Influence of a new antiulcer agent, ammonium 7-oxobicyclo (2, 2, 1) hept-5-ene-3-carbamoyl-2-carboxylate (KF-392) on gastric lesions and gastric mucosal barrier in rats.
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Antiulcer effects of KF-392 were studied in several experimental gastric ulcer models in rats. It was found that KF-392 given orally at 1.0 to 5.0 mg/kg had a marked suppression on the developments of Shay ulcer as well as the aspirin-, stress-, and reserpine-induced gastric lesions. The influence of KF-392 on gastric mucosal barrier was also studied. A back diffusion of H+ into the gastric mucosa and a fall of transmucosal potential difference were induced with KF-392 given orally at the above mentioned doses. KF-392 given s.c. at 5.0 mg/kg showed no inhibition of Shay ulcer and no induction of back diffusion of H+ into the gastric mucosa. (+info)
Metabolism and disposition of 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK) in rhesus monkeys.
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Metabolism and disposition of the tobacco-specific N-nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent rodent lung carcinogen, were studied in rhesus monkeys. In three males receiving a single i.v. dose of [5-3H]NNK (0.72 mCi; 4.6-9.8 microg/kg), urine was collected for 10 days. Within the first 24 h, 86.0 +/- 0.7% of the dose was excreted. NNK-derived radioactivity was still detectable in urine 10 days after dosing (total excretion, 92.7 +/- 0.7%). Decay of urinary radioactivity was biexponential with half-lives of 1.7 and 42 h. Metabolite patterns in urine from the first 6 h closely resembled those reported previously for patas monkeys; end products of metabolic NNK activation represented more than 50% of total radioactivity. At later time points, the pattern shifted in favor of NNK detoxification products (60-70% of total radioactivity in urine), mainly 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its O-glucuronide conjugates. One female rhesus monkey received a single i.v. dose of [5-3H]NNK (1.72 mCi; 28.4 microg/kg) under isoflurane anesthesia; biliary excretion over 6 h (0.6% of the dose) was 10 times less than predicted by our previously reported rat model. No preferential excretion of NNAL glucuronide was observed in monkey bile. Collectively, these results suggest that the rhesus monkey could be a useful model for NNK metabolism and disposition in humans. (+info)
Proximal gastric vagotomy: effects of two operative techniques on clinical and gastric secretory results.
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PGV performed in 39 patients by separating the lesser omentum from the stomach beginning 6 or 7 cm proximal to the pylorus and skeletonizing the distal 1 to 2 cm of esophagus was followed by 15.4% of proven and 10.2 of suspected recurrent ulcers. Insulin tests were done during the first 3 months postoperatively on 31 of the patients, including the 6 with proven and the 4 with suspected recurrent ulcers. The peak acid output to insulin minus tha basal acid output (PAOI-BAO) was less than 5 mEq/hr in 16 cases (52%) and from 5 to 25 mEq/hr in the remaining 15 cases. In 6 patients with proven recurrent ulcer, PAOI-BAO averaged 21.9 mEq/hr (range, 11.3 to 41.8); in the 4 patients with suspected recurrence, 9.5 (range, 4.4 to 11.8). The operative technique was changed in one respect; the distal 5 to 7.5 cm of the esophagus was skeletonized. In 14 patients, the mean PAOI-BAO +/- S.E. within 3 months of PGV was 1985 +/- 0.7 mEq/hr, and 13 of 14 values were less than 5 mEq/hr. One patient developed recurrent ulcer and required re-operation; this patient's value for PAO-BAO was 1.8 mEq/hr. The results show quantitatively that great differences in the completeness of PGV result from differences in the periesophageal dissection and emphasize its importance if optimal results are to be obtained and, especially, if the efficacy of the operation is to be judged. (+info)
Systemic and local immune responses against Helicobacter pylori urease in patients with chronic gastritis: distinct IgA and IgG productive sites.
(4/999)
BACKGROUND: Helicobacter pylori urease is a major target for immune responses among various bacterial components in H pylori infected patients. AIMS: To analyse the relation between systemic and local humoral immune responses to H pylori urease and grades of chronic gastritis. PATIENTS: Seventy five patients with chronic gastritis associated with H pylori infection were classified into three groups (grade I, superficial gastritis; II, atrophic gastritis, quiescent; or III, atrophic gastritis, active). METHODS: Anti-H pylori urease specific antibodies in the serum, gastric juice, and biopsy specimens were determined by ELISA or western blotting analysis. The sites for H pylori urease and its specific antibody producing B lymphocytes were confirmed by immunohistochemical analysis. RESULTS: In the sera of patients with grade I gastritis, weak IgG but relatively strong IgG responses to H pylori urease were observed; dominant strong IgG responses were detected in grade II gastritis. In grade III gastritis, significant IgG and IgA responses were obtained. A similar pattern of IgA and IgG responses was detected in gastric juice and tissue. H pylori urease specific, antibody producing B cells were not found in the gastric mucosa of patients with grade I gastritis despite the presence of such B cells in the duodenal bulb. Specific B cells were observed in the gastric mucosa of patients with grade II and III gastritis with atrophy. CONCLUSIONS: Purified H pylori urease, together with localisation of its specific antibody producing B cells, are useful for serological testing and histopathological analysis for determining the stage of chronic gastritis and studying the pathogenesis of H pylori infection. (+info)
Acute lung injury after instillation of human breast milk into rabbits' lungs: effects of pH and gastric juice.
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BACKGROUND: The authors compared the lung injury in rabbits that occurred after tracheal instillation of human breast milk (HBM) acidified to pH 1.8 with hydrochloric acid (HCl), HBM at its native pH (7.0), and HBM acidified with gastric juice to pH 1.8 and 3.0. METHODS: The alveolar-to-arterial oxygen tension gradient and dynamic compliance were recorded before and hourly for 4 h after intratracheal instillation of 0.8 ml/kg HBM acidified with HCI (pH 1.8), HBM at its native pH (7.0), HBM acidified with gastric juice (pH 1.8 or 3.0), or 5% dextrose solution acidified with gastric juice (pH 1.8) as a control in 30 adult rabbits. The circulating neutrophil count and phagocyte oxidant activity were determined before and 1 and 4 h after instillation. RESULTS: The alveolar-to-arterial oxygen tension gradient increased and dynamic compliance decreased significantly in all groups after instillation of HBM compared with baseline values and those in the control group. The severity of the lung injury after instillation of HBM at all pH values (1.8, 3.0, and 7.0) and after acidification with gastric juice or HCl was similar. The circulating neutrophil count increased steadily for 4 h after instillation (P < 0.013), whereas spontaneous phagocyte oxidant burst activity peaked at 1 h (P < 0.007) and returned to baseline by 4 h after instillation. CONCLUSIONS: The severity of the lung injury after tracheal instillation of 0.8 ml/kg HBM in rabbits is similar at pH values between 1.8 and 7.0 after acidification with HCl or gastric juice. Tracheal instillation of HBM increases the circulating neutrophil count and phagocyte oxidant burst activity. (+info)
Digestion and absorption of bovine milk xanthine oxidase and its role as an aldehyde oxidase.
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The effects of acidic and intestinal proteolytic environments on bovine milk xanthine oxidase (XO) activity were determined in order to evaluate the extent to which this enzyme was absorbed in biologically active form. The inhibition of XO by folic acid and the relative affinities of XO for the oxidation of palmitaldehyde, stearaldehyde, and xanthine were compared. The effects of acid and gastric juice on XO activity were measured by incubating purified enzyme, and non-purified enzyme (milk), in buffers ranging in pH from 2 to 9. Fresh gastric juice was also incubated with milk. Increasing amounts of the enzyme were inactivated as the pH of the incubation mixture was reduced below pH 6.5. Below pH 3.5, the enzyme was completely inactivated. Gastric juice, pH juice incubated with milk. Milk XO activity was reduced 36% when mild was incubated with an equal volume of gastric juice. Homogenized milk had 59% less XO activity compared with raw molk. Fresh raw milk XO, homogenized milk XO, and purified XO were equally susceptible to inactivation by acid or gastric juice. After incubation of milk with gastric juice, or gastric juice followed by pancreatin, XO activity was associated with a macromolecule of 300,000 daltons molecular weight and subunits containg activity were not found. It was estimated that 0.00008% of the XO in the intestine was absorbed. Both folic acid and allopurinol inhibited XO activity in vitro. Allopurinol was 3.5 times more potent an inhibitor than folic acid. A large excess of dietary folic acid did not reduce rat liver or intestinal XO activity in vivo. XO had a much greater affinity for xanthine than for palmitaldehyde or stearaldehyde substrates. It was estimated that of 100 mg of XO in fresh raw milk, 41 mg remained after homogenization, 27 mg entered the intestine and only 20 ng were absorbed as intact enzyme. (+info)
Does Helicobacter pylori infection contribute to gastroesophageal reflux disease?
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Helicobacter pylori organisms that infect the stomach conceivably could contribute to esophageal inflammation in patients with gastroesophageal reflux disease (GERD) through any of at least three potential mechanisms: 1) by causing an increase in gastric acid secretion; 2) by spreading to infect the gastric-type columnar epithelium that occasionally can line the distal esophagus; and/or 3) by secreting noxious bacterial products into the gastric juice. Studies regarding these potential mechanisms are discussed in this report. Most investigations have found no apparent association between H. pylori infection and reflux esophagitis. Presently, infection with H. pylori does not appear to play an important role in the pathogenesis of GERD. (+info)
Detection of anti-VacA antibody responses in serum and gastric juice samples using type s1/m1 and s2/m2 Helicobacter pylori VacA antigens.
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Several different families of vacuolating toxin (vacA) alleles are present in Helicobacter pylori, and they encode products with differing functional activities. H. pylori strains containing certain types of vacA alleles have been associated with an increased risk for peptic ulcer disease. In this study, we tested serum samples and gastric juice from 19 H. pylori-negative and 39 H. pylori-positive patients for enzyme-linked immunosorbent assay reactivity with two different types of VacA antigens (types s1/m1 and s2/m2), which were purified from H. pylori 60190 and 86-338, respectively. Both antigens were recognized better by serum immunoglobulin G (IgG) from H. pylori-positive persons than by serum IgG from H. pylori-negative persons (P < 0.01). The s1/m1 VacA antigen was better recognized by sera from patients carrying vacA type s1/m1 strains than by sera from patients carrying vacA type s2/m2 or s1/m2 strains (P < 0.01). Conversely, the s2/m2 VacA antigen was better recognized by sera from patients carrying type s2/m2 or s1/m2 strains (P = 0.03). Serum IgG anti-VacA antibodies were present more frequently in patients carrying type s1/m1 strains than in other H. pylori-positive patients (P = 0.0002). In addition, the highest levels of IgA anti-VacA antibodies were detected in the gastric juice of patients carrying type s1/m1 strains. These data indicate that different VacA isoforms have distinct antigenic properties and that multiple forms of VacA elicit antibody responses in H. pylori-positive humans. (+info)