omeprazole, Prilosec
Omeprazole attenuates neutrophil-endothelial cell adhesive interaction induced by extracts of Helicobacter pylori.

Suzuki M, Mori M, Fukumura D, Suzuki H, Miura S, Ishii H.

Division of Gastroenterology, National Tokyo Medical Center, Japan. masay-su amy.hi-ho.ne.jp

In this study, the influence of omeprazole on the adhesive activity of neutrophils, provided by an extract of Helicobacter pylori, was determined. Human neutrophils were collected from peripheral blood and labelled with a fluorochrome. Helicobacter pylori (NCTC 11637) was cultured and its water extract was obtained by centrifugation of the bacterial suspension. Neutrophils were incubated with the extract in a plastic plate. Percentage adherence was calculated by measuring the fluorescence of floating and adherent cells. Rat mesenteric venule was prepared on an intravital microscope and the number of neutrophils which adhered to venular endothelium was counted. Neutrophil adherence to the plastic plate was increased by the presence of H. pylori extract. Pretreatment with omeprazole significantly decreased this adherence in a dose-dependent manner (10(-6)-10(-4)mol/L). Neutrophil adherence to the mesenteric venule was also increased by H. pylori extract and significantly inhibited by omeprazole. These results indicate that the neutrophil-endothelial adhesive interaction is inhibited by omeprazole, suggesting that omeprazole prevents neutrophil recruitment to the gastric mucosa associated with H. pylori infection.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10029274&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Healing of Helicobacter pylori-induced gastric ulcers in Mongolian gerbils: combined treatment with omeprazole and clarithromycin.

Keto Y, Takahashi S, Okabe S.

Department of Applied Pharmacology, Kyoto Pharmaceutical University, Misasagi, Yamashina, Japan.

Helicobacter pylori can colonize the stomachs of Mongolian gerbils and subsequently induce penetrating ulcers five months later. Using this gerbil model, the effects of both combined treatment with omeprazole and clarithromycin, as well as treatment with each drug separately, on the healing of H. pylori-induced gastric ulcers, and the effects of the cessation of the drug treatment on healed ulcers were examined. Beginning five months after H. pylori (NCTC11637) inoculation, omeprazole (four weeks), clarithromycin (two weeks), their combination, or the vehicle was orally administered once daily. These drugs, in combination or separately, markedly enhanced ulcer healing and lowered the increased myeloperoxidase (MPO) activity. While omeprazole had no effect on viable H. pylori, clarithromycin and the drug combination significantly reduced viable H. pylori. The degree of bacterial eradication was much higher in the case of the drug combination compared to clarithromycin alone. Four months after cessation of the treatment, visible ulcers, hypertrophic gastritis and increased MPO activity were found in the control animals (all H. pylori-positive). Nonetheless, only one of the eight gerbils subjected to the drug combination developed a small ulcer, although no hypertrophic gastritis was exhibited. It is concluded that: (1) the gerbil model of H. pylori infection is useful for the study of ulcer healing; (2) combined treatment with omeprazole and clarithromycin enhances the ulcer healing in infected gerbils; and (3) healed ulcers do not relapse, despite cessation of the drug treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10063909&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Helicobacter pylori infection potentiates the inhibition of gastric acid secretion by omeprazole.

Gillen D, Wirz AA, Neithercut WD, Ardill JE, McColl KE.

University Department of Medicine and Therapeutics, Western Infirmary, Glasgow G11 6NT, UK.

BACKGROUND: Omeprazole has a greater intragastric pH elevating effect in Helicobacter pylori positive than negative subjects. Ammonia production by H pylori has been suggested as a probable mechanism. AIMS: To assess the effect of H pylori status on gastric acid secretion during omeprazole treatment, and to examine the possible role of ammonia neutralisation of intragastric acid in increased omeprazole efficacy in infected subjects. METHODS: Twenty H pylori positive and 12 H pylori negative healthy volunteers were examined before and six to eight weeks after commencing omeprazole 40 mg/day. On both occasions plasma gastrin and acid output were measured basally and in response to increasing doses of gastrin 17 (G-17). Gastric juice ammonium concentrations were also measured. RESULTS: Prior to omeprazole, measurements were similar in the H pylori positive and negative subjects. During omeprazole, median basal intragastric pH was higher in the H pylori positive (7.95) versus negative (3.75) subjects (p<0.002). During omeprazole basal, submaximal (180 pmol/kg/h G-17), and maximal acid outputs (800 pmol/kg/h G-17) were lower in H pylori positive subjects (0.0, 3.6, 6.0 mmol/h respectively) versus negative subjects (0.3, 14.2, 18.6 mmol/h) (p<0.03 for each). This effect was not explained by neutralisation by ammonia. CONCLUSION: The presence of H pylori infection leads to a more profound suppression of acid secretion during omeprazole treatment. The effect cannot be explained by neutralisation of intragastric acid by bacterial ammonia production and its precise mechanism has to be explained.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10075952&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Omeprazole and dietary nitrate independently affect levels of vitamin C and nitrite in gastric juice.

Mowat C, Carswell A, Wirz A, McColl KE.

University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, Scotland.

BACKGROUND & AIMS: Hypochlorhydria is associated with an increased risk of gastric cancer. We have studied the effect of pharmacologically induced hypochlorhydria on the gastric juice ascorbate/nitrite ratio, which regulates the synthesis of potentially carcinogenic N-nitroso compounds. METHODS: Saliva, gastric juice, and serum from 20 healthy volunteers (9 positive for Helicobacter pylori), with a mean age of 30 years (range, 20-47 years), were analyzed for nitrite, ascorbic acid, and total vitamin C before and for 2 hours after ingestion of 2 mmol [corrected] nitrate (nitrate content of a standard salad meal). This was repeated after 4 weeks of treatment with omeprazole, 40 mg daily. RESULTS: Before omeprazole treatment, the nitrate meal lowered gastric ascorbic acid levels from 3.8 to 0.9 microg/mL (P < 0.05) and increased median salivary nitrite levels from 44 to 262 micromol/L (P < 0.001); gastric nitrite concentration remained undetected in 10 subjects. Omeprazole increased median fasting gastric nitrite levels from 0 to 13 micromol/L (P = 0.001) and decreased fasting gastric ascorbic acid levels from 3.8 to 0.7 microg/mL (P < 0.001). With omeprazole treatment, gastric nitrite levels after the nitrate meal were markedly increased at 154 micromol/L (range, 49-384 micromol/L; P < 0.001). In H. pylori-infected subjects, omeprazole also decreased total vitamin C levels in both gastric juice and serum. CONCLUSIONS: Omeprazole and dietary nitrate independently decrease the ascorbate/nitrite ratio. This may lead to an increased risk of gastric cancer.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10092303&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Species differences in hepatocyte induction of CYP1A1 and CYP1A2 by omeprazole.

Shih H, Pickwell GV, Guenette DK, Bilir B, Quattrochi LC.

Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.

Omeprazole, a proton pump inhibitor therapeutically administered for the treatment of gastric ulcers, induces the expression of cytochromes P4501A1/2 (CYP1A1/2) through transcriptional activation mediated by the Ah-dioxin)-receptor. Primary cultures of hepatocytes isolated from rabbit, rat, mouse and human livers were compared for CYP1A1/2 mRNA inducibility by omeprazole (1 to 100 microM). Primary cultures of human hepatocytes were the most sensitive to the inducing effects of omeprazole. Rabbit hepatocytes were the only other cells studied that showed induced CYP1A1/2 mRNA expression from a concentration lower than 100 microM (i.e., 10 microM). Rat hepatocytes were the least sensitive to omeprazole induction. The response of mouse hepatocytes to omeprazole treatment was variable, with CYP1A1/2 mRNA expression being induced in only two of the three cultures examined. Differences in the time dependence of CYP1A1/2 mRNA expression were observed between species. In general, after treatment of hepatocytes with omeprazole the levels of CYP1A1 mRNA peaked prior to that of CYP1A2 mRNA. Due to the interspecific variability of CYP1A mRNA inducibility by omeprazole, we conclude that human hepatocytes in culture are probably the only appropriate animal model for prediction of CYP1A induction in humans.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10100022&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Structural and mechanistic aspects of transcriptional induction of cytochrome P450 1A1 by benzimidazole derivatives in rat hepatoma H4IIE cells.

Backlund M, Weidolf L, Ingelman-Sundberg M.

Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. maria.backlund imm.ki.se

The effect of several structurally different benzimidazole compounds on CYP1A1 expression at the transcriptional, mRNA and protein levels was investigated in the rat hepatoma H4IIE cell line. Omeprazole, thiabendazole, carbendazim, 2-mercaptobenzimidazole and 2-mercapto-5-methoxybenzimidazole caused a dose-dependent increase in CYP1A1 protein levels that reached maximum effect at 250 microm, as measured by Western blot. In addition, hydroxyomeprazole, 2-aminobenzimidazole and 2-mercapto-5-nitro-benzimidazole caused a notable increase in CYP1A1 protein expression, whereas 5-O-desmethylomeprazole, 2-hydroxybenzimidazole, 2-benzimidazole propionic acid and 5-benzimidazole carboxylic acid were ineffective. Thus, benzimidazole substituted with a thiol or an amino group in the 2-position were active inducers. Northern blot analysis confirmed an extensive increase of CYP1A1 mRNA induced by omeprazole and 2-mercapto-5-methoxybenzimidazole which was 32% and 49% of maximal induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) respectively, whereas thiabendazole and carbendazim showed approximately 15% increase as compared to TCDD. Transient transfection of H4IIE cells, with a XRE-pGL3 reporter gene construct revealed a 2.3-4.3-fold induction by carbendazim, thiabendazole, and 2-mercapto-5-methoxybenzimidazole as compared to a 3.3- and 23-fold induction by omeprazole and TCDD, respectively. Thus, these data indicate that the benzimidazoles utilize the aryl hydrocarbon receptor-arnt-XRE-mediated signal-transduction pathway for induction of the CYP1A1 gene.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10103034&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Effects of pantoprazole, a novel H+/K+-ATPase inhibitor, on duodenal ulcerogenic and healing responses in rats: a comparative study with omeprazole and lansoprazole.

Takeuchi K, Konaka A, Nishijima M, Kato S, Yasuhiro T.

Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Japan. takeuchi mb.kyoto-phu.ac.jp

BACKGROUND: Pantoprazole, 2-[(2-pyridylmethyl) sulphinyl] benzimidazole, is a new substituted benzimidazole that inhibits the parietal cell H+/K+-ATPase. METHODS: In the present study, the anti-secretory and anti-ulcer activities of pantoprazole were compared with those of omeprazole and lansoprazole in rats. RESULTS: Pantoprazole (0.3-3 mg/kg, p.o.) as well as omeprazole (1-10 mg/kg, p.o.) and lansoprazole (1-10 mg/kg, p.o.) dose-dependently decreased both basal acid secretion in pylorus-ligated rats and the stimulated acid secretion induced by mepirizole in acute fistula rats, and the effects of pantoprazole were more potent than those of omeprazole and lansoprazole, the ED50 values for the stimulated acid secretion being 0.8, 2.0 and 1.2 mg/kg, respectively. Neither of these drugs had any effect on duodenal HCO3- secretion. These pump inhibitors prevented the development of duodenal lesions in response to mepirizole in a dose-related manner, the ED50 values for pantoprazole, omeprazole and lansoprazole being 0.4, 2.0 and 1.3 mg/kg, respectively. Likewise, pantoprazole showed the healing promoting action on chronic duodenal ulcers induced by acetic acid, and this effect was also more potent when compared to omeprazole or lansoprazole. CONCLUSIONS: We conclude that pantoprazole exhibited both anti-ulcer and healing promoting effects on duodenal ulcers in rats, and the effects may be attributable to its potent anti-secretory action. Other pump inhibitors such as omeprazole and lansoprazole were almost equally effective as pantoprazole, yet this drug was most potent on the basis of ED50 values.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10197495&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Helicobacter pylori and the efficacy of omeprazole therapy for gastroesophageal reflux disease.

Schenk BE, Kuipers EJ, Klinkenberg-Knol EC, Eskes SA, Meuwissen SG.

The Department of Gastroenterology, Free University Hospital, Amsterdam, The Netherlands.

OBJECTIVE: Helicobacter pylori infection may affect gastric acid output and intragastric pH. In patients with an insufficient lower esophageal sphincter, this effect may theoretically influence the severity of reflux disease, as well as the efficacy of acid suppressive therapy. To evaluate whether the H. pylori status of patients with gastroesophageal reflux disease (GERD) affects the severity of disease and the efficacy of omeprazole therapy to maintain disease remission, we conducted this study. METHODS: Patients with GERD were prospectively studied by upper gastrointestinal endoscopy with biopsy sampling for histology and H. pylori culture before start of treatment and at annual follow-up. At endoscopy, esophagitis was graded according to the criteria of Savary-Miller, and the presence of Barrett's esophagus, hiatal herniation, or other abnormalities was recorded. Omeprazole was started at an initial dose of 20 mg daily; the dose was adjusted based on symptoms and the endoscopical findings. RESULTS: One hundred thirty-seven GERD patients were included and followed up for a mean 56.6 months; 49 (36%) of them were infected with H. pylori. H. pylori-infected and -uninfected patients did not differ with respect to age (60 +/- 13 vs 61 +/- 14 yr, p = 0.65) or duration of follow-up (54 +/- 30 vs 58 +/- 31 months, p = 0.12). H. pylori-negative patients tended to present with more severe esophagitis at baseline (median Savary-Miller score 3 vs 2, p = 0.06) and had a higher prevalence of Barrett's esophagus (39/88 vs 10/49, p = 0.006). However, no difference was found with respect to the dose of omeprazole needed for maintained relief of symptoms and endoscopical signs of esophagitis (median 40 mg in both groups, p = 0.35). CONCLUSIONS: H. pylori-negative GERD patients have a higher prevalence of Barrett's esophagus, but do not need a higher dose of omeprazole to maintain symptomatic and endoscopical disease remission.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10201451&dopt=Abstract omeprozole Prilosec