6 Ions can pass through a single membrane channel at a rate of 10 ions/second. Over the last decade the ability to measure ion flux so precisely and to document the opening and closing of individual ion channels has provided a powerful tool to those working on smooth muscle physiology and vascular reactivity. The use of potassium channel blockers by Tom Lloyd in the 1960s and calcium channel blockers by Ivan McMurtry in the 1970s indicated the importance of ion flux in regulating pulmonary vascular tone. Recent advances in technology. principally the patch-clamp technique and fluorescent ion-sensitive dyes. now permit a more detailed description of physiologic mechanisms. This volume arises from the Sixth Grover Conference on the Pulmonary Circulation. a NATO Advanced Research Workshop. held in Colorado in October 1992. A group of international sCientists who are leaders in the field of ion flux focused their attention on the problems of the pulmonary vasculature. The chapters in this book describe the present state of knowledge of the movement and storage of ions in vascular endothelial and smooth muscle cells. Those who are not familiar with the techniques of patch clamping and calcium imaging will find an introduction to these methods in the chapters by Leblanc and Wan and Archer et al. The role of potassium channels in oxygen sensing illustrates the rapid progress which the study of ion currents has made possible.
Research centering on blood flow in the heart continues to hold an important position, especially since a better understanding of the subject may help reduce the incidence of coronary arterial disease and heart attacks. This book summarizes recent advances in the field; it is the product of fruitful cooperation among international scientists who met in Japan in May, 1990 to discuss the regulation of coronary blood flow.
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
The partition of fluid between the vascular and interstitial compartments is regulated by forces (hydrostatic and oncotic) operating across the microvascular walls and the surface areas of permeable structures comprising the endothelial barrier to fluid and solute exchange, as well as within the extracellular matrix and lymphatics. In addition to its role in the regulation of vascular volume, transcapillary fluid filtration also allows for continuous turnover of water bathing tissue cells, providing the medium for diffusional flux of oxygen and nutrients required for cellular metabolism and removal of metabolic byproducts. Transendothelial volume flow has also been shown to influence vascular smooth muscle tone in arterioles, hydraulic conductivity in capillaries, and neutrophil transmigration across postcapillary venules, while the flow of this filtrate through the interstitial spaces functions to modify the activities of parenchymal, resident tissue, and metastasizing tumor cells. Likewise, the flow of lymph, which is driven by capillary filtration, is important for the transport of immune and tumor cells, antigen delivery to lymph nodes, and for return of filtered fluid and extravasated proteins to the blood. Given this background, the aims of this treatise are to summarize our current understanding of the factors involved in the regulation of transcapillary fluid movement, how fluid movements across the endothelial barrier and through the interstitium and lymphatic vessels influence cell function and behavior, and the pathophysiology of edema formation. Table of Contents: Fluid Movement Across the Endothelial Barrier / The Interstitium / The Lymphatic Vasculature / Pathophysiology of Edema Formation
Advances in epilepsy in recent decades have allowed for improved algorithms for diagnosis and a common understanding of terminology with the development of the International Classifications of Seizures and the Epilepsies. Nevertheless, no common system exists for the estimation of epilepsy severity or its impact on quality of life. Therefore, epileptologists lack the ability to make quantitative assessments of individual patients for comparison of care or for meta-analyses in clinical trials. This book on the Quantitative Assessment of Epilepsy Care approaches this omission by addressing the potential application of clinimetrics within the framework of epilepsy treatment. Clinimetrics is a fast growing discipline concerned with the quantification of clinical symptoms with respect to decision making relating to diagnosis, treatment, and prognosis. These methods allow for the development and validation of clinical scoring systems. For example, the Glasgow Coma Scale is widely used. As a chronic disorder, epilepsy would benefit from clinimetric methodology to create uniformity and to allow for comparisons among evaluations. In addition, epileptologists have not yet developed assessments of health related quality of life to define the overall condition of the chronic epilepsy patient and various therapeutic endpoints. While clini metric tools are essential for research, they will also be useful in clinical practice for the care of individual patients by documenting status and changes over time. This treatise will provide critical analyses of whether existing rating scales and techniques are valid to use, and which types of scales and techniques require further development.
This volume is based on the proceedings of a NATO Advanced Research Workshop on Slow Potential Changes in the Human Brain that was held at II Ciocco, Tuscany, Italy over the period 13-16th May, 1990. The Workshop Director was Dr. W. C. McCallum of the Burden Neurological Institute, Bristol, England. The meeting was superbly organised and proved to be both stimulating and productive. On behalf of everyone who attended the meeting, I would like to II Ciocco for express my appreciation to NATO for the provision of funding and to providing such a marvellous conference venue. I must apologise to everyone who has contributed to this volume for the length of time it has taken to produce a finished book. As you are all aware, the untimely death of Cheyne McCallum, who was to have been the sole editor of this volume, was very disruptive to both the book and myself. Following Cheyne's death I assumed the responsibility for completing the book as was his wish. I would like to thank you all for your patience and understanding. I would like to acknowledge my indebtedness to the Burden Neurological Institute in general and very specifically to Mrs. Chris Gough who has laboured extensively in the production of this volume.
The aim of this treatise is to summarize the current understanding of the mechanisms for blood flow control to skeletal muscle under resting conditions, how perfusion is elevated (exercise hyperemia) to meet the increased demand for oxygen and other substrates during exercise, mechanisms underlying the beneficial effects of regular physical activity on cardiovascular health, the regulation of transcapillary fluid filtration and protein flux across the microvascular exchange vessels, and the role of changes in the skeletal muscle circulation in pathologic states. Skeletal muscle is unique among organs in that its blood flow can change over a remarkably large range. Compared to blood flow at rest, muscle blood flow can increase by more than 20-fold on average during intense exercise, while perfusion of certain individual white muscles or portions of those muscles can increase by as much as 80-fold. This is compared to maximal increases of 4- to 6-fold in the coronary circulation during exercise. These increases in muscle perfusion are required to meet the enormous demands for oxygen and nutrients by the active muscles. Because of its large mass and the fact that skeletal muscles receive 25% of the cardiac output at rest, sympathetically mediated vasoconstriction in vessels supplying this tissue allows central hemodynamic variables (e.g., blood pressure) to be spared during stresses such as hypovolemic shock. Sympathetic vasoconstriction in skeletal muscle in such pathologic conditions also effectively shunts blood flow away from muscles to tissues that are more sensitive to reductions in their blood supply that might otherwise occur. Again, because of its large mass and percentage of cardiac output directed to skeletal muscle, alterations in blood vessel structure and function with chronic disease (e.g., hypertension) contribute significantly to the pathology of such disorders. Alterations in skeletal muscle vascular resistance and/or in the exchange properties of this vascular bed also modify transcapillary fluid filtration and solute movement across the microvascular barrier to influence muscle function and contribute to disease pathology. Finally, it is clear that exercise training induces an adaptive transformation to a protected phenotype in the vasculature supplying skeletal muscle and other tissues to promote overall cardiovascular health. Table of Contents: Introduction / Anatomy of Skeletal Muscle and Its Vascular Supply / Regulation of Vascular Tone in Skeletal Muscle / Exercise Hyperemia and Regulation of Tissue Oxygenation During Muscular Activity / Microvascular Fluid and Solute Exchange in Skeletal Muscle / Skeletal Muscle Circulation in Aging and Disease States: Protective Effects of Exercise / References
Membrane Receptors, Channels and Transporters in Pulmonary Circulation is a proceeding of the 2008 Grover Conference (Lost Valley Ranch and Conference Center, Sedalia, Colorado; September 3-7, 2008), which provided a forum for experts in the fields of those receptors, channels and transporters that have been identified as playing key roles in the physiology and pathophysiology of the pulmonary circulation. The book rigorously addresses: i) recent advances in our knowledge of receptors, channels and transporters and their role in regulation of pulmonary vascular function; ii) how modulation of expression and function of receptors, channels and transporters and their interrelationships contribute to the pathogenesis of pulmonary vascular disease; and iii) the therapeutic opportunities that may be revealed by enhancing our understanding of this area. The overall goal was to explore the mechanisms by which specific receptors, channels and transporters contribute to pulmonary vascular function in both health and disease, and how this knowledge may lead to novel interventions in lung dysplasia, pulmonary edema, lung injury, and pulmonary and systemic hypertension to reduce and prevent death from lung disease. Membrane Receptors, Channels and Transporters in Pulmonary Circulation is divided into six parts. Part 1 (Ion Channels in the Pulmonary Vasculature: Basics and New Findings) is designated for basic knowledge and recent findings in the research field of ion channels in pulmonary circulation. There are five chapters in Part I discussing the function, expression, distribution and regulation of various ion channels present in pulmonary vascular smooth muscle cells and how these channels are integrated to regulate intracellular Ca2+ and cell functions. Part II (TRP Channels in the Pulmonary Vasculature: Basics and New Findings) is composed of five chapters that are exclusively designed to discuss the role of a recently identified family of cation channels, transient receptor potential (TRP) channels, in the regulation of pulmonary vascular tone and arterial structure. Part III (Pathogenic Role of Ion Channels in Pulmonary Vascular Disease) includes four chapters that discuss how abnormal function and expression of various ion channels contribute to changes in cell functions and the development of pulmonary hypertension. Part IV (Receptors and Signaling Cascades in Pulmonary Arterial Hypertension) consists of five chapters devoted to the role of bone morphogenetic protein receptors, Notch receptors, serotonin receptors, Rho kinase and vascular endothelial growth factor receptors in the development of pulmonary arterial hypertension. Part V (Receptors and Transporters: Role in Cell Function and Hypoxic Pulmonary Vasoconstriction) includes four chapters designed to illustrate the potential mechanisms involved in oxygen sensing and hypoxia-induced pulmonary vasoconstriction and hypertension. Part VI (Targeting Ion Channels and Membrane Receptors in Developing Novel Therapeutic Approaches for Pulmonary Vascular Disease) consists five chapters which discuss the translational research involving on membrane receptors, channels and transporters, including their potential as novel drug targets. We hope that Membrane Receptors, Channels and Transporters in Pulmonary Circulation will allow readers to foster new concepts and new collaborations and cooperations among investigators so as to further understand the role of receptors, channels and transporters in lung pathophysiology. The ultimate goal is to identify new mechanisms of disease, as well as new therapeutic targets for pulmonary vascular diseases. An additional outcome should be enhanced understanding of the role of these entities in systemic vascular pathophysiology, since the conference will include researchers and clinicians with interests in both pulmonary and systemic circulations.
Edited by renowned protein scientist and bestselling author Roger L. Lundblad, with the assistance of Fiona M. Macdonald of CRC Press, this fourth edition of the Handbook of Biochemistry and Molecular Biology represents a dramatic revision — the first in two decades — of one of biochemistry's most referenced works. This edition gathers a wealth of information not easily obtained, including information not found on the web. Offering a molecular perspective not available 20 years ago, it provides physical and chemical data on proteins, nucleic acids, lipids, and carbohydrates. Presented in an organized, concise, and simple-to-use format, this popular reference allows quick access to the most frequently used data. Covering a wide range of topics, from classical biochemistry to proteomics and genomics, it also details the properties of commonly used biochemicals, laboratory solvents, and reagents. Just a small sampling of the wealth of information found inside the handbook: Buffers and buffer solutions Heat capacities and combustion levels Reagents for the chemical modification of proteins Comprehensive classification system for lipids Biological characteristics of vitamins A huge variety of UV data Recommendations for nomenclature and tables in biochemical thermodynamics Guidelines for NMR measurements for determination of high and low pKa values Viscosity and density tables Chemical and physical properties of various commercial plastics Generic source-based nomenclature for polymers Therapeutic enzymes About the Editors: Roger L. Lundblad, Ph.D. Roger L. Lundblad is a native of San Francisco, California. He received his undergraduate education at Pacific Lutheran University and his PhD degree in biochemistry at the University of Washington. After postdoctoral work in the laboratories of Stanford Moore and William Stein at the Rockefeller University, he joined the faculty of the University of North Carolina at Chapel Hill. He joined the Hyland Division of Baxter Healthcare in 1990. Currently Dr. Lundblad is an independent consultant and writer in biotechnology in Chapel Hill, North Carolina. He is an adjunct Professor of Pathology at the University of North Carolina at Chapel Hill and Editor-in-Chief of the Internet Journal of Genomics and Proteomics. Fiona M. Macdonald, Ph.D., F.R.S.C. Fiona M. Macdonald received her BSc in chemistry from Durham University, UK. She obtained her PhD in inorganic biochemistry at Birkbeck College, University of London, studying under Peter Sadler. Having spent most of her career in scientific publishing, she is now at Taylor and Francis and is involved in developing chemical information products.
