This topical volume provides an overview of clinically relevant data on anticancer agents. It is not only intended medical doctors working with cancer patients, and for medical researchers and students. The different classes of anticancer drugs are described by international authorities on the various topics. Apart from new targets for anticancer agents, attention is also focused on improving efficacy and tolerability of existing compounds.

Pharmaceutics: Basic Principles and Application to Pharmacy Practice, Second Edition is a valuable textbook covering the role and application of pharmaceutics within pharmacy practice. This updated resource is geared toward meeting and incorporating the current curricular guidelines on pharmaceutics and laboratory skills mandated by the American Council for Pharmacy Education. It includes a number of student-friendly features, including chapter objectives and summaries, practical examples, case studies, numerous images and key-concept text boxes. Two new chapters are included, as well as a new end of chapter section covering "critical reflections and practice applications". Divided into three sections – Physical Principles and Properties of Pharmaceutics; Practical Aspects of Pharmaceutics; and Biological Applications of Pharmaceutics – this new edition covers all aspects of pharmaceutics and providing a single and compelling source for students.

Following the testing of therapeutic sera, the quantified evaluation of a pharmaceutical's efficacy became a key feature of medicine in the twentieth century. The case studies in this volume offer comparisons across Europe, from the diphtheria antitoxin in the late 1800s to the introduction of the Salk polio vaccine in the 1950s.

This volume will address an important emergent area within the field of immunomics: the discovery of antigens and adjuvants within the context of reverse vaccinology. Conventional approaches to vaccine design and development requires pathogens to be cultivated in the laboratory and the immunogenic molecules within them to be identifiable. Conventional vaccinology is no longer universally successful, particularly for recalcitrant pathogens. By using genomic information we can study vaccine development in silico: 'reverse vaccinology', can identify candidate subunits vaccines by identifying antigenic proteins and by using equally rational approaches to identify novel immune response-enhancing adjuvants.

Endotoxins are potentially toxic compounds produced by Gram-negative bacteria including some pathogens. Unlike exotoxins, which are secreted in soluble form by live bacteria, endotoxins are comprised of structural components of bacteria. Endotoxins can cause a whole-body inflammatory state, sepsis, leading to low blood pressure, multiple organ dysfunction syndrome and death. This book brings together contributions from researchers in the forefront of these subjects. It is divided into two sections: the first dealing with how endotoxins are synthesized and end up on the bacterial surface. The second discussed how endotoxins activate the Toll-like receptor TLR4 and, in turn, how TLR4 generates the molecular signals leading to infectious and inflammatory diseases. The way endotoxins interact with the host cells is fundamental to understanding the mechanism of sepsis, and recent research on these aspects of endotoxins has served to illuminate previously undescribed functions of the innate immune system. This volume presents a description of endotoxins according to their genetic constitution, structure, function and mode of interaction with host cells.

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.

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.

Therapeutic regimens for visceral leishmaniasis (also Kala-azar, Dum-dum fever or black fever), caused by parasitic protozoa of the Leishmania genus, evolve at a pace never seen before. Spread by tiny and abundant sand flies, the parasite infects internal organs and bone marrow and if left untreated will almost always result in the death of the host. In developing countries successful diagnosis and treatment are complicated by asymptomatic cases, undernutrition and Kala-azar/HIV co-infections.

This book brings together world-renown experts writing state-of-arts review on the progress in diagnosis and treatment of visceral leishmaniasis, ultimately leading to the complete elimination of this fatal disease from South Asia. The chapters provide valuable information for disease control as well as therapy and the diagnostic improvements necessary for early treatment, subclinical detection and drug-resistant cases. The presented methods allow for points-of-care testing in the endemic area, enabling rapid detection in resource-poor settings with easy handling and low costs.

This book provides essential information for scientists, medical practitioners and policy makers involved in the diagnosis, treatment and elimination of Kala-azar.

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.