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sjoints. Future cohort and controlled studies are mandated to further evaluate the relationshipbetween IBD and osteonecrosis.Results

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Depression in Inflammatory Bowel Disease PatientsKatja Grubelic Ravic, Zeljko Krznaric, Silvija Cukovic-Cavka, Marko Brinar, MarinaGrubic, Boris N. Vucelic

Psychological disorders are highly prevalent in patients with inflammatory bowel disease(IBD). Depression may influence the clinical course of IBD and affect patient's quality oflife. Objective. To determine the prevalence of depression in patient with IBD and thecorrelation between depression , patients age, disease duration and number of hospitaliza-tions. Methods. 157 IBD patients from tertiary referral centre( 91 with Crohn's disease (CD),62 with ulcerrative colitis (UC) and 3 unspecified ) completed the Zung Self-rating DepressionScale (SDS). The mean age of patients was 40 yr (15 - 69), and the mean duration of diseasewere 11,64 yr (1-40), the mean of number of hospitalization was 6,85 (0 - 30). Results.The mean SDS scores for the entire group were 43,43 (st.dev. 11.17) and the percentageof subjects with depression is 51,6%. There is no differences bettween patients with CDand those with UC in depression scores. There is no statistically significant correlationneither between patients age and depression scores nor between duration of illness anddepression scores. Though, significant correlation has been found between depression andnumber of hospitalization. Conclusion. The patients with IBD have high rate of depression,independently to their age and disease duration. Patients who experience more hospitaliza-tions score higher on depression scale. It is important for clinicians to assess depressionamong patients with IBD and recommend psychological treatment.

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History of Medical Hospitalization Predicts Future Need for Colectomy inPatients with Ulcerative ColitisAshwin N. Ananthakrishnan, Mazen Issa, Dawn B. Beaulieu, Susan Skaros, Joshua F.Knox, Kathryn Lemke, Jeanne Emmons, Sarah J. Lundeen, Mary F. Otterson, David G.Binion

Introduction: Patients who require hospitalization for the management of ulcerative colitis(UC) form a subset with severe disease. These patients may be more likely to requirecolectomy. There is limited data examining whether medical hospitalization is predictive ofsubsequent colectomy. Methods: This was a retrospective case control study utilizing theInflammatory Bowel Disease center database at our academic referral center. Cases comprisedUC patients who underwent colectomy for disease refractory to medical management. Patientswho underwent colectomy for other reasons including dysplasia were excluded. Patientswho had undergone colectomy elsewhere prior to seeking care at our center were alsoexcluded. The control population comprised of all patients with UC who had not undergonecolectomy. Results: There were a total of 246 UC patients included in our study with 103being hospitalized sometime in their disease course (41.9%). A total of 27 patients underwentcolectomy (11%). The mean age of the patients was 43.6 years (range 19 - 87 years) with53% women. Colectomy patients had a younger mean age of diagnosis (29.0 years vs. 35.6

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years, p=0.03) and a shorter disease duration (5.6 years vs. 8.6 years, p=0.04) than thosewho had not required colectomy. Seven colectomies were at the time of or within 1 yearof diagnosis, a further 3 colectomies were within 2 years. Colectomy patients were significantlymore likely to have been on infliximab therapy (51.8% vs. 22.4%, p=0.001) but no morelikely to have been on immunomodulator therapy (74.1% vs. 59.4%, p=0.14). Patients whorequired medical hospitalization for UC were more likely to require future colectomy (20.4%vs. 4.2%, p <0.001) than those who had not required hospitalization. On multivariateanalysis after adjusting for age of onset, extent and duration of disease, immunomodulatoror biologic therapy, and smoking history, the only significant variables predictive of futurecolectomy were requiring medical hospitalization for management of UC (OR 5.37, 95%CI 2.00 - 14.46) and ever requiring infliximab therapy (OR 3.12, 95% CI 1.21 - 8.07).Conclusion: Requiring medical hospitalization predicts future need for colectomy in UCpatients. This data implies that prevention of clinical deterioration requiring hospitalizationis an important goal in UC medical management. Aggressive medical management withbiologic and immunomodulator therapy may help decrease the likelihood of needing colec-tomy.

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Bacterial Effector Avra Stabilizes Cell Tight Junctions to Inhibit Inflammationin Intestinal Epithelial CellsAnne P. Liao, Elaine O. Petrof, Sumalatha Kuppireddi, Erika C. Claud, Jun Sun

The type III secretory system (TTSS) is a protein transport device using by Gram-negativepathogenic bacteria, including Salmonella, enteropathogenic Escherichia coli, enterohae-morrhagic E. coli, or Pseudomonas spp. The TTSS allows bacteria to inject virulence proteins,called effectors, into the cytosol of their eukaryotic host cells. These effectors are responsiblefor the alteration of tight junction (TJ) structure and function in intestinal epithelial cells.AvrA is a newly described bacterial effector found in Salmonella and E. coli. We report herethat AvrA expression stabilizes cell permeability/tight junctions in intestinal epithelial cells.Cells colonized with an AvrA-deficient bacterial strain (AvrA-) had decrease of cell permeabil-ity, disruption of TJs, and increased inflammatory response. In contrast, cells colonizedwith AvrA-sufficient bacteria maintained cell permeability and stabilized TJ structure. Thetranselectrical resistance decreased and this occurred after AvrA- colonization for only 30min. Western blot data showed that TJ proteins, such as ZO-1, claudin, decreased afterAvrA- colonization for only I hour, and this decrease lasted for over 24 hours. This differencewas confirmed In Vivo. Fluorescent tracer showed that increased fluorescence was found inthe blood of mice infected with AvrA- compared to those infected with the AvrA sufficientstrains. AvrA- disrupted TJ structure and function and increased inflammation In Vivo,compared to the AvrA sufficient strain. Our data further demonstrate that the TJ disruptionis regulated directly by AvrA rather than indirectly through inflammatory cytokine regulation.An intriguing aspect of this study is that AvrA stabilized the TJs, even though the otherTTSS proteins, SopB, SopE, SopE2, and SpiA, are known to disrupt TJs. This is consistentwith other studies demonstrating a different role of AvrA in eliciting fluid accumulationcompared to the other effector proteins such as sopA, sopB, sopD, or sopE2. We have alsopreviously shown that AvrA attenuates the key proinflammatory NF-κB transcription factor,activate the β-catenin transcription factor, and inhibit cell apoptosis in mouse epithelialcells. Thus, AvrA may play a role as an anti-inflammatory protein to stabilize TJs and preventcell death, and balance the opposing action of other bacterial effectors. Our findings indicatean important role for the bacterial effector AvrA in regulating on TJs of intestinal epithelialcells during inflammation. The role of AvrA represents a highly refined bacterial strategythat helps the bacteria survive in the host and dampen inflammatory response.

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PepT1 Associated with Lipid Rafts Modulates Bacterial-Epithelial InteractionsHang Thi Thu Nguyen, Guillaume Dalmasso, Shanthi V. Sitaraman, Didier Merlin

Background and Aims: PepT1 is a di/tripeptide transporter normally expressed in the smallintestine and induced in colon under inflammatory conditions such as inflammatory boweldisease. We previously showed the localization of PepT1 in lipid rafts (LR) of epithelialcells. Our aim was to investigate the role of PepT1associated with LR in inflamed colonicepithelial cells. Methods: human colonic epithelial HT29-Cl.19A cells, which do not expresshuman PepT1 (hPepT1) under normal conditions, were infected with enteropathogenic E.coli (EPEC). hPepT1 promoter activity was determined by luciferase assay. hPepT1 expressionwas assessed by RT-PCR, Western blot and immunofluorescence staining. hPepT1 transportactivity was measured by uptake experiments. The presence of hPepT1 in LR fractionsprepared from EPEC-infected HT29-Cl.19A cells was determined by Western blot analysis.HT29-Cl.19A cells stably transfected with wild type hPepT1 (HT29-Cl.19A/hPepT1) or itsmutated forms that were not found in LR were examined for EPEC-induced expression ofpro-inflammatory cytokine IL8 by real time RT-PCR and ELISA. Results: EPEC inducedhPepT1 promoter activity, mRNA and protein expression and transport activity in HT29-Cl.19A cells. Furthermore, hPepT1 co-localized with LR marker GM1 in EPEC-infectedHT29-Cl.19A cells indicating its association with LR. Remarkably, expression of PepT1 inLR resulted in reduced EPEC attachment on HT29-Cl.19A/hPepT1 cells. Higher IL8 expres-sion level and stronger activation of p38 MAP kinase were detected in HT29-Cl.19A/hPepT1cells compared to cells transfected with empty vector upon EPEC infection. Conclusion: 1)EPEC induces functional expression of hPepT1 in colonocytes, 2) hPepT1 is involved inEPEC-mediated inflammation, and 3) LR-associated PepT1 plays a role in modulating bac-terial-epithelial interactions in the colon, suggesting a novel function of this transporter inepithelial cells.