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The complement system is a multi-tasking gatekeeper of innate immunity thatintricately interacts with other key defense systems, such as the endothelial barrier,contact activation and coagulation systems, in maintaining tissue immunosurveillanceand homeostasis. Its rapid and forceful activation in the bloodstream not onlyensures the effective containment of microbial infections through potent cytolyticmechanisms, but also alerts the adaptive immune compartment to ensure the mountingof a proper humoral immune response against foreign antigens. However, there isa lurking ‘dark side’ that can lead complement astray, fueling a self-perpetuatingvicious cycle of inflammation, exuberant immune activation and irreversible tissueinjury that collectively exacerbate both acute and chronic pathologies. Indeed,complement dysregulation or excessive activation have been widely recognized askey pathogenic drivers in a wide spectrum of inflammatory or immune-mediateddiseases. Targeted modulation of the complement system at various points ofthe cascade has revealed promising therapeutic targets for ameliorating diseasescores in a number of conditions ranging from ocular, neurodegenerative andthromboinflammatory disorders, to cancer, periodontal diseases, chronic hemolyticanemias, ischemia-reperfusion organ injury, antibody-mediated transplant rejectionand hemodialysis-triggered inflammation. Elegant pre-clinical studies employing a diversified toolbox of highly specificcomplement inhibitors in rodent or primate models of disease have opened newavenues of therapeutic exploration by providing proof of concept for the therapeuticefficacy of complement modulation. At the same time, the clinical experience gainedduring this last decade with the sole complement-specific drug currently in the clinic,eculizumab, has rekindled the interest of biopharmaceutical companies in developingnew and potent complement therapeutics for complement-driven diseases. In this respect, the complement field is witnessing a new surge of clinical trialsthat are evaluating the safety, PK/PD profile and clinical efficacy of promising drugcandidates in a number of clinical conditions driven by complement imbalance orover-activation.
This book comprises an integrated review of ocular therapeutics across all relevant fields. It addresses the real-world requirements of ophthalmologists, pharmacists and optometrists, as observed through working alongside these practitioners for two decades. Knowledge surrounding agents used in ophthalmic practice has, historically, been scattered. The book facilitates understanding of ocular drug therapy by compiling all key aspects of the pharmacology, toxicology, pharmaceutical science, ocular biochemistry and cell biology of these agents. Chapters detail drug transfer across barriers, systemic toxicity of topically applied drugs, autonomic drugs used for diagnostics, as well as anti-inflammatory, antiallergic, glaucoma and antimicrobial therapies, and avenues for the development of new ocular drugs. Applications of extemporaneously prepared formulations are described to inform day-to-day clinical practice. The use of mucoadhesive polymers in tear substitutes, ocular drug delivery systems, stem cell therapy, pharmacogenomics and antiangiogenic ocular chemotherapy are also explored. The book also provides insights from drugs of herbal origin, and a historical perspective on drugs for ocular use. Practicing and resident ophthalmologists, optometrists, pharmacists, nursing professionals, scholars in ocular drug research and students will equally benefit from this comprehensive guide.
Viral Infections and Antiviral Therapies provides comprehensive coverage of viral infections and their transmission. Coverage includes antiviral agents, therapeutics, their mechanisms and treatment strategies. The book is organized into four sections, including an introduction to antiviral therapies, viral infections and their transmission, antiviral agents and therapeutics, and a market overview and future developments. The chapters in each section of the book discuss various key topics that are contributed to by an international group of leading experts. - Covers emerging and sexually transmitted viruses, including mode of transmission and pathophysiology of viral infections - Describes antiviral agents and therapeutics for viruses such as rotaviruses, enteroviruses and coronaviruses - Discusses strategies for the delivery of antiviral agents and vaccinations
Entries in a practical A to Z Format Highly therapy-focused Uniform and clearly arranged entries for ease of reference Comprehensive information on symptoms and therapeutical possibilities of rheumatologic and musculoskeletal diseases as well as drugs Written by leading experts in the field
From small beginnings in the early 1970s, the study of complement regulatory proteins has grown in the last decade to the point where it dominates the complement field. This growth has been fueled by the discovery of new regulators, the cloning of old and new regulators, the discovery that many of the regulators are structurally and evolutionarily related to each other and the development of recombinant forms for use in therapy. There are now more proteins known to be involved in controlling the complement system than there are components of the system and the list continues to grow. The time is ripe for a comprehensive review of our current knowledge of these intriguing proteins. This book does just that. The first few chapters discuss the "nuts-and-bolts" of the complement regulators, describing their structures, functional roles and modes of action. The roles of the complement regulators in vivo are then described, focusing on the consequences of deficiency, roles in the reproductive system, interactions with pathogens and exploitation for therapy. The interesting developments in defining the complement regulators expressed in other species are also discussed. The book is written as a monograph, albeit by two people. The text is as readable as possible without compromising on scientific accuracy and completeness. The conversational style very evident in some sections is deliberate! Placing all references in a single bibliography at the end of the text further improves readability. The reader will go to the book to discover a specific fact but be persuaded to read more and derive pleasure from the process. The authors' enthusiasm for the subject comes over strongly in the text, and this enthusiasm proves infectious. - Complement regulators--structure, functional roles and mode of action - Comprehensive reviews of each of the individual regulators - Roles of Complement regulators in vivo,in health and disease: - Consequences of deficiency - Roles in the reproductive system - Interactions with pathogens - Exploitation for therapy - Complement regulators in other species
This book highlights progress and trends in the rapidly evolving field of complement-related drug discovery and spotlights examples of clinical applications. As an integral part of innate immunity and critical mediator in homeostatic and inflammatory processes, the human complement system has been identified as contributor to a large number of disorders including ocular, cardiovascular, metabolic, autoimmune, and inflammatory diseases as well as in ischemia/reperfusion injury, cancer and sepsis. In addition, complement is often involved in adverse immune reactions to biomaterials, cell and organ transplants or drug delivery systems. Although the complement cascade with its close to 50 extracellular protein targets has long been recognized as an attractive system for therapeutic modulation, the past few years have seen a particularly strong boost in interest. Fueled by novel research insight and the marketing of the first complement-targeted drugs, a plethora of highly creative treatment approaches and potent drug candidates have recently emerged and are currently evaluated in disease models and clinical trials. The chapters in this book cover a wide range of topics related to the development of complement therapeutics, ranging from the molecular and functional description of complement targets to the presentation of novel inhibitors, improved treatment strategies as well as examples of disease models and clinical applications. The broad and up-to-date overview on a highly versatile and dynamic field renders this book an indispensable source of information for researchers and clinicians dealing with therapeutic and disease-related aspects of the human complement system.
Humans coexist with millions of harmless microorganisms, but emerging diseases, resistance to antibiotics, and the threat of bioterrorism are forcing scientists to look for new ways to confront the microbes that do pose a danger. This report identifies innovative approaches to the development of antimicrobial drugs and vaccines based on a greater understanding of how the human immune system interacts with both good and bad microbes. The report concludes that the development of a single superdrug to fight all infectious agents is unrealistic.
While biomedical investigation has greatly advanced, investigators have lost touch with and inadvertently corrupted significant nomenclature at the foundation of their science. Nowadays, one has to be an insider to even understand the titles of journals, as modern biochemists have a tendency to invent new terms to describe old phenomena and apply a
Covering both the scientific basis of rheumatology and practical, clinical information for rheumatologists and trainees, Rheumatology, 8th Edition, remains a leading text in this fast-changing field. Dr. Marc Hochberg and his team of worldwide editors and authors keep you abreast of recent advances in the field— all in a user-friendly, accessible manner. Fully updated from cover to cover, this two-volume text is designed to meet the needs of all practicing and academic rheumatologists as well as arthritis-related health care professionals and scientists interested in rheumatic and musculoskeletal diseases. - Covers the epidemiology, pathogenesis, clinical manifestations, therapeutic approach, and management of all major as well as rarely encountered rheumatic and musculoskeletal diseases. - Discusses clinical examination, imaging principles, differential diagnosis, established and novel therapies, perioperative evaluation, pain management, basic science, and genetics of rheumatic and musculoskeletal diseases. - Uses a consistent, logical, reader-friendly format with templated chapters, concise text, and large-scale, state-of-the-art illustrations for efficient visual reference. - Contains new chapters covering pre-clinical disease and how to address these patients, common comorbidities in rheumatoid arthritis; emerging therapies for systemic sclerosis; immune mediated complications of checkpoint inhibitors; the epidemiology of COVID-19 and rheumatic and musculoskeletal diseases, emerging treatments for osteoarthritis, and big data analytics. - Provides updates to key topics such as systems biology and its impact on our understanding of the pathogenesis of rheumatic and musculoskeletal diseases, the microbiome in rheumatic musculoskeletal diseases, how to manage chronic pain in the patient with a rheumatic disease, drugs and reproductive health, and emerging therapies for patients with RA, SLE, spondyloarthritis, inflammatory muscle disease, and vasculitis. - Shares the knowledge and expertise of numerous new contributing authors, as well as new co-editor Dr. Désirée van der Heijde, who is an expert in psoriatic arthritis, spondyloarthritis, imaging, and clinical epidemiology. - Provides access to concise videos depicting the use of ultrasound for diagnosis and treatment. - Enhanced eBook version included with purchase. Your enhanced eBook allows you to access all of the text, figures, and references from the book on a variety of devices. If you encounter issues with your eBook please contact Elsevier eBook+ support via [email protected].