Effect of the histamine-1 antagonist astemizole alone or with omeprazole on rat gastric mucosa.

The stimulation of acid secretion by gastrin may in the rat be explained solely by gastrin-induced histamine release. This study was done to examine whether histamine could mediate the general trophic effect of gastrin on the oxyntic mucosa, by using a long-acting selective histamine-1 antagonist (astemizole) alone or with omeprazole-induced hypergastrinaemia for 90 days in female Sprague-Dawley rats. At day 90, isolated vascularly perfused rat stomachs were prepared to study maximal gastrin- and histamine-stimulated acid and pepsinogen outputs and maximal gastrin-stimulated histamine release. Oxyntic mucosa morphometry, mucosal histamine and pepsinogen contents, and plasma gastrin and histamine levels were also determined. For the first time, omeprazole has been found to inhibit gastric emptying and to increase plasma histamine. As compared with controls, astemizole alone did not influence plasma gastrin, increased plasma histamine in only some rats, and gave a slight increase in all other variables. Together with omeprazole, it further increased variables already stimulated by omeprazole. Thus, mucosal thickness, histamine concentration, and chief-cell density in oxyntic mucosa were significantly higher in astemizole/omeprazole-treated rats than in omeprazole-treated rats. Gastrin-stimulated histamine release was increased in both astemizole- and omeprazole-treated rats. For all rats plasma histamine was significantly correlated with plasma gastrin and with numerical fundic argyrophil cell density. In conclusion, the present study confirms the trophic effect of gastrin and shows a slight trophic effect of astemizole on the oxyntic mucosa. It also shows that plasma histamine may reflect the argyrophil cell density in the oxyntic mucosa and that omeprazole inhibits gastric emptying.     

Eradication therapy with rabeprazole versus omeprazole in the treatment of active duodenal ulcer

BACKGROUND: Rabeprazole has been demonstrated to be a potent antisecretory agent and has been shown to be clinically effective in the treatment of acid-related diseases. AIMS: It was to determine the efficacy of rabeprazole at 20 and 40 mg in addition to amoxicillin and clarithromycin in the treatment of active Helicobacter pylori-positive duodenal ulcers compared with omeprazole 40 mg. PATIENTS AND METHODS: One hundred and twenty-seven patients were randomised into three treatment groups: 40 patients were treated with rabeprazole 40 mg daily, 42 patients with rabeprazole 20 mg daily and 45 patients with omeprazole 40 mg daily for 10 days. All patients received amoxicillin 1 g twice a day and clarithromycin 500 mg twice a day for 5 days. All patients were re-assessed at least 4 weeks after the end of the treatment. RESULTS: According to the intention-to-treat (ITT) protocol, ulcer healing was observed in 90% of patients in the rabeprazole 40 group, in 85.7% in the rabeprazole 20 group and in 93.3% in the omeprazole 40 group. We observed H. pylori eradication in 90% ITT in the rabeprazole 40 group, in 80.9% ITT in the rabeprazole 20 group and in 88.8% ITT in the omeprazole 40 group. Statistical analysis did not show significant differences among the three groups. CONCLUSIONS: A 10-day rabeprazole 20 mg regimen represents an efficacious and safe regimen for H. pylori eradication and ulcer healing.     

Histopathology of the gastric oxyntic mucosa in two different patient groups during long-term treatment with omeprazole

OBJECTIVES: Hypochlorhydria, hypergastrinaemia, inflammation and Helicobacter pylori infection, dose and duration of omeprazole treatment may separately, or in combination, influence the proliferation of enterochromaffin-like (ECL) cells and parietal cell changes in gastric mucosa. To assess the effects of these variables comparisons were carried out in patients with the acid related Zollinger-Ellison syndrome (ZES) versus patients with progressive systemic sclerosis (PSS) and gastro-oesophageal reflux disease. METHODS: Twenty-five patients with PSS and 16 patients with ZES were included and received continuous omeprazole treatment for a mean of 7.5 and 9 years. The patients were investigated every 6-12 months with endoscopy, biopsies and histology, and plasma gastrin measurements. PSS patients were titrated by 24 h pH-metry to oesophageal pH>4, and all ZES patients were titrated to a basal acid output of zero H+. RESULTS: Changes towards diffuse and linear ECL cell hyperplasia were observed in 41% of the PSS patients. Micronodular hyperplasia and neoplasia were not seen. In the ZES patients changes towards linear and micronodular hyperplasia were observed in all patients. Two patients developed ECL cell carcinoids; one of these had MEN-1 syndrome. Also parietal cell changes were more pronounced in the ZES group than in the PSS group. CONCLUSIONS: In patients without intrinsic acid hypersecretion and hypergastrinaemia significant proliferation of ECL cells is not an issue irrespective of gastric mucosal inflammation, omeprazole dose, duration of treatment and acid inhibition. The level of gastrin secretion and high plasma gastrin appear to accelerate ECL cell proliferation and parietal cell changes possibly influenced by chronic gastritis and H. pylori infection.     

Effects of 6-12 months of esomeprazole treatment on the gastric mucosa

OBJECTIVE: The aim of this study was to determine the effect of 6-12 months of treatment with esomeprazole on the histopathology of the gastric mucosa. METHODS: Two identically designed, randomized, placebo-controlled trials of esomeprazole 40, 20, or 10 mg daily for up to 6 months, as well as a noncomparative, multicenter trial of esomeprazole 40 mg daily for up to 12 months, were conducted in 1326 patients with healed erosive esophagitis (1294 negative for Helicobacter pylori [H. pylori]). Gastric biopsy samples were obtained before treatment and on completion of (or discontinuation from) the trials. Samples were evaluated for the presence of H. pylori, characteristics of acute gastritis or atrophic gastritis, and enterochromaffin-like cell pathology. RESULTS: During treatment with esomeprazole, the number of patients with an improvement in gastric histological scores was typically greater than or equal to the number who worsened. Gastric histological scores worsened for each corporal or antral characteristic of gastritis in <6.2% of patients. Histological scores with esomeprazole and placebo were similar throughout the 6-month trials. Only one among 1326 patients treated with esomeprazole (H. pylori negative) had evidence of treatment-emergent atrophic gastritis. On final biopsy, 5-12% of patients had abnormal enterochromaffin-like cell scores (simple, linear, or micronodular hyperplasia). There were no instances of enterochromaffin-like cell dysplasia, carcinoids, or neoplasia. CONCLUSIONS: Patients with healed erosive esophagitis receiving esomeprazole for up to 12 months had minor fluctuations in gastric histological scores, similar to those experienced in untreated populations. Use of esomeprazole did not raise any safety concerns with respect to the development of atrophic gastritis, or cause clinically significant changes in enterochromaffin-like cells.     

Long-term omeprazole treatment in resistant gastroesophageal reflux disease: efficacy, safety, and influence on gastric mucosa

BACKGROUND & AIMS: The efficacy and safety of long-term acid suppression remains a subject for debate. We report data from patients with refractory reflux esophagitis who were undergoing maintenance therapy with >/=20 mg omeprazole daily for a mean period of 6.5 years (range, 1.4-11.2 years). METHODS: Patients with severe reflux esophagitis resistant to long-term therapy with H(2)-receptor antagonists and who were not eligible for surgery were evaluated at least annually for endoscopic relapse and histological changes in the gastric corpus. RESULTS: In 230 patients (mean age, 63 years at entry; 36% were >/=70 years), there were 158 relapses of esophagitis during 1490 treatment years (1 per 9.4 years), with no significant difference in relapse rates between Helicobacter pylori-positive and -negative patients. All patients rehealed during continued therapy with omeprazole at the same or higher dose. The annual incidence of gastric corpus mucosal atrophy was 4.7% and 0.7% in H. pylori-positive and -negative patients, respectively, which was mainly observed in elderly patients who had moderate/severe gastritis at entry. In patients with baseline moderate/severe gastritis, the incidences were similar: 7.9% and 8.4%, respectively. Corpus intestinal metaplasia was rare, and no dysplasia or neoplasms were observed. The adverse event profile was as might be expected from this elderly group of patients. CONCLUSIONS: Long-term omeprazole therapy (up to 11 years) is highly effective and safe for control of reflux esophagitis.     

雷贝拉唑对胃溃疡患者胃内pH值的影响

目的　评价顿服雷贝拉唑 10mg对胃溃疡患者的抑酸效果和症状缓解情况 ,并以奥美拉唑 2 0mg作为对照。 方法　采用随机、平行、双盲临床对照研究 ,患者随机进入雷贝拉唑组和奥美拉唑组。结果　 (1)两组用药后症状均明显改善 ,但治疗 1d后症状改善的程度差异无显著性 (P >0 0 5 ) ;(2 )两组抑酸药物的起效时间均在用药后 2h ;用药后 1h和 2h ,两组患者胃内pH值差异无显著性 (P >0 0 5 ) ;(3)雷贝拉唑组 2 4h总的、夜间 pH >4及夜间 pH >3的百分比明显高于奥美拉唑组(P <0 0 5 ) ,而白天pH >4和 pH >3及总的 pH >3的百分比两组之间差异无显著性 (P >0 0 5 ) ;(4 )雷贝拉唑组白天、夜间 pH >4及 2 4h总的、白天和夜间pH >3超过 30 %的百分率明显高于奥美拉唑组 (P <0 0 5 ) ,而只有总的pH >4超过 30 %的百分率 ,两组之间比较差异无显著性 (P >0 0 5 ) ;(5 )雷贝拉唑组无反应率明显低于奥美拉唑组 (7 8%比 16 4 % ) ,两组比较差异有显著性 (P <0 0 5 )。结论　雷贝拉唑顿服能有效缓解消化性溃疡症状 ,其抑酸效果优于奥美拉唑     

Effect of high-dose omeprazole administration on histamine storage and formation in canine gastric mucosa

The effect of a high dose of omeprazole on the plasma gastrin response to feeding and gastric mucosal histamine formation and storage in the dog has been studied. Tissue from the oxyntic gland area was obtained by introduction of an endoscope through a gastric fistula, and biopsies were taken before, after 4 weeks of oral administration of omeprazole and 1 month after withdrawal of the drug. Omeprazole administration increased the basal plasma concentration of gastrin and induced a substantial increase in the feeding response. Histidine-decarboxylase activity was significantly increased after 4 weeks of omeprazole administration, whereas no effect was found on histamine content and mucosal mast cell density. One month after drug withdrawal, the enzyme activity had returned to pretreatment levels.     

Effects of electro-acupuncture on 5-HT,NOS and the gastric mucosa of stress rats

AIM: To study the effects of electro-acupuncture (EA) on 5-hydroxytryptophan (5-HT) levels, nitrous oxide (NOS) levels, nitric oxide (NO) levels, and the gastric mucosa in stress rats.METHODS: The changes of 5-HT and NOS were measured in the gastric mucosa, and NO and 5-HT were measured in the serum by biochemical methods. The gastric mucosa was examined pathohistologically in the stress rats with gastric mucosa damage after EA. The changes before and after stress by EA were compared.RESULTS: EA decreased the gastric mucosa damage index in the stress rats (2.71 ± 0.40 to 1.86 ± 0.69, P < 0.01). EA normalized NOS level in gastric mucosa to the control group. The changes before stress by EA was more obvious than that after stress. EA lowered the 5-HT levels in the gastric mucosa (μg/g wet weight, 6.91 ± 3.08 to 4.51 ± 1.62, P < 0.01). EA recovered the NO level in serum of the stress rats (μmol/L, 5.78 ± 1.49 to 7.91 ± 1.11, P < 0.05), and increased the levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in serum continuously.CONCLUSION: EA stimulation normalizes the NOS and NO levels in the gastric mucosa of stress rats. EA also lowers the high 5-HT levels and induces NO release.     

Effects of rabeprazole sodium on gastric emptying,electrogastrography, and fullness

Proton pump inhibitors have been reported to delay gastric emptying, but this effect is controversial. Our aim was to determine the effect of rabeprazole sodium on several parameters of gastric function including gastric emptying, myoelectrical activity and ingested water volume required to produce fullness. Fifteen healthy males underwent assessment of solid-phase gastric emptying with the [¹³C] Spirulina platensis breath test as well as electrogastrography and satiety testing using a 5-min water load. Subjects were evaluated at baseline, after administration of placebo, and after rabeprazole sodium 20 mg daily for one week. No significant differences were seen between groups with respect to solid-phase gastric emptying as measured by T _1/2 or T _lag. No differences were seen between baseline, placebo, and rabeprazole with respect to the number of normal electrogastrograms and the volume of water required to produce fullness. In conclusion, one week of therapy with rabeprazole sodium does not significantly alter gastric emptying, myoelectrical activity or threshold to fullness.     

Effects of omeprazole on gastric mucosal blood flow in the conscious rat

Regional blood flow in the gastrointestinal tract (forestomach, corpus, antrum, duodenum, jejunum, and colon) was determined in the conscious rat by means of the microsphere technique. The effects on blood flow were determined after omeprazole (orally and intravenously) and cimetidine (intravenously) during both basal and pentagastrin-stimulated gastric acid secretion. Under basal conditions neither omeprazole nor cimetidine decreased the blood flow in the gastrointestinal tract in spite of pronounced inhibition of acid secretion. On the contrary, there was a tendency towards an increased blood flow in the mucosal layer of the corpus after the oral (80 mumol/kg) and the high intravenous (10 mumol/kg) dose of omeprazole. When omeprazole was given intravenously to rats during pentagastrin-stimulated acid secretion, blood flow in the gastric mucosa was unaffected in spite of complete or almost complete inhibition of acid secretion. In contrast, cimetidine decreased the mucosal blood flow, indicating that the pentagastrin-induced increase in blood flow to some extent is mediated by H2 receptors.     

Effects of combination treatment with famotidine and methylmethionine sulfonium chloride on the mucus barrier of rat gastric mucosa

Background and Aim:  In Japan, peptic ulcer disease (PUD) is treated clinically with a combination of a mucosal protectant and acid suppressants, but there is scant information regarding the effects of these drugs on normal gastric mucus cells. In the present study, the effects of co-administration of methylmethionine sulfonium chloride (MMSC) and famotidine on rat gastric mucus cells were investigated using both biochemical and histological methods.
Methods:  Rats were divided into four groups: controls were given carboxymethylcellulose orally once daily for 7 days and the second, third and fourth groups were treated similarly with famotidine (famotidine group), MMSC (MMSC group) or famotidine plus MMSC (combination group). After killing the rats on the 8th day, the stomachs were removed and the biosynthesis and amount of mucin in different areas of the gastric mucosa were compared among groups. Using anti-mucin monoclonal antibodies, the mucin content and immunoreactivity were also compared.
Results:  Both the biosynthesis and accumulation of mucin were significantly decreased in the famotidine group, but increased in the MMSC and combination groups. The amount and immunoreactivity of surface mucus cell-derived mucin were both reduced in the famotidine group, and increased in the MMSC and combination groups. There was no difference among the groups in the content and immunoreactivity of gland mucus cell-derived mucin.
Conclusion:  Famotidine-induced suppression of gastric surface mucus cell function is prevented by combined treatment with MMSC, raising the possibility of a more effective cure of PUD.     

Effects of a proton pump inhibitor,omeprazole, on gastric secretion and gastric and duodenal ulcers or erosions in rats

The effects of omeprazole, a proton pump inhibitor, on gastric secretion and gastric or duodenal ulcers or erosions in rats were studied. Omeprazole, given intraduodenally, dose-dependently inhibited the gastric secretion (volume, acid and pepsin output) of pylorus-ligated rats. The antisecretory activity of omeprazole at 100 mg/kg persisted for 14 hr after treatment. Acutely induced gastric ulcers or erosions such as Shay ulcers, water-immersion stress-, indomethacin-, aspirin-, or prednisolone-induced erosions were all markedly inhibited by oral or intraduodenal administration of 10–100 mg/kg of omeprazole. The development of duodenal ulcers and gastric erosions caused by mepirizole was also potently inhibited by omeprazole at 3–10 mg/kg given orally. Repeated administration of omeprazole, 200 mg/kg/day in two divided doses for 14 days, significantly accelerated the spontaneous healing of acetic acid-induced gastric ulcers. The mechanism by which omeprazole inhibits the development of acute ulcers and accelerates healing of preexisting ulcers appears to be mainly due to its potent and longlasting antisecretory activity. The antisecretory and antiulcer activities of omeprazole are equal to or exceed those of cimetidine, both in the maximum inhibitory response and ED₅₀ values.     

Effects of alendronate on gastric and duodenal mucosa

Objectives: This single-center, double-blind, randomized study assessed the effect of alendronate 5 and 10 mg on the gastroduodenal mucosa.
Methods: Overall, 95 postmenopausal women without a recent history of major upper gastrointestinal (GI) disease and not taking gastric-irritant drugs, were screened with an upper GI endoscopy. Fourteen women (15% of the total) were found to have baseline endoscopic gastric and/or duodenal abnormalities, including mucosal hemorrhages (  n = 4  ), erosions (  n = 11  ), and ulcers (  n = 3  ). Two additional women had baseline esophageal abnormalities. Thus, 79 postmenopausal women (mean age 51 yr, range 41–64 yr), free of esophageal, gastric and/or duodenal erosions or ulcer, were enrolled. Subjects received placebo, alendronate 5 mg/day or 10 mg/day, or aspirin 650 mg q.i.d. for 14 days. Endoscopy was repeated on Day 8 and on Day 15. Gastric and duodenal mucosae were graded separately using a 5-point scale for erosive mucosal injury.
Results: The proportions of subjects with a gastric or duodenal erosion score ≥ 2 (presence of at least one mucosal erosion) on either Day 8 or 15 were four of 22 (18.2%) in the placebo group; four of 22 (18.2%) in the alendronate 5 mg group; five of 21 (23.8%) in the alendronate 10 mg group; and 14 of 14 (100.0%) in the aspirin group. Thirty-five of 76 (46%) subjects were H. pylori -positive (Pyloritek test), and were equally distributed across treatment groups.
Conclusions: Alendronate 5 and 10 mg/day for 2 wk was associated with a lower incidence of gastric erosions than aspirin. The incidence of gastric erosions in the alendronate groups did not differ significantly from the placebo group. In this study, unlike aspirin, alendronate did not induce gastric erosions.     

辣椒素对胃黏膜的作用及其机制

辣椒素(capsaicin)、辣椒素敏感传入神经元(CSAN)及辣椒素受体(VR1)与胃黏膜损伤及修复密切地相关.研究显示辣椒素对胃黏膜具有保护作用,可能与其增加胃黏膜血流、促进胃动力、调节胃酸和前列腺素分泌等因素有关.本文对辣椒素对胃黏膜的作用及其机制的研究进展进行综述.     

Effect of rabeprazole and omeprazole on the onset of gastro-oesophageal reflux disease symptom relief during the first seven days of treatment

Objective. Gastro-oesophageal reflux disease (GORD) symptoms have a significant impact on patients’ well-being. Onset of symptom relief is therefore an important consideration in GORD treatment. The primary objective was to compare the efficacy of rabeprazole (20?mg) and omeprazole (20?mg) regarding onset of heartburn control during the first 7 days of treatment in patients with erosive oesophagitis. Secondary objectives included maintenance of sustained heartburn control, control of other GORD symptoms (e.g. acid regurgitation, epigastric pain, dysphagia), effect on quality of life, patient satisfaction with treatment, and adverse events. Material and methods. In this multicentre, randomized, parallel-group, double-blind, comparative study, performed in Europe and Iceland, patients with endoscopically confirmed erosive oesophagitis were randomized to receive once-daily treatment with rabeprazole 20?mg (n=358) or omeprazole 20?mg (n=359) for 7 days. Symptoms were recorded (scored on a 5-point Likert scale) twice daily by the patients on their diary cards. Results. Median time to reach heartburn control was 1.5 days for both the rabeprazole and omeprazole groups (p<0.43). The results were similar between treatments for other study parameters. Both treatments were well tolerated. Conclusions. Unlike previous studies, no significant differences were found between treatments with rabeprazole (20?mg) and omeprazole (20?mg) in this study. Further studies are needed to evaluate the potential benefit of fast-acting proton-pump inhibitors, such as rabeprazole, with respect to onset of symptom control in erosive GORD.