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Acid Inhibition (acid + inhibition)
Selected AbstractsDiazoxide, a KATP opener, accelerates restitution of ethanol or indomethacin-induced gastric ulceration in rats independent of polyaminesJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 3 2001M Rahgozar Abstract Background and Aims: Experimental acute gastric ulcerations (EAGU) are healed very rapidly. This healing process has two steps; mucosal restitution and delayed repair. Adenosine 5,-triphosphate (ATP)-dependent potassium channels (KATP) have a regulatory role in the gastrointestinal physiology. In the present study, the effects of KATP channel modulators; diazoxide (channel opener) and glibenclamide (channel antagonist) on the healing of EAGU were investigated. The effect of polyamine (mediators presumably responsible for restitution) biosynthesis by difluoromethylornithine (DFMO) on diazoxide-induced alterations, and the effects of acid secretion inhibitors (cimetidine, omeprazole and atropine) on the mucosal restitution of EAGU were also studied. Methods: Groups of 10 male rats were starved for 24 h and EAGU was induced by oral administration of 1 mL 60% ethanol or a subcutaneous injection of 30 mg/kg indomethacin. Different groups were subjected to various doses of diazoxide (5, 15, 45 mg/kg) and/or glibenclamide (2, 6, 18 mg/kg) administered intraperitoneally (i.p.) after EAGU induction. Polyamine biosynthesis was inhibited by a single i.p. injection of DFMO (500 mg/kg), administered 10 min before EAGU induction. Cimetidine, omeprazole or atropine were administered intraperitoneally at doses of 200, 5 and 1 mg/kg, respectively, after EAGU induction. Animals were killed and their gastric mucosa was examined for ulcerations. Results: Diazoxide accelerated the healing of EAGU, whereas glibenclamide aggravated EAGU. The concomitant administration of glibenclamide antagonized the diaoxide effect. Diazoxide-induced acceleration of mucosal restitution was not abolished by DFMO. Cimetidine, omeprazole and atropine had no effect on the healing of EAGU. Conclusion: The KATP channels may play an important role in the gastric mucosal restitution independent of polyamines. Acid inhibition cannot reverse EAGU. [source] Effect of concomitant dosing of famotidine with lansoprazole on gastric acid secretion in relation to CYP2C19 genotype statusALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2005T. FURUTA Background :,Famotidine increases Helicobacter pylori -eradication rates by a triple lansoprazole/amoxicillin/clarithromycin therapy in patients with the rapid extensive metabolizer genotype of CYP2C19. Aim :,To determine the effect of famotidine on the gastric acid inhibition by lansoprazole in relation to CYP2C19 genotypes. Methods :,Twenty healthy volunteers with different CYP2C19 genotypes , consisting of six rapid extensive metabolizers, nine intermediate metabolizers and five poor metabolizers , underwent three 7-day courses with placebo, lansoprazole 30 mg twice daily, and lansoprazole 30 mg twice plus famotidine 20 mg twice daily. Lansoprazole was dosed after breakfast and dinner. Famotidine was dosed after lunch and at bedtime. Intragastric pH monitoring was performed for 24 h on day 7 of each course. Results :,With placebo, no difference was observed in intragastric pH profiles among the three CYP2C19 genotype groups. With lansoprazole 30 mg twice daily, the median of 24-h intragastric pH in poor metabolizers (6.1) was significantly higher than those of rapid extensive metabolizers (4.5) and intermediate metabolizers (5.0), respectively (P = 0.0176 and 0.0388), whereas with lansoprazole 30 mg twice and famotidine 20 mg twice daily, the medians were 5.4, 5.7, and 6.1, respectively (not significant). Conclusion :,Acid inhibition by lansoprazole was influenced by CYP2C19 genotype status. This influence was offset by the concomitant use of famotidine. [source] Low-dose intravenous pantoprazole for optimal inhibition of gastric acid in Korean patientsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2007Jung-Hwan Oh Abstract Background and Aim:, Proton-pump inhibitor (PPI) therapy for bleeding ulcers is more efficacious in Asian patients than in non-Asian patients. The aim of this study was to evaluate the efficacy of various doses of pantoprazole on intragastric acidity in Korean patients. Methods:, A prospective randomized study was conducted in 52 patients either with bleeding peptic ulcers after successful endotherapy or who received endoscopic mucosal resection for gastric neoplasms. Patients were randomized into two doses of intravenous pantoprazole: 40 mg q.d. and 40 mg b.i.d. We compared these results with our preliminary study utilizing high-dose pantoprazole (80 mg + 8 mg/h). The potential contribution of CYP2C19 genetic polymorphisms and the presence of Helicobacter pylori were also assessed. Results:, Pantoprazole 40 mg b.i.d. and high-dose pantoprazole demonstrated better inhibition of intragastric acid than pantoprazole q.d. (P < 0.05). The pantoprazole 40 mg q.d. group exhibited significant variations in acid inhibition correlating with CYP2C19 genotype. Median 24 h pH values did not differ significantly between the pantoprazole b.i.d. and high-dose pantoprazole groups, regardless of H. pylori infection status. A median intragastric pH < 6.0 was observed in only three of 28 patients in the 40 mg b.i.d. group; these three patients were extensive metabolizers. Conclusion:, A 40 mg b.i.d. dose of pantoprazole is sufficient to maintain pH > 6.0 in Korean patients, except for patients with extensive metabolizing CYP2C19 genotypes. [source] Factors affecting the sensitivity to acid inhibition in novel acrylates characterized by secondary functionalitiesJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 7 2007Harini Kilambi Abstract Here we demonstrate that acrylates exhibit significant rate reductions in the presence of small concentrations of protic acids (0.1,0.5 wt %) compared with the bulk monomer concentration. Dramatically different sensitivities to acid inhibition, differing by up to 2 orders of magnitude, are exhibited for various acrylates. This study examines the various factors that cause enhanced sensitivity toward acid inhibition in novel acrylates characterized by carbamate and cyclic carbonate secondary functionalities. Acid inhibition studies conducted in the presence of a highly polar solvent, such as propylene carbonate, have been performed to determine the impact of overall medium polarity and the extent of acid dissociation on the sensitivity to acid inhibition. The studies depict only a twofold increase in the parameters associated with acid inhibition, upon the addition of 70 wt % propylene carbonate, in comparison with an increase of 2 orders of magnitude for the novel acrylates. These studies indicate that the susceptibility to acid inhibition is primarily determined by the stability of the hypothesized radical,acid complex as well as its propensity to terminate with other species in the system and not by the extent of acid dissociation in the system. Furthermore, it is implied that the stability of the radical,acid complex and its propensity to terminate with other species in the system are dominated by intramolecular interactions. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 1287,1295, 2007 [source] Effects of long-term cyclo-oxygenase 2 selective and acid inhibition on Barrett's oesophagusALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2007A. LANAS Summary Background There is an overexpression of cyclo-oxygenase 2 (COX-2) in Barrett's oesophagus (BO). Aim To determine the long-term effect of a COX-2 inhibitor on cellular mechanisms involved in BO. Methods A randomized controlled trial was conducted in BO patients allocated to continue the usual proton pump inhibitor (PPI) alone treatment, or PPI combined with rofecoxib (25 mg/day) for 6 months. Cell proliferation index and COX-2 expression in BO glands was determined in biopsy specimens at baseline and after treatment. Cell apoptosis, cyclin D1, p53 and vascular endothelial growth factor (VEGF) expression was also explored in a subset of patients. Student- t test and the U-Mann,Whitney test were used for quantitative and ordinal variables. Results Of 62 patients, 58 completed the study. A higher proportion of patients on rofecoxib + PPI exhibited a decrease in COX-2 expression compared to those treated with PPI alone, but cell proliferation index was not affected. Unlike PPI alone, rofecoxib + PPI was associated with an increase in the apoptotic cell index, a decrease in p53 cell staining and VEGF expression in mucosal vessels. No effect on low-grade dysplasia or cyclin D1 was observed. Conclusions The addition of rofecoxib to PPI therapy does not affect cell proliferation index in BO cells after 6 months of therapy, but does reduce COX-2 and VEGF expression and increases cell apoptosis. [source] Effect of concomitant dosing of famotidine with lansoprazole on gastric acid secretion in relation to CYP2C19 genotype statusALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2005T. FURUTA Background :,Famotidine increases Helicobacter pylori -eradication rates by a triple lansoprazole/amoxicillin/clarithromycin therapy in patients with the rapid extensive metabolizer genotype of CYP2C19. Aim :,To determine the effect of famotidine on the gastric acid inhibition by lansoprazole in relation to CYP2C19 genotypes. Methods :,Twenty healthy volunteers with different CYP2C19 genotypes , consisting of six rapid extensive metabolizers, nine intermediate metabolizers and five poor metabolizers , underwent three 7-day courses with placebo, lansoprazole 30 mg twice daily, and lansoprazole 30 mg twice plus famotidine 20 mg twice daily. Lansoprazole was dosed after breakfast and dinner. Famotidine was dosed after lunch and at bedtime. Intragastric pH monitoring was performed for 24 h on day 7 of each course. Results :,With placebo, no difference was observed in intragastric pH profiles among the three CYP2C19 genotype groups. With lansoprazole 30 mg twice daily, the median of 24-h intragastric pH in poor metabolizers (6.1) was significantly higher than those of rapid extensive metabolizers (4.5) and intermediate metabolizers (5.0), respectively (P = 0.0176 and 0.0388), whereas with lansoprazole 30 mg twice and famotidine 20 mg twice daily, the medians were 5.4, 5.7, and 6.1, respectively (not significant). Conclusion :,Acid inhibition by lansoprazole was influenced by CYP2C19 genotype status. This influence was offset by the concomitant use of famotidine. [source] Effect of low-dose rabeprazole and omeprazole on gastric acidity: results of a double blind, randomized, placebo-controlled, three-way crossover study in healthy subjectsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2004S. Bruley des Varannes Summary Background :,The treatment of acid-related symptoms requires rapid and consistent acid suppression, especially with on-demand regimens. Aim :,To compare the antisecretory activity of low-dose rabeprazole and omeprazole in healthy, Helicobacter pylori -negative subjects. Methods :,In this randomized, double-blind, placebo-controlled, three-way crossover study, 27 volunteers were given rabeprazole 10 mg, omeprazole 10 mg, or placebo once daily for 7 days with a 10,14-day washout between treatments. Intragastric pH was monitored for 24-h on days 1 and 7 of each treatment. Results :,Median gastric pH was significantly higher with rabeprazole than with omeprazole or placebo: day 1: 2.3, 1.4 and 1.3, respectively (P = 0.0056, rabeprazole vs. omeprazole; P < 0.0001, rabeprazole vs. placebo); day 7: 3.7, 2.2 and 1.3, respectively (P = 0.0016 rabeprazole vs. omeprazole; P < 0.0001, rabeprazole vs. placebo). Time with gastric pH above 4 was significantly higher with rabeprazole than with omeprazole: day 1, 5.8 h vs. 3.7 h, respectively (P < 0.02); day 7, 10.5 h vs. 4.6 h, respectively (P = 0.0008). Conclusions :,Rabeprazole 10 mg provides more rapid acid inhibition compared with omeprazole 10 mg. After 7 days, the time with pH above 4 is more than doubled with rabeprazole 10 mg vs. omeprazole 10 mg. [source] Double gastric infection with Helicobacter pylori and non- Helicobacter pylori bacteria during acid-suppressive therapy: increase of pro-inflammatory cytokines and development of atrophic gastritisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2001S. Sanduleanu Background: Long-term acid suppression may accelerate the development of atrophic gastritis in Helicobacter pylori -positive subjects. The pathogenetic mechanism remains unclear. Aim: To test the hypothesis that gastric double infection with H. pylori and non -H. pylori bacterial species,during acid suppression,may result in an enhanced inflammatory response, contributing to the development of atrophic gastritis. Patients and methods: A consecutive series of patients with gastro-oesophageal reflux disease undergoing treatment with proton pump inhibitors (n=113) or histamine2 -receptor antagonists (H2 -RAs) (n=37), and 76 non-treated dyspeptic controls were investigated. Gastric mucosal H. pylori and non- H. pylori bacteria, histological gastritis, H. pylori serology, and circulating interleukin (IL)-1,, IL-6, and IL-8 were examined. Results: Patients on acid suppression with either proton pump inhibitors or H2 -RAs had a similar prevalence of H. pylori infection to the controls, but a higher prevalence of non- H. pylori bacteria (61% and 60% vs. 29%, P < 0.0001 and P < 0.002). Both the presence of H. pylori and non- H. pylori bacteria were independent risk factors of atrophic gastritis (antrum: relative risks (RRs), 10.1 and 5.07; corpus: RRs, 11.74 and 6.38). A simultaneous presence of H. pylori and non- H. pylori bacteria was associated with a markedly increased risk of atrophic gastritis (antrum: RR, 20.25; corpus: RR, 20.38), compatible with a synergistic effect. Furthermore, the simultaneous presence of both types of bacteria was associated with higher cytokine levels than in patients without any type of bacteria. This increase was also greater than in patients with H. pylori infection alone (P < 0.001, for both IL-1, and IL-8). Summary and conclusions: H. pylori -positive patients on long-term acid inhibition displayed three features: non- H. pylori bacterial growth; increased cytokine levels; and a higher risk of atrophic gastritis. We suggest that double infection with H. pylori and non- H. pyloribacteria is a major factor in the development of atrophic gastritis during gastric acid inhibition. [source] Methotrexate catabolism to 7-hydroxymethotrexate in rheumatoid arthritis alters drug efficacy and retention and is reduced by folic acid supplementationARTHRITIS & RHEUMATISM, Issue 8 2009Joseph E. Baggott Objective To assess the catabolism of methotrexate (MTX) to 7-hydroxy-MTX (7-OH-MTX) in patients with rheumatoid arthritis as well as the effect of folic acid and folinic acid on this catabolism. Methods Urinary excretion of MTX and its catabolite, 7-OH-MTX, was measured in 2 24-hour urine specimens collected after MTX therapy. Urine samples were collected from patients after the sixth and seventh weekly doses of MTX. MTX and 7-OH-MTX concentrations were determined by high-performance liquid chromatography mass spectrometry. Swelling and pain/tenderness indices were used to measure symptoms before and at 6 and 7 weeks of therapy. Patients received either folic acid or folinic acid supplements (1 mg/day) from week 6 to week 7. Results Folic acid inhibited aldehyde oxidase (AO), the enzyme that produces 7-OH-MTX, but folinic acid did not. Excretion of 7-OH-MTX (determined as a percentage of the dose of MTX or as mg 7-OH-MTX/gm creatinine) was not normally distributed (n = 39). Patients with marked improvement in swelling and pain/tenderness indices had a lower mean 7-OH-MTX excretion level (P < 0.05). Patients who received folic acid supplements had decreased 7-OH-MTX excretion (P = 0.03). Relatively high 7-OH-MTX excretion was correlated with relatively high MTX excretion and with relatively low MTX retention in vivo (P < 0.05) (n = 35). Conclusion Our findings of a non-normal distribution of 7-OH-MTX excretion suggest that there are at least 2 phenotypes for this catabolism. Decreased 7-OH-MTX formation suggests folic acid inhibition of AO and a better clinical response, while increased 7-OH-MTX formation may interfere with MTX polyglutamylation and binding to enzymes and, therefore, may increase MTX excretion and decrease MTX retention and efficacy in vivo. [source] Reduced Blood Platelet Sensitivity to Aspirin in Coronary Artery Disease: Are Dyslipidaemia and Inflammatory States Possible Factors Predisposing to Sub-optimal Platelet Response to Aspirin?BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2006Leszek Markuszewski Platelet non-responsiveness to aspirin is associated with an increased risk of serious cardiovascular events. Several environmental and hereditary factors are reportedly involved in sub-optimal acetylsalicylic acid response. Forty-five coronary artery disease patients and 45 non-coronary artery disease controls received acetylsalicylic acid at a daily dose of 75,150 mg. Controls were examined twice: on the day of entering the study and 10 days later. Urinary 11-dehydrothromboxane B2 was assessed as the marker of platelet thromboxane generation. Aggregation was studied in platelet-rich plasma using turbidimetric aggregometry with collagen and arachidonic acid. Fifty to seventy percent of coronary artery disease patients showed an extent of collagen-induced aggregation above the upper quartile of the reference range compared with 8,15% in controls (P<0.003). For arachidonic acid-activated aggregation these proportions were 45,50% in coronary artery disease versus 7% in controls (P<0.007). In coronary artery disease patients, the acetylsalicylic acid-mediated platelet inhibition positively correlated with increased triglycerides (in arachidonic acid-stimulated platelets, r=0.30, P=0.0018), total cholesterol (r=0.33, P<0.0001 in coll and arachidonic acid-activated platelets) and elevated serum C-reactive protein (CRP) (r=0.27, P=0.0024). In coronary artery disease patients urine 11-dehydrothromboxane B2 concentrations were significantly increased compared to controls after 10 day acetylsalicylic acid intake (563; 313,728 pg/mg creatinine versus 321; 246,488 pg/mg creatinine, P=0.04). The incidence of suboptimal acetylsalicylic acid response incidence was more common in patients with coronary artery disease. Acetylsalicylic acid inhibition of blood platelet reactivity and thromboxane generation was less effective in these patients. Dyslipidaemia and chronic inflammatory states may promote suboptimal acetylsalicylic acid response in coronary artery disease patients. [source] The Choice of Proton Pump Inhibitor: Does it matter?BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2004Per M. Hellström Comparisons of four different proton pump inhibitors: lansoprazole, omeprazole, pantoprazole, and rabeprazole show that they all have similar potency and efficacy. Rabeprazole, however, displays a slightly more rapid onset of acid inhibition than the others; the clinical advantage of this seems limited. The S-isomer of omeprazole, esomeprazole, exhibits a somewhat higher potency than the other proton pump inhibitors. Reports supporting a clinical advantage of this property are not convincing. To conclude, all inhibitors seem comparable as regards inhibition of gastric acid secretion. [source] Engineering Propionibacterium acidipropionici for enhanced propionic acid tolerance and fermentationBIOTECHNOLOGY & BIOENGINEERING, Issue 4 2009An Zhang Abstract Propionibacterium acidipropionici, a Gram-positive, anaerobic bacterium, has been the most used species for propionic acid production from sugars. In this study, the metabolically engineered mutant ACK-Tet, which has its acetate kinase gene knocked out from the chromosome, was immobilized and adapted in a fibrous bed bioreactor (FBB) to increase its acid tolerance and ability to produce propionic acid at a high final concentration in fed-batch fermentation. After about 3 months adaptation in the FBB, the propionic acid concentration in the fermentation broth reached ,100,g/L, which was much higher than the highest concentration of ,71,g/L previously attained with the wild-type in the FBB. To understand the mechanism and factors contributing to the enhanced acid tolerance, adapted mutant cells were harvested from the FBB and characterized for their morphology, growth inhibition by propionic acid, protein expression profiles as observed in SDS,PAGE, and H+ -ATPase activity, which is related to the proton pumping and cell's ability to control its intracellular pH gradient. The adapted mutant obtained from the FBB showed significantly reduced growth sensitivity to propionic acid inhibition, increased H+ -ATPase expression and activity, and significantly elongated rod morphology. Biotechnol. Bioeng. 2009; 104: 766,773 © 2009 Wiley Periodicals, Inc. [source] Genetic factors involved in the development of Helicobacter pylori -related gastric cancerCANCER SCIENCE, Issue 11 2006Nobuyuki Hamajima Developmental process to gastric cancer by Helicobacter pylori infection consists of three steps: (1) H. pylori infection; (2) gastric atrophy development; and (3) carcinogenesis. In each step, genetic traits may influence the process, interacting with lifestyle. In the step of H. pylori infection, two lines of genetic polymorphisms were assumed: one influencing gastric acid inhibition interacting with smoking, and the other concerning innate immune response attenuation. The former includes functional polymorphisms of IL-1B (C-31T or tightly linked T-511C), and TNF-A (T-1031C and C-857T), and the latter possibly includes NQO1 C609T. In the step to gastric atrophy, polymorphisms pertaining to the signal transduction from cytotoxin-associated gene A (PTPN11 A/G at intron 3) and to T-cell responses (IL-2 T-330G and IL-13 C-1111T) were hypothesized. There are a limited number of epidemiological genotype studies on the final step of literal carcinogenesis, potentially interacting with smoking, a low vegetable and fruit intake, and salty foods, the well-documented risk factors. In past case-control studies on the associations between genotype and gastric cancer risk, the cases consisted of H. pylori -related and unrelated gastric cancer patients and the controls consisted of individuals including the uninfected (H. pylori unexposed and exposed) and the infected with and without gastric atrophy. Accordingly, it was not clear whether the observed risk was for H. pylori -related or -unrelated gastric cancer, nor which step was involved in the observed associations even when nearly all cases were H. pylori -related. In order to elucidate the genetic traits of H. pylori -related gastric cancer, stepwise evaluation will be required. (Cancer Sci 2006; 97: 1129,1138) [source] | ||||||||||