In this fast moving field the main goal of this volume is to provide up-to-date information on the molecular and functional properties and pharmacology of mammalian TRP channels. Leading experts in the field describe properties of a single TRP protein/channel or portray more general principles of TRP function and important pathological situations linked to mutations of TRP genes or their altered expression. Thereby this volume on Transient Receptor Potential (TRP) Channels provides valuable information for readers with different expectations and backgrounds, for those who are approaching this field of research as well as for those wanting to make a trip to TRPs."

This book seeks to unravel the mysteries of wolfberry, and systematically introduces its mechanisms in preventing aging-associated diseases, such as cardiovascular diseases, inflammation, liver and neurodegenerative diseases. Wolfberry, the dried fruit of Lycium barbarum, is an anti-aging herbal medicine. There have been numerous reports investigating the underlying mechanisms of its anti-aging effects and its role in preventing pathological changes in many aging-associated diseases. Its holistic effects on the body can attenuate liver toxicity and combat the spread of cancer; it also prevents degeneration in the central nervous system, and can even positively affect the skin. As such, wolfberry has become a very popular food supplement around the world. This book will serve as an excellent reference source for researchers and graduate students studying herbal medicine and aging-associated diseases, while also providing insights for the pharmaceutical industry with regard to developing potential drugs for these diseases.

Currently, few drugs are available for the effective treatment of neurodegenerative diseases and neurodevelopmental disorders. Recent advances in neuroscience research offer hope that future strategies for treating these brain disorders will include neurogenesis and neuroenhancement as therapeutic endpoints. This volume reviews cutting-edge findings related to the pharmacological aspects of neurogenesis and neuroprotection. A broad range of topics are covered from basic lab bench research to drug discovery efforts and important clinical issues. This collection of reviews is a perfect way to become acquainted with these exciting new fields in the space of a single volume. Chapters are written with a general audience in mind, but with enough high-level discussion to appeal to specialists and experts as well. The authors have done an excellent job of challenging current paradigms and pushing the boundaries of exploration in keeping with the pioneering spirit that gave rise to these emerging areas of research. Consequently, this will be an indispensable resource for many years to come.
* Provides state-of-the-art reviews spanning significant emerging fields
* Discusses future directions and questions for future studies
* Includes informative illustrations
*

This volume provides a comprehensive overview of the current issues facing scientists working on delivering drugs locally and systemically via the membranes that line the mouth. The book describes the anatomical and physiological challenges of this route for drug delivery and how they impact the design of oral mucosal drug delivery systems. It also provides a detailed description of current oral mucosal drug delivery technologies that overcome these challenges alongside research, development and assessment methods. In 11 authoritative chapters, the book affords an in-depth evaluation of the major issues associated with this route of administration, namely the retention of the drug/product at the site of administration and increasing drug permeability through the oral mucosa. The book provides insights into the in vitro and in vivo methods available to assess drug permeability and retention, offers solutions on how to improve the permeation of the drugs through the oral mucosa, and explores approaches to prolong drug/product retention at the site of administration. It also indicates future directions in research and product development. Oral Mucosal Drug Delivery and Therapy is a key resource for those wishing to extend their knowledge of this field.

Mitochondria are far more than the "powerhouse" of the cell as they have classically been described. In fact, mitochondria biological activities have progressively expanded to include not only various bioenergetic processes but also important biosynthetic pathways, calcium homeostasis and thermogenesis, cell death by apoptosis, several different signal transduction pathways mainly related to redox control of gene expression and so on. This functional and structural complexity may undergo important derangements so to justify the definition of 'mitochondrial medicine', which should include all the clinical consequences of congenital or acquired mitochondrial dysfunctions. There are actually a growing number of studies which assign a significant pathogenic role to damaged mitochondria in different diseases: ischemia/reperfusion injury, neurodegenerative diseases, cancer with its dramatic sequelae (i.e, metastasis), metabolic syndrome, hyperlipidemias, just to mention a few of the most important pathologies. In this context, a further aspect that should not be disregarded is the interaction of pharmacological agents with mitochondria, not only in regard of the toxicological aspects but, above all, of the potential therapeutic applications. In fact, it is interesting to note that, while the properties of different so-called "mitoxicants" are well-known, the subtle linkages between drugs and mitochondria is still in need of a real pharmacological and therapeutic control at the clinical level. This lack of consideration can often lead to an underestimation of unwanted toxic effects but also of desirable therapeutic activities. A reevaluation of the potential clinical role of mitochondria could give a new light on some yet obscure aspects of human pathophysiology.

In the view of most experts pharmacology is on drugs, targets, and actions. In the context the drug as a rule is seen as an active pharmaceutical ingredient and not as a complex mixture of chemical entities of a well defined structure. Today, we are becoming more and more aware of the fact that delivery of the active compound to the target site is a key. The present volume gives a topical overview on various modern approaches to drug targeting covering today s options for specific carrier systems allowing successful drug treatment at various sites of the body difficult to address and allowing to increase the benefit-risk-ratio to the optimum possible."

Contents

E.I. Christensen and R. Nielsen: Role of Megalin and Cubilin in Renal Physiology and Pathophysiology

G. Zifarelli and M. Pusch: CLC Chloride Channels and Transporters: A Biophysical and Physiological Perspective

S.F.J. van de Graaf, R.J.M. Bindels and J.G.J. Hoenderop: Physiology of Epithelial Ca2 and Mg2+ Transport

PEGylation technology and key applications are introduced by this topical volume. Basic physical and chemical properties of PEG as basis for altering/improving in vivo behaviour of PEG-conjugates such as increased stability, improved PK/PD, and decreased immunogenicity, are discussed. Furthermore, chemical and enzymatic strategies for the coupling and the conjugate characterization are reported. Following chapters describe approved and marketed PEG-proteins and PEG-oligonucleotides as well as conjugates in various stages of clinical development. The volume closes with chapters on FDA regulations and EMEA guidelines for these drugs and general perspectives for future developments.

Germination of the thought of "Enzymatic- and Transporter-Based Drug-Drug Interactions: Progress and Future Challenges" Proceedings came about as part of the annual meeting of The American Association of Pharmaceutical Scientists (AAPS) that was held in San Diego in November of 2007. The attendance of workshop by more than 250 pharmaceutical scientists reflected the increased interest in the area of drug-drug interactions (DDIs), the greater focus of PhRMA, academia, and regulatory agencies, and the rapid pace of growth in knowledge. One of the aims of the workshop was to address the progress made in quantitatively predicting enzyme- and transporter-based DDIs as well as highlighted areas where such predictions are poor or areas that remain challenging for the future. Because of the serious clinical implications, initiatives have arisen from the FDA (http://www.fda.gov/cber/gdlns/interactstud.htm) to highlight the importance of enzyme- and transporter-based DDIs. During the past ten to fifteen years, we have come to realize that transporters, in addition to enzymes, play a vital role in drug elimination. Such insight has been possible because of the continued growth in PK-ADME (pharmacokinetics-absorption-distribution-metabolism-excretion) knowledge, fueled by further advances in molecular biology, greater availability of human tissues, and the development of additional and sophisticated model systems and sensitive assay methods for studying drug metabolism and transport in vitro and in vivo. This has sparked an in-depth probing into mechanisms surrounding DDIs, resulting from ligand-induced changes in nuclear receptors, as well as alterations in transporter and enzyme expression and function. Despite such advances, the in vitro and in vivo study of drug interactions and the integration of various data sets remain challenging. Therefore, it has become apparent that a proceeding that serves to encapsulate current strategies, approaches, methods and applications is necessary. As Editors, we have assembled a number of opinion leaders and asked them to contribute chapters surrounding these issues. Many of these are the original Workshop speakers whereas others had been selected specially to contribute on topics related to basic and applied information that had not been covered in other reference texts on DDI. The resulting tome, entitled Enzyme- and Transporter-Based Drug Interactions: Progress and Future Challenges, comprises of four sections. Twenty-eight chapters covering various topics and perspectives related to the subject of metabolic and transporter-based drug-drug interactions are presented.

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.