Pharmacology and Toxicology of Cytochrome P450 - 60th Anniversary, Volume 95 highlights the extensive contributions by worldwide researchers in the cytochrome P450 (P450) field over the past six decades, and since the first article on P450 was published in 1962. Chapters in this new release include Multiple conformations of cytochromes P450 and the relevance to predicting SAR, Pharmacogenetics of the cytochromes P450 and relevance to drug metabolism, Cytochromes P450 drug metabolism within the brain, Mammalian cytochrome P450 biodiversity: Physiological importance, function, and protein and genomic structures of cytochromes P4502B in multiple species of woodrats with different dietary preferences, and more. Additional section cover Atypical kinetics of cytochrome P450 enzymes in drug metabolism, Biosynthesis using cytochrome P450 Enzymes: focus on synthesis of drug metabolites, Use of engineered cytochrome P450s for accelerating drug discovery and development, Assessing cytochrome P450 function using genetically engineered mouse models, Use of the biologicals with sustainable reproducibility for phenotyping study of cytochrome P450 enzymes involved in the biotransformation of test compounds and calculating the fraction unbound parameter, for anticipating drug Interactions, and much more. Research on many forms of P450s has been extended into different fields, from molecules to in vivo situations because pharmacologists and toxicologists appreciate and are attracted to the potential therapeutics. The purpose of this volume is to collect a comprehensive description of major progress to date, to discuss possible future directions, and to invite young researchers to join this important and exciting world of P450.

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.

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.

Side Effects of Drugs Annual: A Worldwide Yearly Survey of New Data in Adverse Drug Reactions, Volume 40, first published in 1977, and continually published as a yearly update to the voluminous encyclopedia Meyler's Side Effects of Drugs, presents clinicians and medical investigators with a reliable and critical survey of new data and trends in the area of adverse drug reactions and interactions, with an international team of specialists contributing each year. Topics covered in this release include Central Nervous System Stimulants and Drugs that Suppress Appetite, Antidepressant drugs, Lithium, Drugs of abuse, Hypnotics and sedatives, Antipsychotic Drugs, and much more.

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.

This book presents formulations for over-the-counter (OTC) or nonprescription drugs. The phrase "over-the-counter" implies that the product may be purchased by the consumer without the need for a physician's prescription. The terms "nonprescription" and "OTC" are synonymous.

The OTC drug formulations in this book are organized according to their therapeutic effect. There are 19 categories of OTC drugs included. Each category is presented in a single chapter that consists of two parts; Part I presents the composition of brand name products, and Part II presents starting or prototype formulations contributed by suppliers of raw materials for OTC drugs.

The brand name products are listed alphabetically in Part I of each chapter, followed by the name of the manufacturer, the type and concentration of the active ingredient(s) and the product form(s). It is also customary, but not required, for the manufacturer to list the so-called "inactive ingredients" on the label of the product.

Part II of each chapter (except Chapter 17) includes starting formulations, developed by a number of raw material suppliers. Those formulations that are included, contain not only the concentration of the active ingredients but also the concentration of the other ingredients and, in most cases, a recommended procedure for mixing the formulation.

This book includes 559 brand name formulations of 63 manufacturers and 270 supplier's suggested formulations for a total of 829 formulations.

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 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."

This book discusses the recent developments in the therapeutic implications of cancer stem cells for the effective diagnosis, prognosis, and treatment of cancer. It summarizes the various stem cells of common cancers including colon, pancreas, lungs, prostate, melanoma, and glioblastoma, and reviews the potential role of cancer stem cells in tissue aggressiveness, examining the functional contribution of cancer stem cells in the establishment and recurrence of cancerous tumors. Further, it explores the potential of cancer stem cells as novel therapeutic targets for the treatment and prevention of tumor progression. The book also discusses the various approaches for detecting, isolating, and characterizing different cancer stem cells and signaling pathways that control their replication, survival, and differentiation. Lastly, it explores the key features and mechanisms of drug resistance, chemo-resistance, and radio-resistance in cancer stem cells to improve therapeutic rationale.

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.

Antibiotics are truly miracle drugs. As a class, they are one of the only ones that actually cure disease as opposed to most drugs that only help relieve symptoms or control disease. Since bacteria that cause serious disease in humans are becoming more and more resistant to the antibiotics we have today, and because they will ultimately become resistant to any antibiotic that we use for treatment or for anything else, we need a steady supply of new antibiotics active against any resistant bacteria that arise. However, the antibiotics marketplace is no longer attractive for large pharmaceutical companies, the costs of development are skyrocketing because of ever more stringent requirements by the regulatory agencies, and finding new antibiotics active against resistant strains is getting harder and harder. These forces are all combining to deny us these miracle drugs when we need them the most. I provide a number of possible paths to shelter from this perfect storm.

The goal of this work is summarize the contribution that insertional mutagenesis has made to our understanding of cancer. A variety of insertional mutagens are presented that have been used to study a variety of tumor types in several model organisms. In addition, the impact of insertional mutagenesis in several gene therapy trials is discussed along with strategies to avoid such complications in future clinical trials.

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. "

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).

This book provides in-depth information on the applications of cannabis products as a legitimate medicine in treating a variety of diseases and disorders in domestic animals. Pharmacology and toxicology of cannabinoids and their effects on the endocannabinoid system, which is involved in the regulation of diverse physiological and cognitive processes, are discussed in detail. Furthermore, the book reviews development and testing of cannabis based medical products and introduces the nutritional components of cannabis plants. Cannabis as a therapeutic in veterinary medicine is gaining interest among owners and practitioners. Numerous studies have been completed or are currently underway that analyze the potential of clinical application of cannabinoid and terpenoid molecules. In this book the authors take a comprehensive look at previous studies in animal and human models and discuss translational applications based on these scientific data. This seminal text serves as a go-to resource for veterinary practitioners on cannabinoid therapy. It will also serve as a foundation for clinicians and researchers interested in this emerging field of veterinary medicine.