Effects of a bicarbonate-alkaline mineral water on digestive motility in experimental models of functional and inflammatory gastrointestinal disorders

This study investigates the effects of Uliveto, a bicarbonate-alkaline mineral water, in experimental models of diarrhea, constipation and colitis. Rats were allowed to drink Uliveto or oligomineral water (control) for 30 days. Diarrhea and constipation were evoked by 16,16-dimethyl-prostaglandin E(2) (dmPGE(2)) or loperamide, respectively. Colitis was induced by 2,4-dinitrobenzenesulfonic acid (DNBS) or acetic acid. Gastric emptying, small-intestinal and colonic transit were evaluated. dmPGE(2)-induced diarrhea reduced gastric emptying and increased small-intestinal and colonic transit. In this setting, Uliveto water enhanced gastric emptying, and this effect was prevented by L-365,260 (gastrin receptor antagonist). Loperamide-induced constipation reduced gastric emptying, small-intestinal and colonic transit, and these effects were prevented by Uliveto water. L-365,260 counteracted the effects of Uliveto on gastric emptying, while alosetron (serotonin 5-HT(3) receptor antagonist) blunted the effect of Uliveto on colonic transit. Gastric emptying, small-intestinal and colonic transit were reduced in DNBS-induced colitis, and Uliveto water enhanced gastric emptying and normalized small-intestinal and colonic transit. Gastric emptying, small-intestinal and colonic transit were also reduced in acetic acid-induced colitis, and Uliveto increased both gastric emptying and small-intestinal transit. In conclusion, Uliveto water exerts beneficial effects on gastrointestinal motility in the presence of bowel motor dysfunctions. The effects of Uliveto water on gastric emptying depend on gastrin-mediated mechanisms, whereas the activation of serotonergic pathways accounts for the modulation of colonic functions.     

The eflects of levosulpiride on gastric and gall-bladder emptying in functional dyspepsia

Background: 50 % of patients with functional dyspepsia have delayed gastric emptying. Levosulpiride is an orthopramide drug that stimulates gastrointestinal motility. Aim of our study was to evaluate the effect of levosulpiride on symptoms and gastric and gall-bladder emptying, in dyspeptic patients. Methods: Thirty adult patients, treated for 20 days with levosulpiride (75 mg/day) or placebo, were evaluated in a randomized double-blind study. Symptoms were assessed by a cumulative index and overall intensity (visual analogue line). Gastric and gall-bladder emptying were evaluated by epigastric impedance (liquid meal) and real-time ultrasonography (mixed meal). Results: Levosulpiride, with respect to placebo, accelerated the mean gastric half-emptying time of liquids (P < 0.05), gastric emptying (P < 0.001 at 180 min; P < 0.05 at 240 min), and gall-bladder emptying (P < 0.05 at 60 and 120 min) emptying after a solid-liquid mixed meal. Both the mean cumulative index (P < 0.05) and the overall intensity (P < 0.025) of dyspeptic symptoms were reduced significantly by levosulpiride. Conclusions: Our results showed that levosulpiride can be usefully employed in patients affected by functional dyspepsia.     

Comparative effects of levosulpiride and cisapride on gastric emptying and symptoms in patients with functional dyspepsia and gastroparesis

BACKGROUND: The efficacy of several prokinetic drugs on dyspeptic symptoms and on gastric emptying rates are well-established in patients with functional dyspepsia, but formal studies comparing different prokinetic drugs are lacking. AIM: To compare the effects of chronic oral administration of cisapride and levosulpiride in patients with functional dyspepsia and delayed gastric emptying. METHODS: In a double-blind crossover comparison, the effects of a 4-week administration of levosulpiride (25 mg t.d.s.) and cisapride (10 mg t.d.s.) on the gastric emptying rate and on symptoms were evaluated in 30 dyspeptic patients with functional gastroparesis. At the beginning of the study and after levosulpiride or cisapride treatment, the gastric emptying time of a standard meal was measured by 13C-octanoic acid breath test. Gastrointestinal symptom scores were also evaluated. RESULTS: The efficacy of levosulpiride was similar to that of cisapride in significantly shortening (P < 0.001) the t1/2 of gastric emptying. No significant differences were observed between the two treatments with regards to improvements in total symptom scores. However, levosulpiride was significantly more effective (P < 0.01) than cisapride in improving the impact of symptoms on the patients' every-day activities and in improving individual symptoms such as nausea, vomiting and early postprandial satiety. CONCLUSION: The efficacy of levosulpiride and cisapride in reducing gastric emptying times with no relevant side-effects is similar. The impact of symptoms on patients' everyday activities and the improvement of some symptoms such as nausea, vomiting and early satiety was more evident with levosulpiride than cisapride.     

Domperidone is more effective than cisapride in children with diabetic gastroparesis

BACKGROUND: Disorders of gastrointestinal motility are commonly detected in patients with insulin-dependent diabetes mellitus and are associated with significant morbidity. They contribute to poor metabolic control of diabetes. AIM: To assess the effect of an 8-week course of domperidone or cisapride on gastric electrical activity, gastric emptying time and dyspeptic symptoms in children with insulin-dependent diabetes mellitus and gastroparesis. METHODS: Dyspeptic symptoms were assessed by a score system, gastric emptying time was measured by ultrasonography and gastric electrical activity was obtained by electrogastrography. Fourteen children received domperidone and 14 received cisapride. The median (range) ages were 11.6 years (5-15 years) and 12 years (6-16.9 years), respectively. Symptom assessment, ultrasonography and electrogastrography were repeated at the end of the trial. Fasting and fed (180 min after feeding) glycaemia and haemoglobin A, C (HbA1c) levels were also measured. RESULTS: At the end of the trial both groups showed a significant decrease in symptomatic score; however, the score was markedly lower in the domperidone group than in the cisapride group (P < 0.01). Domperidone was significantly more effective than cisapride in reducing the gastric emptying time (P < 0.05), normalizing gastric electrical activity (P < 0.05) and decreasing the prevalence of episodes of gastric dysrhythmia (P < 0.01). Domperidone was also more effective than cisapride in improving diabetic metabolic control. No potentially drug-related adverse effects occurred. CONCLUSIONS: In children with insulin-dependent diabetes mellitus complicated by dyspeptic symptoms and gastroparesis, domperidone is superior to cisapride in reversing gastric emptying delay and gastric electrical abnormalities, as well as in improving dyspeptic symptoms and diabetic metabolic control.     

Correlation between symptoms of diabetic gastroparesis and results of gastric scintigraphy

Background  

delayed gastric emptying is detectable in 20–40% of patients with type 1 and type 2 diabetes. The prevalence of symptoms suggestive for diabetic gastroparesis is much lower. The aim of the study was to evaluate the gastric emptying and to correlate the results with dyspeptic symptoms.     

Influence of delaying gastric emptying on meal-related symptoms in healthy subjects

BACKGROUND: Although delayed gastric emptying is often found in functional dyspepsia, a causal role for delayed emptying in inducing symptoms has not been demonstrated. AIM: To investigate the influence of delaying gastric emptying rate in healthy volunteers on the occurrence of meal-related symptoms. METHODS: Fourteen healthy subjects (six men, mean age 23 +/- 1) underwent gastric emptying studies twice using the 14C octanoic acid and 13C glycin breath test after pre-treatment with saline or sumatriptan 6 mg s.c. Breath samples were taken before meal and at 15-min intervals for a period of 360 min postprandially. At each breath sampling, the subject was asked to grade the intensity (0-6) of four dyspeptic symptoms. RESULTS: Sumatriptan pre-treatment significantly delayed solid but not liquid gastric emptying (t1/2 respectively 159 +/- 11 vs. 112 +/- 9 min, P < 0.005 and 134 +/- 11 vs. 116 +/- 12 min, N.S.). Sumatriptan significantly decreased the mean cumulative symptom score (21.3 +/- 5.5 vs. 8.0 +/- 2.6, P = 0.01), as well as scores for each individual symptom. CONCLUSION: A moderate delay in gastric emptying in health is not associated with an increase of meal-related symptoms. This observation argues against a causal role for delayed gastric emptying in the pathogenesis of dyspeptic symptoms.     

The effects of fusidic acid on the inflammatory response in rats.

In the present study the antiinflammatory activity of fusidic acid was investigated in a model of formalin-induced edema formation in rats. Fusidic acid at doses of 50 and 100 mg kg (-1) was administered p.o. to rats for ten days. It was observed that fusidic acid inhibited edema formation significantly (P< 0.05). After this period, gastric mucus secretions were evaluated by the Alcian blue dye binding method. Mucus secretion decreased significantly in the control group. Fusidic acid increased the amount of gastric mucus. Moreover, in all of the animals with paw edema, platelet count was also increased. Red blood cell count, haemoglobin concentration and haematocrit were all higher in the control group than those of the fusidic acid groups. The present observations suggest that fusidic acid suppressed the inflammatory response and stimulated the gastric mucus secretion and it prompts further experiments for delineation of the mechanism of these actions as well as clinical trials.     

Effect of a mineral water on gastric emptying of patients with idiopathic dyspepsia

The antidyspeptic property of mineral waters has for many years been based on empirical data. In the present paper we evaluated the effects of one type of mineral water, Tettuccio water from Montecatini, on gastric emptying in patients with idiopathic dyspepsia. Fourteen subjects, eight patients with idiopathic dyspepsia and delayed gastric emptying at scintigraphy and six healthy subjects with normal gastric emptying were studied. The gastric emptying of mineral water was studied with a scintigraphic method and compared with that of tap water. In patients with idiopathic dyspepsia, gastric emptying of both waters was slower than in controls but the gastric emptying of mineral water was significantly faster than that of tap water, both in dyspeptic patients and in healthy subjects. In conclusion, this mineral water stimulates gastric emptying. Further studies are needed on the possible role of this water in the management of chronic idiopathic dyspepsia.     

Does lansoprazole influence postprandial digestive function?

The effects of a potent proton pump inhibitor on postprandial digestive functions were compared with those of a placebo in a double-blind randomized crossover study. Six healthy male volunteers received 30 mg/day of lansoprazole or placebo for 7 days, with a wash-out period of 14 days. As compared to placebo, lansoprazole induced a marked decrease of mean ± S.E.M. 3-h gastric acid secretion from 46.8 ± 10.8 mmol to 10.9 ± 2.5 mmol (P < 0.05), and a decrease of the volume of gastric contents emptying into the duodenum from 1043 ± 139 ml to 660 ± 87 ml (P < 0.05). However, gastric emptying remained unchanged with meal gastric emptying half times of 66 ± 5 min and 67 ± 13 min, respectively. During the 3-h postprandial period, duodenal lipase and chymotrypsin outputs were 366 ± 123 KIU and 56 ± 11 KIU with lansoprazole and 436 ± 119 KIU and 49 ± 8 KIU with placebo (N.S.). Bile acid outputs were 5.3 ± 0.7 mmol and 6.0 ± 1.0 mmol, respectively (N.S.) There was no change in kinetic profiles of biliarypancreatic secretion. We conclude that potent inhibition of gastric secretion by chronic administration of a proton pump inhibitor at usual therapeutic dose alters neither meal gastric emptying nor postprandial biliary-pancreatic secretion.     

功能性消化不良病人胃排空功能改变的危险因素

目的 :研究功能性消化不良病人胃排空功能的异常与症状之间的关系及西沙比利疗效。方法 :对 36例功能性消化不良病人 4种症状进行分级 ,并行胃排空检查 ,分别与健康人对照组 12例比较 ,并与西沙比利 5mg ,po ,tid治疗后自身对照比较。结果 :半排时间固体实验组治疗前为 5 9min±s 10min ,健康人对照组为 5 0min± 11min(P <0 .0 5 ) ,治疗后为 4 9min± 9min(P <0 .0 5 ) ;液体半排时间分别为 13min± 4min ,15min± 6min (P >0 .0 5 ) ,治疗后为 13min± 3min与治疗前比较P >0 .0 5。腹胀、腹痛、恶心、呕吐与固体胃排空延迟的回归系数分别为 0 .381,0 .5 43,0 .178,0 .4 63。结论 :功能性消化不良病人固体胃排空延迟 ,且可被西沙比利纠正 ,腹胀、腹痛、呕吐是固体胃排空延迟的危险因素     

Prokinetic effect of gut-oriented hypnosis on gastric emptying

BACKGROUND: No data are available on the effect of hypnosis on gastric emptying. AIM: To determine the effect of a hypnosis session on gastric emptying and dyspeptic symptoms. METHODS: We studied emptying by ultrasonography and epigastric sensations in 11 healthy subjects and in 15 patients affected by functional dyspepsia under three conditions according to a fixed schedule: (a) basal, (b) after cisapride and (c) during a 90 min hypnotic trance. Eight healthy subjects repeated an emptying study listening to relaxing music. Statistical analysis was performed using the Friedman test or RM-ANOVA. RESULTS: In dyspeptics, the postprandial increase in the antral area was significantly smaller during the hypnosis trance than under the basal and the cisapride conditions. For the patients gastric emptying was significantly shortened by cisapride, and even more by hypnosis (basal 274 +/- 16.8 min; cisapride 227 +/- 13.2; hypnosis 150 +/- 9.7) whereas for healthy subjects it was shortened only by hypnosis. The repeated study in healthy subjects listening to relaxing music showed no significant difference compared with the basal. Epigastric sensations were improved in dyspeptics by hypnosis, but not by cisapride. CONCLUSIONS: Gut-oriented hypnosis is effective in shortening gastric emptying both in dyspeptic and in healthy subjects.     

New Frontiers in Gut Nutrient Sensor Research: Monosodium l-Glutamate Added to a High-Energy,High-Protein Liquid Diet Promotes Gastric Emptying: a Possible Therapy for Patients With Functional Dyspepsia

Functional dyspepsia is a clinical syndrome that features abdominal symptoms centered in the upper abdomen without an organic basis. Three possible mechanisms of gastric dysfunction could be related to functional dyspepsia: 1) delayed gastric emptying, 2) impaired gastric accommodation to food intake, and 3) hypersensitivity to gastric distention. Delayed gastric emptying has been suggested to lead to prolonged antral distension that causes dyspeptic symptoms. Delayed gastric emptying is therefore a focal point of debate about anorexia caused by dyspepsia, and prokinetic agents are often administered in Japan for its treatment. Recently, we found that addition of monosodium l-glutamate (MSG) to a high-energy liquid diet rich in casein promoted gastric emptying in healthy men. Therefore, another potential method to improve delayed gastric emptying could be enhancement of chemosensors that activate the autonomic nervous system innervating the gastrointestinal tract. In conclusion, enrichment with glutamate promoted gastric emptying after intake of a high-protein meal, suggesting that free glutamate is important for protein digestion and that MSG may be helpful for management of delayed gastric emptying in patients with functional dyspepsia.     

The long-term effect of Helicobacter pylori eradication therapy on symptoms in dyspeptic patients with fundic atrophic gastritis

AIM: To investigate whether curing Helicobacter pylori infection improves symptoms over the long-term in Japanese patients with nonulcer dyspepsia and fundic atrophic gastritis. METHODS: Ninety H. pylori-positive dyspeptic patients with fundic atrophic gastritis were enrolled in this study. We performed a randomized double-blind placebo-controlled trial comparing triple therapy (n=45) with that of placebo alone (n=45). Inflammation and mucosal atrophy were scored according to the Updated Sydney System. Symptoms were scored on a scale of 0 to 3 for six items. Fasting samples of gastric juice were taken before endoscopy, and gastric pH was determined. Serum gastrin and pepsinogen levels were measured, and body mass index was determined. These patients were followed up for 3 years, and all measures were evaluated both before and after therapy. RESULTS: Significant improvement in dyspeptic symptoms and gastritis scores, significant decrease in gastric pH, and significant increase in body mass index were found after 3 years eradication in nonulcer dyspepsia patients treated successfully for H. pylori infection. There were no significant changes in the placebo group. CONCLUSION: Our study shows that eradicating of H. pylori results in significant long-term reduction in symptoms of nonulcer dyspepsia with fundic atrophic gastritis.     

腹部手术后胃排空障碍15例临床分析

目的探讨腹部手术后功能性胃排空障碍的病因、诊断及治疗。方法对15例腹部术后功能性胃排空障碍病例的病因及诊治进行回顾性分析。结果功能性胃排空障碍均发生于腹部手术4~14d,经非手术治疗后,恢复胃动力出院,7例患者30d内恢复,7例患者30~50d内恢复,1例术后72d出院。结论腹部术后功能性胃排空障碍是多因素的,上消化道造影及胃镜检查是诊断本病的主要辅助检查方法,一般采取非手术治疗可治愈。     

Extrathyroidal actions of antithyroid thionamides

Some compounds having thionamide structure inhibit thyroid functions. Such antithyroid thionamides include mercaptomethylimidazole (methimazole), thiourea and propylthiouracil, of which mercaptomethylimidazole is widely used to treat hyperthyroidism. Undesirable side effects develop from these drugs due to extrathyroidal actions. Antithyroid thionamides inhibit lactoperoxidase which contributes to the antibacterial activities of a number of mammalian exocrine gland secretions that protect a variety of mucosal surfaces. These drugs stimulate both gastric acid and pepsinogen secretions, thereby augmenting the severity of gastric ulcers and preventing wound healing. Increased gastric acid secretion is partially due to the H2 receptor activation, and also through the stimulation of the parietal cell by intracellular generation of H2O2 following inactivation of the gastric peroxidase-catalase system. Severe abnormalities may develop in blood cells and the immune system after thionamide therapy. It causes agranulocytosis, aplastic anemia, and purpura along with immune suppression. Olfactory and auditory systems are also affected by these drugs. Thionamide affects the sense of smell and taste and also causes loss of hearing. It binds to the Bowman's glands in the olfactory mucosa and causes extensive lesion in the olfactory mucosa. Thionamides also affect gene expression and modulate the functions of some cell types. A brief account of the chemistry and metabolism of antithyroid thionamides, along with their biological actions are presented.     

Omeprazole-induced slowing of gastrointestinal transit in mice can be countered with tegaserod

Omeprazole, besides suppressing gastric acid, causes delayed gastric emptying, which may be associated with aggravated dyspeptic symptoms. Effects of omeprazole on small intestinal transit are unknown. In this study, we evaluated in mice if (a) omeprazole affects transit of a meal through the stomach and small intestine and (b) co-treatment with the promotility agent, tegaserod, can prevent the slowing effect of omeprazole. Omeprazole (40-150 mg/kg, i.p. once daily for 5 days) delayed gastric emptying of the meal in a dose-related manner. Small intestinal transit was then evaluated at the lowest dose of omeprazole (40 mg/kg) that did not retard gastric emptying. Such transit was significantly delayed after this dose of omeprazole compared with vehicle-treated controls. When tegaserod (0.10 mg/kg) was administered concomitantly with the omeprazole, small intestinal transit of the meal was not slowed and was not different from controls. These results show that omeprazole reduces aboral transit of luminal contents through the stomach and small bowel of mice and that this delay is reversed by tegaserod.     

Gastric function measurements in drug development

The function of the stomach includes initiation of digestion by exocrine secretions such as acid and pepsin, which are under the control of the endocrine secretion of hormones that also coordinate intestinal motility. The stomach also stores and mechanically disrupts ingested food. Various techniques have been developed to assess gastric physiology, the most important of which is assessment of acid secretion, as well as gastric motility and gastric emptying. The influence of drugs on gastric function and the effect of gastric secretion and mechanical actions on the bioavailability of novel compounds are of critical importance in drug development and hence to clinical pharmacologists. The control of acid secretion is essential in the treatment of peptic ulcer disease as well as gastrooesophageal reflux disease (GORD); pH-metry can be used to determine the necessary dose of an acid suppressant to heal mucosal damage. Disturbed gastric myoelectric activity leading to gastroparesis can cause delayed gastric emptying, often found in patients with diabetes mellitus. Electrogastrography (EGG) may be used to evaluate the influence of prokinetics and other drugs on this condition and aid in determining effective therapy.     

Effects of fedotozine on gastric emptying and upper gastrointestinal symptoms in diabetic gastroparesis

BACKGROUND: Delayed gastric emptying and upper gastrointestinal symptoms occur frequently in patients with diabetes mellitus. AIM: To evaluate the effects of fedotozine on gastric emptying and gastrointestinal symptoms in diabetic gastroparesis. METHODS: Thirty-one diabetic patients (20 type 1, 11 type 2) with gastroparesis were randomized to receive fedotozine (30 mg as the tartrate) or placebo t.d.s. Measurements of gastric emptying (100 g ground beef labelled with 20 MBq 99mTc-sulphur colloid chicken liver and 150 mL 10% dextrose labelled with 10 MBq 113mIn-DTPA) and gastrointestinal symptoms were performed before and after 12-16 days of treatment. Data are the mean +/- s.d. RESULTS: Of the 31 patients enrolled, two were excluded from analysis. Data from the remaining 29 patients (18 type 1, 11 type 2; 22 female, seven male), aged 42.7 +/- 11.1 years (of whom 14 were randomized to fedotozine and 15 to placebo), were analysed. Fedotozine had no effect on either gastric emptying (solid retention at 100 min; fedotozine: baseline, 84 +/- 15%; treatment, 73 +/- 23% vs. placebo: baseline, 83 +/- 10%; treatment, 70 +/- 20%) or liquid 50% emptying time (fedotozine: baseline, 59 +/- 32 min; treatment, 58 +/- 38 min vs. placebo: baseline, 44 +/- 9 min; treatment, 43 +/- 21 min) or gastrointestinal symptoms (fedotozine: baseline, 4.4 +/- 2.9; treatment, 4.1 +/- 3.9 vs. placebo: baseline, 4.9 +/- 4.2; treatment, 4.8 +/- 3.9). CONCLUSIONS: Fedotozine has no effect on gastric emptying in patients with diabetic gastroparesis.     

Effect of a proton pump inhibitor on postprandial gastric volume, emptying and symptoms in healthy human subjects: a pilot study

BACKGROUND: In consensus guidelines, proton pump inhibitors (PPIs) are recommended for the treatment of functional dyspepsia. It is unclear whether PPIs change gastric volume or emptying. AIM: To assess the effect of a PPI, rabeprazole, on gastric volume and emptying and postprandial symptoms. METHODS: In a double-blind, parallel-group placebo-controlled trial, 13 healthy participants were randomized to rabeprazole, 20 mg b.d., or placebo. On day 3, fasting gastric volume was measured using intravenous (99m)Tc-pertechnate and single photon emission computed tomography (SPECT). After the last dose of study medication, an (111)In-chloride egg meal (300 kcal) was ingested, and postprandial gastric volume and emptying were measured by SPECT. Symptom ratings using a visual analogue scale (fullness, nausea, bloating, abdominal pain, aggregate score) were obtained at baseline and 15, 30, 45, 60 and 75 min postprandially. Group comparisons were performed using Mann-Whitney rank sum test. RESULTS: There were no statistically significant differences in gastric volume or emptying in the two groups. However, there was a borderline increase in gastric volume with rabeprazole compared with placebo. Rabeprazole treatment reduced aggregate postprandial symptoms, particularly fullness, 30 min after the meal (P = 0.01). CONCLUSIONS: In healthy participants, rabeprazole, 20 mg b.d., did not significantly change gastric emptying, but reduced symptoms and had a borderline effect on gastric volume postprandially. The mechanism of reduced postprandial symptoms with a PPI requires further study.     

Effects of lanreotide, a somatostatin analogue, on postprandial gastric functions and biliopancreatic secretions in humans

Aims Lanreotide is a novel synthetic somatostatin analogue. A long-acting formulation of lanreotide has been shown to be effective for the treatment of gastroentero-pancreatic hormone-producing tumours but effects on postprandial digestive and absorptive functions remain obscure. The aim of the present study was to evaluate the effects of intravenous lanreotide on gastric and biliopancreatic secretions in man as well as the absorption of nutrients and the duodeno-caecal transit time after ingestion of an homogenized meal (500 kcal, 55% carbohydrates, 15% proteins, 30% lipids).
Methods Eight healthy male volunteers were studied on two occasions within a 2 weeks interval, using a perfusion method. They received in single-blind and random order continuous i.v. infusion of either placebo or lanreotide (100 μg h⁻¹ after a bolus of 100 μg 15 min before the beginning of the study).
Results Lanreotide significantly decreased gastric acid secretion (90%) for the initial 3 h period. Gastric emptying was not significantly molfied by lanreotide infusion. Compared with placebo, lanreotide almost completely abolished both bile salts and lipase responses to the meal. It largely increased the duodeno-caecal transit time and decreased significantly the duodenal absorption of carbohydrates and triglycerides.
Conclusions Since lanreotide has powerful effects on gastrointestinal functions, it could be useful in the prevention or in the treatment of pancreatic and bowel fistulas as well as short bowel syndrome.