Nefise B. Ulusoy

Glucagon-like peptide-1 inhibits gastric emptying via vagal afferent-mediated central mechanisms

Exogenous administration of glucagon-like peptide-1-(7-36) amide (GLP-1), an insulinotropic hormone, inhibits gastric emptying and acid secretion in humans. The role of GLP-1 as a regulator of gastric function is elusive. In gastric fistula rats, vagal afferent denervation and peripheral administration of the GLP-1 receptor antagonist exendin(9-39) amide enhanced emptying of a glucose meal, whereas intracerebroventricular exendin was ineffective. The rate of saline emptying was attenuated by peripheral as well as by central administration of GLP-1, and pretreatment with exendin by the respective routes reversed the inhibition by GLP-1. Vagal afferent denervation abolished the central and peripheral action of GLP-1 on gastric emptying. Neither peripheral cholinergic nor adrenergic blockade altered the delay of methyl cellulose meal emptying by intracisternal GLP-1 injection. Acid secretion in conscious pylorus-ligated rats was inhibited by intracisternal GLP-1 administration, whereas systemic GLP-1 was ineffective. These results support the notion that GLP-1 receptors participate in the central and peripheral regulation of gastric function. Furthermore, vagal afferent nerves mediate the inhibitory action of GLP-1 on gastric motor function. GLP-1 may be a candidate brain-gut peptide that acts as a physiological modulator of gastric function.Exogenous administration of glucagon-like peptide-1-(7-36) amide (GLP-1), an insulinotropic hormone, inhibits gastric emptying and acid secretion in humans. The role of GLP-1 as a regulator of gastric function is elusive. In gastric fistula rats, vagal afferent denervation and peripheral administration of the GLP-1 receptor antagonist exendin-(9-39) amide enhanced emptying of a glucose meal, whereas intracerebroventricular exendin was ineffective. The rate of saline emptying was attenuated by peripheral as well as by central administration of GLP-1, and pretreatment with exendin by the respective routes reversed the inhibition by GLP-1. Vagal afferent denervation abolished the central and peripheral action of GLP-1 on gastric emptying. Neither peripheral cholinergic nor adrenergic blockade altered the delay of methyl cellulose meal emptying by intracisternal GLP-1 injection. Acid secretion in conscious pylorus-ligated rats was inhibited by intracisternal GLP-1 administration, whereas systemic GLP-1 was ineffective. These results support the notion that GLP-1 receptors participate in the central and peripheral regulation of gastric function. Furthermore, vagal afferent nerves mediate the inhibitory action of GLP-1 on gastric motor function. GLP-1 may be a candidate brain-gut peptide that acts as a physiological modulator of gastric function.

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

BackgroundAlthough 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.MethodsPatients 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.ResultsTwenty-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.ConclusionLateral internal sphincterotomy and botulinum toxin injection treatments both seem to be equally effective in the treatment of chronic anal fissure.

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.

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.

Corticosteroid therapy augments gastroduodenal permeability to sucrose

Objective:The aim of the present study was to investigate whether corticosteroid therapy alters gastroduodenal mucosal permeability and whether permeability alteration is associated with macroscopic mucosal damage.Methods:Eight patients taking oral corticosteroid therapy (total prednisone-equivalent dose, 1.5 ± 0.1 g; duration, ∼30 days), nine patients with multiple sclerosis taking high-dose intravenous methyl-prednisolone therapy (total dose, 11.7 ± 0.5 g; duration, ∼9 days), and 20 age- and gender-matched controls were studied. Gastroduodenal permeability was determined using sucrose as a site-specific permeability probe. Five-hour urine was collected after ingesting 100 g of sucrose and its urinary excretion rate was measured using high-pressure liquid chromatography. Gastroduodenal endoscopy was performed before steroid therapy to exclude subjects with evidence of macroscopic mucosal lesions. The sucrose test and endoscopy were repeated after completion of corticosteroid therapy.Results:The urinary sucrose excretion rates were similar in the control group and in patient groups before corticosteroid therapy. The median excretion rate of sucrose increased four (one to 28)- and eight (two to 35)-fold, respectively, as compared with pretreatment values in patients taking oral steroid and high-dose intravenous methyl-prednisolone therapy (p < 0.01). Considering all patients together, subjects who received a mean prednisone-equivalent dose of 8.4 ± 1.5 g exhibited mucosal lesions, whereas patients who received 3.3 ± 1.8 g did not (p= 0.06). The posttherapy increments in sucrose excretion rates were associated with neither the presence of macroscopic lesions nor with the total steroid dose received.Conclusion:Corticosteroid therapy augments gastroduodenal permeability and high doses are associated with macroscopic mucosal lesions. Steroid-induced permeability increase does not appear to be associated with the presence of macroscopic mucosal lesions.

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.

Hyperglycemia-induced attenuation of rectal perception depends upon pattern of rectal balloon inflation

This study investigated the effects of acutehyperglycemia on conscious rectal perception in responseto two different rectal distension paradigms. Elevenhealthy males were studied in random order on two separate days during euglycemia andhyperglycemia with blood glucose concentrations clampedto 3.8 ± 0.6 and 14.8 ± 0.86 mmol/liter,respectively. In order to evoke sensory responses, rapidphasic and ramplike distensions were applied to anintrarectal balloon. Rectal sensation thresholds forinitial sensation, sensation of stool and discomfort,and sensory intensities were recorded. Additionally,anorectal motor responses were investigated during phasicdistension. Acute hyperglycemia did not modify rectalsensory pressure thresholds and perception scores inresponse to phasic distension. Neither did hyperglycemia alter the resting anal sphincter pressure, thepressure threshold for eliciting the rectoanalinhibitory reflex, or the maximal anal squeeze pressure.In contrast, hyperglycemia attenuated rectal perception in response to ramplike distension. Thepressure thresholds, 10.0 ± 1.8 and 17.0 ±3.6 mm Hg for initial sensation and discomfort,respectively, during hyperglycemia were significantlyhigher than the corresponding thresholds of 4.4 ± 1.4and 11.4 ± 1.9 mm Hg observed during euglycemia(P < 0.01). Higher rectal pressures were observed atall intensities of sensation of stool and discomfortduring hyperglycemia than those obtained duringeuglycemia (P < 0.01). Hyperglycemia did not alterthe compliance of the rectum. The results of this studydemonstrate that acute hyperglycemia attenuates rectal perception, and this attenuation depends uponthe type of distension employed. Our findings alsodemonstrate that anal sphincter motor function is notappreciably modified by hyperglycemia.

Inhibition of cholecystokinin-induced gallbladder contraction by atropine and pirenzepine in man

The effect of pirenzepine on cholecystokinin (CCK)-stimulated gallbladder contraction in man was compared with that of atropine. Following pretreatment with atropine, pirenzepine or physiological saline in a random order, 6 healthy male volunteers were infused for 75 min with CCK-octapeptide in doses that are reported to mimic physiological plasma concentrations. Gallbladder volumes were determined by real-time ultrasonography. Pirenzepine inhibited CCK-induced gallbladder volume reduction significantly up to 30 min (p less than 0.01) and the magnitude of this inhibition was similar to that of atropine. The results demonstrate that M1 neural muscarinic receptors are involved in the anticholinergic inhibition of CCK-induced gallbladder contraction in man.

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.

Influence of Pirenzepine on Gallbladder Contraction in Man Induced by Sham Feeding or an Intraduodenal Meal

Pirenzepine, an M1 muscarinic receptor antagonist, was tested for its ability to antagonize sham feeding- and intraduodenal fatty meal-stimulated gallbladder contraction in man. Intravenously administered pirenzepine abolished sham feeding-induced gallbladder contraction. Pirenzepine also inhibited contraction induced by intraduodenal meal, but this inhibition was of a lesser magnitude than the inhibition of sham feeding-induced contraction. The results demonstrate that the cephalic phase of gallbladder contraction is probably mediated by M1 muscarinic receptors while the duodenal phase of gallbladder contraction is partially mediated by M1 receptors.