ABSTRACT: BACKGROUND: It has been reported that the acidity of gastric contents could be an important factor in regulating jejunal flora. AIMS: To investigate the effects of omeprazole induced changes in gastric pH on jejunal flora and bile acid metabolism. METHODS: Twenty one patients with gastric ulcer and 19 healthy volunteers were studied. Deconjugation of bile acids was detected using a bile acid breath test. Jejunal fluid was aspirated using a double lumen tube with a rubber cover on the tip and deconjugation was examined using thin layer chromatography. Fat malabsorption was detected by a triolein breath test. RESULTS: In the bile acid breath test, expired breath samples from all patients and healthy volunteers showed significantly greater 14CO2 specific activity after omeprazole treatment (20 mg/day) than before treatment. Bacterial overgrowth was found in the jejunal fluid and gastric juice of both ulcer patients and healthy volunteers after omeprazole treatment. The following species were identified: Escherichia coli, Candida albicans, enterococcus, Lactobacillus bifidus, Bacteroides vulgatus, B uniformis, Eubacterium lentum, Eu parvum, and Corynebacterium granulosum. All of these species, except E coli and C albicans, deconjugate bile acids. There was a significant correlation between 14CO2 activity and gastric pH, both before and after omeprazole treatment in both groups. The triolein breath test revealed impaired fat absorption in both groups after omeprazole treatment. CONCLUSIONS: Both patients with gastric ulcer and healthy volunteers exhibited increased deconjugation of bile acids caused by bacterial overgrowth in the jejunum and fat malabsorption after omeprazole treatment. The bacterial over-growth consisted of both anaerobes and aerobes with deconjugation ability and was probably associated with an omeprazole induced shift to neutral pH in the gastric juice.
Project description:<h4>Background</h4>GastroGard, an omeprazole powder paste formulation, is considered the standard treatment for gastric ulcers in horses and is highly effective. Gastrozol, an enteric-coated omeprazole formulation for horses, has recently become available, but efficacy data are controversial and sparse.<h4>Objectives</h4>To investigate the efficacy of GastroGard and Gastrozol at labeled doses (4 and 1 mg of omeprazole per kg bwt, respectively, PO q24h) in healing of gastric ulcers.<h4>Animals</h4>40 horses; 9.5 ± 4.6 years; 491 ± 135 kg.<h4>Methods</h4>Prospective, randomized, blinded study. Horses with an ulcer score ?1 (Equine Gastric Ulcer Council) were randomly divided into 2 groups and treated for 2 weeks each with GastroGard followed by Gastrozol (A) or vice versa (B). After 2 and 4 weeks, scoring was repeated and compared with baseline. Plasma omeprazole concentrations were measured on the first day of treatment after administration of GastroGard (n = 5) or Gastrozol (n = 5).<h4>Results</h4>Compared with baseline (squamous score (A) 1.65 ± 0.11, (B) 1.98 ± 0.11), ulcer scores at 2 weeks ((A) 0.89 ± 0.11, (B) 1.01 ± 0.11) and 4 weeks ((A) 1.10 ± 0.12, (B) 0.80 ± 0.12) had significantly decreased in both groups (P < .001), independent of treatment (P = .7). Plasma omeprazole concentrations were significantly higher after GastroGard compared with Gastrozol administration (AUCGG = 2856 (1405-4576) ng/mL × h, AUCGZ = 604 (430-1609) ng/mL × h; P = .03). The bioavailability for Gastrozol was 1.26 (95% CI 0.56-2.81) times higher than for GastroGard.<h4>Conclusions and clinical importance</h4>Both Gastrozol and GastroGard, combined with appropriate environmental changes, promote healing of gastric ulcers in horses. However, despite enteric coating of Gastrozol, plasma omeprazole concentrations after single labeled doses were significantly higher with GastroGard.
Project description:The aim of this study was to examine the effects of CYP2C19*2 and *3 genetic polymorphisms on omeprazole pharmacokinetic (PK) and pharmacodynamic (PD) responses. Twenty-four healthy Korean volunteers were enrolled and given 20 mg omeprazole orally once daily for 8 days. The genotypes of CYP2C19 single nucleotide polymorphisms (SNPs) (*2, *3, and *17) were screened. The plasma concentrations of omeprazole, omeprazole sulfone, and 5-hydroxy (5-OH) omeprazole were determined by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The noncompartmental method was used for the determination of PK parameters. Change of mean pH and proportion (%) of time of gastric pH above 4.0 were estimated. The poor metabolizer (PM) group had the lowest metabolic ratio and exhibited the highest area under the curve (AUC) for omeprazole among the CYP2C19 phenotype groups. The PM group showed the greatest change of mean pH and the highest % time of gastric pH above 4.0. The relationship between AUC of omeprazole and % time of gastric pH above 4.0 was confirmed. The study demonstrates that CYP2C19*2 and *3 influence the PKs and PDs of omeprazole in Korean healthy volunteers.
Project description:A series of new 2-(ethylthio)benzohydrazone derivatives (1-6) were prepared and characterised by IR, 1H NMR, and 13C NMR spectroscopy and mass spectrometry. The newly prepared compounds were screened for their in vitro antioxidant activities using free radical scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Among them, most powerful antioxidant, compound 1 has been selected in order to illustrate anti-ulcer effect on ethanol-induced gastric mucosal lesions in rats. Four groups of Sprague Dawley rats were respectively treated with 10% Tween 20 as ulcer control group, 20 mg/kg omeprazole as reference group, 50 mg/kg and 100 mg/kg compound 1 as experimental animals. Macroscopically, ulcer control group showed extensive hemorrhagic lesions of gastric mucosa compared with omeprazole or compound 1. Rats pre-treated with compound 1 showed increased in gastric pH and gastric mucus. Histologically, ulcer control group showed severe damage to gastric mucosa with edema and leucocytes infiltration of submucosal layer. In immunohistochemical analysis, rats which were pre-treated with compound 1 showed up-regulation of HSP70 and down-regulation of Bax proteins. In conclusion, the gastroprotective effect of compound 1 may be due to its antioxidant activity, and/or due to up-regulation of HSP70 and down-regulation of Bax protein in stained tissue section.
Project description:BACKGROUND: Although the effects of resistant starch (RS) on postprandial glycemia and insulinemia have been extensively studied, little is known about the impact of RS on fat metabolism. This study examines the relationship between the RS content of a meal and postprandial/post-absorbative fat oxidation. RESULTS: 12 subjects consumed meals containing 0%, 2.7%, 5.4%, and 10.7% RS (as a percentage of total carbohydrate). Blood samples were taken and analyzed for glucose, insulin, triacylglycerol (TAG) and free fatty acid (FFA) concentrations. Respiratory quotient was measured hourly. The 0%, 5.4%, and 10.7% meals contained 50 muCi [1-14C]-triolein with breath samples collected hourly following the meal, and gluteal fat biopsies obtained at 0 and 24 h. RS, regardless of dose, had no effect on fasting or postprandial insulin, glucose, FFA or TAG concentration, nor on meal fat storage. However, data from indirect calorimetry and oxidation of [1-14C]-triolein to 14CO2 showed that addition of 5.4% RS to the diet significantly increased fat oxidation. In fact, postprandial oxidation of [1-14C]-triolein was 23% greater with the 5.4% RS meal than the 0% meal (p = 0.0062). CONCLUSIONS: These data indicate that replacement of 5.4% of total dietary carbohydrate with RS significantly increased post-prandial lipid oxidation and therefore could decrease fat accumulation in the long-term.
Project description:Oesophagitis might result from the effects of chemokines produced by oesophageal cells in response to gastro-oesophageal reflux, and not solely from the direct, caustic effects of refluxed gastric juice. Proton pump inhibitors (PPI) can block chemokine production through mechanisms independent of their antisecretory effects. We studied omeprazole effects on chemokine production by oesophageal epithelial cells exposed to acidic bile salts.Human primary and telomerase-immortalised oesophageal squamous cells were exposed to acidic bile salt medium with or without omeprazole pretreatment. Interleukin (IL)-8 expression was determined by RT-PCR and ELISA. IL-8 promoter activity was measured by luciferase reporter assay. Binding of NF-?B and AP-1 subunits to the IL-8 promoter was assessed by chromatin immunoprecipitation (ChIP) assay. Immune cell migration induced by conditioned medium was determined by a double-chamber migration assay system.Acidic bile salt medium caused oesophageal epithelial cells to express IL-8 mRNA and protein by activating the IL-8 promoter through NF-?B and AP-1 binding. Omeprazole inhibited that acidic bile salt-stimulated IL-8 expression by blocking the nuclear translocation of p65 (an NF-?B subunit), and by blocking the binding of p65, c-jun and c-fos (AP-1 subunits) to the IL-8 promoter. Omeprazole also blocked the ability of conditioned medium from cells exposed to acidic bile salts to induce immune cell migration.In oesophageal squamous epithelial cells, omeprazole inhibits IL-8 expression through effects on NF-?B and AP-1 that are entirely independent of effects on gastric acid secretion. These previously unrecognised PPI effects might contribute to the healing of reflux oesophagitis.
Project description:Although physiological functions of the CCK-B/gastrin receptor are well explored, little is known about its role during healing. Here, we evaluated the role of this receptor in the rat oxyntic mucosa following the introduction of a cryoulcer. In this model, we located and quantified CCK-B/gastrin receptors by reverse transcriptase PCR and receptor autoradiography. Rats with cryoulcers were treated with placebo, omeprazole, the CCK-B/gastrin receptor antagonist YF-476, omeprazole plus YF-476, gastrin-17, and gastrin 17 plus YF-476. During wound healing, CCK-B/gastrin receptors were specifically expressed and localized to the regenerative mucosal ulcer margin. This high expression was limited in time, and the pattern of expression of CCK-B/gastrin receptors correlated closely with the proliferative activity of the regenerative mucosa. Functionally, omeprazole and gastrin-17 caused profound hypergastrinemia, increased cell proliferation in the mucosal ulcer margin and accelerated the late ulcer healing phase. These effects were completely reversed by cotherapy with YF-476. These in vivo and vitro data suggest that CCK-B/gastrin receptors in regenerative rat gastric oxyntic mucosa enhance trophic effects during wound healing.
Project description:The data present in this article is related to evaluation of standardized methanolic extract of Vernonia elaeagnifolia aerial parts [MEVE], a species of Asteraceae family for antiulcer potential. Antiulcer activity of MEVE (200 and 400 mg/kg, b.w., p.o.) was evaluated with ethanol and aspirin induced ulcer models and pylorus ligation induced gastric ulcer model. The antioxidant potential of MEVE was evaluated with nitric oxide radicals, hydroxyl radical and H2O2 radical scavenging assay against standard ascorbic acid to correlate antioxidant and antiulcerogenic action. MEVE significantly protects the gastric mucosa against the ethanol and aspirin induced ulcer and pylorus ligation induced ulcer challenge. MEVE had shown significant [normal control: p < 0.0001, disease control: p < 0.0001, standard: p < 0.0001] decrease in the ulcer index produced by all three models in rats as compared to the standard drug omeprazole [20 mg/kg, b.w., p.o.]. The present data suggest that aerial parts of Vernonia elaeagnifolia possess significant antiulcer activity, which may attributed to its antioxidant mechanism of action.
Project description:This study was conducted to investigate the effects of nitric oxide (NO) in acetic acid-induced gastric ulcer of rats and the underlying mechanisms. We found that peritoneal injection of sodium nitroprusside (SNP), a NO donor, decreased the ulcer area, inflammatory cell infiltration and MPO degree in acetic acid-induced gastric ulcer in rats. This effect was abolished by a transient receptor potential vanilloid 1 (TRPV1) antagonist or prior subdiaphragmatic vagotomy. SNP increased the jejunal mesenteric afferent discharge in a dose-depended manner, which was largely diminished by pretreatment of S-nitrosylation blocker N-ethylmaleimide, TRPV1 antagonist capsazepine, genetic deletion of TRPV1, or vagotomy. Whole-cell patch clamp recording showed that SNP depolarized the resting membrane potential of NG neurons, and enhanced capsaicin-induced inward current, which were both blocked by N-ethylmaleimide. Our results suggest that NO donor SNP alleviates acetic acid-induced gastric ulcer in rats via vagus nerve, while S-nitrosylation of TRPV1 may participate in this route. Our findings reveal a new mechanism for vagal afferent activation, and a new potential anti-inflammatory target.
Project description:Helicobacter pylori infection (HPI) is a prevalent infectious disease associated with gastric ulcer, gastric cancer, and many nongastrointestinal disorders. To identify genes that may serve as microbial markers for HPI, we performed shotgun metagenomic sequencing of fecal samples from 313 Chinese volunteers who had undergone a C14 breath test. Through comparing differences in intestinal microbial community structure between H. pylori-positive and H. pylori-negative individuals, we identified 58 HPI-associated microbial species (P < 0.05, Wilcoxon test). A classifier based on microbial species markers showed high diagnostic ability for HPI (AUC = 0.84). Furthermore, levels of gut microbial vitamin B12 (VB12) biosynthesis and plasma VB12 were significantly lower in H. pylori-positive individuals compared with H. pylori-negative individuals (P < 0.05, Wilcoxon test). This study reveals that certain alterations in gut microbial species and functions are associated with HPI and shows that gut microbial shift in HPI patients may indirectly elevate the risk of VB12 deficiency.
Project description:Ethanol consumption is one of the common causative agents implicated in gastric ulcer development. Oxidative stress plays a major role in the induction and development of gastric ulceration. NADPH oxidases (NOXs) and Nuclear factor erythroid 2-related factor 2 (Nrf2) are key players in ethanol-induced ulcers. High-mobility group box 1 (HMGB1), a ubiquitous nuclear protein, mediates various inflammation functions. However, the role of HMGB1 in ethanol-induced gastric ulcer is not yet elucidated. Raspberry Ketone (RK) is a natural phenolic compound with antioxidant and anti-inflammatory properties. In the present study, absolute ethanol (7.5 ml/kg) was used to induce gastric ulceration in rats. Raspberry Ketone (RK) (50 mg/kg) was given orally one hour before the administration of absolute ethanol. Interestingly, ethanol-induced gastric ulcer was associated with Nrf2 downregulation, which was correlated with NOX-1, 2 NOX-4, and HMGB1 upregulation, and was significantly reversed by RK pre-treatment. RK pre-treatment provided 80% gastroprotection. Gastroprotective properties of RK were mediated via antioxidant, anti-inflammatory (suppression of NF-kB and tumor necrosis factor-α), and antiapoptotic activities (reduction of Bax/Bcl2 ratio). Gastroprotective properties of RK were confirmed by histopathological examination. In conclusion, this study is the first to provide evidence to the role of HMGB1 in ethanol-induced gastric ulcer, and the crosstalk of Nrf2, NOXs and HMGB1. It also demonstrates that RK represents a promising gastroprotective activity comparable to omeprazole.