The last decade or so has seen remarkable advances in our knowledge of cough. This applies especially to its basic mechanisms: the types of airway sensors, the phar- cological receptors on their membranes, the brainstem organization of the 'cough centre', and the involvement of the cerebral cortex in the sensations and the vol- tary control of cough. With the exception of the last of these, nearly all the studies have been on experimental animals rather than humans, for obvious reasons. One group of experimental studies has particular relevance to human patients, and that is the demonstration of the sensitization of cough pathways both in the periphery and in the brainstem. Similar sensitizations have been shown for patients with chronic cough or who have been exposed to pollutants, and it is reasonable to suppose that this is the basis of their cough and that the underlying mechanisms are generally similar in humans and other species. Important advances are also being made in clinical cough research. For the three main causes of clinical cough, asthma, post-nasal drip syndrome, and gast- oesophageal re?ux disease, we are beginning to understand the pathological processes involved. There remains a diagnostically obdurate group of idiopathic chronic coughers, but even for them approaches are being devised to clarify und- lying mechanisms and to establish diagnoses. Perhaps surprisingly, the ?eld in which there has been the least spectacular - vance is the therapy of cough.

Anesthesia for the New Millenium: Modern Anesthetic Clinical Pharmacology contains the refresher course lectures of the 1999 meeting and is a review of the current state of the art in anesthesia clinical pharmacology. The authors of the individual chapters are among the world's most widely recognized experts in the pharmacology of perioperative medicine. The book features sections on new pharmacology concepts, new drug delivery techniques, recently released drugs and novel thinking about older drugs. It also addresses several areas that have recently emerged as very hot clinical and research topics, including depth of anesthesia monitoring technology and anesthesia drug interactions. The textbook is the seventeenth in a continuing series documenting the proceedings of the postgraduate course.

Offers a state-of-the-art review by international experts on all aspects of tachykinin receptors, including neuropeptide/peptide and G-protein-linked receptors in general. It covers the physiology, pharmacology, biochemistry, and molecular biology of these receptors from both clinical and basic research points of view.
Topics treated by the distinguished contributors include the characterization of tachykinin receptors, the mechanisms of tachykinin receptor action, a reflection on future prospects, and a historical consideration of tachykinin research.

In recent years there have been a number of significant developments of natural products for the treatment of rheumatic diseases, pain and gastro-intestinal ulcers and inflammation. The volume covers some of these novel developments of natural products which are of current and future interest as therapies for the above-mentioned conditions. Most available volumes cover a wide range of biological and technicological aspects of natural products and their discovery, some involving synthesis and properties of chemical compounds. The difference in this volume is that the natural products have a focus on their therapeutic effects on pain, arthritic and gastrointestinal diseases. Some of the natural products covered are either at the experimental stage of development while others are well-established clinically-used products. Each has its own unique place in therapy.

Bioinformatics and Drug Discovery describes the bioinformatic approaches and techniques employed along the pipeline of drug development from genes to proteins to drugs. The book focuses on gene microarray analysis and techniques for target identification and validation. In addition, clinical applications showing how the analysis can be used for prognostication and diagnosis are described. The second section focuses on protein analysis, including target validation and identification using modern proteomic analysis as well as protein modeling techniques. The third section discusses chemoinformatics, including virtual screening and how to computationally approach chemical space.

This volume describes recent research in the field of metalloproteinas es, in particular their participation in autoimmune diseases such as r heumatoid arthritis. The work updates current progress in matrix metal loproteinase research, reviewing the latest developments in metallopro teinase inhibitor design and the current status of clinical candidates . It elucidates the structural relationships between different members of the MMP family and provides insight into the contributions of diff erent metalloproteinases to normal and pathological processes. Special emphasis is given to the potential of adamlysins as therapeutic targe ts. This volume is intended not only for those active in research into metalloproteinases but also for those with an interest in inflammator y diseases. Thus it addresses both academic and industrial researchers .

Complex chemical mixtures impact our health every day. In the United States, and also in Central and Eastern Europe, there are a number of locations where complex chemical mixtures have been released to environmental media. Although exposure to mixtures is common, minimal information exists to quantify these exposures, or to determine their impact on human or ecological receptors. These proceedings present some of the most current research conducted to quantify complex mixtures in the environment and investigate their potential impact on human health. Many of the manuscripts reported in these proceedings represent the most up-to-date measurements of population exposures in Central and Eastern Europe. These studies are of value to health and environmental professionals around the world as they develop strategies for assessing exposures, remediating contaminated environments, and improving public health.

Understanding the role of hedgehog signaling in cancer is critically important for novel cancer therapeutics. The hedgehog pathway is a major pathway regulating cell differentiation, tissue polarity, stem cell maintenance and cell proliferation. It is known by now that activation of this pathway occurs in a variety of human cancer, including basal cell carcinomas (BCCs), medulloblastomas, leukemia, gastrointestinal, lung, ovarian, breast and prostate cancers. This book provides insightful views suitable for graduate students, medical students, undergraduate students, basic and clinical scientists, cancer patients as well as the general public.

The last four decades have witnessed considerable advances in our knowledge of the pharmacology of sleep. Both basic and clinical pharmacology have made major contributions toward our current understanding of the complex mechanisms of sleep and wakefulness. In addition, these advances in our understanding of the pharmacology of sleep have benefited the treatment of sleep disorders and various neurologic and psychiatric conditions. This volume is organized into three different parts. The first is a review of the basic mechanisms of sleep and wakefulness and the chronobiology of sleep. The second part reviews the basic pharmacology of the various neuro transmitter systems involved in sleep and wakefulness, while the third is clinically oriented and focuses on the effects of a variety of drugs on sleep and wakefulness. The initial part begins with a historical review of the hypotheses of the mechanisms of sleep, evolving from passive to active regulation, and concepts involving sleep-related neurotransmitters and other sleep factors. Then regulation of sleep and wakefulness is discussed in terms of homeostatic, circadian, and ultradian processes. Also discussed is the fact that sleep homeostasis is not disrupted by the administration of hypnotic drugs. This part also reviews time-dependent properties of pharmacologic agents in relation to endogenous biologic rhythms and more specifically to chrono pharmacologic changes."

Large-scale privatization did not emerge spontaneously in China in the late 1990s. Rather, the Chinese state led and carefully "planned" ownership transformation with timetables and measurable privatization quotas, not for the purpose of extracting the state from the economy, but in order to strengthen the rule of the Party. While it is widely believed that authoritarian regimes are better suited than democracies to carry out economic reform, this book provides a more nuanced understanding of reform in China, demonstrating that the Chinese state's capacity to impose unpopular reform is contingent on its control over local state agents and its adaptability to societal demands. Building on rich fieldwork data gathered in three Chinese cities (Shenyang, Shanghai, and Xiamen), this book offers the first comparative study of China's privatization processes at the local level. Instead of focusing solely on political elites, Jin Zeng adopts a multi-level interaction approach to examine how the complex interplay of the central leadership, grassroots officials, and state-owned enterprise managers and workers shaped the contour of privatization in China.The book advances three central arguments. First, local economic structure and cadre evaluation system mediated local officials' incentives to initiate privatization. Second, local officials relied on mobilization campaigns and various appeasement measures to implement privatization. Finally, the dynamics of privatization were fundamentally driven by the central government's reactions to social opposition and by the subsequent responses of local officials to the changed political-regulatory environment. As a detailed analysis of the dual transformation of the property regime and state-society relations in China, this book will be invaluable to students and scholars of Chinese politics, economic reform, as well as those interested in comparative political economy and economic development more broadly.

Protein and peptide therapeutics currently represent eight of the top 100 prescription pharmaceuticals in the U.S., and biotechnology products are projected to account for 15% of the total US. prescription drug market by 2003. Of the protein and peptide products now on the market, many are administered as daily injections, though several are deliveredby noninvasive routes. For example, desmopressin is delivered as a nasal spray, and deoxyribonuclease I is administered by inhalation. Although cyclosporin A is orally active, as yet there are no general means to confer oral bioava- ability to peptides and proteins. A major advance in delivery ofpeptides was achieved with the introduction of a monthly injectable, biodegradable microsphere formulation of LHRH. Despite the enormous success of biotechnology products to date, much effort continues to be focused on the development of more convenient and noninvasive routes of administration for those products that require f- quent and prolonged dosing. Here we present an overview of the te- nologies, both developed and emerging, which are applicable to protein delivery. In addition, chapters 11 through 13 detail case studies on physical methods for delivery ofinsulin and growth hormone

This volume attemptsto provide the formulation scientist with casehistories involving the use of therapeutic proteins and peptides that have been mar- keted or are under clinical testing. In previous volumes of this series,funda- mental theories and principles ofprotein characterization and stability were presented in depth by researchers in their fieldsofexpertise. The way from theory to practice isnot alwaysobvious and straightforward. There isa need for practical examples of how the principles and theories are put into use, specificallyin the development of a pharmaceutical product. It is our hope that this volume will fulfillsuch a need. Itisnot asimple task to choose a panel ofproteinsand peptides from the over 200 agents in human clinical trials. We have tried to collect a wide representation of molecules of different sizes-from 10 amino acids (Leu- prolide) to 1020 amino acids (Muromonab CD3). The examples include agents derived from various sources including monoclonal antibodies (Mur- omonab CD3), recombinant DNA (human and bovine growth hormones), natural source (fibrolase), and chemical synthesis (Leuprolide). Clearly this list is not intended to be encyclopedic. It isthe first time a collection of this sort has been made accessibleto the formulation scientists involved in devel- oping protein and peptide products. Although each chapter in this volume focuses primarily on the charac- terization and stability of a specific molecule, each has unique aspects.

The principal objective of this symposium was to bring together investigators from all over the world who work in diverse areas of research but share a common interest in the physiologic and pathophysiologic funetions of the nueleoside adenosine. In 1978, the "International Conference on Physiological and Regulatory Funetions of Adenosine and Adenine Nueleotides," held in Banff, Canada, served as an effective catalyst in enabling scientists with differ ent points of view to exchange information and ideas on this subject. Since 1978, the amount of research on different as peets of adenosine metabolism, mechanism of action, transport, and function in various tissues (in both nor maI and abnormal states) has increased exponentially, and there was an urgent need for another meeting for updating information on this burgeoning subject. The focus of the meeting was extremely sharp, but the scope of the subject material was very broad. Scientists categorized as chemists, biochemists, physiologists, pharmacologists, and immunologists, working with cells and eelI fragments, with tissues such as heart, brain, musele, fat, kidney, and with human beings having immune deficiency diseases participated in the sym posium. They had an opportunity to air their differences, reinforce their areas of agreement, and, most important, they educated each other with respeet to research on adenosine; it is hoped that they also enriched their own research programs from the information they gained from their fellow participants."

At a time when it is becoming usual for medicines to be developed for a global market and pharmaceutical companies are endeavouring to expedite the drug development process, Regulatory authorities are concentrating on improving their efficiency and effectiveness. Therefore, it is not surprising that questions are being asked as to how performance might be measured and compared between different authorities who are now often in receipt of dossiers that have been submitted to several agencies at the same time. Issues such as "what target should be set for the review of new medicines?" and "how can quality be assured?" are now considered to be of critical importance. The 12th CMR International Workshop, held in January 1997, provided the opportunity for regulatory authority and industry personnel from Europe, North America, Australia and Japan to openly discuss experiences and exchange views on how to improve the review process. The proceedings of this meeting provide a comprehensive overview of the current review process in different countries and the need for performance measures and targets. This volume summarizes the many suggestions that were debated at the workshop, and includes chapters on measuring performance, and on the integration of quality into the review process.

This book presents an essential overview of beta-lactams and their medicinal value and use in the preparation of other biologically active compounds. Written by internationally respected authors, the individual chapters explore beta-lactams' synthesis, their mechanism of formation, biological effects, and function as base materials for other heterocycles of major importance.

The metabolic syndrome is a common syndrome affecting about 20 % of the adult population in Europe, and probably the prevalence is of the same magnitude in other industrialised countries worldwide. It is mainly caused by western lifestyle resulting in abdominal obesity, but also a genetic predisposition plays a role. This syndrome, which is linked to leisure lifestyle and overeating/obesity, can develop into type 2 diabetes, cardiovascular disease and cancer. Therefore, proper treatment and prevention are heavily needed. This book discusses lifestyle intervention and treatment, specifically with pharmacological compounds, in order to formulate a strategy for treating the metabolic syndrome in the daily clinic.

Each year pharmaceutical companies invest billions of dollars in clinical trials of drugs used for the treatment of central nervous system diseases. Due to enormous progress in basic pharmaceutical research in recent years, controlled tests of new medications are flourishing and these trials have rapidly become an intense focus of practical medical research.

Aware of the complexities presented in the design, execution, and evaluation of clinical trials, Marc Hertzman and Douglas E. Feltner bring together a collection of essays that dissect the scientific, psychosocial, political, and ethical concerns that must be examined for any CNS trial. The internationally known contributors examine concerns about ethics and cost; the FDA and its regulatory impact; and the implementation of a variety of trials, for disorders such as schizophrenia, alcoholism, eating disorders, insomnia, and aggression. The editors carefully consider important social issues including the considerations related to women's special needs; and the relative merits of psychotherapy and medications.

The Handbook of Psychopharmocology Trials provides an up-to- date and stimulating exploration of important issues on the subject of CNS Clinical trials.