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Macrophages are core components of the innate immune system. Once activated, they may have either pro- or anti-inflammatory effects that include pathogen killing, safe disposal of apoptotic cells or tissue renewal. The activation state of macrophages is conceptualized by the so-called M1/M2 model of polarization. M2 macrophages are not simply antagonists of M1 macrophages; rather, they represent a network of tissue resident macrophages with roles in tissue development and organ homeostasis. M2 macrophages govern functions at the interfaces of immunity, tissue development and turnover, metabolism, and endocrine signaling. Dysfunction in M2 macrophages can ruin the healthy interplay between the immune system and metabolic processes, and lead to diseases such as insulin resistance, metabolic syndrome, and type 1 and 2 diabetes mellitus. Furthermore, M2 macrophages are essential for healthy tissue development and immunological self-tolerance. Worryingly, these functions of M2 macrophages can also be disrupted, resulting in tumor growth and autoimmunity. This book comprehensively discusses the biology of M2 macrophages, summarizes the current state of knowledge, and highlights key questions that remain unanswered.
During the past decade, the rapid growth of molecular and cellular knowledge of macrophages, as a specialized host defense and homeostatic system, has begun to offer attractive targets for therapeutic intervention. Macrophages play a central role in a wide range of disease processes, from genetically determined lysosomal storage diseases, to acute sepsis, chronic inflammation and repair, tissue injury and cell death. Under- or overactivity of macrophage clearance, immune effector functions and responses to metabolic abnormalities contribute to common disorders such as autoimmunity, atherosclerosis, Alzheimer’s disease and major infections including AIDS and Tuberculosis. Whilst the goals of therapeutic intervention based on improved understanding of macrophage functions and their contribution to pathogenesis may seem self evident, there are considerable difficulties in producing useful new agents. The present volume covers a range of subjects and provides opportunities for a more focused macrophage-targeted approach. The individual chapters review selected topics briefly, to place cellular processes and molecular targets in perspective. Overall, the volume should provide a broad sample of the state of the art. Useful reviews and references in the literature are cited within individual chapters.
The enteric nervous system (ENS) is a complex neural network embedded in the gut wall that orchestrates the reflex behaviors of the intestine. The ENS is often referred to as the “little brain” in the gut because the ENS is more similar in size, complexity and autonomy to the central nervous system (CNS) than other components of the autonomic nervous system. Like the brain, the ENS is composed of neurons that are surrounded by glial cells. Enteric glia are a unique type of peripheral glia that are similar to astrocytes of the CNS. Yet enteric glial cells also differ from astrocytes in many important ways. The roles of enteric glial cell populations in the gut are beginning to come to light and recent evidence implicates enteric glia in almost every aspect of gastrointestinal physiology and pathophysiology. However, elucidating the exact mechanisms by which enteric glia influence gastrointestinal physiology and identifying how those roles are altered during gastrointestinal pathophysiology remain areas of intense research. The purpose of this e-book is to provide an introduction to enteric glial cells and to act as a resource for ongoing studies on this fascinating population of glia. Table of Contents: Introduction / A Historical Perspective on Enteric Glia / Enteric Glia: The Astroglia of the Gut / Molecular Composition of Enteric Glia / Development of Enteric Glia / Functional Roles of Enteric Glia / Enteric Glia and Disease Processes in the Gut / Concluding Remarks / References / Author Biography
As the number of patients with colitis-associated cancer (CAC) is on the increase, the purpose of this book is to review the latest topics concerning management of the disease. In recent years, the diagnostic power of endoscopy and molecular pathology has also grown tremendously, as a result of which they now have a far greater influence on the treatment of CAC. At the moment, appropriate monitoring programs for ulcerative colitis and Crohn’s disease remain uncertain. At the same time, the latest findings on DNA methylation and microRNAs hold the promise of making revolutionary changes in these areas. Moreover, recent drug advances in the treatment of inflammatory bowel diseases have changed surgical indications. On the other hand, the indication of mucosectomy on colorectal cancer in ulcerative colitis and prophylactic abdominoperineal resection for Crohn’s disease remain controversial. This book provides the latest information on the remaining issues of CAC from the point of view of expert surgeons.
This Methods in Molecular Biology book offers methods for studying inflammasome function, including generation of inflammasome stimuli, monitoring of caspase-1 activity and processing, activation of IL-1β cytokines, plus lab protocols, material lists and tips.
Oral Colon-Specific Drug Delivery covers approaches used to deliver a variety of drugs to the colon. Anatomy and physiology of the gastrointestinal tract as it affects colonic drug delivery and pharmacokinetics are reviewed, as well as drug absorption from the colon. The book presents valuable information on a variety of topics, including oral peptide/protein delivery, dextran-based delivery systems, glycoside/glycosidase-based delivery, azo-bond prodrugs, hydroxypropyl methacrylamide copolymers for colonic delivery, and matrices for colonic drug delivery. Special emphasis is placed on delivery systems, especially biochemical approaches to delivery, such as the use of degradable polymers and both low and high molecular weight prodrugs. Oral Colon-Specific Drug Delivery will provide a valuable reference resource for gastroenterologists, pharmaceutical scientists, and other researchers working with drug delivery to the colon.
This volume aims to connect current ideas and concepts about GI disorders with the search for novel therapeutics. Towards this goal, authors provide a timely state-of-the-art overview of the GI tract in health and disease, current treatment approaches and ongoing developments in drug discovery, and their potential for the better treatment of patients with GI disorders.
Gastrointestinal Tissue: Oxidative Stress and Dietary Antioxidants brings together leading experts from world renowned institutions, combining the basic mechanisms of gastrointestinal diseases with information regarding new and alternative treatments. The processes within the science of oxidative stress are described in concert with other processes, including apoptosis, cell signaling and receptor mediated responses, further recognizing that diseases are often multifactorial with oxidative stress as a component. By combining the critical molecular processes underlying free radical mediated pathologies and the role of dietary antioxidant molecules, a connection is made that helps advance therapies and the prevention of gastrointestinal pathological processes. This important reference is well designed with two complementary sections. Section One, Oxidative Stress and Gastroenterology, covers the basic processes of oxidative stress from molecular biology to whole organs, the gastrointestinal anatomy and sources of oxidative stress and free radicals and their products in gastrointestinal diseases. Section Two, Antioxidants and Gastroenterology covers antioxidants in foods, including plants and components. - Covers the science of oxidative stress in gastrointestinal tissue and associated conditions and scenarios - Provides information on optimal levels for human consumption of antioxidants, suggested requirements per day, recommended dietary allowances and curative/preventive effects of dietary antioxidants - Presents an easy to reference guide with two complementary sections that discuss the pathophysiology of gastrointestinal diseases in relation to oxidative stress and antioxidant therapies