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Background and Aim: Carbon dioxide (CO2), contained in carbonated beverages, could increase gastric volume inducing epigastric discomfort and reducing meal intake. We aimed to verify effect of a sugar-free carbonated beverage (CB) preload compared to a CB without CO2 (DCB) and water (W) during a standardized solid (SM) and liquid (LM) meal on gastric volume, gastrointestinal symptoms and eating perceptions. Subjects & Methods: After 300 ml of CB, DCB and W a standardized SM or LM was administered at constant rate (100 kcal/5 min) to ten healthy subjects (4 females, aged 22-30 years; BMI 21-24) on six days in a random order (D1: CB+SM; D2: DCB+SM; D3: W+SM; D4: CB+LM; D5: DCB+LM; D6: W+LM). Gastrointestinal symptoms (bloating and epigastric pain), eating perceptions (desire to eat, hunger, prospective of food consumption) and maximum satiety (MS) as total kcals intake were measured. Total gastric (TGV) and gas volumes by MRI after the beverages and at MS were also evaluated. All data are expressed as mean±SD. Results: Epigastric pain was absent in all experiment. A slight presence of epigastric bloating was found during the SM and LM without differences among beverages. Desire to eat, hunger and prospective of food consumption were not different among beverages and meals. TGV and gas volumes after beverages were significantly higher with CB than DCB and W (TGV: 715±194 ml, 521±83, 478±63, p

Mental stress (MS) may alter gastric sensory-motor function. The aim of the study was to assess postprandial autonomic nervous system activity and stress hormones in response to acute mental stress in dyspeptic patients.A total of 25 patients with postprandial distress syndrome (PDS; 11 mol L(-1), age 35.9 ± 9.3 years) and 12 healthy controls (5 mol L(-1), age 25.8 ± 4.6 years) underwent electrogastrography and (13) C-octanoate gastric emptying study using a 480 kcal solid meal. Heart rate variability (LF/HF ratio) and corticotrophin-releasing factor, adrenocorticotropic hormone (ACTH), and cortisol serum levels were also evaluated. Dyspeptic symptoms were scored by analogue visual scale and expressed as symptoms total score (TS). The protocol was repeated twice in each subject, with and without a mental stress test before the meal.Mental stress significantly increased postprandial symptoms severity in patients (TS: stress 111 ± 18 vs basal 50 ± 10; P0.05). Low-/high-frequency component ratio was significantly higher in patients after MS at 120 min (stress 5.46 ± 0.41 vs basal 3.41 ± 0.64; P0.01) and 180 min (stress 5.29 ± 0.2 vs basal 3.58 ± 0.19; P0.05). During stress session, in patients we found a significantly higher ACTH level than baseline at 30, 60, 90, 150, 210, 240, and 270 min and a significantly higher cortisol level at 30, 60, 90, 120, 210, and 270 min. Gastric emptying rate and electrical activity were not influenced by MS.In PDS patients, administration of MS before meal increases symptoms severity by inducing sympathetic hyperactivity and increased stress hormones levels. As the gastric emptying looks not altered, we conclude that these neurohormonal responses mainly affect sensitive function.

Enteric glial cells (EGCs) have been recently indicated as key regulators of intestinal inflammation in animals. Whether or not this is true and how these cells participate to inflammatory responses in humans is unknown.We isolated primary EGCs from human small bowel and then, we purified and characterized those using specific glial markers, such as S100B and glial fibrillary acidic protein (GFAP). To mimic an inflammatory scenario, we exposed EGCs to exogenous stimuli, such as lipopolysaccharide and interferon-gamma (LPS and IFN-γ), alone or in combination, to evaluate glial activation [measuring GFAP, S100B level together with c-fos, major histocompatibility complex (MHC) class II, inducible nitric oxide (iNOS) proteins expression and nitric oxide (NO) production] and proliferation, respectively.We showed that, when challenged with a combination of LPS and IFN-γ, EGCs are significantly activated, as indicated by their positivity to c-fos and MHC class II. Similarly, pro-inflammatory stimuli significantly increase the cell proliferation rate, the expression of both S100B and GFAP, and the NO production consequent to the induction of EGCs-derived iNOS protein, with the last being dependent on S100B-RAGE (receptor for advanced glycation endproducts) interaction.Our data provide the first evidence that human EGCs directly respond to pro-inflammatory stimuli by changing their expression profile and by proliferating. The finding that stimulated EGCs are able to produce NO points to a role of this cell population in the scenario of intestinal inflammation.

In the central nervous system glial-derived S100B protein has been associated with inflammation via nitric oxide (NO) production. As the role of enteroglial cells in inflammatory bowel disease has been poorly investigated in humans, we evaluated the association of S100B and NO production in ulcerative colitis (UC). S100B mRNA and protein expression, inducible NO synthase (iNOS) expression, and NO production were evaluated in rectal biopsies from 30 controls and 35 UC patients. To verify the correlation between S100B and NO production, biopsies were exposed to S100B, in the presence or absence of specific receptor for advanced glycation end-products (RAGE) blocking antibody, to measure iNOS expression and nitrite production. S100B and iNOS expression were evaluated after incubation of biopsies with lipopolysaccharides (LPS) + interferon-gamma (IFN-gamma) in the presence of anti-RAGE or anti-S100B antibodies or budesonide. S100B mRNA and protein expression, iNOS expression and NO production were significantly higher in the rectal mucosa of patients compared to that of controls. Exogenous S100B induced a significant increase in both iNOS expression and NO production in controls and UC patients; this increase was inhibited by specific anti-RAGE blocking antibody. Incubation with LPS + IFN-gamma induced a significant increase in S100B mRNA and protein expression, together with increased iNOS expression and NO production. LPS + IFN-gamma-induced S100B up-regulation was not affected by budesonide, while iNOS expression and NO production were significantly inhibited by both specific anti-RAGE and anti-S100B blocking antibodies. Enteroglial-derived S100B up-regulation in UC participates in NO production, involving RAGE in a steroid insensitive pathway. ispartof: Neurogastroenterology and Motility vol:21 issue:11 pages:1209- ispartof: location:England status: published

s / Digestive and Liver Disease 41S (2009), S1–S167 S23 to treated CD and normal biopsies. Flow cytometry analysis of T-LPL confirmed that IL-17A is over-produced in CD mucosa, and that both CD4+ and CD8+ cells were major sources of IL-17A (Table). Of the IL-17-producing cells, more than 50% co-expressed IFN-gamma. Blockade of IL-21 activity reduced IL-17A expression in cultures of both untreated CD and PT-stimulated treated CD biopsies. Conclusions: Data indicate that IL-17A expression is up-regulated in CD mucosa, and that IL-21 contributes to sustain IL-17 production. # C. Small bowel diseases 1. Celiac disease OC.05.6 EFFECT OF PROINFLAMMATORY STIMULI ON CELLULAR ACTIVATION AND NITRIC OXIDE PRODUCTION IN HUMAN PRIMARY ENTEROGLIAL CELLS C. Cirillo ∗ , G. Sarnelli, A. Mango, I. Esposito, S. Masone, G. Aprea, R. Cuomo Università degli Studi di Napoli Federico II, Napoli Background and aim: Enteric glial cells (EGC) are involved in intesti- nal inflammation. In humans, there are no in vitro models to study the relationships between EGC and inflammation. Aim: To set up a new method to isolate and purify a primary cul- ture of human EGC and to study EGC activation and responses’ to proinflammatory stimuli. Material and methods: Myenteric plexus preparations were isolated from human ileum of 15 patients undergoing surgery for colon car- cinoma and enzimatically dissociated. Ganglia were plated and cell cultures were grown to subconfluence. After 21 days, EGC were purified of contaminating cells by incubation with the anti-Thy-1.1 ab- coated magnetic beads and separation using a Dynal Magnet ® .Mixed EGC cultures and purified EGC cell line were immunocytochemi- cally characterized with anti-S100B, anti-glial fibrillary acidic protein (GFAP) and anti-alpha-smooth muscle actin antibodies to identify EGC and fibroblasts, respectively. To study the effects of inflammatory stimuli on EGC activation, cells were incubated with lipopolysaccha- ride (LPS, 1 μ g/mL), Tumor Necrosis Factor-alpha (TNF- α , 5ng/ml), interferon-gamma (IFN- γ , 100U/mL) for 32 h alone or in combination. A double labeling immunofluorescence using antibodies to S100B or GFAP was performed to identify EGC expressing c-fos in the nucleus, as a marker of cells activation. S100B mRNA, protein expression and secretion, iNOS expression and NO production were assessed. Results: In mixed EGC cultures, immunocytochemically analysis dis- played that 40% of cultured cells were EGC (S100B and GFAP positives), 50% were fibroblasts and neurons were virtually absent. In contrast, in purified EGC cell line, the presence of contaminating cells was significantly reduced by treatments with Dynabeads ® and the ma- jority of the cells were anti-GFAP and anti-S100B positives. Incubation with LPS and IFN- γ alone, or in combination with TNF- α , resulted in a consistent EGC’s activation (c-fos positive nuclei in S100B/GFAP positive cells), and significantly increased S100B expression, which was able to stimulate iNOS protein expression and NO production. Conclusions: We described for the first time a new method to isolate and purify EGC from human intestine. Proinflammatory cytokines di- rectly activate this cell population and stimulate NO production through the EGC-derived S100B protein

Background and aim: Meal-induced gastric distension and Cholecys- tokinin (CCK) are involved in the food intake. The relationship between meal gastric distension and CCK release have not been studied by non- invasive technique. We studied gastric volumes changes by Magnetic Resonance Imaging (MRI) and CCK serum levels after water preload and liquid (LM) and solid (SM) meals. Material and methods: Ten healthy subjects (4 F; Age 22 ± 3; BMI 23 ± 1) were studied on two days. Two test meals, a SM and LM with a similar nutrient composition (carbohydrate 46%; fat 32%; protein 22%) and energy content were used. Subjects were requested to ingest constant Kcal at 5 min interval (100 kcal/5 min) and to score their satiation level on a visual analogue scale graded 0–5 (1=threshold, 5= maximum satiation- MS). Experiment was scheduled as following: -10 min: 300 ml water preload (WPL); 0 min: solid or liquid meal until MS. CCK levels (ELISA, Phoenix, USA) were measured at baseline, after WPL, at 30, 60, 120 min of meal test. Gastric volume was evaluated by 1.5 T MRI at baseline, after water load, at MS and 120 min. Total (TGV) and proximal (PGV) gastric volumes (as difference respect to baseline) were manually traced by a trained observer. Data are presented as mean ± SD. Results: Kcal ingested and time to reach MS were significantly higher during SM (783 ± 244 kcal; 44 ± 14 min) than LM (630 ± 353 p < 0.01; 31 ± 17 p < 0.01). CCK serum peaks and time to peak were not different in LM and SM (1.62 ± 0.72 ng/ml vs 1.26 ± 0.87, and 41 ± 21 min vs 39 ± 14, respectively). TGV and PGV were not different between the two meal groups after WPL (SM: 271 ± 59 ml, 72 ± 46 vs LM: 309 ± 55, 74 ± 29) and at MS (SM: 554 ± 203 ml, 92 ± 32 vs LM: 560 ± 301, 132 ± 60). However TGV after WPL significantly correlated with CCK peaks in both meal groups (SM: r=0.73; p=0.016 and LM: r=0.62; p=0.049). PGV correlated with CCK peak in LM but not in SM (r=0.72, p=0.015; r=0.026, p=0.82). Conclusions: The MS induced by SM is not depending by GV and by CCK release. In contrast, the ability of LM to induce an earlier satiation is associated to the combined effect of the proximal stomach distension and the maximum CCK release. These results suggest a partial role of both total and proximal gastric distension in to determine CCK release. This relationship appears more evident with a liquid form of meal

Sumatriptan is able to improve symptoms of early satiety in dyspeptic patients by relaxing the gastric fundus. The aim of this study was to verify the efficacy of intranasal administration of sumatriptan on gastric sensory motor function, in order to provide a new pharmacotherapeutic approach to functional dyspepsia. Thirteen healthy subjects were investigated twice on separate days. A gastric barostat was used to study the effect of placebo and sumatriptan, 20 mg intranasally, on basal fundic tone. In addition, stepwise isobaric distensions were performed and perception was measured before and after administration of drugs. Placebo had no effect on gastric tone and on perception. Sumatriptan caused a small, but short-lasting gastric relaxation and had no significant effect on sensitivity to distension and gastric compliance. Unlike the subcutaneous formulation, the intranasal administration of sumatriptan had no effect on gastric sensory motor functions, and this probably reflects a low biovailability of intranasally administered sumatriptan.

The rapid pull-through (RPT) technique during esophageal manometry helps to identify various pressure profiles of hiatal hernia (HH), based on the presence of two high pressure zones: the diaphragmatic crura (DC) and the lower esophageal sphincter (LES). Our aim was to correlate different HH profiles with frequency of reflux episodes in patients with gastroesophageal reflux disease (GERD). Seventy-eight patients with GERD and HH underwent esophageal manometry with RPT and were grouped according to the prevalent pressure profile of HH. Twenty-four-hour pH-metry served to quantify traditional (TR) and nontraditional refluxes (drop of 1 pH unit with pH > 4 or pH < 4 and time < 5 sec) (NTR) during total, upright, and recumbent periods. The group with a prevalent "flat" HH profile, representing LES and DC impairment, had significantly more TRs in total time of reflux (P < 0.01) and in recumbent and upright periods (P < 0.05) compared to the group with a prevalence of the two pressure peaks, corresponding to LES and DC efficiency. However, the group with the flat profile had significantly more NTRs + TRs than the group with pressure peaks in total time (P < 0.01) and recumbent position (P < 0.001) but not in the upright position. Hiatal hernia predisposes to GERD, but only the associated impairment of the LES and diaphragmatic crura pressures represents a condition of high risk for gastroesophageal reflux events

s / Digestive and Liver Disease 42S (2010) S61–S192 S115 volume and carbon dioxide concentration of carbonated beverage must be explored to exclude interference with gastric function. # D. Motility and nerve-gut interactions 1. Upper and lower GI tract

The pathogenesis of gastroesophageal reflux disease (GERD) is considered multifactorial, but alterations of the esophagogastric junction (EGJ) and hiatal hernia play a prominent role. The correlations between hiatal hernia and the other pathogenetic factors are as yet unclear, and they need to be investigated by a methodological approach based on new anatomic and functional criteria. Our aim was to study, by stationary manometry, the relationships between small reducible hiatal hernia, identified by endoscopy, and esophageal peristalsis, in patients with and without GERD. According to the absence or presence of esophagitis (E), and the absence or presence of hiatal hernia (H), 58 subjects were divided into four groups: controls 10; H 14; E 10; and HE 24. Stationary manometry was performed by the rapid pull-through (RPT) technique, with catheter water perfused, to study the lower esophageal high pressure zone [lower esophageal sphincter (LES) and diaphragmatic crura] and the parameters of esophageal peristalsis. In patients with hiatal hernia, the various combinations of peak and/or deflection of manometric line pressure identified five EGJ profiles, only one of which reveals (by one-peak profile due to superimposed LES and diaphragmatic crura) the reducibility of the hernia. The frequency of the five profiles was calculated in the HE and H groups: a two-peak profile was significantly more prevalent in these patients, although less so in the group with esophagitis. In E patients the distal amplitude and the distal propagation of esophageal waves were significantly lower than in the other three groups (P0.05 vs controls and group HE; P0.01 vs group H). Furthermore, the distal amplitude was significantly higher in the group H than in the HE (P0.01). Our results show a better definition of hiatal hernia morphology, via the RPT technique, disclosing five pressure profiles. In addition, a significant link was found between small reducible hiatal hernia without GERD and wave amplitude of the distal esophagus. The amplification of peristaltic clearing may be considered the initial protective process against acid reflux; the breakdown of this mechanism may trigger the pathological sequence of GERD.

Background/Aims: The synthesis of pyridine nucleotides from nicotinamide requires adenosine triphosphate. In man when exogenous nicotinamide is poorly utilized in this synthesis, the excess follows a dissipative metabolic pathway and is excreted in urine as N-methylnicotinamide. In human cirrhosis N-methylnicotinamide serum levels are higher than normal, in basal condition and after nicotinamide oral load, The aim of this study was to verify N-methylnicotinamide production in relation to hepatic content of adenosine triphosphate during in vitro perfusion of rat liver, in normal conditions and after adenosine triphosphate depletion by metabolic stress. Methods: ''Stress'' was obtained by pre-washing with saline for 15 min before the perfusion with nutritive medium. Results: The adenosine triphosphate decrease in the stressed liver was 38% after pre-washing with saline and 80% at the end of nutritive perfusion, In control liver the corresponding decreases were 1% after pre-washing with nutritive medium and 65% at the end of perfusion with the same medium, The total nicotinamide adenine dinucleotide decreases were 44% and 56% in the stressed liver, and 19% and 52% in the control liver, The output levels of N-methylnicotinamide at 90 min of rat liver nutritive perfusion were 31.50+/-4.72 nmol/g for normal liver and 66.40+/-13.17 for stressed liver (p

Background and Aim: Colonic diverticulitis shows an high recurrence rate. Since no conclusive data are available about the optimal strategy in preventing diverticulitis recurrence, aim of our study was to assess three different therapeutic strategies in preventing diverticulitis recurrence Methods: 130 patients suffering from Acute Uncomplicated Diverticulitis (AUD) (81 Males, 49 Females, mean age 64.71 years, range 40-85) were prospectively assessed during a 2-year follow-up. After obtaining remission, the patients were treatedwithmesalazine 1.6 grams every day (59 patients, group A), or rifaximin 800 mg/day for 7 days every month (52 patients, group B), or did not take any therapy (19 patients, group C). Clinical, endoscopic and histological follow-up was performed after six, 12 and therefore every 12 months after diagnosis of AUD. Results: Fifty-four patients were excluded from final evaluation (see figure 1): 17 patients died; 21 were excluded due to taking unprescribed drugs during the scheduled treatment; 16 were lost to follow-up or were excluded because not compliant. Forty-four group A patients, 23 group B patients, 9 group C patients were available for the final assessment. Sustained remission was statistically higher in group A (93.18%) than group B (56.52%) and group C (44.44%) (A vs B: p=0.01; A vs C: p=0.03; B vs C: p=0.072). Persistence of endoscopic and histological damage were the only factors affecting diverticulitis recurrence. Conclusions: Patients taking mesalazine have lower risk of diverticulitis recurrence than patients taking rifaximin or taking no therapy, thanks to lower prevalence of persisting endoscopic and histological inflammation than in patients taking rifaximin or taking no therapy

colitis (mortality; clinical scores, weight loss) was significantly greater in TPH2 KO than in WT animals. The enhanced severity was also evident in enteric histological scores, leukocyte infiltration, and cytokine expression. These data are compatible with the ideas that by promoting inflammation, mucosal 5-HT enhances the defense of the bowel against infection, while neuronal 5-HT makes such an effect less damaging by protecting the ENS from inflammation. Mucosal and neuronal 5-HT may thus exert antagonistic effects on inflammation that are functionally synergistic. Supported by a clinical and translational pilot grant from Columbia University (KGM) and NS12969 (MDG).

Background and aim: Functional bowel disorders may follow acute intestinal infection. A single, retrospective study showed that a subset of dyspeptic patients had a history of gastroenteritis. No data are available in patients with prospectively identified postinfectious dyspepsia (PD). We aimed to characterize frequency, symptoms evolution and underlying mechanisms of functional dyspepsia after acute gastroenteritis. Material and methods: A total of 150 consecutive patients with undergoing acute gastroenteritis were screened and followed-up for 1 month (m). In patients with symptoms persistence upper GI endoscopy, breath test-based gastric emptying study and satiety testing (to estimate gastric fundus accommodation) were performed. Pattern and severity of symptoms were scored at 3, 6 and 12 m by standardized questionnaire. Gastric emptying and satiety testing were repeated at 6 m. Patients with previous diagnosis of FGIDs or organic disease were excluded. Normal values of gastric emptying rate and meal-induced satiety (120 min and 890 kcal, respectively) were obtained on 20 age/sex matched healthy subjects. Results: At baseline no signs of infection were found in the majority of the patients, except than giardia lamblia and salmonella tiphy in 3 and 1 patients. Persistence of dyspeptic symptoms at 1 m was observed in 31 subjects (18 male, age 28±10), with postprandial fullness, bloating, belching, nausea, epigastric pain, early satiety and vomiting being reported by 85, 70, 70, 56, 67, 48 and 19% of the patients, respectively; systematic analysis revealed that such pattern of symptoms was quite stable along the times. Although severity was gradually reducing for the majority of the symptoms, only patients reporting severe belching were significantly reduced at 12 m (70 vs. 12%, p