The over-arching goal of this volume is to help infertility practitioners evaluate and manage their patients with poor semen quality. The authors review the existing literature on the effects of medications on male fertility, and provide detailed information about what is known, giving the number of individuals and population characteristics for studies of medication effects on male fertility. Medications are designed to treat illness and reduce symptoms, but all have undesirable adverse effects such as headache or stomach upset. Some adverse reactions can even be life-threatening, so it is no surprise that some drugs have negative effects on male reproduction. Medical practitioners rarely consider a man's reproductive plans when prescribing medications. Men are routinely treated with drugs that can impair or abolish fertility. Although practitioners in the field of reproductive medicine generally realize that certain drugs impact negatively on reproductive health, there are limited resources providing evidence-based knowledge useful in counseling patients. Tables throughout this volume summarize the information for each drug, providing a handy reference for clinical use.

This book is an essential handbook on bisphosphonates, the most widely used new class of drugs for osteoporosis therapy. It reviews basic physiology in addition to the indications and adverse reactions of these drugs. Bisphosphonates in Bone Disease, 4E, discusses the compounds' chemistry, mechanisms of action, and animal toxicology before presenting a clinical picture of the diseases treated by bisphosphonates. The book provides a table listing the trade names of the commercially available bisphosphonates, registered indications, and the available forms for various countries. The revised Fourth Edition contains approximately 50% new material, including information on all of the latest drugs.
* The revised fourth edition contains approximately 50% new material
* Includes information on all the latest drugs

Antifolates are an important class of anticancer drugs originally developed as anti leu- kemic agents, but now used, usually in combination with other drugs, for the treatment of a wide range of tumors, notably carcinomas of the head and neck, breast, germ cell tumors, non-Hodgkin's lymphoma, acute lymphoblastic leukemia, and osteogenic sar- comas. 5-Fluorouracil and its prodrugs also target, in part, the folate-dependent enzyme, thymidylate synthase. Furthermore, folate supplementation in the form of leucovorin, modulates 5-fluororuacil activity. 5-Fluorouracil is widely used in the treatment of colorectal and gastric cancer and in combination for other solid tumors such as breast and head and neck cancers. Ongoing clinical trials with the newer antifolates suggest that the range of solid tumors where these agents will be of use may broaden further. Half a century ago, interesting scientific and clinical discoveries suggested that folie acid was a vitamin involved in vital cellular metabolic processes. The folate analogs, aminopterin and methotrexate, were synthesized by the American Cyanamid Company in an attempt to interfere with these processes and were shown to have anticancer activity by Farber and his colleagues. Hence, the principle of antimetabolite therapy for the treatment of cancer was established. Biomedical research over the following years led to a deeper understanding of the complex biochemical pharmacology of folates and antifolates. Selective antimicrobial agents were discovered, but more tumor-selective anticancer agents did not immediately emerge.

Volume 3 of "Advances in Antiviral Drug Design" is keeping up with the recent progress made in the field of antiviral drug research and highlights five specific directions that have opened new avenues for the treatment of virus infections.
"First," the use of lamivudine (3TC) for the treatment of HIV infections, and its more recent introduction for the treatment of hepatitis B virus (HBV) infections, has heralded the transition of D- to L-nucleosides in the antiviral nucleoside drug design, and it is likely that the future will provide more nucleosides of the L-configuration, such as (-)FFC (emtricitabine) and L-FMAU, as will be described by J.-C.G. Graciet and R.F. Shinazi.
"Second," the acyclic purine nucleoside phosphonates, i.e. PMEA (adefovir and PMPA (tenofovir), offer great potential as both anti-HIV and anti-HBV agents, and both compounds have been the subject of advanced clinical trials in their oral produrg form (adefovir dipivoxil and tenofovir disoproxyl), as mentioned by M.N. Arimilli, J.P. Dougherty, K.C. Cundy, and N. Bischofberger.
"Third," with the advent of nevirapine, delavirdine, and efavirenz, the NNRTIs have definitely come of age. Emivirine (MKC-442), a derivative of the original HEPT analog that was described in 1989 has now proceeded through pivotal clinical studies, and how this class of compounds evolved is presented in the account of H. Tanaka and his colleagues.
"Fourth," at the end of 1999, anticipating on the next winter influenza offensive, we should have at end two compounds that specifically inhibit influenza A and B virus infections: zanamivir (by the intranasal route) and oseltamivir (by the oral route). Both compounds have proved effective in the prophylaxis and treatment of influenza A and B virus infections and act through the same mechanism; that is by blocking the viral neuraminidase (or sialidase), a key enzyme that allows the virus to spread from one cell to another (within the respiratory mucosal tract). The design of these sialidase inhibitors will be presented by M. von Itzstein and J.C. Dyason.
"Fifth," the discovery (in 1996) of the chemokine receptors CXCR4 and CCR5 as essential coreceptors (in addition to the CD4 receptor) for HIV entry into the cells, has boosted an enormous interest in potential antagonists of these receptors. The bicyclams represent the first low-molecular-weight compounds targeted at CXCR4, the coreceptor used by the more pathogenic, T-lymphotropic, HIV strains, to enter the cells. They will be addressed by G.J. Bridger and R.T. Skerlj.
The five topics covered in this third volume of "Advances in" "Antiviral Drug Design" are in the front line of the present endeavors towards the chemotherapy of virus infections. They pertain to the combat against three of the most important virus infections of current times: HIV, HBV, and influenza virus.

This book introduces some emerging functional foods that are natural resources with tremendous promise as nutraceuticals and pharmaceuticals. The author considers biodiversity and bioprospecting as a response to food security issues, drug-resistance, nutrition-poor diets and other problems, exploring the prospects of several under-utilized nutrients and bioactive repositories. Readers will discover biochemical makeups, validated health benefits, explanations of underlying mechanisms, hurdles in the path of popularity and promotion strategies. Chapters explore particular plants, seeds and fruits including the strawberry guava, opuntia fruits, the Carissa genus, grape seeds, quinoa and the milk thistle (Silybum), amongst others. They are considered as food sources where possible and from the perspective of the roles they can play in complementary and alternative medicine, such as in wound healing, antimicrobial activity, gastroprotective activity in treatment of cancers and as natural antioxidant sources. This rich compilation holds plausible solutions to a range of current issues and it endorses the much-needed goal of sustainability in terms of diet and drugs. It paves the path for further research and development on hitherto obscure natural resources. Scientists working in the area of food development, phytochemical and antioxidant analysis, bioprospecting of low-profile foods and in complementary and alternative medicine will find this work particularly valuable. It will also be of interest to the general reader with an interest in food science, food security, phytochemicals and functional food studies.

Drug development today needs to balance agility, speed, and risk in defining probability of success for molecules, mechanisms, and therapeutic concepts. New techniques such as fMRI promise to be part of a sequence that could transform drug development. Although numerous review articles exist that discuss the use of imaging in drug development, no one source is available that combines the various techniques and includes a discussion of disease mapping.

Imaging in CNS Drug Discovery and Development, Implications for Disease and Therapy will serve to distill the most salient developments in the use of imaging in drug development and disease mapping. It will launch evolving concepts that integrate new imaging technologies and paradigms with molecular medicine and molecular profiling ("monics") as well as consider the ethical issues that arise as a result of disease or state diagnosis and the use of imaging in the public eye.

Recent years have seen unprecedented outbreaks of avian influenza A viruses. In particular, highly pathogenic H5N1 viruses have not only resulted in widespread outbreaks in domestic poultry, but have been transmitted to humans, resulting in numerous fatalities. The rapid expansion in their geographic distribution and the possibility that these viruses could acquire the ability to spread from person to person raises the risk that such a virus could cause a global pandemic with high morbidity and mortality. An effective influenza vaccine represents the best approach to prevent and control such an emerging pandemic. However, current influenza vaccines are directed at existing seasonal influenza viruses, which have little or no antigenic relationship to the highly pathogenic H5N1 strains. Concerns about pandemic preparedness have greatly stimulated research activities to develop eff- tive vaccines for pandemic influenza viruses, and to overcome the limitations inh- ent in current approaches to vaccine production and distribution. These limitations include the use of embryonated chicken eggs as the substrate for vaccine prod- tion, which is time-consuming and could involve potential biohazards in growth of new virus strains. Other limitations include the requirement that the current inac- vated influenza vaccines be administered using needles and syringes, requiring trained personnel, which could be a bottleneck when attempting to vaccinate large populations in mass campaigns. In addition, the current inactivated vaccines that are delivered by injection elicit limited protective immunity in the upper respiratory tract where the infection process is initiated.

In this volume of Reviews of Physiology, Biochemistry and Pharmacology there a contributions by M.D. Swope, E. Lolis, F.Hofmann, L. Lacinova, N. Klugbauer, M. Hermann, P. Berger, S.S. Shen, J.S. Kim, M.E. Weksler, M. Hirsch-Kauffmann and M.Schweiger.

"Clostridium difficile" has been recognized as the cause of a broad spectrum of enteric disease ranging from mild antibiotic-associated diarrhea to pseudomembranous colitis. This volume gives new insights into the microbiology, diagnostics and epidemiology of "Clostridium difficile" and describes recent strategies in treatment of diseases caused by this agent. Main parts of the volume are devoted to "Clostridium difficile" toxins A and B which are the major virulence factors. The molecular biology, biochemistry, pharmacology and cell biology of these toxins which are the prototypes of a new family of large clostridial cytotoxins is described in great detail. "Clostridium difficile" toxins act as glucosyltransferases to inactivate small GTP-binding proteins of the Rho family which are involved in regulation of the actin cytoskeleton, cell adhesion and various signaling processes.

This essential methods manual for immunohematologists (or hematologists and immunohematologists) provides information on genes that encode antigens on red blood cells, platelets and neutrophils. The book begins by covering general concepts in molecular biology and specific protocols such as DNA preparation, PCR-RFLP and allele-specific PCR. Information on the erythrocyte, platelet and neutrophil antigen systems and the molecular basis of polymorphisms are presented clearly in a gene facts sheet format. Database accession numbers and useful adjuncts such as Request forms, worksheets for PCR/enzyme digests also serve to benefit the user. The information is clearly presented and easily accessible and is complemented by the excellent diagrams and tabular material. This book is invaluable for both new and experienced researchers in the field and other related disciplines.
Key Features
* Essential for hematologists and those involoved in tissue typing and the study of human genetic polymorphisms
* Presents clearly and concisely the information on a particular variant and the technique used to detect it
* Organized by antigen and provides sequences of polymorphisms and primers
* Details the general concepts and critical information on genes, their products, and sources of relevant nucleic acids
* Includes protocols that allow investigators to set up assays with minimal effort (protocols include primers, reagents, reaction conditions, sizes of amplified products, restriction fragment digests, and the relevant safety information)
* Provides information that helps interpret results in clinical settings
* Contains additional sources of information (e.g., key references, web site addresses, glossary, Database accession numbers, request
forms, and worksheets for PCR/enzyme digests)

There are only very few chemical classes of antibiotics in medical use, and these have originated over a span of more than 60 years of research. Almost half a century ago, the first member of the macrolides, erythromycin, was introduced as a treatment option for bacterial infections. Erythromycin is a very complex fermentation product obtained from the soil bacterium Saccharopolyspora ery thraea (originally named Streptomyces erythreus). The success of erythromycin, based on its efficacy and tolerability, stimulated researchers throughout the world to undertake intense efforts to understand the biology and chemistry of macrolides and to use this experience to improve the properties of this compound class. The second generation of macrolides, based on chemical modifications of erythromy cin, is currently being in broad use, especially for treatment of respiratory tract infections. We presently foresee the introduction of a new generation of macro lides, i. e. the ketolides, which have the potential to overcome rising resistance problems. This monograph is intended to give the interested reader an overview on "macrolide experience," covering important areas from basic research to clinical use. Starting from a historic overview, the essential basic parameters - efficacy, pharmacokinetics, pharmacodynamics, and pharmacology - are highlighted in order to introduce the reader to the rationale for clinical use of macrolides. The following group of chapters cover the complex chemistry of the macro lactone structures, giving historic background, basic structure-activity relation ships of various derivatization strategies, and perspectives for future discovery of new semisynthetic macrolide antibiotics."

Medicinal and Aromatic Plants XII comprises 18 chapters. It deals with the distribution, importance, conventional propagation, micropropagation, tissue culture studies, and the in vitro production of important medicinal and pharmaceutical compounds in the following plants: Artemisia annua, Coriandrum sativum, Crataegus, Dionaea muscipula, Hyoscyamus reticulatus, Hypericum canariense, Leguminosae, Malva, Ocimum, Pergularia tomentosa, Phellodendron amurense, Sempervivum, Solanum aculeatissimum, S. chrysotrichum, S. kasianum, Stephania, Trigonella, and Vaccinium. It is tailored to the needs of advanced students, teachers, and research scientists in the fields of pharmacy, plant tissue culture, phytochemistry, biomedical engineering, and plant biotechnology in general.

The sixth meeting on the use of resealed annealed red blood cells was held in Irsee, Germany by the International Society for the Use of Resealed Erythrocytes (ISURE) on July 25-28, 1996. Although earlier meetings focused on the technology toward develop ment of methods and standardization for efficient, consistent encapsulation, most of the present studies now are directed toward the application use of these carrier blood cells. Basic studies now have been directed toward exploration of commercial applications. In deed, clinical trials were initiated to evaluate the dose-response curves employing L asparagenase in human patients. Also, studies have shown the use of thrombolytic agent in erythrocyte carriers with the use of human red blood cells to provide a new conceptual ap proach in thrombolytic therapy to prevent thrombosis in individuals with higher risk fac tors. For example, with the use of carrier red blood cells, the thrombolytic agents will have a greater potential of acting on clot formation without systemic activation and thus lower the risk of hemorrhage, which is always prevalent in the thrombolytic therapy."

Heparins remain amongst the most commonly used drugs in clinical practice. Almost 100 years have passed since the initial discovery of this complex substance and, during this time, understanding of the nature and uses of heparin and related molecules has grown dramatically. The aim of this volume is to summarise the developments that have led to the current status of both heparins as drugs and the field of heparin research, with a focus on the particularly rapid progress that has been made over the past three decades. Individual sections are dedicated to the nature of heparin as a biological molecule, the current approaches and techniques that are used to ensure the safety and reliability of heparin as a medicine, the clinical pharmacology of heparin as an anticoagulant drug, effects and potential applications of heparin aside of those involving haemostasis and, finally, the nature and potential uses of heparin-like materials from both natural and synthetic sources."

A collection of state-of-the-art molecular methods for studying antifungal resistance, for discovering and evaluating both new and existing antifungal drugs, and for understanding the host response and immunotherapy of such agents. The protocols follow the successful Methods in Molecular Medicine (TM) series format, each offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls. Antifungal Agents: Methods and Protocols offers clinician-scientists, microbiologists and molecular biologists the productive tools they need today to understand and successfully develop new therapeutic agents for yeast, mold, and fungal infections.

My journey into this fascinating field of biotechnology started about 26 years ago at a small biotechnology company in South San Francisco called Genentech. I was very fortunate to work for the company that begat the biotech industry during its formative years. This experience established a solid foundation from which I could grow in both the science and business of biotechnology. After my fourth year of working on Oyster Point Boulevard, a close friend and colleague left Genentech to join a start-up biotechnology company. Later, he approached me to leave and join him in of all places - Oklahoma. He persisted for at least a year before I seriously considered his proposal. After listening to their plans, the opportunity suddenly became more and more intriguing. Finally, I took the plunge and joined this ent- preneurial team in cofounding and growing a start-up biotechnology company. Making that fateful decision to leave the security of a larger company was extremely difficult, but it turned out to be the beginning of an entrepreneurial career that forever changed how I viewed the biotechnology industry. Since that time, I have been fortunate to have cofounded two other biotechnology com- nies and even participated in taking one of them public. During my career in these start-ups, I held a variety of positions, from directing the science, operations, regulatory, and marketing components, to subsequently becoming CEO.

Introductory Immunology: Basic Concepts for Interdisciplinary Applications, Third Edition includes aspects of microbiology and related immune defense mechanisms important in combating disease, as well as critical components related to the field of vaccine development. Knowledge on effector mechanisms addressing components inherent within cellular responses that are either newly discovered or missing from the previous edition are covered. The book puts an extra emphasis on aspects related to mechanisms important in combating microbial agents, with critical sections on how vaccines protect against pathogenic invaders to limit associated pathology. This new edition has been completely updated and revised, offering an expanded concise, conceptual approach to understanding immune systems as a primary defense to maintain health and homeostasis. It is specifically focused towards an educated audience that does not have a deep understanding of medical, biochemical or cellular knowledge.

In the future' the decade of the 1990s will likely be viewed as a Golden Age for retinoid research. There have been unprecedented research gains in the understanding of retinoid actions and physiology; since the retinoid nuclear receptors were first identified and the importance of retinoic acid in develop mental processes was first broadly recognized in the late 1980s. Between then and now, our knowledge of retinoid action has evolved from one of a near complete lack of understanding of how retinoids act within cells to one of sophisticated understanding of the molecular processes through which retinoids modulate transcription. In this volume, we have tried to provide a comprehensive update of the present understanding of retinoid actions, with an emphasis on re cent advances. The initial chapters of the volume, or Section A, focus on the physicochemical properties and metabolism of naturally occurring retinoids: - N OY provides an uncommonly encountered view of retinoid effects from the perspective of the physiochemical properties of retinoids. - V AKIANI and BUCK lend a perspective on the biological occurrence and actions of retro- and anhydro-retinoids. Section B considers both the retinoid nuclear receptors and their mechanisms of action as well as synthetic retinoids that have been used exper imentally to provide mechanistic insights into receptor actions and have potential therapeutic use for treating disease: - PIEDRAFITA and PFAHL provide a comprehensive review of retinoid nuclear receptor biochemistry and molecular biology.

Leading physicians and scientists from around the world critically examine the pharmacological and molecular basis of the therapeutic properties of marihuana and its active ingredient, THC. They detail the broad array of marihuana's effects on brain function, the immune system, male and female reproductive functions, and cardiac and pulmonary functions, as well as evaluate its clinical applications in psychiatry, glaucoma, pain management, cancer chemotherapy, and AIDS treatment. Their studies indicate that marihuana persistently impairs the brain and reproductive function, and that marihuana smoke is more toxic and damaging to the lung than tobacco smoke. Marihuana and Medicine's reports of the latest findings on the pharmacological and molecular mechanisms of marihuana and of its clinical manifestations will be essential reading for physicians, psychiatrists, pharmacologists, health-care professionals, policy makers, public health officials, and attorneys.

This book puts hydrogen sulfide in context with other gaseous mediators such as nitric oxide and carbon monoxide, reviews the available mechanisms for its biosynthesis and describes its physiological and pathophysiological roles in a wide variety of disease states. Hydrogen sulfide has recently been discovered to be a naturally occurring gaseous mediator in the body. Over a relatively short period of time this evanescent gas has been revealed to play key roles in a range of physiological processes including control of blood vessel caliber and hence blood pressure and in the regulation of nerve function both in the brain and the periphery. Disorders concerning the biosynthesis or activity of hydrogen sulfide may also predispose the body to disease states such as inflammation, cardiovascular and neurological disorders. Interest in this novel gas has been high in recent years and many research groups worldwide have described its individual biological effects. Moreover, medicinal chemists are beginning to synthesize novel organic molecules that release this gas at defined rates with a view to exploiting these new compounds for therapeutic benefit.