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Integration of Pharmaceutical Discovery and Development
In the late 1980s, it became painfully evident to the pharmaceutical industry that the old paradigm of drug discovery, which involved highly segmented drug - sign and development activities, would not produce an acceptable success rate in the future. Therefore, in the early 1990s a paradigm shift occurred in which drug design and development activities became more highly integrated. This new str- egy required medicinal chemists to design drug candidates with structural f- tures that optimized pharmacological (e. g. , high affinity and specificity for the target receptor), pharmaceutical (e. g. , solubility and chemical stability), bioph- maceutical (e. g. , cell membrane permeability), and m...
Endothelin Receptors
Since the discovery of endothelin, major advances have been made in understanding the molecular structure and function of the endothelin receptors. At least two subtypes of receptors, designated ETA and ETB, have been identified through biochemical and pharmacological techniques. These subtypes are cloned and expressed and additional subtypes appear to exist. The biochemical events involved in the signal transduction processes that ultimately activate the cellular machinery involved in the end-organ responses are presented, as are the mechanisms by which the receptors recognize specific and different G-proteins. Functions mediated by the receptors at the cellular, tissue and, organ level are reviewed in detail, as well as the roles that they may play a part in the physiologic and pathophysiologic processes in animals and in humans. This book is unique in its breadth of scope. The most recent and important advances, from the intracellular level of the nucleus to the functional effect that endothelin receptors mediate in intact organs, are compiled and reviewed.
Chemical and Structural Approaches to Rational Drug Design
This book is the first to provide both a broad overview of the current methodologies being applied to drug design and in-depth analyses of progress in specific fields. It details state-of-the-art approaches to pharmaceutical development currently used by some of the world's foremost laboratories. The book features contributors from a variety of fields, new techniques, previously unpublished data, and extensive reference lists.
Cardiovascular Remodeling
Although the treatment has greatly progressed, the mortality of cardiovascular diseases remains the leading cause of death worldwide. Serious cardiovascular diseases, e.g., myocardial infarction, heart failure, cardiac dysrhythmias, and stroke, are resulted from cardiovascular remodeling secondary to the cardiovascular risk factors, including hypertension, atherosclerosis, cigarette smoking, diabetes mellitus, hyperlipidemia, aging, etc. Cardiac remodeling involves a series of molecular, cellular, and interstitial alterations, which manifest clinically as changes in size, mass, geometry, and function of the heart. In addition, vascular remodeling is an active process of structural alteration...
Diabetes and cardiovascular disease: new therapeutic interventions
Diabetes, also known as diabetes mellitus (DM), is a disease that occurs when the glucose level in the blood becomes too high (hyperglycaemia). Chronic hyperglycaemia is accompanied by both biochemical and pathological complications such as retinopathy, nephropathy, neuropathy, and cardiovascular diseases. Diabetes mellitus can be classified into two types: type I which results from the destruction of pancreatic β-cells, leading to insulin insufficiency and type II diabetes mellitus, which is mainly related to insulin resistance. Optimal control of blood glucose levels remains the cornerstone of managing DM. To date, the major classes of antidiabetic medications used to treat diabetes include: biguanides, dipeptidyl peptidase 4 (DPP-4) inhibitors, sulfonylureas, meglitinides, thiazolidinediones (TZDs), sodium-glucose cotransporter (SGLT2) inhibitors, α-glucosidase inhibitors, glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonists and the various types of insulin. Several of these drugs may have, besides their antidiabetic properties, also important cardiovascular complications for the patients taking them.
Hormones and the Heart in Health and Disease
The maintenance of arterial blood pressure and the distribution of blood flow to the various organs of the body depends on the control of the pumping action of the heart and of the resistance of the vascular beds in the individual organs in accordance with their metabolic needs. These controls are achieved through the integrated actions of circulat ing hormones, humoral factors that are synthesized and released in the heart and blood vessels, and the autonomic nervous system. The heart, however, is not only the target for the direct and indirect actions of a number of hormones and humoral factors, it is also an endocrine organ in the traditional sense, synthesizing and secreting into the cir...
The Quest for Human Longevity
"Many scientists today are working to retard the aging process in humans so as to increase both life expectancy and the quality of life. Over the past decade impressive results have been achieved in targeting the mechanisms and pathways of aging. In The Quest for Human Longevity, Lewis D. Solomon considers these scientific studies by exploring the principal biomedical anti-aging techniques. The book also considers cutting edge research on mental enhancements and assesses the scientific doubts of skeptics. The Quest for Human Longevity is also about business. Solomon examines eight corporations pursuing various age-related interventions, profiling their scientific founders and top executives,...
Endothelin: Tole in Health &
This study summarizes the progress made in the field of endothelin research since its discovery. It focuses on the role of endothelin in the pathophysiology of several diseases, both cardiovascular and non-cardiovascular, and its role in inflammation.
