Orlistat accelerates gastric emptying and attenuates GIP release in healthy subjects.

Orlistat, an inhibitor of digestive lipases, is widely used for the treatment of obesity. Previous reports on the effect of orally ingested orlistat together with a meal on gastric emptying and secretion of gut peptides that modulate postprandial responses are controversial. We investigated the effect of ingested orlistat on gastric emptying and plasma responses of gut peptides in response to a solid mixed meal with a moderate energy load. In healthy subjects, gastric emptying was determined using scintigraphy and studies were performed without and with 120 mg of orlistat in pellet form in random order. Orlistat shortened t lag and t half and decreased the area under the gastric emptying curve. Orlistat significantly attenuated the secretion of glucose-dependent insulinotropic polypeptide (GIP) but did not alter the plasma responses of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), pancreatic polypeptide (PP), and insulin. There was no peptide YY (PYY) response. Area under the curve of gastric emptying was positively correlated with integrated secretion of GIP (r=0.786) in orlistat and was negatively correlated with integrated plasma response of GLP-1 (r=-0.75) in control experiments, implying that inhibition of fat absorption modifies determinants of gastric emptying of a meal. Orlistat administered similar to its use in obesity treatment accelerates gastric emptying of a solid mixed meal with a moderate energy load and profoundly attenuates release of GIP without appreciably altering plasma responses of CCK, GLP-1, and PP. Since GIP is being implemented in the development of obesity, its role in weight control attained by orlistat awaits further investigation.

Impact of Helicobacter pylori eradication on the anti-secretory efficacy of lansoprazole in gastroesophageal reflux disease patients.

BACKGROUND: Helicobacter pylori eradication was recommended for the prevention of atrophic gastritis in gastroesophageal reflux disease (GERD) patients on long-term omeprazole treatment. It has been also shown that the treatment with proton pump inhibitors produces lower intragastric pH after H. pylori eradication in subjects with peptic ulcer and healthy individuals. The aim of the present study was to test the hypothesis of whether the efficacy of lansoprazole is reduced after the eradication of H. pylori in GERD patients with peptic esophagitis. METHODS: Eight-hour intragastric pH recordings were performed before and after an 8-day course of lansoprazole (30 mg once daily) in 10 H. pylori-positive male patients with reflux esophagitis and were repeated after the H. pylori eradication. Intragastric acidity was measured by using an antimony electrode placed 10 cm below the cardia. RESULTS: Baseline median preprandial, post-prandial, total intragastric pH and the percentage of time with pH < 3 were not different before and after H. pylori eradication without lansoprazole treatment. During lansoprazole treatment, median post-prandial intragastric pH was lower (4 vs 2.7; P < 0.05) and the percentage of time with pH < 3 was longer (3.4%vs 41.8%; P < 0.05) after H. pylori eradication. Median total intragastric pH tended to be lower after eradication but no difference was found in preprandial median pH. CONCLUSIONS: In patients with reflux esophagitis treated with lansoprazole, intragastric pH increased significantly when H. pylori was present, especially in the post-prandial period, whereas baseline pH remained unchanged after H. pylori eradication.

Protective effect of melatonin and omeprazole against alendronat-induced gastric damage.

Alendronate causes serious gastrointestinal adverse effects. We aimed to investigate if free radicals have any role in the damage induced by alendronate and if melatonin or omeprazole is protective against this damage. Rats were administered 20 mg/kg alendronate by gavage for 4 days, either alone or following treatment with melatonin or omeprazole. On the last day, following drug administration, pilor ligation was performed, and 2 hr later rats were killed and stomachs were removed. Gastric acidity and tissue ulcer index values, lipid peroxidation, and myeloperoxidase and glutathione levels, as well as the histologic appearance of the stomach tissues, were determined. Chronic oral administration of alendronate induced significant gastric damage, increasing lipid peroxidation and myeloperoxidase activity, while tissue glutathione levels decreased. Treatment with omeprazole or melatonin prevented this damage as well as the changes in biochemical parameters, and melatonin appeared to be more efficient than omeprazole in protecting the mucosa. Intraperitoneal administration of alendronate did not cause much gastric irritation. Findings of the present study suggest that alendronate induces oxidative gastric damage by a local irritant effect and that melatonin and omeprazole are protective against this damage due to their antioxidant properties.

Effect of Helicobacter pylori eradication on anti-thrombotic dose aspirin-induced gastroduodenal mucosal injury.

BACKGROUND: Helicobacter pylori infection and non-steroidal anti-inflammatory drugs are two major causes of gastric injury but the effect of H. pylori eradication on the development of aspirin-induced gastric mucosal injury is unclear. The aim of the present study was to investigate the effect of Helicobacter pylori eradication on gastroduodenal mucosal injury induced by antithrombotic doses of aspirin. METHODS: Patients who had been planned to start on medium-dose aspirin (300 mg) for any kind of indication were included in the study. All subjects underwent upper gastrointestinal endoscopy for determination of H. pylori status and Lanza score. The H. pylori-positive patients were randomized to receive either aspirin + eradication (omeprazole 20 mg b.i.d. and amoxicillin 500 mg q.i.d. for 2 weeks) or aspirin + placebo eradication. Endoscopic reassessment was done 4 months after the onset of aspirin or when symptoms developed. RESULTS: Thirty-two patients (placebo group n = 16, H. pylori-eradicated group n = 16) completed the study and Lanza scores of both groups were similar before treatment. Lanza scores significantly increased in the placebo group (0.69 +/- 0.87 vs 2.25 +/- 1.3, P < 0.0001) and did not change in the H. pylori-eradicated group after aspirin treatment (0.43 +/- 0.72 vs 0.75 +/- 0.93, P > 0.05). CONCLUSION: Helicobacter pylori eradication may prevent medium-dose aspirin-induced gastroduodenal mucosal injury.

Botulinum toxin injection versus lateral internal sphincterotomy in the treatment of chronic anal fissure: a non-randomized controlled trial.

BACKGROUND: Although lateral internal sphincterotomy is the gold-standard treatment for chronic anal fissure, intrasphincteric injection of botulinum toxin seems to be a reliable new option. The aim of this non-randomized study is to compare the effect of lateral internal sphincterotomy and botulinum toxin injection treatments on the outcome and reduction of anal sphincter pressures in patients with chronic anal fissure. METHODS: Patients with chronic anal fissure were treated with either botulinum toxin injection or lateral internal sphincterotomy by their own choice. Maximal resting pressure and maximal squeeze pressure measurements were performed before and 2 weeks after treatments by anal manometry. Patients were followed for fissure relapse during 14 months. RESULTS: Twenty-one consecutive outpatients with posterior chronic anal fissure were enrolled. Eleven patients underwent surgery and ten patients received botulinum toxin injection treatment. Before the treatment, anal pressures were found to be similar in both groups. After the treatment, the maximal resting pressures were reduced from 104 +/- 22 mmHg to 86 +/- 15 mmHg in the surgery group (p < 0.05) and from 101 +/- 23 mmHg to 83 +/- 24 mmHg in the botulinum toxin group (p < 0.05). The mean maximal squeeze pressures were reduced from 70 +/- 27 mmHg to 61 +/- 32 mmHg (p > 0.05) in the surgery group, and from 117 +/- 62 mmHg to 76 +/- 34 (p < 0.01) in the botulinum toxin group. The fissures were healed in 70 percent of patients in the botulinum group and 82 percent in the surgery group (p > 0.05). There were no relapses during the 14 months of follow up. CONCLUSION: Lateral internal sphincterotomy and botulinum toxin injection treatments both seem to be equally effective in the treatment of chronic anal fissure.