Author: Melissa Ann Allwood
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Hypoxia is an essential physiological element and a main feature of all pathophysiological states. While severe hypoxia is used in research, moderate is typical for many physiological and pathological states. Despite this, our understanding of moderate hypoxia is limited. One of the defining outcomes of hypoxia is a subsequent increase in erythropoiesis. While erythropoietin (EPO) is considered the master regulator of erythropoiesis, additional roles in cytoprotection, embryogenesis, and inotropy have recently emerged. The kidney is considered the primary source of EPO in health and pathology, however multiple tissues are capable of expression. These sources have largely been uninvestigated and are considered physiologically irrelevant in health. The aims of this thesis were to address our limited understanding of the pathophysiology of moderate hypoxia and determine the physiological significance of extrarenal sources of EPO. We hypothesize that (1) severe and moderate hypoxia will invoke opposing cardiovascular responses and (2) extrarenal EPO is required for hematopoiesis and cardiogenesis. Exposure to 24 hours of either moderate or severe hypoxia resulted in hypotension and hypertension, respectively, following normoxic recovery. This was mediated by heterogeneous autonomic activation, despite similar vasodilatory responses via up-regulation of heme oxygenase-1. Subsequently, the molecular response to moderate and severe hypoxia was compared via whole-body analysis of EPO expression. Critically, we identified that the brain was the sole responder to moderate hypoxia. To further our understanding of extrarenal EPO expression, we investigated the physiological significance of cardiac-derived EPO. We showed that cardiac EPO expression is a complex interplay of multiple cell types that is differentially expressed throughout life. Generation of cardiomyocyte-specific EPO knockout mice resulted in increased cardiac EPO expression suggesting over-compensation from another cardiac cell type. This resulted in both systemic and cardiac-specific effects in adult animals. These findings expand our knowledge of hypoxia to include responses at moderate levels. We propose that there is neither a primary site of EPO nor a singular effect. Rather, our data indicates that EPO is expressed by multiple tissues in a time and pathology dependent manner. Further, tissue EPO production is not always for hematopoiesis but is required for both paracrine and endocrine functions.
Author: Sukhamay Lahiri
Publisher: Springer
ISBN: 1461475740
Category : Medical
Languages : en
Pages : 251
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Book Description
The underlying theme of this book is the biology of oxygen. The 22 chapters cover aspects of molecular, cellular, and integrative physiological functions. A fundamental evolutionary feature of the oxygen-consuming organism is that it developed a oxygen-sensing mechanism as apart of feedback control at the levels of molecules, organelles, organs, and systems. Oxygen sensing is partic ularly expressed in certain specific cells and tissues like peripheral chemore ceptors, erythroprotein-producing cells, and vascular smooth muscle. Apart of the book is focused on the current issues of this basic question of chemosen sing. Mitrochondria as the major site for cellular oxygen consumption is a nat ural candidate for cellular oxygen sensitivity and adaptation. A section deals with this question. A perennial question concerns chronic environment al oxy gen and the organism's response and adaptation to it. This theme runs through several chapters. Because comparative physiology often provides insight into the mechanisms of environment al adaptation, a chapter on respiration of high altitude birds has been incorporated. Obviously this book gives only glimpses of the immense field of oxygen biology. The book grew out of two meetings where these subjects were discussed. These meetings were sponsored by the American Physiological Society and the Federation of American Societies for Experimental Biology. We are grateful to the FASEB Program Committee and APS publication committee for their sup port. We owe much to Ms. Anne Miller for her editorial assistance. S. L. Philadelphia N. S . C. Cleveland R. S. F.
Author: Hoi I Cheong
Publisher:
ISBN:
Category : Anoxemia
Languages : en
Pages : 106
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Book Description
Life-sustaining responses to hypoxia rely on the transcription factor, Hypoxia Inducible Factor-1 (HIF-1). Under hypoxia, HIF-1 accumulates and regulates multifaceted cellular responses. However, many underlying mechanisms of HIF-1 regulation are incompletely understood. Previous studies suggest a link between HIF-1 and beta-adrenergic receptors (ßAR). Here, we interrogated the role of ßARs in hypoxia responses by ß-blocker treatment of mice with hypoxia-inducible erythropoiesis. ß-blocker suppressed renal accumulation of HIF-1a, erythropoietin production and the generation of erythroid progenitor cells. Likewise, ß-blocker treatment of human endothelial cells attenuated HIF-1a accumulation and binding to target genes under hypoxia, and subsequent downstream gene expression. Consistently, ß-agonist increased HIF-1a accumulation in a dose- and time-dependent manner, an effect that was blocked by both ß1- and ß2-blockers, indicating a general property of this receptor class. ßAR signal transduction involves cyclic adenosine monophosphate (cAMP)-activated protein kinase A (PKA) and G protein-coupled receptor kinases (GRK). Direct activation of cAMP/ PKA pathways did not increase HIF-1a accumulation, and inhibition of PKA did not suppress HIF-1a by hypoxia. In contrast, pharmacological inhibition of GRK, or genetic mutation of ßAR that impairs GRK phosphorylation, blocked hypoxia-mediated HIF-1a accumulation. Mass spectrometry analyses revealed a unique hypoxia ßAR phosphorylation barcode different from the classical agonist. These findings identify an unknown role of ßAR in hypoxia responses. Another determinant of HIF-1 regulation is nitric oxide, a potent vasodilator. A natural experiment of genetically similar Ethiopians at high altitude (>3000 m), the Amhara and Oromo, revealed a dampened hemoglobin response in Amhara compared to Oromo. We hypothesized that Amhara highlanders offset their dampened hemoglobin response with the vascular nitric oxide response. We identified high levels of urinary nitrate and its bioactive signal molecule cyclic guanosine monophosphate (cGMP) in high-altitude Amhara, but not Oromo. Consistently, high-altitude Amhara have lower diastolic blood pressure than Oromo, an indicator of vasomotor tone. Both Amhara and Oromo maintained the amount of oxyhemoglobin at high altitudes, but the high-altitude Oromo suffered a much higher deoxyhemoglobin level. In conclusion, high-altitude Amhara offset a dampened hemoglobin response with the vasodilatory nitric oxide, whereas the Oromo mount a bigger hemoglobin response at the cost of circulating deoxyhemoglobin.
Author:
Publisher: Elsevier
ISBN: 0080497195
Category : Science
Languages : en
Pages : 867
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Book Description
The ability of cells to sense and respond to changes in oxygenation underlies a multitude of developmental, physiological, and pathological processes. This volume provides a comprehensive compendium of experimental approaches to the study of oxygen sensing in 48 chapters that are written by leaders in their fields.
Author: Sandro Malacrida
Publisher: Frontiers Media SA
ISBN: 2889762122
Category : Science
Languages : en
Pages : 111
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Book Description
Author: Robert C. Roach
Publisher: Springer
ISBN: 1489976787
Category : Medical
Languages : en
Pages : 765
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Book Description
The latest in a series of books from the International Hypoxia Symposia, this volume spans reviews on key topics in hypoxia, and abstracts from poster and oral presentations. The biannual International Hypoxia Symposia are dedicated to hosting the best basic scientific and clinical minds to focus on the integrative and translational biology of hypoxia. Long before ‘translational medicine’ was a catchphrase, the founders of the International Hypoxia Symposia brought together basic scientists, clinicians and physiologists to live, eat, ski, innovate and collaborate in the Canadian Rockies. This collection of reviews and abstracts is divided into six sections, each covering new and important work relevant to a broad range of researchers interested in how humans adjust to hypoxia, whether on the top of Mt. Everest or in the pulmonary or cardiology clinic at low altitude. The sections include: Epigenetic Variations in Hypoxia High Altitude Adaptation Hypoxia and Sleep Hypoxia and the Brain Molecular Oxygen Sensing Physiological Responses to Hypoxia
Author: Ajay K. Singh
Publisher: Academic Press
ISBN: 0080920462
Category : Medical
Languages : en
Pages : 534
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Book Description
The Textbook of Nephro-Endocrinology is the definitive translational reference in the field of nephro-endocrinology, investigating both the endocrine functions of the kidneys and how the kidney acts as a target for hormones from other organ systems. It offers researchers and clinicians expert, gold-standard analyses of nephro-endocrine research and translation into the treatment of diseases such as anemia, chronic kidney disease (CKD), rickets, osteoporosis, and, hypoparathyroidism. Investigates both the endocrine functions of the kidneys and how the kidney acts as a target for hormones from other organ systems Presents a uniquely comprehensive and cross-disciplinary look at all aspects of nephro-endocrine disorders in one reference work Clear translational presentations by the top endocrinologists and nephrologists in each specific hormone or functional/systems field
Author: Mohammad Resa Nowrousian
Publisher: Springer Science & Business Media
ISBN: 3709176581
Category : Medical
Languages : en
Pages : 524
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Book Description
Anemia is a frequent complication of cancer and its treatment. A number of clinical studies shows that the impact of anemia is much greater than previously thought. Beyond clinical symptoms, anemia significantly impairs physical and metabolic functions as well as patients' activity, well-being and quality of life. Life expectancy is also affected. In this book, written by a group of outstanding international experts, the current knowledge on anemia in cancer and its treatment with rhEPO is presented. Future developments are also discussed. Based on a broad spectrum of topics, the book describes the scientific and clinical aspects of anemia in various fields of oncology and gives diagnostic and therapeutic recommendations on when and how to use rhEPO.
Author: Anne Waugh
Publisher: Elsevier Health Sciences
ISBN: 0702072842
Category : Medical
Languages : en
Pages : 584
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Book Description
The new edition of the hugely successful Ross and Wilson Anatomy & Physiology in Health and Illness continues to bring its readers the core essentials of human biology presented in a clear and straightforward manner. Fully updated throughout, the book now comes with enhanced learning features including helpful revision questions and an all new art programme to help make learning even easier. The 13th edition retains its popular website, which contains a wide range of ‘critical thinking’ exercises as well as new animations, an audio-glossary, the unique Body Spectrum© online colouring and self-test program, and helpful weblinks. Ross and Wilson Anatomy & Physiology in Health and Illness will be of particular help to readers new to the subject area, those returning to study after a period of absence, and for anyone whose first language isn’t English. Latest edition of the world’s most popular textbook on basic human anatomy and physiology with over 1.5 million copies sold worldwide Clear, no nonsense writing style helps make learning easy Accompanying website contains animations, audio-glossary, case studies and other self-assessment material, the unique Body Spectrum© online colouring and self-test software, and helpful weblinks Includes basic pathology and pathophysiology of important diseases and disorders Contains helpful learning features such as Learning Outcomes boxes, colour coding and design icons together with a stunning illustration and photography collection Contains clear explanations of common prefixes, suffixes and roots, with helpful examples from the text, plus a glossary and an appendix of normal biological values. Particularly valuable for students who are completely new to the subject, or returning to study after a period of absence, and for anyone whose first language is not English All new illustration programme brings the book right up-to-date for today’s student Helpful ‘Spot Check’ questions at the end of each topic to monitor progress Fully updated throughout with the latest information on common and/or life threatening diseases and disorders Review and Revise end-of-chapter exercises assist with reader understanding and recall Over 150 animations – many of them newly created – help clarify underlying scientific and physiological principles and make learning fun
Author: Kusal Das
Publisher: BoD – Books on Demand
ISBN: 1789848288
Category : Medical
Languages : en
Pages : 146
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Book Description
The molecular deprivation of oxygen is manifested by hypoxia, a deficiency of oxygen and anoxia, or the absence of oxygen supply to the tissues. This book entitled Hypoxia and Anoxia will cover a broad range of understanding on hypoxia and anoxia from molecular mechanisms to pathophysiology. Hypoxia and anoxia stimulate multiple systems through specific cell signal transduction pathways and regulate several transcriptional factors like HIF-1, REST to encode genes for VEGF, Epo, etc. This book will also highlight different types of hypoxia and anoxia along with their impact on apoptosis, cardiovascular pathophysiology, and glucose regulatory mechanisms. This book will be a ready reckoner to give a deep understanding of the oxygen-sensing environment in vivo for researchers, academicians, and clinicians throughout the world.
