Dietary antioxidants and DNA damage in patients on long-term acid-suppression therapy: a randomized controlled study.

Free radicals and reactive species produced in vivo can trigger cell damage and DNA modifications resulting in carcinogenesis. Dietary antioxidants trap these species limiting their damage. The present study evaluated the role of vitamins C and E in the prevention of potentially premalignant modifications to DNA in the human stomach by supplementing patients who, because of hypochlorhydria and possible depletion of gastric antioxidants, could be at increased risk of gastric cancer. Patients undergoing surveillance for Barrett's oesophagus (n 100), on long-term proton pump inhibitors were randomized into two groups: vitamin C (500 mg twice/d) and vitamin E (100 mg twice/d) for 12 weeks (the supplemented group) or placebo. Those attending for subsequent endoscopy had gastric juice, plasma and mucosal measurements of vitamin levels and markers of DNA damage. Seventy-two patients completed the study. Plasma ascorbic acid, total vitamin C and vitamin E were elevated in the supplemented group consistent with compliance. Gastric juice ascorbic acid and total vitamin C levels were raised significantly in the supplemented group (P=0.01) but supplementation had no effect on the mucosal level of this vitamin. However, gastric juice ascorbic acid and total vitamin C were within normal ranges in the unsupplemented group. Mucosal malondialdehyde, chemiluminescence and DNA damage levels in the comet assay were unaffected by vitamin supplementation. In conclusion, supplementation does not affect DNA damage in this group of patients. This is probably because long-term inhibition of the gastric proton pump alone does not affect gastric juice ascorbate and therefore does not increase the theoretical risk of gastric cancer because of antioxidant depletion.

A standardized mouse model of Helicobacter pylori infection: introducing the Sydney strain.

BACKGROUND & AIMS: Currently available Helicobacter pylori models show variable and, in some instances, poor colonization. There is a need for a strain with high colonizing ability to act as a standard for animal studies. METHODS: After screening a range of fresh clinical isolates and long-term adaptation in mice, a strain of H. pylon has been isolated with a very good colonizing ability. RESULTS: This strain, named the Sydney strain of H. pylori (strain SS1), is cagA and vacA positive. High levels of colonization (10(6)-10(7) colony-forming units/g tissue) were achieved consistently in C57BL/6 mice. Colonization levels varied depending on the mouse strain used with BALB/c, DBA/2, and C3H/He, all being colonized but in lower numbers. In all strains of mice, bacteria were clearly visible at the junctional zone between the antrum and the body. The phenotype was stable with colonizing ability remaining after 20 subcultures in vitro. The bacterium attached firmly to gastric epithelium. During 8 months, a chronic active gastritis slowly developed, progressing to severe atrophy in both C57BL/6 and BALB/c mice. CONCLUSIONS: The Sydney strain of H. pylori is available to all and will provide a standardized mouse model for vaccine development, compound screening, and studies in pathogenesis.

Ascorbic acid and total vitamin C concentrations in plasma, gastric juice, and gastrointestinal mucosa: effects of gastritis and oral supplementation.

Epidemiological evidence suggests that high dietary ascorbic acid reduces gastric cancer risk. It may do this by either reducing N-nitroso compound formation in gastric juice, or by scavenging reactive oxygen species in gastric mucosa. The aim of this study was to discover if potential ascorbic acid protection might be increased by supplementation. Thirty two patients were supplemented with ascorbic acid, 500 mg twice daily for two weeks. Gastric juice, plasma, and upper gastrointestinal biopsy ascorbate concentrations were measured and compared with values in 48 unsupplemented patients. It was found that ascorbic acid and total vitamin C concentrations were considerably higher in biopsy specimens from oesophagus, body, antrum, duodenum, and rectum, compared with values in plasma or gastric juice. Plasma and mucosal concentrations were unaffected by the presence of chronic gastritis but gastric juice concentrations were substantially lower in patients with chronic gastritis than in patients with normal histological assessment (p < 0.01). Patients receiving ascorbic acid supplements had higher ascorbic acid concentrations in plasma (p < 0.001), gastric juice (p < 0.001), and at all biopsy sites in the upper gastrointestinal tract (p < 0.05). Gastric juice ascorbic acid and total vitamin C concentrations in gastritic patients, however, were still less after supplementation than in normal subjects (p < 0.01). These data suggest that high ascorbic acid intake could reduce gastric cancer risk, but its protective effect might be greater if gastritis is treated (for example, by Helicobacter pylori eradication).

The barium enema appearances in solitary rectal ulcer syndrome.

Solitary rectal ulcer syndrome is a benign condition of unknown aetiology, usually found in young adults. The main clinical complaint is of rectal bleeding, often with change in bowel habit. The radiological findings in 17 patients with histologically proven solitary rectal ulcer syndrome, seen at the General Infirmary at Leeds over an 8-year period, are presented. Ulceration, polypoid lesion, stricture, granularity or a normal rectal mucosa may all be found on barium enema. The histological findings and pathogenesis of the condition are discussed.

A comparison of prednisolone enemas with low-dose oral prednisolone in the treatment of acute distal ulcerative colitis.

The therapeutic efficacy of prednisolone metasulphobenzoate enemas in the treatment of distal colitis has been compared with that of low-dose oral prednisolone, in a single-blind, cross-over trial. Treatment with steroid enemas resulted in symptomatic and sigmoidoscopic evidence of improvement more frequently than treatment with a dosage of oral steroid calculated to achieve similar plasma prednisolone levels. In addition to demonstrating, for the first time, that prednisolone metasulphobenzoate enemas are effective in the treatment of colitis, this study suggests that their efficacy is due to a local action rather than systemic absorption.

Treatment of distal ulcerative colitis (proctosigmoiditis) in relapse: comparison of hydrocortisone enemas and rectal hydrocortisone foam.

Thirty patients with distal colitis (proctosigmoiditis) in relapse were randonly allocated to twice daily treatment with traditional aqueous hydrocotrisone enemas (Cortenemas) or a suspension of hydrocortisone in an inert foam base (Colifoam). Each treatment contained the same amount of hydrocortisone. Clinical, sigmoidoscopic, and histological response was assessed after two weeks. Both agents were effective, and broadly similar in terms of objective improvement, but subjective improvement was greater with the foam preparation, and several patients expressed a preference to this mode of treatment.