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.

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.

This book provides the reader with a contemporary and comprehensive overview about the molecular, cellular and system-wide principles of circadian clock regulation. Emphasis is placed on the importance of circadian clocks for the timing of therapeutic interventions.

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.

This book offers an unparalleled source of information on in vivo assessment of nanoparticle toxicity by using Drosophila as a model organism. Nanoparticles have emerged as an useful tool for wide variety of biomedical, cosmetics, and industrial applications. However, our understanding of nanomaterial-mediated toxicity under in vivo condition remains limited. The book begins with a chapter on synthesis and characterization of nanoparticles used for various biological, medical and commercial purposes. The rest of the chapters deal with the impact of nanoparticles on different biological aspects like behavior, physiology and metabolic homoeostasis using Drosophila as a model organism. Lastly, the book summarizes how proper characterization and evaluation of safe dosage of nanoparticles can be a boon if incorporated in consumer goods and for biomedical applications. Overall, the book pursues an interdisciplinary approach by connecting nanotechnology and biology from various angles using Drosophila as a model system, so as to develop more efficient, safe and effective use of nanoparticles for human beings.

This timely desk reference focuses on marine-derived bioactive substances which have biological, medical and industrial applications. The medicinal value of these marine natural products are assessed and discussed. Their function as a new and important resource in novel, anticancer drug discovery research is also presented in international contributions from several research groups. For example, the potential role of Spongistatin, Apratoxin A, Eribulin mesylate, phlorotannins, fucoidan, as anticancer agents is explained. The mechanism of action of bioactive compounds present in marine algae, bacteria, fungus, sponges, seaweeds and other marine animals and plants are illustrated via several mechanisms. In addition, this handbook lists various compounds that are active candidates in chemoprevention and their target actions. The handbook also places into context the demand for anticancer nutraceuticals and their use as potential anti-cancer pharmaceuticals and medicines. This study of advanced and future types of natural compounds from marine sources is written to facilitate the understanding of Biotechnology and its application to marine natural product drug discovery research.

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.

Forensic professionals, particularly medical examiners-often working through heavy caseloads-require quick and easy access to reliable sources of information to help interpret toxicology results. While several in-depth resources are available, they are often large, cumbersome, and contain more information than is often needed. The Handbook of Forensic Toxicology for Medical Examiners is a concise handbook referencing the most common toxic substances and their reported non-toxic, toxic, and lethal concentrations, making it an ideal text for quick reference in the lab or autopsy room. Features of the Second Edition: Explains the principles of postmortem toxicology and the factors which must be considered Provides tables of toxicologic data for over 200 commonly encountered substances, including drugs of abuse, poisons, prescription drugs, and over-the-counter medications Includes discussion and description of the novel psychoactive drugs-including synthetic opioids, cannabinoids, stimulants and hallucinogens Supplemental appendices provide additional information regarding specimen types and selection, testing methodologies, normal laboratory values, and conversion charts The busy forensic professional needs a concise handbook that provides critical information quickly and accurately. This heavily referenced text offers an easy-to-use format allowing for rapid access for both routine daily use and preparation for courtroom testimony.

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.

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. "

Introductory Address.- The New Biology and Vaccine Research.- Keynote Presentation.- Mucosal Immunity To Vaccines: Current Concepts for Vaccine Development and Immune Response Analysis.- Session I: Oral Diseases and Host Immune Responses.- Prospects for Human Mucosal Vaccines.- Bacterial Diseases of the Oral Tissues.- Oral Virus Infections: The Potential for Gene Transfer in Treatment and Prevention.- Session II: Update on Vaccines and Vaccine Development.- Bacterial Mucosal Vaccines.- A General Overview of Viral Vaccine Development.- Session III: Vaccines and the Mucosal Immune System.- An Update on the "Jennerian" and Modified "Jennerian" Approach to Vaccination of Infants and Young Children Against Rota Virus Diarrhea.- Induction of Mucosal and Serum Immune Responses to a Specific Antigen of Peridontal Bacteria.- IgA1 Proteases and Host-Parasite Relationships in the Oral Cavity.- Transport of Iga Immune Complexes Across Epithelial Membranes: New Concepts n Mucosal Immunity.- Effect of Mucosal Microenvironment on Immune Response to Viruses.- Session IV: Optimizing Mucosal and Systemic Immune Responses.- Induction of T Helper Cells and Cytokines For Mucosal IgA Responses.- Cytokine Production and T Cell Receptor Expression by Salivary Gland T Cell and Intraepithelial T Lymphocytes for the Regulation of the IgA Response.- Immunological Adjuvants.- Session V: Delivery Systems and Immune Analysis.- M Cell-Mediated Antigen Transport and Monoclonal IgA Antibodies For MucosalImmune Protection.- A Mechanism of Passive Immunization with Monoclonal Antibodies to a 185,000Mr Streptococcal Antigen.- Delivery of Antigens by Recombinant Avirulent Salmonella Strains.- Use of Recombinant BCG as a Vaccine Delivery Vehicle.- Vaccinia Virus Recombinants as Potential Herpes Simplex Virus Vaccines.- Liposomes and Conjugate Vaccines for Antigen Delivery and Induction of Mucosal Immune Responses.- Peroral Immunization with a Cholera Toxin-Linked Bacterial Protein Antigen and Synthetic Peptide.- Peptomers as Vaccine Candidates.- Session VI: Target Antigen Selection and Vaccine Development.- Structural and Functional Studies of Herpes Simplex Virus Glycoprotein D.- Molecular, Immunological and Functional Characterization of the Major Surfae Adhesin of Streptococcus Mutans.- Reacitve Antigens of the Periodontopathic Bacterium Actinobacillus Actinmycetemcomitans.- Immunization with Fimbrial Protein and Peptide Protects Against Porphyromonas Gingivalis- Induced Periodontal Tissue Destruction.- Vaccine Development: Progression from Target Antigen to Product.- Session VII: Immunological Correlates of Protection.- Significance of Immune Responses to Oral Antigens in Dental Diseases.- Laboratory Correlates of Protection and Protective Immunity to Bordetella Pertussis.- Future Directions.- Challenges and Opportunities in Vaccine Research.- Summary and Recommendations for Future Research.- Speakers and Moderators.- Author Index.

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 book continues as volume 4 of a multi-compendium on Edible Medicinal and Non-Medicinal Plants. It covers edible fruits/seeds used fresh or processed, as vegetables, spices, stimulants, edible oils and beverages. It encompasses selected species from the following families: Fagaceae, Grossulariaceae, Hypoxidaxeae, Myrsinaceae Olacaceae, Oleaceae, Orchidaceae, Oxalidaceae, Pandanaceae, Passifloraceae, Pedaliaceae, Phyllanthaceae, Pinaceae, Piperaceae, Rosaceae and Rutaceae . This work will be of significant interest to scientists, researchers, medical practitioners, pharmacologists, ethnobotanists, horticulturists, food nutritionists, agriculturists, botanists, 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 and pharmacological properties, medicinal uses and research findings; nonedible uses; and selected references.

The development of liposomes as a drug delivery system has fluctuated since its introduction in the late 1960's by A.D. Bangham. While academic research of liposomes as a model membrane system has always flourished, as the exponential growth of papers can testify, the application of these findings to medically useful products has gone through several crises. Following the original optimism in the 70's and early 80's, a period of severe skepticism ensued at the end of the 80's and beginning of the 90's, culminating in a moderate but real optimism in the mid 90's, as a result of a successful launch of the first products in the US and Europe.

In this collection of papers, the editors have gathered the most promising ideas, approaches, applications and commercial developments, thereby presenting an up-to-date compilation of the present status of the field. This includes such broad areas as anti-cancer chemotherapy immune stimulation and infectious diseases. Currently, the major areas of progress are in delivery of anti-fungal agents by conventional liposomes or lipid-based carriers and systemic anticancer therapy using long-circulating liposomes. The future applications as characterized by the direction of present day research is in specific targeting and delivery of informational molecules such as DNA plasmids (genes), antisense oligonucleotides or ribozymes. Other future developments may be in topical delivery, vaccination and in diagnostics.

Features of this book:

Contributions from almost all the leading labs in the field

Up-to-date, critical reviews bridged by editors' introductions

Organized into a logical framework."

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.

Hardbound. Eminent scientists at the cutting edge of pharmacology and medicinal chemistry research provide us with yet another excellent addition to this famous series. The focus on bacterial resistance mechanisms serves to highlight an important area of unmet medical need requiring the attention of medicinal chemists.Five topical subjects are reviewed: the biosynthesis, metabolism and function of Vitamin D3 and the potential application of its analogues in bone disorders and immune-related diseases; the therapeutic potential of neurokinin antagonists; opioid receptor antagonists; the mechanisms of bacterial resistance; and a survey of recent advances in cannabinoid research.This volume will deservedly take its place in clinical and industrial pharmaceutical libraries, and will prove invaluable to medicinal chemists.

This book describes antibiotic resistance amongst pathogenic bacteria. It starts with an overview of the erosion of the efficacy of antibiotics by resistance and the decrease in the rate of replacement of redundant compounds. The origins of antibiotic resistance are then described. It is proposed that there is a large bacterial resistome which is a collection of all resistance genes and their precursors in both pathogenic and non-pathogenic bacteria. Ongoing resistance surveillance programs are also discussed, together with the perspective of a clinical microbiologist. The book then turns to specific themes such as the most serious area of resistance in pathogens, namely in Gram-negative organisms. The role of combinations of antibiotics in combating resistance emergence is discussed, particularly in the tuberculosis field, and then the importance of non-multiplying and persistent bacteria which are phenotypically resistant to antibiotics and prolong the duration of therapy of antibiotics which leads to poor compliance and resistance emergence. The role of anti-microbial compounds in textiles is covered, with its potential to exacerbate the spread of resistance. Then, efflux pumps are discussed. The final chapter describes the compounds which are in late stage clinical development, illustrating the paucity of the antibiotic pipeline, especially for Gram-negative bacteria.

Following the success of the first edition, this book is designed to provide practical and timely information for toxicologic pathologists working in pharmaceutical drug discovery and development. The majority of the book (Organ Systems) will provide detailed descriptions of histopathological lesions observed in drug development. In addition, it will provide information to assist the pathologist in making determinations of the origin of lesions as well as its relevance to human risk. Toxicologic Pathology: Nonclinical Safety Assessment, Second Edition includes 2 new concept chapters. The first of the new chapters address approaches for the evaluation of unique therapeutic modalities such as cell therapies, gene therapies, and gene expression knockdown therapies. While these still represent new developing therapeutic approaches, there has been significant experience with the therapeutic modalities in the last 5 years. The second new chapter addresses the nonclinical safety assessment of medical devices, a topic of increasing importance that was not addressed in a unique chapter in the first edition. The other concept chapters have been updated and cover important topics including the overview of drug development; principles of nonclinical safety assessment; an introduction to toxicologic pathology; techniques used in toxicologic pathology, clinical pathology, toxicokinetics, and drug development toxicogenomics; and spontaneous lesions. The 13 organ system chapters provide the specifics related to pathologic characteristics, differential diagnosis, and interpretation of toxic responses in each organ system. These chapters are specifically important for the bench pathologist but also for the toxicologist who interacts with pathologists and function as study toxicologists and project team representatives in the drug development arena.

This detailed volume brings together leading practitioners in the freeze-drying community to address recent progress, not only in new analytical tools and applications of the data derived in cycle design but also in the manufacturing of lyophilized products in the healthcare sector - whether these be therapeutics, vaccines or diagnostic products - and indeed the equipment to deliver this scale of freeze-drying. Areas of focus include analytical and formulation issues, process monitoring and control, as well as post-lyophilization analysis. Written for the Methods in Pharmacology and Toxicology series, chapters include the type of expert advice that leads to superior results in the lab. Authoritative and practical, Lyophilization of Pharmaceuticals and Biologicals: New Technologies and Approaches serves as an ideal guide for researchers working in or just seeking an update on this rapidly changing field.

This book, Medicinal and Aromatic Plants IX, like the previous eight volumes published in 1988, 1989, 1991, 1993, 1994, and 1995, is unique in its approach. It comprises twenty-four chapters dealing with the distribution, importance, conventional propagation, micropropagation, tissue culture studies, and the in vitro production of important medicinal and pharmaceutical compounds in various species of Agave, Anthemis, Aralia, Blackstonia, Catha, Catharanthus, Cephalocereus, Clerodendron, Coronilla, Gloeophyllum, Liquidambar, Marchantia, Mentha, Onosma, Paeonia, Parthenium, Petunia, Phyllanthus, Populus, Portulaca, Sandersonia, Serratula, Scoparia, and Thapsia. It is tailored to the needs of advanced students, teachers, and research scientists in the field of pharmacy, plant tissue culture, phytochemistry, biochemical engineering, and plant biotechnology in general.

This volume covers several aspects of rational drug design, such as synthesis of novel bioactive drugs; development and application of new methodologies; computational methods valuable for the establishment of new approaches in drug discovery; and the effects of physical-chemical and ADMET properties of the designed potential drugs. Chapters guide readers through amyloid deposits, Saturation Transfer Difference (STD) NMR, methods on bioguided design, the importance of lipophilicity in drug design, ADMET, FRET, structural biology, and homology modeling. Written in the highly successful Methods in Molecular Biology 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. Authoritative and cutting-edge, Rational Drug Design: Methods and Protocols aims to ensure successful results in the further study of this vital field.

Malnutrition: Malnutrition and the Developing Central Nervous System (P.J. Morgane et al.). Prolonged Dietary Restriction and its Effects on Dopamine Systems of the Brain (F.M. Scalzo). Dietary Factors that Influence the Neural Substrates of Memory (G.L. Wenk). Neurotoxins in Herbs and Food Plants (R.J. Huxtable). Malnutrition and the Vulnerable Brain (R.W. Russell). Methods: The Evaluation of Behavioral Changes Produced by Consumption of Environmentally Contaminated Fish (H.B. Daly). Animal Models of Cognitive Development in Neurotoxicity (M.E. Stanton). Neurotoxicants and Limbic Kindling (M.E. Gilbert). Testing Visual System Toxicity Using Visual Evoked Potentials (W.K. Boyes). The Use of Selective Silver Degeneration Stains in Neurotoxicity (C.D. Balaban). Caveats in Hazard Assessment (D.B. Miller). Index.

The first authoritative textbook specifically addressing issues of the field, this book delivers a focused discussion on several themes in psychiatry while providing a sound background on pharmacovigilance. Internationally-recognised researchers, clinicians and pharmacovigilance experts contributed to this textbook, giving it the benefit of different perspectives and years of experience. Pharmacovigilance in psychiatry provides a thorough introduction to this field but goes on to explore advanced themes such as methodologies and resources used for pharmacovigilance in psychiatry, challenges as well as most recent developments to this field, making it suitable for under-graduates, graduate and post-doctoral students and persons working pharmacovigilance who seek to broaden their knowledge on this subject.

The application of molecular techniques to gastroenterology continues to yield important advances in the development of drugs to treat gastrointestinal disorders. Important new drugs have emerged through the collaborative and complementary efforts of basic scientists, clinicians, and clinical researchers in academia and the pharmaceutical industry. The challenge has been exciting, with a few surprises along the way. Consider peptic ulcer disease as an example. The discovery of H receptors and the availability of potent and 2 selective H-receptor antagonists signaled the beginning of a new era 2 in the treatment of gastric hypersecretory states and peptic ulcers. Introduction of proton pump inhibitors offered another therapeutic option. Though H-receptor antagonists and proton pump inhibitors 2 are important and useful drugs, the discovery of the link between H. pylori infection and peptic ulcer disease has led to even more effective pharmacotherapeutic regimens. Our intent in Drug Development: Molecular Targets for GI Diseases is to bring together hands-on experts to review promising areas of gastrointestinal pharmacology. The contemporary topics covered, from a mechanistic viewpoint, are relevant to gastrointestinal inflammation and motility disorders. Authoritative opinions are offered on both future research directions and potential applications for new therapies.