Cytochrome P450 Function and Pharmacological Roles in Inflammation and Cancer, the latest volume in the Advances in Pharmacology series, presents not only the function of cytochrome P450 but also its pharmacological roles in inflammation and cancer.

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.

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.

This latest addition to the Methods in Molecular Medicine series, Anti- ral Methods and Protocols, is opportune because there is an increasing int- est in discovering compounds that are effective against both chronic and acute viral infections. A number of the methods described in the volume are unp- lished and their inclusion indicates the speed at which this field is moving. This volume is not a review but each chapter contains methods validated by the experts who have spent time in developing the protocols. The hallmark of this series is the comprehensive way in which the me- ods are described, which includes a list of all the reagents needed for each protocol. Of importance is the section on tips and pitfalls that the authors have discovered while developing their protocols. The manual itself is designed to be used by researchers in universities and industry who are familiar with a range of biological techniques but who want to set up quickly a novel assay system. We encourage a dialog between readers and authors, which may also result in useful collaborations.

This new, and heavily revised, edition of Psychopharmacology, provides a comprehensive scientific study of the effects of drugs on the mind and behaviour. With the growing prevalence of psychiatric and behavioral disorders and the rapid advances in the development of new drug therapies, this textbook offers an essential understanding of the necessary details of drug action. The book presents its coverage in the context of the behavioral disorders they are designed to treat, rather than by traditional drug classifications, to strengthen understanding of the underlying physiology and neurochemistry, as well as the approaches to treatment. Each disorder from the major diagnostic categories is discussed from a historical context along with diagnostic criteria and descriptions of typical cases. In addition, what we presently know about the underlying pathology of each disorder is carefully described. Providing a solid foundation in psychology, neuroanatomy and physiology, the book also offers a critical examination of drug claims, as well as coverage of evidence-based alternatives to traditional drug therapies. Throughout, this text discusses how drug effectiveness is measured in both human and animal studies. Topics new to this edition include: a stronger emphasis on the environmental impacts on drug effectiveness; more on the mechanisms of adverse reactions to drugs and information on managing drug side effects; the risks and benefits of using "mood stabilizing drugs" to address behavior in youth with ADHD or ASD; and discussion of the research-to-practice gap in pharmacological care for children and adolescents. Accompanied by a robust companion website of instructor materials, this textbook is ideal for undergraduate and pre-professional students on courses in Psychopharmacology, Clinical Psychopharmacology, Drugs and Behavior. It is a valuable contribution to highlight the symbiotic relationship between psychopharmacology and the neural and behavioral sciences.

"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."

This book contains contributions presented at the last of the Alcuin Symposia, held in April 2000, as a Festschrift to honour Prof. Axel Wollmer on the occasion of his retirement from the Rheinisch-Westfalische Technische Hochschule (RWTH) Aachen. The Alcuin Symposia were initially held alternatively in York and Aachen, in recent years in Aachen only, as joint workshops on insulin between the groups of Prof. Guy Dodson in York and the groups of Profs Dietrich Brandenburg and Axel Wollmer in Aachen. The Symposium was named after Alcuin, an Anglo-Latin poet, educator and cleric from York, who was invited to join the court of Charlemagne at Aachen. Alcuin's first 50 years were spent in Yorkshire, were he was first a pupil, later headmaster of the cathedral school of York, the most renowned of its day. Charlemagne was gathering at Aachen the leading Irish, English and Italian scholars of the age. Alcuin was appointed head of the Palatine school, where Charlemagne himself, his family, his friends, and his friends's sons were taught. Alcuin introduced the traditions of Anglo-Saxon humanism into Western Europe and was the foremost scholar of the revival of learning known as the Carolingian Renaissance. He also promoted the use of the beautiful Carolingian minuscule script, the ancestor of modern Roman typefaces."

This book provides information on best practices and new thinking regarding the validation of alternative methods for toxicity testing. It covers the validation of experimental and computational methods and integrated approaches to testing and assessment. Validation strategies are discussed for methods employing the latest technologies such as tissue-on-a-chip systems, stem cells and transcriptomics, and for methods derived from pathway-based concepts in toxicology. Validation of Alternative Methods for Toxicity Testing is divided into two sections, in the first, practical insights are given on the state-of-the-art and on approaches that have resulted in successfully validated and accepted alternative methods. The second section focuses on the evolution of validation principles and practice that are necessary to ensure fit-for-purpose validation that has the greatest impact on international regulatory acceptance of alternative methods. In this context validation needs to keep pace with the considerable scientific advancements being made in toxicology, the availability of sophisticated tools and techniques that can be applied in a variety of ways, and the increasing societal and regulatory demands for better safety assessment. This book will be a useful resource for scientists in the field of toxicology, both from industry and academia, developing new test methods, strategies or techniques, as well as Governmental and regulatory authorities interested in understanding the principles and practicalities of validation of alternative methods for toxicity testing.

There are various species of fungi which like to grow on food, thereby releasing toxins which might bear a health risk for the consumer. All foods which have been reported to be contaminated with mycotoxins are listed, including data on the degree of contamination, the concentration of the toxins and the country of origin and/or detection of the contaminated food. All relevant toxin producing fungi, their natural occurence, the possible mycotoxicosis, further the biochemical and physiological effects of mycotoxins, their chemical data and toxicity are treated comprehensively. For each mycotoxin, reference is given to the food at risk.

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.

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.

Medicinal Agroecology: Reviews, Case Studies and Research Methodologies presents information on applications of 'green therapies' in restoration towards global sustainability. These practices connect the world of medicinal plants with ecologic farming practice creating a compassionate socio-political worldview and heartfelt scientific research towards food sovereignty and a healthier future on planet Earth. The book communicates benefits of using plant-based solutions to manage the challenges of unsustainable practices in human healthcare, veterinary medicine, agriculture, forestry, and water management. The contributions introduce advances around plants and their active components to potentially treat disease, regulate dysfunction, and balance ecosystems. These practices are explored in further depth through three sections - I. POLICIES & FRAMEWORKS, II. INSIGHTS & OVERVIEWS, III. CASE STUDIES & RESEARCH METHODS. Edited by Immo Fiebrig, Medicinal Agroecology: Reviews, Case Studies and Research Methodologies appeals to those in various disciplines including agriculture and agroecology, healthcare, environmental sciences, and veterinary medicine.

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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.

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.

Anesthesia for the New Millenium: Modern Anesthetic Clinical Pharmacology contains the refresher course lectures of the 1999 meeting and is a review of the current state of the art in anesthesia clinical pharmacology. The authors of the individual chapters are among the world's most widely recognized experts in the pharmacology of perioperative medicine. The book features sections on new pharmacology concepts, new drug delivery techniques, recently released drugs and novel thinking about older drugs. It also addresses several areas that have recently emerged as very hot clinical and research topics, including depth of anesthesia monitoring technology and anesthesia drug interactions. The textbook is the seventeenth in a continuing series documenting the proceedings of the postgraduate course.