Role of the Endothelin System in the Development of Kidney Disease and the Associated Inflammation, Hypertension and Vascular Dysfunction

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ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (16 download)

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Book Synopsis Role of the Endothelin System in the Development of Kidney Disease and the Associated Inflammation, Hypertension and Vascular Dysfunction by : Rebecca Claire Moorhouse

Download or read book Role of the Endothelin System in the Development of Kidney Disease and the Associated Inflammation, Hypertension and Vascular Dysfunction written by Rebecca Claire Moorhouse and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Endothelin in Renal Physiology and Disease

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Publisher : Karger Medical and Scientific Publishers
ISBN 13 : 3805597959
Total Pages : 276 pages
Book Rating : 4.8/5 (55 download)

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Book Synopsis Endothelin in Renal Physiology and Disease by : M. Barton

Download or read book Endothelin in Renal Physiology and Disease written by M. Barton and published by Karger Medical and Scientific Publishers. This book was released on 2011-09-01 with total page 276 pages. Available in PDF, EPUB and Kindle. Book excerpt: Endothelin is a 21-amino acid peptide that exerts uniquely potent and long-lasting effects on the kidney, including regulation of water and electrolyte excretion, blood pressure, cell growth, inflammation and fibrosis. During the past 10 years, the field has evolved rapidly; we are now uncovering the potential importance of endothelin receptor antagonists (ERAs) in the treatment of kidney disease.This book reviews experimental concepts, preclinical studies and clinical data which form the basis of our current understanding of the association between endothelin and kidney disease. Acclaimed experts in pharmacology, molecular biology, physiology, cardiovascular medicine, and nephrology have contributed timely reviews dealing with renal pharmacology and physiology of endothelin, the role of endothelin in renal disease development and ERAs in preclinical studies, and the current state of clinical development of ERA therapy in renal medicine.The publication at hand will be a valuable reference source for nephrologists, internists and other healthcare professionals, renal physiologists and molecular biologists, post-doctoral researchers and students in the life sciences, as well as for scientists and decision makers in drug research and development.

Endothelin in the Kidney

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Publisher : Biota Publishing
ISBN 13 : 1615042113
Total Pages : 90 pages
Book Rating : 4.6/5 (15 download)

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Book Synopsis Endothelin in the Kidney by : David Pollock

Download or read book Endothelin in the Kidney written by David Pollock and published by Biota Publishing. This book was released on 2011-11-01 with total page 90 pages. Available in PDF, EPUB and Kindle. Book excerpt: The discovery of a potent vasoconstrictor, endothelin (ET)-1, derived from vascular endothelial cells was among a variety of key lines of investigation that helped to fuel a major explosion of studies related to endothelial cell biology. This was particularly evident within the pharmaceutical industry where receptor antagonists were quickly developed and are now on the market for treatment of pulmonary hypertension and in development for other diseases such as diabetic nephropathy and cancer. Importantly, we know that the kidney contains the highest level of ET-1 production and receptor expression in the body where it has been demonstrated to function as a pro-natriuretic autocrine and paracrine factor that is activated in conditions of high salt intake. This eBook provides a review of the various mechanisms whereby ET-1 has been shown to function within the kidney through a wide range of actions that include direct effects on tubular transport, intrarenal hemodynamics, as well as neural and endocrine functions. Much has yet to be discerned, but it is clear that the ET system is a major physiological regulator of fluid-electrolyte balance and blood pressure through these renal actions. Table of Contents: Discovery of Endothelin / Basic Biology of the Endothelin System / Renal Localization / Renal Hemodynamics / Renal Tubular Actions of Endothelin / Endothelin in Neural Modulation of Renal Function / Physiological Role of Endothelin / Endothelin in Renal Pathology / References / Author Biographies

The Endothelium

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Publisher : Morgan & Claypool Publishers
ISBN 13 : 1615041230
Total Pages : 309 pages
Book Rating : 4.6/5 (15 download)

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Book Synopsis The Endothelium by : Michel Félétou

Download or read book The Endothelium written by Michel Félétou and published by Morgan & Claypool Publishers. This book was released on 2011 with total page 309 pages. Available in PDF, EPUB and Kindle. Book excerpt: The endothelium, a monolayer of endothelial cells, constitutes the inner cellular lining of the blood vessels (arteries, veins and capillaries) and the lymphatic system, and therefore is in direct contact with the blood/lymph and the circulating cells. The endothelium is a major player in the control of blood fluidity, platelet aggregation and vascular tone, a major actor in the regulation of immunology, inflammation and angiogenesis, and an important metabolizing and an endocrine organ. Endothelial cells controls vascular tone, and thereby blood flow, by synthesizing and releasing relaxing and contracting factors such as nitric oxide, metabolites of arachidonic acid via the cyclooxygenases, lipoxygenases and cytochrome P450 pathways, various peptides (endothelin, urotensin, CNP, adrenomedullin, etc.), adenosine, purines, reactive oxygen species and so on. Additionally, endothelial ectoenzymes are required steps in the generation of vasoactive hormones such as angiotensin II. An endothelial dysfunction linked to an imbalance in the synthesis and/or the release of these various endothelial factors may explain the initiation of cardiovascular pathologies (from hypertension to atherosclerosis) or their development and perpetuation. Table of Contents: Introduction / Multiple Functions of the Endothelial Cells / Calcium Signaling in Vascular Cells and Cell-to-Cell Communications / Endothelium-Dependent Regulation of Vascular Tone / Conclusion / References

Endothelial Function in Hypertension

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Publisher : Springer Science & Business Media
ISBN 13 : 3642608116
Total Pages : 249 pages
Book Rating : 4.6/5 (426 download)

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Book Synopsis Endothelial Function in Hypertension by : David Webb

Download or read book Endothelial Function in Hypertension written by David Webb and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 249 pages. Available in PDF, EPUB and Kindle. Book excerpt: The vascular endothelium has become an increasing focus of research over the last 15 years. Nitric oxide and endothelin appear to have important and opposing actions on vascular tone, smooth muscle proliferation and platelet/monocyte activation, and endothelial dysfunction affecting the L-arginine/nitric oxide and endothelin systems both appear to be crucial to atherogenesis and to the pathophysiology of many forms of cardiovascular disease. Additionally, a number of new drugs of major clinical interest are now emerging that act favourably to modulate endothelial function and alter the outcome in these conditions. Here, a synthesis of the current understanding of endothelial dysfunction in hypertension and related disorders - and future therapeutic prospects - has been drawn together by a series of internationally recognised leaders in the field.

Endothelin System & Its Antagonism in Chronic Kidney Disease

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Publisher :
ISBN 13 :
Total Pages : 156 pages
Book Rating : 4.:/5 (827 download)

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Book Synopsis Endothelin System & Its Antagonism in Chronic Kidney Disease by : Neeraj Dhaun

Download or read book Endothelin System & Its Antagonism in Chronic Kidney Disease written by Neeraj Dhaun and published by . This book was released on 2012 with total page 156 pages. Available in PDF, EPUB and Kindle. Book excerpt: Since its discovery in 1988 the powerful vasoconstrictor endothelin-1 (ET-1) has been widely implicated in the pathophysiology of chronic kidney disease (CKD) as well as the cardiovascular disease with which it is associated. ET receptor antagonists have favourable effects in experimental models of these conditions and orally acting antagonists are now licensed for the treatment of pulmonary arterial hypertension. However, there is a paucity of human data regarding the role of ET-1 in CKD. In this thesis, I have therefore explored the utility of ET-1 as a biomarker in CKD, and, using selective ET receptor antagonists, the beneficial renal and cardiovascular effects of ET receptor antagonism in CKD. I have shown that as glomerular filtration rate (GFR) declines plasma ET-1 increases linearly whereas urinary ET-1 shows an exponential increase. Furthermore, urinary ET-1 may be a useful marker of disease activity in patients with lupus nephritis. Its levels are high in those with biopsy-proven active renal inflammation and these fall with treatment. I have shown that in subjects with stable non-diabetic proteinuric CKD, acute selective ETA receptor antagonism reduces blood pressure and arterial stiffness and that these systemic benefits are associated with an increase in renal blood flow and reduction in proteinuria. Importantly, these effects are seen on top of those achieved with maximal therapy with angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers. Following a study confirming unchanged pharmacokinetics in CKD, I have used an oral selective ETA receptor antagonist to show that the reductions in BP, arterial stiffness and proteinuria seen in my acute studies are maintained longer term. This results of this study also suggest that the mechanism for the reduction in proteinuria is haemodynamic and relates to a reduction in GFR and filtration fraction. In summary, these studies suggest that ET-1 may act as a potential biomarker of renal inflammation, and confirm its role in the pathophysiology of the systemic and renal vasoconstriction seen in CKD. They also suggest that selective ETA receptor antagonism may provide a novel therapeutic approach in proteinuric CKD on top of standard therapies. Larger and longer term studies are now warranted to confirm this potential.

Pediatric Hypertension

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Publisher : Springer Science & Business Media
ISBN 13 : 1627034900
Total Pages : 597 pages
Book Rating : 4.6/5 (27 download)

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Book Synopsis Pediatric Hypertension by : Joseph Flynn

Download or read book Pediatric Hypertension written by Joseph Flynn and published by Springer Science & Business Media. This book was released on 2013-06-26 with total page 597 pages. Available in PDF, EPUB and Kindle. Book excerpt: The field of pediatric hypertension has undergone important changes in the time since the second edition of Pediatric Hypertension published. Much new information on hypertension in the young has become available. Previous chapters have been fully revised and new chapters have been added to cover important topics of recent interest such as consensus recommendations, the prevalence of hypertension in the young due to the obesity epidemic, studies of antihypertensive agents, and ambulatory blood pressure monitoring. Pediatric Hypertension, Third Edition is a comprehensive volume featuring 38 chapters covering the breadth of the current knowledge. It is divided into four sections: Regulation of Blood Pressure in Children; Assessment of Blood Pressure in Children: Measurement, Normative Data, Epidemiology; and Hypertension in Children: Predictors, Risk Factors, and Special Populations; Evaluation and Management of Pediatric Hypertension. Filled with the most up-to-date information, Pediatric Hypertension, Third Edition is an invaluable resource for clinicians and researchers interested in childhood hypertension.

Mechanisms of Vascular Disease

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Publisher : University of Adelaide Press
ISBN 13 : 1922064009
Total Pages : 589 pages
Book Rating : 4.9/5 (22 download)

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Book Synopsis Mechanisms of Vascular Disease by : Robert Fitridge

Download or read book Mechanisms of Vascular Disease written by Robert Fitridge and published by University of Adelaide Press. This book was released on 2011 with total page 589 pages. Available in PDF, EPUB and Kindle. Book excerpt: New updated edition first published with Cambridge University Press. This new edition includes 29 chapters on topics as diverse as pathophysiology of atherosclerosis, vascular haemodynamics, haemostasis, thrombophilia and post-amputation pain syndromes.

Endothelial Signaling in Vascular Dysfunction and Disease

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Publisher : Academic Press
ISBN 13 : 0128163828
Total Pages : 279 pages
Book Rating : 4.1/5 (281 download)

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Book Synopsis Endothelial Signaling in Vascular Dysfunction and Disease by : Shampa Chatterjee

Download or read book Endothelial Signaling in Vascular Dysfunction and Disease written by Shampa Chatterjee and published by Academic Press. This book was released on 2021-01-20 with total page 279 pages. Available in PDF, EPUB and Kindle. Book excerpt: Endothelial Signaling in Vascular Dysfunction and Disease: From Bench to Bedside provides a detailed understanding of the endothelium, its activation and their link to some common clinical disorders. In addition, the book covers earlier discoveries, including those from the last and 19th centuries. It is split into five sections that cover the vascular tree as an integrative structure, the endothelium in inflammation, endothelial signaling, activation and toxicity with chemotherapy, radiation induced endothelial dysfunction and vascular disease, and therapies in combating vascular diseases. Each section is discussed with a translational approach in order to make the content truly applicable. This book is a valuable source for basic researchers, clinicians in the fields of Oncology, Cardiovascular Medicine and Radiology, and members of the biomedical field who are conducting studies related to the endothelium and vascular disease. Discusses the most relevant discoveries in endothelial biology and their link to manifestations of clinical disease Presents history and diagrams in each section to highlight the original biological discovery and its link of clinical manifestations of vascular disease Includes recent findings on the relationship between endothelial signaling, chemotherapy and radiation induced endothelial dysfunction

The ESC Textbook of Vascular Biology

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Publisher : Oxford University Press
ISBN 13 : 0198755775
Total Pages : 347 pages
Book Rating : 4.1/5 (987 download)

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Book Synopsis The ESC Textbook of Vascular Biology by : Rob Krams

Download or read book The ESC Textbook of Vascular Biology written by Rob Krams and published by Oxford University Press. This book was released on 2017 with total page 347 pages. Available in PDF, EPUB and Kindle. Book excerpt: The ESC Textbook of Vascular Biology is a rich and clearly laid-out guide by leading European scientists providing comprehensive information on vascular physiology, disease, and research.

Endothelial Dysfunction and Inflammation

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Publisher : Springer Science & Business Media
ISBN 13 : 3034601689
Total Pages : 243 pages
Book Rating : 4.0/5 (346 download)

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Book Synopsis Endothelial Dysfunction and Inflammation by : Shauna Dauphinee

Download or read book Endothelial Dysfunction and Inflammation written by Shauna Dauphinee and published by Springer Science & Business Media. This book was released on 2010-09-24 with total page 243 pages. Available in PDF, EPUB and Kindle. Book excerpt: Endothelial dysfunction is broadly defined as a disruption of the balance between vasoactive mediators and a propensity towards an inflammatory state. This volume provides an overview of the fields of endothelial dysfunction and inflammation through the discussion of topics ranging from the molecular biology of activated endothelial cells to the endothelium in inflammatory disease and therapeutic approaches targeting endothelial dysfunction. Topics include: Heterogeneity of the endothelium during inflammation, oxidative stress and endothelial dysfunction, biology and regulation of nitric oxide in inflammatory pathologies, endothelial dysfunction in inflammatory diseases, such as diabetes and atherosclerosis and Clinical methods used to assess endothelial function. This book brings together basic and clinical research to assist the reader in bridging connections from bench-to-bedside. Written by expert researchers in the fields of endothelial biology, inflammation research and clinical science, it serves as a useful reference for academic and industrial researchers, clinicians, and trainees in the medical profession.

Endothelium and Cardiovascular Diseases

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Publisher : Academic Press
ISBN 13 : 0128125519
Total Pages : 760 pages
Book Rating : 4.1/5 (281 download)

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Book Synopsis Endothelium and Cardiovascular Diseases by : Protasio L. Da Luz

Download or read book Endothelium and Cardiovascular Diseases written by Protasio L. Da Luz and published by Academic Press. This book was released on 2018-02-03 with total page 760 pages. Available in PDF, EPUB and Kindle. Book excerpt: Endothelium and Cardiovascular Diseases: Vascular Biology and Clinical Syndromes provides an in-depth examination of the role of endothelium and endothelial dysfunction in normal vascular function, and in a broad spectrum of clinical syndromes, from atherosclerosis, to cognitive disturbances and eclampsia. The endothelium is a major participant in the pathophysiology of diseases, such as atherosclerosis, diabetes and hypertension, and these entities are responsible for the largest part of cardiovascular mortality and morbidly. Over the last decade major new discoveries and concepts involving the endothelium have come to light. This important reference collects this data in an easy to reference resource. Written by known experts, and covering all aspects of endothelial function in health and disease, this reference represents an assembly of recent knowledge that is essential to both basic investigators and clinicians. Provides a complete overview of endothelial function in health and diseases, along with an assessment of new information Includes coverage of groundbreaking areas, including the artificial LDL particle, the development of a new anti-erectile dysfunction agent, a vaccine for atherosclerosis, coronary calcification associated with red wine, and the interplay of endoplasmic reticulum/oxidative stress Explores the genetic features of endothelium and the interaction between basic knowledge and clinical syndromes

Endothelial Dysfunction and Inflammation

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Publisher : Springer Science & Business Media
ISBN 13 : 3034601689
Total Pages : 243 pages
Book Rating : 4.0/5 (346 download)

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Book Synopsis Endothelial Dysfunction and Inflammation by : Shauna Dauphinee

Download or read book Endothelial Dysfunction and Inflammation written by Shauna Dauphinee and published by Springer Science & Business Media. This book was released on 2010-09-24 with total page 243 pages. Available in PDF, EPUB and Kindle. Book excerpt: Endothelial dysfunction is broadly defined as a disruption of the balance between vasoactive mediators and a propensity towards an inflammatory state. This volume provides an overview of the fields of endothelial dysfunction and inflammation through the discussion of topics ranging from the molecular biology of activated endothelial cells to the endothelium in inflammatory disease and therapeutic approaches targeting endothelial dysfunction. Topics include: Heterogeneity of the endothelium during inflammation, oxidative stress and endothelial dysfunction, biology and regulation of nitric oxide in inflammatory pathologies, endothelial dysfunction in inflammatory diseases, such as diabetes and atherosclerosis and Clinical methods used to assess endothelial function. This book brings together basic and clinical research to assist the reader in bridging connections from bench-to-bedside. Written by expert researchers in the fields of endothelial biology, inflammation research and clinical science, it serves as a useful reference for academic and industrial researchers, clinicians, and trainees in the medical profession.

Silva's Diagnostic Renal Pathology

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Publisher : Cambridge University Press
ISBN 13 : 1316613984
Total Pages : 691 pages
Book Rating : 4.3/5 (166 download)

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Book Synopsis Silva's Diagnostic Renal Pathology by : Xin J. Zhou

Download or read book Silva's Diagnostic Renal Pathology written by Xin J. Zhou and published by Cambridge University Press. This book was released on 2017-03-02 with total page 691 pages. Available in PDF, EPUB and Kindle. Book excerpt: An algorithmic approach to interpreting renal pathology, updated in light of recent advances in understanding and new classification schemes.

The Role of Non-coding RNAs in Vascular Damage in Hypertension and CKD

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Publisher :
ISBN 13 :
Total Pages : pages
Book Rating : 4.:/5 (13 download)

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Book Synopsis The Role of Non-coding RNAs in Vascular Damage in Hypertension and CKD by : Kugeng Huo

Download or read book The Role of Non-coding RNAs in Vascular Damage in Hypertension and CKD written by Kugeng Huo and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Hypertension and chronic kidney disease (CKD) are two of the most prevalent global health concerns that account for millions of deaths per year. They are both associated with vascular damage that is characterized by vascular remodeling and stiffening, as well as endothelial dysfunction, which contribute to further development of the disease and lead to end organ damage. MicroRNAs (miRNAs) are important non-coding RNA regulators of gene expression that cause translational repression and transcript degradation upon binding to their target mRNAs. miRNAs have been demonstrated to be associated with hypertension and CKD, and play a critical role in vascular cell development and function. However, their role in vascular damage is still poorly studied. We hypothesized that vascular and circulating miRNAs are dysregulated in hypertension and CKD; the dysregulation of vascular miRNAs is a key driving force of pathological gene expression changes that contribute to vascular damage; key dysregulated vascular miRNAs are potential therapeutic targets and key dysregulated circulating miRNAs are potential biomarkers for vascular damage in hypertension and CKD. The thesis contains 3 studies testing our hypotheses.In the first study, we profiled miRNAs using RNA sequencing in mesenteric arteries of mice infused or not with angiotensin (Ang) II for 7 or 14 days. We observed that both 7-day and 14-day Ang II infusion induced blood pressure (BP) elevation, oxidative stress and vascular stiffening, whereas only 14-day Ang II-infusion caused endothelial dysfunction and vascular remodeling. Using a candidate approach, we have identified miR-431-5p and its target Ets Homologous Factor (Ehf) as key regulators in Ang II-induced hypertension and vascular damage. miR-431-5p and Ehf were up- and down-regulated by 14-day Ang II-infusion, respectively, and were both correlated with BP. We demonstrated that miR-431-5p targets EHF in human aortic vascular smooth muscle cells, where EHF down-regulates collagen type I alpha 1 chain (Col1a1), and miR-382-5p. Intravenous injection of miR-431-5p inhibitors down-regulated miR-431-5p, Col1a1 and miR-382-5p, and up-regulated Ehf in mesenteric arteries, delayed BP elevation and reduced vascular damage in mice infused with Ang II for 14 days.In the second study, we profiled miRNAs as above but this time in small arteries dissected from subcutaneous gluteal biopsies performed in normotensive, hypertensive and CKD subjects to identify differentially expressed vascular miRNAs. Combined with the data from the first study, we found a common miRNA, miR-145-3p, that was down-regulated in both 7-day Ang II-infused mice and CKD patients. Whether miR-145-3p mediates vascular damage in Ang II-induced hypertension model and CKD remains to be elucidated.In the third study, we profiled circulating miRNAs from plasma of the same cohort of normotensive hypertensive and CKD subjects as in the second study. We identified and validated 4 differentially expressed miRNAs, let-7g-5p, miR-26a-5p, miR-191-5p and let-7b-5p, among which let-7g-5p was correlated with estimated glomerular filtration rate. We also found a correlation between circulating let-7g-5p and genes that were differentially expressed in small arteries of CKD patients.To summarize, miR-431-5p and its target Ehf are potential important regulators in the pathophysiology of vascular damage in hypertension, and may serve as novel therapeutic targets in the clinic. miR-145-3p may play a role in the development of Ang II-induced and CKD-associated vascular injury. Let-7g-5p has potential clinical value to serve as a biomarker for vascular damage in CKD." --

Vitamin D in Chronic Kidney Disease

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Publisher : Springer
ISBN 13 : 3319325078
Total Pages : 583 pages
Book Rating : 4.3/5 (193 download)

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Book Synopsis Vitamin D in Chronic Kidney Disease by : Pablo A. Ureña Torres

Download or read book Vitamin D in Chronic Kidney Disease written by Pablo A. Ureña Torres and published by Springer. This book was released on 2016-09-21 with total page 583 pages. Available in PDF, EPUB and Kindle. Book excerpt: Vitamin D deficiency, circulating levels lower than 15 ng/ml, is an epidemic disease worldwide with more than a billion people suffering of it in the beginning of the 21-century. Besides its impact on mineral and bone metabolism, these low vitamin D levels are also associated with a diversity of non-skeletal complications, among them cardiovascular disease, diabetes mellitus, multiple sclerosis, cancer, tuberculosis, and immune system dysfunction. Chronic Kidney Disease is also a very common disease, affecting more than 10% of the world population, ranging from stage 1 to stage 5 before dialysis. Approximately 1% of the population in industrialized countries is affected by end-stage renal disease (ESRD), needing a renal replacement therapy either hemodialysis or peritoneal dialysis, and ultimately by renal transplantation. Those CKD patients are more susceptible to exhibit reduced vitamin D stocks. Consequently, more than eighty percent of CKD patients have either insufficient or deficient vitamin D levels for multiple reasons.

Mechanisms of Indoxyl Sulfate-induced Vascular Endothelial Dysfunction and Compromised Innate Immunity

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Publisher :
ISBN 13 : 9781303153587
Total Pages : pages
Book Rating : 4.1/5 (535 download)

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Book Synopsis Mechanisms of Indoxyl Sulfate-induced Vascular Endothelial Dysfunction and Compromised Innate Immunity by : Keri Akemi Hayakawa

Download or read book Mechanisms of Indoxyl Sulfate-induced Vascular Endothelial Dysfunction and Compromised Innate Immunity written by Keri Akemi Hayakawa and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Chronic kidney disease (CKD) is a widespread disorder in the United States and around the world. CKD is a complex disease that is associated with several other diseases, such as cardiovascular disease, hypertension, anemia, inflammation, immune dysfunction and neuropathy. The mechanism(s) underlying the increased incidence of these associated diseases with CKD are not fully understood. Uremic specific factors, such as uremic toxins, may contribute to the morbidity and mortality of CKD patients.Uremic toxins are substances that accumulate in the circulation of CKD and end-stage renal disease (ESRD) patients due to decreased renal clearance. Indoxyl sulfate is a protein-bound, uremic toxin that is produced by the intestinal microflora from the amino acid tryptophan. The concentration of plasma indoxyl sulfate has been correlated with a higher rate of renal dysfunction, cardiovascular disease and mortality in hemodialysis patients. Although indoxyl sulfate concentration has been linked with cardiovascular disease and death the direct role of indoxyl sulfate remain unclear. I hypothesize that uremic toxins, particularly indoxyl sulfate, are not only biomarkers of impaired renal function but can directly contribute to morbidity and mortality of CKD patients by directly compromising vascular and innate immune functions. Cardiovascular disease is the leading cause of mortality in CKD patients. Endothelial-dysfunction is recognized as a precursor to cardiovascular disease and is a widespread observation in CKD patients, but is not well explained by traditional risk factors. In chapter 2 my data indicate indoxyl sulfate promotes a hypercontractile state in rat aortic arteries by synergistically increasing vasoconstriction and inhibiting endothelium-dependent vasodilation. In chapter 3 I further explore the mechanism underlying indoxyl sulfate induced endothelium dysfunction. The data indicate indoxyl sulfate can inhibit NO production in activated primary rat aortic endothelial cells (RAEC) and in recombinant eNOS protein. Western blot analyses of RAECs incubated with indoxyl sulfate reveal indoxyl sulfate may be inhibiting NO production through promoting the monomerization of eNOS. Immune dysfunction and chronic infection are widely observed in CKD and ESRD patients. Infection related complications is the second leading cause of death in CKD and ESRD patients. Uremic patients have been shown to have impaired neutrophil function, an important part of the immune response. Myeloperoxidase (MPO) is a hemoprotein abundant in neutrophils that can produce hypochlorous acid (HOCl), a potent antimicrobial oxidant. It has been shown that tryptophan and indole derivatives can inhibit MPO. I hypothesized indoxyl sulfate could inhibit MPO activity and contribute to immune dysfunction in CKD patients. In chapter 4 my data reveal that indoxyl sulfate is a potent inhibitor of MPO. I also show evidence that indoxyl sulfate can inhibit MPO-dependent killing of Staphylococcus aureus. Collectively, the data presented herein indicate indoxyl sulfate is not only a biomarker of renal dysfunction, but can be a direct contributor to cardiovascular and immune dysfunction observed in CKD and ESRD patients. Determining the physiological effects of uremic toxins, such as indoxyl sulfate, will be important to better understand and treat CKD and its associated diseases to decrease morbidity and mortality in CKD and ESRD patients.