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.

The treatment of attention deficit/hyperactivity disorder (ADHD) is a complex challenge. This book provides comprehensive, scientific coverage of the numerous different types of drugs that are used to treat ADHD, and it examines the historical, sociological, and policy-related factors involved in the use of ADHD medications. A national study indicated that 11 percent of U.S. children and teens were diagnosed with attention deficit/hyperactivity disorder (ADHD) in 2011-a figure 43 percent higher than in 2003. The incidence of ADHD diagnoses among females has also increased significantly. For the millions of Americans of all ages who are diagnosed with ADHD, the proper treatment of this disorder is critically important. ADHD Medications: History, Science, and Issues provides readers with the complete story of ADHD drugs. The book discusses the pharmacological basis of the effects of these powerful drugs; examines the myriad social dimensions of the use, misuse, and abuse of these substances; and identifies the range of issues that affect the recognition, diagnosis, and treatment of ADHD. After an introductory case study of an individual with ADHD and this individual's problems and successes with ADHD medicines, this new book in the Story of a Drug series provides an overview of ADHD and its various symptoms, as well as the causes, prevalence, and diagnosis of ADHD. Various treatment approaches-including information about the many medications used-are discussed in detail, as well as other substances and alternative ways used to treat individuals with ADHD. Readers will also gain an understanding of neurotransmission and the specific mechanism of action of ADHD medications; the effects and applications of these drugs, plus their associated risks, misuse, and abuse; as well as related policy issues, with special focus on the controversial issues regarding ADHD drug scheduling (categorization). Provides broad background coverage of ADHD and of various types of drugs that can be used to treat symptoms of ADHD Explains how different types of ADHD medications work in the body Delves into issues and controversies related to ADHD medications, including their prescription to young children and recreational use by individuals without ADHD

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.

The discipline of developmental toxicology is an integration of concepts, models, and methodologies based heavily on the superimposition of toxicology principles upon the science of developmental biology. The science of developmental toxicology also borrows from other research areas that are concerned with regulation of cell growth, migration, differentiation and cell death, as such are central to the study of stem cells, cancer, and chronic diseases. In Developmental Toxicology: Methods and Protocols expert researchers in the field detail many of the methods which are now commonly used to study developmental toxicology highlighting the evolution of methods from classical teratology approaches to the dynamic, state-of-the-art molecular methods, systems biology, and next generation models and procedures. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Developmental Toxicology: Methods and Protocols is a valuable resource to those planning experiments to investigate consequences of environmental, nutritional, or chemical effects caused during development.

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.

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

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

Volksgeneeskuns in Suid-Afrika is ’n versameling van 8705 boererate en het die eerste keer in 1965 verskyn. Vandag, 60 jaar later, lyk die mediese en farmakologiese landskap totaal anders. Daarom is dit so interessant – en soms lagwekkend – om te sien hoe vinnig ons mediese en farmakologiese kennis intussen gevorder het.

Die versameling bevat rate wat op bygeloof of tradisionele mondelinge oorlewering berus. Ander rate maak staat op veldkennis en die botaniese name van middels word verstrek. Daar word raat uitgedeel vir kwale van asma tot ylhoofdigheid.

“Vermaaklike oomblikke is talryk vir die moderne leser – en die algemene gebruik van hondebloed, velle van pas geslagte katte, luislange en dies meer, laat ’n mens verbysterd – tot jy besef met hoeveel radeloosheid daar voor sekere siektes te staan gekom is.” Dr. Dione Prinsloo – geskiedkundige.

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

Currently, there are tremendous advances being made in understanding the basic science of both the structure and function of botulinum neurotoxins. This knowledge is opening up opportunities in regard to both therapeutic uses and treatment and protection options for civil and bio-defense applications. This volume fully evaluates the status of neurotoxin research and exploitation. The book is a multi-authored collection of chapters written by the leading authorities responsible for the current scientific and clinical research that is advancing the understanding and exploitation of the neurotoxins and is both up to date and authoritative.