stems mainly from individual case reports. The purpose of this study was to provide a better understanding of the epidemiology of APL-related thrombosis as a first step towards developing preventive strategies.  MATERIALS AND METHODS : We report a rare case of catastrophic acute myocardial infarction in a patient with APL while she developed the all-trans retinoic acid (ATRA) syndrome. We describe the pathogenesis of APL-related thrombosis and review all previously reported cases of major thromboses in APL.  RESULTS : We found 94 cases of major thromboses in patients with APL. Both genders were almost equally affected. More than 80% of events occurred before or during induction therapy with deep vein thrombosis/pulmonary embolism (DVT/PE), cardiac events, and cerebrovascular accidents (CVA) constituting more than 75% of all cases. Arterial events were slightly more common than venous events. Only 2 arterial events occurred after completion of induction therapy. Thrombosis was associated with life-threatening hemorrhage in about 15%, significant coagulative defects in about 50%, and ATRA syndrome in about 13% of cases. Cardiac thrombotic events, DVT/PE, and CVA were associated with ATRA syndrome in 24%, 4.5%, and 5% of cases, respectively (p=0.09). None of the observed trends and associations reached statistical significance.  CONCLUSIONS : This review advances our understanding of the epidemiology of major thromboses in APL. With accumulation of more cases in the literature, some of our results may become statistically significant."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I233,I233)","v":23214308},{"$f":"(LEN($J233) - LEN(SUBSTITUTE(LOWER($J233),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J233) - LEN(SUBSTITUTE(LOWER($J233),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J233) - LEN(SUBSTITUTE(LOWER($J233),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B233:D233)","v":1},2012,"Antioxidant vitamins in atherosclerosis--animal experiments and clinical studies.","Ozkanlar",23214308,"Antioxidant vitamins in atherosclerosis--animal experiments and clinical studies.    Abstract:   Atherosclerotic heart diseases are universal problems in modern society. Oxidative damage to lipids is a primary cause of atherosclerosis. There are many choices for treatment, but no definite recommendations to prevent the occurrence of the disease. There is a relationship between atherosclerotic risk factors and increased vascular production of reactive oxygen species (ROS). Oxidized low-density lipoproteins (LDL) and ROS may directly cause endothelial dysfunction by reducing endothelial nitric oxide (NO) bioavailability. Vitamin E can to some degree prevent the consequences of oxidized LDL, and vitamin C provides NO synthase activity. Although prolonged use of vitamin A, C, and E supplementation in pharmaceutical forms has been proven to be effective in preventing atherosclerosis in animal experiments, this has not yet been demonstrated in clinical trials with human beings. It should be taken into account that the evidence has been gathered from young/adult experimental animals with early stages of arthrosclerosis and from in-vitro studies, while most of the clinical trials have involved older patients with late stages of the disease. Prolonged use of vitamins in the diet has not yet been recommended in human beings. There is some indication that a diet rich in antioxidant fruit and vegetables may be beneficial in the prevention of cardiovascular events."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I234,I234)","v":23175346},{"$f":"(LEN($J234) - LEN(SUBSTITUTE(LOWER($J234),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J234) - LEN(SUBSTITUTE(LOWER($J234),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J234) - LEN(SUBSTITUTE(LOWER($J234),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B234:D234)","v":1},2012,"[Morphogenesis, structure and properties of lymphatic vessels].","Ratajska",23175346,"[Morphogenesis, structure and properties of lymphatic vessels].    Abstract:   In this paper, we present literature results related to structure and various manners of lymphatic vessel formation during embryonic development and in pathological events, such as tumorigenesis, wound healing, and other diseases. The functions of the lymphatic system include the collection of fluids that enter tissues from the circulation, absorption of lipids and lipid-soluble vitamins from the intestine and their subsequent transport, participation in antigen, dendritic cell, and lymphocyte migration. The lymphatic system is also a route for tumor cell and inflammatory cell transport. Native lymphatic capillaries differ from blood capillaries by having an irregular lumen, a discontinuous basement membrane, absence of pericytes, and a strong anchorage of their endothelial cells to the extracellular matrix via microfibrils built of emilin and fibrillin. Lymphatic endothelial cells express surface antigens such as Lyve-1, podoplanin, VEGFR3 (Flk4) and transcription factor Prox-1, as well as molecules which are common for blood endothelial cells and lymphatic endothelial cells (CD31, CD34, Flk-1, Tie-1, Tie-2, neuropilin 2). Lymphatic vessel formation during embryonic development starts with the occurrence of lymphatic sacs sprouting from systemic jugular veins and/or by co-option of lymphangioblasts or hematopoietic-derived cells. It can also proceed by dedifferentiation of venous endothelial cells after their detachment from the venous system, migration to the target places within the body and assembly in the lymphatic lumen. Mechanisms of lymphatic vessel formation during embryonic development and in pathological conditions, such as tumorigenesis, wound healing, and metastasis, is regulated by a plethora of growth factors and molecules, among which the most important are VEGF-C, VEGF-D, HGF, FGF, retinoic acid, IL-3, and IL-7. Macrophages and cells bearing CD45 phenotype seem to take part in the formation of lymphatics. Macrophages might act as a source of growth factors and/or as modulators playing a role in vessel caliber regulation during lymphangiogenesis. We discuss the most important diseases of the lymphatic system, their molecular basis and tumors derived from lymphatic vessels. "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I235,I235)","v":22782502},{"$f":"(LEN($J235) - LEN(SUBSTITUTE(LOWER($J235),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J235) - LEN(SUBSTITUTE(LOWER($J235),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J235) - LEN(SUBSTITUTE(LOWER($J235),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B235:D235)","v":1},2013,"Molecular mechanisms of vitamin D action.","Haussler",22782502,"Molecular mechanisms of vitamin D action.    Abstract:   The hormonal metabolite of vitamin D, 1α,25-dihydroxyvitamin D(3) (1,25D), initiates biological responses via binding to the vitamin D receptor (VDR). When occupied by 1,25D, VDR interacts with the retinoid X receptor (RXR) to form a heterodimer that binds to vitamin D responsive elements in the region of genes directly controlled by 1,25D. By recruiting complexes of either coactivators or corepressors, ligand-activated VDR-RXR modulates the transcription of genes encoding proteins that promulgate the traditional functions of vitamin D, including signaling intestinal calcium and phosphate absorption to effect skeletal and calcium homeostasis. Thus, vitamin D action in a particular cell depends upon the metabolic production or delivery of sufficient concentrations of the 1,25D ligand, expression of adequate VDR and RXR coreceptor proteins, and cell-specific programming of transcriptional responses to regulate select genes that encode proteins that function in mediating the effects of vitamin D. For example, 1,25D induces RANKL, SPP1 (osteopontin), and BGP (osteocalcin) to govern bone mineral remodeling; TRPV6, CaBP(9k), and claudin 2 to promote intestinal calcium absorption; and TRPV5, klotho, and Npt2c to regulate renal calcium and phosphate reabsorption. VDR appears to function unliganded by 1,25D in keratinocytes to drive mammalian hair cycling via regulation of genes such as CASP14, S100A8, SOSTDC1, and others affecting Wnt signaling. Finally, alternative, low-affinity, non-vitamin D VDR ligands, e.g., lithocholic acid, docosahexaenoic acid, and curcumin, have been reported. Combined alternative VDR ligand(s) and 1,25D/VDR control of gene expression may delay chronic disorders of aging such as osteoporosis, type 2 diabetes, cardiovascular disease, and cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I236,I236)","v":22684632},{"$f":"(LEN($J236) - LEN(SUBSTITUTE(LOWER($J236),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J236) - LEN(SUBSTITUTE(LOWER($J236),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J236) - LEN(SUBSTITUTE(LOWER($J236),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B236:D236)","v":1},2012,"Antioxidant vitamins and mineral supplementation, life span expansion and cancer incidence: a critical commentary.","Dolara",22684632,"Antioxidant vitamins and mineral supplementation, life span expansion and cancer incidence: a critical commentary.    Abstract:    PURPOSE : Experimental evidence indicates a strong connection between oxidative damage, cancer, and aging. Epidemiological observations suggest that a diet rich in fruits and vegetables is associated with lower incidence of some cancers and longer life expectancy; since fruits and vegetables contain natural antioxidants, a considerable effort has been dedicated to understanding their effects in experimental studies and in human trials.  RESULTS : A: Effects of antioxidant-containing food and supplements on oxidation damage in humans. Intervention trials employing a variety of biomarkers have shown either a slight decrease in oxidation damage or no effect. B: Effects of selected antioxidants on mortality and cancer incidence. β-carotene and α-tocopherol, alone or in combination, increase cardiovascular and all-cause mortality or have no effect. In some studies, β-carotene and retinyl palmitate significantly increase the progression of lung cancer and aggressive prostate cancer. Protection against cardiovascular mortality or no effect of vitamin E has been reported, with an increase of all-cause mortality at dosages greater than 150 IU/day. Selenium showed beneficial effects on gastrointestinal cancer and reduced the risk of lung cancer in populations with lower selenium status. For multivitamin and mineral supplementation, no significant reduction of mortality or cancer incidence was observed, but some reports indicate a possible preventive effect in cervical cancer.  CONCLUSIONS : The majority of supplementation studies indicate no variation of general mortality and of cancer incidence or a detrimental effect on both. Antioxidant supplements so far tested seem to offer no improvement over a well-balanced diet, possibly because of the choice of the substances tested or of an excessive dosage. However, new natural or synthetic compounds effective in vitro and in experimental studies might still be worth investigating in human trials."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I237,I237)","v":22656374},{"$f":"(LEN($J237) - LEN(SUBSTITUTE(LOWER($J237),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J237) - LEN(SUBSTITUTE(LOWER($J237),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J237) - LEN(SUBSTITUTE(LOWER($J237),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B237:D237)","v":1},2012,"Nutrigenomics and nutrigenetics of ω3 polyunsaturated fatty acids.","Vanden Heuvel",22656374,"Nutrigenomics and nutrigenetics of ω3 polyunsaturated fatty acids.    Abstract:   Diets rich in ω3 polyunsaturated fatty acids (ω3-PUFAs) such as alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid are associated with decreased incidence and severity of several chronic diseases including cardiovascular disease (CVD) and cancer. At least some of the beneficial effects of these dietary fatty acids are via metabolites such as prostaglandins, leukotrienes, thromboxanes, and resolvins. The effects of ω3-PUFAs are in contrast to those of fatty acids with virtually identical structures, such as the ω6-PUFAs linoleic acid and arachidonic acid, and their corresponding metabolites. The purpose of this chapter is to discuss both the nutrigenomics (nutrient-gene interactions) and nutrigenetics (genetic variation in nutrition) of dietary fatty acids with a focus on the ω3-PUFAs (Gebauer et al., 2007(1)). Important in the biological response for these fatty acids or their metabolites are cognate receptors that are able to regulate gene expression and coordinately affect metabolic or signaling pathways associated with CVD and cancer. Four nuclear receptor (NR) subfamilies will be emphasized as receptors that respond to dietary and endogenous ligands: (1) peroxisome proliferator-activated receptors, (2) retinoid X receptors, (3) liver X receptors, and (4) farnesoid X receptor. In addition to the different responses elicited by varying structures of fatty acids, responses may vary because of genetic variation in enzymes that metabolize ω3- and ω6 fatty acids or that respond to them. In particular, polymorphisms in the fatty acid desaturases and the aforementioned NRs contribute to the complexity of nutritional effects seen with ω3-PUFAs. Following a brief introduction to the health benefits of ω3-PUFAs, the regulation of gene expression by these dietary fatty acids via NRs will be characterized. Subsequently, the effects of single-nucleotide polymorphisms (SNPs) in key enzymes involved in the metabolism and response to ω3-PUFAs will be described. An outline of the events to be explored is shown in Fig. 1. Understanding the nutrigenomics and nutrigenetics of dietary fatty acids is key to understanding the etiology, as well as prevention, of critically important human diseases including CVD and cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I238,I238)","v":22573366},{"$f":"(LEN($J238) - LEN(SUBSTITUTE(LOWER($J238),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J238) - LEN(SUBSTITUTE(LOWER($J238),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J238) - LEN(SUBSTITUTE(LOWER($J238),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B238:D238)","v":1},2012,"Stem cells, cancer stem-like cells, and natural products.","Efferth",22573366,"Stem cells, cancer stem-like cells, and natural products.    Abstract:   Somatic stem cells can be found in many rapidly regenerating tissues, e.g., the skin, gastrointestinal mucosa, and hematopoietic system, but are also present at low numbers in non-regenerative organs such as the heart and brain. In these organs, somatic stem cells aid in normal tissue homeostasis and repair after injury as well as self-renewal and the generation of specific progenitor cells during differentiation. Cancer stem-like cells are a small subpopulation of self-renewing cells that are able to proliferate upon appropriate stimulation and differentiate into heterogeneous lineages in tumors. Modulation of the behavior of normal tissue stem cells and cancer stem-like cells is an emerging and thriving new field of research. The present review gives an overview of the state-of-the-art findings and highlights perspectives for future scientific developments and clinical application."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I239,I239)","v":22419222},{"$f":"(LEN($J239) - LEN(SUBSTITUTE(LOWER($J239),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J239) - LEN(SUBSTITUTE(LOWER($J239),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J239) - LEN(SUBSTITUTE(LOWER($J239),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B239:D239)","v":1},2012,"Liver X receptors, atherosclerosis and inflammation.","Michael",22419222,"Liver X receptors, atherosclerosis and inflammation.    Abstract:   Liver X receptors (LXRs) belong to the nuclear receptor superfamily of ligand-dependent transcription factors. LXRs are activated by oxysterols, metabolites of cholesterol, and therefore act as intracellular sensors of this lipid. There are two LXR genes (α and β) that display distinct tissue/cell expression profiles. LXRs interact with regulatory sequences in target genes as heterodimers with retinoid X receptor. Such direct targets of LXR actions include important genes implicated in the control of lipid homeostasis, particularly reverse cholesterol transport. In addition, LXRs attenuate the transcription of genes associated with the inflammatory response indirectly by transrepression. In this review, we describe recent evidence that both highlights the key roles of LXRs in atherosclerosis and inflammation and provides novel insights into the mechanisms underlying their actions. In addition, we discuss the major limitations of LXRs as therapeutic targets for the treatment of atherosclerosis and how these are being addressed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I240,I240)","v":22342903},{"$f":"(LEN($J240) - LEN(SUBSTITUTE(LOWER($J240),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J240) - LEN(SUBSTITUTE(LOWER($J240),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J240) - LEN(SUBSTITUTE(LOWER($J240),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B240:D240)","v":1},2012,"Up- and down-regulation of adiponectin expression and multimerization: mechanisms and therapeutic implication.","Liu",22342903,"Up- and down-regulation of adiponectin expression and multimerization: mechanisms and therapeutic implication.    Abstract:   Adiponectin has been receiving a great deal of attention due to its potential therapeutic use for metabolic and cardiovascular disorders. Adiponectin expression levels and multimerization are down-regulated in obesity and up-regulated by insulin sensitizers such as thiazolidinediones (TZDs), metformin, sulfonylurea and resveratrol (RSV). The precise mechanisms underlying adiponectin up- and down-regulation remain largely unknown, but recent studies indicate that the cellular and plasma levels of adiponectin could be regulated at both transcriptional and post-transcriptional levels. At the post-translational level, TZDs and resveratrol promote adiponectin levels and multimerization via up-regulation of disulfide-bond-A oxidoreductase-like protein (DsbA-L). Adiponectin levels are also stimulated by FOXO1 and AMP-activated protein kinase (AMPK), and are suppressed by PKA or silencing mediator of retinoid and thyroid hormone receptors (SMRT). Since multimerization is important not only for adiponectin function but also for stability, increasing adiponectin multimerization has become a promising drug target for the treatment of metabolic diseases and other related disorders."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I241,I241)","v":22271680},{"$f":"(LEN($J241) - LEN(SUBSTITUTE(LOWER($J241),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J241) - LEN(SUBSTITUTE(LOWER($J241),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J241) - LEN(SUBSTITUTE(LOWER($J241),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B241:D241)","v":1},2011,"Disruption of embryonic vascular development in predictive toxicology.","Knudsen",22271680,"Disruption of embryonic vascular development in predictive toxicology.    Abstract:   Toxicity testing in the 21st century is moving toward using high-throughput screening assays to rapidly test thousands of chemicals against hundreds of molecular targets and biological pathways, and to provide mechanistic information on chemical effects in human cells and small model organisms. First-generation predictive models for prenatal developmental toxicity have revealed a complex web of biological processes with many connections to vasculogenesis and angiogenesis. This review examines disruption of embryonic vascular development as a potential adverse outcome pathway leading to developmental toxicity. We briefly review embryonic vascular development and important signals for vascular development (local growth factors and cytokines such as vascular endothelial growth factor-A and TGF-beta, components in the plasminogen activator system, and chemotactic chemokines). Genetic studies have shown that perturbing these signals can lead to varying degrees of adverse consequences, ranging from congenital angiodysplasia to fetal malformations and embryolethality. The molecular targets and cellular behaviors required for vascular development, stabilization and remodeling are amenable to in vitro evaluation. Evidence for chemical disruption of these processes is available for thalidomide, estrogens, endothelins, dioxin, retinoids, cigarette smoke, and metals among other compounds. Although not all compounds with developmental toxicity show an in vitro vascular bioactivity signature, many putative vascular disruptor compounds invoke adverse developmental consequences. As such, an adverse outcome pathway perspective of embryonic vascular development can help identify useful information for assessing adverse outcomes relevant to risk assessment and efficient use of resources for validation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I242,I242)","v":22240062},{"$f":"(LEN($J242) - LEN(SUBSTITUTE(LOWER($J242),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J242) - LEN(SUBSTITUTE(LOWER($J242),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J242) - LEN(SUBSTITUTE(LOWER($J242),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B242:D242)","v":1},2012,"Drugs in the brain--cellular imaging with receptor microscopic autoradiography.","Stumpf",22240062,"Drugs in the brain--cellular imaging with receptor microscopic autoradiography.    Abstract:   For cell and tissue localization of drugs, receptor microscopic autoradiography is reviewed, including its development history, multiple testing, extensive applications and significant discoveries. This sensitive high-resolution imaging method is based on the use of radiolabeled compounds (esp. tagged with (3)H or (125)I), preservation through freezing of in vivo localization of tissue constituents, cutting thin frozen sections, and close contact with the recording nuclear emulsion. After extensive testing of the utility of this method, the distribution of radiolabeled compounds has been identified and characterized for estradiol, progestagens, adrenal steroids, thyroid hormone, ecdysteroids, vitamin D, retinoic acid, metabolic indicators glucose and 2-deoxyglucose, as well as extracellular space indicators. Target cells and associated tissues have been characterized with special stains, fluorescing compounds, or combined autoradiography-immunocytochemistry with antibodies to dopamine-beta-hydroxylase, GABA, enkephalin, specific receptor proteins, or other cellular products. Blood-brain barrier and brain entries via capillary endothelium, ependyma, or circumventricular recess organs have been visualized for (3)H-dexamethasone, (210)Pb lead, and (3)H-1,25(OH)(2) vitamin D(3). With this histopharmacologic approach, cellular details and tissue integrative overviews can be assessed in the same preparation. As a result, information has been gained that would have been difficult or impossible otherwise. Maps of brain drug distribution have been developed and relevant target circuits have been recognized. Examples include the stria terminalis that links septal-amygdaloid-thalamic-hypothalamic structures and telencephalic limbic system components which extend as the periventricular autonomic-neuroendocrine ABC (Allocortex-Brainstem-Circuitry) system into the mid- and hindbrain. Discoveries with radiolabeled substances challenged existing paradigms, engendering new concepts and providing seminal incentives for further research toward understanding drug actions. Most notable are discoveries made during the 1980s with vitamin D in the brain together with over 50 target tissues that challenged the century-old doctrine of vitamin Ds main role as the calcitropic hormone, when the new data made it apparent that the main biological function of this multifunctional sunshine hormone rather is maintenance of life and adapting vital functions to the solar environment. In the brain, vitamin D, in close relation to sex and adrenal steroids, participates in the regulation of the secretion of neuro-endocrines, such as, serotonin, dopamine, nerve growth factor, acetyl choline, with importance in prophylaxis and therapy of neuro-psychiatric disorders. Histochemical imaging with high cellular-subcellular resolution is necessary for obtaining detailed information, as this review indicates. New spectrometric methods, like MALDI-MSI, are unlikely to furnish the same information as receptor microautoradiography does, but can provide important correlative molecular information."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I243,I243)","v":22214468},{"$f":"(LEN($J243) - LEN(SUBSTITUTE(LOWER($J243),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J243) - LEN(SUBSTITUTE(LOWER($J243),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J243) - LEN(SUBSTITUTE(LOWER($J243),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B243:D243)","v":1},2012,"Congenital diaphragmatic hernia.","Tovar",22214468,"Congenital diaphragmatic hernia.    Abstract:   Congenital Diaphragmatic Hernia (CDH) is defined by the presence of an orifice in the diaphragm, more often left and posterolateral that permits the herniation of abdominal contents into the thorax. The lungs are hypoplastic and have abnormal vessels that cause respiratory insufficiency and persistent pulmonary hypertension with high mortality. About one third of cases have cardiovascular malformations and lesser proportions have skeletal, neural, genitourinary, gastrointestinal or other defects. CDH can be a component of Pallister-Killian, Fryns, Ghersoni-Baruch, WAGR, Denys-Drash, Brachman-De Lange, Donnai-Barrow or Wolf-Hirschhorn syndromes. Some chromosomal anomalies involve CDH as well. The incidence is lt; 5 in 10,000 live-births. The etiology is unknown although clinical, genetic and experimental evidence points to disturbances in the retinoid-signaling pathway during organogenesis. Antenatal diagnosis is often made and this allows prenatal management (open correction of the hernia in the past and reversible fetoscopic tracheal obstruction nowadays) that may be indicated in cases with severe lung hypoplasia and grim prognosis. Treatment after birth requires all the refinements of critical care including extracorporeal membrane oxygenation prior to surgical correction. The best hospital series report 80% survival but it remains around 50% in population-based studies. Chronic respiratory tract disease, neurodevelopmental problems, neurosensorial hearing loss and gastroesophageal reflux are common problems in survivors. Much more research on several aspects of this severe condition is warranted."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I244,I244)","v":22167840},{"$f":"(LEN($J244) - LEN(SUBSTITUTE(LOWER($J244),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J244) - LEN(SUBSTITUTE(LOWER($J244),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J244) - LEN(SUBSTITUTE(LOWER($J244),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B244:D244)","v":1},2011,"[Matrix Gla-protein and its role in vascular wall calcification].","Harbuzova",22167840,"[Matrix Gla-protein and its role in vascular wall calcification].    Abstract:   Data on the structure of matrix Gla-protein (MGP), its chemical characteristics, regulation of synthesis and post-translational modifications are described. The information on the structure of the MGP gene, its well distributed polymorphisms are presented. Factors that regulate expression and activity of MGP include vitamin D, retinoic acid, extracellular calcium ions, cytokines, and some hormones. It is emphasized that MGP is an important inhibitor of calcification of soft tissues. These properties of this protein are associated with the presence of residues of gamma-carboxiglutamic acid of its molecule. Four possible mechanisms of anticalcinogenic action of MGP are described: binding with calcium ions and crystals of hydroxyapatite, binding to extracellular matrix components, interaction with bone morphogenetic protein (BMP-2) and elimination the effects of the latter, participation in the regulation of apoptosis. It is emphasized that the study of allelic variants of the MGP gene is important in the context of their possible association with the development of cardiovascular and other diseases."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I245,I245)","v":22130718},{"$f":"(LEN($J245) - LEN(SUBSTITUTE(LOWER($J245),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J245) - LEN(SUBSTITUTE(LOWER($J245),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J245) - LEN(SUBSTITUTE(LOWER($J245),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B245:D245)","v":1},2012,"Endogenous inhibitory mechanisms and the regulation of platelet function.","Jones",22130718,"Endogenous inhibitory mechanisms and the regulation of platelet function.    Abstract:   The response of platelets to changes in the immediate environment is always a balance between activatory and inhibitory signals, the cumulative effect of which is either activation or quiescence. This is true of platelets in free flowing blood and of their regulation of haemostasis and thrombosis. In this review, we consider the endogenous inhibitory mechanisms that combine to regulate platelet activation. These include those derived from the endothelium (nitric oxide, prostacyclin, CD39), inhibitory receptors on the surface of platelets (platelet endothelial cell adhesion molecule-1, carcinoembryonic antigen cell adhesion molecule 1, G6b-B - including evidence for the role of Ig-ITIM superfamily members in the negative regulation of ITAM-associated GPVI platelet-collagen interactions and GPCR-mediated signalling and in positive regulation of quot;outside-inquot; integrin α(IIb)β(3)-mediated signalling), intracellular inhibitory receptors (retinoic X receptor, glucocorticoid receptor, peroxisome proliferator-activated receptors, liver X receptor), and emerging inhibitory pathways (canonical Wnt signalling, Semaphorin 3A, endothelial cell specific adhesion molecule, and junctional adhesion molecule-A)."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I246,I246)","v":22051144},{"$f":"(LEN($J246) - LEN(SUBSTITUTE(LOWER($J246),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J246) - LEN(SUBSTITUTE(LOWER($J246),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J246) - LEN(SUBSTITUTE(LOWER($J246),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B246:D246)","v":1},2012,"Nutritional influences on epigenetics and age-related disease.","Park",22051144,"Nutritional influences on epigenetics and age-related disease.    Abstract:   Nutritional epigenetics has emerged as a novel mechanism underlying gene-diet interactions, further elucidating the modulatory role of nutrition in aging and age-related disease development. Epigenetics is defined as a heritable modification to the DNA that regulates chromosome architecture and modulates gene expression without changes in the underlying bp sequence, ultimately determining phenotype from genotype. DNA methylation and post-translational histone modifications are classical levels of epigenetic regulation. Epigenetic phenomena are critical from embryonic development through the aging process, with aberrations in epigenetic patterns emerging as aetiological mechanisms in many age-related diseases such as cancer, CVD and neurodegenerative disorders. Nutrients can act as the source of epigenetic modifications and can regulate the placement of these modifications. Nutrients involved in one-carbon metabolism, namely folate, vitamin B12, vitamin B6, riboflavin, methionine, choline and betaine, are involved in DNA methylation by regulating levels of the universal methyl donor S-adenosylmethionine and methyltransferase inhibitor S-adenosylhomocysteine. Other nutrients and bioactive food components such as retinoic acid, resveratrol, curcumin, sulforaphane and tea polyphenols can modulate epigenetic patterns by altering the levels of S-adenosylmethionine and S-adenosylhomocysteine or directing the enzymes that catalyse DNA methylation and histone modifications. Aging and age-related diseases are associated with profound changes in epigenetic patterns, though it is not yet known whether these changes are programmatic or stochastic in nature. Future work in this field seeks to characterise the epigenetic pattern of healthy aging to ultimately identify nutritional measures to achieve this pattern."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I247,I247)","v":21718345},{"$f":"(LEN($J247) - LEN(SUBSTITUTE(LOWER($J247),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J247) - LEN(SUBSTITUTE(LOWER($J247),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J247) - LEN(SUBSTITUTE(LOWER($J247),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B247:D247)","v":1},2011,"Whats new in psoriasis? An analysis of guidelines and systematic reviews published in 2009-2010.","Foulkes",21718345,"Whats new in psoriasis? An analysis of guidelines and systematic reviews published in 2009-2010.    Abstract:   This review summarizes key clinical findings from 5 guidelines and 21 systematic reviews on psoriasis published or indexed in the period November 2009 to October 2010. The highlights include the British Association of Dermatologists guidelines on the use of biological interventions in psoriasis, and guidelines on the efficacy and use of acitretin. Biological therapies were reviewed for use in specific patient groups (such as those with hepatitis C) and from a health-economics perspective. Another systematic review focused on outcome measures used to assess the severity of psoriasis. Finally, comorbidities including cardiovascular risk were the topic of four systematic reviews."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I248,I248)","v":21575313},{"$f":"(LEN($J248) - LEN(SUBSTITUTE(LOWER($J248),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J248) - LEN(SUBSTITUTE(LOWER($J248),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J248) - LEN(SUBSTITUTE(LOWER($J248),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B248:D248)","v":1},2011,"Inpatient management of severe malnutrition: time for a change in protocol and practice.","Brewster",21575313,"Inpatient management of severe malnutrition: time for a change in protocol and practice.    Abstract:   This review focuses on how to reduce the high mortality of severe acute malnutrition (SAM) in African hospitals. The World Health Organizations 1999 manual for physicians (protocol) has not resulted in case-fatality rates of under 5%, even in published research studies from Africa, far less in district and central hospitals which do not record case-fatality rates. It is suggested that the following eight changes to the protocol need to be considered if we are serious about reducing case-fatality rates in African hospitals: (1) use of low lactose, low osmolality milk feeds during the early stage of treatment, especially for HIV-exposed infants and diarrhoeal cases; (2) more cautious use of high carbohydrate loads (ORS, ReSoMal, sucrose and 10% dextrose) during initial stabilisation; (3) more careful grading up and down of feed volumes according the childs responses during the early rehabilitation phase; (4) rapid rehydration of children in shock with Ringers lactate, as for well-nourished children, with closer monitoring for heart failure; (5) greater use of 3rd-generation cephalosporin and fluoroquinolone antibiotics (e.g. ceftriaxone, ciprofloxacin) to treat sepsis owing to resistant organisms; (6) consider adding glutamine-arginine supplements as gut-protective agents in addition to zinc and vitamin A; (7) the addition of phosphate to existing potassium and magnesium supplements for those at risk of the refeeding syndrome; and (8) introduce better tools for diagnosis and clearer management of combined HIV and tuberculous infections in infants. Many will argue that these suggestions are unaffordable or impractical. On the contrary, cases of SAM requiring hospital admission need to be allocated more resources, including better nursing care, better diet and better medication. Resources made available for other childhood inpatient services such as ID and HIV dwarf those for severe malnutrition. Of course, prevention is always a better investment, including improving breastfeeding rates, improving complementary feeding practices and using ready-to-use therapeutic foods (RUTF) or similar supplements for those failing to thrive in the community, but SAM is unlikely to disappear from our hospitals, and these children need to be better managed if we are serious about reducing mortality."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I249,I249)","v":21466970},{"$f":"(LEN($J249) - LEN(SUBSTITUTE(LOWER($J249),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J249) - LEN(SUBSTITUTE(LOWER($J249),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J249) - LEN(SUBSTITUTE(LOWER($J249),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B249:D249)","v":1},2011,"Toll-like receptor, RIG-I-like receptors and the NLRP3 inflammasome: key modulators of innate immune responses to double-stranded RNA viruses.","Yu",21466970,"Toll-like receptor, RIG-I-like receptors and the NLRP3 inflammasome: key modulators of innate immune responses to double-stranded RNA viruses.    Abstract:   Double-stranded RNA (dsRNA), the genetic material for many RNA viruses, induces robust host immune responses via pattern recognition receptors, which include Toll-like receptor 3 (TLR3), retinoic acid-inducible gene-I-like receptors (RLRs) and the multi-protein NLRP3 inflammasome complex. The engagement of dsRNA receptors or inflammasome activation by viral dsRNA initiates complex intracellular signaling cascades that play essential roles in inflammation and innate immune responses, as well as the resultant development of adaptive immunity. This review focuses on signaling pathways mediated by TLR3, RLRs and the NLRP3 inflammasome, as well as the potential use of agonists and antagonists that target these pathways to treat disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I250,I250)","v":20957457},{"$f":"(LEN($J250) - LEN(SUBSTITUTE(LOWER($J250),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J250) - LEN(SUBSTITUTE(LOWER($J250),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J250) - LEN(SUBSTITUTE(LOWER($J250),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B250:D250)","v":1},2011,"Metabolic syndrome: from the genetics to the pathophysiology.","Sookoian",20957457,"Metabolic syndrome: from the genetics to the pathophysiology.    Abstract:   The metabolic syndrome (MS) constitutes a combination of underlying risk factors for an adverse outcome, cardiovascular disease. Thus, the clinical behavior of the MS can be regarded as a whole. Nevertheless, from a pathogenic point of view, understanding of the underlying mechanisms of each MS intermediate phenotype is far beyond their understanding as an integrative process. Systems biology introduces a new concept for revealing the pathogenesis of human disorders and suggests the presence of common physiologic processes and molecular networks influencing the risk of a disease. This paper shows a model of this concept to explain the genetic determinants of MS-associated phenotypes. Based on the hypothesis that common physiologic processes and molecular networks may influence the risk of MS disease components, we propose two systems-biology approaches: a gene enrichment analysis and the use of a protein-protein interaction network. Our results show that a network driven by many members of the nuclear receptor superfamily of proteins, including retinoid X receptor and farnesoid X receptor (FXR), may be implicated in the pathogenesis of the MS by its interactions at multiple levels of complexity with genes associated with metabolism, cell differentiation, and oxidative stress. In addition, we review two alternative genetic mechanisms that are gaining acceptance in the physiopathology of the MS: the regulation of transcriptional and post-transcriptional gene expression by microRNAs and epigenetic modifications such as DNA methylation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I251,I251)","v":20824955},{"$f":"(LEN($J251) - LEN(SUBSTITUTE(LOWER($J251),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J251) - LEN(SUBSTITUTE(LOWER($J251),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J251) - LEN(SUBSTITUTE(LOWER($J251),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B251:D251)","v":1},2010,"Effect of selected drugs on plasma asymmetric dimethylarginine (ADMA) levels.","Trocha",20824955,"Effect of selected drugs on plasma asymmetric dimethylarginine (ADMA) levels.    Abstract:   Asymmetric dimethylarginine (ADMA) is an endogenous methylated amino acid derived from arginine which can inhibit the activity of nitric oxide synthases. In various pathological states such as hypercholesterolemia, hyperglycemia, hyperhomocysteinemia, hypertension, coronary artery disease, heart failure, and stroke, plasma levels of ADMA may be increased and lead to inhibition of NO synthesis and endothelial dysfunction. Inhibition of ADMA synthesis or intensification of metabolism of this compound might indirectly lower ADMA. Antioxidants, estrogen, vitamin A, angiotensin converting enzyme inhibitors, angiotensin AT1 receptor antagonists, and also some hypolipemic, hypoglycemic and beta-adrenoreceptor blocking drugs decrease ADMA levels. In some situations like neurological disorders, decreased plasma levels of ADMA are noticed and drugs increasing the concentration of this compound could exert protective effects. It is reasonable to explore which drugs can increase or decrease ADMA levels and what their mechanism of that action is."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I252,I252)","v":20637526},{"$f":"(LEN($J252) - LEN(SUBSTITUTE(LOWER($J252),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J252) - LEN(SUBSTITUTE(LOWER($J252),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J252) - LEN(SUBSTITUTE(LOWER($J252),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B252:D252)","v":1},2011,"Acute respiratory distress syndrome complicating generalized pustular psoriasis (psoriasis-associated aseptic pneumonitis).","Kluger",20637526,"Acute respiratory distress syndrome complicating generalized pustular psoriasis (psoriasis-associated aseptic pneumonitis).    Abstract:   Generalized pustular and/or erythrodermic psoriasis may have severe or even lethal complications. A peculiar noninfectious acute respiratory distress syndrome (so-called quot;sterile pneumonitisquot;) has been described in generalized pustular psoriasis and/or erythrodermic psoriasis. We report a new case in a 14-year-old girl with a long history of pustular psoriasis and review the published work on this complication. The girl developed sterile pneumonitis during a disease flare-up, and high-dose corticosteroid therapy was quickly initiated. Within a few days, her clinical and radiological status was dramatically improved. The pathogenesis of aseptic pneumonitis is unknown, but various proinflammatory cytokines have been implicated, especially tumor necrosis factor-alpha, which could play a role in the recruitment of leukocytes to the lung. This complication has rarely been reported but should be more widely known as the differential diagnoses include congestive heart failure, acute lung infection related or unrelated to immunosuppressive therapy, and drug hypersensitivity reaction. Early recognition would avoid delays in the correct management of this potentially lethal complication, which requires high-dose systemic corticosteroid therapy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I253,I253)","v":23554628},{"$f":"(LEN($J253) - LEN(SUBSTITUTE(LOWER($J253),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J253) - LEN(SUBSTITUTE(LOWER($J253),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J253) - LEN(SUBSTITUTE(LOWER($J253),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B253:D253)","v":1},2010,"Vascular smooth muscle cell differentiation-2010.","Miano",23554628,"Vascular smooth muscle cell differentiation-2010.    Abstract:   Vascular smooth muscle cells have attracted considerable interest as a model for a flexible program of gene expression. This cell type arises throughout the embryo body plan via poorly understood signaling cascades that direct the expression of transcription factors and microRNAs which, in turn, orchestrate the activation of contractile genes collectively defining this cell lineage. The discovery of myocardin and its close association with serum response factor has represented a major break-through for the molecular understanding of vascular smooth muscle cell differentiation. Retinoids have been shown to improve the outcome of vessel wall remodeling following injury and have provided further insights into the molecular circuitry that defines the vascular smooth muscle cell phenotype. This review summarizes the progress to date in each of these areas of vascular smooth muscle cell biology."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I254,I254)","v":20054531},{"$f":"(LEN($J254) - LEN(SUBSTITUTE(LOWER($J254),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J254) - LEN(SUBSTITUTE(LOWER($J254),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J254) - LEN(SUBSTITUTE(LOWER($J254),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B254:D254)","v":1},2010,"22q11 deletion syndrome: a role for TBX1 in pharyngeal and cardiovascular development.","Scambler",20054531,"22q11 deletion syndrome: a role for TBX1 in pharyngeal and cardiovascular development.    Abstract:   Tbx1 is a member of the Tbox family of binding domain transcription factors. TBX1 maps within the region of 22q11 deleted in humans with DiGeorge or velocardiofacial syndrome. Mice haploinsufficient for Tbx1 have phenotypes that recapitulate major features of the syndrome, notably abnormal growth and remodelling of the pharyngeal arch arteries. The Tbx1 haploinsufficiency phenotype is modified by genetic background and by mutations in putative downstream targets. Homozygous null mutations of Tbx1 have more severe defects including failure of outflow tract septation, and absence of the caudal pharyngeal arches. Tbx1 is a transcriptional activator, and loss of this activity has been linked to alterations in the expression of various genes involved in cardiovascular morphogenesis. In particular, Fgf and retinoic acid signalling are dysregulated in Tbx1 mutants. This article summarises the tissue specific and temporal requirements for Tbx1, and attempts to synthesis what is know about the developmental pathways under its control."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I255,I255)","v":19852886},{"$f":"(LEN($J255) - LEN(SUBSTITUTE(LOWER($J255),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J255) - LEN(SUBSTITUTE(LOWER($J255),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J255) - LEN(SUBSTITUTE(LOWER($J255),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B255:D255)","v":1},2009,"Cardiovascular disease-related genes and regulation by diet.","Vanden Heuvel",19852886,"Cardiovascular disease-related genes and regulation by diet.    Abstract:   Diets rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs) such as alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid are associated with decreased incidence and severity of cardiovascular disease (CVD). At least some of the beneficial effects of these dietary fatty acids are mediated by metabolites such as prostaglandins, leukotrienes, thromboxanes, and resolvins. The effects of n-3 PUFAs often differ from those of other fatty acids with very similar structures, such as linoleic acid and arachidonic acid (n-6 PUFAs) and their corresponding metabolites. This article reviews the evidence that specific receptors exist for fatty acids or their metabolites that are able to regulate gene expression and coordinately affect metabolic or signaling pathways associated with CVD. Four nuclear receptor subfamilies that respond to dietary and endogenous ligands and have implications for CVD are emphasized in this article: peroxisome proliferator-activated receptors, retinoid X receptors, liver X receptors, and the farnesoid X receptor."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I256,I256)","v":19837721},{"$f":"(LEN($J256) - LEN(SUBSTITUTE(LOWER($J256),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J256) - LEN(SUBSTITUTE(LOWER($J256),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J256) - LEN(SUBSTITUTE(LOWER($J256),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B256:D256)","v":1},2010,"Liver X receptor in cholesterol metabolism.","Zhao",19837721,"Liver X receptor in cholesterol metabolism.    Abstract:   The liver X receptors (LXRs) are nuclear receptors that are activated by endogenous oxysterols, oxidized derivatives of cholesterol. There are two isoforms of LXR, LXRalpha (NR1H3) and LXRbeta (NR1H2). Both LXRalpha and LXRbeta regulate gene expression by binding to DNA sequences associated with target genes as heterodimers with isoforms of the retinoid X receptor (RXR), RXRalpha (NR2B1), RXRbeta (NR2B2), and RXRgamma (NR2B3). LXRs act as cholesterol sensors: when cellular oxysterols accumulate as a result of increasing concentrations of cholesterol, LXR induces the transcription of genes that protect cells from cholesterol overload. In this review, we summarize the roles of LXRs in controlling cholesterol homeostasis, including their roles in bile acid synthesis and metabolism/excretion, reverse cholesterol transport, cholesterol biosynthesis and uptake, and cholesterol absorption/excretion in the intestine. The overlapping and distinct roles of the LXRalpha and LXRbeta isoforms, and the potential use of LXRs as attractive targets for treatment of cardiovascular disease are also discussed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I257,I257)","v":19778546},{"$f":"(LEN($J257) - LEN(SUBSTITUTE(LOWER($J257),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J257) - LEN(SUBSTITUTE(LOWER($J257),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J257) - LEN(SUBSTITUTE(LOWER($J257),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B257:D257)","v":1},2010,"The platelet as a model system for the acute actions of nuclear receptors.","Bishop-Bailey",19778546,"The platelet as a model system for the acute actions of nuclear receptors.    Abstract:   Platelets are circulating cell fragments which play a critical role in thrombosis, and whose activity is associated with the progress of cardiovascular diseases, diabetes, inflammation, and cancer cell metastasis. Recently, a number of nuclear receptors have been found present in human platelets, including the receptors for sex steroids, and glucocorticoids, along with peroxisome proliferator-activated receptors (PPAR)s and retinoid X receptors (RXR)s. Although the platelet contains no nucleus, selective ligands for these receptors activate their respective platelet nuclear receptors and regulate platelet aggregation and activation. The human platelet, because of its abundance and accessibility therefore represents an excellent model system to study the rapid non-genomic mechanism of nuclear receptors. Moreover, since targeting platelets is a major clinical therapeutic area, analysis of platelet nuclear receptors may provide clues for new drug targets as well as provide important information regarding the physiological roles of nuclear receptors in the circulation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I258,I258)","v":19758111},{"$f":"(LEN($J258) - LEN(SUBSTITUTE(LOWER($J258),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J258) - LEN(SUBSTITUTE(LOWER($J258),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J258) - LEN(SUBSTITUTE(LOWER($J258),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B258:D258)","v":1},2010,"Reactive oxygen species and antioxidants in the pathophysiology of cardiovascular disease: does the actual knowledge justify a clinical approach?","De Rosa",19758111,"Reactive oxygen species and antioxidants in the pathophysiology of cardiovascular disease: does the actual knowledge justify a clinical approach?    Abstract:   There is evidence that reactive oxygen species (ROS) are related to the development of cardiovascular disease (CVD). Results from many studies support the hypothesis that ROS released from various sources or dysfunctional mitochondrial respiratory chain play a role in the development of atherosclerosis and its complications. This phenomenon is due to ROS-mediated signalling pathways that are involved in the modulation of several vascular mechanisms. Various animal models have demonstrated that ROS have a causal role in atherothrombosis and other vascular diseases. Oxidative stress is being proposed as the unifying mechanism for many CVD risk factors. In particular, ROS may be responsible for plaque rupture and subsequent thrombosis which lead to myocardial infarction and stroke. Many drugs or agents have been tested to prevent or block oxidation underlying atherothrombotic processes, often with discordant outcomes. We observed that pre-treatment with some antioxidants, such as pyrrolidine dithiocarbamate (PDTC) or N-acetylcysteine, as well as some vitamins with recognized antioxidant properties, namely ascorbic acid (vitamin C), all-trans Retinoic Acid (atRA) and alpha-tocopherol (vitamin E) can suppress oxidative stress (OS)-induced Tissue Factor (TF) expression in human coronary artery endothelial cells. The present review, starting from our experimental observations, focuses on the influence of redox balance on atherothrombotic processes and on the effects of antioxidant treatment. A better understanding of the complex regulation of cellular redox balance could facilitate the development of newer antioxidants aimed at specific cellular targets. Research could also help assess the role of combination pharmacological intervention for the treatment and prevention of vascular disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I259,I259)","v":19659982},{"$f":"(LEN($J259) - LEN(SUBSTITUTE(LOWER($J259),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J259) - LEN(SUBSTITUTE(LOWER($J259),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J259) - LEN(SUBSTITUTE(LOWER($J259),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B259:D259)","v":1},2009,"Recurrent keratoacanthoma with vascular invasion: a diagnostic and management dilemma.","Kurien",19659982,"Recurrent keratoacanthoma with vascular invasion: a diagnostic and management dilemma.    Abstract:   A 71-year-old man with chronic renal failure and on peritoneal dialysis presented with recurrence of multiple keratotic nodules along a surgical scar. This was 6 months after the excision of a recurrent keratotic nodule reported as squamous cell carcinoma from the same site. The lesions were initially reported as squamous cell carcinomas, but on review of histology were consistent with keratoacanthomas. One of the keratoacanthomas showed vascular invasion. These responded well to low-dose acitretin at 10 mg three times per week and the patient stayed in remission after 18 months of follow up."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I260,I260)","v":19502515},{"$f":"(LEN($J260) - LEN(SUBSTITUTE(LOWER($J260),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J260) - LEN(SUBSTITUTE(LOWER($J260),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J260) - LEN(SUBSTITUTE(LOWER($J260),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B260:D260)","v":1},2009,"Endocrine-disrupting chemicals: an Endocrine Society scientific statement.","Diamanti-Kandarakis",19502515,"Endocrine-disrupting chemicals: an Endocrine Society scientific statement.    Abstract:   There is growing interest in the possible health threat posed by endocrine-disrupting chemicals (EDCs), which are substances in our environment, food, and consumer products that interfere with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. In this first Scientific Statement of The Endocrine Society, we present the evidence that endocrine disruptors have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology. Results from animal models, human clinical observations, and epidemiological studies converge to implicate EDCs as a significant concern to public health. The mechanisms of EDCs involve divergent pathways including (but not limited to) estrogenic, antiandrogenic, thyroid, peroxisome proliferator-activated receptor gamma, retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways that are highly conserved in wildlife and humans, and which can be modeled in laboratory in vitro and in vivo models. Furthermore, EDCs represent a broad class of molecules such as organochlorinated pesticides and industrial chemicals, plastics and plasticizers, fuels, and many other chemicals that are present in the environment or are in widespread use. We make a number of recommendations to increase understanding of effects of EDCs, including enhancing increased basic and clinical research, invoking the precautionary principle, and advocating involvement of individual and scientific society stakeholders in communicating and implementing changes in public policy and awareness."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I261,I261)","v":19405812},{"$f":"(LEN($J261) - LEN(SUBSTITUTE(LOWER($J261),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J261) - LEN(SUBSTITUTE(LOWER($J261),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J261) - LEN(SUBSTITUTE(LOWER($J261),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B261:D261)","v":1},2009,"Age-associated decrease of high-density lipoprotein-mediated reverse cholesterol transport activity.","Berrougui",19405812,"Age-associated decrease of high-density lipoprotein-mediated reverse cholesterol transport activity.    Abstract:   High-density lipoproteins (HDL) are considered atheroprotective in contrast to low-density lipoproteins (LDL), which are atherogenic in their oxidized form. A growing body of evidence suggests that HDL exert part of their antiatherogenic effect by counteracting LDL oxidation as well as their proinflammatory effect. However, a number of studies, carried over the past 30 years, have shown that cholesterol efflux plays a major role in the atheroprotective effects of HDL and cholesterol homeostasis. These studies have further identified the scavenger receptor type B-I (SR-BI), the adenosine triphosphate (ATP)-binding cassette transporters ATP-binding cassette subfamily A1 (ABCA1), ATP-binding cassette subfamily G1 (ABCG1) and ABCG4, the liver X receptor/retinoid X receptor (LXR/RXR) and peroxisome proliferator-activated receptorgamma(PPAR gamma) transcription factors, the HDL components apolipoprotein A-I (apoA-I), lecithin-cholesterol acyltransferase (LCAT), and phospholipids as additional mediators of cholesterol transport. Cholesterol efflux occurs via three independent pathways: (1) aqueous diffusion, (2) nonspecific efflux via SR-BI receptors, and (3) specific efflux via cholesterol-responsive members of the ABC superfamily. Whereas aqueous diffusion and scavenger receptor class B, type I (SR-BI)-mediated efflux transport free cholesterol to a wide variety of cholesterol acceptors (particles containing phospholipids, HDL, and lipidated apo-lipoproteins; LDL, etc), the ABCA1 pathway mediates the transport of cholesterol in a unidirectional manner, mainly to lipid-poor apoA-I. In contrast, the ABCG1 pathway is responsible for the transport of cholesterol to all the subfamily members of HDL. Although HDL-mediated cholesterol efflux is apoA-I-dependent, recent studies have suggested an involvement of the enzyme paraoxonase 1 (PON1). Cholesterol efflux is carried on by a number of factors such as genetic mutations, smoking, stress, and high-fat diets. It is attenuated with aging due to changes in the composition and structure of HDL, especially the phosphatidylcholine/sphingomyelin ratio, the fluidity of the phospholipidic layer, the concentration of apoA-I, and the activity of PON1. This review summarizes the findings that cholesterol homeostasis is disrupted with aging as a consequence of dysfunctional cholesterol efflux and the impairment of physiological functions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I262,I262)","v":19357619},{"$f":"(LEN($J262) - LEN(SUBSTITUTE(LOWER($J262),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J262) - LEN(SUBSTITUTE(LOWER($J262),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J262) - LEN(SUBSTITUTE(LOWER($J262),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B262:D262)","v":1},2009,"Whats new in the management of psoriasis?","Kinney",19357619,"Whats new in the management of psoriasis?    Abstract:   Psoriasis treatment is evolving through better understanding of patients with psoriasis and the pathogenesis of the disease itself. Current treatment plans for psoriasis consist of topical medications for mild-moderate or localized psoriasis and more systemic agents for more generalized and moderate-severe psoriasis. New methods of treatment involve not only prescriptions, but patient education and support through organizations such as the National Psoriasis Foundation. The effectiveness of topical treatments have been improved by a better understanding of increasing patients adherence to medications and new treatments--new vehicles and combination treatments--that enhance patients adherence behaviors. Phototherapy, with or without an oral retinoid, remains a key component of psoriasis treatment. More convenient and specific monitoring of methotrexate and biologic medications provide these standards of care in psoriasis better and safer patient outcomes. New anti-IL-12/23 therapies offer another more specific option in the management of chronic plaque psoriasis. Dermatologists should recognize and educate patients about the recently recognized association between psoriasis and vascular disease. Psoriasis management can include counseling patients to obtain appropriate screening for cardiovascular risk."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I263,I263)","v":19213570},{"$f":"(LEN($J263) - LEN(SUBSTITUTE(LOWER($J263),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J263) - LEN(SUBSTITUTE(LOWER($J263),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J263) - LEN(SUBSTITUTE(LOWER($J263),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B263:D263)","v":1},2009,"Anti-angiogenic activity of a novel class of chemopreventive compounds: oleanic acid terpenoids.","Sogno",19213570,"Anti-angiogenic activity of a novel class of chemopreventive compounds: oleanic acid terpenoids.    Abstract:   Angiogenesis is the base for solid tumour growth and dissemination, and anti-angiogenic drugs have been demonstrated to be active in clinical trials. In addition, it has become increasingly clear that inflammation is a key component in tumour insurgence. Chemoprevention focuses on the primary or secondary prevention of cancer using natural or synthetic agents that usually show mild or no collateral effects. We have noted that angiogenesis, particularly inflammatory angiogenesis, is a common target of many chemopreventive molecules, where they most likely suppress the angiogenic switch in pre-malignant tumours, a concept we have termed angioprevention. We have shown that various molecules, such as flavonoids, antioxidants and retinoids, act in the tumour microenvironment inhibiting the recruitment and/or activation of endothelial cells and phagocytes of the innate immunity. We have recently assessed the activity of novel compounds derived from the oleanolic acid triterpenoid, called CDDO-Me and CDDO-Imm. These compounds show a potent anti-angiogenic activity at low dosages. In vivo they inhibit angiogenesis in the Matrigel sponge assay and in KS-Imm (an immortalized Kaposis sarcoma cell line) tumour growth. In vitro they are able to prevent endothelial cell tubulogenesis when cultured on Matrigel. In human umbilical vein endothelial (HUVE) cells these compounds can inhibit the activation of the extracellular signal-regulated kinase ERK1/2 pathway after stimulation with vascular endothelial growth factor (VEGF). Moreover, from immunofluorescence experiments we observed that treatment with these triterpenoids prevents nuclear factor NF-kappaB translocation into the nucleus and thereby the activation of downstream pathways. The particularly potent anti-angiogenic activity seen in vivo suggest that CDDO-Me may be interacting with an important network of molecular and cellular targets, on endothelial cells, and could be employed for angioprevention. These substances are being assessed in phase I trials in humans in the United States."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I264,I264)","v":19129679},{"$f":"(LEN($J264) - LEN(SUBSTITUTE(LOWER($J264),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J264) - LEN(SUBSTITUTE(LOWER($J264),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J264) - LEN(SUBSTITUTE(LOWER($J264),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B264:D264)","v":1},2009,"Peroxisome proliferator-activated receptor gamma and cardiovascular diseases.","Takano",19129679,"Peroxisome proliferator-activated receptor gamma and cardiovascular diseases.    Abstract:   Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily and form heterodimers with retinoid X receptor. Three PPAR isoforms have been isolated and termed alpha, beta (or delta) and gamma. Although PPARgamma is expressed predominantly in adipose tissue and associated with adipocyte differentiation and glucose homeostasis, PPARgamma is also present in a variety of cell types. Synthetic antidiabetic thiazolidinediones (TZDs) are well known as ligands and activators for PPARgamma. After it was reported that activation of PPARgamma suppressed production of pro-inflammatory cytokines in activated macrophages, medical interest in PPARgamma has grown and there has been a huge research effort. PPARgamma is currently known to be implicated in various human chronic diseases such as diabetes mellitus, atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, and Alzheimers disease. Many studies suggest that TZDs not only ameliorate insulin sensitivity, but also have pleiotropic effects on many tissues and cell types. Although activation of PPARgamma seems to have beneficial effects on cardiovascular diseases, the mechanisms by which PPARgamma ligands prevent their development are not fully understood. Recent data about the actions and its mechanisms of PPARgamma-dependent pathway in cardiovascular diseases are discussed here."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I265,I265)","v":19124421},{"$f":"(LEN($J265) - LEN(SUBSTITUTE(LOWER($J265),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J265) - LEN(SUBSTITUTE(LOWER($J265),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J265) - LEN(SUBSTITUTE(LOWER($J265),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B265:D265)","v":1},2008,"PPARs as new therapeutic targets for the treatment of cerebral ischemia/reperfusion injury.","Collino",19124421,"PPARs as new therapeutic targets for the treatment of cerebral ischemia/reperfusion injury.    Abstract:   Stroke is a leading cause of death and long-term disability in industrialized countries. Despite advances in understanding its pathophysiology, little progress has been made in the treatment of stroke. The currently available therapies have proven to be highly unsatisfactory (except thrombolysis) and attempts are being made to identify and characterize signaling proteins which could be exploited to design novel therapeutic modalities. The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that control lipid and glucose metabolism. PPARs regulate gene expression by binding with the retinoid X receptor (RXR) as a heterodimeric partner to specific DNA sequences, termed PPAR response elements. In addition, PPARs may modulate gene transcription also by directly interfering with other transcription factor pathways in a DNA-binding independent manner. To date, three different PPAR isoforms, designated alpha, beta/delta, and gamma, have been identified. Recently, they have been found to play an important role for the pathogenesis of various disorders of the central nervous system and accumulating data suggest that PPARs may serve as potential targets for treating ischemic stroke. Activation of all PPAR isoforms, but especially of PPARgamma, was shown to prevent post-ischemic inflammation and neuronal damage in several in vitro and in vivo models, negatively regulating the expression of genes induced by ischemia/ reperfusion (I/R). This paper reviews the evidence and recent developments relating to the potential therapeutic effects of PPAR-agonists in the treatment of cerebral I/R injury."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I266,I266)","v":18341851},{"$f":"(LEN($J266) - LEN(SUBSTITUTE(LOWER($J266),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J266) - LEN(SUBSTITUTE(LOWER($J266),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J266) - LEN(SUBSTITUTE(LOWER($J266),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B266:D266)","v":1},2008,"[Long-term control of psoriasis is necessary].","Sánchez Carazo",18341851,"[Long-term control of psoriasis is necessary].    Abstract:   Psoriasis is an immune mediated, inflammatory skin condition affecting approximately 1.43% of Spanish population. In clinical practice, physicians use PASI index to assess the severity. Psoriasis causes physical and mental disability comparable to other chronic diseases and affects seriously the patients quality of life. For treatment we have different options. Conventional systemic treatment such as methotrexate, cyclosporine and acitretin may be associated with relevant side effects, and organ toxicity that avoid long term therapy. Several psoriasis patients have other comorbid disorders like obesity, diabetes, dyslipemia, hypertension and an increased rate of cardiovascular disease and metabolic syndrome and these patients need safer treatments. The accumulating clinical experience with new therapies consistent on biological agents like efalizumab indicates that are effective therapies, with safety profile and no evidence of cumulative toxicity that allows a long term use. A better control of psoriasis improves patients quality of life."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I267,I267)","v":18830624},{"$f":"(LEN($J267) - LEN(SUBSTITUTE(LOWER($J267),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J267) - LEN(SUBSTITUTE(LOWER($J267),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J267) - LEN(SUBSTITUTE(LOWER($J267),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B267:D267)","v":1},2009,"Acute febrile neutrophilic dermatosis (Sweets syndrome) in childhood and adolescence: two new patients and review of the literature on associated diseases.","Hospach",18830624,"Acute febrile neutrophilic dermatosis (Sweets syndrome) in childhood and adolescence: two new patients and review of the literature on associated diseases.    Abstract:    OBJECTIVES : The objectives of this study were to analyse the literature on Sweets syndrome in childhood focussing on associated diseases and to suggest possible screening procedures for this group of patients. Furthermore, two new patients with Sweets syndrome are reported.  METHODS : A literature search was performed on Pub med using search terms quot;sweet* syndrome*quot; and neutrophil* dermatos*. Patients were subdivided into the following groups: classic/idiopathic, paraneoplastic, and parainflammatory Sweets syndrome.  RESULTS : The literature search revealed 64 patients (including our two patients) who were diagnosed with Sweets syndrome in childhood and adolescence; 27 (42%) patients were categorized as quot;classic/idiopathic Sweets syndromequot;. In 37 patients (58%) chronic associated diseases were reported. Out of these, 21 (33%) patients were categorized as quot;parainflammatory Sweets syndromequot; including chronic recurrent multifocal osteomyelitis, vasculitis with aortitis, recurrent infections due to immunodeficiencies, arthritis, and systemic lupus erythematosus. Sixteen (25%) patients were categorized as quot;paraneoplastic Sweets syndromequot; comprising both malignant and premalignant diseases like leukemia, aplastic anaemia, and Fanconi anaemia. As all five (8%) patients treated with drugs (granulocyte-colony stimulating factor, retinoid acid) suffered from malignant, premalignant, or parainflammatory diseases, these patients were categorized according to the underlying disease. Two new children with Sweets syndrome and associated diseases are presented here, one of them suffering from recurrent infections and trisomy 21, while the other was diagnosed with CNS vasculitis 5(1/2) years after the primary diagnosis.  CONCLUSIONS : Sweets syndrome should be considered in differential diagnosis of prolonged fever with cutaneous involvement. As most cases of pediatric Sweets syndrome are associated with other diseases we suggest careful screening and monitoring of these patients especially concerning malignant/premalignant diseases, immunodeficiencies, cardiovascular involvement, autoimmune diseases, and drug associations."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I268,I268)","v":18611256},{"$f":"(LEN($J268) - LEN(SUBSTITUTE(LOWER($J268),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J268) - LEN(SUBSTITUTE(LOWER($J268),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J268) - LEN(SUBSTITUTE(LOWER($J268),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B268:D268)","v":1},2008,"Abetalipoproteinemia: two case reports and literature review.","Zamel",18611256,"Abetalipoproteinemia: two case reports and literature review.    Abstract:   Abetalipoproteinemia (ABL, OMIM 200100) is a rare, autosomal recessive disorder, characterized by fat malabsorption, acanthocytosis and hypocholesterolemia in infancy. Later in life, deficiency of fat-soluble vitamins is associated with development of atypical retinitis pigmentosa, coagulopathy, posterior column neuropathy and myopathy. ABL results from mutations in the gene encoding the large subunit of microsomal triglyceride transfer protein (MTP; OMIM 157147). To date at least 33 MTP mutations have been identified in 43 ABL patients. We describe the clinical progress of two patients, both currently in the fifth decade of life, who were diagnosed with ABL as children and were treated with high oral doses of fat soluble vitamins, including vitamin E over the last three decades. Treatment appears to have been associated with arrest of the neuropathy and other complications in both patients. Because pharmacologic inhibition of MTP is being developed as a novel approach to reduce plasma cholesterol for prevention of cardiovascular disease, defining the long-term clinical features of patients with a natural deficiency in MTP might provide some insight into the possible effects of such treatments. We review the range of clinical, biochemical and molecular perturbations in ABL."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I269,I269)","v":18510488},{"$f":"(LEN($J269) - LEN(SUBSTITUTE(LOWER($J269),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J269) - LEN(SUBSTITUTE(LOWER($J269),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J269) - LEN(SUBSTITUTE(LOWER($J269),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B269:D269)","v":1},2008,"Antioxidant plasma concentration and supplementation in carotid intima media thickness.","Riccioni",18510488,"Antioxidant plasma concentration and supplementation in carotid intima media thickness.    Abstract:   Cerebrovascular diseases represent a major problem in Western countries. Oxidative stress, an important condition of increased amounts of reactive oxygen species, is now recognized to be a prominent feature of many acute and chronic diseases, and even of the normal aging process. Carotid intima media thickness is an important marker of atherosclerosis that correlates with established coronary heart disease. Changes in carotid intima media thickness, measured by B-mode high-resolution carotid ultrasonography, represent an important and early step in carotid plaque formation and progression and are the most common currently used marker to evaluate the progression of atherosclerotic processes. Several therapeutic strategies have been adopted to slow the early atherosclerotic process in asymptomatic subjects in order to reduce the risk of cardiovascular events. An additional step to slow the atherosclerotic process may include interventions to decrease newly emerging coronary risk factors, such as oxidative stress and inflammation. Consuming a diet rich in fruits and vegetables will provide antioxidant vitamins, and carotenoids, which are believed to inhibit tissue damage derived from oxidative processes and may slow the progression of early atherosclerosis, modify the increase in carotid intima media thickness and, consequently, reduce cardiovascular events. This review synthesizes the published literature regarding antioxidant vitamins plasma concentration and supplementation and carotid intima media thickness."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I270,I270)","v":18318655},{"$f":"(LEN($J270) - LEN(SUBSTITUTE(LOWER($J270),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J270) - LEN(SUBSTITUTE(LOWER($J270),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J270) - LEN(SUBSTITUTE(LOWER($J270),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B270:D270)","v":1},2008,"Nanodisks: hydrophobic drug delivery vehicles.","Ryan",18318655,"Nanodisks: hydrophobic drug delivery vehicles.    Abstract:   Members of the class of exchangeable apolipoproteins possess the unique capacity to transform phospholipid vesicle substrates into nanoscale disk-shaped bilayers. This reaction can proceed in the presence of exogenous hydrophobic biomolecules, resulting in the formation of novel transport vehicles termed nanodisks (NDs). The objective of this study is to describe the structural organization of NDs and evaluate the utility of these complexes as hydrophobic biomolecule transport vehicles. The topics presented focus on two distinct water insoluble drugs, amphotericin B (AMB) and all trans retinoic acid (ATRA). In vitro and in vivo studies reveal that AMB-ND display potent anti-fungal and anti-protozoal activity, while ATRA-ND show promise in the treatment of cancer. The versatility conferred by the presence of a polypeptide component provides opportunities for targeted delivery of ND to cells."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I271,I271)","v":18316956},{"$f":"(LEN($J271) - LEN(SUBSTITUTE(LOWER($J271),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J271) - LEN(SUBSTITUTE(LOWER($J271),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J271) - LEN(SUBSTITUTE(LOWER($J271),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B271:D271)","v":1},2008,"Glitazones and the cardiovascular system.","Devchand",18316956,"Glitazones and the cardiovascular system.    Abstract:    PURPOSE OF REVIEW : To chart recent progress on molecular mechanisms of rosiglitazone and pioglitazone in the cardiovascular system.  RECENT FINDINGS : Several classes of oral antidiabetic drugs are available to treat type 2 diabetes, but glitazones offer the unique promise of insulin-sensitizing ability coupled with potential to reverse cardiovascular abnormalities associated with insulin resistance. Currently the two drugs used are rosiglitazone and pioglitazone, marketed as Avandia and Actos. Recent results of different metaanalyses were inconclusive as to whether rosiglitazone caused real adverse effects of myocardial ischemia. Thus, the US Food and Drugs Administration placed a black box warning on Avandia to signal potential of myocardial infarction and heart-related deaths, as a precautionary measure until analyses of all available data provide clarity. Also unresolved is the extent to which the two compounds share modes of action.  SUMMARY : Type II diabetes affects more than 160 million people, approximately 5% of the worlds population (http://www.who.org). Recently, questions have been raised about the cardiovascular safety of glitazone antidiabetic drugs. Clearly, there is an urgency to define molecular mechanisms of rosiglitazone and pioglitazone and understand how these drugs may impact patients."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I272,I272)","v":18221121},{"$f":"(LEN($J272) - LEN(SUBSTITUTE(LOWER($J272),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J272) - LEN(SUBSTITUTE(LOWER($J272),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J272) - LEN(SUBSTITUTE(LOWER($J272),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B272:D272)","v":1},2007,"HDL elevation and lipid lowering therapy: current scenario and future perspectives.","Chhabria",18221121,"HDL elevation and lipid lowering therapy: current scenario and future perspectives.    Abstract:   High density lipoprotein (HDL) has proven its role in reverse cholesterol transport and cellular cholesterol efflux thus acting as a protective factor against atherogenic cardiovascular diseases. The article focuses primarily on structure and function of genes influencing HDL metabolism. Various novel targets involve liver X receptor, retinoid X receptor, peroxisome proliferators activated receptor agonists and apoA-I mimetics. New molecules targeting these nuclear receptors are described. Phospholipid transfer protein and scavenger receptor B1 are also attractive targets in HDL metabolism. ATP-Binding Cassette transporter A1 and several lipases also play a crucial role in HDL metabolism and are very useful target for atherogenic dyslipidemia. Cholesteryl ester transfer protein inhibitors have shown great promise as possible drug candidates of future. Notably, JTT-705 (Japan Tobacco, Roche) is of great interest in spite of withdrawal of torcetrapib. Considering modest effect of currently available therapeutic options on HDL, these novel HDL elevating targets are doubtlessly the target for future atherosclerotic intervention."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I273,I273)","v":18221072},{"$f":"(LEN($J273) - LEN(SUBSTITUTE(LOWER($J273),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J273) - LEN(SUBSTITUTE(LOWER($J273),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J273) - LEN(SUBSTITUTE(LOWER($J273),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B273:D273)","v":1},2006,"Non-steroidal LXR agonists; an emerging therapeutic strategy for the treatment of atherosclerosis.","Bennett",18221072,"Non-steroidal LXR agonists; an emerging therapeutic strategy for the treatment of atherosclerosis.    Abstract:   The Liver X Receptor (LXR) alpha and beta isoforms are members of the type II nuclear receptor family which function as obligate heterodimers with the Retinoid X Receptor (RXR). Upon agonist binding, the DNA Binding Domain (DBD) of LXR interacts with LXR response elements on target genes to initiate transcription. A number of genes have been shown to be modulated by LXR function, including the ATP-binding cassette transporter A1 (ABCA1). ABCA1 is involved in the process of reverse cholesterol transport (RCT) from macrophages in atherosclerotic plaques to high-density lipoproteins (HDL) in the plasma. Both homozygous and heterozygous mutations in ABCA1 result in conditions characterised by decreased levels of HDL and an earlier onset of atherosclerosis. A number of other genes are upregulated by LXR activation which would be expected to have either pro- or anti-atherogenic effects. One such target gene is sterol regulatory element binding protein-1c (SREBP-1c), which is involved in the process of lipogenesis leading to increased levels of triglycerides which are pro-atherogenic. The complexity of LXR responses, however, makes it difficult to extrapolate the positive or negative effects of each target gene in isolation to a conclusion as to the outcome in humans when all target genes are being modulated in concert. This review will cover the structural features and associated biological data of non-steroidal LXR modulators claimed for the treatment of cardiovascular disease, as well as highlighting preferred compounds where this information can be discerned. In addition to this patent information a précis of literature data relevant to the utility of specific compounds in the treatment of cardiovascular disease will be given where available."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I274,I274)","v":18177744},{"$f":"(LEN($J274) - LEN(SUBSTITUTE(LOWER($J274),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J274) - LEN(SUBSTITUTE(LOWER($J274),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J274) - LEN(SUBSTITUTE(LOWER($J274),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B274:D274)","v":1},2008,"Bioactive lipids in metabolic syndrome.","Nagao",18177744,"Bioactive lipids in metabolic syndrome.    Abstract:   The metabolic syndrome is a cluster of metabolic disorders, such as abdominal obesity, dyslipidemia, hypertension and impaired fasting glucose that contribute to increased cardiovascular morbidity and mortality. Although the pathogenesis of metabolic syndrome is complicated and the precise mechanisms have not been elucidated, dietary lipids have been recognized as contributory factors in the development and the prevention of cardiovascular risk clustering. This review explores the physiological functions and molecular actions of bioactive lipids, such as n-3 polyunsaturated fatty acids, conjugated fatty acids, sterols, medium-chain fatty acids, diacylglycerols and phospholipids, in the development of metabolic syndrome. Dietary bioactive lipids suppress the accumulation of abdominal adipose tissue and lipids in the liver and serum, and alleviate hypertension and type 2 diabetes through the transcriptional regulation of lipid and glucose metabolism. Peroxisome proliferator-activated receptors (PPARs), sterol regulatory element binding proteins, liver X receptor alpha, retinoid X receptor alpha, farnesoid X receptor alpha, hepatic nuclear factor 4alpha and nuclear factor kappaB contribute to these nuclear actions of bioactive lipids with complex interactions. Recent studies have demonstrated the striking ability of bioactive lipids to regulate the production of physiologically active adipocytokines through PPARgamma activation. In particular, the function of bioactive lipids as dietary adiponectin inducers (dietary insulin sensitizers) deserves attention with respect to alleviation of metabolic syndrome by dietary manipulation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I275,I275)","v":17665093},{"$f":"(LEN($J275) - LEN(SUBSTITUTE(LOWER($J275),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J275) - LEN(SUBSTITUTE(LOWER($J275),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J275) - LEN(SUBSTITUTE(LOWER($J275),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B275:D275)","v":1},2007,"The importance of beta-carotene as a source of vitamin A with special regard to pregnant and breastfeeding women.","Strobel",17665093,"The importance of beta-carotene as a source of vitamin A with special regard to pregnant and breastfeeding women.    Abstract:   Vitamin A is essential for growth and differentiation of a number of cells and tissues. Notably during pregnancy and throughout the breastfeeding period, vitamin A has an important role in the healthy development of the fetus and the newborn, with lung development and maturation being particularly important. The German Nutrition Society (DGE) recommends a 40% increase in vitamin A intake for pregnant women and a 90% increase for breastfeeding women. However, pregnant women or those considering becoming pregnant are generally advised to avoid the intake of vitamin A rich liver and liver foods, based upon unsupported scientific findings. As a result, the provitamin A carotenoid beta-carotene remains their essential source of vitamin A. Basic sources of provitamin A are orange and dark green vegetables, followed by fortified beverages which represent between 20% and 40% of the daily supply. The average intake of beta-carotene in Germany is about 1.5-2 mg a day. Assuming a vitamin A conversion rate for beta-carotene for juices of 4:1, and fruit and vegetables between 12:1 and 26:1; the total vitamin A contribution from beta-carotene intake represents 10-15% of the RDA. The American Pediatrics Association cites vitamin A as one of the most critical vitamins during pregnancy and the breastfeeding period, especially in terms of lung function and maturation. If the vitamin A supply of the mother is inadequate, her supply to the fetus will also be inadequate, as will later be her milk. These inadequacies cannot be compensated by postnatal supplementation. A clinical study in pregnant women with short birth intervals or multiple births showed that almost 1/3 of the women had plasma retinol levels below 1.4 micromol/l corresponding to a borderline deficiency. Despite the fact that vitamin A and beta-carotene rich food is generally available, risk groups for low vitamin A supply exist in the western world. It is therefore highly critical to restrict the beta-carotene supply from diet, particularly from sources of beta-carotene with high consumer acceptance such as fortified juices (e.g. quot;ACE juicesquot;) or dietary supplements (e.g. multivitamins for pregnant women). For the part of the population unable to meet vitamin A requirements according to the DACH recommendations, sufficient intake of beta-carotene may be crucial to help improve and maintain adequate vitamin A status and prevention of developmental disorders. At this time it has to be urgently advised against restricting the beta-carotene supply or putting warning labels on beta-carotene fortified products. It is, however, highly recommended to improve the available data on nutrient intakes in Germany, especially for pregnant and breastfeeding women. For them, recommendations to be aware of potential nutrient intake inadequacies might prove useful."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I276,I276)","v":17727362},{"$f":"(LEN($J276) - LEN(SUBSTITUTE(LOWER($J276),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J276) - LEN(SUBSTITUTE(LOWER($J276),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J276) - LEN(SUBSTITUTE(LOWER($J276),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B276:D276)","v":1},2007,"Angiogenesis in skin aging and photoaging.","Chung",17727362,"Angiogenesis in skin aging and photoaging.    Abstract:   Angiogenesis, the process of generating new blood vessels, is affected by various physiological and pathological conditions of skin. The skin aging process can be divided into intrinsic aging and photoaging. With aging, cutaneous blood vessels undergo pronounced alterations. A reduction of the cutaneous microvasculature has been observed in the skin of elderly individuals. Human skin is exposed daily to solar ultraviolet (UV) radiation, infrared rays and heat, and these stimuli are known to induce skin angiogenesis. Interestingly, although acute UV irradiation stimulates skin angiogenesis, cutaneous blood vessels are decreased in chronically photodamaged skin. The reason for the differential effects of acute and chronic UV exposure on skin angiogenesis remains to be elucidated. This review discusses the vascularization changes in intrinsically aged and photoaged human skin, the effects of UV irradiation, infrared rays and heat on skin angiogenesis, and the effects of topical retinoic acid treatment on UV-induced angiogenesis and cutaneous vascularity in aged and photoaged human skin. An understanding of the molecular mechanisms of aging- and photoaging-dependent changes of skin angiogenesis may provide us with new insights to prevent and treat the skin aging process."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I277,I277)","v":17627554},{"$f":"(LEN($J277) - LEN(SUBSTITUTE(LOWER($J277),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J277) - LEN(SUBSTITUTE(LOWER($J277),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J277) - LEN(SUBSTITUTE(LOWER($J277),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B277:D277)","v":1},2007,"Visceral fat as target of highly active antiretroviral therapy-associated metabolic syndrome.","Barbaro",17627554,"Visceral fat as target of highly active antiretroviral therapy-associated metabolic syndrome.    Abstract:   HIV-associated lipodystrophy or lipoatrophy, unreported before the introduction of highly active antiretroviral therapy (HAART), was first described in 1998, and has a prevalence ranging from 18% to 83%. As in genetic lipodystrophy syndromes, fat redistribution may precede the development of metabolic complications (dyslipidemia, insulin resistance) in HIV-infected patients receiving HAART. The pathogenesis of HAART-associated lipodystrophy and metabolic syndrome is complex and a number of factors are involved, including direct effects of HAART on lipid metabolism, endothelial and adipocyte cell function, and mitochondria. Protease inhibitors are responsible for a decrease in cytoplasmic retinoic-acid protein-1, in low density lipoprotein-receptor-related protein and in peroxisome proliferator activated receptor type-gamma. Nucleoside reverse transcriptase inhibitors, and thymidine analogues, are responsible for mitochondrial dysfunction as demonstrated by a decrease in subcutaneous adipose tissue mitochondrial DNA content. Both phenomena are responsible for a decreased differentiation of adipocytes, increased levels of free fatty acids and lipoatrophy. The increased levels of proinflammatory cytokines, such as tumor necrosis factor (TNF)-alpha and interleukin-6 may further contribute in development of lipodystrophy. TNF-alfa activates 11-beta-hydroxysteroid dehydrogenase type-1, which converts inactive cortisone to active cortisol, resulting in increased lipid accumulation in adipocytes and insulin resistance. HAART drugs and inflammatory cytokines are associated with a decrease in adiponectin. The levels of adiponectin and adiponectin-to-leptin ratio correlate positively with insulin resistance in HIV-infected patients with lipodystrophy. HAART-associated metabolic syndrome is an increasingly recognized clinical entity. The atherogenic profile of this syndrome may increase the risk of cardiovascular disease even in young HIV-infected patients. A better understanding of the molecular mechanisms responsible for this syndrome will lead to the discovery of new drugs that will reduce the incidence of lipodystrophy and related metabolic complications in HIV-infected patients receiving HAART."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I278,I278)","v":17619879},{"$f":"(LEN($J278) - LEN(SUBSTITUTE(LOWER($J278),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J278) - LEN(SUBSTITUTE(LOWER($J278),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J278) - LEN(SUBSTITUTE(LOWER($J278),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B278:D278)","v":1},2007,"Two cases of isolated symptomatic myocarditis induced by all-trans retinoic acid (ATRA).","Klein",17619879,"Two cases of isolated symptomatic myocarditis induced by all-trans retinoic acid (ATRA).    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I279,I279)","v":17305523},{"$f":"(LEN($J279) - LEN(SUBSTITUTE(LOWER($J279),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J279) - LEN(SUBSTITUTE(LOWER($J279),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J279) - LEN(SUBSTITUTE(LOWER($J279),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B279:D279)","v":1},2005,"Emerging targets for COPD therapy.","Barnes",17305523,"Emerging targets for COPD therapy.    Abstract:   No currently available treatments reduce the progression of COPD or suppress the inflammation in small airways and lung parenchyma. However, several new treatments that target the inflammatory process are in clinical development. A group of specific therapies are directed against the influx of inflammatory cells into the airways and lung parenchyma that occurs in COPD; these include adhesion molecule and chemokine-directed therapy, as well as therapies to combat tumour necrosis factor-alpha and augment interleukin-10. Broad spectrum anti-inflammatory drugs are now in phase III development for COPD, and include phosphodiesterase-4 inhibitors. Other drugs that inhibit cell signalling include inhibitors of p38 mitogen-activated protein kinase, nuclear factor-kappaB and phosphoinositide-3 kinase-gamma. More specific approaches are to give antioxidants, inhibitors of inducible nitric oxide synthase, and leukotriene B4 receptor antagonists. Epidermal growth factor receptor kinase inhibitors and calcium-activated chloride channel inhibitors have potential to combat mucus overproduction. Therapy to inhibit fibrosis is being developed against transforming growth factor-beta1 and protease activated receptor-2. There is also a search for serine proteinase and matrix metalloproteinase inhibitors to prevent lung destruction and the development of emphysema, as well as drugs such as retinoids that may even reverse this process. Effective delivery of drugs to the sites of disease in the peripheral lung is an important consideration, and there is the need for validated biomarkers and monitoring techniques in early clinical studies with new therapies for COPD."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I280,I280)","v":17146999},{"$f":"(LEN($J280) - LEN(SUBSTITUTE(LOWER($J280),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J280) - LEN(SUBSTITUTE(LOWER($J280),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J280) - LEN(SUBSTITUTE(LOWER($J280),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B280:D280)","v":1},2005,"The role of airway secretions in COPD: pathophysiology, epidemiology and pharmacotherapeutic options.","Rogers",17146999,"The role of airway secretions in COPD: pathophysiology, epidemiology and pharmacotherapeutic options.    Abstract:   Often considered an aggravating but otherwise benign component of chronic obstructive pulmonary disease (COPD), airway mucus hypersecretion is now recognised as a potential risk factor for an accelerated loss of lung function in COPD and is a key pathophysiological feature in many patients, particularly those prone to respiratory tract infection. Consequently, it is important to develop drugs that inhibit mucus hypersecretion in these susceptible patients. Conventional therapy including anticholinergics, beta2-adrenoceoptor agonists, alone or in combination with corticosteroids, mucolytics and macrolide antibiotics are not entirely or consistently effective in inhibiting airway mucus hypersecretion in COPD. Novel pharmacotherapeutic targets are being investigated, including inhibitors of nerve activity (e.g., BK(Ca) channel activators), tachykinin receptor antagonists, epoxygenase inducers (e.g., benzafibrate), inhibitors of mucin exocytosis (e.g., anti-MARCKS peptide and Munc-18B blockers), inhibitors of mucin synthesis and goblet cell hyperplasia (e.g., EGF receptor tyrosine kinase inhibitors, p38 MAP kinase inhibitors, MEK/ERK inhibitors, hCACL2 blockers and retinoic acid receptor-alpha antagonists), inducers of goblet cell apoptosis (e.g., Bax inducers or Bcl-2 inhibitors), and purinoceptor P(2Y2) antagonists to inhibit mucin secretion or P(2Y2) agonists to hydrate secretions. However, real and theoretical differences delineate the mucus hypersecretory phenotype in COPD from that in other hypersecretory diseases of the airways. More information is required on these differences to identify therapeutic targets pertinent to COPD which, in turn, should lead to rational design of anti-hypersecretory drugs for specific treatment of airway mucus hypersecretion in COPD."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I281,I281)","v":17020459},{"$f":"(LEN($J281) - LEN(SUBSTITUTE(LOWER($J281),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J281) - LEN(SUBSTITUTE(LOWER($J281),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J281) - LEN(SUBSTITUTE(LOWER($J281),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B281:D281)","v":1},2006,"Cardiac and cardiovascular toxicity of nonanthracycline anticancer drugs.","Jones",17020459,"Cardiac and cardiovascular toxicity of nonanthracycline anticancer drugs.    Abstract:   Anthracyclines are a well-known cause of cardiotoxicity, but a number of other drugs used to treat cancer can also result in cardiac and cardiovascular adverse effects. Cardiotoxicity can result in the alteration of cardiac rhythm, changes in blood pressure and ischemia, and can also alter the ability of the heart to contract and/or relax. The clinical spectrum of these toxicities can range from subclinical abnormalities to catastrophic life-threatening, and sometimes fatal, sequelae. These events may occur acutely or may only become apparent months or years following completion of oncological treatment. Ischemia and rhythm abnormalities are treated symptomatically in most cases. Knowledge of these toxicities can aid clinicians to choose the optimal and least toxic regimen suitable for an individual patient."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I282,I282)","v":17014561},{"$f":"(LEN($J282) - LEN(SUBSTITUTE(LOWER($J282),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J282) - LEN(SUBSTITUTE(LOWER($J282),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J282) - LEN(SUBSTITUTE(LOWER($J282),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B282:D282)","v":1},2006,"Molecular mechanisms mediating vascular calcification: role of matrix Gla protein.","Proudfoot",17014561,"Molecular mechanisms mediating vascular calcification: role of matrix Gla protein.    Abstract:   Patients with chronic kidney disease (CKD) have a higher incidence of vascular calcification and a greatly increased risk of cardiovascular death. The mechanisms involved in the accelerated vascular calcification observed in CKD have recently become clearer, leading to the hypothesis that a lack of natural inhibitors of calcification may trigger calcium deposition. One of these inhibitory factors, matrix Gla protein (MGP), is the focus of the present review. MGP, originally isolated from bone, is a vitamin K-dependent protein that is also highly expressed by vascular smooth muscle cells. MGP has been confirmed as a calcification-inhibitor in numerous studies; however, its mechanism of action is not completely understood. It potentially acts in several ways to regulate calcium deposition including: (i) binding calcium ions and crystals; (ii) antagonizing bone morphogenetic protein and altering cell differentiation; (iii) binding to extracellular matrix components; and (iv) regulating apoptosis. Its expression is regulated by several factors including retinoic acid, vitamin D and extracellular calcium ions, and a reduced form of vitamin K (KH2) is important in maintaining MGP in an active form. Therefore, strategies aimed at increasing its expression and activity may be beneficial in tipping the balance in favour of inhibition of calcification in CKD."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I283,I283)","v":16972684},{"$f":"(LEN($J283) - LEN(SUBSTITUTE(LOWER($J283),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J283) - LEN(SUBSTITUTE(LOWER($J283),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J283) - LEN(SUBSTITUTE(LOWER($J283),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B283:D283)","v":1},2006,"[Nutrition-related bone disease].","Hirota",16972684,"[Nutrition-related bone disease].    Abstract:   Bone disorders clearly related to nutrition are osteomalacia and osteoporosis. Osteomalacia is caused by a deficiency of vitamin D or a disturbance of its metabolism. Dietary deficiency of phosphate or excess of aluminum or cadmium will also cause osteomalacia. Osteoporosis is associated with low intake of calcium and other nutrients. Dietary copper deficiency might stimulate bone metabolism and increase in hip fractures. Excess vitamin A intake was also associated with lower bone mineral density and higher risk of hip fractures. Excess vitamin D sometimes causes mental simplicity, congenital heart disease and calcification of soft tissue. Therefore not only diet but also drugs and supplements of nutrients should be carefully observed in older women."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I284,I284)","v":16915864},{"$f":"(LEN($J284) - LEN(SUBSTITUTE(LOWER($J284),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J284) - LEN(SUBSTITUTE(LOWER($J284),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J284) - LEN(SUBSTITUTE(LOWER($J284),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B284:D284)","v":1},2006,"Nuclear receptors: potential biomarkers for assessing physiological functions of soy proteins and phytoestrogens.","Xiao",16915864,"Nuclear receptors: potential biomarkers for assessing physiological functions of soy proteins and phytoestrogens.    Abstract:   Soy consumption is associated with decreased incidence of chronic diseases, including cardiovascular diseases, atherosclerosis, diabetes, osteoporosis, and certain types of cancers. However, consumption of high amounts of soy isoflavones may adversely influence endocrine functions, such as thyroid function and reproductive performance, because of their structural similarity to endogenous estrogens. Nuclear receptors are a group of transcription factors that play critical roles in the regulation of gene expression and physiological functions through direct interaction with target genes. Modulation of the abundance of these receptors, such as changing their gene expression, alters the sensitivity of the target cells or tissues to the stimulation of ligands, and eventually affects the relevant physiological functions, such as growth, development, osteogenesis, immune response, lipogenesis, reproductive process, and anticarcinogenesis. A number of studies have shown that the bioactive components in soy can modify the expression of these receptors in various tissues and cancer cells, which is believed to be a key intracellular mechanism by which soy components affect physiological functions. This review summarizes the current understanding of the modulation of nuclear receptors by soy proteins and isoflavones, and focuses especially on the receptors for estrogens, progesterone, androgen, vitamin D, retinoic acid, and thyroid hormones as well as the potential impact on physiological functions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I285,I285)","v":16794439},{"$f":"(LEN($J285) - LEN(SUBSTITUTE(LOWER($J285),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J285) - LEN(SUBSTITUTE(LOWER($J285),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J285) - LEN(SUBSTITUTE(LOWER($J285),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B285:D285)","v":1},2006,"Treatment of nonexudative (dry) age-related macular degeneration.","Donaldson",16794439,"Treatment of nonexudative (dry) age-related macular degeneration.    Abstract:    PURPOSE OF REVIEW : The purpose of this report is to review the recent literature and summarize currently available and potential new treatment options for nonexudative age-related macular degeneration.  RECENT FINDINGS : High-dose vitamin supplementation may have some associated systemic toxicity. It is important to check that the patient is taking beta-carotene and not vitamin A as retinal acetate or palmitate, which have been associated with osteoporosis and hepatotoxicity. High-dose vitamins E and C may be associated with cardiovascular disease. Decreasing inflammation by lowering systemic cardiac C-reactive protein, fibrinogen and cholesterol may be important, especially in light of recent epidemiologic and genetic data. The results of randomized trials of laser treatment for drusen and rheopheresis should be available during 2006. Treatment with these modalities before the results of the trials are evaluated should be avoided.  SUMMARY : The holy grail of therapy for age-related macular degeneration is to avoid the development of choroidal neovascularization. High-dose vitamin supplementation should be used only in those in whom it is indicated and inflammatory parameters including highly sensitive C-reactive protein, fibrinogen and cholesterol should be stabilized because there are data associating these parameters with age-related macular degeneration and also with cardiovascular disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I286,I286)","v":16782410},{"$f":"(LEN($J286) - LEN(SUBSTITUTE(LOWER($J286),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J286) - LEN(SUBSTITUTE(LOWER($J286),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J286) - LEN(SUBSTITUTE(LOWER($J286),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B286:D286)","v":1},2006,"Peroxisome proliferator-activated receptors in vascular biology-molecular mechanisms and clinical implications.","Touyz",16782410,"Peroxisome proliferator-activated receptors in vascular biology-molecular mechanisms and clinical implications.    Abstract:   Peroxisome proliferator-activated receptors (PPAR)alpha, gamma and beta/delta belong to the nuclear receptor family of ligand-activated transcription factors. PPARs heterodimerize with the retinoid X receptor (RXR) and then act as transcription factors to modulate the function of many target genes. PPARalpha, gamma and beta/delta subtypes have significant differences in their ligand and gene specificities. PPARalpha is activated by polyunsaturated fatty acids and by fibrate drugs (fenofibrate and gemfibrozil) and controls expression of genes involved in lipid metabolism. PPARgamma is activated by fatty acid derivatives, such as hydroxyoctadecadienoic acid (HODEs), prostaglandin derivatives, such as 15-deoxy-Delta12,14-prostaglandin J2, and thiazolidinedione (glitazone) drugs, such as pioglitazone and rosiglitazone. PPARgamma is a key regulator of glucose homeostasis and adipogenesis. PPARbeta/delta ligands include polyunsaturated fatty acids, prostaglandins and synthetic compounds and stimulate fatty acid oxidation. All PPARs are expressed in vascular cells where they exert antiatherogenic, anti-inflammatory and vasculoprotective actions. Activators of PPARalpha (fibrates) and PPARgamma (thiazolidinediones or glitazones) antagonize angiotensin II effects in vivo and in vitro and have cardiovascular antioxidant and anti-inflammatory actions. PPAR agonists slightly reduce blood pressure are cardio-protective and correct vascular structure and endothelial dysfunction in experimental models of hypertension. Because of these beneficial effects, activators of PPARs may have therapeutic potential in the prevention of cardiovascular disease beyond their actions on carbohydrate and lipid metabolism. The present chapter focuses on the role of PPARs in vascular biology and discusses the clinical implications of using PPAR agonists in the management of vascular disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I287,I287)","v":16711261},{"$f":"(LEN($J287) - LEN(SUBSTITUTE(LOWER($J287),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J287) - LEN(SUBSTITUTE(LOWER($J287),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J287) - LEN(SUBSTITUTE(LOWER($J287),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B287:D287)","v":1},2006,"[Recent changes in concepts of antioxidant treatment].","Matkovics",16711261,"[Recent changes in concepts of antioxidant treatment].    Abstract:   The promising theoretical possibilities of antioxidant prevention and protection against vascular diseases and neoplasms could not have been realized as yet. The author searches into the causes of this failure by analyzing data of recent literature. Previous preventive trials as well as newly discovered pharmacological and molecular biological effects of antioxidants are reviewed. Results of meta-analyses on prevention trials of vascular disease by vitamin-E and those of gastrointestinal cancers are also included. The lately recognized properties of antioxidants are surveyed with special regard to their capability of modulating apoptosis, inducing gene expressions and their transformation into pro-oxidants. The harmful consequence of high doses of a single antioxidant is emphasized. The retinoids, vitamins D and K possess both pro-apoptotic and antiproliferative activity, while N-acetylcysteine exerts mainly anti-apoptotic effects. Since the effects of the eight vitamin E homologues are different in many respects, alpha-tocopherol can not be regarded as vitamin E of full value. Antioxidant supply from natural sources does not seem to be sufficient for an adequate preventive effect. The author recommends such a combination in which physiological amounts of vitamins C, D, K and B-complex, N-acetylcysteine, vitamin E of natural origin might be complemented by allopurinol, co-enzyme Q-10 and alpha-lipoic acid. A diet rich in flavonoids and carotenoids is essential. Application of appropriate laboratory methods is of great value in the individualization, monitoring and control of antioxidant treatment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I288,I288)","v":16581697},{"$f":"(LEN($J288) - LEN(SUBSTITUTE(LOWER($J288),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J288) - LEN(SUBSTITUTE(LOWER($J288),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J288) - LEN(SUBSTITUTE(LOWER($J288),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B288:D288)","v":1},2006,"Treatment of airway mucus hypersecretion.","Rogers",16581697,"Treatment of airway mucus hypersecretion.    Abstract:   Airway mucus hypersecretion is now recognized as a key pathophysiological feature in many patients with asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis. Consequently, it is important to develop drugs that inhibit mucus hypersecretion in these susceptible patients. Conventional therapies, including anticholinergics, ss2-adrenoceptor agonists, corticosteroids, mucolytics and macrolide antibiotics, have variable efficacy in inhibiting airway mucus hypersecretion, and are less effective in COPD than in asthma. Novel pharmacotherapeutic targets are being investigated, including inhibitors of nerve activity (e.g. large conductance calcium-activated potassium, BKCa, channel activators), tachykinin receptor antagonists, epoxygenase inducers (e.g. benzafibrate), inhibitors of mucin exocytosis (e.g. anti-myristoylated alanine-rich C kinase substrate (MARCKS), peptide and Munc-18B blockers), inhibitors of mucin synthesis and goblet cell hyperplasia (e.g. epidermal growth factor (EGF), receptor tyrosine kinase inhibitors, p38 mitogen-activated protein (MAP), kinase inhibitors, MAP kinase kinase/extracellular signal-regulated kinase (MEK/ERK), inhibitors, human calcium-activated chloride (hCACL2), channel blockers and retinoic acid receptor-a antagonists), inducers of goblet cell apoptosis (e.g. Bax inducers or Bcl-2 inhibitors), and purinoceptor P(2Y2) antagonists to inhibit mucin secretion or P(2Y2) agonists to hydrate secretions. However, real and theoretical differences delineate the mucus hypersecretory phenotype in asthma from that in COPD. More information is required on these differences to identify specific therapeutic targets which, in turn, should lead to rational design of anti-hypersecretory drugs for treatment of airway mucus hypersecretion in asthma and COPD."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I289,I289)","v":16448612},{"$f":"(LEN($J289) - LEN(SUBSTITUTE(LOWER($J289),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J289) - LEN(SUBSTITUTE(LOWER($J289),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J289) - LEN(SUBSTITUTE(LOWER($J289),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B289:D289)","v":1},2006,"[Hepatic stellate cells: its role in normal and pathological conditions].","Sarem",16448612,"[Hepatic stellate cells: its role in normal and pathological conditions].    Abstract:   Hepatic fibrosis is a dynamic and sophisticatedly regulated wound healing response to chronic hepatocellular injury. This fibrotic process results from the accumulation of extracellular matrix (ECM) including collagen, proteoglycan, and adhesive glycoproteins which are principally produced by hepatic stellate cells (HSC), a mesenchymal cell type located between parenchymal cell plates and sinusoidal endothelial cells in the space of Disse. In physiological conditions, quiescent HSCs play important roles in the regulation of retinoid homeostasis and ECM remodeling by producing ECM components as well as metalloproteases and its inhibitor. However during hepatic fibrogenesis, HSCs are known to be activated or quot;transdifferentiatedquot; to myofibroblast-like cells which play a pivotal role in ECM remodeling and hepatic blood flow regulation. Activation of HSC is now well established as the key process involved in the development of hepatic fibrosis. Both basic morphology and functions of HSCs in normal conditions and its role in pathological fibrosis will be discussed in this review."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I290,I290)","v":16344101},{"$f":"(LEN($J290) - LEN(SUBSTITUTE(LOWER($J290),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J290) - LEN(SUBSTITUTE(LOWER($J290),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J290) - LEN(SUBSTITUTE(LOWER($J290),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B290:D290)","v":1},2005,"The choroid plexus-cerebrospinal fluid system: from development to aging.","Redzic",16344101,"The choroid plexus-cerebrospinal fluid system: from development to aging.    Abstract:   The function of the cerebrospinal fluid (CSF) and the tissue that secretes it, the choroid plexus (CP), has traditionally been thought of as both providing physical protection to the brain through buoyancy and facilitating the removal of brain metabolites through the bulk drainage of CSF. More recent studies suggest, however, that the CP-CSF system plays a much more active role in the development, homeostasis, and repair of the central nervous system (CNS). The highly specialized choroidal tissue synthesizes trophic and angiogenic factors, chemorepellents, and carrier proteins, and is strategically positioned within the ventricular cavities to supply the CNS with these biologically active substances. Through polarized transport systems and receptor-mediated transcytosis across the choroidal epithelium, the CP, a part of the blood-CSF barrier (BCSFB), controls the entry of nutrients, such as amino acids and nucleosides, and peptide hormones, such as leptin and prolactin, from the periphery into the brain. The CP also plays an important role in the clearance of toxins and drugs. During CNS development, CP-derived growth factors, such as members of the transforming growth factor-beta superfamily and retinoic acid, play an important role in controlling the patterning of neuronal differentiation in various brain regions. In the adult CNS, the CP appears to be critically involved in neuronal repair processes and the restoration of the brain microenvironment after traumatic and ischemic brain injury. Furthermore, recent studies suggest that the CP acts as a nursery for neuronal and astrocytic progenitor cells. The advancement of our knowledge of the neuroprotective capabilities of the CP may therefore facilitate the development of novel therapies for ischemic stroke and traumatic brain injury. In the later stages of life, the CP-CSF axis shows a decline in all aspects of its function, including CSF secretion and protein synthesis, which may in themselves increase the risk for development of late-life diseases, such as normal pressure hydrocephalus and Alzheimers disease. The understanding of the mechanisms that underlie the dysfunction of the CP-CSF system in the elderly may help discover the treatments needed to reverse the negative effects of aging that lead to global CNS failure."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I291,I291)","v":16105480},{"$f":"(LEN($J291) - LEN(SUBSTITUTE(LOWER($J291),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J291) - LEN(SUBSTITUTE(LOWER($J291),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J291) - LEN(SUBSTITUTE(LOWER($J291),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B291:D291)","v":1},2005,"Impact of thiazolidinedione therapy on atherogenesis.","van Wijk",16105480,"Impact of thiazolidinedione therapy on atherogenesis.    Abstract:   Thiazolidinediones (TZDs), which are synthetic ligands for peroxisome proliferator activated receptor g (PPARg) activation, have been introduced in clinical medicine to improve insulin resistance and glycemic control in patients with type 2 diabetes. The metabolic effects of TZDs are mediated by receptor-dependent activation of the PPARg-retinoid X receptor (RXR) complex and subsequent transcriptional activation of target genes. The PPARg1 isoform is also expressed in endothelial cells, vascular smooth muscle cells, and monocytes/macrophages in the vasculature. TZDs have been shown to have anti-atherosclerotic effects on these cells in vitro, which appear to be partially independent of the PPARg-RXR-mediated transcriptional effects. Direct anti-atherosclerotic effects of TZDs include increased nitric oxide bioavailability, decreased leukocyte/endothelial cell interaction, reduced vascular smooth muscle cell migration and proliferation, and cholesterol efflux from macrophages. So far, there are no data on the effects of TZDs on cardiovascular events, but studies using surrogate markers of vascular disease provide preliminary evidence that TZDs delay progression of atherosclerosis in different patient groups. TZDs interfere with key processes in atherogenesis and may, therefore, offer additional opportunities to improve cardiovascular risk beyond treatment of glycemic control in patients with type 2 diabetes."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I292,I292)","v":15821783},{"$f":"(LEN($J292) - LEN(SUBSTITUTE(LOWER($J292),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J292) - LEN(SUBSTITUTE(LOWER($J292),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J292) - LEN(SUBSTITUTE(LOWER($J292),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B292:D292)","v":1},2005,"Cetuximab: an epidermal growth factor receptor chemeric human-murine monoclonal antibody.","Harding",15821783,"Cetuximab: an epidermal growth factor receptor chemeric human-murine monoclonal antibody.    Abstract:   The epidermal growth factor receptor (EGFR) is a member of the ErbB family of receptors. It is composed of extracellular domains, including a ligand-binding domain, a hydrophobic transmembrane region and a tyrosine kinase-containing cytoplasmic region. Stimulation of the EGFR by endogenous ligands, EGF or transforming growth factor-alpha (TGF-alpha), results in a conformational change in the receptor, permitting it to enter into dimers and other oligomers. Dimerization results in activation of intracellular tyrosine kinase, protein phosphorylation and stimulation of various cell signaling pathways that mediate gene transcription and cell cycle progression. The EGFR is expressed on normal human cells but higher levels of expression of the receptor have also been shown to be correlated with malignancy in a variety of cancers. In addition, expression of the EGFR by malignant cells is associated with poor prognosis and resistance to therapy. Cetuximab is a chimeric human-murine monoclonal antibody that binds competitively and with high affinity to the EGFR. Binding of the antibody to the EGFR prevents stimulation of the receptor by endogenous ligands and results in inhibition of cell proliferation, enhanced apoptosis, and reduced angiogenesis, invasiveness and metastasis. Binding of cetuximab to the receptor also results in internalization of the antibody-receptor complex which leads to an overall downregulation of EGFR expression. The EGFR is a prime target for new anticancer therapy, and other agents in development include small molecular tyrosine kinase inhibitors and antisense therapies. Preclinical studies have demonstrated that cetuximab reduces chemotherapy and radiotherapy resistance in human tumor cell lines in vitro and in nude mice bearing xenografts of human tumors. In clinical and preclinical studies cetuximab has been shown to induce response to treatment when used in combination with chemotherapy in patients previously refractory to chemotherapy. Based on these studies, cetuximab can be added to regimens using docetaxel, cisplatin, carboplatin, irinotecan, paclitaxel and fluorouracil and may add to treatment efficacy. Phase I dose-finding studies showed that saturation of cetuximab clearance occurred after administration of 400 mg/m2 as a loading dose followed by weekly infusions of 250 mg/m2. The most commonly reported adverse event associated with cetuximab treatment is an acneiform rash that occurs in 70-80% of patients treated with cetuximab. The rash is rarely dose- or treatment-limiting, and may diminish in intensity with continued exposure to cetuximab. Improvement may be seen after treatment with topical antibiotic preparations, topical steroids or topical retinoids. The rash resolves fully after discontinuation of cetuximab treatment. EGFR is widely expressed in skin and skin biopsies in areas involved with the characteristic cetuximab eruption demonstrate neutrophilic folliculitis. In fact, analysis of four phase II clinical trials of cetuximab in combination with chemotherapy in patients with colorectal cancer, squamous cell carcinoma of the head and neck, or pancreatic cancer showed that development of the acneiform rash was significantly correlated with response to treatment; grade 3 rash may be especially predictive of response. It is possible that development of acneiform rash may become an important clinical prognostic marker. Serious cetuximab-related toxicities include hypersensitivity, infusion reactions and interstitial lung disease. Results of a large phase II study have shown response when used in combination with irinotecan in 22.9% of patients with EGFR-expressing, irinotecan-refractory, colorectal cancer. Cetuximab has recently been approved for this indication in the United States, Switzerland, Iceland, Norway and the 25 member states of the European Union. Other phase II and III studies show significant response to treatment in variable proportions of patients with squamous cell carcinoma of the head and neck, non-small cell lung cancer and pancreatic cancer when cetuximab is used first or second line in combination with chemotherapy. Thus, cetuximab is emerging as a very promising new therapy to be used in conjunction with existing therapies for the treatment of a spectrum of solid tumors."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I293,I293)","v":15653094},{"$f":"(LEN($J293) - LEN(SUBSTITUTE(LOWER($J293),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J293) - LEN(SUBSTITUTE(LOWER($J293),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J293) - LEN(SUBSTITUTE(LOWER($J293),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B293:D293)","v":1},2004,"Peroxisome proliferator-activated receptors gamma ligands and ischemia and reperfusion injury.","Cuzzocrea",15653094,"Peroxisome proliferator-activated receptors gamma ligands and ischemia and reperfusion injury.    Abstract:   Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors that are related to retinoid, steroid and thyroid hormone receptors. The PPAR subfamily comprises of three members, PPAR-alpha, PPAR-beta and PPAR-gamma. PPAR-gamma has recently been implicated as a regulator of cellular proliferation and inflammatory responses. There is good evidence that ligands of PPAR-gamma, including certain thiazolinediones, reduce tissue injury associated with ischemia and reperfusion. The potential utility of PPAR-gamma ligands in ischemia and reperfusion will be discussed in this review."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I294,I294)","v":15611620},{"$f":"(LEN($J294) - LEN(SUBSTITUTE(LOWER($J294),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J294) - LEN(SUBSTITUTE(LOWER($J294),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J294) - LEN(SUBSTITUTE(LOWER($J294),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B294:D294)","v":1},2004,"Red light, green light: signals that control endothelial cell proliferation during embryonic vascular development.","Bohnsack",15611620,"Red light, green light: signals that control endothelial cell proliferation during embryonic vascular development.    Abstract:   The proper regulation of endothelial cell proliferation is critical for vascular development in the embryo. VEGF-A and bFGF, which are important in the induction of mesodermal progenitors to form a capillary plexus, are also key mitogenic signals. Disruption in VEGF-A or bFGF decreases endothelial cell proliferation and halts vascular development. While stimulation of endothelial cell proliferation is necessary during vasculogenesis, inhibitory signals such as TGF-beta1 and retinoic acid are equally important and required to inhibit endothelial cell proliferation. These signals and activation of numerous downstream pathways must be properly integrated with extracellular matrix proteins and integrin receptor signaling in order to form the embryonic vasculature. This coordination of mitogenic and anti-proliferative signals needed to form a circulatory network in the embryo may be unique relative to neovascularization in adult tissues where mitogenic stimulation promotes proliferation of previously quiescent endothelial cells to repair and expand existing vasculature."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I295,I295)","v":15364192},{"$f":"(LEN($J295) - LEN(SUBSTITUTE(LOWER($J295),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J295) - LEN(SUBSTITUTE(LOWER($J295),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J295) - LEN(SUBSTITUTE(LOWER($J295),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B295:D295)","v":1},2004,"Prospects for new drugs for chronic obstructive pulmonary disease.","Barnes",15364192,"Prospects for new drugs for chronic obstructive pulmonary disease.    Abstract:   No currently available treatments have been shown to slow the progression of chronic obstructive pulmonary disease (COPD) or suppress the inflammation in small airways and lung parenchyma. However, several new treatments are in clinical development; some target the inflammatory process and others are directed against structural cells. A group of specific therapies are directed against the influx of inflammatory cells into the airways and lung parenchyma that occurs in COPD; these include agents directed against adhesion molecules and chemokines, as well as therapies to oppose tumour necrosis factor alpha and increase interleukin 10. Broad-range anti-inflammatory drugs are now in phase III development for COPD; they include inhibitors of phosphodiesterase 4. Other drugs that inhibit cell signalling include inhibitors of p38 mitogen-activated protein kinase, nuclear factor kappaB, and phosphoinositide-3-kinase gamma. More specific approaches are to give antioxidants, inhibitors of inducible nitric oxide synthase, and antagonists of leukotriene B4 receptor. Inhibitors of epidermal-growth-factor-receptor kinase and calcium-activated chloride channels have the potential to prevent overproduction of mucus. Therapy to inhibit fibrosis is being developed against transforming growth factor beta1 and protease-activated receptor 2. There is also a search for inhibitors of serine proteinases and matrix metalloproteinases to prevent lung destruction and the development of emphysema, as well as drugs such as retinoids that might even reverse this process. Effective delivery of drugs to the sites of disease in the peripheral lung is an important consideration, and there is a need for validated biomarkers and monitoring techniques in early clinical studies with new therapies for COPD."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I296,I296)","v":15193450},{"$f":"(LEN($J296) - LEN(SUBSTITUTE(LOWER($J296),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J296) - LEN(SUBSTITUTE(LOWER($J296),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J296) - LEN(SUBSTITUTE(LOWER($J296),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B296:D296)","v":1},2004,"Gene silencing by nuclear orphan receptors.","Zhang",15193450,"Gene silencing by nuclear orphan receptors.    Abstract:   Nuclear orphan receptors represent a large and diverse subgroup in the nuclear receptor superfamily. Although putative ligands for these orphan members remain to be identified, some of these receptors possess intrinsic activating, inhibitory, or dual regulatory functions in development, differentiation, homeostasis, and reproduction. In particular, gene-silencing events elicited by chicken ovalbumin upstream promoter-transcription factors (COUP-TFs); dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (DAX-1); germ cell nuclear factor (GCNF); short heterodimer partner (SHP); and testicular receptors 2 and 4 (TR2 and TR4) are among the best characterized. These orphan receptors are critical in controlling basal activities or hormonal responsiveness of numerous target genes. They employ multiple and distinct mechanisms to mediate target gene repression. Complex cross-talk exists between these orphan receptors at their cognate DNA binding elements and an array of steroid?nonsteroid hormone receptors, other transcriptional activators, coactivators and corepressors, histone modification enzyme complexes, and components of basal transcriptional components. Therefore, perturbation induced by these orphan receptors at multiple levels, including DNA binding activities, receptor homo- or heterodimerization, recruitment of cofactor proteins, communication with general transcriptional machinery, and changes at histone acetylation status and chromatin structures, may contribute to silencing of target gene expression in a specific promoter or cell-type context. Moreover, the findings derived from gene-targeting studies have demonstrated the significance of these orphan receptors function in physiologic settings. Thus, COUP-TFs, DAX-1, GCNF, SHP, and TR2 and 4 are known to be required for multiple physiologic and biologic functions, including neurogenesis and development of the heart and vascular system steroidogenesis and sex determination, gametogenesis and embryonic development, and cholesterol?lipid homeostasis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I297,I297)","v":15153273},{"$f":"(LEN($J297) - LEN(SUBSTITUTE(LOWER($J297),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J297) - LEN(SUBSTITUTE(LOWER($J297),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J297) - LEN(SUBSTITUTE(LOWER($J297),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B297:D297)","v":1},2004,"Factors to consider in Micronesian food-based interventions: a case study of preventing vitamin A deficiency.","Englberger",15153273,"Factors to consider in Micronesian food-based interventions: a case study of preventing vitamin A deficiency.    Abstract:    BACKGROUND : Many factors need to be considered in a food-based intervention. Vitamin A deficiency and chronic diseases, such as diabetes, heart disease and cancer, have become serious problems in the Federated States of Micronesia (FSM) following the decreased production and consumption of locally grown foods. However, agricultural and social conditions are still favourable for local food production.  AIM : To identify key factors to consider in a Micronesian food-based intervention focusing on increased production and consumption of four major Micronesian staple foods: banana, breadfruit, giant swamp taro and pandanus.  METHODS : Ethnographic methods including key informant interviews and a literature review.  RESULTS : Pacific and Micronesian values, concepts of food and disease, and food classifications differ sharply from Western concepts. There are few FSM professionals with nutrition expertise. Traditional foods and food cultivars vary in nutrient content, consumption level, cost, availability, status, convenience in growing, storing and cooking, and organoleptic factors.  CONCLUSIONS : A systematic consideration of the factors that relate to a food-based intervention is critical to its success. The evaluation of which food and cultivar of that food that might be most effectively promoted is also critical. Regional differences, for example FSM inter-island differences between the staple foods and cultivars, must be considered carefully. The evaluation framework presented here may be relevant to Pacific Island and other countries with similar foods where food-based interventions are being planned. An ethnographic approach was found to be essential in understanding the cultural context and in data collection and analysis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I298,I298)","v":15034284},{"$f":"(LEN($J298) - LEN(SUBSTITUTE(LOWER($J298),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J298) - LEN(SUBSTITUTE(LOWER($J298),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J298) - LEN(SUBSTITUTE(LOWER($J298),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B298:D298)","v":1},2004,"[Reverse cholesterol transport in cultured gallbladder epithelial cells].","Lee",15034284,"[Reverse cholesterol transport in cultured gallbladder epithelial cells].    Abstract:   Bile is the major route of cholesterol excretion from the body. It is concentrated in the gallbladder, and often results in supersaturation of cholesterol. The high levels of cholesterol in gallbladder bile has clinical implications with respect to cholesterol gallstone formation and cholesterolosis of the gallbladder wall. Gallbladder epithelial cells (GBEC) are exposed to high cholesterol concentrations on their apical surfaces. Therefore, GBEC are uniquely positioned to play an important role in modulating biliary cholesterol concentrations. Recently, it has been documented that the key-transporter for polarized cholesterol and phospholipid efflux in GBEC is ATP-binding cassette transporter A1 (ABCA1) and Liver X receptor (LXR) and retinoid X receptor (RXR) in the nucleus of GBEC have a role that regulates ABCA1 expression. In addition, GBEC synthesize apolipoprotein A-I and E as cholesterol acceptors. These results indicate that GBEC has a perfect system for reverse cholesterol transport. We introduce the roles and mechanisms of ABCA1, scavenger receptor class B-I, LXR and RXR related to reverse cholesterol transport in GBEC with a review of our study experience and related literature."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I299,I299)","v":14751813},{"$f":"(LEN($J299) - LEN(SUBSTITUTE(LOWER($J299),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J299) - LEN(SUBSTITUTE(LOWER($J299),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J299) - LEN(SUBSTITUTE(LOWER($J299),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B299:D299)","v":1},2004,"The quot;CholesteRORquot; protective pathway in the vascular system.","Boukhtouche",14751813,"The quot;CholesteRORquot; protective pathway in the vascular system.    Abstract:   Retinoic acid receptor-related Orphan Receptor alpha (RORalpha) is a member of the nuclear hormone receptor superfamily. RORalpha has long been considered as a constitutive activator of transcription in the absence of exogenous ligand; however, cholesterol has recently been identified as a natural ligand of RORalpha. The spontaneous staggerer (sg/sg) mutation is a deletion in the Rora gene that prevents the translation of the ligand-binding domain (LBD), leading to the loss of RORalpha activity. The homozygous Rora(sg/sg) mutant mouse, of which the most obvious phenotype is ataxia associated with cerebellar degeneration, also displays a variety of other phenotypes, including several vascular ones; in particular, dysfunction of smooth muscle cells and enhanced susceptibility to atherosclerosis. Moreover, RORalpha appears to participate in the regulation of plasma cholesterol levels, and has been shown to positively regulate apolipoprotein (apo)A-I and apoC-III gene expression. Yet its activity is regulated by cholesterol itself, making RORalpha an intracellular cholesterol target."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I300,I300)","v":14730505},{"$f":"(LEN($J300) - LEN(SUBSTITUTE(LOWER($J300),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J300) - LEN(SUBSTITUTE(LOWER($J300),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J300) - LEN(SUBSTITUTE(LOWER($J300),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B300:D300)","v":1},2004,"Vitamin D receptor and analogs.","Dusso",14730505,"Vitamin D receptor and analogs.    Abstract:   In chronic kidney disease (CKD), high circulating levels of parathyroid hormone (PTH) cause osteitis fibrosa, bone loss, and cardiovascular complications that increase morbidity and mortality. Impaired production of 1,25-dihydroxyvitamin D (calcitriol), the hormonal form of vitamin D, is a major contributor to the generation and maintenance of parathyroid hyperplasia and increased synthesis and secretion of PTH. Calcitriol inhibits PTH gene transcription and ameliorates parathyroid hyperplasia by suppressing the expression of and growth signals from the autocrine transforming growth factor alpha (TGFalpha)/epidermal growth factor receptor (EGFR)-growth loop, a main determinant of parathyroid cell proliferation. Calcitriol reduction of parathyroid hyperplasia and serum PTH levels demands a functional vitamin D receptor (VDR). Although VDR is normal in CKD, parathyroid VDR content is reduced markedly. Furthermore, VDR function, as a transcriptional regulator of vitamin D responsive genes, is impaired by several factors including hypocalcemia, hyperphosphatemia, accumulation of uremic toxins, and reduction in cellular levels of the VDR partner, retinoid X receptor. Therapy with calcitriol analogs can overcome the antagonism on calcitriol-VDR actions induced by CKD. Although not all analog formulations are equally effective, they offer a wider therapeutic window in counteracting vitamin D resistance and survival advantage over exclusive calcitriol therapy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I301,I301)","v":14680462},{"$f":"(LEN($J301) - LEN(SUBSTITUTE(LOWER($J301),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J301) - LEN(SUBSTITUTE(LOWER($J301),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J301) - LEN(SUBSTITUTE(LOWER($J301),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B301:D301)","v":1},2004,"Drug-induced nail abnormalities.","Piraccini",14680462,"Drug-induced nail abnormalities.    Abstract:   A large number of drugs may be responsible for the development of nail changes, including cancer chemotherapeutic agents and retinoids, however, only a few classes of drugs are consistently associated with nail symptoms. Drug-induced nail abnormalities result from toxicity to the matrix, the nail bed, the periungual tissues or the digit blood vessels. The most common symptoms include Beaus lines, onychomadesis, melanonychia, onycholysis and periungual pyogenic granulomas. Drug-induced nail changes usually involve several or all of the nails. In most cases, nail abnormalities are asymptomatic, but can sometimes cause pain and impair manual activities."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I302,I302)","v":14563626},{"$f":"(LEN($J302) - LEN(SUBSTITUTE(LOWER($J302),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J302) - LEN(SUBSTITUTE(LOWER($J302),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J302) - LEN(SUBSTITUTE(LOWER($J302),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B302:D302)","v":1},2003,"The antioxidants--vitamin C,vitamin E, selenium, and carotenoids.","Johnson",14563626,"The antioxidants--vitamin C,vitamin E, selenium, and carotenoids.    Abstract:   This is the second in a series of articles reviewing the recent revisions of the Recommended Dietary Allowances (RDA) and the resulting Dietary Reference Intakes (DRI). In April of 2000, the Food and Nutrition Board of the National Academy of Sciences released Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. The central premise of the report did not perpetuate the prevailing popular thought that large doses of antioxidants will prevent chronic diseases. Instead the panel concluded that at this time, insufficient scientific evidence exists to sustain claims that ingesting megadoses of dietary antioxidants can prevent certain chronic illnesses such as cardiovascular disease or cancer. In some instances recommended nutrient levels were reduced from the previous report in 1989; e.g., for the first time upper tolerable levels of ingestion (UL) were established to prevent the harmful effects of over consumption of essential nutrients, such as vitamin C, vitamin E, and selenium. Although dietary recommendations do exist for vitamin A, the panel did not set recommendations for beta-carotene or the other carotenoids due to lack of sufficient research to support recommended intakes or upper tolerable levels of intake. However, the panel advises the public to avoid intakes of provitamin A compounds, such as the numerous carotenoids, beyond the levels required to prevent vitamin A deficiency. Changes were also made with regard to estimating the amount of provitamin A carotenoids required to make a unit of retinal. The revised estimate suggests a twofold higher conversion rate than previously believed. Although this comprehensive report on the dietary reference intakes for vitamin C, vitamin E, selenium, and the carotenoids did not decisively confirm the role of antioxidants for the prevention of chronic diseases in humans, many research studies have generated new data to support this concept. Additional research is needed to define the attributes of antioxidants as studies progress from in vitro and animal studies to human nutrition."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I303,I303)","v":14559106},{"$f":"(LEN($J303) - LEN(SUBSTITUTE(LOWER($J303),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J303) - LEN(SUBSTITUTE(LOWER($J303),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J303) - LEN(SUBSTITUTE(LOWER($J303),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B303:D303)","v":1},2003,"Role of nuclear receptors in the regulation of gene expression by dietary fatty acids (review).","Khan",14559106,"Role of nuclear receptors in the regulation of gene expression by dietary fatty acids (review).    Abstract:   Long chain fatty acids, derived either from endogenous metabolism or by nutritional sources play significant roles in important biological processes of membrane structure, production of biologically active compounds, and participation in cellular signaling processes. Recently, the structure of dietary fatty acids has become an important issue in human health because ingestion of saturated fats (containing triglycerides composed of saturated fatty acids) is considered harmful, while unsaturated fats are viewed as beneficial. It is important to note that the molecular reason for this dichotomy still remains elusive. Since fatty acids are important players in development of pathology of cardiovascular and endocrine system, understanding the key molecular targets of fatty acids, in particular those that discriminate between saturated and unsaturated fats, is much needed. Recently, insights have been gained on several fatty acid-activated nuclear receptors involved in gene expression. In other words, we can now envision long chain fatty acids as regulators of signal transduction processes and gene regulation, which in turn will dictate their roles in health and disease. In this review, we will discuss fatty acid-mediated regulation of nuclear receptors. We will focus on peroxisome proliferators-activated receptors (PPARs), liver X receptors (LXR), retinoid X receptors (RXRs), and Hepatocyte Nuclear Factor alpha (HNF-4alpha), all of which play pivotal roles in dietary fatty acid-mediated effects. Also, the regulation of gene expression by Conjugated Linoleic Acids (CLA), a family of dienoic fatty acids with a variety of beneficial effects, will be discussed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I304,I304)","v":12969306},{"$f":"(LEN($J304) - LEN(SUBSTITUTE(LOWER($J304),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J304) - LEN(SUBSTITUTE(LOWER($J304),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J304) - LEN(SUBSTITUTE(LOWER($J304),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B304:D304)","v":1},2003,"Lymphoid organ development and cell migration.","Cyster",12969306,"Lymphoid organ development and cell migration.    Abstract:   As we travel into a new century, confronted with new infectious diseases and bioweapon threats, with surgeons continuing to push the boundaries of what is transplantable, and with gene therapists working on ways to remedy a myriad of genetic diseases, the need for improved methods to augment and suppress immune function is paramount. The recent discovery that a novel immunosuppressant works by blocking lymphocyte egress from lymphoid organs provides a compelling example of how improved understanding of lymphoid organ function will contribute to future drug development and human health. This volume brings together reviews from leaders in the field of thymus and secondary lymphoid organ biology, including discussions on the roles of transcriptional regulators Foxn1, retinoid-related orphan receptor gamma and nuclear factor-kappaB in lymphoid organ development, the function of lymphotoxin and other cytokines in lymphoid tissue organization, the guidance activity of chemokines in a multitude of immune cell-positioning events, the mechanism of action of the immunosuppressant FTY720, and the application of two-photon laser scanning microscopy to reveal the dynamic behavior of lymphoid cells in the depths of these essential tissues."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I305,I305)","v":12875617},{"$f":"(LEN($J305) - LEN(SUBSTITUTE(LOWER($J305),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J305) - LEN(SUBSTITUTE(LOWER($J305),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J305) - LEN(SUBSTITUTE(LOWER($J305),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B305:D305)","v":1},2003,"Targeting angiogenesis -- a novel mode in cancer chemoprevention.","Vainio",12875617,"Targeting angiogenesis -- a novel mode in cancer chemoprevention.    Abstract:   Cancer prevention is fast emerging as a discipline with a promising potential. Chemoprevention has its rationale in the multistage process of carcinogenesis which provides an option for development of preventive approaches in the early, premalignant stages, before appearance of clinical symptoms. Evidence is mounting that the angiogenic switch may be an early event in carcinogenesis. Most chemopreventive agents currently under development probably act via multiple mechanisms. The chemopreventives used in clinical trials, such as nonsteroidal anti-inflammatories, tamoxifen and retinoids, have been shown to inhibit angiogenesis, the formation of new vessels from existing vasculature, which may contribute to their protective effect. Development and use, alone or in combination with other agents with other mechanisms of action, of specific antiangiogenic agents is likely to open new possibilities in cancer chemoprevention."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I306,I306)","v":12858562},{"$f":"(LEN($J306) - LEN(SUBSTITUTE(LOWER($J306),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J306) - LEN(SUBSTITUTE(LOWER($J306),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J306) - LEN(SUBSTITUTE(LOWER($J306),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B306:D306)","v":1},2002,"Regulatory networks controlling mitochondrial energy production in the developing, hypertrophied, and diabetic heart.","Finck",12858562,"Regulatory networks controlling mitochondrial energy production in the developing, hypertrophied, and diabetic heart.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I307,I307)","v":12858522},{"$f":"(LEN($J307) - LEN(SUBSTITUTE(LOWER($J307),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J307) - LEN(SUBSTITUTE(LOWER($J307),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J307) - LEN(SUBSTITUTE(LOWER($J307),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B307:D307)","v":1},2002,"Erythropoietin and retinoic acid signaling in the epicardium is required for cardiac myocyte proliferation.","Stuckmann",12858522,"Erythropoietin and retinoic acid signaling in the epicardium is required for cardiac myocyte proliferation.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I308,I308)","v":12699068},{"$f":"(LEN($J308) - LEN(SUBSTITUTE(LOWER($J308),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J308) - LEN(SUBSTITUTE(LOWER($J308),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J308) - LEN(SUBSTITUTE(LOWER($J308),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B308:D308)","v":1},2003,"Antiangiogenic activity of chemopreventive drugs.","Pfeffer",12699068,"Antiangiogenic activity of chemopreventive drugs.    Abstract:   Tumors growing within the host form dynamic aberrant tissue that consists of host components, including the stroma, an expanding vasculature and often chronic inflammation, in addition to the tumor cells themselves. These host components can contribute to, rather than limit, tumor expansion, whereas deprivation of vessel formation has the potential to confine tumors in small, clinically silent foci. Therapeutic inhibition of vessel formation could be best suited to preventive strategies aimed at the suppression of angiogenesis in primary tumors in subjects at risk, or of micrometastases after surgical removal of a primary tumor. Our analysis of potential cancer chemopreventive molecules including N-acetylcysteine, green tea flavonoids and 4-hydroxyphenyl-retinamide has identified antiangiogenic activities that could account--at least in part--for the tumor prevention effects observed with these compounds. These drugs appear to target common mechanisms of tumor angiogenesis that may permit identification of critical targets for antiangiogenic therapy and antiangiogenic chemoprevention."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I309,I309)","v":12602939},{"$f":"(LEN($J309) - LEN(SUBSTITUTE(LOWER($J309),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J309) - LEN(SUBSTITUTE(LOWER($J309),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J309) - LEN(SUBSTITUTE(LOWER($J309),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B309:D309)","v":1},2002,"Palm oil: biochemical, physiological, nutritional, hematological, and toxicological aspects: a review.","Edem",12602939,"Palm oil: biochemical, physiological, nutritional, hematological, and toxicological aspects: a review.    Abstract:   The link between dietary fats and cardiovascular diseases has necessitated a growing research interest in palm oil, the second largest consumed vegetable oil in the world. Palm oil, obtained from a tropical plant, Elaeis guineensis contains 50% saturated fatty acids, yet it does not promote atherosclerosis and arterial thrombosis. The saturated fatty acid to unsaturated fatty acid ratio of palm oil is close to unity and it contains a high amount of the antioxidants, beta-carotene, and vitamin E. Although palm oil-based diets induce a higher blood cholesterol level than do corn, soybean, safflower seed, and sunflower oils, the consumption of palm oil causes the endogenous cholesterol level to drop. This phenomenon seems to arise from the presence of the tocotrienols and the peculiar isomeric position of its fatty acids. The benefits of palm oil to health include reduction in risk of arterial thrombosis and atherosclerosis, inhibition of endogenous cholesterol biosynthesis, platelet aggregation, and reduction in blood pressure. Palm oil has been used in the fresh state and/or at various levels of oxidation. Oxidation is a result of processing the oil for various culinary purposes. However, a considerable amount of the commonly used palm oil is in the oxidized state, which poses potential dangers to the biochemical and physiological functions of the body. Unlike fresh palm oil, oxidized palm oil induces an adverse lipid profile, reproductive toxicity and toxicity of the kidney, lung, liver, and heart. This may be as a result of the generation of toxicants brought on by oxidation. In contrast to oxidized palm oil, red or refined palm oil at moderate levels in the diet of experimental animals promotes efficient utilization of nutrients, favorable body weight gains, induction of hepatic drug metabolizing enzymes, adequate hemoglobinization of red cells and improvement of immune function. Howerer, high palm oil levels in the diet induce toxicity to the liver as shown by loss of cellular radial architecture and cell size reductions which are corroborated by alanine transaminase to asparate transaminase ratios which are higher than unity. The consumtion of moderate amounts of palm oil and reduction in the level of oxidation may reduce the health risk believed to be associated with the consumption of palm oil. Red palm oil, by virtue of its beta-carotene content, may protect against vitamin A deficiency and certain forms of cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I310,I310)","v":12431818},{"$f":"(LEN($J310) - LEN(SUBSTITUTE(LOWER($J310),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J310) - LEN(SUBSTITUTE(LOWER($J310),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J310) - LEN(SUBSTITUTE(LOWER($J310),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B310:D310)","v":1},2002,"Angiogenesis in prostate cancer: its role in disease progression and possible therapeutic approaches.","van Moorselaar",12431818,"Angiogenesis in prostate cancer: its role in disease progression and possible therapeutic approaches.    Abstract:   The interaction between cancer cells and their microenvironment is a promising area for the development of novel therapeutic anti-cancer modalities. The formation of new blood vessels, angiogenesis, is an important step in cancer progression. Angiogenesis is a complex multistep process involving close orchestration of endothelial cells, extracellular matrix, and soluble factors. Essentially every step has been found to be regulated by inducers and inhibitors. Prostate cancer has the ability to produce angiogenic factors such as metalloproteinases, vascular endothelial growth factor, fibroblast growth factor 2, transforming growth factor-beta and cyclooxygenase-2. In several studies in prostate cancer an increased microvessel density is associated with poorer prognosis. On the other hand several endogenous inhibitors of angiogenesis have been described in prostate cancer e.g., angiostatin, endostatin, prostate specific antigen (PSA), thrombospondin-1, interleukin 10, interferons and retinoids. The expanding insight in the process of angiogenesis has resulted in a large number of pharmaceutical agents that have been tested in preclinical studies and are currently tested in clinical trials. These agents inhibit endothelial cell proliferation or migration and induce apoptosis. This ultimately will affect the formation of new vessels thereby inducing tumor dormancy. Because antiangiogenic treatment is cytostatic rather than cytotoxic, patients will need long-term therapy to prevent regrowth of the tumor. Prostate cancer is an ideal tumor for antiangiogenic studies because of the availability of a reliable tumor marker, PSA, the indolent clinical course of this cancer and the low rate of proliferation even in metastatic sites. Furthermore, clinical studies showed limited side effects, which is advantageous in this elderly patient group. Whether the ultimate antiangiogenic treatment is effective as a single agent or in combination with radiation therapy, chemotherapy or immunotherapy remains to be determined."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I311,I311)","v":12419571},{"$f":"(LEN($J311) - LEN(SUBSTITUTE(LOWER($J311),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J311) - LEN(SUBSTITUTE(LOWER($J311),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J311) - LEN(SUBSTITUTE(LOWER($J311),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B311:D311)","v":1},2002,"Peripartum cardiomyopathy: a selenium disconnection and an autoimmune connection.","Fett",12419571,"Peripartum cardiomyopathy: a selenium disconnection and an autoimmune connection.    Abstract:    BACKGROUND : Increased incidence and prevalence of peripartum cardiomyopathy (PPCM) have been documented in the Hospital Albert Schweitzer (HAS) District of Haiti. Although the basis for this increased incidence of PPCM remains unclear, there is growing evidence for an underlying autoimmune process. One potential risk factor for increased autoreactivity is a micronutrient deficiency. In Africa, low plasma selenium (Se) level has been reported as a possible risk factor for PPCM. This report details results of initial studies to test the hypothesis that plasma levels of Se and/or other micronutrients may be related to PPCM risk in this population.  METHODS : Under the direction of the Institutional Review Board (HAS Ethics Committee) and with informed consent, levels of Se and other micronutrients were measured in plasma samples obtained from PPCM mothers and parity-matched control mothers from the HAS District of Haiti.  RESULTS : Mean plasma Se level in 18 PPCM patients was 110 ng/ml (range 67-145) compared to mean plasma Se level in 34 control mothers of 121 ng/ml (range 98-172) (P=0.1748). These levels are substantially greater than those reported for pediatric patients with Keshan cardiomyopathy, which can be prevented by Se prophylaxis. No deficiency or significant difference was found in any other micronutrient tested (Vitamin A (retinol), Vitamin B(12), Vitamin C, Vitamin E, and B-Carotene) for these PPCM and control mothers.  CONCLUSION : Although there are several possible mechanisms by which Se could play a role in the pathobiology of PPCM, there is no evidence that Se deficiency is a cause of PPCM or a risk factor for the development of PPCM in this district of Haiti. The results of this investigation indicate that future studies of PPCM in this population should focus on other potential etiologic and risk factors."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I312,I312)","v":12383393},{"$f":"(LEN($J312) - LEN(SUBSTITUTE(LOWER($J312),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J312) - LEN(SUBSTITUTE(LOWER($J312),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J312) - LEN(SUBSTITUTE(LOWER($J312),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B312:D312)","v":1},2002,"[The epicardium and epicardial-derived cells: multiple functions in cardiac development].","Muñoz-Chápuli",12383393,"[The epicardium and epicardial-derived cells: multiple functions in cardiac development].    Abstract:   The epicardium develops from an extracardiac primordium, the proepicardium, which is constituted by a cluster of mesothelial cells located on the cephalic and ventral surface of the liver-sinus venosus limit (avian embryos) or on the pericardial side of the septum transversum (mammalian embryos). The proepicardium contacts the myocardial surface and gives rise to a mesothelium, which grows and progressively lines the myocardium. The epicardium generates, through a process of epithelial-mesenchymal transition, a population of epicardial-derived cells (EPDC). EPDC contribute to the development of cardiac connective tissue, fibroblasts, and the smooth muscle of cardiac vessels. Recent data suggest that EPDC can also differentiate into endothelial cells of the primary subepicardial vascular plexus. If this is confirmed, EPDC would show the same developmental properties that characterize the stem-cell-derived bipotential vascular progenitors recently described, whose differentiation into endothelium and smooth muscle is regulated by exposure to VEGF and PDGF-BB, respectively. Aside from their function in the development of cardiac connective and vascular tissue, EPDC also play an essential modulating role in the differentiation of the compact ventricular layer of the myocardium, a role which might be regulated by the transcription factor WT1 and the production of retinoic acid."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I313,I313)","v":12324201},{"$f":"(LEN($J313) - LEN(SUBSTITUTE(LOWER($J313),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J313) - LEN(SUBSTITUTE(LOWER($J313),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J313) - LEN(SUBSTITUTE(LOWER($J313),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B313:D313)","v":1},2002,"Antioxidant nutrients and adriamycin toxicity.","Quiles",12324201,"Antioxidant nutrients and adriamycin toxicity.    Abstract:   The anthracycline antibiotic adriamycin (doxorubicin) is one of the most effective chemotherapeutic agents against a wide variety of cancers. However, its use is seriously limited by the development in the heart of acute and chronic toxic effects. Mechanisms of action and toxicity of adriamycin are briefly revised in this review. Among followed strategies to attenuate adriamycin toxicity are dosage optimisation, synthesis and use of analogues or combined therapy with antioxidants. The most promising results come from the combination of the drug delivery together with an antioxidant in order to reduce oxidative stress. Many antioxidants have been assayed with very different results. Among these molecules, metal ions chelators and low-molecular-mass agents that scavenge reactive oxygen species and that are synthesised in vivo have been widely studied. However, the present review will be exclusively focused on the antioxidants that are derived from the diet, in particular the role of vitamin E, vitamin C, vitamin A, coenzyme Q, flavonoids, antioxidant components of virgin olive oil and selenium."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I314,I314)","v":12229281},{"$f":"(LEN($J314) - LEN(SUBSTITUTE(LOWER($J314),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J314) - LEN(SUBSTITUTE(LOWER($J314),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J314) - LEN(SUBSTITUTE(LOWER($J314),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B314:D314)","v":1},2002,"[Basic aspects and measurement of the antioxidant vitamins A and E].","Márquez",12229281,"[Basic aspects and measurement of the antioxidant vitamins A and E].    Abstract:   Vitamin E usually works as a biological antioxidant, preventing the oxidation of polyunsaturated fatty acids and proteins, for which it is considered an important protective factor in the development of diseases related to oxidative processes. Beyond its antioxidant properties, it has been involved also in genetic expression, mitochondrial metabolism, cell differentiation and immune system regulation. From the point of view of its antioxidant protection properties, values gt; or = 1200-1300 micrograms/dL are considered optimum levels (standardized according to plasmatic lipid levels). In relation to the beneficial advantage effects of vitamin E on primary or secondary atherosclerotic disease, data are not conclusive. Vitamin A is part of the organisms defense barrier against free radicals. Its antioxidant mechanism of action includes scavenging of single oxygen and thiol free radicals, and it also could be related to processes that involve genetic expression and cell differentiation. As an antioxidant, vitamin A plasmatic levels gt; or = 80 micrograms/dL are considered optimal. The highest risk of using this vitamin is related to its acute or chronic toxicity. Quantification of serum vitamin E (alpha tocopherol) and vitamin A (retinol) are made by high performance liquid chromatography (HPLC), method of high precision, sensitivity and reproducibility."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I315,I315)","v":12223078},{"$f":"(LEN($J315) - LEN(SUBSTITUTE(LOWER($J315),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J315) - LEN(SUBSTITUTE(LOWER($J315),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J315) - LEN(SUBSTITUTE(LOWER($J315),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B315:D315)","v":1},2002,"Tissue factor - a therapeutic target for thrombotic disorders.","Houston",12223078,"Tissue factor - a therapeutic target for thrombotic disorders.    Abstract:   Exposure of blood to tissue factor (TF) sets off the coagulation cascade. TF is a transmembrane protein that serves as an essential cofactor for activated coagulation factor VII (FVIIa). TF may be exposed locally by vascular injury (such as balloon angioplasty) or by spontaneous rupture of an atherosclerotic plaque. Expression of TF may also be induced on monocytes and endothelial cells in conditions like sepsis and cancer, causing a more generalised activation of clotting. TF may thus play a central role in thrombosis in a number of settings, and attention has turned to blocking TF as a means to prevent thrombosis. Inhibiting the inducible expression of TF by monocytes can be achieved by deactivating cytokines, such as interleukin (IL)-4, -10 and -13, or by certain prostanoids; by drugs that modify signal transduction, such as pentoxifylline, retinoic acid or vitamin D(3), or by antisense oligonucleotides. Such approaches are for the most part at a preclinical stage. The function of TF can be blocked by antibodies that prevent the binding of FVIIa to TF; by active site-inhibited FVIIa, which competes with native FVIIa for binding; by antibodies or small molecules that block the function of the TF/FVIIa complex; and by molecules, such as TF pathway inhibitor or nematode anticoagulant peptide C2, which inhibit the active site of FVIIa in the TF/FVIIa complex after first binding to activated factor X. The latter two agents have entered Phase II clinical trials. Perhaps most intriguing is the use of anti-TF agents locally, which holds the promise of stopping thrombosis at a specific site of injury without the bleeding risk associated with systemic anticoagulation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I316,I316)","v":11984869},{"$f":"(LEN($J316) - LEN(SUBSTITUTE(LOWER($J316),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J316) - LEN(SUBSTITUTE(LOWER($J316),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J316) - LEN(SUBSTITUTE(LOWER($J316),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B316:D316)","v":1},2002,"Constructing the hindbrain: insights from the zebrafish.","Moens",11984869,"Constructing the hindbrain: insights from the zebrafish.    Abstract:   The hindbrain is responsible for controlling essential functions such as respiration and heart beat that we literally do not think about most of the time. In addition, cranial nerves projecting from the hindbrain control muscles in the jaw, eye, and face, and receive sensory input from these same areas. In all vertebrates that have been studied, the hindbrain passes through a segmented phase shortly after the neural tube has formed, with a series of seven bulges--the rhombomeres--forming along the anterior-posterior extent of the neural tube. Our current understanding of vertebrate hindbrain development comes from integrating data from several model systems. Work on the chick has helped us to understand the cell biology of the rhombomeres, whereas the power of mouse molecular genetics has allowed investigation of the molecular mechanisms underlying their development. This review focuses on the special insights that the zebrafish system has provided to our understanding of hindbrain development. As we will discuss, work in the zebrafish has elucidated inductive events that specify the presumptive hindbrain domain and has identified genes required for hindbrain segmentation and the specification of segment identities."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I317,I317)","v":11755917},{"$f":"(LEN($J317) - LEN(SUBSTITUTE(LOWER($J317),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J317) - LEN(SUBSTITUTE(LOWER($J317),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J317) - LEN(SUBSTITUTE(LOWER($J317),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B317:D317)","v":1},2002,"Is there a genetic basis for resistance to atherosclerosis?","Stein",11755917,"Is there a genetic basis for resistance to atherosclerosis?    Abstract:   Atherosclerosis and its major clinical manifestation, coronary heart disease, is and will remain the main cause of mortality. Reviews on this subject dealt with factors that enhance development of atherosclerosis. This review deals with a new facet, that some individuals are less prone to develop atherosclerosis: (1) despite high cholesterol intake or (2) despite hypercholesterolemia with elevated low-density lipoprotein cholesterol (LDL-C) levels. The variability of response of plasma cholesterol to dietary intake was shown to be regulated by liver x receptor (LXR) that determines the rate of intestinal cholesterol absorption through the ATP-binding cassette (ABC) gene family. Other gene products, such as apolipoprotein-E (apo-E), scavenger receptor-B1 (SR-B1) and acyl coenzyme: cholesterol acyltransferase-2 (ACAT-2) affect cholesterol absorption also. The role of a genetic background for relative resistance to atherosclerosis is highlighted by subjects with familial hypercholesterolemia in whom high plasma cholesterol levels has not curtailed their expected life span. Studies in animals have shown that resistance to atherosclerosis in spite of hypercholesterolemia is affected by factors such as high-density lipoprotein (HDL) phospholipids that enhance reverse cholesterol transport, non-responsiveness to induction or lack of monocyte chemotactic protein-1 (MCP-1), C-C chemokine receptor 2 (CCR2), macrophage colony stimulating factor (MCSF), or vascular cell adhesion molecule-1 (VCAM-1). Since macrophages have been regarded as pro- or anti-atherogenic, evidence was collated that the high activity of scavenger receptors may contribute towards resistance to atherosclerosis if accompanied by adequate amounts of apo-E for cholesterol removal."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I318,I318)","v":11735646},{"$f":"(LEN($J318) - LEN(SUBSTITUTE(LOWER($J318),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J318) - LEN(SUBSTITUTE(LOWER($J318),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J318) - LEN(SUBSTITUTE(LOWER($J318),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B318:D318)","v":1},2001,"Drug-induced congenital defects: strategies to reduce the incidence.","De Santis",11735646,"Drug-induced congenital defects: strategies to reduce the incidence.    Abstract:   Approximately 1% of congenital anomalies relate to pharmacological exposure and are. in theory, preventable. Prevention consists of controlled administration of drugs known to have teratogenic properties (e.g. retinoids, thalidomide). When possible, prevention could take the form of the use of alternative pharmacological therapies during the pre-conception period for certain specific pathologies, selecting the most appropriate agent for use during pregnancy [e.g. haloperidol or a tricyclic antidepressant instead of lithium; anticonvulsant drug monotherapy in place of multitherapy; propylthiouracil instead of thiamazole (methimazole)], and substitution with the most suitable therapy during pregnancy (e.g. insulin in place of oral antidiabetics; heparin in place of oral anticoagulants; alpha-methyldopa instead of ACE inhibitors). Another strategy is the administration of drugs during pregnancy taking into account the pharmacological effects in relation to the gestation period (e.g. avoidance of chemotherapy during the first trimester, avoidance of nonsteroidal anti-inflammatory drugs in the third trimester, and avoidance of high doses of benzodiazepines in the period imminent to prepartum)."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I319,I319)","v":11584078},{"$f":"(LEN($J319) - LEN(SUBSTITUTE(LOWER($J319),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J319) - LEN(SUBSTITUTE(LOWER($J319),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J319) - LEN(SUBSTITUTE(LOWER($J319),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B319:D319)","v":1},2001,"Molecular mechanisms of sterol absorption.","Chen",11584078,"Molecular mechanisms of sterol absorption.    Abstract:   Recent studies have significantly advanced our understanding of intestinal sterol absorption at the molecular level. Nuclear hormone receptors (such as liver X receptor, farnesoid X receptor and retinoid X receptor) regulate the absorption of dietary sterols by modulating the transcription of several important genes involved in cholesterol metabolism. One of these genes encodes a molecule [adenosine triphosphate-binding cassette (ABC) transporter] that transports dietary cholesterol from enterocytes back out to the intestinal lumen, thereby limiting the amount of cholesterol absorbed. ABC transporters also provide an efficient barrier against the absorption of plant sterols. Another key process that affects intestinal sterol absorption is the synthesis of cholesterol esters. Mice lacking the enzyme for cholesterol esterification in the small intestine have a reduced capacity to absorb dietary cholesterol and are protected against diet-induced hypercholesterolemia and gallstone formation. In addition to elucidating some of the molecular mechanisms of sterol absorption, these recent findings may lead to new therapeutic options to treat hypercholesterolemia."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I320,I320)","v":11376439},{"$f":"(LEN($J320) - LEN(SUBSTITUTE(LOWER($J320),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J320) - LEN(SUBSTITUTE(LOWER($J320),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J320) - LEN(SUBSTITUTE(LOWER($J320),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B320:D320)","v":1},2000,"Molecular determinants of neural crest migration.","Maschhoff",11376439,"Molecular determinants of neural crest migration.    Abstract:   Normal septation of the cardiac outflow tract requires migration of neural crest cells from the posterior rhombencephalon to the branchial arches and developing conotruncal endocardial cushions. Proper migration of these cells is mediated by a variety of molecular cues. Adhesion molecules, such as integrins, are involved in the interaction of neural crest cells with the extracellular matrix, while cadherins allow neural crest cells to interact with each other during their migration. Pax3 appears to be important for proliferation of neural crest precursors, and connexin-43-mediated gap junction communication influences the rate of migration. Endothelin and its receptors are required for normal postmigratory differentiation. Platelet-derived growth factor and retinoic acid have roles in neural crest migration and differentiation as well. Finally, the similarity between the cardiovascular malformations seen in the DiGeorge and 22q11 deletion syndromes and animal models of neural crest deficiency has led to the examination of the role of genes located near or within the DiGeorge critical region in neural crest migration."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I321,I321)","v":11194782},{"$f":"(LEN($J321) - LEN(SUBSTITUTE(LOWER($J321),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J321) - LEN(SUBSTITUTE(LOWER($J321),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J321) - LEN(SUBSTITUTE(LOWER($J321),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B321:D321)","v":1},2000,"Update on pharmacologic therapy for chronic obstructive pulmonary disease.","Ferguson",11194782,"Update on pharmacologic therapy for chronic obstructive pulmonary disease.    Abstract:   As described throughout this article, significant improvements continue to occur in the pharmacologic management of COPD. These improvements range from improved medication targeting to better understanding of mechanisms of action, to better delivery of medications, to lower side effects. New areas of pharmacologic intervention, if not ready for use today, hold great promise for the not-too-distant future. In addition to the many agents described here, multiple mediator antagonists and anti-inflammatory agents are also under investigation for use in COPD. Interestingly, repair of alveolar tissue may be possible. Indeed, preliminary animal studies suggest that retinoic acid may be able to induce regeneration of lung alveoli. Overall, more effort is needed to broaden awareness and provide for the appropriate diagnosis of COPD, better explain pharmacologic therapies for COPD, simplify and disseminate guidelines, and highlight key differences between asthma and COPD, including their treatment strategies. As interest in COPD continues to grow, future updates on COPD management will continue to add new pharmacologic options for this devastating and preventable disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I322,I322)","v":11123853},{"$f":"(LEN($J322) - LEN(SUBSTITUTE(LOWER($J322),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J322) - LEN(SUBSTITUTE(LOWER($J322),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J322) - LEN(SUBSTITUTE(LOWER($J322),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B322:D322)","v":1},2001,"The role of fibric acids in atherosclerosis.","Fruchart",11123853,"The role of fibric acids in atherosclerosis.    Abstract:   The hypolipidemic fibric acid drugs are peroxisome proliferator-activated receptor a (PPAR alpha) ligands. PPAR alpha activated by fibric acids form heterodimers with the 9-cis retinoic acid receptor (RXR). The PPAR/RXR heterodimers bind to peroxisome proliferator response elements (PPRE), which are located in numerous gene promoters and increase the level of the expression of mRNAs encoded by PPAR alpha target genes. Fibric acids decrease triglyceride plasma levels through increases in the expression of genes involved in fatty acid-beta oxidation. Furthermore, they decrease triglycerides by increasing lipoprotein lipase gene expression and by decreasing apolipoprotein C-III gene expression. Fibric acids increase high-density lipoprotein (HDL) cholesterol partly by increasing apolipoprotein A-I and apolipoprotein A-II gene expression. Fibric acids also reduce vascular wall inflammation and the expression of genes involved in different vascular functions (ie, vasomotricity, thrombosis). Fibric acids are used to treat primary hypertriglyceridemia and mixed hyperlipidemia. Some fibric acid molecules are active in essential hypercholesterolemia. Clinical evidence shows that fibric acids reduce coronary atherosclerosis progression in dyslipidemic patients (eg, bezafibrate, gemfibrozil) and in type 2 diabetic patients (fenofibrate). Gemfibrozil decreases coronary morbidity and mortality in patients with low HDL cholesterol, normal triglycerides,and normal low-density lipoprotein (LDL) cholesterol plasma levels. Further clinical studies are necessary to investigate if fibric acids decrease cardiovascular mortality in type 2 diabetes and in primary prevention of hypertriglyceridemia and hypolipidemia."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I323,I323)","v":11121509},{"$f":"(LEN($J323) - LEN(SUBSTITUTE(LOWER($J323),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J323) - LEN(SUBSTITUTE(LOWER($J323),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J323) - LEN(SUBSTITUTE(LOWER($J323),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B323:D323)","v":1},2000,"Multiple actions of steroid hormones--a focus on rapid, nongenomic effects.","Falkenstein",11121509,"Multiple actions of steroid hormones--a focus on rapid, nongenomic effects.    Abstract:   According to the traditional model, steroid hormones bind to intracellular receptors and subsequently modulate transcription and protein synthesis, thus triggering genomic events finally responsible for delayed effects. Based upon similarities in molecular structure, specific receptors for steroids, vitamin D(3) derivatives, thyroid hormone, retinoids, and a variety of orphan receptors are considered to represent a superfamily of steroid receptors. In addition, very rapid effects of steroids mainly affecting intracellular signaling have been widely recognized that are clearly incompatible with the genomic model. These rapid, nongenomic steroid actions are likely to be transmitted via specific membrane receptors. Evidence for nongenomic steroid effects and distinct receptors involved is presented for all steroid groups including related compounds like vitamin D(3) and thyroid hormones. The physiological and clinical relevance of these rapid effects is still largely unclear, but their existence in vivo has been clearly shown in various settings including human studies. Drugs that specifically affect nongenomic steroid action may find applications in various clinical areas such as cardiovascular and central nervous disorders, electrolyte homeostasis, and infertility. In addition to a short description of genomic steroid action, this review pays particular attention to the current knowledge and important results on the mechanisms of nongenomic steroid action. The modes of action are discussed in relation to their potential physiological or pathophysiological relevance and with regard to a cross-talk between genomic and nongenomic responses."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I324,I324)","v":10969032},{"$f":"(LEN($J324) - LEN(SUBSTITUTE(LOWER($J324),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J324) - LEN(SUBSTITUTE(LOWER($J324),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J324) - LEN(SUBSTITUTE(LOWER($J324),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B324:D324)","v":1},2000,"Retinoids: versatile biological response modifiers of vascular smooth muscle phenotype.","Miano",10969032,"Retinoids: versatile biological response modifiers of vascular smooth muscle phenotype.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I325,I325)","v":10968474},{"$f":"(LEN($J325) - LEN(SUBSTITUTE(LOWER($J325),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J325) - LEN(SUBSTITUTE(LOWER($J325),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J325) - LEN(SUBSTITUTE(LOWER($J325),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B325:D325)","v":1},2000,"Nongenomic actions of steroids--from the laboratory to clinical implications.","Gerdes",10968474,"Nongenomic actions of steroids--from the laboratory to clinical implications.    Abstract:   In the classical concept of steroid action, steroids bind to cytoplasmic receptors and modulate nuclear transcription after translocation of steroid-receptor complexes into the nucleus. Due to similarities of molecular structure, receptors for steroids, retinoids, vitamin D3 and thyroid hormone are considered to represent a superfamily of receptors. While genomic steroid effects been evident for several decades, rapid effects of steroids have been characterized only recently. These rapid actions are likely to be transmitted by specific membrane receptors. Binding sites in membranes have been characterized which display binding features compatible with an involvement in rapid steroid signaling. Characteristics of putative membrane receptors are completely distinct from those of intracellular steroid receptors, a fact which is further supported by the inability of classic steroid receptor antagonists to suppress nongenomic steroid actions. The cloning and functional expression of a putative progesterone membrane receptor has been achieved. Drugs that specifically modulate nongenomic action alone or even both genomic and nongenomic actions may be applied in various areas such as the cardiovascular and central nervous systems, and treatment of infertility and electrolyte homeostasis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I326,I326)","v":10944947},{"$f":"(LEN($J326) - LEN(SUBSTITUTE(LOWER($J326),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J326) - LEN(SUBSTITUTE(LOWER($J326),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J326) - LEN(SUBSTITUTE(LOWER($J326),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B326:D326)","v":1},2000,"[Recent studies on anti-angiogenesis in cancer therapy].","Kishi",10944947,"[Recent studies on anti-angiogenesis in cancer therapy].    Abstract:   Angiogenesis is known to be a critical process for the tumor growth and metastasis. There are many indigenous role-players in tumor angiogenesis and anti-angiogenesis, where tumor-host interaction may work. A lot of agents with anti-angiogenic activity have been developed for anti-cancer treatment. Several agents including Marimastat, Primostat, Neovastat, Bay-12-9566m, Interferon-alpha, SU101, retinoids, and IM862, are/were under phase-three study. There are still many future-promising results of basic or clinical studies on inhibitors of MMPs, and inhibitors of VEGF/R, Endostatin, somatostatin analogues, COX-2 inhibitors, and others. Most of the combination treatments of antiangiogenetic agent and conventional anticancer agents therapy, or radiation therapy as we reported, showed relatively small or minute increase in toxicity of these cytotoxic treatments."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I327,I327)","v":10938007},{"$f":"(LEN($J327) - LEN(SUBSTITUTE(LOWER($J327),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J327) - LEN(SUBSTITUTE(LOWER($J327),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J327) - LEN(SUBSTITUTE(LOWER($J327),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B327:D327)","v":1},2000,"Retinoids and arterial smooth muscle cells.","Neuville",10938007,"Retinoids and arterial smooth muscle cells.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I328,I328)","v":10897129},{"$f":"(LEN($J328) - LEN(SUBSTITUTE(LOWER($J328),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J328) - LEN(SUBSTITUTE(LOWER($J328),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J328) - LEN(SUBSTITUTE(LOWER($J328),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B328:D328)","v":1},2000,"Cutaneous promyelocytic sarcoma at sites of vascular access and marrow aspiration. A characteristic localization of chloromas in acute promyelocytic leukemia?","Sanz",10897129,"Cutaneous promyelocytic sarcoma at sites of vascular access and marrow aspiration. A characteristic localization of chloromas in acute promyelocytic leukemia?    Abstract:   Extramedullary disease (EMD) is a rare clinical event in acute promyelocytic leukemia (APL). Although the skin is involved in half of the reported EMD cases, the occurrence of cutaneous promyelocytic sarcoma (PS) has been described very rarely. We report here three cases of PS which have the peculiarity of appearing at sites of punctures for arterial and venous blood and marrow samples (sternal manubrium, antecubital fossa, wrist over the radial artery pulse, catheter insertion scar). At presentation, all patients had hyperleukocytosis and a morphologic diagnosis of microgranular acute promyelocytic leukemia variant confirmed at the genetic level by demonstration of the specific chromosomal translocation t(15;17). A BCR3 type PML/RARa transcript was documented in the two patients for whom diagnostic RT-PCR was available. Patients had morphologic bone marrow remission at the time the PS appeared. A predilection for the development of cutaneous PS at sites of previous vascular damage has been noted, but the pathogenesis remains largely unknown. A potential role for all-trans retinoic acid has been advocated, although one of the three patients in our series had received no ATRA. A review of the literature revealed six similar cases and hyperleukocytosis at diagnosis was a consistent finding in all of them. A careful physical examination of these particular sites in the follow-up of patients at risk, as well as cutaneous biopsy and laboratory examination of suspected lesions are strongly recommended."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I329,I329)","v":10870177},{"$f":"(LEN($J329) - LEN(SUBSTITUTE(LOWER($J329),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J329) - LEN(SUBSTITUTE(LOWER($J329),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J329) - LEN(SUBSTITUTE(LOWER($J329),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B329:D329)","v":1},2000,"Is lycopene beneficial to human health?","Bramley",10870177,"Is lycopene beneficial to human health?    Abstract:   Since humans cannot synthesise carotenoids de novo, we depend upon the diet exclusively for the source of these micronutrients. Although the necessity for beta-carotene, as the precursor of vitamin A has been recognised for many years, it is lycopene that has attracted substantial interest more recently. Lycopene is the red-coloured carotenoid predominantly found in tomato fruit, but in few other fruits or vegetables. It has claimed that it may alleviate chronic diseases such as cancers and coronary heart disease. This possibility has been studied extensively, by epidemiological studies and biochemical investigations of its properties and its bioavailability from tomato-based diets. This article summarises the current state of knowledge of the properties of lycopene, its possible role in human health and areas for future research."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I330,I330)","v":10830735},{"$f":"(LEN($J330) - LEN(SUBSTITUTE(LOWER($J330),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J330) - LEN(SUBSTITUTE(LOWER($J330),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J330) - LEN(SUBSTITUTE(LOWER($J330),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B330:D330)","v":1},2000,"Arsenic trioxide therapy for relapsed acute promyelocytic leukemia: an useful salvage therapy.","Huan",10830735,"Arsenic trioxide therapy for relapsed acute promyelocytic leukemia: an useful salvage therapy.    Abstract:   Arsenic trioxide (As2O3) was recently identified as a very potent agent against acute promyelocytic leukemia (APL). Intravenous infusion of 10 mg As2O3 daily for one to two months can induce significant complete remission (CR) of APL, and there is no cross drug-resistance between As2O3 and other antileukemic agents, including all-trans retinoic acid (ATRA). The CR rate of relapsed and/or refractory APL patients who received As2O3 treatment ranged from 52.3% to 93.3%. The median duration to CR ranged from 38 to 51 days, with accumulative As2O3 dosage of 340-430 mg. Although most adverse reactions of As2O3 treatment were tolerable, certain infrequent but severe toxicities related to As2O3 were observed, including renal failure, hepatic damage, cardiac arrhythmia and chronic neuromuscular degeneration, which should be monitored carefully. As2O3 can induce partial differentiation and subsequent apoptosis of APL cells through degradation of wild type PML and PML/RAR alpha chimeric proteins and possible anti-mitochondrial effects. Like the treatment of ATRA in APL, early relapses from As2O3 treatment within a few months were not infrequently seen, indicating that rapid emerging resistance to As2O3 can occur. Nevertheless, the PML/RAR alpha fusion protein was reported to disappear in some APL patients who received As2O3, and who might earn long-survival. However, the follow-up is still too short to draw the conclusion. Intriguingly, it has been shown that As2O3 can also induce apoptosis of other non-APL tumor cells with clinical achievable concentrations. However, the detailed molecular mechanisms are not yet fully understood. Further studies regarding to the pharmacological characters, clinical efficacies, toxicities, apoptogenic mechanisms, and spectrum of anti-tumor activity of As2O3 are warranted."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I331,I331)","v":10768602},{"$f":"(LEN($J331) - LEN(SUBSTITUTE(LOWER($J331),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J331) - LEN(SUBSTITUTE(LOWER($J331),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J331) - LEN(SUBSTITUTE(LOWER($J331),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B331:D331)","v":1},2000,"Novel investigative approaches for advanced renal cell carcinoma.","Berg",10768602,"Novel investigative approaches for advanced renal cell carcinoma.    Abstract:   Metastatic renal cell carcinoma remains one of the most treatment-resistant malignancies in humans. As such, long-term survival is limited to a minority of patients. Interferon-alpha and interleukin-2 induced major responses in some patients with renal cell carcinoma, and in so doing generated a great deal of interest and hope. However, clinical benefit is limited to relatively few patients. Here, we briefly discuss the management of metastatic renal cell carcinoma, and then elaborate on several novel treatment approaches in development, including retinoids, monoclonal antibodies, and antiangiogenesis strategies."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I332,I332)","v":10748653},{"$f":"(LEN($J332) - LEN(SUBSTITUTE(LOWER($J332),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J332) - LEN(SUBSTITUTE(LOWER($J332),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J332) - LEN(SUBSTITUTE(LOWER($J332),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B332:D332)","v":1},2000,"[Dysmetabolic syndrome related to HIV-1 protease inhibitors. Review of the literature and personal data].","Urso",10748653,"[Dysmetabolic syndrome related to HIV-1 protease inhibitors. Review of the literature and personal data].    Abstract:   HIV-positive patients receiving antiretroviral therapy with HIV-1 protease-inhibitors (PI) frequently show insulin-resistance, impaired glucose tolerance, hypertriglyceridaemia and lipodystrophy (LD). LD has often been reported only after the beginning of PI therapy. Some authors link LD to HIV chronic infection, some others suggest that PIs increase pre-existent disturb. Preliminary data of an observational study drawn in IV day-hospital of Spallanzani Institute in Rome showed hypertriglyceridaemia in 36.4% and hyperglycaemia in 11.2% of patients treated with PI. Carr suggests that such drugs should have this lipid-increasing effect because of their inhibition of low density lipoprotein-receptor-related protein, cytoplasmic retinoic-acid binding protein type 1 and P450 3A cytochrome. This theory doesnt explain why both untreated patients and treated with only reverse transcriptase inhibitors show sometimes the same disorders. According to another hypothesis Tumor necrosis factor-alpha, through inhibition of lipoprotein-lipase, would determine high fat-storage in the adipose tissue. Cardiovascular risk factors have always to be assessed before starting a therapy with PI. Glycaemia, triglyceridaemia, cholesterolaemia have to be performed every three months during the treatment and, if necessary, C-Peptide and insulinaemia too. A treatment with lipid-lowering drugs is always recommended in patients with hypertriglyceridaemia gt; 500 mg/dl and/or hypercholesterolaemia LDL gt; 190 mg/dl in two following checks. Fibrates have proven to be effective in reducing hypertriglyceridaemia, but there is no certainty that such therapies could have good effects on the LD itself too."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I333,I333)","v":10748547},{"$f":"(LEN($J333) - LEN(SUBSTITUTE(LOWER($J333),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J333) - LEN(SUBSTITUTE(LOWER($J333),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J333) - LEN(SUBSTITUTE(LOWER($J333),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B333:D333)","v":1},2000,"[Environment and genetics in the etiology of cleft lip and cleft palate with reference to the role of folic acid].","Bianchi",10748547,"[Environment and genetics in the etiology of cleft lip and cleft palate with reference to the role of folic acid].    Abstract:   The combined birth prevalence of cleft palate [CP] and cleft lip with or without cleft palate [CL(P)] in Europe is approximately one in 700 with characteristic regional variations. Orofacial clefting (OC) is therefore now one of the most frequent congenital anomalies, with a higher birth prevalence that Downs Syndrome or Neural Tube defects, but still lower than cardiovascular malformation. Babies with OC require a multidisciplinary medical approach, surgery and rehabilitative treatments over time. This means an important effort in terms of social organization as well as economical costs for the health care system. In Italy, the health care costs for approximately 800 children born with orofacial clefting per year has been estimated at around 150 billion Lire (80 million Euros). The etiology of OC is complex and heterogeneous both for isolated and associated defects; causes linked to environment, genetics and gene-environment interaction are known, although there is still a lot to do, especially in clarifying the role of genetics in producing susceptibility to the environment. Four categories of genes for which there are results suggestive of a genetic susceptibility to OCs are: 1) genes expressed in a particular area of the embryo or in a particular period of the palatine arch development, such as the transforming growth factors alpha and beta (TGF alpha, TGF beta 2, TGF beta 3); 2) genes having biological activities linked to the OCs pathogenesis without direct involvement (e.g. the retinoic acid receptor (RARA), the methylenetetrahydrofolate reductase receptor (MTHFR) and the folic acid receptor (FOLR1); 3) genes or locus identified in experimental animals as the homeotic genes MSX-1 and MSX-2; 4) genes involved in the interaction with the xenobiotics metabolism as those in P-450 cytochrome system. Several environmental factors have been implicated in the OC etiology; among those, the folic acid supplementation during the periconceptional period that was found effective in the prevention of neural tube defects. In fact, folic acid deficiency may be responsible for different malformations through a common mechanism that interferes with the embryonic development, depending on the maternal or embryo genotype. Further investigation is required to study in depth how the genotype would modify the role of environmental factors like folic acid. Well-designed and conducted epidemiological studies seem to be able to give worthwhile information. Studies carried out in Europe on these issues are a few, particularly those on gene-environment interaction. Recent results obtained in molecular biology and the availability of wealth of data can allow to perform ad hoc investigations, being important not only for the basic research but also for their public health implications. For this objective a specific scientific network at the European level has been set by the European Science Foundation (ESF), whose first step will be to establish consistent case ascertainment and data collection across Europe and to develop standardized protocols and methods of analysis. It is hoped that in the longer term such multicentre collaborative research will enable combined analysis and lead to the identification of genetic susceptibility to certain environmental factors, including nutrition. Such studies would inform the current debate about the efficacy of folic acid and other nutritional factors in prevention of disease in the developing embryo. Subsequent public health measures targeted according to risk might reduce the prevalence of disorders such as orofacial clefting."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I334,I334)","v":10696077},{"$f":"(LEN($J334) - LEN(SUBSTITUTE(LOWER($J334),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J334) - LEN(SUBSTITUTE(LOWER($J334),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J334) - LEN(SUBSTITUTE(LOWER($J334),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B334:D334)","v":1},2000,"Peroxisome proliferator-activated receptors in the cardiovascular system.","Bishop-Bailey",10696077,"Peroxisome proliferator-activated receptors in the cardiovascular system.    Abstract:   Peroxisome proliferator-activated receptor (PPAR)s are a family of three nuclear hormone receptors, PPARalpha, -delta, and -gamma, which are members of the steriod receptor superfamily. The first member of the family (PPARalpha) was originally discovered as the mediator by which a number of xenobiotic drugs cause peroxisome proliferation in the liver. Defined functions for all these receptors, until recently, mainly concerned their ability to regulate energy balance, with PPARalpha being involved in beta-oxidation pathways, and PPARgamma in the differentiation of adipocytes. Little is known about the functions of PPARdelta, though it is the most ubiquitously expressed. Since their discovery, PPARs have been shown to be expressed in monocytes/macrophages, the heart, vascular smooth muscle cells, endothelial cells, and in atherosclerotic lesions. Furthermore, PPARs can be activated by a vast number of compounds including synthetic drugs, of the clofibrate, and anti-diabetic thiazoldinedione classes, polyunsaturated fatty acids, and a number of eicosanoids, including prostaglandins, lipoxygenase products, and oxidized low density lipoprotein. This review will aim to introduce the field of PPAR nuclear hormone receptors, and discuss the discovery and actions of PPARs in the cardiovascular system, as well as the source of potential ligands."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I335,I335)","v":10582064},{"$f":"(LEN($J335) - LEN(SUBSTITUTE(LOWER($J335),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J335) - LEN(SUBSTITUTE(LOWER($J335),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J335) - LEN(SUBSTITUTE(LOWER($J335),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B335:D335)","v":1},1999,"The epidemiology of respiratory syncytial virus (RSV) infections in South African children.","Vardas",10582064,"The epidemiology of respiratory syncytial virus (RSV) infections in South African children.    Abstract:    OBJECTIVES : To review the incidence, outcomes and risk factors associated with respiratory syncytial virus (RSV) infection in South African children.  DESIGN : Review of published literature and laboratory records.  METHODS : Review of the published literature. Articles listed on MEDLINE with South African or children and respiratory syncytial virus or acute respiratory tract infections as text words were retrieved. We analysed the data on respiratory virus activity from January 1990 to June 1996. Data were obtained from the National Institute for Virology database, which includes information on viral respiratory infections from the seven academic virology departments in South Africa.  RESULTS : Acute respiratory tract infections cause approximately 8% of all deaths in the under-5 age group in South Africa. The published hospital-based incidence of RSV infection varies from 3% to 18%. Mortality rates in these studies were between 12% and 43%. Risk factors identified for severe RSV infection requiring hospitalisation were malnutrition, prematurity, age lt; 6 months, vitamin A deficiency, environmental pollution and congenital heart disease. There is a seasonal peak in RSV cases, with the majority occurring in winter.  CONCLUSIONS : Acute respiratory tract infections and RSV infections are an important cause of mortality and morbidity in young children in South Africa. However, currently available information from laboratory records and published South African literature is not sufficient to assess the impact of this infection. Age-specific incidence data in the 0-5-year age group are essential for the rational planning and implementation of future vaccine strategies, public health interventions and treatment of RSV infections."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I336,I336)","v":10573562},{"$f":"(LEN($J336) - LEN(SUBSTITUTE(LOWER($J336),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J336) - LEN(SUBSTITUTE(LOWER($J336),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J336) - LEN(SUBSTITUTE(LOWER($J336),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B336:D336)","v":1},1999,"Review of animal models in carotenoid research.","Lee",10573562,"Review of animal models in carotenoid research.    Abstract:   Foods containing provitamin A carotenoids are the primary source of vitamin A in many countries, despite the poor bioavailability of carotenoids. In addition, epidemiologic studies suggest that dietary intake of carotenoids influences the risk for certain types of cancer, cardiovascular disease and other chronic diseases. Although it would be ideal to use humans directly to answer critical questions regarding carotenoid absorption, metabolism and effects on disease progression, appropriate animal models offer many advantages. This paper will review recent progress in the development of animal models with which to study this class of nutrients. Each potential model has strengths and weaknesses. Like humans, gerbils, ferrets and preruminant calves all absorb beta-carotene (betaC) intact, but only gerbils and calves convert betaC to vitamin A with efficiency similar to that of humans. Mice and rats efficiently convert betaC to vitamin A but absorb carotenoids intact only when they are provided in the diet at supraphysiologic levels. Mice, rats and ferrets can be used to study cancer, whereas primates and gerbils are probably more appropriate for studies on biomarkers of heart disease. No one animal model completely mimics human absorption and metabolism of carotenoids; thus the best model must be chosen with consideration of the specific application being studied, characteristics of the model, and the available funding and facilities."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I337,I337)","v":10556174},{"$f":"(LEN($J337) - LEN(SUBSTITUTE(LOWER($J337),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J337) - LEN(SUBSTITUTE(LOWER($J337),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J337) - LEN(SUBSTITUTE(LOWER($J337),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B337:D337)","v":1},1999,"Novel approaches and targets for treatment of chronic obstructive pulmonary disease.","Barnes",10556174,"Novel approaches and targets for treatment of chronic obstructive pulmonary disease.    Abstract:   There is a driving need to develop new and effective treatments for COPD. Bronchodilators are now the mainstay of symptomatic therapy and a new long-acting anticholinergic bronchodilator, tiotropium bromide, is now in advanced clinical trials as a once daily dry powder inhaler. Several inflammatory mediators are involved in the chronic neutrophilic inflammation that typifies COPD, including leukotriene B(4) and interleukin 8, for which specific receptor antagonists have been developed. Since the inflammatory process in COPD is essentially steroid resistant, new antiinflammatory treatments are needed. Drugs that may be effective include phosphodiesterase 4 inhibitors, NF-kappaB inhibitors, and interleukin 10. Inhibition of proteases is another approach and inhibitors of neutrophil elastase, cathepsins, and matrix metalloproteases are now in clinical development. Supply of endogenous antiproteases, such as alpha(1)-antitrypsin and secretory leukocyte protease inhibitors as recombinant proteins or by gene transfer, is also being explored. In future drugs that may stimulate alveolar repair might be developed, including retinoid receptor agonists and hepatic growth factor. Future directions will include earlier detection of disease, gene profiling to identify which smokers are at risk of COPD, and the development of noninvasive surrogate markers to monitor disease activity in order to monitor new therapies. Identification of genes that confer a risk for COPD in smokers may identify novel targets for drug development. Barnes PJ. Novel approaches and targets for treatment of chronic obstructive pulmonary disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I338,I338)","v":10487397},{"$f":"(LEN($J338) - LEN(SUBSTITUTE(LOWER($J338),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J338) - LEN(SUBSTITUTE(LOWER($J338),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J338) - LEN(SUBSTITUTE(LOWER($J338),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B338:D338)","v":1},1999,"Drug-induced nail disorders: incidence, management and prognosis.","Piraccini",10487397,"Drug-induced nail disorders: incidence, management and prognosis.    Abstract:   A large number of drugs of different classes, ranging from antibacterials to chemotherapeutic agents to psoralens, can be responsible for the development of nail changes. Drug-induced nail changes usually involve several or all 20 nails and appear in temporal correlation with drug intake. Some nail changes are asymptomatic and only cause cosmetic problems, while others cause pain and discomfort and impair manual activities or deambulation. Drug-induced nail abnormalities are usually transitory and disappear with drug withdrawal, but sometimes persist in time. The pathogenesis of the nail changes is usually a toxic effect of the drug on the different nail constituents, but other mechanisms can be involved. Drugs that are well known to produce nail abnormalities include cancer chemotherapeutic agents, psoralens, retinoids, tetracyclines, antimalarials and zidovudine. Arsenic poisoning is also always associated with nail changes that have medico-legal importance. Some drugs taken during pregnancy may impair nail development of the fetus, and nail hypoplasia or other nail dystrophies will be evident in the newborn."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I339,I339)","v":10363157},{"$f":"(LEN($J339) - LEN(SUBSTITUTE(LOWER($J339),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J339) - LEN(SUBSTITUTE(LOWER($J339),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J339) - LEN(SUBSTITUTE(LOWER($J339),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B339:D339)","v":1},1998,"[Control of tumor-related angiogenesis].","Oikawa",10363157,"[Control of tumor-related angiogenesis].    Abstract:   Tumor-related angiogenes is expected to become an important target for improving treatment of cancer, because it plays key roles in tumor growth, invasion and metastasis. We considered that the successful development of such angiostatic treatment depended entirely upon the development of useful anti-angiogenic agents, and attempted to find novel angiogenesis inhibitors by using three in vivo assays, based on an idea of ours. As a result we have demonstrated that different types of agents with low molecular weight including microbial metabolites, cell differentiation modulators like retinoids and steroids, exhibit anti-angiogenic activity, anti-metastatic activity and/or antitumor activity. Taken these findings, an ideal anti-angiogenic agent is discussed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I340,I340)","v":10355033},{"$f":"(LEN($J340) - LEN(SUBSTITUTE(LOWER($J340),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J340) - LEN(SUBSTITUTE(LOWER($J340),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J340) - LEN(SUBSTITUTE(LOWER($J340),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B340:D340)","v":1},1999,"Patterning during organogenesis: genetic analysis of cardiac chamber formation.","Yelon",10355033,"Patterning during organogenesis: genetic analysis of cardiac chamber formation.    Abstract:   A classical genetic approach, in which mutagenized organisms are screened for phenotypes of interest, is appealing for the analysis of developmental processes. Here, we describe the advantages of zebrafish genetics for the study of heart development. As an example of the utility of this strategy, we discuss its potential to illuminate the molecular mechanisms of cardiac chamber formation. The signals that specify ventricular and atrial lineages and the differentiation pathways that produce distinct chambers are poorly understood. Recently identified zebrafish mutations that disrupt ventricular or atrial development promise to reveal genes essential for these processes."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I341,I341)","v":9914859},{"$f":"(LEN($J341) - LEN(SUBSTITUTE(LOWER($J341),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J341) - LEN(SUBSTITUTE(LOWER($J341),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J341) - LEN(SUBSTITUTE(LOWER($J341),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B341:D341)","v":1},1999,"Role of retinoids in renal development: pathophysiological implication.","Merlet-Bénichou",9914859,"Role of retinoids in renal development: pathophysiological implication.    Abstract:   Vitamin A closely modulates nephron endowment at birth. It is also required for the development of renal vasculature. Fetal vitamin A status may thus be responsible for most of the variations in nephron number found in the general population, and may play a major role in the intrauterine programming of chronic renal disease and hypertension."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I342,I342)","v":9717061},{"$f":"(LEN($J342) - LEN(SUBSTITUTE(LOWER($J342),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J342) - LEN(SUBSTITUTE(LOWER($J342),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J342) - LEN(SUBSTITUTE(LOWER($J342),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B342:D342)","v":1},1998,"Metabolic basis for hypertriglyceridaemia in familial combined hyperlipidaemia.","Erkelens",9717061,"Metabolic basis for hypertriglyceridaemia in familial combined hyperlipidaemia.    Abstract:   Familial combined hyperlipidaemia (FCH) is not a single entity with a clearly defined cause but can occur through an increased fatty acid flux from adipose cells, lipoprotein lipase dysfunction or apolipoprotein CIII abnormalities. A dynamic model of the metabolic processes of FCH has been used to describe how lipolysis of adipose cells may ultimately contribute to the formation of atherosclerotic plaques. Elevated circulating levels of chylomicrons are broken down to produce atherogenic remnants. One of the roles of lipoprotein lipase is in the low density lipoprotein (LDL) receptor-like protein-mediated uptake of lipoprotein remnants in the liver and up to 20% of FCH patients show a genetic abnormality of this enzyme. Vitamin A loading and measurement of chylomicron retinyl palmitate levels has further demonstrated impaired chylomicron remnant metabolism in these patients. Macrophages located in the vascular walls engulf remnants but are unable to metabolize their cholesterol. These cells contribute to atherosclerotic plaques. In terms of atherogenic potential, triglyceride levels are found to be higher and the hypertriglyceridaemia more severe in fed than in fasted patients. A case study of a patient with abetalipoproteinaemia suggests that the hypertriglyceridaemia seen in patients with FCH may be the result of an abnormality in microsomal triglyceride transport protein function. Studies also suggest a direct relationship between the post-prandial triglyceride levels and LDL cholesterol levels in the fasting state of patients with FCH and sporadic hypercholesterolaemia."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I343,I343)","v":9704544},{"$f":"(LEN($J343) - LEN(SUBSTITUTE(LOWER($J343),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J343) - LEN(SUBSTITUTE(LOWER($J343),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J343) - LEN(SUBSTITUTE(LOWER($J343),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B343:D343)","v":1},1998,"Vitamins and coronary heart disease: where do we stand?","Mendis",9704544,"Vitamins and coronary heart disease: where do we stand?    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I344,I344)","v":9642691},{"$f":"(LEN($J344) - LEN(SUBSTITUTE(LOWER($J344),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J344) - LEN(SUBSTITUTE(LOWER($J344),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J344) - LEN(SUBSTITUTE(LOWER($J344),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B344:D344)","v":1},1998,"[Pre- and/or postoperative adjuvant therapy for hepatocellular carcinoma].","Imaoka",9642691,"[Pre- and/or postoperative adjuvant therapy for hepatocellular carcinoma].    Abstract:   Pre- and/or postoperative adjuvant therapy for hepatocellular carcinoma (HCC) is discussed. There is a high recurrence rate of HCC of up to 50% or more within three years after hepatectomy. More than 80% of those recurrences are in the form of intrahepatic metastases. Therefore it is extremely important to administer successful adjuvant therapy to prevent intrahepatic recurrence. There are two types of intrahepatic recurrence: simple dissemination from the primary focus of HCC; and newly developed HCC in the remnant liver. TAE is one option for preoperative adjuvant therapy to prevent intrahepatic recurrence. Postoperative adjuvant chemotherapy via the hepatic artery has occasionally been administered, but it is not yet established as an effective adjuvant therapy. However, a report by Muto et al showed that retinoid administration can prevent intrahepatic recurrence of newly developed HCC after hepatectomy. On the other hand, adjuvant therapy must not be tooaggressive, because: 1) HCC develops mainly in cirrhotic liver (with poor liver function); and 2) locoregional therapy for intrahepatic recurrence results in good survival rats even after detection of an established recurrence."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I345,I345)","v":9611613},{"$f":"(LEN($J345) - LEN(SUBSTITUTE(LOWER($J345),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J345) - LEN(SUBSTITUTE(LOWER($J345),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J345) - LEN(SUBSTITUTE(LOWER($J345),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B345:D345)","v":1},1998,"Chemoprevention of lung cancer: the rise and demise of beta-carotene.","Omenn",9611613,"Chemoprevention of lung cancer: the rise and demise of beta-carotene.    Abstract:   Beta-carotene and retinoids were the most promising agents against common cancers when the National Cancer Institute mounted a substantial program of population-based trials in the early 1980s. Both major lung cancer chemoprevention trials not only showed no benefit, but had significant increases in lung cancer incidence and in cardiovascular and total mortality. A new generation of laboratory research has been stimulated. Rational public health recommendations at this time include: 1. Five-A-Day servings of fruits and vegetables, a doubling of current mean intake; 2. systematic investigation of the covariates of extremes of fruit and vegetable intake; 3. discouragement of beta-carotene supplement use, due to adverse effects in smokers and no evidence of benefit in non-smokers; 4. multilevel research to develop and evaluate candidate chemoprevention agents to prevent lung and other common cancers; and 5. continued priority for smoking prevention, smoking cessation, and avoidance of known carcinogens in the environment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I346,I346)","v":9504139},{"$f":"(LEN($J346) - LEN(SUBSTITUTE(LOWER($J346),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J346) - LEN(SUBSTITUTE(LOWER($J346),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J346) - LEN(SUBSTITUTE(LOWER($J346),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B346:D346)","v":1},1997,"Carotenoids: biology and treatment.","Rock",9504139,"Carotenoids: biology and treatment.    Abstract:   Carotenoids are pigments found in plants and microorganisms, but not synthesized in animals. Fewer than 10% of the carotenoids can function as vitamin A precursors in mammals. Carotenoids and retinoids have chemical and metabolic similarities and differences, and some overlap in biological activities. Carotenoids in tissues reflect food choices. Carotenoids exhibit biological activities as antioxidants, affect cell growth regulation, and modulate gene expression and immune response. Epidemiologic evidence links higher carotenoid intakes and tissue concentrations with reduced cancer and cardiovascular disease risk, although results from clinical trials do not support beta-carotene supplementation as a strategy to reduce risk. Continued research in this area is likely to stimulate better intervention strategies with clinical and public health applications."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I347,I347)","v":9498311},{"$f":"(LEN($J347) - LEN(SUBSTITUTE(LOWER($J347),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J347) - LEN(SUBSTITUTE(LOWER($J347),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J347) - LEN(SUBSTITUTE(LOWER($J347),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B347:D347)","v":1},1998,"Hepatic and other medical disorders of alcoholism: from pathogenesis to treatment.","Lieber",9498311,"Hepatic and other medical disorders of alcoholism: from pathogenesis to treatment.    Abstract:   The medical risks of moderate and excessive alcohol consumption are reviewed. Current knowledge of metabolism of alcohol, including effects of moderate amounts, on hepatic metabolism and toxicity is summarized, with an evaluation of the relationship between the level of consumption and its effects on nutrients (including retinoids, carotenoids and folate), liver disease and other medical complications of alcoholism, including cardiovascular diseases and cancer. Putative benefits are also considered. Promising therapeutic approaches evolving from newly gained insight in the pathogenesis of medical complications of alcoholism are outlined."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I348,I348)","v":9413701},{"$f":"(LEN($J348) - LEN(SUBSTITUTE(LOWER($J348),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J348) - LEN(SUBSTITUTE(LOWER($J348),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J348) - LEN(SUBSTITUTE(LOWER($J348),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B348:D348)","v":1},1997,"Vitamin supplementation therapy in the elderly.","Thurman",9413701,"Vitamin supplementation therapy in the elderly.    Abstract:   Vitamin supplementation in large dosages is increasingly common in the older population. Often, such supplementation is used in an attempt to improve an individuals health status. There have been claims that the effects of vitamins halt the normal aging process or prevent and cure disease. However, several recent studies have failed to demonstrate the efficacy of vitamin supplementation in preventing several types of cancer. In moderate dosages, supplementation with vitamin E (tocopherols) shows promise as a lipid antioxidant, and may reduce the risk of coronary heart disease. However, before vitamin E becomes an accepted medical therapy, further long term studies must be undertaken to examine the safety and efficacy of such therapy. An adequate intake of vitamins should be ensured by adherence to a well balanced diet. However, the elderly are prone to circumstances that may prevent them from eating a balanced diet. In addition, there are several age-related medical conditions that may predispose individuals to dietary and vitamin deficiencies. To prevent vitamin deficiency diseases and their associated morbidity, modest vitamin supplementation may be necessary. However, supplementation should be reserved for individuals with documented deficiency or who are at risk of developing such deficiencies, especially those who are homebound or institutionalised. Vitamins taken in large dosages should be considered as drugs. These medicines, which are obtainable over-the-counter, should be carefully regulated to prevent toxicity."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I349,I349)","v":8886320},{"$f":"(LEN($J349) - LEN(SUBSTITUTE(LOWER($J349),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J349) - LEN(SUBSTITUTE(LOWER($J349),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J349) - LEN(SUBSTITUTE(LOWER($J349),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B349:D349)","v":1},1996,"Current food and nutrition situation in south Asian and south-east Asian countries.","Gopalan",8886320,"Current food and nutrition situation in south Asian and south-east Asian countries.    Abstract:   Food production in the countries of South and South-East Asia has shown a general upward trend during the last decade. Despite the considerable increase in population in many of these countries, food production per capita in 1988-90 was significantly higher as compared to 1979-81 figures, the increase being specially marked in such countries as Vietnam, Cambodia, Indonesia, and Malaysia. Available daily calorie supply was adequate to meet the requirement. The overall pattern of food production however has shown little change, with cereal production continuing to account for a predominant part of food production. There is no evidence of a significant uptrend with respect to production of pulses, milk, horticultural products, poultry or meat production in most countries. A unique and unfortunate feature of the nutrition situation in South-Asian countries is that the incidence of low birth weight deliveries is as high as 34% (1990), ranging from 25% in Sri Lanka to 50% in Bangladesh (as against less than 7% in the countries of Europe and North America). Even in countries of Africa where the overall food and nutrition situation is worse than in South Asia, the incidence is well below 20%. This is a reflection of the poor state of maternal nutrition in pregnancy. Florid nutritional deficiency diseases have shown a steep decline over the last two decades, but goitre and iron deficiency anaemia continue to be major public health problems, though some headway has been made with regard to the control of the former. Severe forms of growth retardation in children have declined but the majority suffer from mild and moderate forms of growth retardation. Countries of the Region are in varying stages of developmental transition. Among the burgeoning middle classes in some of these countries there are evidences of escalation of degenerative diseases such as diabetes and coronary heart disease. With increasing life expectancy, geriatric nutritional problems will demand increasing attention. This article discusses the Human Development Index levels in southern and southeastern Asia, food production and availability, soil and water erosion and fishery depletion, undernutrition, anemia, child mortality, and low birth weight. Urbanization is rapidly increasing. There is a growing affluent middle class. Public health is being threatened by new diseases such as AIDS. An estimated 33% of populations in South and Southeast Asia will be living in urban areas. Urbanization influences are expected to change life styles and patterns of food consumption. It is argued that the future will pose challenges to food resource allocation. Nutrition will be an emerging issue on the national agenda. South Asians and Southeast Asians now comprise about 56% of Asias total population and about 33% of total world population. Most South and Southeast Asian countries rank in the medium and low levels of the Human Development Index. Only Singapore, Thailand, and Malaysia are ranked high. Proper management of Asias land and water resources suggest the ability to feed their growing populations. In 1992 cereal and pulse production kept pace with population growth. However, the estimated per capita daily food availability barely met estimated requirements, and food availability was deficient in some countries. The Green Revolution emphasized the production of wheat and rice at the expense of legumes and pulses. Fruits and vegetables were sufficiently available but seasonally unequally distributed due to storage and refrigeration problems. Soil quality and fish stocks declined during the Green Revolution. Many programs are working to increase nutrition among low-income groups. The widespread health problems include growth retardation, anemia, iodine deficiency, and vitamin A deficiency. Other measures of health, such as prevalence of low birth weight, are based on old studies."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I350,I350)","v":8836870},{"$f":"(LEN($J350) - LEN(SUBSTITUTE(LOWER($J350),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J350) - LEN(SUBSTITUTE(LOWER($J350),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J350) - LEN(SUBSTITUTE(LOWER($J350),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B350:D350)","v":1},1996,"Expression of bone-specific genes by hypertrophic chondrocytes: implication of the complex functions of the hypertrophic chondrocyte during endochondral bone development.","Gerstenfeld",8836870,"Expression of bone-specific genes by hypertrophic chondrocytes: implication of the complex functions of the hypertrophic chondrocyte during endochondral bone development.    Abstract:   Endochondral bone formation is one of the most extensively examined developmental sequences within vertebrates. This process involves the coordinated temporal/spatial differentiation of three separate tissues (cartilage, bone, and the vasculature) into a variety of complex structures. The differentiation of chondrocytes during this process is characterized by a progressive morphological change associated with the eventual hypertrophy of these cells. These cellular morphological changes are coordinated with proliferation, a columnar orientation of the cells, and the expression of unique phenotypic properties including type X collagen, high levels of bone, liver, and kidney alkaline phosphatase, and mineralization of the cartilage matrix. Several studies indicate that hypertrophic chondrocytes also express osteocalcin, osteopontin, and bone sialoprotein, three proteins which until very recently were widely believed to be restricted in their expression to osteoblasts. Recent studies suggest that the hypertrophic chondrocytes are regulated by the calcitropic hormones, morphogenic steroids, and local tissue factors. These considerations are based on the regulation by 1,25 (OH)2D3 and retinoids of the cartilage specific genes as well as osteopontin and osteocalcin expression in hypertrophic chondrocytes. They are also based on the effects on growth plate development caused by 1) transgenic ablation of autocrine/paracrine regulators such as PTHrP and of the transcriptional regulator c-fos and 2) naturally occurring genetic mutations of the FGF receptor. These studies further suggest that specific transcriptional factors mediate exogenous regulatory signals in a coordinated manner with the development of bone. While it has been widely demonstrated that the majority of hypertrophic chondrocytes undergo apoptosis during terminal stages of the developmental sequence, their response to specific exogenous regulatory signals and their expression of bone-specific proteins give rise to questions about whether all growth chondrocytes have the same developmental fates and have identical functions. Furthermore, specific questions arise as to whether there are similar mechanisms of regulation for commonly expressed genes found in both cartilage and bone or whether these genes have unique regulatory mechanisms in these different tissues. These recent findings suggest that hypertrophic chondrocytes are functionally coupled during endochondral bone formation to the recruitment of osteoblasts, vascular cells, and osteoclasts."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I351,I351)","v":8882470},{"$f":"(LEN($J351) - LEN(SUBSTITUTE(LOWER($J351),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J351) - LEN(SUBSTITUTE(LOWER($J351),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J351) - LEN(SUBSTITUTE(LOWER($J351),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B351:D351)","v":1},1996,"Modulation of elastin expression and cell proliferation in vascular smooth muscle cells in vitro.","Tajima",8882470,"Modulation of elastin expression and cell proliferation in vascular smooth muscle cells in vitro.    Abstract:   Elastin expression in cultured vascular smooth muscle cell (VSMC) was found to be enhanced by potent inhibitors of VSMC proliferation including minoxidil, heparin and retinoic acid. By contrast, elastin expression was declined by potent stimulators of VSMC proliferation like epidermal growth factor, high K+, angiotension II and phorbol ester. To elucidate the relationship between elastin expression and cell proliferation, the elastin expression in the different cell growth states brought by cell-synchronizing culture or suspension culture, a culture system independent of potent modulators of VSMC proliferation. Elastin was found to be expressed maximally at G0 and minimally at G2/M phases, suggesting that cell growth state regulates elastin expression in VSMC culture. Synthetic elastin peptide VPGVG or its polymeric form (VPGVG)n enhanced VSMC proliferation, which resulted in the reduction of elastin expression. The results suggests that elastin fragment regulates VSMC proliferation. These correlation between elastin expression and cell growth state may play an essential role in elastin metabolism under the normal and diseased conditions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I352,I352)","v":9077255},{"$f":"(LEN($J352) - LEN(SUBSTITUTE(LOWER($J352),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J352) - LEN(SUBSTITUTE(LOWER($J352),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J352) - LEN(SUBSTITUTE(LOWER($J352),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B352:D352)","v":1},1996,"Fish and healthy pregnancy: more than just a red herring!","Rice",9077255,"Fish and healthy pregnancy: more than just a red herring!    Abstract:   In modern Western diets we eat predominantly omega-6 essential fatty acids from vegetable oils, and too little omega-3. The Department of Health recommends doubling the amount of omega-3s we eat. Omega-3 essential fatty acids (EFAs) are derived mainly from fish oils. Omega-3s are believed to help reduce the risks of cardiovascular disease. Among the main materials required for fetal brain and CNS growth in late pregnancy are omega-3s (mainly docosahexaenoic acid [DHA]) and omega-6 EFAs (mainly arachidonic acid [AA]). These come from the mothers diet. Several formulae for preterm infants now contain DHA and AA to aid optimum brain, nerve and retinal development. One manufacturer has begun to include DHA and AA in formulae for term babies. Breast milk contains DHA and AA, derived from the mothers diet. Eating oily fish in pregnancy has been found to have a slight beneficial effect on birthweight and length of gestation. Eating fresh or canned oil-rich fish (e.g. kippers, herring, mackerel, salmon, sardine, pilchards, tuna) twice or three times a week can be encouraged as part of a healthy balanced diet, in pregnancy and for all the family. As well as containing omega-3 polyunsaturates, oily fish is a good source of protein and vitamins A and D. Alternatively, a fish-oil supplement may be taken. Cod liver oil is best avoided during pregnancy, because of concerns over the possible teratogenicity of vitamin A."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I353,I353)","v":7614708},{"$f":"(LEN($J353) - LEN(SUBSTITUTE(LOWER($J353),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J353) - LEN(SUBSTITUTE(LOWER($J353),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J353) - LEN(SUBSTITUTE(LOWER($J353),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B353:D353)","v":1},1995,"Diversification of cardiomyogenic cell lineages during early heart development.","Yutzey",7614708,"Diversification of cardiomyogenic cell lineages during early heart development.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I354,I354)","v":8578472},{"$f":"(LEN($J354) - LEN(SUBSTITUTE(LOWER($J354),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J354) - LEN(SUBSTITUTE(LOWER($J354),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J354) - LEN(SUBSTITUTE(LOWER($J354),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B354:D354)","v":1},1995,"Cancer and thrombosis: from Phlegmasia alba dolens to transgenic mice.","Donati",8578472,"Cancer and thrombosis: from Phlegmasia alba dolens to transgenic mice.    Abstract:   Thrombosis is the most frequent complication and the second cause of death in patients with overt malignant diseases. Increasing evidence suggests that thrombotic episodes may also precede the diagnosis of cancer by months or years thus representing a potential marker for occult malignancy. Recently, emphasis has been given to the potential risk of cancer therapy (both surgery and chemotherapy) in enhancing the risk for thromboembolic disease. Post-operative deep-vein thrombosis is indeed more frequent in patients operated for malignant diseases than for other disorders. On the other hand, both chemotherapy and hormone therapy are associated with an increased thrombotic risk, which can be prevented by low-dose oral anticoagulation. Possible contributory causes for thromboembolic disease in cancer include the capacity of tumor cells and their products to interact with platelets, clotting and fibrinolytic systems, as well as their interactions with endothelial cells and tumor-associated macrophages. In particular, procoagulant activities of tumor cells have been extensively studied; one of these, cancer procoagulant, could represent a novel marker of malignancy in both solid tumors and acute promyelocytic leukemia (APL). In solid tumors, CP, a vitamin K dependent enzyme could represent the selective target of the antimetastatic effects of warfarin treatment. In APL, CP may contribute to trigger the well known intravascular coagulation syndrome accompanying the early manifestations of the disease and is depressed by all-trans-retinoic acid, an agent capable to determine complete remission with a rapid amelioration of the bleeding syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I355,I355)","v":7704185},{"$f":"(LEN($J355) - LEN(SUBSTITUTE(LOWER($J355),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J355) - LEN(SUBSTITUTE(LOWER($J355),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J355) - LEN(SUBSTITUTE(LOWER($J355),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B355:D355)","v":1},1995,"Free radicals in foods.","Donnelly",7704185,"Free radicals in foods.    Abstract:   During the last decade increasing attention has been given to the role of free radicals in biological oxidations. The subject has been of increasing interest to both the food scientist and the physiologist. Free radical scavengers in the form of both indigenous and added antioxidants are necessary for the successful preservation of food; free radicals are increasingly being implicated in the onset of, among others, ischaemic heart disease and for protection against these diseases it is suggested that the dietary intake of the antioxidant vitamins should be increased especially for diets high in polyunsaturated fats. Convenience and snack foods which absorb substantial amounts of frying oils are being increasingly consumed. Since poly-unsaturated fatty acids are particularly susceptible to oxidation by free radicals during the storage, cooking and frying of foods, the potential risk of exposure to lipid degradation products is likely to have increased. In foods the non-enzymic and lipoxy-genase catalysed oxidation of polyunsaturated fatty acids, beta-carotene and vitamin A can result in the loss of essential nutrients and the development of off-flavours."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I356,I356)","v":7598011},{"$f":"(LEN($J356) - LEN(SUBSTITUTE(LOWER($J356),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J356) - LEN(SUBSTITUTE(LOWER($J356),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J356) - LEN(SUBSTITUTE(LOWER($J356),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B356:D356)","v":1},1995,"Genetic engineering of foods to reduce the risk of heart disease and cancer.","Knauf",7598011,"Genetic engineering of foods to reduce the risk of heart disease and cancer.    Abstract:   Gene manipulation techniques can be used to increase, decrease, or add specific proteins to the edible parts of transgenic crop plants. With some basic understanding of plant biosynthetic pathways, then, the targeting of genes encoding specific enzymes allows the direct modification of the biochemical composition of foods. At Calgene, we have engineered the chemical composition of canola vegetable oils. Transgenic canola which are otherwise exactly like regular canola plants produce seed with oils a) that are modified in average fatty acid carbon chain length, b) that are modified in content of saturated fatty acids (both lower and higher), or c) that contain structured lipids. In principle, although the gene target may not be obvious, the relative amount of lipids compared to other nutrients can be decreased or increased in foods like peanut or soybean. The oil content of some food products might be modified to enhance levels of medium chain triglycerides or to contain quot;fish oilquot; fatty acids--without the cost or olfactory disadvantages. On a broader scope, the amino acid composition of proteins in basic grains is being pursued by several groups. Specific vitamin contents such as Vitamin A or E might be enhanced in basic foodstuffs; type and content of fiber may eventually be manipulated. Specific components such as caffeine or phytic acid conceivably can be eliminated in the source plant, negating the need for processing steps that add cost and that lessen flavor and nutrition. Clearly, the biochemical compositions of foods is complex and varied. Moreover, tailoring foods to better meet our needs is an expensive and lengthy process. The best possible understanding of how nutrition promotes good health is necessary to direct and prioritize our efforts to improve plants as food sources.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I357,I357)","v":8060275},{"$f":"(LEN($J357) - LEN(SUBSTITUTE(LOWER($J357),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J357) - LEN(SUBSTITUTE(LOWER($J357),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J357) - LEN(SUBSTITUTE(LOWER($J357),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B357:D357)","v":1},1994,"Free radicals, antioxidants and preventive geriatrics.","Ward",8060275,"Free radicals, antioxidants and preventive geriatrics.    Abstract:   Despite a realisation that antioxidants will not delay ageing in healthy older people, there is increasing scientific interest in the role of free radical oxidants in a number of diseases associated with older age. For most of these diseases there is suggestive theoretical and laboratory evidence but not confirmatory clinical evidence. Free radical damage seems likely to be significant in the pathophysiology of atherosclerosis, ischaemia-reperfusion injury, Parkinsons disease, cataract, some cancers and rheumatoid arthritis. Evidence to suggest a protective effect from antioxidant vitamins exists for ischaemic heart disease, cataract and some cancers. Attempts to influence the outcome of other diseases such as ischaemia-reperfusion injury, Parkinsons disease and rheumatoid arthritis have so far failed to achieve positive results. Research interest in the field is increasing although hampered by methodological difficulties and the limited financial return for drug companies. In the meantime there seems no reason to discourage older people who wish to ingest extra vitamin E and vitamin C. A diet with adequate vegetables and fruits should provide sufficient beta carotene."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I358,I358)","v":8221032},{"$f":"(LEN($J358) - LEN(SUBSTITUTE(LOWER($J358),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J358) - LEN(SUBSTITUTE(LOWER($J358),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J358) - LEN(SUBSTITUTE(LOWER($J358),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B358:D358)","v":1},1993,"Prospects for the prevention of free radical disease, regarding cancer and cardiovascular disease.","Gey",8221032,"Prospects for the prevention of free radical disease, regarding cancer and cardiovascular disease.    Abstract:   Free radicals may be involved in the aetiology of cancer and cardiovascular diseases. In epidemiological studies poor plasma levels of all essential antioxidants are associated with increased relative risks; in particular, low levels of carotene and vitamin E with the risk of cancer and ischemic heart disease, respectively. The studies suggest that for optimal synergistic protection the plasma antioxidant levels should simultaneously exceed the threshold values of 28-30 mumol/l lipid-standardized vitamin E, 40-50 mumol/l vitamin C, 0.4-0.5 mumol/l carotene and 2.2-2.8 mumol/l lipid-standardized vitamin A. However the preventive efficacy of an optional antioxidant status is still to be proven in randomized intervention trials. Although these antioxidant micronutrients may be the primary protective components of vegetable-rich preventive diets, the potentials of other plant components await exploration, eg carotenoids other than beta-carotene, bioflavonoids and oxygen-sensitive B-vitamins."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I359,I359)","v":8475897},{"$f":"(LEN($J359) - LEN(SUBSTITUTE(LOWER($J359),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J359) - LEN(SUBSTITUTE(LOWER($J359),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J359) - LEN(SUBSTITUTE(LOWER($J359),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B359:D359)","v":1},1993,"Increased risk of cardiovascular disease at suboptimal plasma concentrations of essential antioxidants: an epidemiological update with special attention to carotene and vitamin C.","Gey",8475897,"Increased risk of cardiovascular disease at suboptimal plasma concentrations of essential antioxidants: an epidemiological update with special attention to carotene and vitamin C.    Abstract:   For the prolongation of life expectancy and reduction of ischemic heart disease (IHD) dietary guidelines generally recommend lowering saturated mammalian fat with partial replacement by vegetable oils and increasing generously vegetables, legumes, and fruits, which provide more essential antioxidants. Plasma antioxidants as assayed in epidemiological studies of complementary type (ie the cross-cultural MONICA Vitamin Substudy reevaluation considering the quot;Finland-Factorquot;, the Edinburgh Angina-Control Study, and the Basel Prospective Study) consistently revealed an increased risk of IHD (and stroke) at low plasma concentrations of antioxidants, with the rank order as follows: lipid-standardized vitamin E gt; carotene = vitamin C gt; vitamin A, independently of classical IHD risk factors. Decreasing IHD risk through nutrition may be possible when plasma concentrations have the following values: gt; 27.5-30.0 mumol vitamin E/L, 0.4-0.5 mumol carotene/L, 40-50 mumol vitamin C/L and 2.2-2.8 mumol vitamin A/L. Thus, previous prudent regimens may now be updated, aiming at an optimal status of all essential and synergistically linked antioxidants."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I360,I360)","v":12288485},{"$f":"(LEN($J360) - LEN(SUBSTITUTE(LOWER($J360),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J360) - LEN(SUBSTITUTE(LOWER($J360),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J360) - LEN(SUBSTITUTE(LOWER($J360),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B360:D360)","v":1},1992,"Vitamin A in pregnancy: a review.","Sharma",12288485,"Vitamin A in pregnancy: a review.    Abstract:   In recent years several studies have demonstrated the close association of vitamin A deficiency and increased neonatal and childhood morbidity. The breast-fed infant depends on its vitamin A supply solely from maternal milk. Neonatal serum concentration of vitamin A is about one half that found in their mothers. As long as adequate lactational levels of the vitamin are present, the infants vitamin A status improves over the first 12 months. If maternal vitamin A status is poor in pregnancy it may contribute to the high infant mortality observed in poorly nourished communities. Clinical proof was established only very recently demonstrating a strong correlation between vitamin A status of the mother and intake of the infant. Thus, an adequate vitamin A status during lactation prevents respiratory and diarrheal diseases in breast-fed infants and averts death caused by the diseases. The International Vitamin A Consultative Group (IVACG) suggested that the recommended daily allowance (RDA) of vitamin A in the diet of pregnant women should be 9.3 retinol equivalent (RE)/kg body weight + 100 RE. In marginally nourished populations such as western Rajasthan, it is recommended that daily supplemental doses of 3000 RE (10,000 IU) vitamin A be given during pregnancy provided that the dietary intake is inadequate. For lactating women, the goal is to maintain the highest vitamin A concentration in breast milk. The dietary RDA should be 9.3 RE/kg body weight + 350 RE, provided that the lactating woman did not enter the lactation period in a deficient state. If she did, megadoses of vitamin A (200,000-300,000 IU) may be safely given at parturition or within the first month after birth. This is adequate to maintain a normal range of vitamin A in maternal blood and milk for at least a month."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I361,I361)","v":1759070},{"$f":"(LEN($J361) - LEN(SUBSTITUTE(LOWER($J361),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J361) - LEN(SUBSTITUTE(LOWER($J361),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J361) - LEN(SUBSTITUTE(LOWER($J361),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B361:D361)","v":1},1991,"[Portal hypertension and hypervitaminosis A. Apropos of 2 cases and review of the literature].","Dubois",1759070,"[Portal hypertension and hypervitaminosis A. Apropos of 2 cases and review of the literature].    Abstract:   Portal hypertension consecutive to hypervitaminosis A has seldom been well documented. Two cases are reported here. The first case concerns a 39-year old woman who had taken meladinine (8-methoxypsoralen) for the purpose of tanning. In the second case, a 43-year old woman had absorbed Plethoryl (a combination of tiratricol, cyclovalone and retinol) in order to lose weight. Both patients had histological hepatic lesions, such as hypertrophic Ito cells, perisinusoidal cirrhosis and spontaneous autofluorescence, suggestive of vitamin A overload, associated with a hepatic vein pressure gradient of 10 mmHg or more and high liver concentrations of vitamin A. The responsibility of Plethoryl in case 2 is beyond any doubt, but the mechanism of hypervitaminosis in case 1 is controverted. A review of the literature has provided detailed information on the signs of vitamin A overload, the frequency of which is probably underestimated. Patients with portal hypertension of unknown origin should be investigated for hypervitaminosis A."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I362,I362)","v":2192646},{"$f":"(LEN($J362) - LEN(SUBSTITUTE(LOWER($J362),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J362) - LEN(SUBSTITUTE(LOWER($J362),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J362) - LEN(SUBSTITUTE(LOWER($J362),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B362:D362)","v":1},1990,"Cardiovascular defects associated with alcohol, retinoic acid, and other agents.","Ruckman",2192646,"Cardiovascular defects associated with alcohol, retinoic acid, and other agents.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I363,I363)","v":3313139},{"$f":"(LEN($J363) - LEN(SUBSTITUTE(LOWER($J363),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J363) - LEN(SUBSTITUTE(LOWER($J363),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J363) - LEN(SUBSTITUTE(LOWER($J363),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B363:D363)","v":1},1987,"Inequalities in nutrition.","Wynn",3313139,"Inequalities in nutrition.    Abstract:   Inequalities in nutrition are associated with inequalities in health. Many surveys, mainly American, show that there are large variations between individuals in the quality and quantity of food consumed. Variations depend upon up-bringing, education, income and availability of food. In the United Kingdom there is a steep social-class gradient in age-specific death-rates for heart disease and other diseases including cancer. Of all the many possible nutritional factors the strongest inverse correlates with death-rates within the United Kingdom and in other developed countries are the consumption of fresh vegetables and fruit. Among the individual nutrients a low consumption of vitamin A, or its precursor carotene is associated with an increased cancer risk. Whole milk is a major source of vitamin A and carotene in the British diet and is also reported to be protective against osteoporosis and some forms of hypertension including preeclampsia. School meals can set a pattern of life-long eating habits."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I364,I364)","v":3538052},{"$f":"(LEN($J364) - LEN(SUBSTITUTE(LOWER($J364),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J364) - LEN(SUBSTITUTE(LOWER($J364),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J364) - LEN(SUBSTITUTE(LOWER($J364),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B364:D364)","v":1},1986,"Potential responses to and impacts of epidemiological and experimental data on dietary fat and cancer. Dietary guidelines.","OConnor",3538052,"Potential responses to and impacts of epidemiological and experimental data on dietary fat and cancer. Dietary guidelines.    Abstract:   The majority of dietary guidelines discussed above suggest a reduction in the % of dietary calories derived from fat. Currently, approximately 40% of calories in Western countries come from fat. Some of the more recent guidelines call for a reduction in fat intake to 30% of calories. Indeed, the Committee on Diet, Nutrition and Cancer (National Academy of Sciences 1982) and the World Health Organization Report on Prevention of Coronary Heart Disease (WHO 1982) suggested that the evidence warranted an even lower fat intake, but 30% of calories is a moderate and practical target. Diets containing 30% of calories as fat are undoubtedly safe for the general population. During and immediately after the Second World War in Britain, dietary fat intake was at or about this level and no deleterious effects in the population were noted. (Greaves and Hollingsworth 1966). Indeed, the overall state of health of the population seemed improved. Furthermore, most of the world population exists and has existed on a primarily plant based diet, low in fat content, with no apparent ill effects and lower rates of chronic disease. (Mintz 1985). Most dietary guidelines recommend a reduction in saturated fat intake. The more recent guidelines suggest saturated fat should be restricted to less than 10% of total calories. While some of the earlier guidelines suggested an increase in polyunsaturated fat intake, more recent guidelines stress that polyunsaturated fat intake should not exceed 10% of calories. Thus, the focus of more recent guidelines appears to be to decrease total fat intake. Essentially all guidelines stress avoidance of obesity by avoiding excess caloric intake and increasing caloric expenditure. Diets low in total fat content are beneficial in this regard, a fact acknowledged in the Food and Nutrition Boards report quot;Towards Healthful Diets.quot; (Food and Nutrition Board 1980 b) Most guidelines advise a decrease in calories derived from processed sugars and a concomitant increase in complex carbohydrate intake. This is best achieved by stressing whole grain cereals, fruits and vegetables in the diet. More recent recommendations advise moderation in the use of alcohol. Moderation in salt use is also a common theme. It is our belief that guidelines should be general in nature and not identify specific nutrients, e.g. vitamin A and C in foods, or specific foods themselves, e.g. cabbage, as conferring special benefits. The available data base does not support such specific claims.(ABSTRACT TRUNCATED AT 400 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I365,I365)","v":3005956},{"$f":"(LEN($J365) - LEN(SUBSTITUTE(LOWER($J365),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J365) - LEN(SUBSTITUTE(LOWER($J365),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J365) - LEN(SUBSTITUTE(LOWER($J365),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B365:D365)","v":1},1986,"Nutrition and infant lung functions: report of a National Heart, Lung and Blood Institute symposium.","OConnor",3005956,"Nutrition and infant lung functions: report of a National Heart, Lung and Blood Institute symposium.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I366,I366)","v":6428773},{"$f":"(LEN($J366) - LEN(SUBSTITUTE(LOWER($J366),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J366) - LEN(SUBSTITUTE(LOWER($J366),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J366) - LEN(SUBSTITUTE(LOWER($J366),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B366:D366)","v":1},1984,"Implications of nutritional status on human biochemistry, physiology, and health.","Sauberlich",6428773,"Implications of nutritional status on human biochemistry, physiology, and health.    Abstract:   Optimum nutrition is the level of intake that should promote the highest level of health. Although excess caloric intake will lead to obesity, a deficit in nutrition may result in a tissue depletion of essential nutrients that can lead to biochemical changes and eventually to clinical signs and symptoms. Nutrition requirements may differ according to sex, age, activity, or physiological state and can be influenced by drugs, smoking, alcohol, and other factors. With ever-increasing sedentary life styles and less physically demanding jobs, the resulting reduced caloric requirements have made it more difficult to make nutritionally sound food choices. Nutrition is the single most important component of preventive health care. Diet has been associated with cancer, heart disease, diabetes, stroke and hypertension, arteriosclerosis, and cirrhosis of the liver. The ability of the human to respond to stresses, such as altitude, heat, trauma, surgery, and infection can be influenced by nutritional status. Nutritional status is reflected in a variety of metabolic processes that provide the basis for a number of methods for its assessment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I367,I367)","v":4114167},{"$f":"(LEN($J367) - LEN(SUBSTITUTE(LOWER($J367),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J367) - LEN(SUBSTITUTE(LOWER($J367),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J367) - LEN(SUBSTITUTE(LOWER($J367),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B367:D367)","v":1},1972,"[Experimental congenital heart diseases].","Onishi",4114167,"[Experimental congenital heart diseases].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I368,I368)","v":4899660},{"$f":"(LEN($J368) - LEN(SUBSTITUTE(LOWER($J368),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J368) - LEN(SUBSTITUTE(LOWER($J368),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J368) - LEN(SUBSTITUTE(LOWER($J368),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B368:D368)","v":1},1969,"The pathophysiological morphology of the pigment epithelium and its importance for retinal structures and functions.","Meier-Ruge",4899660,"The pathophysiological morphology of the pigment epithelium and its importance for retinal structures and functions.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I369,I369)","v":27548214},{"$f":"(LEN($J369) - LEN(SUBSTITUTE(LOWER($J369),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J369) - LEN(SUBSTITUTE(LOWER($J369),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J369) - LEN(SUBSTITUTE(LOWER($J369),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B369:D369)","v":0},2016,"Assessment of the Dietary Intake of Schoolchildren in South Africa: 15 Years after the First National Study.","Steyn",27548214,"Assessment of the Dietary Intake of Schoolchildren in South Africa: 15 Years after the First National Study.    Abstract:   There has not been a national dietary study in children in South Africa since 1999. Fortification of flour and maize meal became mandatory in October 2003 to address micronutrient deficiencies found in the national study in 1999. The purpose of this review was to identify studies done after 1999 in schoolchildren, 6-15 years old, in order to determine whether dietary intakes reflected improvements in micronutrients, namely: iron, zinc, vitamin A, folate, thiamine, riboflavin, vitamin B6, and niacin. An electronic and hand search was done to identify all studies complying with relevant inclusion criteria. The search yielded 10 studies. Overall, there is a paucity of dietary studies which have included the fortified nutrients; only four, of which only one, reported on all micronutrients; making it difficult to determine whether fortification has improved the micronutrient intake of schoolchildren. This is further complicated by the fact that different dietary methods were used and that studies were only done in three of the nine provinces and thus are not generalizable. The results of these studies clearly point to the importance of doing a national study on the dietary intake of schoolchildren in order to confirm the outcomes of the fortification process."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I370,I370)","v":27439768},{"$f":"(LEN($J370) - LEN(SUBSTITUTE(LOWER($J370),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J370) - LEN(SUBSTITUTE(LOWER($J370),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J370) - LEN(SUBSTITUTE(LOWER($J370),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B370:D370)","v":0},2016,"Is the Association between Vitamin D and Metabolic Syndrome Independent of Other Micronutrients.","Khosravi-Boroujeni",27439768,"Is the Association between Vitamin D and Metabolic Syndrome Independent of Other Micronutrients.    Abstract:    NlmCategory=UNASSIGNEDThe incidence of metabolic syndrome (MetS) has been increasing globally and it is recognized as a major public health problem because MetS is associated with increased risk of diabetes, stroke, cancer, and other chronic diseases. Recently, MetS has been linked to vitamin D deficiency. However, the evidence on the association between vitamin D deficiency and the risk of MetS remains inconclusive. This review therefore aims to depict the existing evidence related to MetS and vitamin D deficiency, and examined some of the possible confounders which may affect the association between vitamin D status and risk of MetS. Earlier studies on the association between vitamin D deficiency and MetS have adjusted for the effect of some confounders including, age, sex, body mass index, race, physical activity, smoking, alcohol consumption, and energy intake. However, these studies failed to consider other potential confounders. There is evidence that vitamin A, zinc (Zn), and magnesium (Mg) play important roles in the activation and function of vitamin D and interact with gene expression. Furthermore, these micronutrients are also related to several components of the MetS including glucose intolerance, dyslipidemia, and obesity. Thus, there could be an interaction between these micronutrients, vitamin D, and MetS. This review highlights the possible interactions of vitamin A, Zn, Mg, and vitamin D with MetS and its components. The findings reinforce the need for further well-designed studies that take into account all potential confounders, including other micronutrients such as vitamin A, Zn, and Mg status, to investigate the independent association of vitamin D status with MetS and its components, and also to scrutinize for possible interactions among other nutrients which may have similar confounding effects."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I371,I371)","v":26849156},{"$f":"(LEN($J371) - LEN(SUBSTITUTE(LOWER($J371),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J371) - LEN(SUBSTITUTE(LOWER($J371),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J371) - LEN(SUBSTITUTE(LOWER($J371),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B371:D371)","v":0},2016,"Specification and function of hemogenic endothelium during embryogenesis.","Gritz",26849156,"Specification and function of hemogenic endothelium during embryogenesis.    Abstract:   Hemogenic endothelium is a specialized subset of developing vascular endothelium that acquires hematopoietic potential and can give rise to multilineage hematopoietic stem and progenitor cells during a narrow developmental window in tissues such as the extraembryonic yolk sac and embryonic aorta-gonad-mesonephros. Herein, we review current knowledge about the historical and developmental origins of hemogenic endothelium, the molecular events that govern hemogenic specification of vascular endothelial cells, the generation of multilineage hematopoietic stem and progenitor cells from hemogenic endothelium, and the potential for translational applications of knowledge gained from further study of these processes."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I372,I372)","v":26593077},{"$f":"(LEN($J372) - LEN(SUBSTITUTE(LOWER($J372),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J372) - LEN(SUBSTITUTE(LOWER($J372),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J372) - LEN(SUBSTITUTE(LOWER($J372),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B372:D372)","v":0},2015,"Evidence-Based Pharmacologic Therapies for Prevention of Bronchopulmonary Dysplasia: Application of the Grading of Recommendations Assessment, Development, and Evaluation Methodology.","Jensen",26593077,"Evidence-Based Pharmacologic Therapies for Prevention of Bronchopulmonary Dysplasia: Application of the Grading of Recommendations Assessment, Development, and Evaluation Methodology.    Abstract:   Bronchopulmonary dysplasia (BPD) is the most common chronic complication of extreme preterm birth. The authors applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to pharmacologic therapies found to prevent BPD. Caffeine and vitamin A are the only medications shown in high-quality studies to prevent BPD without the risk of clinically important adverse effects. Dexamethasone is effective for the prevention of BPD; but for many infants, the increased risks of hypertrophic cardiomyopathy, gastrointestinal perforation, and cerebral palsy outweigh this benefit. Several medications are currently under investigation for the prevention of BPD, but few are novel agents."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I373,I373)","v":25875487},{"$f":"(LEN($J373) - LEN(SUBSTITUTE(LOWER($J373),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J373) - LEN(SUBSTITUTE(LOWER($J373),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J373) - LEN(SUBSTITUTE(LOWER($J373),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B373:D373)","v":0},2015,"Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a protocol for a systematic review and network meta-analysis of primary prevention trials.","Schwingshackl",25875487,"Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a protocol for a systematic review and network meta-analysis of primary prevention trials.    Abstract:    BACKGROUND : In the Western world, dietary supplements are commonly used to prevent chronic diseases, mainly cardiovascular disease and cancer. However, there is inconsistent evidence on which dietary supplements actually lower risk of chronic disease, and some may even increase risk. We aim to evaluate the comparative safety and/or effectiveness of dietary supplements for the prevention of mortality (all-cause, cardiovascular, and cancer) and cardiovascular and cancer incidence in primary prevention trials.  METHODS/DESIGN : We will search PubMed, EMBASE, Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Cochrane Central Register of Controlled Trials, clinical trials.gov, and the World Health Organization International Trial Registry Platform. Randomized controlled trials will be included if they meet the following criteria: (1) minimum intervention period of 12 months; (2) primary prevention of chronic disease (is concerned with preventing the onset of diseases and conditions); (3) minimum mean age ≥18 years (maximum mean age 70 years); (4) intervention(s) include vitamins (beta-carotene, vitamin A, B vitamins, Vitamin C, Vitamin D, Vitamin E, and multivitamin supplements); fatty acids (omega-3 fatty acids, omega-6 fatty acids, monounsaturated fat); minerals (magnesium, calcium, selenium, potassium, iron, zinc, copper, iodine; multiminerals); supplements containing combinations of both vitamins and minerals; protein (amino acids); fiber; prebiotics; probiotics; synbiotics; (5) supplements are orally administered as liquids, pills, capsules, tablets, drops, ampoules, or powder; (6) report results on all-cause mortality (primary outcome) and/or mortality from cardiovascular disease or cancer, cardiovascular and/or cancer incidence (secondary outcomes). Pooled effects across studies will be calculated using Bayesian random effects network meta-analysis. Sensitivity analysis will be performed for trials lasting ≥5 years, trials with low risk of bias, trials in elderly people (≥65 years), ethnicity, geographical region, and trials in men and women. The results of the corresponding fixed effects models will also be compared in sensitivity analyses.  DISCUSSION : This is a presentation of the study protocol only. Results and conclusions are pending completion of this study. Our systematic review will be of great value to consumers of supplements, healthcare providers, and policy-makers, regarding the use of dietary supplements.  SYSTEMATIC REVIEW REGISTRATION : /                <AbstractText PROSPERO NlmCategory=UNASSIGNEDCRD42014014801 ."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I374,I374)","v":25774260},{"$f":"(LEN($J374) - LEN(SUBSTITUTE(LOWER($J374),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J374) - LEN(SUBSTITUTE(LOWER($J374),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J374) - LEN(SUBSTITUTE(LOWER($J374),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B374:D374)","v":0},2014,"Night blindness and ancient remedy.","Al Binali",25774260,"Night blindness and ancient remedy.    Abstract:   The aim of this article is to briefly review the history of night blindness and its treatment from ancient times until the present. The old Egyptians, the Babylonians, the Greeks and the Arabs used animal liver for treatment and successfully cured the disease. The author had the opportunity to observe the application of the old remedy to a patient. Now we know what the ancients did not know, that night blindness is caused by Vitamin A deficiency and the animal liver is the store house for Vitamin A."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I375,I375)","v":25485314},{"$f":"(LEN($J375) - LEN(SUBSTITUTE(LOWER($J375),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J375) - LEN(SUBSTITUTE(LOWER($J375),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J375) - LEN(SUBSTITUTE(LOWER($J375),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B375:D375)","v":0},2014,"Molecular Mechanisms of Podocyte Development Revealed by Zebrafish Kidney Research.","Miceli",25485314,"Molecular Mechanisms of Podocyte Development Revealed by Zebrafish Kidney Research.    Abstract:   Elucidating the gene regulatory networks that control kidney development can provide information about the origins of renal birth defects and kidney disease, as well as insights relevant to the design of clinical interventions for these conditions. The kidney is composed of functional units termed nephrons. Renal malfunction often arises from damage to cells known as podocytes, which are highly specialized epithelial cells that comprise the blood filter, or glomerulus, located on each nephron. Podocytes interact with the vasculature to create an elaborate sieve that collects circulatory fluid, and this filtrate enters the nephron where it is modified to produce urine and balance water homeostasis. Podocytes are an essential cellular component of the glomerular filtration barrier, helping to protect nephrons from the entry of large proteins and circulatory cells. Podocyte loss has catastrophic consequences for renal function and overall health, as podocyte destruction leads to nephron damage and pathological conditions like chronic kidney disease. Despite their importance, there is still a rather limited understanding about the molecular pathways that control podocyte formation. In recent years, however, studies of podocyte development using the zebrafish embryonic kidney, or pronephros, have been an expanding area of nephrology research. Zebrafish form an anatomically simple pronephros comprised of two nephrons that share a single blood filter, and podocyte progenitors can be easily visualized throughout the process of glomerular development. The zebrafish is an especially useful system for studying the mechanisms that are essential for formation of nephron cell types like podocytes due to the high genetic conservation between vertebrate species, including humans. In this review, we discuss how research using the zebrafish has provided new insights into the molecular regulation of the podocyte lineage during kidney ontogeny, complementing contemporary research in other animal models."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I376,I376)","v":25412782},{"$f":"(LEN($J376) - LEN(SUBSTITUTE(LOWER($J376),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J376) - LEN(SUBSTITUTE(LOWER($J376),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J376) - LEN(SUBSTITUTE(LOWER($J376),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B376:D376)","v":0},2015,"Psoriasis is a systemic disease with multiple cardiovascular and metabolic comorbidities.","Ryan",25412782,"Psoriasis is a systemic disease with multiple cardiovascular and metabolic comorbidities.    Abstract:   There is evidence that patients with moderate to severe psoriasis have an increased risk of conditions such as cardiovascular disease, obesity, diabetes mellitus, and metabolic syndrome. The precise mechanisms underlying the observed increase in cardiovascular disease in psoriasis remain to be defined but inflammatory pathways mutual to both conditions are probably involved. Suppression of systemic inflammation in psoriasis could help reduce cardiovascular inflammation but robust evidence is still lacking evidence is lacking. This article summarizes the current literature on cardiovascular and metabolic comorbidities in psoriasis, identifies research gaps, and suggests management strategies to reduce cardiovascular risk in patients with moderate to severe psoriasis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I377,I377)","v":25050077},{"$f":"(LEN($J377) - LEN(SUBSTITUTE(LOWER($J377),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J377) - LEN(SUBSTITUTE(LOWER($J377),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J377) - LEN(SUBSTITUTE(LOWER($J377),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B377:D377)","v":0},2014,"Intrauterine nutrition: long-term consequences for vascular health.","Szostak-Wegierek",25050077,"Intrauterine nutrition: long-term consequences for vascular health.    Abstract:   There is a growing body of evidence that improper intrauterine nutrition may negatively influence vascular health in later life. Maternal malnutrition may result in intrauterine growth retardation and, in turn, metabolic disorders such as insulin resistance, diabetes, hypertension, and dyslipidemia, and also enhanced risk of atherosclerosis and cardiovascular death in the offspring. Energy and/or protein restriction is the most critical determinant for fetal programming. However, it has also been proposed that intrauterine n-3 fatty acid deficiency may be linked to later higher blood pressure levels and reduced insulin sensitivity. Moreover, it has been shown that inadequate supply of micronutrients such as folate, vitamin B12, vitamin A, iron, magnesium, zinc, and calcium may contribute to impaired vascular health in the progeny. In addition, hypertensive disorders of pregnancy that are linked to impaired placental blood flow and suboptimal fetal nutrition may also contribute to intrauterine growth retardation and aggravated cardiovascular risk in the offspring. On the other hand, maternal overnutrition, which often contributes to obesity and/or diabetes, may result in macrosomia and enhanced cardiometabolic risk in the offspring. Progeny of obese and/or diabetic mothers are relatively more prone to develop obesity, insulin resistance, diabetes, and hypertension. It was demonstrated that they may have permanently enhanced appetites. Their atheromatous lesions are usually more pronounced. It seems that, particularly, a maternal high-fat/junk food diet may be detrimental for vascular health in the offspring. Fetal exposure to excessive levels of saturated fatty and/or n-6 fatty acids, sucrose, fructose and salt, as well as a maternal high glycemic index diet, may also contribute to later enhanced cardiometabolic risk."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I378,I378)","v":24907019},{"$f":"(LEN($J378) - LEN(SUBSTITUTE(LOWER($J378),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J378) - LEN(SUBSTITUTE(LOWER($J378),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J378) - LEN(SUBSTITUTE(LOWER($J378),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B378:D378)","v":0},2014,"Treatment of paediatric APL: how does the therapeutic approach differ from adults?","Kutny",24907019,"Treatment of paediatric APL: how does the therapeutic approach differ from adults?    Abstract:   Acute promyelocytic leukaemia (APL) in children and adolescents shares many features with APL in adults. There are important distinctions, however, between these age groups in the presentation, complications and treatment outcomes. Paediatric patients are more likely to present with high risk features including elevated WBC count or microgranular variant (M3v). Yet the early death rate is lower in paediatric patients compared to adult patients. Overall outcomes such as CR, OS and EFS appear similar in paediatric and adult patients treated on similar regimens except that very young children may have a higher risk of relapse. While contemporary studies have clearly demonstrated improved survival in adults receiving ATO therapy, currently there is more limited data on the role of ATO in paediatric patients. Here we highlight the similarities and important distinctions between paediatric and adult APL while reviewing available data on treatment of paediatric APL."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I379,I379)","v":24845336},{"$f":"(LEN($J379) - LEN(SUBSTITUTE(LOWER($J379),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J379) - LEN(SUBSTITUTE(LOWER($J379),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J379) - LEN(SUBSTITUTE(LOWER($J379),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B379:D379)","v":0},2014,"Potential applications of plant based derivatives as fat replacers, antioxidants and antimicrobials in fresh and processed meat products.","Hygreeva",24845336,"Potential applications of plant based derivatives as fat replacers, antioxidants and antimicrobials in fresh and processed meat products.    Abstract:   Growing concern about diet and health has led to development of healthier food products. In general consumer perception towards the intake of meat and meat products is unhealthy because it may increase the risk of diseases like cardiovascular diseases, obesity and cancer, because of its high fat content (especially saturated fat) and added synthetic antioxidants and antimicrobials. Addition of plant derivatives having antioxidant components including vitamins A, C and E, minerals, polyphenols, flavanoids and terpenoids in meat products may decrease the risk of several degenerative diseases. To change consumer attitudes towards meat consumption, the meat industry is undergoing major transformations by addition of nonmeat ingredients as animal fat replacers, natural antioxidants and antimicrobials, preferably derived from plant sources."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I380,I380)","v":24742849},{"$f":"(LEN($J380) - LEN(SUBSTITUTE(LOWER($J380),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J380) - LEN(SUBSTITUTE(LOWER($J380),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J380) - LEN(SUBSTITUTE(LOWER($J380),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B380:D380)","v":0},2014,"The spectrum of oculocutaneous disease: Part II. Neoplastic and drug-related causes of oculocutaneous disease.","Day",24742849,"The spectrum of oculocutaneous disease: Part II. Neoplastic and drug-related causes of oculocutaneous disease.    Abstract:   There are a multitude of diseases that commonly affect both the skin and the eye. Part II of this 2-part series reviews the oculocutaneous manifestations of neoplasms, both benign and malignant, and adverse drug reactions affecting the skin and the eye. Though rare, a number of neoplasms that primarily involve the skin, such as melanoma and basal cell carcinoma, can metastasize to the eye, leading to permanent damage if not properly treated. In addition, periocular neoplasms can irritate the conjunctiva and lid, reducing a patients ability to see clearly. Neoplastic diseases, such as xeroderma pigmentosum, Sturge-Weber syndrome, and multiple myeloma, can also lead to permanent changes in the eye if not discovered and managed promptly. Furthermore, there are a multitude of drugs, including those commonly used by dermatologists, which can result in permanent damage to the eye. With proper knowledge of the ocular manifestations and treatment recommendations described in this 2-part series, dermatologists with the assistance of their ophthalmology colleagues can help avoid the complications, including permanent blindness, associated with infectious, inflammatory, genetic, neoplastic, and drug-related conditions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I381,I381)","v":24672185},{"$f":"(LEN($J381) - LEN(SUBSTITUTE(LOWER($J381),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J381) - LEN(SUBSTITUTE(LOWER($J381),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J381) - LEN(SUBSTITUTE(LOWER($J381),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B381:D381)","v":0},2013,"The role of oxidative stress in menopause.","Doshi",24672185,"The role of oxidative stress in menopause.    Abstract:   This review will discuss the concept of reproductive aging, which includes the definition of menopause, its symptoms, and predisposing conditions. It will elaborate upon the contributory factors implicated in the pathogenesis of menopause, focusing most prominently on oxidative stress. Specifically, this paper will explain how oxidative stress, in the form of free radicals and antioxidant deficiencies, has been directly linked to the decline of estrogen during reproductive aging. Additionally, this paper will elaborate upon the treatment options aimed at mitigating the menopausal symptoms and hormonal deficiencies that can lead to various disease processes. Treatment options such as hormonal therapy, antioxidant supplementation, and lifestyle modification have been explored for their effectiveness in treating and preventing the symptoms and sequelae of menopause. The majority of information in this review was obtained through PubMed and the National Library of Medicine. While most references in this paper are original research articles, a limited number of references are comprehensive reviews on the topic."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I382,I382)","v":24655404},{"$f":"(LEN($J382) - LEN(SUBSTITUTE(LOWER($J382),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J382) - LEN(SUBSTITUTE(LOWER($J382),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J382) - LEN(SUBSTITUTE(LOWER($J382),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B382:D382)","v":0},2014,"The interaction of malnutrition and neurologic disability in Africa.","Kerac",24655404,"The interaction of malnutrition and neurologic disability in Africa.    Abstract:   Malnutrition and neurodisability are both major public health problems in Africa. This review highlights key areas where they interact. This happens throughout life and starts with maternal malnutrition affecting fetal neurodevelopment with both immediate (eg, folate deficiency causing neural tube defects) and lifelong implications (eg, impaired cognitive function). Maternal malnutrition can also increase the risk of perinatal problems, including birth asphyxia, a major cause of neurologic damage and cerebral palsy. Macronutrient malnutrition can both cause and be caused by neurodisability. Mechanisms include decreased food intake, increased nutrient losses, and increased nutrient requirement. Specific micronutrient deficiencies can also lead to neurodisability, for example, blindness (vitamin A), intractable epilepsy (vitamin B6), and cognitive impairment (iodine and iron). Toxin ingestion (eg, from poorly processed cassava) can cause neurodisability including a peripheral polyneuropathy and a spastic paraparesis. We conclude that there is an urgent need for nutrition and disability programs to work more closely together."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I383,I383)","v":24334113},{"$f":"(LEN($J383) - LEN(SUBSTITUTE(LOWER($J383),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J383) - LEN(SUBSTITUTE(LOWER($J383),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J383) - LEN(SUBSTITUTE(LOWER($J383),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B383:D383)","v":0},2014,"Long-chain polyunsaturated fatty acids (LCPUFA) from genesis to senescence: the influence of LCPUFA on neural development, aging, and neurodegeneration.","Janssen",24334113,"Long-chain polyunsaturated fatty acids (LCPUFA) from genesis to senescence: the influence of LCPUFA on neural development, aging, and neurodegeneration.    Abstract:   Many clinical and animal studies demonstrate the importance of long-chain polyunsaturated fatty acids (LCPUFA) in neural development and neurodegeneration. This review will focus on involvement of LCPUFA from genesis to senescence. The LCPUFA docosahexaenoic acid and arachidonic acid are important components of neuronal membranes, while eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid also affect cardiovascular health and inflammation. In neural development, LCPUFA deficiency can lead to severe disorders like schizophrenia and attention deficit hyperactivity disorder. Perinatal LCPUFA supplementation demonstrated beneficial effects in neural development in humans and rodents resulting in improved cognition and sensorimotor integration. In normal aging, the effect of LCPUFA on prevention of cognitive impairment will be discussed. LCPUFA are important for neuronal membrane integrity and function, and also contribute in prevention of brain hypoperfusion. Cerebral perfusion can be compromised as result of obesity, cerebrovascular disease, hypertension, or diabetes mellitus type 2. Last, we will focus on the role of LCPUFA in most common neurodegenerative diseases like Alzheimers disease and Parkinsons disease. These disorders are characterized by impaired cognition and connectivity and both clinical and animal supplementation studies have shown the potential of LCPUFA to decrease neurodegeneration and inflammation. This review shows that LCPUFA are essential throughout life."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I384,I384)","v":24276888},{"$f":"(LEN($J384) - LEN(SUBSTITUTE(LOWER($J384),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J384) - LEN(SUBSTITUTE(LOWER($J384),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J384) - LEN(SUBSTITUTE(LOWER($J384),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B384:D384)","v":0},2014,"Development of secondary lymphoid organs in relation to lymphatic vasculature.","van de Pavert",24276888,"Development of secondary lymphoid organs in relation to lymphatic vasculature.    Abstract:   Although the initial event in lymphatic endothelial specification occurs slightly before the initiation of lymph node formation in mice, the development of lymphatic vessels and lymph nodes occurs within the same embryonic time frame. Specification of lymphatic endothelial cells starts around embryonic day 10 (E10), followed by endothelial cell budding and formation of the first lymphatic structures. Through lymphatic endothelial cell sprouting these lymph sacs give rise to the lymphatic vasculature which is complete by E15.5 in mice. It is within this time frame that lymph node formation is initiated and the first structure is secured in place. As lymphatic vessels are crucially involved in the functionality of the lymph nodes, the recent insight that both structures depend on common developmental signals for their initiation provides a molecular mechanism for their coordinated formation. Here, we will describe the common developmental signals needed to properly start the formation of lymphatic vessels and lymph nodes and their interdependence in adult life."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I385,I385)","v":24241129},{"$f":"(LEN($J385) - LEN(SUBSTITUTE(LOWER($J385),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J385) - LEN(SUBSTITUTE(LOWER($J385),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J385) - LEN(SUBSTITUTE(LOWER($J385),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B385:D385)","v":0},2014,"Antioxidant supplements and mortality.","Bjelakovic",24241129,"Antioxidant supplements and mortality.    Abstract:    PURPOSE OF REVIEW : Oxidative damage to cells and tissues is considered involved in the aging process and in the development of chronic diseases in humans, including cancer and cardiovascular diseases, the leading causes of death in high-income countries. This has stimulated interest in the preventive potential of antioxidant supplements. Today, more than one half of adults in high-income countries ingest antioxidant supplements hoping to improve their health, oppose unhealthy behaviors, and counteract the ravages of aging.  RECENT FINDINGS : Older observational studies and some randomized clinical trials with high risks of systematic errors (bias) have suggested that antioxidant supplements may improve health and prolong life. A number of randomized clinical trials with adequate methodologies observed neutral or negative results of antioxidant supplements. Recently completed large randomized clinical trials with low risks of bias and systematic reviews of randomized clinical trials taking systematic errors (bias) and risks of random errors (play of chance) into account have shown that antioxidant supplements do not seem to prevent cancer, cardiovascular diseases, or death. Even more, beta-carotene, vitamin A, and vitamin E may increase mortality. Some recent large observational studies now support these findings. According to recent dietary guidelines, there is no evidence to support the use of antioxidant supplements in the primary prevention of chronic diseases or mortality.  SUMMARY : Antioxidant supplements do not possess preventive effects and may be harmful with unwanted consequences to our health, especially in well-nourished populations. The optimal source of antioxidants seems to come from our diet, not from antioxidant supplements in pills or tablets."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I386,I386)","v":23774609},{"$f":"(LEN($J386) - LEN(SUBSTITUTE(LOWER($J386),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J386) - LEN(SUBSTITUTE(LOWER($J386),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J386) - LEN(SUBSTITUTE(LOWER($J386),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B386:D386)","v":0},2013,"Postprandial lipoproteins and the molecular regulation of vascular homeostasis.","Botham",23774609,"Postprandial lipoproteins and the molecular regulation of vascular homeostasis.    Abstract:   Blood levels of triglyceride-rich lipoproteins (TRL) increase postprandially, and a delay in their clearance results in postprandial hyperlipidemia, an important risk factor in atherosclerosis development. Atherosclerosis is a multifactorial inflammatory disease, and its initiation involves endothelial dysfunction, invasion of the artery wall by leukocytes and subsequent formation of foam cells. TRL are implicated in several of these inflammatory processes, including the formation of damaging free radicals, leukocyte activation, endothelial dysfunction and foam cell formation. Recent studies have provided insights into the mechanisms of uptake and the signal transduction pathways mediating the interactions of TRL with leukocytes and vascular cells, and how they are modified by dietary lipids. Multiple receptor and non-receptor mediated pathways function in macrophage uptake of TRL. TRL also induce expression of adhesion molecules, cyclooxygenase-2 and heme-oxygenase-1 in endothelial cells, and activate intracellular signaling pathways involving mitogen-activated protein kinases, NF-κB and Nrf2. Many of these effects are strongly influenced by dietary components carried in TRL. There is extensive evidence indicating that raised postprandial TRL levels are a risk factor for atherosclerosis, but the molecular mechanisms involved are only now becoming appreciated. Here, we review current understanding of the mechanisms by which TRL influence vascular cell function."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I387,I387)","v":23638933},{"$f":"(LEN($J387) - LEN(SUBSTITUTE(LOWER($J387),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J387) - LEN(SUBSTITUTE(LOWER($J387),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J387) - LEN(SUBSTITUTE(LOWER($J387),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B387:D387)","v":0},2013,"Hass avocado composition and potential health effects.","Dreher",23638933,"Hass avocado composition and potential health effects.    Abstract:   Hass avocados, the most common commercial avocado cultivars in the world, contain a variety of essential nutrients and important phytochemicals. Although the official avocado serving is one-fifth of a fruit (30 g), according to NHANES analysis the average consumption is one-half an avocado (68 g), which provides a nutrient and phytochemical dense food consisting of the following: dietary fiber (4.6 g), total sugar (0.2 g), potassium (345 mg), sodium (5.5 mg), magnesium (19.5 mg), vitamin A (43 μg), vitamin C (6.0 mg), vitamin E (1.3 mg), vitamin K1 (14 μg), folate (60 mg), vitamin B-6 (0.2 mg), niacin (1.3 mg), pantothenic acid (1.0 mg), riboflavin (0.1 mg), choline (10 mg), lutein/zeaxanthin (185 μg), phytosterols (57 mg), and high-monounsaturated fatty acids (6.7 g) and 114 kcals or 1.7 kcal/g. The avocado oil consists of 71% monounsaturated fatty acids (MUFA), 13% polyunsaturated fatty acids (PUFA), and 16% saturated fatty acids (SFA), which helps to promote healthy blood lipid profiles and enhance the bioavailability of fat soluble vitamins and phytochemicals from the avocado or other fruits and vegetables, naturally low in fat, which are consumed with avocados. There are eight preliminary clinical studies showing that avocado consumption helps support cardiovascular health. Exploratory studies suggest that avocados may support weight management and healthy aging."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I388,I388)","v":23292551},{"$f":"(LEN($J388) - LEN(SUBSTITUTE(LOWER($J388),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J388) - LEN(SUBSTITUTE(LOWER($J388),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J388) - LEN(SUBSTITUTE(LOWER($J388),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B388:D388)","v":0},2013,"Hepatic stellate cells--the pericytes in the liver.","Hellerbrand",23292551,"Hepatic stellate cells--the pericytes in the liver.    Abstract:   Hepatic stellate cells (HSCs) are pericytes of liver in the space between parenchymal cells and sinusoidal endothelial cells of the hepatic lobule. HSCs comprise specialized functions such as vitamin A storage, hemodynamic functions, support of liver regeneration, and immunoregulation. In pathological conditions, HSCs transform to an activated myofibroblasts-like phenotype, start to proliferate, and de novo express several proinflammatory and profibrogenic genes. These processes are particularly important in the development of cirrhosis, portal hypertension, and hepatocellular cancer. This review highlights recent findings in understanding the biology of HSCs and discusses the physiological functions of HSCs and the role of activated HSCs in pathophysiology and disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I389,I389)","v":23246696},{"$f":"(LEN($J389) - LEN(SUBSTITUTE(LOWER($J389),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J389) - LEN(SUBSTITUTE(LOWER($J389),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J389) - LEN(SUBSTITUTE(LOWER($J389),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B389:D389)","v":0},2013,"Regulation of the MIR155 host gene in physiological and pathological processes.","Elton",23246696,"Regulation of the MIR155 host gene in physiological and pathological processes.    Abstract:   MicroRNAs (miRNAs), a family of small nonprotein-coding RNAs, play a critical role in posttranscriptional gene regulation by acting as adaptors for the miRNA-induced silencing complex to inhibit gene expression by targeting mRNAs for translational repression and/or cleavage. miR-155-5p and miR-155-3p are processed from the B-cell Integration Cluster (BIC) gene (now designated, MIR155 host gene or MIR155HG). MiR-155-5p is highly expressed in both activated B- and T-cells and in monocytes/macrophages. MiR-155-5p is one of the best characterized miRNAs and recent data indicate that miR-155-5p plays a critical role in various physiological and pathological processes such as hematopoietic lineage differentiation, immunity, inflammation, viral infections, cancer, cardiovascular disease, and Down syndrome. In this review we summarize the mechanisms by which MIR155HG expression can be regulated. Given that the pathologies mediated by miR-155-5p result from the over-expression of this miRNA it may be possible to therapeutically attenuate miR-155-5p levels in the treatment of several pathological processes."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I390,I390)","v":23114975},{"$f":"(LEN($J390) - LEN(SUBSTITUTE(LOWER($J390),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J390) - LEN(SUBSTITUTE(LOWER($J390),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J390) - LEN(SUBSTITUTE(LOWER($J390),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B390:D390)","v":0},2012,"Etiological and pathogenic factors in congenital diaphragmatic hernia.","Sluiter",23114975,"Etiological and pathogenic factors in congenital diaphragmatic hernia.    Abstract:   Congenital diaphragmatic hernia (CDH) is a congenital anomaly associated with an increased mortality and morbidity. In this article, we review the currently known etiological and pathogenic factors in CDH."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I391,I391)","v":23085014},{"$f":"(LEN($J391) - LEN(SUBSTITUTE(LOWER($J391),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J391) - LEN(SUBSTITUTE(LOWER($J391),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J391) - LEN(SUBSTITUTE(LOWER($J391),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B391:D391)","v":0},2013,"Vitamin D: health panacea or false prophet?","Glade",23085014,"Vitamin D: health panacea or false prophet?    Abstract:   Vitamin D deficiency, diagnosed when the serum 25-hydroxyvitamin D (25-OHD(3)) concentration is less than 20 ng/mL, has joined vitamin A deficiency as two of the most common nutrition-responsive medical conditions worldwide. There have been more scientific articles published about vitamin D in the 21st century than about any other vitamin, reflecting the massive expansion of the field of vitamin D research. Adequate vitamin D status has been linked to decreased risks of developing specific cancers, including cancers of the esophagus, stomach, colon, rectum, gallbladder, pancreas, lung, breast, uterus, ovary, prostate, urinary bladder, kidney, skin, thyroid, and hematopoietic system (e.g., Hodgkins lymphoma, non-Hodgkins lymphoma, multiple myeloma); bacterial infections; rheumatoid arthritis; Crohns disease; periodontal disease; multiple sclerosis; asthma; type 2 diabetes; cardiovascular disease; stroke; peripheral artery disease; hypertension; chronic kidney disease; muscle weakness; cognitive impairment; Alzheimers disease; clinical depression; and premature death. On the other hand, inadequate vitamin D status during human pregnancy may be associated with increased risk for the development of type 1 diabetes in the offspring. However, this point of view may be excessively optimistic. There also is evidence that despite the current heavy reliance on serum 25-OHD(3) concentration for the diagnosis of an individuals vitamin D status, local tissue vitamin D intoxication may be present in individuals with much lower serum 25-OHD(3) concentrations than are currently appreciated. Only rarely are the symptoms of local tissue vitamin D intoxication associated with vitamin D status or intake. An individuals serum 25-OHD(3) concentration may appear to be quot;lowquot; for reasons totally independent of sunlight exposure or vitamin D intake. Serum 25-OHD(3) concentration is only poorly responsive to increases in vitamin D intake, and the prolonged routine consumption of thousands of international units of vitamin D may interfere with the regulation of phosphate homeostasis by fibroblast growth factor-23 (FGF23) and the Klotho gene product, with consequences that are detrimental to human health. In light of these counterbalancing observations, curbing excessive enthusiasm for universally increasing vitamin D intake recommendations may be in order."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I392,I392)","v":23000736},{"$f":"(LEN($J392) - LEN(SUBSTITUTE(LOWER($J392),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J392) - LEN(SUBSTITUTE(LOWER($J392),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J392) - LEN(SUBSTITUTE(LOWER($J392),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B392:D392)","v":0},2012,"Understanding velocardiofacial syndrome: how recent discoveries can help you improve your patient outcomes.","Chinnadurai",23000736,"Understanding velocardiofacial syndrome: how recent discoveries can help you improve your patient outcomes.    Abstract:    PURPOSE OF REVIEW : Improved recognition of velocardiofacial syndrome (VCFS) has led to increasing awareness of VCFS by otolaryngologists. Understanding the developmental biologic processes affected in VCFS patients will help improve treatment and outcomes. Advanced application of molecular labeling techniques has better outlined the role of T-Box transcription factor 1 (TBX1) as the primary genetic anomaly leading to VCFS. TBX1 plays multiple roles during branchial, cardiac, and craniofacial development and increased understanding of how these systems are affected by TBX1 mutations will improve patient outcomes. Furthermore, additional modifiers of TBX1 expression have been identified that may explain the variability of VCFS phenotypes. The phenotypic spectrum of VCFS may include cardiac anomalies, velopharyngeal insufficiency, aberrant calcium metabolism, and immune dysfunction. Recent interest has focused on the cognitive and neuropsychiatric manifestations of VCFS. Improved understanding of the biology of VCFS associated mutations has the potential to improve therapeutic outcomes.  RECENT FINDINGS : This article will discuss recent developmental biologic understanding of the role of TBX1 and genetic modifiers generating the phenotypic variability seen in VCFS patients. Special attention is given to advances in the realms of immunodeficiency, hypocalcemia, cardiac and arterial patterning anomalies, velopharyngeal insufficiency, as well as cognitive and psychiatric problems.  SUMMARY : Enhanced understanding of the multiple systems affected by TBX1 mutations will result in improved patient outcomes and improved family education. Future research will lead to improved detection of potential targets for gene therapy and change the way physicians counsel families and treat patients."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I393,I393)","v":24279770},{"$f":"(LEN($J393) - LEN(SUBSTITUTE(LOWER($J393),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J393) - LEN(SUBSTITUTE(LOWER($J393),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J393) - LEN(SUBSTITUTE(LOWER($J393),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B393:D393)","v":0},2012,"The potential of rice to offer solutions for malnutrition and chronic diseases.","Dipti",24279770,"The potential of rice to offer solutions for malnutrition and chronic diseases.    Abstract:   It is internationally accepted that malnutrition and chronic diseases in developing countries are key limitations to achieving the Millennium Development Goals. In many developing countries, rice is the primary source of nutrition. In those countries, the major forms of malnutrition are Fe-induced anaemia, Zn deficiency and Vitamin A deficiency, whereas the major chronic disease challenges are Type II diabetes, cardiovascular disease and some cancers. There is a growing corpus of evidence regarding both limitations and opportunities as to how rice could be an effective vehicle by which to tackle key nutrition and health related problems in countries with limited resources. Rice breeding programs are able to focus on developing new varieties carrying enhanced amounts of either Fe, Zn or beta-carotene because of large public investment, and the intuitive link between providing a mineral/vitamin to cure a deficiency in that mineral/vitamin. By contrast, there has been little investment in progressing the development of particular varieties for potential impact on chronic diseases. In this review article we focus on the broad battery of evidence linking rice-related nutritional limitations to their impact on a variety of human health issues. We discuss how rice might offer sometimes even simple solutions to rectifying key problems through targeted biofortification strategies and finally, we draw attention to how recent technological (-omics) developments may facilitate untold new opportunities for more rapidly generating improved rice varieties specifically designed to meet the current and future nutritional needs of a rapidly expanding global population."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I394,I394)","v":22105725},{"$f":"(LEN($J394) - LEN(SUBSTITUTE(LOWER($J394),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J394) - LEN(SUBSTITUTE(LOWER($J394),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J394) - LEN(SUBSTITUTE(LOWER($J394),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B394:D394)","v":0},2011,"Nutritional aspects of Helicobacter pylori infection.","Vitale",22105725,"Nutritional aspects of Helicobacter pylori infection.    Abstract:   H. pylori is a gram-negative pathogen, etiologically associated with atrophic and non-atrophic gastritis, peptic ulcer, primary gastric B-cell lymphoma and gastric carcinoma. Several observations demonstrated a correlation between H. pylori and malabsorption of essential nutrients; epidemiological studies have shown an association between H. pylori infection and iron deficiency anemia, while the absorption of some vitamins such as vitamin B12, vitamin A, vitamin C, folic acid and Vitamin E may be affected by the infection. The main mechanism related to malabsorption of this components is the modified intragastric pH (hypo- achlorhydria) due to H. pylori infection. Moreover H. pylori is also able to determine a modification of gastrointestinal hormones by reducing plasma levels of ghrelin and increasing those of leptin and gastrin, thus affecting appetite and promoting the occurrence of dyspeptic symptoms. On the other hand, H. pylori eradication has been shown to improve serum level of iron and vitamin B12, has some effects on Vitamin A and Vitamin E absorption and has a late effects on ghrelin levels. As a consequence of those effects, H. pylori is also associated with childhood malnutrition in developing countries either for the occurrence of malabsorption or for an increased susceptibility to enteric infections caused by hypochlorhydria."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I395,I395)","v":22054961},{"$f":"(LEN($J395) - LEN(SUBSTITUTE(LOWER($J395),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J395) - LEN(SUBSTITUTE(LOWER($J395),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J395) - LEN(SUBSTITUTE(LOWER($J395),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B395:D395)","v":0},2011,"Seaweed vitamins as nutraceuticals.","Škrovánková",22054961,"Seaweed vitamins as nutraceuticals.    Abstract:   Seaweeds are a good source of some water- (B(1), B(2), B(12), C) and fat-soluble (β-carotene with vitamin A activity, vitamin E) vitamins. To ensure that the adequate intake of all vitamins is received in the diet, people (especially people on special diet, strict vegetarians, and vegans) can consume foods enriched with vitamins, for example, in the form of functional foods with vitamins as nutraceuticals, extracted from natural sources such as seaweeds. Seaweed vitamins are important not only due to their biochemical functions and antioxidant activity but also due to other health benefits such as decreasing of blood pressure (vitamin C), prevention of cardiovascular diseases (β-carotene), or reducing the risk of cancer (vitamins E and C, carotenoids)."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I396,I396)","v":21830468},{"$f":"(LEN($J396) - LEN(SUBSTITUTE(LOWER($J396),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J396) - LEN(SUBSTITUTE(LOWER($J396),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J396) - LEN(SUBSTITUTE(LOWER($J396),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B396:D396)","v":0},2010,"Local therapy as basic anti-aging prevention.","Delalle-Lozica",21830468,"Local therapy as basic anti-aging prevention.    Abstract:   Skin, the largest organ of the body, is the organ in which changes associated with aging are most visible. Intrinsic (chronologic) skin aging is characterized by atrophy of the skin with loss of elasticity and slowed metabolic activity. With superposition of environmental damage, particularly exposure to ultraviolet radiation (photodamage) on the intrinsic aging, the process results, at least initially, in hypertrophic repair response with thickened epidermis and increased melanogenesis. Even more striking changes occur in the dermis, i.e., massive elastosis (deposition of abnormal elastic fibers), collagen degeneration, and twisted, dilated microvasculature. Regular use of a sunscreen alone appears to allow for some repair as well as protection from further photodamage. Local anti-aging therapy has been shown to partially reverse the clinical and histologic changes induced by the combination of sunlight exposure and chronologic aging. Histologic changes in the epidermis and dermis noted after 12 months suggest repair of photodamage by reconstitution of rete pegs, repair of keratinocyte ultrastructural damage, more even distribution of melanocytes and melanin pigment, deposition of new papillary dermal collagen, and improvements in vasculature. Hyperkeratinization is normalized, while epidermal thickness and dermal glycosaminoglycan content are increased. Briefly, many of the unwanted changes can be improved by topical therapy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I397,I397)","v":21324803},{"$f":"(LEN($J397) - LEN(SUBSTITUTE(LOWER($J397),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J397) - LEN(SUBSTITUTE(LOWER($J397),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J397) - LEN(SUBSTITUTE(LOWER($J397),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B397:D397)","v":0},2011,"[Cod liver oil. A natural Vitamin D for preserving health].","Fehér",21324803,"[Cod liver oil. A natural Vitamin D for preserving health].    Abstract:   Vitamin D deficiency is pandemic in industrialized countries due to life-style changes. Recent studies suggest that besides bone-metabolism, vitamin D plays a central role in basic cell function like multiplication, differentiation and metabolism. This may explain that low vitamin D levels represent a risk factor for several apparently different diseases such as infective, autoimmune, neurodegenerative and cardiovascular diseases, as well as diabetes, osteoporosis and cancer. Accumulating evidences suggest that an adequate intake of vitamin D may significantly decrease prevalence and clinical outcome of these diseases. Estimated reduction of the economic burden might reach about 10 percent through normalizing vitamin D levels for these diseases. However, high doses of vitamin D monotherapy needs precaution for potential adverse effects and it should be substituted with the recommended doses of vitamin D in combination with synergistic vitamin A and omega 3 fatty acids, such as cod liver oil."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I398,I398)","v":21291369},{"$f":"(LEN($J398) - LEN(SUBSTITUTE(LOWER($J398),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J398) - LEN(SUBSTITUTE(LOWER($J398),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J398) - LEN(SUBSTITUTE(LOWER($J398),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B398:D398)","v":0},2011,"Lycopene and cardiovascular diseases: an update.","Mordente",21291369,"Lycopene and cardiovascular diseases: an update.    Abstract:   Cardiovascular disease (CVD) is the leading cause of death in Western societies and accounts for up to a third of all deaths worldwide. In comparison to the Northern European or other Western countries, the Mediterranean area has lower rates of mortality from cardiovascular diseases and cancer, and this is attributed, at least in part, to the so-called Mediterranean diet, which is rich in plantderived bioactive phytochemicals. Identification of the active constituents of the Mediterranean diet is therefore crucial to the formulation of appropriate dietary guidelines. Lycopene is a natural carotenoid found in tomato, an essential component of the Mediterranean diet, which, although belonging to the carotenoid family, does not have pro-vitamin A activity but many other biochemical functions as an antioxidant scavenger, hypolipaemic agent, inhibitor of pro-inflammatory and pro-thrombotic factors, thus potentially of benefit in CVD. In particular, the review intends to conduct a systematic analysis of the literature (epidemiological studies and interventional trials) in order to critically evaluate the association between lycopene (or tomato products) supplementation and cardiovascular diseases and/or cardiovascular disease risk factors progression, and to prepare provision of evidence-based guidelines for patients and clinicians. Several reports have appeared in support of the role of lycopene in the prevention of CVD, mostly based on epidemiological studies showing a dose-response relationship between lycopene and CVD. A less clear and more complex picture emerges from the interventional trials, where several works have reported conflicting results. Although many aspects of lycopene in vivo metabolism, functions and clinical indications remain to be clarified, supplementation of low doses of lycopene has been already suggested as a preventive measure for contrasting and ameliorating many aspects of CVD."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I399,I399)","v":21108073},{"$f":"(LEN($J399) - LEN(SUBSTITUTE(LOWER($J399),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J399) - LEN(SUBSTITUTE(LOWER($J399),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J399) - LEN(SUBSTITUTE(LOWER($J399),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B399:D399)","v":0},2010,"Dietary lipophilic antioxidants: implications and significance in the aging process.","Chong-Han",21108073,"Dietary lipophilic antioxidants: implications and significance in the aging process.    Abstract:   Longevity can be explained by the free radical theory of aging, and caloric restriction (CR) studies showed that CR-induced lifespan extension is associated with the prevention of a decrease in oxidative stress. Non-enzymatic lipophilic antioxidants may play a pivotal role in our aging process, and are reflected in our dietary lifestyle and dietary supplementation. Their significance lies in their general good absorption and slow excretion within our body. Although difficulties exist with human aging studies due to the nature of our longevity in comparison with other species, findings have implied a relationship between non-enzymatic antioxidants and longevity. Common non-enzymatic antioxidants found in our dietary intake include vitamin A and E supplementation, flavanoids (major source includes tea, one of our main fluid intake), resveratrol (its protective role in cardiovascular disease and aging having stemmed from the quot;French Paradoxquot;), as well as coenzyme Q₁₀ supplementation. The review discusses current findings and their implication in the aging process. This review concludes by asserting that although none of these antioxidants has yet provided clear-cut evidence toward longevity and the aging process, they have certainly demonstrated other potential health benefits."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I400,I400)","v":20580500},{"$f":"(LEN($J400) - LEN(SUBSTITUTE(LOWER($J400),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J400) - LEN(SUBSTITUTE(LOWER($J400),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J400) - LEN(SUBSTITUTE(LOWER($J400),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B400:D400)","v":0},2010,"A review of select vitamins and minerals used by postmenopausal women.","Dennehy",20580500,"A review of select vitamins and minerals used by postmenopausal women.    Abstract:    OBJECTIVES : The purpose of this review is to summarize the effectiveness of select vitamins, minerals and trace elements in postmenopausal women for their effects on bone health, cardiovascular health, breast cancer, cognition and vasomotor symptoms.  METHODS : Review of the relevant literature and results from recent clinical studies, as well as critical analyses of published systematic reviews and meta-analyses were obtained from PubMed and Cochrane Library of Reviews. Vitamin A, the B vitamins, vitamin C, calcium, vitamin D, vitamin E, vitamin K, magnesium, selenium and zinc were selected for review. In circumstances where the vitamin, mineral or trace element has not been studied for a given condition, no information was provided.  RESULTS AND DISCUSSION : All vitamins, minerals and trace elements play an important role in maintaining health and wellbeing among menopausal women. Adequate dietary intake is essential and supplementation should be considered in women with documented malabsorption syndromes or deficiencies. Based on a review of the literature, supplementation with vitamin C, D, K and calcium can also be recommended for proper maintenance of bone health. The only supplement studied for vasomotor symptoms was vitamin E and this vitamin lacked clinical support. Supplementation in healthy postmenopausal women with vitamins and minerals in diet or pill forms cannot be recommended currently for any other indications."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I401,I401)","v":20508199},{"$f":"(LEN($J401) - LEN(SUBSTITUTE(LOWER($J401),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J401) - LEN(SUBSTITUTE(LOWER($J401),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J401) - LEN(SUBSTITUTE(LOWER($J401),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B401:D401)","v":0},2010,"Introduction to the nuclear receptor review series.","Kelly",20508199,"Introduction to the nuclear receptor review series.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I402,I402)","v":20465659},{"$f":"(LEN($J402) - LEN(SUBSTITUTE(LOWER($J402),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J402) - LEN(SUBSTITUTE(LOWER($J402),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J402) - LEN(SUBSTITUTE(LOWER($J402),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B402:D402)","v":0},2010,"Cutaneous vascular patterns in psoriasis.","Micali",20465659,"Cutaneous vascular patterns in psoriasis.    Abstract:   Microvascular abnormalities are a characteristic feature of psoriasis and play a crucial role in its pathogenesis. Investigational studies have shown that activated keratinocytes in lesional skin undergo an accelerated epidermal cell turnover and are a major source of pro-angiogenic cytokines, like as VEGF, ESAF, PDECGE/TP, TNF-alpha, TGF-alpha and PDGF, suggesting that the epidermis is capable of inducing vascular proliferation. On the other hand, microvascular alterations are essential for the development and persistence of the psoriatic lesions as they provide cellular and tissue nutrition to hyperplastic keratinocytes and promote inflammatory cell migration. Also, dilated and slightly tortuous blood vessels within dermal papillae represent one of the earliest detectable histological changes for all stages of lesional development. Videodermatoscopy is a new non invasive imaging technique able to identify modifications of microvascular architecture in vivo and such evaluation will be useful for the dermatologist both for diagnostic and prognostic evaluation, as well as for post-therapeutic follow-up. In this review, the role of microvascular abnormalities in the pathogenesis of psoriasis as well as the mechanisms underlying vascular changes and their primary therapeutic implications will be reviewed and discussed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I403,I403)","v":20412095},{"$f":"(LEN($J403) - LEN(SUBSTITUTE(LOWER($J403),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J403) - LEN(SUBSTITUTE(LOWER($J403),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J403) - LEN(SUBSTITUTE(LOWER($J403),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B403:D403)","v":0},2011,"Antioxidants in the chemoprevention of colorectal cancer and colorectal adenomas in the general population: a systematic review and meta-analysis.","Papaioannou",20412095,"Antioxidants in the chemoprevention of colorectal cancer and colorectal adenomas in the general population: a systematic review and meta-analysis.    Abstract:    AIM : Antioxidants, such as vitamin A, C and E, selenium and β-carotene, have been proposed as possible agents in the chemoprevention of colorectal cancer and have been the subject of recent trials and reviews. This review aimed to assess the present evidence on the effect of antioxidants on the incidence of colorectal neoplasms in the general population.  METHOD : A systematic review of randomized controlled trials was undertaken comparing antioxidants alone or in combination with other agents vs placebo. The following databases were searched for published and unpublished literature: Cochrane Library, MEDLINE, PreMEDLINE, CINAHL, EMBASE, Web of Science, and Biological Abstracts and Research Registers. Studies were quality appraised and extracted. Meta-analysis was performed.  RESULTS : Twelve studies were identified as relevant. In the nine comparing antioxidants with no antioxidants (n=148 922), there was no difference in the incidence of colorectal cancer [relative risk (RR) 1.00, 95% confidence interval (CI) 0.88-1.13]. One study assessed the effect of antioxidants on adenoma formation (n=15 538) and did not demonstrate a statistically significant effect (RR 1.47, 95% CI 0.97-2.23). Of 14 discrete analyses for different combinations of antioxidants, only one reported a statistically significant increase in relative risk of adenoma formation in participants receiving vitamin E (RR 1.74, 95% CI 1.09-1.79, P=0.02) or vitamin E plus β-carotene (RR 1.63, 95% CI 1.01-2.63, P=0.04). Effectiveness did not seem to differ between healthy populations, participants with cardiovascular risk factors or populations exposed to smoking or asbestos.  CONCLUSION : The review demonstrates that antioxidants (vitamin A, C and E, selenium and β-carotene), as single agents, in combination with other antioxidants or in combination with other agents, are not effective in the chemoprevention of colorectal neoplasia in the general population. This questions their involvement in future randomized controlled trials of chemoprevention in colorectal cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I404,I404)","v":20207525},{"$f":"(LEN($J404) - LEN(SUBSTITUTE(LOWER($J404),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J404) - LEN(SUBSTITUTE(LOWER($J404),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J404) - LEN(SUBSTITUTE(LOWER($J404),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B404:D404)","v":0},2010,"Fatty acids and signalling in endothelial cells.","Ringseis",20207525,"Fatty acids and signalling in endothelial cells.    Abstract:   The endothelium is critical for the maintenance of a proper vessel function. Disturbances of endothelial function, called endothelial dysfunction, have serious implications, and lead to the development of atherosclerosis. It is well established that the risk for atherosclerosis development is influenced by nutritional factors such as the intake of certain fatty acids. Due to the fundamental role of the endothelium for atherosclerosis development, it is, therefore, likely that fatty acids directly influence the function of endothelial cells. The present review aims to explain the divergent effects of different types of fatty acids on cardiovascular disease risk by summarizing in vitro-data on the effects of fatty acids on (1) important signalling pathways involved in the modulation of endothelial cell function, and (2) endothelial cell functional properties, namely vasoactive mediator release and mononuclear cell recruitment, both of which are typically dysregulated during endothelial dysfunction."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I405,I405)","v":20095133},{"$f":"(LEN($J405) - LEN(SUBSTITUTE(LOWER($J405),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J405) - LEN(SUBSTITUTE(LOWER($J405),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J405) - LEN(SUBSTITUTE(LOWER($J405),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B405:D405)","v":0},2009,"Red palm oil: nutritional, physiological and therapeutic roles in improving human wellbeing and quality of life.","Oguntibeju",20095133,"Red palm oil: nutritional, physiological and therapeutic roles in improving human wellbeing and quality of life.    Abstract:   The link between dietary fats and cardiovascular disease has created a growing interest in dietary red palm oil research. Also, the link between nutrition and health, oxidative stress and the severity or progression of disease has stimulated further interest in the potential role of red palm oil (a natural antioxidant product) to improve oxidative status by reducing oxidative stress in patients with cardiovascular disease, cancer and other chronic diseases. In spite of its level of saturated fatty acid content (50%), red palm oil has not been found to promote atherosclerosis and/or arterial thrombosis. This is probably due to the ratio of its saturated fatty acid to unsaturated fatty acid content and its high concentration of antioxidants such as beta-carotene, tocotrienols, tocopherols and vitamin E. It has also been reported that the consumption of red palm oil reduces the level of endogenous cholesterol, and this seems to be due to the presence of the tocotrienols and the peculiar isomeric position of its fatty acids. The benefits of red palm oil to health include a reduction in the risk of arterial thrombosis and/or atherosclerosis, inhibition of endogenous cholesterol biosynthesis, platelet aggregation, a reduction in oxidative stress and a reduction in blood pressure. It has also been shown that dietary red palm oil, taken in moderation in animals and humans, promotes the efficient utilisation of nutrients, activates hepatic drug metabolising enzymes, facilitates the haemoglobinisation of red blood cells and improves immune function. This review provides a comprehensive overview of the nutritional, physiological and biochemical roles of red palm oil in improving wellbeing and quality of life."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I406,I406)","v":19962259},{"$f":"(LEN($J406) - LEN(SUBSTITUTE(LOWER($J406),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J406) - LEN(SUBSTITUTE(LOWER($J406),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J406) - LEN(SUBSTITUTE(LOWER($J406),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B406:D406)","v":0},2010,"[Acute lower limb ischemia revealing acute leukemia. Case report and review of the literature].","Azghari",19962259,"[Acute lower limb ischemia revealing acute leukemia. Case report and review of the literature].    Abstract:   Large vessel thrombosis is a very rare clinical presentation of acute leukemia which is usually revealed by hemorrhagic complications or thrombosis of small vessels. We present here the case of a patient with previously undiagnosed acute myeloid leukemia who was referred to our hospital with symptoms of acute ischemia of the left lower limb. Occlusion of the left popliteal artery due to a leucostasis was noted and successfully treated with emergency surgical thromboembolectomy and chemotherapy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I407,I407)","v":19803427},{"$f":"(LEN($J407) - LEN(SUBSTITUTE(LOWER($J407),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J407) - LEN(SUBSTITUTE(LOWER($J407),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J407) - LEN(SUBSTITUTE(LOWER($J407),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B407:D407)","v":0},2009,"[The research progress of ATP binding cassette transporter G1].","Liu",19803427,"[The research progress of ATP binding cassette transporter G1].    Abstract:   ATP binding cassette transporter G1 (ABCG1) is a membrane half-transporter which is the member of ATP-binding cassette (ABC) transporter super-family, it has an important role of regulating the cholesterol and phospholipids effluence. ABCG1 and ABCA1 synergize to mediate cholesterol effluence to HDL (high density lipoprotein). The expression of ABCG1 is mainly regulated by the liver X receptor/the lactochrome receptor system (LXR/RXR). Although the ABCG1 plays an important role in balancing the lipids, its role in cardiovascular disease (CVD) in the animal studies is still controversial. The issue focuses the ABCG1 on the structure, the function, the regulation and the contribution to CVD."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I408,I408)","v":19768246},{"$f":"(LEN($J408) - LEN(SUBSTITUTE(LOWER($J408),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J408) - LEN(SUBSTITUTE(LOWER($J408),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J408) - LEN(SUBSTITUTE(LOWER($J408),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B408:D408)","v":0},2009,"[Vitamins and minerals with antioxidant properties and cardiometabolic risk: controversies and perspectives].","Catania",19768246,"[Vitamins and minerals with antioxidant properties and cardiometabolic risk: controversies and perspectives].    Abstract:   Oxygen reactive species (ROS) are generated during cellular processes. In excess, they may cause damages to the cell. Oxidative stress is an imbalance in the redox state that favors oxidation. Endogenous enzymes and some vitamins and minerals participate in the plasma antioxidant defense. Vitamin E is found in the plasma and in the LDL particle, avoiding lipid peroxidation. Observational studies reported an inverse association between vitamin E consumption and cardiometabolic (CM) risk. However, clinical trials were not able to prove the efficacy of its supplementation on CM endpoints. Vitamin C participates in the vitamin E regeneration system, keeping the plasmas antioxidant potential. Data about beneficial effects of its supplementation in CM risk reduction are inconclusive. The antioxidant activity of carotenoids is partially responsible for its protective role against cardiovascular diseases and cancer. Supplementation of this nutrient did not provide consistent findings in terms of CM risk reduction. Recently, zinc and seleniums participation in the antioxidant defense has been studied, yet its supplementation in individuals with normal levels and adequate ingestion of these nutrients does not seem necessary. In summary, the role of these micronutrients for CM risk is still very controversial. Epidemiological studies suggest that diets rich in antioxidants, or simply in fruit and vegetables intake, can reduce CM risk. Further studies are needed before recommending antioxidant supplements for this purpose."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I409,I409)","v":19158321},{"$f":"(LEN($J409) - LEN(SUBSTITUTE(LOWER($J409),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J409) - LEN(SUBSTITUTE(LOWER($J409),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J409) - LEN(SUBSTITUTE(LOWER($J409),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B409:D409)","v":0},2009,"Intestinal lipid absorption.","Iqbal",19158321,"Intestinal lipid absorption.    Abstract:   Our knowledge of the uptake and transport of dietary fat and fat-soluble vitamins has advanced considerably. Researchers have identified several new mechanisms by which lipids are taken up by enterocytes and packaged as chylomicrons for export into the lymphatic system or clarified the actions of mechanisms previously known to participate in these processes. Fatty acids are taken up by enterocytes involving protein-mediated as well as protein-independent processes. Net cholesterol uptake depends on the competing activities of NPC1L1, ABCG5, and ABCG8 present in the apical membrane. We have considerably more detailed information about the uptake of products of lipid hydrolysis, the active transport systems by which they reach the endoplasmic reticulum, the mechanisms by which they are resynthesized into neutral lipids and utilized within the endoplasmic reticulum to form lipoproteins, and the mechanisms by which lipoproteins are secreted from the basolateral side of the enterocyte. apoB and MTP are known to be central to the efficient assembly and secretion of lipoproteins. In recent studies, investigators found that cholesterol, phospholipids, and vitamin E can also be secreted from enterocytes as components of high-density apoB-free/apoAI-containing lipoproteins. Several of these advances will probably be investigated further for their potential as targets for the development of drugs that can suppress cholesterol absorption, thereby reducing the risk of hypercholesterolemia and cardiovascular disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I410,I410)","v":19075805},{"$f":"(LEN($J410) - LEN(SUBSTITUTE(LOWER($J410),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J410) - LEN(SUBSTITUTE(LOWER($J410),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J410) - LEN(SUBSTITUTE(LOWER($J410),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B410:D410)","v":0},2008,"Tricyclic structures in medicinal chemistry: an overview of their recent uses in non-CNS pathologies.","Fedi",19075805,"Tricyclic structures in medicinal chemistry: an overview of their recent uses in non-CNS pathologies.    Abstract:   Tricyclic compounds are sometimes considered as synonima of drugs healing central nervous system pathologies, although there are some well known examples of tricyclic derivatives marketed for different indications, such as antihistamines, antivirals and antiulceratives. Following the insertion of tricyclic structures in the quot;privileged structuresquot; pool, several compounds bearing a central 7-membered ring and two aryl rings at its sides have been reported, and some of them have been progressed to advanced clinical trials. An overview of tricyclic derivatives reported in the literature since 1995, that are investigated for indications not directly related to central nervous system affections, shows the potential of these structures in a broad range of therapeutical indications, going from antiviral and anticancer compounds to the therapy of cardiovascular diseases. Very recent examples confirm the usefulness of tricyclic structures for the modern medicinal chemists."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I411,I411)","v":19032739},{"$f":"(LEN($J411) - LEN(SUBSTITUTE(LOWER($J411),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J411) - LEN(SUBSTITUTE(LOWER($J411),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J411) - LEN(SUBSTITUTE(LOWER($J411),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B411:D411)","v":0},2008,"Nevoid basal cell carcinoma syndrome (Gorlin syndrome).","Lo Muzio",19032739,"Nevoid basal cell carcinoma syndrome (Gorlin syndrome).    Abstract:   Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1. Main clinical manifestations include multiple basal cell carcinomas (BCCs), odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic calcifications, and facial dysmorphism (macrocephaly, cleft lip/palate and severe eye anomalies). Intellectual deficit is present in up to 5% of cases. BCCs (varying clinically from flesh-colored papules to ulcerating plaques and in diameter from 1 to 10 mm) are most commonly located on the face, back and chest. The number of BBCs varies from a few to several thousand. Recurrent jaw cysts occur in 90% of patients. Skeletal abnormalities (affecting the shape of the ribs, vertebral column bones, and the skull) are frequent. Ocular, genitourinary and cardiovascular disorders may occur. About 5-10% of NBCCS patients develop the brain malignancy medulloblastoma, which may be a potential cause of early death. NBCCS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. Clinical diagnosis relies on specific criteria. Gene mutation analysis confirms the diagnosis. Genetic counseling is mandatory. Antenatal diagnosis is feasible by means of ultrasound scans and analysis of DNA extracted from fetal cells (obtained by amniocentesis or chorionic villus sampling). Main differential diagnoses include Bazex syndrome, trichoepithelioma papulosum multiplex and Torres syndrome (Muir-Torres syndrome). Management requires a multidisciplinary approach. Keratocysts are treated by surgical removal. Surgery for BBCs is indicated when the number of lesions is limited; other treatments include laser ablation, photodynamic therapy and topical chemotherapy. Radiotherapy should be avoided. Vitamin A analogs may play a preventive role against development of new BCCs. Life expectancy in NBCCS is not significantly altered but morbidity from complications can be substantial. Regular follow-up by a multi-specialist team (dermatologist, neurologist and odontologist) should be offered. Patients with NBCCS should strictly avoid an excessive sun exposure."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I412,I412)","v":18296313},{"$f":"(LEN($J412) - LEN(SUBSTITUTE(LOWER($J412),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J412) - LEN(SUBSTITUTE(LOWER($J412),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J412) - LEN(SUBSTITUTE(LOWER($J412),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B412:D412)","v":0},2008,"To what extent can food-based approaches improve micronutrient status?","Allen",18296313,"To what extent can food-based approaches improve micronutrient status?    Abstract:   The main dietary sources of micronutrients are animal source foods, fruits, vegetables and legumes. Animal source foods are the only source of some micronutrients and the main dietary source of others. Micronutrient status and child development are improved by animal source food interventions in populations that habitually consume low amounts. Of particular concern is the high global prevalence of vitamin B12 depletion, which is associated with low animal source food intake. Some fruits and vegetables can supply vitamin A requirements even with the lower amounts of fat typically consumed in many countries. However, plant source foods are unlikely to supply enough iron, zinc and vitamin B12, even if strategies such as consuming ascorbic-acid rich foods to increase iron absorption are adopted. Identification of mineral-rich varieties of cereals and legumes may improve the future situation. Complementary foods for infants and young children are unlikely to meet micronutrient requirements, especially for iron and zinc, unless they are fortified. Other strategies to improve micronutrient status, such as fortification and supplementation, have limitations and should not replace food-based strategies. Moreover, food-based strategies will improve dietary quality in general and are consistent with the global need to lower the risk of chronic disease and overweight."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I413,I413)","v":18484612},{"$f":"(LEN($J413) - LEN(SUBSTITUTE(LOWER($J413),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J413) - LEN(SUBSTITUTE(LOWER($J413),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J413) - LEN(SUBSTITUTE(LOWER($J413),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B413:D413)","v":0},2008,"The hepatic microvascular system in health and its response to toxicants.","McCuskey",18484612,"The hepatic microvascular system in health and its response to toxicants.    Abstract:   This review briefly summarizes what is known about the dynamic morphology of the hepatic microvascular system that includes all vessels in the liver with a diameter less than 300 microm and various morphological sites within these vessels that regulate the distribution of blood flow. The latter include the various segments of the afferent portal venules and hepatic arterioles, the sinusoids, and central and hepatic venules. Sinusoids are unique exchange vessels lined by fenestrated endothelial cells which have important endocytotic functions and phagocytic Kupffer cells which are important for host defense. These are encircled by extraluminal stellate cells that are specialized pericytes containing fat droplets that store vitamin A. The principle sites for regulating blood flow are in the sinusoidal network with stellate and endothelial cells playing a major role in regulating the diameters of sinusoids and the distribution of blood flow in individual sinusoids, lobules, or segments of lobules. The sinusoidal endothelial cells are a sensitive and early target for several toxicants. For example, as early as 30 minutes after the administration of acetaminophen, the endothelial cells become swollen and begin to lose the ability to endocytose ligands. Within 2 hr, gaps through the cytoplasm appear formed by the destruction and/or coalescence of fenestrae which permit red blood cells to penetrate into the space of Disse. Subsequently, the sinusoid may collapse or disintegrate reducing blood flow."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I414,I414)","v":18430162},{"$f":"(LEN($J414) - LEN(SUBSTITUTE(LOWER($J414),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J414) - LEN(SUBSTITUTE(LOWER($J414),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J414) - LEN(SUBSTITUTE(LOWER($J414),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B414:D414)","v":0},2008,"Elucidation of the role of activin in organogenesis using a multiple organ induction system with amphibian and mouse undifferentiated cells in vitro.","Asashima",18430162,"Elucidation of the role of activin in organogenesis using a multiple organ induction system with amphibian and mouse undifferentiated cells in vitro.    Abstract:   Studies performed over the last century have clarified the mechanisms of organ and tissue formation. Mesoderm formation is one of the most important events in early body pattern determination during embryogenesis. In 1988, we found that activin A has mesoderm-inducing activity. As activin A could induce dorsal mesoderm formation, unlike fibroblast growth factor and bone morphogenetic protein, this factor was thought to be the molecular entity of the Spemann-Mangold organizer. Subsequently, the mechanisms of early embryogenesis have been clarified using molecular biological techniques, resulting in the identification of many genes that are involved in organ and tissue development. This finding that activin A could induce dorsal mesoderm formation spurred research into the application of agents that induce organs and tissues in vitro. In this regard, we have shown that many organ types can be induced by activin A in vitro. Moreover, we have found that other types of organs can be induced by changing the conditions of treatment. To date, more than 20 different types of tissues and organs have been successfully induced from Xenopus undifferentiated cells in vitro. In recent years, we have applied these protocols to mouse embryonic stem cells, and we have successfully induced several tissues, such as the pancreas and cardiomyocytes. We are also investigating how the pluripotency of undifferentiated stem cells is regulated. In this review, we summarize the current knowledge regarding activin as a mesoderm-inducing factor and its application for the induction of tissues and organs from undifferentiated cells. Moreover, we provide some examples of in vitro tissue differentiation from mouse embryonic stem cells, which may prove useful in regenerative medicine."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I415,I415)","v":18425980},{"$f":"(LEN($J415) - LEN(SUBSTITUTE(LOWER($J415),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J415) - LEN(SUBSTITUTE(LOWER($J415),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J415) - LEN(SUBSTITUTE(LOWER($J415),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B415:D415)","v":0},2008,"Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases.","Bjelakovic",18425980,"Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases.    Abstract:    BACKGROUND : Animal and physiological research as well as observational studies suggest that antioxidant supplements may improve survival.  OBJECTIVES : To assess the effect of antioxidant supplements on mortality in primary or secondary prevention randomised clinical trials.  SEARCH STRATEGY : We searched The Cochrane Library (Issue 3, 2005), MEDLINE (1966 to October 2005), EMBASE (1985 to October 2005), and the Science Citation Index Expanded (1945 to October 2005). We scanned bibliographies of relevant publications and wrote to pharmaceutical companies for additional trials.  SELECTION CRITERIA : We included all primary and secondary prevention randomised clinical trials on antioxidant supplements (beta-carotene, vitamin A, vitamin C, vitamin E, and selenium) versus placebo or no intervention. Included participants were either healthy (primary prevention trials) or had any disease (secondary prevention trials).  DATA COLLECTION AND ANALYSIS : Three authors extracted data. Trials with adequate randomisation, blinding, and follow-up were classified as having a low risk of bias. Random-effects and fixed-effect meta-analyses were performed. Random-effects meta-regression analyses were performed to assess sources of intertrial heterogeneity.  MAIN RESULTS : Sixty-seven randomised trials with 232,550 participants were included. Forty-seven trials including 180,938 participants had low risk of bias. Twenty-one trials included 164,439 healthy participants. Forty-six trials included 68111 participants with various diseases (gastrointestinal, cardiovascular, neurological, ocular, dermatological, rheumatoid, renal, endocrinological, or unspecified). Overall, the antioxidant supplements had no significant effect on mortality in a random-effects meta-analysis (relative risk [RR] 1.02, 95% confidence interval [CI] 0.99 to 1.06), but significantly increased mortality in a fixed-effect model (RR 1.04, 95% CI 1.02 to 1.06). In meta-regression analysis, the risk of bias and type of antioxidant supplement were the only significant predictors of intertrial heterogeneity. In the trials with a low risk of bias, the antioxidant supplements significantly increased mortality (RR 1.05, 95% CI 1.02 to 1.08). When the different antioxidants were assessed separately, analyses including trials with a low risk of bias and excluding selenium trials found significantly increased mortality by vitamin A (RR 1.16, 95% CI 1.10 to 1.24), beta-carotene (RR 1.07, 95% CI 1.02 to 1.11), and vitamin E (RR 1.04, 95% CI 1.01 to 1.07), but no significant detrimental effect of vitamin C (RR 1.06, 95% CI 0.94 to 1.20). Low-bias risk trials on selenium found no significant effect on mortality (RR 0.91, 95% CI 0.76 to 1.09).  AUTHORS CONCLUSIONS : We found no evidence to support antioxidant supplements for primary or secondary prevention. Vitamin A, beta-carotene, and vitamin E may increase mortality. Future randomised trials could evaluate the potential effects of vitamin C and selenium for primary and secondary prevention. Such trials should be closely monitored for potential harmful effects. Antioxidant supplements need to be considered medicinal products and should undergo sufficient evaluation before marketing."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I416,I416)","v":18423260},{"$f":"(LEN($J416) - LEN(SUBSTITUTE(LOWER($J416),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J416) - LEN(SUBSTITUTE(LOWER($J416),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J416) - LEN(SUBSTITUTE(LOWER($J416),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B416:D416)","v":0},2008,"Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics.","Menter",18423260,"Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics.    Abstract:   Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this first of 5 sections of the guidelines of care for psoriasis, we discuss the classification of psoriasis; associated comorbidities including autoimmune diseases, cardiovascular risk, psychiatric/psychologic issues, and cancer risk; along with assessment tools for skin disease and quality-of-life issues. Finally, we will discuss the safety and efficacy of the biologic treatments used to treat patients with psoriasis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I417,I417)","v":17764205},{"$f":"(LEN($J417) - LEN(SUBSTITUTE(LOWER($J417),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J417) - LEN(SUBSTITUTE(LOWER($J417),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J417) - LEN(SUBSTITUTE(LOWER($J417),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B417:D417)","v":0},2006,"Multivitamin/mineral supplements and prevention of chronic disease.","Huang",17764205,"Multivitamin/mineral supplements and prevention of chronic disease.    Abstract:    OBJECTIVES : To review and synthesize published literature on the efficacy of multivitamin/mineral supplements and certain single nutrient supplements in the primary prevention of chronic disease in the general adult population, and on the safety of multivitamin/mineral supplements and certain single nutrient supplements, likely to be included in multivitamin/mineral supplements, in the general population of adults and children.  DATA SOURCES : All articles published through February 28, 2006, on MEDLINE, EMBASE, and the Cochrane databases.  REVIEW METHODS : Each article underwent double reviews on title, abstract, and inclusion eligibility. Two reviewers performed data abstraction and quality assessment. Differences in opinion were resolved through consensus adjudication.  RESULTS : Few trials have addressed the efficacy of multivitamin/mineral supplement use in chronic disease prevention in the general population of the United States. One trial on poorly nourished Chinese showed supplementation with combined Beta-carotene, vitamin E and selenium reduced gastric cancer incidence and mortality, and overall cancer mortality. In a French trial, combined vitamin C, vitamin E, Beta-carotene, selenium, and zinc reduced cancer risk in men but not in women. No cardiovascular benefit was evident in both trials. Multivitamin/mineral supplement use had no benefit for preventing cataract. Zinc/antioxidants had benefits for preventing advanced age-related macular degeneration in persons at high risk for the disease. With few exceptions, neither Beta-carotene nor vitamin E had benefits for preventing cancer, cardiovascular disease, cataract, and age-related macular degeneration. Beta-carotene supplementation increased lung cancer risk in smokers and persons exposed to asbestos. Folic acid alone or combined with vitamin B12 and/or vitamin B6 had no significant effects on cognitive function. Selenium may confer benefit for cancer prevention but not cardiovascular disease prevention. Calcium may prevent bone mineral density loss in postmenopausal women, and may reduce vertebral fractures, but not non-vertebral fractures. The evidence suggests dose-dependent benefits of vitamin D with/without calcium for retaining bone mineral density and preventing hip fracture, non-vertebral fracture and falls. We found no consistent pattern of increased adverse effects of multivitamin/mineral supplements except for skin yellowing by Beta-carotene.  CONCLUSIONS : Multivitamin/mineral supplement use may prevent cancer in individuals with poor or suboptimal nutritional status. The heterogeneity in the study populations limits generalization to United States population. Multivitamin/mineral supplements conferred no benefit in preventing cardiovascular disease or cataract, and may prevent advanced age-related macular degeneration only in high-risk individuals. The overall quality and quantity of the literature on the safety of multivitamin/mineral supplements is limited."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I418,I418)","v":17691927},{"$f":"(LEN($J418) - LEN(SUBSTITUTE(LOWER($J418),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J418) - LEN(SUBSTITUTE(LOWER($J418),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J418) - LEN(SUBSTITUTE(LOWER($J418),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B418:D418)","v":0},2007,"Maternal nutrition and predisposition to later kidney disease.","Woods",17691927,"Maternal nutrition and predisposition to later kidney disease.    Abstract:   Although it is well-accepted that size at birth is inversely related to adult blood pressure and cardiovascular risk in humans, the majority of information available with regard to maternal nutrition, prenatal growth, and subsequent renal disease comes from animal models. Restriction of food or protein during specific windows of pregnancy leads to hypertension in adult offspring. Depending on the degree of maternal restriction, nephron number and renal function in the offspring may be reduced, and proteinuria and histological signs of renal disease are present. All of these abnormalities appear to worsen with age. Female gender is relatively protective against these prenatal insults, but with more severe maternal dietary restriction female offspring are also affected. In addition to macronutrients, roles for several micronutrients have been identified in fetal programming for hypertension and renal disease. Ongoing investigations into the roles of sex hormones, the renin-angiotensin system, and vitamin A in these developmental processes may lead to strategies for prevention of dietary programming for hypertension and renal disease in humans."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I419,I419)","v":17508558},{"$f":"(LEN($J419) - LEN(SUBSTITUTE(LOWER($J419),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J419) - LEN(SUBSTITUTE(LOWER($J419),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J419) - LEN(SUBSTITUTE(LOWER($J419),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B419:D419)","v":0},2007,"[KLF5].","Manabe",17508558,"[KLF5].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I420,I420)","v":17416041},{"$f":"(LEN($J420) - LEN(SUBSTITUTE(LOWER($J420),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J420) - LEN(SUBSTITUTE(LOWER($J420),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J420) - LEN(SUBSTITUTE(LOWER($J420),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B420:D420)","v":0},2007,"Recommendations from SPNS/GEAM/SENBA/SENPE/AEDN/SEDCA/GESIDA on nutrition in the HIV-infected patient.","Polo",17416041,"Recommendations from SPNS/GEAM/SENBA/SENPE/AEDN/SEDCA/GESIDA on nutrition in the HIV-infected patient.    Abstract:    OBJECTIVE : to make recommendations on the approach to nutritional problems (malnutrition, cachexia, micronutrient deficiency, obesity, lipodystrophy) affecting HIV-infected patients.  METHODS : these recommendations have been agreed upon by a group of expertes in the nutrition and care of HIV-infected patients, on behalf of the different groups involved in drafting them. Therefore, the latest advances in pathophysiology, epidemiology, and clinical care presented in studies published in medical journals or at scientific meetings were evaluated.  RESULTS : there is no single method of evaluating nutrition, and diferent techniques--CT, MRI, and DXA--must be combined. The energy requirements of symptomatic patients increase by 20-30%. There is no evidence to support the increase in protein or fat intake. Micronutrient supplementation in only necessary in special circumstances (vitamin A in children and pregnant woman). Aerobic and resistance excercise is beneficial both for cardiovascular health and for improving lean mass and muscular strength. It is important to follow the rules of food safety at every stage in the chain. Therapeutic intervention in anorexia and cachexia must be tailored, by combining nutritional and pharmacological support (appetite stimulants, anabolic steroids, and, in some cases, testosterone). Artificial nutrition (oral supplementation, enteral or parenteral nutrition) is safe and efficacious, and improves nutritional status and response to therapy. In children, nutritional recommendations must be made early, and are a necessary component of therapy.  CONCLUSION : appropriate nutritional evaluation and relevant therapeutic action are an essential part of the care of HIV-infected patients."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I421,I421)","v":17349800},{"$f":"(LEN($J421) - LEN(SUBSTITUTE(LOWER($J421),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J421) - LEN(SUBSTITUTE(LOWER($J421),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J421) - LEN(SUBSTITUTE(LOWER($J421),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B421:D421)","v":0},2007,"Carotenoids and human health.","Rao",17349800,"Carotenoids and human health.    Abstract:   Oxidative stress is an important contributor to the risk of chronic diseases. Dietary guidelines recommend increased consumption of fruits and vegetables to combat the incidence of human diseases such as cancer, cardiovascular disease, osteoporosis and diabetes. Fruits and vegetables are good sources of antioxidant phytochemicals that mitigate the damaging effect of oxidative stress. Carotenoids are a group of phytochemicals that are responsible for different colors of the foods. They are recognized as playing an important role in the prevention of human diseases and maintaining good health. In addition to being potent antioxidants some carotenoids also contribute to dietary vitamin A. There is scientific evidence in support of the beneficial role of phytochemicals in the prevention of several chronic diseases. Although the chemistry of carotenoids has been studied extensively, their bioavailability, metabolism and biological functions are only now beginning to be investigated. Recent interest in carotenoids has focused on the role of lycopene in human health. Unlike some other carotenoids, lycopene does not have pro-vitamin A properties. Because of the unsaturated nature of lycopene it is considered to be a potent antioxidant and a singlet oxygen quencher. This article will review carotenoids in general and lycopene in particular for their role in human health."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I422,I422)","v":17311876},{"$f":"(LEN($J422) - LEN(SUBSTITUTE(LOWER($J422),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J422) - LEN(SUBSTITUTE(LOWER($J422),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J422) - LEN(SUBSTITUTE(LOWER($J422),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B422:D422)","v":0},2007,"Antioxidant vitamin supplementation in cardiovascular diseases.","Riccioni",17311876,"Antioxidant vitamin supplementation in cardiovascular diseases.    Abstract:   Cardiovascular disease is the most important adult health problem in wealthy countries, where biological factors such as obesity, hypertension, dyslipidemia, diabetes, inappropriate diet, cigarette smoking, and sedentary life-style have contributed to its dissemination. Research concerning nutritional regimens has shown that persons who consume large amounts of fruit and vegetables have lower incidences of cardiovascular diseases, stroke, and tumors, although the precise mechanisms for this protective effect are elusive. Possible explanations include (a) increased consumption of dietary fiber, (b) reduced consumption of dietary cholesterol and other lipids, and (c) increased intake of the antioxidant vitamins (A, C, and E). Numerous studies have raised the question whether vitamin supplements help to prevent cardiovascular diseases. Results of randomized controlled trials of antioxidant vitamin supplements in large numbers of participants has been ambiguous or contradictory. This minireview examines the relevant clinical reports on dietary supplements of vitamins A, C, and E to determine whether they support the premise that patients at risk of cardiovascular disease may be candidates for this therapeutic option."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I423,I423)","v":16787256},{"$f":"(LEN($J423) - LEN(SUBSTITUTE(LOWER($J423),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J423) - LEN(SUBSTITUTE(LOWER($J423),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J423) - LEN(SUBSTITUTE(LOWER($J423),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B423:D423)","v":0},2006,"Molecularly guided therapy of neuroblastoma: a review of different approaches.","Tonini",16787256,"Molecularly guided therapy of neuroblastoma: a review of different approaches.    Abstract:   Neuroblastoma (NB) is the most frequent extra-cranial solid tumor and the first cause of lethality in pre-school age children. NB accounts for 9-10% of pediatric tumors and affects more than ten thousand children a year. It originates from the sympathetic nervous system and is characterized by heterogeneous pathological and clinical presentation. Stage 4 NB represents approximately 50% of the cases and shows metastatic dissemination at onset; its prognosis is grim, with 20% of the patients surviving at 5 years from diagnosis in spite of aggressive chemotherapy with autologous hematopoietic stem cell support. Novel therapeutic strategies are urgently needed to improve the prognosis of stage 4 NB patients. Here we review the most promising approaches to NB treatment that have already reached clinical testing or have proved to be successful in preclinical models of the disease. All of these approaches are molecularly guided, since their rational development has benefited from the enormous amount of information on the biology of neuroblastoma gathered through molecular biology and genetics studies. The following topics are reviewed: MYCN oncogene amplification as parameter for therapeutic decision, minimal residual disease, immunotherapy, gene therapy, differentiation and apoptotic therapy, anti-angiogenic therapy, gene expression profiling as tool for generating novel therapeutic approaches. Although several efforts are still needed to reach a significant cure of patients with neuroblastoma, molecularly guided approaches have opened new ways to neuroblastoma treatment and can represent useful models for other cancers of either childhood or adulthood."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I424,I424)","v":21289965},{"$f":"(LEN($J424) - LEN(SUBSTITUTE(LOWER($J424),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J424) - LEN(SUBSTITUTE(LOWER($J424),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J424) - LEN(SUBSTITUTE(LOWER($J424),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B424:D424)","v":0},2006,"Antioxidative vitamines for prevention of cardiovascular disease for patients after renal transplantation and patients with chronic renal failure.","Schnell-Inderst",21289965,"Antioxidative vitamines for prevention of cardiovascular disease for patients after renal transplantation and patients with chronic renal failure.    Abstract:    INTRODUCTION : The mortality from cardiovascular disease in patients with chronic renal failure is much higher than in the general population. In particular, patients with chronic renal failure with replacement therapies (dialysis patients and patients with renal transplantation) show both increased traditional risk factors and risk factors due to the dysfunction of the renal system. In combination with necessary medication for renal insufficiency oxidative stress is elevated. Progression of atherosclerosis is promoted due to increased oxidation of lipids and endothelium damage. This link between lipid oxidation and artherogenesis provides the rationale for the supposed beneficial effect of supplementation with antioxidative vitamins (vitamin A, C and E). Such an effect could not be demonstrated for patients with a history of cardiovascular disease and without kidney diseases. However, in high risk patients with chronic renal failure and renal replacement therapies this could be different.  OBJECTIVES : The objective of this systematic literature review was to assess the clinical effectiveness and cost-effectiveness of supplementation with antioxidative vitamins A, C or E to reduce cardiovascular events in patients with chronic kidney diseases, dialysis-requiring patients and patients after a renal transplantation with or without cardiovascular diseases.  METHODS : A systematic literature review was conducted with documented search and selection of the literature, using a priori defined inclusion and exclusion criteria as well as a documented extraction and assessment of the literature according to the methods of evidence-based medicine.  RESULTS : 21 publications met the inclusion criteria for the evaluation of clinical effectiveness. No study could be identified for the economic evaluation. Two studies (four publications) analysed the effect of oral supplementation on the secondary prevention of clinical cardiovascular endpoints. Studies analysing the effect on patients without a history of cardiovascular disease could not be identified. 17 studies analysed the effect of oral supplementation or infusion with antioxidative vitamins or the supplementation with dialysis membranes coated with vitamin E on intermediate outcomes like oxidative stress or vessel parameters. The two randomized clinical trials analysing the effect of orally supplemented vitamin E on clinical endpoints in patients with mild-to-moderate renal insufficiency and for haemodialysis patients respectively reported different results. After 4.5 years supplementation with a daily dose of 400 IU vitamin E renal insufficiency patients showed neither a beneficial nor a harmful effect on a combined event rate of myocardial infarction, stroke or death by cardiovascular causes. The second study reported a 50% risk reduction (RR=0.46, 95%-KI: 0.27-0.78, p=0.014) on the combined event rate of fatal myocardial infarction, nonfatal myocardial infarction, stroke, peripheral vascular disease or unstable angina pectoris in the study arm with vitamin E-Supplementation of 800 IU daily. In 16 of 17 studies with intermediate endpoints the supplementation with vitamins was associated with a change of one or several of the examined endpoints in the expected direction. This means that the concentrations of the markers for oxidative stress decreased in the Vitamin E-group, the progression of aortic calcification (only one study) was reduced, the intima media thickness decreased and the lipid profile improved. No studies regarding costs or cost-effectiveness were identified.  DISCUSSION : A possible explanation for the different results in the two studies with clinical endpoints may be due to the different study populations with different risk profiles, to different dosage during the intervention or to variation by chance. Due to the absence of clinically meaningful endpoints, the relevance of studies analysing the effect of antioxidative vitamins on intermediate endpoints like oxidative stress markers is basically limited to show single intermediate steps of the postulated biological effect mechanisms by which a potentially preventive effect could possibly be mediated. The mainly unsatisfactory planning and reporting quality of the 17 identified studies and a possible quot;publication biasquot; are further limitations.  CONCLUSION : The available evidence is not sufficient to support or to reject an effect of antioxidative vitamins on secondary prevention for cardiovascular disease for patients with chronic renal insufficiency or renal replacement therapy. There is a lack of randomized, placebo-controlled studies with a sufficient number of cases and clinical endpoints of cardiovascular disease, on the effect of antioxidative vitamins either orally applied or given by vitamin E-modified dialysers. No data are available about supplementation with antioxidative vitamins for primary prevention of cardiovascular disease. Therefore the current evidence does not allow to draw conclusions concerning this subject either. As opposed to patients with a history of cardiovascular disease without kidney diseases where there is enough evidence to exclude a beneficial effect on secondary prevention of cardiovascular disease for patients with chronic renal insufficiency and renal replacement therapy this question remains unanswered. Conclusions about costs and cost-effectiveness also cannot be drawn."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I425,I425)","v":16309738},{"$f":"(LEN($J425) - LEN(SUBSTITUTE(LOWER($J425),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J425) - LEN(SUBSTITUTE(LOWER($J425),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J425) - LEN(SUBSTITUTE(LOWER($J425),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B425:D425)","v":0},2005,"Carotenoid actions and their relation to health and disease.","Krinsky",16309738,"Carotenoid actions and their relation to health and disease.    Abstract:   Based on extensive epidemiological observation, fruits and vegetables that are a rich source of carotenoids are thought to provide health benefits by decreasing the risk of various diseases, particularly certain cancers and eye diseases. The carotenoids that have been most studied in this regard are beta-carotene, lycopene, lutein and zeaxanthin. In part, the beneficial effects of carotenoids are thought to be due to their role as antioxidants. beta-Carotene may have added benefits due its ability to be converted to vitamin A. Additionally, lutein and zeaxanthin may be protective in eye disease because they absorb damaging blue light that enters the eye. Food sources of these compounds include a variety of fruits and vegetables, although the primary sources of lycopene are tomato and tomato products. Additionally, egg yolk is a highly bioavailable source of lutein and zeaxanthin. These carotenoids are available in supplement form. However, intervention trials with large doses of beta-carotene found an adverse effect on the incidence of lung cancer in smokers and workers exposed to asbestos. Until the efficacy and safety of taking supplements containing these nutrients can be determined, current dietary recommendations of diets high in fruits and vegetables are advised."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I426,I426)","v":16201577},{"$f":"(LEN($J426) - LEN(SUBSTITUTE(LOWER($J426),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J426) - LEN(SUBSTITUTE(LOWER($J426),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J426) - LEN(SUBSTITUTE(LOWER($J426),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B426:D426)","v":0},2005,"[Anti-angiogenesis treatment for brain tumors--present and future].","Takano",16201577,"[Anti-angiogenesis treatment for brain tumors--present and future].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I427,I427)","v":20527403},{"$f":"(LEN($J427) - LEN(SUBSTITUTE(LOWER($J427),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J427) - LEN(SUBSTITUTE(LOWER($J427),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J427) - LEN(SUBSTITUTE(LOWER($J427),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B427:D427)","v":0},2005,"[Unexpected failure of antioxidant clinical trials].","Wierzba",20527403,"[Unexpected failure of antioxidant clinical trials].    Abstract:   Data from a variety of experimental studies suggesting benefits of the antioxidant supplementation were confronted with those from clinical trials and large metaanalyses which have failed to prove those benefits. Major directions of the biological effects of reactive oxygen species (ROS) and antioxidants were specified. In particular, plausible mechanisms through antioxidants may disturb physiological functions were discussed. The regulatory aspects of ROS potency, and the ways antioxidants may disturb homeostasis were taken particularly into account. Directions of prospective research towards practical use of antioxidants were suggested."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I428,I428)","v":16182194},{"$f":"(LEN($J428) - LEN(SUBSTITUTE(LOWER($J428),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J428) - LEN(SUBSTITUTE(LOWER($J428),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J428) - LEN(SUBSTITUTE(LOWER($J428),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B428:D428)","v":0},2005,"Emerging role of high-density lipoprotein in the prevention of cardiovascular disease.","Brousseau",16182194,"Emerging role of high-density lipoprotein in the prevention of cardiovascular disease.    Abstract:   In major statin trials, the relative risk reduction is typically in the range 25-35%, thus indicating that the majority of cardiac events continues to occur despite statin therapy. Hence, there is a considerable interest in identifying novel therapies capable of further reducing cardiovascular disease risk. One such potential therapeutic target is a low level of high-density lipoprotein (HDL) cholesterol. Emerging targets involved in HDL metabolism are: (i) liver X receptor and peroxisome proliferator-activated receptor agonists; (ii) cholesteryl ester transfer protein inhibitors; (iii) HDL mimetics (ETC-216); (iv) apolipoprotein A-I synthetic peptides; and (v) HDL delipidation and reinfusion. Although they are at various stages of development, each of these therapies has promise for the treatment of cardiovascular disease in humans."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I429,I429)","v":16158610},{"$f":"(LEN($J429) - LEN(SUBSTITUTE(LOWER($J429),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J429) - LEN(SUBSTITUTE(LOWER($J429),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J429) - LEN(SUBSTITUTE(LOWER($J429),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B429:D429)","v":0},2005,"[Lycopene--a natural antioxidant].","Bánhegyi",16158610,"[Lycopene--a natural antioxidant].    Abstract:   Lycopene is a carotenoid found predominantly in tomatoes and tomato products. In contrast to beta-carotene it is not a precursor of vitamin A in humans. Lycopene is not destroyed during food processing, moreover its bioavailability improves. Lycopene is the most powerful antioxidant amongst carotenoids. Beside the antioxidant effect it influences the expression of various proteins (enzymes of biotransformation, cyclin D1, connexins). According to epidemiologic studies tomato lycopene may reduce the risk of prostate cancer and cardiovascular diseases. Positive effects are also hypothesized in case of other diseases such as osteoporosis, neurodegenerative diseases and hypertension. Neither adverse effects upon lycopene supplementation nor lycopene toxicity have been reported. Therefore, several arguments support the consumption of natural lycopene, whilst there are no contraindications according to the present knowledge."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I430,I430)","v":16048032},{"$f":"(LEN($J430) - LEN(SUBSTITUTE(LOWER($J430),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J430) - LEN(SUBSTITUTE(LOWER($J430),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J430) - LEN(SUBSTITUTE(LOWER($J430),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B430:D430)","v":0},2005,"[Diet, nutrition and rheumatoid arthritis].","Miggiano",16048032,"[Diet, nutrition and rheumatoid arthritis].    Abstract:   Rheumatoid Arthritis (RA) is a chronic inflammatory disease resulting in diarthrodial joints inflammation (particularly joints of hands, wrists, feet, knees, cubitus, ankles, shoulder, etc.) that is manifested by swelling and functional impairment. The associated complications, osteoporosis and cardiovascular disease, make RA important in public health terms. During the active phase of disease, elevated plasma concentrations of inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and acute-phase proteins, lead to reduction of fat free body mass (FFM) with a loss mean of 15% of cell body mass (CM) and consequent reduction of muscle strength. The pharmacological therapy (non steroidal anti inflammatory drugs (NSAIDs), slow acting antirheumatic drugs and corticosteroids), have the potential to cause side-effects, such as gastrointestinal bleeding, bone loss beyond to increase the requirement of some nutrients and reduce their absorption. The diet may play role in the management of RA, particularly in alleviating the symptoms of the disease, combating the side-effects of therapy and reducing the risk of complications. The increase of the caloric and proteic intake is not sufficient to offset a increased metabolic rhythm and important proteic catabolism but a diet balanced may warrant an adequate intake of nutrients. The carbohydrates of the diet provide 55-60% of the caloric intake, the diet is normo-proteinic or hyper-proteinic in the active phase of disease, and lipids represent 25-30% of the caloric intake (saturated, monounsaturated, polyunsaturated fatty acids in the ratio 1:1:1). omega-3 fatty acids supplementation, in combination with reduction of fatty acids omega-6 and adequate intake of monounsaturated fatty acids induce improvement in symptoms and sometimes a reduction in NSAIDs usage. Proper antioxidant nutrients (Vitamin A, Vitamin C, selenium) may provide an important defence against the increased oxidant stress and a supplementation of folate and vitamin B12, in patients treated with methotrexate (MTX), reduce the incidence of side effects and offset the elevation in plasma homocysteine frequent in these patients. Calcium and vitamin D, in patients treated with corticosteroids, reduce the bone loss, while a supplementation with iron may prevent anaemia. Finally, elimination diets may be feasible therapy only in patients with positive skin prick test."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I431,I431)","v":16040282},{"$f":"(LEN($J431) - LEN(SUBSTITUTE(LOWER($J431),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J431) - LEN(SUBSTITUTE(LOWER($J431),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J431) - LEN(SUBSTITUTE(LOWER($J431),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B431:D431)","v":0},2005,"Medical bioremediation: prospects for the application of microbial catabolic diversity to aging and several major age-related diseases.","de Grey",16040282,"Medical bioremediation: prospects for the application of microbial catabolic diversity to aging and several major age-related diseases.    Abstract:   Several major diseases of old age, including atherosclerosis, macular degeneration and neurodegenerative diseases are associated with the intracellular accumulation of substances that impair cellular function and viability. Moreover, the accumulation of lipofuscin, a substance that may have similarly deleterious effects, is one of the most universal markers of aging in postmitotic cells. Reversing this accumulation may thus be valuable, but has proven challenging, doubtless because substances resistant to cellular catabolism are inherently hard to degrade. We suggest a radically new approach: augmenting humans natural catabolic machinery with microbial enzymes. Many recalcitrant organic molecules are naturally degraded in the soil. Since the soil in certain environments - graveyards, for example - is enriched in human remains but does not accumulate these substances, it presumably harbours microbes that degrade them. The enzymes responsible could be identified and engineered to metabolise these substances in vivo. Here, we survey a range of such substances, their putative roles in age-related diseases and the possible benefits of their removal. We discuss how microbes capable of degrading them can be isolated, characterised and their relevant enzymes engineered for this purpose and ways to avoid potential side-effects."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I432,I432)","v":15926502},{"$f":"(LEN($J432) - LEN(SUBSTITUTE(LOWER($J432),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J432) - LEN(SUBSTITUTE(LOWER($J432),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J432) - LEN(SUBSTITUTE(LOWER($J432),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B432:D432)","v":0},2005,"[In vitro organogenesis using amphibian pluripotent cells].","Ito",15926502,"[In vitro organogenesis using amphibian pluripotent cells].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I433,I433)","v":15922648},{"$f":"(LEN($J433) - LEN(SUBSTITUTE(LOWER($J433),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J433) - LEN(SUBSTITUTE(LOWER($J433),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J433) - LEN(SUBSTITUTE(LOWER($J433),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B433:D433)","v":0},2005,"Skeletal muscle and nuclear hormone receptors: implications for cardiovascular and metabolic disease.","Smith",15922648,"Skeletal muscle and nuclear hormone receptors: implications for cardiovascular and metabolic disease.    Abstract:   Skeletal muscle is a major mass peripheral tissue that accounts for approximately 40% of the total body mass and a major player in energy balance. It accounts for gt;30% of energy expenditure, is the primary tissue of insulin stimulated glucose uptake, disposal, and storage. Furthermore, it influences metabolism via modulation of circulating and stored lipid (and cholesterol) flux. Lipid catabolism supplies up to 70% of the energy requirements for resting muscle. However, initial aerobic exercise utilizes stored muscle glycogen but as exercise continues, glucose and stored muscle triglycerides become important energy substrates. Endurance exercise increasingly depends on fatty acid oxidation (and lipid mobilization from other tissues). This underscores the importance of lipid and glucose utilization as an energy source in muscle. Consequently skeletal muscle has a significant role in insulin sensitivity, the blood lipid profile, and obesity. Moreover, caloric excess, obesity and physical inactivity lead to skeletal muscle insulin resistance, a risk factor for the development of type II diabetes. In this context skeletal muscle is an important therapeutic target in the battle against cardiovascular disease, the worlds most serious public health threat. Major risk factors for cardiovascular disease include dyslipidemia, hypertension, obesity, sedentary lifestyle, and diabetes. These risk factors are directly influenced by diet, metabolism and physical activity. Metabolism is largely regulated by nuclear hormone receptors which function as hormone regulated transcription factors that bind DNA and mediate the patho-physiological regulation of gene expression. Metabolism and activity, which directly influence cardiovascular disease risk factors, are primarily driven by skeletal muscle. Recently, many nuclear receptors expressed in skeletal muscle have been shown to improve glucose tolerance, insulin resistance, and dyslipidemia. Skeletal muscle and nuclear receptors are rapidly emerging as critical targets in the battle against cardiovascular disease risk factors. Understanding the function of nuclear receptors in skeletal muscle has enormous pharmacological utility for the treatment of cardiovascular disease. This review focuses on the molecular regulation of metabolism by nuclear receptors in skeletal muscle in the context of dyslipidemia and cardiovascular disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I434,I434)","v":15876415},{"$f":"(LEN($J434) - LEN(SUBSTITUTE(LOWER($J434),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J434) - LEN(SUBSTITUTE(LOWER($J434),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J434) - LEN(SUBSTITUTE(LOWER($J434),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B434:D434)","v":0},2005,"Phytoestrogens derived from red clover: an alternative to estrogen replacement therapy?","Beck",15876415,"Phytoestrogens derived from red clover: an alternative to estrogen replacement therapy?    Abstract:   The benefits of plant extracts from soy and red clover as alternatives to conventional hormone replacement therapy (HRT) have been debated in the past. Here, an attempt has been made to summarize the biochemical and pharmacological data in the light of clinical aspects. Red clover and soy extracts contain isoflavones, which have a high affinity to estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), progesterone receptor (PR) and androgen receptor (AR). The higher affinity to ERbeta compared to ERalpha has been used as an explanation why red clover extracts function as food additives to treat menopausal disorders and may reduce risk of breast cancer. Biochemical analysis shows that these representatives of phytoestrogens have multiple actions beside selective estrogen receptor modulator (SERM)-activity. They act as selective estrogen enzyme modulators (SEEMs), have antioxidant activity and interact with transcription factors such as NF-kappaB. Furthermore, it is indicated that they have protective effects on osteoporosis and the cardiovascular system. Currently 40-50mg of isoflavones (biochanin A, daidzein, formononetin and genistein) are recommended as daily dose. This recommendation is based on the daily intake of phytoestrogens in a traditional Japanese diet."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I435,I435)","v":15770336},{"$f":"(LEN($J435) - LEN(SUBSTITUTE(LOWER($J435),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J435) - LEN(SUBSTITUTE(LOWER($J435),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J435) - LEN(SUBSTITUTE(LOWER($J435),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B435:D435)","v":0},2005,"Endothelial dysfunction and antioxidants.","Duvall",15770336,"Endothelial dysfunction and antioxidants.    Abstract:   The vascular endothelium plays a crucial role in the physiology of blood vessels and the pathological processes of atherosclerotic disease and acute coronary syndromes. Endothelial dysfunction is the core problem; it is an impairment of endothelium-dependent vasorelaxation caused by a loss of nitric oxide activity in the vessel wall, which results in impairment in the regulation of vascular homeostasis. Further understanding of its mechanisms of action and possible therapeutic targets will be of great importance. The group of antioxidant vitamins, A, C and E, would seem uniquely situated to reduce cardiovascular events by improving endothelial function by reducing the concentration of reactive oxygen species in the vessel wall and by preventing oxidative modification of low-density lipoprotein. Unfortunately, despite extensive studies in both observational and randomized trials, the weight of evidence points to little or no benefit from antioxidant therapy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I436,I436)","v":15707702},{"$f":"(LEN($J436) - LEN(SUBSTITUTE(LOWER($J436),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J436) - LEN(SUBSTITUTE(LOWER($J436),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J436) - LEN(SUBSTITUTE(LOWER($J436),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B436:D436)","v":0},2005,"Antiangiogenic strategies in neuroblastoma.","Ribatti",15707702,"Antiangiogenic strategies in neuroblastoma.    Abstract:   Promising new antiangiogenic strategies are emerging for the treatment of cancer and the inhibition of angiogenesis could represent a powerful adjunct to traditional therapy of malignant tumors. Over the last ten years several reports have been published concerning the relationship between tumor progression and angiogenesis in neuroblastoma in experimental models in vitro and in vivo. Moreover, a high vascular index in neuroblastoma correlates with poor prognosis, suggesting dependence of aggressive tumor growth on active angiogenesis. Here, we present an overview of recent advances in antiangiogenesis in neuroblastoma and describe the most important active substances, preclinical and clinical data, as well as future perspectives."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I437,I437)","v":15682880},{"$f":"(LEN($J437) - LEN(SUBSTITUTE(LOWER($J437),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J437) - LEN(SUBSTITUTE(LOWER($J437),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J437) - LEN(SUBSTITUTE(LOWER($J437),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B437:D437)","v":0},2004,"Diffuse idiopathic skeletal hyperostosis: Forestiers disease.","Childs",15682880,"Diffuse idiopathic skeletal hyperostosis: Forestiers disease.    Abstract:   Diffuse idiopathic skeletal hyperostosis (DISH) or Forestiers disease is characterized by calcification and ossification of soft tissue entheses of ligaments and tendons. DISH is believed to be a variant of osteoarthritis (OA) without the degenerative intervertebral disc and joint degenerative qualities seen in classic OA. The likely pathoetiologic causes of DISH are presented."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I438,I438)","v":15658253},{"$f":"(LEN($J438) - LEN(SUBSTITUTE(LOWER($J438),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J438) - LEN(SUBSTITUTE(LOWER($J438),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J438) - LEN(SUBSTITUTE(LOWER($J438),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B438:D438)","v":0},2004,"[Clinical significance of remnant-lipoprotein].","Nakamura",15658253,"[Clinical significance of remnant-lipoprotein].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I439,I439)","v":15543094},{"$f":"(LEN($J439) - LEN(SUBSTITUTE(LOWER($J439),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J439) - LEN(SUBSTITUTE(LOWER($J439),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J439) - LEN(SUBSTITUTE(LOWER($J439),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B439:D439)","v":0},2004,"Possible pathomechanisms of sudden infant death syndrome: key role of chronic hypoxia, infection/inflammation states, cytokine irregularities, and metabolic trauma in genetically predisposed infants.","Prandota",15543094,"Possible pathomechanisms of sudden infant death syndrome: key role of chronic hypoxia, infection/inflammation states, cytokine irregularities, and metabolic trauma in genetically predisposed infants.    Abstract:   Chronic hypoxia, viral infections/bacterial toxins, inflammation states, biochemical disorders, and genetic abnormalities are the most likely trigger of sudden infant death syndrome (SIDS). Autopsy studies have shown increased pulmonary density of macrophages and markedly more eosinophils in the lungs accompanied by increased T and B lymphocytes. The elevated levels of immunoglobulins, about 20% more muscle in the pulmonary arteries, increased airway smooth muscle cells, and increased fetal hemoglobin and erythropoietin are evidence of chronic hypoxia before death. Other abnormal findings included mucosal immune stimulation of the tracheal wall, duodenal mucosa, and palatine tonsils, and circulating interferon. Low normal or higher blood levels of cortisol often with petechiae on intrathoracic organs, depleted maternal IgG antibodies to endotoxin core (EndoCAb) and early IgM EndoCAb triggered, partial deletions of the C4 gene, and frequent IL-10-592*A polymorphism in SIDS victims as well as possible hypoxia-induced decreased production of antiinflammatory, antiimmune, and antifibrotic cytokine IL-10, may be responsible for the excessive reactions to otherwise harmless infections. In SIDS infants, during chronic hypoxia and times of infection/inflammation, several proinflammatory cytokines are released in large quantities, sometimes also representing a potential source of tissue damage if their production is not sufficiently well controlled, eg, by pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP). These proinflammatory cytokines down-regulate gene expression of major cytochrome P-450 and/or other enzymes with the specific effects on mRNA levels, protein expression, and enzyme activity, thus affecting metabolism of several endogenous lipophilic substances, such as steroids, lipid-soluble vitamins, prostaglandins, leukotrienes, thromboxanes, and exogenous substances. In SIDS victims, chronic hypoxia, TNF-alpha and other inflammatory cytokines, and arachidonic acid (AA) as well as n-3 polyunsaturated fatty acids (FA), stimulated and/or augmented superoxide generation by polymorphonuclear leukocytes, which contributed to tissue damage. Chronic hypoxia, increased amounts of nonheme iron in the liver and adrenals of these infants, enhanced activity of CYP2C9 regarded as the functional source of reactive oxygen species (ROS) in some endothelial cells, and nicotine accumulation in tissues also intensified production of ROS. These increased quantities of proinflammatory cytokines, ROS, AA, and nitric oxide (NO) also resulted in suppression of many CYP450 and other enzymes, eg, phosphoenolpyruvate carboxykinase (PEPCK), an enzyme important in the metabolism of FA during gluconeogenesis and glyceroneogenesis. PEPCK deficit found in SIDS infants (caused also by vitamin A deficiency) and eventually enhanced by PACAP lipolysis of adipocyte triglycerides resulted in an increased FA level in blood because of their impaired reesterification to triacylglycerol in adipocytes. In turn, the overproduction and release of FA into the blood of SIDS victims could lead to the metabolic syndrome and an early phase of type 2 diabetes. This is probably the reason for the secondary overexpression of the hepatic CYP2C8/9 content and activity reported in SIDS infants, which intensified AA metabolism. Pulmonary edema and petechial hemorrhages often present in SIDS victims may be the result of the vascular leak syndrome caused by IL-2 and IFN-alpha. Chronic hypoxia with the release of proinflammatory mediators IL-1alpha, IL-1beta and IL-6, and overloading of the cardiovascular and respiratory systems due to the narrowing airways and small pulmonary arteries of these children could also contribute to the development of these abnormalities. Moreover, chronic hypoxia of SIDS infants induced also production of hypoxia-inducible factor 1alpha (HIF-1alpha), which stimulated synthesis and release of different growth factors by vascular endothelial cells and intensified subclinical inflammatory reactions in the central nervous system, perhaps potentiated also by PACAP and VIP gene mutations. These processes could lead to the development of brainstem gliosis and disorders in the release of neuromediators important for physiologic sleep regulation. All these changes as well as eventual PACAP abnormalities could result in disturbed homeostatic control of the cardiovascular and respiratory responses of SIDS victims, which, combined with the nicotine effects and metabolic trauma, finally lead to death in these often genetically predisposed children."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I440,I440)","v":15496804},{"$f":"(LEN($J440) - LEN(SUBSTITUTE(LOWER($J440),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J440) - LEN(SUBSTITUTE(LOWER($J440),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J440) - LEN(SUBSTITUTE(LOWER($J440),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B440:D440)","v":0},2004,"Nutrients and gene expression.","De Caterina",15496804,"Nutrients and gene expression.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I441,I441)","v":15332354},{"$f":"(LEN($J441) - LEN(SUBSTITUTE(LOWER($J441),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J441) - LEN(SUBSTITUTE(LOWER($J441),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J441) - LEN(SUBSTITUTE(LOWER($J441),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B441:D441)","v":0},2004,"[Role of black bean Phaseolus vulgaris on the nutritional status of Guatemalan population].","Serrano",15332354,"[Role of black bean Phaseolus vulgaris on the nutritional status of Guatemalan population].    Abstract:   Guatemala provides an example of epidemiological superposition, in which health problems typical of developed countries and developing countries are both observed. Nutritional deficiencies in some micronutrients like vitamin A and iron coexist alongside chronic diseases such as diabetes type II and cardiovascular diseases. The importance of black beans in the normal Guatemala diet is well known:70g per capita of black beans are consumed daily. Black beans are an important sources of protein and energy in the diet. They contain quot;lentequot; digestion carbohydrates and a high proportion of non-digested carbohydrates that may be fermented in the large intestine. Theses types of carbohydrates are associated with a low glycemic response, low serum cholesterol levels, and a decrease of colon cancer risk factors. These physiological effects may be related to colonic fermentation end products (propionic and butyric acids). Black beans also contain several antinutritional compounds (enzymatic inhibitors, haemaglutenins, saponins and phytic acid, etc.), some of them thermolabiles that are partially eliminated during culinary processes and may modify the nutritional quality of beans. Black beans play a crucial role in the etiology of several diseases in Guatemala."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I442,I442)","v":15174602},{"$f":"(LEN($J442) - LEN(SUBSTITUTE(LOWER($J442),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J442) - LEN(SUBSTITUTE(LOWER($J442),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J442) - LEN(SUBSTITUTE(LOWER($J442),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B442:D442)","v":0},2003,"TSC and hemorrhagic shock.","Giassi",15174602,"TSC and hemorrhagic shock.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I443,I443)","v":15142970},{"$f":"(LEN($J443) - LEN(SUBSTITUTE(LOWER($J443),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J443) - LEN(SUBSTITUTE(LOWER($J443),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J443) - LEN(SUBSTITUTE(LOWER($J443),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B443:D443)","v":0},2004,"Peroxisome proliferator-activated receptors and atherogenesis: regulators of gene expression in vascular cells.","Marx",15142970,"Peroxisome proliferator-activated receptors and atherogenesis: regulators of gene expression in vascular cells.    Abstract:   A large body of data gathered over the past couple of years has identified the peroxisome proliferator-activated receptors (PPAR) alpha, gamma, and beta/delta as transcription factors exerting modulatory actions in vascular cells. PPARs, which belong to the nuclear receptor family of ligand-activated transcription factors, were originally described as gene regulators of various metabolic pathways. Although the PPARalpha, gamma, and beta/delta subtypes are approximately 60% to 80% homologous in their ligand- and DNA-binding domains, significant differences in ligand and target gene specificities are observed. PPARalpha is activated by polyunsaturated fatty acids and oxidized derivatives and by lipid-modifying drugs of the fibrate family, including fenofibrate or gemfibrozil. PPARalpha controls expression of genes implicated in lipid metabolism. PPARgamma, in contrast, is a key regulator of glucose homeostasis and adipogenesis. Ligands of PPARgamma include naturally occurring FA derivatives, such as hydroxyoctadecadienoic acids (HODEs), prostaglandin derivatives such as 15-deoxyDelta12,14-prostaglandin J2, and glitazones, insulin-sensitizing drugs presently used to treat patients with type 2 diabetes. Ligands for PPARbeta/delta are polyunsaturated fatty acids, prostaglandins, and synthetic compounds, some of which are presently in clinical development. PPARbeta/delta stimulates fatty acid oxidation predominantly acting in muscle. All PPARs are expressed in vascular cells, where they exhibit antiinflammatory and antiatherogenic properties. In addition, studies in various animal models as well as clinical data suggest that PPARalpha and PPARgamma activators can modulate atherogenesis in vivo. At present, no data are available relating to possible effects of PPARbeta/delta agonists on atherogenesis. Given the widespread use of PPARalpha and PPARgamma agonists in patients at high risk for cardiovascular disease, the understanding of their function in the vasculature is not only of basic interest but also has important clinical implications. This review will focus on the role of PPARs in the vasculature and summarize the present understanding of their effects on atherogenesis and its cardiovascular complications."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I444,I444)","v":15117174},{"$f":"(LEN($J444) - LEN(SUBSTITUTE(LOWER($J444),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J444) - LEN(SUBSTITUTE(LOWER($J444),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J444) - LEN(SUBSTITUTE(LOWER($J444),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B444:D444)","v":0},2004,"Recent trials of antioxidant therapy: what should we be telling our patients?","Hasnain",15117174,"Recent trials of antioxidant therapy: what should we be telling our patients?    Abstract:   The current evidence does not support the indiscriminate use of vitamins A, C, or E or beta carotene to prevent or reduce cardiovascular disease. Despite a plausible theory that antioxidants can prevent diseases caused by oxidative damage, trials thus far have not proven this. In fact, some studies found antioxidants may be harmful in some people. We review important studies of the effects of four antioxidants (vitamins A, C, and E, and beta carotene) and analyze whether the current evidence supports or confirms or rejects the presumed protective role."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I445,I445)","v":15003396},{"$f":"(LEN($J445) - LEN(SUBSTITUTE(LOWER($J445),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J445) - LEN(SUBSTITUTE(LOWER($J445),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J445) - LEN(SUBSTITUTE(LOWER($J445),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B445:D445)","v":0},2004,"The biosynthesis and nutritional uses of carotenoids.","Fraser",15003396,"The biosynthesis and nutritional uses of carotenoids.    Abstract:   Carotenoids are isoprenoid molecules that are widespread in nature and are typically seen as pigments in fruits, flowers, birds and crustacea. Animals are unable to synthesise carotenoids de novo, and rely upon the diet as a source of these compounds. Over recent years there has been considerable interest in dietary carotenoids with respect to their potential in alleviating age-related diseases in humans. This attention has been mirrored by significant advances in cloning most of the carotenoid genes and in the genetic manipulation of crop plants with the intention of increasing levels in the diet. The aim of this article is to review our current understanding of carotenoid formation, to explain the perceived benefits of carotenoids in the diet and review the efforts that have been made to increase carotenoids in certain crop plants."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I446,I446)","v":14870618},{"$f":"(LEN($J446) - LEN(SUBSTITUTE(LOWER($J446),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J446) - LEN(SUBSTITUTE(LOWER($J446),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J446) - LEN(SUBSTITUTE(LOWER($J446),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B446:D446)","v":0},2003,"Carotenoid-rich bananas: a potential food source for alleviating vitamin A deficiency.","Englberger",14870618,"Carotenoid-rich bananas: a potential food source for alleviating vitamin A deficiency.    Abstract:   This review article points out that bananas are an important food for many people in the world. Thus, banana cultivars rich in provitamin A carotenoids may offer a potential food source for alleviating vitamin A deficiency, particularly in developing countries. Many factors are associated with the presently known food sources of vitamin A that limit their effectiveness in improving vitamin A status. Acceptable carotenoid-rich banana cultivars have been identified in Micronesia, and some carotenoid-rich bananas have been identified elsewhere. Bananas are an ideal food for young children and families for many regions of the world, because of their sweetness, texture, portion size, familiarity, availability, convenience, versatility, and cost. Foods containing high levels of carotenoids have been shown to protect against chronic disease, including certain cancers, cardiovascular disease, and diabetes. Because the coloration of the edible flesh of the banana appears to be a good indicator of likely carotenoid content, it may be possible to develop a simple method for selecting carotenoid-rich banana cultivars in the community. Research is needed on the identification of carotenoid-rich cultivars, targeting those areas of the world where bananas are a major staple food; investigating factors affecting production, consumption, and acceptability; and determining the impact that carotenoid-rich bananas may have on improving vitamin A status. Based on these results, interventions should be undertaken for initiating or increasing homestead and commercial production."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I447,I447)","v":14704330},{"$f":"(LEN($J447) - LEN(SUBSTITUTE(LOWER($J447),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J447) - LEN(SUBSTITUTE(LOWER($J447),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J447) - LEN(SUBSTITUTE(LOWER($J447),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B447:D447)","v":0},2004,"Carotenoid action on the immune response.","Chew",14704330,"Carotenoid action on the immune response.    Abstract:   Early studies demonstrating the ability of dietary carotenes to prevent infections have left open the possibility that the action of these carotenoids may be through their prior conversion to vitamin A. Subsequent studies to demonstrate the specific action of dietary carotenoids have used carotenoids without provitamin A activity such as lutein, canthaxanthin, lycopene and astaxanthin. In fact, these nonprovitamin A carotenoids were as active, and at times more active, than beta-carotene in enhancing cell-mediated and humoral immune response in animals and humans. Another approach to study the possible specific role of dietary carotenoids has used animals that are inefficient converters of carotenoids to vitamin A, for example the domestic cat. Results have similarly shown immuno-enhancement by nonprovitamin A carotenoids, based either on the relative activity or on the type of immune response affected compared to beta-carotene. Certain carotenoids, acting as antioxidants, can potentially reduce the toxic effects of reactive oxygen species (ROS). These ROS, and therefore carotenoids, have been implicated in the etiology of diseases such as cancer, cardiovascular and neurodegenerative diseases and aging. Recent studies on the role of carotenoids in gene regulation, apoptosis and angiogenesis have advanced our knowledge on the possible mechanism by which carotenoids regulate immune function and cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I448,I448)","v":13677624},{"$f":"(LEN($J448) - LEN(SUBSTITUTE(LOWER($J448),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J448) - LEN(SUBSTITUTE(LOWER($J448),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J448) - LEN(SUBSTITUTE(LOWER($J448),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B448:D448)","v":0},2002,"Oxidant-antioxidant system: role and significance in human body.","Irshad",13677624,"Oxidant-antioxidant system: role and significance in human body.    Abstract:   Present article gives a holistic view of the causes, role and conrol of oxidative stress in the development and progression of various human diseases. Several types of reactive species are generated in the body as a result of metabolic reactions in the form of free radicals or non-radicals. These species may be either oxygen derived or nitrogen derived and called prooxidants. They attack macromolecules including protein, DNA and lipid etc. causing cellular/tissue damage. To counter their effect, the body is endowed with another category of compounds called antioxidants. These antioxidants are produced either endogenously or received from exogenous sources and include enzymes like superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, minerals like Se, Mn, Cu and Zn, and vitamins like vitamin A, C and E. Other compounds with antioxidant activity include glutathione, flavonoids, bilirubin and uric acid etc.. In a healthy body, prooxidants and antioxidants maintain a ratio and a shift in this ratio towards prooxidants gives rise to oxidative stress. This oxidative stress may be either mild or severe depending on the extent of shift and remains the cause of several diseases such as cardiovascular diseases, neurological diseases, malignancies, renal diseases, diabetes, inflammatory problems, skin diseases, aging, respiratory diseases, liver diseases and different types of viral infections. As more and more reports are pouring in, a lot of information is being unfolded about oxidative stress in relation to several other diseases."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I449,I449)","v":12964804},{"$f":"(LEN($J449) - LEN(SUBSTITUTE(LOWER($J449),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J449) - LEN(SUBSTITUTE(LOWER($J449),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J449) - LEN(SUBSTITUTE(LOWER($J449),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B449:D449)","v":0},2003,"Biofactors in the Mediterranean diet.","Gerber",12964804,"Biofactors in the Mediterranean diet.    Abstract:   This Review covers the sources and the main effects on human health of well-known micronutrients such as minerals and vitamins and also of microconstituents contained in the Mediterranean diet. Vitamins were first identified because of deficiency diseases still present in certain parts of the world. Hydrosoluble vitamins, among them folic acid and vitamin C, also play a role in chronic degenerative diseases, not only the main cause of mortality in the Western world but also increasingly common in developing countries. Hydrosoluble vitamins are well represented in the Mediterranean diet, more so than vitamin A, a liposoluble vitamin obtained primarily from animal foods. Vitamin E is important for antioxidant and cellular functions. The Mediterranean diet is also rich in provitamins A, such as alpha- and beta-carotene and beta-cryptoxanthine. Microconstituents are non-nutritional compounds known to protect plants and more recently suspected to have a protective effect in humans. They play a role in the antioxidant defense of the organism, but their effect on various enzyme activities appears even more promising and is still under investigation. It is nevertheless difficult to isolate the effect of the numerous biofactors present in the Mediterranean diet from the foods themselves, especially because of the possible synergy between the various biofactors."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I450,I450)","v":12963947},{"$f":"(LEN($J450) - LEN(SUBSTITUTE(LOWER($J450),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J450) - LEN(SUBSTITUTE(LOWER($J450),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J450) - LEN(SUBSTITUTE(LOWER($J450),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B450:D450)","v":0},2003,"Benefits of fish oil supplementation for hemodialysis patients.","Vergili-Nelsen",12963947,"Benefits of fish oil supplementation for hemodialysis patients.    Abstract:   A literature review on fish oil supplementation in the population undergoing chronic hemodialysis therapy suggests that supplementation may be beneficial for various challenges to health and well-being prevalent in this population. One study indicated that pruritus symptoms improved with fish oil supplementation, but not with supplementation with two other oils. In a study designed to determine whether fish oils could prevent vascular access graft thrombosis, graft patency rates were approximately 76% in the fish oil and approximately 15% in the placebo group (Pgt;.03). In a pilot study, subjects given fish oil required 16% less erythropoietin and experienced a 3.6% increase in serum albumin levels. Some studies suggest that fish oil supplementation in hemodialysis patients is cardioprotective, with one study finding that quot;fish eatersquot; are half as likely to die as quot;non-fish eaters.quot; Potential risks of supplementation include gastrointestinal distress, prolonged bleeding, and vitamin A toxicity, although the likelihood of serious side effects is probably low. Dietitians are in a position to advise physicians and/or patients regarding appropriate dosages and ways to minimize risks when supplementation seems warranted. Future research could compare the benefits of fish consumption with those of fish oil supplementation and explore the benefits of other n-3 fatty acid sources, such as flaxseed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I451,I451)","v":12915216},{"$f":"(LEN($J451) - LEN(SUBSTITUTE(LOWER($J451),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J451) - LEN(SUBSTITUTE(LOWER($J451),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J451) - LEN(SUBSTITUTE(LOWER($J451),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B451:D451)","v":0},2003,"Metabolic effects of plant sterols and stanols (Review).","de Jong",12915216,"Metabolic effects of plant sterols and stanols (Review).    Abstract:   High serum LDL cholesterol concentration is a major risk factor for cardiovascular complications. This risk can be lowered by diet. In this respect foods containing plant sterol or stanol esters can be useful for mildly- and hypercholesteraemic subjects. Plant sterols and stanols, which are structurally related to cholesterol, decrease the incorporation of dietary and biliary cholesterol into micelles. This lowers cholesterol absorption. Furthermore, these components increase ABC-transporter expression, which may also contribute to the decreased cholesterol absorption. Consequently, cholesterol synthesis and LDL receptor activity increase, which ultimately leads to decreased serum LDL cholesterol concentrations. Animal studies have further shown that these dietary components may also lower atherosclerotic lesion development. Plant sterols and stanols also lower plasma lipid-standardized concentrations of the hydrocarbon carotenoids, but not those of the oxygenated cartenoids and tocopherols. Also, vitamin A and D concentrations are not affected. Although absorption of plant sterols and stanols (0.02-3.5%) is low compared to cholesterol (35-70%), small amounts are found in the circulation and may influence other physiological functions. However, there is no consistent evidence that plant sterols or stanols can change the risk of colon or prostate cancer, or immune status. In conclusion, plant sterols and stanols effectively reduce serum LDL cholesterol and atherosclerotic risk. In addition potential effects of plant sterols and stanols on other metabolic processes remain to be elucidated."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I452,I452)","v":12885273},{"$f":"(LEN($J452) - LEN(SUBSTITUTE(LOWER($J452),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J452) - LEN(SUBSTITUTE(LOWER($J452),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J452) - LEN(SUBSTITUTE(LOWER($J452),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B452:D452)","v":0},2003,"Molecular targets as therapeutic strategies in the management of breast cancer.","Russo",12885273,"Molecular targets as therapeutic strategies in the management of breast cancer.    Abstract:   Although the molecular and genetic determinants of most sporadic breast cancers remain unknown, increasing understanding of molecular and genetic events affecting breast carcinogenesis has provided information about the potential roles of specific biomarkers in tumour development and spread. It is now recognised that mutations of some tumour suppressor genes appear to play important early roles in the formation of some breast cancers. In addition, alterations in proto-oncogenes may contribute to the development of some breast cancers. The study of breast tumour biology at the molecular level has led to the development of targeted drug design, which provides a variety of agents targeted at specific molecules for the prevention, diagnosis and treatment of breast cancer. This review will describe the recognised molecular targets in breast cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I453,I453)","v":12842416},{"$f":"(LEN($J453) - LEN(SUBSTITUTE(LOWER($J453),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J453) - LEN(SUBSTITUTE(LOWER($J453),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J453) - LEN(SUBSTITUTE(LOWER($J453),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B453:D453)","v":0},2003,"Programming the cardiovascular system, kidney and the brain--a review.","Wintour",12842416,"Programming the cardiovascular system, kidney and the brain--a review.    Abstract:   The concept that life before birth or the first environment is important in determining subsequent risk for the development of cardiovascular/metabolic disease is now gaining acceptance. There are substantial data from animal experiments that complement and enhance the epidemiological data from human studies. We argue that any factor which disrupts nephrogenesis, and lowers nephron number, during the period of active nephrogenesis, will induce malapadaptive changes in the future functioning of that kidney and predispose to the onset of adult hypertension. Such factors include exposure of the mother, to a particular low-protein diet, excess synthetic or natural glucocorticoid at certain critical periods, mild vitamin A deficiency, elevated blood glucose, unilateral nephrectomy during the period of nephrogenesis, as well as the deletion of one allele of a gene (GDNF) involved in normal metanephric development. All of these stresses are associated with a reduction (20-40 per cent) in total nephron number in the adult, and the development of hypertension. In some hypertensive models, (rats) there is evidence of alterations in the components of the hippocampal/hypothalamic/pituitary/adrenal axis, whereas in others (sheep) there are alterations in the expression of angiotensinogen (hypothalamus) and angiotensin II receptor type I (AT(1)) in the medulla oblongata. The surprising finding is that the period when the kidney and brain are most vulnerable is very early in development, when both organs are in an extremely primitive state of development."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I454,I454)","v":12747216},{"$f":"(LEN($J454) - LEN(SUBSTITUTE(LOWER($J454),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J454) - LEN(SUBSTITUTE(LOWER($J454),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J454) - LEN(SUBSTITUTE(LOWER($J454),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B454:D454)","v":0},2003,"Non-nutritive bioactive constituents of plants: lycopene, lutein and zeaxanthin.","Sies",12747216,"Non-nutritive bioactive constituents of plants: lycopene, lutein and zeaxanthin.    Abstract:   Lycopene, lutein, and zeaxanthin are major carotenoids in human blood and tissues but unlike beta-carotene do not contribute to vitamin A supply. These carotenoids are efficient antioxidants quenching singlet molecular oxygen which is formed in photooxidative processes and thus may contribute to the prevention of light-exposed tissue, skin and eyes, from light-induced damage. Increasing lycopene intake by daily consumption of tomato paste over a period of ten weeks provides protection against erythema formation following UV-irradiation. Lycopene and other carotenoids may be used as oral sun protectants and contribute to the maintenance of skin health. The yellow color of the macula lutea is due to the presence of the carotenoid pigments lutein and zeaxanthin. These macula carotenoids are suggested to play a role in protection against light-dependent damage. Filtering of blue light and scavenging of reactive intermediates generated in photooxidation are considered to be the underlying protective mechanisms. Epidemiological studies provide evidence that an increased consumption of lutein is associated with a lowered risk for age-related macular degeneration, a disease with increasing incidence in the elderly."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I455,I455)","v":12675072},{"$f":"(LEN($J455) - LEN(SUBSTITUTE(LOWER($J455),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J455) - LEN(SUBSTITUTE(LOWER($J455),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J455) - LEN(SUBSTITUTE(LOWER($J455),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B455:D455)","v":0},1998,"A review of vitamins A, C, and E and their relationship to cardiovascular disease.","Brown",12675072,"A review of vitamins A, C, and E and their relationship to cardiovascular disease.    Abstract:   Cardiovascular disease (CVD), particularly in the form of coronary artery disease, is the leading cause of death in the United States. Research in the past 10 years links pathogenic low-density lipoprotein (LDL) modification to oxidation damage by free radicals. This review summarizes the major findings of CVD-related epidemiologic research and clinical trials conducted in the past 5 years on vitamins A, C, and E. Vitamin supplementation behaviors are discussed. In prospective studies, the intake of vitamins A, C, and E has been correlated with lower mortality rates. When recent clinical trials and oxidation studies are analyzed, the weight of evidence suggests that 100-400 IU of daily vitamin E over 2 years or more may be most efficacious in reducing low-density lipoprotein oxidation and positively influencing mortality rates from CVD in primary care. Research also supports vitamin E supplementation in patients with known CAD or a history of transient ischemic attacks. Persons with diabetes or hypertension as well as smokers may benefit from supplemental vitamin C intake. Targeted antioxidant vitamin intake should be included in CVD risk assessment and primary preventive counseling efforts."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I456,I456)","v":12667888},{"$f":"(LEN($J456) - LEN(SUBSTITUTE(LOWER($J456),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J456) - LEN(SUBSTITUTE(LOWER($J456),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J456) - LEN(SUBSTITUTE(LOWER($J456),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B456:D456)","v":0},2003,"Muscarinic acetylcholine receptors and airway diseases.","Coulson",12667888,"Muscarinic acetylcholine receptors and airway diseases.    Abstract:   Parasympathetic nerves provide the dominant autonomic innervation of the airways. Release of acetylcholine from parasympathetic nerves activates postjunctional muscarinic receptors present on airway smooth muscle, submucosal glands, and blood vessels to cause bronchoconstriction, mucus secretion, and vasodilatation, respectively. Acetylcholine also feeds back onto prejunctional muscarinic receptors to enhance or inhibit further acetylcholine release. In asthma and chronic obstructive pulmonary disease, bronchoconstriction and mucus secretion is increased and the airways are hyperresponsive to contractile agents. These changes are due to increased parasympathetic nerve activity. The number and function of postjunctional muscarinic receptors in the airways are unchanged in animal models of asthma. Rather, it is the supply of acetylcholine to the postjunctional cells (smooth muscle and submucosal gland) that is increased. The increase in acetylcholine release occurs because prejunctional, inhibitory M(2) muscarinic receptors on the parasympathetic nerves are dysfunctional. M(2) muscarinic receptor dysfunction and subsequent airway hyperreactivity have been demonstrated to occur in animals in response to a variety of triggers, including antigen challenge, virus infection, ozone exposure, and vitamin A deficiency. In humans, there is evidence that loss of M(2) muscarinic receptor function is related to asthma. The mechanisms by which neuronal M(2) muscarinic receptor function is lost and its relevance to human airway disease are discussed in this review."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I457,I457)","v":12643171},{"$f":"(LEN($J457) - LEN(SUBSTITUTE(LOWER($J457),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J457) - LEN(SUBSTITUTE(LOWER($J457),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J457) - LEN(SUBSTITUTE(LOWER($J457),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B457:D457)","v":0},2002,"Antioxidant vitamins and their influence in diabetes mellitus.","Hasanain",12643171,"Antioxidant vitamins and their influence in diabetes mellitus.    Abstract:   Diabetes mellitus is a chronic disease associated with serious complications. A number of studies have suggested that enhanced oxidation is the underlying abnormality responsible for some of the complications of diabetes. It is not known whether the ingestion of antioxidant vitamins could retard or perhaps reverse the oxidative damage. The information regarding the benefit of antioxidant vitamin supplementation is conflicting some trials have demonstrated adverse effects of excessive consumption of vitamin supplements. In this article, we review the available literature on the association of cardiovascular events and ingestion of vitamins with antioxidant properties. Given the lack of data to substantiate the benefit and safety of ingestion of antioxidant vitamins in excess of the recommended dietary allowance, physicians should avoid the recommendation of vitamin supplementation to their patients."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I458,I458)","v":12608503},{"$f":"(LEN($J458) - LEN(SUBSTITUTE(LOWER($J458),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J458) - LEN(SUBSTITUTE(LOWER($J458),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J458) - LEN(SUBSTITUTE(LOWER($J458),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B458:D458)","v":0},2002,"Vitamin nutrition in older adults.","Johnson",12608503,"Vitamin nutrition in older adults.    Abstract:   Proper vitamin nutrition is essential for all people but especially for elderly persons, because they are at higher risk for deficiency than younger adults. A review of the clinical effects of vitamin deficiency shows how easily deficiency can masquerade as other morbidities, such as skin, neurologic, and gait abnormalities. Given the numerous readily available forms and sources of supplementation, their low cost, and their rather limited potential for harm, the goal of good vitamin nutrition for the elderly is easily attainable. To be successful in this goal, physicians must look for patients at risk and for those with features of frank vitamin deficiency. Laboratory testing is most helpful with respect to vitamin B12 and folate deficiency. Given the great value of clinical assessment, the low cost of vitamins, and the higher cost of laboratory testing, the authors do not recommend testing before instituting multivitamin use or extra supplementation with individual vitamins unless the diagnosis of deficiency is in question or the use of supplementation would put the patient at risk. The authors general recommendations are * one multivitamin daily * extra vitamin E for patients with cardiovascular risk factors or Alzheimers dementia * extra vitamin D for patients with known osteoporosis, osteoporosis risk factors, or strong risk factors for vitamin D deficiency * extra folate for patients with cardiovascular risk factors (especially smokers) and alcoholics * extra thiamine for alcoholics."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I459,I459)","v":12452732},{"$f":"(LEN($J459) - LEN(SUBSTITUTE(LOWER($J459),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J459) - LEN(SUBSTITUTE(LOWER($J459),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J459) - LEN(SUBSTITUTE(LOWER($J459),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B459:D459)","v":0},2002,"Minimising the long-term adverse effects of childhood leukaemia therapy.","Langebrake",12452732,"Minimising the long-term adverse effects of childhood leukaemia therapy.    Abstract:   Malignancies in childhood occur with an incidence of 13-14 per 100,000 children under the age of 15 years. Acute lymphoblastic leukaemia with an incidence of 29% is the most common paediatric malignancy, whereas acute myeloid leukaemias account for about 5%. The treatment of acute leukaemias consists of sequential therapy cycles (induction, consolidation, intensification, maintenance therapy) with different cytostatic drugs over a time period of up to 1.5-3 years. Over the last 25 years of clinical trials, a significant rise in the rate of complete remissions as well as an increase in long-term survival has been achieved. Therefore, growing attention is now focused on the long-term effects of antileukaemic treatment. Several cytostatic drugs administered in the treatment of acute leukaemia in childhood are known to cause long-term adverse effects. Anthracyclines may induce chronic cardiotoxicity, alkylating agents are likely to cause gonadal damage and secondary malignancies and the use of glucocorticoids may cause osteonecrosis. Most of the long-term adverse effects have not been analysed systematically. Approaches to minimising long-term adverse effects without jeopardising outcome have included: the design of new drugs such as a liposomal formulation of anthracyclines, the development of anthracycline-derivates with lower toxicity, the development of cardioprotective agents or, more recently, the use of targeted therapy;alternative administration schedules like continuous infusion or timed sequential therapy; and risk group stratification by the monitoring of minimal residual disease. Several attempts have been made to minimise the cardiotoxicity of anthracyclines: decreasing concentrations delivered to the myocardium by either prolonging infusion time or using liposomal formulated anthracyclines or less cardiotoxic analogues, or the additional administration of cardioprotective agents. The advantage of these approaches is still controversial, but there are ongoing clinical trials to evaluate the long-term effects. The use of new diagnostic methods, such as diagnosis of minimal residual disease, which allow reduction or optimisation of dose, offer potential advantages compared with conventional treatment in terms of reducing the risk of severe long-term adverse effects. Most options for minimising long-term adverse effects have resulted from theoretical models and in vitro studies, but only some of the modalities such as the use of dexrazoxane, the continuous infusion of anthracyclines or timed sequential therapy, have been evaluated in prospective, randomised studies in patients. Future approaches to predict severe toxicity may be based upon pharmacogenetics and gene profiling."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I460,I460)","v":12410622},{"$f":"(LEN($J460) - LEN(SUBSTITUTE(LOWER($J460),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J460) - LEN(SUBSTITUTE(LOWER($J460),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J460) - LEN(SUBSTITUTE(LOWER($J460),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B460:D460)","v":0},2002,"The interaction of cigarette smoking and antioxidants. Part I: diet and carotenoids.","Kelly",12410622,"The interaction of cigarette smoking and antioxidants. Part I: diet and carotenoids.    Abstract:   It is logical that the requirement for antioxidant nutrients depends on a persons exposure to endogenous and exogenous reactive oxygen species. Since cigarette smoking results in an increased cumulative exposure to reactive oxygen species from both sources, it would seem cigarette smokers would have an increased requirement for antioxidant nutrients. Logic dictates that a diet high in antioxidant-rich foods such as fruits, vegetables, and spices would be both protective and a prudent preventive strategy for smokers. This review examines available evidence of fruit and vegetable intake, and supplementation of antioxidant compounds by smokers in an attempt to make more appropriate nutritional recommendations to this population."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I461,I461)","v":12296961},{"$f":"(LEN($J461) - LEN(SUBSTITUTE(LOWER($J461),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J461) - LEN(SUBSTITUTE(LOWER($J461),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J461) - LEN(SUBSTITUTE(LOWER($J461),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B461:D461)","v":0},2002,"Mesenchymal cells in the liver--one cell type or two?","Ramadori",12296961,"Mesenchymal cells in the liver--one cell type or two?    Abstract:   The wall of the liver sinusoid is made of highly specialized cells, the hepatic stellate cells (HSC) which together with the sinusoidal endothelial cells represent a loose barrier to the corpusculate part of the blood flowing through the liver. Quiescent stellate cells (quiescent HSC) store Vitamin A; quot;activatedquot; stellate cells become involved in the reaction to acute or chronic noxae damaging the liver parenchyma. Activated HSC show increased protein synthesis capacity, increased DNA-synthesis and acquire a myofibroblast-like phenotype. Under similar conditions liver myofibroblasts (MF) of the portal field and of the pericentral area may also become quot;activatedquot; by increasing protein synthesis, DNA synthesis and cell division. They express the fibulin-2 gene and produce large amounts of IL-6. In contrast to quot;activatedquot; HSC they do not undergo spontaneous apoptosis in vitro and do not express the CD95-ligand gene. So far no definite prove has been found for a quot;transdifferentiationquot; of HSC to myofibroblasts. On the contrary an increasing amount of data support the conviction that HSC and MF represent two similar but not identical cell populations the latter being comparable to those of other organs."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I462,I462)","v":12243361},{"$f":"(LEN($J462) - LEN(SUBSTITUTE(LOWER($J462),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J462) - LEN(SUBSTITUTE(LOWER($J462),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J462) - LEN(SUBSTITUTE(LOWER($J462),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B462:D462)","v":0},2002,"Oxidative stress and chronic renal failure: markers and management.","Massy",12243361,"Oxidative stress and chronic renal failure: markers and management.    Abstract:   New reliable oxidative stress markers are present in chronic renal failure (CRF) patients, indicating that CRF is a pro-oxidant state. However, the pathogenesis of oxidative stress in CRF patients remains poorly defined. Moreover, the limited data available provide no clear-cut evidence in favor of the clinical benefit of antioxidant manoeuvres aimed at reducing cardiovascular disease in CRF patients or in the general population as well. Therefore, no practical recommendations can be given at this stage, and further studies are clearly needed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I463,I463)","v":11769876},{"$f":"(LEN($J463) - LEN(SUBSTITUTE(LOWER($J463),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J463) - LEN(SUBSTITUTE(LOWER($J463),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J463) - LEN(SUBSTITUTE(LOWER($J463),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B463:D463)","v":0},2001,"Results and lessons from clinical trials using dietary supplements for cancer: direct and indirect investigations.","Moyad",11769876,"Results and lessons from clinical trials using dietary supplements for cancer: direct and indirect investigations.    Abstract:   Randomized controlled trials are generally regarded as the standard of study designs to determine potential causality. The inclusion of a placebo group in these trials, when appropriate, is generally needed to access the efficacy of a drug or dietary supplement. The recent increasing use of dietary supplements and herbal medications by patients makes it imperative to reevaluate the past findings of clinical studies. Several large-scale trials of dietary supplements have been tested in various populations to determine their effect on cancer prevention. Other trials have focused on patients already diagnosed with cancer. In the latter case, it is difficult to involve a placebo because of the serious nature of the disease. Nevertheless, much has been gleaned from these trials directly and indirectly. Overall, when analyzing primary endpoints in these trials, the results have been discouraging and even support the nonuse of certain supplements because of potential adverse effects. Other secondary endpoints in these same trials have revealed some potential encouraging and discouraging data. Individuals who currently qualify for the potential use of dietary supplements for cancer may be restricted to those who have a deficiency in a certain compound despite adequate dietary sources or lifestyle changes. Those individuals with a smoking history or other unhealthy lifestyle seem to have the most to gain or lose from taking certain dietary supplements for cancer. The time seems more than ripe to evaluate past adequate trials with supplements, such as beta-carotene, N-acetyl-cysteine, selenium, shark cartilage, vitamin C, vitamin E, and others. Again, these studies have been disappointing, but they provide insight for the clinician and patient of what to potentially expect when using these supplements for cancer. In addition, indirect trials for other conditions (cardiovascular) may provide future insight into possible results for future cancer prevention trials."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I464,I464)","v":11519231},{"$f":"(LEN($J464) - LEN(SUBSTITUTE(LOWER($J464),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J464) - LEN(SUBSTITUTE(LOWER($J464),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J464) - LEN(SUBSTITUTE(LOWER($J464),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B464:D464)","v":0},2001,"[The role of alimentary oxidants and antioxidants in carcinogenesis].","Vizer",11519231,"[The role of alimentary oxidants and antioxidants in carcinogenesis].    Abstract:   Malignancies have a distinguished role among leading causes of death around the world. As a result of more effective preventive efforts of cardiovascular diseases malignancies will reach the top of death statistics in the near future. The increased incidence of malignant tumors may be attributed to smoking, in temperate alcohol abuse, as well as inappropriate nutrition. Inappropriate nutrition is thought to be responsible for the development of about 30-50% of malignancies. In the present review the authors analyze the uniform theory of carcinogenesis and the possible mechanisms by which certain nutritive factors may interfere with the complex process of carcinogenesis. The mechanism of quot;oxidative stressquot; is detailed, in particular the impact of prooxidants (also referred to as free radicals) on tumor development and the central role of lipid peroxidation. In addition to alimentary free radicals the relevance of alcohol abuse in carcinogenesis is also studied. Against the undesirable free radical reactions a complex natural antioxidant (free radical scavenger) system exists, that is responsible for anticarcinogenesis. The authors introduce the dietary antioxidants, their known effects of mechanisms, and their possible role in chemoprevention and therapy of malignancies, based on several experimental and epidemiological data."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I465,I465)","v":11505163},{"$f":"(LEN($J465) - LEN(SUBSTITUTE(LOWER($J465),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J465) - LEN(SUBSTITUTE(LOWER($J465),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J465) - LEN(SUBSTITUTE(LOWER($J465),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B465:D465)","v":0},2001,"Additional insights into the etiology of cardiac anomalies.","Werler",11505163,"Additional insights into the etiology of cardiac anomalies.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I466,I466)","v":11450594},{"$f":"(LEN($J466) - LEN(SUBSTITUTE(LOWER($J466),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J466) - LEN(SUBSTITUTE(LOWER($J466),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J466) - LEN(SUBSTITUTE(LOWER($J466),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B466:D466)","v":0},2001,"Professor Toshio Ito: a clairvoyant in pericyte biology.","Suematsu",11450594,"Professor Toshio Ito: a clairvoyant in pericyte biology.    Abstract:   Ito cells are liver-specific pericytes which were first described as Fett Speicherung Zellen, the fat-storing cells encircling outside sinusoidal endothelial cells, in 1951 by the late professor Toshio Ito. His pioneering approaches for morphological characterization of the cells stimulate investigators to further examine their functional roles in liver homeostasis: a body of evidence has been accumulated in recent years showing that the cells play a crucial role in storage and delivery of vitamin A, regulation of sinusoidal tone and local blood supply, and tissue repair and fibrosis. It is now widely accepted that microvascular pericytes including Ito cells serve as a key player that controls angiogenesis. Furthermore, recent studies support a concept that Ito cells constitutes a bridging apparatus mediating bidirectional metabolic interactions between sinusoids and hepatocytes, utilizing prostanoids and/or gaseous mediators such as nitric oxide and carbon monoxide as signaling molecules. This article reviews researches on this liver-specific pericyte and its leading roles in recent development of pericyte biology."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I467,I467)","v":11385132},{"$f":"(LEN($J467) - LEN(SUBSTITUTE(LOWER($J467),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J467) - LEN(SUBSTITUTE(LOWER($J467),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J467) - LEN(SUBSTITUTE(LOWER($J467),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B467:D467)","v":0},2001,"Maternal vitamin A administration and the fetal ductus arteriosus.","Shaul",11385132,"Maternal vitamin A administration and the fetal ductus arteriosus.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I468,I468)","v":11263011},{"$f":"(LEN($J468) - LEN(SUBSTITUTE(LOWER($J468),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J468) - LEN(SUBSTITUTE(LOWER($J468),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J468) - LEN(SUBSTITUTE(LOWER($J468),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B468:D468)","v":0},2001,"[Are there effective dietary recommendations for patients with rheumatoid arthritis?].","Keysser",11263011,"[Are there effective dietary recommendations for patients with rheumatoid arthritis?].    Abstract:   Patients with rheumatic diseases frequently ask the physician for diet recommendations. Although much has been written about this subject, scientifically validated studies investigating the impact of certain diets on rheumatoid arthritis are scant and often inconclusive. Elimination diets or total fasting is believed to eliminate food ingredients that cause or aggravate arthritis. In contrast, supplementation with fish oil, gamma-linoleic acid or vitamin E is directed at anti-oxidative and anti-inflammatory effects of these food compounds. So far, both approaches have failed to reveal a significant benefit with respect to objective signs of inflammation. Supplementation with other vitamins such as vitamin A and C, or with trace elements like selenium and zinc are of no proven influence on the disease activity as well. There is a higher request for calcium and vitamin D in patients with active RA under steroid treatment to prevent osteoporosis. In addition, patients with active RA have a slightly increased risk for cardiovascular events. Therefore, cholesterol-lowering diets and drugs should be applied early."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I469,I469)","v":11245279},{"$f":"(LEN($J469) - LEN(SUBSTITUTE(LOWER($J469),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J469) - LEN(SUBSTITUTE(LOWER($J469),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J469) - LEN(SUBSTITUTE(LOWER($J469),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B469:D469)","v":0},2000,"Antiangiogenesis -- therapeutic strategies and clinical implications for brain tumors.","Puduvalli",11245279,"Antiangiogenesis -- therapeutic strategies and clinical implications for brain tumors.    Abstract:   The poor prognosis of patients with malignant brain tumors in spite of aggressive multimodality therapy has led to the search for novel therapeutic strategies. Among the targets for such treatment approaches, tumor angiogenesis has captured the attention of not only the medical field but also of the lay public because of its conceptual departure from traditional methods of cancer therapy. Angiogenesis and vascular proliferation are particularly important in the growth and progression of malignant gliomas and are used as indicators of the degree of malignancy. Recent studies have helped us gain a better understanding of the molecular mediators of this process. It is now evident that after the initial formation of malignancy the continued growth of a glioma is critically dependent on its angiogenic potential. Hence, several approaches to control angiogenesis are being developed and tested. In the present review, we examine some of these approaches from a therapeutic perspective and summarize the findings from early human trials of such agents."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I470,I470)","v":11220289},{"$f":"(LEN($J470) - LEN(SUBSTITUTE(LOWER($J470),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J470) - LEN(SUBSTITUTE(LOWER($J470),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J470) - LEN(SUBSTITUTE(LOWER($J470),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B470:D470)","v":0},1999,"The relation between insulin resistance and cardiovascular complications of the insulin resistance syndrome.","Rett",11220289,"The relation between insulin resistance and cardiovascular complications of the insulin resistance syndrome.    Abstract:   It has been known for years that cardiovascular disease frequently precedes the development of type 2 diabetes, and that atherosclerosis might not be a complication of type 2 diabetes, but rather the consequence of common genetic and environmental factors (the common soil hypothesis). The insulin resistance syndrome (IRS) is a cluster of closely associated and interdependent abnormalities, including insulin resistance, hyperinsulinaemia, android fat distribution, progressive glucose intolerance, dyslipidaemia (increased triglycerides, decreased HDL, increased small dense LDL), increased prothrombotic and antifibrinolytic factors, and hypertension. Many of these abnormalities are risk factors for type 2 diabetes, and most of them explain the predilection for atherosclerosis to occur in conjunction with IRS. Insulin resistance is a key feature of IRS, and has been suggested to be the common pathophysiological basis of atherosclerosis and type 2 diabetes. The term insulin resistance denotes resistance to insulin-mediated glucose uptake into skeletal muscle, which can be measured by the glucose clamp technique. There are, however, other less understood sites of abnormal insulin action that may also be relevant in IRS. These include liver, adipose, and kidney tissue, and systems such as muscle perfusion, antilipolysis, lipoprotein lipase activity, and cation transport. The development of clinical cardiovascular end-points in a patient with insulin resistance is complex, as it includes the degree of the defect, its associated abnormalities, its consequences, and the ability to compensate for the underlying defect. It is therefore more appropriate to consider the different facets and risk factors of IRS in aggregate, rather than seeking independent effects. Accordingly, treatment of insulin resistance per se has not yet been shown to reduce the incidence of cardiovascular complications. At the cellular level, excess insulin is involved in various elements of atherogenesis. It interacts with cytokines and growth factors in a cross talk among vascular wall cells and a variety of mediators that play a role in the establishment of atheroma. Excess insulin also plays an important role in concert with lipoproteins when they exhibit an abnormal pattern and become modified by oxidation and glycation. It is therefore currently hoped that the introduction of a new class of insulin-sensitizing agents, the thiazolidinediones, may attenuate these processes. The thiazolidinediones act through ligand activation of a nuclear transcription factor, the peroxisomal proliferator-activated receptor-gamma (PPARgamma). Although this receptor was initially linked to lipid and glucose metabolism, recent data suggest that PPARgamma is also involved in the differentiation of mononuclear phagocytes, their inflammatory reactions, and macrophage conversion to foam cells. Thus, PPARgamma ligands may also be important regulators of monocyte/ macrophage gene expression during atherogenesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I471,I471)","v":10849120},{"$f":"(LEN($J471) - LEN(SUBSTITUTE(LOWER($J471),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J471) - LEN(SUBSTITUTE(LOWER($J471),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J471) - LEN(SUBSTITUTE(LOWER($J471),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B471:D471)","v":0},2000,"The effects of drugs on wound healing--part II. Specific classes of drugs and their effect on healing wounds.","Karukonda",10849120,"The effects of drugs on wound healing--part II. Specific classes of drugs and their effect on healing wounds.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I472,I472)","v":10681665},{"$f":"(LEN($J472) - LEN(SUBSTITUTE(LOWER($J472),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J472) - LEN(SUBSTITUTE(LOWER($J472),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J472) - LEN(SUBSTITUTE(LOWER($J472),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B472:D472)","v":0},1999,"Vitamin replacement therapy in renal failure patients.","Makoff",10681665,"Vitamin replacement therapy in renal failure patients.    Abstract:   Renal failure patients require vitamin replacement therapy that addresses the specialized needs of renal failure. Four factors including restricted diet, uremic toxins, drug-nutrient interactions, and in ESRD, the dialysis process, affect the normal absorption, retention and activity of necessary micronutrients which support all aspects of carbohydrate, protein, lipid and nucleic acid metabolism. Studies have shown that the typical renal failure diet is low in B vitamins, that uremic factors affect folate and pyridoxine activities and that many B vitamins are lost on dialysis at a rate greater than are lost with normal urinary excretion. In addition, retention of vitamin A or inappropriately high supplementation of vitamin C may cause toxicities which exacerbate existing pathologies. Further, emerging research suggests some vitamins such as folic acid and pyridoxine, if provided in higher than normal amounts, may have an impact on reducing the risk of some aspects of renal cardiovascular disease. It is therefore important to supplement some vitamins, and use restraint in the supplementation of others. It is clear that renal failure patients, including predialysis, ESRD and transplant patients need specialized supplementation that meets the requirements of disease and its management."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I473,I473)","v":9739768},{"$f":"(LEN($J473) - LEN(SUBSTITUTE(LOWER($J473),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J473) - LEN(SUBSTITUTE(LOWER($J473),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J473) - LEN(SUBSTITUTE(LOWER($J473),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B473:D473)","v":0},1998,"[Antioxidative vitamins: prevention of cardiovascular diseases].","Lengfelder",9739768,"[Antioxidative vitamins: prevention of cardiovascular diseases].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I474,I474)","v":9669730},{"$f":"(LEN($J474) - LEN(SUBSTITUTE(LOWER($J474),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J474) - LEN(SUBSTITUTE(LOWER($J474),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J474) - LEN(SUBSTITUTE(LOWER($J474),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B474:D474)","v":0},1998,"Mechanisms of hepatic fibrosis.","Benyon",9669730,"Mechanisms of hepatic fibrosis.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I475,I475)","v":9523035},{"$f":"(LEN($J475) - LEN(SUBSTITUTE(LOWER($J475),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J475) - LEN(SUBSTITUTE(LOWER($J475),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J475) - LEN(SUBSTITUTE(LOWER($J475),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B475:D475)","v":0},1998,"Vitamins E plus C and interacting conutrients required for optimal health. A critical and constructive review of epidemiology and supplementation data regarding cardiovascular disease and cancer.","Gey",9523035,"Vitamins E plus C and interacting conutrients required for optimal health. A critical and constructive review of epidemiology and supplementation data regarding cardiovascular disease and cancer.    Abstract:    UNLABELLEDAntioxidants are crucial components of fruit/vegetable rich diets preventing cardiovascular disease (CVD) and cancer: plasma vitamins C, E, carotenoids from diet correlate prevalence of CVD and cancer inversely, low levels predict an increased risk of individuals which is potentiated by combined inadequacy (e.g., vitamins C + E, C + carotene, A + carotene); self-prescribed rectification of vitamins C and E at adequacy of other micronutrients reduce forthcoming CVD, of vitamins A, C, E, carotene and conutrients also cancer; randomized exclusive supplementation of beta-carotene +/- vitamin A or E lack benefits except prostate cancer reduction by vitamin E, and overall cancer reduction by selenium; randomized intervention with synchronous rectification of vitamins A + C + E + B + minerals reduces CVD and counteracts precancerous lesions; high vitamin E supplements reveal potentials in secondary CVD prevention. Plasma values desirable for primary prevention: gt; or = 30 mumol/l lipid-standardized vitamin E (alpha-tocopherol/cholesterol gt; or = 5.0 mumol/mmol); gt; or = 50 mumol/l vitamin C aiming at vitamin C/vitamin E ratio gt; 1.3-1.5; gt; or = 0.4 mumol/l beta- (gt; or = 0.5 mumol/l alpha+ beta-) carotene.  CONCLUSIONS : In CVD vitamin E acts as first risk discriminator, vitamin C as second one; optimal health requires synchronously optimized vitamins C + E, A, carotenoids and vegetable conutrients."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I476,I476)","v":9152642},{"$f":"(LEN($J476) - LEN(SUBSTITUTE(LOWER($J476),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J476) - LEN(SUBSTITUTE(LOWER($J476),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J476) - LEN(SUBSTITUTE(LOWER($J476),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B476:D476)","v":0},1997,"Antioxidant vitamins in the prevention of cardiovascular disease. The epidemiological evidence.","Price",9152642,"Antioxidant vitamins in the prevention of cardiovascular disease. The epidemiological evidence.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I477,I477)","v":9195289},{"$f":"(LEN($J477) - LEN(SUBSTITUTE(LOWER($J477),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J477) - LEN(SUBSTITUTE(LOWER($J477),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J477) - LEN(SUBSTITUTE(LOWER($J477),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B477:D477)","v":0},1997,"An overview of clinical trials involving inhibitors of angiogenesis and their mechanism of action.","Gradishar",9195289,"An overview of clinical trials involving inhibitors of angiogenesis and their mechanism of action.    Abstract:   Angiogenesis is a biologic process whereby endothelial cells divide and migrate to form new blood vessels. This process is required in physiological conditions, but is also a necessary requirement for solid tumors to grow and metastasize. Over the last several years, the growth factors that have both a positive and negative influence on tumor angiogenesis have been delineated. Interfering with tumor angiogenesis was considered a potential therapeutic strategy 25 years ago, but only recently have compounds with an ability to interfere with angiogenesis entered clinical trials. This review will discuss the first generation of angiogenesis inhibitors, their mechanism of action and data from clinical trials."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I478,I478)","v":9131249},{"$f":"(LEN($J478) - LEN(SUBSTITUTE(LOWER($J478),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J478) - LEN(SUBSTITUTE(LOWER($J478),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J478) - LEN(SUBSTITUTE(LOWER($J478),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B478:D478)","v":0},1997,"Transgenic animals as new approaches in pharmacological studies.","Wei",9131249,"Transgenic animals as new approaches in pharmacological studies.    Abstract:   Transgenic animals are becoming useful tools for pharmacological studies. The use of transgenic technology raises two types of questions, quot;How are transgenic animals made?quot; and quot;What types of pharmacological questions can be answered using transgenic technologies?quot; Answers to these questions are discussed in this review. The production of animals with specific genetic alteration can be achieved by two strategies. The first involves the simple addition of DNA sequences to the chromosomes. The second strategy is to select particular genetic loci for site-specific changes. There are two well-established procedures for simple introduction of DNA into an animal genome, pronuclear DNA injection and transduction using a retrovirus. In contrast, methods for targeting specific DNA sequences to definite sites in the chromosomes are evolving rapidly. Some of these procedures can be used in combination to make a different variety of gene alterations in animals. Pharmacological studies where transgenic technology has been extensively used are discussed, including studies in the cardiovascular system, the nervous system, the endocrine system, cancer, and toxicology."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I479,I479)","v":9117986},{"$f":"(LEN($J479) - LEN(SUBSTITUTE(LOWER($J479),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J479) - LEN(SUBSTITUTE(LOWER($J479),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J479) - LEN(SUBSTITUTE(LOWER($J479),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B479:D479)","v":0},1996,"Wound healing in elderly human skin.","Strigini",9117986,"Wound healing in elderly human skin.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I480,I480)","v":8839287},{"$f":"(LEN($J480) - LEN(SUBSTITUTE(LOWER($J480),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J480) - LEN(SUBSTITUTE(LOWER($J480),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J480) - LEN(SUBSTITUTE(LOWER($J480),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B480:D480)","v":0},1996,"Structure and function of sinusoidal lining cells in the liver.","Wisse",8839287,"Structure and function of sinusoidal lining cells in the liver.    Abstract:   The hepatic sinusoid harbors 4 different cells: endothelial cells (100, 101), Kupffer cells (96, 102, 103), fat-storing cells (34, 51, 93), and pit cells (14, 107, 108). Each cell type has its own specific morphology and functions, and no transitional stages exist between the cells. These cells have the potential to proliferate locally, either in normal or in special conditions, that is, experiments or disease. Sinusoidal cells from a functional unit together with the parenchymal cells. Isolation protocols exist for all sinusoidal cells. Endothelial cells filter the fluids, exchanged between the sinusoid and the space of Disse through fenestrae (100), which measure 175 nm in diameter and are grouped in sieve plates. Fenestrae occupy 6-8% of the surface (106). No intact basal lamina is present under these cells (100). Various factors change the number and diameter of fenestrae [pressure, alcohol, serotonin, and nicotin; for a review, see Fraser et al (32)]. These changes mainly affect the passage of lipoproteins, which contain cholesterol and vitamin A among other components. Fat-storing cells are pericytes, located in the space of Disse, with long, contractile processes, which probably influence liver (sinusoidal) blood flow. Fat-storing cells possess characteristic fat droplets, which contain a large part of the bodys depot of vitamin A (91, 93). These cells play a major role in the synthesis of extracellular matrix (ECM) (34, 39-41). Strongly reduced levels of vitamin A occur in alcoholic livers developing fibrosis (56). Vitamin A deficiency transforms fat-storing cells into myofibroblast-like cells with enhanced ECM production (38). Kupffer cells accumulate in periportal areas. They specifically endocytose endotoxin (70), which activates these macrophages. Lipopolysaccharide, together with interferon gamma, belongs to the most potent activators of Kupffer cells (28). As a result of activation, these cells secrete oxygen radicals, tumor necrosis factor, interleukin 1, interleukin 6, and a series of eicosanoids (28) and become cytotoxic against tumor cells [e.g., colon carcinoma cells (19, 22, 48)]. Toxic secretory products can cause necrosis of the liver parenchyma, which constitutes a crucial factor in liver transplantation (55). Pit cells possess characteristic azurophylic granules and display a high level of spontaneous cytolytic activity against various tumor cells, identifying themselves as natural killer cells (10). The number and cytotoxicity of pit cells can be considerably enhanced with biological response modifiers, such as Zymosan or interleukin 2 (8). Pit cell proliferation occurs within the liver, but recent evidence indicates that blood large granular lymphocytes develop into pit cells in 2 steps involving high- and low-density pit cells (88). Kupffer cells control the motility, adherence, viability, and cytotoxicity of pit cells (89), whereas cytotoxicity against tumor cells is synergistically enhanced (80, 81)."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I481,I481)","v":7585282},{"$f":"(LEN($J481) - LEN(SUBSTITUTE(LOWER($J481),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J481) - LEN(SUBSTITUTE(LOWER($J481),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J481) - LEN(SUBSTITUTE(LOWER($J481),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B481:D481)","v":0},1995,"Antioxidants in the Mediterranean diet.","Mancini",7585282,"Antioxidants in the Mediterranean diet.    Abstract:   It has been suggested that antioxidant vitamins or other antioxidants might inhibit the oxidation of low density lipoproteins into a particularly atherogenic form and preserve endothelial function. Antioxidants in the Mediterranean diet have been evaluated in relation to cardiovascular disease protection in this area. Observational epidemiologic data obtained from case-control, cohort or cross-cultural studies have consistently suggested that persons, such as those living in the Mediterranean area, who consume large amounts of antioxidant vitamins have a lower than average risk of cardiovascular disease. In another cross-cultural comparison, dietary intake, antioxidant status and plasma lipid peroxidation were compared in healthy young persons in Naples (Southern Italy) who consumed typical regional foods, and in Bristol (UK). The Naples group consumed more tomatoes and tomato juice, a higher proportion of monounsaturated fatty acids (from olive oil) and had a higher level of lipid antioxidant vitamin E (P = 0.005) and of beta carotene (P lt; 0.001) than the Bristol group. The intake of vitamin C, fresh fruit and vegetables, plasma vitamin A, serum selenium and copper levels did not differ. Several indices of plasma lipid peroxidation were significantly lower in the Naples group: conjugated dienes (P lt; 0.001), diene conjugation index (P = 0.019), lipid peroxides (P lt; 0.001). Dietary habits leading to relatively low levels of oxidized lipoproteins might contribute to the lower risk of coronary artery disease in Southern Italy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I482,I482)","v":7755274},{"$f":"(LEN($J482) - LEN(SUBSTITUTE(LOWER($J482),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J482) - LEN(SUBSTITUTE(LOWER($J482),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J482) - LEN(SUBSTITUTE(LOWER($J482),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B482:D482)","v":0},1995,"Stimulation of proliferative events in the adult amphibian cardiac myocyte.","Oberpriller",7755274,"Stimulation of proliferative events in the adult amphibian cardiac myocyte.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I483,I483)","v":8779654},{"$f":"(LEN($J483) - LEN(SUBSTITUTE(LOWER($J483),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J483) - LEN(SUBSTITUTE(LOWER($J483),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J483) - LEN(SUBSTITUTE(LOWER($J483),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B483:D483)","v":0},1995,"Cardiovascular disease and vitamins. Concurrent correction of suboptimal plasma antioxidant levels may, as important part of optimal nutrition, help to prevent early stages of cardiovascular disease and cancer, respectively.","Gey",8779654,"Cardiovascular disease and vitamins. Concurrent correction of suboptimal plasma antioxidant levels may, as important part of optimal nutrition, help to prevent early stages of cardiovascular disease and cancer, respectively.    Abstract:   Epidemiological surveys provided abundant evidence that under steady-state conditions diets rich in antioxidants (from vegetables/fruits and suitable vegetable oils) reduce the relative risk of premature death from CVD and cancer. Material relative risks seem to disappear at optimal antioxidant plasma levels in the order of gt; or = 50 micromol/l vitamin C, gt; or = 30 micromol/l lipid-standardized vitamin E (alpha-tocopherol/cholesterol ratio gt; or = 5.1-5.2), gt; or = 2.2 micromol/l vitamin A, and gt; or = 0.4 micromol/l beta-carotene or gt; or = 0.4-0.5 micromol/l alpha-plus beta-carotene. Levels 25-35% below these thresholds predict an at least 2-fold higher risk. Suboptimal levels of any single antioxidant may increase the relative risk independently. Accordingly, suboptimal levels of several antioxidants predict a further increase of risk. Data on habitual voluntary multivitamin supplements providing an adequate supply of either vitamins A, C or E, and of beta-carotene in smokers, indicates that steady-state optimization reduces more or less regularly the relative risk of CVD and cancer respectively. Simple counting of multivitamins regardless of their composition did not reveal any risk reduction. The antioxidant-related health benefits seem to depend on an adequacy of all antioxidants, and possibly of nonantioxidant nutrients as well. Thereby, an overall optimal antioxidant defense system may be more important than excess of any particular magic bullet antioxidant. Although antioxidants may represent a crucially important fraction within a health-maintaining diet, any nonantioxidant conutrients remain to be identified which could condition the health benefits of antioxidants. In randomized antioxidant intervention trials during 5-6 years in middle-aged to elderly subjects in China and Finland, only earlier stages of CVD and cancer respectively were prevented by rectifying previously poor levels. Correspondingly, the incidence of prostate cancer (developing mostly not until the male menopause) was reduced by correction of a previously poor vitamin E status in Finland. In contrast, irreversible precancerous lesions (such as esophageal dysplasia), clonically established common cancers (highly probable for the lung of elderly heavy smokers) as well as (presumably advanced, complicated) vascular lesions of chronic smokers did not respond favorably. (ABSTRACT TRUNCATED)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I484,I484)","v":7721539},{"$f":"(LEN($J484) - LEN(SUBSTITUTE(LOWER($J484),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J484) - LEN(SUBSTITUTE(LOWER($J484),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J484) - LEN(SUBSTITUTE(LOWER($J484),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B484:D484)","v":0},1995,"Molecular genetic approaches to the study of human craniofacial dysmorphologies.","Moore",7721539,"Molecular genetic approaches to the study of human craniofacial dysmorphologies.    Abstract:   Craniofacial dysmorphologies are common, ranging from simple facial disfigurement to complex malformations involving the whole head. With the advent of gene mapping and cloning techniques, the genetic element of both simple and complex human craniofacial dysmorphologies can be investigated. For many of the dysmorphic syndromes, it is possible to find families that display a particular phenotype in either an autosomal dominant, recessive, or X-linked manner. This article focuses on a subgroup of craniofacial dysmorphologies, covering these three main inheritance patterns, that are being studied using molecular biology techniques: DiGeorge syndrome, Treacher Collins syndrome, Greig cephalopolysyndactyly syndrome, acrocallosal syndrome, amelogenesis imperfecta, and X-linked cleft palate with ankyloglossia. Once the mutated or deleted gene or genes for each syndrome have been cloned, patterns of normal and abnormal craniofacial development should be elucidated. This should enhance both diagnosis and treatment of these common and disfiguring disorders."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I485,I485)","v":7486827},{"$f":"(LEN($J485) - LEN(SUBSTITUTE(LOWER($J485),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J485) - LEN(SUBSTITUTE(LOWER($J485),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J485) - LEN(SUBSTITUTE(LOWER($J485),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B485:D485)","v":0},1995,"DiGeorge syndrome and related syndromes associated with 22q11.2 deletions. A review.","Demczuk",7486827,"DiGeorge syndrome and related syndromes associated with 22q11.2 deletions. A review.    Abstract:   DiGeorge syndrome (DGS) is a developmental defect which associates hypo- or aplasia of the thymus and parathyroids, facial dysmorphism and conotruncal cardiac malformations. The etiological factor in a great majority of DGS patients is monosomy for the 22q11.2 chromosomal region either through a large interstitial deletion of that region (inherited or de novo) or through an unbalanced translocation involving chromosome 22. In one instance, a balanced translocation of chromosome 22 was associated with a DGS phenotype. Extensive analyses of this region of chromosome 22 has led to the obtention of precise physical maps of the corresponding genomic region, to the cloning of the balanced translocation breakpoint and to the isolation of different genes from the minimal critical deleted region."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I486,I486)","v":7977023},{"$f":"(LEN($J486) - LEN(SUBSTITUTE(LOWER($J486),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J486) - LEN(SUBSTITUTE(LOWER($J486),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J486) - LEN(SUBSTITUTE(LOWER($J486),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B486:D486)","v":0},1994,"Oxygen free radicals and antioxidants: a review.","Barber",7977023,"Oxygen free radicals and antioxidants: a review.    Abstract:   In 1989, nearly 43% of deaths in the United States were due to some form of cardiovascular disease, and 23% were caused by cancer. Thus, two of every three people in this country die from either cardiovascular disease or cancer. Based on both experimental and epidemiological evidence, investigators believe that free radicals play a critical role in the development of both diseases. Low levels of antioxidants, which increases free radical activity, are clearly associated with an increased risk of these diseases. This link has led to the conclusion that use of antioxidant vitamin supplements to scavenge free radicals could potentially decrease the risks of cancer and cardiovascular disease. Results from numerous studies to date have been very promising, although a true protective or preventive causal relationship has not yet been established. Numerous primary and secondary intervention trials currently underway should more definitively assess the role of antioxidants in disease prevention. In the interim, many people feel the evidence is now strong enough to begin supplementation on their own. The pharmacist is in a position to advise patients on the safe and moderate use of antioxidants. The antioxidants discussed in this article are relatively non-toxic, with the exception of vitamin A. The possible benefits of vitamin A are better achieved with the use of beta-carotene. Megadose antioxidant supplementation does not appear to provide any additional benefit beyond what a more moderate supplement can provide and should therefore be discouraged. Taking a trace mineral with antioxidant potential is generally a waste of money, provided the patient is not initially deficient in the element.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I487,I487)","v":8129416},{"$f":"(LEN($J487) - LEN(SUBSTITUTE(LOWER($J487),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J487) - LEN(SUBSTITUTE(LOWER($J487),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J487) - LEN(SUBSTITUTE(LOWER($J487),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B487:D487)","v":0},1994,"Rosacea. Pathophysiology and treatment.","Wilkin",8129416,"Rosacea. Pathophysiology and treatment.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I488,I488)","v":8031675},{"$f":"(LEN($J488) - LEN(SUBSTITUTE(LOWER($J488),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J488) - LEN(SUBSTITUTE(LOWER($J488),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J488) - LEN(SUBSTITUTE(LOWER($J488),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B488:D488)","v":0},1994,"Miscellaneous neurologic, cardiac, pulmonary, and metabolic disorders with rheumatic manifestations.","Larkin",8031675,"Miscellaneous neurologic, cardiac, pulmonary, and metabolic disorders with rheumatic manifestations.    Abstract:   The First International Workshop on Hypertrophic Osteoarthropathy crystallized the current knowledge of this puzzling syndrome. Cytokine release by large thrombocytes in the periphery is the favored etiology, although specific therapy remains unavailable. An article on the rheumatologic consequences of alcohol is reviewed, along with a number of case reports of joint problems in rare skin and metabolic diseases. Understanding the mechanisms of rarities, including rheumatic fever, interleukin-2-induced arthritis, and a unique quot;menstrual arthritisquot; might give insight into the etiology of more common arthropathies."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I489,I489)","v":7905651},{"$f":"(LEN($J489) - LEN(SUBSTITUTE(LOWER($J489),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J489) - LEN(SUBSTITUTE(LOWER($J489),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J489) - LEN(SUBSTITUTE(LOWER($J489),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B489:D489)","v":0},1994,"[Regulation of vascular endothelial cell functions by vitamin A].","Kojima",7905651,"[Regulation of vascular endothelial cell functions by vitamin A].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I490,I490)","v":8495162},{"$f":"(LEN($J490) - LEN(SUBSTITUTE(LOWER($J490),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J490) - LEN(SUBSTITUTE(LOWER($J490),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J490) - LEN(SUBSTITUTE(LOWER($J490),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B490:D490)","v":0},1993,"ABC of sleep disorders. Non-Psychotropic drugs and sleep.","Idzikowski",8495162,"ABC of sleep disorders. Non-Psychotropic drugs and sleep.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I491,I491)","v":8433528},{"$f":"(LEN($J491) - LEN(SUBSTITUTE(LOWER($J491),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J491) - LEN(SUBSTITUTE(LOWER($J491),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J491) - LEN(SUBSTITUTE(LOWER($J491),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B491:D491)","v":0},1993,"[Thrombotic microangiopathy (DIC,TTP and HUS)--recent advances in pathogenesis and management].","Saito",8433528,"[Thrombotic microangiopathy (DIC,TTP and HUS)--recent advances in pathogenesis and management].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I492,I492)","v":8414273},{"$f":"(LEN($J492) - LEN(SUBSTITUTE(LOWER($J492),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J492) - LEN(SUBSTITUTE(LOWER($J492),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J492) - LEN(SUBSTITUTE(LOWER($J492),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B492:D492)","v":0},1993,"Antioxidant nutrients and disease.","Diplock",8414273,"Antioxidant nutrients and disease.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I493,I493)","v":1296855},{"$f":"(LEN($J493) - LEN(SUBSTITUTE(LOWER($J493),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J493) - LEN(SUBSTITUTE(LOWER($J493),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J493) - LEN(SUBSTITUTE(LOWER($J493),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B493:D493)","v":0},1992,"[Biological effects of selenium].","Brtková",1296855,"[Biological effects of selenium].    Abstract:   The role of selenium concerning its biological effects particularly in relation to cardiovascular and tumor diseases has been in the focus of intensive studies. Selenium is a constituent part of the enzyme glutathion peroxidase (E.C.1.11.1.9) which catalyzes the conversion of hydrogen peroxide and organic hydroperoxides into water and corresponding alcohols. A review of epidemiological studies is presented focusing predominantly on countries where a low concentration of selenium in blood serum was found. The role of selenium in the etiology of cardiovascular diseases may probably be accounted for by its protective effect as it prevents platelet aggregation and protects the arterial endothelium from being damaged by lipid peroxides. The results of experimental studies, carried out in research institutes in many parts of the world, suggest that coordinated supplementation of food with selenium may reduce the risk of cancer and moreover, the effect of selenium can be modified by other dietary factors, such as vitamin A and E. (Fig. 2, Ref. 29.)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I494,I494)","v":2187027},{"$f":"(LEN($J494) - LEN(SUBSTITUTE(LOWER($J494),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J494) - LEN(SUBSTITUTE(LOWER($J494),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J494) - LEN(SUBSTITUTE(LOWER($J494),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B494:D494)","v":0},1990,"Selenium status and cardiovascular risk factors in healthy Dutch subjects.","Bukkens",2187027,"Selenium status and cardiovascular risk factors in healthy Dutch subjects.    Abstract:   To provide further insight into the possible role of selenium in cardiovascular disease, we examined the relationship between cardiovascular risk factors, some nutritional parameters, and short- and long-term selenium status. A total of 82 healthy Dutch volunteers, 59 men and 23 women, aged 40-75 years, were studied. Means and standard deviations of selenium parameters were: plasma selenium 106.4 +/- 23.7 micrograms/L, erythrocyte selenium 0.59 +/- 0.19 microgram/g Hb, toenail selenium 0.78 +/- 0.17 ppm, and erythrocyte glutathione peroxidase activity 28.0 +/- 8.1 U/g Hb. No association was found between selenium status and gender, age, serum total-, LDL-, and HDL-cholesterol, systolic and diastolic blood pressure, alcohol intake, and body mass index. A significantly lower plasma selenium level was observed among smokers compared to nonsmokers (101.0 micrograms/L, SE = 3.9 vs 112.0 micrograms/L, SE = 3.6, p = 0.04). A significant negative association was found between erythrocyte selenium and serum levels of vitamin A and ferritin. No relevant relationship was observed between selenium status and serum fatty acid composition, vitamin E, vitamin B6, and iron. Apart from an association between smoking and short-term selenium status, we found no indications that a possible effect of selenium on cardiovascular disease may operate through the known risk factors."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I495,I495)","v":2191671},{"$f":"(LEN($J495) - LEN(SUBSTITUTE(LOWER($J495),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J495) - LEN(SUBSTITUTE(LOWER($J495),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J495) - LEN(SUBSTITUTE(LOWER($J495),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B495:D495)","v":0},1990,"Nutrition: prospects for the 1990s.","Scrimshaw",2191671,"Nutrition: prospects for the 1990s.    Abstract:   For many decades there has been adequate information for the elimination of acute dietary deficiency diseases. Scurvy, beri-beri, and pellagra, once serious scourges, are now seen only rarely. The severe forms of protein-energy malnutrition, kwashiorkor and marasmus, have also decreased greatly. Nonetheless, mild to moderate forms of protein-energy deficiency, exacerbated by infection, continue to impair growth and development in a majority of the low-income pre-school age populations of most developing countries. Deficiencies of iron, iodine, and vitamin A are still widespread in developing countries. Fortunately, the success of the WHO/UNICEF quot;Child Survival and Development Revolutionquot; in persuading most developing countries to introduce expanded programs of immunization, growth monitoring, and appropriate feeding of young children, control of diarrheal disease, and specific campaigns against avitaminosis A, iodine deficiency disorders, and the functional consequences of iron deficiency, will accelerate the decline of acute deficiency diseases in the developing world. Diets are changing among the more affluent in these countries, however, and it is time for them to stress dietary goals for the health of rich and poor alike. For the first time there is enough information regarding dietary risk factors for chronic disease to provide an opportunity in the 1990s to accelerate the dietary changes that have already brought significant health benefits to some populations in North America and Europe. The changes, which include a lower dietary intake of fat, particularly saturated fat, less salt, and more green and yellow vegetable and whole grain cereals, can be expected to influence favorably morbidity from cardiovascular diseases and some kinds of cancer. For maximum benefit, these measures need to be combined with the avoidance of obesity, reasonable physical activity, abstention from, or moderate use of, alcohol, and avoidance of tobacco in any form. Since there is already considerable momentum toward these changes in North America and some European countries, the 1990s are likely to see substantial further progress in the reduction of chronic diseases known to be influenced by diet."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I496,I496)","v":3292794},{"$f":"(LEN($J496) - LEN(SUBSTITUTE(LOWER($J496),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J496) - LEN(SUBSTITUTE(LOWER($J496),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J496) - LEN(SUBSTITUTE(LOWER($J496),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B496:D496)","v":0},1988,"Clinical applications of fish oils.","Yetiv",3292794,"Clinical applications of fish oils.    Abstract:   Fish oil supplements are currently being nationally advertised, and many physicians are being queried about their clinical utility. Epidemiologic studies reveal a low incidence of cardiovascular disease in people, such as the Eskimos, who eat large amounts of seafood. Cardiovascular health may be improved because fish and fish oil supplements lower plasma lipid levels (especially triglycerides), inhibit platelet aggregation, and may decrease blood pressure and viscosity and increase high-density lipoprotein (HDL) levels. Preliminary observations also suggest a potential future role for fish oils in the treatment of some autoimmune diseases, such as atopic dermatitis, psoriasis, and rheumatoid arthritis. Patients with serum triglyceride levels greater than 5.64 mmol/L and/or cholesterol levels greater than 7.75 mmol/L refractory to dietary management may benefit from a medically supervised trial of fish oil supplements. Data currently available are insufficient to recommend fish oil supplements for the general public, or for patients with other diseases, and side effects must also be considered. These include occasional adverse lipid changes, potential for bleeding and vitamin E deficiency, and, with some preparations, vitamin A and D toxicity."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I497,I497)","v":3317083},{"$f":"(LEN($J497) - LEN(SUBSTITUTE(LOWER($J497),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J497) - LEN(SUBSTITUTE(LOWER($J497),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J497) - LEN(SUBSTITUTE(LOWER($J497),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B497:D497)","v":0},1987,"Recent insights into the function of hepatic sinusoidal cells.","Bouwens",3317083,"Recent insights into the function of hepatic sinusoidal cells.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I498,I498)","v":2941237},{"$f":"(LEN($J498) - LEN(SUBSTITUTE(LOWER($J498),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J498) - LEN(SUBSTITUTE(LOWER($J498),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J498) - LEN(SUBSTITUTE(LOWER($J498),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B498:D498)","v":0},1986,"Soft tissue mineralization: roentgen analysis.","Feldman",2941237,"Soft tissue mineralization: roentgen analysis.    Abstract:   Numerous, incompletely understood, and undetermined physiologic factors may exert further but unappreciated influences on the development of ectopic calcification and ossification. In the former instance, in addition to serum calcium and phosphorous ion concentrations, tissue pH, blood supply, hormones, i.e., vitamin D, vitamin A, and various enzymes (e.g., alkaline phosphatase and pyrophosphatase) may all play significant, ancillary, time-dependent, but as yet undetermined roles. Ossification, like calcification, may occur in association with many types of disorders and under a variety of circumstances, some of which, such as trauma, have been reduplicated in the laboratory. However, experimental conditions that produce ectopic bone, as well as the species that are predilected do not always coincide with clinical observations in man. Not only are there differences between species in regard to susceptibility to ectopic bone production under particular circumstances, i.e., rabbits are the most susceptible and mice the least to mechanical injury, but there are differences between individuals. Individual variability in susceptibility to soft tissue ossification suggests either a personal or familial predilection. If such liability is inherited, this would be an example of an ecogenetic condition, in which someone is susceptible to an environmental agent by virtue of genetic constitution. Histocompatibility (HLS) antigens have provided substantiation of this concept. In the case of soft tissue ossification, causative environmental agents could include trauma, burns, hip replacement, and immobility secondary to neurological insults. In the case of soft tissue calcification, trauma, infections, or repeated injections could constitute the triggering environmental event. Not only do individuals at risk develop bone, but those that do tend to do so in characteristic places. Therefore, there is an additional differential susceptibility at various sites in the same individual. In cases with neurological conditions, thigh muscles are more susceptible than paraspinal muscles. The underlying condition is a further moderator, i.e., in paraplegics, thigh muscles are most apt to be involved. Elbows are most commonly affected after burns regardless of the site of the burn. Ectopic ossification also has a further predilection for distribution. Not only are muscle groups unequal in risk in terms of site, but the type of muscle affected is relevant, since skeletal muscles are involved in these same conditions to the exclusion of smooth muscles.(ABSTRACT TRUNCATED AT 400 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I499,I499)","v":2419928},{"$f":"(LEN($J499) - LEN(SUBSTITUTE(LOWER($J499),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J499) - LEN(SUBSTITUTE(LOWER($J499),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J499) - LEN(SUBSTITUTE(LOWER($J499),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B499:D499)","v":0},1985,"[Progress in the field of drug development. 18].","Délenk-Heydenreich",2419928,"[Progress in the field of drug development. 18].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I500,I500)","v":2408489},{"$f":"(LEN($J500) - LEN(SUBSTITUTE(LOWER($J500),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J500) - LEN(SUBSTITUTE(LOWER($J500),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J500) - LEN(SUBSTITUTE(LOWER($J500),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B500:D500)","v":0},1985,"Regulation of gap junctional conductance.","Spray",2408489,"Regulation of gap junctional conductance.    Abstract:   Gap junctional conductance is regulated by the number of channels between coupled cells (the balance between formation and loss of these channels) and by the fraction of these channels that are open (gating mechanisms). A variety of treatments are known to affect junction formation. Adenosine 3,5-cyclic monophosphate (cAMP) is involved in some cases, and protein synthesis may be required but precursor molecules can also exist. Junction removal occurs both by dispersion of particles and by internalization of junctional membrane. Factors promoting removal are not well understood. A variety of gating mechanisms exist. Coupling may be controlled by changes in conductance of nonjunctional membranes. Several kinds of voltage dependence of junctional conductance are known, but rat ventricular junctions at least are electrically linear. Cytoplasmic acidification decreases conductance of most gap junctions. Sensitivity in rat ventricular myocytes allows modulation of coupling by moderate changes near normal internal pH. Increasing intracellular Ca also decreases junctional conductance, but in the better studied cases sensitivity is much lower to Ca than H. A few data support low sensitivity to Ca in cardiac cells, but quantitative studies are lacking. Higher alcohols such as octanol block junctional conductance in a wide range of tissues including rat ventricular myocytes. An antibody to liver gap junctions blocks junctions between rat ventricular myocytes. Cross reactivity indicates at least partial homology between many gap junctions. Although differences among gap junctions are known, a general physiology is being developed, which may have considerable relevance to normal cardiac function and also to conduction disorders of that tissue."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I501,I501)","v":6230219},{"$f":"(LEN($J501) - LEN(SUBSTITUTE(LOWER($J501),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J501) - LEN(SUBSTITUTE(LOWER($J501),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J501) - LEN(SUBSTITUTE(LOWER($J501),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B501:D501)","v":0},1984,"Vitamin therapy in the absence of obvious deficiency. What is the evidence?","Ovesen",6230219,"Vitamin therapy in the absence of obvious deficiency. What is the evidence?    Abstract:   Vitamins are a group of organic compounds occurring naturally in food and are necessary for good health. Lack of a vitamin may lead to a specific deficiency syndrome, which may be primary (due to inadequate diet) or secondary (due to malabsorption or to increased metabolic need), and it is rational to use high-dose vitamin supplementation in situations where these clinical conditions exist. However, pharmacological doses of vitamins are claimed to be of value in a wide variety of conditions which have no, or only a superficial, resemblance to the classic vitamin deficiency syndromes. The enormous literature on which these claims are based consists mainly of uncontrolled clinical trials or anecdotal reports. Only a few studies have made use of the techniques of randomisation and double-blinding. Evidence from such studies reveals a beneficial therapeutic effect of vitamin E in intermittent claudication and fibrocystic breast disease and of vitamin C in pressure sores, but the use of vitamin A in acne vulgaris, vitamin E in angina pectoris, hyperlipidaemia and enhancement of athletic capacity, of vitamin C in advanced cancer, and niacin in schizophrenia has been rejected. Evidence is conflicting or inconclusive as to the use of vitamin C in the common cold, asthma and enhancement of athletic capacity, of pantothenic acid in osteoarthritis, and folic acid (folacin) in neural tube defects. Most of the vitamins have been reported to cause adverse effects when ingested in excessive doses. It is therefore worthwhile to consider the risk-benefit ratio before embarking upon the use of high-dose vitamin supplementation for disorders were proof of efficacy is lacking."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I502,I502)","v":7009064},{"$f":"(LEN($J502) - LEN(SUBSTITUTE(LOWER($J502),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J502) - LEN(SUBSTITUTE(LOWER($J502),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J502) - LEN(SUBSTITUTE(LOWER($J502),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B502:D502)","v":0},1981,"The nutrition significance of sucrose consumption, 1970-1980.","Lee",7009064,"The nutrition significance of sucrose consumption, 1970-1980.    Abstract:   Sucrose consumption is a controversial issue. Part of the difficulty arises because of inadequate knowledge about the actual consumption of populations, as well as individuals within a population. Data on the sucrose content of foods are lacking. This review presents information published in the 1970s on these topics as well as current research and thinking about possible relationships of sucrose consumption to dental caries, cardiovascular disease, diabetes, obesity, and other disease conditions. Current attitudes toward recommendations concerning sugar consumption in the U.S. Dietary Goals are examined, as are data on the use of sugar as a fortification vehicle."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I503,I503)","v":793064},{"$f":"(LEN($J503) - LEN(SUBSTITUTE(LOWER($J503),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J503) - LEN(SUBSTITUTE(LOWER($J503),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J503) - LEN(SUBSTITUTE(LOWER($J503),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B503:D503)","v":0},1976,"Stress ulcers: their pathogenesis, diagnosis, and treatment.","Moody",793064,"Stress ulcers: their pathogenesis, diagnosis, and treatment.    Abstract:   Stress ulcers are multiple, superficial erosions which occur mainly in the fundus and body of the stomach. They develop after shock, sepsis, and trauma and are ofter found in patients with peritonitis and other chronic medical illness. Stress ulcers should be differentiated from reactivation of chronic duodenal or gastric ulcers. Cushings ulcer following head injury, or drug-induced gastritis. Digestive symptoms are usually absent, hemorrhage is the most common manifestation, and perforation and obstruction are rare. The presence of luminal acid and ischemia are necessary for the production of stress ulcer, while disruption of the gastric mucosal barrier by refluxed duodenal content may contribute to the pathogenesis. Endoscopy is the mainstay of the diagnostic procedure, and angiography should be used if endoscopy fails to identify the bleeding lesions. Medical management should include volume replacement, nasogastric aspiration, and the use of antacid. Selective intraarterial infusion of pitressin has shown encouraging preliminary results. Surgical treatment is reserved only for those patients who continue to bleed despite all medical management. The operation of choice is open to question. We prefer vagotomy, pyloroplasty, and oversewing the ulcers as an initial operation. Since the result of all forms of therapy has been poor, it seems resonable to try to prevent ulcer development. The use of vitamin A, hyperalimentation, and growth hormones is still in an experimental stage. Large clinical studies with case control are necessary before recommendations can be made. The use of potent and frequent antacid to buffer the gastric content has shown promising results; however, these observations need to be confirmed in a properly controlled and randomized study."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I504,I504)","v":770204},{"$f":"(LEN($J504) - LEN(SUBSTITUTE(LOWER($J504),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J504) - LEN(SUBSTITUTE(LOWER($J504),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J504) - LEN(SUBSTITUTE(LOWER($J504),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B504:D504)","v":0},1976,"Nutrition and cancer.","Wynder",770204,"Nutrition and cancer.    Abstract:   There is increasing epidemiological evidence that nutrition plays a dominant role in the pathogenesis of several types of human cancers. There is considerable epidemiological evidence showing that alcoholism in part because of associated nutritional deficiencies, significantly increases the risk of smokers for cancer of the alimentary tract. There is also some suggestion that nutritional deficiencies may relate to cancers of the stomach, cervix, and thyroid. Of particular importance, and based on relatively new concepts, are data indicating that overnutrition significantly affects the development of certain cancers, including cancers of the colon and pancreas, kidney, breast, ovary endometrium, and prostate. Except for cancer of the endometrium, and kidney cancer in women, there is no significant relationship to obesity. Rather, the evidence suggests both epidemiologically and experimentally that the etiological factors relate to a high intake of fats and possibly other variables associated with high fat intake. While we are investigating the mechanistic nature of the epidemiological and experimental observations, the question that needs to be asked is whether it is not prudent for us to associate ourselves with the recommendation of our colleagues in the cardiovascular disease field who call on both individuals and the food industry to practice a quot;Prudent Diet,quot; i.e., one that is lower in total calories, total fat, saturated fats and cholesterol than is the present American diet."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I505,I505)","v":768933},{"$f":"(LEN($J505) - LEN(SUBSTITUTE(LOWER($J505),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J505) - LEN(SUBSTITUTE(LOWER($J505),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J505) - LEN(SUBSTITUTE(LOWER($J505),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B505:D505)","v":0},1976,"[Side effects of oral contraceptives].","Kuczyńska-Sicińska",768933,"[Side effects of oral contraceptives].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I506,I506)","v":1090354},{"$f":"(LEN($J506) - LEN(SUBSTITUTE(LOWER($J506),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J506) - LEN(SUBSTITUTE(LOWER($J506),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J506) - LEN(SUBSTITUTE(LOWER($J506),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B506:D506)","v":0},1975,"Some aspects of wound healing research: a review.","Heughan",1090354,"Some aspects of wound healing research: a review.    Abstract:   Mammalian response to injury essentially is that of tissue repair and re-epithelialization. The most important component of repair tissue is collagen, and after injury collagen turnover is greatly increased. Collagen biosynthesis is initiated by nuclear DNA of fibroblasts; the steps in biosynthesis are complex but studies of collagen biosynthesis may eventually have clinical potential. Normally, wound healing lasts for up to 2 years but nutritional and metabolic factors, such as malnutrition, delay healing; hyperalimentation would likely be beneficial under these conditions. Other factors that influence wound healing are the oxygen tension in tissues, the hemodynamic status, and the effects of substances such as cortisone, vitamins A and C, and zinc."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I507,I507)","v":1101403},{"$f":"(LEN($J507) - LEN(SUBSTITUTE(LOWER($J507),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J507) - LEN(SUBSTITUTE(LOWER($J507),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J507) - LEN(SUBSTITUTE(LOWER($J507),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B507:D507)","v":0},1975,"Experimental stress ulcers: a review.","Butterfield",1101403,"Experimental stress ulcers: a review.    Abstract:   The restraint model and other models for the production of experimental stress ulcers have been reviewed. The mechanism of experimental stress ulcers appears to depend on an interaction between the presence of acid, changes in mucosal circulation, an increase in the excretion of glycoproteins in the mucus, and a decrease in mitotic activity of the mucosal lining of the stomach. Factors enhancing ulceration are cold, starvation, increased acidity, burns, reflux of bile, endotoxin, adrenalectomy, and hemorrhage. Factors inhibiting ulceration are vagotomy, anticholinergics, elemental diets, vitamin A, antacids, prevention of bile reflux, corticosteroids, epinephrine and norepinephrine, serotonin antagonists, and immediate replacement of blood loss with low molecular weight dextran. The role of sepsis is unclear and more work is needed in this area. Ulcers from intracranial injury are usually associated with the hypersecretion of gastric acid. Stimulation of the hypothalamus, directly or indirectly, with resultant vagal stimulation is thought to be the responsible mechanism for the increase in acid."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I508,I508)","v":4616467},{"$f":"(LEN($J508) - LEN(SUBSTITUTE(LOWER($J508),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J508) - LEN(SUBSTITUTE(LOWER($J508),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J508) - LEN(SUBSTITUTE(LOWER($J508),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B508:D508)","v":0},1974,"The manifestations and management of severe protein-calorie malnutrition (kwashiorkor).","Pereira",4616467,"The manifestations and management of severe protein-calorie malnutrition (kwashiorkor).    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I509,I509)","v":4609496},{"$f":"(LEN($J509) - LEN(SUBSTITUTE(LOWER($J509),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J509) - LEN(SUBSTITUTE(LOWER($J509),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J509) - LEN(SUBSTITUTE(LOWER($J509),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B509:D509)","v":0},1974,"Methods of studying intestinal absorption.","Smyth",4609496,"Methods of studying intestinal absorption.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I510,I510)","v":4597845},{"$f":"(LEN($J510) - LEN(SUBSTITUTE(LOWER($J510),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J510) - LEN(SUBSTITUTE(LOWER($J510),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J510) - LEN(SUBSTITUTE(LOWER($J510),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B510:D510)","v":0},1973,"Some factors affecting wound healing.","Silver",4597845,"Some factors affecting wound healing.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I511,I511)","v":4571746},{"$f":"(LEN($J511) - LEN(SUBSTITUTE(LOWER($J511),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J511) - LEN(SUBSTITUTE(LOWER($J511),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J511) - LEN(SUBSTITUTE(LOWER($J511),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B511:D511)","v":0},1973,"Nutrition in our society.","Compton",4571746,"Nutrition in our society.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I512,I512)","v":4201469},{"$f":"(LEN($J512) - LEN(SUBSTITUTE(LOWER($J512),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J512) - LEN(SUBSTITUTE(LOWER($J512),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J512) - LEN(SUBSTITUTE(LOWER($J512),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B512:D512)","v":0},1973,"Nutrition and disease.","Gopalan",4201469,"Nutrition and disease.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I513,I513)","v":4562259},{"$f":"(LEN($J513) - LEN(SUBSTITUTE(LOWER($J513),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J513) - LEN(SUBSTITUTE(LOWER($J513),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J513) - LEN(SUBSTITUTE(LOWER($J513),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B513:D513)","v":0},1972,"[Lysosomes and collagen diseases].","Kaĭnova",4562259,"[Lysosomes and collagen diseases].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I514,I514)","v":4319586},{"$f":"(LEN($J514) - LEN(SUBSTITUTE(LOWER($J514),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J514) - LEN(SUBSTITUTE(LOWER($J514),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J514) - LEN(SUBSTITUTE(LOWER($J514),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B514:D514)","v":0},1970,"[Mucopolysaccharides of bone and cartilage tissue in normal and pathological conditions].","Kasavina",4319586,"[Mucopolysaccharides of bone and cartilage tissue in normal and pathological conditions].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I515,I515)","v":4369119},{"$f":"(LEN($J515) - LEN(SUBSTITUTE(LOWER($J515),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J515) - LEN(SUBSTITUTE(LOWER($J515),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J515) - LEN(SUBSTITUTE(LOWER($J515),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B515:D515)","v":0},1970,"Recent advances in wound healing.","Hunt",4369119,"Recent advances in wound healing.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I516,I516)","v":4898010},{"$f":"(LEN($J516) - LEN(SUBSTITUTE(LOWER($J516),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J516) - LEN(SUBSTITUTE(LOWER($J516),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J516) - LEN(SUBSTITUTE(LOWER($J516),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B516:D516)","v":0},1969,"Absorption of vitamin A.","Ganguly",4898010,"Absorption of vitamin A.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I517,I517)","v":14318831},{"$f":"(LEN($J517) - LEN(SUBSTITUTE(LOWER($J517),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J517) - LEN(SUBSTITUTE(LOWER($J517),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J517) - LEN(SUBSTITUTE(LOWER($J517),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B517:D517)","v":0},1965,"VITAMIN A AND VASCULARIZATION.","HODGES",14318831,"VITAMIN A AND VASCULARIZATION.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I518,I518)","v":14181603},{"$f":"(LEN($J518) - LEN(SUBSTITUTE(LOWER($J518),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J518) - LEN(SUBSTITUTE(LOWER($J518),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J518) - LEN(SUBSTITUTE(LOWER($J518),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B518:D518)","v":0},1964,"MANIFESTATIONS OF ARTERIOSCLEROSIS IN THE BACKGROUND OF THE EYE.","SAUTTER",14181603,"MANIFESTATIONS OF ARTERIOSCLEROSIS IN THE BACKGROUND OF THE EYE.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I519,I519)","v":14204173},{"$f":"(LEN($J519) - LEN(SUBSTITUTE(LOWER($J519),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J519) - LEN(SUBSTITUTE(LOWER($J519),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J519) - LEN(SUBSTITUTE(LOWER($J519),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B519:D519)","v":0},1963,"[MICROBIOLOGY AND DRUG SYNTHESIS].","GROEGER",14204173,"[MICROBIOLOGY AND DRUG SYNTHESIS].    Abstract:  "]

{"sheet":"Abstract","index":1,"n_rows":5,"n_cols":4,"rows_kept":5,"cut":false,"hidden":false,"merged":[[0,0,0,1]]}
["Abstract with highlights"]
["Article:",{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & C2,C2)","v":24099071},24099071,"Pub Yr: 2013"]
[]
["Title:","Oral retinoids and plasma lipids.",null,"Fauthor: Lilley"]
["Title and Abstract:","Oral retinoids and plasma lipids.    Abstract:   Retinoids and rexinoids are prescribed for conditions ranging from acne vulgaris to hyperkeratosis to cutaneous T cell lymphoma. Dyslipidemia is a frequent consequence of the use of these drugs, with more than one-third of patients manifesting aberrations in triglyceride (TG) levels. The efficacy of retinoic acid derivatives is linked to their influence on lipid metabolism in the skin, which can impair systemic lipid trafficking and metabolism in some patients. Thus, baseline screening for preexisting dyslipidemia and regular follow-up lipid panels are mandated, especially when powerful agents such as bexarotene are used. Dietary modification, increased physical activity, and weight management are the cornerstones of initial management for mild hypertriglyceridemia, which is a contributor to cardiovascular risk. More severe impairments (fasting TG gt; 500 mg/dL) warrant pharmacologic interventions early on to reduce the risk of pancreatitis. Retinoic acid derivative action, lipid metabolism, and treatment of incident dyslipidemias are reviewed to empower prescribers in management of adverse lipid effects."]

{"sheet":"Notes","index":2,"n_rows":3,"n_cols":8,"rows_kept":3,"cut":false,"hidden":false,"merged":[]}
[null,"My Notes"]
["Chemical","PMID ","DOI","Note ","Title","LinkDOI","LinkID","Link"]
[null,{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & G3,G3)","v":15374828},null,"example - might be useful","Peroxisome proliferator-activated receptors and cardiovascular remodeling.",null,15374828]