In this book, a worldwide panel of leading experts discuss the role of inflammation in the pathogenesis of major chronic diseases and the current controversy regarding risk versus benefit of selective cyclooxygenase-2 (COX-2) inhibitors. The authors provide exciting and enlightening perspectives on COX-2 and related molecular targets in the future of medicine, including historical perspectives.

Tamoxifen is a pioneering medicine for the treatment and prevention of breast cancer. It is the first drug targeted therapy in cancer to be successful. Tamoxifen targets the tumor estrogen receptor. The therapy is known to have saved the lives of millions of women over the past 40 years. This monograph, written by V. Craig Jordan - known as the "father of tamoxifen" - and his Tamoxifen Team at the Georgetown University Washington DC, illustrates the journey of this milestone in medicine. It includes a personal interview with V. Craig Jordan about his four decades of discovery in breast cancer research and treatment. V. Craig Jordan was there for the birth of tamoxifen as he is credited for reinventing a "failed morning after contraceptive" to become the "gold standard" for the treatment of breast cancer. He contributed to every aspect of tamoxifen application in therapeutics and all aspects of tamoxifen's pharmacology. He discovered the selective estrogen receptor modulators (SERMs) and explored the new biology of estrogen-induced apoptosis.

This handbook provides key information on the clinical use of nutraceuticals, an increasingly common practice grounded in an understanding of the pharmacological activities of natural compounds and clinical evidence of efficacy and safety. Each chapter examines the effects of nutraceuticals in different therapeutic contexts, including nutraceuticals active on the digestive system, heart, lipid and glucose metabolism, and immune system. The authors also address relevant concerns such as relative and absolute contraindications, range of tested doses (efficacious and safe), possible side effects and pharmacological interactions, and the scientific level of clinical evidence for each product. Despite the availability of a large number of nutraceuticals on the market, the same compound is often offered by different industries at different dosages and concentrations, with different titration and often with different suggestions of efficacy. Available academic books on nutraceuticals prioritize summarizing information or focus on the pharmacological aspects on cells or animals models rather than on proof in humans. The handbook takes a unique and practical approach intended to assist clinicians, pharmacologists, nutritionists, and dietitians considering prescribing nutraceuticals for therapeutic use. Renowned expert Professor Arrigo Cicero is known internationally for his work in nutraceuticals, and currently serves as President of the Italian Nutraceutical Society.

Much work over the last two decades has firmly established that loss of cell cycle checkpoint regulation, and resultant unabated cellular proliferation, is an inherent characteristic of cancer. This loss may occur through aberration in any single component involved in signal transduction pathways that orchestrate checkpoint regulation, which may manifest through either a failure to activate the checkpoint or a failure to respond to the activated checkpoint. In normal cells, checkpoint pathways are activated when genetic or cellular homeostasis is compromised, and signals are then transduced to re-stabilize homeostasis, and, failing this, to activate the apoptotic machinery to induce a cellular suicidal response. This implies that both survival and cell death pathways are induced following checkpoint activation, and that the final decision is dependant on the net result of integrating the two sets of signals.

It is intriguing that checkpoint pathways are also critical in cancer therapy to provide an apoptotic stimulus when cellular damage induced by the therapeutic agent is detected by the sensor system. Therefore, it is not surprising that failure in pro-survival checkpoint response will render tumor cells hypersensitive to cytotoxics and, conversely, failure in pro-apoptotic checkpoint response will induce genetic instability and/or therapeutic resistance. Understanding the intricacies of checkpoint response is, therefore, central to the design of therapeutic regimen that will enhance antitumor effects. Although early versions of this design entail combination of cytotoxic agents with cell cycle or checkpoint inhibitors, a greater understanding of the concepts could make such combinations clinically more effective. The contributions in this book will consolidate the current state of knowledge on checkpoint responses that may lay the foundation for hypothesis-driven rational approaches in advancing the management of cancer.

The immediate attraction of the book to the scientific community is that it represents a timely opportunity to build upon existing concepts of checkpoints to expand our understanding of the inner workings of the critical checkpoint machinery. The present understanding has provided ample appreciation that response to checkpoint activation is manifested through coordinated inhibition of cyclin-dependent kinase (CDK) complexes in G1, S and/or the G2 phase in order to arrest the cell cycle. Kinase inhibition can occur through several mechanisms, including inhibitory phosphorylation of CDK, destruction of the cognate cyclins, and recruitment of CDK inhibitors from the INK and WAF1/CIP1 families. However, the wealth of information from recent discoveries needs to be examined critically to consolidate our conceptual knowledge of checkpoints. At the same time, there is acute awareness in the diversity of checkpoint response between cytotoxic agents, and this serves as a reminder of the magnitude of complexity that is inherent in checkpoint regulation. This volume is intended to bring the cancer research community closer toward an improved understanding of this regulation, how checkpoint abnormalities can impact negatively on cancer therapy, and emerging strategies to target checkpoint response as a therapeutic end-point.

Driving further the research on mammalian alkaline phosphatase structure and function, Phosphatase Modulators collects expert contributions into one "how to" manual for basic scientists interested in initiating a drug discovery effort. While this book contains the traditional method chapters and some typical reviews on the structure and known functions of phosphatases, other contributions are meant to discuss approaches and alternatives useful in making "go/no-go" decisions in high throughput screening (HTS) and lead optimization campaigns. Many chapters focus on tissue-nonspecific alkaline phosphatase (TNAP) as well as protein phosphatases. Written for the highly successful Methods in Molecular Biology series, chapters in this volume include the kind of detail and key implementation advice that promotes reproducible results. Step-by-step and practical, Phosphatase Modulators offers a path to understanding many of the facets and complexities associated with undertaking a drug discovery effort and will serve as a roadmap to initiating those efforts.

Comprehensive and authoritative, Opioid Receptors and Antagonists: From Bench to Clinic offers neuroscientists, pharmacologists and interested clinicians a unique survey of the extensive and diverse research efforts currently employed with opioid antagonists to develop novel innovative drug therapies. Summarizes the present understanding of the chemistry, pharmacology and molecular biology of opioid receptors and their subtypes Highlights differences and similarities between the opioid pharmacology of animals and human Describes current and potential therapeutic areas for opioid antagonists, including substance abuse, alcohol and ingestive behaviors, behavioral disorders and other medical indications, supported by nonclinical and clinical evidence Focuses on the development of exciting and innovative drug delivery approaches that are being used with opioid antagonists for the above medical indications

H. Wegele, L. M ller, and J. Buchner: Hsp70 and Hsp90 A Relay Team for Protein Folding

R. Sch lein: The Early Stages of the Intracellular Transport of Membrane Proteins: Clinical and Pharmacological Implications

L. Schild: The Epithelial Sodium Channel: From Molecule to Disease

This volume describes methods and protocols for a number of drugs and toxins in a stepwise manner. Chapters in the book cover a wide array of topics such as: quantitation of Flecainide, Mexiletine, Propafenone, and Amiodarone in Serum or Plasma; quantitation of total Buprenorphine and Norbuprenorphine in Meconium; quantitation or Carisoprodol and Meprobamate in Urine; and quantitation of Tricyclic Antidepressants in Serum. Each chapter contains a brief introduction to the topic, clinical utility of the analyte(s), and useful notes to help laboratorians easily reproduce the protocols discussed. 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 thorough, Clinical Applications of Mass Spectrometry in Drug Analysis: Methods and Protocols, is a great resource for laboratorians who are already using mass spectrometry or thinking of introducing this technology to their laboratories.

A revision book to help pharmacist students prepare for the pre-registration exam of the Royal Pharmaceutical Society of Great Britain (RPSGB) and other similar exams. It consists of over 400 multiple choice questions (MCQs), with explanatory answers, as well as an introductory chapter on exam preparation and four useful appendixes of abbreviations and symbols used in pharmacy. All the MCQs are written in the same style as the RPSGB pre-registration exam. The topics covered are core aspects of any pharmacy curriculum, making the book suitable for pharmacy students preparing for undergraduate exam and similar pre-registration exams in all parts of the world. Over 400 multiple-choice questions cover all the topics in the pre-registration exam of the RPSGB. All questions are written in the style of the RPSGB exam. Four types of multiple-choice questions are given, covering all three parts of the pre-registration RPSGB - all in the same style as the exam. Questions are grouped according to core pharmacy topics. Explanations are thorough and helpful. Four appendices provide helpful summaries of abbreviations and symbols used in pharmacy.

The intent of this volume of Current Topics in Microbiology and Immunology was to bring together a collection of in-depth and cutting edge reviews that highlight our current understanding of the biology of ricin and Shiga toxin (Stx), with the long term goal of advancing the development of countermeasures against these toxic agents. In May of 2011, Western Europe experienced a severe outbreak of Stx-producing E. coli (STEC) that culminated in more than 3200 cases and 39 deaths. While Stx is not the only virulence factor associated with STEC, it is certainly the primary determinant associated with the onset of hemolytic uremic syndrome (HUS). At the present time, there are no clinically approved measures to neutralize Stx in individuals suffering from STEC infection. Nor are there any preventatives or therapeutics for ricin toxin. Although incidents of ricin exposure are largely unheard of, federal agencies and public health officials consider it a significant threat. It is well documented that domestic and international terrorist groups have stockpiled, and in some cases weaponized ricin with the intent of releasing it into the public sphere and causing panic, illness and/or death on a local, regional, or possibly national scale. As the title of this volume indicates, the chapters, written by leading experts in the field, are organized so as to cover all aspects of ricin and Stx, including pathogenesis, immunity, vaccines and therapeutics. This outstanding collection of reviews will serve as an important and readily accessible resource for the research community in the coming years.

Recent advances in drug discovery have been rapid. The second edition of Bioinformatics and Drug Discovery has been completely updated to include topics that range from new technologies in target identification, genomic analysis, cheminformatics, protein analysis, and network or pathway analysis. Each chapter provides an extended introduction that describes the theory and application of the technology. In the second part of each chapter, detailed procedures related to the use of these technologies and software have been incorporated. Written in the highly successful Methods in Molecular Biology (TM) series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results in the laboratory. Thorough and intuitive, Bioinformatics and Drug Discovery, Second Edition seeks to aid scientists in the further study of the rapidly expanding field of drug discovery.

The eukaryotic translation machinery must recognize the site on a messenger RNA (mRNA) where decoding should begin and where it should end. The selection of the translation start site is generally given by the ?rst AUG codon encoding the amino acid methionine. D- ing initiation soluble translation initiation factors (eukaryotic translation initiation factors [eIFs] in eukaryotes and prokaryotic translation initiation factors [IFs] in prokaryotes) bind the mRNA, deliver the initiator Met-tRNA, and assemble to form a complete 80S ribosome from the 40S and 60S subunits. By progressing along the mRNA in the 5 -to-3 direction the ribosome decodes the information and translates it into the polypeptide chain. During this process, repeated delivery of amino-acyl tRNA (aa-tRNA) to the ribosome, peptide bond formation, movement of the mRNA, and the growing peptidyl-tRNA is mediated by both soluble elongation factors (eukaryotic translation elongation factors [eEFs] in euka- otes and prokaryotic translation elongation factors [EFs] in prokaryotes) and the activity of the ribosome. The ?nal step in the translation process occurs when one of the three t- mination codons occupies the ribosomal A-site. Translation comes to an end and soluble release factors (eukaryotic translation termination factors [eRFs] in eukaryotes and proka- otic translation termination factors [RFs] in prokaryotes) facilitate hydrolytical release of the polypeptide chain (for recent reviews, see Inge-Vechtomov et al. 2003; Kisselev et al. 2003; Wilson and Nierhaus 2003; Kapp and Lorsch 2004).

This book offers pertinent basic science information on strategies used for the rational design and discovery of novel anticancer agents, and, in addition, translational studies involving clinical trial design and execution with these novel, mostly cytostatic agents. This book covers basic science strategies that are being used in drug discovery and preclinical evaluation focused on novel molecular targets, as well as clinical trial methodology including clinical pharmacokinetics and imaging to address issues of efficacy evaluation of the new, relatively non-cytotoxic anticancer agents.
At present, there is no book that provides such an integration of basic and clinical studies of novel anticancer agents, covering both drug discovery and translational research extensively.
* Addresses the critical issues involved in the development of novel agents for cancer therapy by experts in the field
* Presents drug discovery strategies
* Discusses regulatory issues surrounding drug development
*

Deciphers amylin's physiology and reveals previously unrecognized mechanisms fundamental to control body weight and fuel homeostasis. Also discusses therapeutic utility of amylin as the first new medicine to treat diabetes since insulin.
*Provides a current comprehensive treatment of amylin the hormone
*Identifies the majority of amylin's physiologic functions

A cutting-edge review of the major research areas of adjuvant discovery, design, development, and use. The authors lay down a rational basis for vaccine adjuvant function and analyze a number of significantly distinct adjuvant-active molecules to illuminate the principles of their function and use. The focus is on specific receptor-ligand interactions, including the molecular features needed for a compound to possess adjuvant activity. The critical interface zone between the innate and adaptive immune systems is also analyzed to show how adjuvants exert their effects on T- and B-cell activation. Additional chapters address the possibility of tailoring adjuvants to yield optimally safe and effective responses.

This volume describes the mechanisms which bacteria have created to secure their survival, proliferation and dissemination by subverting the actin cytoskeleton of host cells. Bacteria have developed a veritable arsenal of toxins, effector proteins and virulence factors that allow them to modify the properties of the intracellular actin cytoskeleton for their own purposes. Bacterial factors either modify actin directly as the main component of this part of the cytoskeleton or functionally subvert regulatory or signalling proteins terminating at the actin cytoskeleton. In short, this volume provides an overview of the various tricks bacteria have evolved to "act on actin" in order to hijack this essential host cell component for their own needs. As such, it will be of interest to scientists from many fields, as well as clinicians whose work involves infectious diseases.

As cells mature they naturally stop dividing and enter a period called senescence. But cellular senescence can also be induced prematurely by certain oncogenes involved in cancer development. Cellular senescence, a growth-arrest program that limits the lifespan of mammalian cells and prevents unlimited cell proliferation, is attracting considerable interest because of its links to tumor suppression.

Chemical Drug Design provides a compact overview on recent advances in this rapidly developing field. With contributions on in silico drug design, natural product based compounds, as well as on ligand- and structure-based approaches, the authors present innovative methods and techniques for identifying and synthetically designing novel drugs.

In recent years, the need to develop acceptable alternatives to conventional animal testing for neurotoxicity and developmental neurotoxicity has been increasingly recognized, and much effort is being directed toward the development of alternative models, utilizing mostly mammalian cells in culture but also non-mammalian model systems. "In Vitro Neurotoxicology: Methods and Protocols" presents a series of cellular, biochemical, and molecular methodological protocols in the area of in vitro neurotoxicology, with an emphasis on mammalian cell culture systems. Opening with a section on methodologies for preparing several cellular systems of variable complexity, amenable for in vitro neurotoxicological studies, the thorough volume continues with coverage of methods to measure cellular death and major mechanisms, methods for assessing mechanisms of nervous system cell toxicity related to impairment of cell signaling, while a final section illustrates additional methods for assessing important nervous system processes such as cell proliferation, neuritogenesis, and synaptogenesis. Written in the highly successful "Methods in Molecular Biology " series format, chapters include introductions to their respective subjects, 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, "In Vitro Neurotoxicology: Methods and Protocols" serves researchers with an interest in assessing or characterizing the potential neurotoxicity of environmental contaminants, drugs, or other chemicals."

Platelets and Aspirin-Induced Asthma is the first book to be published that reflects research conducted on aspirin-induced asthma pathogenesis. It is examined through positions of neuroimmunoendocrine interactions in organism. The Melatonin hormone plays a key role, being the regulator and coordinator of complicated and interrelated biological processes. This new concept of aspirin-induced asthma pathogenesis suggests new methods for treatment of this disease by means of correcting the melatonin content in the patient s organism. Investigations into the mechanisms of aspirin-induced asthma as a pathology of melatonin producing cells of platelets helps to determine high-risk groups and develop preventive measures and adequate therapy.
The first book to examine the role of platelets, melatonin and diffuse neuroimmunoendocrine system in the pathogenesis of aspirin-induced asthmaProposes a new concept of aspirin-induced asthma pathogenesis that suggests new diagnostic and treatment methods for the disease
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