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After the discovery of endogenous NO formation in the late '80s and the 1998 Nobel Prize in Physiology or Medicine, many researchers and physicians again became interested in the NO/sGC interaction and cGMP-dependent signaling. This book is an enthusiastic celebration of cyclic guanosine monophosphate (cGMP) and amply illustrates the importance of this field of science to patients and the way in which the field has evolved. It is exclusively devoted to this exciting and important signaling molecule, addressing all recent advances in understanding guanylate cyclase regulation, NO/sGC interactions, cGMP effector mechanisms and their pathophysiological and pharmacological implications. Particular attention will also be given to clinical applications of the novel cGMP-elevating drugs which are on the horizon, thus spanning the continuum from basic science to clinic.
Reactive oxygen species (ROS) have been implicated in almost every human disease phenotype, without much, if any, therapeutic consequence foremost exemplified by the failure of the so-called anti-oxidants. This book is a game changer for the field and many clinical areas such as cardiology and neurology. The term ‘oxidative stress’ is abandoned and replaced with a systems medicine and network pharmacology-based mechanistic approach to disease. The ROS-related drugs discussed here target either ROS- forming or ROS -modifying enzymes for which there is strong clinical evidence. In addition, ROS targets are included as they jointly participate in causal mechanisms of disease. This approach is transforming the ROS field and represents a breakthrough in redox medicine indicating a path to patient benefit. In the coming years more targets and drugs may be discovered, but the approach will remain the same and this book will thus become, and for many years remain, the leading reference for ROSopathies and their treatment by network pharmacology. Chapter "Soluble Guanylate Cyclase Stimulators and Activators" is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
From somewhat enigmatic beginnings 40 years ago, guanylate cyclase research has emerged to occupy a position of prominence in the study of signal transduction. Guanylate cyclase has several intriguing features, including existence in two major forms, membrane and soluble, each independently regulated by distinct mechanisms. The membrane form gives rise to a fascinating signal transduction story important to both peptide hormones and sensory neurons. This volume covers the evolution of the field, peptide hormone receptor work, membrane guanylate cycles, related retinal diseases, and the biochemistry and physiology of the soluble form. The 16 chapters are written by leaders in the field.
This comprehensive book contains the latest information on diverse biological functions of relaxin and related peptide found since the recent discovery of relaxin receptors. It also describes the evolution of relaxin family peptides and their receptors, molecular mechanisms of ligand/receptor interaction and the analysis of activated signaling pathways.
Biological processes are driven by complex systems of functionally interacting signaling molecules. Thus, understanding signaling molecules is essential to explain normal or pathological biological phenomena. A large body of clinical and experimental data has been accumulated over these years, albeit in fragmented state. Hence, systems biological approaches concomitant with the understanding of each molecule are ideal to delineate signaling networks/pathways involved in the biologically important processes. The control of these signaling pathways will enrich our healthier life. Currently, there are more than 30,000 genes in human genome. However, not all the proteins encoded by these genes work equally in order to maintain homeostasis. Understanding the important signaling molecules as completely as possible will significantly improve our research-based teaching and scientific capabilities. This encyclopedia presents 350 biologically important signaling molecules and the content is built on the core concepts of their functions along with early findings written by some of the world’s foremost experts. The molecules are described by recognized leaders in each molecule. The interactions of these single molecules in signal transduction networks will also be explored. This encyclopedia marks a new era in overview of current cellular signaling molecules for the specialist and the interested non-specialist alike During past years, there were multiple databases to gather this information briefly and very partially. Amidst the excitement of these findings, one of the great scientific tasks of the coming century is to bring all the useful information into a place. Such an approach is arduous but at the end will infuse the lacunas and considerably be a streamline in the understanding of vibrant signaling networks. Based on this easy-approach, we can build up more complicated biological systems.
Nitroglycerin and other organic nitrates have been used for over a century in the treatment of angina pectoris. Millions of patients, throughout the world, have placed nitroglycerin tablets under the tongue and have experienced rapid and dramatic relief from the chest pain that frequently occurs as a manifestation of disease of the coronary arteries. The empirical observation of the safe use of nitrates for tile alleviation of the symptoms of angina have led to their widespread medical acceptance. The use of organic nitrates preceded any knowledge of their mechanism of action or their ultimate metabolic fate. Thus, more simply stated, although sub lingual nitrates helped the patients, little was known concerning what these drugs do to the body or what the body does to the drugs. A substantial number of investigators have focused on these questions especially during the last two decades. We now have considerably more insight into the pathways of degradation of organic nitrates and the relationship of the metabolic processes to the biological action of these agents. Similarly, considerable effort has been expended in understanding the mechanism of action of these agents directly on vascular smooth muscle and on cardiac work and performance. Finally, there is a more substantive understanding of the physiology of the coronary circulation as well as the" pathophysiologic manifestations of myocardial disease.
Expert biochemist N.V. Bhagavan's new work condenses his successful Medical Biochemistry texts along with numerous case studies, to act as an extensive review and reference guide for both students and experts alike. The research-driven content includes four-color illustrations throughout to develop an understanding of the events and processes that are occurring at both the molecular and macrolecular levels of physiologic regulation, clinical effects, and interactions. Using thorough introductions, end of chapter reviews, fact-filled tables, and related multiple-choice questions, Bhagavan provides the reader with the most condensed yet detailed biochemistry overview available. More than a quick survey, this comprehensive text includes USMLE sample exams from Bhagavan himself, a previous coauthor. - Clinical focus emphasizing relevant physiologic and pathophysiologic biochemical concepts - Interactive multiple-choice questions to prep for USMLE exams - Clinical case studies for understanding basic science, diagnosis, and treatment of human diseases - Instructional overview figures, flowcharts, and tables to enhance understanding
This unique work presents one of the most significant organ failure condition – cardiocirculatory shock – and the prominent role of Methylene Blue (MB). Through their extensive experience, the authors’ consider that the lifesaving feature of MB is still underestimated. For this reason they outline key concepts of MB, mentioning essential experimental data, yet focusing mainly on its application in the care of critically ill patients. In an easy-to-read format, the 18 chapters were organized in a didactically structured order, distributed in four parts. The first part introduces the general conceptual aspects and physiology of the endothelium. The second part presents the particularities of endothelial dysfunction in different types of shock. Methylene blue is discussed in detail in the third part. In the fourth part, particular situations of endothelial dysfunction, such as heart surgery and organ transplantation, are described. Additionally, the two complementary subjects of acid-base balance and the therapeutic use of inhaled nitric oxide are mentioned. Finally, looking for therapeutic alternatives for what we classify as "vasoplegic endothelial dysfunction", MB remains promising as an adjuvant to sympathomimetic amines. The combination of three recently proposed concepts may be useful in obtaining better results against the high mortality rates in critically ill patients. These three concepts are "wide-spectrum vasopressors", vasopressor economy strategies, and microcirculation protection against the harmful effects of using high concentrations of amines. This book ́s translational approach will appeal to a variety of readers within the health specialties of medicine, biomedicine, physiotherapy, nursing, odontology, and basic science.
Due to population aging, calcific aortic valve disease (CAVD) has become the most common heart valve disease in Western countries. No therapies exist to slow this disease progression, and surgical valve replacement is the only effective treatment. Calcific Aortic Valve Disease covers the contemporary understanding of basic valve biology and the mechanisms of CAVD, provides novel insights into the genetics, proteomics, and metabolomics of CAVD, depicts new strategies in heart valve tissue engineering and regenerative medicine, and explores current treatment approaches. As we are on the verge of understanding the mechanisms of CAVD, we hope that this book will enable readers to comprehend our current knowledge and focus on the possibility of preventing disease progression in the future.
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