The Endothelin System & Its Antagonism in Chronic Kidney Disease PDF Download
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Author: Neeraj Dhaun
Publisher:
ISBN:
Category :
Languages : en
Pages : 156
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Book Description
Author: Neeraj Dhaun
Publisher:
ISBN:
Category :
Languages : en
Pages : 156
Get Book Here
Book Description
Author: Neeraj Dhaun
Publisher:
ISBN:
Category :
Languages : en
Pages : 156
Get Book Here
Book Description
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.
Author: Matthias Barton
Publisher: Karger Medical and Scientific Publishers
ISBN: 3805597940
Category : Medical
Languages : en
Pages : 276
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Book Description
A comprehensive reference book on basic and clinical aspects 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.
Author: David Pollock
Publisher: Biota Publishing
ISBN: 1615042113
Category : Medical
Languages : en
Pages : 90
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Book Description
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
Author: Rebecca Claire Moorhouse
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Author: M. Barton
Publisher: Karger Medical and Scientific Publishers
ISBN: 3805597959
Category : Medical
Languages : en
Pages : 276
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Book Description
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.
Author: David Abraham
Publisher: Springer Science & Business Media
ISBN: 0857299204
Category : Medical
Languages : en
Pages : 268
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Book Description
Translational medicine underpins vascular medicine. It is fundamental to understanding how we treat patients with vascular disease and more importantly, how to prevent it. It is the rationale for drug design and production. Vascular medicine and translational medicine will take over and become the main reason for referring patients to hospital. Therefore, hospital-based clinicians working with basic scientists need to know about translational medicine, which educates and informs them about vascular medicine and how management should be based. This book is a primer for translational vascular medicine and discusses the evolving and exciting areas of basic science applied to vascular medicine. The book is based on the third vascular biology conference held at The Royal College of Physicians in 2008. It provides a large amount of new basic and clinical information and the contributors are world leaders.
Author: Vinood B. Patel
Publisher: Springer
ISBN: 9789400776982
Category : Medical
Languages : en
Pages : 0
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Book Description
In the past decade there has been a major sea change in the way disease is diagnosed and investigated due to the advent of high throughput technologies, such as microarrays, lab on a chip, proteomics, genomics, lipomics, metabolomics etc. These advances have enabled the discovery of new and novel markers of disease relating to autoimmune disorders, cancers, endocrine diseases, genetic disorders, sensory damage, intestinal diseases etc. In many instances these developments have gone hand in hand with the discovery of biomarkers elucidated via traditional or conventional methods, such as histopathology or clinical biochemistry. Together with microprocessor-based data analysis, advanced statistics and bioinformatics these markers have been used to identify individuals with active disease or pathology as well as those who are refractory or have distinguishing pathologies. New analytical methods that have been used to identify markers of disease and is suggested that there may be as many as 40 different platforms. Unfortunately techniques and methods have not been readily transferable to other disease states and sometimes diagnosis still relies on single analytes rather than a cohort of markers. There is thus a demand for a comprehensive and focused evidenced-based text and scientific literature that addresses these issues. Hence the formulation of Biomarkers in Disease. The series covers a wide number of areas including for example, nutrition, cancer, endocrinology, cardiology, addictions, immunology, birth defects, genetics, and so on. The chapters are written by national or international experts and specialists.
Author: Denis F. Geary
Publisher: Springer
ISBN: 3662529726
Category : Medical
Languages : en
Pages : 1968
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Book Description
The new edition of this valuable clinical resource offers a state of the art, comprehensive review on every clinical condition encountered in pediatric nephrology. International experts present the latest knowledge on epidemiology, diagnosis, management, and prognosis in one concise, clinically focused text, in which care has been taken to couple just the right amount of "need-to-know" basic science with practical clinical guidance that will enable the reader to make efficient, informed decisions. The topics covered include: disorders of renal development, glomerular disorders, the kidney and systemic disease, renal tubular disorders, tubulointerstitial disease, urinary tract disorders, acute kidney injury, hypertension, chronic and end-stage renal disease, and renal replacement therapy. The full-color, highly visual, meticulously crafted format will ensure that the practitioner is able to source and apply information with remarkable ease.
Author: Michel Félétou
Publisher: Morgan & Claypool Publishers
ISBN: 1615041230
Category : Science
Languages : en
Pages : 309
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Book Description
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
