mechanisms involved with gastrointestinal electrical stimulation and also indicate intestinal- gastro reflexes associated with electrical stimulation. S1856 Hunger Scores Correlate with the Occurrence of Pharmacologically Induced Gastric Phase 3 in Man Daphne C. Ang, Heleen Nicolai, Rita Vos, Pieter Vanden Berghe, Daniel Sifrim, Inge Depoortere, Theo L. Peeters, Jozef Janssens, Jan F. Tack Introduction:The control of appetite is regulated by the central nervous system (CNS) based on input from the periphery, especially the gastrointestinal tract (GIT). In its earliest description phase 3 of the migrating motor complex (MMC) was called ‘hunger contractions' (Itoh 1975). However the true relationship between hunger and phase 3 has never been described in detail. Aims: To investigate whether hunger scores vary with pharmacologically induced gastric and small intestinal phase 3 by administration of erythromycin (EM) and octreotide (OCT). Materials and Methods: 12 healthy subjects(6 males; 30.9±2.0 years) underwent antroduodenojejunal manometry on 2 separate occasions ≥1 week apart. Twenty minutes after a spontaneous phase 3, we administered EM 40mg i.v. or OCT 100µg s.c. Hunger was scored on 100 mm visual analogue scales (VAS) at 5-min intervals. Analysis of motility recordings used visual recognition of phases of the MMC and a semi-automated computer programme to quantify the motility index (MI). We compared hunger scores in different MMC phases, and analyzed linear correlation with the MI. Results: A mean number of 1.2±0.1 and 2.7±0.3 spontaneous gastric and small intestinal phase 3s occurred in all 12 subjects after a mean of 46±12 mins and 102±11 mins respectively. A total of 12 EM- induced and 27 OCT-induced phase3s were studied. Mean recording time for the study was 268±10 mins. Administration of EM was followed by a gastric phase 3 in all subjects after 17±2 mins, while OCT induced a first small intestinal phase 3 in all subjects after 2.3±0.2 mins. Compared to values 15 min before drug administration, EM induced a significant rise in hunger scores (29.2±7.0 vs. 61.7±8.0, p=0.02), and the peak hunger coincided with the EM-induced gastric phase 3. A significant correlation was found between antral MI and hunger scores before and after EM-induced gastric phase 3 (r=0.2428, p<0.05). In contrast, OCT did not induce a rise in hunger scores (31.1± 9.9 vs. 30.4±7.6, NS). No significant correlation was found for small intestinal MI and hunger scores before and after OCT-induced small intestinal phase 3 (r=0.0235, NS) although a weak but significant correlation was seen for antral MI with hunger scores (r=0.1961, p=0.03).Hunger scores recorded during EM induced gastric phase 3 were significantly higher than during OCT induced small intestinal phase 3 (61.7±8.0 vs 30.4±7.6, p=0.01). Conclusions: In the interdi- gestive state in man, EM-induced gastric phase 3, and not OCT-induced intestinal phase 3, is associated with a hunger peak. These data support the hypothesis that gastric phase 3 is a hunger signal from the GIT in the fasting state. S1857 Peripheral Obestatin Has No Effect On Fos Induction in Hypothalamic and Brainstem Nuclei Which Are Involved in Feeding Behavior Miriam Goebel, Anna-Sophia Wisser, Peter Kobelt, Andreas Stengel, Ivo R. van der Voort, Bertram Wiedenmann, Burghard F. Klapp, Yvette Tache, Hubert Monnikes Obestatin is a 23-amino acid peptide hormone produced in the stomach. This peptide originates from pro-ghrelin by post-translational cleavage. In contrast to ghrelin, it has been described that obestatin elicits anorexigenic effects in rodents. However, several studies showed that obestatin has no inhibitory effect on short term food intake in rodents. Therefore, the aim of the present study was to determine if the conflicting results could be due to environmental factors, e.g. influences of dark and light phases. Methods: Food intake was monitored in the dark or light phase in male Sprague-Dawley rats in response to intraperi- toneal (IP) injection of obestatin (1 or 5 µmol/kg), CCK-8S (3.5 nmol/kg, serving as a positive control) or 0.15 M NaCl after fasting (16 h, n=8/group) or ad libitum food intake (n=12-18/group) immediately before the dark or light phase started. The effect of these peptides on Fos expression pattern in hypothalamic (paraventricular nucleus, PVN; dorsom- edial hypothalamus, DMH) and brainstem nuclei (nucleus tractus solitarii, NTS) was exam- ined after IP injection of 5 µmol/kg obestatin compared to 1.75 nmol CCK-8S/kg or 0.15 M NaCl (n=4/group). Results: Obestatin had no effect on food intake during the light and dark phase in fed or fasted rats while CCK-8S induced a significant reduction of food intake in fasted as well as fed rats both in the light and dark phase during the first 30 min post injection. Likewise the number of Fos-ir positive neurons was not modulated by obestatin injection while CCK-8S increased neuronal activity in PVN, DMH and NTS. Conclusion: These data support that obestatin does not influence energy homeostasis in rodents. S1858 Long-Term High Lipids or High Carbohydrates Diets Alter Antro-Duodenal Motor Patterns Irrespective of Their Caloric Contents Dominique Bligny, Sylvie Guérin, Alain Chauvin, Benoit Janson, Charles-Henri Malbert Delayed gastric emptying induced by duodenal lipids is abolished in animals chronically fed by high lipids or high carbohydrates diets with a caloric concentration identical to a balanced diet (Bligny D. et al, 2007). This phenomenon might originate from the suppression of the duodenal lipids induced increase in proximal gastric tone. However, in humans, changes in antropyloroduodenal motility were also observed after high lipids but high caloric diet (Boyd K.A. et al, 2003). The aim of this study is to evaluate the possibility of similar alterations in distal gastric motor patterns after isocaloric but high lipids or high carbohydrates diets. Antropyloroduodenal motility was measured by low compliance manometry in 9 awake pigs (35 ± 3 kg) chronically fitted with a gastric and a duodenal canula. The animals were divided in three groups depending on the nature of their diet: normal (N), high fat (40% lipids, HF) and high carbohydrates (68% carbohydrates, HG). The energy density of each of these diets was identical (4.95 kcal.g-1). These diets were ingested equally in each group for at least 2 weeks. Afterwards, a side holes manometry catheter including a dent A-285 AGA Abstracts sleeve was placed astride the pylorus. The position of the catheter was constantly monitored by transmucosal potential difference measurement. Once the catheter in position, a duodenal intralipid infusion (1 ml.min-1) was started. Individual antral and duodenal pressure waves characteristics, antro-pyloro-duodenal propagation patterns, isolated pyloric pressure waves frequency and basal pyloric pressure were measured 30 minutes before and after a test meal (350 g Porridge). Before and after the test meal, the amplitude and frequency of antral and duodenal pressure waves were not significantly different between the three groups. Similarly, the number of pressure waves propagated either from the antrum to the duodenum or vice versa were not affected by the diet. The frequency of IPPW's was not different between groups either before or after the meal. However, basal pyloric pressure was significantly less for HF and HG compared to N group (8 ± 1.8, 9 ± 2.6, 12 ± 3.0 mmHg, p<0.05 for HF, HG and N respectively). Similar reduction has been already observed in humans with high fat but high caloric diet. Since our experimental design preserve the caloric concentration between diets, we demonstrate here that this effect relies only on the nature of the diet. Furthermore, this phenomenon, together with changes in proximal gastric tone, is likely causative for the suppression of lipid induced delayed emptying after HL and HG diets. S1869 TGFβ-Dependent Polyamine Depletion Is Associated with Cell Growth Inhibitory Effects of Isothiocyanate Sulforaphane in Colon Cancer Cells Bettina M. Ecker, Christoph Jochem, Waranya Kampan, Stefan Loitsch, Jürgen Stein, Sandra Ulrich Introduction: Sulforaphane (SFN), a naturally occurring isothiocyanate present in cruciferous vegetables, is an attractive agent due to its potent anticancer effects. SFN was shown to suppress the proliferation of various cancer cells In Vitro and In Vivo, whereas the underlying molecular mechanisms remain largely unknown. Previous studies could demonstrate, that modulation of polyamine metabolism provides a chemopreventive strategy of different phyto- chemicals. Thus, the objective of this study was to elucidate a possible regulation of ornithine decarboxylase (ODC), the key enzyme of polyamine biosynthesis, by SFN in a cell culture model of colorectal cancers. Methods: Caco-2 and SW620 cells were cultures under standard conditions. Cell growth was determined by BrdU incorporation and crystal violet staining. Protein levels of TGFβ and phospho-Smad were examined by Western blot analysis. TGFβ secretion was measured in cell culture supernatants by a commercially available ELISA. Ornithine decarboxylase activity was assayed radiometrically measuring [14CO2] liberation. Results: Sulforaphane [5-50µM] inhibits cell growth significantly both in Caco-2- and SW620 cells in a dose and time dependent manner (***p<0.001). Antiproliferative effects of Sulfor- phane closely correlate with a dose-dependent reduction of ODC activity (~50% at [50µM], ***p<0.001) after 24h. This was further confirmed by the addition of exogenous polyamine spermine [5µM] and spermidine [10µM], which significantly counteracted cell growth inhib- itory effects of SNF after 24h. Furthermore, sulforaphane causes a concentration dependent induction of TGFβ protein expression after 1 to 6 h (~100% at [50µM]) and TGFβ secretion after 24 h as well as a prominent phosphorylation of Smad2 (~40% at [50µM], a downstream component of TGFβ signaling. Moreover, co-treatment with TGFβ receptor kinase inhibitor SB431542 [10µM] largely abolished inhibitory effects of SFN on ODC activity. Conclusion: These data provide evidence for the involvement of TGFβ signaling in SFN mediated inhibition of ODC activity and thus polyamine depletion in colorectal cancer cells. S1870 Nutrient Intake and Microsatellite Instability in Sporadic Colon Cancers Sung-Wook Oh, Young-Ho Kim, Dong Kyung Chang, Hee Jung Son, Poong-lyul Rhee, Jae J Kim, Jong Chul Rhee, Woo-Yong Lee, Ho Kyung Chun, Duk-Hwan Kim PURPOSE: Microsatellite instability (MSI) occurs in 10-20% of the sporadic colon cancer. However, little is known about the role of diet in MSI-related colon carcinogenesis. The purpose of this study was to determine if dietary intake of nutrients previously reported as being associated with colon cancer was related specifically to the MSI disease pathway. METHODS: During June 2003 to December 2005, 389 patients who were diagnosed as colon cancer were assessed by an interview-based questionnaire for diet habit. The consumption frequency and sizes per consumption of 191 food items in the preceding year were collected and average daily intake of nutrient was calculated using software developed by the Korean Nutritional Society. Eligible criteria for study included ages 25 to 90 years at the time of diagnosis and ability to give informed consent and complete the interview. We compared dietary intake for cases with and without MSI to further determine associations that are specific to the MSI disease pathway. RESULTS: Riboflavin intake was inversely associated with microsatellite instability-high (MSI-H) tumor when compared with microsatellite stable/ microsatellite instability-low (MSS/MSI-L) tumor [odds ratio (OR), 0.335; 95% confidence interval (CI), 0.142-0.791, P=0.013]. Most other evaluated nutrients were not distinctively associated with a specific MSI status. CONCLUSION: Our data suggest that riboflavin may decrease the risk of MSI-H carcinomas. Most other dietary factors do not appear operate exclusively in the MSI disease pathway. [Keywords: Diet; Riboflavin; Microsatellite Instability; Colorectal Neoplasms] Characteristics of the study population AGA Abstracts