The biology of the family of endogenous autocrine peptides known as the endothelins (ETs) has been a source of intense study for researchers since 1988, following the identification of ET-l as the previously described endothelium-derived contractile factor. Initial interest focussed on the actions of the ETs in the cardiovascular system, and this remains the pri mary source of published work involving these peptides. Importantly, evi dence is mounting for a significant mediator role for ET-l in cardiovascu lar diseases including systemic hypertension and congestive heart failure. However, it was also recognized early on that the ETs exert an array of powerful actions in the respiratory tract, many of which prompted specula tion concerning mediator roles for ET-l in several lung diseases including asthma and pulmonary hypertension. In recent years the evidence for the involvement of ET-l in lung diseases has become more compelling. There is now real hope and anticipation that novel ET receptor antagonists may eventually be used therapeutically against asthma and other major lung pathologies. It is this atmosphere of excitement created by new discoveries and the increasing scientific ratio nale for a significant impact ofthe ETs in pulmonary diseases that prompt ed the creation of this book, the first on this topic. Most of the information presented relates to ET-l, which is the most widely studied member of the ET family.

The Pulmonary Endothelium is a uniquely comprehensive compendium of our current knowledge of the pulmonary endothelium and is the first book dedicated specifically to the subject, offering insights into current and future approaches to management. The text provides the clinician with the most up-to-date information on one of the core physiological processes in airway disease and is an ideal point of reference for both postgraduates and professionals – specialist physicians in pulmonology and allergy and workers in biomedical and pharmaceutical research.

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

Pulmonary endothelium forms the inner lining of blood vessels, where it interprets the complex mechanical and chemical environment within the circulation and adjusts its behavior to facilitate vascular homeostasis. Although endothelium fulfills many essential functions, including regulation of vascular pressure, circulating cell transmigration, coagulation, and hormone metabolism and/or delivery, a principal role is to form a semi-permeable barrier that limits fluid, solute and macromolecular access to the interstitial space. Physiological properties that govern such permeability characteristics are defined by the Starling equation, which assumes that endothelial cells throughout the circulation are all alike. However, in recent years it has become evident that endothelial cells in pulmonary arteries, capillary and veins are heterogeneous in structure and function. Here, we review evidence for endothelial heterogeneity among these pulmonary vascular segments, and consider the implications for such heterogeneity in lung fluid balance, especially as it relates to the Starling equation.

Featuring more than 4100 references, Drug-Induced Liver Disease will be an invaluable reference for gastroenterologists, hepatologists, family physicians, internists, pathologists, pharmacists, pharmacologists, and clinical toxicologists, and graduate and medical school students in these disciplines.

Written by the foremost authority in the field, this volume is a comprehensive review of the multifaceted phenomenon of hepatotoxicity. Dr. Zimmerman examines the interface between chemicals and the liver; the latest research in experimental hepatotoxicology; the hepatotoxic risks of household, industrial, and environmental chemicals; and the adverse effects of drugs on the liver. This thoroughly revised, updated Second Edition features a greatly expanded section on the wide variety of drugs that can cause liver injury. For quick reference, an appendix lists these medications and their associated hepatic injuries. Also included are in-depth discussions of drug metabolism and factors affecting susceptibility to liver injury.