Effect of vitamin E in gastric mucosal injury induced by ischaemia-reperfusion in nitric oxide-depleted rats.
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BACKGROUND: Neutrophil infiltration and lipid peroxide accumulation are involved in reperfusion-induced gastric mucosal injury in nitric oxide-depleted rats. AIM: To assess the effect of vitamin E on this injury. METHODS: After ischaemia-reperfusion, the total area of erosions, lipid peroxide contents in gastric mucosa, and gastric neutrophil accumulation were compared between nitric oxide-depleted rats with deficient, normal, and increased vitamin E intake over 8 weeks. Thiobarbituric acid-reactive substances and tissue-associated myeloperoxidase activity were measured in gastric mucosa as indices of lipid peroxidation and neutrophil infiltration. RESULTS: The total area of erosions was significantly increased in the vitamin E-deficient group compared with the sufficient-intake and vitamin-supplemented groups. Both thiobarbituric acid-reactive substances and myeloperoxidase activity also were significantly increased in the vitamin E-deficient group compared with others. The total area of erosions closely paralleled the increases in both thiobarbituric acid-reactive substances and myeloperoxidase activity. CONCLUSION: These results indicate that the inhibition of lipid peroxidation and interference with neutrophil infiltration by vitamin E may be responsible for its cytoprotective effect in ischaemia-reperfusion. (+info)
Promoting effects of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone on rat glandular stomach carcinogenesis initiated with N-methyl-N'-nitro-N-nitrosoguanidine.
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The modifying effects of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a mutagenic by-product in chlorinated water, on the development of glandular stomach cancers were investigated in Wistar rats. A total of 120 males, 6 weeks of age, were divided into six groups. After initiation with 100 ppm N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) solution and 5% NaCl diet for 8 weeks, 30 rats each in groups 1-3 were given MX in the drinking water at concentrations of 30, 10, or 0 ppm for the following 57 weeks. Ten animals each in groups 4-6 were administered the MX without prior carcinogen exposure. There were no statistical significant differences in final body weights between the groups. The incidences and multiplicities of adenocarcinomas in the glandular stomachs were significantly higher (P < 0.05) in the initiated 30 ppm MX group than those in the MNNG/NaCl group. The incidences of atypical hyperplasias in the glandular stomachs were also significantly increased (P < 0.05 or 0.01) by the MX treatments. With their multiplicity, the effects were clearly dose dependent. Interestingly, the 30 ppm MX alone itself induced atypical hyperplasias in the pylorus, although the incidences and severity were low. Moreover, MX showed a tendency to enhance the development of intrahepatic cholangiocellular tumors and thyroid follicular cell tumors in the MNNG-treated animals. The results of the present study thus indicate that MX exerts promoting effects when given during the postinitiation phase of two-stage glandular stomach carcinogenesis in rats. (+info)
Helicobacter felis infection in dogs: effect on gastric structure and function.
(11/688)
The relationship of Helicobacter felis, an organism that is observed in the stomachs of dogs, to gastric disease in dogs is unclear. The objective of this study was to determine if Helicobacter felis infection alters gastric morphology and gastric secretory function in dogs. Five specific-pathogen-free (SPF), Helicobacter-free Beagle dogs were examined before and for 26 weeks after inoculation with H. felis (ATCC 49179). Three SPF uninfected dogs served as controls. All five dogs became colonized by H. felis as determined by urease activity, histopathology, polymerase chain reaction, and transmission electron microscopic examination of serial gastric biopsies. The degree of colonization ranged from < 1 organism/400 x field to > 10 organisms/400 x field. The fundus, body, and cardia were most heavily colonized. Evaluation of gastric biopsies showed mild gastric inflammation and lymphoid follicles in both infected and uninfected dogs. There was no correlation between the number of organisms observed and the degree of gastric inflammation or number of lymphoid follicles. The gastric secretory axis, assessed by fasting and meal-stimulated plasma gastrin, mucosal gastrin and somatostatin immunoreactivity, fasting gastric pH, and pentagastrin-stimulated gastric acid secretion, was similar in both infected and uninfected dogs. Fasting gastric pH was not a reliable indicator of gastric secretory function. These findings suggest that H. felis may not be a gastric pathogen in dogs. However, the density of colonization and limited duration of infection should be considered when interpreting these findings. (+info)
The influence of CYP2D6 activity on the kinetics of propafenone enantiomers in Chinese subjects.
(12/688)
AIMS: To determine role of CYP2D6 activity in the pharmacokinetics of propafenone (PPF) enantiomers in native Chinese subjects. METHODS: Sixteen extensive metabolizers (EMs) and one poor metabolizer (PM), whose phenotype had been previously assessed with dextromethorphan metabolic phenotyping, were enrolled. Blood samples (0 approximately 15 h) were taken after oral administration of a single dose (400 mg) of racemic-propafenone hydrochloride. A reverse-phase h.p.l.c. method with pre-column derivatization was employed to quantitate enantiomeric concentrations of propafenone in plasma. RESULTS: For the EM subjects, S-PPF was less rapidly metabolized and had higher peak plasma concentrations than R-PPF (413+/-143 vs 291+/-109 ng ml-1, P<0.001). The AUC was markedly higher for S-PPF than for R-PPF (2214+/-776 vs 1639+/-630 microg h l-1, P<0.001), whereas the clearance of S-PPF was significantly lower than that of R-PPF (96.0+/-39.0 vs 138+/-78 l h-1, P<0.01). There were no differences in t1/2, and Cmax between the two isomers (P >0.05). In the one PM subject, not only did S-PPF appear to undergo less rapid metabolism than R-PPF, but the subject also showed 2 approximately 3 fold differences in Cmax, CL and AUC compared with EMs. The correlation coefficients (rs ) between dextromethorphan metabolic ratio (lg MR) and pharmacokinetic parameters (Cmax, CL and AUC) were 0.63, -0.87, 0.87 for S-PPF and 0. 57, -0.73, 0.86 for R-PPF, respectively. CONCLUSIONS: Our results suggest that CYP2D6 activity contributes to the pharmacokinetic variability of propafenone enantiomers in Chinese subjects. (+info)
Are all helicobacters equal? Mechanisms of gastroduodenal pathology and their clinical implications.
(13/688)
Most cases of peptic ulcer disease, gastric mucosa associated lymphoid tissue (MALT) lymphoma and cancer of the distal stomach are complications of Helicobacter pylori infection. However, as with most infections not all patients who contract the infection develop the complications of the disease. The other factors that influence the likelihood of problems arising are the virulence of the infecting organism, the genetic constitution and age of the host, and environmental factors. This paper focuses mainly upon the effect of strain differences and the causation of serious disease. There is considerable genetic variation between the different strains of H pylori, some causing a more severe inflammatory response in the host than others. These strains are also associated with a greater likelihood of causing peptic ulcer, atrophic gastritis and intestinal metaplasia and gastric cancer. There is some evidence to suggest that these more virulent organisms may also protect the host from the development of reflux oesophagitis and possibly cancer in the region of the gastro-oesophageal junction. The major difference between virulent and relatively avirulent organisms depends upon the presence of the cag pathogenicity island, a segment of DNA that has been acquired possibly from another organism and is now incorporated within the helicobacter genome. Its presence is associated with the secretion of the vacuolating toxin which is a protein known to cause damage in cell culture and in vivo. As CagA, one of the proteins produced by the pathogenicity island, is highly antigenic, people infected with more virulent strains can be identified by a blood test. Currently controversy surrounds the question as to whether all patients with H pylori should be treated for infection or whether medication should be reserved for those who already have the complications of the infection, or individuals infected with the more virulent strain of the organism. (+info)
Lack of association between Helicobacter pylori infection and extracardiac atherosclerosis in dyspeptic elderly subjects.
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BACKGROUND: There are conflicting data on the association between Helicobacter pylori (HP) infection and cardiovascular diseases. AIM: To determine if there is an association between gastric HP infection and atherosclerosis of cerebral or peripheral arteries in elderly subjects. METHODS: 90 dyspeptic elderly subjects had upper gastro-intestinal endoscopy and the gastroduodenal pathology was identified. HP infection was confirmed by gastric histology and the rapid urease test. Vascular ultrasonography of extracranial cerebral arteries and leg arteries was performed to evaluate (i) the presence of an atherosclerotic lesion, (ii) the total length of all plaques documented and (iii) the number of arteries with atherosclerotic lesions. Statistical analysis was by the chi2 test, Yates's corrected chi2 test, the Mann-Whitney test and logistic regression. RESULTS: 59 subjects were HP-positive. These had a higher prevalence of peptic ulcer disease (P = 0.01) and higher serum levels of IgG anti-HP antibodies (P = 0.0001), but no significant differences in the number of atherosclerotic lesions, the total length of the plaques or the number of arteries with lesions. No significant association of HP positivity was found with diabetes mellitus, hypertension, cigarette smoking or coronary heart disease, nor with serum concentrations of HDL-cholesterol, fibrinogen, triglycerides or glucose. CONCLUSIONS: Elderly dyspeptic subjects with gastric HP infection had significantly more peptic ulcer disease but no more atherosclerotic lesions than those who were HP-negative. Atherosclerosis was not associated with HP infection. In this cross-sectional study of elderly patients with dyspepsia, no association between HP infection and extracardiac atherosclerosis was found. (+info)
Enteric coating of aspirin significantly decreases gastroduodenal mucosal lesions.
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BACKGROUND: Low-dose aspirin (acetylsalicylic acid, ASA) increases the risk of developing peptic ulceration. AIM: To investigate the gastroduodenal mucosal tolerability of enteric-coated ASA (EC-ASA) 100 mg/day compared to either placebo (study 1) or plain ASA 100 mg/day (study 2) in healthy volunteers. METHODS: Study 1: In this double-blind study 18 volunteers received randomized dosing with either EC-ASA 100 mg or placebo for 15 days. Study 2: 41 volunteers underwent randomized 7-day dosing of either EC-ASA 100 mg or plain ASA 100 mg in this double-blind, parallel-group, comparison study. In both studies acute gastroduodenal mucosal lesions were assessed endoscopically before treatment, on the morning of day 1 after the first dose (only in study 2), and on the morning after the last dose of the test medication. RESULTS: Study 1 did not reveal any significant differences between the lesion scores of EC-ASA and placebo. In contrast, in study 2 significantly higher total gastroduodenal mucosal lesion scores were observed on day 1 after the first dose and after 7 days of dosing with plain ASA (mean sum of the lesion scores in the gastric fundus, body, antrum and in the duodenal bulb: day 1: plain ASA 3.95+/-3.38 vs. EC-ASA 1.43+/-1.91, P = 0.03; day 7: plain ASA 6.35+/-4.10 vs. EC-ASA 2.00+/-2.02, P = 0.0004). Tolerance of the test drugs was good, and no other adverse events were observed. CONCLUSIONS: Enteric-coated aspirin 100 mg/day causes significantly less gastroduodenal damage over 7 days than the same dose of plain aspirin, when given to healthy subjects. There was little gastric injury and no significant differences between EC-ASA and placebo in this respect. (+info)
Intracisternal PYY increases gastric mucosal resistance: role of cholinergic, CGRP, and NO pathways.
(16/688)
The influence of intracisternal injection of peptide YY (PYY) on gastric lesions induced by ethanol was studied in urethan-anesthetized rats. Gastric lesions covered 15-22% of the corpus as monitored 1 h after intragastric administration of 45% ethanol (5 ml/kg) in intracisternal vehicle control groups. PYY, at doses of 23, 47, or 117 pmol 30 min before ethanol, decreased gastric lesions by 27%, 63%, and 59%, respectively. Thyrotropin-releasing hormone (TRH) receptor antisense oligodeoxynucleotide pretreatment (intracisternally, 48 and 24 h before intracisternal PYY) did not influence the gastroprotective effect of intracisternal PYY (47 pmol) but abolished that of intracisternal TRH analog RX-77368 (4 pmol). RX-77368 (2.6 pmol) and PYY (6 pmol) were ineffective when injected intracisternally alone but reduced ethanol lesions by 44% when injected simultaneously. Atropine (subcutaneously), the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) (intravenously), or the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, intravenously) completely abolished the gastroprotective effect of intracisternal PYY (47 pmol), whereas indomethacin (intraperitoneally) had no effect. The L-NAME action was reversed by L-arginine but not by D-arginine (intravenously). These results suggest that intracisternal PYY acts independently of medullary TRH to decrease ethanol-induced gastric lesions. The PYY action involves vagal cholinergic-mediated CGRP/NO protective mechanisms. (+info)