T2060 The Clinical Course of Post-Infectious Irritable Bowel Syndrome: An Eight-Year Follow-up Study

can contribute to disrupted motility in the inflamed colon and that dampening the hyperexcitability of AH neurons can restore colonic motor function. These findings support the concept that increases in sensory neuron activity (reflected in changes to AH cell excitability) in a given region of the bowel can have a deleterious effect on motor function.

T2060

Background and Aims: Bacterial gastroenteritis has been known as a risk factor of irritable bowel syndrome(IBS). The incidence of post-infectious IBS (PI-IBS) was known in the range of 7-31%, but few studies have long term follow up results. The aims of this study were to evaluate the clinical course, risk factor, and prognosis of PI IBS 8 years after shigella infection. Methods: We recruited 133 patients with shigellosis during its outbreak and 105 healthy controls. We used a questionnaire to investigate their current bowel habits and other functional bowel disorders (FBDs). The shigella-exposed group was consisted of hospital employees who experienced abdominal pain, diarrhea, or fever during the shigellosis outbreak and control group was consisted of age and sex matched hospital employees who corresponded with patient and were not infected with shigella. Results: Complete data were obtained from 71 patients (53.4%) and 65 healthy controls (61.9%) and there was no significant demographic difference between both group. The prevalence of IBS in the shigellaexposed group and control group was 11(15.4%) and 6(9.2%) in 8 years after shigella infection. The incidence of newly developed IBS in the shigella-exposed group and control group was 4/71(5.6%) and 3/61(4.61%) in 8 years after shigella infection. There was no significant difference in incidence of IBS in 8 years after shigellosis. In shigella-exposed group, 2 out of 12 cases of PI-IBS showed persistent IBS after 8 years. The prevalence of PI-IBS after 8 years in the previous FBDs groups was 26.7%, whereas the prevalence of PIIBS without history of FBDs group was 10.7%(p<0.05). Previous FBDs history, female sex, and presence of fever at the time of infection were risk factors of IBS after 8 years follow up study. Conclusions: Two in 12 patients (18.8%) of PI-IBS patients had persistent IBS over 8 year. . Overall prevalence of IBS was higher in shigella-exposed group compared with control group, but there was no difference in IBS incidence after 3 years. Shigella infection and previous functional bowel disorder history, female sex, and fever during admission were risk factors of IBS after 8 years follow up study.

T2058 Colitis Alters the Function of Chromaffin Cells of the Adrenal Medulla Mark K. Lukewich, Alan Lomax Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the gastrointestinal (GI) tract. Catecholamines, which are released synaptically released by the axons of postganglionic sympathetic neurons and systemically by adrenal chromaffin cells (ACC), modulate GI motility, secretion, blood flow and inflammation, and may therefore play an important role in IBD. The present study tested the hypothesis that colitis impairs the release of catecholamines from ACC by examining ACC excitability and voltage-dependent Ca2+ influx with patch clamp and intracellular Ca2+ imaging techniques. Colitis was induced in male CD1 mice by 5% dextran sulfate sodium (DSS) in drinking water for 5 days followed by 2 days of normal drinking water. Controls were given normal drinking water for 7 days. In other experiments, colitis was induced by the intracolonic injection of 4.5 mg of trinitrobenzene sulfuonic acid (TNBS) in 40% ethanol, and saline injected mice were used as controls. ACC were enzymatically dissociated from the adrenal medullae and isolated cells were cultured overnight before recordings commenced. Population data were compared using unpaired t-tests, the Mann Whitney test or two-way ANOVA, as appropriate. Statistical significance was reached when P < 0.05. The n value refers to the number of cells. RESULTS and CONCLUSIONS: The resting membrane potential of ACC isolated from DSS-treated mice was significantly hyperpolarized compared to controls (DSS: -61.2 ± 1.8 mV, n = 32; Control: -50.7 ± 1.6 mV n = 24). Colitis significantly enhanced voltage-gated K+ current (DSS: n = 13 cells; Control: n = 30 cells). Importantly, voltage-gated Ca2+ current was significantly decreased in ACC from DSS-treated mice at membrane potentials between -25 and +25 mV (DSS: n = 11 cells; Control: n = 16 cells). Ca2+ influx in response to KClinduced depolarization was significantly reduced to 62.2% of the control response during colitis (DSS: n = 114 cells; Control n = 61 cells). Similar to our findings in the DSS model, Ca2+ influx in ACC from TNBS-treated mice was significantly reduced to 68.3% of the control response (TNBS: n = 323 cells; Control: n = 330 cells). Our findings indicate that ACC become hyperpolarized and voltage-dependent Ca2+ influx is reduced during colitis. Given the important roles of cellular excitability and intracellular Ca2+ signaling in secretion, these alterations will likely result in decreased systemic catecholamine levels, which may play an important role in IBD. These data also provide further evidence that localized inflammation of the GI tract during colitis can alter the physiology of distant tissues.

T2061 The Proinflammatory Cytokines Expression in Colon Can Be Induced by Chronic Variable Stress and Can Be Prevented by High Caloric Food in Rat Sang Kyun Noh, Yong Sung Kim, Moon Young Lee, Jung Taek Oh, Young Woo Sohn, Yong Leol Oh, Han Seung Ryu, Suck Chei Choi Backgrounds and Aims : Stress plays an important role in functional bowel disorder and inflammatory bowel disease. The purpose of this study was to evaluate the effect of stress on the hypothalamic-pituitary-adrenal (HPA) axis and colonic inflammatory cytokines according to stress mode and duration. We also want to evaluate the effect of high caloric (sweet) food on changes of behavior, HPA axis and cytokines induced by stress. Materials and Methods: Twenty-seven adult male rats, weighing about 290 g, were divided into 5 groups: control(CON), restraint stress with regular food (Res A), restraint stress with sweet food (Res B), chronic variable stress with regular food (CVS A), chronic variable stress with sweet food (CVS B). Before and after the experiment, all rats were evaluated and analyzed their exploring behavioral activity using activity monitor system. After 6 weeks of stress period, the weight of body adrenal gland,and the levels of the plasma ACTH and corticosterone were measured. Plasma and colonic levels of pro- and anti-inflammatory cytokines (TGF-β, IL-2, IL-10 and interferon-γ) were measured by Western blotting assay. Results: Body weight gain was decreased in Res A, CVS A and CVS B group compared to control group. The amount of food consumption was lower in CVS A or CVS B group compared to other groups, however in terms of caloric intake, there was no difference between all groups. All stress groups showed significantly increase in the relative adrenal weight compared to the control group. Although there was no significant difference in the plasma corticosterone concentration between all groups, the levels of the plasma ACTH concentration in CVS A group was significantly decreased and therefore corticosterone/ACTH ratio was significantly higher than other groups. In open field test before the experiment, there were no activity differences between all groups. However, after the experiment, CVS B group showed significantly increase their exploring activity compared to CVS A and control group. In western blotting assays of plasma and colon, IL-2 and interferon-γ were significantly increased in CVS A group, but Res A, Res B and CVS B group did not show this change. There was no difference in TGF- β and IL-10 expression between all groups. Conclusions: Chronic nonadaptable stress, not simple adaptable stress, could induce the proinflammatory cytokines in plasma and colon as well as behavioral change. High caloric food ingestion could reduce the production of proinflammatory cytokines induced by the chronic non-adaptable stress.

T2059 Persistent Epithelial Barrier Alterations in a Rat Model of Post-Inflammatory Gut Dysfunction Joan Antoni Fernandez-Blanco, Vicente Martinez, Maite Martin, Patri Vergara Introduction: Altered epithelial barrier function (EBF) and mucosal mast cells (MMCs) contribute to the initiation and perpetuation of defective intestinal immune responses as a pathogenic basis for gastrointestinal inflammatory and functional disorders. Aim: To characterize alterations in the intestinal EBF in a model of post-inflammatory gut dysfunction in rats. Methods: Male SD rats were infected with Trichinella spiralis (TS) (7500 larvae/rat, PO). At the post-inflammatory phase (day 30±2 post-infection) animals were euthanized and jejunal EBF assessed in Ussing chambers. Transepithelial voltage (Vte), short-circuit current (SCC), conductance (G) and FITC-dextran (4 & 40 kD) flux were determined as measures of EBF. Responses to 5-HT (10-7-10-4M), substance P (SP, 3.3x10-8-10-6M), the PAR-2 agonist SL-NH2 (10-6-3x10-5M), and capsaicin (2x10-6M) were evaluated. Histological alterations and MMCs (immunohistochemistry for RMCPII) were also assessed. Results: During the post-inflammatory phase basal EBF was significantly altered (Table). 5-HT, SLNH2 and SP induced concentration-dependent increases in SCC. In TS-infected rats, secretory responses to 5-HT [SCC increase (μA/cm2): TS-infected:12.7±2.8; Control:17.5±1.7; N=1113; P<0.05] and SL-NH2 [SCC increase (μA/cm2): TS-infected: 28.2±3.3; Control: 55.3±8.6; N=8-12; P<0.05] were reduced, while responses to SP were unaffected [SCC increase (μA/ cm2): TS-infected: 35.7±1.8; Control: 36.5±2.5; N=10 each]. Only responses to SP in TSinfected animals were affected by pretreatment with tetrodotoxin (TTX) (μA/cm2; TSinfected+TTX: 22.18±3.6 P<0.05 vs control+TTX: 34.0±4.0; N=10 each). Capsaicin augmented SCC similarly in both groups. No histological signs of active inflammation were observed; however, the number of MMCs was increased in TS-infected animals (39.1±2.3 MMCs/villi P<0.0001 vs control: 13.9±0.9 MMCs/villi; N=7-9). Conclusions: TS infection in rats results in persistent, post-infective intestinal barrier dysfunctions and mucosal mastocytosis without signs of active inflammation. Hyporesponsiveness to 5-HT and SL-NH2 and altered permeability suggest alterations of epithelial function likely associated to increased release of MMC mediators. Decreased responses to SP after neuronal blockage suggests an enteric nervous system remodelling. These alterations might contribute to the epithelial barrier dysfunctions observed in IBD and IBS patients. Basal EBF during the post-inflammtory phase

T2062 Clinical Evidence of Autonomic Dysfunction in Inflammatory Bowel Disease Jutta Keller, Viola Andresen, Peter H. Layer Background: The autonomic nervous system (ANS) is a critical regulator of gastrointestinal motility and much evidence now exists on cellular and molecular levels to suggest that the ANS also plays an important role in the development of inflammatory bowel disease (IBD). Clinical evidence of autonomic dysfunction and its role for regulation of motility in IBD is sparse. Aims: To investigate autonomic function in patients with Crohn's disease (CD) and ulcerative colitis (UC) compared with healthy volunteers and to associate it with gastric emptying (GE) parameters. Methods: 13 healthy subjects (CON), 12 CD and 10 UC patients underwent standardized tests of parasympathetic (Ewing test (ET): heart rate variation (ratio of 30th and 15th RR-interval) in response to tiliting) and sympathetic function (sustained handgrip test (SHGT): increase in diastolic blood pressure in response to sustained muscle contraction). Within 2 weeks all subjects also underwent a standardized 13C-octanoic acid gastric emptying breath test. Results: Patients with inflammatory bowel disease (IBD) were in remission or had mild to moderate disease activity (Crohn's disease activity index: 29252, Clinical Acitivity Index for UC: 5-13). Compared with healthy controls, mean diastolic blood pressure after 5 min of SHGT was significantly decreased in CD and UC patients

*: P<0.05 vs control

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AGA Abstracts

AGA Abstracts

The Clinical Course of Post-Infectious Irritable Bowel Syndrome: An EightYear Follow-up Study Hyun Chul Lim, Jie-Hyun Kim, Young Hoon Youn, Hyojin Park, Sang In Lee