Comparative Pathophysiology and Toxicology of Cyclooxygenases


Book Description

The first thorough review of cyclooxygenase inhibitors, including their toxicity mechanisms and toxicopathological risks Cyclooxygenases (COXs) are enzymes responsible for the formation of an important class of biological mediators called prostanoids. Prostanoids such as prostaglandins mediate inflammatory and anaphylactic reactions. For those suffering from inflammation and pain, the pharmacological inhibition of COXs, with non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, can provide relief. Yet the use of NSAIDs can trigger toxicological effects as well, leading to potential health risks. Comparative Pathophysiology and Toxicology of Cyclooxygenases provides a comprehensive overview of how COX inhibitors affect various bodily systems, specifically the toxicity mechanisms triggered when the COX enzyme is inhibited. The book provides an introduction to the discovery of cyclooxygenases, their use as therapeutic agents, as well as an historical perspective. Shedding light on the differences in expression, pathophysiology, and toxicology of COX inhibitors across species, the book offers a systematic examination of the effects and pathophysiology of COX inhibitors and their mechanisms of toxicity, beginning with the GI tract. Subsequent chapters cover: The pathophysiology of COX inhibition on bone, tendon, and ligament healing COX inhibitors and renal system pathophysiology and mechanisms of toxicity The pathophysiologic role of COX inhibition in the ocular system COX inhibition and the respiratory and cardiovascular systems The book also sheds light on the latest research devoted to developing COX inhibitors with no adverse side-effects. The first book to offer a thorough comparative look at the toxicological effects of COX inhibitors throughout the body, this invaluable resource will help advance the research and development of safer and more effective COX drugs.




Selective COX-2 Inhibitors


Book Description

The mainstay of therapy for rheumatoid disease is the non-steroid antiinflammatory drugs (NSAIDs), despite their inherent gastrointestinal toxicity and ability to cause renal damage in susceptible patients. The theory that the beneficial and toxic effects of NSAIDs stem from a reduction in prostanoid production through inhibition of cyclooxygenase implied that particular toxicities were inevitable with NSAIDs and would always be correlated with efficacy. However, over the years, it became apparent that at therapeutic doses, some NSAIDs had greater toxic side-effects than others, a fact not explained by the general theory. A significant clarification arose from the discovery that there are two distinct isoforms of COX, a constitutive enzyme (COX-I) responsible for the production of prostanoids necessary for platelet aggregation and protection of the gastric mucosa and kidney; and an inducible enzyme (COX-2) that is newly synthesized at sites of tissue damage and produces prostaglandins that manifest pathological effects. It became clear that different NSAIDs had greater or lesser effects on COX-I when used in therapeutic doses, explaining the variation in side-effects. ' The elucidation of the crystal structure of these different enzymes and the skills of medicinal chemists have led to the synthesis of new chemicals with a selectivity for the inducible enzyme, and thus with therapeutic efficacy without those toxic effects result ing from inhibition of the constitutive enzyme.




Cyclooxygenases


Book Description

Since the discovery of the pharmacological and toxicological importance of inhibiting the cyclooxygenase (COX) enzymes by non-steroidal anti-inflammatory drugs (NSAIDs), much research has gone into the development of methods to study the biological functions of COX-1 and COX-2. In Cyclooxygenases: Methods and Protocols, experts and pioneers in the field present the most up-to-date in vitro and in vivo techniques routinely used in COX research. The volume delves into essential topics such as the purification, cloning, and expression of COX enzymes as well as in vitro assays aimed at determining the inhibitory potency of drugs on COX-1 and COX-2 activities, with chapters describing protocols used for the extraction and measurement of the prostanoids. This volume also describes in vivo disease models used to study the roles of COX-1 and COX-2 in gastrointestinal injury, inflammation, and pain. As a book in the highly successful Methods in Molecular BiologyTM series, the protocols chapters include brief introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Cyclooxygenases: Methods and Protocols serves as an indispensable tool for all scientists seeking the treatment of inflammation, pain, fever, and other harmful conditions.




The Endothelium


Book Description

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 Essence of Analgesia and Analgesics


Book Description

The Essence of Analgesia and Analgesics is an invaluable practical resource for clinicians giving pain relief in any clinical setting, describing the pharmacologic principles and clinical use of all available pain medications. As well as detailed overviews of pain processing and analgesic theory, sections are dedicated to oral and panteral opioid analgesics, neuraxial opioids, NSAIDs, local anesthetics, anticonvulsant type analgesics, NMDA antagonists, alpha adrenergic analgesics, antidepressant analgesics, muscle relaxants, adjuvant medications, and new and emerging analgesics. The concise format of the chapters allows for quick and easy reading and assimilation of information. Enhanced by summary tables and figures, each chapter provides an overview of a particular drug, covering chemical structure, mode of activity, indications, contraindications, common doses and uses, advantages and disadvantages, and drug related adverse events. Key references are also provided. Edited by leading experts in pain management, this is essential reading for any clinician involved in pain management.




The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease


Book Description

The medicinal uses of Curcumin (also called turmeric) have been known and described for more than 5000 years. A large body of recent research suggests that curcumin is potentially useful in the treatment of inflammatory diseases, through modulation of numerous molecular targets. This is the first monograph to focus on the potential use of curcumin in the treatment of cancer, diabetes, cardiovascular diseases, arthritis, Alzheimer’s, psoriasis and more.




Encyclopedia of Pain


Book Description

The Encyclopedia of Pain includes more than 3,000 entries and provides clear, detailed and up-to-date coverage of the current state of research, and treatment of pain. In addition, detailed essays provide in-depth information on all aspects of nociception and pain, including substrates, causes, pathophysiology, symptoms and signs, diagnoses and treatment. A thousand color figures enhance understanding of this too-little-understood topic. The book is available in print, in online only form, or in a print-online bundle.




The Eicosanoids


Book Description

This comprehensive reference work, updated from the first edition, brings together the knowledge and expertise of contributors from around the world. It includes new topics such as prostaglandin synthetase enzyme, new synthetic eicosanoids, innovative analytical methods, the influence of cytokines in the regulation of synthesis and actions, newer eicosanoids that influence the cardiovascular system, and newly discovered roles in reproduction and interactions with nitric oxide. This book satisfies a surge of interest in prostaglandins—NSAIDS (e.g. aspirin) are the biggest selling drugs of all time, and the field has been refreshed by the advent of new types (selective COX-2 inhibitors, anti-leukotiene drugs).




Ocular Transporters and Receptors


Book Description

Ocular transporters and receptors contains detailed descriptions of major transporters and receptors expressed in the eye, with special emphasis on their role in drug delivery. The complex anatomy and the existence of multiple barriers in the eye pose a considerable challenge to successful drug delivery to the eye. Hence ocular transporters and receptors are important targets for drug delivery. A significant advancement has been made in the field of ocular transport research and their role in drug delivery. In this book the cutting edge research being carried out in this field is compiled and summarized. The book focuses on key areas, including the anatomy and physiology of the eye, biology of ocular transporters and receptors, techniques in characterization of transporters and receptors, transporters and receptors in the anterior and posterior segment in the eye, the role of ocular transporters and receptors in drug delivery, and transporter-metabolism interplay in the eye. Highly focused on ocular transporters Most up-to-date research compilation Detailed description of role of transporters and receptors in ocular drug discovery and delivery




Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids


Book Description

This volume is the newest release in the authoritative series of quantitative estimates of nutrient intakes to be used for planning and assessing diets for healthy people. Dietary Reference Intakes (DRIs) is the newest framework for an expanded approach developed by U.S. and Canadian scientists. This book discusses in detail the role of vitamin C, vitamin E, selenium, and the carotenoids in human physiology and health. For each nutrient the committee presents what is known about how it functions in the human body, which factors may affect how it works, and how the nutrient may be related to chronic disease. Dietary Reference Intakes provides reference intakes, such as Recommended Dietary Allowances (RDAs), for use in planning nutritionally adequate diets for different groups based on age and gender, along with a new reference intake, the Tolerable Upper Intake Level (UL), designed to assist an individual in knowing how much is "too much" of a nutrient.