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."

The reader will be introduced to various aspects of the fundamentals of nanotechnology based drug delivery systems and the application of these systems for the delivery of small molecules, proteins, peptides, oligonucleotides and genes. How these systems overcome challenges offered by biological barriers to drug absorption and drug targeting will also be described.

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.

About 8000 clinical trials are undertaken annually in all areas of medicine, from the treatment of acne to the prevention of cancer. Correct interpretation of the data from such trials depends largely on adequate design and on performing the appropriate statistical analyses. In this book, the statistical aspects of both the design and analysis of trials are described, with particular emphasis on recently developed methods of analysis.

"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.

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."

Histamine is an important mediator of allergic diseases such as hay fever and bronchial asthma, food allergies, urticaria, and drug hypersensitivity. Knowledge of histamine as a cause of numerous non-allergic symptoms and signs is, however, limited. In fact, histamine intolerance can be responsible for conditions as diverse as seasickness, headaches and migraine, tachycardia, gastric disorders, diarrhea, intolerance to contrast media, parodontosis, period pains, nausea and vomiting in pregnancy, atopic dermatitis, and osteoporosis. This book offers wide-ranging coverage of histamine intolerance. There is extensive background discussion of the origin of histamine, its content in food and alcoholic beverages, and intolerance to red wine. Diagnosis of histamine intolerance is explained, and the various symptoms of histamine intolerance are clearly described. Subsequent chapters cover the conditions mentioned above and also consider the relation of histamine to vitamin B6 and the specific immunotherapy of allergies. This book will prove of value in clinical practice by facilitating differential diagnosis, which is by no means straightforward given the multiplicity of symptoms of histamine intolerance, and by assisting in the selection of therapeutic measures.

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.

Presenting the thirteenth edition of the popular introductory text for nurses. This completely updated text is a lucid, clearly written guide to the actions and clinical applications of a wide range of drugs in common use. Also includes appendices on drug reactions, weights and measures, abbreviations, approved and brand names of drugs, and a glossary.

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.

This book continues as volume 5 of a multicompendium on Edible Medicinal and Non-Medicinal Plants. It covers edible fruits/seeds used fresh, cooked or processed as vegetables, cereals, spices, stimulant, edible oils and beverages. It covers selected species from the following families: Apiaceae, Brassicaceae, Chenopodiaceae, Cunoniaceae, Lythraceae, Papaveraceae, Poaceae, Polygalaceae, Polygonaceae, Proteaceae, Ranunculaceae, Rhamnaceae, Rubiaceae, Salicaceae, Santalaceae, Xanthorrhoeaceae and Zingiberaceae. This work will be of significant interest to scientists, medical practitioners, pharmacologists, ethnobotanists, horticulturists, food nutritionists, botanists, agriculturists, conservationists, lecturers, students and the general public. Topics covered include: taxonomy; common/English and vernacular names; origin and distribution; agroecology; edible plant parts and uses; botany; nutritive/pharmacological properties, medicinal uses, nonedible uses; and selected references.

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.

The book covers recent developments in research and practice of allergy and immunology. Special emphasis has been given to epidemiology and the relation of genetic and environmental factors in allergic diseases. Occupational aspects and the pathophysiology are additionally covered and an overview of the current pharmacotherapy and immunotherapy is provided.

Annual Reports in Medicinal Chemistry continues to focus on providing timely and critical reviews of important topics in medicinal chemistry together with an emphasis on emerging topics in the biological sciences, which are expected to provide the basis for entirely new future therapies.
Sections I-IV are disease orientated and generally report on specific medicinal agents.
Sections V and VI continue to emphasize important topics in medicinal chemistry, biology, and drug design.
* Annual comprehensive reviews of the past year literature in many topics of interest to medicinal chemists
* Includes a comprehensive set of indices to easily locate topics in Volumes 1-38 of this series
* Provides critical review on hot topics in medicinal chemistry

The modern fascination with micro- and nano-sized materials can actually be traced back further to the 1960s and '70s when the first few reported attempts were made to use nanoparticles for controlled drug delivery. In Nanoparticles in Biology and Medicine: Methods and Protocols, experts in the field present a wide range of methods for synthesis, surface modification, characterization, and application of nano-sized materials (nanoparticles) in life science and medical fields, mostly for drug delivery. The methods presented cover all stages of nanoparticle manufacturing, modification, analysis, and applications. Written in the highly successful Methods in Molecular Biology trademark] series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and cutting-edge, Nanoparticles in Biology and Medicine: Methods and Protocols will help the beginner become familiar with this fascinating field and will provide scientists at all levels of expertise with easy-to-follow practical advice needed to make, modify, and analyze nanoparticles of their choice and to use them in a wide range of biomedical and pharmaceutical applications, including functional protein studies, drug delivery, immunochemistry, imaging, and many others.

Volume 47 of "Progress in Drug Research" contains eight reviews and the various indexes which facilitate its use and establish the connection with the previous volumes. The articles in this volume deal with inotropic steroids, with chemokines and their involvement in a wide range of inflam matory diseases, with the subclassification and nomenclature of ul- and Uz-adrenoceptors, with Chinese traditional medicine, with drug targets in the molecular pathogenesis of asthma, with cytokines and their therapeutic application in immunosuppression and immunostimulation, with alter native medicine and with the potential use of calcium blockers in psy chiatry. These reviews and the quotations of original articles provide the reader with valuable information on several new developments in the world-wide search for new and better medicines. In 1959, when the Editor started this series of monographs, it was his intention to help disseminate informa tion on the vast and fast growing domain of drug research. Already at that time,it was not possible to follow the major individual publications in this field, and the reader was thereby provided with a tool to keep abreast of the latest developments and trends. This goal remained unchanged over the last 37 years, and I believe that the reviews in PDR are useful to the non-specialist who can obtain an overview of a particular field of drug research in a relatively short time.

Pancreatic cancer is the fourth leading cause of cancer death in the United States. Every year, about 33,700 people in the United States will be diagnosed with pancreatic cancer and over 32,000 patients will die from the disease. The median survival of patients with advanced pancreatic cancer is about 6-months. This dismal picture of pancreatic cancer is mainly due to the lack of early diagnosis and effective treatment for patients with advanced disease. To increase the survival rate of pancreatic cancer patients, better tumor markers for diagnosis and new molecular targets for drug development are desperately needed. A lot of effort has been made in searching for pancreatic cancer-causing genes or genes associated with progression of malignant behavior in pancreatic cancer. As a result, alterations in the expression of several cancer-related genes have been identified in pancreatic tumors. The identification and characterization of these cancer-related genes have significantly increased our understanding of pancreatic cancer development, but unfortunately the treatment of pancreatic cancer has not advanced as much in the past 20 years.

Over the past decade, tremendous advances have been made in the field of cancer drug discovery, particularly, in the area of molecular and genetic models and technologies. Many of those advanced models and technologies have been applied to the drug discovery processes for pancreatic cancer. In this book, a team of experts will describe the latest development in the application of these models and technologies in pancreatic cancer. The authors include basic researchers as well as clinicians who work in the front-line of the war against pancreatic cancer and have the first-hand experience on these cutting-edge tools and techniques. The book can be divided into two general areas: 1) model systems and 2) genomics and proteomics tools. In recent years there have been a lot of advances in the model systems for pancreatic cancer, including the further characterization of normal and cancerous pancreatic cell lines, the establishment of transgenic mouse models that recapitulate the initiation and progression of human pancreatic cancer, the development of a new xenograft model system for the evaluation of novel agents, and the establishment of a zebrafish pancreatic cancer model. The first four chapters of the book will be devoted to these models. The advances in genomics and proteomics research have made a major impact in cancer drug discovery. A number of these omics-based tools and techniques have been applied in the pancreatic cancer drug discovery. Chapters 5-9 of the book will discuss techniques for genome-wide examination of gene expression, copy number, methylation, function and regulation. Chapters 10-11 will discuss in situ techniques for studying chromosomal and gene copy number abnormalities as well protein expression changes in cancer samples. Chapters 12-14 will focus on techniques for global examination of protein expression levels in biospecimens obtained from pancreatic cancer patients. Cancer drug discovery has become more and more target-centric. "

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.

In the past decade we have witnessed the birth and maturing of a field of research centering on the Ca2+ signaling functions of cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP), which structures and mechanisms of action are truly unique among all Ca2+ messengers. A wide range of physiological functions are now known to be mediated by them in cells spanning three biological kingdoms from protist, plant to animal. This is the first book devoted entirely to the field. The story behind the emergence of the field is told and followed by comprehensive reviews of the enzymology, regulations and gene structures of ADP-ribosyl cyclases responsible for metabolizing cADPR and NAADP. Also covered is some of the current methodology developed for and widely used in the field. The rest of the book focuses on and details the Ca2+ signaling mechanisms and specific physiological functions of these two messengers in various cellular systems.

This volume comprehensively covers the multiplicity and diversity of mechanisms underlying patient resistance to currently approved anti-cancer drugs, including tyrosine kinase inhibitors and monoclonal antibodies, blockers of growth factor receptors and their downstream pathways, which play essential functions in cancer progression. Each chapter will cover a specific group of targets and the cognate drugs, along with molecular modes of innate and evolving resistance.