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Many new antileukotriene drugs are now marketed as antiasthma drugs and represent the first new drugs in this field since the 1970s. This book covers the steps that have led to the discovery and development of these new drugs and offers detailed descriptions of their clinical applications. The review chapters on the main aspects of basic and applied leukotriene research are written by leading specialists in the field, and the volume takes a new approach in presenting information of particular interest to both scientists and clinicians in the fields of asthma, inflammation and allergic diseases.
In the two decades since the elusive "slow reacting substance of anaphylaxis" (SRS-A) was identified as a product of the action of the 5-lipoxygenase enzyme on arachidonic acid, it has been well established that the leukotrienes are key mediators of both alIergy and inflammation. Their release by alIergen or other challenge has been demonstrated in the lungs of asthmatic subjects, and measurement of urinary leukotriene concentrations in such patients has been shown to be a valuable, non invasive indicator. Significant progress has been made towards the characterization of the leukotriene receptor subtypes, exemplified by the cloning of the LTB4 receptor earlier this year. Coupled with this there has been a continued elucidation of signal transduction mechanisms underlying receptor activation. Consequent upon these advances has been the development of potent antagonists of the CysLT receptor, J and both these and inhibitors of leukotriene biosynthesis have entered clinical practice in the therapy of asthma. In this clinical setting antagonists of the CysLTJ receptor have been shown to be an effective therapy in chronic asthmatics, against antigen- and exercise-induced bronchoconstriction, and in aspirin-intolerant asthmatics. The advent of this new class of agents promises to change the way in which asthmatic patients are currently treated.
This volume is the proceedings of the 11th International Conference on Advances in Prostaglandin and Leukotriene Research: Basic Science and New Clinical Applications, held in Florence, Italy, on June 4-8, 2000, which continues the tradition of covering both basic and clinical aspects of prostaglandin and leukotriene research. At this meeting particular emphasis was given to the potential application of the novel COX-2 inhibitors, the genetics of asthma relating to the production of leukotrienes, and novel cellular networks for the production of leukotrienes and lipoxins. Traditionally, as has been done in past meetings of this series, a considerable amount of new material was presented and discussed this year, with particular attention given to the newest clinical data.
Lipoxygenases and Their Products provides a cogent summary of the advances in understanding lipoxygenases and their products, emphasizing their pharmacology and pathophysiology; regulation and structure; physiological role; and receptors and receptor antagonists. This text also reviews the literature where specific receptor antagonists (as opposed to enzymatic inhibitors) have been used to characterize the pharmacologic action and the pathophysiologic roles of some of lipoxygenase products of arachidonic acid metabolism. This book is organized into 11 chapters and begins with an overview of the biochemical, pharmacological, and pathophysiological aspects of 5-lipoxygenase products of arachidonic acid metabolism in the respiratory, cardiovascular, renal, gastrointestinal, and central nervous systems. The discussion then shifts to human 5-lipoxygenase, emphasizing this enzyme purification, stimulatory factors, and membrane translocation. The reader is methodically introduced to 5-lipoxygenase activity in rats and pigs; the potential and therapeutic value of 5-lipoxygenase inhibitors; the distribution of 15-lipoxygenase in cells or tissues; and products formed through the 15-lipoxygenase pathway. This book also considers lipoxins and third-generation peptidoleukotriene receptor antagonists, and then concludes with a summary of the physiological and pathophysiological effects of leukotrienes and lipoxins in a variety of organs. This book is of interest to scientists interested in arachidonic acid and its metabolites, to scientists engaged in drug discovery-and-development activities in academia and the pharmaceutical industry, and to clinicians interested in diseases associated with leukotrienes and related products.
Severe asthma is a form of asthma that responds poorly to currently available medication, and its patients represent those with greatest unmet needs. In the last 10 years, substantial progress has been made in terms of understanding some of the mechanisms that drive severe asthma; there have also been concomitant advances in the recognition of specific molecular phenotypes. This ERS Monograph covers all aspects of severe asthma – epidemiology, diagnosis, mechanisms, treatment and management – but has a particular focus on recent understanding of mechanistic heterogeneity based on an analytic approach using various ‘omics platforms applied to clinically well-defined asthma cohorts. How these advances have led to improved management targets is also emphasised. This book brings together the clinical and scientific expertise of those from around the world who are collaborating to solve the problem of severe asthma.
Mast Cells and Basophils will be essential reading for immunologists, biochemists and medical researchers. Detailed chapters cover all aspects of mast cell and basophil research, from cell development, proteases, histamine, cysteinyl leukotrienes, physiology and pathology to the role of these cells in health and disease. Chapters also discuss the clinical implications of histamine receptor antagonists.