INFLAMMATORY BOWEL DISEASE – ADVANCES IN PATHOGENESIS AND MANAGEMENT Edited by Sami Karoui Inflammatory Bowel Disease – Advances in Pathogenesis and Management Edited by Sami Karoui Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. 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Publishing Process Manager Bojan Rafaj Technical Editor Teodora Smiljanic Cover Designer InTech Design Team First published January, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Inflammatory Bowel Disease – Advances in Pathogenesis and Management, Edited by Sami Karoui p. cm. ISBN 978-953-307-891-5 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Part 1 Pathogenesis of Inflammatory Bowel Disease 1 Chapter 1 The Role of COX-2 Inhibitors on Experimental Colitis 3 Ana Paula R. Paiotti, Ricardo Artigiani-Neto, Daniel A. Ribeiro, Sender J. Miszputen and Marcello Franco Chapter 2 Intestinal Barrier Dysfunction: The Primary Driver of IBD? 23 Pieter Hindryckx and Debby Laukens Chapter 3 Adenosine Receptors: New Targets to Protect Against Tissue Damage in Inflammatory Bowel Symptoms 41 Sebastian Michael, H W. Rauwald, Haba Abdel-Aziz, Dieter Weiser, Christa E. Müller, Olaf Kelber and Karen Nieber Chapter 4 Role of Dipeptidyl Peptidase IV/CD26 in Inflammatory Bowel Disease 59 Dijana Detel, Lara Batičić Pučar, Ester Pernjak Pugel, Natalia Kučić, Sunčica Buljević, Brankica Mijandrušić Sinčić, Mladen Peršić and Jadranka Varljen Chapter 5 The Roles of Interleukin-17 and T Helper 17 Cells in Intestinal Barrier Function 89 Elizabeth Trusevych, Leanne Mortimer and Kris Chadee Chapter 6 Pathogenesis of Inflammatory Bowel Diseases 111 Yutao Yan Part 2 Advances in Diagnosis of Inflammatory Bowel Disease 135 Chapter 7 The Role of Imaging in Inflammatory Bowel Disease Evaluation 137 Rahul A. Sheth and Michael S. Gee VI Contents Chapter 8 Health-Related Quality of Life in Inflammatory Bowel Disease 151 Ramiro Veríssimo Chapter 9 Validation of a Quantitative Determination Method of Paramino-Salicylic Acid by High-Performance Liquid Chromatography and Its Application in Rat Plasma 165 Ibrahima Youm, Malika Lahiani-Skiba and Mohamed Skiba Chapter 10 Approach to the Management of the Pregnant Inflammatory Bowel Disease Patient: Successful Outcome 177 Flavio M. Habal Chapter 11 Bone Morphogenetic Proteins and Signaling Pathway in Inflammatory Bowel Disease 199 Ivana Maric, Tamara Turk Wensveen, Ivana Smoljan, Zeljka Crncevic Orlic and Dragica Bobinac Chapter 12 Genetic Differentiation of Fungi of the Genus Candida Isolated from Patients with Inflammatory Bowel Diseases 221 Danuta Trojanowska, Marianna Tokarczyk, Małgorzata Zwolińska-Wcisło, Paweł Nowak, Sebastian Różycki and Alicja Budak Chapter 13 A 9-Year Retrospective Study of Hospitalized IBD Patients in Shanghai Rui Jin Hospital 233 Tianle Ma, Lulu Sheng, Xiaodi Yang, Shuijin Zhu, Jie Zhong, Yaozong Yuan and Shihu Jiang Part 3 Management of Inflammatory Bowel Disease 247 Chapter 14 The Role of Diet, Prebiotic and Probiotic in the Development and Management of Inflammatory Bowel Diseases (IBD) 249 A.S. Abdulamir, Muhammad Zukhrufuz Zaman, R.R. Hafidh and F. Abu Bakar Chapter 15 The Use of Pomegranate (Punica granatum L.) Phenolic Compounds as Potential Natural Prevention Against IBDs 275 Sylvie Hollebeeck, Yvan Larondelle, Yves-Jacques Schneider and Alexandrine During Chapter 16 Drug Targeting in IBD Treatment – Existing and New Approaches 301 Katerina Goracinova, Marija Glavas-Dodov, Maja Simonoska-Crcarevska and Nikola Geskovski Preface Inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease, are chronic and relapsing conditions, characterized by abdominal pain, diarrhea, bleeding and malabsorption. IBD is considered to be a hyper-inflammatory state due to disturbed interactions between the immune system and the commensal bacterial flora of the gut. In recent years, many studies have focused on etiopathogeny of IBD, as well as on advances in diagnosis tools. A better comprehension of mechanisms of the new drugs used for treatment of IBD has enabled new approach strategies in the management of Crohn’s disease and ulcerative colitis. There is accumulating evidence on the importance of microbes in the development and maintenance of both the intestinal and immune systems. No evidence that inflammatory bowel disease is caused by a single agent has been found, whereas a number of microbes have been strongly associated with the presence of disease. The majority of recent studies support a role for the ability of intestinal pathogens to promote chronic inflammation in individuals with genetic susceptibility and/or other environmental factors, which remain to be identified. The lower gastrointestinal tract houses trillions of microbial cells, representing a large diversity of species in relatively well-defined phylogenetic ratios that are associated with maintenance of key aspects of host physiology and immune homeostasis. It is therefore not surprising that many GI inflammatory diseases, including inflammatory bowel disease, are associated with substantial changes in the composition of these microbial assemblages, either as a cause or consequence of host inflammatory response. Inflammatory bowel diseases are the consequence of a dysregulated mucosal immune system. The mucosal immune system consists of two arms, innate and adaptive immunity, that have been studied separately for a long time. In the last several years, there has been a huge increase in the discovery of inflammatory bowel disease susceptibility genes. However, similar advances in identifying and defining environmental risk factors associated with IBD have lagged behind. Treatment of inflammatory bowel disease has changed in recent years. Potential future treatment goals in Crohn’s disease include reduction in bowel damage, prevention of complications and maintaining long term remission. Combination therapy with X Preface infliximab and azathioprine demonstrated superior rates of sustained clinical remission, when compared to standard therapy. In ulcerative colitis, potential treatment goals include sustained clinical remission, sustained mucosal healing and reduction of rates of colorectal dysplasia and cancer. Although tumor necrosis factor antagonists are effective for the treatment of Crohn's disease and ulcerative colitis, lack and loss of clinical response is a clinical challenge. Accordingly, the use of therapeutic drug monitoring has been proposed as a means to optimize treatment. Several observational studies have demonstrated a relationship between anti-TNF agent serum drug concentrations and/or antidrug antibody presence, and various symptomatic and objective clinical endpoints. However, these relationships are not absolute, and although some algorithms for the use of therapeutic drug monitoring in clinical practice have been proposed, none have yet been validated in a prospective clinical trial. Dr. Sami Karoui Department of Gastroenterology A. La Rabta Hospital Tunis [...]... a final point, the different therapeutic strategies for protecting or restoring the barrier function of the gut during IBD are discussed 24 Inflammatory Bowel Disease – Advances in Pathogenesis and Management 2 Components of the normal intestinal barrier 2.1 The physical barrier is composed of a tightly linked intestinal epithelial cell layer and a mucus shield The surface lining of the intestine... of proinflammatory cytokines Prostaglandins are capable of reducing the production of reactive oxygen metabolites and a number of inflammatory mediators suggested to contribute to the pathogenesis of human and experimental colitis, included leukotriene B4 and TNF-α In addition prostaglandins increase the secretion of water and electrolytes into the intestinal tract and in the acute stage of UC and CD,... a key role in induction of mucosal injury but does not represent the only pathway by which NSAIDs can damage the gastrointestinal mucosa NSAIDs can also induce local damage at the site of their contact with the gastrointestinal mucosa Topical 8 Inflammatory Bowel Disease – Advances in Pathogenesis and Management application of NSAIDs increases gastrointestinal permeability allowing luminal aggressive... though increased levels of prostaglandins (PGE2 and PGI2) and other eicosanoids were detected in both colitis models and patients with chronic inflammatory bowel disease, which correlates well with the disease activity PGE2 is produced by mononuclear cells in the lamina propria and is dependent on COX-2 expresion It modulates the intestinal immune response, including the differentiation of T cells and. .. seems to occur when luminal antigens from the bacterial flora stimulate the immune system 4 Inflammatory Bowel Disease – Advances in Pathogenesis and Management in the gut barrier towards an exacerbated, genetically defined response Patients present an increase in the amount of intestinal bacterial antigen compared to healthy individuals (Bonen & Cho, 2003) In particular, some human and animal studies... in various tissues 2.3 Chronic inflammatory bowel disease and COX-2 The potential role for prostaglandins in the inflammatory process underlying chronic IBD has been a focus of controversy Under the hypothesis that prostaglandins may be protective, treatment with exogenous prostaglandins was investigated but found to exacerbate the diarrhea The possibility that proinflammatory mechanisms might be involved... cohort study of nonsteroidal anti -inflammatory drug use and disease activity in outpatients with inflammatory bowel disease Inflamm Bowel Dis, Nov; 10(6):751-757 ISSN 1078-0998 Bonner GF, Walczak M, Kitchen L, et al (2000) Tolerance of nonsteroidal antiinflammatory drugs in patients with inflammatory bowel disease Am J Gastroenterol, Aug; 95(8):1946-1948 ISSN 0002-9270 Botting RM (2010) Vane’s discovery... and intestine to maintain the integrity of the mucosal epithelium and its inhibition leads to gastric damage, hemorrhage and ulceration 2.2 Mechanisms of NSAID injury to the gastrointestinal mucosa For evaluation of the validity of new potentially less toxic NSAIDs it is mandatory to clearly understand the pathogenesis of NSAID induced ulceration (Figure 2) Both aspirin and nonaspirin NSAIDs inhibit... inflammation Mediat Inflamm, Oct; 5(5):305-23 ISSN 0962-9351 Barbieri D (2000) Inflammatory bowel diseases J Pediatr (Rio J), Jul; 76(suppl 1):S173-S180 ISSN 0021-7557 Bhattacharyya DK, Lecomte M, Rieke CJ, et al (1996) Involvement of arginine 120, glutamate 524 and tyrosine 355 in the binding of arachidonate and 2-phenylpropionic acid inhibitors to the cyclooxygenase active site of ovine prostaglandin endoperoxide... the effects of these COX-2 inhibitors on differents studies on experimental colitis models 12 Inflammatory Bowel Disease – Advances in Pathogenesis and Management Fig 3 The chemical structures of some COX-2 inhibitors 2.5 COX-2 inhibitors on experimental colitis models The role of selective inhibition of COX-2 for the inflammatory process and the course of experimental and human colitis is controversially . INFLAMMATORY BOWEL DISEASE – ADVANCES IN PATHOGENESIS AND MANAGEMENT Edited by Sami Karoui Inflammatory Bowel Disease – Advances in Pathogenesis and Management. Chapter 6 Pathogenesis of Inflammatory Bowel Diseases 111 Yutao Yan Part 2 Advances in Diagnosis of Inflammatory Bowel Disease 135 Chapter 7 The Role of Imaging in Inflammatory Bowel Disease. gastrointestinal mucosa. Topical Inflammatory Bowel Disease – Advances in Pathogenesis and Management 8 application of NSAIDs increases gastrointestinal permeability allowing luminal aggressive