ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS302

reduced postoperative adhesions by 45% (71.3% vs. 39.4%; p<0.001).A single IP injection of VPA in nonop animals increased peritoneal fi-brinolytic activity by 213% (0.83U/ml vs. 1.77U/ml) compared tononop controls (p¼0.03). in operated animals, peritoneal fibrinolyticactivity was not significantly different between animals administeredsaline and VPA (2.61U/ml vs 2.08U/ml, respectively). There was nosignificant difference in colonic burst pressure between animals ad-ministered a single dose of 50mg/kg VPA and those given saline(221 mmHg vs. 264 mmHg). Conclusions: the significant reductionin postoperative adhesions by a single intraoperative dose of VPAindicates a novel mechanism of action for this HDAC inhibitor andsuggests a new role for HDAC inhibitors in adhesion prevention.

38.7. Breast Milk and Formula Feeding Affect Intestinal Epi-thelial Barrier Function in Vivo and in Vitro. V.Poroyko,1 T. Mirzapoiazova,2 E. M. Carlisle,1 M. S. Caplan,3

J. Alverdy,1 M. J. Morowitz,4 P. A. Singleton,2 D. Liu1;1University of Chicago Medical Center, Department ofSurgery, Chicago, IL; 2University of Chicago, Department ofMedicine, Chicago, IL; 3Northshore University HealthSystem, Department of Pediatrics, Evanston, IL; 4Universityof Pittsburg Medical Center, Department of Surgery,Pittsburg, PA

Introduction:While it is well established that breast fed (BF) com-pared to formula-fed (FF) pre-term infants have a lower incidenceof necrotizing enterocolitis (NEC), the exact mechanism for this isstill unknown. the objective of this study is to investigate effect ofBF and FF on intestinal epithelial function using in vivo and in vi-tro models. Methods: In vivo: C3HeB/FeJ pups were fed by motheruntil DOL7. on DOL7 half of each litter was assigned to formulafeeding (liquid puppy formula via orogastric catheter 4x/day) (FF)while the remaining pups were allowed exposure to maternal feed-ing (BF). All pups were euthanized at 72h, and colonic tissue wascollected. cDNA libraries (FF n¼4, BF n¼4) were constructed andsequenced using Solexa sequencing platform, 16sRNA tags werePCR amplified and sequenced using 454 platform. cDNA readswere annotated by BLAST search against mouse RNA database(NCBI build 37). The differentially abundant features were identi-fied using Metastats. Biological Pathways were assembled using In-genuity software (Ingenuity Systems Inc. USA); 16sRNA tags wereprocessed using Mothur software and annotated according to RDBdatabase. In vitro: Human Normal Colon Cells (HNCC) were usedfor examination of epithelial barrier function regulation usingtrans-endothelial electrical resistance (TER). Lipopolysaccharide(LPS) (5mg/ml) was utilized to induce barrier disruption effectcaused by Gram (-) bacteria. the 1/100 dilutions of breast milk of3 healthy volunteers and Similac Special Care premature InfantFormula, normalized to the total protein content, were used to treatcells in TER experiments. Results: In vivo: BF decreased numberof Firmicutes (p<0.001) and enhanced growth of Proteobacteria(p<0.001) and Bacteroidetes(p<0.001). Sequencing revealed 149mRNAs differentially expressed between BF and FF groups; 65transcripts were FF and 84 were BF specific. the Tight junction sig-naling (p¼0.026), Integrin signaling (p¼0.008), Actin cytoskeletonSignaling (p¼0.011) and FAK signaling (p¼0.006) were among bio-logical pathways suppressed by FF indicating processes of intesti-nal barrier disruption. In vitro, LPS treatment (6h) of HNCC cellsincreased epithelial barrier permeability as detected by TER, treat-ment with 1/100 diluted human breast milk completely inhibitedbarrier disruptive effect of LPS. The barrier protective effect of pre-mature formula was less pronounced. Conclusions: The studyevaluated effect of diet on juvenile intestine. In vivo: FF decreasednumber of Firmicutes, enhanced growth of Gram(-) bacteria andhas negative effect on epithelial barrier function in murine model.in vitro: Human breast milk causes strong protective effect againstLPS-mediated intestinal barrier disruption in HNCC model.

38.8. Impact of IL-18 on Dendritic Cells in a Murine Model ofInflammatory Bowel Disease. M. J. Wheeler,1 V. C.Hardie,1 R. Z. Harms,1,2 C. W. Boyer,1 A. J. Lazenby,3 J. M.Bowen,3 D. W. Mercer,1 N. E. Sarvetnick1,2; 1University ofNebraska Medical Center, Omaha, NE; 2University ofNebraska Medical Center, Omaha, NE; 3University ofNebraska Medical Center, Omaha, NE

Introduction: Inflammatory Bowel Disease (IBD) is a painful andmorbid disease affecting 1.4M patients in the US alone. the pathogen-esis of the disease is believed to involve a loss of barrier function withan abberant inflammatory response. Dextran SodiumSulfate (DSS) iscommonly used tomimic the epithelial barrier breakdown and inflam-matory response seen in IBD. Dendritic Cells (DC) play a central roleinmonitoring the luminal environment andmodulating inflammationat mucosal sites. IL18, a cytokine associated with DC activation, hasbeen implicated in IBD and other auto-inflammatory diseases. It isour hypothes is that changes in DC populations, and disease severityare IL18 and IL18R dependent. Methods: Wild Type (WT), IL18Knockout (18KO) and IL18 Receptor Knockout (18RKO) mice (n¼6/group) were administered DSS in cage drinking water for 7 days,then returned to sterile drinking water. An equal number of controlswere given sterile water the same conditions. Weight loss and colitisscores were monitored daily. Mice were sacrificed at day 10 and tis-sues were collected. Colon and small intestine were stained withH&E. Spleen, Mesenteric Lymph Nodes (MLN) and Peyer’s Patches(PP) were processed into single cell suspensions and stained for 12-color Flow Cytometry (FC). Mann-Whitney U test was run for statis-tics. Results: Treated mice experienced a colitis demonstrated byweight loss (p<0.05), daily colitis score (p<0.05), colon length(p<0.05) and H&E pathological findings. 18KO mice experienced co-litis so severe it was lethal and dose had to be reduced. While18RKO had a more severe colitis than WT, it was not lethal. FC anal-ysis on Spleen and PP revealed an increase in percent of DC express-ing CD103 and an increase in DC expressing CD103 and CD80 in bothWT and 18KO (p<0.05), but not 18RKO mice. FC on MLN revealeda decrease in percent DC, a decrease in DCs expressing CD103 anda decrease in DC expressing CD103 and CD80 in both WT and18RKO (p<0.05), but not 18KO mice. FC on PP revealed an increasein percent of DCs expressing CD103, and increases in percent of DC inboth WT and 18RKO (p<0.05), but not 18KO mice. Conclusions: InDC, CD103 is a marker of an anti-inflammatory regulatory popula-tion. CD80 expression denotes an activated cell capable of interactingwith T cells. Increasing CD103/CD80 expression in PP and spleen inWT and 18KOmice indicate there is an important increase of anti-in-flammatory mature DC, which is IL18R dependent, but not IL18 de-pendent. the decrease in CD103 and CD103/CD80 DC in MLNwould indicate a decrease of anti-inflammatory regulation which isIL18 dependent, but independent of the IL18R. Recent reports haveindicated that there is a second ligand, other than IL18 actingthrough the IL-18R. Our results show that DC from distinct cellularcompartments respond distinctly to IBD-like inflammation, as eitherIL18 or IL18R dependent. in the future, modulation of IL18, IL18R orDC may be an attractive target for treatment of IBD.

38.9. Absence of BH3-only ProteinsMitigates Accentuation ofHepatic Ischemia-Reperfusion Injury Caused by Steato-sis. B. J. DuBray,1 K. L. Gunter,1 H. A. Hassan,1 P.Balachandran,1 G. A. Upadhya,1 B. L. Knolhoff,1 J. Jia,1 S.Ramachandran,1 R. S. Hotchkiss,1 T. Mohanakumar,1 W. C.Chapman,1 C. D. Anderson2; 1Washington University Schoolof Medicine, St. Louis, MO; 2University of Mississippi MedicalCenter, Jackson, MS

Introduction: Hepatic steatosis is the most prevalent chronic liverdisease in the world and its recognition as a major clinical risk factorfor ischemia-reperfusion injury (IRI) has become increasingly impor-tant given the epidemic rise of obesity and diabetes. BH3-only proteinsBimandBid of theBcl-2 family are regulators of the intrinsic pathway