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.

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

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."

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.

The majority of cancers present at a relatively advanced stage in which invasion within the primary organ is well established and metastases to lymph and distant organs are either clinically apparent or present at the microscopic level. However, it is increasingly recognized that the natural history of cancer formation is a long and complex path taking many years to develop to a clinically apparent stage in most cases. Furthermore, for most solid tumours there is a pre-invasive or intraepithelial stage of disease. This affords the opportunity for early detection and prevention of invasive disease and hence a cure. However, with this advancing knowledge comes a whole plethora of questions which will be explored in this monograph. Firstly, we need to understand the global burden of pre-invasive disease and what the public health implications might be for wide-scale screening programmes. In the western world we already have experience of screening for cervical, breast, prostate and more recently colon cancer. As well as their potential benefits these programmes have financial and psychosocial implications which need to be carefully weighed. This is especially true since many pre-invasive lesions will not progress to cancer in a individual's lifetime. In addition, there are questions concerning whether screening reduces the cancer burden or in fact distorts the survival figures through lead-time bias. Secondly, at the level of epidemiology and molecular pathogenesis there are important questions regarding the aetiology of pre-invasive lesions; an understanding of which might lead to possible chemopreventive strategies. For example, it would be helpful to know the extent to which the likelihood of developing a pre-invasive lesion is influenced by lifestyle or genetic factors and how these factors influence the risk of progression to invasive disease. At the molecular level we need to understand the pathways and molecular mechanisms, both genetic and epigenetic, by which cells achieve the capacity to invade. Thirdly, in order make clinical progress we need biomarkers to identify and risk stratify individuals with pre-invasive lesions. These biomarkers might be applied to the serum as in Prostate Specific Antigen in prostate cancer or be applied to tissue samples, such as oestrogen receptor status in breast cancer. In order to utilize biomarkers in the context of a screening programme there are issue around the invasiveness of the test as well as its positive and negative predictive value. With advances in molecular imaging there is now the exciting possibility of incorporating a molecular tag to a non-invasive imaging modality. Fourthly, in order to justify screening early detection must be coupled to a treatment strategy. If the chemopreventive agent is very well tolerated, then as well as targeting high risk groups, one might consider treatment at the population level. Aspirin is one such drug which has been extensively assessed in the context of colon cancer chemoprevention trials. Trials of aspirin chemoprevention are now being applied to other cancers such as oesophageal adenocarcinoma and since many individuals take aspirin for .chemoprevention of cardiovascular disease the cancer incidence can be ascertained in these populations. In order to understand the more general issues raised from the discussions above it is useful to consider disease specific examples. Our understanding of pre-invasive disease varies according to the organ site and there are lessons to be learned from these experiences. For example, there is now the prospect of a vaccine for cervical cancer with important questions about how this might be applied to the high incidence areas of the developing world. On the other hand, ductal carcinoma in situ is currently treated by mastectomy which is more radical than the treatment received by many women with invasive disease. Oesophageal adenocarcinoma, which is my own area of expertise is interesting because of the rapid rise in incidence in the western world and the clinically accessible pre-invasive lesion called Barrett's oesophagus. However, most cases of Barrett's oesophagus remain undiagnosed and it is not yet clear how to effectively diagnose, monitor and treat this condition without recourse to mass endoscopy with substantial cost implications. In conclusion, in an era in which preventive medicine is a major concern for consumers, health-policy makers and politicians pre-invasive disease is likely to become a major part of cancer medicine.

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.

Volume 8 is part of a multicompendium Edible Medicinal and Non-Medicinal Plants, on plants with edible flowers from Geraniaceae to Zingiberaceae (tabular) and 82 species in Geraniaceae, Iridaceae, Lamiaceae, Liliaceae, Limnocharitaceae, Magnoliaceae, Malvaceae, Meliaceae, Myrtaceae, Nyctaginaceae, Nymphaeaceae, Oleaceae, Onagraceae, Orchidaceae, Paeoniaceae, Papaveraceae, Plantaginaceae, Poaceae, Polygonaceae, Primulaceae, Proteaceae, Ranunculaceae, Rosaceae, Rubiaceae, Rutaceae, Solanaceae, Theaceae, Tropaeolaceae, Tyhpaceae, Violaceae, Xanthorrhoeaceae and Zingiberaceae in detail. This work is of significant interest to medical practitioners, pharmacologists, ethnobotanists, horticulturists, food nutritionists, botanists, agriculturists, conservationists and general public. Topics covered include: taxonomy; common/ vernacular names; origin/ distribution; agroecology; edible plant parts/uses; botany; nutritive/medicinal properties, nonedible uses and selected references.

Information Resources in Toxicology, Third Edition is a sourcebook for anyone who needs to know where to find toxicology information. It provides an up-to-date selective guide to a large variety of sources--books, journals, organizations, audiovisuals, internet and electronic sources, and more. For the Third Edition, the editors have selected, organized, and updated the most relevant information available. New information on grants and other funding opportunities, physical hazards, patent literature, and technical reports have also been added.
This comprehensive, time-saving tool is ideal for toxicologists, pharmacologists, drug companies, testing labs, libraries, poison control centers, physicians, legal and regulatory professionals, and chemists.
Key Features
* Serves as an all-in-one resource for toxicology information
* New edition includes information on publishers, grants and other funding opportunities, physical hazards, patent literature, and technical reports
* Updated to include the latest internet and electronic sources, e-mail addresses, etc.
* Provides valuable data about the new fields that have emerged within toxicological research; namely, the biochemical, cellular, molecular, and genetic aspects

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.

Unique analysis of drugs and poisons to facilitate testing in all laboratories even by inexperienced chemists

Includes source of chemicals needed for the experiments

Texts are composed by 67 experts in analyzing the respective compounds

Clear and uniform structure of chapters for ease of reading

The text is illustrated by many diagrams and tables

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.

"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.

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 volume provides extensive health (toxicological) and safety handling information and data on over 1,000 chemicals of commercial and industrial importance.
This volume will provide extensive health (toxicological) and safe-handling information and data on more than 1000 chemicals of commercial and industrial importance. It provides chemical specific information pertinent to safe handling and transportation of chemicals, worker protection, emergency response information to address spills, explosions on fire situations, and chemical stability/reactivity data. It is designed as a standard reference handbook for chemical engineers, safety engineers, toxicologists, fire safety specialists, chemists, laboratory and plant technicians.
Provides extensive health and safe-handling information on more than 1,000
Standard reference work for those involved in chemical engineering and related fields

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.

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.

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."

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.

The herbai medicine industry is growing at an astounding rate. Trade group estimates suggest that total sales exceeded $4 billion dollars in 1999. Herbai remedies are for sale not just in health food stores, but in supermar kets, drug stores, and even discount warehouses. Along with the proliferation in sales has come a proliferation ofinformation sources. Not all ofthe sources are equally reliable, or even intelligible. Traditional herbalists c1assify thistle and mugwort as "cholagogues," substances used to make the gallbladder con tract and release bile. Medical school graduates are unlikely to have ever heard the term, or even accept the notion that most right-sided abdominal pain is a result of diminished bile flow. Heroin and cocaine may not be the only drugs to come from plants, but a practicing physician or toxicologist might be forgiven for thinking so. In 1998, 1264 papers were published about cocaine and only 17 about kava kava, an abused herb that is not without toxic side effects. Unfortunately, the majority of the papers about kava kava were published in journals not found in ordi nary hospitallibraries. In recognition ofthis fact, and ofthe obvious need for a reliable reference work on herbai toxicology, The Toxicology and Clinical Pharmacology 0/ Herbal Products was an early addition to our new series in Forensie Science and Medicine. It is very badly needed.

In this book, both basic and advanced concepts are discussed for considering mixtures from initial exposure characterization through evaluation of risk associated with combined exposures. This book will provide an introduction to key issues and multiple options for evaluating both the toxicity of mixtures as well as the risk associated with exposure to mixtures. Additionally, promising tools adapted from other disciplines will be discussed in the context of mixtures toxicology and risk assessment. Finally, the discussion will move beyond chemical mixtures to address incorporating non-chemical stressors into toxicity studies and cumulative risk assessments. Although exposure to multiple chemical and non-chemical stressors is the rule, not the exception, consideration of mixtures in toxicology and risk assessment continues to be a significant challenge. This book will be an essential resource for researchers and professionals in the fields of toxicology, epidemiology, exposure science, risk assessment, and statistics.

Handbook of Animal Models of Infection is a complete revision of a three-volume text that was published in 1986. It incorporates the major advances in the field during the past decade, in particular those concerning molecular biological procedures and new models that have been developed. It focuses on both methods and techniques, which makes it an essential and comprehensive reference as well as a benchtop manual. The Handbook will help investigators save time and effort in formulating an approach to test a new potential therapeutic agent or combination of agents for "in vivo" efficacy and to position the therapy for specific infections where it may have therapeutic promise. The book is divided into five sections; the first covering the general methodologies, followed by sections describing experimental bacterial, mycotic, parasitic, and viral infections.
Key Features
* Discusses ethical and safety aspects in an introductory background section
* Covers principles of animal care and current techniques appropriate for the use of animal models of infection
* Details a wide range of animals including rodents, rabbits, cats, and primates
* Provides hands-on descriptions of how to set up the model
* Discusses the major advantages and limitations of each model
* Ensures full coverage of bacterial, fungal, viral, and parasitic infections

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.