(basal: >10 PPM and/or post-lactulose rise by >10 PPM) were randomized (double-blind) to rifaximin (400-mg thrice/d, 2-weeks) or placebo. Post-treatment stool forms, frequency, methane and CTT were recorded. Results: CC patients tended to be methane-producer more often (13/23 [56.5%] vs. 25/68 [36.5%]; p=0.07) and had greater area under curve (AUC) for methane (2415 [435-23580] vs. 1335 [0-6562.5], p=0.02) than non-constipating IBS. 8/13 (61.5%) methane-producers and 5/10 (50%) non-producers had abnormal CTT (marker retention: 36-h: 53 [0-60] vs. 19 [8-56], p=0.06; 60-h: 16 [0-57] vs. 13 [3-56], p=0.877). 6 (46.2%) and 7/13 (53.8%) methane-producers were randomized to rifaximin and placebo, respectively. Rifaximin reduced AUC for methane more (6697.5 [1777.5- 23580] vs. 2617.5 [562.5-19867.5], p=0.005) than placebo (3945 [2415-12952.5] vs. 3720 [502.5-9210, p=0.118) at 1-month. CTT normalized in 4/6 (66.7%) on rifaximin (36-h retention: 54 [44-57] vs. 36 [23-60], p=0.05; 60-h: 45 [3-57] vs. 14 [11-51], p=0.09) but none on placebo (p=0.02) (36-h: 31 [0-60] vs. 25 [0-45], p=0.078; 60-h: 6 [0-54] vs. 12 [0-28], p=0.2). Weekly stool frequency (pre vs. post: 3 [1-9] and 7 [1-14], p=0.05) and forms tended to improve with rifaximin than with placebo. Conclusion: Rifaximin improves constipation by reducing breath methane and colon transit time. (Registration number in Clinical Trial Registry India: REF/2012/01/003216). Sa1379 VIP Expression in the Submucosal Plexus in Patients With Parkinson Disease and Chronic Constipation Fiorella Giancola, Rocco Latorre, Francesca Bianco, Francesco Torresan, Alexandros Ioannou, Maria Guarino, Giovanni Barbara, Roberto Chiocchetti, Paolo Clavenzani, Vincenzo Stanghellini, Catia Sternini, Roberto De Giorgio Background and Aims: Chronic constipation (CC) represents one of the most common gastrointestinal complaints in Parkinson's disease (PD), being diagnosed in about 80% of patients. Furthermore, CC often precedes the somatic motor impairment in PD. The enteric nervous system (ENS), which controls gut functions, can be a target of PD although the precise neurochemical ENS abnormalities underlying CC in PD patients remain largely unknown. We aimed to: 1) characterize constipation by assessing colonic transit time (TT) and anorectal manometry (AM) in CC/PD patients; and 2) analyze colonic submucosal neurons of PD patients vs controls, with emphasis on the secretomotor neuron component. Methods: GI symptoms were evaluated by the Rome III questionnaire, while PD severity was established by a Unified Parkinson's Disease Rating Scale (part III). CC was studied in 26 PD patients (6F, 20M; age range: 64-85 yrs) by TT, AM and colonoscopy; and 16 control subjects (6F, 10M; age range: 44-77 yrs) undergoing screening colonoscopy. Using routine biopsies during colonoscopy, we obtained submucosal specimens with related neural network in 10 CC/PD patients and 16 controls. The submucosal plexus was studied by immunohisto- chemistry on whole mount preparations using a mouse monoclonal anti-HuC/D as pan- neuronal marker (Invitrogen, 1:50) and two rabbit polyclonal anti-VIP (vasoactive intestinal peptide-7913; CURE/DDRC, UCLA, 1:2500) and anti-pChAT (peripheral choline acetyl transferase, Justus-Liebig-University Giessen, Germany; 1:100) antibodies. RT-q PCR was also performed to assess relative expression of VIP mRNA (18S reference gene) on biopsies from 4 CC/PD patients and 8 controls. Results: Four groups of CC/PD patients were characterized: a) 64% (n= 16) with a delayed TT and altered AM; b) 14% (n= 4) with a delayed TT; c) 18% (n= 5) with an altered AM; d) the remaining 4% (n= 1) with no evident functional impairment. There were no significant differences in the number of HuC/D immunoreactive (-IR) neurons/ganglion between CC/PD (4.5±0.7) and controls (3.9±1.3); however, a reduced number of HuC/D/VIP-IR neurons was found in CC/PD (73.3±17.1) vs. controls (85.8±9.4) (P<0.05). No significant changes were detected for HuC/D/ChAT neurons in both groups (85.6±11.1 vs. 89.9±10.3). RT-q PCR confirmed a significant reduc- tion of VIP mRNA expression in CC/PD patients (0.035±0.067) vs. controls (1.085±0.593) (P<0.05).Conclusion: Most (96%) of CC/PD patients showed an impairment of colonic motor and rectal sensory functions. The decrease in density of VIP containing secretomotor neurons and in VIP mRNA expression suggests the existence of altered secretory mechanisms in addition to sensorymotor dysfunction in CC/PD. Sa1380 A Novel Approach to Identify Genes Related to Functional Gastrointestinal Disorders Sara E. Gombash Lampe, Christopher Cowley, Julie Fitzgerald, Chitra C. Iyer, Vicki L. McGovern, David E. Fried, Arthur H. Burghes, Kent C. Williams, Fievos L. Christofi, Brian D. Gulbransen, Kevin Foust To investigate novel genes involved in functional gastrointestinal disorders, we disrupted a master regulator of mRNA splicing, the survival motor neuron (SMN) protein. SMN disruption leads to widespread changes in gene expression but has not been evaluated for effects in the gastrointestinal (GI) tract. Mice with a Nestin-cre transgene were crossed to cre reporter mice to analyze expression in the enteric nervous system (ENS). Gene expression was detected in excitatory and sensory neurons, interneurons, and intraganglionic glia throughout the myenteric plexus but not muscle. Next, nestin-cre mice were crossed to mice with a floxed Smn allele on a SMNΔ7 background (SMN2 +/+ ;SMNΔ7 +/+ ;Smn F7/- ) to produce Nestin- F7 mice. In organ baths, SMN reduction disrupted colon longitudinal muscle contraction during high frequency electrical field stimulation (EFS). Muscle relaxation was consistently greater in control tissue. The addition of nitric oxide synthase inhibitor, L-NAME, had no effect on differences between control and Nestin-F7 responses. Tissues showed no morphological changes or cell loss. Gastric emptying and intestinal transit were significantly slower in Nestin-F7 mice compared to controls. Nestin-F7 mice had dry, infrequent stool that corresponded to reduced colonic motility in the bead latency test. Collectively, these data suggest that SMN reduction results in impaired GI function. Future studies will identify specific enteric cell types sensitive to SMN reduction and evaluate mRNA expression in those cells. S-309 AGA Abstracts Sa1381 The Effect of Chang Run Tong on Biomechanical Colon Remodeling in STZ- Induced Type I Diabetic Rats - Is It Related to Advanced Glycation End Product Formation? Jingbo Zhao, Hans Gregersen BACKGROUND AND AIM: The Chinese medicine Chang Run Tong (CRT) effectively improved senile constipation in the clinics. The aims of the present study were to investigate the effect of CRT on colonic remodeling in streptozotocin (STZ) induced diabetic rats and to explore the mechanisms of the CRT effects. Meterials and METHODS: Morphometric properties, residual strains and stress-strain of the wall were studied in colonic segments obtained from diabetic (DM), CRT treated diabetic (T1, high dosage: 50g/kg; T2, low dosage: 25g/kg) and normal (Con) rats. Diabetes was induced by a single tail vein injection 40mg/ kg of STZ. CRT was poured directly into the stomach by gastric lavage once daily. The experimental period was 60 days. Blood glucose level, serum insulin level and body weight were measured. At the end of the experiment, morphometric data such as the circumferential length, the wall thickness and the opening angle were measured from the digitized images of the segments in the no-load state and zero-stress state. The residual strain was computed from the morphometry data. Step-wise distension was done (from 0 to 20 cmH 2 O). Circum- ferential and longitudinal stresses and strains were computed from the length, diameter and pressure data and from the zero-stress state geometry. The expression of advanced glycation end products (AGE) and receptor of AGE (RAGE) were detected in different layers by using immunohistochemistry method and quantitatively analyzed by using imaging analysis software. Linear regression analysis was done to study association between AGE/RAGE expression with the histomorphometric and biomechanical parameters. RESULTS: The wet weight per unit length to body weight ratio, wall thickness, the cross-sectional wall area,open- ing angle and absolute values of inner and outer residual strain of colonic segments in the DM group were significantly higher than those in Con group (P<0.05 and P<0.01). The circumferential and longitudinal stiffness of the wall increased in the DM group compared those with Con group (P<0.01). These parameters in the T1 group but not in the T2 group were significantly lower than those in DM group (P<0.05). Furthermore, it was demonstrated that the expression of AGEs and RAGE in different colon layers was significantly higher in the DM group than in Con group (P<0.05, P<0.01). The AGE/RAGE expressions were highly correlated to the histomorphometric and biomechanical remodeling parameters. The AGE/ RAGE expressions were significantly decreased in the T1 group (P<0.05, P<0.01) but not in the T2 group (P>0.05). CONCLUSIONS: CRT (high dose) treatment could partly restore the morphometric and biomechanical remodeling of colon in diabetic rats. One mechanism for CRT to improve colon remodeling is down-regulation of the expression of AGEs and RAGE in the diabetic colon wall. Sa1382 Gastrointestinal Problems Associated With Multiple Sclerosis: Results From the Nationwide Inpatient Sample for 2010 and 2011 Tariq A. Hammad, Yaseen Alastal, Hanan Almaimani, Monica A. Williams, Sadik A. Khuder, Ali Nawras BACKGROUND: Multiple Sclerosis (MS) is a common autoimmune disorder that affects the central nervous system. MS patients often suffer from gastrointestinal (GI) problems that adversely affect their quality of life. Dysphagia, constipation and fecal incontinence are of a particular concern among patients living with MS. This association has not been established in large scale studies. In this study, we investigated the prevalence and risk for a broad spectrum of GI problems among patients with MS in the United States. METHODS: The Health Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) data was utilized. MS hospitalizations ("cases") were identified by ICD-9-CM code 340. Non-MS hospitalizations ("control") were matched to cases 4:1 by age and gender. We examined demographics, clinical characteristics, and a range of gastrointestinal problems. RESULTS: Between the years 2010 to 2011 there were 59,721 admissions with MS listed as principal diagnosis (16.1%) and secondary diagnosis (83.9%). Compared with controls, MS patients had significantly higher prevalence of GI problems (34.3% vs. 28.7%). The significantly increased GI problems include (Table - 1): dysphagia (OR=2.47, 95% CI: 2.34-2.61), esophageal reflex (OR=1.19, 95% CI: 1.16-1.22), fecal incontinence (OR=4.44, 95% CI: 4.01-4.91), constipation (OR=2.41, 95% CI: 2.33-2.50), irritable bowel syndrome (OR= 1.31, 95% CI: 1.22-1.42), and diarrhea (OR=1.16, 95% CI: 1.09-1.23). Among MS patients, older age, female, white, depression and obesity were significant predictors of GI problems. The prevalence of other GI problems (such as bloating, celiac, cholecystitis, diverticulosis, gastric and peptic ulcer disease) was similar in both groups. LIMITATIONS: This data includes only hospitalized cases, which couldn't represent all MS population. Additionally, multiple admissions for the same patient might be problematic. However, there is no reason to believe that the pattern of admission is different between cases and controls. CONCLUSIONS: This study affirms a significant association between MS and GI problems based on a large scale population in about one third of MS cases. Dysphagia, fecal incontinence and constipation have the strongest association. Furthermore, addressing GI problems in MS patients should be an essential part of their management to improve their quality of life. Table 1 Shows the Significantly Higher GI Problems Among MS Patients OR odds ratio, CI confidence interval AGA Abstracts