Less than 20 years ago the ?eld of cannabis and the cannabinoids was still c- sidered a minor, somewhat quaint, area of research. A few groups were active in the ?eld, but it was already being viewed as stagnating. The chemistry of cannabis 9 9 was well known, ? -tetrahydrocannabinol (? -THC), identi?ed in 1964, being the only major psychoactive constituent and cannabidiol, which is not psychoactive, possibly contributing to some of the effects. These cannabinoids and several s- thetic analogs had been thoroughly investigated for their pharmacological effects. Their mode of action was considered to be non-speci?c. The reasons for this - sumption were both technical and conceptual. On the technical side, it had been shown that THC was active in both enantiomeric forms (though with a different level of potency) and this observation was incompatible with action on biological substrates-a receptor, an enzyme, an ion channel-which react with a single stereoisomer only. The conceptual problem related to THC activity. This had been pointed out by several highly regarded research groups that had shown that many of the effects seen with cannabinoids were related to those of biologically active lipophiles, and that many of the effects of THC, particularly chronic ones, were comparable to those seen with anaesthetics and solvents.

A clinical handbook for practitioners of Traditional Chinese Medicine (TCM) that provides quick and easy reference to the selection of herbs for treatment and their action alone and in combination. This is a handbook from two eminent teachers from the Nanjing College of Traditional Chinese Medicine who have between them accumulated over 60 years of clinical practice and teaching. They emphasise how to combine herbs and differentiate between single herbs and formulae depending on the treatment strategy adopted. It contains case histories illustrating how to adapt formulae in practice.A practical, easy-to-use guide for the busy practitioner or student A glossary explains unfamiliar terms Information in tables - for quick identification of herbs and combination of herbs Illustrated with line diagrams showing where the herbs act on the body The authors teach at China's leading college of TCM

In Hormone Therapy in Breast and Prostate Cancer, many of today's leading researchers and clinicians describe the principles underlying targeted hormonal treatments, assess the actions of new and established agents, and illustrate the new applications of hormonal chemoprevention for breast cancer. Topics range from preclinical and clinical antiestrogens to the inhibition of estrogen synthesis and the effects of androgen withdrawal. A wide variety of proven and new agents are discussed-antiestrogens, including aromatase inhibitors (anastrozole, letrozole, and others), SERMs (tamoxifen, raloxifene, and others), and such antiandrogenic strategies as goserelin and bicalutamide.

The enormous potential of siRNA as a therapeutic has led to an explosion of interest from the scientific community. There has been intense interest from Big Pharma to capitalise on this new technology but the fact remains that delivery is a key determinant in realizing the full clinical potential of RNA interference. There is an urgent need for better delivery methods to take this technology forward. This book addresses the role of different RNAi molecules in cellular processes as rational for diagnostic and therapeutic approaches. This book will cover RNAi therapeutic design to optimize siRNA potency and reduce off-target effects and current delivery technologies to overcome both intracellular and extracellular barriers. The reader will gain an insight into RNA interference from the cellular mechanisms to screening to siRNA design right through to diagnostic and therapeutic applications.

One: Registration, Toxicity and Quality Control.- 1. Toxicity testing of rDNA products.- 2. Experiences with the EC "high tech" procedure.- 3. The regulation of pharmaceuticals: philosophy and principles.- 4. Quality control of vaccines.- 5. Regulatory affairs and biotechnology in Europe: the CPMP "high tech" and multistate procedures.- 6. Formulating biotechnology products.- 7. Development of analytical methods for monitoring the stability of antibody formation by hybridoma cells in continuous culture systems.- Two: Monoclonal Antibodies.- 8. Toward human monoclonal antibodies.- 9. Biodistribution, binding and internalisation of monoclonal antibodies to human ovarian carcinoma cells.- 10. Pharmacokinetics and tissue distribution of Indium-111-labeled OV-TL 3 F(ab')2 in ovarian cancer patients.- 11. Characterization of human monoclonal antibodies specific for the rabies virus.- 12. Biochemical and immunological evaluation of an anti-fibrin monoclonal antibody complex containing T2Gls Fab' intended for imaging venous thrombi.- 13. Monoclonal antibodies in radioimmunoscintigraphy. Some hurdles between clone and clinic.- 14. Clinical relevance of the tumor marker CA 15.3 in the management of cancer patients.- 15. Practical applications of monoclonal antibodies against polymorphic epithelial mucin in the differential diagnosis of human tumors.- 16. Selection of monoclonal anti-digoxin antibodies suitable for monitoring of cardiac glycosides.- 17. Diagnostic use of anti-modified nucleoside monoclonal antibodies.- 18. Monoclonal antibodies radiolabeled with different radioisotopes for biodistribution and radioimmunodetection of tumor xenografts in the nude rat.- 19. Bispecific monoclonal antibody (BIAB)-retargeted cellular therapy for local treatment of cancer patients.- 20. Enhanced binding of t-PA to fibrin using bispecific monoclonal antibodies.- 21. Recent developments and perspectives on the future of human and murine monoclonal antibodies in the diagnosis and treatment of cancer.- 22. Pharmacokinetics and safety of a human IGM antibody, HA-1A.- 23. Development and clinical experience with humanised monoclonal antibodies.- 24. A method for the transformation of hybridoma cell lines with improved efficiency: its use in the production of bispecific monoclonal antibodies.- 25. To an optimal design of an airlift bioreactor for the cultivation of hybridomas.- Three: Marketed Products.- 26. Experience with marketed biotech products: rt-PA.- 27. Clinical trial of recombinant human IL-2 in the treatment of Mycobacterium Avium complex infection.- 28. Use of recombinant human erythropoietin in anemic dialysis patients.- 29. Experience with biosynthetic growth hormone.- Four: New Products.- 30. Recombinant follicle stimulating hormone. I. Construction, selection and characterization of a cell line.- 31. Recombinant human follicle stimulating hormone. II. Biochemical and biological characteristics.- 32. Heterologous expression of human Interleukin-3.- 33. Purification of recombinant human Interleukin-3 from Bacillus Licheniformis.- 34. The acid- and thermolabile interferon alpha: a subtype, or a new cell inhibitor?.- 35. The IFN? receptor as tool for the discovery of new immunomodulatory drugs.- 36. Cloned receptors and transfected cell lines in the design of new drugs: muscarinic cholinergic receptors.- Five: Drug Delivery.- 37. Structural analysis of carbohydrate chains of native and recombinant-DNA glycoproteins.- 38. The role of protein structure in surface tension kinetics.- 39. Antigen carriers: a success determining factor for subunit vaccines?.- 40. Intranasal delivery of insulin: absorption enhancement by the fusidate derivative STDHF in rabbits and rats and effects on human nasal ciliary movement in vitro.- 41. Improved oral peptide delivery by means of mucoadhesion.- 42. Delivery of therapeutic peptides and proteins.- 43. Compatibility studies of a soluble T4 receptor with a microinfusion pump for continuous intravenous thera...

The title of this proceedings comes from the book The Antibiotic Paradox by Stuart B. Levy (Plenum Publishing Corporation, 1992), referring to the paradox that the more antibiotics are used to treat infectious diseases, the less effective they become. When antibiotics were first introduced, they were considered wonder drugs because they were so effective. But with time bacteria have become resistant to nearly all antibiotics, and resistance is spreading faster than new antibiotics are being developed. This book will identify the issues concerning resistance, as well as describe efforts to develop new drugs that overcome the problem of resistance.

Specialist Periodical Reports provide systematic and detailed review coverage of progress in the major areas of chemical research. Written by experts in their specialist fields the series creates a unique service for the active research chemist, supplying regular critical in-depth accounts of progress in particular areas of chemistry. For over 80 years the Royal Society of Chemistry and its predecessor, the Chemical Society, have been publishing reports charting developments in chemistry, which originally took the form of Annual Reports. However, by 1967 the whole spectrum of chemistry could no longer be contained within one volume and the series Specialist Periodical Reports was born. The Annual Reports themselves still existed but were divided into two, and subsequently three, volumes covering Inorganic, Organic and Physical Chemistry. For more general coverage of the highlights in chemistry they remain a 'must'. Since that time the SPR series has altered according to the fluctuating degree of activity in various fields of chemistry. Some titles have remained unchanged, while others have altered their emphasis along with their titles; some have been combined under a new name whereas others have had to be discontinued. The current list of Specialist Periodical Reports can be seen on the inside flap of this volume.

Sodium channels confer excitability on neurons in nociceptive pathways and exhibit neuronal tissue specific and injury regulated expression. This volume provides recent insights into the control of expression, functioning and membrane trafficking of nervous system sodium channels and reviews why sodium channel sub-types are potentially important drug targets in the treatment of pain. The roles of sodium channels in dental and visceral pain are also addressed. The emerging role of sodium channel Nav1.3 in neuropathic states is another important theme.

Authors from the pharmaceutical industry discuss pharmacological approaches to the drug targeting of sodium channels, and in particular Nav1.8, exclusively expressed in nociceptive neurons. The final chapter highlights the functional diversity of sodium channels in part provided by post-transcriptional processing and the insights into sodium channel function that are being provided by tissue specific and inducible gene knock-out technology.

'It is indeed the merit of Dr. Alan F. Casy to bring in these pages a clear and comprehensive view of medicinal stereochemistry, a discipline in which he has been active and successful for many years both as a teacher and a researcher. Written for graduate students and research workers in medicinal chemistry and pharmacology, this book will contribute significantly towards a better education of scientists by removing the fear of stereochemistry caused by ignorance, moderating the overconfidence of possible zealots, and outlining a broader context.'-from the foreword by Bernard Testa

RNA Interference: Challenges and Therapeutic Opportunities provides readers with recent advances in siRNA design, delivery, targeting and methods to minimize siRNA's unwanted effects. Preclinical and clinical use of synthetic siRNAs, the roles of miRNAs in cancer and the promise of extracellular miRNAs for diagnosis are also covered in this meticulous collection, along with novel methods for identifying endogenous siRNAs and the annotation of small RNA transcriptomes. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detail and key implementation advice that ensures successful results in the laboratory. Comprehensive and cutting-edge, RNA Interference: Challenges and Therapeutic Opportunities will aid researchers, clinicians, teachers and biotechnologists interested in the power of RNA-based therapies.

Infectious diseases caused by viruses, parasites, bacteria, and fungi are the number one cause of death worldwide. Although new technologies have improved diagnosis of infectious diseases, the efficacy of all known current anti-infective agents is threatened by the spread of drug-resistant forms of the pathogens. Hence, there remains an urgent need to develop anti-infective agents that target drug-resistant pathogens. In Silico Models for Drug Discovery presents a comprehensive look at the role in silico models play in understanding infectious diseases and in developing novel therapeutics to treat them. Written by leading experts in the field, chapters cover topics such as techniques to derive novel antimicrobial targets, methods of interpreting polypharmacology-based drug target networks, and molecular dynamics techniques used to compute binding energies of drugs to their target proteins, to name a few. Written in the successful Methods in Molecular Biology (TM) series or in review article format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, In Silico Models for Drug Discovery seeks to serve both professionals and novices involved in the study and treatment of infectious diseases.

An in-depth exploration of the applications of plant bioactive metabolites in drug research and development

Highlighting the complexity and applications of plant bioactive metabolites in organic and medicinal chemistry, "Plant Bioactives and Drug Discovery: Principles, Practice, and Perspectives" provides an in-depth overview of the ways in which plants can inform drug research and development. An edited volume featuring multidisciplinary international contributions from acclaimed scientists researching bioactive natural products, the book provides an incisive overview of one of the most important topics in pharmaceutical studies today.

With coverage of strategic methods of natural compound isolation, structural manipulation, natural products in clinical trials, quality control, and more, and featuring case studies on medicinal plants, the book serves as a definitive guide to the field of plant biodiversity as it relates to medicine. In addition, chapters on using natural products as drugs that target specific disease areas, including neurological disorders, inflammation, infectious diseases, and cancer, illustrate the myriad possibilities for therapeutic applications.

Wide ranging and comprehensive, "Plant Bioactives and Drug Discovery" also includes important information on marketing, regulations, intellectual property rights, and academic-industry collaboration as they relate to plant-based drug research, making it an essential resource for advanced students and academic and industry professionals working in biochemical, pharmaceutical, and related fields.

During the last decade or so vaccine development has been facilitated by rapid advances in molecular and cell biology. These have laid the foundations of a new generation of vaccines exemplified by subunit vaccines produced through gene cloning and by synthetic peptides mimicking small regions of proteins on the outer coat of viruses. Such peptide~ are capable of eliciting virus-neutralizing antibodies. Unfortunately, subunit and peptide vaccines are only weakly or non immunogenic in the absence of immunological adjuvants that are known to augment specific cell-mediated immune responses to the antigens and to promote the formation of protective antibodies. This book contains the proceedings of the 4th NATO Advanced Studies Institute (ASI) "Vaccines: New Generation Immunological Adjuvants" held at Cape Sounion Beach, Greece, during 24 June -5 . July 1994 and deals in depth with both theoretical and practical aspects of vaccinology. These include the role of antigen presenting cells in the induction of immune responses. immunopotentiation by a variety of new generation immunological adjuvants and vaccine carriers. and recent advances and perspectives in experimental vaccines as well as vaccinatioll with nucleic acids. We express our appreciation to Dr. K. Dalsgaard and Dr. J. L. Virelizier for their cooperatioll in planning the ASI and to Mrs. Concha Pening for her excellent production of the manuscripts. The ASI was held under the sponsorship of NATO Scientific Affairs Division and generously co-sponsored by SmithKline Beecham Pharmaceuticals (Philadelphia).

Each chapter of this volume is a contribution from an expert in the field, chosen by the editors to contribute to the 1997 "Current Issues in Blood Substitute Research and Development" course given in San Diego, March 17-19. The contributors were selected because of their expertise in areas which the editors believe to be critical to the advancement of the field, and which reflect activity in "hot" areas of relevant research. While there is a continuity in style for the annual course, each year brings changes in emphasis and content. In previous years, we were often not able to provide time for participants to present their views and opinions. Consequently, this year we encouraged discussion after each presentation. These sessions were recorded, transcribed, and are printed with the chapters herein. We believe that the product is very close to the capturing this year's course in print, and trust readers will enjoy reading the always candid and often provocative remarks from the audience. The price paid for inclusion of the discussion transcriptions was a delay in publication. Each author was allowed to edit his/her discussion section as well as the final version of the chapters prior to publication. The changes are mainly for grammar, and we tried, when possible, not to alter the conversational style of these interchanges.

t Heinz Red! and Gunther Sch!ag Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria The word "sepsis" derives from the Greek meaning decay or rottenness. Tradition ally this term has been used to describe the process of infection accompanied by the host's systemic inflammatory response. Based on that understanding, previous clin ical studies have been designed to include only patients with positive blood cultures [1, 2]. However, the frequent occurrence of a septic response without the demon stration of microorganisms in the circulation has led to a new definition and under standing of sepsis, mainly as the systemic response of the host to an often unde tectable microbiological or non-microbiological process [3]. The general consensus is that cytokines are central to the inflammatory response, particularly in sepsis. It is now known that not only Gram-negative but also Gram positive, viral, and fungal infections initiate the complex cascades of cytokine release. Probably the most important aspect of bacterial action is the release of toxic bacterial products. In particular endotoxin from Gram-negative bacteria (see chap ter by Schade) and super antigens (see chapter by Neumann and Holzmann), as well as pore-forming toxins [4] from Gram-positive bacteria, induce cytokine formation. The importance of this cytokine release is evident from both diagnostic and thera peutic (mostly experimental) studies, and the action of cytokines may be the key to our understanding of the pathophysiology of the sepsis syndrome.

The inspiration for this text was the 1988 volume by Alder and Zbinden, written before the ICH harmonization process for drug safety evaluation (or its ISO analog for device biocompatibility evaluation) had been initiated or come to force. Since then, much has changed in both the world and practice of medicine and the regulation of drugs. The intent of this volume is to provide similar guidance as to what nonclinical safety assessment tests need to be performed to move a drug into man, through development and to market approved (this intent was subsequently extended to cover the closely related medical device biotechnology, and combination product fields) in a concise, abbreviated manner for all the major world market countries.

After the successful introduction of acupuncture to the West, recent advances in analytical methods in chemistry, molecular biology and systems biology especially the development of the omic technologies have again brought Chinese drugs into the focus of research on Traditional Chinese Medicine (TCM). With more than 1000 publications on the chemistry, molecular biology and pharmacology of TCM drugs in international journals over the last 10 years, Chinese drugs are gaining increasingly reputation and impact. These data offer great opportunities for the development of new pharmaceuticals for various clinical applications. International scientists have compiled relevant and trend setting research results in this book. Topics range from the latest methods of quality and safety assurance by chemical and genetic fingerprints to the development of new pharmaceuticals for a future evidence-based therapy e.g. for cancer, cardiovascular, inflammatory or infectious diseases as well as to recent experimental results on multitarget and synergy research for the preparation of multi-extract-pharmaceuticals from TCM.

The last decade has seen a renaissance of the concept of individualized chemotherapy in oncology, markedly stimulated by the development of new in vitro chemosensitivity assays. The clinical utility of drug response assays has been evaluated in clinical trials and the results suggest that assay-assisted therapy selection may improve survival as well as economic outcomes. This volume comprises the proceedings of the first Symposium of the International Society for Chemosensitivity Testing in Oncology, ISCO-1, held in Homburg/Saar, Germany, in September 2001. The topics include: new in vitro drug-testing methods, tumor chemosensitivity assays, and the clinical relevance of assay-directed therapy.

This volume explores the considerable efforts that have been directed towards the development of G Protein-Coupled Receptors (GPCR) screening assays in order to disclose GPCR acting compounds, elucidate signaling mechanisms or evaluate compound's efficacy. New discoveries in the field, along with the widely recognized need for better and safer pharmaceutical drugs constitute the main motivation for this book. Readers, both beginners and experienced researchers, will receive an updated overview of not only the established, but also the innovative technologies that promise to advance GPCR drug research. This book is organized into two major parts: the introductory part discusses the necessary foundations for the understanding of GPCR action and the rationale behind the design of the available screening assays; and part two provides detailed protocols for different screening approaches. Written in the highly successful Methods in Molecular Biology series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results in the laboratory. Practical and innovative, G Protein-Coupled Receptor Screening Assays: Methods and Protocols reaches out to everyone involved in the discovery of GPCR-active drugs, and provides a transversal overview of the different levels of GPCR signaling addressable in the different screening strategies and presents practical examples of how current assay technologies are contributing to new paradigms in GPCR drug research.

Antibody-drug conjugates (ADCs) represent a promising therapeutic approach for cancer patients by combining the antigen-targeting specificity of monoclonal antibodies (mAbs) with the cytotoxic potency of chemotherapeutic drugs. In Antibody-Drug Conjugates, expert researchers provide detailed protocols for many of the key ADC techniques necessary for working in the field. These chapters and methodologies are aimed at the key tasks necessary to identify a suitable target, properly design the mAb, the linker and the payload, as well as to conjugate them in a reproducible and scalable fashion. Written in the highly successful Methods in Molecular Biology (TM) format, these detailed chapters include the kind of practical implementation advice that guarantees quality results. Authoritative and timely, Antibody-Drug Conjugates aims to further drive ADC development and thus help toward improving cancer treatments of the future.

This work stems from the activities carried out under the European Science Foundation's Environmental Toxicology Programme and its daughter programme, Environmental Damage and its Assessment. The work served also as a pilot study for the ESF Scientific programme on Environment, Science and Society (ESS), thus demonstrating the interdependence of the natural and social sciences with respect to environmental issues. The book is unique in the sense that it records the results of a four year collaboration between environmental toxicologists, economists and institutionalists. Its objective was to achieve better characterized or even novel insights into the theory and practice of water resource management, quality assurance and chemical safety regulation.

This is an overview of the fast-moving field of purinergic signalling through adenosine and ATP receptors.

Authors are the leading authorities in their fields

Subject matter is important for understanding tissue protection

Subject matter is of intense interest for new drug development

Prevention of infectious diseases by vaccination is one of the most significant achievements of modern medicine. During the 20th century, the average human life span in the developed world was about 70 years and it is expected to increase, with a significant portion of this increase directly attributed to vaccination. Since the first empiric vaccination trials, knowledge and technology have enormously evolved and new vaccination strategies are emerging on the market. Indeed, in spite of the great success, conventional vaccination strategies sometimes may result ineffective and, above all, may raise safety concerns. The aim of this book is to provide an overview of some of the technology platforms that have been realized or are currently under development to try to address unsolved and new issues in the field of vaccine development. Common denominator of all thematic areas described herein is the multidisciplinary teamwork. Most of the enabling technologies have been established by putting in the "melting pot" expertise in fields that, at first glance, may appear very far apart. I hope that this collection of articles will make the readers aware that vaccinology is rapidly taking a new direction, ceasing to be an empirical science.

The purpose of Applications Therapeutic of Ribozymes is to provide an overview of the utility of ribozymes to selectively inhibit the expression of RNA. The ribozyme applications appearing in this book should benefit not only those experienced in ribozymes, but also those applying this ribozyme technology for the first time. It is hoped that a better understanding of the therapeutic application ofribozymes will have a significant impact on human disease in the near future. The field ofribozyme biochemistry has come a long way since the initial observation that RNA is capable of catalysis, initially in cis during processing of larger molecules and ultimately the use of ribozymes in trans to achieve cleavage of target sequence. The fundamental observation that hammerhead (and subsequently hairpin) ribozymes could be designed to cleave a target messenger RNA, and the clarification of sequence restrictions in both the ribozyme and the target RNA, have paved the ways for the use of ribozymes as a tool to manipulate gene expression at the molecular level. This had pre- ously been a domain of antisense oligonucleotides and triplex DNA. Sub- quent studies have explored the myriad biological systems in which ribozyme-mediated inhibition of genes involved in various cellular processes may be used to uncouple important signaling pathways or to reverse the p- notypic expression of a pathologic process.