Aerosol therapy has significantly improved the treatment of a variety of respiratory diseases. Besides the treatment of respiratory diseases there is currently also a great interest to use the lungs as a portal to introduce drugs for systemic therapy.
The success of therapy with the application of aerosolized medicaments depends on the possibility to deliver the proper amount of drug to the appropriate sites in the respiratory system, thus limiting the side effects to a minimum. Aerosolized delivery of drugs to the lung is optimized if, for a given chemical composition of a medicine, the target of deposition and the required mass of drug to be deposited are precisely defined.
The next step is the specification of the number of respirable particles or droplets, to be generated by appropriate devices. Another very important factor for successful aerosol therapy is the condition of the patient coupled with his or her inhalation technique.

We are now on the verge of viewing effector molecules and other regulatory sites as therapeutic targets for the amelioration of human and animal disease. The recognition, for example, that mutant proteins are frequently misrouted molecules, rather than functionally defective ones, changes our approach to "inborn errors of metabolism" and offers new approaches for pharmacological discovery, based on rescue of receptors, ion channels and enzymes with pharmacoperones. Ion channels, regulators of G-protein signaling and enzymes engaged in regulation, now present opportunities for drug development.

The state of our art also benefits by the availability of superior tools that allow measurement of interactions and afford unprecedented insight into the biomolecular interactions that present novel approaches to drug design.

"Mycobacterium tuberculosis" is one of the most notorious pathogens on earth, causing the death of approximately 1.5 million people annually. A major problem in the fight against tuberculosis is the emergence of strains that have acquired resistance to all available antibiotics. One key to the success of "M. tuberculosis" as a pathogen is its ability to circumvent host immune responses at different levels. This is not only a result of the special makeup of "M. tuberculosis" in terms of genetic diversity and DNA metabolism and its possession of specialized secretion systems, but also of its ability to hijack the host s innate immune defence mechanisms.

In this volume, researchers from different disciplines provide a topical overview of the diverse mechanisms that contribute to the virulence of "M. tuberculosis," ranging from their genetic, metabolic and molecular makeup, as well as the complex strategies these bacteria utilize to escape immune destruction within infected hosts."

Cancer care is undergoing a radical transformation as novel technologies are directed toward new treatments and personalized medicine. The most dramatic advances in the treatment of cancer have come from therapeutics that augment the immune response to tumors. The immune checkpoint inhibitors are the best-known and most highly advanced examples of Immune Therapeutics targeting tumor cells and include approved antibody drugs directed at the cell surface proteins CTLA4 and PD-1. These are now considered foundational treatments for several solid tumor indications, and that list of indications is growing quickly. More broadly, antibodies have become workhorse molecules across the entire immunotherapy landscape. Antibodies to novel targets modulate the activity of diverse immune cell regulatory proteins. Engineered antibodies can induce tumor cell death or expose tumor cells to poisonous toxins (ADCC and ADC, respectively). Bi-specific antibodies can engage multiple tumor targets simultaneously, or can redirect lymphocytes to attack tumor cells. The antigen-binding domains within antibodies can be spliced onto cell stimulatory domains and transduced into T cells or NK cells, creating remarkable tumor-specific cellular therapeutics (CAR-T, CAR-NK). Beyond antibody-based therapies there are highly diverse and differentiated technology tool kits being applied to immunotherapy. Small molecule drugs are being developed to attack the tumor microenvironment, novel tumor vaccine approaches are showing great promise, patient lymphocytes are being isolated, expanded and reintroduced to patients, gene-editing techniques are becoming widely deployed, and a vast number of new tumor targets, and mutated tumor proteins (neoantigens), are being discovered. The past decade has seen unprecedented success in the treatment of diverse cancers. The authors of this volume have been asked to not only review progress to date, but importantly, to look ahead, and anticipate the evolution of cancer treatment across diverse Immune Therapeutic approaches. Our hypothesis is that the advances we are seeing across the immunotherapy landscape will further evolve and synergize, leading us finally to outright cures for many cancers.

Liquid-Chromatography-Mass-Spectrometry procedures have been shown to be successful when applied to drug development and analysis. LC-MS in Drug Analysis: Methods and Protocols provides detailed LC-MS/MS procedures for the analysis of several compounds of clinical significance. The first chapters provide the reader with an overview of mass spectroscopy, its place in clinical practice, its application of MS to TDM and toxicology, and the merits of LC-MS(/MS) and new sample preparation techniques. The following chapters discuss different approaches to screening for drugs of abuse and for general unknowns, as well as targeted measurement of specific analytes or classes of analytes including abused drugs, toxic compounds, and therapeutic agents. Written in the 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 protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, LC-MS in Drug Analysis: Methods and Protocols seeks to serve both professionals and novices with its well-honed methodologies.

Disease-relevant intracellular protein-protein interactions occurring at defined cellular sites possess great potential as drug targets. They permit highly specific pharmacological interference with defined cellular functions. Drugs targeting such interactions are likely to act with fewer side effects than conventional medication influencing whole cell functions.

This book discusses therapeutically relevant protein-protein interactions with a major focus on scaffolding proteins tethering signal transduction processes to defined cellular compartments by direct protein-protein interactions. Recent advances in the development of pharmacological agents interfering with protein-protein interactions are highlighted.

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Bioinformatics and Drug Discovery describes the bioinformatic approaches and techniques employed along the pipeline of drug development from genes to proteins to drugs. The book focuses on gene microarray analysis and techniques for target identification and validation. In addition, clinical applications showing how the analysis can be used for prognostication and diagnosis are described. The second section focuses on protein analysis, including target validation and identification using modern proteomic analysis as well as protein modeling techniques. The third section discusses chemoinformatics, including virtual screening and how to computationally approach chemical space.

The many drawbacks of conventional dosage forms and delivery systems are overcome by designing and developing controlled release drug delivery systems, and pharmaceutical and other scientists have carried out extensive and intensive investigations in the field to explore their applications. A controlled-release drug formulation can improve product efficacy and extend patent protection. As controlled drug delivery systems continue to play a vital role in delivering various types of therapeutic agents in a controlled manner, researchers are only just scratching the surface of their full potential. Advancements in Controlled Drug Delivery Systems supplies information on translating the physicochemical properties of drugs into drug delivery systems, explores how drugs are administered via various routes, and discusses recent advancements in the fabrication and development of controlled drug delivery systems. It also underlines the methodology of controlled drug delivery system preparation and the significance, disadvantages, detailed classifications, and relevant examples. Covering topics such as machine learning and oral-controlled drug delivery, this book is ideal for pharmacists, healthcare professionals, researchers, academicians, research centers, health units, students, and pharmaceutical and scientific laboratories.

The last decade or so has seen remarkable advances in our knowledge of cough. This applies especially to its basic mechanisms: the types of airway sensors, the phar- cological receptors on their membranes, the brainstem organization of the 'cough centre', and the involvement of the cerebral cortex in the sensations and the vol- tary control of cough. With the exception of the last of these, nearly all the studies have been on experimental animals rather than humans, for obvious reasons. One group of experimental studies has particular relevance to human patients, and that is the demonstration of the sensitization of cough pathways both in the periphery and in the brainstem. Similar sensitizations have been shown for patients with chronic cough or who have been exposed to pollutants, and it is reasonable to suppose that this is the basis of their cough and that the underlying mechanisms are generally similar in humans and other species. Important advances are also being made in clinical cough research. For the three main causes of clinical cough, asthma, post-nasal drip syndrome, and gast- oesophageal re?ux disease, we are beginning to understand the pathological processes involved. There remains a diagnostically obdurate group of idiopathic chronic coughers, but even for them approaches are being devised to clarify und- lying mechanisms and to establish diagnoses. Perhaps surprisingly, the ?eld in which there has been the least spectacular - vance is the therapy of cough.

This volume describes recent research in the field of metalloproteinas es, in particular their participation in autoimmune diseases such as r heumatoid arthritis. The work updates current progress in matrix metal loproteinase research, reviewing the latest developments in metallopro teinase inhibitor design and the current status of clinical candidates . It elucidates the structural relationships between different members of the MMP family and provides insight into the contributions of diff erent metalloproteinases to normal and pathological processes. Special emphasis is given to the potential of adamlysins as therapeutic targe ts. This volume is intended not only for those active in research into metalloproteinases but also for those with an interest in inflammator y diseases. Thus it addresses both academic and industrial researchers .

This book provides a comprehensive overview of chitin biology and chitin metabolism related enzymes. Chitin, the second most abundant biopolymer in nature after to cellulose, is a linear biopolymer composed of -1,4-linked N-acetylglucosamine (GlcNAc), and an essential component in the exoskeletons of insects, mites, ticks and crustaceans, the egg shells of parasitic nematodes, and fungal cell walls. Although some chitin-containing organisms are a threat to human health, food safety and agricultural production, non-chitin containing organisms like humans, mammals and plants have an innate immune response to these hazardous organisms. The book provides researchers and students with information on the recent research advances concerning the biology of chitin-containing organisms as well as cross-talks between chitin-containing and non-chitin-containing organisms. Highlighting chitin remodeling enzymes and inhibitors, it also offers drug developers essential insights into designing specific molecules for the control of hazardous chitin-containing organisms.

Complex chemical mixtures impact our health every day. In the United States, and also in Central and Eastern Europe, there are a number of locations where complex chemical mixtures have been released to environmental media. Although exposure to mixtures is common, minimal information exists to quantify these exposures, or to determine their impact on human or ecological receptors. These proceedings present some of the most current research conducted to quantify complex mixtures in the environment and investigate their potential impact on human health. Many of the manuscripts reported in these proceedings represent the most up-to-date measurements of population exposures in Central and Eastern Europe. These studies are of value to health and environmental professionals around the world as they develop strategies for assessing exposures, remediating contaminated environments, and improving public health.

In recent years there have been a number of significant developments of natural products for the treatment of rheumatic diseases, pain and gastro-intestinal ulcers and inflammation. The volume covers some of these novel developments of natural products which are of current and future interest as therapies for the above-mentioned conditions. Most available volumes cover a wide range of biological and technicological aspects of natural products and their discovery, some involving synthesis and properties of chemical compounds. The difference in this volume is that the natural products have a focus on their therapeutic effects on pain, arthritic and gastrointestinal diseases. Some of the natural products covered are either at the experimental stage of development while others are well-established clinically-used products. Each has its own unique place in therapy.

The last four decades have witnessed considerable advances in our knowledge of the pharmacology of sleep. Both basic and clinical pharmacology have made major contributions toward our current understanding of the complex mechanisms of sleep and wakefulness. In addition, these advances in our understanding of the pharmacology of sleep have benefited the treatment of sleep disorders and various neurologic and psychiatric conditions. This volume is organized into three different parts. The first is a review of the basic mechanisms of sleep and wakefulness and the chronobiology of sleep. The second part reviews the basic pharmacology of the various neuro transmitter systems involved in sleep and wakefulness, while the third is clinically oriented and focuses on the effects of a variety of drugs on sleep and wakefulness. The initial part begins with a historical review of the hypotheses of the mechanisms of sleep, evolving from passive to active regulation, and concepts involving sleep-related neurotransmitters and other sleep factors. Then regulation of sleep and wakefulness is discussed in terms of homeostatic, circadian, and ultradian processes. Also discussed is the fact that sleep homeostasis is not disrupted by the administration of hypnotic drugs. This part also reviews time-dependent properties of pharmacologic agents in relation to endogenous biologic rhythms and more specifically to chrono pharmacologic changes."

This volume attemptsto provide the formulation scientist with casehistories involving the use of therapeutic proteins and peptides that have been mar- keted or are under clinical testing. In previous volumes of this series,funda- mental theories and principles ofprotein characterization and stability were presented in depth by researchers in their fieldsofexpertise. The way from theory to practice isnot alwaysobvious and straightforward. There isa need for practical examples of how the principles and theories are put into use, specificallyin the development of a pharmaceutical product. It is our hope that this volume will fulfillsuch a need. Itisnot asimple task to choose a panel ofproteinsand peptides from the over 200 agents in human clinical trials. We have tried to collect a wide representation of molecules of different sizes-from 10 amino acids (Leu- prolide) to 1020 amino acids (Muromonab CD3). The examples include agents derived from various sources including monoclonal antibodies (Mur- omonab CD3), recombinant DNA (human and bovine growth hormones), natural source (fibrolase), and chemical synthesis (Leuprolide). Clearly this list is not intended to be encyclopedic. It isthe first time a collection of this sort has been made accessibleto the formulation scientists involved in devel- oping protein and peptide products. Although each chapter in this volume focuses primarily on the charac- terization and stability of a specific molecule, each has unique aspects.

The metabolic syndrome is a common syndrome affecting about 20 % of the adult population in Europe, and probably the prevalence is of the same magnitude in other industrialised countries worldwide. It is mainly caused by western lifestyle resulting in abdominal obesity, but also a genetic predisposition plays a role. This syndrome, which is linked to leisure lifestyle and overeating/obesity, can develop into type 2 diabetes, cardiovascular disease and cancer. Therefore, proper treatment and prevention are heavily needed. This book discusses lifestyle intervention and treatment, specifically with pharmacological compounds, in order to formulate a strategy for treating the metabolic syndrome in the daily clinic.