Randomised clinical trial: twice daily esomeprazole 40 mg vs. pantoprazole 40 mg in Barrett's oesophagus for 1 year.

BACKGROUND: Barrett's oesophagus is regarded as the most important risk factor for development of oesophageal adenocarcinoma. According to current guidelines, treatment should be limited to symptomatic Barrett's oesophagus. AIM: To evaluate the expression of Ki67, cyclooxygenase-2 (COX-2) and apoptosis in Barrett's oesophagus after 12 months of double-dose proton pump inhibitor therapy. The effectiveness of esomeprazole and pantoprazole was also compared. METHODS: Seventy-seven nondysplastic Barrett's oesophagus patients underwent baseline upper endoscopy. Patients were then randomised into two groups: one group was allocated to receive esomeprazole 40 mg b.d. and the other group pantoprazole 40 mg b.d. for 12 months. A follow-up endoscopy was performed at the end of treatment. Sixty-five of 77 patients agreed to undergo oesophageal manometry and 24-h pH-metry. Barrett's oesophagus biopsies, obtained at baseline and after treatment, were analysed using immunohistochemistry to assess Ki67 and COX-2 expression; apoptosis was evaluated using TUNEL. RESULTS: In the esomeprazole group, a significant decrease in Ki67 and COX-2 expression, as well as an increase in apoptosis, were observed (P < 0.05). By contrast, in the pantoprazole group Ki67, COX-2 and apoptosis did not vary significantly from baseline. By 24-h oesophageal pH-monitoring, a normal acid exposure time was recorded in patients treated with esomeprazole, while those allocated to pantoprazole displayed abnormal acid exposure (P < 0.05). CONCLUSIONS: Treatment of Barrett's oesophagus patients with high-dose esomeprazole, but not pantoprazole, promoted a decrease in proliferative markers, concomitantly with a decrease in apoptotic cell death. Moreover, esomeprazole allowed a better oesophageal acid control than pantoprazole.

Effects of a bicarbonate-alkaline mineral water on digestive motility in experimental models of functional and inflammatory gastrointestinal disorders.

This study investigates the effects of Uliveto, a bicarbonate-alkaline mineral water, in experimental models of diarrhea, constipation and colitis. Rats were allowed to drink Uliveto or oligomineral water (control) for 30 days. Diarrhea and constipation were evoked by 16,16-dimethyl-prostaglandin E(2) (dmPGE(2)) or loperamide, respectively. Colitis was induced by 2,4-dinitrobenzenesulfonic acid (DNBS) or acetic acid. Gastric emptying, small-intestinal and colonic transit were evaluated. dmPGE(2)-induced diarrhea reduced gastric emptying and increased small-intestinal and colonic transit. In this setting, Uliveto water enhanced gastric emptying, and this effect was prevented by L-365,260 (gastrin receptor antagonist). Loperamide-induced constipation reduced gastric emptying, small-intestinal and colonic transit, and these effects were prevented by Uliveto water. L-365,260 counteracted the effects of Uliveto on gastric emptying, while alosetron (serotonin 5-HT(3) receptor antagonist) blunted the effect of Uliveto on colonic transit. Gastric emptying, small-intestinal and colonic transit were reduced in DNBS-induced colitis, and Uliveto water enhanced gastric emptying and normalized small-intestinal and colonic transit. Gastric emptying, small-intestinal and colonic transit were also reduced in acetic acid-induced colitis, and Uliveto increased both gastric emptying and small-intestinal transit. In conclusion, Uliveto water exerts beneficial effects on gastrointestinal motility in the presence of bowel motor dysfunctions. The effects of Uliveto water on gastric emptying depend on gastrin-mediated mechanisms, whereas the activation of serotonergic pathways accounts for the modulation of colonic functions.

Effect of a novel mucoadhesive polysaccharide obtained from tamarind seeds on the intraocular penetration of gentamicin and ofloxacin in rabbits.

This report describes the efficacy of a novel mucoadhesive polymer, the tamarind seed polysaccharide, as a delivery system for the ocular administration of hydrophilic and hydrophobic antibiotics. Healthy rabbits were subjected to repeated ocular instillations with either conventional gentamicin or ofloxacin or these agents viscosified with the tamarind seed polysaccharide. Administration of viscosified preparations produced antibiotic concentrations both in the aqueous humour and cornea that were significantly higher than those achieved with the drugs alone. The increased drug absorption and the prolonged drug elimination phase obtained with the viscosified formulations indicate the usefulness of the tamarind seed polysaccharide as an ophthalmic delivery system for topical administration of antibiotics.

Periodontal tissue disposition of azithromycin in patients affected by chronic inflammatory periodontal diseases.

BACKGROUND: The recognition that periodontal diseases are associated with specific pathogens has led to interest in the use of antibacterial drugs for inhibition of these microorganisms. On these bases, the present study was aimed at evaluating the tissue distribution of the new macrolide antibiotic azithromycin in patients subjected to oral surgery for chronic inflammatory diseases of both marginal and periapical periodontium. METHODS: Thirty-two patients were treated with azithromycin 500 mg/day orally for 3 consecutive days, and drug concentrations in plasma, saliva, normal gingiva, and pathological periodontal tissues were evaluated. For this purpose, samples of blood, saliva, normal gingiva, granulation tissue, and radicular granuloma or cyst wall (from dentigerous cyst) were collected during oral surgery or 0.5, 2.5, 4.5, and 6.5 days after the end of pharmacological treatment; then, azithromycin levels were measured by a microbiological plate assay, using Micrococcus luteus NCTC 8440 as the indicator organism. RESULTS: The concentrations of azithromycin in plasma, saliva, normal gingiva, and pathological tissues reached the highest values 12 hours after the last dose (0.37+/-0.05 mg/l, 2.12+/-0.30 mg/l, 6.30+/-0.68 mg/kg, and 11.60+/-1.50 mg/kg, respectively) and then declined gradually. Consistent levels of the drug in normal gingiva and pathological tissues could be detected, however, up to 6.5 days, indicating that azithromycin was retained in target tissues for a long time after the end of treatment. Moreover, azithromycin levels in both normal gingiva and pathological tissues exceeded the minimum inhibitory concentrations of most pathogens involved in the pathophysiology of chronic inflammatory periodontal diseases. Notably, azithromycin levels in pathological tissues were significantly higher than those in normal gingiva 0.5, 2.5, and 4.5 days after the last dose. CONCLUSIONS: The present results indicate a marked penetration of azithromycin into both normal and pathological periodontal tissues, suggesting that azithromycin represents a promising option in both adjunctive and prophylactic treatments of chronic inflammatory periodontal diseases.

Protective action of omeprazole against gastric mucosal injury induced by hemorrhagic shock in rats.

The efficacy of omeprazole in preventing gastric mucosal injury induced by hemorrhagic shock in rats and the putative mechanisms involved in this effect were investigated in the present study. Omeprazole did not affect mean arterial blood pressure under both basal conditions and induction of hemorrhagic shock, but it evoked a marked increase in Alcian blue recovery from gastric preepithelial mucus. The morphometric analysis of histological sections revealed that omeprazole caused a significant reduction of hemorrhagic shock-induced damage of gastric mucosa. Ranitidine, used as the reference drug, failed to affect mean arterial blood pressure, Alcian blue recovery from gastric mucus, or hemorrhagic shock-induced damage of gastric mucosa. Both omeprazole and ranitidine exerted a significant inhibition of gastric acid output from anesthetized pylorus-ligated rats. Overall, the present results indicate that omeprazole is effective in protecting gastric mucosa from necrotic damage induced by hemorrhagic shock and suggest that an enhancement of gastric mucus secretion contributes to this protective action.

Macrolide antibiotics as antiinflammatory agents: roxithromycin in an unexpected role.

The antiinflammatory activity of a new 14-membered macrolide antibiotic, roxithromycin, was evaluated in various rat models including carrageenan- and poly-L-arginine-induced hind-paw oedema, croton oil inflamed ear assay and polyester sponge granuloma. When administered orally to animals, roxithromycin displayed an atypical profile in the assays utilized, including: (1) marked antioedema activity similar to that of indomethacin in poly-L-arginine assay, (2) significant inhibition of lambda-carrageenan hind-paw oedema and croton-oil-induced inflammation in the ear, although indomethacin was more effective, and (3) failure to reduce the development of granuloma induced by implanted polyester sponges, while indomethacin significantly reduced the chronic inflammatory reaction. Based on these results, it is concluded that roxithromycin is active in reducing the acute inflammatory reaction in rat models through mechanisms different from conventional nonsteroidal antiinflammatory agents such as indomethacin. Therefore, roxithromycin may have a favorable impact on skin inflammatory reactions accompanying microbial infections.