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

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

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

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

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. "

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

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.

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 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."

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.

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.

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.

As the number of people aged 65 years and above rises, physicians are increasingly confronted by elderly patients with impaired renal function, altered drug metabolism and multiple comorbidities. This book examines in detail the nature of renal injury in the elderly and its optimal management. A wide range of key topics are covered, including end-stage renal disease, diabetic nephropathy, acute kidney injury, drug metabolism and renal toxicity, dialysis and its complications and the use of renal transplantation. In addition, the assessment of glomerular filtration rate in the elderly and the role of novel renal biomarkers are carefully examined. Quality of life issues, the significance of other age-related medical problems and end of life care are also discussed. This book will be of value not only to nephrologists but also to general practitioners, medical students, intensivists, cardiologists, pharmacologists and those working in related specialties. "

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.

Stable isotope techniques offer advantages in safety, sensitivity, specificity, and economy for many types of pharmaceutical investigations when compared to conventional techniques. Nevertheless, pharmaceutical researchers are slow to embrace stable isotope techniques.

This book assembles in one place comprehensive reviews of the many applications of stable isotopes and the background material necessary to understand the application. This approach is a deliberate attempt to encourage the usage of stable isotopes in pharmaceutical research. A bonus to the reader is the high standard of contributions from a very talented and diverse group of investigators.

The tetracyclines have an illustrious history as therapeutic agents which dates back over half a century. Initially discovered as an antibiotic in 1947, the four ringed molecule has captured the fancy of chemists and biologists over the ensuing decades. Of further interest, as described in the chapter by George Armelagos, tetracyclines were already part of earlier cultures, 1500-1700 years ago, as revealed in traces of drug found in Sudanese Nubian mummies. The diversity of chapters which this book presents to the reader should illus trate the many disciplines which have examined and seen benefits from these fascinating natural molecules. From antibacterial to anti-inflammatory to anti autoimmunity to gene regulation, tetracyclines have been modified and redesigned for various novel properties. Some have called this molecule a biol ogist's dream because of its versatility, but others have seen it as a chemist's nightmare because of the synthetic chemistry challenges and "chameleon-like" properties (see the chapter by S. Schneider).