dinoprost and Helicobacter-Infections

Aspirin causes peptic ulcers predominately by reducing gastric mucosal cyclooxygenase (COX) activity and prostaglandin synthesis. Because aspirin circulates for only a few hours, we hypothesized that aspirin's inhibitory effect on gastric COX activity must be prolonged. We performed a placebo-controlled experiment in healthy humans to determine the duration of inhibition of aspirin on gastric mucosal COX activity (PGE(2) and PGF(2alpha) synthesis rates). Recovery of gastric COX activity after stopping aspirin was slow and linear. Seventy-two hours after 325-mg aspirin, gastric COX activity was still reduced by 57% (P < 0.001). Duration of inhibition of gastric COX activity was estimated to be 7-8 days after 325-mg aspirin and 5 days after 81-mg aspirin. Recovery of gastric prostaglandin synthesis after 325-mg but not after 81-mg aspirin occurred at slower rates in subjects with Helicobacter pylori-associated gastritis than in those with normal histology. In conclusion, aspirin inhibits gastric COX activity for much longer than predicted from its pharmacokinetic profile, explaining why aspirin at widely spaced intervals is ulcerogenic.

Topics: Adolescent; Adult; Aspirin; Blood Platelets; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Prostaglandin-Endoperoxide Synthases; Regression Analysis; Stomach Ulcer; Thromboxane A2; Time Factors

Helicobacter pylori (H. pylori) infection triggers both local inflammation, usually in gastric mucosa, and chronic systemic inflammation. It is assumed that this local and systemic inflammation is caused by extracellular products excreted by H. pylori. The aim of this study was to investigate the possible association between H. pylori infection and a local inflammatory response in the airway by using exhaled breath condensate technique.. This study includes 41 H. pylori seropositive patients who have gastric symptoms and 27 healthy control subjects. Pulmonary function tests (PFT), chest X ray, and physical examination were performed in all patients and interleukin-6 (IL-6), 8-isoprostane and nitrotyrosine levels were measured in exhaled breath condensate.. Levels of IL-6 and 8-isoprostane in exhaled breath condensate (EBC) were significantly higher in H. pylori positive patients than control subjects (p < 0.05). Nitrotyrosine levels were also higher in H. pylori positive patients but the difference was not statistically significant. Both groups had similar leukocyte counts, C-reactive protein (CRP) levels and PFT parameters.. H. pylori infection causes an asymptomatic airway inflammation which can be detected by exhaled breath condensate. The clinical importance of this inflammation remains unclear.

Topics: Adult; Breath Tests; Dinoprost; Female; Helicobacter Infections; Humans; Interleukin-6; Male; Middle Aged; Tyrosine

We aimed at investigating the relationship between Helicobacter pylori infection and in vivo lipid peroxidation and platelet activation, as reflected by urinary 8-iso-prostaglandin (PG)F(2alpha) and 11-dehydro-thromboxane (TX)B2, respectively, in otherwise healthy dyspeptic subjects.. We measured urinary 8-iso-PGF2alpha and 11-dehydro-TXB2 excretion in 40 dyspeptic subjects with a positive 13C-urea breath test and 38 dyspeptic individuals with a negative test. Moreover, we investigated the effects of H pylori eradication on prostanoid metabolite excretion in 23 H pylori-positive subjects. We also measured prostanoid metabolite excretion before and after selective cyclooxygenase-2 inhibition with rofecoxib in 4 H pylori-positive subjects. Urinary 8-iso-PGF2alpha and 11-dehydro-TXB2 excretion was significantly higher in the H pylori-positive individuals than in controls. A significant direct correlation was found between the degree of positivity to the 13C-urea breath test and urinary 8-iso-PGF2alpha excretion. The latter was linearly correlated with urinary 11-dehydro-TXB2. Successful eradication of H pylori infection led to a significant reduction in both 8-iso-PGF(2alpha) and 11-dehydro-TXB2. Furthermore, their levels were unaffected after treatment with rofecoxib.. Our study provides evidence of enhanced in vivo lipid peroxidation and platelet activation in association with H pylori infection and suggests a novel mechanism by which an infectious agent could contribute to atherothrombosis.

Topics: Adult; Aged; Cross-Sectional Studies; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprost; Fasting; Helicobacter Infections; Helicobacter pylori; Humans; Lipid Peroxidation; Male; Membrane Proteins; Middle Aged; Platelet Activation; Prostaglandin-Endoperoxide Synthases; Thromboxane B2

We measured gastric and duodenal mucosal prostaglandin concentrations in 69 patients with active or inactive duodenal or gastric ulcer disease and 26 non-ulcer controls. Each underwent endoscopy enabling us to obtain multiple biopsies from the gastric body and antrum and from the duodenal bulb and postbulbar duodenum for measurement of mucosal prostaglandin concentrations, as well as a single biopsy from each region for mucosal histology. Using a multivariate linear regression model, we found that neither gastric nor duodenal ulcer disease significantly affected gastric or duodenal mucosal prostaglandin concentrations. Mucosal prostaglandin concentrations were similar at the edge of the ulcer and in the adjacent non-ulcerated mucosa. Neither gender symptoms, smoking, use of H2-receptor antagonists, disease activity, nor Helicobacter pylori infection had an independent effect on mucosal prostaglandins in any region. Gastritis in the body of the stomach was associated with significantly higher prostaglandins, while older age was associated with significantly lower gastric and duodenal prostaglandins. Gastroduodenal mucosal prostaglandins are thus not altered in patients with active or inactive peptic ulcer disease, even when multiple demographic and histologic variables are taken into consideration.

Topics: Age Factors; Dinoprost; Dinoprostone; Duodenal Ulcer; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Male; Metaplasia; Middle Aged; Prevalence; Prospective Studies; Stomach Ulcer

To evaluate behavioral, demographic, clinical, and histologic variables that independently influence gastroduodenal mucosal prostaglandin concentrations.. Prospective study.. A clinical research laboratory located in a Department of Veterans Affairs hospital.. Fifty-two healthy adults who had no history of peptic ulcer disease and who were not receiving nonsteroidal anti-inflammatory drugs.. Mucosal biopsy specimens were obtained endoscopically from the stomach (body and antrum) and the duodenum (bulb and postbulbar area). Mucosal extracts from each of these four regions were assessed by radioimmunoassay to determine prostaglandin E2 and prostaglandin F2 alpha concentrations. Specimens were also examined histologically for inflammation and the presence of Helicobacter pylori. A multivariate linear regression model was used to determine which behavioral, demographic, and histologic variables significantly and independently influenced gastroduodenal mucosal prostaglandin concentrations.. Smoking and older age were independently associated with lower prostaglandin concentrations in all four mucosal regions (P = 0.0001 to P = 0.05). Compared with results in young nonsmokers, mucosal prostaglandin concentrations were reduced by 70% to 80% in older smokers. Gender, alcohol use, endoscopic appearance, dyspeptic symptoms, mucosal inflammation, and the presence of H. pylori had no consistent effect on prostaglandin content.. Smoking and older age are associated with significantly reduced gastric and duodenal prostaglandin concentrations. These observations may help explain the predisposition to ulcer disease in smokers and older persons.

Topics: Adult; Aged; Aged, 80 and over; Aging; Alcohol Drinking; Dinoprost; Dinoprostone; Duodenum; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Intestinal Mucosa; Male; Middle Aged; Multivariate Analysis; Regression Analysis; Sex Characteristics; Smoking