Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors

This book covers new techniques in protein NMR, from basic principles to state-of-the-art research. It covers a spectrum of topics ranging from a "toolbox" for how sequence-specific resonance assignments can be obtained using a suite of 2D and 3D NMR experiments and tips on how overlap problems can be overcome. Further topics include the novel applications of Overhauser dynamic nuclear polarization methods (DNP), assessing protein structure, and aspects of solid-state NMR of macroscopically aligned membrane proteins. This book is an ideal resource for students and researchers in the fields of biochemistry, chemistry, and pharmacology and NMR physics. Comprehensive and intuitively structured, this book examines protein NMR and new novel applications that include the latest technological advances. This book also has the features of: * A selection of various applications and cutting-edge advances, such as novel applications of Overhauser dynamic nuclear polarization methods (DNP) and a suite of 2D and 3D NMR experiments and tips on how overlap problems can be overcome * A pedagogical approach to the methodology * Engaging the reader and student with a clear, yet critical presentation of the applications

An authority on anti-drug policy and crack since it became a popular street drug in the mid-1980s, Belenko traces the development of America's policy response in the context of changes in policy that were underway when crack first appeared. He summarizes the state of our knowledge about crack, its pharmacological properties, its use and effects on health and behavior, and its distribution. Moreover, he makes recommendations about policies to deal with the next drug epidemic. This empirical analysis and public policy study is intended for teachers, graduate students, researchers, practitioners, and policymakers in drug control and treatment, criminal justice law enforcement, and in public administration.

There is a high demand for antimicrobials for the treatment of new and emerging microbial diseases. In particular, microbes developing multidrug resistance have created a pressing need to search for a new generation of antimicrobial agents, which are effective, safe and can be used for the cure of multidrug-resistant microbial infections. Nano-antimicrobials offer effective solutions for these challenges; the details of these new technologies are presented here.

The book includes chapters by an international team of experts. Chemical, physical, electrochemical, photochemical and mechanical methods of synthesis are covered. Moreover, biological synthesis using microbes, an option that is both eco-friendly and economically viable, is presented. The antimicrobial potential of different nanoparticles is also covered, bioactivity mechanisms are elaborated on, and several applications are reviewed in separate sections. Lastly, the toxicology of nano-antimicrobials is briefly assessed."

Each volume of Advances in Pharmacology provides a rich collection of reviews on timely topics. Emphasis is placed on the molecular basis of drug action, both applied and experimental.

This is the very first book to deal with sex and gender differences in drug therapy - an increasingly recognized medical need. It starts with an overview on S/G in clinical syndromes and a documentation of the medical and socioeconomic damage caused by gender specific adverse drug effects. Part I covers S/G differences in pharmacokinetics. Researchers will be satisfied by the detailed discussion of the mechanisms of S/G differences in drug effects that represents cutting edge science and includes interaction of drugs with sex hormones, genomic and epigenetic mechanisms. It also covers S/G in drug development, in animal models and clinical development and S/G in drug prescriptions. Part II targets S/G differences in drug effects in cardiovascular, pulmonary, CNS, neuromuscular, neuropsychiatric and metabolic diseases, in cancer, inflammation, and rheumatic diseases, in bacterial and retroviral infections, thrombosis, embolism. New drugs will be discussed.

This new volume of "Advances in Pharmacology" explores the current state of Alzheimer's disease research and therapeutics. Chapters cover such topics as the B cell targeted therapies, Lymphotoxin family receptors in inflammation, and allergic inflammation and thymic stromal lymphopoietin. With a variety of chapters and the best authors in the field, the volume is an essential resource for pharmacologists, immunologists and biochemists alike.
Explores the current state of Alzheimer's disease research and therapeutics Chapters cover a variety of topics such as the B cell targeted therapies, lymphotoxin family receptors in inflammation, and allergic inflammation and thymic stromal lymphopoietinWith the best authors in the field, the volume is an essential resource for pharmacologists, immunologists and biochemists alike

The field of eicosanoid metabolism and function continues to grow. Synthesis of the prostaglandins from essential fatty acids was first described by Bergstrom and Sarnuelsson in 1964. The thromboxanes were discovered in 1975, the prostacyclins, by Moncada and Vane, in 1976, and the leukotrienes by Samuelsson in 1979. A new class of biologically active arachidonic acid metabolites named lipoxins was announced by Bengt Samuelsson in May 1984. Since that time major advances have been made in the molecular biology of the eicosanoids including the cloning of prostaglandin synthases and 5, 12, and 15-lipoxygenases from several different species, including man. This volume, Prostaglandins, Leukotrienes, Lipoxins, and P AF: Their Mechanism of Action, Molecular Biology, and Clinical Applications contains most of the papers presented in the plenary sessions of the Xlth International Washington Spring Symposium on Health Sciences. The book is divided into six parts, each covering a different aspect of this rapidly expanding field, and contains a total of 42 chapters by an internationally recognized group of authors in each area. Part I contains 11 chapters and covers the molecular biology and enzymology of prostaglandins and leukotrienes. Chapter 1 by the Editor details new mechanisms for the antiinflammatory glucocorticoids involving translational control of the messenger RNA for prostaglandin synthase. Chapter 2 by Yamamoto describes the molecular evolution of two distinct mammalian 12-lipoxygenases.

Although the official compendia define a drug substance as to identity, purity, strength, and quality, they normally do not provide other physical or chemical data, nor do they list methods of synthesis or pathways of physical or biological degradation and metabolism. Such information is scattered throughout the scientific literature and the files of pharmaceutical laboratories. Edited by the Associate Director of Analytical Research and Development for the American Association of Pharmaceutical Scientists, Analytical Profiles of Drug Substances and Excipients brings this information together into one source. The scope of the series has recently been expanded to include profiles of excipient materials.

The Symposium on New Drugs provides for an annual forum for academic investigators, research and development personnel from the pharmaceutical and related health care industries, and members of the Food and Drug Administration to discuss important clinical research issues. The Tenth Annual Symposium on New Drugs addressed the problem of whether it was still appropriate to approve antihypertensive agents soley on the endpoint of lowering cuff blood pressure. The initial discussions at this symposium related to the approaches and methods to studying antihypertensive agents. Dr. William Frishman provided a detailed list of the new approaches to the treatment of hypertension and pointed out the many new concepts that are currently active in the development of many new antihypertensive agents. Dr. William White detailed the growing importance of ambulatory blood pressure monitoring to define hypertension and to determine the change in blood pressure due to pharmacologically active agents. Dr. Jay Cohn pointed out the flaws in using cuff blood pressure and detailed the potential virtues of using vascular compliance to identify patients requiring treatment for hypertension. Dr. Thomas Pickering also discussed the potential value of evaluating changes in left ventricular hypertrophy a finding which identifies high risk patients who need to be included in clinical trials. Dr. Michael Weber detailed the issues and suggested refinements in the approaches to clinical trial designs for antihypertensive agents and Dr. Raymond Lipicky discussed the definition of dose-duration and the role of non-Mem and Peak/Through measurements in defining an antihypertensive drug effect.

Etienne-Emile Baulieu, the discoverer of neurosteroids, and a panel of distinguished scientists and clinical researchers exhaustively and critically review all facets of neurosteroids involved in behavior, stress, memory, depression, anxiety, aging of the brain, and neurodegenerative diseases. These contributors illuminate the role of neurosteroids in brain development and plasticity and detail their neuromodulatory influence on GABAA, ionotropic glutamate receptors, acetylcholine receptors, sigma receptors, and calcium channels. Clearly pointing the way toward novel pharmaceutical agents that may be of significant therapeutic value, particularly with regard to aging mental functions, Neurosteroids: A New Regulatory Function in the Nervous System offers neurobiologists, psychiatrists, neurosurgeons, pharmacologists, and geriatricians the first comprehensive, state-of-the-art review of these important bioactive molecules.

Part B explores protein degradation occuring in vivo during protein synthesis in cells, examines the isolation and purification of proteins, details protein use in organisms, and reviews techniques to enhance protein stability.

At the Mie International Symposium held in Japan in April 1994, leading scientists reviewed recent advances in the understanding of the contractile mechanism in smooth muscle. The present volume collects the papers presented at the symposium, summarizing the latest advances in smooth muscle function and emphasizing important components of the contraction-relaxation cycle. Topics include a discussion of the smooth muscle cell membrane, with emphasis on its ion channels; the regulation of cytosolic Ca2+ levels and the relationship to force in smooth muscle; aspects of the two key regulatory enzymes involved with myosin phosphorylation-dephosphorylation; the molecular basis for pharmacomechanical coupling in smooth muscle; developments in the basic contractile mechanisms involving the crossbridge cycle of tonic and phasic muscle; the role of myosin light chains; and many others. The approach is broad and presents contemporary opinions in pharmacology, physiology, and biochemistry as they relate to smooth muscle function. The book will appeal not only to those working in these disciplines, but to vascular clinicians, obstetric-gynecological physicians, and gastroenterologists as well.

Recombinant proteins and polypeptides continue to be the most important class of biotechnology-derived agents in today's pharmaceutical industry. Over the past few years, our fundamental understanding of how proteins degrade and how stabilizing agents work has made it possible to approach formulation of protein pharmaceuticals from a much more rational point of view.

This book describes the current level of understanding of protein instability and the strategies for stabilizing proteins under a variety of stressful conditions.

Contents. List of Contributors. Preface. T.J. Mitchell and T.J. Williams: The role of eotaxin and related CC-chemokines in asthma and allergy. Roger J. Davis: Signal transduction by the JNK group of MAP kinases. Marie Chabot-Fletcher: TNF and IL-1 signaling to NF-kB. Anthony M. Manning: Small molecule regulators of AP-1 and NF-kB. Robert T. Abraham: Mammalian target of rapamycin: Immunosuppressive drugs offer new insights into cell growth regulation. Catherine A. Burton, John Boylan, Candy Robinson, Janet Kerr and Pamela Benfield: Constitutive expression of a tumor suppressor leads to tumor regression in a xenograft model. Steven D. Shapiro: Macrophage metalloproteinases in destructive inflammatory diseases. Nancy H. Ruddle: Lymphotoxin in inflammation and lymphoid organ development: Variations on a theme. Steven L. Kunkel, Sem H. Phan, Nicholas W. Lukacs, Cory Hogaboam and Stephen W. Chensue: Chemokine/cytokine biology during the evolution of fibrotic disease. Long Gu, Susan C. Tseng and Barrett J. Rollins: The role of MCP-1 in disease. Lisa A. Beck, Cristiana Stellato, Syed Shahabuddin, Renate Nickel and Robert P. Schleimer: The role of chemokines in allergic diseases of the airways. James Winkler and Ken Tramposch (coordicators): Ninth International Conference of the Inflammation Research Association, November 1-5, 1998: Summaries of workshops and poster discussions. William Williams and Elizabeth Arner (chair persons): Targets in rheumatoid and osteoarthritis. Lawrence Wennogle and Nancy Cusack (chair persons): Signal transduction and regulation of gene expression. James Burke and Floyd Chilton (chair persons): Mediators in inflammation and their enzymes. Denis Schrier and Fandrew Issekutz (chair persons): Cell adhesion molecules and leukocyte trafficking. Robert M. Strieter and David Underwood (chair persons): Pulmonary inflammation, fibrosis, and disease. W. Hunter and E. Turley (chair persons): Angiogenesis, wound repair and skin inflammation. Index.

This work describes the importance of tumor microenvironment in favouring tumor progression and angiogenesis. Under physiological conditions, angiogenesis is dependent on the balance of positive and negative angiogenic modulators within the vascular microenvironment and requires the functional activities of a number of molecules, including angiogenic factors, extracellular matrix proteins, adhesion molecules and proteolytic enzymes. In normal tissues, vascular quiescence is maintained by the dominant influence of endogenous angiogenesis inhibitors over angiogenic stimuli. Tumor angiogenesis is linked to a switch in the balance between positive and negative regulators, and mainly depends on the release by inflammatory or neoplastic cells of specific growth factors for endothelial cells, that stimulate the growth of the blood vessels of the host or the down-regulation of natural angiogenesis inhibitors. In particular, the inflammatory infiltrate may contribute to tumor angiogenesis, and there are many reports of associations between tumor inflammatory infiltrate, vascularity and prognosis. New therapeutic approaches have been developed with the aim to control tumor angiogenesis through targeting of different components of tumor microenvironment.

Nanophytomedicine is a field that involves the application of nanomedicine-based systems to phytotherapy and phytopharmacology. This book assesses the clinical successes and failures of nanophytomedicine and also highlights emerging concepts in this field. The content is divided into three sections, the first of which describes core issues in the pharmaceuticals industry in connection with the successes, failures and prospects of nanophytomedicine. The second section highlights recent advances in phytomedicine formulation development based on nanotechnology approaches, while also discussing a variety of nanocarrier systems for the successful delivery of phytomedicines. Focusing on the clinical perspective, the third section addresses the current clinical status of nanophytomedicine as a single drug therapy or combinatorial drug therapy, pharmacovigilance, pharmacokinetics, drug interactions and toxicological profiles, while also providing concluding remarks on recent experimental findings, and considering ethical issues & regulatory challenges in nanophytomedicine. Given its scope, the book offers a valuable guide for early career researchers, young scientists, master level students, academics and industrial scientists working in various healthcare fields, e.g. the pharmaceutical and biological sciences, life sciences, biotechnology, biomedical engineering, and nanobiotechnology.

Influenza continues to be an ongoing problem despite the existence of vaccines and drugs. Disease outbreaks can occur relatively quickly as witnessed with the recent emergence of the influenza virus A/H1N1 pandemic. The development of new anti-influenza drugs is thus a major challenge. This volume describes all aspects of the virus structure and function relevant to infection. The focus is on drug discovery of inhibitors to the enzyme sialidase, which plays a key role in the infectious lifecycle of the virus. Following an overview of the influenza virus, the haemagglutinin, the interactions with the cell receptors and the enzymology of virus sialidase, recent results in drug design are presented. These include a full coverage of the design, synthesis and evaluation of carbohydrate as well as non-carbohydrate influenza virus sialidase inhibitors. Further reviews of the clinical experience with influenza virus sialidase inhibitors and of the development of resistance to these inhibitor drugs complement the topic.

The Pope's Piano is a collection of three short fiction stories. The first two tales, "Violin Master" and "The Pope's Piano," have central music themes. Several cats are side characters in the last two stories. All three are best described as religious mysteries where strange, magical things happen that are best attributed to the workings of God.

The third story, "The Kitten with the Bent Ear," describes a college professor leading class discussions on important and difficult topics that affect our daily lives, like the death penalty, expensive medical procedures, abortion, immigration, and end-of-life medical decisions. Interspersed with the class discussion is the story of the professor's cats, including one with several deformities. In "The Kitten with the Bent Ear," the harsh and pragmatic decisions animals in the wild take is contrasted to what are man's options. This story will allow each of us to see all sides of controversial issues and help you solidify your thinking as to what are practical and just solutions.

The trilogy may bring the reader closer to God and let you enjoy the mysteries of life. With love and belief, anything is possible, even miracles.

A comprehensive review of the science of drug testing in all its aspects, placing emphasis on technologies that use body fluids other than urine for determining the presence of drugs of abuse. The authors discuss the various body fluid specimens suitable for testing for illicit drugs-particularly saliva, sweat, and hair-describe the structural and manufacturing aspects of on-site testing devices based on lateral flow immunoassay, and detail the pitfalls of using these specimens. They also discuss in detail the problem of sample adulteration and its detection. Since oral fluid has the best potential of succeeding urine as the next matrix of choice for drug detection, four popular saliva testing devices are examined: Intercept (R), the Drager Drug Test (R), Oratect (R), and Drugwipe. Political, social, and legal issues are also considered in articles on privacy, the use of drug testing in courts, and the problem of sample adulteration.

Investigation of the pharmacokinetics and metabolism of human proteins has escalated over the last two decades because of the use of recombinant human proteins as therapeutic agents. In addition, the development and improvement of analytical techniques enabling the detection of minute quantities of proteins in biological matrices have aided this process. In assembling this volume, we sought to provide a state-of-the-art as sessment of the pharmacokinetics and metabolism of protein therapeutics through complete reviews of selected examples. A comprehensive review of all protein therapeutics was not attempted; the majority -of the therapeutic protein classes and crucial scientific issues have been addressed, however. Therefore, we are confident that this volume will provide a useful reference for scientists in this field. The volume has been divided into two general parts. The first part (Chapters 1-3) is composed of general reviews of topics of importance in pharmacokinetic/metabolism studies of proteins: goals and analytical meth odologies, effects of binding proteins, and effects of antibody induction, respectively. The second part (Chapters 4-8) consists of specific, detailed reviews by therapeutic protein class: growth factors and hormones, cyto kines, cardiovascular proteins, hematopoietic proteins, and antibodies, respectively. The editors are grateful to the contributors for the patience, personal sacrifice and perseverance required to complete this volume. BoDDE L. FERRAIOLO MARJORIE A. MOHLER CAROL A. GLOFF ix Contents Chapter 1 Goals and Analytical Methodologies for Protein Disposition Studies Bobbe L. Ferraiolo and Marjorie A. Mohler 1. Introduction ................................................. ."

The book is an introduction to nanomedicine informed by a philosophical reflection about the domain and recent developments. It is an overview of the field, sketching out the main areas of current investment and research. The authors present some case-studies illustrating the different areas of research (nanopharmacy, theranostics and patient monitoring) as well as reflecting on the risks that accompany it, such as unanticipated impacts on human health and environmental toxicity. This introduction to a fast-growing field in modern medical research is of great interest to researchers working in many disciplines as well as the general public. In addition to an overview of the work currently ongoing, the authors critically assess these projects from an ethical and philosophical perspective. Key Features Provides an overview of nanomedicine Employs a reflective and coherent critical evaluation of the benefits and risks of nanomedicine Written in an accessible manner intended for a wide audience Related Titles Hehenberger, M. Nanomedicine: Science, Business, and impact (ISBN 978-9-8146-1376-7). Beg, S., et al. Nanomedicine for the treatment of Disease: From Concept to Application (ISBN 978-1-7746-3443-1) Brenner, S. The Clinical Nanomedicine Handbook (ISBN 978-1-1380-7578-8)

In a systematic and clear manner, the authors discuss the problems associated with clinical decision making and explore the current methods to solve them. In this monograph, they examine the results of combining the classical control system approach with the symbolic approaches which have been central to developments in artificial intelligence. Well illustrated with case studies, this volume will prove to be an invaluable resource to system scientists, engineers, computer scientists, and members of the medical community.