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      About Digestion: 3.2 Impact Factor I 6.4 CiteScore I 0.914 Scimago Journal & Country Rank (SJR)

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      Aminosalicylates and Other Anti-Inflammatory Compounds for Irritable Bowel Syndrome

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          Abstract

          Growing evidence suggests that gastrointestinal immune activation may affect intestinal function and sensory perception, which contribute to symptom generation in patients with irritable bowel syndrome (IBS). The identification of higher counts of immunocytes (e.g. T cells and mast cells), mucosal and systemic immune activation, and increased mucosal permeability in patients with IBS has stimulated interest in the potential development of therapeutic approaches aimed at targeting the immune system and inflammation. Although an initial attempt in a pilot trial with steroids in patients with post-infective IBS failed, there has been renewed interest for mast cell stabilizers and the therapeutic potential of aminosalicylates. A recent randomized, double-blind, placebo-controlled pilot trial assessed the effect of mesalazine on intestinal immune cells and symptom perception in patients with IBS. Mesalazine markedly reduced mucosal immune cells and mast cells in particular, compared to placebo. In addition, mesalazine significantly improved general well-being. Mesalazine may enhance epithelial barrier function, and preliminary data suggest that it may alter faecal bacterial profiles in IBS patients. Nevertheless, the exact mechanism through which this drug affects immune activation in the intestine of patients with IBS remains unknown. There is a need for further studies to prove the efficacy of mesalazine for IBS. Further studies aimed at assessing the role of aminosalicylates and other approaches with potential anti-inflammatory activity, including probiotics, non-absorbable antibiotics, histamine receptor antagonists and protease inhibitors on IBS symptoms or pathophysiology are now warranted.

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          Most cited references45

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          Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome.

          The mechanisms underlying abdominal pain perception in irritable bowel syndrome (IBS) are poorly understood. Intestinal mast cell infiltration may perturb nerve function leading to symptom perception. We assessed colonic mast cell infiltration, mediator release, and spatial interactions with mucosal innervation and their correlation with abdominal pain in IBS patients. IBS patients were diagnosed according to Rome II criteria and abdominal pain quantified according to a validated questionnaire. Colonic mucosal mast cells were identified immunohistochemically and quantified with a computer-assisted counting method. Mast cell tryptase and histamine release were analyzed immunoenzymatically. Intestinal nerve to mast cell distance was assessed with electron microscopy. Thirty-four out of 44 IBS patients (77%) showed an increased area of mucosa occupied by mast cells as compared with controls (9.2% +/- 2.5% vs. 3.3 +/- 0.8%, respectively; P < 0.001). There was a 150% increase in the number of degranulating mast cells (4.76 +/- 3.18/field vs. 2.42 +/- 2.26/field, respectively; P = 0.026). Mucosal content of tryptase was increased in IBS and mast cells spontaneously released more tryptase (3.22 +/- 3.48 pmol/min/mg vs. 0.87 +/- 0.65 pmol/min/mg, respectively; P = 0.015) and histamine (339.7 +/- 59.0 ng/g vs. 169.3 +/- 130.6 ng/g, respectively; P = 0.015). Mast cells located within 5 microm of nerve fibers were 7.14 +/- 3.87/field vs. 2.27 +/- 1.63/field in IBS vs. controls (P < 0.001). Only mast cells in close proximity to nerves were significantly correlated with severity and frequency of abdominal pain/discomfort (P < 0.001 and P = 0.003, respectively). Colonic mast cell infiltration and mediator release in proximity to mucosal innervation may contribute to abdominal pain perception in IBS patients.
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            Mast cell-dependent excitation of visceral-nociceptive sensory neurons in irritable bowel syndrome.

            Intestinal mast cell infiltration may participate to abdominal pain in irritable bowel syndrome (IBS) patients. However, the underlying mechanisms remain unknown. We assessed the effect of mast cell mediators released from the colonic mucosa of IBS patients on the activation of rat sensory neurons in vitro. Colonic mast cell infiltration and mediator release were assessed with quantitative immunofluorescence and immunoenzymatic assays. The effect of mucosal mediators was tested on mesenteric sensory nerve firing and Ca(2+) mobilization in dorsal root ganglia in rats. Mediators from IBS patients, but not controls, markedly enhanced the firing of mesenteric nerves (14.7 +/- 3.2 imp/sec vs 2.8 +/- 1.5 imp/sec; P < .05) and stimulated mobilization of Ca(2+) in dorsal root ganglia neurons (29% +/- 4% vs 11% +/- 4%; P < .05). On average, 64% of dorsal root ganglia responsive to mediators were capsaicin-sensitive, known to mediate nociception. Histamine and tryptase were mainly localized to mucosal mast cells. IBS-dependent nerve firing and Ca(2+) mobilization were correlated with the area of the colonic lamina propria occupied by mast cells (r = 0.74; P < .01, and r = 0.78; P < .01, respectively). IBS-dependent excitation of dorsal root ganglia was inhibited by histamine H(1) receptor blockade and serine protease inactivation (inhibition of 51.7%; P < .05 and 74.5%; P < .05; respectively). Mucosal mast cell mediators from IBS patients excite rat nociceptive visceral sensory nerves. These results provide new insights into the mechanism underlying visceral hypersensitivity in IBS.
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              Lactobacillus and bifidobacterium in irritable bowel syndrome: Symptom responses and relationship to cytokine profiles

              The aim of this study was to compare the response of symptoms and cytokine ratios in irritable bowel syndrome (IBS) with ingestion of probiotic preparations containing a lactobacillus or bifidobacterium strain.
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                Author and article information

                Journal
                DDI
                Dig Dis
                10.1159/issn.0257-2753
                Digestive Diseases
                S. Karger AG
                978-3-8055-9385-4
                978-3-8055-9386-1
                0257-2753
                1421-9875
                2009
                March 2010
                04 March 2010
                : 27
                : Suppl 1
                : 115-121
                Affiliations
                Department of Clinical Medicine and Center for Applied Biomedical Research, University of Bologna, Bologna, Italy
                Article
                268131 Dig Dis 2009;27(suppl 1):115–121
                10.1159/000268131
                20203507
                00e1603a-4054-452e-8211-0fbbb3b97388
                © 2010 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Page count
                References: 63, Pages: 7
                Categories
                Paper

                Oncology & Radiotherapy,Gastroenterology & Hepatology,Surgery,Nutrition & Dietetics,Internal medicine
                Mast cells,Irritable bowel syndrome,Immune activation,Aminosalicylates,Abdominal pain

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