Bacterial colonization and healing of gastric ulcers: the effects of epidermal growth factor.
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Experimental gastric ulcers are rapidly colonized by various bacteria, resulting in significantly impaired healing. Epidermal growth factor (EGF) is capable of preventing bacterial colonization of the healthy intestinal mucosa. In this study, we examined the possibility that EGF accelerates gastric ulcer healing by reducing bacterial colonization of the ulcer. Gastric ulcers were induced by serosal application of acetic acid. The effect of daily administration of EGF on ulcer healing and bacterial colonization was assessed and compared with the effect of daily treatment with broad-spectrum antibiotics. EGF administration reduced colonization levels and accelerated ulcer healing as effectively as the antibiotic treatment. EGF was without effect on acid secretion or neutrophil infiltration into the ulcer. Bacterial growth was not inhibited in the presence of EGF in vitro. These results demonstrate that EGF reduces bacterial colonization during an established infection of a compromised mucosal surface. This effect may contribute to the ability of EGF to accelerate gastric ulcer healing. This effect is acid independent and not due to an anti-inflammatory effect or to direct bactericidal actions. (+info)
Inhibition of gastric acid secretion in rat stomach by PACAP is mediated by secretin, somatostatin, and PGE(2).
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Pituitary adenylate cyclase-activating polypeptide (PACAP), existing in two variants, PACAP-27 and PACAP-38, is found in the enteric nervous system and regulates function of the digestive system. However, the regulatory mechanism of PACAP on gastric acid secretion has not been well elucidated. We investigated the inhibitory action of PACAP-27 on acid secretion and its mechanism in isolated vascularly perfused rat stomach. PACAP-27 in four graded doses (5, 10, 20, and 50 microg/h) was vascularly infused to determine its effect on basal and pentagastrin (50 ng/h)-stimulated acid secretion. To study the inhibitory mechanism of PACAP-27 on acid secretion, a rabbit antisecretin serum, antisomatostatin serum, or indomethacin was administered. Concentrations of secretin, somatostatin, PGE(2), and histamine in portal venous effluent were measured by RIA. PACAP-27 dose-dependently inhibited both basal and pentagastrin-stimulated acid secretion. PACAP-27 at 10 microg/h significantly increased concentrations of secretin, somatostatin, and PGE(2) in basal or pentagastrin-stimulated state. The inhibitory effect of PACAP-27 on pentagastrin-stimulated acid secretion was reversed 33% by an antisecretin serum, 80.0% by an antisomatostatin serum, and 46.1% by indomethacin. The antisecretin serum partially reduced PACAP-27-induced local release of somatostatin and PGE(2). PACAP-27 at 10 microg/h elevated histamine level in portal venous effluent, which was further increased by antisomatostatin serum. However, antisomatostatin serum did not significantly increase acid secretion. It is concluded that PACAP-27 inhibits both basal and pentagastrin-stimulated gastric acid secretion. The effect of PACAP-27 is mediated by local release of secretin, somatostatin, and PGE(2) in isolated perfused rat stomach. The increase in somatostatin and PGE(2) levels in portal venous effluent is, in part, attributable to local action of the endogenous secretin. (+info)
The pharmacokinetic responses of humans to 20 g of alanyl-glutamine dipeptide differ with the dosing protocol but not with gastric acidity or in patients with acute Dengue fever.
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Pharmacokinetic responses to oral doses of the dipeptide, L-alanyl-glutamine (Ala-Gln), were evaluated after a single, bolus load or an intermittent dosing in normal healthy subjects (n = 8) to find the optimal mode of oral administration. In a subgroup (n = 4) of the healthy subjects, the influence of a gastric acid suppressor (Omeprazole) was investigated. The influence of an acute episode of classic Dengue fever was examined in eight patients. All modes of administration to healthy subjects significantly increased free plasma Gln and alanine concentrations. Peak increments of plasma Gln concentration were 794+/-107 micromol/L (mean +/- SEM) after bolus intake of 20 g of Ala-Gln and 398+/-61 micromol/L after intermittent intake of the same cumulative dosage of the dipeptide (P<0.01). After intermittent dosing, the maximum peak increase appeared significantly later (P<0.01). Areas under the curve (AUC), expressing the integrated responses over time of plasma free Gln and alanine concentrations, did not differ after bolus and intermittent loads of Ala-Gln. Pretreatment with the acid suppressor, Omeprazole, did not influence Gln (P = 0.79) or alanine (P = 0.90) plasma increment. Dengue patients manifested the same pharmacokinetic responses to a 20 g Ala-Gln bolus as healthy controls. In general, on a micromolar concentration basis, Gln and alanine followed parallel tracks in terms of plasma appearance, clearance and elimination after the oral administration of 20 g of the Ala-Gln dipeptide through the range of conditions and dosing protocols explored here. (+info)
Personal review: alarmism or legitimate concerns about long-term suppression of gastric acid secretion?
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This article responds to controversial issues about the long-term use of acid suppression raised in a recent article in this journal by Waldum & Brenna. Although rebound acid secretion occurs following proton pump inhibitor therapy, the clinical significance of this is unclear, but the proposal that this is a major driver of acid-related diseases is considered implausible. The polypoid deformity of the gastric corpus that can occur with long-term proton pump inhibitor therapy is not neoplastic, and therefore has no bearing on other issues raised about proton pump inhibitor therapy and gastric malignancy. Current data in humans suggest that the magnitude of serum gastrin elevation from proton pump inhibitor treatment of up to 10 years, and any theoretical risks from this, have been overstated by Waldum & Brenna. Pernicious anaemia is a model of very doubtful validity for the risks of proton pump inhibitor therapy on several grounds. The proposal that diffuse gastric carcinoma arises from acid suppression-induced stimulation of enterochromaffin-like cells is challenged vigorously, because this is based on an implausible and substantially criticized interpretation of histopathology. It is agreed that it is appropriate to be cautious about the safety of long-term acid suppression, because no data are available for lifelong treatment in humans. Such caution should be tempered by a critical assessment of the benefits of this treatment in relation to any possible risks. The substantial data that now exist from long-term treatment of humans with proton pump inhibitors has not thus far revealed any definite risks. The risk of death from anti-reflux surgery, although small, would seem to far exceed any possible risks associated with long-term proton pump inhibitor use. Available data suggest that denial of the benefits of effective acid suppressant therapy to patients with clear-cut troublesome acid related disorders is an overreaction to concerns about the biological effects of inhibiting acid secretion with proton pump inhibitors. (+info)
Effect of gastric acid suppression on 13C-urea breath test: comparison of ranitidine with omeprazole.
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BACKGROUND: The assessment of the effect of H2 antagonists on the results of the urea breath test has produced controversial results. AIM: To assess whether standard doses of both omeprazole and H2 blockers can adversely influence the accuracy of the urea breath test. METHODS: Sixty dyspeptic patients with ascertained Helicobacter pylori infection were recruited for this prospective, open study. They were randomized to receive either omeprazole 20 mg at 08:00 hours (n = 30) or ranitidine 300 mg at 22:00 hours (n = 30) for 14 days. The urea breath test was performed at baseline, on day 14, while patients were still taking the antisecretory drugs, and on day 21, 1 week after their cessation. Duplicate breath samples were collected after ingestion of 75 mg 13C-urea + citric acid. A delta value > 5 per thousand was considered positive. RESULTS: On day 14 the median delta values had declined, but not significantly (P = 0. 07) compared to baseline (13.79 vs. 22.39) with omeprazole, while they had increased (P = 0.27) with ranitidine (27.21 vs. 19.46). On the same day there were five out of 30 (17%) and five out of 28 (18%) false-negative results in the omeprazole and ranitidine groups, respectively. All these cases became positive again on day 21. However, in eight cases treated with omeprazole and 13 treated with ranitidine, there was an increase of 14-day delta values compared to baseline. CONCLUSIONS: Our study shows that both omeprazole and ranitidine at standard doses are able to negatively affect the results of the urea breath test. Their adverse effect resolves within 7 days of drug cessation and therefore the withdrawal of these drugs 7 days before testing seems to be sufficient to avoid false-negative results. The surprising finding that both antisecretory drugs reduce delta values in one group and increase them in another group of patients deserves further study. (+info)
Gastric myoelectric activity in older adults treated with cisapride for gastro-oesophageal reflux disease.
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BACKGROUND: The incidence of both gastro-oesophageal reflux disease (GERD) and upper gastrointestinal motility disorders appears to increase with age. However, there is a dearth of data concerning the utility of a prokinetic agent such as cisapride in the treatment of older adults with symptomatic GERD. AIM: To investigate the incidence of electrogastrographic abnormalities in older adults with and without GERD symptoms, as well as the effect of cisapride therapy on symptoms of GERD and electrogastrographic responses. METHODS: We report on 18 older adults with symptomatic GERD and 10 older adult controls (mean ages 71 and 75 years, respectively). Subjects underwent electrogastrographic evaluation pre- and postprandially under baseline conditions and after 1 month of treatment with 10 mg q.d.s. of cisapride. RESULTS: Heartburn frequency and postprandial fullness were both significantly (P < 0. 05) reduced after cisapride treatment. Acid contact time was not significantly changed. The percentage of 2-4 cpm activity in the electrogastrographic analysis was significantly (P < 0.05) increased with cisapride treatment, and the instability coefficient was significantly (P < 0.05) diminished with cisapride treatment. CONCLUSIONS: Enhanced gastric functioning and reduction in heartburn suggest that cisapride is efficacious in the treatment of older adults with symptomatic GERD, and that gastric dysrhythmias and postprandial fullness are resolved with cisapride treatment. (+info)
Gastric acid suppression does not promote clostridial diarrhoea in the elderly.
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Gastric acid prevents bacterial colonization of the stomach and suppression of its secretion might predispose to Clostridium difficile (CD) diarrhoea. We retrospectively studied elderly patients admitted to medical wards of an acute hospital to determine whether the incidence of CD diarrhoea was greater among those previously treated with gastric acid suppressants. From records of stool CD toxin tests undertaken in 1995 and 1996, we found 126 cases with positive results, and selected 126 controls with negative results. Information about pre-morbid illness, predisposing factors for CD and medication received in the preceding 16 weeks was obtained from case-notes. A greater number of CD positive cases had received antibiotics such as Cefuroxime, ciprofloxacin or macrolides with or without metronidazole, were more severely disabled, required assistance for feeding, or had hypoalbuminaemia before the onset of diarrhoea. A greater number of controls had received lactulose, suggesting either that its laxative effect resembled CD infection prompting frequent stool tests, or that it offered protection against CD in this group. Both groups were similar for the use of proton-pump inhibitors or H2-receptor antagonists, suggesting that susceptible elderly patients are not more likely to develop CD diarrhoea after receiving gastric acid suppression therapy. (+info)
Helicobacter pylori infection is associated with milder gastro-oesophageal reflux disease.
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BACKGROUND: We have previously demonstrated a negative relationship between the prevalence of Helicobacter pylori and gastro-oesophageal reflux disease (GERD). AIM: To study the effects of H. pylori infection on the severity of GERD. METHODS: Ethnic Chinese patients with frequent heartburn and/or endoscopic oesophagitis were studied. Endoscopic examination was performed to assess the severity of oesophagitis (modified Savary-Miller grading) and the presence of hiatus hernia. Biopsies were taken for rapid urease testing and confirmation of Barrett's oesophagus. Risk factors which may affect the severity of oesophagitis (age, sex, smoking, drinking, diabetes mellitus, hiatus hernia, H. pylori status and body mass index) were evaluated by a multiple regression model. The cagA status of H. pylori infected GERD and age-and-sex matched controls were determined by Western blot. Age-and-sex matched non-reflux patients were recruited as controls for comparison. RESULTS: Two hundred and twenty-five patients with GERD were studied, of whom 77 (34%) were infected with H. pylori. Oesophagitis and Barrett's oesophagus were found in 140 patients (62%) and six patients (3%), respectively. H. pylori infected patients had significantly less severe oesophagitis compared to the uninfected group (P=0.022). All patients with Barrett's oesophagus were uninfected. Factors that predicted severe oesophagitis included age over 60 years (P < 0.001) and hiatus hernia (P < 0.001). H. pylori infection was the only factor that showed a negative correlation with severe oesophagitis (P=0.011). The prevalence of the cagA positive strain in endoscopy-negative GERD, erosive oesophagitis and control subjects was 70, 76 and 78%, respectively (P=0.75). CONCLUSIONS: H. pylori infection is associated with milder GERD. (+info)