This volume presents the evolution of the authors' ideas about estrogen action and its modulation by a new group of drugs called SERMs (Selective Estrogen Receptor Modulators). The pioneering SERMs OCo tamoxifen and raloxifene OCo are known to have saved the lives of millions of women around the world and improved the health of millions more. Estrogen is the central hormone of women's health and reproduction. The book is a journey through 40 years of discovery and success in advancing women's health, with the prospect of improved innovation through medicinal chemistry for the future.

Experimental and clinical researchers from a wide range of disciplines present a wealth of fresh scientific information on the biochemistry, molecular biology, pharmacology, and clinical activity of SERMs. The basic science chapters of the book focus-with an eye to the development of the ideal SERM-on the complex mechanisms of estrogen action, including ligand-dependent conformational changes in alpha and beta, and the recruitment of co-activators and co-repressors which modulate the estrogen receptor transcriptional activity and contribute to its crosstalk with growth factor signaling. The clinical presentation reviews the data accumulated on currently available SERMs, primarily tamoxifen and raloxifene, in cancer treatment and prevention, as well as their effects on the reproductive, vascular, skeletal, and central nervous systems. A tentative approach to menopause-related health issues is also provided for women with and without a previous diagnosis of localized breast cancer.

The increasing awareness on the varied consequences of hypogonadism in distinct organs and systems has supported the notion of estrogens as systemic agents. This observation is congruent with the variety of tissues affected by - trogens when used in hormone therapy formulations on hypogonadic women. Apart from the genital tract and the breast, recognized as traditional targets for estrogens, the skeleton, the vascular tree, or the central nervous system, are good examples of territories that have demonstrated sensitivity to estrogens. This evidence has created great interest, as shown by the great amount of lit- ature that has been produced on the bene?ts and risks associated with the use of estrogens. In parallel to the clinical interest, basic research has improved our kno- edge on the complexities involved in estrogen action at the molecular level. Together with effects mediated through speci?c receptors, a concept that has been the mainstay of the interpretation of estrogen action for years, there is enough evidence to hold the notion of receptor-independent effects. The substantial advances in modern technology applied to research have helped in enlightening the particulars of this versatile action of estrogens. This more detailed knowledge on the sophisticated mechanism of action of estrogens has nourished the emergence of multiple hypotheses speculating with the p- sibility of manipulating estrogen action. The notion that a widely extended regulatory system of cell function, as it is the estrogen receptor machinery, might be modulated at wish has arisen as an attractive, although still elusive postulate.

Gene therapy, bioengineered skin, and other methods in advanced biology are revolutionizing the treatment of wounds. Written by experts in research and clinical practice, Cutaneous Wound Healing examines the current knowledge and emerging treatment methods. This volume explains the normal molecular and cellular functions that occur when a wound heals, as well as dysfunctional events, such as a chronic wound or an ulcer. Such dysfunctions signal an imbalance in the body, explained here along with possible treatments. The book's mini-atlas is an indispensable reference tool. Dermatologists, plastic surgeons, and general practitioners can benefit from this text.

For anyone who treats postmenopausal women, this latest edition of Rogerio Lobo's classic work combines the best from two well-known references: Menopause, and the second edition of Treatment of the Postmenopausal Woman. By adding significant discussions of the basic science behind menopause, it is possible to objectively assess the clinical value and limitations of current approaches to treatment and provide a basis and rationale for strategies that will result in better individualized and specialized care. Not only does the third edition discuss diagnosis and treatment of menopause but it covers biological, anatomical, physiological, pathobiological, and pharmacological aspects as well bringing together, in one source, all of the information needed to understand and treat postmenopausal conditions. Over 50% new material representing the vast amount of information available since the Women's Health Initiative (WHI) clinical trials were completed making this the most up-to-date reference on postmenopausal women Includes several new sections on comparisons between clinical trials and observational data, urology, and pelvic support Each section is preceded by a preface to put the area into context with many chapters having suggested treatment regimens

This volume examines basic and clinical findings on the role played by the oestrogen receptor (ER) and its modulation in multiple physiologic systems. The authors examine the potential of selective modification of ER actions for preventing chronic diseases and promoting healthy ageing. Research gaps and potential agendas for NIH research of ER action are identified, and related intervention strategies to extend the beneficial clinical outcomes are explored.

This volume presents the evolution of the authors' ideas about estrogen action and its modulation by a new group of drugs called SERMs (Selective Estrogen Receptor Modulators). The pioneering SERMs — tamoxifen and raloxifene — are known to have saved the lives of millions of women around the world and improved the health of millions more. Estrogen is the central hormone of women's health and reproduction. The book is a journey through 40 years of discovery and success in advancing women's health, with the prospect of improved innovation through medicinal chemistry for the future.

Selective oestrogen receptor modulators (SERMs) are now recognised as a valuable method of maintaining the health of postmenopausal women. Aimed at the non-specialist, the book initially discusses the epidemiology of the menopause and the mechanism of action of oestrogen before concentrating specifically on the effect of SERMs, their safety profile and their role in clinical practice.

From our current knowledge, it is obvious that estrogen action in volves more than reproduction and fertility. Rather, estrogens affect and influence a number of other organ systems such as the immune, cardiovascular and central nervous system as well as the gastrointes tinal tract, urinary tract and skeleton. The importance of estrogens and estrogen receptor activity is appreciated from the spectrum of significant physiological dysfunctions that occur when there is a loss The participants of the workshop VI Preface of the hormone or the receptor activity. Loss of estrogen, however (for instance during menopause), occurs with time and results in a variety of clinical conditions. We know that the developmental loss of estrogen, as seen in clinical cases of aromatase gene mutations and experimental models, has dramatic effects in both men and women alike. The evidence that these effects are mediated through the estrogen receptor(s) is based on similar but not always identical phenotypes as observed in experimental animal models of estrogen receptor mutations as well as the single clinical case of an estrogen receptor alpha mutant patient. Developing an understanding of the spectrum of estrogen in a variety of tissues related to the condition of estrogen loss is a major and highly active clinical as well as basic scientific research area. Following the discovery of a second estrogen receptor and possible receptor ligand-independent activity as well as the genomic and non genomic actions of estrogen, it is clear that the mechanisms of the effects of estrogen are multifaceted.

Drug Discovery Approaches for the Treatment of Neurodegenerative Disorders: Alzheimer's Disease examines the drug discovery process for neurodegenerative diseases by focusing specifically on Alzheimer's Disease and illustrating the paradigm necessary to ensure future research and treatment success. The book explores diagnosis, epidemiology, drug discovery strategies, current therapeutics, and much more to provide a holistic approach to the discovery, development, and treatment of Alzheimer's Disease. Through its coverage of the latest research in targeted drug design, preclinical studies, and mouse and rat models, the book is a must-have resource for all pharmaceutical scientists, pharmacologists, neuroscientists, and clinical researchers working in this area. It illustrates why these drugs tend to fail at the clinical stage, and examines Alzheimer's Disease within the overall context of improving the drug discovery process for the treatment of other neurodegenerative disorders. - Provides a compilation of chemical considerations required in drug discovery for the treatment of neurodegenerative disorders - Examines different classes of compounds currently being used in discovery and development stages - Explores in vitro and in vivo models with respect to their ability to translate these models to human conditions - Distills the most significant information across multiple areas of Alzheimer's disease research to provide a single, comprehensive, and balanced resource