Differences in oxidative stress dependence between gastric adenocarcinoma subtypes.

Aim: To investigate the extent of oxidative stress in pre-neoplastic and neoplastic gastric mucosa in relation to their pathological criteria and histological subtypes.

Methods: A total of 104 gastric adenocarcinomas from 98 patients (88 infiltrative and 16 intraepithelial tumors) were assessed immunohistochemically for expression of iNOS and occurrence of nitrotyrosine (NTYR)-containing proteins and 8-hydroxy-2'-deoxyguanosine (8-OH-dG)-containing DNA, as markers of NO production and damages to protein and DNA.

Results: Tumor cells staining for iNOS, NTYR and 8-OH-dG were detected in 41%, 62% and 50% of infiltrative carcinoma, respectively.

Authorship ignorance: views of researchers in French clinical settings.

Objectives: To assess the knowledge and behaviour of researchers regarding criteria for authorship, and the practices of ghost and gift authorship.

Design: Semidirective interviews of senior clinical researchers.

Setting: University hospital.

Oxidative stress in gastric mucosa of asymptomatic humans infected with Helicobacter pylori: effect of bacterial eradication.

Background: Inducible nitric oxide synthase (iNOS) and interleukin 8 (IL-8) are positive in approximately 50% of Helicobacter pylori-related diseases but it is not clear whether oxidative stress is also present in H. pylori asymptomatic humans. Our aim was to study the expression of iNOS, superoxide dismutase, catalase and IL-8 production in H.

Chlorination of guanosine and other nucleosides by hypochlorous acid and myeloperoxidase of activated human neutrophils. Catalysis by nicotine and trimethylamine.

Activated human neutrophils secrete myeloperoxidase, which generates HOCl from H2O2 and Cl(-). We have found that various (2'-deoxy)nucleosides react with HOCl to form chlorinated (2'-deoxy)nucleosides, including novel 8-chloro(2'-deoxy)guanosine, 5-chloro(2'-deoxy)cytidine, and 8-chloro(2'-deoxy)adenosine formed in yields of 1.6, 1.

Helicobacter pylori eradication attenuates oxidative stress in human gastric mucosa.

Objective: Helicobacter pylori infection causes gastric diseases, but the responsible mechanisms are not completely understood. They can involve DNA and tissue damage induced by reactive oxygen and nitrogen species. Our aim is to investigate the effects of bacterial eradication on oxidative stress by measuring changes of relevant markers.

Endogenous N-nitroso compounds, and their precursors, present in bacon, do not initiate or promote aberrant crypt foci in the colon of rats.

Processed meat intake is associated with increased risk of colorectal cancer. This association may be explained by the endogenous formation of N-nitroso compounds (NOC). The hypothesis that meat intake can increase fecal NOC levels and colon carcinogenesis was tested in 175 Fischer 344 rats.

Increased oxidative and nitrative stress in human stomach associated with cagA+ Helicobacter pylori infection and inflammation.

In order to study the role of Helicobacter pylori infection in gastric carcinogenesis, we have measured oxidized (carbonyls) and nitrated (nitrotyrosine-containing) proteins as markers for oxidative and nitrative stress in 216 human gastric biopsies using dot and western immunoblots and correlated the results with H. pylori, cagA status, expression of interleukin-8 and inducible nitric oxide synthase (iNOS) mRNAs, and gastric pathology. Higher levels of both oxidized and nitrated proteins were found in patients with either chronic gastritis or duodenal ulcer than in those with normal mucosa.

Nitrated and oxidized plasma proteins in smokers and lung cancer patients.

Cigarette smoking is a cause of lung cancer and other respiratory diseases. Oxidants either present in cigarette smoke and/or formed in the lung of smokers may trigger oxidative and nitrative damage to DNA and cellular components, contributing to carcinogenesis. We have used immunodot and Western blot analyses to measure nitrated (nitrotyrosine-containing) and oxidized (carbonyl-containing) proteins in plasma samples collected from 52 lung cancer patients and 43 control subjects (heavy and light smokers, nonsmokers with or without exposure to environmental tobacco smoke).

Formation of N-nitrosamines and N-nitramines by the reaction of secondary amines with peroxynitrite and other reactive nitrogen species: comparison with nitrotyrosine formation.

Reactive nitrogen species, including nitrogen oxides (N(2)O(3) and N(2)O(4)), peroxynitrite (ONOO(-)), and nitryl chloride (NO(2)Cl), have been implicated as causes of inflammation and cancer. We studied reactions of secondary amines with peroxynitrite and found that both N-nitrosamines and N-nitramines were formed. Morpholine was more easily nitrosated by peroxynitrite at alkaline pH than at neutral pH, whereas its nitration by peroxynitrite was optimal at pH 8.

The effect of intra-gastric acidity and flora on the concentration of N-nitroso compounds in the stomach.

Background: Correa's hypothesis proposes that gastric carcinogenesis is due to atrophic gastritis and hypochlorhydria which permit gastric bacterial colonization, the reduction of dietary nitrates to nitrites and the formation of potentially carcinogenic N-nitroso compounds (NOCs).

Objective: To test the hypothesis that omeprazole-induced hypochlorhydria is associated with increased intra-gastric concentrations of nitrate-reducing bacteria (NRB), nitrites and NOCs.

Design: Single-blind study in healthy volunteers.

Coexpression of interleukin-8 and inducible nitric oxide synthase in gastric mucosa infected with cagA+ Helicobacter pylori.

The cagA-positive Helicobacter pylori strains are thought to be able to induce interleukin-8 expression and to be associated with gastroduodenal diseases. Inducible nitric oxide synthase (iNOS) may be involved in inflammatory pathogenesis. Our aim was to investigate the interrelationships between cagA and the expression of interleukin-8 and iNOS messenger RNAs, and with the type and degree of inflammation in gastric mucosa.

Peroxynitrite: an endogenous oxidizing and nitrating agent.

Peroxynitrite, the reaction product between nitric oxide (.NO) and superoxide, has been presumed to be a mediator of cellular and tissue injury in various pathological situations. It is formed at the convergence of two independent radical-generating metabolic pathways.

Analysis of 3-nitrotyrosine in biological fluids and protein hydrolyzates by high-performance liquid chromatography using a postseparation, on-line reduction column and electrochemical detection: results with various nitrating agents.

Nitric oxide reacts rapidly with superoxide to form the strong nitrating agent peroxynitrite, which is responsible for much of the tissue damage associated with diverse pathophysiological conditions such as inflammation. The occurrence of free or protein-bound nitrotyrosine (NTYR) has been considered as evidence for in vivo formation of peroxynitrite. However, various agents can nitrate tyrosine, and their relative significance in vivo has not been determined due to lack of a sensitive method to analyze NTYR in tissue proteins and biological fluids.

Inducible nitric oxide synthase, anti-oxidant enzymes and Helicobacter pylori infection in gastritis and gastric precancerous lesions in humans.

Chronic inflammation induced by Helicobacter pylori infection has been associated with an increased risk of stomach cancer. We have analysed 167 stomach biopsies from 99 patients for H. pylori infection and immunohistochemically for the expression of inducible nitric oxide synthase (iNOS), catalase and superoxide dismutases (SODs) as markers of oxidative stress.

Antimutagenic dietary phenolics as antigenotoxic substances in urothelium of smokers.

Human urine is known to contain substances that strongly inhibit bacterial mutagenicity of aromatic and heterocyclic amines in vitro. The biological relevance of these anti-mutagens was examined by comparing levels of tobacco-related DNA adducts in exfoliated urothelial cells from smokers with the anti-mutagenic activity in corresponding 24-h urine samples. An inverse relationship was found between the inhibition of PhIP-mutagenicity by urine extracts in vitro and two DNA adduct measurements: the level of the putatively identified ABP-dG adduct and the total level of all tobacco-smoke-related carcinogen adducts including those probably derived from PhIP.

Dietary phenolics as anti-mutagens and inhibitors of tobacco-related DNA adduction in the urothelium of smokers.

Human urine is known to contain substances that strongly inhibit bacterial mutagenicity of aromatic and heterocyclic amines in vitro. The biological relevance of these anti-mutagens was examined by comparing levels of tobacco-related DNA adducts in exfoliated urothelial cells from smokers with the anti-mutagenic activity in corresponding 24-h urine samples. An inverse relationship was found between the inhibition of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-mutagenicity by urine extracts in vitro and two DNA adduct measurements: the level of the putatively identified N-(deoxyguanosine-8-yl)-4-aminobiphenyl adduct and the total level of all tobacco-smoke-related carcinogen adducts including those probably derived from PhIP.

Bacterial overgrowth during treatment with omeprazole compared with cimetidine: a prospective randomised double blind study.

Background: Gastric and duodenal bacterial overgrowth frequently occurs in conditions where diminished acid secretion is present. Omeprazole inhibits acid secretion more effectively than cimetidine and might therefore more frequently cause bacterial overgrowth.

Aim: This controlled prospective study compared the incidence of gastric and duodenal bacterial overgrowth in patients treated with omeprazole or cimetidine.

Does increased endogenous formation of N-nitroso compounds in the human colon explain the association between red meat and colon cancer?

High red meat diets have been linked with risk of sporadic colorectal cancer; but their effects on mutations which occur in this cancer are unknown. G-->A transitions in K-ras occur in colorectal cancer and are characteristic of the effects of alkylating agents such as N-nitroso compounds (NOC). We studied th effect of red meat consumption on faecal NOC levels in eight male volunteers who consumed diets low or high in meat (60 or 600 g/day), as beef, lamb or pork, whilst living in a metabolic suite.

Formation of 8-nitroguanine by the reaction of guanine with peroxynitrite in vitro.

Nitric oxide and superoxide anion, both formed in inflamed tissues, react rapidly to form the peroxynitrite anion (ONOO-), a strong oxidant which can initiate reactions characteristic of hydroxyl radical (HO.), nitronium ion (NO2+) and nitrogen dioxide radical (NO2.).

Effect of omeprazole on intragastric bacterial counts, nitrates, nitrites, and N-nitroso compounds.

Previous studies have suggested that profound inhibition of gastric acid secretion may increase exposure to potentially carcinogenic N-nitroso compounds. The aim of this study was to find out if the proton pump inhibitor omeprazole (20 mg daily) is associated with increased concentrations of potentially carcinogenic N-nitroso compounds in gastric juice. The volume of gastric contents, number of bacteria, and concentrations of nitrates, nitrites, and N-nitroso compounds was determined in gastric aspirates obtained after an overnight fast in 14 healthy volunteers (7M:7F) after one week of treatment with placebo, and one and two weeks' treatment with omeprazole.

In vivo nitrosoproline formation and other risk factors in Costa Rican children from high- and low-risk areas for gastric cancer.

The hypothesis that intragastric synthesis of N-nitroso compounds (NOC) in early life could play a role in gastric carcinogenesis was tested by applying the N-nitrosoproline (NPRO) test to about 50 children living in high- and low-risk areas for stomach cancer in Costa Rica. The median values of excretion of NPRO and the sum of three nitrosamino acids (micrograms/12 h urine) were 10-20% of those in adults from other geographical high-risk areas for stomach cancer. The urinary NPRO level after proline intake was higher in children from the high-risk area (P < 0.