Induction of DNA damage by risk factors of colon cancer in human colon cells derived from biopsies.

In order to increase the understanding of the factors responsible for causing human colon cancer, a technique was developed to detect genotoxic effects of chemicals in human colon cells. Risk factors suspected to be associated with the aetiology of human colon cancer were subsequently investigated: the method is based on the measurement of DNA damage in primary cells freshly isolated from human colon biopsies with the single cell microgel ectrophoresis technique ('Comet Assay'). 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3-methyl-3H-imidazo[4,5f]quinoline (IQ), N-methyl-N-nitro-N-nitrosoguanidine (MNNG), dinitrosocaffeidine (DNC) lithocholic acid (LCA), hydrogen peroxide (H2O2) and benzo[a]pyrene (B[a]P) were investigated for their genotoxic and cytotoxic effects following 30 min incubation with colon cells of human, and for comparative purposes also of the rat colon.

Detection of genotoxic effects in human gastric and nasal mucosa cells isolated from biopsy samples.

To assess genotoxic burdens from chemicals, it is necessary to relate observations in experimental animals to humans. The success of this extrapolation would be increased by including data on chemical activities in human tissues. Therefore, we have developed techniques to assess DNA damage in human gastric and nasal mucosa (GM, NM) cells.

[Nizatidine in therapy and prevention of non-steroidal anti-rheumatic drug-induced ulcers in rheumatic patients].

269 patients with various rheumatic disorders who had been treated with non-steroidal anti-inflammatory drugs (NSAID) for at least three weeks, were enrolled in this randomised double-blind multicenter trial. Entry criteria were both the presence of an ulcer in gastric and/or duodenal mucosa (> 3 mm and < 20 mm in diameter) as well as dyspeptic symptoms. The patients had been treated with 150 mg nizatidine nocte (n = 86), 2 x 150 mg/d (n = 93) and 2 x 300 mg/d (n = 90) nizatidine.

[High-dose ranitidine protects stomach and duodenum completely against piroxicam. An endoscopic double-blind pilot study].

In a randomized placebo-controlled parallel and double-blind study the gastroduodenal effects of 20 mg piroxicam daily was evaluated endoscopically in the presence of ranitidine 150 mg bid or 300 mg bid in 31 healthy volunteers. Drugs were taken over a period of 14 days. Endoscopies were performed at entry and repeated after 14 days of treatment.

Dose-range finding study with the proton pump inhibitor pantoprazole in acute duodenal ulcer patients.

Pantoprazole is a newly developed benzimidazole derivative with strong inhibitory actions on gastric acid secretion by blocking H(+)-K(+)-ATPase. This randomized double-blind multicenter trial investigated the efficacy of 20 mg, 40 mg and 80 mg pantoprazole o.m.

An alprostadil analogue and human gastric secretion. A double-blind placebo-controlled study of the effects of a capsule and tablet formulation.

The effects of single oral doses of 800 and 1200 micrograms of the new alprostadil analogue mexiprostil (prostaglandin E1 16-methyl-16-methoxy derivative, MDL 646), presented as tablet and capsule formulation, on basal and pentagastrin-stimulated acid secretion, were studied in 10 healthy volunteers, using a randomized, double-blind, placebo-controlled, 5-way crossover design. Compared to placebo, administration of mexiprostil resulted in a significant inhibition of basal gastric acid secretion, at both doses and formulations. Pentagastrin-stimulated gastric secretion was reduced to a lesser degree and the differences compared to placebo did not achieve statistical significance when adjustments were made for basal effects present before starting stimulation.

Human gastric acid secretion following repeated doses of AG-1749.

The effect of increasing doses (15 mg, 30 mg and 60 mg) of the substituted benzimidazole, AG-1749, on gastric acid secretion and fasting serum gastrin concentration has been studied after repeated administration to healthy volunteers. AG-1749 produced a dose-dependent and profound decrease in basal and stimulated gastric acid secretion in all volunteers, with almost total suppression at the highest dose. The extent of inhibition increased between Day 2 and Day 8 with the 15 and 30 mg doses of AG-1749.

[Ranitidine ameliorates acemetacin and indomethacin-induced changes of the gastroduodenal mucosa, without modifying the pharmacokinetic behavior of both antirheumatic drugs].

12 healthy volunteers participated in this double-blind, randomized, cross-over study. All subjects were given indomethacin (50 mg tid) or acemetacin (60 mg tid) for 6 days in the presence and absence of ranitidine 300 mg at night. At day 6 120 minutes after the last morning dose an endoscopy was performed and the appearance of the gastric and duodenal mucosa was noted.

Comparison of the gastroduodenal tolerance of tenoxicam and diclofenac Na. A double-blind, endoscopically controlled study in healthy volunteers.

The gastroduodenal tolerance of Tenoxicam and Diclofenac Na has been evaluated in a double-blind, parallel group study in 36 healthy male volunteers. The doses used were 20 mg Tenoxicam and 100 mg Diclofenac Na daily in a retard formulation for 14 days. Gastric tolerance was assessed by endoscopy, which was performed at base-line, after the 14 day dosing period and after a 14 day follow-up period without treatment.