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."

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

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.

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

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

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

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 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. "

This book contains the selected papers presented at the seventh International Symposium on Blood Substitutes (7th ISBS) held at the International Conference Center of Waseda University in Tokyo on 7-10 September 1997. In keeping with the scientific design of the 7th ISBS Symposium, chapters have been carefully selected and organized to showcase the advancements in recent research. This book includes up-to-date clinical results of leading companies which are manufacturing hemoglobin-based or fluorocarbon-based blood substitutes, and covers issues of hemoglobin toxicity and side effects such as vasoconstriction in more detail using carefully designed in vivo and ex vivo techniques. This book is also a collection of various new types of red cell substitutes such as recombinant Hbs, recombinant albumine-lipidheme complex, modified red blood cells, and perfluorochemicals using material science and molecular engineering.

In the early eighties when the H3 receptor was identified, many thought that an H3 ligand, an agonist or an antagonist, would become available as a therapeutic agent. This has not occurred. The reason for this could be the fact that many investigators consider histamine mainly, if not only, as a mediator present in for example mast cells being released during allergic events. However, it has become apparent that histamine is an important neurotransmitter. Its role in the nervous system, especially in the central part of it, is rather extensive.

The H3 receptor is mainly found as a presynaptic one, both on histaminergic neurons (the auto-type) and on other neuronal systems (the hetero-type). Both the H3 agonist and the H3 antagonist cause important pharmacological effects. Several ligands have become available now, including radiolabelled analogues.

In this book, the current state of affairs with regards to the medicinal chemistry and pharmacology of the H3 receptor and the several ligands available are presented by a number of experts in the field. The book presents an extended review of what has happened since the first H3 paper appeared. The editors hope that publication of this work will lead to an increase in interest of both academia and industry for the H3 receptor, especially as a target for drug development.

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."

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.

Long acting injections and implants improve therapy, enhance patient compliance, improve dosing convenience, and are the most appropriate formulation choice for drugs that undergo extensive first pass metabolism or that exhibit poor oral bioavailability. An intriguing variety of technologies have been developed to provide long acting injections and implants. Many considerations need to go into the design of these systems in order to translate a concept from the lab bench to actual therapy for a patient. This book surveys and summarizes the field. Topics covered in Long Acting Injections and Implants include the historical development of the field, drugs, diseases and clinical applications for long acting injections and implants, anatomy and physiology for these systems, specific injectable technologies (including lipophilic solutions, aqueous suspensions, microspheres, liposomes, in situ forming depots and self-assembling lipid formulations), specific implantable technologies (including osmotic implants, drug eluting stents and microfabricated systems), peptide, protein and vaccine delivery, sterilization, drug release testing and regulatory aspects of long acting injections and implants. This volume provides essential information for experienced development professionals but was also written to be useful for scientists just beginning work in the field and for others who need an understanding of long acting injections and implants. This book will also be ideal as a graduate textbook.

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.

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.

This book offers the most up-to-date information about research surrounding the neurobiology of bipolar disorder as well as currently available and novel therapeutic options. The volume has assembled a widely respected group of preclinical and clinical researchers who bring their expertise to bear upon this illness by reviewing cutting-edge research and clinical evidence regarding the pathophysiology and treatment of bipolar disorder. Early chapters review the course and outcome and genetics of this highly heritable condition, including chapters on epigenetics and clinical endophenotypes. Several chapters offer a remarkably thorough and unique overview of the neurobiology of the disorder, including what is known from neuroimaging work and the development of animal models. Finally, the book covers treatment strategies for bipolar disorder, including both traditional and novel therapeutics, as well as non-pharmacological treatments. It offers both researchers and clinicians key insights into this devastating disorder.

Efforts to describe and model the molecular structure of biological membranes go back to the beginning of the last century. In 1917, Langmuir described membranes as a layer of lipids one molecule thick [1]. Eight years later, Gorter and Grendel concluded from their studies that "the phospholipid molecules that formed the cell membrane were arranged in two layers to form a lipid bilayer" [2]. Danielli and Robertson proposed, in 1935, a model in which the bilayer of lipids is sequestered between two monolayers of unfolded proteins [3], and the currently still accepted fuid mosaic model was proposed by Singer and Nicolson in 1972 [4]. Among those landmarks of biomembrane history, a serendipitous observation made by Alex Bangham during the early 1960s deserves undoubtedly a special place. His fnding that exposure of dry phospholipids to an excess of water gives rise to lamellar structures [5] has opened versatile experimental access to studying the biophysics and biochemistry of biological phospholipid membranes. Although during the following 4 decades biological membrane models have grown in complexity and functionality [6], liposomes are, besides supported bilayers, membrane nanodiscs, and hybrid membranes, still an indisputably important tool for membrane b- physicists and biochemists. In vol. II of this book, the reader will fnd detailed methods for the use of liposomes in studying a variety of biochemical and biophysical membrane phenomena concomitant with chapters describing a great palette of state-of-the-art analytical technologies.

Following the success of the first edition, this pioneering study of pharmaceuticals in the environment has been updated and greatly extended. It includes the status of research on pharmaceuticals in soil, with attention to terrestrial and aquatic environments as well as new substance categories such as tetracylines and chinolones and the latest results concerning contamination of the environment and risk reduction.

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 series ofbooks on the biotechnology of Medicinal and Aromatic Plants provides a survey of the literature focusing on recent information and the state of the art in tissue culture and the in vitro production of secondary metabolites. This book, Medicinal and Aromatic Plants VIII, like the previous seven volumes published in 1988, 1989, 1991, 1993, and 1994, is unique in its approach. It comprises 26 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 Achillea, Anethum, Aquilaria, Arnica, Aspergillus, Astragalus, Catalpa, Chelidonium, Eremo phila, Eucalyptus, Eucommia, Geranium, Heterocentron, Hypericum, Maclura, Morinda, Mortierella, Nicotiana, Phaseolus, Pinellia, Piqueria, Psorales, Rhodiola, Sanguisorba, Valeriana, and Vancouveria. This book 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. New Delhi, July 1995 Professor Y. P. S. BAJAJ Series Editor Contents I Achillea millefolium L. ssp. millefolium (Yarrow): In Vitro Culture and Production of Essential Oils A. C. FIGUEIREDO, M. S. S. PAIS, and J. J. c. SCHEFFER (With 9 Figures) 1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2 In Vitro Culture Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 3 Ultrastructural Study of the Glandular Trichomes and Cell Suspension Cultures . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 4 Composition of the Essential Oils of A. millefolium In Vivo and In Vitro . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 5 Summary and Conc1usion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 6 Protocol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 II Anethum graveolens L."