Fructans, such as inulin, are dietary fibers which stimulate gastro-intestinal (GI) function acting as prebiotics. Lipopolysaccharide (LPS) impairs GI motility, through production of reactive oxygen species. The antioxidant activity of various fructans was tested and the protective effect of inulin on colonic smooth muscle cell (SMC) impairment, induced by exposure of human mucosa to LPS, was assessed in an ex vivo experimental model. The antioxidant capacity of fructans was measured in an in vitro system that simulates cooking and digestion processes. Human colonic mucosa and submucosa, obtained from disease-free margins of resected segments for cancer, were sealed between two chambers, with the mucosal side facing upwards with Krebs solution with or without purified LPS from a pathogenic strain of Escherichia coli (O111:B4) and inulin (Frutafit IQ), and the submucosal side facing downwards into Krebs solution. The solutions on the submucosal side were collected following mucosal exposure to Krebs in the absence (N-undernatant) or presence of LPS (LPS-undernatant) or LPS+inulin (LPS+INU-undernatant). Undernatants were tested for their antioxidant activity and the effects on SMCs contractility. Inulin protective effects on mucosa and submucosa layers were assessed measuring the protein oxidation level in the experimental conditions analyzed. Antioxidant activity of inulin, which was significantly higher compared to simple sugars, remained unaltered despite cooking and digestion processes. Inulin protected the mucosal and submucosal layers against protein oxidation. Following exposure to LPS-undernatant, a significant decrease in maximal acetylcholine (Ach)-induced contraction was observed when compared to the contraction induced in cells incubated with the N-undernatant (4±1% vs 25±5% respectively, P<0.005) and this effect was completely prevented by pre-incubation of LPS with Inulin (35±5%). Inulin protects the human colon mucosa from LPS-induced damage and this effect appears to be related to the protective effect of inulin against LPS-induced oxidative stress.

Objective: To examine the mechanisms of action of ursodeoxycholic acid (UDCA) on gallbladder (GB) muscle cells in patients with symptomatic cholesterol gallstones (GSs) as it reduces the incidence of acute cholecystitis. Design and patients: A double-blind study was performed on 15 patients, 7 randomised to UDCA and 8 to placebo, treated for 4 weeks before cholecystectomy. Muscle contraction induced by cholecystokinin (CCK)-8, acetylcholine (ACh) and potassium chloride (KCl) was determined in enzymatically isolated GB muscle cells, and cholesterol levels were determined in plasma membranes. H₂O₂, lipid peroxidation, platelet-activating factor (PAF)-like lipids, prostaglandin E₂ (PGE₂) and catalase activity were determined as biochemical markers of oxidative stress and inflammation in muscle cells. Results: UDCA significantly increased GB muscle cell contraction induced by all concentrations of CCK-8, ACh and KCl, and reduced the plasma membrane cholesterol (mean (SD) 0.32 (0.16) vs 0.72 (0.5) μmol/mg of protein) compared with placebo. In GB muscle cells, UDCA treatment significantly decreased the levels of H₂O₂ (4.4 (1.9) vs 13.7 (5.3) μmol/mg of protein), lipid peroxidation (malondialdehyde levels 1.3 (0.4) vs 2.52 (0.7) nmol/100 mg of protein), PAF-like lipids (8.9 (4.9) vs 29.6 (7.1) pg/mg of protein) as well as the production of PGE₂ (142 (47) vs 365 (125) pg/mg of protein) and catalase activity (14.5 (9.4) vs 35.8 (12.7) units/mg of protein) when compared with placebo. Conclusion: These studies suggest that UDCA treatment improves GB muscle contractility by decreasing the cholesterol content in the plasma membrane of muscle cells, and the biochemical parameters of oxidative stress, thus explaining its possible therapeutic mechanisms in patients with symptoms of cholesterol GSs.

Aim: To define whether human colonic mucosa exposure to Lactobacillus rhamnosus GG (LGG), American Type Culture Collection (ATCC) 53103, may influence intestinal muscle cell contractility. Methods: Human colon specimens were obtained from disease-free margins of resected segments for cancer. The mucosa and submucosa, after dissection, were scaled between 2 chambers, with the luminal side of the mucosa facing upward and covered with 5 mL of Krebs solution and the submucosal side facing downward into 20 mL of Krebs solution. LGG or normal undernatant (N-undernatant) were added to the luminal side of the mucosa for 30 minutes. Smooth muscle cells (SMCs), isolated from the circular muscle layer, were exposed to undernatant for 30 minutes from the submucosal chamber of mucosa that was either preexposed to N-undernatant or to LGG (36 x 10(-9) colony forming units/mL) (LGG-undernatant). Acetylcholine (Ach) dose-response was obtained for SMCs. Results: SMCs exposed to N-undernatant presented a dose-response to Ach (maximal contraction: 32% +/- 5% with 1-mu M Ach) that is similar to unstimulated SMCs. Exposure to LGG-undernatant resulted both in an 18% +/- 3% cell shortening and a 78% +/- 7% inhibition of maximal Ach-induced contraction. When SMCs were directly exposed to LGG, a significant impairment of contraction (70% +/- 5%, compared with control cells) and a dose-dependent and time-dependent shortening were observed. Conclusions: After acute exposure of colonic mucosa to LGG, a significant shortening of SMCs is observed that possibly contributes to the reduced contractile response to Ach. Further studies are needed to establish the mechanisms of this effect that could account for the clinical efficacy of probiotics in intestinal disorders

Paralytic ileus is a temporary syndrome with impairment of peristalsis and no passage of food through the intestine. Although improvements in supportive measures have been achieved, no therapy useful to specifically reduce or eliminate the motility disorder underlying postoperative ileus has been developed yet. In this paper, we draw a plausible, physiologically fine-tuned scenario, which explains a possible cause of paralytic ileus. To this aim we extend the existing 1D intestinal electrophysiological Aliev-Richards-Wikswo ionic model based on a double-layered structure in two and three dimensions. Thermal coupling is introduced here to study the influence of temperature gradients on intestine tissue which is an important external factor during surgery. Numerical simulations present electrical spiral waves similar to those experimentally observed already in the heart, brain and many other excitable tissues. This fact seems to suggest that such peculiar patterns, here electrically and thermally induced, may play an important role in clinically experienced disorders of the intestine, then requiring future experimental analyses in the search for possible implications for medical and physiological practice and bioengineering.

Background: Gemcitabine is an acceptable alternative to best supportive care in the treatment of advanced biliary tract cancers. The human equilibrative nucleoside transporter 1 (hENT1) is a ubiquitous protein and is the major means by which gemcitabine enters human cells. Moreover, recent reports indicate a significant correlation between immunohistochemical variations of hENT1 in tumor samples and survival after gemcitabine therapy in patients with solid tumors. Materials and methods: We used immunohistochemistry to assess the abundance and distribution of hENT1 in tumor samples from radically resected cancer of the ampulla, and sought correlations between immunohistochemical results and clinical parameters including disease outcomes. Results: In the 41 individual tumors studied, 12 (29.3%) had uniformly high hENT1 immunostaining. Statistical analysis showed a significant correlation between hENT1 and Ki-67 (P = 0.04). No statistical significant differences were found between immunohistochemical findings and patient characteristics (sex, age, and tumor–node–metastasis). On univariate analysis, hENT1 and Ki-67 expression were associated with overall survival (OS). Specifically, those patients with overexpression of hENT1 showed a shorter OS (P = 0.022) and those with high Ki-67 staining showed a shorter survival (P = 0.05). Conclusions: hENT1 expression is a molecular prognostic marker for patients with resected ampullary cancer and holds promise as a predictive factor to assist in chemotherapy decisions.