Cyclooxygenase-1 and an alternatively spliced mRNA in the rat stomach: effects of aging and ulcers.
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Prostaglandins play a critical role in gastric mucosal cytoprotection and decrease progressively with age. Cyclooxygenase (COX), the rate-limiting enzyme for prostaglandin synthesis, exists in two isoforms, COX-1 and COX-2. The rat COX-1 gene expresses an alternatively spliced mRNA COX-1 splice variant (SV) that may, at best, code for a truncated COX-1 protein. With the use of competitive PCR, we determined whether COX gene expression was altered in the stomach with increasing age and after gastric ulcer induction. COX-1 mRNA was significantly reduced in the aged, and COX-1SV mRNA was significantly higher in the adults compared with the young and aged stomach. Levels of COX-1 and COX-2 were similarly expressed in the normal stomach. In acute gastric ulcers, only COX-2 mRNA levels were significantly elevated. When ulcers were undergoing healing and repair, COX-1 and COX-2 mRNA levels were significantly elevated. Age-related changes in COX-1 and COX-1SV but not COX-2 mRNA may alter gastric mucosal cytoprotection. Furthermore, COX-1 and COX-2 may both contribute to the healing of a gastric ulcer. (+info)
Localisation of cyclooxygenase 1 and cyclooxygenase 2 in Helicobacter pylori related gastritis and gastric ulcer tissues in humans.
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BACKGROUND: Prostaglandin endoperoxide synthase/cyclooxygenase (COX) is the key enzyme in gastric mucosal protection and repair but its cellular localisation in the human stomach is still unclear. AIMS: To investigate immunohistochemically the cellular distribution of COX-1 and COX-2 proteins in the human stomach with or without gastritis or ulceration. PATIENTS AND METHODS: Tissues were obtained by surgical resection of gastric ulcers associated with perforation (n = 9) or by biopsy from Helicobacter pylori positive patients with gastric ulcers (n = 45) and H pylori negative healthy subjects (n = 15). COX expression was detected by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and light and electron microscopic immunohistochemistry. RESULTS: COX-2 mRNA and protein were detected in gastric ulcer tissues but not in intact gastric mucosa. COX-1 mRNA and protein were detected in the intact mucosa. COX-2 immunostaining was exclusively localised in macrophages and fibroblasts between necrotic and granulation tissues of the ulcer bed. The percentage of COX-2 expressing cells was significantly higher in open than in closed ulcers, and in gastritis than in gastric mucosa without H pylori infection. COX-1 immunoreactivity localised in lamina propria mesenchymal cells was similar in various stages of ulcer disease and in intact gastric mucosa. Electron microscopic immunohistochemistry revealed both COX-1 and COX-2 on the luminal surfaces of the endoplasmic reticulum and nuclear envelope of macrophages and fibroblasts. CONCLUSIONS: Our results showed that COX-2 protein was induced in macrophages and fibroblasts in gastric ulcers and H pylori related gastritis, suggesting its involvement in the tissue repair process. (+info)
Review article: potential gastrointestinal effects of long-term acid suppression with proton pump inhibitors.
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This review examines the evidence for the development of adverse effects due to prolonged gastric acid suppression with proton pump inhibitors. Potential areas of concern regarding long-term proton pump inhibitor use have included: carcinoid formation; development of gastric adenocarcinoma (especially in patients with Helicobacter pylori infection); bacterial overgrowth; enteric infections; and malabsorption of fat, minerals, and vitamins. Prolonged proton pump inhibitor use may lead to enterochromaffin-like cell hyperplasia, but has not been demonstrated to increase the risk of carcinoid formation. Long-term proton pump inhibitor treatment has not been documented to hasten the development or the progression of atrophic gastritis to intestinal metaplasia and gastric cancer, although long-term studies are required to allow definitive conclusions. At present, we do not recommend that patients be tested routinely for H. pylori infection when using proton pump inhibitors for prolonged periods. Gastric bacterial overgrowth does increase with acid suppression, but important clinical sequelae, such a higher rate of gastric adenocarcinoma, have not been seen. The risk of enteric infection may increase with acid suppression, although this does not seem to be a common clinical problem with prolonged proton pump inhibitor use. The absorption of fats and minerals does not appear to be significantly impaired with chronic acid suppression. However, vitamin B12 concentration may be decreased when gastric acid is markedly suppressed for prolonged periods (e.g. Zolllinger-Ellison syndrome), and vitamin B12 levels should probably be assessed in patients taking high-dose proton pump inhibitors for many years. Thus, current evidence suggests that prolonged gastric acid suppression with proton pump inhibitors rarely, if ever, produces adverse events. Nevertheless, continued follow-up of patients taking proton pump inhibitors for extended periods will provide greater experience regarding the potential gastrointestinal adverse effects of long-term acid suppression. (+info)
A placebo-controlled study to assess the effects of 7-day dosing with 10, 20 and 40 mg rabeprazole on 24-h intragastric acidity and plasma gastrin in healthy male subjects.
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AIM: To compare the effects of rabeprazole 10, 20 and 40 mg o.d. on 24-h intragastric acidity and plasma gastrin concentration in a randomized, double-blind placebo-controlled trial. METHODS: Twenty-four healthy male volunteers were studied on the 7th day of morning dosing with either placebo or rabeprazole 10, 20 or 40 mg in a crossover fashion. On day 7, hourly intragastric acidity was measured for 24 h from 08.00 hours by gastric aspiration. Plasma gastrin concentrations were also measured hourly from 08.00 to 24.00 hours, and 2-hourly thereafter. RESULTS: Compared with placebo, rabeprazole 10, 20 and 40 mg produced significant dose-related decreases in intragastric acidity (median 24-h integrated acidity=697, 186, 129 and 82 mmol h/L, respectively). This was associated with significant elevation of plasma gastrin concentration (median 24-h integrated gastrin=141, 1184, 1484 and 1763 pmol.h/L, respectively). Rabeprazole 40 mg resulted in significantly decreased acidity compared with both 10 and 20 mg, and in longer times for which intragastric pH was maintained at > 3 (19. 2 h vs. 17.3 h and 17.5 h) and > 4 (17 h vs. 14.2 h and 15.2 h), but was accompanied by significantly increased plasma gastrin. There was a consistent trend for greater antisecretory activity for 20 mg compared with 10 mg, but these differences did not reach statistical significance. The interindividual variability in antisecretory response was greatest with 10 mg. CONCLUSIONS: Rabeprazole 10, 20 and 40 mg produce significant, profound dose-related inhibition of gastric acid secretion. Taking into account reciprocal increases in plasma gastrin and the interindividual variation in antisecretory response, 20 mg appears to be the preferred dose for routine clinical use. (+info)
A new highly effective short-term therapy schedule for Helicobacter pylori eradication.
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BACKGROUND: Although triple therapy regimens suggested in the Current European guidelines give fairly good results, several studies have reported an unsatisfactory Helicobacter pylori eradication rate (< 80%). AIM: To evaluate the efficacy of a new short-term treatment sequence on H. pylori eradication. METHODS: A total of 52 patients with H. pylori infection and either non-ulcer dyspepsia (34 patients) or peptic ulcer (18 patients) were enrolled to receive a 10-day therapy: omeprazole 20 mg b.d. plus amoxycillin 1 g b.d. for the first 5 days, followed by omeprazole 20 mg b.d., clarithromycin 500 mg b.d. and tinidazole 500 mg b.d. for the remaining 5 days. H. pylori infection at entry was assessed by rapid urease test and histology on biopsies from the antrum and the corpus. Bacterial eradication was assessed by endoscopy (peptic ulcer patients) or 13C urea breath test (non-ulcer dyspepsia patients) 4-6 weeks after therapy had ended. RESULTS: All patients completed the study. H. pylori eradication was achieved in all but one patient, with an eradication rate of 98% (95% CI: 94.3-100) with intention-to-treat analysis. Patient compliance was good (consumption of prescribed drugs > 95%) for all but one patient, who took the triple therapy regimen for 4 days instead of 5 days. No major side-effects were reported but three (6%) patients complained of mild side-effects. CONCLUSIONS: The use of this 'five plus five' therapy schedule as an initial treatment for H. pylori deserves further investigation. (+info)
Acute gastric changes in patients with acute stroke. Part 1: with reference to gastroendoscopic findings.
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A gastroendoscopic study was performed on 177 patients with acute stroke. Gastric changes were found in 92 among them (52%), including ten with acute ulcer. A high frequency of gastric changes was found in patients with serious stroke and/or in patients whose cerebral lesions were located close to the hypothalamus or its centrifugal tract. The mortality in patients with gastric changes was high, especially in patients with acute ulcers, multiple erosions and petechiae. The frequency of brown gastric juice and coffee grounds at gastroendoscopic examination (gastric hemorrhage) was three times as high as that of melena and/or hematoemesis. On the other hand, the mortality of patients with gastric hemorrhage differed little from that of patients with melena and/or hematoemesis. (+info)
Slaughter pigs are commonly infected by closely related but distinct gastric ulcerative lesion-inducing gastrospirilla.
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An association between (unculturable) gastrospirillum-like organisms (GLO) and ulcerative lesions in the pars oesophagea in stomachs of swine has been claimed. In dogs GLO detected by microscopy may represent several Helicobacter species or subspecies. Therefore we investigated which Helicobacter spp. are present in stomachs of swine and their possible association with ulcerative lesions of the pars oesophagea. The presence of Helicobacter spp. in the antrum and pars oesophagea in 122 stomachs of slaughter swine was determined by microscopy (n = 122), by culture on selective and nonselective media (n = 112), and by a genus-specific 16S ribosomal DNA (rDNA) PCR (n = 80). GLO could not be cultured. Phylogenetic analysis of 43 16S rDNA fragments (out of 54 PCR-positive biopsy specimens) revealed the presence of Helicobacter heilmannii type 1 in 42 of them. This correlated with the presence of bacteria with GLO morphology. Helicobacter bilis 16S rDNA was amplified directly from one sample harboring bacteria with H. bilis morphology. The association between Helicobacter spp. and gastric lesions was investigated with a second group of 41 pigs with (n = 21 cases) or without (n = 20 controls) gastric lesions. Fifteen of the 21 cases were positive by PCR or microscopy, compared to 7 of 20 of the controls (P = 0.03). 16S rDNA sequence analysis of 7 of 14 PCR-positive cases revealed the presence of H. heilmannii type 1. Microscopy showed bacteria with GLO morphology. One sample (cases) was culture negative but PCR positive for Helicobacter pullorum-related 16S rDNA. In conclusion, our findings indicate that H. heilmannii type 1 is the predominant Helicobacter spp. in the stomachs of pigs and that its presence is associated with ulcerative lesions in the pars oesophagea. (+info)
Phenotypical and morphological analyses of intraepithelial and lamina propria lymphocytes in normal and regenerating gastric mucosa of rats in comparison with those in intestinal mucosa.
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While the intestine has abundant intraepithelial lymphocytes (IELs) including extrathymically differentiated T-cell populations and natural killer (NK) cells, the stomach contains only a few IELs. To elucidate whether the gastric epithelium is capable of inducing predominant lymphocyte lodging and subsequent differentiation within, we counted the number of IELs and lamina propria lymphocytes (LPLs) and calculated the percentage of IELs to total lymphocytes for each alpha-beta T cell, gamma-delta T cell, CD4+ cell, CD8+ cell and NK cell in normal and regenerating gastric mucosa as well as the intestinal mucosa of the rat. In the normal rat pylorus, a few alpha-beta T cells but no gamma-delta T cells were found in the epithelium and lamina propria. In regenerating gastric mucosa, all subsets of LPLs increased in number to a degree comparable to those in intestinal mucosa, whereas every IEL subset, though slightly increased, was much smaller in number than in the intestinal mucosa, consequently giving lower percentages of IELs. Electron microscopic observations revealed that all IELs in regenerating gastric mucosa were agranular, while 55% of intestinal IELs were large granular lymphocytes positively stained for an NK-cell, alpha-beta-cell or gamma-delta T-cell marker. The present results indicate that, unlike the intestinal epithelium, the gastric epithelium does not induce the preferential localization of T cells/NK cells and T-cell differentiation into granular lymphocytes in the epithelium even under conditions of prominent LPL infiltration. (+info)