This comprehensive volume provides current state of the art of the use of corticosteroids in the pediatric patient. It consists of 14 chapters written by leading authors from different countries. The first chapters cover historical notes, general concepts on treatment with corticosteroids with regard to indications and side effects, and basic pharmacologic properties of these compounds. The rest of the book is devoted to the specific use of steroids in the different pediatric subspecialties. Despite advances with newer effective immunosuppressive and anti-inflammatory drugs, corticosteroids still remain the mainstay of therapy for many disorders. Leading authors in their field have summarized these concepts to provide an authoritative, comprehensive guide to help clinicians safely and effectively use corticosteroids in their pediatric patients.

This book is intended as a scientific resource for cannabinoid researchers carrying out animal and human experiments, and for those who are interested in learning about future directions in cannabinoid research. Additionally, this book may be of value to investigators currently working outside the field of cannabinoid research who have an interest in learning about these compounds and their atypical cannabinoid signalling. This book provides insight into the potential medical application of cannabinoids and their therapeutic development for the treatment of human disease.

A crucial issue for antiviral therapy is the fact that all antiviral substances rapidly select for resistance; thus, monitoring and overcoming resistance has become a most important clinical paradigm of antiviral therapy. This calls for cautious use of antiviral drugs and implementation of combination therapies. In parallel, efforts in drug discovery have to be continued to develop compounds with novel mode-of-action and activity against resistant strains. This book reviews the current status of antiviral therapy, from the roads to development of new compounds to their clinical use and cost effectiveness. Individual chapters address in more detail all available drug classes and outline new approaches currently under development.

Over the past decade, major advancements in the understanding of the molecular mechanisms and pathophysiology of pulmonary hypertension occurred in parallel with the discovery and development of new therapies. Pharmacological agents that modulate the main pathophysiological pathways of pulmonary arterial hypertension have changed the course of this devastating disease by relieving symptoms and improving and prolonging patients lives.

The first part of the book covers definition, classification, pathophysiology, pathology, biomarkers and animal models of pulmonary hypertension, thus laying the conceptual basis for what follows. The middle section provides an overview of the established therapies, such as calcium channel blockers, prostanoids, endothelin receptor antagonists, phosphodiesterase-5 inhibitors and inhaled nitric oxide. The concluding section explores novel pathways and emerging therapeutic approaches including soluble guanylate cyclase stimulators, Rho-kinase inhibitors, inhibitors of serotonin receptors and transporters, peptide growth factors, vasoactive peptides, modulators of redox equilibrium and cyclic nucleotides homeostasis, as well as immunosuppressive and anti-proliferative agents. Particular attention is given to clinical applications of these experimental therapies. "

About 8000 clinical trials are undertaken annually in all areas of medicine, from the treatment of acne to the prevention of cancer. Correct interpretation of the data from such trials depends largely on adequate design and on performing the appropriate statistical analyses. In this book, the statistical aspects of both the design and analysis of trials are described, with particular emphasis on recently developed methods of analysis.

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."

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.

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.

The aquaporin field has matured at an exceptionally fast pace and we are at the verge to develop serious strategies to therapeutically modulate aquaporin function directly or via regulatory networks. Key prerequisites are available today: i. a considerable (and growing) number of aquaporin crystal structures for the rational design of inhibitory molecules, ii. elaborate molecular dynamics simulation techniques for theoretical analyses of selectivity mechanisms and docking experiments, iii. comprehensive data on aquaporin immunohistochemistry, iv. aquaporin knockout animals for physiological studies, and v. assay systems for compound library screenings. The structure of this volume on aquaporins follows the points laid out above and thus covers the developments from basic research to potential pharmacological use. Situated between pharmacology textbooks and recent scientific papers this book provides a timely overview for readers from the fundamental as well as the applied disciplines.

The field of pharmacogenomics arose to develop personalized medicine, or medicine that deals with the complexity of the human body. In this book, leading experts present methodical, state-of-the-art contributions covering topics from individual molecules to systemic diseases, examining both fundamental concepts and advanced technologies. The volume begins by exploring cutting-edge technologies used to pursue systems-based pharmacogenomics, followed by extensive chapters on gene-drug interactions and the use of pharmacogenomics in therapeutics of diseases. This book is ideal for scientists striving to transform disease treatment into disease prevention.

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.

It is now well established that all living systems emit a weak but permanent photon flux in the visible and ultraviolet range. This biophoton emission is correlated with many, if not all, biological and physiological functions. There are indications of a hitherto-overlooked information channel within the living system. Biophotons may trigger chemical reactivity in cells, growth control, differentiation and intercellular communication, i.e. biological rhythms. The basic experimental and theoretical framework as well as the technical problems and the wide field of applications in the biotechnical, biomedical engineering, engineering, medicine, pharmacology, environmental science and basic science fields are presented in this book. To promote the dialog and mutual penetration between biophoton research and photon technology is one of the important goals for the International Conference on Biophotons & Biophotonics 2003, and is developed and presented in Biophotonics: Optical Science and Engineering in the 21st Century.

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.

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.

Although the importance of calcium (Ca2+) in the maintenance of cardiac contractility was recognized as early as 1880, the critical role of the ion in the contractile process in skeletal, cardiac, and smooth muscle has only been established within the last three decades. As the complexity of the pharmacological actions of the Ca2+ channel inhibitors grows, there is a continued need to further clarify the inhibitors, both chemically and functionally. This volume provides an update of the field based on the work presented at the 5th International Symposium on Calcium Antagonists: Pharmacology and Clinical Research. It reviews the current state of the growing area of molecular biology of Ca2+ channels in the cardiovascular area, in addition to the well-established clinical uses of Ca2+ channel inhibitors, recent work pointing to an application in atherosclerosis is described. The text also includes important uses of Ca2+ antagonists in novel areas of interest such as the gastrointestinal tract, renal protection and multi-drug resistance.

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

This accessible book examines poisoning in various contexts of international conflict. It explores the modern-day use of poison in warfare, terrorism, assassination, mass suicide, serial poisoning within healthcare, and as capital punishment. It examines a broad range of international cases from the Americas, Europe, Japan, India and more in relation to Situational Crime Prevention and its theoretical precursors, in order to explore potential prevention strategies and the ways in which perpetrators circumvent them. Case studies include analysis of attempts on the lives of Sergei and Yulia Skripal, the Tokyo subway attacks, the crimes of Dr. Harold Shipman and the Heaven's Gate and Jonestown cults. For each, the means, motive, opportunity, location, and perpetrator-victim relationship is examined. This accessible book speaks to students of criminology and those interested in penology, careers in criminal justice, homicide detectives, anti-terrorism personnel, forensic pathologists and toxicologists.

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

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.

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.

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.

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.