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Sample records for omeprazole induces gastric

  1. Evaluation of antiulcer activity of indole-3-carbinol and/or omeprazole on aspirin-induced gastric ulcer in rats.

    Science.gov (United States)

    El-Shinnawy, Nashwa A; Abd-Elmageid, Samira A; Alshailabi, Eda M A

    2014-05-01

    The present work is an attempt to elucidate the antiulcer activity of indole-3-carbinol (I3C), which is one of the anticarcinogenic phytochemicals found in the vegetables of Cruciferae family such as broccoli and cauliflower, alone or in combination with omeprazole (OMP), a proton pump inhibitor, to diminish the effects of induced acute gastric ulcer by aspirin (ASA) in male albino rats. A total of 48 adult male albino rats were used in the present study. Animals were divided into eight experimental groups (six animals each group). They were given different experimental inductions of ASA at a dose of 500 mg/kg/body weight, OMP at a dose of 20 mg/kg/body weight and I3C at a dose of 20 mg/kg/body weight either alone or in combination with each other orally for a duration of 7 days. Inner stomach features, ulcer index, pH activity, body weight, stomach weight, hematological investigations, serum total protein albumin and reduced glutathione activity were investigated in addition to the histological, histochemical and immunohistochemical stain of cyclooxygenase-2 to the stomach tissue of normal control, ulcerated and treated ulcerated rats. The results of this study revealed that oral administration of ASA to rats produced the expected characteristic mucosal lesions. OMP accelerated ulcer healing but the administration of I3C either alone or in combination with OMP to ASA-ulcerated rats produced a profound protection to the gastric mucosa from injury induced by ASA. Our results suggested that administration of antiulcer natural substances such as I3C in combination with the perused treatment such as OMP is a very important initiative in the development of new strategies in ulcer healing.

  2. Effect of omeprazole and cimetidine on healing of chronic gastric ulcers and gastric acid secretion in rats

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1988-01-01

    The effect of omeprazole and cimetidine on healing of chronic gastric ulcers and gastric acid secretion was investigated in rats. The effect of three doses of omeprazole given orally once daily for 25 days was investigated. In controls median ulcer healing was 19.6% after 25 days. Omeprazole...... increased median ulcer healing from 36% at 145 mumole/kg/day to 80% at 580 mumole/kg/day. Basal and pentagastrin stimulated gastric acid secretion decreased dose-dependently by nearly 90% at a dose of 580 mumole/kg/day 22-24 hr after the last dose of omeprazole. Cimetidine given twice daily, in a dose...... that initially inhibits gastric acid secretion by 95%, reduced acid secretion by only 50% 11 hr after the last dose. Median ulcer healing after treatment with cimetidine for 25 days was 41%. This study demonstrates that omeprazole has a more long-acting inhibitory effect on gastric acid secretion compared...

  3. Omeprazole

    Science.gov (United States)

    ... backward flow of acid from the stomach causes heartburn and possible injury of the esophagus (the tube ... the-counter) omeprazole is used to treat frequent heartburn (heartburn that occurs at least 2 or more ...

  4. Comparison of aloe vera and omeprazole in the treatment of equine gastric ulcer syndrome.

    Science.gov (United States)

    Bush, J; van den Boom, R; Franklin, S

    2018-01-01

    Anecdotally, aloe vera is used to treat gastric ulceration, although no studies have yet investigated its efficacy in horses. To test the hypothesis that aloe vera would be noninferior to omeprazole in the treatment of equine gastric ulcer syndrome. Randomised, blinded clinical trial. Forty horses with grade ≥2 lesions of the squamous and/or glandular mucosa were randomly assigned to one of two groups. Horses received either aloe vera inner leaf gel (17.6 mg/kg bwt) b.i.d. or omeprazole (4 mg/kg bwt) s.i.d. for approximately 28 days, after which a repeat gastroscopic examination was performed to determine disease resolution. Horses with persistent lesions were offered a further 28 days of treatment with omeprazole (4 mg/kg bwt s.i.d.) and were re-examined on completion of treatment. Efficacy analyses were based on 39 horses that completed the trial. Equine squamous gastric disease (ESGD) was observed in 38 horses; improvement and healing rates in these horses were 56% and 17%, respectively, in the aloe vera group, and 85% and 75%, respectively, in the omeprazole group. Healing was less likely to occur in horses with prolonged gastric emptying. Equine glandular gastric disease (EGGD) was less common than ESGD (n = 14) and numbers were too small to perform meaningful statistical analyses. The hypothesis that aloe vera would be noninferior to omeprazole was not supported. No placebo control group was included. Limited numbers preclude any comment on the efficacy of aloe vera in the treatment of EGGD. Treatment with aloe vera was inferior to treatment with omeprazole. © 2017 EVJ Ltd.

  5. Effects of long-term acid suppressants with ranitidine and omeprazole on gastric mucosa

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    P C Alexander

    2013-01-01

    Full Text Available Background and objectives: Proton pump inhibitors are used widely for gastroesophageal reflux disease and ulcer type dyspepsia. Majority of the patients require long term medication. H2 receptor antagonist are also used for relief of symptoms. Though tachyphylaxis has been reported, symptom response is seen with long term use. The aim of the present study was to study the effects of long-term acid suppressants on gastric antral histology. Methods: Patients who received long-term acid suppressants such as ranitidine and omeprazole for gastroesophageal reflux disease or dyspepsia were included. All of them had an antral biopsy for histology and H. pylori status at baseline, at 6 months and 12 months. Patients on acid suppressants for less than a year or on long-term non-steroidal anti inflammatory drugs were excluded from the study. The grading of gastritis was classified as chronic active gastritis, atrophic gastritis, intestinal metaplasia and dysplasia. Results: Thirty patients received ranitidine and 28 omeprazole. In H. pylori positive group, the median duration of ranitidine and omeprazole were 3 years (1.5 to 8 years and 4 years (1 to 10 years respectively. Two thirds of patients had chronic active gastritis (ranitidine: 35.5%; omeprazole:26.6%; 10 had gastric atrophy (ranitidine: 6.6%; omeprazole:15.5% and 7 had intestinal metaplasia (ranitidine4.4%; omeprazole11.1%. Four of the 10 patients on omeprazole showed progression of histology as against only one of the 13 patients on ranitidine at one year of follow up. In omeprazole pylori negative patients, the median duration of ranitidine and omeprazole was 2.5 years (range 1 to 6 years and 3 years (range 2 to 7 years respectively. Irrespective of the acid suppressants, the baseline histology was either chronic active gastritis (78.5% or gastric atrophy (21.5%. None had intestinal metaplasia. Also there was no progression in histology staging during the follow up. Conclusions: Long-term acid

  6. Histopathology of the gastric oxyntic mucosa in two different patient groups during long-term treatment with omeprazole

    DEFF Research Database (Denmark)

    Hage, Esther; Hendel, Lene; Gustafsen, Jens

    2003-01-01

    OBJECTIVES: Hypochlorhydria, hypergastrinaemia, inflammation and Helicobacter pylori infection, dose and duration of omeprazole treatment may separately, or in combination, influence the proliferation of enterochromaffin-like (ECL) cells and parietal cell changes in gastric mucosa. To assess the ...... of gastric mucosal inflammation, omeprazole dose, duration of treatment and acid inhibition. The level of gastrin secretion and high plasma gastrin appear to accelerate ECL cell proliferation and parietal cell changes possibly influenced by chronic gastritis and H. pylori infection....

  7. A pilot study comparing the effect of orally administered esomeprazole and omeprazole on gastric fluid pH in horses.

    Science.gov (United States)

    Huxford, K E; Dart, A J; Perkins, N R; Bell, R; Jeffcott, L B

    2017-11-01

    AIMS To compare the efficacy of an enteric coated esomeprazole paste with an enteric coated omeprazole paste to increase gastric pH after oral administration in horses. METHODS Nine adult Standardbred horses were randomly assigned to three groups, each containing three horses, for a study comprising three phases of 10 days, with an 18-day washout period between each phase. In each phase, three horses received either 0.5 mg/kg esomeprazole, 1 mg/kg omeprazole or a placebo, as an oral paste, once daily for 10 days (Days 0-9). Over the course of study all horses received all three treatments. Gastric fluid samples were collected using a gastroscope on Days 1, 3, 5, 8 and 10, with food and water withheld for 16 hours prior to collection of samples. The pH of all samples was measured immediately after collection. RESULTS Mean pH (3.38; SD 1.75) of the gastric fluid samples in the horses that received the placebo was lower than in the horses that received esomeprazole (6.28; SD 1.75) or omeprazole (6.13; SD 1.75) (phorses receiving esomeprazole and those receiving omeprazole (p=0.56). CONCLUSIONS AND CLINICAL RELEVANCE Under these study conditions, esomeprazole paste was equally as effective as omeprazole paste in increasing gastric pH in horses. Enteric coated esomeprazole, may be a therapeutic alternative to omeprazole for the prevention of gastric ulcers in horses.

  8. Pharmacokinetic and pharmacodynamic effects of two omeprazole formulations on stomach pH and gastric ulcer scores.

    Science.gov (United States)

    Raidal, S L; Andrews, F M; Nielsen, S G; Trope, G

    2017-11-01

    Limited data are available on the relative pharmacokinetics and pharmacodynamics of different omeprazole formulations. To compare pharmacokinetic and pharmacodynamic effects of a novel omeprazole formulation against a currently registered product. Masked 2 period, 2 treatment crossover. Twelve clinically healthy horses were studied over two 6-day treatment periods. Horses were randomly assigned to receive a novel omeprazole paste (Ulcershield: ULS) or a currently registered reference omeprazole product (OMO). Gastric pH was measured continuously for 10 h on the day prior to commencing treatment (Day -1) and after 6 days of oral treatment (Day 5) using in situ antimony pH probes within an indwelling nasogastric tube. Plasma pharmacokinetics were determined on Days 0 and 6. Treatment significantly (Pulcer severity scores (both P = 0.004), with no difference between treatments (P = 0.688). Comparison of mean log area under time-plasma concentration curves demonstrated that, although the lower limit of the 90% confidence interval was within the -20% limit for bioequivalence, the upper limit was exceeded, suggesting that the test product could have greater bioavailability than the reference product. The small sample size, large interhorse plasma omeprazole concentrations, and low bioavailability of omeprazole impacted the sensitivity of the bioequivalence analysis. ULS matched or slightly exceeded OMO plasma concentrations. Both products resulted in equivalent increases in gastric pH, gastric pH profiles and decrease in gastric ulcer scores. Thus, ULS was pharmacodynamically equivalent to OMO and was associated with an equivalent beneficial effect on gastric squamous mucosal ulceration. © 2017 EVJ Ltd.

  9. A double-blind placebo-controlled study on the effects of omeprazole on gut hormone secretion and gastric emptying rate

    DEFF Research Database (Denmark)

    Rasmussen, L; Qvist, N; Oster-Jørgensen, E

    1997-01-01

    BACKGROUND: The present study was designed to investigate whether an effect of omeprazole on gastric emptying is related to changes in the secretion of selected gut hormones. METHODS: The studies were performed in healthy men after 10 days' treatment with 40 mg omeprazole daily/placebo. Food inge...

  10. Histamine stimulates chloride secretion in omeprazole-inhibited frog gastric mucosa

    International Nuclear Information System (INIS)

    McGreevy, J.; Barton, R.; Housinger, T.

    1986-01-01

    Omeprazole (OME) stops hydrogen ion (H) secretion in the histamine (HIST)-stimulated gastric mucosa while the chloride (Cl) which had accompanied the H continues to be pumped into the lumen. This finding suggests that the Cl pump is independent of the H/K ATP-ase driven H pump. To test this hypothesis, 16 Ussing-chambered frog mucosas were exposed to OME prior to HIST stimulation. If the Cl pump is independent, HIST should stimulate Cl secretion in the OME-inhibited mucosa. A 1 hr control (CON) interval preceded exposure to OME (10 -4 M) in the nutrient solution. Potential difference (PD), short-circuit current (Isc), resistance (R), H flux (J/sup H/) and Cl flux (J/sup Cl/ with 36 Cl) were measured every 15 min. After 1 hr of OME exposure, HIST (10 -5 M) was added to the nutrient solution. The findings demonstrate that HIST stimulates Cl secretion in the OME-inhibited bullfrog gastric mucosa

  11. Addition of all-trans-retinoic acid to omeprazole and sucralfate therapy improves the prognosis of gastric dysplasia.

    Science.gov (United States)

    Jin, Jianjun; Li, Xiaozhen; Xing, Luqi; Chang, Yongchao; Wu, Lijuan; Jin, Zhe; Su, Xiuli; Bai, Yanli; Zheng, Yufeng; Jiang, Yalin; Zhao, Xiao; Lu, Lan; Gao, Qiang

    2015-04-01

    To investigate the efficacy of all-trans retinoic acid (ATRA) in human gastric dysplasia. In this double-blind study, patients with precancerous gastric dysplasia with or without intestinal metaplasia (IM) received either conventional treatment consisting of omeprazole and sucralfate (control group) or conventional treatment plus ATRA. Gastric mucosal biopsies were performed before and after drug treatment and were analysed histologically; expression of retinoblastoma (Rb) protein and HER2 protein in gastric mucosa were measured using immunohistochemistry. A total of 122 patients were included in the study, 63 in the ATRA group and 59 in the control group. In the ATRA group, dysplasia was attenuated in 43 out of 63 patients (68%) compared with 22 out of 59 patients (37%) in the control group; however, IM was not affected by treatment in either group. ATRA treatment was associated with significantly increased Rb expression and decreased HER2 expression in gastric mucosa. The use of conventional therapy plus ATRA for gastric dysplasia was associated with improved efficacy compared with conventional therapy alone. It was also accompanied by increased Rb expression and decreased HER2 expression in gastric mucosa. The addition of ATRA to conventional therapy for gastritis may improve the prognosis of gastric dysplasia. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  12. Prophylactic therapy with omeprazole for prevention of equine gastric ulcer syndrome (EGUS) in horses in active training: A meta-analysis.

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    Mason, L V; Moroney, J R; Mason, R J

    2018-04-17

    Guidelines regarding the impact and value of prophylaxis or maintenance therapy in equine gastric ulcer syndrome (EGUS) are not well-established or defined. The merits and the magnitude of effects of prophylaxis for spontaneous or recurrent squamous gastric ulceration in horses in training are uncertain. To pool data from randomised controlled trials (RCTs) to eliminate reporting bias and evaluate the efficacy of prophylactic omeprazole in the prevention of EGUS in training horses, and secondarily to compare prophylactic dosages of omeprazole. Meta-analysis. This meta-analysis was conducted according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic literature search identified RCTs comparing omeprazole prophylaxis with sham in prevention of EGUS. Data were analysed using the Mantel-Haenszel test method to calculate risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CIs). Primary outcome was efficacy of prophylaxis. Secondary outcome was endoscopic severity of ulceration. The influence of study characteristics on the outcomes was examined by subgroup analyses. In preventing gastric ulcer occurrence, omeprazole prophylaxis was superior to sham in training horses (7 trials, 566 horses, RR 0.28, 95% CI 0.18-0.43; 23.4% in omeprazole prophylaxis vs. 77.2% in sham; high quality evidence). Prevalence of ulceration was 75.3 and 87.2% in the sham arms of the 1 mg/kg and 2 mg/kg omeprazole groups, respectively. Severity scores were significantly lower for omeprazole vs. sham (mean difference [MD] -1.05; 95% CI -1.35 to -0.69). Subgroup analyses comparing prophylactic omeprazole dosages resulted in a mean difference of -0.94 and -1.60 for the 1 and 2 mg/kg groups, respectively. Studies showed heterogeneity with regard to prophylactic dose. Omeprazole prophylaxis in active training horses significantly reduces gastric ulceration compared with no prophylaxis (sham) with the

  13. Omeprazole induces heme oxygenase-1 in fetal human pulmonary microvascular endothelial cells via hydrogen peroxide-independent Nrf2 signaling pathway

    International Nuclear Information System (INIS)

    Patel, Ananddeep; Zhang, Shaojie; Shrestha, Amrit Kumar; Maturu, Paramahamsa; Moorthy, Bhagavatula; Shivanna, Binoy

    2016-01-01

    Omeprazole (OM) is an aryl hydrocarbon receptor (AhR) agonist and a proton pump inhibitor that is used to treat humans with gastric acid related disorders. Recently, we showed that OM induces NAD (P) H quinone oxidoreductase-1 (NQO1) via nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent mechanism. Heme oxygenase-1 (HO-1) is another cytoprotective and antioxidant enzyme that is regulated by Nrf2. Whether OM induces HO-1 in fetal human pulmonary microvascular endothelial cells (HPMEC) is unknown. Therefore, we tested the hypothesis that OM will induce HO-1 expression via Nrf2 in HPMEC. OM induced HO-1 mRNA and protein expression in a dose-dependent manner. siRNA-mediated knockdown of AhR failed to abrogate, whereas knockdown of Nrf2 abrogated HO-1 induction by OM. To identify the underlying molecular mechanisms, we determined the effects of OM on cellular hydrogen peroxide (H 2 O 2 ) levels since oxidative stress mediated by the latter is known to activate Nrf2. Interestingly, the concentration at which OM induced HO-1 also increased H 2 O 2 levels. Furthermore, H 2 O 2 independently augmented HO-1 expression. Although N-acetyl cysteine (NAC) significantly decreased H 2 O 2 levels in OM-treated cells, we observed that OM further increased HO-1 mRNA and protein expression in NAC-pretreated compared to vehicle-pretreated cells, suggesting that OM induces HO-1 via H 2 O 2 -independent mechanisms. In conclusion, we provide evidence that OM transcriptionally induces HO-1 via AhR - and H 2 O 2 - independent, but Nrf2 - dependent mechanisms. These results have important implications for human disorders where Nrf2 and HO-1 play a beneficial role. - Highlights: • Omeprazole induces HO-1 in human fetal lung cells. • AhR deficiency fails to abrogate omeprazole-mediated induction of HO-1. • Nrf2 knockdown abrogates omeprazole-mediated HO-1 induction in human lung cells. • Hydrogen peroxide depletion augments omeprazole-mediated induction of HO-1.

  14. Omeprazole induces heme oxygenase-1 in fetal human pulmonary microvascular endothelial cells via hydrogen peroxide-independent Nrf2 signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Ananddeep; Zhang, Shaojie; Shrestha, Amrit Kumar; Maturu, Paramahamsa; Moorthy, Bhagavatula; Shivanna, Binoy, E-mail: shivanna@bcm.edu

    2016-11-15

    Omeprazole (OM) is an aryl hydrocarbon receptor (AhR) agonist and a proton pump inhibitor that is used to treat humans with gastric acid related disorders. Recently, we showed that OM induces NAD (P) H quinone oxidoreductase-1 (NQO1) via nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent mechanism. Heme oxygenase-1 (HO-1) is another cytoprotective and antioxidant enzyme that is regulated by Nrf2. Whether OM induces HO-1 in fetal human pulmonary microvascular endothelial cells (HPMEC) is unknown. Therefore, we tested the hypothesis that OM will induce HO-1 expression via Nrf2 in HPMEC. OM induced HO-1 mRNA and protein expression in a dose-dependent manner. siRNA-mediated knockdown of AhR failed to abrogate, whereas knockdown of Nrf2 abrogated HO-1 induction by OM. To identify the underlying molecular mechanisms, we determined the effects of OM on cellular hydrogen peroxide (H{sub 2}O{sub 2}) levels since oxidative stress mediated by the latter is known to activate Nrf2. Interestingly, the concentration at which OM induced HO-1 also increased H{sub 2}O{sub 2} levels. Furthermore, H{sub 2}O{sub 2} independently augmented HO-1 expression. Although N-acetyl cysteine (NAC) significantly decreased H{sub 2}O{sub 2} levels in OM-treated cells, we observed that OM further increased HO-1 mRNA and protein expression in NAC-pretreated compared to vehicle-pretreated cells, suggesting that OM induces HO-1 via H{sub 2}O{sub 2}-independent mechanisms. In conclusion, we provide evidence that OM transcriptionally induces HO-1 via AhR - and H{sub 2}O{sub 2} - independent, but Nrf2 - dependent mechanisms. These results have important implications for human disorders where Nrf2 and HO-1 play a beneficial role. - Highlights: • Omeprazole induces HO-1 in human fetal lung cells. • AhR deficiency fails to abrogate omeprazole-mediated induction of HO-1. • Nrf2 knockdown abrogates omeprazole-mediated HO-1 induction in human lung cells. • Hydrogen peroxide depletion augments

  15. Omeprazole and lansoprazole enantiomers induce CYP3A4 in human hepatocytes and cell lines via glucocorticoid receptor and pregnane X receptor axis.

    Science.gov (United States)

    Novotna, Aneta; Dvorak, Zdenek

    2014-01-01

    Benzimidazole drugs lansoprazole and omeprazole are used for treatment of various gastrointestinal pathologies. Both compounds cause drug-drug interactions because they activate aryl hydrocarbon receptor and induce CYP1A genes. In the current paper, we examined the effects of lansoprazole and omeprazole enantiomers on the expression of key drug-metabolizing enzyme CYP3A4 in human hepatocytes and human cancer cell lines. Lansoprazole enantiomers, but not omeprazole, were equipotent inducers of CYP3A4 mRNA in HepG2 cells. All forms (S-, R-, rac-) of lansoprazole and omeprazole induced CYP3A4 mRNA and protein in human hepatocytes. The quantitative profiles of CYP3A4 induction by individual forms of lansoprazole and omeprazole exerted enantiospecific patterns. Lansoprazole dose-dependently activated pregnane X receptor PXR in gene reporter assays, and slightly modulated rifampicin-inducible PXR activity, with similar potency for each enantiomer. Omeprazole dose-dependently activated PXR and inhibited rifampicin-inducible PXR activity. The effects of S-omeprazole were much stronger as compared to those of R-omeprazole. All forms of lansoprazole, but not omeprazole, slightly activated glucocorticoid receptor and augmented dexamethasone-induced GR transcriptional activity. Omeprazole and lansoprazole influenced basal and ligand inducible expression of tyrosine aminotransferase, a GR-target gene, in HepG2 cells and human hepatocytes. Overall, we demonstrate here that omeprazole and lansoprazole enantiomers induce CYP3A4 in HepG2 cells and human hepatocytes. The induction comprises differential interactions of omeprazole and lansoprazole with transcriptional regulators PXR and GR, and some of the effects were enantiospecific. The data presented here might be of toxicological and clinical importance, since the effects occurred in therapeutically relevant concentrations.

  16. Gastroprotective effect of garlic in indomethacin induced gastric ulcer in rats.

    Science.gov (United States)

    El-Ashmawy, Nahla E; Khedr, Eman G; El-Bahrawy, Hoda A; Selim, Hend M

    2016-01-01

    Garlic, in its natural plant state, has a great history in ancient medicine as a remedy for many diseases. In our study, the gastroprotective effect of aged garlic extract (AGE) and the possible underlying mechanisms were investigated in an experimental model of indomethacin-induced gastric ulcer. Male Wistar rats were divided into four groups: (normal control, n = 20), ulcer control (indomethacin group, n = 20), (omeprazole group, n = 30) and (garlic group, n = 20). Each dose of garlic and omeprazole was given to rats orally daily for 10 consecutive days before induction of ulcer by indomethacin. Indomethacin was given as a single oral dose (100 mg/kg). Four hours later after indomethacin treatment, the rats were sacrificed and gastric tissue was obtained for histopathological examination, calculation of ulcer index and measurement of oxidative stress markers as well as gastroprotective mediators. The results showed that indomethacin induced gastric ulcer (ulcer index = 2900), was associated with a significant increase of tumor necrosis factor-alpha and malondialdehyde, and significant decrease of the gastroprotective mediators prostaglandin E2, glutathione (GSH) and nitric oxide (NO) compared with normal control. Pretreatment with AGE produced comparable results with those obtained in the omeprazole group; the preventive index in the AGE group was 83.4% compared with 94.5% in the omeprazole group. The prophylactic role of AGE in indomethacin-induced ulcer was, in part, mediated by decreasing oxidative stress and increasing gastric level of PGE2, GSH, and NO. AGE corrected the histopathological abnormalities in gastric tissue and proved a promising gastroprotective role in gastric ulcer. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Dose-Finding Study of Omeprazole on Gastric pH in Neonates with Gastro-Esophageal Acid Reflux Using a Bayesian Sequential Approach.

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    Florentia Kaguelidou

    Full Text Available Proton pump inhibitors are frequently administered on clinical symptoms in neonates but benefit remains controversial. Clinical trials validating omeprazole dosage in neonates are limited. The objective of this trial was to determine the minimum effective dose (MED of omeprazole to treat pathological acid reflux in neonates using reflux index as surrogate marker.Double blind dose-finding trial with continual reassessment method of individual dose administration using a Bayesian approach, aiming to select drug dose as close as possible to the predefined target level of efficacy (with a credibility interval of 95%.Neonatal Intensive Care unit of the Robert Debré University Hospital in Paris, France.Neonates with a postmenstrual age ≥ 35 weeks and a pathologic 24-hour intra-esophageal pH monitoring defined by a reflux index ≥ 5% over 24 hours were considered for participation. Recruitment was stratified to 3 groups according to gestational age at birth.Five preselected doses of oral omeprazole from 1 to 3 mg/kg/day.Primary outcome, measured at 35 weeks postmenstrual age or more, was a reflux index <5% during the 24-h pH monitoring registered 72±24 hours after omeprazole initiation.Fifty-four neonates with a reflux index ranging from 5.06 to 27.7% were included. Median age was 37.5 days and median postmenstrual age was 36 weeks. In neonates born at less than 32 weeks of GA (n = 30, the MED was 2.5mg/kg/day with an estimated mean posterior probability of success of 97.7% (95% credibility interval: 90.3-99.7%. The MED was 1mg/kg/day for neonates born at more than 32 GA (n = 24.Omeprazole is extensively prescribed on clinical symptoms but efficacy is not demonstrated while safety concerns do exist. When treatment is required, the daily dose needs to be validated in preterm and term neonates. Optimal doses of omeprazole to increase gastric pH and decrease reflux index below 5% over 24 hours, determined using an adaptive Bayesian design differ

  18. Dose-Finding Study of Omeprazole on Gastric pH in Neonates with Gastro-Esophageal Acid Reflux Using a Bayesian Sequential Approach.

    Science.gov (United States)

    Kaguelidou, Florentia; Alberti, Corinne; Biran, Valerie; Bourdon, Olivier; Farnoux, Caroline; Zohar, Sarah; Jacqz-Aigrain, Evelyne

    2016-01-01

    Proton pump inhibitors are frequently administered on clinical symptoms in neonates but benefit remains controversial. Clinical trials validating omeprazole dosage in neonates are limited. The objective of this trial was to determine the minimum effective dose (MED) of omeprazole to treat pathological acid reflux in neonates using reflux index as surrogate marker. Double blind dose-finding trial with continual reassessment method of individual dose administration using a Bayesian approach, aiming to select drug dose as close as possible to the predefined target level of efficacy (with a credibility interval of 95%). Neonatal Intensive Care unit of the Robert Debré University Hospital in Paris, France. Neonates with a postmenstrual age ≥ 35 weeks and a pathologic 24-hour intra-esophageal pH monitoring defined by a reflux index ≥ 5% over 24 hours were considered for participation. Recruitment was stratified to 3 groups according to gestational age at birth. Five preselected doses of oral omeprazole from 1 to 3 mg/kg/day. Primary outcome, measured at 35 weeks postmenstrual age or more, was a reflux index reflux index ranging from 5.06 to 27.7% were included. Median age was 37.5 days and median postmenstrual age was 36 weeks. In neonates born at less than 32 weeks of GA (n = 30), the MED was 2.5mg/kg/day with an estimated mean posterior probability of success of 97.7% (95% credibility interval: 90.3-99.7%). The MED was 1mg/kg/day for neonates born at more than 32 GA (n = 24). Omeprazole is extensively prescribed on clinical symptoms but efficacy is not demonstrated while safety concerns do exist. When treatment is required, the daily dose needs to be validated in preterm and term neonates. Optimal doses of omeprazole to increase gastric pH and decrease reflux index below 5% over 24 hours, determined using an adaptive Bayesian design differ among neonates. Both gestational and postnatal ages account for these differences but their differential impact on omeprazole

  19. Effect of omeprazole and sucralfate on prepyloric gastric ulcer. A double blind comparative trial and one year follow up.

    Science.gov (United States)

    Sørensen, H T; Rasmussen, H H; Balslev, I; Boesby, S; Boné, J; Kruse, A; Rasmussen, S N

    1994-01-01

    This study compared healing rates, relief of symptoms, frequency of adverse events, and proportion of patients in remission after one year follow up in 104 patients with active prepyloric ulcer during treatment with 40 mg omeprazole once daily or 2 g sucralfate twice daily, using a randomised double blind controlled trial. Healing rates after two, four, and six weeks were (omeprazole/sucralfate) 49%/23%; 83%/59%; 90%/70% respectively. After two weeks, omeprazole was more efficient than sucralfate in relief of daytime and nocturnal epigastric pain, nausea, and heartburn. The proportion of patients in remission after one year follow up was significantly higher in the omeprazole group (p < 0.01). Of the healed patients ulcers recurred in 36% in the omeprazole group and in 46% in the sucralfate group. It is concluded that the ulcer healing rate was higher and symptom relief was more pronounced in the omeprazole group compared with the sucralfate group, and that more patients were still in remission after a one year follow up period. PMID:8020815

  20. [Gastroprotective effect of honey in Holtzman rats with piroxicam-induced gastric ulcer].

    Science.gov (United States)

    Roldán-Rodríguez, Aníbal Enrique; Vega-Quispe, Erick Joel; Silva-Ocas, Isabel; Lemus-Arteaga, Kevin Edward; Gonzales-Saldaña, Jaime Gilberto; Ruiz-Urbina, Franklyn Norwich; Urtecho-Gaitan, Iván Freddy; Zamora-Mostacero, Víctor Edwin; Vargas-Ferrer, Juan Edder; Valverde-Quezada, Gillmari Juliza; Vásquez-Sandoval, Kevin Oswaldo; Huamán-Saavedra, Juan Jorge

    2016-01-01

    To determine the effect of treatment with honey in piroxicam-induced gastric ulcer in Holtzman rats. 48 eight-week old female Holtzman rats, weights between 100 and 200 grams, were divided into 6 treatment groups as follow: Group A: water; Group B: piroxicam (30 mg/kg); Group C: omeprazole (5 mg/kg) and piroxicam (30 mg/kg); Group D: honey (2.5 g/kg) and piroxicam (30 mg/kg); Group E: honey (5 g/kg) and piroxicam (30 mg/kg); Group F: honey (7.5 g/kg) and piroxicam (30 mg/kg). Macroscopic studies, using Scion Image, and microscopic histological section of gastric mucosa were performed after the interventions. The results of the macroscopic studies showed statistically significant differences for both doses of honey at 6 g/kg and 7.5 g/kg when compared to piroxicam (p=0.016 and p=0.001 respectively) and the gastroprotective effect was similar when compared to omeprazole (p>0.05). Microscopic studies showed statistically significant differences only for dose at 7.5 g/kg when compared to piroxicam (p=0.0018) and the gastroprotective effect was similar to omeprazole (p=1). Dose of honey at 7.5 g/kg showed gastroprotective effect at microscopic and macroscopic studies when compared to omeprazole.

  1. Drug–drug interaction of microdose and regular-dose omeprazole with a CYP2C19 inhibitor and inducer

    Science.gov (United States)

    Park, Gab-jin; Bae, Soo Hyeon; Park, Wan-Su; Han, Seunghoon; Park, Min-Ho; Shin, Seok-Ho; Shin, Young G; Yim, Dong-Seok

    2017-01-01

    Purpose A microdose drug–drug interaction (DDI) study may be a valuable tool for anticipating drug interaction at therapeutic doses. This study aimed to compare the magnitude of DDIs at microdoses and regular doses to explore the applicability of a microdose DDI study. Patients and methods Six healthy male volunteer subjects were enrolled into each DDI study of omeprazole (victim) and known perpetrators: fluconazole (inhibitor) and rifampin (inducer). For both studies, the microdose (100 μg, cold compound) and the regular dose (20 mg) of omeprazole were given at days 0 and 1, respectively. On days 2–9, the inhibitor or inducer was given daily, and the microdose and regular dose of omeprazole were repeated at days 8 and 9, respectively. Full omeprazole pharmacokinetic samplings were performed at days 0, 1, 8, and 9 of both studies for noncompartmental analysis. Results The magnitude of the DDI, the geometric mean ratios (with perpetrator/omeprazole only) of maximum concentration (Cmax) and area under the curve to the last measurement (AUCt) of the microdose and the regular dose were compared. The geometric mean ratios in the inhibition study were: 2.17 (micro) and 2.68 (regular) for Cmax, and 4.07 (micro), 4.33 (regular) for AUCt. For the induction study, they were 0.26 (micro) and 0.21 (regular) for Cmax, and 0.16 (micro) and 0.15 (regular) for AUCt. There were no significant statistical differences in the magnitudes of DDIs between microdose and regular-dose conditions, regardless of induction or inhibition. Conclusion Our results may be used as partial evidence that microdose DDI studies may replace regular-dose studies, or at least be used for DDI-screening purposes. PMID:28408803

  2. Drug-drug interaction of microdose and regular-dose omeprazole with a CYP2C19 inhibitor and inducer.

    Science.gov (United States)

    Park, Gab-Jin; Bae, Soo Hyeon; Park, Wan-Su; Han, Seunghoon; Park, Min-Ho; Shin, Seok-Ho; Shin, Young G; Yim, Dong-Seok

    2017-01-01

    A microdose drug-drug interaction (DDI) study may be a valuable tool for anticipating drug interaction at therapeutic doses. This study aimed to compare the magnitude of DDIs at microdoses and regular doses to explore the applicability of a microdose DDI study. Six healthy male volunteer subjects were enrolled into each DDI study of omeprazole (victim) and known perpetrators: fluconazole (inhibitor) and rifampin (inducer). For both studies, the microdose (100 μg, cold compound) and the regular dose (20 mg) of omeprazole were given at days 0 and 1, respectively. On days 2-9, the inhibitor or inducer was given daily, and the microdose and regular dose of omeprazole were repeated at days 8 and 9, respectively. Full omeprazole pharmacokinetic samplings were performed at days 0, 1, 8, and 9 of both studies for noncompartmental analysis. The magnitude of the DDI, the geometric mean ratios (with perpetrator/omeprazole only) of maximum concentration (C max ) and area under the curve to the last measurement (AUC t ) of the microdose and the regular dose were compared. The geometric mean ratios in the inhibition study were: 2.17 (micro) and 2.68 (regular) for C max , and 4.07 (micro), 4.33 (regular) for AUC t . For the induction study, they were 0.26 (micro) and 0.21 (regular) for C max , and 0.16 (micro) and 0.15 (regular) for AUC t . There were no significant statistical differences in the magnitudes of DDIs between microdose and regular-dose conditions, regardless of induction or inhibition. Our results may be used as partial evidence that microdose DDI studies may replace regular-dose studies, or at least be used for DDI-screening purposes.

  3. Prophylactic effects of Clausena excavata Burum. f. leaf extract in ethanol-induced gastric ulcers

    Directory of Open Access Journals (Sweden)

    Albaayit SFA

    2016-06-01

    Full Text Available Shaymaa Fadhel Abbas Albaayit,1,2 Yusuf Abba,3 Rasedee Abdullah,4 Noorlidah Abdullah1 1Faculty of Science, Institute of Biological Sciences, University of Malaya, Kuala Lumpur, Malaysia; 2Department of Biology, College of Science, University of Baghdad, Baghdad, Iraq; 3Department of Veterinary Pathology and Microbiology, 4Department of Veterinary Laboratory Diagnosis, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Selangor, Malaysia Abstract: Clausena excavata is a natural herb with both antioxidant and anti-inflammatory properties. It has been used for decades in folkloric practice for the amelioration of various ailments. In this study, the gastroprotective activity of methanolic extract of C. excavata leaves (MECE was determined in the Sprague Dawley rat ethanol-induced gastric ulcer model. Rats were pretreated with a single dose of vehicle (5% Tween 20, 20 mg/mL omeprazole, 400 and 200 mg/mL of MECE dissolved in 5% Tween 20. Ulcer was induced with 5 mL/kg of ethanol and stomach tissue was obtained after 1 hour. Histological examination was done on hematoxylin and eosin, periodic acid-Schiff, and immunochemically stained gastric mucosal tissues. Prostaglandin E2, superoxide dismutase, catalase, glutathione peroxidase, and lipid peroxidation levels of the gastric tissue homogenates were also determined. Significantly (P<0.05 smaller ulcer areas, less intense edema, and fewer leukocytes’ infiltration were observed in MECE- and omeprazole-treated than in untreated gastric mucosa with ulcer. The gastric pH, mucus production, superoxide dismutase, catalase, and glutathione peroxidase contents increased, while the lipid peroxidation content decreased as a result of MECE treatment. Bcl-2-associated X protein was underexpressed, while heat shock protein 70 and transforming growth factor-beta protein were overexpressed in the ulcerated gastric mucosa tissues treated with omeprazole and MECE. Similarly, there was a reduction in

  4. Drug–drug interaction of microdose and regular-dose omeprazole with a CYP2C19 inhibitor and inducer

    Directory of Open Access Journals (Sweden)

    Park G

    2017-03-01

    Full Text Available Gab-jin Park,1 Soo Hyeon Bae,1 Wan-Su Park,1 Seunghoon Han,1 Min-Ho Park,2 Seok-Ho Shin,2 Young G Shin,2 Dong-Seok Yim1,2 1Department of Clinical Pharmacology and Therapeutics, Seoul St Mary’s Hospital, PIPET (Pharmacometrics Institute for Practical Education and Training, College of Medicine, Catholic University of Korea, Seoul, South Korea; 2College of Pharmacy, Chungnam National University, Daejeon, South Korea Purpose: A microdose drug–drug interaction (DDI study may be a valuable tool for anticipating drug interaction at therapeutic doses. This study aimed to compare the magnitude of DDIs at microdoses and regular doses to explore the applicability of a microdose DDI study. Patients and methods: Six healthy male volunteer subjects were enrolled into each DDI study of omeprazole (victim and known perpetrators: fluconazole (inhibitor and rifampin (inducer. For both studies, the microdose (100 µg, cold compound and the regular dose (20 mg of omeprazole were given at days 0 and 1, respectively. On days 2–9, the inhibitor or inducer was given daily, and the microdose and regular dose of omeprazole were repeated at days 8 and 9, respectively. Full omeprazole pharmacokinetic samplings were performed at days 0, 1, 8, and 9 of both studies for noncompartmental analysis. Results: The magnitude of the DDI, the geometric mean ratios (with perpetrator/omeprazole only of maximum concentration (Cmax and area under the curve to the last measurement (AUCt of the microdose and the regular dose were compared. The geometric mean ratios in the inhibition study were: 2.17 (micro and 2.68 (regular for Cmax, and 4.07 (micro, 4.33 (regular for AUCt. For the induction study, they were 0.26 (micro and 0.21 (regular for Cmax, and 0.16 (micro and 0.15 (regular for AUCt. There were no significant statistical differences in the magnitudes of DDIs between microdose and regular-dose conditions, regardless of induction or inhibition. Conclusion: Our results may be

  5. Omeprazole increases the efficacy of a soluble epoxide hydrolase inhibitor in a PGE2 induced pain model

    International Nuclear Information System (INIS)

    Goswami, Sumanta Kumar; Inceoglu, Bora; Yang, Jun; Wan, Debin; Kodani, Sean D.; Trindade da Silva, Carlos Antonio; Morisseau, Christophe; Hammock, Bruce D.

    2015-01-01

    Epoxyeicosatrienoic acids (EETs) are potent endogenous analgesic metabolites produced from arachidonic acid by cytochrome P450s (P450s). Metabolism of EETs by soluble epoxide hydrolase (sEH) reduces their activity, while their stabilization by sEH inhibition decreases both inflammatory and neuropathic pain. Here, we tested the complementary hypothesis that increasing the level of EETs through induction of P450s by omeprazole (OME), can influence pain related signaling by itself, and potentiate the anti-hyperalgesic effect of sEH inhibitor. Rats were treated with OME (100 mg/kg/day, p.o., 7 days), sEH inhibitor TPPU (3 mg/kg/day, p.o.) and OME (100 mg/kg/day, p.o., 7 days) + TPPU (3 mg/kg/day, p.o., last 3 days of OME dose) dissolved in vehicle PEG400, and their effect on hyperalgesia (increased sensitivity to pain) induced by PGE 2 was monitored. While OME treatment by itself exhibited variable effects on PGE 2 induced hyperalgesia, it strongly potentiated the effect of TPPU in the same assay. The significant decrease in pain with OME + TPPU treatment correlated with the increased levels of EETs in plasma and increased activities of P450 1A1 and P450 1A2 in liver microsomes. The results show that reducing catabolism of EETs with a sEH inhibitor yielded a stronger analgesic effect than increasing generation of EETs by OME, and combination of both yielded the strongest pain reducing effect under the condition of this study. - Highlights: • The soluble epoxide hydrolase (sEH) inhibitor TPPU is anti-hyperalgesic. • Omeprazole potentiates the anti-hyperalgesic actions of TPPU. • This potentiation is associated with increased P450 activity. • The potentiation is associated with an increase in fatty acid epoxide/diol ratio. • Joint use of sEH inhibitors and P450 inducers could result in drug–drug interactions.

  6. Beyond gastric acid reduction: Proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells

    International Nuclear Information System (INIS)

    Becker, Jan C.; Grosser, Nina; Waltke, Christian; Schulz, Stephanie; Erdmann, Kati; Domschke, Wolfram; Schroeder, Henning; Pohle, Thorsten

    2006-01-01

    Proton pump inhibitors (PPIs) have been demonstrated to prevent gastric mucosal injury by mechanisms independent of acid inhibition. Here we demonstrate that both omeprazole and lansoprazole protect human gastric epithelial and endothelial cells against oxidative stress. This effect was abrogated in the presence of the heme oxygenase-1 (HO-1) inhibitor ZnBG. Exposure to either PPI resulted in a strong induction of HO-1 expression on mRNA and protein level, and led to an increased activity of this enzyme. Expression of cyclooxygenase isoforms 1 and 2 remained unaffected, and COX-inhibitors did not antagonize HO-1 induction by PPIs. Our results suggest that the antioxidant defense protein HO-1 is a target of PPIs in both endothelial and gastric epithelial cells. HO-1 induction might account for the gastroprotective effects of PPIs independently of acid inhibition, especially in NSAID gastropathy. Moreover, our findings provide additional perspectives for a possible but yet unexplored use of PPIs in vasoprotection

  7. Beyond gastric acid reduction: Proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Becker, Jan C [Department of Medicine B, University of Muenster, 48149 Muenster (Germany); Grosser, Nina [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Waltke, Christian [Department of Medicine B, University of Muenster, 48149 Muenster (Germany); Schulz, Stephanie [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Erdmann, Kati [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Domschke, Wolfram [Department of Medicine B, University of Muenster, 48149 Muenster (Germany); Schroeder, Henning [Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle-Wittenberg, 06099 Halle (Saale) (Germany); Pohle, Thorsten [Department of Medicine B, University of Muenster, 48149 Muenster (Germany)

    2006-07-07

    Proton pump inhibitors (PPIs) have been demonstrated to prevent gastric mucosal injury by mechanisms independent of acid inhibition. Here we demonstrate that both omeprazole and lansoprazole protect human gastric epithelial and endothelial cells against oxidative stress. This effect was abrogated in the presence of the heme oxygenase-1 (HO-1) inhibitor ZnBG. Exposure to either PPI resulted in a strong induction of HO-1 expression on mRNA and protein level, and led to an increased activity of this enzyme. Expression of cyclooxygenase isoforms 1 and 2 remained unaffected, and COX-inhibitors did not antagonize HO-1 induction by PPIs. Our results suggest that the antioxidant defense protein HO-1 is a target of PPIs in both endothelial and gastric epithelial cells. HO-1 induction might account for the gastroprotective effects of PPIs independently of acid inhibition, especially in NSAID gastropathy. Moreover, our findings provide additional perspectives for a possible but yet unexplored use of PPIs in vasoprotection.

  8. Omeprazole increases the efficacy of a soluble epoxide hydrolase inhibitor in a PGE{sub 2} induced pain model

    Energy Technology Data Exchange (ETDEWEB)

    Goswami, Sumanta Kumar; Inceoglu, Bora; Yang, Jun; Wan, Debin; Kodani, Sean D. [Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center, University of California, Davis, CA (United States); Trindade da Silva, Carlos Antonio [Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center, University of California, Davis, CA (United States); Department of Genetics and Biochemistry, Federal University of Uberlandia, MG (Brazil); Morisseau, Christophe [Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center, University of California, Davis, CA (United States); Hammock, Bruce D., E-mail: bdhammock@ucdavis.edu [Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center, University of California, Davis, CA (United States)

    2015-12-15

    Epoxyeicosatrienoic acids (EETs) are potent endogenous analgesic metabolites produced from arachidonic acid by cytochrome P450s (P450s). Metabolism of EETs by soluble epoxide hydrolase (sEH) reduces their activity, while their stabilization by sEH inhibition decreases both inflammatory and neuropathic pain. Here, we tested the complementary hypothesis that increasing the level of EETs through induction of P450s by omeprazole (OME), can influence pain related signaling by itself, and potentiate the anti-hyperalgesic effect of sEH inhibitor. Rats were treated with OME (100 mg/kg/day, p.o., 7 days), sEH inhibitor TPPU (3 mg/kg/day, p.o.) and OME (100 mg/kg/day, p.o., 7 days) + TPPU (3 mg/kg/day, p.o., last 3 days of OME dose) dissolved in vehicle PEG400, and their effect on hyperalgesia (increased sensitivity to pain) induced by PGE{sub 2} was monitored. While OME treatment by itself exhibited variable effects on PGE{sub 2} induced hyperalgesia, it strongly potentiated the effect of TPPU in the same assay. The significant decrease in pain with OME + TPPU treatment correlated with the increased levels of EETs in plasma and increased activities of P450 1A1 and P450 1A2 in liver microsomes. The results show that reducing catabolism of EETs with a sEH inhibitor yielded a stronger analgesic effect than increasing generation of EETs by OME, and combination of both yielded the strongest pain reducing effect under the condition of this study. - Highlights: • The soluble epoxide hydrolase (sEH) inhibitor TPPU is anti-hyperalgesic. • Omeprazole potentiates the anti-hyperalgesic actions of TPPU. • This potentiation is associated with increased P450 activity. • The potentiation is associated with an increase in fatty acid epoxide/diol ratio. • Joint use of sEH inhibitors and P450 inducers could result in drug–drug interactions.

  9. The antiulcer effect of Cibotium barometz leaves in rats with experimentally induced acute gastric ulcer

    Directory of Open Access Journals (Sweden)

    AL-Wajeeh NS

    2017-03-01

    Full Text Available Nahla Saeed Al-Wajeeh,1 Maryam Hajrezaie,1 Nawal Al-Henhena,1 Sareh Kamran,1 Elham Bagheri,1 Maryam Zahedifard,1 Kamelia Saremi,1 Suzita Mohd Noor,1 Hapipah Mohd Ali,2 Mahmood Ameen Abdulla11Department of Biomedical Science, Faculty of Medicine, 2Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, MalaysiaAbstract: Cibotium barometz is a pharmaceutical plant customarily used in traditional medicine in Malaysia for the treatment of different diseases, such as gastric ulcer. The gastroprotective effect of C. barometz leaves against ethanol-induced gastric hemorrhagic abrasions in Sprague Dawley rats has been evaluated in terms of medicinal properties. Seven groups of rats (normal control and ulcerated control groups, omeprazole 20 mg/kg, 62.5, 125, 250, and 500 mg/kg of C. barometz correspondingly were used in antiulcer experiment and pretreated with 10% Tween 20. After 1 hour, the normal group was orally administered 10% Tween 20, whereas absolute alcohol was fed orally to ulcerated control, omeprazole, and experimental groups. Gastric’s homogenate were assessed for endogenous enzymes activities. Stomachs were examined macroscopically and histologically. Grossly, the data demonstrated a significant decrease in the ulcer area of rats pretreated with plant extract in a dose-dependent manner with respect to the ulcerated group. Homogenates of the gastric tissue exhibited significantly increased endogenous enzymes activities in rats pretreated with C. barometz extract associated with the ulcerated control group. Histology of rats pretreated with C. barometz extract group using hematoxylin and eosin staining exhibited a moderate-to-mild disruption of the surface epithelium with reduction in submucosal edema and leucocyte infiltration in a dose-dependent manner. In addition, it showed heat shock protein70 protein up-expression and BCL2-associated X protein downexpression. These outcomes might be attributed to the

  10. Effect of gastric anacidity on the intestinal absorption of liver bound 57Co-labelled cobalamins

    International Nuclear Information System (INIS)

    Kittang, E.

    1987-01-01

    57 Co-labelled cyanocobalamin injected in rabbit was transformed within the liver to 57 Co-labelled desoxyadenosylcobalamin and methylcovalamin. The absorption of 57 Co-labelled liver bound cobalamins could be determined with acceptable accuracy by the double isotope fecal excretion method. Treatment with the H 2-receptor antagonist, ranitidine, did not result in decreased absorption of 57 Co-labelled liver bound cobalamins in healthy individuals. R-protein and the R-proteincobalamin complex were determined by the FPLC Mono S chromatography method with a high degree of correlation to the charcoal method in saliva, gastric and duodenal juice, and with a high degree of reproducibility. Omeprazole markedly inhibited the gastric acid and pepsin secretion, but did nor inhibit the IF secretion. Omeprazole treatment resulted in anacidity in 14 of 17 individuals, but did not reduce the absorption of liver bound 57 Co-labelled cobalamins. The intrinsic factor concentration in gastric aspirates measured during the study was unchanged during omeprazole treatment. The release of cobalamins from liver homogenate was markedly inhibited by neutralized gastric juice in vitro, probably due to decreased pepsin mediated proteolysis. In vivo the cobalamin release from liver homogenate was modestly inhibited in the stomach but was unaffected in jejunum during omeprazole treatment. The major part of 57 Co-labelled liver cobalamins bound to R-protein in acid and neutral gastric juice in vitro, and omeprazole induced anacidity, did not influence the cobalamin binding either in gastric or jejunal juice in vivo

  11. Methanol leaf extract of Actinodaphne sesquipedalis (Lauraceae) enhances gastric defense against ethanol-induced ulcer in rats

    Science.gov (United States)

    Omar, Hanita; Nordin, Noraziah; Hassandarvish, Pouya; Hajrezaie, Maryam; Azizan, Ainnul Hamidah Syahadah; Fadaeinasab, Mehran; Abdul Majid, Nazia; Abdulla, Mahmood Ameen; Mohd Hashim, Najihah; Mohd Ali, Hapipah

    2017-01-01

    Actinodaphne sesquipedalis Hook. F. Var. Glabra (Kochummen), also known as “Medang payung” by the Malay people, belongs to the Lauraceae family. In this study, methanol leaf extract of A. sesquipedalis was investigated for their acute toxicity and gastroprotective effects to reduce ulcers in rat stomachs induced by ethanol. The rats were assigned to one of five groups: normal group (group 1), ulcer group (group 2), control positive drug group (group 3) and two experimental groups treated with 150 mg/kg (group 4) and 300 mg/kg (group 5) of leaf extract. The rats were sacrificed an hour after pretreatment with extracts, and their stomach homogenates and tissues were collected for further evaluation. Macroscopic and histological analyses showed that gastric ulcers in rats pretreated with the extract were significantly reduced to an extent that it allowed leukocytes penetration of the gastric walls compared with the ulcer group. In addition, an ulcer inhibition rate of >70% was detected in rats treated with both doses of A. sesquipedalis extract, showing a notable protection of gastric layer. Severe destruction of gastric mucosa was prevented with a high production of mucus and pH gastric contents in both omeprazole-treated and extract-treated groups. Meanwhile, an increase in glycoprotein uptake was observed in pretreated rats through accumulation of magenta color in Periodic Acid Schiff staining assay. Analysis of gastric homogenate from pretreated rats showed a reduction of malondialdehyde and elevation of nitric oxide, glutathione, prostaglandin E2, superoxide dismutase and protein concentration levels in comparison with group 2. Suppression of apoptosis in gastric tissues by upregulation of Hsp70 protein and downregulation of Bax protein was also observed in rats pretreated with extract. Consistent results of a reduction of gastric ulcer and the protection of gastric wall were obtained for rats pretreated with A. sesquipedalis extract, which showed its

  12. Methanol leaf extract of Actinodaphne sesquipedalis (Lauraceae) enhances gastric defense against ethanol-induced ulcer in rats.

    Science.gov (United States)

    Omar, Hanita; Nordin, Noraziah; Hassandarvish, Pouya; Hajrezaie, Maryam; Azizan, Ainnul Hamidah Syahadah; Fadaeinasab, Mehran; Abdul Majid, Nazia; Abdulla, Mahmood Ameen; Mohd Hashim, Najihah; Mohd Ali, Hapipah

    2017-01-01

    Actinodaphne sesquipedalis Hook. F. Var. Glabra (Kochummen), also known as "Medang payung" by the Malay people, belongs to the Lauraceae family. In this study, methanol leaf extract of A. sesquipedalis was investigated for their acute toxicity and gastroprotective effects to reduce ulcers in rat stomachs induced by ethanol. The rats were assigned to one of five groups: normal group (group 1), ulcer group (group 2), control positive drug group (group 3) and two experimental groups treated with 150 mg/kg (group 4) and 300 mg/kg (group 5) of leaf extract. The rats were sacrificed an hour after pretreatment with extracts, and their stomach homogenates and tissues were collected for further evaluation. Macroscopic and histological analyses showed that gastric ulcers in rats pretreated with the extract were significantly reduced to an extent that it allowed leukocytes penetration of the gastric walls compared with the ulcer group. In addition, an ulcer inhibition rate of >70% was detected in rats treated with both doses of A. sesquipedalis extract, showing a notable protection of gastric layer. Severe destruction of gastric mucosa was prevented with a high production of mucus and pH gastric contents in both omeprazole-treated and extract-treated groups. Meanwhile, an increase in glycoprotein uptake was observed in pretreated rats through accumulation of magenta color in Periodic Acid Schiff staining assay. Analysis of gastric homogenate from pretreated rats showed a reduction of malondialdehyde and elevation of nitric oxide, glutathione, prostaglandin E2, superoxide dismutase and protein concentration levels in comparison with group 2. Suppression of apoptosis in gastric tissues by upregulation of Hsp70 protein and downregulation of Bax protein was also observed in rats pretreated with extract. Consistent results of a reduction of gastric ulcer and the protection of gastric wall were obtained for rats pretreated with A. sesquipedalis extract, which showed its prominent

  13. Omeprazole and misoprostol for preventing gastric mucosa effects caused by indomethacin and celecoxib in rats Omeprazol e misoprostol na prevenção de lesões de mucosa gástrica causadas por indometacina e celecoxib em ratos

    Directory of Open Access Journals (Sweden)

    Míriam Elias Cavallini

    2006-06-01

    Full Text Available PURPOSE: To evaluate and to compare macro and microscopically the intense injuries of the gastric mucosa of rats which were caused by NSAIDS celecoxib and indomethacin and the gastric cytoprotection with omeprazole and misoprostol. METHODS: The sample is formed by one hundred and fifty Wistar rats with average weight 200 g, distributed in four groups, such as: Group A, subdivided in groups A1 and A2 - pre-treatment with omeprazole (20 mg/rat during seven days and on the 8th day - use of NSAIDS, concerning A1 (20 rats were given celecoxib (1mg/rat and A2 (20 rats were given indomethacin. The Group B, subdivided in group B1 and B2 - pre-treatment with misoprostol (20mg/rat during seven days and on the 8th day use of NSAIDS, concerning B1 (20 rats were given celecoxib (1 mg/ rat and B2 (20 rats were given indomethacin (12.5 mg/rat. The Group C: were not given cytoprotection during seven days, from the 7th to the 8th day - fast of food and water ad libitum, on the 8th day of NSAIDS use, concerning C1 (20 rats were given celecoxib, C2 (20 rats were given indomethacin (12.5 mg/ rat, C3 (20 rats were given celecoxib (200mg/rato, and Group D - control group, concerning 10 rats were observed during seven days ingesting food and water ad libitum. On the 9th day, the stomachs were taken out and were macro and microscopically evaluated for the identification of the gastric injuries. RESULTS: On the macroscopic studies, the groups A2, B2 and C2 presented a remarkable high number of injuries for cm² /animal, respectively 18.55 injuries for cm² /animal, 16.25 injuries for cm² /animal and 13.55 injuries for cm²/animal. On the microscopic studies, the percentage of the injured mucosa, presented expressive difference among the groups A1, B1, C1 when compared to the groups A2, B2, C2 (pOBJETIVO: Avaliar e comparar macro e microscopicamente as lesões agudas da mucosa gástrica de ratos provocadas pelos AINEs celecoxib e indometacina e a citoproteção g

  14. Aspirin and Omeprazole

    Science.gov (United States)

    The combination of aspirin and omeprazole is used to reduce the risk of stroke or heart attack in patients who have had or ... risk of developing a stomach ulcer when taking aspirin. Aspirin is in a class of medications called ...

  15. Early or late antibiotic intervention prevents Helicobacter pylori-induced gastric cancer in a mouse model.

    Science.gov (United States)

    Zhang, Songhua; Lee, Dong Soo; Morrissey, Rhiannon; Aponte-Pieras, Jose R; Rogers, Arlin B; Moss, Steven F

    2014-12-01

    H. pylori infection causes gastritis, peptic ulcers and gastric cancer. Eradicating H. pylori prevents ulcers, but to what extent this prevents cancer remains unknown, especially if given after intestinal metaplasia has developed. H. pylori infected wild-type (WT) mice do not develop cancer, but mice lacking the tumor suppressor p27 do so, thus providing an experimental model of H. pylori-induced cancer. We infected p27-deficient mice with H. pylori strain SS1 at 6-8 weeks of age. Persistently H. pylori-infected WT C57BL/6 mice served as controls. Mice in the eradication arms received antimicrobial therapy (omeprazole, metronidazole and clarithromycin) either "early" (at 15 weeks post infection, WPI) or "late" at 45 WPI. At 70 WPI, mice were euthanized for H. pylori determination, histopathology and cytokine/chemokine expression. Persistently infected mice developed premalignant lesions including high-grade dysplasia, whereas those given antibiotics did not. Histologic activity scores in the eradication groups were similar to each other, and were significantly decreased compared with controls for inflammation, epithelial defects, hyperplasia, metaplasia, atrophy and dysplasia. IP-10 and MIG levels in groups that received antibiotics were significantly lower than controls. There were no significant differences in expression of IFN-γ, TNF-α, IL-1β, RANTES, MCP-1, MIP-1α or MIP-1β among the three groups. Thus, H. pylori eradication given either early or late after infection significantly attenuated gastric inflammation, gastric atrophy, hyperplasia, and dysplasia in the p27-deficient mice model of H. pylori-induced gastric cancer, irrespective of the timing of antibiotic administration. This was associated with reduced expression of IP-10 and MIG. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Gastroprotective Effect of Ethanolic Extract of Curcuma xanthorrhiza Leaf against Ethanol-Induced Gastric Mucosal Lesions in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Nurhidayah Ab. Rahim

    2014-01-01

    Full Text Available Herbal medicines appeared promising in prevention of many diseases. This study was conducted to investigate the gastroprotective effect of Curcuma xanthorrhiza leaf in the rats induced gastric ulcer by ethanol. Normal and ulcer control received carboxymethycellulose (5 mL/kg orally, positive control was administered with 20 mg/kg omeprazole (reference drug and 2 groups were received 250 mg/kg and 500 mg/kg of the leaf extract, respectively. To induce of gastric ulcers formation, ethanol (5 mL/kg was given orally to all groups except normal control. Gross ulcer areas, histology, and amount of prostaglandin E2, superoxide dismutase and malondialdehyde were assessed to determine the potentiality of extract in prevention against gastric ulcers. Oral administration of extract showed significant gastric protection effect as the ulcer areas was remarkably decreased. Histology observation showed less edema and leucocytes infiltration as compared with the ulcer control which exhibited severe gastric mucosa injury. Furthermore, the leaf extract elevated the mucus weight, level of prostaglandin E2 and superoxide dismutase. The extract also reduced malondialdehyde amount significantly. Results showed leaf extract of Curcuma xanthorrhiza can enhanced the gastric protection and sustained the integrity of gastric mucosa structure. Acute toxicity test did not showed any sign of toxicity (2 g/kg and 5 g/kg.

  17. The anti-secretory and anti-ulcer activities of esomeprazole in comparison with omeprazole in the stomach of rats and rabbits.

    Science.gov (United States)

    Bastaki, Salim M A; Chandranath, Irwin S; Singh, Jaipaul

    2008-02-01

    Proton pump inhibitors (PPIs) are widely used to treat hyperacid secretion and stomach ulcers. The study investigated the anti-secretory and anti-ulcer effects of esomeprazole, the S-isomer of omeprazole on dimaprit, histamine and dibutyryl adenosine 3, 5 cyclic monophosphate (dbcAMP)-evoked gastric acid secretion, acidified ethanol (AE) and indomethacin (INDO)-induced haemorrhagic lesions and on prostaglandin E2 (PGE2) level in the rat in vivo and rabbit in vitro preparations. The effect of omeprazole was also investigated for comparison. Dimaprit-induced acid secretion was significantly (P stomach tissue homogenate. The results show that esomeprazole and omeprazole were equally effective against gastric haemorrhagic lesions induced by either AE or INDO and in inhibiting dimaprit-, dbcAMP- and histamine-induced gastric acid secretion in the rat and rabbit stomach both in vivo and in vitro. The gastro-protective effect of esomeprazole was found to be proportional to the bound PGE2 levels in the glandular area of the stomach.

  18. Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans

    DEFF Research Database (Denmark)

    Mertz-Nielsen, Anette; Hillingsø, J; Bukhave, Klaus

    1996-01-01

    this incidental finding is explained by more potent gastric acid inhibition by omeprazole or might be caused by the different mode of drug action. Basal and stimulated gastric and duodenal bicarbonate secretion rates were measured in the same subjects in control experiments (n=17) and after pretreatment with high......H 6.9 v 6.8; p>0.05). Omeprazole caused higher rates of basal (mean (SEM)) (597 (48) v 351 (39) mu mol/h; pstimulated (834 (72) v 474 (66) mu mol/h; pstimulated (3351 (678) v 2550 (456) mu mol/h; p>0.05) duodenal bicarbonate secretion compared with control...... experiments. Also the combination of omeprazole and ranitidine increased (p=0.05) duodenal bicarbonate secretion, while ranitidine alone caused no change in either basal or stimulated secretion. In the stomach basal as well as vagally stimulated bicarbonate secretion was independent of the means of acid...

  19. Acid Inhibitory Effect of a Combination of Omeprazole and Sodium Bicarbonate (CDFR0209) Compared With Delayed-Release Omeprazole 40 mg Alone in Healthy Adult Male Subjects.

    Science.gov (United States)

    Kim, Kyu-Nam; Yang, Sung-Won; Kim, Hyunil; Kwak, Seong Shin; Kim, Young-Sang; Cho, Doo-Yeoun

    2018-01-01

    CDFR0209, a combination of an immediate-release formulation of omeprazole 40 mg and sodium bicarbonate 1100 mg, has been developed to treat acid-related disorders. We compared the acid inhibitory effects of CDFR0209 and delayed-release omeprazole (omeprazole-DR, Losec 40 mg) after repeated dosing in Helicobacter pylori-negative healthy adult male subjects. In this 2-period crossover study, 30 subjects were randomized to CDFR0209 or omeprazole-DR daily for 7 days. An ambulatory continuous 24-hour intragastric pH recording was performed at baseline and on days 1 and 7 of each administration period. Integrated gastric acidity was calculated from time-weighted average hydrogen ion concentrations at each hour of the 24-hour record. An analysis of variance model was used to test the pharmacodynamic equivalence of CDFR0209 and omeprazole-DR, using the natural logarithmic transformation of the percent decrease from baseline in integrated gastric acidity for the 24-hour interval after the seventh dose of each omeprazole formulation. The geometric least-squares mean ratios (CDFR0209/omeprazole-DR) of the percent decrease from baseline in integrated gastric acidity was 0.98 (90%CI, 0.93-1.07). Both CDFR0209 and omeprazole-DR are equally effective in decreasing integrated gastric acidity at steady state. © 2017, The American College of Clinical Pharmacology.

  20. Omeprazole induces NAD(P)H quinone oxidoreductase 1 via aryl hydrocarbon receptor-independent mechanisms: Role of the transcription factor nuclear factor erythroid 2–related factor 2

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Shaojie; Patel, Ananddeep; Moorthy, Bhagavatula; Shivanna, Binoy, E-mail: shivanna@bcm.edu

    2015-11-13

    Activation of the aryl hydrocarbon receptor (AhR) transcriptionally induces phase I (cytochrome P450 (CYP) 1A1) and phase II (NAD(P)H quinone oxidoreductase 1 (NQO1) detoxifying enzymes. The effects of the classical and nonclassical AhR ligands on phase I and II enzymes are well studied in human hepatocytes. Additionally, we observed that the proton pump inhibitor, omeprazole (OM), transcriptionally induces CYP1A1 in the human adenocarcinoma cell line, H441 cells via AhR. Whether OM activates AhR and induces the phase II enzyme, NAD(P)H quinone oxidoreductase 1 (NQO1), in fetal primary human pulmonary microvascular endothelial cells (HPMEC) is unknown. Therefore, we tested the hypothesis that OM will induce NQO1 in HPMEC via the AhR. The concentrations of OM used in our experiments did not result in cytotoxicity. OM activated AhR as evident by increased CYP1A1 mRNA expression. However, contrary to our hypothesis, OM increased NQO1 mRNA and protein via an AhR-independent mechanism as AhR knockdown failed to abrogate OM-mediated increase in NQO1 expression. Interestingly, OM activated Nrf2 as evident by increased phosphoNrf2 (S40) expression in OM-treated compared to vehicle-treated cells. Furthermore, Nrf2 knockdown abrogated OM-mediated increase in NQO1 expression. In conclusion, we provide evidence that OM induces NQO1 via AhR-independent, but Nrf2-dependent mechanisms. - Highlights: • We investigated whether omeprazole induces NQO1 in human fetal lung cells. • Omeprazole induces the phase II enzyme, NQO1, in human fetal lung cells. • AhR deficiency fails to abrogate omeprazole-mediated induction of NQO1. • Omeprazole increases phosphoNrf2 (S40) protein expression in human fetal lung cells. • Nrf2 knockdown abrogates the induction of NQO1 by omeprazole in human lung cells.

  1. Dynamics of Serum Pepsinogens on the Background of Double Standard Doses of Omeprazole in Patients with Gastroesophageal Reflux Disease and Functional Gastric Dyspepsia

    Directory of Open Access Journals (Sweden)

    S.G. Melashchenko

    2013-09-01

    Full Text Available In literature it has been reported that concentrations of serum pepsinogens increase during administration of proton pump inhibitors (PPI. However, the magnitude of these changes is still to be assessed. The aim of this study was to evaluate the changes in levels of pepsinogen I (PG-1 and pepsinogen II (PG-2 on the background of therapy with omeprazole which has been administered before breakfast in double standard dose (40 mg. The regimen of PPI administration completely corresponds to conventional PPI-test. There were two groups of patients: 1st one (gastroesophageal reflux desiase — 10 women and 9 men, mean age (52.37 ± 3.25 years; 2nd one (functional dyspepsia — 11 women and 8 men, mean age (48.37 ± 3.56 years. It was found that in 1st group PGI rises from (141.90 ± 7.99 mcg/l to (177.61 ± 7.81 mcg/l, in 2nd group — from (115.02 ± 10.16 mcg/l to (152.37 ± 12.33 mcg/l (p < 0.05. PG-2 level changes in the same. In 1st group PG-2 rises from (21.65 ± 3.13 mcg/l to (32.64 ± 3.42 mcg/l, in 2nd group — from (14.84 ± 1.64 mcg/l to (23.55 ± 2.37 mcg/l (p < 0.05. In 6 cases absolute increase of PGI (ΔPG-2 didn’t reach threshold of 7.0 mcg/l considered by us as level of insufficient acid inhibition. Two of these patients had atrophic gastritis (PG-1 < 50 mcg/l; ratio PG-/PG-2 < 3.0, rest 4 patients didn’t have atrophic gastritis but in half cases they hadn’t adequate answer to PPI administration. There was a significant correlation between increase of PG-1 level and disappearance of reflux complaints evaluated by dynamics in RS-cluster of GSRS-questionnaire.

  2. Effects of sucralfate on gastric irritant-induced necrosis and apoptosis in cultured guinea pig gastric mucosal cells.

    Science.gov (United States)

    Hoshino, Tatsuya; Takano, Tatsunori; Tomisato, Wataru; Tsutsumi, Shinji; Hwang, Hyun-Jung; Koura, Yuko; Nishimoto, Kiyo; Tsuchiya, Tomofusa; Mizushima, Tohru

    2003-01-01

    We previously reported that several gastric irritants, including ethanol, hydrogen peroxide, and hydrochloric acid, induced both necrosis and apoptosis in cultured gastric mucosal cells. In the present study, we examined the effects of sucralfate, a unique gastroprotective drug, on gastric irritant-induced necrosis and apoptosis produced in vitro. Sucralfate strongly inhibited ethanol-induced necrosis in primary cultures of guinea pig gastric mucosal cells. The preincubation of cells with sucralfate was not necessary for its cytoprotective effect to be observed, thus making its mechanism of action different from that of other gastroprotective drugs. Necrosis of gastric mucosal cells induced by hydrogen peroxide or indomethacin was also suppressed by sucralfate. On the other hand, sucralfate only weakly inhibited ethanol-induced apoptosis. These results suggest that the cytoprotective effect of sucralfate on gastric mucosa in vivo can be explained, at least in part, by its inhibitory effect on gastric irritant-induced necrosis.

  3. Pharmacological inhibition of soluble epoxide hydrolase or genetic deletion reduces diclofenac-induced gastric ulcers.

    Science.gov (United States)

    Goswami, Sumanta Kumar; Rand, Amelia Ann; Wan, Debin; Yang, Jun; Inceoglu, Bora; Thomas, Melany; Morisseau, Christophe; Yang, Guang-Yu; Hammock, Bruce D

    2017-07-01

    This research was conducted to evaluate the hypothesis that gastric ulcers caused by the NSAID diclofenac sodium (DCF) can be prevented by the soluble epoxide hydrolase inhibitor TPPU. Mice were administered a single dose of 10, 30 or 100mg/kg of DCF. Once an ulcerative dose of DCF was chosen, mice were pretreated with TPPU for 7days at 0.1mg/kg to evaluate anti-ulcer effects of the sEH inhibitor on anatomy, histopathology, pH, inflammatory markers and epithelial apoptosis of stomachs. Diclofenac caused ulceration of the stomach at a dose of 100mg/kg and a time post dose of 6h. Ulcers generated under these conditions were associated with a significant increase in the levels of TNF-α and IL-6 in serum and increased apoptosis compared to control mice. Pretreatment with TPPU resulted in a decrease of ulceration in mice treated with DCF with a significant decrease in the level of apoptosis, TNF-α and IL-6 in the serum in comparison to diclofenac-treated mice. TPPU did not affect the pH of the stomach, whereas omeprazole elevated the pH of the stomach as expected. A similar anti-ulcer effect was observed in sEH gene knockout mice treated with DCF. The sEH inhibitor TPPU decreases the NSAID-induced stomach ulcers. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. A double-blind placebo-controlled trial of omeprazole on urinary pH in healthy subjects

    DEFF Research Database (Denmark)

    Osther, P J; Rasmussen, L; Pedersen, S A

    1992-01-01

    Urinary pH is related to urinary calculus formation as well as urinary infection. Omeprazole is an effective inhibitor of gastric acid secretion through inhibition of the parietal cell H+K+ATPase. In this study we have evaluated a possible effect of omeprazole on urine acidification. Ten healthy...... male subjects took placebo and omeprazole, 40 mg o.m., for 10 days in a double-blind placebo-controlled trial. Morning fasting urinary pH was measured on day 10 of each treatment course using a pH meter. No effect of omeprazole on urinary pH could be demonstrated. It is thus unlikely...... that it is necessary to take omeprazole treatment into consideration in stone screening. As omeprazole did not affect urinary pH, no urological side effects related to changes in urinary pH can be expected....

  5. The gastro protective effects of Cibotium barometz hair on ethanol-induced gastric ulcer in Sprague-Dawley rats.

    Science.gov (United States)

    Al-Wajeeh, Nahla Saeed; Hajerezaie, Maryam; Noor, Suzita Mohd; Halabi, Mohammed Farouq; Al-Henhena, Nawal; Azizan, Ainnul Hamidah Syahadah; Kamran, Sareh; Hassandarvish, Pouya; Shwter, Abdrabuh N; Karimian, Hamed; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen

    2017-01-19

    Cibotium barometz is a medical herb used traditionally in the Malaysian peninsula for several ailments, including gastric ulcer. The aim of this study was assessment the anti-ulcer effects of C. barometz hair on ethanol-induced stomach hemorrhagic abrasions in animals. Seven groups of Sprague Dawley (SD) rats were administered 10% Tween 20 in the normal control and ulcer control groups, and omeprazole 20 mg/kg and 62.5, 125, 250, and 500 mg/kg of C. barometz hair extract in the experimental groups. After 60 min, the normal control group of rats was orally administered 10% Tween 20, while absolute ethanol was orally administered to the groups of ulcer control, omeprazole and experimental groups. Stomachs of the rats were examined macroscopically and histologically. Homogenates of stomachs were used to evaluate endogenous antioxidant enzyme activities. Rats pre-fed with plant extract presented a significant decrease in the sore area, increased pH of gastric contents and preserved stomach wall mucus compared to the ulcer group. Histologically, rats pre-fed with C. barometz hair extract showed mild to moderate disruptions of the surface epithelium while animals pre-fed with absolute ethanol showed severe disruptions of the stomach epithelium with edema and leucocyte penetration of the submucosal layer. A Periodic acid Schiff (PAS) staining revealed that each rat pre-treated with the plant extract displayed an intense uptake of stomach epithelial glycoprotein magenta color compared to the ulcer control group. Immunohistochemical analysis revealed that rats pre-fed with the plant extract showed an up-regulation of the heat shock protein 70 (HSP70) and down-regulation of Bax proteins compared to ulcer control rats. Homogenates of the stomach tissue demonstrated significant increases in the endogenous antioxidant enzymatic activity and decreased lipid peroxidation (MDA) in rats pre-treated with C. barometz hair extract compared with the ulcer control rats. In acute

  6. Fasting does not induce gastric emptying in rats.

    Science.gov (United States)

    Brito, Marcus Vinicius Henriques; Yasojima, Edson Yuzur; Teixeira, Renan Kleber Costa; Houat, Abdallah de Paula; Yamaki, Vitor Nagai; Costa, Felipe Lobato da Silva

    2015-03-01

    To evaluate the effect of fasting on gastric emptying in mice. Twenty-eight mice were distributed into three study groups: a normal group (N=4): normal standard animals; a total fasting group (N=12): subjected to food and water deprivation and a partial fasting group (N=12): subjected to food deprivation only. The fasting groups were subdivided into three subgroups of four animals each, according to the date of euthanasia: 24, 48 and 72 hours. Was analyzed: the gastric volume, degree of the gastric wall distention and the presence of food debris in gastrointestinal tract. The mean gastric volume was 1601 mm3 in the normal group, 847 mm3 in total fasting group and 997 mm3 in partial fasting group. There was difference between the fasting groups in any analyzed period (pfasting (p>0.05). Total fasting or only-solids deprivation does not induce gastric emptying in mice.

  7. The gastroprotective effects of hydroalcoholic extract of Monolluma quadrangula against ethanol-induced gastric mucosal injuries in Sprague Dawley rats

    Directory of Open Access Journals (Sweden)

    Ibrahim IAA

    2015-12-01

    Full Text Available Ibrahim Abdel Aziz Ibrahim,1 Mahmood Ameen Abdulla,2 Maryam Hajrezaie,2 Ammar Bader,3 Naiyer Shahzad,1 Saeed S Al-Ghamdi,1 Ahmad S Gushash,4 Mohadeseh Hasanpourghadi5 1Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; 2Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 3Department of Pharmacognosy, Faculty of Pharmacy, Umm Al-Qura University, Makkah, 4College of Arts and Science in Baljurashi, Albaha University, Baljurashi, Saudi Arabia; 5Cell Biology and Drug Discovery Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Abstract: Monolluma quadrangula (Forssk. Plowes is used in Saudi traditional medicines to treat gastric ulcers. The hydroalcoholic extract of M. quadrangula (MHAE was used in an in vivo model to investigate its gastroprotective effects against ethanol-induced acute gastric lesions in rats. Five groups of Sprague Dawley rats were used. The first group was treated with 10% Tween 20 as a control. The other four groups included rats treated with absolute ethanol (5 mL/kg to induce an ulcer, rats treated with 20 mg/kg omeprazole as a reference drug, and rats treated with 150 or 300 mg/kg MHAE. One hour later, the rats were administered absolute ethanol (5 mL/kg orally. Animals fed with MHAE exhibited a significantly increased pH, gastric wall mucus, and flattening of the gastric mucosa, as well as a decreased area of gastric mucosal damage. Histology confirmed the results; extensive destruction of the gastric mucosa was observed in the ulcer control group, and the lesions penetrated deep into the gastric mucosa with leukocyte infiltration of the submucosal layer and edema. However, gastric protection was observed in the rats pre-fed with plant extracts. Periodic acid–Schiff staining of the gastric wall revealed a remarkably intensive uptake of magenta color in the

  8. Biochanin a gastroprotective effects in ethanol-induced gastric mucosal ulceration in rats.

    Science.gov (United States)

    Hajrezaie, Maryam; Salehen, NurAin; Karimian, Hamed; Zahedifard, Maryam; Shams, Keivan; Al Batran, Rami; Majid, Nazia Abdul; Khalifa, Shaden A M; Ali, Hapipah Mohd; El-Seedi, Hesham; Abdulla, Mahmood Ameen

    2015-01-01

    Biochanin A notable bioactive compound which is found in so many traditional medicinal plant. In vivo study was conducted to assess the protective effect of biochanin A on the gastric wall of Spraguedawley rats` stomachs. The experimental set included different animal groups. Specifically, four groups with gastric mucosal lesions were receiving either a) Ulcer control group treated with absolute ethanol (5 ml/kg), b) 20 mg/kg of omeprazole as reference group, c) 25 of biochanin A, d) 50 mg/kg of biochanin A. Histopathological sectioning followed by immunohistochemistry staining were undertaken to evaluate the influence of the different treatments on gastric wall mucosal layer. The gastric secretions were collected in the form of homogenate and exposed to superoxide dismutase (SOD) and nitric oxide enzyme (NO) and the level of malondialdehyde (MDA) and protein content were measured. Ulceration and patchy haemorrhage were clearly observed by light microscopy. The morphology of the gastric wall as confirmed by immunohistochemistry and fluorescent microscopic observations, exhibited sever deformity with notable thickness, oedematous and complete loss of the mucosal coverage however the biochanin-pretreated animals, similar to the omeprazole-pretreated animals, showed less damage compared to the ulcer control group. Moreover, up-regulation of Hsp70 protein and down-regulation of Bax protein were detected in the biochanin A pre-treated groups and the gastric glandular mucosa was positively stained with Periodic Acid Schiff (PAS) staining and the Leucocytes infiltration was commonly seen. Biochanin A displayed a great increase in SOD and NO levels and decreased the release of MDA. This gastroprotective effect of biochanin A could be attributed to the enhancement of cellular metabolic cycles perceived as an increase in the SOD, NO activity, and decrease in the level of MDA, and also decrease in level of Bax expression and increase the Hsp70 expression level.

  9. Aspirin-Induced Gastric Lesions Alters EGFR and PECAM-1 Immunoreactivity in Wistar Rats: Modulatory Action of Flavonoid Fraction of Musa Paradisiaca.

    Science.gov (United States)

    Alese, Margaret Olutayo; Adewole, Stephen Olarinde; Akinwunmi, Kemi Feyisayo; Omonisi, Abidemi Emmanuel; Alese, Oluwole Ojo

    2017-08-15

    In this study, Epithelial Growth Factor Receptor and Platelet Endothelial Cell Adhesion Molecule-1 were localised to investigate the healing effects of a flavonoid-rich fraction of M. paradisiaca fruit in the gastric corpus of Wistar rats following aspirin-induced gastric lesion. Mature, unripe fruits of M. paradisiaca were peeled; air dried, pulverised, extracted with 70% methanol, concentrated and partitioned. Ninety male Wistar rats were randomly assigned into 6 groups of 15 rats each. The gastric lesion was induced in groups B, C, D, E and F rats by administration of 400 mg/kg aspirin in distilled water. Group A received distilled water. After 24 hours, flavonoid fraction of M. paradisiaca was administered to groups C, D and E at 100, 200 and 400 mg/kg respectively for 21 days. Group F rats received omeprazole at 1.8 mg/kg for 21 days. Five rats from each group were anaesthetized with ketamine on days 14, 21 and 28. Gastric tissues were excised and fixed in Neutral buffered formalin. This was followed by paraffin wax embedding method and sections stained with haematoxylin and eosin and for immunolocalisation of EGFR and PECAM-1. Data were analysed using descriptive and inferential statistics. There was a significant difference in the ulcer index in the corpus of control and treated rats throughout the experimental period (p = 0.0001). H&E stained sections showed a gradual restoration of the epithelial lining in the treated groups. Immunohistochemical examination showed that M. paradisiaca significantly increased (p Musa paradisiaca in attenuating the damaging effects of aspirin on the gastric mucosa was observed as there was a significantly increased reactivity for EGFR and PECAM-1 in the gastric corpus in a dose-dependent manner.

  10. Evidence for gastroprotective, anti-inflammatory and antioxidant potential of methanolic extract of Cordia dichotoma leaves on indomethacin and stress induced gastric lesions in Wistar rats.

    Science.gov (United States)

    Hatware, Ketan Vinayakrao; Sharma, Sanjay; Patil, Kiran; Shete, Meghanath; Karri, Sravani; Gupta, Gaurav

    2018-07-01

    The Cordia dichotoma (CD) is having anticancer and other pharmacological effects as it contains mainly flavonoids. The present study was aimed to demonstrate the gastroprotective effect of methanolic extract of CD leaves (MECD) obtained using Soxhlet extractor. In this study the qualitative phytochemical analysis of MECD revealed the presence of bioflavonoids and determination of quercetin was confirmed by HPLC analysis. The MECD was administered orally at doses 50 mg/kg, 100 mg/kg and 200 mg/kg against indomethacin induced gastric ulceration and stress-induced gastric ulceration in Wistar rats. Omeprazole at 10 mg/kg orally was used as the reference standard. The various parameters like gastric volume, gastric pH, total acidity, ulcer index, percent protection were estimated for assessment of anti-secretory and gastroprotective effects of MECD. At the same time antioxidant parameters like superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) in addition to that inflammatory parameters such as tumor necrosis factor-α (TNF-α), interleukin-6 and interleukin-10 were also estimated according to their respective method of estimation using analyzing kit. The MECD have reduced gastric volume, total acidity and gastric mucosal damage in both the experimental models significantly and dose dependently as compared with control group. Similarly the antioxidant enzymes like SOD and CAT were increased while MDA levels were decreased significantly, at the same time TNF-α and IL-6 levels were decreased and anti-inflammatory IL-10 levels were increased significantly in MECD treated groups. Thus the pretreatment with MECD has shown significant gastroprotective potential probably due to its antioxidant and anti-inflammatory properties. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  11. Gallic Acid Enriched Fraction of Phyllanthus emblica Potentiates Indomethacin-Induced Gastric Ulcer Healing via e-NOS-Dependent Pathway

    Directory of Open Access Journals (Sweden)

    Ananya Chatterjee

    2012-01-01

    Full Text Available The healing activity of gallic acid enriched ethanolic extract (GAE of Phyllanthus emblica fruits (amla against the indomethacin-induced gastric ulceration in mice was investigated. The activity was correlated with the ability of GAE to alter the cyclooxygenase- (COX- dependent healing pathways. Histology of the stomach tissues revealed maximum ulceration on the 3rd day after indomethacin (18 mg/kg, single dose administration that was associated with significant increase in inflammatory factors, namely, mucosal myeloperoxidase (MPO activity and inducible nitric oxide synthase (i-NOS expression. Proangiogenic parameters such as the levels of prostaglandin (PG E2, vascular endothelial growth factor (VEGF, hepatocyte growth factor (HGF, von Willebrand Factor VIII, and endothelial NOS (e-NOS were downregulated by indomethacin. Treatment with GAE (5 mg/kg/day and omeprazole (3 mg/kg/day for 3 days led to effective healing of the acute ulceration, while GAE could reverse the indomethacin-induced proinflammatory changes of the designated biochemical parameters. The ulcer healing activity of GAE was, however, compromised by coadministration of the nonspecific NOS inhibitor, N-nitro-L-arginine methyl ester (L-NAME, but not the i-NOS-specific inhibitor, L-N6-(1-iminoethyl lysine hydrochloride (L-NIL. Taken together, these results suggested that the GAE treatment accelerates ulcer healing by inducing PGE2 synthesis and augmenting e-NOS/i-NOS ratio.

  12. Induced pneumoperitoneum in spiral CT evaluation of gastric cancer

    International Nuclear Information System (INIS)

    Guo Hua; Gao Jianbo; Li Yintai; Yang Xuehua; Chen Xuejun; Guan Sheng

    2001-01-01

    Objective: To evaluate the diagnostic value and clinical significance of preoperative staging in gastric cancer with induced pneumoperitoneum in spiral CT (SCTPP). Methods: Both routine SCT and SCTPP were performed in 52 lean patients suffered from gastric cancers, and comparison was made between SCT findings and surgical and histopathologic findings. Results: The accuracy of routine SCT and SCTPP in determining the T-staging was 72% and 96%, respectively (x 2 = 8.0, P 2 = 0.006, P > 0.05). The sensitivity in determining M-staging was 61% and 100%, respectively (x 2 = 0.04, P 2 6.03, P < 0.05). Conclusion: The accuracy of SCTPP in determining preoperative staging of gastric cancer was significantly higher than that of routine SCT. SCTPP has important guiding significance for the selection of the treatment strategy in gastric cancer

  13. Honey potentiates the gastric protection effects of sucralfate against ammonia-induced gastric lesions in rats.

    Science.gov (United States)

    Ali, Abu Taib Mohammad Mobarok; Al Swayeh, Othman Abdullah

    2003-09-01

    Natural honey is widely used all over the world as a complementary and alternative medicine in various disorders including gastrointestinal lesions. To evaluate the effects of combination of low dosage of honey (0.312 g/kg) and sucralfate (0.125 or 0.250 g /kg) on gastric protection and to determine any potentiating interactions between them against ammonia-induced gastric lesions in rats. Twenty-four hours fasted rats were given I ml of ammonium hydroxide 1 % intragastrically and they were killed one hour later under deep ether anesthesia. The gastric lesion index was calculated according to the method of Takaishi et al 1998. Non protein sulthydryls level was determined spectrophotometrically as described by Sedlak and Lindsay 1968. Administration of ammonium hydroxide produced red and black linear lesions and significant depletion of gastric nonprotein sulthydryls level. Oral administration of honey (0.312g/kg) or sucralfate (0.125 and 0.250 g/kg) 30 min before ammonium hydroxide reduced the severity of gastric mucosal lesions by 1 I or 18 and 42 % respectively, and has shown the changes in nonprotein sulfhydryls level induced by ammonium hydroxide. Furthermore, pretreatment with a combination of a low dose of honey (0.312 g /kg) and sucralfate (0.125 g or 0.250 g/kg) afforded significantly greater protection (58 and 77 %) than that obtained with either of them administered alone. The present results suggest potentiation of gastric protection effect of sucralfate by honey and this may have a clinical value in the treatment of peptic ulcer diseases in Helicobacter pylori positive patients.

  14. Vanillin abrogates ethanol induced gastric injury in rats via modulation of gastric secretion, oxidative stress and inflammation

    Directory of Open Access Journals (Sweden)

    Abdulrahman Al Asmari

    Full Text Available Vanillin is commonly used as an additive in food, medicine and cosmetics, but its effect has not yet been studied in gastric injury. Therefore the effect of vanillin was studied in experimental gastric ulcer. Gastric secretion and acidity were studied in pylorus ligated rats. Ulcer index, levels of gastric mucus, malondialdehyde (MDA, myeloperoxidase activity (MPO, expression of nuclear factor kappa B (NF-κB p65, and histopathological changes were determined in ethanol induced gastric ulcer. Pre treatment with vanillin significantly reduced gastric secretion (P < 0.001 and acidity (P < 0.0001 and gastric ulcer index scores (P < 0.001. and augmented the gastric mucosal defense. Vanillin significantly restored the depleted gastric wall mucus levels (P < 0.0001 induced by ethanol and also significantly attenuated ethanol induced inflammation and oxidative stress by the suppression of gastric MPO activity (P < 0.001, reducing the expression of NF-κB p65 and the increased MDA levels (P < 0.001. Vanillin was also effective in alleviating the damage to the histological architecture and the activation of mast cells induced by ethanol.Together the results of this study highlight the gastroprotective activity of vanillin in gastric ulcers of rats through multiple actions that include inhibition of gastric secretion and acidity, reduction of inflammation and oxidative stress, suppression of expression of NF-κB, and restoration of the histological architecture. Keywords: Gastric ulcers, Pylorus ligation, Ethanol, Vanillin, Inflammation, Oxidative stress

  15. Gallic Acid Induces Apoptosis in Human Gastric Adenocarcinoma Cells.

    Science.gov (United States)

    Tsai, Chung-Lin; Chiu, Ying-Ming; Ho, Tin-Yun; Hsieh, Chin-Tung; Shieh, Dong-Chen; Lee, Yi-Ju; Tsay, Gregory J; Wu, Yi-Ying

    2018-04-01

    Gastric cancer is one of the most common malignant cancers with a poor prognosis and high mortality rate worldwide. Current treatment of gastric cancer includes surgery and chemotherapy as the main modalities, but the potentially severe side-effects of chemotherapy present a considerable challenge. Gallic acid is a trihydroxybenzoic acid found to exert an anticancer effect against a variety of cancer cells. The purpose of this study was to determine the anti-cancer activity of Galla chinensis and its main component gallic acid on human gastric adenocarcinoma cells. MTT assay and cell death ELISA were used to determine the apoptotic effect of Gallic Chinensis and gallic acid on human gastric adenocarcinoma cells. To determine the pathway and relevant components by which gallic acid-induced apoptosis is mediated through, cells were transfected with siRNA (Fas, FasL, DR5, p53) using Lipofectamine 2000. Reults: Gallic Chinensis and gallic acid induced apoptosis of human gastric adenocarcinoma cells. Gallic acid induced up-regulation of Fas, FasL, and DR5 expression in AGS cells. Transfection of cells with Fas, FasL, or DR5 siRNA reduced gallic acid-induced cell death. In addition, p53 was shown to be involved in gallic acid-mediated Fas, FasL, and DR5 expression as well as cell apoptosis in AGS cells. These results suggest that gallic acid has a potential role in the treatment of gastric cancer. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  16. Effects of Omeprazole on Iron Absorption: Preliminary Study

    Directory of Open Access Journals (Sweden)

    Mahmut Yaşar Çeliker

    2013-09-01

    Full Text Available Objective: Increasing numbers of pediatric and adult patients are being treated with proton pump inhibitors (PPIs. PPIs are known to inhibit gastric acid secretion. Nonheme iron requires gastric acid for conversion to the ferrous form for absorption. Ninety percent of dietary and 100% of oral iron therapy is in the nonheme form. To the best of our knowledge, the effect of PPIs on iron absorption has not been studied in humans. Our study assessed the relationship between omeprazole therapy and iron absorption in healthy subjects. Materials and Methods: We recruited 9 healthy volunteers between June 2010 and March 2011. Subjects with chronic illness, anemia, or use of PPI therapy were excluded. Serum iron concentrations were measured 1, 2, and 3 h after the ingestion of iron (control group. The measurements were repeated on a subsequent visit after 4 daily oral administrations of omeprazole at a dose of 40 mg (treatment group. Results: One female and 8 male volunteers were enrolled in the study with a mean age of 33 years. There was no statistical difference detected between baseline, 1-h, 2-h, and 3-h iron levels between control and treatment groups. Conclusion: Administration of omeprazole for a short duration does not affect absorption of orally administered iron in healthy individuals.

  17. Comparative healing property of kombucha tea and black tea against indomethacin-induced gastric ulceration in mice: possible mechanism of action.

    Science.gov (United States)

    Banerjee, Debashish; Hassarajani, Sham A; Maity, Biswanath; Narayan, Geetha; Bandyopadhyay, Sandip K; Chattopadhyay, Subrata

    2010-12-01

    The healing activity of black tea (BT) and BT fermented with Candida parapsilosis and kombucha culture, designated as CT and KT respectively against the indomethacin-induced stomach ulceration has been studied in a mouse model. The KT sample (KT4) produced by fermenting BT for four days, showed the best DPPH radical scavenging capacity and phenolics contents. Hence the ulcer-healing activity of KT4 was compared with those of CT4 and BT. All the tea extracts (15 mg kg(-1)) could effectively heal the gastric ulceration as revealed from the histopathological and biochemical studies, with relative efficacy as KT4 > CT4 ∼ BT. The healing capacities of the tea extracts could be attributed to their antioxidant activity as well as the ability to protect the mucin content of the gastric tissues. In addition, the ability of KT4 to reduce gastric acid secretion might also contribute to its ulcer-healing activity. The tea preparation KT4 (15 mg kg(-1)) was as effective as the positive control, omeprazole (3 mg kg(-1)) in ulcer healing.

  18. Motilin-induced gastric contractions signal hunger in man.

    Science.gov (United States)

    Tack, J; Deloose, E; Ang, D; Scarpellini, E; Vanuytsel, T; Van Oudenhove, L; Depoortere, I

    2016-02-01

    Hunger is controlled by the brain, which receives input from signals of the GI tract (GIT). During fasting, GIT displays a cyclical motor pattern, the migrating motor complex (MMC), regulated by motilin. To study the relationship between hunger and MMC phases (I-III), focusing on spontaneous and pharmacologically induced phase III and the correlation with plasma motilin and ghrelin levels. The role of phase III was also studied in the return of hunger after a meal in healthy individuals and in patients with loss of appetite. In fasting healthy volunteers, mean hunger ratings during a gastric (62.5±7.5) but not a duodenal (40.4±5.4) phase III were higher (phunger scores from 29.2±7 to 61.7±8. The somatostatin analogue octreotide induced a premature intestinal phase III without a rise in hunger scores. Hunger ratings significantly correlated (β=0.05; p=0.01) with motilin plasma levels, and this relationship was lost after erythromycin administration. Motilin, but not ghrelin administration, induced a premature gastric phase III and a rise in hunger scores. In contrast to octreotide, postprandial administration of erythromycin induced a premature gastric phase III accompanied by an early rise in hunger ratings. In patients with unexplained loss of appetite, gastric phase III was absent and hunger ratings were lower. Motilin-induced gastric phase III is a hunger signal from GIT in man. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  19. EFEITO DA RANITIDINA E DO OMEPRAZOL SOBRE O pH GÁSTRICO EM CÃES

    Directory of Open Access Journals (Sweden)

    Silvio Abrahão

    1999-01-01

    Full Text Available O objetivo deste trabalho foi investigar o efeito da ranitidina e omeprazol sobre o pH gástrico em 24 cães adultos, machos, sem raça definida, distribuídos em 3 grupos: grupo A - controle, grupo B - ranitidina e grupo C - omeprazol. O pH gástrico foi medido, após coleta do suco gástrico, com seringa, em cães submetidos a gastrotomia. Esta medida foi feita no grupo controle nos tempos zero, 30, 60, 90 e 120 minutos, no grupo ranitidina a medida foi feita no tempo zero, seguida de aplicação de 0,85 mg/kg de ranitidina por via endovenosa, sendo realizada nova medida nos tempos 30, 60, 90 e 120 minutos e, no grupo omeprazol a medida foi feita no tempo zero, seguida de aplicação de 0,68 mg/kg de omeprazol por via endovenosa, sendo realizada nova medida nos tempos 30,60, 90 e 120 minutos. A comparação entre os grupos mostrou um aumento significante do pH gástrico após o uso de ranitidina e omeprazol. Entretanto, os efeitos comparados da ranitidina e omeprazol não apresentaram diferenças significantes na variação do pH.The aim of this work was the ranitidine and omeprazole gastric pH effect investigation. 24 adults, male, mongrel dogs were distributed in 3 groups: group A - control, group B - ranitidine and group C - omeprazole. Gastric pH was measured after gastric juice syringe collection in dogs submitted to gastrotomy. Control group measurements were done at times zero, 30, 60, 90 and 120 minutes. Ranitidine group measurements were done at time zero, followed by 0,85 mg/kg endovenous ranitidine, and also at times 30, 60, 90 and 120 minutes. Omeprazole group measurements were done at time zero, followed by 0,68 mg/kg endovenous omeprazole and also at times 30, 60, 90 and 120 minutes. A significant increase in gastric pH, was observed, comparing groups, after ranitidine and omeprazole use. However, ranitidine and omeprazole compared effects presented no significant differences in pH variation.

  20. Vanillin abrogates ethanol induced gastric injury in rats via modulation of gastric secretion, oxidative stress and inflammation.

    Science.gov (United States)

    Al Asmari, Abdulrahman; Al Shahrani, Hamoud; Al Masri, Nasser; Al Faraidi, Ahmed; Elfaki, Ibrahim; Arshaduddin, Mohammed

    2016-01-01

    Vanillin is commonly used as an additive in food, medicine and cosmetics, but its effect has not yet been studied in gastric injury. Therefore the effect of vanillin was studied in experimental gastric ulcer. Gastric secretion and acidity were studied in pylorus ligated rats. Ulcer index, levels of gastric mucus, malondialdehyde (MDA), myeloperoxidase activity (MPO), expression of nuclear factor kappa B (NF-κB) p65, and histopathological changes were determined in ethanol induced gastric ulcer. Pre treatment with vanillin significantly reduced gastric secretion ( P  Vanillin significantly restored the depleted gastric wall mucus levels ( P  Vanillin was also effective in alleviating the damage to the histological architecture and the activation of mast cells induced by ethanol. Together the results of this study highlight the gastroprotective activity of vanillin in gastric ulcers of rats through multiple actions that include inhibition of gastric secretion and acidity, reduction of inflammation and oxidative stress, suppression of expression of NF-κB, and restoration of the histological architecture.

  1. Compound list: omeprazole [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available omeprazole OPZ 00012 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/i...n_vitro/omeprazole.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vi...tro/omeprazole.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liv...er/Single/omeprazole.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/arch...ive/open-tggates/LATEST/Rat/in_vivo/Liver/Repeat/omeprazole.Rat.in_vivo.Liver.Repeat.zip ftp://ftp.bioscienc

  2. Dosimetric Analysis of Radiation-induced Gastric Bleeding

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Mary, E-mail: maryfeng@umich.edu [Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Normolle, Daniel [Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Pan, Charlie C. [Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Dawson, Laura A. [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Amarnath, Sudha [Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Ensminger, William D. [Department of Internal Medicine, Division of Hematology Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States); Lawrence, Theodore S.; Ten Haken, Randall K. [Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan (United States)

    2012-09-01

    Purpose: Radiation-induced gastric bleeding has been poorly understood. In this study, we described dosimetric predictors for gastric bleeding after fractionated radiation therapy. Methods and Materials: The records of 139 sequential patients treated with 3-dimensional conformal radiation therapy (3D-CRT) for intrahepatic malignancies were reviewed. Median follow-up was 7.4 months. The parameters of a Lyman normal tissue complication probability (NTCP) model for the occurrence of {>=}grade 3 gastric bleed, adjusted for cirrhosis, were fitted to the data. The principle of maximum likelihood was used to estimate parameters for NTCP models. Results: Sixteen of 116 evaluable patients (14%) developed gastric bleeds at a median time of 4.0 months (mean, 6.5 months; range, 2.1-28.3 months) following completion of RT. The median and mean maximum doses to the stomach were 61 and 63 Gy (range, 46-86 Gy), respectively, after biocorrection of each part of the 3D dose distributions to equivalent 2-Gy daily fractions. The Lyman NTCP model with parameters adjusted for cirrhosis predicted gastric bleed. Best-fit Lyman NTCP model parameters were n=0.10 and m=0.21 and with TD{sub 50} (normal) = 56 Gy and TD{sub 50} (cirrhosis) = 22 Gy. The low n value is consistent with the importance of maximum dose; a lower TD{sub 50} value for the cirrhosis patients points out their greater sensitivity. Conclusions: This study demonstrates that the Lyman NTCP model has utility for predicting gastric bleeding and that the presence of cirrhosis greatly increases this risk. These findings should facilitate the design of future clinical trials involving high-dose upper abdominal radiation.

  3. Dosimetric Analysis of Radiation-induced Gastric Bleeding

    International Nuclear Information System (INIS)

    Feng, Mary; Normolle, Daniel; Pan, Charlie C.; Dawson, Laura A.; Amarnath, Sudha; Ensminger, William D.; Lawrence, Theodore S.; Ten Haken, Randall K.

    2012-01-01

    Purpose: Radiation-induced gastric bleeding has been poorly understood. In this study, we described dosimetric predictors for gastric bleeding after fractionated radiation therapy. Methods and Materials: The records of 139 sequential patients treated with 3-dimensional conformal radiation therapy (3D-CRT) for intrahepatic malignancies were reviewed. Median follow-up was 7.4 months. The parameters of a Lyman normal tissue complication probability (NTCP) model for the occurrence of ≥grade 3 gastric bleed, adjusted for cirrhosis, were fitted to the data. The principle of maximum likelihood was used to estimate parameters for NTCP models. Results: Sixteen of 116 evaluable patients (14%) developed gastric bleeds at a median time of 4.0 months (mean, 6.5 months; range, 2.1-28.3 months) following completion of RT. The median and mean maximum doses to the stomach were 61 and 63 Gy (range, 46-86 Gy), respectively, after biocorrection of each part of the 3D dose distributions to equivalent 2-Gy daily fractions. The Lyman NTCP model with parameters adjusted for cirrhosis predicted gastric bleed. Best-fit Lyman NTCP model parameters were n=0.10 and m=0.21 and with TD 50 (normal) = 56 Gy and TD 50 (cirrhosis) = 22 Gy. The low n value is consistent with the importance of maximum dose; a lower TD 50 value for the cirrhosis patients points out their greater sensitivity. Conclusions: This study demonstrates that the Lyman NTCP model has utility for predicting gastric bleeding and that the presence of cirrhosis greatly increases this risk. These findings should facilitate the design of future clinical trials involving high-dose upper abdominal radiation.

  4. Omeprazole use at University Hospital in Porto Alegre-RS (Brazil / Uso de omeprazol en el hospital universitario de Porto Alegre-RS (Brasil / Uso de omeprazol em hospital universitário de Porto Alegre-RS (Brasil

    Directory of Open Access Journals (Sweden)

    Morrone FB

    2004-12-01

    Full Text Available Intestinal bleeding are important cause of hospital admissions and death, being relevant in critically weak patients and those with arthritis and osteoarthritis using NSAIDs. Omepazole is the first choice drug for prophylaxis of stress ulcer and NSAID complications prevention, because it prevent not only duodenal but also gastric ulcer and eradication of H pylori used with antibiotics. The aim of this study was to determine frequency of use, indications and characteristics of population using omeprazole. A qualitative and quantitative drug utilization study was done. In-hospital adults at a University Hospital constituted study population. From 91 patients studied, the majority suffered from cancer (24.2%. Average length of stay and omeprazole use time was 20 and 12 days, respectively. Abdominal surgery team was the higher omeprazole prescriber, and main indication was post-surgery. Although most of omeprazole uses was acceptable, those could be better evaluated. T could be useful implementing a pharmaceutical care program and creating a omeprazole use guideline with the objective of prescribing it in a more rationale and adequate way for each patient.

  5. Curcumin-induced histone acetylation inhibition improves stress-induced gastric ulcer disease in rats.

    Science.gov (United States)

    He, Ping; Zhou, Renmin; Hu, Guorui; Liu, Zhifeng; Jin, Yu; Yang, Guang; Li, Mei; Lin, Qian

    2015-03-01

    Curcumin is known to possess anti‑inflammatory properties. Despite the fact that curcumin is known to be a strong inhibitor of H+, K+‑ATPase activity, the mechanism underlying the curcumin‑induced inhibition of the transcription of the H+, K+‑ATPase α subunit in gastric mucosal parietal cells remains unclear. The present study investigated the possible mechanism by which curcumin inhibits stomach H+, K+‑ATPase activity during the acute phase of gastric ulcer disease. A rat model of stress‑induced gastric ulcers was produced, in which the anti‑ulcer effects of curcumin were examined. Curcumin‑induced inhibition of the H+, K+‑ATPase promoter via histone acetylation, was verified using a chromatin immunoprecipitation assay. The results showed that curcumin improved stress‑induced gastric ulcer disease in rats, as demonstrated by increased pH values and reduced gastric mucosal hemorrhage and ulcer index. These effects were accompanied by a significant reduction in the level of histone H3 acetylation at the site of the H+, K+‑ATPase promoter and in the expression of the gastric H+,K+‑ATPase α subunit gene and protein. In conclusion, curcumin downregulated the acetylation of histone H3 at the site of the H+, K+‑ATPase promoter gene, thereby inhibiting the transcription and expression of the H+, K+‑ATPase gene. Curcumin was shown to have a preventive and therapeutic effect in gastric ulcer disease.

  6. Synergistic In Vitro Antimalarial Activity of Omeprazole and Quinine

    OpenAIRE

    Skinner-Adams, T.; Davis, T. M. E.

    1999-01-01

    Previous studies have shown that the proton pump inhibitor omeprazole has antimalarial activity in vitro. The interactions of omeprazole with commonly used antimalarial drugs were assessed in vitro. Omeprazole and quinine combinations were synergistic; however, chloroquine and omeprazole combinations were antagonistic. Artemisinin drugs had additive antimalarial activities with omeprazole.

  7. Gastroprotective activity of polysaccharide from Hericium erinaceus against ethanol-induced gastric mucosal lesion and pylorus ligation-induced gastric ulcer, and its antioxidant activities.

    Science.gov (United States)

    Wang, Xiao-Yin; Yin, Jun-Yi; Zhao, Ming-Ming; Liu, Shi-Yu; Nie, Shao-Ping; Xie, Ming-Yong

    2018-04-15

    The gastroprotective activity of Hericium erinaceus polysaccharide was investigated in rats. The antioxidant activities were also evaluated. Pre-treatment of polysaccharide could reduce ethanol-induced gastric mucosal lesion and pylorus ligation-induced gastric ulcer. The polysaccharide exhibited scavenging activities of 1, 1-diphenyl-2-picryl-hydrozyl and hydroxyl radicals, and ferrous ion-chelating ability. In the pylorus ligation-induced model, gastric secretions (volume of gastric juice, gastric acid, pepsin and mucus) of ulcer rats administrated with polysaccharide were regulated. Levels of tumor necrosis factor-α and interleukins-1β in serum, and myeloperoxidase activity of gastric tissue were reduced, while antioxidant status of gastric tissue was improved. Defensive factors (nitric oxide, prostaglandin E2, epidermal growth factor) in gastric tissue were increased. These results indicate that Hericium erinaceus polysaccharide possess gastroprotective activity, and the possible mechanisms are related to its regulations of gastric secretions, improvements of anti-inflammatory and antioxidant status, as well as increments of defensive factors releases. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Vinorelbine induced perforation of a metastatic gastric lesion.

    Science.gov (United States)

    Mullally, W J; O'Súilleabháin, C B; Brady, C; O'Reilly, S

    2017-08-01

    Breast carcinoma metastasis to the gastrointestinal tract is rare and more frequently associated with lobular than ductal carcinoma (Borst and Ingold, Surg 114(4):637-641 [1]). The purpose of this article is to present a case based review of a unique gastrointestinal metastasis and literature review. A 46 year old lady with metastatic invasive ductal breast cancer was admitted to A&E with sudden onset of epigastric and left shoulder pain. She completed the first cycle of capecitabine/vinorelbine 1 week previously. Clinical examination revealed a tender epigastrium with rigidity in the upper abdomen. Free air under the diaphragm and a positive Rigler's sign was radiologically identified. A laparoscopy demonstrated a fibrinous exudate in the left upper quadrant consistent with a walled off lesser curvature gastric perforation. A subsequent oesophagogastroduodenoscopy (OGD) demonstrated a healed gastric ulcer of benign appearance; however the pathology confirmed metastatic breast carcinoma. Literature review confirmed no previously reported cases of vinorelbine induced gastric perforation. Four cases of metastatic breast cancer with gastric metastasis presenting with perforation were identified; three of these cases (Fra et al., Presse Med 25(26):1215 (1996) [2], Solis-Caxaj et al., Gastroenterol Clin Biol 28(1):91-92 (2004) [3], Ghosn et al., Bull Cancer 78(11):1071-1073 (1991) [4]), were in the French medical literature, including one male patient (Fra et al., Presse Med 25(26):1215 (1996) [2]) and at least one ductal breast carcinoma (Solis-Caxaj et al., Gastroenterol Clin Biol 28(1):91-92 (2004) [3]). The fourth case (van Geel et al., Ned Tijdschr Geneeskd 144(37):1761-1763 (2000) [5]), was in the Dutch medical literature and a lobular breast carcinoma. This case represents a rare complication of breast cancer chemotherapy, the subsequent significant benefit the patient received from treatment is consistent with the chemosensitivity to therapy that also resulted

  9. Using omeprazole to link the components of the post-prandial alkaline tide in the spiny dogfish, Squalus acanthias.

    Science.gov (United States)

    Wood, Chris M; Schultz, Aaron G; Munger, R Stephen; Walsh, Patrick J

    2009-03-01

    After a meal, dogfish exhibit a metabolic alkalosis in the bloodstream and a marked excretion of basic equivalents across the gills to the external seawater. We used the H(+), K(+)-ATPase pump inhibitor omeprazole to determine whether these post-prandial alkaline tide events were linked to secretion of H(+) (accompanied by Cl(-)) in the stomach. Sharks were fitted with indwelling stomach tubes for pretreatment with omeprazole (five doses of 5 mg omeprazole per kilogram over 48 h) or comparable volumes of vehicle (saline containing 2% DMSO) and for sampling of gastric chyme. Fish were then fed an involuntary meal by means of the stomach tube consisting of minced flatfish muscle (2% of body mass) suspended in saline (4% of body mass total volume). Omeprazole pre-treatment delayed the post-prandial acidification of the gastric chyme, slowed the rise in Cl(-) concentration of the chyme and altered the patterns of other ions, indicating inhibition of H(+) and accompanying Cl(-) secretion. Omeprazole also greatly attenuated the rise in arterial pH and bicarbonate concentrations and reduced the net excretion of basic equivalents to the water by 56% over 48 h. Arterial blood CO(2) pressure (Pa(CO(2))) and plasma ions were not substantially altered. These results indicate that elevated gastric H(+) secretion (as HCl) in the digestive process is the major cause of the systemic metabolic alkalosis and the accompanying rise in base excretion across the gills that constitute the alkaline tide in the dogfish.

  10. Protective effects of Ginkgo biloba extract on the ethanol-induced gastric ulcer in rats

    Science.gov (United States)

    Chen, Sheng-Hsuan; Liang, Yu-Chih; Chao, Jane CJ; Tsai, Li-Hsueh; Chang, Chun-Chao; Wang, Chia-Chi; Pan, Shiann

    2005-01-01

    AIM: To evaluate the preventive effect of Ginkgo biloba extract (GbE) on ethanol-induced gastric mucosal injuries in rats. METHODS: Female Wistar albino rats were used for the studies. We randomly divided the rats for each study into five subgroups: normal control, experimental control, and three experimental groups. The gastric ulcers were induced by instilling 1 mL 50% ethanol into the stomach. We gave GbE 8.75, 17.5, 26.25 mg/kg intravenously to the experimental groups respectively 30 min prior to the ulcerative challenge. We removed the stomachs 45 min later. The gastric ulcers, gastric mucus and the content of non-protein sulfhydryl groups (NP-SH), malondialdehyde (MDA), c-Jun kinase (JNK) activity in gastric mucosa were evaluated. The amount of gastric juice and its acidity were also measured. RESULTS: The findings of our study are as follows: (1) GbE pretreatment was found to provide a dose-dependent protection against the ethanol-induced gastric ulcers in rats; (2) the GbE pretreatment afforded a dose-dependent inhibition of ethanol-induced depletion of stomach wall mucus, NP-SH contents and increase in the lipid peroxidation (increase MDA) in gastric tissue; (3) gastric ulcer induced by ethanol produced an increase in JNK activity in gastric mucosa which also significantly inhibited by pretreatment with GbE; and (4) GbE alone had no inhibitory effect on gastric secretion in pylorus-ligated rats. CONCLUSION: The finding of this study showed that GbE significantly inhibited the ethanol-induced gastric lesions in rats. We suggest that the preventive effect of GbE may be mediated through: (1) inhibition of lipid peroxidation; (2) preservation of gastric mucus and NP-SH; and (3) blockade of cell apoptosis. PMID:15968732

  11. Esophagectomy with gastroplasty in advanced megaesophagus: late results of omeprazole use

    Directory of Open Access Journals (Sweden)

    Celso de Castro Pochini

    Full Text Available Objective: To analyze the late results of advanced Chagasic megaesophagus treatment by esophagectomy associated with the use of proton pump inhibitor (omeprazole as for the incidence of esophagitis and Barrett's esophagus in the remaining stump. Methods : We studied patients with advanced megaesophagus undergoing esophagectomy and transmediastinal esophagogastroplasty. Patients were divided into three groups: A (20 with esophageal replacement by full stomach, without the use of omeprazole; B (20 with esophageal replacement by full stomach, with omeprazole 40 mg/day introduced after the first postoperative endoscopy and maintained for six years; and C (30 with esophageal replacement by gastric tube with use of omeprazole. Dysphagia, weight loss and BMI were clinical parameters we analyzed. Upper gastrointestinal endoscopy was performed in all patients, and determined the height of the anastomosis, the aspect of the mucosa, with special attention to possible injuries arising from gastroesophageal reflux, and the patency of the esophagogastric anastomosis. Results : We studied 50 patients, 28 males (56% and 22 (44% females. All underwent endoscopy every year. In the first endoscopy, erosive esophagitis was present in nine patients (18% and Barrett's esophagus, in four (8%; in the last endoscopy, erosive esophagitis was present in five patients (8% and Barrett's esophagus in one (2%. When comparing groups B and C, there was no evidence that the manufacturing of a gastric tube reduced esophagitis and Barrett's esophagus. However, when comparing groups A and C, omeprazole use was correlated with reduction of reflux complications such as esophagitis and Barrett's esophagus (p <0.005. Conclusion : The use of omeprazole (40 mg/day reduced the onset of erosive esophagitis and Barrett's esophagus during the late postoperative period.

  12. The effects of dose and diet on the pharmacodynamics of omeprazole in the horse.

    Science.gov (United States)

    Sykes, B W; Underwood, C; Greer, R; McGowan, C M; Mills, P C

    2017-07-01

    Conflicting data are presented in the current literature regarding the efficacy of omeprazole for suppressing gastric acidity in the horse. The objective of this study was to investigate the duration of intraday acid suppression achieved with two doses of omeprazole under two different dietary conditions. A four-way crossover design. Six adult Thoroughbred horses instrumented with percutaneous gastrotomy tubes were used. Intragastric pH was measured for continuous 23 h periods (08.00-07.00 h) for six consecutive days (Days 0-5). Baseline data was recorded on Day 0 and omeprazole administered on Days 1-5. Two doses (1 mg/kg and 4 mg/kg bwt per os once a day) and two diets (a high grain/low fibre [HG/LF] and ad libitum hay [HAY)] diet) were studied. Data for the percent (%) time pH was above 4 (%tpH>4) and median intraday pH was reported for two measurement locations and analysed using generalised estimating equations. An effect of both diet and dose was evident with mean %tpH>4 and the mean of the median intraday pHs typically higher at the higher (4 mg/kg bwt) dose and in HG/LF diet. The overall efficacy of omeprazole in raising intragastric pH was good under the HG/LF conditions but relatively poor in the HAY diet. A cumulative effect of dosing, not previously reported in the horse, was observed. The overall efficacy of omeprazole in raising ventral gastric pH was less than previously reported. Both dose and diet may play a role in the efficacy of omeprazole in the horse. Therefore, the use of singular dosing recommendations that encompass all horse types and management conditions may not be appropriate and dosing recommendations that take into account the diet of the horse may be advantageous. © 2016 EVJ Ltd.

  13. [Experience of treatment of patients with gastropathy induced by non-steroid anti-inflammatory drugs].

    Science.gov (United States)

    Vakhrushev, Ia M; Loshchakova, O Iu

    2007-01-01

    A complex study of 147 patients who were taking non-steroid anti-inflammatory drugs (NSAIDs) revealed gastric lesions in 120 patients (81.6%). H2 blocker (ranitidine) was used for treating 40 patients with NSAID-induced gastropathy, proton pump inhibitor (omeprazole) was used for 40 patients, and Gastrozepin combined with Misoprostol--for 40 patients. Pain syndrome and dyspepsia were eliminated in most of the patients as a result of the treatment. Using Gastrozepin and Misoprostol produced an active effect on the trophic processes in the gastric mucous coat and caused erosion and ulcer healing. As compared to ranitidine and omeprazole, Gastrozepin used in combination with Cytotec produces a lower effect on the reduction of the acid-producing stomach function, yet it has a considerably greater effect on the normalization of the gastric mucus structure and restoration of metabolism of the gastric mucous coat collagen.

  14. A study of the effect of propolis against gastric ulcers induced in gamma -irradiated rats

    International Nuclear Information System (INIS)

    Abd El-Aziz, R.R

    2009-01-01

    The anti-ulcerogenic activity of propolis or bee glue, a natural product from honey bees, was investigated against indomethacin -induced gastric ulcers in non- irradiated and irradiated rats, and the effects were compared with those of the proton pump inhibitor lansoprazole, as a reference anti-ulcerogenic drug. Indomethacin-induced gastric ulcer was used in this study as a model of experimentally induced gastric ulceration. The anti-ulcerogenic, antisecretory and cytoprotective activities of 13% aqueous propolis extract (APE) were assessed. Gastric contents of animals were sampled for the measurement of free acidity, acid output, mucin and pepsin concentrations in the gastric juice. The stomach was examined macroscopically for the determination of the ulcer index. PGE 2 was assayed in the gastric mucosa, while the pro-inflammatory cytokines TNF-α and IL-1β as well as the oxidative stress marker MDA were determined in the plasma.

  15. Gastric emptying in rats with acetaminophen-induced hepatitis

    Directory of Open Access Journals (Sweden)

    G. Hessel

    1998-09-01

    Full Text Available The objective of this work was to study the gastric emptying (GE of liquids in fasted and sucrose-fed rats with toxic hepatitis induced by acetaminophen. The GE of three test meals (saline, glucose and mayonnaise was evaluated in Wistar rats. For each meal, the animals were divided into two groups (N = 24 each. Group I was fed a sucrose diet throughout the experiment (66 h while group II was fasted. Forty-two hours after the start of the experiment, each group was divided into two subgroups (N = 12 each. Subgroup A received a placebo and subgroup B was given acetaminophen (1 g/kg. Twenty-four hours later, the GE of the three test meals was assessed and blood samples were collected to measure the serum levels of alanine aminotransferase (ALT, aspartate aminotransferase (AST and acetaminophen. In group IB, the mean AST and ALT values were 515 and 263 IU/l, respectively, while for group IIB they were 4014 and 2472 IU/l, respectively. The mean serum acetaminophen levels were higher in group IIB (120 µg/ml than in group IB (87 µg/ml. The gastric retention values were significantly higher in group IIB than in group IIA for all three test meals: saline, 51 vs 35%; glucose, 52 vs 38% and mayonnaise, 51 vs 29% (median values. The correlation between gastric retention and AST levels was significant (P<0.05 for group IIB for the three test meals: r = 0.73, 0.67 and 0.68 for saline, glucose and mayonnaise, respectively. We conclude that GE is altered in rats with hepatic lesions induced by acetaminophen, and that these alterations may be related to the liver cell necrosis caused by the drug.

  16. Gastric electrical stimulation decreases gastric distension-induced central nociception response through direct action on primary afferents.

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    Wassila Ouelaa

    Full Text Available BACKGROUND & AIMS: Gastric electrical stimulation (GES is an effective therapy to treat patients with chronic dyspepsia refractory to medical management. However, its mechanisms of action remain poorly understood. METHODS: Gastric pain was induced by performing gastric distension (GD in anesthetized rats. Pain response was monitored by measuring the pseudo-affective reflex (e.g., blood pressure variation, while neuronal activation was determined using c-fos immunochemistry in the central nervous system. Involvement of primary afferents was assessed by measuring phosphorylation of ERK1/2 in dorsal root ganglia. RESULTS: GES decreased blood pressure variation induced by GD, and prevented GD-induced neuronal activation in the dorsal horn of the spinal cord (T9-T10, the nucleus of the solitary tract and in CRF neurons of the hypothalamic paraventricular nucleus. This effect remained unaltered within the spinal cord when sectioning the medulla at the T5 level. Furthermore, GES prevented GD-induced phosphorylation of ERK1/2 in dorsal root ganglia. CONCLUSIONS: GES decreases GD-induced pain and/or discomfort likely through a direct modulation of gastric spinal afferents reducing central processing of visceral nociception.

  17. Failure of ethamsylate to reduce aspirin-induced gastric mucosal bleeding in humans.

    OpenAIRE

    Daneshmend, T K; Stein, A G; Bhaskar, N K; Hawkey, C J

    1989-01-01

    1. We investigated the effect of the haemostatic agent ethamsylate on aspirin-induced gastric mucosal bleeding. 2. Eighteen healthy subjects were studied three times: at the end of 48 h periods of treatment with (a) placebo, (b) aspirin 600 mg four times daily, (9 doses) and (c) aspirin 600 mg four times daily with each dose preceded by ethamsylate 500 mg. 3. At the end of each treatment period gastric mucosal bleeding into timed gastric washings was quantified using the orthotolidine reactio...

  18. Protective effects of escin against indomethacin-induced gastric ulcer in mice.

    Science.gov (United States)

    Wang, Tian; Zhao, Shanshan; Wang, Yucun; Yang, Yujiao; Yao, Le; Chu, Liuxiang; Du, Hanhan; Fu, Fenghua

    2014-12-01

    Escin, a natural mixture of triterpenoid saponin isolated from the seed of the horse chestnut, is reported to have a potent antiulcer activity against ethanol-induced gastric mucosal lesions. This study investigated the possible mechanisms underlying the gastroprotective effect of escin against indomethacin-induced gastric ulcer in mice. Gastric ulceration was induced by a single intragastric administration of indomethacin (18 mg/kg). The mice underwent intragastric treatment with escin at doses of 0.45, 0.9 or 1.8 mg/kg. Gastric lesion was estimated morphometrically and histopathologically 6 h after the indomethacin administration. The antioxidative parameters in gastric mucosa were measured. Moreover, the activity of myeloperoxidase and the contents of TNF-α, P-selectin and VCAM-1 in gastric tissues were determined. The results showed that escin protected gastric tissues against indomethacin-induced gastropathy as demonstrated from a reduction in the ulcer index and an attenuation of histopathologic changes. Escin caused significant reductions of the contents of malondialdehyde, TNF-α, P-selectin, VCAM-1 and myeloperoxidase activity. The altered activities of superoxide dismutase, catalase and glutathione peroxidase in the stomach tissues were also ameliorated by escin treatment. The present study demonstrated that escin had a protective effect against indomethacin-induced gastric ulcer in mice, not only by virtue of its antioxidant potential, but also due to its anti-inflammatory effect.

  19. Effect of Cissus quadrangularis on gastric mucosal defensive factors in experimentally induced gastric ulcer-a comparative study with sucralfate.

    Science.gov (United States)

    Jainu, Mallika; Devi, C S Shyamala

    2004-01-01

    Cissus quadrangularis is an indigenous plant commonly mentioned in Ayurveda for treatment of gastric ulcers. The ulcer-protective effect of a methanolic extract of C. quadrangularis (CQE) was comparable to that of the reference drug sucralfate. Further, gastric juice and mucosal studies showed that CQE at a dose of 500 mg/kg given for 10 days significantly increased the mucosal defensive factors like mucin secretion, mucosal cell proliferation, glycoproteins, and life span of cells. The present investigation suggests that CQE not only strengthens mucosal resistance against ulcerogens but also promotes healing by inducing cellular proliferation. Thus, CQE has potential usefulness for treatment of peptic ulcer disease.

  20. Gastric vagus mediates immobilization-induced hypocalcemia in rats.

    Science.gov (United States)

    Ma, J; Aou, S; Matsui, H; Hori, T

    1993-09-01

    The involvement of the parasympathetic nervous system in the etiology of stress-induced hypocalcemia was investigated in the rat. Atropine methyl bromide (0.1 and 0.6 mg/kg ip) given 20 min before immobilization (IMB) was observed to suppress the induction of hypocalcemia in a dose-dependent manner. A vagotomy of the bilateral cervical trunks also abolished the IMB-induced hypocalcemia. A vagotomy on either the thyroid/parathyroid branches or the celiac branches had no effect on the IMB-induced hypocalcemia, but a vagotomy on the gastric branches completely abolished it. Pretreatment with either secretin (2 and 6 micrograms/kg ip), an inhibitor of gastrin release, or cimetidine (5 and 10 mg/kg ip), a histamine H2-receptor antagonist, diminished the IMB-induced hypocalcemia. The concentration of serum gastrin increased significantly during IMB. It is thus concluded that the decreased levels of plasma calcium caused by IMB are due to the activation of the vagus innervating the stomach. Gastrin and histamine are also involved as a consequence of the activation of the vagus.

  1. Omeprazole blocks STAT6 binding to the eotaxin-3 promoter in eosinophilic esophagitis cells.

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    Xi Zhang

    Full Text Available Patients who have esophageal eosinophilia without gastroesophageal reflux disease (GERD nevertheless can respond to proton pump inhibitors (PPIs, which can have anti-inflammatory actions independent of effects on gastric acid secretion. In esophageal cell cultures, omeprazole has been reported to inhibit Th2 cytokine-stimulated expression of eotaxin-3, an eosinophil chemoattractant contributing to esophageal eosinophilia in eosinophilic esophagitis (EoE. The objective of this study was to elucidate molecular mechanisms underlying PPI inhibition of IL-4-stimulated eotaxin-3 production by esophageal cells.Telomerase-immortalized and primary cultures of esophageal squamous cells from EoE patients were treated with IL-4 in the presence or absence of acid-activated omeprazole or lansoprazole. We measured eotaxin-3 protein secretion by ELISA, mRNA expression by PCR, STAT6 phosphorylation and nuclear translocation by Western blotting, eotaxin-3 promoter activation by an exogenous reporter construct, and STAT6, RNA polymerase II, and trimethylated H3K4 binding to the endogenous eotaxin-3 promoter by ChIP assay. Omeprazole in concentrations ≥5 µM significantly decreased IL-4-stimulated eotaxin-3 protein secretion and mRNA expression. Lansoprazole also blocked eotaxin-3 protein secretion. Omeprazole had no effect on eotaxin-3 mRNA stability or on STAT6 phosphorylation and STAT6 nuclear translocation. Rather, omeprazole blocked binding of IL-4-stimulated STAT6, RNA polymerase II, and trimethylated H3K4 to the eotaxin-3 promoter.PPIs, in concentrations achieved in blood with conventional dosing, significantly inhibit IL-4-stimulated eotaxin-3 expression in EoE esophageal cells and block STAT6 binding to the promoter. These findings elucidate molecular mechanisms whereby patients with Th2 cytokine-driven esophageal eosinophilia can respond to PPIs, independent of effects on gastric acid secretion.

  2. Lack of drug interaction between omeprazole, lansoprazole, pantoprazole and theophylline

    Science.gov (United States)

    Dilger, Karin; Zheng, Zhichang; Klotz, Ulrich

    1999-01-01

    Aims Theophylline is a model substrate of cytochrome P4501A2. The ability of the proton pump inhibitors (PPI) omeprazole, lansoprazole and pantoprazole to induce cytochrome P4501A2 has not yet been unequivocally resolved. The aim of this comprehensive study was to compare directly the effect of the three PPI on the absorption and disposition of theophylline. Methods Twenty healthy, nonsmoking, male and female volunteers (extensive metabolisers of cytochrome P4502C19 and Helicobacter pylori negative) participated in a randomized, double-blind, four-period, placebo-controlled crossover study. In each of the four periods they received either omeprazole (40 mg), lansoprazole (60 mg), pantoprazole (80 mg) or placebo once daily for 10 days. Sustained release theophylline (350 mg twice daily) was coadministered from day 8–10. Pharmacokinetics of theophylline as well as of all three PPI were determined at steady-state (day 10). Results In all periods, point estimates and 90% confidence intervals of the area under the concentration-time curves (AUC), maximum steady-state concentrations and peak-trough fluctuations of theophylline were not altered by PPI pretreatment and met the required limits for bioequivalence. Point estimates (90% confidence intervals) of the AUC ratios of theophylline plus PPI to theophylline alone were 0.92 (0.87–0.97), 0.90 (0.85–0.95) and 1.00 (0.95–1.06) for omeprazole, lansoprazole and pantoprazole, respectively. Conclusions Concomitant intake of omeprazole, lansoprazole or pantoprazole at high therapeutic doses does not affect the absorption and disposition of theophylline. PMID:10510158

  3. Helicobacter pylori-induced gastric pathology: insights from in vivo and ex vivo models

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    Michael D. Burkitt

    2017-02-01

    Full Text Available Gastric colonization with Helicobacter pylori induces diverse human pathological conditions, including superficial gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT lymphoma, and gastric adenocarcinoma and its precursors. The treatment of these conditions often relies on the eradication of H. pylori, an intervention that is increasingly difficult to achieve and that does not prevent disease progression in some contexts. There is, therefore, a pressing need to develop new experimental models of H. pylori-associated gastric pathology to support novel drug development in this field. Here, we review the current status of in vivo and ex vivo models of gastric H. pylori colonization, and of Helicobacter-induced gastric pathology, focusing on models of gastric pathology induced by H. pylori, Helicobacter felis and Helicobacter suis in rodents and large animals. We also discuss the more recent development of gastric organoid cultures from murine and human gastric tissue, as well as from human pluripotent stem cells, and the outcomes of H. pylori infection in these systems.

  4. Diosmin protects against ethanol-induced gastric injury in rats: novel anti-ulcer actions.

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    Hany H Arab

    Full Text Available Alcohol consumption has been commonly associated with gastric mucosal lesions including gastric ulcer. Diosmin (DIO is a natural citrus flavone with remarkable antioxidant and anti-inflammatory features that underlay its protection against cardiac, hepatic and renal injuries. However, its impact on gastric ulcer has not yet been elucidated. Thus, the current study aimed to investigate the potential protective effects of DIO against ethanol-induced gastric injury in rats. Pretreatment with DIO (100 mg/kg p.o. attenuated the severity of ethanol gastric mucosal damage as evidenced by lowering of ulcer index (UI scores, area of gastric lesions, histopathologic aberrations and leukocyte invasion. These actions were analogous to those exerted by the reference antiulcer sucralfate. DIO suppressed gastric inflammation by curbing of myeloperoxidase (MPO and tumor necrosis factor-α (TNF-α levels along with nuclear factor kappa B (NF-κB p65 expression. It also augmented the anti-inflammatory interleukin-10 (IL-10 levels. Meanwhile, DIO halted gastric oxidative stress via inhibition of lipid peroxides with concomitant enhancement of glutathione (GSH, glutathione peroxidase (GPx and the total antioxidant capacity (TAC. With respect to gastric mucosal apoptosis, DIO suppressed caspase-3 activity and cytochrome C (Cyt C with enhancement of the anti-apoptotic B cell lymphoma-2 (Bcl-2 in favor of cell survival. These favorable actions were associated with upregulation of the gastric cytoprotective prostaglandin E2 (PGE2 and nitric oxide (NO. Together, these findings accentuate the gastroprotective actions of DIO in ethanol gastric injury which were mediated via concerted multi-pronged actions, including suppression of gastric inflammation, oxidative stress and apoptosis besides boosting of the antioxidant and the cytoprotective defenses.

  5. Perbandingan Efektivitas antara Omeprazol dan Lansoprazol terhadap Perbaikan Kualitas Hidup Penderita Rinosinusitis Kronik Akibat Refluks Laringofaring

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    Tantri Kurniawati

    2012-09-01

    Full Text Available Laryngopharyngeal reflux (LPR is the reflux of gastric acid through the esophagus that reaches laringopharyngeal area. The prevalence of LPR in the range 15–20%, and caused chronic rhinosinusitis (CRS. The incidence of LPR in patients with CRS has ranged between 37–72%. The prevalence of CRS 16,3% in adults and affecting quality of life. Omeprazole and lansoprazole are proton pump inhibitors (PPIs for LPR’s therapy and also a therapy for CRS with LPR as the etiology. This research method was randomized clinical trial with open trial observation, conducted in June to December 2009. Twenty subjects with consecutive sampling method, divided into two groups (with simple randomization, the first group received omeprazole and the other lansoprazole. The subjects conducted complete physical otolaryngology examination, sino-nasal outcome test 20, reflux symptom index and reflux finding score with fiber optic rhinolaryngoscopy. These data was obtained before therapy, after 2 weeks and two months therapy, analyzed with Wilcoxon’s and Mann-Whitney’s test. There was no effectivity difference between omperazole and lansoprazole in reducing the level of severity of LPR (p>0.05, but quality of life improvement was better in lansoprazole than omeprazole group (p<0.05. In conclusion, lansoprazole is more effective than omeprazole in improvement of quality of life in patients with chronic rhinosinusitis caused by LPR

  6. Ascorbic acid deficiency aggravates stress-induced gastric mucosal lesions in genetically scorbutic ODS rats.

    Science.gov (United States)

    Ohta, Y; Chiba, S; Imai, Y; Kamiya, Y; Arisawa, T; Kitagawa, A

    2006-12-01

    We examined whether ascorbic acid (AA) deficiency aggravates water immersion restraint stress (WIRS)-induced gastric mucosal lesions in genetically scorbutic ODS rats. ODS rats received scorbutic diet with either distilled water containing AA (1 g/l) or distilled water for 2 weeks. AA-deficient rats had 12% of gastric mucosal AA content in AA-sufficient rats. AA-deficient rats showed more severe gastric mucosal lesions than AA-sufficient rats at 1, 3 or 6 h after the onset of WIRS, although AA-deficient rats had a slight decrease in gastric mucosal AA content, while AA-sufficient rats had a large decrease in that content. AA-deficient rats had more decreased gastric mucosal nonprotein SH and vitamin E contents and increased gastric mucosal lipid peroxide content than AA-sufficient rats at 1, 3 or 6 h of WIRS. These results indicate that AA deficiency aggravates WIRS-induced gastric mucosal lesions in ODS rats by enhancing oxidative damage in the gastric mucosa.

  7. Petroselinum Crispum is Effective in Reducing Stress-Induced Gastric Oxidative Damage

    OpenAIRE

    Ayşin Akıncı; Mukaddes Eşrefoğlu; Elif Taşlıdere; Burhan Ateş

    2017-01-01

    Background: Oxidative stress has been shown to play a principal role in the pathogenesis of stress-induced gastric injury. Parsley (Petroselinum crispum) contains many antioxidants such as flavanoids, carotenoids and ascorbic acid. Aims: In this study, the histopathological and biochemical results of nutrition with a parsley-rich diet in terms of eliminating stress-induced oxidative gastric injury were evaluated. Study Design: Animal experimentation. Methods: Forty male Wistar albino...

  8. Petroselinum Crispum is Effective in Reducing Stress-Induced Gastric Oxidative Damage

    OpenAIRE

    Ak?nc?, Ay?in; E?refo?lu, Mukaddes; Ta?l?dere, Elif; Ate?, Burhan

    2017-01-01

    Background: Oxidative stress has been shown to play a principal role in the pathogenesis of stress-induced gastric injury. Parsley (Petroselinum crispum) contains many antioxidants such as flavanoids, carotenoids and ascorbic acid. Aims: In this study, the histopathological and biochemical results of nutrition with a parsley-rich diet in terms of eliminating stress-induced oxidative gastric injury were evaluated. Study Design: Animal experimentation Methods: Forty male Wistar albino rats were...

  9. A review of omeprazole use in the treatment of acid-related disorders in children.

    Science.gov (United States)

    Zimmermann, A E; Walters, J K; Katona, B G; Souney, P E; Levine, D

    2001-05-01

    Acid peptic disease is a common problem, with a similar prevalence of gastroesophageal reflux disease (GERD) in adults and children. The presentation of GERD in infants and children varies from crying, irritability, or sleep disturbance to feeding difficulties, vomiting, or rumination. Helicobacter pylori (HP)-related diseases and gastric and duodenal ulcers are much more common in adults than in children, who are more likely to have gastritis or duodenitis. However, because HP infection is most likely acquired in childhood, treatment of children with endoscopically documented active HP disease may minimize the potential risk for peptic ulcer or gastric cancer in adulthood, although this is yet to be proved. Omeprazole has been shown to be effective in the treatment of acid-related diseases. This paper reviews the literature on the use and administration of omeprazole for the treatment of GERD, peptic ulcer disease, HP infection, and other acid-related conditions in children. Studies were identified through searches of MEDLINE and Science Citation Index for the period 1986 to November 2000, and from the reference lists of identified articles. The search terms used included omeprazole, proton pump inhibitor (PPI), children, pediatrics, routes of administration, GERD, HP infection, esophagitis, and administration. In addition, the manufacturer of omeprazole was asked for relevant unpublished information. Marketed and extemporaneous formulations of omeprazole have been administered to children aged 2 months to 18 years for the treatment of erosive esophagitis, gastric ulcer, duodenal ulcer, HP infection, and related conditions at dosages of 5 to 80 mg/d (0.2-3.5 mg/kg/d) for periods ranging from 14 days to 36 months with a low incidence of adverse effects. The initial dose most consistently reported to heal esophagitis and provide relief of symptoms of GERD appears to be 1 mg/kg per day. In uncontrolled clinical trials and case reports to date, omeprazole has been

  10. Pathobiology of Helicobacter pylori-induced Gastric Cancer

    Science.gov (United States)

    Amieva, Manuel; Peek, Richard M.

    2015-01-01

    Colonization of the human stomach by Helicobacter pylori and its role in causing gastric cancer is one of the richest examples of complex relationship among human cells, microbes, and their environment. It is also a puzzle of enormous medical importance given the incidence and lethality of gastric cancer worldwide. We review recent findings that have changed how we view these relationships and affected the direction of gastric cancer research. For example, recent data indicate that subtle mismatches between host and microbe genetic traits greatly affect risk of gastric cancer. The ability of H pylori and its oncoprotein CagA to reprogram epithelial cells and activate properties of stemness demonstrates the sophisticated relationship among H pylori and progenitor cells in the gastric mucosa. The observation that cell-associated H pylori can colonize the gastric glands and directly affect precursor and stem cells supports these observations. The ability to mimic these interactions in human gastric organoid cultures as well as animal models will allow investigators to more fully unravel the extent of H pylori control on the renewing gastric epithelium. Finally, our realization that external environmental factors, such as dietary components and essential micronutrients, as well as the gastrointestinal microbiota, can change the balance between H pylori’s activity as a commensal or a pathogen has provided direction to studies aimed at defining the full carcinogenic potential of this organism. PMID:26385073

  11. Role of leukotrienes in NSAID induced gastric ulceration and inflammation in wistar rats

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    Maulik N Gandhi

    2012-06-01

    Full Text Available Objective: To evaluate the effects of Montelukast and Curcumin against indomethacin induced gastric damage in rats in order to assess the role of leukotriene (LTs if any, in non steroidal antiinflammatory drug (NSAID induced gastroinflammation. Methods: The effects of Montelukast (10 mg/kg and Curcumin (100 mg/kg were observed on gastric lesion induced by Indomethacin. The blood samples were analyzed for neutrophil adhesion and lipid peroxide levels in gastric tissue measured spectrophotometrically. The skin vascular permeability study was performed by using compound 48/80 induced vascular permeability model. Results: Montelukast and Curcumin significantly reduced Indomethacin induced gastric lesion score. Pretreatment with Montelukast and Curcumin significantly counteracted Indomethacin induced gastropathy by a combination of its effect on inhibition of neutrophil adherence, through decrease in related production of free radicals that disrupts integrity of stomach mucosa and decrease in vascular permeability as compared to Indomethacin group. The results of the present study further indicates the role of 5-LOX metabolites in NSAIDs induced gastro inflammation and suggests that Montelukast and Curcumin counteracted the Indomethacin induced gastropathy by a combination of its effect on inhibition of neutrophil adherence and through decrease in related production of free radicals that disrupts integrity of stomach mucosa. Conclusions: Experimental data clearly demonstrated the role of LTs was indomethacin induced gastric ulcers. However, inhibition of ulcerogenic events by Montelukast and Curcumin is suggestive of an important balance between COX and 5-LOX products.

  12. Effect of Manilkara hexandra (Roxb.) Dubard against experimentally-induced gastric ulcers.

    Science.gov (United States)

    Shah, Mamta B; Goswami, S S; Santani, D D

    2004-10-01

    Effects of the flavonoid rich fraction of the stem bark of Manilkara hexandra (Roxb.) Dubard, have been studied on ethanol, ethanol-indomethacin and pylorus ligated gastric ulcers in experimental animals. Oral administration of the ethyl acetate extract (extract A3) inhibited the formation of gastric lesions induced by ethanol in a dose dependent manner. The protective effect of extract A3 against ethanol induced gastric lesions was not abolished by pretreatment with indomethacin (10 mg kg(-1)). Further, extract A3 inhibited increase in vascular permeability due to ethanol administration. Extent of lipid peroxidation was significantly reduced in animals treated with extract. Extract A3 also inhibited the formation of gastric ulcers induced by pylorus ligation, when administered both orally and intraperitoneally. Moreover, pretreatment with extract A3 increased mucus production and glycoprotein content, which was evident from the rise in mucin activity and TC: PR ratio. Copyright 2004 John Wiley & Sons, Ltd.

  13. Inhibitors of acid secretion can benefit gastric wound repair independent of luminal pH effects on the site of damage

    Science.gov (United States)

    Demitrack, Elise S; Aihara, Eitaro; Kenny, Susan; Varro, Andrea; Montrose, Marshall H

    2012-01-01

    Background and aims The authors’ goal was to measure pH at the gastric surface (pHo) to understand how acid secretion affects the repair of microscopic injury to the gastric epithelium. Methods Microscopic gastric damage was induced by laser light, during confocal/two-photon imaging of pH-sensitive dyes (Cl-NERF, BCECF) that were superfused over the mucosal surface of the exposed gastric corpus of anaesthetised mice. The progression of repair was measured in parallel with pHo. Experimental conditions included varying pH of luminal superfusates, and using omeprazole (60 mg/kg ip) or famotidine (30 mg/kg ip) to inhibit acid secretion. Results Similar rates of epithelial repair and resting pHo values (~pH 4) were reported in the presence of luminal pH 3 or pH 5. Epithelial repair was unreliable at luminal pH 2 and pHo was lower (2.5±0.2, P pH 3). Epithelial repair was slower at luminal pH 7 and pHo was higher (6.4±0.1, PpH 3 or pH 7, omeprazole reduced maximal damage size and accelerated epithelial repair, although only at pH 3 did omeprazole further increase surface pH above the level caused by imposed damage. At luminal pH 7, famotidine also reduced maximal damage size and accelerated epithelial repair. Neither famotidine nor omeprazole raised plasma gastrin levels during the time course of the experiments. Conclusions Epithelial repair in vivo is affected by luminal pH variation, but the beneficial effects of acutely blocking acid secretion extend beyond simply raising luminal and/or surface pH. PMID:21997560

  14. Ganoderma Lucidum Pharmacopuncture for Teating Ethanol-induced Chronic Gastric Ulcers in Rats

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    Jae-Heung Park

    2015-03-01

    Full Text Available Objectives: The stomach is a sensitive digestive organ that is susceptible to exogenous pathogens from the diet. In response to such pathogens, the stomach induces oxidative stress, which might be related to the development of both gastric organic disorders such as gastritis, gastric ulcers, and gastric cancer, and functional disorders such as functional dyspepsia. This study was accomplished to investigate the effect of Ganoderma lucidum pharmacopuncture (GLP on chronic gastric ulcers in rats. Methods: The rats were divided into 4 groups of 8 animals each: the normal, the control, the normal saline (NP and the GLP groups. In this study, the modified ethanol gastritis model was used. The rats were administrated 56% ethanol orally every other day. The dose of ethanol was 8 g/kg body weight. The normal group received the same amount of normal saline instead of ethanol. The NP and the GLP groups were treated with injection of saline and GLP respectively. The control group received no treatment. Two local acupoints CV12 (中脘 and ST36 (足三里 were used. All laboratory rats underwent treatment for 15 days. On last day, the rats were sacrificed and their stomachs were immediately excised. Results: Ulcers of the gastric mucosa appeared as elongated bands of hemorrhagic lesions parallel to the long axis of the stomach. In the NP and GLP groups, the injuries to the gastric mucosal injuries were not as severe as they were in the control group. Wound healings of the chronic gastric ulcers was promoted by using GLP and significant alterations of the indices in the gastric mucosa were observed. Such protection was demonstrated by gross appearance, histology and immunehistochemistry staining for Bcl-2-associated X (BAX, B-cell lymphoma 2 (Bcl-2 and Transforming growth factor-beta 1 (TGF-β1. Conclusion: These results suggest that GLP at CV12 and ST36 can provide significant protection to the gastric mucosa against an ethanol induced chronic gastric ulcer.

  15. Effects of EGFR Inhibitor on Helicobacter pylori Induced Gastric Epithelial Pathology in Vivo

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    Philip A. Robinson

    2013-10-01

    Full Text Available Helicobacter pylori transactivates the Epidermal Growth Factor Receptor (EGFR and predisposes to gastric cancer development in humans and animal models. To examine the importance of EGFR signalling to gastric pathology, this study investigated whether treatment of Mongolian gerbils with a selective EGFR tyrosine kinase inhibitor, EKB-569, altered gastric pathology in chronic H. pylori infection. Gerbils were infected with H. pylori and six weeks later received either EKB-569-supplemented, or control diet, for 32 weeks prior to sacrifice. EKB-569-treated H. pylori-infected gerbils had no difference in H. pylori colonisation or inflammation scores compared to infected animals on control diet, but showed significantly less corpus atrophy, mucous metaplasia and submucosal glandular herniations along with markedly reduced antral and corpus epithelial proliferation to apoptosis ratios. EKB-569-treated infected gerbils had significantly decreased abundance of Cox-2, Adam17 and Egfr gastric transcripts relative to infected animals on control diet. EGFR inhibition by EKB-569 therefore reduced the severity of pre-neoplastic gastric pathology in chronically H. pylori-infected gerbils. EKB-569 increased gastric epithelial apoptosis in H. pylori-infected gerbils which counteracted some of the consequences of increased gastric epithelial cell proliferation. Similar chemopreventative strategies may be useful in humans who are at high risk of developing H.pylori-induced gastric adenocarcinoma.

  16. Peak distortion in the column liquid chromatographic determination of omeprazole dissolved in borax buffer.

    Science.gov (United States)

    Arvidsson, T; Collijn, E; Tivert, A M; Rosén, L

    1991-11-22

    Injection of a sample containing omeprazole dissolved in borax buffer (pH 9.2) into a reversed-phase liquid chromatographic system consisting of a mixture of acetonitrile and phosphate buffer (pH 7.6) as the mobile phase and a C18 surface-modified silica as the solid phase resulted under special conditions in split peaks of omeprazole. The degree of peak split and the retention time of omeprazole varied with the concentration of borax in the sample solution and the ionic strength of the mobile phase buffer as well as with the column used. Borax is eluted from the column in a broad zone starting from the void volume of the column. The retention is probably due to the presence of polyborate ions. The size of the zone varies with the concentration of borax in the sample injected. In the borax zone the pH is increased compared with the pH of the mobile phase, and when omeprazole (a weak acid) is co-eluting in the borax zone its retention is affected. In the front part and in the back part of the borax zone, pH gradients are formed, and these gradients can induce the peak splitting. When the dissolving medium is changed to a phosphate buffer or an ammonium buffer at pH 9 no peak distortion of omeprazole is observed.

  17. Gastroprotective effect of Cymbopogon citratus infusion on acute ethanol-induced gastric lesions in rats.

    Science.gov (United States)

    Sagradas, Joana; Costa, Gustavo; Figueirinha, Artur; Castel-Branco, Maria Margarida; Silvério Cabrita, António Manuel; Figueiredo, Isabel Vitória; Batista, Maria Teresa

    2015-09-15

    Treatment of gastric ulcers with medicinal plants is quite common in traditional medicine worldwide. Cymbopogon citratus (DC) Stapf. leaves infusion has been used in folk medicine of many tropical and subtropical regions to treat gastric disturbances. The aim of this study was to assess the potential gastroprotective activity of an essential oil-free infusion from C. citratus leaves in acute gastric lesions induced by ethanol in rat. The study was performed on adult male Wistar rats (234.0±22.7g) fasted for 24h but with free access to water. The extract was given orally before (prevention) or after (treatment) intragastric administration of absolute ethanol. Effects of dose (28 or 56mg/kg of body weight) and time of contact of the extract with gastric mucosa (1 or 2h) were also assessed. Animals were sacrificed, being the stomachs removed and the lesions were assessed by macroscopic observation and histopathology. C. citratus extract, given orally before or after ethanol, significantly (P<0.01) reduced gastric mucosal injury compared with control group (vehicle+ethanol). The effect does not appear to be dose-dependent. Results also suggested that the extract is more effective when the time of contact with gastric mucosa increases. The results of this assay confirm the gastroprotective activity of C. citratus extract on experimental gastric lesions induced by ethanol, contributing for the pharmacological validation of its traditional use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice

    International Nuclear Information System (INIS)

    Li, Weifeng; Huang, Huimin; Niu, Xiaofeng; Fan, Ting; Mu, Qingli; Li, Huani

    2013-01-01

    Excessive alcohol consumption can lead to gastric ulcer and the present work was aimed to examine the protective effect of tetrahydrocoptisine (THC) in the model of ethanol-induced gastric ulcer in mice. Fasted mice treated with ethanol 75% (0.5 ml/100 g) were pre-treated with THC (10 or 20 mg/kg, ip), cimetidine (100 mg/kg, ip) or saline in different experimental sets for a period of 3 days, and animals were euthanized 4 h after ethanol ingestion. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that ethanol induced gastric damage, improving nitric oxide (NO) level, increased pro-inflammatory cytokine (TNF-α and IL-6) levels and myeloperoxidase (MPO) activity, as well as the expression of nuclear factor-κB (NF-κB) in the ethanol group. Pretreatment of THC at doses of 10 and 20 mg/kg bodyweight significantly attenuated the gastric lesions as compared to the ethanol group. These results suggest that the gastroprotective activity of THC is attributed to reducing NO production and adjusting the pro-inflammatory cytokine, inhibited neutrophil accumulation and NF-κB expression. - Highlights: • THC decreased ethanol-induced pro-inflammatory cytokine release. • THC inhibited the production of NO in serum and gastric tissue. • THC reduced NF-κB expression and MPO accumulation in ethanol-induced gastric tissue

  19. Is there a role for leukotrienes as mediators of ethanol-induced gastric mucosal damage?

    International Nuclear Information System (INIS)

    Wallace, J.L.; Beck, P.L.; Morris, G.P.

    1988-01-01

    The role of leukotriene (LT) C 4 as a mediator of ethanol-induced gastric mucosal damage was investigated. Rats were pretreated with a number of compounds, including inhibitors of leukotriene biosynthesis and agents that have previously been shown to reduce ethanol-induced damage prior to oral administration of absolute ethanol. Ethanol administration resulted in a fourfold increase in LTC 4 synthesis. LTC 4 synthesis could be reduced significantly by pretreatment with L651,392 or dexamethosone without altering the susceptibility of the gastric mucosa to ethanol-induced damage. Furthermore, changes in LBT 4 synthesis paralleled the changes in LTC 4 synthesis observed after ethanol administration. The effects of ethanol on gastric eicosanoid synthesis were further examined using an ex vivo gastric chamber preparation that allowed for application of ethanol to only one side of the stomach. These studies confirm that ethanol can stimulate gastric leukotriene synthesis independent of the production of hemorrhagic damage. Inhibition of LTC 4 synthesis does not confer protection to the mucosa, suggesting that LTC 4 does not play an important role in the etiology of ethanol-induced gastric damage

  20. Protective effect of tetrahydrocoptisine against ethanol-induced gastric ulcer in mice

    Energy Technology Data Exchange (ETDEWEB)

    Li, Weifeng, E-mail: liwf@mail.xjtu.edu.cn; Huang, Huimin; Niu, Xiaofeng, E-mail: niuxf@mail.xjtu.edu.cn; Fan, Ting; Mu, Qingli; Li, Huani

    2013-10-01

    Excessive alcohol consumption can lead to gastric ulcer and the present work was aimed to examine the protective effect of tetrahydrocoptisine (THC) in the model of ethanol-induced gastric ulcer in mice. Fasted mice treated with ethanol 75% (0.5 ml/100 g) were pre-treated with THC (10 or 20 mg/kg, ip), cimetidine (100 mg/kg, ip) or saline in different experimental sets for a period of 3 days, and animals were euthanized 4 h after ethanol ingestion. Gross and microscopic lesions, immunological and biochemical parameters were taken into consideration. The results showed that ethanol induced gastric damage, improving nitric oxide (NO) level, increased pro-inflammatory cytokine (TNF-α and IL-6) levels and myeloperoxidase (MPO) activity, as well as the expression of nuclear factor-κB (NF-κB) in the ethanol group. Pretreatment of THC at doses of 10 and 20 mg/kg bodyweight significantly attenuated the gastric lesions as compared to the ethanol group. These results suggest that the gastroprotective activity of THC is attributed to reducing NO production and adjusting the pro-inflammatory cytokine, inhibited neutrophil accumulation and NF-κB expression. - Highlights: • THC decreased ethanol-induced pro-inflammatory cytokine release. • THC inhibited the production of NO in serum and gastric tissue. • THC reduced NF-κB expression and MPO accumulation in ethanol-induced gastric tissue.

  1. The Effect of Omeprazole Usage on the Viability of Random Pattern Skin Flaps in Rats.

    Science.gov (United States)

    Şen, Hilmi; Oruç, Melike; Işik, Veysel Murat; Sadiç, Murat; Sayar, Hamide; Çitil, Rana; Korkmaz, Meliha; Koçer, Uğur

    2017-06-01

    Necrosis of random pattern flaps caused by inadequate blood flow, especially in the distal part of the flap is one of the biggest challenges in reconstructive surgery. Various agents have been used to prevent flap ischemia. In this study, we used omeprazole, which is a potent inhibitor of gastric acidity to increase flap viability. In this study, 35 Wistar-Albino type rats which were divided into 5 equal groups were used. Random-pattern dorsal skin flaps were raised in all groups at seventh day of the study. Group 1 was accepted as control group, and the rats in this group was only given distilled water intraperitoneally for 14 days. Group 2 and group 3 received 10 and 40 mg/kg omeprazole daily for 14 days, respectively. Group 4 and group 5 were given distilled water for the first 7 days and then after the operations they received 10 and 40 mg/kg omeprazole daily for 7 days, respectively. Survival rates of the flaps were examined seventh day after elevation of the flaps by digital imaging and scintigraphy. After assessment of the amount of necrosis, number of vascular structures were counted histopathologically. Percentage of flap necrosis was found to be less in all omeprazole received groups. On digital imaging, percentages of flap necrosis in the study groups were statistically significantly lower than that of the control group (P 0.05).In the histopathologic specimens, it was detected that the mean number of vessels in proximal (a) and distal (c) portions of the flap in the study groups showed a significant increase when compared with the control group (P usage of medications increasing gastrin during flap surgeries can be thought as a positive contributor. In this sense, this study showed that parenteral administration of omeprazole in skin flap surgery increases flap viability possibly by increasing gastrin levels.

  2. Appropriateness of Omeprazole Prescribing in Quebec’s Senior Population

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Grégoire

    2000-01-01

    Full Text Available BACKGROUND: Prescribing omeprazole for the treatment of digestive disorders accounts for an important part of the costs in Quebec’s drug benefit plan. In July 1993, the Quebec drug program listed omeprazole, with restriction, in its formulary. On January 1, 1994, this restriction was lifted; since then, omeprazole has been listed in the regular provincial formulary.

  3. Fasting does not induce gastric emptying in rats

    OpenAIRE

    Brito,Marcus Vinicius Henriques; Yasojima,Edson Yuzur; Teixeira,Renan Kleber Costa; Houat,Abdallah de Paula; Yamaki,Vitor Nagai; Costa,Felipe Lobato da Silva

    2015-01-01

    PURPOSE: To evaluate the effect of fasting on gastric emptying in mice.METHODS:Twenty-eight mice were distributed into three study groups: a normal group (N=4): normal standard animals; a total fasting group (N=12): subjected to food and water deprivation and a partial fasting group (N=12): subjected to food deprivation only. The fasting groups were subdivided into three subgroups of four animals each, according to the date of euthanasia: 24, 48 and 72 hours. Was analyzed: the gastric volume,...

  4. Ameliorating effect of transcutaneous electroacupuncture on impaired gastric accommodation induced by cold meal in healthy subjects.

    Science.gov (United States)

    Huang, Zhihui; Zhang, Nina; Xu, Feng; Yin, Jieyun; Dai, Ning; Chen, Jiande D Z

    2016-03-01

    Impaired gastric accommodation is recognized as one of major pathophysiologies in functional dyspepsia and gastroparesis. Electroacupuncture has been shown to improve gastric accommodation in laboratory settings. It is, however, unknown whether it exerts similar ameliorating effect in humans and whether needleless transcutaneous electroacupuncture (TEA) is also effective in improving gastric accommodation. The aim was to investigate the effects of TEA on gastric accommodation, gastric slow waves, and dyspeptic related symptoms. Thirteen healthy volunteers were studied in four randomized sessions: control, cold nutrient liquid, cold nutrient liquid + sham-TEA, and cold nutrient liquid + TEA. The subjects were requested to drink Ensure until reaching maximum satiety. The electrogastrogram (EGG) and electrocardiogram (ECG) were recorded to assess the gastric and autonomic functions respectively. 1) Gastric accommodation was reduced with the cold drink in comparison with the warm drink (P = 0.023). TEA improved the impaired gastric accommodation from 539.2 ± 133.8 ml to 731.0 ± 185.7 ml (P = 0.005). 2) The percentage of normal gastric slow waves in six subjects was significantly decreased in the cold session (P = 0.002) and improved in the TEA session (P = 0.009 vs sham; P  0.05). TEA improves impaired gastric accommodation and slow waves induced by cold drink and the effect does not seem to be mediated via the vagal mechanisms. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  5. Nuclear magnetic resonance-based metabolomics for prediction of gastric damage induced by indomethacin in rats

    International Nuclear Information System (INIS)

    Um, So Young; Park, Jung Hyun; Chung, Myeon Woo; Kim, Kyu-Bong; Kim, Seon Hwa; Choi, Ki Hwan; Lee, Hwa Jeong

    2012-01-01

    Highlights: ► NMR based metabolomics – gastric damage by indomethacin. ► Pattern recognition analysis was performed to biomarkers of gastric damage. ► 2-Oxoglutarate, acetate, taurine and hippurate were selected as putative biomarkers. ► The gastric damage induced by NSAIDs can be screened in the preclinical step of drug. - Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) have side effects including gastric erosions, ulceration and bleeding. In this study, pattern recognition analysis of the 1 H-nuclear magnetic resonance (NMR) spectra of urine was performed to develop surrogate biomarkers related to the gastrointestinal (GI) damage induced by indomethacin in rats. Urine was collected for 5 h after oral administration of indomethacin (25 mg kg −1 ) or co-administration with cimetidine (100 mg kg −1 ), which protects against GI damage. The 1 H-NMR urine spectra were divided into spectral bins (0.04 ppm) for global profiling, and 36 endogenous metabolites were assigned for targeted profiling. The level of gastric damage in each animal was also determined. Indomethacin caused severe gastric damage; however, indomethacin administered with cimetidine did not. Simultaneously, the patterns of changes in their endogenous metabolites were different. Multivariate data analyses were carried out to recognize the spectral pattern of endogenous metabolites related to indomethacin using partial least square-discrimination analysis. In targeted profiling, a few endogenous metabolites, 2-oxoglutarate, acetate, taurine and hippurate, were selected as putative biomarkers for the gastric damage induced by indomethacin. These metabolites changed depending on the degree of GI damage, although the same dose of indomethacin (10 mg kg −1 ) was administered to rats. The results of global and targeted profiling suggest that the gastric damage induced by NSAIDs can be screened in the preclinical stage of drug development using a NMR based metabolomics approach.

  6. Nuclear magnetic resonance-based metabolomics for prediction of gastric damage induced by indomethacin in rats

    Energy Technology Data Exchange (ETDEWEB)

    Um, So Young [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); Park, Jung Hyun [Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); Chung, Myeon Woo [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Kim, Kyu-Bong [College of Pharmacy, Dankook University, Dandae-ro, Cheonan, Chungnam (Korea, Republic of); Kim, Seon Hwa [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of); College of Pharmacy, Dankook University, Dandae-ro, Cheonan, Chungnam (Korea, Republic of); Choi, Ki Hwan, E-mail: hyokwa11@korea.kr [Department of Pharmacology, National Institute of Toxicological Research, Korea Food and Drug Administration, 643 Yeonje-ri, Gangoe-myeon, Cheongwon-gun, Chungbuk (Korea, Republic of); Lee, Hwa Jeong, E-mail: hwalee@ewha.ac.kr [Division of Life and Pharmaceutical Science and College of Pharmacy, Ewha Womans University, 52 Ewahyeodae-gil, Seodaemun-gu, Seoul (Korea, Republic of)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer NMR based metabolomics - gastric damage by indomethacin. Black-Right-Pointing-Pointer Pattern recognition analysis was performed to biomarkers of gastric damage. Black-Right-Pointing-Pointer 2-Oxoglutarate, acetate, taurine and hippurate were selected as putative biomarkers. Black-Right-Pointing-Pointer The gastric damage induced by NSAIDs can be screened in the preclinical step of drug. - Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) have side effects including gastric erosions, ulceration and bleeding. In this study, pattern recognition analysis of the {sup 1}H-nuclear magnetic resonance (NMR) spectra of urine was performed to develop surrogate biomarkers related to the gastrointestinal (GI) damage induced by indomethacin in rats. Urine was collected for 5 h after oral administration of indomethacin (25 mg kg{sup -1}) or co-administration with cimetidine (100 mg kg{sup -1}), which protects against GI damage. The {sup 1}H-NMR urine spectra were divided into spectral bins (0.04 ppm) for global profiling, and 36 endogenous metabolites were assigned for targeted profiling. The level of gastric damage in each animal was also determined. Indomethacin caused severe gastric damage; however, indomethacin administered with cimetidine did not. Simultaneously, the patterns of changes in their endogenous metabolites were different. Multivariate data analyses were carried out to recognize the spectral pattern of endogenous metabolites related to indomethacin using partial least square-discrimination analysis. In targeted profiling, a few endogenous metabolites, 2-oxoglutarate, acetate, taurine and hippurate, were selected as putative biomarkers for the gastric damage induced by indomethacin. These metabolites changed depending on the degree of GI damage, although the same dose of indomethacin (10 mg kg{sup -1}) was administered to rats. The results of global and targeted profiling suggest that the gastric damage induced by

  7. Recent Advances in the Gastric Mucosal Protection Against Stress-induced Gastric Lesions. Importance of Renin-angiotensin Vasoactive Metabolites, Gaseous Mediators and Appetite Peptides.

    Science.gov (United States)

    Brzozowski, Tomasz; Magierowska, Katarzyna; Magierowski, Marcin; Ptak-Belowska, Agata; Pajdo, Robert; Kwiecien, Slawomir; Olszanecki, Rafal; Korbut, Ryszard

    2017-01-01

    Stress is known to cause severe adverse effects in the human gastrointestinal tract including mucosal microbleedings and erosions or even gastric ulceration but the mechanism of these complications has not been fully elucidated. The pathogenesis of stress-induced gastric damage involves the fall in Gastric Blood Flow (GBF), an increase in gastric acid secretion and gastric motility, enhanced adrenergic and cholinergic nerve activity and the rise in gastric mucosal generation of reactive oxygen species. The gastric mucosal defense mechanisms against the deleterious effect of stress include the activation of the hypothalamic-pituitary-adrenal axis which has been linked with glucocorticoids release capable of counteracting of stress-induced gastric lesions. Here we summarize the novel gastroprotective mechanisms against stress damage exhibited by angiotensin-(1-7), the newly discovered metabolite of Renin-Angiotensin System (RAS), the gaseous mediators such as nitric oxide (NO), hydrogen sulfide (H2S) or Carbon Monoxide (CO), and the food intake controlling peptides ghrelin, nesfatin- 1 and apelin possibly acting via brain-gut axis. These bioactive molecules such as RAS vasoactive metabolite angiotensin-(1-7) and appetite peptides have been shown to afford gastroprotective effect against stressinduced gastric lesions mainly mediated by an increase in gastric microcirculation. Gaseous mediators protect the gastric mucosa against stress lesions by mechanism involving the activation of PG/COX and CO/HO-1 biosynthetic pathways, and their anti-inflammatory and anti-oxidizing properties. Thus, these new components add new mechanistic aspects to the common cooperation of NO/NO-synthase, PG/COX systems and vasoactive sensory neuropeptides including CGRP but their gastroprotective efficacy against experimental stress ulcerogenesis requires the confirmation in human clinical trials. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Selective scavenging of intra-mitochondrial superoxide corrects diclofenac-induced mitochondrial dysfunction and gastric injury: A novel gastroprotective mechanism independent of gastric acid suppression.

    Science.gov (United States)

    Mazumder, Somnath; De, Rudranil; Sarkar, Souvik; Siddiqui, Asim Azhar; Saha, Shubhra Jyoti; Banerjee, Chinmoy; Iqbal, Mohd Shameel; Nag, Shiladitya; Debsharma, Subhashis; Bandyopadhyay, Uday

    2016-12-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat multiple inflammatory diseases and pain but severe gastric mucosal damage is the worst outcome of NSAID-therapy. Here we report that mitoTEMPO, a mitochondrially targeted superoxide (O 2 - ) scavenger protected as well as healed gastric injury induced by diclofenac (DCF), the most commonly used NSAID. Common existing therapy against gastric injury involves suppression of gastric acid secretion by proton pump inhibitors and histamine H 2 receptor antagonists; however, dyspepsia, vitamin B12 deficiency and gastric microfloral dysbalance are the major drawbacks of acid suppression. Interestingly, mitoTEMPO did not inhibit gastric acid secretion but offered gastroprotection by preventing DCF-induced generation of O 2 - due to mitochondrial respiratory chain failure and by preventing mitochondrial oxidative stress (MOS)-mediated mitopathology. MitoTEMPO even restored DCF-stimulated reduced fatty acid oxidation, mitochondrial depolarization and bioenergetic crisis in gastric mucosa. MitoTEMPO also prevented the activation of mitochondrial pathway of apoptosis and MOS-mediated proinflammatory signaling through NF-κB by DCF. Furthermore, mitoTEMPO when administered in rats with preformed gastric lesions expedited the healing of gastric injury and the healed stomach exhibited its normal physiology as evident from gastric acid and pepsin secretions under basal or stimulated conditions. Thus, in contrast to the existing antiulcer drugs, mitochondrially targeted O 2 - scavengers like mitoTEMPO may represent a novel class of gastroprotective molecules that does not affect gastric acid secretion and may be used in combination with DCF, keeping its anti-inflammatory action intact, while reducing its gastrodamaging effects. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Antibiotic drug tigecycline inhibited cell proliferation and induced autophagy in gastric cancer cells

    International Nuclear Information System (INIS)

    Tang, Chunling; Yang, Liqun; Jiang, Xiaolan; Xu, Chuan; Wang, Mei; Wang, Qinrui; Zhou, Zhansong; Xiang, Zhonghuai; Cui, Hongjuan

    2014-01-01

    Highlights: • Tigecycline inhibited cell growth and proliferation in human gastric cancer cells. • Tigecycline induced autophagy not apoptosis in human gastric cancer cells. • AMPK/mTOR/p70S6K pathway was activated after tigecycline treatment. • Tigecycline inhibited tumor growth in xenograft model of human gastric cancer cells. - Abstract: Tigecycline acts as a glycylcycline class bacteriostatic agent, and actively resists a series of bacteria, specifically drug fast bacteria. However, accumulating evidence showed that tetracycline and their derivatives such as doxycycline and minocycline have anti-cancer properties, which are out of their broader antimicrobial activity. We found that tigecycline dramatically inhibited gastric cancer cell proliferation and provided an evidence that tigecycline induced autophagy but not apoptosis in human gastric cancer cells. Further experiments demonstrated that AMPK pathway was activated accompanied with the suppression of its downstream targets including mTOR and p70S6K, and ultimately induced cell autophagy and inhibited cell growth. So our data suggested that tigecycline might act as a candidate agent for pre-clinical evaluation in treatment of patients suffering from gastric cancer

  10. Antibiotic drug tigecycline inhibited cell proliferation and induced autophagy in gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Chunling; Yang, Liqun; Jiang, Xiaolan [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Xu, Chuan [Division of Scientific Research and Training, General Hospital of PLA Chengdu Military Area Command, Chengdu, Sichuan 610083 (China); Wang, Mei; Wang, Qinrui [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Zhou, Zhansong, E-mail: zhouzhans@sina.com [Institute of Urinary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Xiang, Zhonghuai [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Cui, Hongjuan, E-mail: hcui@swu.edu.cn [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China)

    2014-03-28

    Highlights: • Tigecycline inhibited cell growth and proliferation in human gastric cancer cells. • Tigecycline induced autophagy not apoptosis in human gastric cancer cells. • AMPK/mTOR/p70S6K pathway was activated after tigecycline treatment. • Tigecycline inhibited tumor growth in xenograft model of human gastric cancer cells. - Abstract: Tigecycline acts as a glycylcycline class bacteriostatic agent, and actively resists a series of bacteria, specifically drug fast bacteria. However, accumulating evidence showed that tetracycline and their derivatives such as doxycycline and minocycline have anti-cancer properties, which are out of their broader antimicrobial activity. We found that tigecycline dramatically inhibited gastric cancer cell proliferation and provided an evidence that tigecycline induced autophagy but not apoptosis in human gastric cancer cells. Further experiments demonstrated that AMPK pathway was activated accompanied with the suppression of its downstream targets including mTOR and p70S6K, and ultimately induced cell autophagy and inhibited cell growth. So our data suggested that tigecycline might act as a candidate agent for pre-clinical evaluation in treatment of patients suffering from gastric cancer.

  11. Protective effect of ginsenoside Re on acute gastric mucosal lesion induced by compound 48/80

    Directory of Open Access Journals (Sweden)

    Sena Lee

    2014-04-01

    Full Text Available The protective effect of ginsenoside Re, isolated from ginseng berry, against acute gastric mucosal lesions was examined in rats with a single intraperitoneal injection of compound 48/80 (C48/80. Ginsenoside Re (20 mg/kg or 100 mg/kg was orally administered 0.5 h prior to C48/80 treatment. Ginsenoside Re dose-dependently prevented gastric mucosal lesion development 3 h after C48/80 treatment. Increases in the activities of myeloperoxidase (MPO; an index of neutrophil infiltration and xanthine oxidase (XO and the content of thiobarbituric acid reactive substances (TBARS; an index of lipid peroxidation and decreases in the contents of hexosamine (a marker of gastric mucus and adherent mucus, which occurred in gastric mucosal tissues after C48/80 treatment, were significantly attenuated by ginsenoside Re. The elevation of Bax expression and the decrease in Bcl2 expression after C48/80 treatment were also attenuated by ginsenoside Re. Ginsenoside Re significantly attenuated all these changes 3 h after C48/80 treatment. These results indicate that orally administered ginsenoside Re protects against C48/80-induced acute gastric mucosal lesions in rats, possibly through its stimulatory action on gastric mucus synthesis and secretion, its inhibitory action on neutrophil infiltration, and enhanced lipid peroxidation in the gastric mucosal tissue.

  12. Attenuation of stress-induced gastric lesions by lansoprazole, PD-136450 and ranitidine in rats.

    Science.gov (United States)

    Chandranath, S I; Bastaki, S M A; D'Souza, A; Adem, A; Singh, J

    2011-03-01

    Combining restraint with cold temperature (4°C) consistently induces gastric ulceration in rats after 3.5 h. The cold restraint-stress (CRS) method provides a suitable model for acute ulcer investigations. This study compares the antiulcer activities of lansoprazole (a proton pump inhibitor), PD-136450 (CCK(2)/gastrin receptor antagonist) and ranitidine (histamine H(2) receptor antagonist) on CRS-induced gastric ulcers in rats. The results have shown that lansoprazole, which is a potent anti-secretory agent, provides complete protection in this model of ulcer formation. The use of indomethacin pretreatment to inhibit the prostaglandin (PG) synthesis and N(G)-nitro L-arginine methyl ester (L-NAME) pretreatment to inhibit nitric oxide synthase did not alter the lansoprazole-induced inhibition of ulcer index obtained in the untreated Wistar rats indicating that these two systems were not involved in the activation of lansoprazole. PD-136450, an effective anti-secretory agent against gastrin- but not dimaprit-induced stimulation, evoked a dose-dependent inhibition of CRS-induced gastric ulcers. The results show that both PG and nitric oxide pathways can influence the inhibitory effect of PD-136450 against CRS-induced gastric ulcer. The antiulcer activities of both lansoprazole and PD-136450 were compared to that of ranitidine. The results showed that ranitidine was more potent than lansoprazole and PD-136450 in inhibiting CRS-induced gastric ulcers and its effect was shown to be influenced by PG as well as nitric oxide synthase. The results of this study have demonstrated that although lansoprazole, PD-136450 and ranitidine were protective against CRS-induced gastric ulcers, the antiulcer activities of PD-136450 and ranitidine involved both PG and nitric oxide pathways, while lansoprazole acted independently of these two systems during CRS.

  13. Endogenous histamine and promethazine-induced gastric ulcers in the guinea pig

    Science.gov (United States)

    Djahanguiri, B.; Hemmati, M.

    1978-01-01

    Experiments performed with an inhibitor of diaminoxydase, aminoguanidine and an inhibitor of histidine decarboxylase, NSD 1055, showed that the frequency of gastric ulcers induced by promethazine was increased with the first inhibitor and decreased with the second. It is suggested that ulcers induced by promethazine in guinea pigs might be due to histamino-liberator effect of the antihistaminio compound.

  14. Protective effect of bovine milk against HCl and ethanol-induced gastric ulcer in mice.

    Science.gov (United States)

    Yoo, Jeong-Hyun; Lee, Jeong-Sang; Lee, You-Suk; Ku, SaeKwang; Lee, Hae-Jeung

    2018-05-01

    The purpose of this study was to investigate the gastroprotective effects of bovine milk on an acidified ethanol (HCl-ethanol) mixture that induced gastric ulcers in a mouse model. Mice received different doses of commercial fresh bovine milk (5, 10, and 20 mL/kg of body weight) by oral gavage once a day for 14 d. One hour after the last oral administration of bovine milk, the HCl-ethanol mixture was orally intubated to provoke severe gastric damage. Our results showed that pretreatment with bovine milk significantly suppressed the formation of gastric mucosa lesions. Pretreatment lowered gastric myeloperoxidase and increased gastric mucus contents and antioxidant enzymes catalase and superoxide dismutase. Administration of bovine milk increased nitrate/nitrite levels and decreased the malondialdehyde levels and the expression of proinflammatory genes, including transcription factor nuclear factor-κB, cyclooxygenase-2, and inducible nitric oxide synthase in the stomach of mice. These results suggest that bovine milk can prevent the development of gastric ulcer caused by acid and alcohol in mice. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  15. Dehydroabietic Acid Derivative QC4 Induces Gastric Cancer Cell Death via Oncosis and Apoptosis

    Directory of Open Access Journals (Sweden)

    Dongjun Luo

    2016-01-01

    Full Text Available Aim. QC4 is the derivative of rosin’s main components dehydroabietic acid (DHA. We investigated the cytotoxic effect of QC4 on gastric cancer cells and revealed the mechanisms beneath the induction of cell death. Methods. The cytotoxic effect of QC4 on gastric cancer cells was evaluated by CCK-8 assay and flow cytometry. The underlying mechanisms were tested by administration of cell death related inhibitors and detection of apoptotic and oncosis related proteins. Cytomembrane integrity and organelles damage were confirmed by lactate dehydrogenase (LDH leakage assay, mitochondrial function test, and cytosolic free Ca2+ concentration detection. Results. QC4 inhibited cell proliferation dose- and time-dependently and destroyed cell membrane integrity, activated calpain-1 autolysis, and induced apoptotic protein cleavage in gastric cancer cells. The detection of decreased ATP and mitochondrial membrane potential, ROS accumulation, and cytosolic free Ca2+ elevation confirmed organelles damage in QC4-treated gastric cancer cells. Conclusions. DHA derivative QC4 induced the damage of cytomembrane and organelles which finally lead to oncosis and apoptosis in gastric cancer cells. Therefore, as a derivative of plant derived small molecule DHA, QC4 might become a promising agent in gastric cancer therapy.

  16. Electroacupuncture improves burn-induced impairment in gastric motility mediated via the vagal mechanism in rats.

    Science.gov (United States)

    Song, J; Yin, J; Sallam, H S; Bai, T; Chen, Y; Chen, J D Z

    2013-10-01

    Delayed gastric emptying (GE) is common in patients with severe burns. This study was designed to investigate effects and mechanisms of electroacupuncture (EA) on gastric motility in rats with burns. Male rats (intact and vagotomized) were implanted with gastric electrodes, chest and abdominal wall electrodes for investigating the effects of EA at ST-36 (stomach-36 or Zusanli) on GE, gastric slow waves, autonomic functions, and plasma interleukin 6 (IL-6) 6 and 24 h post severe burns. (i) Burn delayed GE (P Electroacupuncture improved GE 6 and 24 h post burn (P Electroacupuncture improved burn-induced gastric dysrhythmia. The percentage of normal slow waves was increased with EA 6 and 24 h post burn (P = 0.02). (iii) Electroacupuncture increased vagal activity assessed by the spectral analysis of heart rate variability (HRV). The high-frequency component reflecting vagal component was increased with EA 6 (P = 0.004) and 24 h post burn (P = 0.03, vs sham-EA). (iv) Electroacupuncture attenuated burn-induced increase in plasma IL-6 at both 6 (P = 0.03) and 24 h post burn (P = 0.003). Electroacupuncture at ST-36 improves gastric dysrhythmia and accelerates GE in rats with burns. The improvement seems to be mediated via the vagal pathway involving the inflammatory cytokine IL-6. © 2013 John Wiley & Sons Ltd.

  17. BAK overexpression mediates p53-independent apoptosis inducing effects on human gastric cancer cells

    Directory of Open Access Journals (Sweden)

    Liu Jun

    2004-07-01

    Full Text Available Abstract Background BAK (Bcl-2 homologous antagonist/killer is a novel pro-apoptotic gene of the Bcl-2 family. It has been reported that gastric tumors have reduced BAK levels when compared with the normal mucosa. Moreover, mutations of the BAK gene have been identified in human gastrointestinal cancers, suggesting that a perturbation of BAK-mediated apoptosis may contribute to the pathogenesis of gastric cancer. In this study, we explored the therapeutic effects of gene transfer mediated elevations in BAK expression on human gastric cancer cells in vitro. Methods Eukaryotic expression vector for the BAK gene was constructed and transferred into gastric cancer cell lines, MKN-45 (wild-type p53 and MKN-28 (mutant-type p53. RT-PCR and Western Blotting detected cellular BAK gene expression. Cell growth activities were detected by MTT colorimetry and flow cytometry, while apoptosis was assayed by electronic microscopy and TUNEL. Western Blotting and colorimetry investigated cellular caspase-3 activities. Results BAK gene transfer could result in significant BAK overexpression, decreased in vitro growth, cell cycle G0/G1 arrest, and induced apoptosis in gastric cancer cells. In transferred cells, inactive caspase-3 precursor was cleaved into the active subunits p20 and p17, during BAK overexpression-induced apoptosis. In addition, this process occurred equally well in p53 wild-type (MKN-45, or in p53 mutant-type (MKN-28 gastric cancer cells. Conclusions The data presented suggests that overexpression of the BAK gene can lead to apoptosis of gastric cancer cells in vitro, which does not appear to be dependent on p53 status. The action mechanism of BAK mediated apoptosis correlates with activation of caspase-3. This could be served as a potential strategy for further development of gastric cancer therapies.

  18. BAK overexpression mediates p53-independent apoptosis inducing effects on human gastric cancer cells

    International Nuclear Information System (INIS)

    Tong, Qiang-Song; Zheng, Li-Duan; Wang, Liang; Liu, Jun; Qian, Wei

    2004-01-01

    BAK (Bcl-2 homologous antagonist/killer) is a novel pro-apoptotic gene of the Bcl-2 family. It has been reported that gastric tumors have reduced BAK levels when compared with the normal mucosa. Moreover, mutations of the BAK gene have been identified in human gastrointestinal cancers, suggesting that a perturbation of BAK-mediated apoptosis may contribute to the pathogenesis of gastric cancer. In this study, we explored the therapeutic effects of gene transfer mediated elevations in BAK expression on human gastric cancer cells in vitro. Eukaryotic expression vector for the BAK gene was constructed and transferred into gastric cancer cell lines, MKN-45 (wild-type p53) and MKN-28 (mutant-type p53). RT-PCR and Western Blotting detected cellular BAK gene expression. Cell growth activities were detected by MTT colorimetry and flow cytometry, while apoptosis was assayed by electronic microscopy and TUNEL. Western Blotting and colorimetry investigated cellular caspase-3 activities. BAK gene transfer could result in significant BAK overexpression, decreased in vitro growth, cell cycle G 0 /G 1 arrest, and induced apoptosis in gastric cancer cells. In transferred cells, inactive caspase-3 precursor was cleaved into the active subunits p20 and p17, during BAK overexpression-induced apoptosis. In addition, this process occurred equally well in p53 wild-type (MKN-45), or in p53 mutant-type (MKN-28) gastric cancer cells. The data presented suggests that overexpression of the BAK gene can lead to apoptosis of gastric cancer cells in vitro, which does not appear to be dependent on p53 status. The action mechanism of BAK mediated apoptosis correlates with activation of caspase-3. This could be served as a potential strategy for further development of gastric cancer therapies

  19. Effects of mosapride citrate, a 5-HT4-receptor agonist, on gastric distension-induced visceromotor response in conscious rats.

    Science.gov (United States)

    Seto, Yasuhiro; Yoshida, Naoyuki; Kaneko, Hiroshi

    2011-01-01

    Mosapride citrate (mosapride), a prokinetic agent with 5-HT(4)-receptor agonistic activity, is known to enhance gastric emptying and alleviate symptoms in patients with functional dyspepsia (FD). As hyperalgesia and delayed gastric emptying play an important role in the pathogenesis of FD, we used in this study balloon gastric distension to enable abdominal muscle contractions and characterized the visceromotor response (VMR) to such distension in conscious rats. We also investigated the effects of mosapride on gastric distension-induced VMR in the same model. Mosapride (3-10 mg/kg, p.o.) dose-dependently inhibited gastric distension-induced VMR in rats. However, itopride even at 100 mg/kg failed to inhibit gastric distension-induced VMR in rats. Additionally, a major metabolite M1 of mosapride, which possesses 5-HT(3)-receptor antagonistic activity, inhibited gastric distension-induced VMR. The inhibitory effect of mosapride on gastric distension-induced visceral pain was partially, but significantly inhibited by SB-207266, a selective 5-HT(4)-receptor antagonist. This study shows that mosapride inhibits gastric distension-induced VMR in conscious rats. The inhibitory effect of mosapride is mediated via activation of 5-HT(4) receptors and blockage of 5-HT(3) receptors by a mosapride metabolite. This finding indicates that mosapride may be useful in alleviating FD-associated gastrointestinal symptoms via increase in pain threshold.

  20. The protective activity of Conyza blinii saponin against acute gastric ulcer induced by ethanol.

    Science.gov (United States)

    Ma, Long; Liu, Jiangguang

    2014-12-02

    Conyza blinii H.Lév., is a type of natural plant. Its dried overground section is used to treat infections and inflammations in traditional Chinese medicine. Triterpenoidal saponins have a wide range of bioactivities, for instance, anti-cancer, anti-virus and anti-anaphylaxis. Conyza blinii saponin (CBS), mainly composed of triterpenoidal saponins, is the total saponin of Conyza blinii H.Lév. It has been reported that CBS also has gastric mucous membrane protection activity. This study aims to test CBS׳s protective activity of gastric׳s mucous membrane against ethanol. This investigation may lead to the development of novel drug from natural products as anti-ulcer agent, or as gastric mucous protective against chemical damage. CBS (Conyza blinii saponin) is the total saponin of Conyza blinii H.Lév., which was obtained as described previously. We tested the protective activity of CBS against ethanol-induced ulcer. Thirty six rats were grouped randomly as 'NORMAL', 'CONTROL', 'MODEL', 'LOW DOSE', 'MEDIUM DOSE' and 'HIGH DOSE'. The 'NORMAL' group were rats with no pathological model established within it. The 'CONTROL' group was administrated with colloidal bismuth subcitrate, while 'MODEL' group was not given any active agents apart from absolute ethanol in order to obtain gastric ulcer model. The three 'DOSE' groups were treated with different concentrations of CBS (5, 10, 20mg/mL) before administration followed by absolute ethanol. All rats were sacrificed after the experiment to acquire the gastric tissue. The ulcer index (UI), malondialdehyde (MDA) and superoxide dismutase (SOD) were measured to monitor the activity of CBS. Besides, the rat gastric tissue was made to paraffin section and stained using the Hematoxylin-Eosin (HE) method. The histopathology examination was carried out to examine CBS efficacy in terms of gastric mucous protection. We found that CBS had a profound protection activity against acute gastric ulcer induced by ethanol and this

  1. Gastric injury induced by hemorrhage, local ischemia, and oxygen radical generation

    International Nuclear Information System (INIS)

    Wadhwa, S.S.; Perry, M.A.

    1987-01-01

    Gastric mucosal injury caused by local intra-arterial generation of oxygen-derived free radicals was compared with gastric injury caused by 30 min of hemorrhage-induced ischemia or local ischemia. The index of injury was the loss of 51 Cr-labeled red cells across the gastric mucosa. Generation of oxygen radicals in the celiac artery caused a rapid increase in mucosal blood loss during the period of radical generation, and this loss was maintained after radical production ceased. Local ischemia produced similar mucosal injury; however, this occurred after reperfusion of the stomach and not during the ischemic episode. Hemorrhage-induced ischemia produced a threefold greater mucosal blood loss than local ischemia. The results of this study indicate that (1) oxygen radicals generated enzymatically in the blood supply to the stomach cause mucosal bleeding of similar magnitude to that observed after local ischemia and (2) that gastric ischemia induced by systemic hypotension produces more severe gastric injury than the same level of local hypotension

  2. Shuidouchi (Fermented Soybean Fermented in Different Vessels Attenuates HCl/Ethanol-Induced Gastric Mucosal Injury

    Directory of Open Access Journals (Sweden)

    Huayi Suo

    2015-11-01

    Full Text Available Shuidouchi (Natto is a fermented soy product showing in vivo gastric injury preventive effects. The treatment effects of Shuidouchi fermented in different vessels on HCl/ethanol-induced gastric mucosal injury mice through their antioxidant effect was determined. Shuidouchi contained isoflavones (daidzein and genistein, and GVFS (glass vessel fermented Shuidouchi had the highest isoflavone levels among Shuidouchi samples fermented in different vessels. After treatment with GVFS, the gastric mucosal injury was reduced as compared to the control mice. The gastric secretion volume (0.47 mL and pH of gastric juice (3.1 of GVFS treated gastric mucosal injury mice were close to those of ranitidine-treated mice and normal mice. Shuidouchi could decrease serum motilin (MTL, gastrin (Gas level and increase somatostatin (SS, vasoactive intestinal peptide (VIP level, and GVFS showed the strongest effects. GVFS showed lower IL-6, IL-12, TNF-α and IFN-γ cytokine levels than other vessel fermented Shuidouchi samples, and these levels were higher than those of ranitidine-treated mice and normal mice. GVFS also had higher superoxide dismutase (SOD, nitric oxide (NO and malonaldehyde (MDA contents in gastric tissues than other Shuidouchi samples. Shuidouchi could raise IκB-α, EGF, EGFR, nNOS, eNOS, Mn-SOD, Gu/Zn-SOD, CAT mRNA expressions and reduce NF-κB, COX-2, iNOS expressions as compared to the control mice. GVFS showed the best treatment effects for gastric mucosal injuries, suggesting that glass vessels could be used for Shuidouchi fermentation in functional food manufacturing.

  3. Opioid-induced delay in gastric emptying: a peripheral mechanism in humans.

    LENUS (Irish Health Repository)

    Murphy, D B

    2012-02-03

    BACKGROUND: Opioids delay gastric emptying, which in turn may increase the risk of vomiting and pulmonary aspiration. Naloxone reverses this opiate action on gastric emptying, but it is not known whether this effect in humans is mediated by central or peripheral opiate antagonism. The importance of peripheral opioid receptor antagonism in modulating opioid-induced delay in gastric emptying was evaluated using methylnaltrexone, a quaternary derivative of the opiate antagonist naltrexone, which does not cross the blood-brain barrier. METHODS: In a randomized, double-blind, crossover placebo-controlled study, 11 healthy volunteers were given either placebo (saline), 0.09 mg\\/kg morphine, or 0.09 mg\\/kg morphine plus 0.3 mg\\/kg methylnaltrexone on three separate occasions before ingesting 500 ml deionized water. The rate of gastric emptying was measured by two methods: a noninvasive epigastric bioimpedance technique and the acetaminophen absorption test. RESULTS: The epigastric bioimpedance technique was sufficiently sensitive to detect opioid-induced changes in the rate of gastric emptying. The mean +\\/- SD time taken for the gastric volume to decrease to 50% (t0.5) after placebo was 5.5 +\\/- 2.1 min. Morphine prolonged gastric emptying to (t0.5) of 21 +\\/- 9.0 min (P < 0.03). Methylnaltrexone given concomitantly with morphine reversed the morphine-induced delay in gastric emptying to a t0.5 of 7.4 +\\/- 3.0 (P < 0.04). Maximum concentrations and area under the concentration curve from 0 to 90 min of serum acetaminophen concentrations after morphine were significantly different from placebo and morphine administered concomitantly with methylnaltrexone (P < 0.05). No difference in maximum concentration or area under the concentration curve from 0 to 90 min was noted between placebo and methylnaltrexone coadministered with morphine. CONCLUSIONS: The attenuation of morphine-induced delay in gastric emptying by methylnaltrexone suggests that the opioid effect is

  4. Anti-ulcerogenic effect of methanolic extracts from Enicosanthellum pulchrum (King) Heusden against ethanol-induced acute gastric lesion in animal models.

    Science.gov (United States)

    Nordin, Noraziah; Salama, Suzy Munir; Golbabapour, Shahram; Hajrezaie, Maryam; Hassandarvish, Pouya; Kamalidehghan, Behnam; Majid, Nazia Abdul; Hashim, Najihah Mohd; Omar, Hanita; Fadaienasab, Mehran; Karimian, Hamed; Taha, Hairin; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen

    2014-01-01

    A natural source of medicine, Enicosanthellum pulchrum is a tropical plant which belongs to the family Annonaceae. In this study, methanol extract from the leaves and stems of this species was evaluated for its gastroprotective potential against mucosal lesions induced by ethanol in rats. Seven groups of rats were assigned, groups 1 and 2 were given Tween 20 (10% v/v) orally. Group 3 was administered omeprazole 20 mg/kg (10% Tween 20) whilst the remaining groups received the leaf and stem extracts at doses of 150 and 300 mg/kg, respectively. After an additional hour, the rats in groups 2-7 received ethanol (95% v/v; 8 mL/kg) orally while group 1 received Tween 20 (10% v/v) instead. Rats were sacrificed after 1 h and their stomachs subjected to further studies. Macroscopically and histologically, group 2 rats showed extremely severe disruption of the gastric mucosa compared to rats pre-treated with the E. pulchrum extracts based on the ulcer index, where remarkable protection was noticed. Meanwhile, a significant percentage of inhibition was shown with the stem extract at 62% (150 mg/kg) and 65% (300 mg/kg), whilst the percentage with the leaf extract at doses of 150 and 300 mg/kg was 63% and 75%, respectively. An increase in mucus content, nitric oxide, glutathione, prostaglandin E2, superoxide dismutase, protein and catalase, and a decrease in malondialdehyde level compared to group 2 were also obtained. Furthermore, immunohistochemical staining of groups 4-7 exhibited down-regulation of Bax and up-regulation of Hsp70 proteins. The methanol extract from the leaves and the stems showed notable gastroprotective potential against ethanol.

  5. Anti-inflammatory Activities and Gastric Ulcer-inducing Properties of Tetraacetylquercetin and Tetrapivaloylquercetin

    Directory of Open Access Journals (Sweden)

    Rina Herowati

    2016-12-01

    Full Text Available Quercetin (3,3’4’,5,7-pentahydroxyflavone has been reported to show anti-inflammatory activity. However, its low oral bioavailability limits the application of quercetin in therapy. Ester derivatives of quercetin have been reported to have higher bioavailability than quercetin. This research aimed to study the anti-inflammatory activities and gastric ulcer-inducing properties of tetraacetylquercetinas well as tetrapivaloylquercetin. Synthesis of tetra-acyl derivatives of quercetin was conducted using acetic anhydride or pivaloyl chloride in the presence of pyridine and the structure was confirmed by 1H-NMR and 13C-NMR spectroscopy as well as elemental analysis. At a dose of 20 mg/kg bw, oral administration of quercetin only showed 20% inhibition activity on carragenan induced rat paw edema, while tetraacetyl and tetrapivaloyl derivatives at equimolar dose showed 11-33% and 5-15% inhibition activity respectively. Contrary to the gastric ulcer healing-promoting action of quercetin, tetraacetylquercetin caused mild gastric ulcers. However, no gastric ulcer was observed after administration of tetrapivaloylquercetin. It was concluded that acylation enhances the anti-inflammatory activity of quercetin but causes mild gastric ulcers in the case of tetraacetylation.

  6. Gastroprotective effect of esculin on ethanol-induced gastric lesion in mice.

    Science.gov (United States)

    Li, Weifeng; Wang, Yu; Wang, Xiumei; Zhang, Hailin; He, Zehong; Zhi, Wenbing; Liu, Fang; Niu, Xiaofeng

    2017-04-01

    The gastroprotective effect of esculin was investigated in a mouse model of ethanol-induced gastric lesion. Administration of esculin at doses of 5, 10, and 20 mg/kg body weight prior to ethanol ingestion led to significant gastroprotection compared with untreated mice. Gastric mucosal lesions were evaluated by macroscopic and histopathological alterations, lesion index, and myeloperoxidase (MPO) activity. Pretreatment with esculin significantly reduced macroscopic and histopathological damage, gastric lesion index, and MPO activity in a dose-dependent manner. Moreover, esculin significantly reduced nitric oxide (NO) production, inducible NO synthase (iNOS) levels, and nuclear factor-kappa B (NF-κB) p65 protein expression in gastric tissues after ethanol challenge. Analysis of inflammatory cytokines indicated that esculin pretreatment markedly suppressed the increased expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in ethanol-treated mice. The results demonstrate a protective effect of esculin against gastric injury and suggest that the underlying mechanism might be associated with inhibition of NF-κB activation, which subsequently reduces expression of iNOS, TNF-α, and IL-6. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  7. Testing of 99mTc labelled sucralfate in induced gastric and duodenal ulcers

    International Nuclear Information System (INIS)

    Pallagi, Katalin; Janoki, Gyoezoe

    1988-01-01

    The conditions of in vitro labelling of sucralfate available in medical practice were established according to literature data including some modifications. Labelling efficiency proved to be 98.1%. The radiopharmaceutical is stable over 6 hours in vitro. 99m Tc-sucralfate accumulates in experimentally induced gastric and duodenal ulcers thus tracing the site of the ulcerous lesion. (author) 14 refs.; 3 tabs

  8. Selective binding of sucralfate to endoscopic mucosal resection-induced gastric ulcer: evaluation of aluminium adherence.

    Science.gov (United States)

    Itoh, T; Kusaka, K; Kawaura, K; Kashimura, K; Yamakawa, J; Takahashi, T; Kanda, T

    2004-01-01

    We evaluated the effect of sucralfate in patients with early gastric cancer in endoscopic mucosal resection (EMR)-induced gastric ulcers, and in rats with acetic acid-induced ulcers, by measuring concentrations of aluminium adhering to mucosal lesions. Twenty-two patients who underwent EMR received sucralfate with or without ranitidine and were examined endoscopically after 1 week, 2 weeks and 3 weeks. Gastric juice pH and concentration of aluminium in samples of ulcerated and normal mucosa were measured at various time-points. Good ulcer healing was observed in all patients. Significantly higher concentrations of aluminium were found in ulcerated tissue compared with normal mucosa. This selective binding of sucralfate was even found 12 h after drug administration and was confirmed in acetic acid-induced ulcers in 40 rats. Neutral rather than acid gastric juice was observed up to 12 h after the administration of sucralfate alone. These results suggest that sucralfate with or without ranitidine may contribute to the healing of EMR-induced ulcers by selectively binding to lesions.

  9. Prickly pear cactus (Opuntia ficus indica var. saboten) protects against stress-induced acute gastric lesions in rats.

    Science.gov (United States)

    Kim, Seung Hyun; Jeon, Byung Ju; Kim, Dae Hyun; Kim, Tae Il; Lee, Hee Kyoung; Han, Dae Seob; Lee, Jong-Hwan; Kim, Tae Bum; Kim, Jung Wha; Sung, Sang Hyun

    2012-11-01

    The protective activity of prickly pear cactus (Opuntia ficus indica var. saboten) fruit juice and its main constituent, betanin, were evaluated against stress-induced acute gastric lesions in rats. After 6 h of water immersion restraint stress (WIRS), gastric mucosal lesions with bleeding were induced in Sprague-Dawley rats. Pretreatment of a lyophilized powder containing O. ficus indica var. saboten fruit juice and maltodextrin (OFSM) and betanin significantly reduced stress lesions (800-1600 mg/kg). Both OFSM and betanin effectively prevented the decrease in gastric mucus content as detected by alcian blue staining. In addition, OFSM significantly suppressed WIRS-induced increases in the level of gastric mucosal tumor necrosis factor-α and myeloperoxidase (MPO). Betanin alone was only effective in decreasing MPO. These results revealed the protective activity of OFSM against stress-induced acute gastric lesions and that betanin may contribute to OFSM's gastric protective activity, at least in part. When OFSM and betanin were taken together, OFSM exerted gastroprotective activity against stress-induced gastric lesions by maintaining gastric mucus, which might be related to the attenuation of MPO-mediated damage and proinflammatory cytokine production.

  10. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion.

    Science.gov (United States)

    Shimura, Takaya; Yoshida, Michihiro; Fukuda, Shinji; Ebi, Masahide; Hirata, Yoshikazu; Mizoshita, Tsutomu; Tanida, Satoshi; Kataoka, Hiromi; Kamiya, Takeshi; Higashiyama, Shigeki; Joh, Takashi

    2012-05-30

    Membrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF) yields soluble HB-EGF, which is an epidermal growth factor receptor (EGFR) ligand, and a carboxy-terminal fragment of HB-EGF (HB-EGF-CTF) after ectodomain shedding. We previously reported that HB-EGF-CTF and unshed proHB-EGF which has the cytoplasmic domain of proHB-EGF (HB-EGF-C), translocate from the plasma membrane to the nucleus and regulate cell cycle after shedding stimuli. However, the significance of nuclear exported HB-EGF-C in human gastric cancer is unclear. We investigated the relationship between intracellular localization of HB-EGF-C and clinical outcome in 96 gastric cancer patients treated with gastrectomy. Moreover, we established stable gastric cancer cell lines overexpressing wild-type HB-EGF (wt-HB-EGF) and mutated HB-EGF (HB-EGF-mC), which prevented HB-EGF-C nuclear translocation after shedding. Cell motility between these 2 gastric cancer cell lines was investigated using a transwell invasion assay and a wound healing assay. Of the 96 gastric cancer cases, HB-EGF-C immunoreactivity was detected in both the nucleus and cytoplasm in 19 cases (19.8 %) and in the cytoplasm only in 25 cases (26.0 %). The nuclear immunoreactivity of HB-EGF-C was significantly increased in stage pT3/4 tumors compared with pT1/2 tumors (T1/2 vs. T3/4: 11.1 % vs. 36.4 %, P Gastric cancer cell invasion obviously increased in wt-HB-EGF-expressing cells, but invasion in HB-EGF-mC-expressing cells showed a slight increase compared with control cells. Moreover, wt-HB-EGF overexpression increased the effectiveness of wound healing, but had no significant effect in HB-EGF-mC-expressing cells. Both the function of HB-EGF as an EGFR ligand and a novel signal for HB-EGF-C nuclear translocation induce gastric cancer growth, whereas HB-EGF-C nuclear translocation independently plays a critical role in gastric cancer invasion. The present study demonstrated that HB-EGF-C nuclear translocation

  11. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion

    International Nuclear Information System (INIS)

    Shimura, Takaya; Higashiyama, Shigeki; Joh, Takashi; Yoshida, Michihiro; Fukuda, Shinji; Ebi, Masahide; Hirata, Yoshikazu; Mizoshita, Tsutomu; Tanida, Satoshi; Kataoka, Hiromi; Kamiya, Takeshi

    2012-01-01

    HB-EGF-C nuclear translocation induce gastric cancer growth, whereas HB-EGF-C nuclear translocation independently plays a critical role in gastric cancer invasion. The present study demonstrated that HB-EGF-C nuclear translocation might be crucial in gastric cancer invasion. HB-EGF-C nuclear translocation may offer a prognostic marker and a new molecular target for gastric cancer therapy

  12. Indomethacin-induced gastric ulceration in rats: Protective roles of Spondias mombin and Ficus exasperata

    Directory of Open Access Journals (Sweden)

    Saheed Sabiu

    2015-01-01

    Full Text Available This study investigated the quantitative polyphenolic constituents and gastroprotective effects of aqueous leaf extracts of Spondias mombin and Ficus exasperata against indomethacin-induced gastric ulcer in rats. Ulceration was induced by a single oral administration of indomethacin (30 mg/kg body weight. Wistar rats were pretreated with esomeprazole (reference drug at a dose of 20 mg/kg body weight, S. mombin or F. exasperata at 100 and 200 mg/kg body weight once daily for 21 days prior to ulcer induction. At the end of the experiment, gastric secretions and antioxidant parameters were evaluated. We observed that the significantly increased (p < 0.05 ulcer index, gastric volume, malondialdehyde level and pepsin activity were effectively reduced following treatment with S. mombin and F. exasperata. The extracts also markedly attenuated the reduced activity of superoxide dismutase as well as pH and mucin content in the ulcerated rats. These findings are indicative of gastroprotective and antioxidative potentials of the extracts which is also evident in the degree of % inhibition against ulceration. The available data in this study suggest that the extracts of S. mombin and F. exasperata proved to be capable of ameliorating indomethacin-induced gastric ulceration and the probable mechanisms are via antioxidative and proton pump inhibition.

  13. Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats

    Directory of Open Access Journals (Sweden)

    Pedro M. G. Soares

    2011-03-01

    Full Text Available CONTEXT: Methotrexate and other anticancer agents can induce intestinal mucositis, which is one of the most common limiting factor that prevent further dose escalation of the methotrexate. OBJECTIVES: To evaluate the gastric emptying and gastrointestinal transit of liquids in methotrexate-induced intestinal mucositis. METHODS: Wistar rats received methotrexate (2.5 mg/kg/day for 3 days, subcutaneously or saline. After 1, 3 and 7 days, sections of duodenum, jejunum and ileum were removed for assessment of epithelial damage and myeloperoxidase activity (biochemical marker of granulocyte infiltration. Others rats were pre-treated with methotrexate or saline, gavage-fed after 3 or 7 days with a standard test liquid meal, and sacrificed 10, 20 or 30-min later. Gastric and small intestine dye recoveries were measured by spectrophotometry. RESULTS: After 3 days of methotrexate, there was an epithelial intestinal damage in all segments, with myeloperoxidase activity increase in both in duodenum and ileum. Seven days after methotrexate, we observed a complete reversion of this intestinal damage. There was an increase in gastric dye recoveries after 10, 20, and 30-min post-prandial intervals after 3 days, but not after 7 days, of methotrexate. Intestine dye recoveries were decreased in the first and second segments at 10 min, in the third at 20 min, and in the second and third at 30 min, only after 3 days of methotrexate treatment. CONCLUSION: Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats.

  14. TFF1 inhibits proliferation and induces apoptosis of gastric cancer cells in vitro

    Directory of Open Access Journals (Sweden)

    Yanli Ge

    2012-05-01

    Full Text Available Trefoil Factor Family (TFF plays an essential role in the intestinal epithelial restitution, but the relationship between TFF1 and gastric cancer (GC is still unclear. The present study aimed to determine the role of TFF1 in repairing gastric mucosa and in the pathogenesis of GC.The TFF1 expression in different gastric mucosas was measured with immunohistochemistry. Then, siRNA targeting TFF1 or plasmids expressing TFF1 gene were transfected into BGC823 cells, SGC7901 cells and GES-1 cells. The cell proliferation was detected with MTT assay and apoptosis and cell cycle measured by flow cytometry.From normal gastric mucosa to mucosa with dysplasia and to gastric cancer, the TFF1 expression had a decreasing trend. Down-regulation of TFF1 expression significantly reduced the apoptosis of three cell lines and markedly facilitated their proliferation but had no significant effect on cell cycle. Over-expression of TFF1 could promote apoptosis of three cell lines and inhibit proliferation but had no pronounced effect on cell cycle. TFF1 can inhibit proliferation and induce apoptosis of GC cells in vitro.

  15. Effects of corn oil on the volatile fatty acids in horses with induced gastric ulcers

    Directory of Open Access Journals (Sweden)

    José Martínez A

    2016-09-01

    Full Text Available Objetive. To determine the influence of corn oil on the volatile fatty acids (VFA concentrations in the gastric juice in horses with phenylbutazone (PBZ induced gastric ulcers and Correlate the gastroscopic findings with the VFA concentrations. Materials and methods. 15 horses were allotted in 3 groups. Group I (control received placebo during first 6 days (induction period and was treated with sucralfate for 2 weeks (treatment period. Groups II and III received PBZ during the induction phase. After 6 days, horses from group II received 70 mL of corn oil /100 kg of body weight/ po, twice a day, for 2 weeks and horses from group III received 90 mL of corn oil/100 kg of body weight/ po, twice a day, for 2 weeks. All horses were examined by gastroscopy at days 0, 7 and 21. The lesions were recorded and classified according to the number and severity. Samples from gastric fluid were taken to measure the concentrations of the acetic, propionic, butyric and lactic acids. Results. Both PBZ protocols produced lesions in the both non-glandular and glandular areas of the stomach. All the treatments produced healing of the injured mucosa glandular. Neither of the two corn oil treatments affected healing of the gastric ulcers located in the non-glandular area. Conclusions. The concentrations of acetic and butyric acids were highest in the gastric juice. The corn oil and sucralfate did not lead to differences in the concentration of acetic acid and butyric acid.

  16. Gastroprotective effects of several H2RAs on ibuprofen-induced gastric ulcer in rats.

    Science.gov (United States)

    Liu, Jing; Sun, Dan; He, Jinfeng; Yang, Chengli; Hu, Tingting; Zhang, Lijing; Cao, Hua; Tong, Ai-Ping; Song, Xiangrong; Xie, Yongmei; He, Gu; Guo, Gang; Luo, Youfu; Cheng, Ping; Zheng, Yu

    2016-03-15

    Ibuprofen is the first line of treatment for osteoarthritis and arthritis. The main side effects of ibuprofen especially in long-term treatment include gastric ulcer, duodenal ulcer and indigestion etc. Therefore, screening drugs with effective gastric protective effects and low toxicity for combination therapy with ibuprofen is necessary. The mechanism of gastric damage induced by ibuprofen is still unclear, however, cell damage caused by reactive oxygen species (ROS) is considered as the main reason. Preliminary screening of literature with the criteria of low toxicity led to four histamine-2 receptor antagonists (H2RAs): nizatidine, famotidine, lafutidine, and roxatidine acetate, which were selected for further investigation. These drugs were evaluated systemically by examining the gastric ulcer index, lipid peroxidation (LPO), membrane permeability, toxicity to main organs, and the influence on the activity of antioxidant enzymes, and myeloperoxidase (MPO). Nizatidine was found to be the best gastric protective agent. It exhibited excellent protective effect by increasing antioxidant enzyme activity, decreasing MPO activity, reducing LPO, and membrane permeability. Combination treatment with nizatidine and ibuprofen did not show any significant toxicity. Nizatidine was considered as a good option for combination therapy with ibuprofen especially for diseases that require long-term treatment such as arthritis and osteoarthritis. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. A randomized controlled study comparing omeprazole and cimetidine for the prophylaxis of stress-related upper gastrointestinal bleeding in patients with intracerebral hemorrhage.

    Science.gov (United States)

    Liu, Bo-lin; Li, Bing; Zhang, Xiang; Fei, Zhou; Hu, Shi-jie; Lin, Wei; Gao, Da-kuan; Zhang, Li

    2013-01-01

    Patients with intracerebral hemorrhage (ICH) are at high risk for severe stress-related upper gastrointestinal (UGI) bleeding, which is predictive of higher mortality. The aim of this study was to evaluate the effectiveness of omeprazole and cimetidine compared with a placebo in the prevention and management of stress-related UGI bleeding in patients with ICH. In a single-center, randomized, placebo-controlled study, 184 surgically treated patients with CT-proven ICH within 72 hours of ictus and negative results for gastric occult blood testing were included. Of these patients, 165 who were qualified upon further evaluation were randomized into 3 groups: 58 patients received 40 mg intravenous omeprazole every 12 hours, 54 patients received 300 mg intravenous cimetidine every 6 hours, and 53 patients received a placebo. Patients whose gastric occult blood tests were positive at admission (n = 70) and during/after the prophylaxis procedure (n = 48) were treated with high-dose omeprazole at 80 mg bolus plus 8 mg/hr infusion for 3 days, followed by 40 mg intravenous omeprazole every 12 hours for 7 days. Of the 165 assessable patients, stress-related UGI bleeding occurred in 9 (15.5%) in the omeprazole group compared with 15 patients (27.8%) in the cimetidine group and 24 patients (45.3%) in the placebo group (p = 0.003). The occurrence of UGI bleeding was significantly related to death (p = 0.022). Nosocomial pneumonia occurred in 14 patients (24.1%) receiving omeprazole, 12 (22.2%) receiving cimetidine, and 8 (15.1%) receiving placebo (p > 0.05). In patients with UGI bleeding in which high-dose omeprazole was initiated, UGI bleeding arrested within the first 3 days in 103 patients (87.3%). Omeprazole significantly reduced the morbidity of stress-related UGI bleeding in patients with ICH due to its effective prophylactic effect without increasing the risk of nosocomial pneumonia, but it did not reduce the 1-month mortality or ICU stay. Further evaluation of high

  18. Saffron Aqueous Extract Inhibits the Chemically-induced Gastric Cancer Progression in the Wistar Albino Rat

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    S. Zahra Bathaie

    2013-01-01

    Full Text Available Objective(s: Gastric cancer is the first and second leading cause of cancer related death in Iranian men and women, respectively. Gastric cancer management is based on the surgery, radiotherapy and chemotherapy. In the present study, for the first time, the beneficial effect of saffron (Crocus sativus L. aqueous extract (SAE on the 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG-induced gastric cancer in rat was investigated. Materials and Methods: MNNG was used to induce gastric cancer and then, different concentrations of SAE were administered to rats. After sacrificing, the stomach tissue was investigated by both pathologist and flow cytometry, and several biochemical parameters was determined in the plasma (or serum and stomach of rats. Results: Pathologic data indicated the induction of cancer at different stages from hyperplasia to adenoma in rats; and the inhibition of cancer progression in the gastric tissue by SAE administration; so that, 20% of cancerous rats treated with higher doses of SAE was completely normal at the end of experiment and there was no rat with adenoma in the SAE treated groups. In addition, the results of the flow cytometry/ propidium iodide staining showed that the apoptosis/proliferation ratio was increased due to the SAE treatment of cancerous rats. Moreover, the significantly increased serum LDH and decreased plasma antioxidant activity due to cancer induction fell backwards after treatment of rats with SAE. But changes in the other parameters (Ca2+, tyrosine kinase activity and carcino-embryonic antigen were not significant. Conclusion: SAE inhibits the progression of gastric cancer in rats, in a dose dependent manner.

  19. Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution.

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    Suzuki, Takahiro; Yoshida, Norimasa; Nakabe, Nami; Isozaki, Yutaka; Kajikawa, Hirokazu; Takagi, Tomohisa; Handa, Osamu; Kokura, Satoshi; Ichikawa, Hiroshi; Naito, Yuji; Matsui, Hirofumi; Yoshikawa, Toshikazu

    2008-03-01

    Aspirin and nonsteroidal anti-inflammatory agents are known to induce gastroduodenal complications such as ulcer, bleeding, and dyspepsia. In this study, we examined the prophylactic effect of rebamipide, an anti-ulcer agent with free-radical scavenging and anti-inflammatory effect, on acidified aspirin-induced gastric mucosal injury in rats. In addition, we investigated the mucosal barrier functions disrupted by aspirin. Oral administration of acidified aspirin resulted in linear hemorrhagic erosions with increasing myeloperoxidase activity and thiobarbituric acid-reactive substance concentrations in the gastric mucosa. Rebamipide suppressed these acidified aspirin-induced gastric lesions and inflammatory changes significantly, and its protective effect was more potent in the case of repeated (twice daily for 3 days) treatment than single treatment before aspirin administration. Immunostaining of zonula occludens (ZO)-1, one of the tight junctional proteins, was strengthened in rat gastric mucosa after repeated administration of rebamipide. In addition, aspirin induced the increasing transport of fluorescine isothiocyanate-labeled dextrans with localized disruption and decreased expression of ZO-1 protein on rat gastric mucosal cell line RGM-1. Rebamipide effectively prevented aspirin-induced permeability changes and disruption of ZO-1 distribution. These results suggest that rebamipide protects against aspirin-induced gastric mucosal lesions by preserving gastric epithelial cell-to cell integrity in addition to the anti-inflammatory effects.

  20. Grapefruit-seed extract attenuates ethanol-and stress-induced gastric lesions via activation of prostaglandin, nitric oxide and sensory nerve pathways

    OpenAIRE

    Brzozowski, Tomasz; Konturek, Peter C; Drozdowicz, Danuta; Konturek, Stanislaw J; Zayachivska, Oxana; Pajdo, Robert; Kwiecien, Slawomir; Pawlik, Wieslaw W; Hahn, Eckhart G

    2005-01-01

    AIM: Grapefruit-seed extract (GSE) containing flavonoids, possesses antibacterial and antioxidative properties but whether it influences the gastric defense mechanism and gastroprotection against ethanol- and stress-induced gastric lesions remains unknown.

  1. Successful treatment with a combination of endoscopic injection and irrigation with coca cola for gastric bezoar-induced gastric outlet obstruction.

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    Lin, Chen-Sheng; Tung, Chun-Fang; Peng, Yen-Chun; Chow, Wei-Keung; Chang, Chi-Sen; Hu, Wei-Hsiung

    2008-01-01

    We report a case of gastric bezoar-induced gastric outlet obstruction that was successfully treated with a combination of endoscopic injection and irrigation with Coca Cola. A 73-year-old diabetic woman had a history of perforated peptic ulcer and had received pyloroplasty more than 20 years previously. She had been ingesting Pho Pu Zi (Cordia dichotoma Forst. f.) as an appetizer for 1 month. She presented with epigastric pain, nausea, and vomiting. Upper gastrointestinal endoscopy, performed at a local hospital, showed 2 gastric bezoars in the stomach, and 1 of them impacted at the pylorus. She was referred to our emergency department for removal of the gastric bezoars that were suspected to be causing gastric outlet obstruction. All attempts at endoscopic removal using a polypectomy snare, biopsy forceps and Dormia basket failed. We then injected Coca Cola directly into the bezoar mass, followed by irrigation with Coca Cola. Follow-up endoscopy was performed the next day, which revealed that the gastric bezoars had dissolved spontaneously.

  2. Successful Treatment with a Combination of Endoscopic Injection and Irrigation with Coca Cola for Gastric Bezoar-induced Gastric Outlet Obstruction

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    Chen-Sheng Lin

    2008-01-01

    Full Text Available We report a case of gastric bezoar-induced gastric outlet obstruction that was successfully treated with a combination of endoscopic injection and irrigation with Coca Cola. A 73-year-old diabetic woman had a history of perforated peptic ulcer and had received pyloroplasty more than 20 years previously. She had been ingesting Pho Pu Zi (Cordia dichotoma Forst. f. as an appetizer for 1 month. She presented with epigastric pain, nausea, and vomiting. Upper gastrointestinal endoscopy, performed at a local hospital, showed 2 gastric bezoars in the stomach, and 1 of them impacted at the pylorus. She was referred to our emergency department for removal of the gastric bezoars that were suspected to be causing gastric outlet obstruction. All attempts at endoscopic removal using a polypectomy snare, biopsy forceps and Dormia basket failed. We then injected Coca Cola directly into the bezoar mass, followed by irrigation with Coca Cola. Follow-up endoscopy was performed the next day, which revealed that the gastric bezoars had dissolved spontaneously.

  3. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion

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    Shimura Takaya

    2012-05-01

    Full Text Available Abstract Background Membrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF yields soluble HB-EGF, which is an epidermal growth factor receptor (EGFR ligand, and a carboxy-terminal fragment of HB-EGF (HB-EGF-CTF after ectodomain shedding. We previously reported that HB-EGF-CTF and unshed proHB-EGF which has the cytoplasmic domain of proHB-EGF (HB-EGF-C, translocate from the plasma membrane to the nucleus and regulate cell cycle after shedding stimuli. However, the significance of nuclear exported HB-EGF-C in human gastric cancer is unclear. Methods We investigated the relationship between intracellular localization of HB-EGF-C and clinical outcome in 96 gastric cancer patients treated with gastrectomy. Moreover, we established stable gastric cancer cell lines overexpressing wild-type HB-EGF (wt-HB-EGF and mutated HB-EGF (HB-EGF-mC, which prevented HB-EGF-C nuclear translocation after shedding. Cell motility between these 2 gastric cancer cell lines was investigated using a transwell invasion assay and a wound healing assay. Results Of the 96 gastric cancer cases, HB-EGF-C immunoreactivity was detected in both the nucleus and cytoplasm in 19 cases (19.8 % and in the cytoplasm only in 25 cases (26.0 %. The nuclear immunoreactivity of HB-EGF-C was significantly increased in stage pT3/4 tumors compared with pT1/2 tumors (T1/2 vs. T3/4: 11.1 % vs. 36.4 %, P  Conclusions Both the function of HB-EGF as an EGFR ligand and a novel signal for HB-EGF-C nuclear translocation induce gastric cancer growth, whereas HB-EGF-C nuclear translocation independently plays a critical role in gastric cancer invasion. The present study demonstrated that HB-EGF-C nuclear translocation might be crucial in gastric cancer invasion. HB-EGF-C nuclear translocation may offer a prognostic marker and a new molecular target for gastric cancer therapy.

  4. Lactobacillus fermentum Suo Attenuates HCl/Ethanol Induced Gastric Injury in Mice through Its Antioxidant Effects

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    Huayi Suo

    2016-03-01

    Full Text Available The purpose of the study was to determine the inhibitory effects of Lactobacillus fermentum Suo (LF-Suo on HCl/ethanol induced gastric injury in ICR (Institute for Cancer Research mice and explain the mechanism of these effects through the molecular biology activities of LF-Suo. The studied mice were divided into four groups: healthy, injured, LF-Suo-L and LF-Suo-H group. After the LF-Suo intragastric administration, the gastric injury area was reduced compared to the injured group. The serum MOT (motilin, SP (substance P, ET (endothelin levels of LF-Suo treated mice were lower, and SS (somatostatin, VIP (vasoactive intestinal peptide levels were higher than the injured group mice. The cytokine IL-6 (interleukin 6, IL-12 (interleukin 12, TNF-α (tumor necrosis factor-α and IFN-γ (interferon-γ serum levels were decreased after the LF-Suo treatment. The gastric tissues SOD (superoxide dismutase, GSH-Px (glutathione peroxidase, NO (nitric oxide and activities of LF-Suo treated mice were increased and MDA (malondialdehyde activity was decreased compared to the injured group mice. By the RT-PCR assay, LF-Suo raised the occludin, EGF (epidermal growth factor, EGFR (epidermal growth factor receptor, VEGF (vascular endothelial growth factor, Fit-1 (fms-like tyrosine kinase-1, IκB-α (inhibitor kappaB-α, nNOS (neuronal nitric oxide synthase, eNOS (endothelial nitric oxide synthase, Mn-SOD, Cu/Zn-SOD, CAT (catalase mRNA or protein expressions and reduced the COX-2, NF-κB (nuclear factor kappaB, and iNOS (inducible nitric oxide synthase expressions in gastric tissues compared to the gastric injured group mice. A high concentration (1.0 × 109 CFU/kg b.w. of LF-Suo treatment showed stronger anti-gastric injury effects compared to a low concentration of (0.5 × 109 CFU/kg b.w. of LF-Suo treatment. LF-Suo also showed strong survival in pH 3.0 man-made gastric juice and hydrophobic properties. These results indicate that LF-Suo has potential use as

  5. Failure of ethamsylate to reduce aspirin-induced gastric mucosal bleeding in humans.

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    Daneshmend, T K; Stein, A G; Bhaskar, N K; Hawkey, C J

    1989-07-01

    1. We investigated the effect of the haemostatic agent ethamsylate on aspirin-induced gastric mucosal bleeding. 2. Eighteen healthy subjects were studied three times: at the end of 48 h periods of treatment with (a) placebo, (b) aspirin 600 mg four times daily, (9 doses) and (c) aspirin 600 mg four times daily with each dose preceded by ethamsylate 500 mg. 3. At the end of each treatment period gastric mucosal bleeding into timed gastric washings was quantified using the orthotolidine reaction. 4. Aspirin increased bleeding from a rate on placebo of 1.2 microliters 10 min-1 geometric mean (95% confidence limits) (0.7-1.8) microliters 10 min-1 to 20.0 (11.6-34.2) microliters 10 min-1, (P less than 0.01). The rate of bleeding after aspirin preceded by ethamsylate [14.1 (8.5-23.4) microliters 10 min-1] was not significantly different from that after aspirin alone. 5. We conclude that ethamsylate does not reduce acute aspirin-induced gastric mucosal bleeding in healthy humans.

  6. Antioxidant effects of betaine against Indomethacin-induced gastric damage in rats

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    M Alirezaei

    2016-10-01

    Full Text Available Introduction: Betaine (trimethyl glycine is known as methyl group donor and antioxidant in previous reports. The aim of this study was to assess the antioxidant effects of betaine in Indomethacin-induced gastric damages. Methods: Thirty-two adult male Sprague–Dawley rats in an experimental study were divided into four equal groups as follow: Control, Indomethacin, Betaine-indomethacin and Ascorbic acid-indomethacin. Control and indomethacin groups received normal saline and betaine and ascorbic acid-pretreated rats were administrated betaine (1.5% of the total diet and ascorbic acid (50 mg/kg body weight for 15 consecutive days, respectively. After 24 h fasting, all of the groups received indomethacin (48 mg/kg body weight and control group received distilled water. Results: Indomethacin administration increased gastric ulcer occurrence (% in comparison with control group and betaine pretreatment significantly decreased ulcer occurrence (% when compared to the other groups (P=0.0017. Gastric wall glutathione peroxidase (GPx activity was significantly lower in indomethacin group in comparison with the other groups (P=0.0012 while, betaine and ascorbic acid pretreatment increased GPx activity in comparison with indomethacin group (P=0.0012. Catalase activity was significantly higher in betaine-pretreated rats in comparison with indomethacin and ascorbic acid-indomethacin groups (P=0.0015. Lipid peroxidation significantly decreased in betaine and ascorbic acid pretreated groups (P=0.0013. Conclusion: These results showed beneficial antioxidant effects of betaine against gastric damages induced by indomethacin in rats.

  7. Methyl and isopropyl N-methylanthranilates attenuate diclofenac- and ethanol-induced gastric lesions in rats.

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    Radulović, Niko S; Jovanović, Ivan; Ilić, Ivan R; Randjelović, Pavle J; Stojanović, Nikola M; Miltojević, Ana B

    2013-11-19

    Two natural alkaloids, methyl (M) and isopropyl (I) N-methylanthranilates, with recently demonstrated significant pharmacological activities, were assayed for their possible overall effect on intact gastric mucosa and their protective properties towards the onset of gastric lesions induced by diclofenac (a non-steroidal anti-inflammatory drug, NSAID) or ethanol. The influence of I and M on gastric mucosa integrity was assessed by oral administration in doses of 200mg/kg. The gastroprotective action of I and M in doses of 50, 100 and 200mg/kg was analyzed in the diclofenac and ethanol-induced gastric lesion models in rats. After the treatment, the stomachs of the animals were analyzed (captured by a digital camera). Ulcer scoring, morphometric and histopathological analyses of the stomachs were done. The oral application of these compounds on their own, even in quite high doses (200mg/kg) did not induce gastric lesions. Both alkaloids exerted a very strong antiulcer activity, even in low doses (50mg/kg), by decreasing the number of lesions caused by the application of either diclofenac or ethanol, eliminating them completely or reducing them to a form of mucosal hyperemia. Their possible mechanism of action was discussed and due to their many positive properties including anxiolytic, antidepressant, antinociceptive, anti-inflammatory and gastroprotective activities, as well as a cheap and simple synthetic route for their preparation, methyl and isopropyl N-methylanthranilates, both alike, might represent a cost effective alternative sought for in the treatment of peptic ulcers and/or new safer NSAIDs for pain management. © 2013.

  8. Fisetin inhibits cellular proliferation and induces mitochondria-dependent apoptosis in human gastric cancer cells.

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    Sabarwal, Akash; Agarwal, Rajesh; Singh, Rana P

    2017-02-01

    The anticancer effects of fisetin, a dietary agent, are largely unknown against human gastric cancer. Herein, we investigated the mechanisms of fisetin-induced inhibition of growth and survival of human gastric carcinoma AGS and SNU-1 cells. Fisetin (25-100 μM) caused significant decrease in the levels of G1 phase cyclins and CDKs, and increased the levels of p53 and its S15 phosphorylation in gastric cancer cells. We also observed that growth suppression and death of non-neoplastic human intestinal FHs74int cells were minimally affected by fisetin. Fisetin strongly increased apoptotic cells and showed mitochondrial membrane depolarization in gastric cancer cells. DNA damage was observed as early as 3 h after fisetin treatment which was accompanied with gamma-H2A.X(S139) phosphorylation and cleavage of PARP. Fisetin-induced apoptosis was observed to be independent of p53. DCFDA and MitoSOX analyses showed an increase in mitochondrial ROS generation in time- and dose-dependent fashion. It also increased cellular nitrite and superoxide generation. Pre-treatment with N-acetyl cysteine (NAC) inhibited ROS generation and also caused protection from fisetin-induced DNA damage. The formation of comets were observed in only fisetin treated cells which was blocked by NAC pre-treatment. Further investigation of the source of ROS, using mitochondrial respiratory chain (MRC) complex inhibitors, suggested that fisetin caused ROS generation specifically through complex I. Collectively, these results for the first time demonstrated that fisetin possesses anticancer potential through ROS production most likely via MRC complex I leading to apoptosis in human gastric carcinoma cells. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. A biochemical study on the gastroprotective effect of andrographolide in rats induced with gastric ulcer.

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    Saranya, P; Geetha, A; Selvamathy, S M K Narmadha

    2011-09-01

    The major objective of the study was to evaluate the gastroprotective property of andrographolide, a chief component of the leaves of Andrographis paniculata in terms of the ulcer preventive effect in rats. An acute toxicity test was conducted with different concentrations of andrographolide to determine the LD(50) value. The dose responsive study was conducted in rats pretreated with andrographolide (1, 3 and 5 mg/kg) for a period of 30 days, prior to ulcer induction by administering ethanol, aspirin or by pyloric ligation. The ulcer protective efficacy was tested by determining the ulcer score, pH, pepsin, titrable acidity, gastric mucin, lipid peroxides, reduced glutathione, and enzymatic antioxidants superoxide dismutase, catalase and glutathione peroxidase in gastric tissue. The activities of H(+)-K(+) ATPase and myeloperoxidase were also determined in gastric tissue. The LD(50) value was found to be 48 mg/kg b. wt and the effective dose was found to be 3 mg/kg. We have observed a significant reduction in the ulcer score in rats pretreated with 3 mg of andrographolide/kg body weight. A favourable increase in the pH and decrease in titrable acidity were observed in the gastric fluid of rats pretreated with the test drug. The gastric tissue H(+)-K(+) ATPase and myeloperoxidase activities were elevated in ulcer-induced animals. The elevation in the enzyme activity was significantly minimized in the andrographolide received animals. The antioxidants and mucin levels were significantly maintained in the gastric tissue of drug-pretreated animals. Andrographolide did not produce any toxic effects in normal rats. This study reveals that the ulcer preventive efficacy of andrographolide may probably due to its antioxidant, cytoprotective and antiacid secretory effects.

  10. Differential effects of omeprazole and lansoprazole enantiomers on aryl hydrocarbon receptor in human hepatocytes and cell lines.

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    Novotna, Aneta; Srovnalova, Alzbeta; Svecarova, Michaela; Korhonova, Martina; Bartonkova, Iveta; Dvorak, Zdenek

    2014-01-01

    Proton pump inhibitors omeprazole and lansoprazole contain chiral sulfur atom and they are administered as a racemate, i.e. equimolar mixture of S- and R-enantiomers. The enantiopure drugs esomeprazole and dexlansoprazole have been developed and introduced to clinical practice due to their improved clinical and therapeutic properties. Since omeprazole and lansoprazole are activators of aryl hydrocarbon receptor (AhR) and inducers of CYP1A genes, we examined their enantiospecific effects on AhR-CYP1A pathway in human cancer cells and primary human hepatocytes. We performed gene reporter assays for transcriptional activity of AhR, RT-PCR analyses for CYP1A1/2 mRNAs, western blots for CYP1A1/2 proteins and EROD assay for CYP1A1/2 catalytic activity. Lansoprazole and omeprazole enantiomers displayed differential effects on AhR-CYP1A1/2 pathway. In general, S-enantiomers were stronger activators of AhR and inducers of CYP1A genes as compared to R-enantiomers in lower concentrations, i.e. 1-10 µM for lansoprazole and 10-100 µM for omeprazole. In contrast, R-enantiomers were stronger AhR activators and CYP1A inducers than S-enantiomers in higher concentrations, i.e. 100 µM for lansoprazole and 250 µM for omeprazole. In conclusion, we provide the first evidence of enantiospecific effects of omeprazole and lansoprazole on AhR signaling pathway.

  11. Changes in gastric microbiota induced by Helicobacter pylori infection and preventive effects of Lactobacillus plantarum ZDY 2013 against such infection.

    Science.gov (United States)

    Pan, Mingfang; Wan, Cuixiang; Xie, Qiong; Huang, Renhui; Tao, Xueying; Shah, Nagendra P; Wei, Hua

    2016-02-01

    Helicobacter pylori is a gram-negative pathogen linked to gastric ulcers and stomach cancer. Gastric microbiota might play an essential role in the pathogenesis of these stomach diseases. In this study, we investigated the preventive effect of a probiotic candidate Lactobacillus plantarum ZDY 2013 as a protective agent against the gastric mucosal inflammation and alteration of gastric microbiota induced by H. pylori infection in a mouse model. Prior to infection, mice were pretreated with or without 400 µL of L. plantarum ZDY 2013 at a concentration of 10(9) cfu/mL per mouse. At 6 wk postinfection, gastric mucosal immune response and alteration in gastric microbiota mice were examined by quantitative real-time PCR and high-throughput 16S rRNA gene amplicon sequencing, respectively. The results showed that L. plantarum ZDY 2013 pretreatment prevented increase in inflammatory cytokines (e.g., IL-1β and IFN-γ) and inflammatory cell infiltration in gastric lamina propria induced by H. pylori infection. Weighted UniFrac principal coordinate analysis showed that L. plantarum ZDY 2013 pretreatment prevented the alteration in gastric microbiota post-H. pylori infection. Linear discriminant analysis coupled with effect size identified 22 bacterial taxa (e.g., Pasteurellaceae, Erysipelotrichaceae, Halomonadaceae, Helicobacteraceae, and Spirochaetaceae) that overgrew in the gastric microbiota of H. pylori-infected mice, and most of them belonged to the Proteobacteria phylum. Lactobacillus plantarum ZDY 2013 pretreatment prevented this alteration; only 6 taxa (e.g., Lachnospiraceae, Ruminococcaceae, and Clostridiaceae), mainly from the taxa of Firmicutes and Bacteroidetes, were dominant in the gastric microbiota of the L. plantarum ZDY 2013 pretreated mice. Administration of L. plantarum ZDY 2013 for 3 wk led to increase in several bacterial taxa (e.g., Rikenella, Staphylococcus, Bifidobacterium), although a nonsignificant alteration was found in the gastric microbiota

  12. Comparison of the effect of a single dose of omeprazole or lansoprazole on intragastric pH in Japanese participants: a two-way crossover study.

    Science.gov (United States)

    Funaki, Yasushi; Tokudome, Kentaro; Izawa, Shinya; Tamura, Yasuhiro; Kondo, Yoshihiro; Iida, Akihito; Mizuno, Mari; Ogasawara, Naotaka; Sasaki, Makoto; Kasugai, Kunio

    2013-03-01

    It is known that the pharmacokinetic profile of proton pump inhibitors (PPIs) after postprandial administration may differ among PPIs. The purpose of this study was to compare the inhibitory effects of gastric acid secretion by PPIs administered after a meal, based on a 24-hour intragastric pH monitoring. Ten healthy men who provided written informed consent participated in the study. They were given a 20-mg omeprazole tablet and a 30-mg lansoprazole orally dispersing tablet in a two-way crossover manner. At baseline, the anti-HP-IgG antibody levels in blood and the pepsinogen (PG) I/II ratio were measured. Participants were given a standardized meal and 200 mL of water at 9:30 am, 13:30 pm, and 18.30 pm. Participants took the PPI after breakfast. Two of the ten participants tested positive for Helicobacter pylori infection. The PG I/II ratio indicated negative gastric atrophy in all the participants. The percentage 24-hour intragastric pH > 4 holding times (median, range) with omeprazole and lansoprazole were 29.3, 19.3-50.0% and 27.8, 13.0-42.3%, respectively, which shows that with the administration of omeprazole, the pH was maintained at >4 for a longer period (p lansoprazole (p lansoprazole, a single postprandial dose of omeprazole showed a more rapid and sustained acid-inhibitory effect. Copyright © 2012. Published by Elsevier B.V.

  13. Amiodarone-induced hyperthyroidism during massive weight loss following gastric bypass.

    Science.gov (United States)

    Bourron, Olivier; Ciangura, Cécile; Bouillot, Jean-Luc; Massias, Laurent; Poitou, Christine; Oppert, Jean-Michel

    2007-11-01

    Gastric bypass is increasingly used in morbidly obese patients to achieve significant reduction of body weight and fat mass and concurrent improvement in co-morbidities. We report the case of a 53-year-old male patient (141 kg, BMI 50 kg/m2), successfully treated by amiodarone for supraventricular arrythmia, who underwent Roux-en-Y gastric bypass (RYGBP). 6 months after surgery, he had lost 45% of his preoperative weight (44.8% of weight loss was lean mass) and developed amiodarone-induced subclinical hyperthyroidism. We hypothesize the following sequence of events: weight loss after RYGBP, therefore fat loss, decrease in distribution volume of amiodarone inducing iodine overload and hyperthyroidism, reinforcing weight loss and particularly loss of lean mass. This report emphasizes the importance of careful monitoring of weight and body composition changes after RYGBP. In this situation, checking thyroid status is recommended, especially when there is a history of thyroid disease or potentially toxic thyroid medication.

  14. Remodeling of the residual gastric mucosa after roux-en-y gastric bypass or vertical sleeve gastrectomy in diet-induced obese rats.

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    Konstantinos Arapis

    Full Text Available Whereas the remodeling of intestinal mucosa after bariatric surgeries has been the matter of numerous studies to our knowledge, very few reported on the remodeling of the residual gastric mucosa. In this study, we analyzed remodeling of gastric mucosa after Roux-en-Y gastric bypass (RYGB and vertical sleeve gastrectomy (VSG in rats. Diet-induced obese rats were subjected to RYGB, VSG or sham surgical procedures. All animals were assessed for food intake, body-weight, fasting blood, metabolites and hormones profiling, as well as insulin and glucose tolerance tests before and up to 5 weeks post-surgery. Remodeling of gastric tissues was analyzed by routine histology and immunohistochemistry studies, and qRT-PCR analyses of ghrelin and gastrin mRNA levels. In obese rats with impaired glucose tolerance, VSG and RYGB caused substantial weight loss and rats greatly improved their oral glucose tolerance. The remaining gastric mucosa after VSG and gastric pouch (GP after RYGB revealed a hyperplasia of the mucous neck cells that displayed a strong immunoreactivity for parietal cell H+/K+-ATPase. Ghrelin mRNA levels were reduced by 2-fold in remaining fundic mucosa after VSG and 10-fold in GP after RYGB. In the antrum, gastrin mRNA levels were reduced after VSG in line with the reduced number of gastrin positive cells. This study reports novel and important observations dealing with the remaining gastric mucosa after RYGB and VSG. The data demonstrate, for the first time, a hyperplasia of the mucous neck cells, a transit cell population of the stomach bearing differentiating capacities into zymogenic and peptic cells.

  15. Curcumin Inhibits Gastric Inflammation Induced by Helicobacter Pylori Infection in a Mouse Model

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    António M. Santos

    2015-01-01

    Full Text Available Helicobacter pylori (H. pylori infection triggers a sequence of gastric alterations starting with an inflammation of the gastric mucosa that, in some cases, evolves to gastric cancer. Efficient vaccination has not been achieved, thus it is essential to find alternative therapies, particularly in the nutritional field. The current study evaluated whether curcumin could attenuate inflammation of the gastric mucosa due to H. pylori infection. Twenty-eight C57BL/6 mice, were inoculated with the H. pylori SS1 strain; ten non-infected mice were used as controls. H. pylori infection in live mice was followed-up using a modified 13C-Urea Breath Test (13C-UBT and quantitative real-time polymerase chain reaction (PCR. Histologically confirmed, gastritis was observed in 42% of infected non-treated mice at both 6 and 18 weeks post-infection. These mice showed an up-regulation of the expression of inflammatory cytokines and chemokines, as well as of toll-like receptors (TLRs and MyD88, at both time points. Treatment with curcumin decreased the expression of all these mediators. No inflammation was observed by histology in this group. Curcumin treatment exerted a significant anti-inflammatory effect in H. pylori-infected mucosa, pointing to the promising role of a nutritional approach in the prevention of H. pylori induced deleterious inflammation while the eradication or prevention of colonization by effective vaccine is not available.

  16. Milk fermented by Propionibacterium freudenreichii induces apoptosis of HGT-1 human gastric cancer cells.

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    Fabien J Cousin

    Full Text Available Gastric cancer is one of the most common cancers in the world. The "economically developed countries" life style, including diet, constitutes a risk factor favoring this cancer. Diet modulation may lower digestive cancer incidence. Among promising food components, dairy propionibacteria were shown to trigger apoptosis of human colon cancer cells, via the release of short-chain fatty acids acetate and propionate.A fermented milk, exclusively fermented by P. freudenreichii, was recently designed. In this work, the pro-apoptotic potential of this new fermented milk was demonstrated on HGT-1 human gastric cancer cells. Fermented milk supernatant induced typical features of apoptosis including chromatin condensation, formation of apoptotic bodies, DNA laddering, cell cycle arrest and emergence of a subG1 population, phosphatidylserine exposure at the plasma membrane outer leaflet, reactive oxygen species accumulation, mitochondrial transmembrane potential disruption, caspase activation and cytochrome c release. Remarkably, this new fermented milk containing P. freudenreichii enhanced the cytotoxicity of camptothecin, a drug used in gastric cancer chemotherapy.Such new probiotic fermented milk may thus be useful as part of a preventive diet designed to prevent gastric cancer and/or as a food supplement to potentiate cancer therapeutic treatments.

  17. Neural Mechanisms and Delayed Gastric Emptying of Liquid Induced Through Acute Myocardial Infarction in Rats

    International Nuclear Information System (INIS)

    Nunez, Wilson Ranu Ramirez; Ozaki, Michiko Regina; Vinagre, Adriana Mendes; Collares, Edgard Ferro; Almeida, Eros Antonio de

    2015-01-01

    In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABA B receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABA B receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABA B receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN

  18. β-Elemene-induced autophagy protects human gastric cancer cells from undergoing apoptosis

    International Nuclear Information System (INIS)

    Liu, Jing; Zhang, Ye; Qu, Jinglei; Xu, Ling; Hou, Kezuo; Zhang, Jingdong; Qu, Xiujuan; Liu, Yunpeng

    2011-01-01

    β-Elemene, a compound found in an herb used in traditional Chinese medicine, has shown promising anti-cancer effects against a broad spectrum of tumors. The mechanism by which β-elemene kills cells remains unclear. The aim of the present study is to investigate the anti-tumor effect of β-elemene on human gastric cancer cells and the molecular mechanism involved. β-Elemene inhibited the viability of human gastric cancer MGC803 and SGC7901 cells in a dose-dependent manner. The suppression of cell viability was due to the induction of apoptosis. A robust autophagy was observed in the cells treated with β-elemene; it was characterized by the increase of punctate LC3 dots, the cellular morphology, and the increased levels of LC3-II protein. Further study showed that β-elemene treatment up-regulated Atg5-Atg12 conjugated protein but had little effect on other autophagy-related proteins. PI3K/Akt/mTOR/p70S6K1 activity was inhibited by β-elemene. Knockdown of Beclin 1 with small interfering RNA, or co-treatment with the autophagy inhibitor, 3-methyladenine or chlorochine enhanced significantly the antitumor effects of β-elemene. Our data provides the first evidence that β-elemene induces protective autophagy and prevents human gastric cancer cells from undergoing apoptosis. A combination of β-elemene with autophagy inhibitor might thus be a useful therapeutic option for advanced gastric cancer

  19. Milk Fermented by Propionibacterium freudenreichii Induces Apoptosis of HGT-1 Human Gastric Cancer Cells

    Science.gov (United States)

    Cousin, Fabien J.; Jouan-Lanhouet, Sandrine; Dimanche-Boitrel, Marie-Thérèse; Corcos, Laurent; Jan, Gwénaël

    2012-01-01

    Background Gastric cancer is one of the most common cancers in the world. The “economically developed countries” life style, including diet, constitutes a risk factor favoring this cancer. Diet modulation may lower digestive cancer incidence. Among promising food components, dairy propionibacteria were shown to trigger apoptosis of human colon cancer cells, via the release of short-chain fatty acids acetate and propionate. Methodology/Principal Findings A fermented milk, exclusively fermented by P. freudenreichii, was recently designed. In this work, the pro-apoptotic potential of this new fermented milk was demonstrated on HGT-1 human gastric cancer cells. Fermented milk supernatant induced typical features of apoptosis including chromatin condensation, formation of apoptotic bodies, DNA laddering, cell cycle arrest and emergence of a subG1 population, phosphatidylserine exposure at the plasma membrane outer leaflet, reactive oxygen species accumulation, mitochondrial transmembrane potential disruption, caspase activation and cytochrome c release. Remarkably, this new fermented milk containing P. freudenreichii enhanced the cytotoxicity of camptothecin, a drug used in gastric cancer chemotherapy. Conclusions/Significance Such new probiotic fermented milk may thus be useful as part of a preventive diet designed to prevent gastric cancer and/or as a food supplement to potentiate cancer therapeutic treatments. PMID:22442660

  20. Cryptolepine, isolated from Sida acuta, sensitizes human gastric adenocarcinoma cells to TRAIL-induced apoptosis.

    Science.gov (United States)

    Ahmed, Firoj; Toume, Kazufumi; Ohtsuki, Takashi; Rahman, Mahmudur; Sadhu, Samir Kumar; Ishibashi, Masami

    2011-01-01

    Bioassay guided separation of Sida acuta whole plants led to the isolation of an alkaloid, cryptolepine (1), along with two kaempferol glycosides (2-3). Compound 1 showed strong activity in overcoming TRAIL-resistance in human gastric adenocarcinoma (AGS) cells at 1.25, 2.5 and 5 μm. Combined treatment of 1 and TRAIL sensitized AGS cells to TRAIL-induced apoptosis at the aforementioned concentrations. Copyright © 2010 John Wiley & Sons, Ltd.

  1. Anthraquinone G503 Induces Apoptosis in Gastric Cancer Cells through the Mitochondrial Pathway

    Science.gov (United States)

    Li, Shuai; Duan, Junting; Ye, Fang; Li, Hanxiang; She, Zhigang; Gao, Guoquan; Yang, Xia

    2014-01-01

    G503 is an anthraquinone compound isolated from the secondary metabolites of a mangrove endophytic fungus from the South China Sea. The present study elucidates the anti-tumor activity and the underlying mechanism of G503. Cell viability assay performed in nine cancer cell lines and two normal cell lines demonstrated that the gastric cancer cell line SGC7901 is the most G503-sensitive cancer cells. G503 induced SGC7901 cell death via apoptosis. G503 exposure activated caspases-3, -8 and -9. Pretreatment with the pan-caspase inhibitor Z-VAD-FMK and caspase-9 inhibitor Z-LEHD-FMK, but not caspase-8 inbibitor Z-IETD-FMK, attenuated the effect of G503. These results suggested that the intrinsic mitochondrial apoptosis pathway, rather than the extrinsic pathway, was involved in G503-induced apoptosis. Furthermore, G503 increased the ratio of Bax to Bcl-2 in the mitochondria and decreased the ratio in the cytosol. G503 treatment resulted in mitochondrial depolarization, cytochrome c release and the subsequent cleavage of caspase -9 and -3. Moreover, it is reported that the endoplasmic reticulum apoptosis pathway may also be activated by G503 by inducing capase-4 cleavage. In consideration of the lower 50% inhibitory concentration for gastric cancer cells, G503 may serve as a promising candidate for gastric cancer chemotherapy. PMID:25268882

  2. Protective Effect of Repeatedly Preadministered Brazilian Propolis Ethanol Extract against Stress-Induced Gastric Mucosal Lesions in Rats

    Directory of Open Access Journals (Sweden)

    Tadashi Nakamura

    2014-01-01

    Full Text Available The present study was conducted to clarify the protective effect of Brazilian propolis ethanol extract (BPEE against stress-induced gastric mucosal lesions in rats. The protective effect of BPEE against gastric mucosal lesions in male Wistar rats exposed to water-immersion restraint stress (WIRS for 6 h was compared between its repeated preadministration (50 mg/kg/day, 7 days and its single preadministration (50 mg/kg. The repeated BPEE preadministration attenuated WIRS-induced gastric mucosal lesions and gastric mucosal oxidative stress more largely than the single BPEE preadministration. In addition, the repeated BPEE preadministration attenuated neutrophil infiltration in the gastric mucosa of rats exposed to WIRS. The protective effect of the repeated preadministration of BPEE against WIRS-induced gastric mucosal lesions was similar to that of a single preadministration of vitamin E (250 mg/kg in terms of the extent and manner of protection. From these findings, it is concluded that BPEE preadministered in a repeated manner protects against gastric mucosal lesions in rats exposed to WIRS more effectively than BPEE preadministered in a single manner possibly through its antioxidant and anti-inflammatory actions.

  3. Healing Potential of Picrorhiza kurroa (Scrofulariaceae rhizomes against indomethacin-induced gastric ulceration: a mechanistic exploration.

    Directory of Open Access Journals (Sweden)

    Bandyopadhyay Sandip K

    2008-01-01

    Full Text Available Abstract Background The present study was undertaken to evaluate the potential of the rhizomes of the Indian medicinal plant, Picrorhiza kurroa in healing indomethacin-induced acute stomach ulceration in mice and examine its capacity to modulate oxidative stress and the levels of prostaglandin (PGE2 and EGF during the process. Methods Male swiss albino mice, ulcerated with indomethacin (18 mg/kg, p. o., single dose were treated up to 7 days with different doses of the methanol extract of P. kurroa rhizomes (designated as PK. The healing capacity of the most effective dose of PK (20 mg/kg, p. o. × 3 d was compared with that of omeprazole (Omez (3 mg/kg, p. o. × 3 d. The effects of the drug-treatment for one and three days on the biochemical parameters were assessed by comparing the results with that of untreated mice of the 1st and 3rd day of ulceration. The stomach tissues of the mice were used for the biochemical analysis. Results The macroscopic indices revealed maximum ulceration on the 3rd day after indomethacin administration, which was effectively healed by PK. Under the optimized treatment regime, PK and Omez reduced the ulcer indices by 45.1% (P P Compared to the ulcerated untreated mice, those treated with PK for 3 days showed decreased the levels of thiobarbituric acid reactive substances (TBARS (32.7%, P P P 2 (21.4%, P P P P P P P Conclusion PK (20 mg/kg, p. o. × 3 days could effectively heal indomethacin-induced stomach ulceration in mice by reducing oxidative stress, and promoting mucin secretion, prostaglandin synthesis and augmenting expressions of cyclooxygenase enzymes and growth factors.

  4. Protective effect of Korean Red Ginseng extract against Helicobacter pylori-induced gastric inflammation in Mongolian gerbils

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    Minkyung Bae

    2014-01-01

    Full Text Available Helicobacter pylori-induced gastric inflammation includes induction of inflammatory mediators interleukin (IL-8 and inducible nitric oxide synthase (iNOS, which are mediated by oxidant-sensitive transcription factor NF-κB. High levels of lipid peroxide (LPO and increased activity of myeloperoxidase (MPO, a biomarker of neutrophil infiltration, are observed in H. pylori-infected gastric mucosa. Panax ginseng Meyer, a Korean herb medicine, is widely used in Asian countries for its biological activities including anti-inflammatory efficacy. The present study aims to investigate whether Korean Red Ginseng extract (RGE inhibits H. pylori-induced gastric inflammation in Mongolian gerbils. One wk after intragastric inoculation with H. pylori, Mongolian gerbils were fed with either the control diet or the diet containing RGE (200 mg RGE/gerbil for 6 wk. The following were determined in gastric mucosa: the number of viable H. pylori in stomach; MPO activity; LPO level; mRNA and protein levels of keratinocyte chemoattractant factor (KC, a rodent IL-8 homolog, IL-1β, and iNOS; protein level of phospho-IκBα (which reflects the activation of NF-κB; and histology. As a result, RGE suppressed H. pylori-induced mRNA and protein levels of KC, IL-1β, and iNOS in gastric mucosa. RGE also inhibited H. pylori-induced phosphorylation of IκBα and increases in LPO level and MPO activity of gastric mucosa. RGE did not affect viable H. pylori colonization in the stomach, but improved the histological grade of infiltration of polymorphonuclear neutrophils, intestinal metaplasia, and hyperplasia. In conclusion, RGE inhibits H. pylori-induced gastric inflammation by suppressing induction of inflammatory mediators (KC, IL-1β, iNOS, MPO activity, and LPO level in H. pylori-infected gastric mucosa.

  5. Petroselinum Crispum is Effective in Reducing Stress-Induced Gastric Oxidative Damage

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    Ayşin Akıncı

    2017-02-01

    Full Text Available Background: Oxidative stress has been shown to play a principal role in the pathogenesis of stress-induced gastric injury. Parsley (Petroselinum crispum contains many antioxidants such as flavanoids, carotenoids and ascorbic acid. Aims: In this study, the histopathological and biochemical results of nutrition with a parsley-rich diet in terms of eliminating stress-induced oxidative gastric injury were evaluated. Study Design: Animal experimentation. Methods: Forty male Wistar albino rats were divided into five groups: control, stress, stress + standard diet, stress + parsley-added diet and stress + lansoprazole (LPZ groups. Subjects were exposed to 72 hours of fasting and later immobilized and exposed to the cold at +4 degrees for 8 hours to create a severe stress condition. Samples from the animals’ stomachs were arranged for microscopic and biochemical examinations. Results: Gastric mucosal injury was obvious in rats exposed to stress. The histopathologic damage score of the stress group (7.00±0.57 was higher than that of the control group (1.50±0.22 (p<0.05. Significant differences in histopathologic damage score were found between the stress and stress + parsley-added diet groups (p<0.05, the stress and stress + standard diet groups (p<0.05, and the stress and stress + LPZ groups (p<0.05. The mean tissue malondialdehyde levels of the stress + parsley-added group and the stress + LPZ group were lower than that of the stress group (p<0.05. Parsley supported the cellular antioxidant system by increasing the mean tissue glutathione level (53.31±9.50 and superoxide dismutase (15.18±1.05 and catalase (16.68±2.29 activities. Conclusion: Oral administration of parsley is effective in reducing stress-induced gastric injury by supporting the cellular antioxidant defence system

  6. Helicobacter pylori induces cell migration and invasion through casein kinase 2 in gastric epithelial cells.

    Science.gov (United States)

    Lee, Yeo Song; Lee, Do Yeon; Yu, Da Yeon; Kim, Shin; Lee, Yong Chan

    2014-12-01

    Chronic infection with Helicobacter pylori (H. pylori) is causally linked with gastric carcinogenesis. Virulent H. pylori strains deliver bacterial CagA into gastric epithelial cells. Induction of high motility and an elongated phenotype is considered to be CagA-dependent process. Casein kinase 2 plays a critical role in carcinogenesis through signaling pathways related to the epithelial mesenchymal transition. This study was aimed to investigate the effect of H. pylori infection on the casein kinase 2-mediated migration and invasion in gastric epithelial cells. AGS or MKN28 cells as human gastric epithelial cells and H. pylori strains Hp60190 (ATCC 49503, CagA(+)) and Hp8822 (CagA(-)) were used. Cells were infected with H. pylori at multiplicity of infection of 100 : 1 for various times. We measured in vitro kinase assay to examine casein kinase 2 activity and performed immunofluorescent staining to observe E-cadherin complex. We also examined β-catenin transactivation through promoter assay and MMP7 expression by real-time PCR and ELISA. H. pylori upregulates casein kinase 2 activity and inhibition of casein kinase 2 in H. pylori-infected cells profoundly suppressed cell invasiveness and motility. We confirmed that casein kinase 2 mediates membranous α-catenin depletion through dissociation of the α-/β-catenin complex in H. pylori-infected cells. We also found that H. pylori induces β-catenin nuclear translocation and increases MMP7 expressions mediated through casein kinase 2. We show for the first time that CagA(+) H. pylori upregulates cellular invasiveness and motility through casein kinase 2. The demonstration of a mechanistic interplay between H. pylori and casein kinase 2 provides important insights into the role of CagA(+) H. pylori in the gastric cancer invasion and metastasis. © 2014 John Wiley & Sons Ltd.

  7. Preformulation Studies for Generic Omeprazole Magnesium Enteric Coated Tablets

    Directory of Open Access Journals (Sweden)

    C. O. Migoha

    2015-01-01

    Full Text Available Preformulation is an important step in the rational formulation of an active pharmaceutical ingredient (API. Micromeritics properties: bulk density (BD and tapped density (TD, compressibility index (Carr’s index, Hauser’s ratio (H, and sieve analysis were performed in order to determine the best excipients to be used in the formulation development of omeprazole magnesium enteric coated tablets. Results show that omeprazole magnesium has fair flow and compressibility properties (BD 0.4 g/mL, TD 0.485 g/mL, Carr’s index 17.5%, Hauser’s ratio 1.2, and sieve analysis time 5 minutes. There were no significant drug excipient interactions except change in colour in all three conditions in the mixture of omeprazole and aerosil 200. Moisture content loss on drying in all three conditions was not constant and the changes were attributed to surrounding environment during the test time. Changes in the absorption spectra were noted in the mixture of omeprazole and water aerosil only in the visible region of 350–2500 nm. Omeprazole magnesium alone and with all excipients showed no significant changes in omeprazole concentration for a 30-day period. Omeprazole magnesium formulation complies with USP standards with regards to the fineness, flowability, and compressibility of which other excipients can be used in the formulation.

  8. Helicobacter pylori induces vascular endothelial growth factor production in gastric epithelial cells through hypoxia-inducible factor-1α-dependent pathway.

    Science.gov (United States)

    Kang, Min-Jung; Song, Eun-Jung; Kim, Bo-Yeon; Kim, Dong-Jae; Park, Jong-Hwan

    2014-12-01

    Although Helicobacter pylori have been known to induce vascular endothelial growth factor (VEGF) production in gastric epithelial cells, the precise mechanism for cellular signaling is incompletely understood. In this study, we investigated the role of bacterial virulence factor and host cellular signaling in VEGF production of H. pylori-infected gastric epithelial cells. We evaluated production of VEGF, activation of nuclear factor nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs) and hypoxia-inducible factor-1α (HIF-1α) stabilization in gastric epithelial cells infected with H. pylori WT or isogenic mutants deficient in type IV secretion system (T4SS). H. pylori induced VEGF production in gastric epithelial cells via both T4SS-dependent and T4SS-independent pathways, although T4SS-independent pathway seems to be the dominant signaling. The inhibitor assay implicated that activation of NF-κB and MAPKs is dispensable for H. pylori-induced VEGF production in gastric epithelial cells. H. pylori led to HIF-1α stabilization in gastric epithelial cells independently of T4SS, NF-κB, and MAPKs, which was essential for VEGF production in these cells. N-acetyl-cysteine (NAC), a reactive oxygen species (ROS) inhibitor, treatment impaired H. pylori-induced HIF-1α stabilization and VEGF production in gastric epithelial cells. We defined the important role of ROS-HIF-1α axis in VEGF production of H. pylori-infected gastric epithelial cells, and bacterial T4SS has a minor role in H. pylori-induced VEGF production of gastric epithelial cells. © 2014 John Wiley & Sons Ltd.

  9. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion

    Science.gov (United States)

    2012-01-01

    and a novel signal for HB-EGF-C nuclear translocation induce gastric cancer growth, whereas HB-EGF-C nuclear translocation independently plays a critical role in gastric cancer invasion. The present study demonstrated that HB-EGF-C nuclear translocation might be crucial in gastric cancer invasion. HB-EGF-C nuclear translocation may offer a prognostic marker and a new molecular target for gastric cancer therapy. PMID:22646534

  10. Allium Cepa Ameliorates Ethanol-Induced Gastric Injury in Rats Via ...

    African Journals Online (AJOL)

    ACER

    (SOD) and Catalase (CAT) activities) were carried out in plasma and gastric tissue. ... glandular destruction in the gastric mucosa and infiltration of inflammatory ... Gastric injury is one of major diseases affecting ..... inflammatory bowel disease.

  11. on indomethacin-induced gastric ulcer in rats

    African Journals Online (AJOL)

    Balogun

    2013-08-07

    Aug 7, 2013 ... gastroprotective activity in animal studies (Malairajan et al., 2007; Rao et al., ... of the stem in water has been demonstrated to exhibit a high anti-parasitic .... kidney and blood cells, it induces single strand breaks. (Traore et al.

  12. Pharmacological Correction of Stress-Induced Gastric Ulceration by Novel Small-Molecule Agents with Antioxidant Profile

    Directory of Open Access Journals (Sweden)

    Konstantin V. Kudryavtsev

    2014-01-01

    Full Text Available This study was designed to determine novel small-molecule agents influencing the pathogenesis of gastric lesions induced by stress. To achieve this goal, four novel organic compounds containing structural fragments with known antioxidant activity were synthesized, characterized by physicochemical methods, and evaluated in vivo at water immersion restraint conditions. The levels of lipid peroxidation products and activities of antioxidative system enzymes were measured in gastric mucosa and correlated with the observed gastroprotective activity of the active compounds. Prophylactic single-dose 1 mg/kg treatment with (2-hydroxyphenylthioacetyl derivatives of L-lysine and L-proline efficiently decreases up to 86% stress-induced stomach ulceration in rats. Discovered small-molecule antiulcer agents modulate activities of gastric mucosa tissue superoxide dismutase, catalase, and xanthine oxidase in concerted directions. Gastroprotective effect of (2-hydroxyphenylthioacetyl derivatives of L-lysine and L-proline at least partially depends on the correction of gastric mucosa oxidative balance.

  13. A Prospective, Placebo-Controlled Pilot Evaluation of the Effect of Omeprazole on Serum Calcium, Magnesium, Cobalamin, Gastrin Concentrations, and Bone in Cats.

    Science.gov (United States)

    Gould, E; Clements, C; Reed, A; Giori, L; Steiner, J M; Lidbury, J A; Suchodolski, J S; Brand, M; Moyers, T; Emery, L; Tolbert, M K

    2016-05-01

    Chronic proton pump inhibitor administration has been associated with electrolyte and cobalamin deficiency, disrupted bone homeostasis, hypergastrinemia, and rebound acid hypersecretion in humans. It is unknown if this occurs in cats. Prolonged oral omeprazole results in altered bone mineral density or content, serum calcium, magnesium, cobalamin, and gastrin concentrations in healthy cats. Six healthy adult DSH cats. In a within subjects, before and after design, cats received placebo followed by omeprazole (0.83-1.6 mg/kg PO q12h) for 60 days each. Analysis of serum calcium, magnesium, cobalamin, and gastrin concentrations was performed on days 0, 30, and 60. Bone density and content were evaluated on days 0 and 60 of each intervention. Continuous data were analyzed using a two-way ANOVA (α = 0.006). On day 60 of omeprazole administration, continuous intragastric pH monitoring was performed in 2 cats to evaluate the effects of abrupt withdrawal of omeprazole. No significant changes were detected between treatments for any variables, except serum gastrin, which was significantly higher during omeprazole treatment in comparison to placebo (P = 0.002). Evidence of gastric hyperacidity was seen in both cats in which intragastric pH monitoring was performed following cessation of omeprazole. Although further studies with larger populations of cats will be needed to draw any definitive conclusions, these preliminary results suggest that prolonged PPI treatment results in hypergastrinemia and abrupt PPI withdrawal might result in RAH in cats. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  14. Aloe vera attenuated gastric injury on indomethacin-induced gastropathy in rats.

    Science.gov (United States)

    Werawatganon, Duangporn; Rakananurak, Narisorn; Sallapant, Sasipim; Prueksapanich, Piyapan; Somanawat, Kanjana; Klaikeaw, Naruemon; Rerknimitr, Rungsun

    2014-12-28

    To evaluate the protective effects of Aloe vera on gastric injury in rats with indomethacin (IMN)-induced gastropathy. Male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control, n = 6) was given distilled water (DW) orally. Group 2 (IMN, n = 6) was given oral IMN (150 mg/kg) dissolved in 5% sodium bicarbonate (NaHCO3 (-)) at time 0 and 4 h. Group 3 (Aloe vera-treated, n = 6) was given oral Aloe vera (150 mg/kg) dissolved in DW and IMN at time 0 and 4 h. Eight hours later, the stomach was removed to determine gastric malondialdehyde (MDA), the number of interleukin (IL)-18 positive stained cells (%) by immunohistochemistry, and for histopathological examination. Then, the serum was collected to determine tumor necrosis factor (TNF)-α and cytokine-induced neutrophil chemoattractant (CINC)-1 by sandwich enzyme linked immunosorbent assay method. In the IMN group, serum TNF-α, CINC-1 and gastric MDA were significantly increased when compared to the control group (27.78 ± 1.52 pg/mL vs 85.07 ± 49.11 pg/mL, P = 0.009; 104.55 ± 45.80 pg/mL vs 1054.70 ± 20.38 pg/mL, and 1.74 ± 0.21 nmol/mg vs 9.36 ± 1.07 nmol/mg protein, P = 0.000, respectively). The mean level of TNF-α, CINC-1 and gastric MDA in the Aloe vera-treated group were improved as compared with the IMN group (85.07 ± 49.11 pg/mL vs 35.19 ± 1.61 pg/mL, P = 0.021; 1054.70 ± 20.38 pg/mL vs 813.56 ± 239.04 pg/mL, P = 0.025; and 9.36 ± 1.07 nmol/mg vs 2.67 ± 0.64 nmol/mg protein, P = 0.000, respectively). The number of IL-18 positive stained cells (%) in the gastric epithelial cells of the IMN group was significantly higher than the control group (5.01% ± 3.73% vs 30.67% ± 2.03%, P = 0.000, respectively). In contrast, Aloe vera treatment decreased the number of IL-18 positive stained cells (%) significantly when compared with the IMN group (30.67% ± 2.03% vs 13.21% ± 1.10%, P = 0.000, respectively). Most rats in the IMN group developed moderate to severe gastric inflammation

  15. Low concentrations of zinc in gastric mucosa are associated with increased severity of Helicobacter pylori-induced inflammation.

    Science.gov (United States)

    Sempértegui, Fernando; Díaz, Myriam; Mejía, Ricardo; Rodríguez-Mora, Oswaldo G; Rentería, Edgar; Guarderas, Carlos; Estrella, Bertha; Recalde, Ramiro; Hamer, Davidson H; Reeves, Philip G

    2007-02-01

    Chronic Helicobacter pylori infection is the most common cause of gastric cancer. H. pylori induces oxidative stress while zinc deficiency results in increased sensitivity to it. In Ecuador, the prevalence of gastric cancer and zinc deficiency are high. We hypothesized that zinc deficiency in Ecuadorian people would cause increased H. pylori-induced inflammation in the gastric mucosa associated with lower tissue zinc concentrations. Three hundred and fifty-two patients with dyspepsia underwent endoscopy to obtain gastric mucosa biopsies. Diagnosis of H. pylori infection and its severity, histopathology, mucosal zinc concentration, and inflammation intensity were determined. H. pylori-infected patients with non-atrophic chronic gastritis had lower concentrations of zinc in gastric mucosa than uninfected patients with the same type of gastritis (251.3 +/- 225.3 vs. 426.2 +/- 279.9 ng/mg of protein; p = .016). Considering all patients, the more severe the H. pylori infection, the higher the percentage of subjects with infiltration by polymorphonuclear (PMN) cells (p = .0001). Patients with high PMN infiltration had lower mucosal zinc concentrations than patients with low PMN infiltration (35.2 +/- 20.7 vs. 242.9 +/- 191.8 ng/mg of protein; p = .021). The degree of inflammation in H. pylori-induced gastritis appears to be modulated by gastric tissue zinc concentrations.

  16. Suppressed Gastric Mucosal TGF-β1 Increases Susceptibility to H. pylori-Induced Gastric Inflammation and Ulceration: A Stupid Host Defense Response

    Science.gov (United States)

    Jo, Yunjeong; Han, Sang Uk; Kim, Yoon Jae; Kim, Ju Hyeon; Kim, Shin Tae; Kim, Seong-Jin

    2010-01-01

    Background/Aims Loss of transforming growth factor β1 (TGF-β1) exhibits a similar pathology to that seen in a subset of individuals infected with Helicobacter pylori, including propagated gastric inflammation, oxidative stress, and autoimmune features. We thus hypothesized that gastric mucosal TGF-β1 levels could be used to determine the outcome after H. pylori infection. Methods Northern blot for the TGF-β1 transcript, staining of TGF-β1 expression, luciferase reporter assay, and enzyme-linked immunosorbent assay for TGF-β1 levels were performed at different times after H. pylori infection. Results The TGF-β1 level was markedly lower in patients with H. pylori-induced gastritis than in patients with a similar degree of gastritis induced by nonsteroidal anti-inflammatory drugs. There was a significant negative correlation between the severity of inflammation and gastric mucosal TGF-β1 levels. SNU-16 cells showing intact TGF-β signaling exhibited a marked decrease in TGF-β1 expression, whereas SNU-638 cells defective in TGF-β signaling exhibited no such decrease after H. pylori infection. The decreased expressions of TGF-β1 in SNU-16 cells recovered to normal after 24 hr of H. pylori infection, but lasted very spatial times, suggesting that attenuated expression of TGF-β1 is a host defense mechanism to avoid attachment of H. pylori. Conclusions H. pylori infection was associated with depressed gastric mucosal TGF-β1 for up to 24 hr, but this apparent strategy for rescuing cells from H. pylori attachment exacerbated the gastric inflammation. PMID:20479912

  17. Suppressed Gastric Mucosal TGF-beta1 Increases Susceptibility to H. pylori-Induced Gastric Inflammation and Ulceration: A Stupid Host Defense Response.

    Science.gov (United States)

    Jo, Yunjeong; Han, Sang Uk; Kim, Yoon Jae; Kim, Ju Hyeon; Kim, Shin Tae; Kim, Seong-Jin; Hahm, Ki-Baik

    2010-03-01

    Loss of transforming growth factor beta1 (TGF-beta1) exhibits a similar pathology to that seen in a subset of individuals infected with Helicobacter pylori, including propagated gastric inflammation, oxidative stress, and autoimmune features. We thus hypothesized that gastric mucosal TGF-beta1 levels could be used to determine the outcome after H. pylori infection. Northern blot for the TGF-beta1 transcript, staining of TGF-beta1 expression, luciferase reporter assay, and enzyme-linked immunosorbent assay for TGF-beta1 levels were performed at different times after H. pylori infection. The TGF-beta1 level was markedly lower in patients with H. pylori-induced gastritis than in patients with a similar degree of gastritis induced by nonsteroidal anti-inflammatory drugs. There was a significant negative correlation between the severity of inflammation and gastric mucosal TGF-beta1 levels. SNU-16 cells showing intact TGF-beta signaling exhibited a marked decrease in TGF-beta1 expression, whereas SNU-638 cells defective in TGF-beta signaling exhibited no such decrease after H. pylori infection. The decreased expressions of TGF-beta1 in SNU-16 cells recovered to normal after 24 hr of H. pylori infection, but lasted very spatial times, suggesting that attenuated expression of TGF-beta1 is a host defense mechanism to avoid attachment of H. pylori. H. pylori infection was associated with depressed gastric mucosal TGF-beta1 for up to 24 hr, but this apparent strategy for rescuing cells from H. pylori attachment exacerbated the gastric inflammation.

  18. Phenobarbital Treatment at a Neonatal Age Results in Decreased Efficacy of Omeprazole in Adult Mice.

    Science.gov (United States)

    Tien, Yun-Chen; Piekos, Stephanie C; Pope, Chad; Zhong, Xiao-Bo

    2017-03-01

    Drug-drug interactions (DDIs) occur when the action of one drug interferes with or alters the activity of another drug taken concomitantly. This can lead to decreased drug efficacy or increased toxicity. Because of DDIs, physicians in the clinical practice attempt to avoid potential interactions when multiple drugs are coadministrated; however, there is still a large knowledge gap in understanding how drugs taken in the past can contribute to DDIs in the future. The goal of this study was to investigate the consequence of neonatal drug exposure on efficacy of other drugs administered up through adult life. We selected a mouse model to test phenobarbital exposure at a neonatal age and its impact on efficacy of omeprazole in adult life. The results of our experiment show an observed decrease in omeprazole's ability to raise gastric pH in adult mice that received single or multiple doses of phenobarbital at a neonatal age. This effect may be associated with the permanent induction of cytochrome P450 enzymes in adult liver after neonatal phenobarbital treatment. Our data indicates that DDIs may result from drugs administered in the past in an animal model and should prompt re-evaluation of how DDIs are viewed and how to avoid long-term DDIs in clinical practice. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  19. Dietary Composition Influences Incidence of Helicobacter pylori-Induced Iron Deficiency Anemia and Gastric Ulceration

    Science.gov (United States)

    Beckett, Amber C.; Piazuelo, M. Blanca; Noto, Jennifer M.; Peek, Richard M.; Washington, M. Kay; Algood, Holly M. Scott

    2016-01-01

    Epidemiologic studies have provided conflicting data regarding an association between Helicobacter pylori infection and iron deficiency anemia (IDA) in humans. Here, a Mongolian gerbil model was used to investigate a potential role of H. pylori infection, as well as a possible role of diet, in H. pylori-associated IDA. Mongolian gerbils (either H. pylori infected or uninfected) received a normal diet or one of three diets associated with increased H. pylori virulence: high-salt, low-iron, or a combination of a high-salt and low-iron diet. In an analysis of all infected animals compared to uninfected animals (independent of diet), H. pylori-infected gerbils had significantly lower hemoglobin values than their uninfected counterparts at 16 weeks postinfection (P Anemia was associated with the presence of gastric ulceration but not gastric cancer. Infected gerbils consuming diets with a high salt content developed gastric ulcers significantly more frequently than gerbils consuming a normal-salt diet, and the lowest hemoglobin levels were in infected gerbils consuming a high-salt/low-iron diet. These data indicate that H. pylori infection can cause IDA and that the composition of the diet influences the incidence and severity of H. pylori-induced IDA. PMID:27620719

  20. Omeprazole for Refractory Gastroesophageal Reflux Disease during Pregnancy and Lactation

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    John K Marshall

    1998-01-01

    Full Text Available Symptomatic gastroesophageal reflux is a common complication of pregnancy and lactation. However, the safety of many effective medical therapies, including oral proton pump inhibitors, has not been well defined. The administration of oral omeprazole to a 41-year-old female during the third trimester of pregnancy, after ranitidine and cisapride failed to control her refractory gastroesophageal reflux, is reported. No adverse fetal effects were apparent, and the patient elected to continue omeprazole therapy (20 mg/day while breastfeeding. Peak omeprazole concentrations in breast milk (58 nM, 3 h after ingestion were less than 7% of the peak serum concentration (950 nM at 4 h, indicating minimal secretion. Although omeprazole is a potentially useful therapy for refractory gastroesophageal reflux during pregnancy and lactation, further data are needed to define better its safety and efficacy.

  1. Nutrient Induced Type 2 and Chemical Induced Type 1 Experimental Diabetes Differently Modulate Gastric GLP-1 Receptor Expression

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    Olga Bloch

    2015-01-01

    Full Text Available T2DM patients demonstrate reduced GLP-1 receptor (GLP-1R expression in their gastric glands. Whether induced T2DM and T1DM differently affect the gastric GLP-1R expression is not known. This study assessed extrapancreatic GLP-1R system in glandular stomach of rodents with different types of experimental diabetes. T2DM and T1DM were induced in Psammomys obesus (PO by high-energy (HE diet and by streptozotocin (STZ in Sprague Dawly (SD rats, respectively. GLP-1R expression was determined in glandular stomach by RT PCR and immunohistomorphological analysis. The mRNA expression and cellular association of the GLP-1R in principal glands were similar in control PO and SD rats. However, nutrient and chemical induced diabetes resulted in opposite alterations of glandular GLP-1R expression. Diabetic PO demonstrated increased GLP-1R mRNA expression, intensity of cellular GLP-1R immunostaining, and frequency of GLP-1R positive cells in the neck area of principal glands compared with controls. In contrast, SD diabetic rats demonstrated decreased GLP-1 mRNA, cellular GLP-1R immunoreactivity, and frequency of GLP-1R immunoreactive cells in the neck area compared with controls. In conclusion, nutrient and chemical induced experimental diabetes result in distinct opposite alterations of GLP-1R expression in glandular stomach. These results suggest that induced T1DM and T2DM may differently modulate GLP-1R system in enteropancreatic axis.

  2. Strawberry polyphenols attenuate ethanol-induced gastric lesions in rats by activation of antioxidant enzymes and attenuation of MDA increase.

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    José M Alvarez-Suarez

    Full Text Available BACKGROUND AND AIM: Free radicals are implicated in the aetiology of gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. Strawberries are common and important fruit due to their high content of essential nutrient and beneficial phytochemicals which seem to have relevant biological activity on human health. In the present study we investigated the antioxidant and protective effects of three strawberry extracts against ethanol-induced gastric mucosa damage in an experimental in vivo model and to test whether strawberry extracts affect antioxidant enzyme activities in gastric mucosa. METHODS/PRINCIPAL FINDINGS: Strawberry extracts were obtained from Adria, Sveva and Alba cultivars. Total antioxidant capacity and radical scavenging capacity were performed by TEAC, ORAC and electron paramagnetic resonance assays. Identification and quantification of anthocyanins was carried out by HPLC-DAD-MS analyses. Different groups of animals received 40 mg/day/kg body weight of strawberry crude extracts for 10 days. Gastric damage was induced by ethanol. The ulcer index was calculated together with the determination of catalase and SOD activities and MDA contents. Strawberry extracts are rich in anthocyanins and present important antioxidant capacity. Ethanol caused severe gastric damage and strawberry consumption protected against its deleterious role. Antioxidant enzyme activities increased significantly after strawberry extract intake and a concomitantly decrease in gastric lipid peroxidation was found. A significant correlation between total anthocyanin content and percent of inhibition of ulcer index was also found. CONCLUSIONS: Strawberry extracts prevented exogenous ethanol-induced damage to rats' gastric mucosa. These effects seem to be associated with the antioxidant activity and phenolic content in the extract as well as with the capacity of promoting the action of antioxidant enzymes. A diet rich in

  3. Strawberry Polyphenols Attenuate Ethanol-Induced Gastric Lesions in Rats by Activation of Antioxidant Enzymes and Attenuation of MDA Increase

    Science.gov (United States)

    Alvarez-Suarez, José M.; Dekanski, Dragana; Ristić, Slavica; Radonjić, Nevena V.; Petronijević, Nataša D.; Giampieri, Francesca; Astolfi, Paola; González-Paramás, Ana M.; Santos-Buelga, Celestino; Tulipani, Sara; Quiles, José L.; Mezzetti, Bruno; Battino, Maurizio

    2011-01-01

    Background and Aim Free radicals are implicated in the aetiology of gastrointestinal disorders such as gastric ulcer, colorectal cancer and inflammatory bowel disease. Strawberries are common and important fruit due to their high content of essential nutrient and beneficial phytochemicals which seem to have relevant biological activity on human health. In the present study we investigated the antioxidant and protective effects of three strawberry extracts against ethanol-induced gastric mucosa damage in an experimental in vivo model and to test whether strawberry extracts affect antioxidant enzyme activities in gastric mucosa. Methods/Principal Findings Strawberry extracts were obtained from Adria, Sveva and Alba cultivars. Total antioxidant capacity and radical scavenging capacity were performed by TEAC, ORAC and electron paramagnetic resonance assays. Identification and quantification of anthocyanins was carried out by HPLC-DAD-MS analyses. Different groups of animals received 40 mg/day/kg body weight of strawberry crude extracts for 10 days. Gastric damage was induced by ethanol. The ulcer index was calculated together with the determination of catalase and SOD activities and MDA contents. Strawberry extracts are rich in anthocyanins and present important antioxidant capacity. Ethanol caused severe gastric damage and strawberry consumption protected against its deleterious role. Antioxidant enzyme activities increased significantly after strawberry extract intake and a concomitantly decrease in gastric lipid peroxidation was found. A significant correlation between total anthocyanin content and percent of inhibition of ulcer index was also found. Conclusions Strawberry extracts prevented exogenous ethanol-induced damage to rats' gastric mucosa. These effects seem to be associated with the antioxidant activity and phenolic content in the extract as well as with the capacity of promoting the action of antioxidant enzymes. A diet rich in strawberries might exert a

  4. TRPV1 Channels and Gastric Vagal Afferent Signalling in Lean and High Fat Diet Induced Obese Mice.

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    Stephen J Kentish

    Full Text Available Within the gastrointestinal tract vagal afferents play a role in control of food intake and satiety signalling. Activation of mechanosensitive gastric vagal afferents induces satiety. However, gastric vagal afferent responses to mechanical stretch are reduced in high fat diet mice. Transient receptor potential vanilloid 1 channels (TRPV1 are expressed in vagal afferents and knockout of TRPV1 reduces gastro-oesophageal vagal afferent responses to stretch. We aimed to determine the role of TRPV1 on gastric vagal afferent mechanosensitivity and food intake in lean and HFD-induced obese mice.TRPV1+/+ and -/- mice were fed either a standard laboratory diet or high fat diet for 20wks. Gastric emptying of a solid meal and gastric vagal afferent mechanosensitivity was determined.Gastric emptying was delayed in high fat diet mice but there was no difference between TRPV1+/+ and -/- mice on either diet. TRPV1 mRNA expression in whole nodose ganglia of TRPV1+/+ mice was similar in both dietary groups. The TRPV1 agonist N-oleoyldopamine potentiated the response of tension receptors in standard laboratory diet but not high fat diet mice. Food intake was greater in the standard laboratory diet TRPV1-/- compared to TRPV1+/+ mice. This was associated with reduced response of tension receptors to stretch in standard laboratory diet TRPV1-/- mice. Tension receptor responses to stretch were decreased in high fat diet compared to standard laboratory diet TRPV1+/+ mice; an effect not observed in TRPV1-/- mice. Disruption of TRPV1 had no effect on the response of mucosal receptors to mucosal stroking in mice on either diet.TRPV1 channels selectively modulate gastric vagal afferent tension receptor mechanosensitivity and may mediate the reduction in gastric vagal afferent mechanosensitivity in high fat diet-induced obesity.

  5. Neural Mechanisms and Delayed Gastric Emptying of Liquid Induced Through Acute Myocardial Infarction in Rats

    Energy Technology Data Exchange (ETDEWEB)

    Nunez, Wilson Ranu Ramirez; Ozaki, Michiko Regina; Vinagre, Adriana Mendes; Collares, Edgard Ferro; Almeida, Eros Antonio de, E-mail: erosaa@cardiol.br [Universidade Estadual de Campinas, Campinas, SP (Brazil)

    2015-02-15

    In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABA{sub B} receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABA{sub B} receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABA{sub B} receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN.

  6. Contractile profile of esophageal and gastric fundus strips in experimental doxorubicin-induced esophageal atresia

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    F.A. Capeto

    2015-05-01

    Full Text Available Esophageal atresia (EA is characterized by esophageal and gastric motility changes secondary to developmental and postsurgical damage. This study evaluated the in vitro contractile profile of the distal esophagus and gastric fundus in an experimental model of EA induced by doxorubicin (DOXO. Wistar pregnant rats received DOXO 2.2 mg/kg on the 8th and 9th gestational days. On day 21.5, fetuses were collected, sacrificed, and divided into groups: control, DOXO without EA (DOXO-EA, and DOXO with EA (DOXO+EA. Strips from the distal esophagus and gastric fundus were mounted on a wire myograph and isolated organ-bath system, respectively, and subjected to increasing concentrations of carbamylcholine chloride (carbachol, CCh. The isolated esophagus was also stimulated with increasing concentrations of KCl. In esophagus, the concentration-effect curves were reduced in response to CCh in the DOXO+EA and DOXO-EA groups compared to the control group (P0.05. In response to KCl, the distal esophagus samples in the three groups were not statistically different with regard to Emax or EC50 values (P>0.05. No significant difference was noted for EC50 or Emax values in fundic strips stimulated with CCh (P>0.05. In conclusion, exposure of dams to DOXO during gestation inhibited the contractile behavior of esophageal strips from offspring in response to CCh but not KCl, regardless of EA induction. The gastric fundus of DOXO-exposed offspring did not have altered contractile responsiveness to cholinergic stimulation.

  7. Neural Mechanisms and Delayed Gastric Emptying of Liquid Induced Through Acute Myocardial Infarction in Rats

    Directory of Open Access Journals (Sweden)

    Wilson Ranu Ramirez Nunez

    2015-02-01

    Full Text Available Background: In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE of liquid in rats. Objective: Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN of the hypothalamus in GE and gastric compliance (GC in infarcted rats. Methods: Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular. Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR of a saline meal. Results: No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Conclusion: Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN.

  8. Study of Clinical and Genetic Risk Factors for Aspirin-induced Gastric Mucosal Injury

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    Yun Wu

    2016-01-01

    Full Text Available Background: Current knowledge about clinical and genetic risk factors for aspirin-induced gastric mucosal injury is not sufficient to prevent these gastric mucosal lesions. Methods: We recruited aspirin takers as the exposed group and healthy volunteers as the control group. The exposed group was categorized into two subgroups such as subgroup A as gastric mucosal injury diagnosed by gastroscopy, including erosion, ulcer or bleeding of the esophagus, stomach, or duodenum; subgroup B as no injury of the gastric mucosa was detected by gastroscopy. Clinical information was collected, and 53 single nucleotide polymorphisms were evaluated. Results: Among 385 participants, 234 were in the aspirin-exposed group. According to gastroscopy, 82 belonged to subgroup A, 91 belonged to subgroup B, and gastroscopic results of 61 participants were not available. Using the Chi-square test and logistic regression, we found that peptic ulcer history (odds ratio [OR] = 5.924, 95% confidence intervals [CI]: 2.115-16.592, dual anti-platelet medication (OR = 3.443, 95% CI: 1.154-10.271, current Helicobacter pylori infection (OR = 2.242, 95% CI: 1.032-4.870, male gender (OR = 2.211, 95% CI: 1.027-4.760, GG genotype of rs2243086 (OR = 4.516, 95% CI: 1.180-17.278, and AA genotype of rs1330344 (OR = 2.178, 95% CI: 1.016-4.669 were more frequent in subgroup A than subgroup B. In aspirin users who suffered from upper gastrointestinal bleeding, the frequency of the TT genotype of rs2238631 and TT genotype of rs2243100 was higher than in those without upper gastrointestinal bleeding. Conclusions: Peptic ulcer history, dual anti-platelet medication, H. pylori current infection, and male gender were possible clinical risk factors for aspirin-induced gastric mucosal injury. GG genotype of rs2243086 and AA genotype of rs1330344 were possible genetic risk factors. TT genotype of rs2238631 and TT genotype of rs2243100 may be risk factors for upper gastrointestinal bleeding in

  9. Inducible nitric oxide synthase, nitrotyrosine and apoptosis in gastric adenocarcinomas and their correlation with a poor survival

    Science.gov (United States)

    Li, Long-Gang; Xu, Hui-Mian

    2005-01-01

    AIM: To detect the presence of inducible nitric oxide synthase (iNOS), nitrotyrosine (NT) and apoptosis in gastric adenocarcinomas and their possible correlations with the clinicopathological characteristics and prognosis of gastric adenocarcinoma. METHODS: Sixty-six specimens of gastric adenocarcinoma and corresponding adjacent normal gastric tissues were studied. Immunohistochemistry was employed to localize iNOS and NT protein and an immunohistochemical scoring system was used. The occurrence of apoptotic cell death (apoptotic index [AI]) was analyzed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling (TUNEL) method. RESULTS: Results showed that iNOS expression was detected at an intermediate or high level in 41 of 66 (62%) specimens of gastric adenocarcinoma. NT expression was 58%. Neither of them was found in the normal gastric tissues; there were significant positive correlations among iNOS expression, NT expression and AI. Many clinicopathologic characteristics of gastric adenocarcinoma, such as tumor size, depth of invasion, lymph node metastasis and TNM staging, were related to iNOS and NT expressions (P<0.05). In 66 surviving patients, the 5-year survival rate of 41 patients who had tumors with intermediate or high iNOS expressions and high AIs (4.09%; 19.96%) was significantly lower than that of 25 patients who had tumors with negative or low iNOS expressions and low AIs (0.79%; 47.14%) (P = 0.001). COX’s multivariate analysis revealed that the iNOS expression was identified as one of the significant independent prognostic factors predictive of a poor survival (relative risk [RR] = 2.69). CONCLUSION: NO produced by iNOS may play a stronger role in promoting gastric adenocarcinoma growth than in suppressing its growth. iNOS and NT expressions by gastric adenocarcinoma may correlate with a poor survival. PMID:15849807

  10. Akebia saponin PA induces autophagic and apoptotic cell death in AGS human gastric cancer cells.

    Science.gov (United States)

    Xu, Mei-Ying; Lee, Dong Hwa; Joo, Eun Ji; Son, Kun Ho; Kim, Yeong Shik

    2013-09-01

    In this study, we investigated the anticancer mechanism of akebia saponin PA (AS), a natural product isolated from Dipsacus asperoides in human gastric cancer cell lines. It was shown that AS-induced cell death is caused by autophagy and apoptosis in AGS cells. The apoptosis-inducing effect of AS was characterized by annexin V/propidium (PI) staining, increase of sub-G1 phase and caspase-3 activation, while the autophagy-inducing effect was indicated by the formation of cytoplasmic vacuoles and microtubule-associated protein 1 light chain-3 II (LC3-II) conversion. The autophagy inhibitor bafilomycin A1 (BaF1) decreased AS-induced cell death and caspase-3 activation, but caspase-3 inhibitor Ac-DEVD-CHO did not affect LC3-II accumulation or AS-induced cell viability, suggesting that AS induces autophagic cell death and autophagy contributes to caspase-3-dependent apoptosis. Furthermore, AS activated p38/c-Jun N-terminal kinase (JNK), which could be inhibited by BaF1, and caspase-3 activation was attenuated by both SB202190 and SP600125, indicating that AS-induced autophagy promotes mitogen-activated protein kinases (MAPKs)-mediated apoptosis. Taken together, these results demonstrate that AS induces autophagic and apoptotic cell death and autophagy plays the main role in akebia saponin PA-induced cell death. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. [Effect of Capsicum annum L (pucunucho, ají mono) in gastric ulcer experimentally induced in rats].

    Science.gov (United States)

    Delgado Montero, Rocío; Flores Cortez, Daisy; Villalobos Pacheco, Eduardo

    2015-01-01

    To examine the effects of the Capsicum annum L lyophilized fruit extract in experimentally-induced gastric ulcer in rats. We used the model of indomethacin gastric ulcer-induced and the gastric ulcer model induced by pylorus ligation in rats. The rats were divided in five treatment groups as follow: G1: Distilled water 1 ml/Kg; G2: Ranitidine 50 mg/kg, G3: Capsicum 10mg/kg, G4: Capsicum 100 mg/kg, G5: Capsicum 1000 mg/kg. The results of the first model showed an ulcer inhibition of 60,4% and 66,7% using the doses of Capsicum at 10 mg/kg and 100 mg/kg, respectively. The results of the second model showed that neither the pH nor the volume of the gastric content were modified by the administered extract (p >0.05); however, by using the doses of Capsicum at 100 mg/kg and 1000 mg/kg, there was clearly an ulcer inhibition of 75.59% and 81.63% respectively, which were even greater than the inhibition obtained by ranitidine (75.51%). Therefore, in this experiment we demonstrated that the Capsicum annum L lyophilized fruit extract has a gastroprotective effect in experimentally-induced gastric ulcer in rats.

  12. Potentiation of the action of metronidazole on Helicobacter pylori by omeprazole and bismuth subcitrate

    DEFF Research Database (Denmark)

    Andersen, L P; Colding, H; Kristiansen, J E

    2000-01-01

    test (Etest). With 0.5 MIC of either of the two drugs, the susceptibility of all H. pylori4 mg/l) reverted to being metronidazole sensitive. These results suggested that either bismuth salts or proton pump inhibitors may be effective in the treatment of some infections with metronidazole-resistant H...... to regimens that include proton pump inhibitors. In the present study, the synergistic effect of subinhibitory concentrations (0.25-0.5 MIC) of either bismuth subcitrate or omeprazole with metronidazole on the susceptibility of 42 H. pylori strains was investigated by agar dilution method and the Epsilometer......Treatment failures using triple therapy that include metronidazole, are common in patients infected with metronidazole-resistant Helicobacter pylori in the gastric mucosa. Higher eradication rates in such patients have been described when treatment regimens include bismuth salts compared...

  13. Residual solvent determination by head space gas chromatography with flame ionization detector in omeprazole API

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    Saurabh Pandey

    2011-06-01

    Full Text Available Residual solvents in pharmaceutical samples are monitored using gas chromatography with head space. Based on good manufacturing practices, measuring residual solvents is mandatory for the release testing of all active pharmaceutical ingredients (API. The analysis of residual organic solvents (methanol, acetone, cyclohexane, dichloromethane, toluene in Omeprazole, an active pharmaceutical ingredient was investigated. Omeprazole is a potent reversible inhibitor of the gastric proton pump H+/K+-ATPase. The Head space gas chromatography (HSGC method described in this investigation utilized a SPB TM-624, Supelco, 30 m long x 0.25 mm internal diameter, 1.4µm-thick column. Since Omeprazole is a thermally labile compound, the selection of the proper injector temperature is critical to the success of the analysis. The injector temperature was set at 170ºC to prevent degradation. The initial oven temperature was set at 40ºC for 12 min and programmed at a rate of 10ºC min-1 to a final temperature of 220ºC for 5 min. Nitrogen was used as a carrier gas. The sample solvent selected was N,N-dimethylacetamide. The method was validated to be specific, linear, precise, sensitive, rugged and showed excellent recovery.Solventes residuais em amostras farmacêuticas são monitoradas utilizando-se cromatografia a gás "headspace". Com base nas boas práticas de fabricação, a medida de solventes residuais é obrigatória para o teste de liberação de todos os ingredientes farmacêuticos (API. Efetuou-se a análise de solventes orgânicos residuais (metanol, acetona, cicloexano, diclorometano, tolueno em omeprazol, ingrediente farmacêutico ativo. O omeprazol é potente inibidor reversível da bomba de prótons H+/K+-ATPase. A cromatografia a gás "headspace" (HSGC descrita nessa pesquisa utilizou um SPB TM-624, Supelco, de 30 m de comprimento x 0,25 mm de diâmetro interno, e coluna de 1,4 µm de espessura. Considerando-se que o omeprazol é termicamente l

  14. A novel vitamin E derivative (TMG) protects against gastric mucosal damage induced by ischemia and reperfusion in rats.

    Science.gov (United States)

    Ichikawa, Hiroshi; Yoshida, Norimasa; Takano, Hiroshisa; Ishikawa, Takeshi; Handa, Osamu; Takagi, Tomohisa; Naito, Yuji; Murase, Hironobu; Yoshikawa, Toshikazu

    2003-01-01

    The aim of the present study was to investigate the antioxidative effects of water-soluble vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol (TMG), on ischemia-reperfusion (I/R) -induced gastric mucosal injury in rats. Gastric ischemia was induced by applying a small clamp to the celiac artery and reoxygenation was produced by removal of the clamp. The area of gastric mucosal erosion, the concentration of thiobarbituric acid-reactive substances, and the myeloperoxidase activity in gastric mucosa significantly increased in I/R groups compared with those of sham-operated groups. These increases were significantly inhibited by pretreatment with TMG. The contents of both mucosal TNF-alpha and CINC-2beta in I/R groups were also increased compared with the levels of those in sham-operated groups. These increases of the inflammatory cytokines were significantly inhibited by the treatment with TMG. It is concluded that TMG inhibited lipid peroxidation and reduced development of the gastric mucosal inflammation induced by I/R in rats.

  15. The hydrogen sulfide donor, Lawesson's reagent, prevents alendronate-induced gastric damage in rats

    Energy Technology Data Exchange (ETDEWEB)

    Nicolau, L.A.D. [Núcleo de Pesquisa em Produtos Naturais, Departamento de Farmacologia, Universidade Federal do Piauí, Teresina, PI (Brazil); Silva, R.O.; Damasceno, S.R.B.; Carvalho, N.S.; Costa, N.R.D. [Laboratório de Fisiofarmacologia Experimental, Centro de Pesquisa em Biodiversidade e Biotecnologia, Universidade Federal do Piauí, Parnaíba, PI (Brazil); Aragão, K.S. [Laboratório de Farmacologia da Inflamação e do Câncer, Departamento de Farmacologia, Universidade Federal do Ceará, Fortaleza, CE (Brazil); Barbosa, A.L.R. [Núcleo de Pesquisa em Produtos Naturais, Departamento de Farmacologia, Universidade Federal do Piauí, Teresina, PI (Brazil); Laboratório de Fisiofarmacologia Experimental, Centro de Pesquisa em Biodiversidade e Biotecnologia, Universidade Federal do Piauí, Parnaíba, PI (Brazil); Soares, P.M.G.; Souza, M.H.L.P. [Laboratório de Farmacologia da Inflamação e do Câncer, Departamento de Farmacologia, Universidade Federal do Ceará, Fortaleza, CE (Brazil); Medeiros, J.V.R. [Núcleo de Pesquisa em Produtos Naturais, Departamento de Farmacologia, Universidade Federal do Piauí, Teresina, PI (Brazil); Laboratório de Fisiofarmacologia Experimental, Centro de Pesquisa em Biodiversidade e Biotecnologia, Universidade Federal do Piauí, Parnaíba, PI (Brazil)

    2013-08-16

    Our objective was to investigate the protective effect of Lawesson's reagent, an H{sub 2}S donor, against alendronate (ALD)-induced gastric damage in rats. Rats were pretreated with saline or Lawesson's reagent (3, 9, or 27 µmol/kg, po) once daily for 4 days. After 30 min, gastric damage was induced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, the animals were killed 4 h after ALD administration. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1β], and myeloperoxidase (MPO). Other groups were pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5 mg/kg, ip)+diazoxide (3 mg/kg, ip). After 1 h, 27 µmol/kg Lawesson's reagent was administered. After 30 min, 30 mg/kg ALD was administered. ALD caused gastric damage (63.35±9.8 mm{sup 2}); increased levels of TNF-α, IL-1β, and MDA (2311±302.3 pg/mL, 901.9±106.2 pg/mL, 121.1±4.3 nmol/g, respectively); increased MPO activity (26.1±3.8 U/mg); and reduced GSH levels (180.3±21.9 µg/g). ALD also increased cystathionine-γ-lyase immunoreactivity in the gastric mucosa. Pretreatment with Lawesson's reagent (27 µmol/kg) attenuated ALD-mediated gastric damage (15.77±5.3 mm{sup 2}); reduced TNF-α, IL-1β, and MDA formation (1502±150.2 pg/mL, 632.3±43.4 pg/mL, 78.4±7.6 nmol/g, respectively); lowered MPO activity (11.7±2.8 U/mg); and increased the level of GSH in the gastric tissue (397.9±40.2 µg/g). Glibenclamide alone reversed the gastric protective effect of Lawesson's reagent. However, glibenclamide plus diazoxide did not alter the effects of Lawesson's reagent. Our results suggest that Lawesson's reagent plays a protective role against ALD-induced gastric damage through mechanisms that depend at least in part on activation of ATP-sensitive potassium (K

  16. Antioxidant-mediated preventative effect of Dragon-pearl tea crude polyphenol extract on reserpine-induced gastric ulcers.

    Science.gov (United States)

    Yi, Ruokun; Wang, Rui; Sun, Peng; Zhao, Xin

    2015-07-01

    Dragon-pearl tea is a type of green tea commonly consumed in Southwest China. In the present study, the antioxidative and anti-gastric ulcer effects of Dragon-pearl tea crude polyphenols (DTCP) were determined in vitro and in vivo . Treatment with 25, 50 or 100 µg/ml DTCP resulted in notable antioxidant effects in vitro , which manifested as 2,2-diphenyl-1-picrylhydrazyl and OH radical-scavenging activity. Furthermore, using an in vivo mouse model, DTCP was shown to reduce the gastric ulcer area in the stomach, in which the 200 mg/kg DTCP dose exhibited the most marked effect, with a gastric ulcer index inhibitory rate of 72.63%. In addition, DTCP was demonstrated to improve stomach acidity conditions in vivo by increasing the pH and reducing the level of gastric juice, as compared with the reserpine-induced gastric ulcer control mice. Furthermore, DTCP altered the serum levels of a number of oxidation-related biomolecules, including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), lipid peroxidation (LPO) and catalase (CAT), to subsequently exert an anti-gastric ulcer effect. Treatment with 50, 100 and 200 mg/kg DTCP increased the SOD, GSH-Px and CAT levels and reduced the MDA and LPO levels in the mouse model of gastric ulcers. These serum level alterations resulted in the modified serum levels of prostaglandin E2 (PGE2) and nitric oxide (NO), which are associated with gastric mucosal protection. A reverse transcription-quantitative polymerase chain reaction (RT-PCR) assay is a molecular biology experiment which could determine the changes of mRNA in tissues. Using the RT-PCR assay, DTCP was observed to increase the mRNA expression levels of certain genes associated with gastric ulcers: Epidermal growth factor, epidermal growth factor receptor, vascular endothelial growth factor and vascular endothelial growth factor receptor 1, while reducing gastrin expression levels. Therefore, the results indicated that DTCP induced a

  17. The hydrogen sulfide donor, Lawesson's reagent, prevents alendronate-induced gastric damage in rats

    International Nuclear Information System (INIS)

    Nicolau, L.A.D.; Silva, R.O.; Damasceno, S.R.B.; Carvalho, N.S.; Costa, N.R.D.; Aragão, K.S.; Barbosa, A.L.R.; Soares, P.M.G.; Souza, M.H.L.P.; Medeiros, J.V.R.

    2013-01-01

    Our objective was to investigate the protective effect of Lawesson's reagent, an H 2 S donor, against alendronate (ALD)-induced gastric damage in rats. Rats were pretreated with saline or Lawesson's reagent (3, 9, or 27 µmol/kg, po) once daily for 4 days. After 30 min, gastric damage was induced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, the animals were killed 4 h after ALD administration. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1β], and myeloperoxidase (MPO). Other groups were pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5 mg/kg, ip)+diazoxide (3 mg/kg, ip). After 1 h, 27 µmol/kg Lawesson's reagent was administered. After 30 min, 30 mg/kg ALD was administered. ALD caused gastric damage (63.35±9.8 mm 2 ); increased levels of TNF-α, IL-1β, and MDA (2311±302.3 pg/mL, 901.9±106.2 pg/mL, 121.1±4.3 nmol/g, respectively); increased MPO activity (26.1±3.8 U/mg); and reduced GSH levels (180.3±21.9 µg/g). ALD also increased cystathionine-γ-lyase immunoreactivity in the gastric mucosa. Pretreatment with Lawesson's reagent (27 µmol/kg) attenuated ALD-mediated gastric damage (15.77±5.3 mm 2 ); reduced TNF-α, IL-1β, and MDA formation (1502±150.2 pg/mL, 632.3±43.4 pg/mL, 78.4±7.6 nmol/g, respectively); lowered MPO activity (11.7±2.8 U/mg); and increased the level of GSH in the gastric tissue (397.9±40.2 µg/g). Glibenclamide alone reversed the gastric protective effect of Lawesson's reagent. However, glibenclamide plus diazoxide did not alter the effects of Lawesson's reagent. Our results suggest that Lawesson's reagent plays a protective role against ALD-induced gastric damage through mechanisms that depend at least in part on activation of ATP-sensitive potassium (K ATP ) channels

  18. Effect of Evodiamine on Inducing Apoptosis of Human Gastric Cancer Cell Line SGC-7901 in Vitro

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    LIU Shao-ping

    2014-09-01

    Full Text Available Objective: To explore the proliferation inhibition and apoptosis-inducing effect of evodiamine in human gastric cancer SGC-7901 cells. Methods: After 48 or 24 h exposure to different concentrations of evodiamine, cell proliferation was analyzed using tetrazolium blue (MTT assay while apoptosis and cell-cycle phase distribution using flow cytometry. Results: In 0.01~30.00 μg/mL range of concentrations, evodiamine inhibited the proliferation of SGC-7901 cells in dose-dependent manner, and the overall mean IC50 was (3.79±0.16 μg/mL; the apoptosis rate was increased from 3.4% to 7.0%, 13.8% and 36.3% at concentrations of 0, 0.5, 1.5 and 30 μg/mL of evodiamine, respectively; the percentage of cells accumulated in G2/M phase was increased from 17.26% to 98.92% in the cells treated with evodiamine for 24 h in 0.01~30.00 μg/mL range of concentrations. Conclusion: Evodiamine can inhibit the proliferation, induce apoptosis in human gastric cancer cell line SGC-7901 in vitro and arrest the cell cycle at the G2/M phase.

  19. Detouring the Undesired Route of Helicobacter pylori-Induced Gastric Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun-Hee; Hong, Kyung-Sook; Hong, Hua [Lab of Translational Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, 7-45 Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Hahm, Ki Baik, E-mail: hahmkb@gachon.ac.kr [Lab of Translational Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, 7-45 Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Department of Gastroenterology, Gachon Graduate School of Medicine, Gil Hospital, Incheon 406-840 (Korea, Republic of)

    2011-07-25

    Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori) infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis.

  20. Detouring the Undesired Route of Helicobacter pylori-Induced Gastric Carcinogenesis

    International Nuclear Information System (INIS)

    Kim, Eun-Hee; Hong, Kyung-Sook; Hong, Hua; Hahm, Ki Baik

    2011-01-01

    Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori) infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis

  1. Helicobacter pylori-Induced Chronic Gastritis and Assessing Risks for Gastric Cancer

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    Gonzalo Carrasco

    2013-01-01

    Full Text Available Chronic gastritis is an inflammation of the gastric mucosa and has multiple etiologies. Here we discuss the pathological alterations induced by Helicobacter pylori (HP leading to chronic gastritis and the epigenetic bases underlying these changes. We review the histology of the normal gastric mucosa and overview the role of HP in the multistep cascade of GC. We attempt to define the role of the Operative Link for Gastritis Assessment (OLGA staging system in assessing the risk of GC. The epigenetic bases of chronic gastritis, mainly DNA methylation, are presented through examples such as (i the methylation of the promoter region of E-cadherin in HP-induced chronic gastritis and its reversion after HP eradication and (ii the association of methylation of the promoter region of Reprimo, a p53-mediated cell cycle arrest gene, with aggressive HP strains in high risk areas for GC. In addition, we discuss the finding of RPRM as a circulating cell-free DNA, offering the opportunity for noninvasive risk assessment of GC. Finally, the integration of OLGA and tissue biomarkers, by systems pathology approach, suggests that severe atrophy has a greater risk for GC development if, in addition, overexpressed p73. This trial is registered with ClinicalTrials.gov NCT01774266.

  2. Detouring the Undesired Route of Helicobacter pylori-Induced Gastric Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Ki Baik Hahm

    2011-07-01

    Full Text Available Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis.

  3. Gastroprotective effect of small centaury (Centaurium erythraea L) on aspirin-induced gastric damage in rats.

    Science.gov (United States)

    Tuluce, Yasin; Ozkol, Halil; Koyuncu, Ismail; Ine, Hatice

    2011-09-01

    The aim of this study was to determine the antiulcer and antioxidant activities of Centaurium erythraea L (small centaury) in aspirin (ASA) induced acute gastric ulcer model. The gastroprotective effect of the 50% aqueous-ethanolic small centaury (SC) extract was investigated in rats at a dose of ASA 200 mg/kg body weight. Twenty-one Sprague-Dawley albino rats were divided into three groups of seven rats each as follows: (1) control group; (2) acute ASA-treated group and (3) ASA plus SC group. At the end of the 4-h drug administration, ulcer index, oxidant and antioxidant levels were measured and compared between the groups. The percentage of lesion area to total gastric surface area (ulcer index) was significantly reduced (77%) in ASA plus SC group as compared with acute ASA-treated group. The oral administration of ASA decreased catalase (CAT), reduced glutathione (GSH), and increased lipid peroxidation (LPO) levels. Although myeloperoxidase (MPO) activity was increased by ASA, it was found to be lower in the ASA plus SC group. GSH and Vitamin A levels were determined higher in the ASA plus SC group compared with ASA group. These results suggest that SC extract protects against ASA-induced damage due to its antioxidizing activity.

  4. Radiation-induced Epstein-Barr virus reactivation in gastric cancer cells with latent EBV infection.

    Science.gov (United States)

    Nandakumar, Athira; Uwatoko, Futoshi; Yamamoto, Megumi; Tomita, Kazuo; Majima, Hideyuki J; Akiba, Suminori; Koriyama, Chihaya

    2017-07-01

    Epstein-Barr virus, a ubiquitous human herpes virus with oncogenic activity, can be found in 6%-16% of gastric carcinomas worldwide. In Epstein-Barr virus-associated gastric carcinoma, only a few latent genes of the virus are expressed. Ionizing irradiation was shown to induce lytic Epstein-Barr virus infection in lymphoblastoid cell lines with latent Epstein-Barr virus infection. In this study, we examined the effect of ionizing radiation on the Epstein-Barr virus reactivation in a gastric epithelial cancer cell line (SNU-719, an Epstein-Barr virus-associated gastric carcinoma cell line). Irradiation with X-ray (dose = 5 and 10 Gy; dose rate = 0.5398 Gy/min) killed approximately 25% and 50% of cultured SNU-719 cells, respectively, in 48 h. Ionizing radiation increased the messenger RNA expression of immediate early Epstein-Barr virus lytic genes (BZLF1 and BRLF1), determined by real-time reverse transcription polymerase chain reaction, in a dose-dependent manner at 48 h and, to a slightly lesser extent, at 72 h after irradiation. Similar findings were observed for other Epstein-Barr virus lytic genes (BMRF1, BLLF1, and BcLF1). After radiation, the expression of transforming growth factor beta 1 messenger RNA increased and reached a peak in 12-24 h, and the high-level expression of the Epstein-Barr virus immediate early genes can convert latent Epstein-Barr virus infection into the lytic form and result in the release of infectious Epstein-Barr virus. To conclude, Ionizing radiation activates lytic Epstein-Barr virus gene expression in the SNU-719 cell line mainly through nuclear factor kappaB activation. We made a brief review of literature to explore underlying mechanism involved in transforming growth factor beta-induced Epstein-Barr virus reactivation. A possible involvement of nuclear factor kappaB was hypothesized.

  5. Spectroscopic Characterization of Omeprazole and Its Salts

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    Tomislav Vrbanec

    2017-01-01

    Full Text Available During drug development, it is important to have a suitable crystalline form of the active pharmaceutical ingredient (API. Mostly, the basic options originate in the form of free base, acid, or salt. Substances that are stable only within a certain pH range are a challenge for the formulation. For the prazoles, which are known to be sensitive to degradation in an acid environment, the formulation is stabilized with alkaline additives or with the application of API formulated as basic salts. Therefore, preparation and characterization of basic salts are needed to monitor any possible salinization of free molecules. We synthesized salts of omeprazole from the group of alkali metals (Li, Na, and K and alkaline earth metals (Mg, Ca. The purpose of the presented work is to demonstrate the applicability of vibrational spectroscopy to discriminate between the OMP and OMP-salt molecules. For this reason, the physicochemical properties of 5 salts were probed using infrared and Raman spectroscopy, NMR, TG, DSC, and theoretical calculation of vibrational frequencies. We found out that vibrational spectroscopy serves as an applicable spectroscopic tool which enables an accurate, quick, and nondestructive way to determine the characteristic of OMP and its salts.

  6. Raddeanin A induces human gastric cancer cells apoptosis and inhibits their invasion in vitro

    International Nuclear Information System (INIS)

    Xue, Gang; Zou, Xi; Zhou, Jin-Yong; Sun, Wei; Wu, Jian; Xu, Jia-Li; Wang, Rui-Ping

    2013-01-01

    Highlights: •Raddeanin A is a triterpenoid saponin in herb medicine Anemone raddeana Regel. •Raddeanin A can inhibit 3 kinds of gastric cancer cells’ proliferation and invasion. •Caspase-cascades’ activation indicates apoptosis induced by Raddeanin A. •MMPs, RECK, Rhoc and E-cad are involved in Raddeanin A-induced invasion inhibition. -- Abstract: Raddeanin A is one of the triterpenoid saponins in herbal medicine Anemone raddeana Regel which was reported to suppress the growth of liver and lung cancer cells. However, little was known about its effect on gastric cancer (GC) cells. This study aimed to investigate its inhibitory effect on three kinds of different differentiation stage GC cells (BGC-823, SGC-7901 and MKN-28) in vitro and the possible mechanisms. Proliferation assay and flow cytometry demonstrated Raddeanin A’s dose-dependent inhibitory effect and determined its induction of cells apoptosis, respectively. Transwell assay, wounding heal assay and cell matrix adhesion assay showed that Raddeanin A significantly inhibited the abilities of the invasion, migration and adhesion of the BGC-823 cells. Moreover, quantitative real time PCR and Western blot analysis found that Raddeanin A increased Bax expression while reduced Bcl-2, Bcl-xL and Survivin expressions and significantly activated caspase-3, caspase-8, caspase-9 and poly-ADP ribose polymerase (PARP). Besides, Raddeanin A could also up-regulate the expression of reversion inducing cysteine rich protein with Kazal motifs (RECK), E-cadherin (E-cad) and down-regulate the expression of matrix metalloproteinases-2 (MMP-2), MMP-9, MMP-14 and Rhoc. In conclusion, Raddeanin A inhibits proliferation of human GC cells, induces their apoptosis and inhibits the abilities of invasion, migration and adhesion, exhibiting potential to become antitumor drug

  7. Raddeanin A induces human gastric cancer cells apoptosis and inhibits their invasion in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Gang [Department of Oncology, Nanjing University of Chinese Medicine, Nanjing (China); Zou, Xi [Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Zhou, Jin-Yong [Laboratory Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Sun, Wei [Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Wu, Jian [Laboratory Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Xu, Jia-Li [Department of Oncology, Nanjing University of Chinese Medicine, Nanjing (China); Wang, Rui-Ping, E-mail: ruipingwang61@hotmail.com [Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China)

    2013-09-20

    Highlights: •Raddeanin A is a triterpenoid saponin in herb medicine Anemone raddeana Regel. •Raddeanin A can inhibit 3 kinds of gastric cancer cells’ proliferation and invasion. •Caspase-cascades’ activation indicates apoptosis induced by Raddeanin A. •MMPs, RECK, Rhoc and E-cad are involved in Raddeanin A-induced invasion inhibition. -- Abstract: Raddeanin A is one of the triterpenoid saponins in herbal medicine Anemone raddeana Regel which was reported to suppress the growth of liver and lung cancer cells. However, little was known about its effect on gastric cancer (GC) cells. This study aimed to investigate its inhibitory effect on three kinds of different differentiation stage GC cells (BGC-823, SGC-7901 and MKN-28) in vitro and the possible mechanisms. Proliferation assay and flow cytometry demonstrated Raddeanin A’s dose-dependent inhibitory effect and determined its induction of cells apoptosis, respectively. Transwell assay, wounding heal assay and cell matrix adhesion assay showed that Raddeanin A significantly inhibited the abilities of the invasion, migration and adhesion of the BGC-823 cells. Moreover, quantitative real time PCR and Western blot analysis found that Raddeanin A increased Bax expression while reduced Bcl-2, Bcl-xL and Survivin expressions and significantly activated caspase-3, caspase-8, caspase-9 and poly-ADP ribose polymerase (PARP). Besides, Raddeanin A could also up-regulate the expression of reversion inducing cysteine rich protein with Kazal motifs (RECK), E-cadherin (E-cad) and down-regulate the expression of matrix metalloproteinases-2 (MMP-2), MMP-9, MMP-14 and Rhoc. In conclusion, Raddeanin A inhibits proliferation of human GC cells, induces their apoptosis and inhibits the abilities of invasion, migration and adhesion, exhibiting potential to become antitumor drug.

  8. Dipyrone in association with atropine inhibits the effect on gastric emptying induced by hypoglycemia in rats

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    E.F. Collares

    2017-08-01

    Full Text Available Atropine (AT and dipyrone (Dp induce a delay of gastric emptying (GE of liquids in rats by inhibiting muscarinic receptors and activating β2-adrenergic receptors, respectively. The objective of the present study was to determine the effects of pretreatment with AT and Dp, given alone or in combination, on the effect of hypoglycemia in the liquid GE in rats. Male Wistar adult rats (280-310 g were pretreated intravenously with AT, Dp, AT plus Dp or their vehicle and then treated 30 min later with iv insulin or its vehicle (n=8-10 animals/group. Thirty min after treatment, GE was evaluated by determining, in awake rats, the percent gastric retention (%GR of a saline meal labeled with phenol red administered by gavage. The results indicated that insulin induced hypoglycemia in a dose-dependent manner resulting in a significant reduction in %GR of liquid only at the highest dose tested (1 U/kg. Pretreatment with AT significantly increased %GR in the rats treated with 1 U/kg insulin. Surprisingly, after pretreatment with AT, the group treated with the lowest dose of insulin (0.25 U/kg displayed significantly lower %GR compared to its control (vehicle-treated group, which was not seen in the non-pretreated animals. Pretreatment with Dp alone at the dose of 40 mg/kg induced an increase in %GR in both vehicle and 0.25 U/kg-treated rats. A higher dose of Dp alone (80 mg/kg significantly reduced the effect of a marked hypoglycemia induced by 1 U/kg of insulin on GE while in combination with AT the effect was completely abolished. The results with AT suggest that moderate hypoglycemia may render the inhibitory mechanisms of GE ineffective while Dp alone and in combination with AT significantly overcame the effect of hypoglycemia on GE.

  9. [Protective effect of compound bismuth and magnesium granules on aspirin-induced gastric mucosal injury in rats].

    Science.gov (United States)

    Mu, F H; Hu, F L; Wei, H; Zhang, Y Y; Yang, G B; Lei, X Y; Yang, Y P; Sun, W N; Cui, M H

    2016-02-01

    To investigate the protective effect of compound bismuth and magnesium granules on aspirin-induced gastric mucosal injury in rats and its possible mechanism. Acute gastric mucosal injury model was developed with intraperitoneal injection of aspirin in Wistar rats. The rats were divided into normal control group, injury group, sucralfate protection group, compound bismuth and magnesium granules protection group and its herbal components protection group(each group 12 rats). In the protection groups, drugs as mentioned above were administered by gavage before treated with intraperitoneal injection of aspirin. To evaluate the extent of gastric mucosal injury and the protective effect of drugs, gastric mucosal lesion index, gastric mucosal blood flow, content of gastric mucosal hexosamine, prostaglandins (PG), nitric oxide(NO), tumor necrosis factor (TNF), and interleukin (IL) -1, 2, 8 were measured in each group, and histological changes were observed by gross as well as under microscope and electron microscope. Contents of hexosamine, NO, and PG in all the protection groups were significantly higher than those in the injury group (all Pcompound bismuth and magnesium granules group was significantly higher than that in the sucralfate group ((11.29±0.51) vs(10.80±0.36)nmol/ml, Pcompound bismuth and magnesium granules group were significantly lower than those in the sucralfate group ((328.17±6.56) vs(340.23±8.05)pg/ml, PCompound bismuth and magnesium granules and its herbal components may have significant protective effect on aspirin-induced gastric mucosal injury.

  10. Altered expression of hypoxia-inducible factor-1α (HIF-1α and its regulatory genes in gastric cancer tissues.

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    Jihan Wang

    Full Text Available Tissue hypoxia induces reprogramming of cell metabolism and may result in normal cell transformation and cancer progression. Hypoxia-inducible factor 1-alpha (HIF-1α, the key transcription factor, plays an important role in gastric cancer development and progression. This study aimed to investigate the underlying regulatory signaling pathway in gastric cancer using gastric cancer tissue specimens. The integration of gene expression profile and transcriptional regulatory element database (TRED was pursued to identify HIF-1α ↔ NFκB1 → BRCA1 → STAT3 ← STAT1 gene pathways and their regulated genes. The data showed that there were 82 differentially expressed genes that could be regulated by these five transcription factors in gastric cancer tissues and these genes formed 95 regulation modes, among which seven genes (MMP1, TIMP1, TLR2, FCGR3A, IRF1, FAS, and TFF3 were hub molecules that are regulated at least by two of these five transcription factors simultaneously and were associated with hypoxia, inflammation, and immune disorder. Real-Time PCR and western blot showed increasing of HIF-1α in mRNA and protein levels as well as TIMP1, TFF3 in mRNA levels in gastric cancer tissues. The data are the first study to demonstrate HIF-1α-regulated transcription factors and their corresponding network genes in gastric cancer. Further study with a larger sample size and more functional experiments is needed to confirm these data and then translate into clinical biomarker discovery and treatment strategy for gastric cancer.

  11. Inhibitory effect of ramosetron on corticotropin releasing factor- and soybean oil-induced delays in gastric emptying in rats.

    Science.gov (United States)

    Hirata, Takuya; Keto, Yoshihiro; Yamano, Mayumi; Yokoyama, Toshihide; Sengoku, Takanori; Seki, Nobuo

    2012-09-01

    Symptoms of functional dyspepsia (FD) are highly prevalent in patients with irritable bowel syndrome (IBS). However, the effects of therapeutic agents for IBS on the pathophysiology of FD are unclear. In this study, therefore, we examined the effects of ramosetron, a serotonin 5-HT(3) receptor antagonist, on corticotropin releasing factor (CRF)- and soybean oil-induced delays in gastric emptying of rats, in comparison with anti-diarrheal agent and spasmolytics. The involvement of 5-HT and the 5-HT(3) receptor in delayed gastric emptying was also evaluated. Corticotropin releasing factor was administered intravenously to rats 10min before oral administration of 0.05% phenol red solution, and the amount remaining in the stomach was measured after 30min. Soybean oil was administered orally with glass beads, and the number of residual beads in the stomach was counted 1h later. Both CRF and soybean oil inhibited gastric emptying dose-dependently. Ramosetron and itopride, a gastro-prokinetic agent, significantly reduced both CRF- and soybean oil-induced delays in gastric emptying, while an anti-diarrheal agent and spasmolytics aggravated them. Pretreatment with p-chlorophenylalanine for 2days to reduced the synthesis of endogenous 5-HT diminished the effects of both CRF and soybean oil on gastric emptying. A 5-HT(3) receptor agonist m-chlorophenylbiguanide suppressed gastric emptying of both phenol red and glass beads, and those effects were reversed by ramosetron. These results suggest that CRF and soybean oil suppress gastric emptying in rats by activating 5-HT(3) receptors, and that by antagonizing these receptors, ramosetron may ameliorate symptoms of FD in clinical settings. © 2012 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

  12. Carbon Monoxide (CO Released from Tricarbonyldichlororuthenium (II Dimer (CORM-2 in Gastroprotection against Experimental Ethanol-Induced Gastric Damage.

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    Katarzyna Magierowska

    Full Text Available The physiological gaseous molecule, carbon monoxide (CO becomes a subject of extensive investigation due to its vasoactive activity throughout the body but its role in gastroprotection has been little investigated. We determined the mechanism of CO released from its donor tricarbonyldichlororuthenium (II dimer (CORM-2 in protection of gastric mucosa against 75% ethanol-induced injury. Rats were pretreated with CORM-2 30 min prior to 75% ethanol with or without 1 non-selective (indomethacin or selective cyclooxygenase (COX-1 (SC-560 and COX-2 (celecoxib inhibitors, 2 nitric oxide (NO synthase inhibitor L-NNA, 3 ODQ, a soluble guanylyl cyclase (sGC inhibitor, hemin, a heme oxygenase (HO-1 inductor or zinc protoporphyrin IX (ZnPPIX, an inhibitor of HO-1 activity. The CO content in gastric mucosa and carboxyhemoglobin (COHb level in blood was analyzed by gas chromatography. The gastric mucosal mRNA expression for HO-1, COX-1, COX-2, iNOS, IL-4, IL-1β was analyzed by real-time PCR while HO-1, HO-2 and Nrf2 protein expression was determined by Western Blot. Pretreatment with CORM-2 (0.5-10 mg/kg dose-dependently attenuated ethanol-induced lesions and raised gastric blood flow (GBF but large dose of 100 mg/kg was ineffective. CORM-2 (5 mg/kg and 50 mg/kg i.g. significantly increased gastric mucosal CO content and whole blood COHb level. CORM-2-induced protection was reversed by indomethacin, SC-560 and significantly attenuated by celecoxib, ODQ and L-NNA. Hemin significantly reduced ethanol damage and raised GBF while ZnPPIX which exacerbated ethanol-induced injury inhibited CORM-2- and hemin-induced gastroprotection and the accompanying rise in GBF. CORM-2 significantly increased gastric mucosal HO-1 mRNA expression and decreased mRNA expression for iNOS, IL-1β, COX-1 and COX-2 but failed to affect HO-1 and Nrf2 protein expression decreased by ethanol. We conclude that CORM-2 released CO exerts gastroprotection against ethanol-induced gastric

  13. Helicobacter pylori infection-induced H3Ser10 phosphorylation in stepwise gastric carcinogenesis and its clinical implications.

    Science.gov (United States)

    Yang, Tao-Tao; Cao, Na; Zhang, Hai-Hui; Wei, Jian-Bo; Song, Xiao-Xia; Yi, Dong-Min; Chao, Shuai-Heng; Zhang, Li-Da; Kong, Ling-Fei; Han, Shuang-Yin; Yang, Yu-Xiu; Ding, Song-Ze

    2018-04-15

    Our previous works have demonstrated that Helicobacter pylori (Hp) infection can alter histone H3 serine 10 phosphorylation status in gastric epithelial cells. However, whether Helicobacter pylori-induced histone H3 serine 10 phosphorylation participates in gastric carcinogenesis is unknown. We investigate the expression of histone H3 serine 10 phosphorylation in various stages of gastric disease and explore its clinical implication. Stomach biopsy samples from 129 patients were collected and stained with histone H3 serine 10 phosphorylation, Ki67, and Helicobacter pylori by immunohistochemistry staining, expressed as labeling index. They were categorized into nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, and intestinal-type gastric cancer groups. Helicobacter pylori infection was determined by either 13 C-urea breath test or immunohistochemistry staining. In Helicobacter pylori-negative patients, labeling index of histone H3 serine 10 phosphorylation was gradually increased in nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia groups, peaked at low-grade intraepithelial neoplasia, and declined in high-grade intraepithelial neoplasia and gastric cancer groups. In Helicobacter pylori-infected patients, labeling index of histone H3 serine 10 phosphorylation followed the similar pattern as above, with increased expression over the corresponding Helicobacter pylori-negative controls except in nonatrophic gastritis patient whose labeling index was decreased when compared with Helicobacter pylori-negative control. Labeling index of Ki67 in Helicobacter pylori-negative groups was higher in gastric cancer than chronic atrophic gastritis and low-grade intraepithelial neoplasia groups, and higher in intestinal metaplasia group compared with chronic atrophic gastritis group. In Helicobacter pylori-positive groups, Ki67 labeling index was increased

  14. Acid-base chemistry of omeprazole in aqueous solutions

    International Nuclear Information System (INIS)

    Yang Rong; Schulman, Stephen G.; Zavala, Pedro J.

    2003-01-01

    Omeprazole is a potent anti-acid drug. Its absorption and mode of action are closely related to its prototropic behavior. In the present study, omeprazole samples from different sources and in different forms were studied spectrophotometrically to obtain pK a values. In the neutral to alkaline pH region, two consistent pK a values of 7.1 and 14.7 were obtained from various samples. The assignment of these pK a values was realized by comparison with the prototropic properties of N(1)-methylated omeprazole substituted on the nitrogen at the 1-position of the benzimidazole ring, which was found to have a pK a of 7.5. The omeprazole pK a of 14.7 is assigned to the dissociation of the hydrogen from the 1-position of the benzimidazole ring and the pK a of 7.1 is assigned to the dissociation from the protonated pyridine nitrogen of omeprazole. The results presented are at variance with those of earlier work

  15. Transcriptome Reveals 1400-Fold Upregulation of APOA4-APOC3 and 1100-Fold Downregulation of GIF in the Patients with Polycythemia-Induced Gastric Injury.

    Science.gov (United States)

    Li, Kang; Gesang, Luobu; Dan, Zeng; Gusang, Lamu; Dawa, Ciren; Nie, Yuqiang

    2015-01-01

    High-altitude polycythemia (HAPC) inducing gastric mucosal lesion (GML) is still out of control and molecular mechanisms remain widely unknown. To address the issues, endoscopy and histopathological analyses were performed. Meanwhile, microarray-based transcriptome profiling was conducted in the gastric mucosa from 3 pairs of healthy subjects and HAPC-induced GML patients. HAPC caused morphological changes and pathological damages of the gastric mucosa of GML patients. A total of 10304 differentially expressed genes (DEGs) were identified, including 4941 up-regulated and 5363 down-regulated DEGs in gastric mucosa of GML patients compared with healthy controls (fold change ≥2, Ppolycythemia while polycythemia raises the risk of GML. Therefore, the present findings reveal that HAPC-induced GML inspires the protection responses by up-regulating APOA4 and APOC3, and down-regulating GIF. These results may offer the basic information for the treatment of HAPC-induced gastric lesion in the future.

  16. 3,3'-diindolylmethane potentiates tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of gastric cancer cells.

    Science.gov (United States)

    Ye, Yang; Miao, Shuhan; Wang, Yan; Zhou, Jianwei; Lu, Rongzhu

    2015-05-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) specifically kills cancer cells without destroying the majority of healthy cells. However, numerous types of cancer cell, including gastric cancer cells, tend to be resistant to TRAIL. The bioactive product 3,3'-diindolylmethane (DIM), which is derived from cruciferous vegetables, is also currently recognized as a candidate anticancer agent. In the present study, a Cell Counting Kit 8 cell growth assay and an Annexin V-fluorescein isothiocyanate apoptosis assay were performed to investigate the potentiating effect of DIM on TRAIL-induced apoptosis in gastric cancer cells, and the possible mechanisms of this potentiation. The results obtained demonstrated that, compared with TRAIL or DIM treatment alone, co-treatment with TRAIL (25 or 50 ng/ml) and DIM (10 µmol/l) induced cytotoxic and apoptotic effects in BGC-823 and SGC-7901 gastric cancer cells. Furthermore, western blot analysis revealed that the protein expression levels of death receptor 5 (DR5), CCAAT/enhancer binding protein homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) were upregulated in the co-treated gastric cancer cells. To the best of our knowledge, the present study is the first to provide evidence that DIM sensitizes TRAIL-induced inhibition of proliferation and apoptosis in gastric cancer cells, accompanied by the upregulated expression of DR5, CHOP and GRP78 proteins, which may be involved in endoplasmic reticulum stress mechanisms.

  17. Therapeutics for Equine Gastric Ulcer Syndrome.

    Science.gov (United States)

    Zavoshti, Fereydon Rezazadeh; Andrews, Frank M

    2017-04-01

    Equine gastric ulcer syndrome (EGUS) is an umbrella term used to describe ulcers in the nonglandular squamous and glandular mucosa, terminal esophagus, and proximal duodenum. Gastric ulcers in the squamous and glandular regions occur more often than esophageal or duodenal ulcers and likely have a different pathogenesis. At present, omeprazole is accepted globally as the best pharmacologic therapy for both regions of the stomach; however, the addition of coating agents and synthetic prostaglandins could add to its effectiveness in treatment of EGUS. Dietary and environmental management are necessary for prevention of recurrence. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Study of Cyclooxygenase-2 Expression in Sprague Dawley Rat Gastric Cancer Induced by H. Pylori

    Directory of Open Access Journals (Sweden)

    Pooladi A

    2011-01-01

    Full Text Available Background and Objectives: Gastric cancer is one of the most common gastrointestinal tumors; the incidence and mortality of gastric cancer are on the increase nowadays. Helicobacter pylori(H.Pylori causes chronic active gastritis and peptic ulcer disease. Cycloocygenase-2 (COX-2 is the central enzyme in the biosynthetic pathway to prostaglandins. Studies from different laboratories suggested that over-expression of COX-2 was detected in colon and other tumors. To obtain direct evidence concerning this relationship, we investigated the immunohistochemical findings of gastric mucosa using an animal model of gastric cancer induced by H. pylori in sprague dawley rat.Methods: The rats were randomly assigned into three groups(n=5. Those of experimental group2 were given MNU. one week after completion of MNU administration, rats in experimental groups 1 were inoculated with H. pylori three times every other day. Rats in control group(group 3 received neither MNU nor H. pylori. Rats of groups 1, 2, and control group were maintained on standard diets throughout the experiment. Rat were weighed and sacrificed under anesthesia with ether at 20 weeks after infection. One half of the excised stomachs, were fixed in neutral-buffered 10% formalin and were cut into approximately six strips, which were processed by standard methods, embedded in paraffin, sectioned at 6 µm, and stained with hematoxylin and eosin (H&E and immunohistochemistry for Cox-2 protein detection. To confirm H. pylori infection, samples ( 3-mm2 of stomach mucosa transferred to appropriate medium and Colonies were identified by characteristic Gram’s stain morphology, and by urease, catalase, and oxidase activity sample was also placed into the gel of a rapid urease test kit.Results: Data showed a significant decrease of animal body weight in experimental groups compared with control group. Histopathological studies showed severe infiltration of the lamina propria and submucusaal layer by

  19. Study of Cyclooxygenase-2 Expression in Sprague Dawley Rat Gastric Cancer Induced by H. Pylori

    Directory of Open Access Journals (Sweden)

    F Aeini

    2012-05-01

    Full Text Available

    Background and Objectives: Gastric cancer is one of the most common gastrointestinal tumors; the incidence and mortality of gastric cancer are on the increase nowadays. Helicobacter pylori(H.Pylori causes chronic active gastritis and peptic ulcer disease. Cycloocygenase-2 (COX-2 is the central enzyme in the biosynthetic pathway to prostaglandins. Studies from different laboratories suggested that over-expression of COX-2 was detected in colon and other tumors. To obtain direct evidence concerning this relationship, we investigated the immunohistochemical findings of gastric mucosa using an animal model of gastric cancer induced by H. pylori in sprague dawley rat. Methods: The rats were randomly assigned into three groups(n=5. Those of experimental group2 were given MNU. one week after completion of MNU administration, rats in experimental groups 1 were inoculated with H. pylori three times every other day. Rats in control group(group 3 received neither MNU nor H. pylori. Rats of groups 1, 2, and control group were maintained on standard diets throughout the experiment. Rat were weighed and sacrificed under anesthesia with ether at 20 weeks after infection. One half of the excised stomachs, were fixed in neutral-buffered 10% formalin and were cut into approximately six strips, which were processed by standard methods, embedded in paraffin, sectioned at 6 µm, and stained with hematoxylin and eosin (H&E and immunohistochemistry for Cox-2 protein detection. To confirm H. pylori infection, samples ( 3-mm2 of stomach mucosa transferred to appropriate medium  and Colonies were identified by characteristic Gram’s stain morphology, and by urease, catalase, and oxidase activity sample was also placed into the gel of a rapid urease test kit. Results: Data showed a significant decrease of animal body weight in experimental groups compared with control group

  20. Saccharomyces boulardii administration can inhibit the formation of gastric lymphoid follicles induced by Helicobacter suis infection.

    Science.gov (United States)

    Yang, Lin; Tian, Zi-Bin; Yu, Ya-Nan; Zhang, Cui-Ping; Li, Xiao-Yu; Mao, Tao; Jing, Xue; Zhao, Wen-Jun; Ding, Xue-Li; Yang, Ruo-Ming; Zhang, Shuai-Qing

    2017-01-01

    Helicobacter suis has a greater tendency to induce gastric mucosa-associated lymphoid tissue lymphoma compared with other Helicobacter species in humans and animals. Saccharomyces boulardii has been established as an adjunct to H. pylori eradication treatment, but the effect of S. boulardii administration alone on Helicobacter infection remains unclear. Here, we found that S. boulardii administration effectively decreased the bacterial load of H. suis and inhibited the formation of lymphoid follicles in the stomach post-infection. The levels of H. suis-specific immunoglobulin A (IgA) and secretory IgA in the gastric juice and small intestinal secretions and the production of mouse β-defensin-3 in the small intestinal secretions were significantly increased by S. boulardii administration at 12 weeks after H. suis infection. In addition, feeding with S. boulardii inhibited the expression of inflammatory cytokines and lymphoid follicle formation-related factors after H. suis infection. These results suggested that S. boulardii may be useful for the prevention and treatment of Helicobacter infection-related diseases in humans. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Effect of the GABA B agonist baclofen on dipyrone-induced delayed gastric emptying in rats

    Directory of Open Access Journals (Sweden)

    E.F. Collares

    2005-01-01

    Full Text Available Dipyrone administered intravenously (iv or intracerebroventricularly (icv delays gastric emptying (GE in rats. Gamma-aminobutyric acid (GABA is the most potent inhibitory neurotransmitter of the central nervous system. The objective of the present study was to determine the effect of icv baclofen, a GABA B receptor agonist, on delayed GE induced by dipyrone. Adult male Wistar rats received a saline test meal containing phenol red as a marker. GE was indirectly evaluated by determining the percent of gastric retention (%GR of the meal 10 min after orogastric administration. In the first experiment, the animals were injected iv with vehicle (Civ or 80 mg/kg (240 µmol/kg dipyrone (Dp iv, followed by icv injection of 10 µl vehicle (bac0, or 0.5 (bac0.5, 1 (bac1 or 2 µg (bac2 baclofen. In the second experiment, the animals were injected icv with 5 µl vehicle (Cicv or an equal volume of a solution containing 4 µmol (1333.2 µg dipyrone (Dp icv, followed by 5 µl vehicle (bac0 or 1 µg baclofen (bac1. GE was determined 10 min after icv injection. There was no significant difference between control animals from one experiment to another concerning GR values. Baclofen at the doses of 1 and 2 µg significantly reduced mean %GR induced by iv dipyrone (Dp iv bac1 = 35.9% and Dp iv bac2 = 26.9% vs Dp iv bac0 = 51.8%. Similarly, baclofen significantly reduced the effect of dipyrone injected icv (mean %GR: Dp icv bac1 = 30.4% vs Dp icv bac0 = 54.2%. The present results suggest that dipyrone induces delayed GE through a route in the central nervous system that is blocked by the activation of GABA B receptors.

  2. Prolyl oligopeptidase inhibition-induced growth arrest of human gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Kanayo [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Sakaguchi, Minoru, E-mail: sakaguti@gly.oups.ac.jp [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Tanaka, Satoshi [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan); Yoshimoto, Tadashi [Department of Life Science, Setsunan University, 17-8 Ikeda-Nakamachi, Neyagawa, Osaka 572-8508 (Japan); Takaoka, Masanori [Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094 (Japan)

    2014-01-03

    Highlights: •We examined the effects of prolyl oligopeptidase (POP) inhibition on p53 null gastric cancer cell growth. •POP inhibition-induced cell growth suppression was associated with an increase in a quiescent G{sub 0} state. •POP might regulate the exit from and/or reentry into the cell cycle. -- Abstract: Prolyl oligopeptidase (POP) is a serine endopeptidase that hydrolyzes post-proline peptide bonds in peptides that are <30 amino acids in length. We recently reported that POP inhibition suppressed the growth of human neuroblastoma cells. The growth suppression was associated with pronounced G{sub 0}/G{sub 1} cell cycle arrest and increased levels of the CDK inhibitor p27{sup kip1} and the tumor suppressor p53. In this study, we investigated the mechanism of POP inhibition-induced cell growth arrest using a human gastric cancer cell line, KATO III cells, which had a p53 gene deletion. POP specific inhibitors, 3-((4-[2-(E)-styrylphenoxy]butanoyl)-L-4-hydroxyprolyl)-thiazolidine (SUAM-14746) and benzyloxycarbonyl-thioprolyl-thioprolinal, or RNAi-mediated POP knockdown inhibited the growth of KATO III cells irrespective of their p53 status. SUAM-14746-induced growth inhibition was associated with G{sub 0}/G{sub 1} cell cycle phase arrest and increased levels of p27{sup kip1} in the nuclei and the pRb2/p130 protein expression. Moreover, SUAM-14746-mediated cell cycle arrest of KATO III cells was associated with an increase in the quiescent G{sub 0} state, defined by low level staining for the proliferation marker, Ki-67. These results indicate that POP may be a positive regulator of cell cycle progression by regulating the exit from and/or reentry into the cell cycle by KATO III cells.

  3. AA-PMe, a novel asiatic acid derivative, induces apoptosis and suppresses proliferation, migration, and invasion of gastric cancer cells.

    Science.gov (United States)

    Jing, Yue; Wang, Gang; Ge, Ying; Xu, Minjie; Tang, Shuainan; Gong, Zhunan

    2016-01-01

    Asiatic acid (AA; 2α,3β,23-trihydroxyurs-12-ene-28-oic acid) is widely used for medicinal purposes in many Asian countries due to its various bioactivities. A series of AA derivatives has been synthesized in attempts to improve its therapeutic potencies. Herein we investigated the anti-tumor activities of N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-l-proline methyl ester (AA-PMe), a novel AA derivative. AA-PMe exhibited a stronger anti-cancer activity than its parent compound AA. AA-PMe inhibited the proliferation of SGC7901 and HGC27 human gastric cancer cells in a dose-dependent manner but had no significant toxicity in human gastric mucosa epithelial cells (GES-1). AA-PMe induced cell cycle arrest in G0/G1 phase and blocked G1-S transition, which correlated well with marked decreases in levels of cyclin D1, cyclin-dependent kinase CKD4, and phosphorylated retinoblastoma protein, and increase in cyclin-dependent kinase inhibitor P15. Further, AA-PMe induced apoptosis of human gastric cancer cells by affecting Bcl-2, Bax, c-Myc, and caspase-3. Moreover, AA-PMe suppressed the migration and invasion of human gastric cancer cells (SGC7901 and HGC27) cells by downregulating the expression of MMP-2 and MMP-9. Overall, this study investigated the potential anti-cancer activities of AA-PMe including inducing apoptosis and suppressing proliferation, migration and invasion of gastric cancer cells, as well as the underlying mechanisms, suggesting that AA-PMe is a promising anti-cancer drug candidate in gastric cancer therapy.

  4. AA-PMe, a novel asiatic acid derivative, induces apoptosis and suppresses proliferation, migration, and invasion of gastric cancer cells

    Science.gov (United States)

    Jing, Yue; Wang, Gang; Ge, Ying; Xu, Minjie; Tang, Shuainan; Gong, Zhunan

    2016-01-01

    Asiatic acid (AA; 2α,3β,23-trihydroxyurs-12-ene-28-oic acid) is widely used for medicinal purposes in many Asian countries due to its various bioactivities. A series of AA derivatives has been synthesized in attempts to improve its therapeutic potencies. Herein we investigated the anti-tumor activities of N-(2α,3β,23-acetoxyurs-12-en-28-oyl)-l-proline methyl ester (AA-PMe), a novel AA derivative. AA-PMe exhibited a stronger anti-cancer activity than its parent compound AA. AA-PMe inhibited the proliferation of SGC7901 and HGC27 human gastric cancer cells in a dose-dependent manner but had no significant toxicity in human gastric mucosa epithelial cells (GES-1). AA-PMe induced cell cycle arrest in G0/G1 phase and blocked G1-S transition, which correlated well with marked decreases in levels of cyclin D1, cyclin-dependent kinase CKD4, and phosphorylated retinoblastoma protein, and increase in cyclin-dependent kinase inhibitor P15. Further, AA-PMe induced apoptosis of human gastric cancer cells by affecting Bcl-2, Bax, c-Myc, and caspase-3. Moreover, AA-PMe suppressed the migration and invasion of human gastric cancer cells (SGC7901 and HGC27) cells by downregulating the expression of MMP-2 and MMP-9. Overall, this study investigated the potential anti-cancer activities of AA-PMe including inducing apoptosis and suppressing proliferation, migration and invasion of gastric cancer cells, as well as the underlying mechanisms, suggesting that AA-PMe is a promising anti-cancer drug candidate in gastric cancer therapy. PMID:27073325

  5. 3-bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth.

    Science.gov (United States)

    Wang, Ting-An; Zhang, Xiao-Dong; Guo, Xing-Yu; Xian, Shu-Lin; Lu, Yun-Fei

    2016-03-01

    Glycolysis is the primary method utilized by cancer cells to produce the energy (adenosine triphosphate, ATP) required for cell proliferation. Therefore, inhibition of glycolysis may inhibit tumor growth. We previously found that both 3-bromopyruvate (3-BrPA) and sodium citrate (SCT) can inhibit glycolysis in vitro; however, the underlying inhibitory mechanisms remain unclear. In the present study, we used a human gastric cancer cell line (SGC-7901) and an orthotopic transplantation tumor model in nude mice to explore the specific mechanisms of 3-BrPA and SCT. We found that both 3-BrPA and SCT effectively suppressed cancer cell proliferation, arrested the cell cycle, induced apoptosis, and decreased the production of lactate and ATP. 3-BrPA significantly reduced the glycolytic enzyme hexokinase activity, while SCT selectively inhibited phosphofructokinase-1 activity. Furthermore, 3-BrPA and SCT upregulated the expression of pro-apoptotic proteins (Bax, cytochrome c, and cleaved caspase-3) and downregulated the expression of anti-apoptotic proteins (Bcl-2 and survivin). Finally, our animal model of gastric cancer indicated that intraperitoneal injection of 3-BrPA and SCT suppressed orthotopic transplantation tumor growth and induced tumor apoptosis. Taken together, these results suggest that 3-BrPA and SCT selectively suppress glycolytic enzymes, decrease ATP production, induce mitochondrial-mediated apoptosis, downregulate survivin, and inhibit tumor growth. Moreover, an intraperitoneal injection is an effective form of administration of 3-BrPA and SCT.

  6. PIV and CFD studies on analyzing intragastric flow phenomena induced by peristalsis using a human gastric flow simulator.

    Science.gov (United States)

    Kozu, Hiroyuki; Kobayashi, Isao; Neves, Marcos A; Nakajima, Mitsutoshi; Uemura, Kunihiko; Sato, Seigo; Ichikawa, Sosaku

    2014-08-01

    This study quantitatively analyzed the flow phenomena in model gastric contents induced by peristalsis using a human gastric flow simulator (GFS). Major functions of the GFS include gastric peristalsis simulation by controlled deformation of rubber walls and direct observation of inner flow through parallel transparent windows. For liquid gastric contents (water and starch syrup solutions), retropulsive flow against the direction of peristalsis was observed using both particle image velocimetry (PIV) and computational fluid dynamics (CFD). The maximum flow velocity was obtained in the region occluded by peristalsis. The maximum value was 9 mm s(-1) when the standard value of peristalsis speed in healthy adults (UACW = 2.5 mm s(-1)) was applied. The intragastric flow-field was laminar with the maximum Reynolds number (Re = 125). The viscosity of liquid gastric contents hardly affected the maximum flow velocity in the applied range of this study (1 to 100 mPa s). These PIV results agreed well with the CFD results. The maximum shear rate in the liquid gastric contents was below 20 s(-1) at UACW = 2.5 mm s(-1). We also measured the flow-field in solid-liquid gastric contents containing model solid food particles (plastic beads). The direction of velocity vectors was influenced by the presence of the model solid food particle surface. The maximum flow velocity near the model solid food particles ranged from 8 to 10 mm s(-1) at UACW = 2.5 mm s(-1). The maximum shear rate around the model solid food particles was low, with a value of up to 20 s(-1).

  7. Accumulation of 8-nitroguanine in human gastric epithelium induced by Helicobacter pylori infection

    International Nuclear Information System (INIS)

    Ma, Ning; Adachi, Yukihiko; Hiraku, Yusuke; Horiki, Noriyuki; Horiike, Shinichirou; Imoto, Ichiro; Pinlaor, Somchai; Murata, Mariko; Semba, Reiji; Kawanishi, Shosuke

    2004-01-01

    Helicobacter pylori infection causes chronic inflammation, which can lead to gastric carcinoma. A double immunofluorescence labeling study demonstrated that the level of 8-nitroguanine and 8-oxo-7,8-dihydro-2 ' -deoxyguanosine (8-oxodG) apparent in gastric gland epithelium was significantly higher in gastritis patients with H. pylori infection than in those without infection. A significant accumulation of proliferating cell nuclear antigen, a prognostic factor for gastric cancer, was observed in gastric gland epithelial cells in patients with H. pylori infection as compared to those without infection, and its accumulation was closely correlated with the formation of 8-nitroguanine and 8-oxodG. These results suggest that nitrosative and oxidative DNA damage in gastric epithelial cells and their proliferation by H. pylori infection may lead to gastric carcinoma. 8-Nitroguanine could be not only a promising biomarker for inflammation but also a useful indicator of the risk of gastric cancer development in response to chronic H. pylori infection

  8. Helicobacter pylori infection induces genetic instability of nuclear and mitochondrial DNA in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel Dantas; Figueiredo, Ceu; Touati, Eliette

    2009-01-01

    of genetic instabilities in the nuclear and mitochondrial DNA (mtDNA) were examined. EXPERIMENTAL DESIGN: We observed the effects of H. pylori infection on a gastric cell line (AGS), on C57BL/6 mice, and on individuals with chronic gastritis. In AGS cells, the effect of H. pylori infection on base excision...... cells and chronic gastritis tissue were determined by PCR, single-stranded conformation polymorphism, and sequencing. H. pylori vacA and cagA genotyping was determined by multiplex PCR and reverse hybridization. RESULTS: Following H. pylori infection, the activity and expression of base excision repair...... and MMR are down-regulated both in vitro and in vivo. Moreover, H. pylori induces genomic instability in nuclear CA repeats in mice and in mtDNA of AGS cells and chronic gastritis tissue, and this effect in mtDNA is associated with bacterial virulence. CONCLUSIONS: Our results suggest that H. pylori...

  9. Potentiation of the gastric antisecretory activity of histamine H2-receptor antagonists by clebopride.

    Science.gov (United States)

    Fernández, A G; Massingham, R; Roberts, D J

    1988-05-01

    The substituted benzamide, clebopride, at doses (0.03-3 mg kg-1 i.p.) that were without effect per se on the secretion of gastric acid in pylorus ligated (Shay) rats, potentiated the antisecretory effects of the histamine H2 receptor antagonists cimetidine and ranitidine in this model but not those of the muscarine receptor antagonist pirenzepine nor those of the proton pump inhibitor omeprazole. By contrast, clebopride was without influence on the inhibitory effects of cimetidine on pentagastrin-induced secretion in perfused stomach (Ghosh and Schild) preparations in anaesthetized rats. The significance of these findings is discussed in relation to the previously described potentiating effects of clebopride on the anti-ulcer activity of cimetidine in various experimental models, and the potential beneficial effects of such combined therapy in the clinic.

  10. Prevention of experimentally-induced gastric ulcers in rats by an ethanolic extract of "Parsley" Petroselinum crispum.

    Science.gov (United States)

    Al-Howiriny, Tawfeq; Al-Sohaibani, Mohammed; El-Tahir, Kamal; Rafatullah, Syed

    2003-01-01

    An ethanolic extract of Parsley, Petroselinum crispum (Mill.) Nym.ex A.W. Hill (Umbelliferae), was tested for its ability to inhibit gastric secretion and to protect gastric mucosa against the injuries caused by pyloric ligation, hypothermic restraint stress, indomethacin and cytodestructive agents (80% ethanol, 0.2 M NaOH and 25% NaCl) in rats. The extract in doses of 1 and 2 g/kg body weight had a significant antiulcerogenic activity on the models used. Besides, ethanol-induced depleted gastric wall mucus and non-protein sulfhydryl contents were replenished by pretreatment with Parsley extract. Acute toxicity tests showed a large margin of safety for the extract. The phytochemical screening of Parsley leaves revealed the presence of tannins, flavonoids, sterols and/or triterpenes.

  11. Antioxidant Action of Mangrove Polyphenols against Gastric Damage Induced by Absolute Ethanol and Ischemia-Reperfusion in the Rat

    Directory of Open Access Journals (Sweden)

    Felipe Meira de-Faria

    2012-01-01

    Full Text Available Rhizophora mangle, the red mangrove, has long been known as a traditional medicine. Its bark has been used as astringent, antiseptic, hemostatic, with antifungic and antiulcerogenic properties. In this paper, we aimed to evaluate the antioxidant properties of a buthanolic fraction of the R. mangle bark extract (RM against experimental gastric ulcer in rats. Unib-Wh rats received pretreatment of R. mangle after the induction of gastric injury with absolute ethanol and ischemia-reperfusion. Gastric tissues from both methods were prepared to the enzymatic assays, the levels of sulfhydril compounds (GSH, lipid peroxides (LPO, and the activities of glutathione reductase (GR, glutathione peroxidase (GPx, superoxide dismutase (SOD and myeloperoxidase (MPO were measured. The RM protected the gastric mucosa in both methods used, ethanol-induced gastric ulcer and ischemia-reperfusion, probably, by modulating the activities of the enzymes SOD, GPx, and GR and increasing or maintaining the levels of GSH; in adittion, LPO levels were reduced. The results suggest that the RM antioxidant activity leads to tissue protection; thus one of the antiulcer mechanisms present on the pharmacological effects of R. mangle is the antioxidant property.

  12. Non-steroidal anti-inflammatory drugs and gastroprotection with proton pump inhibitors: a focus on ketoprofen/omeprazole.

    Science.gov (United States)

    Gigante, Antonio; Tagarro, Ignacio

    2012-04-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed agents for rheumatic disorders such as osteoarthritis (OA), rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Despite the known association between NSAID use and gastropathy, however, only around one-third of patients at risk of NSAID-induced gastrointestinal toxicity receive adequate gastroprotection, and as many as 44% of these patients are non-adherent. We review the co-prescription of proton pump inhibitors (PPIs) for the prevention of NSAID-induced gastropathy, with a particular focus on the first fixed-dose NSAID/PPI formulation: ketoprofen/omeprazole modified-release capsules. The ketoprofen/omeprazole fixed-dose combination is available in doses of 100 mg/20 mg, 150 mg/20 mg or 200 mg/20 mg as a single capsule for once-daily administration. Ketoprofen monotherapy has been shown to be generally equivalent to other NSAIDs when used in the treatment of OA. In RA, ketoprofen has demonstrated equivalent efficacy to diclofenac, indometacin, piroxicam, aceclofenac, phenylbutazone, naproxen and flurbiprofen. Studies comparing ketoprofen with ibuprofen and sulindac in patients with RA have, in general, favoured ketoprofen. Studies in AS have generally reported similar efficacy between ketoprofen and phenylbutazone and pirprofen. Prophylaxis with omeprazole is effective for the prevention of gastroduodenal ulcers, maintenance of remission and alleviation of dyspeptic symptoms in NSAID recipients. Omeprazole is well tolerated, and adverse events are generally gastrointestinal in nature. The fixed-dose combination of ketoprofen and omeprazole has demonstrated bioequivalence to the respective monotherapies. The incidence of digestive symptoms and the need for dose reduction was reported to be lower with the combination than with its components. Ketoprofen/omeprazole modified-release capsules are the first fixed-dose NSAID/PPI formulation to be approved. This formulation

  13. Attenuated expression of the tight junction proteins is involved in clopidogrel-induced gastric injury through p38 MAPK activation

    International Nuclear Information System (INIS)

    Wu, Hai-Lu; Gao, Xin; Jiang, Zong-Dan; Duan, Zhao-Tao; Wang, Shu-Kui; He, Bang-Shun; Zhang, Zhen-Yu; Xie, Hong-Guang

    2013-01-01

    Highlights: ► Clopidogrel suppressed GES-1 cell viability in a concentration- and time-dependent manner. ► Clopidogrel significantly increased dextran permeability, reduced occludin and ZO-1 expression, and induced cell apoptosis. ► Clopidogrel activated p38 MAPK signaling pathway. ► Activation of p38 activity was involved in clopidogrel-induced increase in gastric epithelial cells permeability and disruption of TJ. -- Abstract: Bleeding complications and delayed healing of gastric ulcer associated with use of clopidogrel is a common clinical concern; however, the underlying mechanisms remain to be determined. This study aimed to clarify whether clopidogrel could cause the damage of the human gastric epithelial cells and to further elucidate the mechanisms involved. After human gastric epithelial cell line GES-1 had been treated with clopidogrel (0.5–2.5 mM), the cell proliferation was examined by MTT assay, apoptosis was measured with DAPI staining and flow cytometry analysis, and the barrier function of the tight junctions (TJ) was evaluated by permeability measurement and transmission electron microscopy. Moreover, expression of the TJ proteins occludin and ZO-1 and the phosphorylation of the mitogen-activated protein kinases (MAPK) p38, ERK, and JNK were examined by western blot. In addition, three MAPK inhibitors specific to p38, ERK and JNK were used, respectively, to verify the signaling pathways responsible for regulating the expression of the TJ proteins being tested. Results showed that clopidogrel significantly increased dextran permeability, induced apoptosis, suppressed GES-1 cell viability, and reduced the expression of the TJ proteins (occludin and ZO-1), acting through p38 MAPK phosphorylation. Furthermore, these observed effects were partially abolished by SB-203580 (a p38 MAPK inhibitor), rather than by either U-0126 (an ERK inhibitor) or SP-600125 (a JNK inhibitor), suggesting that clopidogrel-induced disruption in the gastric

  14. Gastroprotective actions of Taraxacum coreanum Nakai water extracts in ethanol-induced rat models of acute and chronic gastritis.

    Science.gov (United States)

    Yang, Hye Jeong; Kim, Min Jung; Kwon, Dae Young; Kang, Eun Seon; Kang, Suna; Park, Sunmin

    2017-08-17

    Taraxacum coreanum Nakai has been traditionally used for treating inflammatory diseases including gastrointestinal diseases. We studied whether water extracts of Taraxacum coreanum Nakai (TCN) had a protective effect on acute and chronic gastritis induced by ethanol/HCl in an animal model of gastritis and its mechanism was also explored. In the acute study, rats were orally administered 0.15g/mL dextrin (normal-control), 0.15g/mL dextrin (control), 0.05g/mL TCN (TCN-L), 0.15g/mL TCN (TCN-H), or 0.01g/mL omeprazole (orally; positive-control), followed by oral administration of 1mL of 60% ethanol plus 150mM HCl (inducer). In the chronic study, rats were administered 10% diluted inducer in drinking water, and 0.6% dextrin, 0.2% or 0.6% TCN, and 0.05% omeprazole were administered in chow for 4 weeks. Acid content, gastric structure, oxidative stress, and markers of inflammation in the stomach tissue were measured at the end of experiment. Acute and chronic ethanol/HCl administration caused the inner layer of the stomach to redden, hemorrhage, and edema in the control group; TCN-H reduced these symptoms more effectively than did the omeprazole positive-control. Acid production and total acidity in the stomach increased in the control group, which was markedly suppressed by omeprazole. TCN also reduced the acid production and acidity, but not to the same degree as omeprazole. H-E and PAS staining revealed that in the inner layer of the stomach, cellular structure was disrupted, with an increased nuclear size and thickness, disarrangement, and decreased mucin in the control group. TCN prevented the cellular disruption in the inner layer, and TCN-H was more effective than the positive-control. This was associated with oxidative stress and inflammation. TCN dose-dependently reduced the infiltration of mast cells and TNF-α expression in the inner layer of the stomach, and decreased lipid peroxides by increasing superoxide dismutase and glutathione peroxidase expression. TCN

  15. Efficacy of omeprazole/sodium bicarbonate treatment in gastroesophageal reflux disease: a systematic review.

    Science.gov (United States)

    Higuera-de-la-Tijera, Fátima

    2018-03-14

    Proton pump inhibitors are the most effective medical therapy for gastroesophageal reflux disease, but their onset of action may be slow. To assess the available literature regarding the efficacy of omeprazole/sodium bicarbonate in gastroesophageal reflux patients. A systematic review was conducted. A systematic literature search starting from 2000. Reviewed manuscripts concerning the effectiveness of omeprazole/sodium bicarbonate treatment in gastroesophageal reflux disease were reviewed and the data were extracted. Data were subsequently analyzed with descriptive statistics. This review included information of four studies. Two trials compared the efficacy of omeprazole/sodium bicarbonate versus omeprazole. One study compared the efficacy of once-daily morning or nighttime dosing. And another study compared omeprazole/sodium bicarbonate/alginate versus omeprazole. In total, there was no difference between omeprazole/sodium bicarbonate and omeprazole. However, there is a trend towards more sustained response and a greater proportion of patients with sustained total relief by 30 minutes with omeprazole/sodium bicarbonate. Omeprazole/sodium bicarbonate therapy is not more effective than omeprazole in the treatment of gastroesophageal reflux disease. However, data obtained suggest that it can have a more sustained response and sustained total relief.

  16. Gastro-protective effect of methanol extract of Vernonia amygdalina (del. leaf on aspirin-induced gastric ulcer in Wistar rats

    Directory of Open Access Journals (Sweden)

    Modinat A. Adefisayo

    Full Text Available This study investigated the protective effects of methanol extract of Vernonia amygdalina leaf (MEVA on aspirin induced gastric ulcer in rats. Thirty Wistar rats, 150–200 g were divided into six groups as follows: Group 1 (control rats received 2 mL/kg of propylene glycol for 28 consecutive days. Group 2 (Ulcer Control received 150 mg/kg/day of aspirin suspended in 3 mL of 1% carboxymethylcellulose in water orally for 3 consecutive days during which the rats were fasted for the induction of ulcer. Group 3 received cimetidine at 100 mg/kg/day orally for 28 consecutive days and thereafter treated as group 2. Groups 4, 5 and 6 received MEVA orally at 200, 300 and 400 mg/kg/day respectively for 28 consecutive days and thereafter were treated with aspirin as group 2. All the animals were sacrifice at the end of the study to determine the gastric pH, gastric acidity, gastric ulcer score, haematological indices, superoxide dismutase (SOD activity, reduced glutathione (GSH and Lipid peroxidation (LPO levels. The result showed that aspirin significantly (p < 0.05 increased gastric ulcer score and index, decreased gastric pH, gastric acidity, SOD activity, GSH level as well as increased LPO level. It induced significant necrosis of the stomach tissue. Administration of MEVA significantly (p < 0.05 increased gastric pH, but decreased gastric acid secretion and reversed alteration of haematological parameters. It also significantly (p < 0.05 increased SOD activity, GSH level and decreased LPO level. The results suggest that Vernonia amygdalina possesses gastro-protective properties against aspirin-induced gastric ulcer. Keywords: Vernonia amygdalina, Aspirin, Gastric ulcer, Antioxidant, Rat

  17. Reversing gastric mucosal alterations during ethanol-induced chronic gastritis in rats by oral administration of Opuntia ficus-indica mucilage

    Science.gov (United States)

    Vázquez-Ramírez, Ricardo; Olguín-Martínez, Marisela; Kubli-Garfias, Carlos; Hernández-Muñoz, Rolando

    2006-01-01

    AIM: To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica (Cactaceae) on the healing of ethanol-induced gastritis in rats. METHODS: Chronic gastric mucosa injury was treated with mucilage (5 mg/kg per day) after it was induced by ethanol. Lipid composition, activity of 5’-nucleotidase (a membrane-associated ectoenzyme) and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined. Histological studies of gastric samples from the experimental groups were included. RESULTS: Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes. Phosphatidylcholine (PC) decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect. The activity of 5’-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes. CONCLUSION: The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids, mainly PC and phosphatidylethanolamine (PE), may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage. PMID:16865772

  18. Reversing gastric mucosal alterations during ethanol-induced chronic gastritis in rats by oral administration of Opuntia ficus-indica mucilage.

    Science.gov (United States)

    Vázquez-Ramírez, Ricardo; Olguín-Martínez, Marisela; Kubli-Garfias, Carlos; Hernández-Muñoz, Rolando

    2006-07-21

    To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica (Cactaceae) on the healing of ethanol-induced gastritis in rats. Chronic gastric mucosa injury was treated with mucilage (5 mg/kg per day) after it was induced by ethanol. Lipid composition, activity of 5'-nucleotidase (a membrane-associated ectoenzyme) and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined. Histological studies of gastric samples from the experimental groups were included. Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes. Phosphatidylcholine (PC) decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect. The activity of 5'-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes. The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids, mainly PC and phosphatidylethanolamine (PE), may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage.

  19. The effects of lycopene on DNA damage and oxidative stress on indomethacin-induced gastric ulcer in rats.

    Science.gov (United States)

    Boyacioglu, Murat; Kum, Cavit; Sekkin, Selim; Yalinkilinc, Hande Sultan; Avci, Hamdi; Epikmen, Erkmen Tugrul; Karademir, Umit

    2016-04-01

    Lycopene, the main antioxidant compound present in tomatoes, has high singlet oxygen- and peroxyl radicals-quenching ability, resulting in protection against oxidative damage in aerobic cell. Indomethacin is a nonsteroidal anti-inflammatory drug, and can promote oxidative damage in gastric tissue. The aim of this study was to investigate the protective effects of lycopene on an indomethacin-induced gastric ulcer model. A total of 42 adult male Wistar rats were divided into six groups of seven animals as follows: control, indomethacin, lansoprazole, lycopene 10 mg/kg, lycopene 50 mg/kg and lycopene 100 mg/kg. Gastric ulcers were induced by oral administration of indomethacin, after which the differing doses of lycopene were administered by oral gavage. The efficacy of lycopene was compared with lansoprazole. DNA damage of lymphocytes was measured by comet assay. Activities of superoxide dismutase, catalase and myeloperoxidase, as well as malondialdehyde and glutathione levels were determined in stomach tissue. This tissue was also taken for pathological investigations. The TUNEL method was used to detect apoptotic cells in paraffin sections. The results showed that 100 mg/kg lycopene administration significantly decreased % Tail DNA and Mean Tail Moment in the gastric ulcer group, compared with the other treatment groups. This same dose of lycopene also significantly decreased high malondialdehyde level and myeloperoxidase activity, and increased the activity of antioxidant enzymes (with the exception of catalase) in tissue. Apoptosis rates in the stomachs of the rats correlated with the biochemical and histopathological findings. These results indicated that lycopene might have a protective effect against indomethacin-induced gastric ulcer and oxidative stress in rats. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  20. The dipeptidyl peptidase 4 inhibitor vildagliptin does not accentuate glibenclamide-induced hypoglycemia but reduces glucose-induced glucagon-like peptide 1 and gastric inhibitory polypeptide secretion

    DEFF Research Database (Denmark)

    El-Ouaghlidi, Andrea; Rehring, Erika; Holst, Jens Juul

    2007-01-01

    BACKGROUND/AIMS: Inhibition of dipeptidyl peptidase 4 by vildagliptin enhances the concentrations of the active form of the incretin hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP). The present study asked whether vildagliptin accentuates glibenclamide-induced hy...

  1. Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans

    DEFF Research Database (Denmark)

    Mertz-Nielsen, A; Hillingsø, Jens; Bukhave, K

    1996-01-01

    with control experiments. Also the combination of omeprazole and ranitidine increased (p = 0.05) duodenal bicarbonate secretion, while ranitidine alone caused no change in either basal or stimulated secretion. In the stomach basal as well as vagally stimulated bicarbonate secretion was independent of the means...

  2. Neurokinin-1 receptor blocker CP-99 994 improved emesis induced by cisplatin via regulating the activity of gastric distention responsive neurons in the dorsal motor nucleus of vagus and enhancing gastric motility in rats.

    Science.gov (United States)

    Sun, X; Xu, L; Guo, F; Luo, W; Gao, S; Luan, X

    2017-10-01

    Nowadays, chemotherapy induced nausea and vomiting (CINV) is still common in patients with cancer. It was reported that substance P mediated CINV via neurokinin-1 (NK 1 ) receptor and antagonists of NK 1 receptor has been proved useful for treating CINV but the mechanism are not fully understood. This study aimed to examine the role of NK 1 receptor blocker, CP-99 994, when administrated into dorsal motor nucleus of vagus (DMNV), on the cisplatin-induced emesis in rats and the possible mechanism. Rats' kaolin intake, food intake, and bodyweight were recorded every day; gastric contraction activity was recorded in conscious rats through a force transducer implanted into the stomach; gastric emptying was monitored using the phenol red method; single unit extracellular firing in the DMNV were recorded. DMNV microinjection of CP-99 994 reduced the changes of increased kaolin consumption and suppressed food intake in cisplatin-treated rats; enhanced the gastric contraction activity dose-dependently in control and cisplatin-treated rats but enhanced gastric emptying only in cisplatin-treated rats; reduced the firing rate of gastric distention inhibited (GD-I) neurons but increased the firing rate of GD excited (GD-E) neurons in the DMNV. The effects of CP-99 994 on gastric motility and neuronal activity were stronger in cisplatin-treated rats than those of control rats. Our results suggested that CP-99 994 could improve emesis induced by cisplatin by regulating gastric motility and gastric related neuronal activity in the DMNV. © 2017 John Wiley & Sons Ltd.

  3. Irigenin sensitizes TRAIL-induced apoptosis via enhancing pro-apoptotic molecules in gastric cancer cells.

    Science.gov (United States)

    Xu, Ying; Gao, Cheng-Cheng; Pan, Zhen-Guo; Zhou, Chuan-Wen

    2018-02-12

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) holds promising value for cancer therapy due to its capacity to induce apoptosis in cancer cells. Nevertheless, TRAIL therapy is greatly hampered by its resistance. Irigenin (Iri), isoflavonoids, can be isolated from the rhizome of Belamcanda chinensis, and has been shown anti-cancer properties. In this study, we explored if Iri could enhance TRAIL-regulated apoptosis in TRAIL resistant gastric cancer cells. Iri significantly potentiated TRAIL-triggered cytotoxicity. Iri alone and TRAIL alone showed no effective role in apoptosis induction, whereas combined treatment with Iri and TRAIL markedly induced apoptosis in cancer cells, as evidenced by the up-regulation of cleaved Caspase-8/-9/-3 and PARP. Additionally, the sensitization to TRAIL was along with the enhancement of pro-apoptotic proteins, including FAS-associated protein with death domain (FADD), death receptor 5 (DR5) and Bax. And suppressing FADD, DR5 and Bax by si RNA significantly reduced the apoptosis and enhanced the cell viability induced by the co-application of Iri and TRAIL. Moreover, the sensitization to TRAIL was accompanied by the decrease of Cellular-FLICE inhibitory protein (c-FLIP), Bcl-2 and Survivin. Additionally, Iri could sensitize TRAIL to produce reactive oxygen species (ROS). Pre-treatment of N-acetyl-cysteine (NAC), ROS scavenger, attenuated Iri plus TRAIL-induced apoptosis and improved cell viability. Finally, combination of Iri and TRAIL inhibited tumor growth in the xenograft model. Collectively, our present study gave new insights into the effects of Iri on potentiating TRAIL-sensitivity, and suggested that Iri could be a potential candidate for sensitizer of TRAIL-resistant cancer cell treatment. Copyright © 2018. Published by Elsevier Inc.

  4. A new technique for continuous measurement and recording of gastric potential difference in the rat: evaluation of NSAID-induced gastric mucosal damage.

    Science.gov (United States)

    Scarpignato, C; Corradi, C; Gandolfi, M A; Galmiche, J P

    1995-10-01

    Disruption of the gastric mucosal barrier by the so-called "barrier breakers" such as ethanol, aspirin, and bile is associated with an increase in gastric potential difference (GPD), that is, a decrease in its negativity. Because a good correlation between the degree of histological damage and changes in GPD has been observed, this parameter has been used increasingly as an index of mucosal integrity. However, the current methodology for measuring GPD is laborious due to the preparation and checking of KCl-agarose bridges prior to each experiment, and calculations--usually handmade--are time-consuming and inaccurate. In this paper, a new method allowing simultaneous measurement and recording of GPD in the rat is described. The method allows a simultaneous recording of intragastric pH and an automatic data analysis. The new technique has been validated by studying mucosal damage induced by aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) (namely indomethacin and droxicam) as well as the mucosal protective activity of an antacid and sucralfate. The similarity between the results obtained in this rat model and those derived from human experiments clearly show that the developed methodology yields results that are predictive for human pharmacology.

  5. Effect of DA-9701 on the Normal Motility and Clonidine-induced Hypomotility of the Gastric Antrum in Rats.

    Science.gov (United States)

    Kang, Je Wook; Han, Dae Kyeong; Kim, Ock Nyun; Lee, Kwang Jae

    2016-04-30

    DA-9701 is a novel prokinetic agent. In the present study, we investigated the effect of DA-9701 on the motility of the gastric antrum in the normal and clonidine-induced hypomotility in an in vivo animal model. A strain gauge force transducer was sutured on the gastric antrum to measure the contractile activity in rats. A total of 28 rats were subclassified into the 4 groups: (1) the placebo group, (2) the DA-9701 group, (3) the placebo group in the clonidine-pretreated rats, and (4) the DA-9701 group in the clonidine-pretreated rats. After the basal recording, either placebo (3% [w/v] hydroxypropylmethyl cellulose) or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. In the clonidinepretreated rats, either placebo or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. Oral administration of DA-9701 did not significantly alter the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the placebo group. The administration of clonidine decreased the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the administration of placebo. This reduction of the antral motility by the administration of clonidine was not observed in the clonidine-pretreated DA-9701 group. The percentage of the motility index in the postprandial period was significantly greater in the clonidine-pretreated DA-9701 group, compared with the clonidine-pretreated placebo group. DA-9701 improves the hypomotility of the gastric antrum induced by clonidine, suggesting its gastroprokinetic effect in the pathologic condition.

  6. Andrographolide induces apoptotic and non-apoptotic death and enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in gastric cancer cells

    OpenAIRE

    Lim, Sung-Chul; Jeon, Ho Jong; Kee, Keun Hong; Lee, Mi Ja; Hong, Ran; Han, Song Iy

    2017-01-01

    Andrographolide, a natural compound isolated from Andrographis paniculata, has been reported to possess antitumor activity. In the present study, the effect of andrographolide in human gastric cancer (GC) cells was investigated. Andrographolide induced cell death with apoptotic and non-apoptotic features. At a low concentration, andrographolide potentiated apoptosis and reduction of clonogenicity triggered by recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL)....

  7. induced gastric acid secretion in the common african toad – bufo

    African Journals Online (AJOL)

    admin

    supported by the report of Sitmewoka (2000) which showed that absence of NO inhibits the secretion of gastric acid. However, Kato et al. (1998) observed that either exogenous or endogenous NO has inhibitory action on gastric acid secretion in mammals. This observation was supported by. Takeuchi et al. (1994) who also ...

  8. Apoptosis induced by GanoPoly in human gastric cancer cell line ...

    African Journals Online (AJOL)

    In order to investigate polysaccharide effect on the cultured human gastric cancer cells (SGC7901), DNA ladder, flow cytometry and western blot were used to examine the morpholog, proliferation and apoptosis of human gastric cancer SGC-7901 cells when they were affected by polysaccharide. Results show that ...

  9. Human induced pluripotent stem cells labeled with fluorescent magnetic nanoparticles for targeted imaging and hyperthermia therapy for gastric cancer

    International Nuclear Information System (INIS)

    Li, Chao; Ruan, Jing; Yang, Meng; Pan, Fei; Gao, Guo; Qu, Su; Shen, You-Lan; Dang, Yong-Jun; Wang, Kan; Jin, Wei-Lin; Cui, Da-Xiang

    2015-01-01

    Human induced pluripotent stem (iPS) cells exhibit great potential for generating functional human cells for medical therapies. In this paper, we report for use of human iPS cells labeled with fluorescent magnetic nanoparticles (FMNPs) for targeted imaging and synergistic therapy of gastric cancer cells in vivo. Human iPS cells were prepared and cultured for 72 h. The culture medium was collected, and then was co-incubated with MGC803 cells. Cell viability was analyzed by the MTT method. FMNP-labeled human iPS cells were prepared and injected into gastric cancer-bearing nude mice. The mouse model was observed using a small-animal imaging system. The nude mice were irradiated under an external alternating magnetic field and evaluated using an infrared thermal mapping instrument. Tumor sizes were measured weekly. iPS cells and the collected culture medium inhibited the growth of MGC803 cells. FMNP-labeled human iPS cells targeted and imaged gastric cancer cells in vivo, as well as inhibited cancer growth in vivo through the external magnetic field. FMNP-labeled human iPS cells exhibit considerable potential in applications such as targeted dual-mode imaging and synergistic therapy for early gastric cancer

  10. Delayed-release oral suspension of omeprazole for the treatment of erosive esophagitis and gastroesophageal reflux disease in pediatric patients: a review

    Directory of Open Access Journals (Sweden)

    Alice Monzani

    2010-03-01

    Full Text Available Alice Monzani, Giuseppina Oderda1Department of Pediatrics, Università del Piemonte Orientale, Novara, ItalyAbstract: Omeprazole is a proton-pump inhibitor indicated for gastroesophageal reflux disease and erosive esophagitis treatment in children. The aim of this review was to evaluate the efficacy of delayed-release oral suspension of omeprazole in childhood esophagitis, in terms of symptom relief, reduction in reflux index and/or intragastric acidity, and endoscopic and/or histological healing. We systematically searched PubMed, Cochrane and EMBASE (1990 to 2009 and identified 59 potentially relevant articles, but only 12 articles were suitable to be included in our analysis. All the studies evaluated symptom relief and reported a median relief rate of 80.4% (range 35%–100%. Five studies reported a significant reduction of the esophageal reflux index within normal limits (<7% in all children, and 4 studies a significant reduction of intra-gastric acidity. The endoscopic healing rate, reported by 9 studies, was 84% after 8-week treatment and 95% after 12-week treatment, the latter being significantly higher than the histological healing rate (49%. In conclusion, omeprazole given at a dose ranging from 0.3 to 3.5 mg/kg once daily (median 1 mg/kg once daily for at least 12 weeks is highly effective in childhood esophagitis.Keywords: proton pump inhibitors, children, ranitidine, H2-blockers

  11. Poncirin Induces Apoptosis in AGS Human Gastric Cancer Cells through Extrinsic Apoptotic Pathway by up-Regulation of Fas Ligand.

    Science.gov (United States)

    Saralamma, Venu Venkatarame Gowda; Nagappan, Arulkumar; Hong, Gyeong Eun; Lee, Ho Jeong; Yumnam, Silvia; Raha, Suchismita; Heo, Jeong Doo; Lee, Sang Joon; Lee, Won Sup; Kim, Eun Hee; Kim, Gon Sup

    2015-09-18

    Poncirin, a natural bitter flavanone glycoside abundantly present in many species of citrus fruits, has various biological benefits such as anti-oxidant, anti-microbial, anti-inflammatory and anti-cancer activities. The anti-cancer mechanism of Poncirin remains elusive to date. In this study, we investigated the anti-cancer effects of Poncirin in AGS human gastric cancer cells (gastric adenocarcinoma). The results revealed that Poncirin could inhibit the proliferation of AGS cells in a dose-dependent manner. It was observed Poncirin induced accumulation of sub-G1 DNA content, apoptotic cell population, apoptotic bodies, chromatin condensation, and DNA fragmentation in a dose-dependent manner in AGS cells. The expression of Fas Ligand (FasL) protein was up-regulated dose dependently in Poncirin-treated AGS cells Moreover, Poncirin in AGS cells induced activation of Caspase-8 and -3, and subsequent cleavage of poly(ADP-ribose) polymerase (PARP). Inhibitor studies' results confirm that the induction of caspase-dependent apoptotic cell death in Poncirin-treated AGS cells was led by the Fas death receptor. Interestingly, Poncirin did not show any effect on mitochondrial membrane potential (ΔΨm), pro-apoptotic proteins (Bax and Bak) and anti-apoptotic protein (Bcl-xL) in AGS-treated cells followed by no activation in the mitochondrial apoptotic protein caspase-9. This result suggests that the mitochondrial-mediated pathway is not involved in Poncirin-induced cell death in gastric cancer. These findings suggest that Poncirin has a potential anti-cancer effect via extrinsic pathway-mediated apoptosis, possibly making it a strong therapeutic agent for human gastric cancer.

  12. Effects on gastric mucosa induced by dental bleaching – an experimental study with 6% hydrogen peroxide in rats

    Directory of Open Access Journals (Sweden)

    Anabela Baptista PAULA

    2015-10-01

    Full Text Available The value of aesthetic dentistry has precipitated several developments in the investigation of dental materials related to this field. The free marketing of these products is a problem and it is subject to various interpretations regarding its legality. There are several techniques for tooth whitening, the most used one being the external bleaching. It is the later version of such technique that poses the greatest danger of ingesting the product. The present study analysed the systemic effect of these products when they are swallowed.Objective This experimental study aimed to observe the effects of a tooth whitening product, whose active agent is 6% hydrogen peroxide, on the gastric mucosa of healthy and non-tumour gastric pathology animals.Material and Methods Fifty Wistar-Han rats were used and then distributed into 5 groups, one for control and four test groups in which the bleaching product was administered in animals with and without non-tumour gastric pathology (induced by the administration of 1 sample of 50% ethanol and 5% of drinking water during 6 days at different times of study by gavage. There was a decrease in body weight in animals of groups handled during the study period, which was most pronounced in IV and VA groups. Changes in spleen weight relative to body weight revealed no statistically significant changes. An analysis of the frequency was performed on the results of macroscopic observation of the gastric mucosa.Results The gastric mucosa revealed lesions in all manipulated groups, being more frequent in groups III and IV. It appears that there is a synergism when using hydrogen peroxide and 50% ethanol in the same group.Conclusion Therefore, it seems that there are some signs of toxicity 3 to 4 days after administration of 6% hydrogen peroxide. The prescription of these therapies must be controlled by the clinician and the risks must be minimized.

  13. Effects on gastric mucosa induced by dental bleaching--an experimental study with 6% hydrogen peroxide in rats.

    Science.gov (United States)

    Paula, Anabela Baptista; Dias, Maria Isabel; Ferreira, Manuel Marques; Carrilho, Teresa; Marto, Carlos Miguel; Casalta, João; Cabrita, António Silvério; Carrilho, Eunice

    2015-10-01

    The value of aesthetic dentistry has precipitated several developments in the investigation of dental materials related to this field. The free marketing of these products is a problem and it is subject to various interpretations regarding its legality. There are several techniques for tooth whitening, the most used one being the external bleaching. It is the later version of such technique that poses the greatest danger of ingesting the product. The present study analysed the systemic effect of these products when they are swallowed. This experimental study aimed to observe the effects of a tooth whitening product, whose active agent is 6% hydrogen peroxide, on the gastric mucosa of healthy and non-tumour gastric pathology animals. Fifty Wistar-Han rats were used and then distributed into 5 groups, one for control and four test groups in which the bleaching product was administered in animals with and without non-tumour gastric pathology (induced by the administration of 1 sample of 50% ethanol and 5% of drinking water during 6 days) at different times of study by gavage. There was a decrease in body weight in animals of groups handled during the study period, which was most pronounced in IV and VA groups. Changes in spleen weight relative to body weight revealed no statistically significant changes. An analysis of the frequency was performed on the results of macroscopic observation of the gastric mucosa. The gastric mucosa revealed lesions in all manipulated groups, being more frequent in groups III and IV. It appears that there is a synergism when using hydrogen peroxide and 50% ethanol in the same group. Therefore, it seems that there are some signs of toxicity 3 to 4 days after administration of 6% hydrogen peroxide. The prescription of these therapies must be controlled by the clinician and the risks must be minimized.

  14. Effects on gastric mucosa induced by dental bleaching – an experimental study with 6% hydrogen peroxide in rats

    Science.gov (United States)

    PAULA, Anabela Baptista; DIAS, Maria Isabel; FERREIRA, Manuel Marques; CARRILHO, Teresa; MARTO, Carlos Miguel; CASALTA, João; CABRITA, António Silvério; CARRILHO, Eunice

    2015-01-01

    The value of aesthetic dentistry has precipitated several developments in the investigation of dental materials related to this field. The free marketing of these products is a problem and it is subject to various interpretations regarding its legality. There are several techniques for tooth whitening, the most used one being the external bleaching. It is the later version of such technique that poses the greatest danger of ingesting the product. The present study analysed the systemic effect of these products when they are swallowed. Objective This experimental study aimed to observe the effects of a tooth whitening product, whose active agent is 6% hydrogen peroxide, on the gastric mucosa of healthy and non-tumour gastric pathology animals. Material and Methods Fifty Wistar-Han rats were used and then distributed into 5 groups, one for control and four test groups in which the bleaching product was administered in animals with and without non-tumour gastric pathology (induced by the administration of 1 sample of 50% ethanol and 5% of drinking water during 6 days) at different times of study by gavage. There was a decrease in body weight in animals of groups handled during the study period, which was most pronounced in IV and VA groups. Changes in spleen weight relative to body weight revealed no statistically significant changes. An analysis of the frequency was performed on the results of macroscopic observation of the gastric mucosa. Results The gastric mucosa revealed lesions in all manipulated groups, being more frequent in groups III and IV. It appears that there is a synergism when using hydrogen peroxide and 50% ethanol in the same group. Conclusion Therefore, it seems that there are some signs of toxicity 3 to 4 days after administration of 6% hydrogen peroxide. The prescription of these therapies must be controlled by the clinician and the risks must be minimized. PMID:26537721

  15. Comparative gastroprotective effects of natural honey, nigella sativa and cimetidine against acetylsalicylic acid Induced gastric ulcer in albino rats

    International Nuclear Information System (INIS)

    Bukhari, M.H.; Khalil, J.; Zahid, M.; Ansari, N.

    2011-01-01

    Natural honey (NH) and Nigella sativa (NS) seeds have been in use as a natural remedy for over thousands of years in various parts of the world. The aim of this study was to assess the protective effects of NS (Nigella sativa) and NH (natural honey) on acetylsalicylic acid induced gastric ulcer in an experimental model with comparison to Cimetidine (CD). The study was conducted on 100 male albino rats, divided into 5 groups, with 20 animals in each group. Group A was used as a control and treated with Gum Tragacanth (GT). Eighty animals of the other groups were given acetylsalicylic acid (0.2 gm/kg body weight for 3 days) to produce ulcers by gavage. Two animals from each group were sacrificed for the detection of gastric ulcers. The remaining 72 animals were equally divided in four groups (B, C, D and E). The rats in group B, C and D were given NS, NH, and CD respectively while those in E were kept as such. No gastric lesions were seen in control group A while all the animals in group E revealed gastric ulcers. The animals of group B, C and D showed healing effects in 15/18 (83%), 14/18 (78%) and 17/18 (94%) animals grossly; 13/18 (72%), 14/18 (78%) and 16/18 (89%) rats showed recovery on microscopic examination respectively. The healing effects were almost the same in all three groups therefore, the statistical difference was not significant among them (p =0.40 and 0.65) while significant from group E (p=0.0000075, 0.0000016 and 0.0000012 respectively). NS and NH are equally effective in healing of gastric ulcer similar to cimetidine. Further broad spectrum studies as well as clinical trials should be conducted before the use of these products as routine medicines. (author)

  16. Gastroprotective and ulcer healing effects of Piptadeniastrum Africanum on experimentally induced gastric ulcers in rats.

    Science.gov (United States)

    Ateufack, Gilbert; Domgnim Mokam, Elisabeth Carol; Mbiantcha, Marius; Dongmo Feudjio, Rostand Breuil; David, Nana; Kamanyi, Albert

    2015-07-08

    Gastric peptic ulcer is one of the common disorders of gastrointestinal tract, which occur due to an imbalance between the offensive and defensive factors. It is an illness that affects a considerable number of people worldwide. This study was conducted to evaluate the antiulcerogenic and antiulcer effects and recognize the basic mechanism of action of Piptadeniastrum africanum stem bark extracts. The aqueous and methanol extracts of Piptadeniastrum africanum were administered at the doses 125, 250 and 500 mg/kg to evaluate their effects on gastric ulcer induced by the HCl/ethanol mixture, indomethacin and acetic acid in Wistar strain male adult rats, aged between 12 and 16 weeks and weighing between 180 and 220 g. Ranitidine, Maalox and Misoprostol were used as standard drugs. Histopathological examination and nitric oxide level were performed to evaluate the basic mechanism of action of Piptadeniastrum africanum. Phytochemical screening was carried out to identify known phytochemicals present in these extracts. The aqueous and methanol extracts of stem bark of Piptadeniastrum africanum significantly inhibited (p ulceration induced by HCl/ethanol to the percentages of inhibition of 81.38; 98.75 and 100 % for the aqueous extract and then 75.83, 89.76 and 96.52 % for the methanol extract, and with the Indomethacin-induced ulcers, aqueous and methanol extracts of bark of Piptadeniastrum africanum reduce significantly (p cure 35.75; 52.33 and 98.58 % for the aqueous extract, and 33.7; 51.97; and 65.93 to the methanol extract. The results revealed a significant reduction of ulcerated surface in both extracts and increase of nitric oxide (NO) level with methanol extract. When compared to methanol extract, aqueous extract showed more pronounced effects, corresponding to percentages of healing of 59. 92; 84.12 and 59.65 % for the aqueous extract; and 70.43; 55.49 and 57.59 % for the methanol extract in the ulcer induced by acetic acid, all at the respective doses of

  17. Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use.

    Directory of Open Access Journals (Sweden)

    Bryony N Parsons

    2017-11-01

    Full Text Available Several conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk. 95 patients (in groups representing normal stomach, PPI treated, H. pylori gastritis, H. pylori-induced atrophic gastritis and autoimmune atrophic gastritis were selected from a cohort of 1400. RNA extracted from gastric corpus biopsies was analysed using 16S rRNA sequencing (MiSeq. Samples from normal stomachs and patients treated with PPIs demonstrated similarly high microbial diversity. Patients with autoimmune atrophic gastritis also exhibited relatively high microbial diversity, but with samples dominated by Streptococcus. H. pylori colonisation was associated with decreased microbial diversity and reduced complexity of co-occurrence networks. H. pylori-induced atrophic gastritis resulted in lower bacterial abundances and diversity, whereas autoimmune atrophic gastritis resulted in greater bacterial abundance and equally high diversity compared to normal stomachs. Pathway analysis suggested that glucose-6-phospahte1-dehydrogenase and D-lactate dehydrogenase were over represented in H. pylori-induced atrophic gastritis versus autoimmune atrophic gastritis, and that both these groups showed increases in fumarate reductase. Autoimmune and H. pylori-induced atrophic gastritis were associated with different gastric microbial profiles. PPI treated patients showed relatively few alterations in the gastric microbiota compared to healthy subjects.

  18. Comparison of the human gastric microbiota in hypochlorhydric states arising as a result of Helicobacter pylori-induced atrophic gastritis, autoimmune atrophic gastritis and proton pump inhibitor use

    Science.gov (United States)

    Eccles, Richard; Duckworth, Carrie A.; Varro, Andrea

    2017-01-01

    Several conditions associated with reduced gastric acid secretion confer an altered risk of developing a gastric malignancy. Helicobacter pylori-induced atrophic gastritis predisposes to gastric adenocarcinoma, autoimmune atrophic gastritis is a precursor of type I gastric neuroendocrine tumours, whereas proton pump inhibitor (PPI) use does not affect stomach cancer risk. We hypothesised that each of these conditions was associated with specific alterations in the gastric microbiota and that this influenced subsequent tumour risk. 95 patients (in groups representing normal stomach, PPI treated, H. pylori gastritis, H. pylori-induced atrophic gastritis and autoimmune atrophic gastritis) were selected from a cohort of 1400. RNA extracted from gastric corpus biopsies was analysed using 16S rRNA sequencing (MiSeq). Samples from normal stomachs and patients treated with PPIs demonstrated similarly high microbial diversity. Patients with autoimmune atrophic gastritis also exhibited relatively high microbial diversity, but with samples dominated by Streptococcus. H. pylori colonisation was associated with decreased microbial diversity and reduced complexity of co-occurrence networks. H. pylori-induced atrophic gastritis resulted in lower bacterial abundances and diversity, whereas autoimmune atrophic gastritis resulted in greater bacterial abundance and equally high diversity compared to normal stomachs. Pathway analysis suggested that glucose-6-phospahte1-dehydrogenase and D-lactate dehydrogenase were over represented in H. pylori-induced atrophic gastritis versus autoimmune atrophic gastritis, and that both these groups showed increases in fumarate reductase. Autoimmune and H. pylori-induced atrophic gastritis were associated with different gastric microbial profiles. PPI treated patients showed relatively few alterations in the gastric microbiota compared to healthy subjects. PMID:29095917

  19. Protective effect of N-Acetylcysteine against ethanol-induced gastric ulcer: a pharmacological assessment in mice

    Directory of Open Access Journals (Sweden)

    Ausama Ayoob Jaccob

    2015-06-01

    Aim: Since there is an increasing need for gastric ulcer therapies with optimum benefit-risk profile. This study was conducted to investigate gastro-protective effects of N-Acetylcysteine (NAC against ethanol-induced gastric ulcer models in mice. Materials and Methods: Forty-two mice were allocated into six groups consisting of 7 mice each. Groups 1 (normal control and 2 (ulcer control received distilled water at a dose of 10 ml/kg, groups 3, 4 and 5 were given NAC at doses 100, 300 and 500 mg/kg, respectively, and the 6th group received ranitidine (50 mg/kg. All drugs administered orally once daily for 7 days, on the 8th day absolute ethanol (7 ml/kg was administrated orally to all mice to induce the acute ulcer except normal control group. Then 3 h after, all animals were sacrificed then consequently the stomachs were excised for examination. Results: NAC administration at the tested doses showed a dose-related potent gastro-protective effect with significant increase in curative ratio, PH of gastric juice and mucus content viscosity seen with the highest dose of NAC and it is comparable with that observed in ranitidine group. Conclusion: The present findings demonstrate that, oral NAC shows significant gastro-protective effects comparable to ranitidine confirmed by antisecretory, cytoprotective, histological and biochemical data but the molecular mechanisms behind such protection are complex. [J Intercult Ethnopharmacol 2015; 4(2.000: 90-95

  20. The effects of Pretreatment with stomach extract on the incidence of x-ray-induced gastric tumor in ICR mice

    International Nuclear Information System (INIS)

    Watanabe, Hiromitsu; Naito, Masashi; Kawashima, Kengo; Ito, Akihiro

    1984-01-01

    The effect of crude stomach extracts (CSE) on X-ray-induced gastric tumorigenesis was examined. ICR mice were treated with two or four administrations of CSE at one-week intervals then irradiated with 20 Gy of X-rays one week after the final CSE administration. Unexpectedly, the incidence of X-ray-induced tumors was not significantly altered by two CSE pretreatments but was markedly reduced by four CSE pretreatments. Similarly, erosion and squamous metaplasia produced in the glandular stomach a week after X-irradiation were markedly diminished by four CSE pretreatments but not by two CSE pretreatments. (author)

  1. How host regulation of Helicobacter pylori-induced gastritis protects against peptic ulcer disease and gastric cancer.

    Science.gov (United States)

    Dhar, Poshmaal; Ng, Garrett Z; Sutton, Philip

    2016-09-01

    The bacterial pathogen Helicobacter pylori is the etiological agent of a range of gastrointestinal pathologies including peptic ulcer disease and the major killer, gastric adenocarcinoma. Infection with this bacterium induces a chronic inflammatory response in the gastric mucosa (gastritis). It is this gastritis that, over decades, eventually drives the development of H. pylori-associated disease in some individuals. The majority of studies investigating H. pylori pathogenesis have focused on factors that promote disease development in infected individuals. However, an estimated 85% of those infected with H. pylori remain completely asymptomatic, despite the presence of pathogenic bacteria that drive a chronic gastritis that lasts many decades. This indicates the presence of highly effective regulatory processes in the host that, in most cases, keeps a check on inflammation and protect against disease. In this minireview we discuss such known host factors and how they prevent the development of H. pylori-associated pathologies. Copyright © 2016 the American Physiological Society.

  2. Apoptosis induced by GanoPoly in human gastric cancer cell line ...

    African Journals Online (AJOL)

    use

    2011-12-12

    Dec 12, 2011 ... ... cancer's active therapy. Key words: Apoptosis, polysaccharide, human gastric cancer cells. ... The active components of polysaccharides are all glucans, which have a ... for the treatment of alleviated fatigue, night sweating,.

  3. Murine models of H. pylori-induced gastritis and gastric adenocarcinoma.

    Science.gov (United States)

    Krueger, Sabine; Roessner, Albert; Kuester, Doerthe

    2011-10-15

    Laboratory mice have become one of the best animal species for mechanistic studies in gastrointestinal research. Their abundant genetic information, the way of causing carcinogenesis easily by transgenic and gene knockout techniques, limited effort in time and costs, and their practicability provide advantages over other animal models. Meanwhile, several murine practical models have been established for the investigation of the initiation, expansion, and progression of gastritis and gastric carcinoma, for assessing the effects of bacterial, genetic and environmental factors, and for evaluating therapeutic and preventive strategies in gastric diseases. This article gives a review of murine models of gastritis and gastric cancer, placing emphasis on the models associated with Helicobacter pylori infection and techniques used in our laboratory. We discuss matters of murine gastric anatomy, as well as techniques of infection, tissue preparation, and histology. Copyright © 2011 Elsevier GmbH. All rights reserved.

  4. Gastrointestinal motor mechanisms in hyperglycaemia induced delayed gastric emptying in type I diabetes mellitus

    NARCIS (Netherlands)

    Samsom, M.; Akkermans, L. M.; Jebbink, R. J.; van Isselt, H.; vanBerge-Henegouwen, G. P.; Smout, A. J.

    1997-01-01

    BACKGROUND: Hyperglycaemia delays gastric emptying, both in healthy controls and in patients with diabetes mellitus. The effect of hyperglycaemia on antroduodenal motility in diabetes has not yet been studied. AIM: To investigate the gastrointestinal motor mechanisms involved in the hyperglycaemia

  5. Omeprazole-Domperidone Fixed Dose Combination vs Omeprazole Monotherapy: A Phase 4, Open-Label, Comparative, Parallel Randomized Controlled Study in Mild to Moderate Gastroesophageal Reflux Disease

    Directory of Open Access Journals (Sweden)

    KY Marakhouski

    2017-05-01

    Full Text Available Aim: To compare the efficacy and safety of omeprazole-domperidone combination vs omeprazole monotherapy in gastroesophageal reflux disease (GERD. Methods: In a comparative, randomized controlled, phase 4 study, outpatients with GERD were randomly allocated to either group 1 (omeprazole 20 mg + domperidone 30 mg or group 2 (omeprazole 20 mg in an equal ratio; 2 capsules daily in the morning were administered for 8 weeks. Results: Sixty patients were enrolled. Esophagitis reversal was observed in 92% patients in group 1 vs 65.2% in group 2. Approximately, 83.3% patients in group 1 vs 43.3% patients in group 2 demonstrated full cupping of reflux symptoms at 8 weeks. Combined therapy resulted in significantly longer period of heartburn-free days (23 vs 12 days on omeprazole. There were no safety concerns. Conclusions: Omeprazole-domperidone combination was more effective than omeprazole alone in providing complete cupping of reflux symptoms and healing of esophagitis in patients with GERD. Both the treatments were well tolerated with few reports of adverse events. Trial registration: This trial is registered with http://clinicaltrials.gov , number NCT02140073.

  6. Remodeling of the pulmonary artery induced by metastatic gastric carcinoma: a histopathological analysis of 51 autopsy cases

    International Nuclear Information System (INIS)

    Ishiwatari, Takao; Yamamoto, Yoshiro; Nakayama, Haruo; Shibuya, Kazutoshi; Okubo, Yoichiro; Tochigi, Naobumi; Wakayama, Megumi; Nemoto, Tetsuo; Kobayashi, Junko; Shinozaki, Minoru; Aki, Kyoko; Sasai, Daisuke

    2014-01-01

    Gastric carcinoma remains the second commonest cause of cancer deaths worldwide. Presence of the carcinoma cell in the pulmonary artery is serious condition that might cause remodeling of the pulmonary artery. The present study conducted detailed histopathological analyses to elucidate how gastric carcinoma cells may affect the structure and hemodynamics of pulmonary arteries. Remodeling of the pulmonary artery was assessed based on measurements of arterial diameters and stenosis rates from the autopsies, and their correlation were also validated. We additionally calculated 95 percent confidential intervals (CIs) for the rate of stenosis in groups of pulmonary arteries of different caliber zones (under 100, 100 to 300, and over 300 micrometer). The right ventricular thickness was measured and examined whether it correlated with the rate of pulmonary arterial stenosis. A total of 4612 autopsy cases were recorded at our institute, among which 168 had gastric carcinoma. Finally, 51 cases of the gastric carcinoma were employed for the study which had carcinoma cells in the lumen of the pulmonary artery. The mean right ventricular wall thickness of these cases was 3.14 mm. There were significant positive associations between the rates of pulmonary arterial stenosis and right ventricular thickness from pulmonary arteries of diameter under 100, 100 to 300, and over 300 micrometer. In these zones, 31, 31, and 33 cases had rates of pulmonary arterial stenosis that were below the lower limit of the 95 percent CI values, respectively. On the other hand, among cases with significant pulmonary stenosis, 17 of 18 cases with stenosis in the over 300 micrometer zone involved pulmonary arteries of both in the under 100 and 100 to 300 micrometer zones. One-third of autopsy with advanced gastric carcinoma had carcinoma cells in lumen of pulmonary artery, but implantation and proliferation may be essential to induce intimal thickening that causes an increasing of pulmonary arterial

  7. High-Fat Diet Induces Dysbiosis of Gastric Microbiota Prior to Gut Microbiota in Association With Metabolic Disorders in Mice.

    Science.gov (United States)

    He, Cong; Cheng, Dandan; Peng, Chao; Li, Yanshu; Zhu, Yin; Lu, Nonghua

    2018-01-01

    Accumulating evidence suggests that high-fat diet (HFD) induced metabolic disorders are associated with dysbiosis of gut microbiota. However, no study has explored the effect of HFD on the gastric microbiota. This study established the HFD animal model to determine the impact of HFD on the gastric microbiota and its relationship with the alterations of gut microbiota. A total of 40 male C57BL/6 mice were randomly allocated to receive a standard chow diet (CD) or HFD for 12 weeks (12CD group and 12HFD group) and 24 weeks (24CD group and 24HFD group) ( n = 10 mice per group). Body weight and length were measured and Lee's index was calculated at different time points. The insulin sensitivity and serum levels of metabolic parameters including blood glucose, insulin and lipid were also evaluated. The gastric mucosa and fecal microbiota of mice were characterized by 16S rRNA gene sequencing. The body weight was much heavier and the Lee's index was higher in 24HFD group than 12HFD. The insulin resistance and serum level of lipid were increased in 24HFD group compared to 12HFD, indicating the aggravation of metabolic disorders as HFD went on. 16S rRNA gene sequencing showed dysbiosis of gastric microbiota with decreased community diversity while no significant alteration in gut microbiota after 12 weeks of HFD. The phyla Firmicutes and Proteobacteria tended to increase whereas Bacteroidetes and Verrucomicrobia decrease in the gastric microbiota of 12HFD mice compared to 12CD. Moreover, a remarkable reduction of bacteria especially Akkermansia muciniphila , which has beneficial effects on host metabolism, was observed firstly in the stomach of 12HFD group and then in the gut of 24HFD group, indicating the earlier alterations of microbiota in stomach than gut after HFD. We also found structural segregation of microbiota in the stomach as well as gut between 12HFD and 24HFD group, which is accompanied by the aggregation of metabolic disorders. These data suggest that HFD

  8. Rhein induces apoptosis of human gastric cancer SGC-7901 cells via an intrinsic mitochondrial pathway

    Directory of Open Access Journals (Sweden)

    Yiwen Li

    2012-11-01

    Full Text Available Rhein is a primary anthraquinone found in the roots of a traditional Chinese herb, rhubarb, and has been shown to have some anticancer effects. The aim of the present study was to investigate the effect of rhein on the apoptosis of the human gastric cancer line SGC-7901 and to identify the mechanism involved. SGC-7901 cells were cultured and treated with rhein (0, 50, 100, 150, and 200 µM for 24, 48, or 72 h. Relative cell viability assessed by the MTT assay after treatment was 100, 99, 85, 79, 63% for 24 h; 100, 98, 80, 51, 37% for 48 h, and 100, 97, 60, 36, 15% for 72 h, respectively. Cell apoptosis was detected with TUNEL staining and quantified with flow cytometry using annexin FITC-PI staining at 48 h after 100, 200 and 300 µm rhein. The percentage of apoptotic cells was 7.3, 21.9, 43.5%, respectively. We also measured the mRNA levels of caspase-3 and -9 using real-time PCR. Treatment with 100 µM rhein for 48 h significantly increased mRNA expression of caspase-3 and -9. The levels of apoptosis-related proteins including Bcl-2, Bax, Bcl-xL, and pro-caspase-3 were evaluated in rhein-treated cells. Rhein increased the Bax:Bcl-2 ratio but decreased the protein levels of Bcl-xL and pro-caspase-3. Moreover, rhein significantly increased the expression of cytochrome c and apoptotic protease activating factor 1, two critical components involved in mitochondrial pathway-mediated apoptosis. We conclude that rhein inhibits SGC-7901 proliferation by inducing apoptosis and this antitumor effect of rhein is mediated in part by an intrinsic mitochondrial pathway.

  9. Rhein induces apoptosis of human gastric cancer SGC-7901 cells via an intrinsic mitochondrial pathway

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yiwen; Xu, Yuqing [Department of Oncology,Second Affiliated Hospital, Harbin Medical University, Nangang District, Harbin, Heilongjiang (China); Lei, Bo [Department of Breast Surgery, Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang (China); Wang, Wenxiu [Department of Oncology,Second Affiliated Hospital, Harbin Medical University, Nangang District, Harbin, Heilongjiang (China); Ge, Xin; Li, Jingrui [Department of General Surgery, Heilongjiang Province Hospital, Harbin, Heilongjiang (China)

    2012-08-03

    Rhein is a primary anthraquinone found in the roots of a traditional Chinese herb, rhubarb, and has been shown to have some anticancer effects. The aim of the present study was to investigate the effect of rhein on the apoptosis of the human gastric cancer line SGC-7901 and to identify the mechanism involved. SGC-7901 cells were cultured and treated with rhein (0, 50, 100, 150, and 200 µM) for 24, 48, or 72 h. Relative cell viability assessed by the MTT assay after treatment was 100, 99, 85, 79, 63% for 24 h; 100, 98, 80, 51, 37% for 48 h, and 100, 97, 60, 36, 15% for 72 h, respectively. Cell apoptosis was detected with TUNEL staining and quantified with flow cytometry using annexin FITC-PI staining at 48 h after 100, 200 and 300 µm rhein. The percentage of apoptotic cells was 7.3, 21.9, 43.5%, respectively. We also measured the mRNA levels of caspase-3 and -9 using real-time PCR. Treatment with 100 µM rhein for 48 h significantly increased mRNA expression of caspase-3 and -9. The levels of apoptosis-related proteins including Bcl-2, Bax, Bcl-xL, and pro-caspase-3 were evaluated in rhein-treated cells. Rhein increased the Bax:Bcl-2 ratio but decreased the protein levels of Bcl-xL and pro-caspase-3. Moreover, rhein significantly increased the expression of cytochrome c and apoptotic protease activating factor 1, two critical components involved in mitochondrial pathway-mediated apoptosis. We conclude that rhein inhibits SGC-7901 proliferation by inducing apoptosis and this antitumor effect of rhein is mediated in part by an intrinsic mitochondrial pathway.

  10. The healing effects of Teucrium polium in the repair of indomethacin-induced gastric ulcer in rats

    International Nuclear Information System (INIS)

    Mehrabani, Davood; Fattahi, Mohammad R; Saberi-Firouzi, Mehdi; Rezaee, Aminallah; Azarpira, Negar; Amini, Masoud; Tanideh, Nader; Panjehshahin, Mohammad R

    2009-01-01

    To determine the healing effect of Teucrium polium (T. polium) in indomethacin-induced gastric ulcer in rats. In the fall of 2007, 250 Sprague-Dawley rats provided by the Shiraz University Laboratory Animal Center were divided into 4 equal groups including control (70 rats), and 3 experimental groups (60 rats each), and each group received different doses of T. polium. Ten rats were used to study the induction of gastric ulcer by indomethacin (25 mg/kg/stat). After 24 hours, their stomachs were evaluated for any mucosal ulcer. The T. polium extract was administered orally, 24 hours after indomethacin administration. In the experimental group, 10 animals were sacrificed after 24, 48, and 72 hours, after administration of T. polium, and at one, 2, and 4 weeks, and in the control group identically after the administration of distilled water. In rats treated with indomethacin, multiple ulcers were evident. After 4 weeks of treatment with T. polium, more re-epithelialization, proliferation, mucosal hyperplasia, migration of the gastric epithelial cells, and decrease in inflammatory cells were observed. The T. polium reduced the ulcer indices by >50% after one week, >80% after 2 weeks, and >90% after 4 weeks. The healing effect of T. polium may be due to antioxidant activity along with the ability to modulate the mucin secretion, prostaglandin synthesis, and epidermal growth factor receptor expression. These results along with the non-toxicity properties of T. polium suggests it as a promising anti-ulcer compound. (author)

  11. Suppression of alkylating agent induced cell transformation and gastric ulceration by low-dose alkylating agent pretreatment

    International Nuclear Information System (INIS)

    Onodera, Akira; Kawai, Yuichi; Kashimura, Asako; Ogita, Fumiya; Tsutsumi, Yasuo; Itoh, Norio

    2013-01-01

    Highlights: •Low-dose MNNG pretreatment suppresses high-dose MNNG induced in vitro transformation. •Gastric ulcers induced by high-dose MNNG decreased after low-dose MNNG pretreatment. •Efficacy of low-dose MNNG related to resistance of mutation and oxidative stress. -- Abstract: Exposure to mild stress by chemicals and radiation causes DNA damage and leads to acquired stress resistance. Although the linear no-threshold (LNT) model of safety assessment assumes risk from any dose, evidence from radiological research demonstrates a conflicting hormetic phenomenon known as the hormesis effect. However, the mechanisms underlying radiation hormesis have not yet been clarified, and little is known about the effects of low doses of chemical carcinogens. We analyzed the efficacy of pretreatment with low doses of the alkylating agent N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) on the subsequent induction of cell transformation and gastric ulceration by high-dose MNNG. We used an in vitro Balb/3T3 A31-1-1 cell transformation test and monitored the formation of gastric ulcers in 5-week-old male ICR mice that were administered MNNG in drinking water. The treatment concentrations of MNNG were determined by the cell survival rate and past reports. For low-dose in vitro and in vivo experiments, MNNG was used at 0.028 μM, and 2.8 μg/mL, respectively. The frequency of cell transformation induced by 10 μm MNNG was decreased by low-dose MNNG pretreatment to levels similar to that of spontaneous transformation. In addition, reactive oxygen species (ROS) and mutation frequencies induced by 10 μm MNNG were decreased by low-dose MNNG pretreatment. Importantly, low-dose MNNG pretreatment had no effect on cell proliferation. In vivo studies showed that the number of gastric ulcers induced by 1 mg/mL MNNG decreased after low-dose MNNG pretreatment. These data indicate that low-dose pretreatment with carcinogens may play a beneficial role in the prevention of chemical toxicity

  12. Suppression of alkylating agent induced cell transformation and gastric ulceration by low-dose alkylating agent pretreatment

    Energy Technology Data Exchange (ETDEWEB)

    Onodera, Akira, E-mail: onodera@pharm.kobegakuin.ac.jp [Department of Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871 (Japan); Department of Pharmaceutical Sciences, Kobegakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586 (Japan); Kawai, Yuichi [Department of Pharmaceutical Sciences, Kobegakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586 (Japan); Kashimura, Asako; Ogita, Fumiya; Tsutsumi, Yasuo; Itoh, Norio [Department of Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871 (Japan)

    2013-06-14

    Highlights: •Low-dose MNNG pretreatment suppresses high-dose MNNG induced in vitro transformation. •Gastric ulcers induced by high-dose MNNG decreased after low-dose MNNG pretreatment. •Efficacy of low-dose MNNG related to resistance of mutation and oxidative stress. -- Abstract: Exposure to mild stress by chemicals and radiation causes DNA damage and leads to acquired stress resistance. Although the linear no-threshold (LNT) model of safety assessment assumes risk from any dose, evidence from radiological research demonstrates a conflicting hormetic phenomenon known as the hormesis effect. However, the mechanisms underlying radiation hormesis have not yet been clarified, and little is known about the effects of low doses of chemical carcinogens. We analyzed the efficacy of pretreatment with low doses of the alkylating agent N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) on the subsequent induction of cell transformation and gastric ulceration by high-dose MNNG. We used an in vitro Balb/3T3 A31-1-1 cell transformation test and monitored the formation of gastric ulcers in 5-week-old male ICR mice that were administered MNNG in drinking water. The treatment concentrations of MNNG were determined by the cell survival rate and past reports. For low-dose in vitro and in vivo experiments, MNNG was used at 0.028 μM, and 2.8 μg/mL, respectively. The frequency of cell transformation induced by 10 μm MNNG was decreased by low-dose MNNG pretreatment to levels similar to that of spontaneous transformation. In addition, reactive oxygen species (ROS) and mutation frequencies induced by 10 μm MNNG were decreased by low-dose MNNG pretreatment. Importantly, low-dose MNNG pretreatment had no effect on cell proliferation. In vivo studies showed that the number of gastric ulcers induced by 1 mg/mL MNNG decreased after low-dose MNNG pretreatment. These data indicate that low-dose pretreatment with carcinogens may play a beneficial role in the prevention of chemical toxicity

  13. TGF{beta} induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Ebi, Masahide [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Kataoka, Hiromi, E-mail: hkataoka@med.nagoya-cu.ac.jp [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Shimura, Takaya; Kubota, Eiji; Hirata, Yoshikazu; Mizushima, Takashi; Mizoshita, Tsutomu; Tanaka, Mamoru; Mabuchi, Motoshi; Tsukamoto, Hironobu; Tanida, Satoshi; Kamiya, Takeshi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan); Higashiyama, Shigeki [Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime (Japan); Joh, Takashi [Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya (Japan)

    2010-11-19

    Research highlights: {yields} TGF{beta} induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. {yields} TGF{beta} induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. {yields} TGF{beta} enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. {yields} Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGF{beta}. {yields} ADAM17 may play a crucial role in this TGF{beta}-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGF{beta}) is known to potently inhibit cell growth. Loss of responsiveness to TGF{beta} inhibition on cell growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGF{beta} and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGF{beta}. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGF{beta} was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGF{beta} was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGF{beta}-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGF{beta} induced shedding of proHB-EGF allowing HB-EGF-CTF to

  14. TGFβ induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

    International Nuclear Information System (INIS)

    Ebi, Masahide; Kataoka, Hiromi; Shimura, Takaya; Kubota, Eiji; Hirata, Yoshikazu; Mizushima, Takashi; Mizoshita, Tsutomu; Tanaka, Mamoru; Mabuchi, Motoshi; Tsukamoto, Hironobu; Tanida, Satoshi; Kamiya, Takeshi; Higashiyama, Shigeki; Joh, Takashi

    2010-01-01

    Research highlights: → TGFβ induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. → TGFβ induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. → TGFβ enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. → Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGFβ. → ADAM17 may play a crucial role in this TGFβ-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGFβ) is known to potently inhibit cell growth. Loss of responsiveness to TGFβ inhibition on cell growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGFβ and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGFβ. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGFβ was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGFβ was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGFβ-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGFβ induced shedding of proHB-EGF allowing HB-EGF-CTF to translocate to the nucleus. ADAM inhibitors blocked this nuclear translocation. TGF

  15. Regulation of basal gastric acid secretion by the glycogen synthase kinase GSK3.

    Science.gov (United States)

    Rotte, Anand; Pasham, Venkanna; Eichenmüller, Melanie; Yang, Wenting; Qadri, Syed M; Bhandaru, Madhuri; Lang, Florian

    2010-10-01

    According to previous observations, basal gastric acid secretion is downregulated by phosphoinositol-3-(PI3)-kinase, phosphoinositide-dependent kinase (PDK1), and protein kinase B (PKBβ/Akt2) signaling. PKB/Akt phosphorylates glycogen synthase kinase GSK3. The present study explored whether PKB/Akt-dependent GSK3-phosphorylation modifies gastric acid secretion. Utilizing 2',7'-bis-(carboxyethyl)-5(6')-carboxyfluorescein (BCECF)-fluorescence, basal gastric acid secretion was determined from Na(+)-independent pH recovery (∆pH/min) following an ammonium pulse, which reflects H(+)/K(+)-ATPase activity. Experiments were performed in gastric glands from gene-targeted mice (gsk3 ( KI )) with PKB/serum and glucocorticoid-inducible kinase (SGK)-insensitive GSKα,β, in which the serines within the PKB/SGK phosphorylation site were replaced by alanine (GSK3α(21A/21A), GSK3β(9A/9A)). The cytosolic pH in isolated gastric glands was similar in gsk3 ( KI ) and their wild-type littermates (gsk3 ( WT )). However, ∆pH/min was significantly larger in gsk3 ( KI ) than in gsk3 ( WT ) mice and ∆pH/min was virtually abolished by the H(+)/K(+)-ATPase inhibitor omeprazole (100 μM) in gastric glands from both gsk3 ( KI ) and gsk3 ( WT ). Plasma gastrin levels were lower in gsk3 ( KI ) than in gsk3 ( WT ). Both, an increase of extracellular K(+) concentration to 35 mM [replacing Na(+)/N-methyl-D: -glucamine (NMDG)] and treatment with forskolin (5 μM), significantly increased ∆pH/min to virtually the same value in both genotypes. The protein kinase A (PKA) inhibitor H89 (150 nM) and the H(2)-receptor antagonist ranitidine (100 μM) decreased ∆pH/min in gsk3 ( KI ) but not gsk3 ( WT ) and again abrogated the differences between the genotypes. The protein abundance of phosphorylated but not of total PKA was significantly larger in gsk3 ( KI ) than in gsk3 ( WT ). Basal gastric acid secretion is enhanced by the disruption of PKB/SGK-dependent phosphorylation and the

  16. P27Kip1, regulated by glycogen synthase kinase-3β, results in HMBA-induced differentiation of human gastric cancer cells

    International Nuclear Information System (INIS)

    Wei, Min; Gu, Qinlong; Wang, Zhiwei; Yao, Hongliang; Yang, Zhongyin; Zhang, Qing; Liu, Bingya; Yu, Yingyan; Su, Liping; Zhu, Zhenggang

    2011-01-01

    Gastric cancer is the second most common cause of global cancer-related mortality. Although dedifferentiation predicts poor prognosis in gastric cancer, the molecular mechanism underlying dedifferentiation, which could provide fundamental insights into tumor development and progression, has yet to be elucidated. Furthermore, the molecular mechanism underlying the effects of hexamethylene bisacetamide (HMBA), a recently discovered differentiation inducer, requires investigation and there are no reported studies concerning the effect of HMBA on gastric cancer. Based on the results of FACS analysis, the levels of proteins involved in the cell cycle or apoptosis were determined using western blotting after single treatments and sequential combinations of HMBA and LiCl. GSK-3β and proton pump were investigated by western blotting after up-regulating Akt expression by Ad-Akt infection. To investigate the effects of HMBA on protein localization and the activities of GSK-3β, CDK2 and CDK4, kinase assays, immunoprecipitation and western blotting were performed. In addition, northern blotting and RNase protection assays were carried out to determine the functional concentration of HMBA. HMBA increased p27Kip1 expression and induced cell cycle arrest associated with gastric epithelial cell differentiation. In addition, treating gastric-derived cells with HMBA induced G0/G1 arrest and up-regulation of the proton pump, a marker of gastric cancer differentiation. Moreover, treatment with HMBA increased the expression and activity of GSK-3β in the nucleus but not the cytosol. HMBA decreased CDK2 activity and induced p27Kip1 expression, which could be rescued by inhibition of GSK-3β. Furthermore, HMBA increased p27Kip1 binding to CDK2, and this was abolished by GSK-3β inhibition. The results presented herein suggest that GSK-3β functions by regulating p27Kip1 assembly with CDK2, thereby playing a critical role in G0/G1 arrest associated with HMBA-induced gastric epithelial

  17. Zinc salt enhances gastroprotective activity of risperidone in indomethacin-induced gastric ulcer.

    Science.gov (United States)

    Oluwole, F S; Onwuchekwa, C

    2016-09-01

    Zinc has been reported to mediate cellular responses to injury by producing cytoprotection via the scavenging of reactive oxygen species. Anti-stress medications are generally anti-psychotic drugs and anti- depressants. Some Anti-psychotic drugs such as risperidone have been reported to possess anti-ulcer activity. Risperidone as an antipsychotic drug blocks several neurotransmitter systems including dopaminergic, adrenergic, histaminergic and serotonergic pathways. The study investigated the antiulcer activity of Zinc Chloride (ZnCl(2)) in combination with risperidone in male Wistar rats. The animals were divided into two groups of twenty animals each for ZnCl(2) and risperidone groups. Each group was further divided into four subgroups. ZnCl(2) was administered orally at 20mg/kg, 40mg/kg and 80mg/kg to a subgroup, while 80mg/kg of ZnCl(2) was administered in combination with risperidone (0.1mg/kg, 0.3mg/kg and 0.5mg/kg) orally once daily for 21 days. The controls were treated with distilled water. Ulcer was induced using indomethacin. Histology of the stomach tissues was prepared with PAS and H& E stains. Ulcer score and ulcer area were assessed using standard methods. Data were analysed using student t-test and Graphpad Prism 5. There were decreases in ulcer scores using the different doses of ZnCl, (20mg/kg, 40mg/kg and 80mg/kg). Also using the highest dose ZnCl(2) (80mg/ kg) and different doses of risperidone there were decreases in ulcer scores compared to the control. This effect of the risperidone showed a significant dose- dependent reduction. The effect ZnCl(2), and risperidone were also reflected in the ulcer area and in the histology. These findings suggest that ZnCl(2), enhances the gastroprotective activity ofrisperidone in indomethacin- induced gastric ulcer. However, more detailed studies are necessary to confirm the relevance of this finding and its implications in clinical settings.

  18. Rapid tachyphylaxis of the glucagon-like peptide 1-induced deceleration of gastric emptying in humans

    DEFF Research Database (Denmark)

    Nauck, Michael A; Kemmeries, Guido; Holst, Jens Juul

    2011-01-01

    DESIGN AND METHODS: Nine healthy volunteers (25 ± 4 years old, BMI: 24.6 ± 4.7 kg/m(2)) were examined with intravenous infusion of GLP-1 (0.8 pmol · kg(-1) · min(-1)) or placebo over 8.5 h. Two liquid mixed meals were administered at a 4-h interval. Gastric emptying was determined, and blood samples were...... drawn frequently. RESULTS: GLP-1 decelerated gastric emptying significantly more after the first meal compared with the second meal (P = 0.01). This was associated with reductions in pancreatic polypeptide levels (marker of vagal activation) after the first but not the second meal (P ... but increased after the second test meal (P gastric emptying is subject to rapid tachyphylaxis at the level of vagal nervous activation. As a consequence, postprandial glucose control by GLP-1 is attenuated after its chronic administration...

  19. Hypoxic inactivation of glycogen synthase kinase-3β promotes gastric tumor growth and angiogenesis by facilitating hypoxia-inducible factor-1 signaling.

    Science.gov (United States)

    Ko, Young San; Cho, Sung Jin; Park, Jinju; Choi, Yiseul; Lee, Jae-Seon; Youn, Hong-Duk; Kim, Woo Ho; Kim, Min A; Park, Jong-Wan; Lee, Byung Lan

    2016-09-01

    Since the molecular mechanism of hypoxic adaptation in cancer cells is cell-type specific, we investigated whether glycogen synthase kinase-3β (GSK-3β) activation is involved in hypoxia-induced gastric tumor promotion. Stable gastric cancer cell lines (SNU-638, SNU-484, MKN1, and MKN45) were cultured under hypoxic conditions. Cells overexpressing wild-type GSK-3β (WT-GSK-3β) or kinase-dead mutant of GSK-3β (KD-GSK-3β) were generated and used for cell culture and animal studies. In cell culture experiments, hypoxia decreased GSK-3β activation in gastric cancer cells. Cell viability and the expressions of HIF-1α protein and VEGF mRNA in gastric cancer cells were higher in KD-GSK-3β transfectants than in WT-GSK-3β transfectants under hypoxic conditions, but not under normoxic conditions. Gastric cancer xenografts showed that tumor growth, microvessel area, HIF-1α activation, and VEGF expression were higher in KD-GSK-3β tumors than in WT-GSK-3β tumors in vivo. In addition, the expression of hypoxia-induced HIF-1α protein was regulated by GSK-3β at the translational level. Our data suggest that GSK-3β is involved in hypoxic adaptation of gastric cancer cells as an inhibitory upstream regulator of the HIF-1α/VEGF signaling pathway. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  20. Anti-Ulcerogenic Properties of Lycium chinense Mill Extracts against Ethanol-Induced Acute Gastric Lesion in Animal Models and Its Active Constituents

    Directory of Open Access Journals (Sweden)

    Opeyemi J. Olatunji

    2015-12-01

    Full Text Available The objective of this study was to explore the gastroprotective properties of the aerial part of Lycium chinense Mill (LCA against ethanol-induced gastric mucosa lesions in mice models. Administration of LCA at doses of 50, 100, 200 and 400 mg/kg body weight prior to ethanol consumption dose dependently inhibited gastric ulcers. The gastric mucosal injury was analyzed by gastric juice acidity, glutathione (GSH, superoxide dismutase (SOD, malondialdehyde (MDA, myeloperoxidase (MPO activities. Furthermore, the levels of the inflammatory mediators, tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6 and interleukin-1β (IL-1β in serum were also analyzed using ELISA. Pathological changes were also observed with the aid of hematoxylin-eosin (HE staining. Our results indicated that LCA significantly reduced the levels of MPO, MDA and increased SOD and GSH activities. Furthermore, LCA also significantly inhibited the levels of TNF-α, IL-6, and IL-1β in the serum of ulcerated mice in a dose dependent manner. Immunohistological analysis indicated that LCA also significantly attenuated the overexpression of nuclear factor-κB in pretreated mice models. This findings suggests Lycium chinense Mill possesses gastroprotective properties against ethanol-induced gastric injury and could be a possible therapeutic intervention in the treatment and management of gastric ulcers.

  1. A Phase 1 Pharmacokinetic Study of Cysteamine Bitartrate Delayed-Release Capsules Following Oral Administration with Orange Juice, Water, or Omeprazole in Cystinosis.

    Science.gov (United States)

    Armas, Danielle; Holt, Robert J; Confer, Nils F; Checani, Gregg C; Obaidi, Mohammad; Xie, Yuli; Brannagan, Meg

    2018-02-01

    Cystinosis is a rare, metabolic, autosomal recessive, genetic lysosomal storage disorder characterized by an accumulation of cystine in various organs and tissues. Cysteamine bitartrate (CB) is a cystine-depleting aminothiol agent approved in the United States and Europe in immediate-release and delayed-release (DR) formulations for the treatment of nephropathic cystinosis in children and adults. It is recommended that CBDR be administered with fruit juice (except grapefruit juice) for maximum absorption. Omeprazole is a proton pump inhibitor that inhibits gastric acid secretion and, theoretically, may cause the premature release of cysteamine by increasing intragastric pH, thereby affecting the PK of CBDR. This open-label, three-period, randomized study in healthy adult subjects was designed primarily to compare the pharmacokinetics of CBDR capsules after a single oral dose administered with orange juice, water, or multiple oral doses of omeprazole with water at steady state. A total of 32 subjects were randomly assigned to receive study agents in one of two treatment sequences. All subjects completed the study and baseline characteristics of the overall population and the two treatment sequence populations were similar. Peak mean plasma cysteamine concentrations following co-administration of CBDR capsules with orange juice (1892 ng/mL) were higher compared with co-administration with water (1663 ng/mL) or omeprazole 20 mg and water (1712 ng/mL). Mean time to peak plasma concentration was shorter with omeprazole co-administration (2.5 h) compared with orange juice (3.5 h) or water (3.0 h). Statistical comparisons between treatment groups indicated that exposure as assessed by AUC 0-t , AUC 0-∞ , and C max were all within the 80-125% bioequivalence ranges for all comparisons. All treatments were generally well tolerated. Overall, the pharmacokinetics of cysteamine bitartrate DR capsules are not significantly impacted by co-administration with orange juice

  2. Carbon monoxide releasing molecule-2 ameliorates IL-1β-induced IL-8 in human gastric cancer cells

    International Nuclear Information System (INIS)

    Lian, Sen; Xia, Yong; Ung, Trong Thuan; Khoi, Pham Ngoc; Yoon, Hyun Joong; Kim, Nam Ho; Kim, Kyung Keun; Jung, Young Do

    2016-01-01

    Carbon monoxide (CO), a byproduct of heme oxygenase (HO), presents antioxidant, anti-inflammatory, and anti-tumor properties. Accumulating evidence supports that interleukin (IL)-8 contribute to the vascularity of human gastric cancer. However, the inhibition of IL-8 expression by CO is yet to be elucidated. Here, we utilized CO releasing molecule-2 (CORM-2) to investigate the effect of CO on IL-1β-induced IL-8 expression and the underlying molecular mechanisms in human gastric cancer AGS cells. CORM-2 dose-dependently suppressed IL-1β-induced IL-8 mRNA and protein expression as well as IL-8 promoter activity. IL-1β induced the translocation of p47 phox to activate reactive oxygen species (ROS)-producing NADPH oxidase (NOX). Moreover, IL-1β activated MAPKs (Erk1/2, JNK1/2, and p38 MAPK) and promoted nuclear factor (NF)-kB and activator protein (AP)-1 binding activities. Pharmacological inhibition and mutagenesis studies indicated that NOX, ROS, Erk1/2, and p38 MAPK are involved in IL-1β-induced IL-8 expression. Transient transfection of deletion mutant constructs of the IL-8 promoter in cells suggested that NF-kB and AP-1 are critical for IL-1β-induced IL-8 transcription. NOX-derived ROS and MAPKs (Erk1/2 and p38 MAPK) functioned as upstream activators of NF-κB and AP-1, respectively. CORM-2 pretreatment significantly mitigated IL-1β-induced activation of ROS/NF-kB and Erk1/2/AP-1 cascades, blocking IL-8 expression and thus significantly reducing endothelial cell proliferation in the tumor microenvironment.

  3. Nilotinib Induced Recurrent Gastric Polyps: Case Report and Review of Literature.

    Science.gov (United States)

    Kassem, Nancy; Ismail, Omar M; Elomri, Halima; Yassin, Mohamad A

    2017-07-14

    BACKGROUND Tyrosine kinase inhibitors (TKIs) are currently an important targeted drug class in the treatment of chronic myeloid leukemia (CML). Imatinib was the first approved TKI for CML in 2001. Nilotinib is a second-generation TKI, approved in 2007; it inhibits BCR-ABL, PDGFR, and c-KIT, and is 30 times more potent than imatinib. Tyrosine kinase enzymes are expressed in multiple tissues and are involved in several signaling pathways; they have been shown to have several off-target side effects. CASE REPORT We report a case of an elderly male with CML and no history of gastrointestinal diseases, treated with nilotinib, and developed recurrent gastric polyps after three years of treatment. We excluded common causes of gastric polyps and therefore considered nilotinib as a probable cause of recurrent gastric polyps. CONCLUSIONS Recurrent gastric polyps could be a potential side effect of nilotinib treatment. Careful long-term monitoring of patients on TKI therapy is necessary and further long-term studies of TKI side effects are needed.

  4. Autophagy Facilitates Metadherin-Induced Chemotherapy Resistance Through the AMPK/ATG5 Pathway in Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Guoqing Pei

    2018-04-01

    Full Text Available Background/Aims: Metadherin (MTDH is overexpressed in some malignancies and enhances drug resistance; however, its role in gastric cancer (GC and the underlying mechanisms remain largely unexplored. Here, we explore the mechanism by which MTDH induces drug resistance in GC. Methods: We analysed the level of MTDH in GC and adjacent normal gastric mucosal tissues by real-time quantitative PCR (q-PCR. We also analysed the level of autophagy by western blot analysis, confocal microscopy, and transmission electron microscopy after MTDH knockdown and overexpression, and examined fluorouracil (5-FU resistance by Cell Counting Kit-8 at the same time. Finally, GC patient-derived xenograft tumours were used to demonstrate 5-FU resistance. An AMPK pathway inhibitor was applied to determine the molecular mechanisms of autophagy. Results: MTDH expression was significantly increased in the GC specimens compared with that in the adjacent normal gastric mucosal tissues. Further study showed a positive correlation between the expression level of MTDH and 5-FU resistance. MTDH overexpression in MKN45 cells increased the levels of P-glycoprotein (P-gp and promoted 5-FU resistance, while inhibition of MTDH showed the opposite result. The simultaneous inhibition of autophagy and overexpression of MTDH decreased the levels of P-gp and inhibited 5-FU resistance. Moreover, MTDH induced AMPK phosphorylation, regulated ATG5 expression, and finally influenced autophagy, suggesting that MTDH may activate autophagy via the AMPK/ATG5 signalling pathway. Our findings reveal a unique mechanism by which MTDH promotes GC chemoresistance and show that MTDH is a potential target for improved chemotherapeutic sensitivity and GC patient survival. Conclusions: MTDH-stimulated cancer resistance to 5-FU may be mediated through autophagy activated by the AMPK/ATG5 pathway in GC.

  5. Efficacy of omeprazole/sodium bicarbonate treatment in gastroesophageal reflux disease: a systematic review

    Directory of Open Access Journals (Sweden)

    Fátima Higuera-de-la-Tijera

    2018-04-01

    Full Text Available Resumen INTRODUCCIÓN Los inhibidores de la bomba de protones son la terapia médica más efectiva para la enfermedad de reflujo gastroesofágico, pero su inicio de acción puede ser lento. OBJETIVO Evaluar la literatura referida a la eficacia del omeprazol y bicarbonato de sodio en la enfermedad por reflujo gastroesofágico. MÉTODOS Revisión sistemática de la literatura desde el año 2000. Se revisaron los manuscritos relativos a la efectividad del tratamiento de la enfermedad por reflujo gastroesofágico. Se extrajo la información relevante, la cual fue subsecuentemente analizada con estadística descriptiva. RESULTADOS Se incluyó información de cuatro estudios. Dos estudios compararon la eficacia de omeprazol y bicarbonato de sodio versus omeprazol, y un estudio comparó la eficacia de la dosis diaria matutina con la nocturna. El otro estudio comparó omeprazol más bicarbonato de sodio y alginato versus omeprazol. No hubo diferencia entre omeprazol con bicarbonato de sodio y omeprazol. Sin embargo, hubo una tendencia hacia una respuesta más sostenida y una mayor proporción de alivio total sostenido por 30 minutos con omeprazol y bicarbonato de sodio. CONCLUSIÓN La terapia con omeprazol y bicarbonato de sodio no es más efectiva que el omeprazol en el tratamiento de la enfermedad por reflujo gastroesofágico. Sin embargo, la información sugiere que puede tener una respuesta más sostenida y un alivio total de mayor duración.

  6. Grapefruit-seed extract attenuates ethanol-and stress-induced gastric lesions via activation of prostaglandin, nitric oxide and sensory nerve pathways.

    Science.gov (United States)

    Brzozowski, Tomasz; Konturek, Peter C; Drozdowicz, Danuta; Konturek, Stanislaw J; Zayachivska, Oxana; Pajdo, Robert; Kwiecien, Slawomir; Pawlik, Wieslaw W; Hahn, Eckhart G

    2005-11-07

    Grapefruit-seed extract (GSE) containing flavonoids, possesses antibacterial and antioxidative properties but whether it influences the gastric defense mechanism and gastroprotection against ethanol- and stress-induced gastric lesions remains unknown. We compared the effects of GSE on gastric mucosal lesions induced in rats by topical application of 100% ethanol or 3.5 h of water immersion and restraint stress (WRS) with or without (A) inhibition of cyclooxygenase (COX)-1 activity by indomethacin and rofecoxib, the selective COX-2 inhibitor, (B) suppression of NO-synthase with L-NNA (20 mg/kg ip), and (C) inactivation by capsaicin (125 mg/kg sc) of sensory nerves with or without intragastric (ig) pretreatment with GSE applied 30 min prior to ethanol or WRS. One hour after ethanol and 3.5 h after the end of WRS, the number and area of gastric lesions were measured by planimetry, the gastric blood flow (GBF) was assessed by H2-gas clearance technique and plasma gastrin levels and the gastric mucosal generation of PGE2, superoxide dismutase (SOD) activity and malonyldialdehyde (MDA) concentration, as an index of lipid peroxidation were determined. Ethanol and WRS caused gastric lesions accompanied by the significant fall in the GBF and SOD activity and the rise in the mucosal MDA content. Pretreatment with GSE (8-64 mg/kg i g) dose-dependently attenuated gastric lesions induced by 100% ethanol and WRS; the dose reducing these lesions by 50% (ID50) was 25 and 36 mg/kg, respectively, and this protective effect was similar to that obtained with methyl PGE2 analog (5 microg/kg i g). GSE significantly raised the GBF, mucosal generation of PGE2, SOD activity and plasma gastrin levels while attenuating MDA content. Inhibition of PGE2 generation with indomethacin or rofecoxib and suppression of NO synthase by L-NNA or capsaicin denervation reversed the GSE-induced protection and the accompanying hyperemia. Co-treatment of exogenous calcitonine gene-related peptide (CGRP) with

  7. Effect of sucralfate and its components on taurocholate-induced damage to rat gastric mucosal cells in tissue culture

    Energy Technology Data Exchange (ETDEWEB)

    Romano, M.; Razandi, M.; Ivey, K.J. (Long Beach VA Medical Center, CA (USA))

    1990-04-01

    The present study evaluated the effect of sucralfate and its components, sucrose octasulfate and aluminum hydroxide, on: (1) damage to rat cultured gastric mucosal cells induced by sodium taurocholate in a neutral environment and in conditions independent of systemic factors, (2) prostaglandin E2 and on 6-keto prostaglandin F1 alpha release by cultured cells, and (3) sulfhydryl content of cultured cells. Cell damage was quantitated by chromium-51 release assay. Prostaglandin E2 and 6-keto prostaglandin F1 alpha were measured by radioimmunoassay. Total sulfhydryl content of cultured cells was determined calorimetrically. Microscopically, sucralfate was found to adhere tightly to epithelial cell surfaces despite frequent washings. Sucralfate 2 mg/ml and 5 mg/ml significantly decreased taurocholate-induced damage, reducing taurocholate-induced specific 51Cr release by 11.8 points (equal to 29% decrease in cell damage, P less than 0.01) and 22.9 points (equal to 56% decrease in cell damage, P less than 0.001), respectively. Sucrose octasulfate and aluminum hydroxide did not exert significant protection against damage induced by sodium taurocholate. The protective effect of sucralfate was not prevented by indomethacin, nor was it counteracted by the sulfhydryl blocker, iodoacetamide. Sucralfate, but not its components, significantly and dose-dependently stimulated prostaglandin E2 (r = 0.94, P less than 0.05) and 6-keto prostaglandin F1 alpha (r = 0.89, P less than 0.05) production by cultured cells. Neither sucralfate nor its components affected sulfhydryl content of cultured cells. In conclusion, sucralfate, but not its components, (1) protects rat gastric mucosal cells against taurocholate-induced damage in conditions independent of systemic factors and in a neutral environment and (2) significantly stimulates prostaglandin production by cultured cells.

  8. Effect of sucralfate and its components on taurocholate-induced damage to rat gastric mucosal cells in tissue culture

    International Nuclear Information System (INIS)

    Romano, M.; Razandi, M.; Ivey, K.J.

    1990-01-01

    The present study evaluated the effect of sucralfate and its components, sucrose octasulfate and aluminum hydroxide, on: (1) damage to rat cultured gastric mucosal cells induced by sodium taurocholate in a neutral environment and in conditions independent of systemic factors, (2) prostaglandin E2 and on 6-keto prostaglandin F1 alpha release by cultured cells, and (3) sulfhydryl content of cultured cells. Cell damage was quantitated by chromium-51 release assay. Prostaglandin E2 and 6-keto prostaglandin F1 alpha were measured by radioimmunoassay. Total sulfhydryl content of cultured cells was determined calorimetrically. Microscopically, sucralfate was found to adhere tightly to epithelial cell surfaces despite frequent washings. Sucralfate 2 mg/ml and 5 mg/ml significantly decreased taurocholate-induced damage, reducing taurocholate-induced specific 51Cr release by 11.8 points (equal to 29% decrease in cell damage, P less than 0.01) and 22.9 points (equal to 56% decrease in cell damage, P less than 0.001), respectively. Sucrose octasulfate and aluminum hydroxide did not exert significant protection against damage induced by sodium taurocholate. The protective effect of sucralfate was not prevented by indomethacin, nor was it counteracted by the sulfhydryl blocker, iodoacetamide. Sucralfate, but not its components, significantly and dose-dependently stimulated prostaglandin E2 (r = 0.94, P less than 0.05) and 6-keto prostaglandin F1 alpha (r = 0.89, P less than 0.05) production by cultured cells. Neither sucralfate nor its components affected sulfhydryl content of cultured cells. In conclusion, sucralfate, but not its components, (1) protects rat gastric mucosal cells against taurocholate-induced damage in conditions independent of systemic factors and in a neutral environment and (2) significantly stimulates prostaglandin production by cultured cells

  9. Ethanolic extract of roots from Arctium lappa L. accelerates the healing of acetic acid-induced gastric ulcer in rats: Involvement of the antioxidant system.

    Science.gov (United States)

    da Silva, Luisa Mota; Allemand, Alexandra; Mendes, Daniel Augusto G B; Dos Santos, Ana Cristina; André, Eunice; de Souza, Lauro Mera; Cipriani, Thales Ricardo; Dartora, Nessana; Marques, Maria Consuelo Andrade; Baggio, Cristiane Hatsuko; Werner, Maria Fernanda

    2013-01-01

    We evaluate the curative efficacy of the ethanolic extract (EET) of roots from Arctium lappa (bardana) in healing of chronic gastric ulcers induced by 80% acetic acid in rats and additionally studies the possible mechanisms underlying this action. Oral administration of EET (1, 3, 10 and 30mg/kg) reduced the gastric lesion area in 29.2%, 41.4%, 59.3% and 38.5%, respectively, and at 10mg/kg promoted significant regeneration of the gastric mucosa, which was confirmed by proliferating cell nuclear antigen immunohistochemistry. EET (10mg/kg) treatment did not increase the gastric mucus content but restored the superoxide dismutase activity, prevented the reduction of glutathione levels, reduced lipid hydroperoxides levels, inhibited the myeloperoxidase activity and reduced the microvascular permeability. In addition, EET reduced the free radical generation and increased scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals in vitro. Furthermore, intraduodenal EET (10 and 30mg/kg) decreased volume and acidity of gastric secretion. Total phenolic compounds were high in EET (Folin-Ciocalteau assay) and the analysis by liquid chromatography-mass spectrometry revealed that the main compounds present in EET were a serie of hydroxycinnamoylquinic acid isomers. In conclusion, these data reveal that EET promotes regeneration of damaged gastric mucosa, probably through its antisecretory and antioxidative mechanisms. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. IMMUNOHISTOCHEMICAL APPROACH REVEALS LOCALIZATION OF CYSTATHIONINE-?-LYASE AND CYSTATHIONINE-ß-SYNTHETASE IN ETHANOL-INDUCED GASTRIC MUCOSA DAMAGE IN MICE

    Directory of Open Access Journals (Sweden)

    Jand-Venes Rolim MEDEIROS

    2013-04-01

    Full Text Available Context Hydrogen sulphide (H2S has been proved to be a neuromodulator and contributes to the maintenance of gastric mucosal integrity in damage caused by anti-inflammatory nonsteroidal drugs. Previously, we demonstrated that H2S synthesis is essential to gastric protection against ethanol. Objective To better understanding the role of H2S and the detailed localization of its production in both normal and injured stomach due to ethanol injection, we studied the expression of cystathionine-γ-lyase (CSE and cystathionine-β-synthetase (CBS isoforms in gastric mucosa of mice treated with saline or 50% ethanol. Methods Mice were treated by gavage with saline or 50% ethanol (0.5 mL/25 g. After 1 hour, mice were sacrificed, and gastric tissue was evaluated by histological and immunohistochemical analysis specific for CSE and CBS. Results We have demonstrated a non-specific expression of CBS in the normal gastric mucosa and expression of CSE occurring mainly in the parietal cells of the animals treated with ethanol. Conclusion Thus, we demonstrated that the expression of CBS appears to be constitutive and diffuse across the gastric epithelium, while the expression of CSE appears to be induced in parietal cells by damage agents such as ethanol.

  11. [Expression of tumor necrosis factor-like weak inducer of apoptosis in patients with gastric cancer and its relationship with nutritional status].

    Science.gov (United States)

    Lu, Hang; Sun, Yuanshui

    2016-10-25

    To investigate the expression of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in the serum and the rectus abdominis muscle in patients with gastric cancer and its relationship with the nutritional status. Method Clinical data of 102 patients with gastric cancer (gastric cancer group) and 53 patients with benign abdominal disease (control group) who were admitted to Zhejiang Province People's Hospital from January 2008 to October 2013 were analyzed retrospectively. Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum expression of TWEAK. Reverse transcription polymerase chain reaction (RT-PCR) and Western blot were used to detect the mRNA and protein expression of TWEAK in the rectus abdominis muscle. Relationship between TWEAK expression and nutritional status of gastric cancer patients was examined. The relative expression level of TWEAK protein in serum of gastric cancer group and control group was 0.403±0.065 and 0.148±0.036 respectively. The relative expression of TWEAK mRNA in the rectus abdominis muscle tissue was 0.313±0.089 (gastric cancer group) and 0.118±0.005 (control group). The relative expression of TWEAK protein in the rectus abdominis muscle tissue was 0.197±0.064 (gastric cancer group) and 0.066±0.014 (control group), and the differences were statistically significant (both P=0.000). The high expression of TWEAK (high than median) in rectus abdominis muscle of gastric cancer patients was related to the percentage of more than 10% decline in body weight (P=0.000), the small percentage of ideal body weight at the time of admission (P=0.000), BMInutritional risk screening score (P=0.000), lower prognostic nutrition index (P=0.000) and serum albumin gastric cancer patients up-regulates compared to non-tumor patients. The expression level of TWEAK in the rectus abdominis muscle of gastric cancer patients is closely related to poor nutritional status, suggesting that TWEAK may play a key role in the process of

  12. Bovine lactoferricin B induces apoptosis of human gastric cancer cell line AGS by inhibition of autophagy at a late stage.

    Science.gov (United States)

    Pan, W-R; Chen, P-W; Chen, Y-L S; Hsu, H-C; Lin, C-C; Chen, W-J

    2013-01-01

    Gastric cancer is one of the most common malignant cancers, with poor prognosis and high mortality rates worldwide. Therefore, development of an effective therapeutic method without side effects is an urgent need. It has been reported that cationic antimicrobial peptides can selectively bind to negatively charged prokaryotic and cancer cell membranes and exert cytotoxicity without causing severe drug resistance. In the current study, we prepared a series of peptide fragments derived from bovine lactoferrin and evaluated their anticancer potency toward the gastric cancer cell line AGS. Cell viability assay revealed that a 25-AA peptide fragment, lactoferricin B25 (LFcinB25), exhibited the most potent anticancer capability against AGS cells. Lactoferricin B25 selectively inhibited AGS cell growth in a dose-dependent manner, exhibiting a half-maximal inhibitory concentration (IC50) value of 64 μM. Flow cytometry showed a notable increment of the sub-G1 populations of the cell cycle, indicating the induction of apoptosis by LFcinB25. Western blot analysis further revealed that upon LFcinB25 treatment for 2 to 6h, apoptosis-related caspases-3, 7, 8, 9, and poly(ADP-ribose) polymerase (PARP) were cleaved and activated, whereas autophagy-related LC3-II and beclin-1 were concomitantly increased. Thus, both apoptosis and autophagy are involved in the early stage of LFcinB25-induced cell death of AGS cells. However, upon treatment with LFcinB25 for 12 to 24h, LC3-II began to decrease, whereas cleaved beclin-1 increased in a time-dependent manner, suggesting that consecutive activation of caspases cleaved beclin-1 to inhibit autophagy, thus enhancing apoptosis at the final stage. These findings provide support for future application of LFcinB25 as a potential therapeutic agent for gastric cancer. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  13. Fisetin inhibits the proliferation of gastric cancer cells and induces apoptosis through suppression of ERK 1/2 activation.

    Science.gov (United States)

    Yan, Weixin; Chen, Shouhui; Zhao, Yiyang; Ye, Xiaoyu

    2018-06-01

    The present study aimed to investigate the effect of fisetin on proliferation and apoptosis of gastric cancer cells, as well as the underlying mechanism. Proliferation in SGC7901 cancer and GES-1 normal cells was analyzed using a CCK-8 assay. Apoptosis was analyzed using an Annexin V/Propidium Iodide apoptosis kit and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 was analyzed by western blot assay. Treatment of SGC7901 cells with various concentrations (1, 5, 10, 15 and 20 µM) of fisetin for 48 h resulted in a concentration dependent reduction in proliferation. Flow cytometry revealed a marked increase in apoptosis from 5 µM concentration of fisetin after 48 h. The percentage of apoptotic cells increased to 87% following treatment with 15 µM fisetin for 48 h, compared with 2% in control. Treatment of SGC7901 cells with fisetin for 48 h resulted in a reduction in the activation of ERK 1/2 in a concentration-dependent manner. The reduction in activation of ERK 1/2 was significant following treatment with 15 µM fisetin for 48 h. The inhibitory effect of fisetin on activation of ERK 1/2 was further demonstrated using the ERK 1/2 inhibitor, PD98059. The results indicated a significant reduction in the proliferation of SGC7901 cells following treatment with PD98059 (P<0.002). The reduction by PD98059 administration was comparable to that observed following fisetin treatment for 48 h. In conclusion, the current study demonstrates that fisetin inhibits the proliferation of gastric cancer cells and induces apoptosis through suppression of ERK 1/2 activation. Thus, fisetin may have therapeutic applications in the treatment of gastric cancer.

  14. Gastric Varices with Remarkable Collateral Veins in Valpronic Acid-Induced Chronic Pancreatitis

    Directory of Open Access Journals (Sweden)

    Y. Hattori

    2008-08-01

    Full Text Available Valproic acid (VPA is a commonly prescribed and approved treatment for epilepsy, including Angelman syndrome, throughout the world. However, the long-term administration of drugs like VPA is associated with the possible development of gastric varices and splenic obstruction as a result of chronic pancreatitis. Such cases can be difficult to treat using endoscopy or interventional radiology because of hemodynamic abnormalities; therefore, surgical treatment is often necessary.

  15. Lactobacillus acidophilus ameliorates H. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways

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    Yang Yao-Jong

    2012-03-01

    Full Text Available Abstract Background H. pylori infection may trigger Smad7 and NFκB expression in the stomach, whereas probiotics promote gastrointestinal health and improve intestinal inflammation caused by pathogens. This study examines if probiotics can improve H. pylori-induced gastric inflammation by inactivating the Smad7 and NFκB pathways. Results Challenge with H. pylori increased IL-8 and TNF-α expressions but not TGF-β1 in MKN45 cells. The RNA levels of Smad7 in AGS cells increased after H. pylori infection in a dose-dependent manner. A higher dose (MOI 100 of L. acidophilus pre-treatment attenuated the H. pylori-induced IL-8 expressions, but not TGF-β1. Such anti-inflammatory effect was mediated via increased cytoplasmic IκBα and depletion of nuclear NFκB. L. acidophilus also inhibited H. pylori-induced Smad7 transcription by inactivating the Jak1 and Stat1 pathways, which might activate the TGF-β1/Smad pathway. L. acidophilus pre-treatment ameliorated IFN-γ-induced Smad7 translation level and subsequently reduced nuclear NF-κB production, as detected by western blotting. Conclusions H. pylori infection induces Smad7, NFκB, IL-8, and TNF-α production in vitro. Higher doses of L. acidophilus pre-treatment reduce H. pylori-induced inflammation through the inactivation of the Smad7 and NFκB pathways.

  16. Tryptamine-gallic acid hybrid prevents non-steroidal anti-inflammatory drug-induced gastropathy: correction of mitochondrial dysfunction and inhibition of apoptosis in gastric mucosal cells.

    Science.gov (United States)

    Pal, Chinmay; Bindu, Samik; Dey, Sumanta; Alam, Athar; Goyal, Manish; Iqbal, Mohd Shameel; Sarkar, Souvik; Kumar, Rahul; Halder, Kamal Krishna; Debnath, Mita Chatterjee; Adhikari, Susanta; Bandyopadhyay, Uday

    2012-01-27

    We have investigated the gastroprotective effect of SEGA (3a), a newly synthesized tryptamine-gallic acid hybrid molecule against non-steroidal anti-inflammatory drug (NSAID)-induced gastropathy with mechanistic details. SEGA (3a) prevents indomethacin (NSAID)-induced mitochondrial oxidative stress (MOS) and dysfunctions in gastric mucosal cells, which play a pathogenic role in inducing gastropathy. SEGA (3a) offers this mitoprotective effect by scavenging of mitochondrial superoxide anion (O(2)(·-)) and intramitochondrial free iron released as a result of MOS. SEGA (3a) in vivo blocks indomethacin-mediated MOS, as is evident from the inhibition of indomethacin-induced mitochondrial protein carbonyl formation, lipid peroxidation, and thiol depletion. SEGA (3a) corrects indomethacin-mediated mitochondrial dysfunction in vivo by restoring defective electron transport chain function, collapse of transmembrane potential, and loss of dehydrogenase activity. SEGA (3a) not only corrects mitochondrial dysfunction but also inhibits the activation of the mitochondrial pathway of apoptosis by indomethacin. SEGA (3a) inhibits indomethacin-induced down-regulation of bcl-2 and up-regulation of bax genes in gastric mucosa. SEGA (3a) also inhibits indometacin-induced activation of caspase-9 and caspase-3 in gastric mucosa. Besides the gastroprotective effect against NSAID, SEGA (3a) also expedites the healing of already damaged gastric mucosa. Radiolabeled ((99m)Tc-labeled SEGA (3a)) tracer studies confirm that SEGA (3a) enters into mitochondria of gastric mucosal cell in vivo, and it is quite stable in serum. Thus, SEGA (3a) bears an immense potential to be a novel gastroprotective agent against NSAID-induced gastropathy.

  17. [Comparison of anti-inflammatory activity between crude Atractylodes lancea and their processed products by stir-baking with bran in rat models of gastric ulcer].

    Science.gov (United States)

    Yu, Yan; Jia, Tian-Zhu; Cai, Qian

    2016-02-01

    To compare the anti-inflammatory activity of the crude Atractylodes lancea (AL) and AL processed products by stir-baking with bran in rat models of gastric ulcer, and preliminarily explore the anti-ulcer mechanisms of AL, the model of gastric ulcer was imitated by local acetic acid injection into gastric mucosa in rats by surgery according to the modified Okabe method. All rats were randomly divided into the following 10 groups: sham-operation group, model group, omeprazole group, Sanjiu Weitai granule group, crude AL low dose group, crude AL middle dose group, crude AL high dose group, processed AL low dose group, processed AL middle dose group, and processed AL high dose group. Rats were administered via intragastric (ig) two times each day, for 10 consecutive days. Blood was collected from the abdominal aorta, serum was separated, and the ulcer tissues were taken. The levels of inflammatory factors interleukin 6, 8 (IL-6, 8), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) in serum and gastric tissues were determined by enzyme-linked immunosorbent assay (ELISA), and the mRNA expressions of TNF-α and IL-8 in gastric tissues were detected by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). The protein expressions of TNF-α and IL-8 in gastric tissues were detected by immunohistochemistry. Compared with sham-operation group, the levels of TNF-α, IL-8, IL-6, PGE2 as well as the mRNA expressions and protein expressions of TNF-α, IL-8 in gastric tissues were significantly higher in model group. The above levels were reduced in different degrees in all treatment groups. Compared with the crude AL, same dose of processed AL was more effective in decreasing the levels of TNF-α, IL-8, IL-6, PGE2 in serum and gastric tissues and down-regulating the mRNA expressions of TNF-α and IL-8 in gastric tissues, with significant difference in middle dose groups and high dose groups. The results showed that AL had potent anti

  18. Variations in gastric compliance induced by acute blood volume changes in anesthetized rats

    Directory of Open Access Journals (Sweden)

    Graça J.R.V.

    2002-01-01

    Full Text Available The impact of acute volume imbalances on gastric volume (GV was studied in anesthetized rats (250-300 g. After cervical and femoral vessel cannulation, a balloon catheter was positioned in the proximal stomach. The opposite end of the catheter was connected to a barostat with an electronic sensor coupled to a plethysmometer. A standard ionic solution was used to fill the balloon (about 3.0 ml and the communicating vessel system, and to raise the reservoir liquid level 4 cm above the animals' xiphoid appendix. Due to constant barostat pressure, GV values were considered to represent the gastric compliance index. All animals were monitored for 90 min. After a basal interval, they were randomly assigned to normovolemic, hypervolemic, hypovolemic or restored protocols. Data were compared by ANOVA followed by Bonferroni's test. Mean arterial pressure (MAP, central venous pressure (CVP and GV values did not change in normovolemic animals (N = 5. Hypervolemic animals (N = 12 were transfused at 0.5 ml/min with a suspension of red blood cells in Ringer-lactate solution with albumin (12.5 ml/kg, which reduced GV values by 11.3% (P0.05. MAP and CVP values increased (P<0.05 after hypervolemia but decreased (P<0.05 with hypovolemia. In conclusion, blood volume level modulates gastric compliance, turning the stomach into an adjustable reservoir, which could be part of the homeostatic process to balance blood volume.

  19. Multipathway Integrated Adjustment Mechanism of Glycyrrhiza Triterpenes Curing Gastric Ulcer in Rats.

    Science.gov (United States)

    Wang, Ying; Wang, Shuai; Bao, Yongrui; Li, Tianjiao; Chang, Xin; Yang, Guanlin; Meng, Xiansheng

    2017-01-01

    Gastric ulcer is a common chronic disease in human digestive system, which is difficult to cure, easy to relapse, and endangers human health seriously. Compared with western medicine, traditional Chinese medicine has a unique advantage in improving the general situation, stablizing medical condition, and with little side effects. Glycyrrhiza known as "king of all the medicine", has a range of pharmacological activities and is commonly used in a variety of proprietary Chinese medicines and formulations. On the basis of explicit antiulcer effect of Glycyrrhiza triterpenes, the molecular mechanisms of its therapeutic effect on acetic acid induced gastric ulcer in rats were explored. Acetic acid induced gastric ulcer model in rats was established to evaluate the curing effect of G. triterpenes and all of the rats were randomised into six groups: Control group, model group, omeprazole group (0.8 mg/mL), triterpenes high dose group (378.0 mg/mL), triterpenes middle dose group (126.0 mg/mL), and triterpenes low dose group (42.0 mg/mL). All rats in groups were orally administered the active group solution 1.5 mL once daily (model and control groups with saline) for 7 days. HPLC-TOF-MS analysis method was performed to obtain the plasma metabolites spectrums of control group, model group, triterpenes high, middle and low dose groups. A total of 11 differential endogenous metabolites related to the therapeutic effect of G. triterpenes were identified, including tryptophan, phingosine-1-phosphate, pantothenic acid, and so on, among which tryptophan and phingosine-1-phosphate are related with the calcium signaling pathway and arachidonic acid (AA) metabolism. At the same time, in order to verify the above results, quantitative real time polymerase chain reaction were performed to evaluate the expression of H + -K + -ATPase alpha mRNA and phospholipase a 2 mRNA in relational signaling pathways. Combined with statistical analysis of plasma metabolic spectrum and gene expression

  20. FoxP3 inhibits proliferation and induces apoptosis of gastric cancer cells by activating the apoptotic signaling pathway

    International Nuclear Information System (INIS)

    Ma, Gui-Fen; Chen, Shi-Yao; Sun, Zhi-Rong; Miao, Qing; Liu, Yi-Mei; Zeng, Xiao-Qing; Luo, Tian-Cheng; Ma, Li-Li; Lian, Jing-Jing; Song, Dong-Li

    2013-01-01

    Highlights: ► The article revealed FoxP3 gene function in gastric cancer firstly. ► Present the novel roles of FoxP3 in inhibiting proliferation and promoting apoptosis in gastric cancer cells. ► Overexpression of FoxP3 increased proapoptotic molecules and repressed antiapoptotic molecules. ► Silencing of FoxP3 reduced the expression of proapoptotic genes, such as PARP, caspase-3 and caspase-9. ► FoxP3 is sufficient for activating the apoptotic signaling pathway. -- Abstract: Forkhead Box Protein 3 (FoxP3) was identified as a key transcription factor to the occurring and function of the regulatory T cells (Tregs). However, limited evidence indicated its function in tumor cells. To elucidate the precise roles and underlying molecular mechanism of FoxP3 in gastric cancer (GC), we examined the expression of FoxP3 and the consequences of interfering with FoxP3 gene in human GC cell lines, AGS and MKN45, by multiple cellular and molecular approaches, such as immunofluorescence, gene transfection, CCK-8 assay, clone formation assay, TUNEL assay, Flow cytometry, immunoassay and quantities polymerase chain reaction (PCR). As a result, FoxP3 was expressed both in nucleus and cytoplasm of GC cells. Up-regulation of FoxP3 inhibited cell proliferation and promoted cell apoptosis. Overexpression of FoxP3 increased the protein and mRNA levels of proapoptotic molecules, such as poly ADP-ribose polymerase1 (PARP), caspase-3 and caspase-9, and repressed the expression of antiapoptotic molecules, such as cellular inhibitor of apoptosis-1 (c-IAP1) and the long isoform of B cell leukemia/lymphoma-2 (Bcl-2). Furthermore, silencing of FoxP3 by siRNA in GC cells reduced the expression of proapoptotic genes, such as PARP, caspase-3 and caspase-9. Collectively, our findings identify the novel roles of FoxP3 in inhibiting proliferation and inducing apoptosis in GC cells by regulating apoptotic signaling, which could be a promising therapeutic approach for gastric cancer.

  1. FoxP3 inhibits proliferation and induces apoptosis of gastric cancer cells by activating the apoptotic signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Gui-Fen [Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai (China); Chen, Shi-Yao, E-mail: shiyao_chen@163.com [Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai (China); Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai (China); Sun, Zhi-Rong [Department of Anesthesiology, Cancer Center, Fudan University, Shanghai (China); Miao, Qing; Liu, Yi-Mei; Zeng, Xiao-Qing; Luo, Tian-Cheng [Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai (China); Ma, Li-Li; Lian, Jing-Jing [Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai (China); Song, Dong-Li [Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai (China)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer The article revealed FoxP3 gene function in gastric cancer firstly. Black-Right-Pointing-Pointer Present the novel roles of FoxP3 in inhibiting proliferation and promoting apoptosis in gastric cancer cells. Black-Right-Pointing-Pointer Overexpression of FoxP3 increased proapoptotic molecules and repressed antiapoptotic molecules. Black-Right-Pointing-Pointer Silencing of FoxP3 reduced the expression of proapoptotic genes, such as PARP, caspase-3 and caspase-9. Black-Right-Pointing-Pointer FoxP3 is sufficient for activating the apoptotic signaling pathway. -- Abstract: Forkhead Box Protein 3 (FoxP3) was identified as a key transcription factor to the occurring and function of the regulatory T cells (Tregs). However, limited evidence indicated its function in tumor cells. To elucidate the precise roles and underlying molecular mechanism of FoxP3 in gastric cancer (GC), we examined the expression of FoxP3 and the consequences of interfering with FoxP3 gene in human GC cell lines, AGS and MKN45, by multiple cellular and molecular approaches, such as immunofluorescence, gene transfection, CCK-8 assay, clone formation assay, TUNEL assay, Flow cytometry, immunoassay and quantities polymerase chain reaction (PCR). As a result, FoxP3 was expressed both in nucleus and cytoplasm of GC cells. Up-regulation of FoxP3 inhibited cell proliferation and promoted cell apoptosis. Overexpression of FoxP3 increased the protein and mRNA levels of proapoptotic molecules, such as poly ADP-ribose polymerase1 (PARP), caspase-3 and caspase-9, and repressed the expression of antiapoptotic molecules, such as cellular inhibitor of apoptosis-1 (c-IAP1) and the long isoform of B cell leukemia/lymphoma-2 (Bcl-2). Furthermore, silencing of FoxP3 by siRNA in GC cells reduced the expression of proapoptotic genes, such as PARP, caspase-3 and caspase-9. Collectively, our findings identify the novel roles of FoxP3 in inhibiting proliferation and inducing apoptosis

  2. Gastroprotective effect of Byrsonima sericea DC leaf extract against ethanol-induced gastric injury and its possible mechanisms of action

    Directory of Open Access Journals (Sweden)

    Patrícia A. Rodrigues

    2012-03-01

    Full Text Available Byrsonima sericea leaves are extensively used in folk medicine in Brazil against gastric disorders. This study investigated the chemical constituents of B. sericea leaf ethanolic extract (BSLE and its potential gastroprotective activity, with its possible mechanism of the action using ethanol to induce gastric mucosal damage in mice. The phytochemical analysis was carried out to identify the active constituents present in the extract, and the HPLC analysis was performed for the identification of flavonoids. BSLE at oral doses of 125, 250 and 500 mg/kg markedly attenuated the ethanol-evoked gastric lesions by 53.2, 84.9 and 87.6 %, respectively. The BSLE (250 mg/kg prevented the depletion of gastric mucus and gastric mucosal nonproteic-sulfhydryl groups, SOD and CAT, as well as the increase in the MDA content promoted by absolute ethanol. Moreover, the effect of BSLE against ethanol damage was found to be significantly reduced in mice pretreated with Capsazepine (i.p., L-NAME (i.p. or glibenclamide (i.p., the respective blockers/inhibitors of TRPV1, NO synthase and K+ATP channel. The phytochemical investigation on BSLE revealed the presence of flavonoids rutin, isoquercitrin, kaempferol 3-O-rutinoside and quercetin, which are compounds well known for their antioxidant and gastroprotective properties. These results suggest that BSLE affords gastroprotection through multiple mechanisms, which may be helpful in the treatment of pathologies associated with gastric dysfunctions.Folhas de Byrsonima sericea são amplamente utilizadas na medicina popular no Brasil no tratamento de distúrbios gástricos. Este estudo investigou os constituintes químicos do extrato etanólico das folhas de B. sericea (BSLE e sua atividade gastroprotetora com seus possíveis mecanismos de ação utilizando o modelo de lesão gástrica induzida por etanol em camundongos. A análise fitoquímica foi realizada para identificar os componentes ativos presentes no extrato e an

  3. Compound 13, an α1-selective small molecule activator of AMPK, inhibits Helicobacter pylori-induced oxidative stresses and gastric epithelial cell apoptosis

    International Nuclear Information System (INIS)

    Zhao, Hangyong; Zhu, Huanghuang; Lin, Zhou; Lin, Gang; Lv, Guoqiang

    2015-01-01

    Half of the world's population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel α1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPKα1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPKα1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced AMPK-dependent expression of anti-oxidant gene heme oxygenase (HO-1) in GECs. Zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), two HO-1 inhibitors, not only suppressed C13-mediated ROS scavenging activity, but also alleviated its activity in GECs against H. pylori. Together, these results indicate that C13 inhibits H. pylori-induced ROS production and GEC apoptosis through activating AMPK–HO–1 signaling. - Highlights: • We synthesized compound 13 (C13), a α1-selective small molecule AMPK activator. • C13-induced AMPK activation requires α1 subunit in gastric epithelial cells (GECs). • C13 enhances Helicobacter pylori-induced pro-survival AMPK activation to inhibit GEC apoptosis. • C13 inhibits H. pylori-induced reactive oxygen species (ROS) production in GECs. • AMPK-heme oxygenase (HO-1) activation is required for C13-mediated anti-oxidant activity

  4. Compound 13, an α1-selective small molecule activator of AMPK, inhibits Helicobacter pylori-induced oxidative stresses and gastric epithelial cell apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Hangyong; Zhu, Huanghuang; Lin, Zhou; Lin, Gang; Lv, Guoqiang, E-mail: lvguoqiangwuxivip@163.com

    2015-08-07

    Half of the world's population experiences Helicobacter pylori (H. pylori) infection, which is a main cause of gastritis, duodenal and gastric ulcer, and gastric cancers. In the current study, we investigated the potential role of compound 13 (C13), a novel α1-selective small molecule activator of AMP-activated protein kinase (AMPK), against H. pylori-induced cytotoxicity in cultured gastric epithelial cells (GECs). We found that C13 induced significant AMPK activation, evidenced by phosphorylation of AMPKα1 and ACC (acetyl-CoA carboxylase), in both primary and transformed GECs. Treatment of C13 inhibited H. pylori-induced GEC apoptosis. AMPK activation was required for C13-mediated GEC protection. Inhibition of AMPK kinase activity by the AMPK inhibitor Compound C, or silencing AMPKα1 expression by targeted-shRNAs, alleviated C13-induced GEC protective activities against H. pylori. Significantly, C13 inhibited H. pylori-induced reactive oxygen species (ROS) production in GECs. C13 induced AMPK-dependent expression of anti-oxidant gene heme oxygenase (HO-1) in GECs. Zinc protoporphyrin (ZnPP) and tin protoporphyrin (SnPP), two HO-1 inhibitors, not only suppressed C13-mediated ROS scavenging activity, but also alleviated its activity in GECs against H. pylori. Together, these results indicate that C13 inhibits H. pylori-induced ROS production and GEC apoptosis through activating AMPK–HO–1 signaling. - Highlights: • We synthesized compound 13 (C13), a α1-selective small molecule AMPK activator. • C13-induced AMPK activation requires α1 subunit in gastric epithelial cells (GECs). • C13 enhances Helicobacter pylori-induced pro-survival AMPK activation to inhibit GEC apoptosis. • C13 inhibits H. pylori-induced reactive oxygen species (ROS) production in GECs. • AMPK-heme oxygenase (HO-1) activation is required for C13-mediated anti-oxidant activity.

  5. Comparison of the efficacy of 4- and 8-week lansoprazole treatment for ESD-induced gastric ulcers: a randomized, prospective, controlled study.

    Science.gov (United States)

    Park, Ji Hoon; Baek, Eun Kyung; Choi, Chang Hwan; Lee, Kyung Hun; Kim, Beom Jin; Kim, Jeong Wook; Kim, Jae Gyu; Chang, Sae Kyung

    2014-01-01

    Although endoscopic submucosal dissection (ESD) is widely used to treat gastric neoplasms, there is no consensus for the optimal treatment for ESD-induced ulcers. We compared efficacy between 4 and 8 weeks of lansoprazole treatment for iatrogenic gastric ulcers that developed after ESD. Eighty-four patients who were diagnosed with gastric adenoma or early gastric cancer were enrolled and randomly assigned to treatment with lansoprazole (30 mg/day) for 4 or 8 weeks. Eight weeks after ESD, we conducted follow-up endoscopy to compare ulcer stage and ulcer reduction ratio (dividing the ulcer dimension at 8 weeks by the initial ulcer dimension) between the two groups. From the 84 patients, 69 patients were included in the final analysis, with 34 in the 4-week group and 35 in the 8-week group. Eight weeks after ESD, there were no significant difference observed between the two groups in terms of the ulcer stage (68 % in the scar stage in the 4-week group vs. 69 % in the 8-week group, P = 0.93) or the ulcer reduction ratio (0.0081 ± 0.015 in the 4-week group vs. 0.0037 ± 0.008 in the 8-week group, P = 0.15). Also, in the subgroup analysis among the patients with large ulcers (>30 mm), those parameters were not different. For ESD-induced gastric ulcers, treatment with lansoprazole for 4 weeks was as effective as treatment for 8 weeks. Considering cost-effectiveness, proton pump inhibitor therapy for 4 weeks may be sufficient for ESD-induced gastric ulcers.

  6. Endoscopic appearance of irradiated gastric mucosa

    Energy Technology Data Exchange (ETDEWEB)

    De Sagher, L I; Van den Heule, B; Van Houtte, P; Engelholm, L; Balikdjan, D; Bleiberg, H

    1979-09-01

    Irradiation of the epigastric area for gastric cancer may induce actinic lesions of the stomach characterized on endoscopic examination by ulcerations, haemorrhagic gastritis, fragility of the mucosa, thickening and congestion of the gastric folds.

  7. Pre-treatment with mild whole-body heating prevents gastric ulcer induced by restraint and water-immersion stress in rats.

    Science.gov (United States)

    Itoh, Y H; Noguchi, R

    2000-01-01

    The purpose of this study was to assess the preventive effect of pre-mild whole-body heating (WBH) on gastric ulcer induced by restraint and water-immersion stress. The ulcer index and ulcer area ratio in rats exposed to restraint and water-immersion stress were significantly decreased (p immersion stress alone (p immersion, thereby preventing gastric ulcer formation. Pre-treatment with mild WBH is the safest cytoprotective method through the accumulation of HSP 70f. The concentration of HSP 70f in peripheral lymphocytes may be a useful clinical laboratory indicator for assessing the level of HSP 70f as having cytoprotective activity.

  8. Measurement of gastric emptying by intragastric gamma scintigraphy.

    Science.gov (United States)

    Malbert, C H; Mathis, C; Bobillier, E; Laplace, J P; Horowitz, M

    1997-09-01

    Gastric emptying is usually measured in animals and humans by dilution/sampling or external scintigraphy. These methods are either time consuming or require expensive equipment. The capacity of a miniature gamma counter positioned in the stomach to measure emptying of liquid and solid meals was evaluated. In eight conscious pigs fitted with gastric and duodenal cannulae, gastric emptying of saline (500 mL), dextrose (20%, 500 mL), porridge (300 g) and scrambled eggs (300 g), all labelled with 3.5 MBq 99mTC, was evaluated. When positioned in the antrum the probe was unable to quantify gastric emptying. In contrast, measurements of the fractional emptying of saline over 4-min periods by the probe positioned in the corpus and quantification of radioactivity in the duodenal effluent correlated closely (r = 0.88, P < 0.05). Gastric emptying (50% emptying time) of saline and both solid meals measured by the probe was not significantly different from quantification of the duodenal effluent volume. No difference was observed also for the dextrose meal but only while gastric acid secretion was suppressed by omeprazole. We conclude that an intragastric gamma counter permits measurement of gastric emptying of homogeneous meals provided meal stimulation of gastric secretion was not extensive. This was possible probably by monitoring emptying from the proximal stomach.

  9. Endoscopic laser-induced steam generator: a new method of treatment for early gastric cancer

    Science.gov (United States)

    Hayashi, Takuya; Arai, Tsunenori; Tajiri, Hisao; Nogami, Yashiroh; Hino, Kunihiko; Kikuchi, Makoto

    1996-05-01

    The minimum invasive endoscopic treatment for early gastric cancer has been popular in Japan. The endoscopic mucosal resection and laser coagulation by Nd:YAG laser irradiation has been the popular treatment method in this field. However, the submucosal cancer has not been successfully treated by these methods. To treat the submucosal cancer endoscopically, we developed a new coagulation therapy using hot steam generated by Nd:YAG laser. The steam of which temperature was over 10 deg. in Celsius was generated by the laser power of 30 W with 5 ml/min. of saline. The steam was emitted to canine gastric wall under laparotomy or endoscopy for 50 s respectively. Follow up endoscopy was performed on 3, 7, 14, 28 days after the treatment. Histological examination was studied on 7, 28 days, and just after the emission. In the acute observation, the submucosal layer was totally coagulated. On the 7th day, ulceration with white coat was seen. The mucosal defect, submucosal coagulation, and marked edema without muscle degeneration were found by the histological study. On the 14th day, the ulcer advanced in the scar stage. On the 28th day, it completely healed into white scar with mucosal regeneration and mucosal muscle thickening. We could obtain reproducible coagulation up to deep submucosal layer with large area in a short operation time. Moreover there were no degeneration of proper muscle. This treatment effectiveness could be easily controlled by the steam temperature and emission duration. We think that this method can be applied to early gastric cancer including the submucosal cancer, in particular poor risk case for operation. Further study should be done to apply this method to clinical therapy.

  10. Protective effects of amphetamine on gastric ulcerations induced by indomethacin in rats

    Institute of Scientific and Technical Information of China (English)

    Vlaicu Sandor; Barbu Cuparencu; Dan L Dumitrascu; Mircea A Birt; Tibor L Krausz

    2006-01-01

    AIM: To study the effects of amphetamine, an indirectacting adrenomimetic compound on the indomethacininduced gastric ulcerations in rats.METHODS: Male Wistar-Bratislava rats were randomly divided into four groups: Group 1 (control), received an ulcerogenic dose of indomethacin (50 μmol/kg) and Groups 2, 3 and 4, treated with amphetamine (10, 25and 50 μmol/kg). The drug was administered simultaneously with indomethacin and once again 4 h later.The animals were sacrificed 8 h after indomethacin treatment. The stomachs were opened and the incidence, the number of lesions and their severity were evaluated. The results were expressed as percentage and as mean ± standard error (mean ± SE).RESULTS: The incidence of ulceration in the control group was 100%. Amphetamine, at doses of 10, 25 and 50 μmol/kg, lowered the incidence to 88.89%, 77.78%and 37.5% respectively. The protection ratio was positive: 24.14%, 55.17% and 80.6% respectively. The total number of ulcerations/rat was 12.44 ± 3.69 in the control group. It decreased to 7.33 ± 1.89, 5.33 ± 2.38 and 2.25 ± 1.97 under the effects of the above-mentioned doses of amphetamine.CONCLUSION: Amphetamine affords a significant dose-dependent protection against the indomethacininduced gastric ulcerations in rats. It is suggested that the adrenergic system is involved in the gastric mucosa protection.

  11. Expression of p53, inducible nitric oxide synthase and vascular endothelial growth factor in gastric precancerous and cancerous lesions: correlation with clinical features

    International Nuclear Information System (INIS)

    Feng, Chang Wei; Wang, Li Dong; Jiao, Lian Hua; Liu, Bin; Zheng, Shu; Xie, Xin Ji

    2002-01-01

    The growth and metastasis of tumors depend on the development of an adequate blood supply via angiogenesis. Recent studies indicate that the inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF) and the tumor suppressor p53 are fundamental play-markers of the angiogenic process. Overexpression of iNOS and VEGF has been shown to induce angiogenesis in tumors. P53 suppresses angiogenesis by down-regulating VEGF and iNOS. The correlation of expression of p53, VEGF and iNOS and clinical features in gastric carcinogenesis, however, has not been well characterized. The expression of p53, iNOS and VEGF in gastric precancerous and cancerous lesions and its relation with the clinical features was determined with immunohistochemistry (avidin-biotin-peroxidase complex method) on 55 randomly selected GC patients and 60 symptom-free subjects from the mass survey in the high-incidence area for GC in Henan, northern China. The positive immunostainig rates for p53, iNOS and VEGF in gastric carcinomas were 51%, 44% and 51%, respectively, and correlated well with TNM stages, but did not show significant difference among the groups with different degrees of gastric wall invasion depth by GC. A positive immunostaining reaction for the iNOS protein was significantly correlated with lymph node metastasis (p = 0.019; Spearman correlation coefficient). P53 protein accumulation was higher in the poorly-differentiated gastric carcinoma than in well-differentiated one. In gastric biopsies, no positive immunosatining was observed for p53, iNOS and VEGF in the histologically normal tissue and chronic superficial gastritis (CSG). However, p53, iNOS and VEGF positive immunostaining was observed in the tissues with different severities of lesions of chronic atrophic gastritis (CAG), intestinal metaplasia (IM) and dysplasia (DYS), and the positive rates increased with the lesion progression from CAG to IM to DYS. A high coincidental positive and negative immunostaining

  12. Irradiation-induced telomerase activity and gastric cancer risk: a case-control analysis in a Chinese Han population

    International Nuclear Information System (INIS)

    He, Xianli; Qiao, Qing; Ge, Naijian; Nan, Jing; Shen, Shuqun; Wang, Zizhong; Yang, Yefa; Bao, Guoqiang

    2010-01-01

    Telomerase expression is one of the characteristics of gastric cancer (GC) cells and telomerase activity is frequently up-regulated by a variety of mechanisms during GC development. Therefore, we hypothesized that elevated levels of activated telomerase might enhance GC risk due to increased propagation of cells with DNA damage, such as induced by γ-radiation. To explore this hypothesis, 246 GC cases and 246 matched controls were recruited in our case-control study. TRAP-ELISA was used to assess the levels of telomerase activity at baseline and after γ-radiation and the γ-radiation-induced telomerase activity (defined as after γ-irradiation/baseline) in cultured peripheral blood lymphocytes (PBLs). Our data showed that there was no significant difference for the baseline telomerase activity between GC cases and controls (10.17 ± 7.21 vs. 11.02 ± 8.03, p = 0.168). However, after γ-radiation treatment, γ-radiation-induced telomerase activity was significantly higher in the cases than in the controls (1.51 ± 0.93 vs. 1.22 ± 0.66, p < 0.001). Using the median value of γ-radiation-induced telomerase activity in the controls as a cutoff point, we observed that high γ-radiation-induced telomerase activity was associated with a significantly increased GC risk (adjusted odds ratio, 2.45; 95% confidence interval, 1.83-3.18). Moreover, a dose response association was noted between γ-radiation-induced telomerase activity and GC risk. Age, but not sex, smoking and drinking status seem to have a modulating effect on the γ-radiation-induced telomerase activities in both cases and controls. Overall, our findings for the first time suggest that the increased γ-radiation-induced telomerase activity in PBLs might be associated with elevated GC risk. Further confirmation of this association using a prospective study design is warranted

  13. Helicobacter and Gastric Malignancies

    OpenAIRE

    Ferreira, António Carlos; Isomoto, Hajime; Moriyama, Masatsugu; Fujioka, Toshio; Machado, José Carlos; Yamaoka, Yoshio

    2008-01-01

    Individuals infected with Helicobacter pylori, a stomach colonizing bacteria, have an increased risk of developing gastric malignancies. The risk for developing cancer relates to the physiologic and histologic changes that H. pylori infection induces in the stomach. In the last year numerous studies have been conducted in order to characterize the association between H. pylori infection and gastric cancer. These studies range from epidemiologic approaches aiming at the identification of envir...

  14. Polysaccharides of Dendrobium officinale Kimura & Migo protect gastric mucosal cell against oxidative damage-induced apoptosis in vitro and in vivo.

    Science.gov (United States)

    Zeng, Qiang; Ko, Chun-Hay; Siu, Wing-Sum; Li, Long-Fei; Han, Xiao-Qiang; Yang, Liu; Bik-San Lau, Clara; Hu, Jiang-Miao; Leung, Ping-Chung

    2017-08-17

    Dendrobium officinale Kimura & Migo (DO) is a valuable Traditional Chinese Medicine to nourish stomach, in which polysaccharides are identified as active ingredients. However, limited scientific evidences have been reported on the gastroprotective efficacy of DO. The aim of the current study was to investigate the protective effects and underlying mechanism of polysaccharides from DO(DOP) on gastric mucosal injury. For in vitro study, HFE145 cells were pretreated with DOP before induction of cell apoptosis by H 2 O 2 . Cell apoptosis and related proteins expression were detected. In the in vivo study, absolute ethanol was administered orally to induce gastric mucosal injury in rat. The gastric mucosal injury area and histological examination were used to evaluate the effects of DOP treatment on the recovery of the gastric mucosal injury. H 2 O 2 treatment for 6h significantly induced cell apoptosis in HFE145 cells. However, the destructive effects of H 2 O 2 on HFE 145 cells could be reversed by the pretreatment with DOP. The increased ROS level induced by H 2 O 2 for 4h was reduced after DOP pretreatment. The number of apoptotic cells in both early and late apoptosis stages decreased significantly and the nuclei morphology changes were improved with DOP pretreatment. Furthermore, DOP inhibited caspase 3 activation and PARP cleavage, downregulated Bax expression and upregulated Bcl2 expression in cell model. Further study revealed that pretreatment of DOP inhibited p -NF-κBp65/NF-κBp65 level, indicating DOP inhibited H 2 O 2 -mediated apoptosis via suppression of NF-κB activation. In addition, DOP treatment could ameliorate gastric mucosal injury and inhibit mucin loss induced by ethanol in animal model. DOP treatment also interfered with ethanol-induced apoptosis process by downregulating Bax/Bcl2 ratio in gastric mucosa. The present study was the first one to demonstrate the gastroprotective effect of DOP through inhibiting oxidative stress-induced apoptosis

  15. Roux-en-Y Gastric Bypass Surgery Induces Early Plasma Metabolomic and Lipidomic Alterations in Humans Associated with Diabetes Remission

    DEFF Research Database (Denmark)

    Arora, Tulika; Velagapudi, Vidya; Pournaras, Dimitri J

    2015-01-01

    -surgery levels. At 4 days after surgery, insulin levels correlated positively with metabolites of branched chain and aromatic amino acid metabolism and negatively with triglycerides with long-chain fatty acids. Of the 14 subjects with diabetes prior to surgery, 7 were in remission 2 years after surgery....... The subjects in remission displayed higher pre-surgery levels of tricarboxylic acid cycle intermediates and triglycerides with long-chain fatty acids compared with subjects not in remission. Thus, metabolic alterations are induced soon after surgery and subjects with diabetes remission differ in the metabolic......Roux-en-Y gastric bypass (RYGB) is an effective method to attain sustained weight loss and diabetes remission. We aimed to elucidate early changes in the plasma metabolome and lipidome after RYGB. Plasma samples from 16 insulin-resistant morbidly obese subjects, of whom 14 had diabetes, were...

  16. The anti-inflammatory and anti-apoptotic effects of gallic acid against mucosal inflammation- and erosions-induced by gastric ischemia-reperfusion in rats.

    Science.gov (United States)

    Mard, Seyyed Ali; Mojadami, Shahnaz; Farbood, Yaghoob; Gharib Naseri, Mohammad Kazem

    2015-01-01

    The present study aimed to evaluate the protective effect of gallic acid on gastric mucosal lesions caused by ischemia-reperfusion (I/R) injury in rat. Forty male rats were randomly divided into sham, control (I/R injury) and three gallic acid-pretreated groups. To induce I/R lesions, the celiac artery was clamped for 30 min and then the clamp was removed to allow reperfusion for 6 hr. Pretreated rats received gallic acid (15, 30 or 60 mg kg(-1), intraperitoneally) 30 min prior to the induction of I/R injury. Macroscopic and microscopic evaluations of the areas of ulceration were compared. Samples of gastric mucosa were collected to evaluate the protein expression of pro-apoptotic factor, caspase-3, and pro-inflammatory enzyme, inducible nitric oxide synthase (iNOS) using western blot. Pretreatment with gallic acid decreased the total area of gastric lesions. Gallic acid at 30 mg kg(-1) decreased the levels of protein expression of caspase-3 and iNOS induced by I/R injury. Our findings showed the protective effect of gallic acid on gastric mucosa against ischemia-reperfusion injury. This effect of gallic acid was mainly mediated by reducing protein expression of iNOS and caspase-3.

  17. Bcl-w, a Radio-resistant Protein, Promotes the Gastric Cancer Cell Migration by inducing the phosphorylation of Focal Adhesion Kinase

    International Nuclear Information System (INIS)

    Bae, In Hwa; Yoon, Sung Hwan; Um, Hong Duck

    2008-01-01

    Gastric cancer is one of the leading malignancies in many countries and lethal for the high incidence of recurrence even after drastic surgical resection. Because local invasion and subsequent metastasis contributes to the failure of anticancer treatments of gastric cancer, a better understanding of the mechanisms involved in tumor invasiveness within the stomach seems to be essential for the control of this disease. Bcl-w is a prosurvival member of the Bcl-2 protein family, and thus protects cells from γ-irradiation. Recent reports suggest that Bcl-w can be upregulated in gastric cancer cells in a manner associated with the infiltrative (diffuse) types of the tumor. An analysis of Bcl-w function consistently revealed that Bcl-w can also promote the migratory and invasive potentials of gastric cancer cells. While it was shown that Bcl-w increases the invasiveness of cancer cells by sequentially inducing PI3K, Akt, SP1, and MMP-2, cellular components involved in Bcl-w-induced cell migration remain to be determined. This was the reason why we undertook the present study, which shows that FAK is a critical mediator of the cell migration induced by Bcl-w

  18. A Polysaccharide Isolated from Mycelia of the Lion's Mane Medicinal Mushroom Hericium erinaceus (Agaricomycetes) Induced Apoptosis in Precancerous Human Gastric Cells.

    Science.gov (United States)

    Wang, Mingxing; Zhang, Yanqiu; Xiao, Xulang; Xu, Duoduo; Gao, Yang; Gao, Qipin

    2017-01-01

    Hericium erinaceus is typically used in traditional Chinese medicine for mucosal protection, healing of gastric ulcers, and treatment of gastritis. We purified from the cultured mycelia of H. erinaceus a polysaccharide with anti-gastric ulcer and antigastritis activity, but its effects on gastric malignancy have not been elucidated. We examined the differential effects of this purified polysaccharide, named EP-1, on the human gastric (GES-1) cell line and a precancerous cell line (MC) that was transformed from GES-1 using N-methyl-N'-nitro-N-nitrosoguanidine. We observed that the polysaccharide potently induced cell apoptosis and cell cycle arrest at the G0/G1 phase in the MC cell line but did not have any effect on the GES-1 cell line at the same doses. Further mechanistic studies revealed that the polysaccharide exerted its activity through an apoptosis-associated pathway by modulating the expression of Bax, Bcl-2, and caspase-3. Differential effects of the polysaccharide on the GES-1 and MC cell lines indicate that the polysaccharide was effective in preventing gastric cancer progression.

  19. [Nuclear factor-kappaB mRNA and protein expression in stomach tissue of rats with gastric ulcer recurrence and effect of jianwei yuyang granule on its expression].

    Science.gov (United States)

    Ling, Jiang-Hong; Li, Jia-Bang; Shen, Ding-Zhu; Zhou, Bing

    2006-03-01

    To observe the inflammatory reaction, nuclear factor-kappaB (NF-kappaB) mRNA and protein expression in stomach tissue of rats with gastric ulcer recurrence and the effect of Jianwei Yuyang granule (JYG) on them. Gastric ulcer and its recurrent lesion were successively induced by acetic acid and interliukin1-beta (IL-1beta), and the model rats were divided into the sham operation group, the model group, the omeprazole (correction of omepraxole) group and the JYG group to observe the state of chronic inflammatory cell, neutrophil count, NF-kappaBmRNA and protein expression in stomach tissue. On the 16th and 92th day after administration, the increase of chronic inflammatory cell, neutrophil, NF-kappaBmRNA and protein expression in the model group was more significant than those in the sham operated group (P ulcer induced by acetic acid. JYG may suppress inflammatory reaction by inhibiting the activation and expression of NF-kappaB in stomach tissue, which may be one of the mechanisms of JYG in preventing the recurrence of gastric ulcer.

  20. Comparison of the therapeutic effects of sildenafil citrate, heparin and neuropeptides in a rat model of acetic acid-induced gastric ulcer.

    Science.gov (United States)

    Kalayci, Mehmet; Kocdor, Mehmet Ali; Kuloglu, Tuncay; Sahin, İbrahim; Sarac, Mehmet; Aksoy, Aziz; Yardim, Meltem; Dalkilic, Semih; Gursu, Onur; Aydin, Suna; Akkoc, Ramazan Fazil; Ugras, Meltem; Artas, Gokhan; Ozercan, İbrahim Hanifi; Ugur, Kader; Aydin, Suleyman

    2017-10-01

    The purpose of our investigative work has been to determine whether there can be therapeutic roles in the administration of sildenafil citrate, heparin and several neuropeptides on an animal model where gastric ulcers were induced with acetic acid, and to compare their efficacy. The animals were divided into 13 groups, with 4 animals in each. Gastric ulcers was induced in the animals of 12 groups with one untreated group being left as the control (Group I - control; given normal saline (NS)). The other groups were: Group II (ulcer+NS); Group III (5mg/kg sildenafil citrate, low dose); Group IV (10mg/kg sildenafil citrate, high dose); Group V (0.6mg/kg heparin, low dose); Group VI (6mg/kg heparin, high dose); Group VII (20nmol/kg des-acyl ghrelin); Group VIII (40nmol/kg des-acyl ghrelin); Group IX (4nmol/kg acyl ghrelin); Group X (8nmol/kg acly ghrelin); Group XI (20pmol/kg Nesfatin-1); Group XII (15nmol/kg Obestatin) and Group XIII (5nmol/kg Neuropeptide Y). Gastric neuropeptide expression was measured using an immunohistochemical method, and the amount in circulation was detected using ELISA. To compare with no treatment, the controls and other treatment groups, we recorded loss of the surface epithelium of the stomach, erosion, bleeding and inflammatory cell infiltration in the upper halves of the gastric glands. The muscularis and the layers beneath it were, however, apparently normal. The gastric mucosa healed with little or no inflammation when sildenafil citrate, low dose heparin, ghrelin, NUCB2/Nesfatin-1, obestatin, Neuropeptide Y were administered. Overall the data indicate that low dose heparin, and especially sildenafil citrate and neuropeptides, can be used clinically as an alternative approach in the treatment of the gastric ulcer. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Enantioselective disposition of omeprazole, pantoprazole, and lansoprazole in a same Brazilian subjects group.

    Science.gov (United States)

    Cassiano, Neila M; Oliveira, Regina V; Bernasconi, Gilberto C R; Cass, Quezia B

    2012-04-01

    This work reports the result of the enantioselective disposition of pantoprazole, omeprazole, and lansoprazole in a same group of Brazilian health subjects. Ten nongenotyped healthy subjects were used for this study. Each subject received a single oral dose of 80 mg of pantoprazole, 40 mg of omeprazole, and 30 mg of lansoprazole, and the plasma concentrations of the enantiomers were measured for 8 h postdose. For pantoprazole and omeprazole, among the 10 volunteers investigated, only one volunteer (Subject # 4) presented higher plasma concentrations of the (+)-enantiomer than those of (-)-enantiomer. Nevertheless, the area under the concentration-time curve of the (+)-lansoprazole was higher than those the (-)-lansoprazole for all subjects. The comparison of proton pump inhibitors' enantiomers disposition from a single group volunteer demonstrated that pantoprazole and omeprazole can be used to differentiate extensive from poor CYP2C19 metabolizer while lansoprazole cannot do it. Copyright © 2011 Wiley Periodicals, Inc.

  2. Gastric cancer

    International Nuclear Information System (INIS)

    Douglass, H.O.

    1988-01-01

    This book contains 10 selections. Some of the titles are: Radiation therapy for gastric cancer; Experimental stomach cancer: Drug selection based on in vitro testing; Western surgical adjuvant trials in gastric cancers: Lessons from current trials to be applied in the future; and Chemotherapy of gastric cancer

  3. Gastric dysregulation induced by microinjection of 6-OHDA in the substantia nigra pars compacta of rats is determined by alterations in the brain-gut axis.

    Science.gov (United States)

    Toti, Luca; Travagli, R Alberto

    2014-11-15

    Idiopathic Parkinson's disease (PD) is a late-onset, chronic, and progressive motor dysfunction attributable to loss of nigrostriatal dopamine neurons. Patients with PD experience significant gastrointestinal (GI) issues, including gastroparesis. We aimed to evaluate whether 6-hydroxy-dopamine (6-OHDA)-induced degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) induces gastric dysmotility via dysfunctions of the brain-gut axis. 6-OHDA microinjection into the SNpc induced a >90% decrease in tyrosine hydroxylase-immunoreactivity (IR) on the injection site. The [13C]-octanoic acid breath test showed a delayed gastric emptying 4 wk after the 6-OHDA treatment. In control rats, microinjection of the indirect sympathomimetic, tyramine, in the dorsal vagal complex (DVC) decreased gastric tone and motility; this inhibition was prevented by the fourth ventricular application of either a combination of α1- and α2- or a combination of D1 and D2 receptor antagonists. Conversely, in 6-OHDA-treated rats, whereas DVC microinjection of tyramine had reduced effects on gastric tone or motility, DVC microinjection of thyrotropin-releasing hormone induced a similar increase in motility as in control rats. In 6-OHDA-treated rats, there was a decreased expression of choline acetyl transferase (ChAT)-IR and neuronal nitric oxide synthase (NOS)-IR in DVC neurons but an increase in dopamine-β-hydroxylase-IR in the A2 area. Within the myenteric plexus of the esophagus, stomach, and duodenum, there were no changes in the total number of neurons; however, the percentage of NOS-IR neurons increased, whereas that of ChAT-IR decreased. Our data suggest that the delayed gastric emptying in a 6-OHDA rat model of PD may be caused by neurochemical and neurophysiological alterations in the brain-gut axis. Copyright © 2014 the American Physiological Society.

  4. Impact of Gastric Acid Induced Surface Changes on Mechanical Behavior and Optical Characteristics of Dental Ceramics.

    Science.gov (United States)

    Kulkarni, Aditi; Rothrock, James; Thompson, Jeffery

    2018-01-14

    To test the impact of exposure to artificial gastric acid combined with toothbrush abrasion on the properties of dental ceramics. Earlier research has indicated that immersion in artificial gastric acid has caused increased surface roughness of dental ceramics; however, the combined effects of acid immersion and toothbrush abrasion and the impact of increased surface roughness on mechanical strength and optical properties have not been studied. Three commercially available ceramics were chosen for this study: feldspathic porcelain, lithium disilicate glass-ceramic, and monolithic zirconium oxide. The specimens (10 × 1 mm discs) were cut, thermally treated as required, and polished. Each material was divided into four groups (n = 8 per group): control (no exposure), acid only, brush only, acid + brush. The specimens were immersed in artificial gastric acid (50 ml of 0.2% [w/v] sodium chloride in 0.7% [v/v] hydrochloric acid mixed with 0.16 g of pepsin powder, pH = 2) for 2 minutes and rinsed with deionized water for 2 minutes. The procedure was repeated 6 times/day × 9 days, and specimens were stored in deionized water at 37°C. Toothbrush abrasion was performed using an ISO/ADA design brushing machine for 100 cycles/day × 9 days. The acid + brush group received both treatments. Specimens were examined under SEM and an optical microscope for morphological changes. Color and translucency were measured using spectrophotometer CIELAB coordinates (L*, a*, b*). Surface gloss was measured using a gloss meter. Surface roughness was measured using a stylus profilometer. Biaxial flexural strength was measured using a mechanical testing machine. The data were analyzed by one-way ANOVA followed by Tukey's HSD post hoc test (p gloss, and surface roughness for porcelain and e.max specimens. No statistically significant changes were found for any properties of zirconia specimens. The acid treatment affected the surface roughness, color, and gloss of porcelain and e

  5. Jaspine B induces nonapoptotic cell death in gastric cancer cells independently of its inhibition of ceramide synthase.

    Science.gov (United States)

    Cingolani, Francesca; Simbari, Fabio; Abad, Jose Luis; Casasampere, Mireia; Fabrias, Gemma; Futerman, Anthony H; Casas, Josefina

    2017-08-01

    Sphingolipids (SLs) have been extensively investigated in biomedical research due to their role as bioactive molecules in cells. Here, we describe the effect of a SL analog, jaspine B (JB), a cyclic anhydrophytosphingosine found in marine sponges, on the gastric cancer cell line, HGC-27. JB induced alterations in the sphingolipidome, mainly the accumulation of dihydrosphingosine, sphingosine, and their phosphorylated forms due to inhibition of ceramide synthases. Moreover, JB provoked atypical cell death in HGC-27 cells, characterized by the formation of cytoplasmic vacuoles in a time and dose-dependent manner. Vacuoles appeared to originate from macropinocytosis and triggered cytoplasmic disruption. The pan-caspase inhibitor, z-VAD, did not alter either cytotoxicity or vacuole formation, suggesting that JB activates a caspase-independent cell death mechanism. The autophagy inhibitor, wortmannin, did not decrease JB-stimulated LC3-II accumulation. In addition, cell vacuolation induced by JB was characterized by single-membrane vacuoles, which are different from double-membrane autophagosomes. These findings suggest that JB-induced cell vacuolation is not related to autophagy and it is also independent of its action on SL metabolism. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  6. ADMINISTRATION OF H2 BLOCKERS IN NSAID INDUCED GASTROPATHY IN RATS: effect on histopathological changes in gastric, hepatic and renal tissues

    Directory of Open Access Journals (Sweden)

    Sachin MANOCHA

    Full Text Available ABSTRACT Background Nonsteroidal anti-inflammatory drugs induces gastric mucosal lesions because of its acidic properties. Ranitidine, an H2 receptor antagonist, has proved beneficial in patients with gastric ulcers. Objective The present study was performed to assess the effect of administering ranitidine in Nonsteroidal anti-inflammatory drugs (diclofenac, nimesulide induced gastropathy, and their effect on the histopathology of stomach, kidney and liver. Methods Diclofenac, nimesulide, and ranitidine were administered in doses of 2, 4, and 6 mg/kg, p.o. once daily for 14 days, and their effect on gastric volume, acidity, mean ulcer number, and gastric pH. In addition, histopathological examination was also performed on sections of stomach, kidney and liver. Results Following the administration of diclofenac or nimesulide, all the gastric parameters were significantly altered as well as the histopathology of stomach, liver and kidney. In the control group, the renal sections showed normal glomeruli with no thickening of glomerular basement membrane, while in diclofenac alone, nimesulide alone, and ranitidine with nimesulide groups, the thickening of glomerular basement membrane was observed. These alterations were observed to be reversed in the ranitidine with diclofenac group. In the sections from the liver, the control group showed anastomosing plates and cords of cuboidal hepatocytes with round well stained nuclei and abundant cytoplasm. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, mild dilatation of sinusoids is seen coupled with prominence of central vein. In the diclofenac alone and nimesulide alone groups, the proximal and distal convoluted tubules show mild focal tubular necrosis. In the gastric sections, the control group showed several folds forming villi, and the epithelial lining surface of the mucosa. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, the duodenum showed

  7. ADMINISTRATION OF H2 BLOCKERS IN NSAID INDUCED GASTROPATHY IN RATS: effect on histopathological changes in gastric, hepatic and renal tissues.

    Science.gov (United States)

    Manocha, Sachin; Lal, Dushyant; Venkataraman, Subramanian

    2016-01-01

    Nonsteroidal anti-inflammatory drugs induces gastric mucosal lesions because of its acidic properties. Ranitidine, an H2 receptor antagonist, has proved beneficial in patients with gastric ulcers. The present study was performed to assess the effect of administering ranitidine in Nonsteroidal anti-inflammatory drugs (diclofenac, nimesulide) induced gastropathy, and their effect on the histopathology of stomach, kidney and liver. Diclofenac, nimesulide, and ranitidine were administered in doses of 2, 4, and 6 mg/kg, p.o. once daily for 14 days, and their effect on gastric volume, acidity, mean ulcer number, and gastric pH. In addition, histopathological examination was also performed on sections of stomach, kidney and liver. Following the administration of diclofenac or nimesulide, all the gastric parameters were significantly altered as well as the histopathology of stomach, liver and kidney. In the control group, the renal sections showed normal glomeruli with no thickening of glomerular basement membrane, while in diclofenac alone, nimesulide alone, and ranitidine with nimesulide groups, the thickening of glomerular basement membrane was observed. These alterations were observed to be reversed in the ranitidine with diclofenac group. In the sections from the liver, the control group showed anastomosing plates and cords of cuboidal hepatocytes with round well stained nuclei and abundant cytoplasm. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, mild dilatation of sinusoids is seen coupled with prominence of central vein. In the diclofenac alone and nimesulide alone groups, the proximal and distal convoluted tubules show mild focal tubular necrosis. In the gastric sections, the control group showed several folds forming villi, and the epithelial lining surface of the mucosa. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, the duodenum showed scattered inflammatory cells composed predominantly of lymphocytes. In

  8. Mastication suppresses initial gastric emptying by modulating gastric activity.

    Science.gov (United States)

    Ohmure, H; Takada, H; Nagayama, K; Sakiyama, T; Tsubouchi, H; Miyawaki, S

    2012-03-01

    Because various mastication-related factors influence gastric activity, the functional relationship between mastication and gastric function has not been fully elucidated. To investigate the influence of mastication on gastric emptying and motility, we conducted a randomized trial to compare the effects of mastication on gastric emptying and gastric myoelectrical activity under conditions that excluded the influences of food comminution, taste, and olfaction. A (13)C-acetate breath test with electrogastrography and electrocardiography was performed in 14 healthy men who ingested a test meal with or without chewing gum. Autonomic nerve activity was evaluated by fluctuation analysis of heart rate. Gastric emptying was significantly delayed in the 'ingestion with mastication' group. Gastric myoelectrical activity was significantly suppressed during mastication and increased gradually in the post-mastication phase. A decrease in the high-frequency power of heart rate variability was observed coincidentally with gastric myoelectrical activity suppression. These findings suggest that initial gastric emptying is suppressed by mastication, and that the suppression is caused by mastication-induced inhibition of gastric activity (UMIN Clinical Trial Registration no. UMIN000005351).

  9. Andrographolide induces apoptotic and non-apoptotic death and enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in gastric cancer cells.

    Science.gov (United States)

    Lim, Sung-Chul; Jeon, Ho Jong; Kee, Keun Hong; Lee, Mi Ja; Hong, Ran; Han, Song Iy

    2017-05-01

    Andrographolide, a natural compound isolated from Andrographis paniculata , has been reported to possess antitumor activity. In the present study, the effect of andrographolide in human gastric cancer (GC) cells was investigated. Andrographolide induced cell death with apoptotic and non-apoptotic features. At a low concentration, andrographolide potentiated apoptosis and reduction of clonogenicity triggered by recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL). Exposure of GC cells to andrographolide altered the expression level of several growth-inhibiting and apoptosis-regulating proteins, including death receptors. It was demonstrated that activity of the TRAIL-R2 (DR5) pathway was critical in the development of andrographolide-mediated rhTRAIL sensitization, since its inhibition significantly reduced the extent of apoptosis induced by the combination of rhTRAIL and andrographolide. In addition, andrographolide increased reactive oxygen species (ROS) generation in a dose-dependent manner. N-acetyl cysteine prevented andrographolide-mediated DR5 induction and the apoptotic effect induced by the combination of rhTRAIL and andrographolide. Collectively, the present study demonstrated that andrographolide enhances TRAIL-induced apoptosis through induction of DR5 expression. This effect appears to involve ROS generation in GCs.

  10. Peritoneal milky spots serve as a hypoxic niche and favor gastric cancer stem/progenitor cell peritoneal dissemination through hypoxia-inducible factor 1α.

    Science.gov (United States)

    Miao, Zhi-Feng; Wang, Zhen-Ning; Zhao, Ting-Ting; Xu, Ying-Ying; Gao, Jian; Miao, Feng; Xu, Hui-Mian

    2014-12-01

    Peritoneal dissemination is the most common cause of death in gastric cancer patients. The hypoxic microenvironment plays a major role in controlling the tumor stem cell phenotype and is associated with patients' prognosis through hypoxia-inducible factor-1α (HIF-1α), a key transcriptional factor that responds to hypoxic stimuli. During the peritoneal dissemination process, gastric cancer stem/progenitor cells (GCSPCs) are thought to enter into and maintained in peritoneal milky spots (PMSs), which have hypoxic microenvironments. However, the mechanism through which the hypoxic environment of PMSs regulated GCSPC maintenance is still poorly understood. Here, we investigated whether hypoxic PMSs were an ideal cancer stem cell niche suitable for GCSPC engraftment. We also evaluated the mechanisms through which the HIF-1α-mediated hypoxic microenvironment regulated GCSPC fate. We observed a positive correlation between HIF-1α expression and gastric cancer peritoneal dissemination (GCPD) in gastric cancer patients. Furthermore, the GCSPC population expanded in primary gastric cancer cells under hypoxic condition in vitro, and hypoxic GCSPCs showed enhanced self-renewal ability, but reduced differentiation capacity, mediated by HIF-1α. In an animal model, GCSPCs preferentially resided in the hypoxic zone of PMSs; moreover, when the hypoxic microenvironment in PMSs was destroyed, GCPD was significantly alleviated. In conclusion, our results demonstrated that PMSs served as a hypoxic niche and favored GCSPCs peritoneal dissemination through HIF-1α both in vitro and in vivo. These results provided new insights into the GCPD process and may lead to advancements in the clinical treatment of gastric cancer. © 2014 The Authors. STEM CELLS Published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  11. Lansoprazole prevents experimental gastric injury induced by non-steroidal anti-inflammatory drugs through a reduction of mucosal oxidative damage

    Science.gov (United States)

    Blandizzi, Corrado; Fornai, Matteo; Colucci, Rocchina; Natale, Gianfranco; Lubrano, Valter; Vassalle, Cristina; Antonioli, Luca; Lazzeri, Gloria; Tacca, Mario Del

    2005-01-01

    AIM: This study investigated the mechanisms of protection afforded by the proton pump inhibitor lansoprazole against gastric injury induced by different non-steroidal anti-inflammatory drugs (NSAIDs) in rats. METHODS: Male Sprague-Dawley rats were orally treated with indomethacin (100 µmol/kg), diclofenac (60 µmol/kg), piroxicam (150 µmol/kg) or ketoprofen (150 µmol/kg). Thirty minutes before NSAIDs, animals were orally treated with lansoprazole 18 or 90 µmol/kg. Four hours after the end of treatments, the following parameters were assessed: gastric mucosal PGE2, malondialdehyde (MDA), myeloperoxidase (MPO) or non-proteic sulfhydryl compounds (GSH) levels; reverse transcription-polymerase chain reaction (RT-PCR) of mucosal COX-2 mRNA; gastric acid secretion in pylorus-ligated animals; in vitro effects of lansoprazole (1-300 µmol/L) on the oxidation of low density lipoproteins (LDLs) induced by copper sulphate. RESULTS: All NSAIDs elicited mucosal necrotic lesions which were associated with neutrophil infiltration and reduction of PGE2 levels. Increments of MPO and MDA contents, as well as a decrease in GSH levels were detected in the gastric mucosa of indomethacin- or piroxicam-treated animals. Indomethacin enhanced mucosal cyclooxygenase-2 expression, while not affecting cyclooxygenase-1. At the oral dose of 18 µmol/kg lansoprazole partly counteracted diclofenac-induced mucosal damage, whereas at 90 µmol/kg it markedly prevented injuries evoked by all test NSAIDs. Lansoprazole at 90 µmol/kg reversed also the effects of NSAIDs on MPO, MDA and GSH mucosal contents, without interfering with the decrease in PGE2 levels or indomethacin-induced cyclooxygenase-2 expression. However, both lansoprazole doses markedly inhibited acid secretion in pylorus-ligated rats. Lansoprazole concentration-dependently reduced the oxidation of LDLs in vitro. CONCLUSION: These results suggest that, besides the inhibition of acid secretion, lansoprazole protection against NSAID-induced

  12. Menadione induces G2/M arrest in gastric cancer cells by down-regulation of CDC25C and proteasome mediated degradation of CDK1 and cyclin B1

    OpenAIRE

    Lee, Min Ho; Cho, Yoonjung; Kim, Do Hyun; Woo, Hyun Jun; Yang, Ji Yeong; Kwon, Hye Jin; Yeon, Min Ji; Park, Min; Kim, Sa-Hyun; Moon, Cheol; Tharmalingam, Nagendran; Kim, Tae Ue; Kim, Jong-Bae

    2016-01-01

    Menadione (vitamin K3) has been reported to induce apoptotic cell death and growth inhibition in various types of cancer cells. However, involvement of menadione in cell cycle control has not been considered in gastric cancer cells yet. In the current study, we have investigated whether menadione is involved in the cell cycle regulation and suppression of growth in gastric cancer cells. In the cell cycle analysis, we found that menadione induced G2/M cell cycle arrest in AGS cells. To elucida...

  13. A comparison of oral omeprazole and intravenous cimetidine in reducing complications of duodenal peptic ulcer

    Directory of Open Access Journals (Sweden)

    Khaleghian Farzaneh

    2006-01-01

    Full Text Available Abstract Background Gastrointestinal bleeding is a common problem and its most common etiology is peptic ulcer disease. Ulcer rebleeding is considered a perilous complication for patients. To reduce the rate of rebleeding and to fasten the improvement of patients' general conditions, most emergency departments in Iran use H2-blockers before endoscopic procedures (i.e. intravenous omeprazole is not available in Iran. The aim of this study was to compare therapeutic effects of oral omeprazole and intravenous cimetidine on reducing rebleeding rates, duration of hospitalization, and the need for blood transfusion in duodenal ulcer patients. Methods In this clinical trial, 80 patients with upper gastrointestinal bleeding due to duodenal peptic ulcer and endoscopic evidence of rebleeding referring to emergency departments of Imam and Sina hospitals in Tabriz, Iran were randomly assigned to two equal groups; one was treated with intravenous cimetidine 800 mg per day and the other, with 40 mg oral omeprazole per day. Results No statistically significant difference was found between cimetidine and omeprazole groups in regards to sex, age, alcohol consumption, cigarette smoking, NSAID consumption, endoscopic evidence of rebleeding, mean hemoglobin and mean BUN levels on admission, duration of hospitalization and the mean time of rebleeding. However, the need for blood transfusion was much lower in omeprazole than in cimetidine group (mean: 1.68 versus 3.58 units, respectively; p Conclusion This study demonstrated that oral omeprazole significantly excels intravenous cimetidine in reducing the need for blood transfusion and lowering rebleeding rates in patients with upper gastrointestinal bleeding. Though not statistically significant (p = 0.074, shorter periods of hospitalization were found for omeprazole group which merits consideration for cost minimization.

  14. Role of lipoxygenases and the lipoxin A(4)/annexin 1 receptor in ischemia-reperfusion-induced gastric mucosal damage in rats.

    Science.gov (United States)

    Peskar, Brigitta M; Ehrlich, Karlheinz; Schuligoi, Rufina; Peskar, Bernhard A

    2009-01-01

    Rat gastric mucosal damage was induced by ischemia-reperfusion. The 5-lipoxygenase inhibitors MK886 and A63162, the 12-lipoxygenase inhibitor baicalein, the 15-lipoxygenase inhibitor PD146176 and the lipoxin (LX) A(4)/annexin 1 antagonist Boc1 increased mucosal damage in a dose-dependent manner. Low doses of these compounds, which have no effects on mucosal integrity, cause severe damage when combined with low doses of indomethacin, celecoxib or dexamethasone. 16,16-Dimethylprostaglandin (PG) E(2) and LXA(4) can replace each other in preventing mucosal injury induced by either cyclooxygenase or lipoxygenase inhibitors. The results suggest that not only cyclooxygenases, but also lipoxygenases have a role in limiting gastric mucosal damage during ischemia-reperfusion. Copyright 2009 S. Karger AG, Basel.

  15. Recurrent Fusion Genes in Gastric Cancer: CLDN18-ARHGAP26 Induces Loss of Epithelial Integrity

    Directory of Open Access Journals (Sweden)

    Fei Yao

    2015-07-01

    Full Text Available Genome rearrangements, a hallmark of cancer, can result in gene fusions with oncogenic properties. Using DNA paired-end-tag (DNA-PET whole-genome sequencing, we analyzed 15 gastric cancers (GCs from Southeast Asians. Rearrangements were enriched in open chromatin and shaped by chromatin structure. We identified seven rearrangement hot spots and 136 gene fusions. In three out of 100 GC cases, we found recurrent fusions between CLDN18, a tight junction gene, and ARHGAP26, a gene encoding a RHOA inhibitor. Epithelial cell lines expressing CLDN18-ARHGAP26 displayed a dramatic loss of epithelial phenotype and long protrusions indicative of epithelial-mesenchymal transition (EMT. Fusion-positive cell lines showed impaired barrier properties, reduced cell-cell and cell-extracellular matrix adhesion, retarded wound healing, and inhibition of RHOA. Gain of invasion was seen in cancer cell lines expressing the fusion. Thus, CLDN18-ARHGAP26 mediates epithelial disintegration, possibly leading to stomach H+ leakage, and the fusion might contribute to invasiveness once a cell is transformed.

  16. Gastric pseudolymphoma

    International Nuclear Information System (INIS)

    Blum, U.; Hellerich, U.; Bodendoerfer, G.; Wimmer, B.; Ruf, G.; Freiburg Univ.; Freiburg Univ.

    1989-01-01

    Gastric pseudolymphoma is an uncommon benign lesion which poses a difficult problem in diagnosis and management. Lymphoid hyperplasia of the stomach, however, may occasionally precede true gastric lymphoma. Endoscopic, radiologic and pathological findings are not generally helpful in establishing the diagnosis preoperatively. Benign gastric lymphoid hyperplasia could be mistaken radiologically for ulcerated gastric carcinoma and pathologically for malignant lymphoma. Recognition of this condition is important to prevent unnecessary treatment by surgery or radiotherapy. About 140 case reports have been published to date. This paper describes the cases of two further patients. (orig.) [de

  17. Sinularin Induces Apoptosis through Mitochondria Dysfunction and Inactivation of the pI3K/Akt/mTOR Pathway in Gastric Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Yu-Jen Wu

    2016-07-01

    Full Text Available Sinularin is an active compound isolated from the cultured soft coral Sinularia flexibilis. In this study, we investigated the effects of sinularin on two human gastric cancer cell lines, AGS and NCI-N87. Our results demonstrated that sinularin suppressed the proliferation of gastric cancer cells in a dose-dependent manner and induced apoptosis. In addition, the loss of mitochondrial membrane potential, the release of cytochrome C, the activation of Bax, Bad and caspase-3/9, and the suppression of p-Bad, Bcl-xL and Bcl-2 were observed in the cells treated with sinularin. This finding suggests that sinularin-induced apoptosis is associated with mitochondria-mediated apoptosis and occurs through caspase-dependent pathways. Furthermore, sinularin inhibited the phosphoinositol 3-kinase/Akt/mechanistic target of the rapamycin signaling pathway. Taken together, our results show that sinularin-induced apoptosis is mediated by activation of the caspase cascade and mitochondrial dysfunction. Our findings suggest that sinularin merits further evaluation as a chemotherapeutic agent for human gastric cancer.

  18. Preventive effects of lansoprazole and famotidine on gastric mucosal injury induced by low-dose aspirin in Helicobacter pylori-negative healthy volunteers.

    Science.gov (United States)

    Nishino, Masafumi; Sugimoto, Mitsushige; Kodaira, Chise; Yamade, Mihoko; Uotani, Takahiro; Shirai, Naohito; Ikuma, Mutsuhiro; Tanaka, Tatsuo; Sugimura, Haruhiko; Hishida, Akira; Furuta, Takahisa

    2011-07-01

    The preventive effects of lansoprazole and famotidine on low-dose aspirin-induced gastric mucosal injury in relation to gastric acidity were compared in healthy Japanese volunteers. Fifteen Helicobacter pylori-negative volunteers with different CYP2C19 genotypes were randomly administered aspirin 100 mg, aspirin plus famotidine 20 mg twice daily, or aspirin plus lansoprazole 15 mg once daily for 7 days each in a crossover fashion. Gastroscopy for the evaluation of mucosal injury based on modified Lanza score (MLS) and 24-hour intragastric pH monitoring were performed on day 7 of each regimen. Aspirin induced gastric mucosal injury (median MLS = 3). Lansoprazole significantly decreased MLS to 0, which was significantly lower than that by famotidine (MLS = 1) (P lansoprazole regimen were significantly higher than those with famotidine (P lansoprazole appeared to be more protective than famotidine against low-dose aspirin-induced mucosal injury but a larger well-controlled study is necessary to establish a definitive clinical benefit.

  19. Preventive effect of Oenothera rosea on N-methyl-N-nitrosourea-(NMU) induced gastric cancer in rats.

    Science.gov (United States)

    Almora-Pinedo, Yuan; Arroyo-Acevedo, Jorge; Herrera-Calderon, Oscar; Chumpitaz-Cerrate, Víctor; Hañari-Quispe, Renán; Tinco-Jayo, Aldo; Franco-Quino, Cesar; Figueroa-Salvador, Linder

    2017-01-01

    Currently, gastric cancer (GC) is considered a public health problem worldwide. Using medicinal plants for the prevention of chronic diseases such as cancer constitutes new alternatives in traditional medicine. Oenothera rosea (OR) could be an option, but it needs to be evaluated. The main objective of this study was to evaluate the protective effect of OR extract on N-methyl-N-nitrosourea (NMU)-induced GC in rats. In total, 80 male Holtzman rats were randomized into five groups. Group A received the saline solution (5mL/kg), group B received NMU 500 μg/kg (cancer inductor) by oral administration for 16 weeks, and groups C, D, and E were treated with OR extract (100, 200, and 300 mg/kg, respectively) and NMU in order to evaluate the preventive effect on cancer induced by NMU for 16 weeks. Blood and histological samples of stomachs were collected to determine histopathological, biochemical, and hematological parameters between different experimental groups. Groups C, D, and E presented less histopathological changes such as anaplastic and hyperplastic cells, compared with group B. Hematological and biochemical parameters were recorded, and superoxide dismutase, malondialdehyde, and nitric oxide levels were statistically less than those of NMU group ( P <0.05, P <0.01, and P <0.01). Considering the histopathological signs and the antioxidant activity in vivo as well as hematological and biochemical parameters of ethanolic extract of OR, we concluded that its administration in rats has a protective effect on GC, which is induced experimentally. This species could be studied in clinical trials for patients with GC in the future.

  20. Gene polymorphisms of micrornas in Helicobacter pylori-induced high risk atrophic gastritis and gastric cancer.

    Directory of Open Access Journals (Sweden)

    Juozas Kupcinskas

    Full Text Available BACKGROUND AND AIMS: MicroRNAs (miRNAs are known for their function as translational regulators of tumor suppressor or oncogenes. Single nucleotide polymorphisms (SNPs in miRNAs related genes have been shown to affect the regulatory capacity of miRNAs and were linked with gastric cancer (GC and premalignant gastric conditions. The purpose of this study was to evaluate potential associations between miRNA-related gene polymorphisms (miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608 and the presence of GC or high risk atrophic gastritis (HRAG in European population. METHODS: Gene polymorphisms were analyzed in 995 subjects (controls: n = 351; GC: n = 363; HRAG: n = 281 of European descent. MiR-27a T>C (rs895819, miR-146a G>C (rs2910164, miR-196a-2 C>T (rs11614913, miR-492 G>C (rs2289030 and miR-608 C>G (rs4919510 SNPs were genotyped by RT-PCR. RESULTS: Overall, SNPs of miRNAs were not associated with the presence of GC or HRAG. We observed a tendency for miR-196a-2 CT genotype to be associated with higher risk of GC when compared to CC genotype, however, the difference did not reach the adjusted P-value (odds ratio (OR - 1.46, 95% confidence interval (CI 1.03-2.07, P = 0.032. MiR-608 GG genotype was more frequent in GC when compared to controls (OR -2.34, 95% CI 1.08-5.04, but significance remained marginal (P = 0.029. A similar tendency was observed in a recessive model for miR-608, where CC + CG vs GG genotype comparison showed a tendency for increased risk of GC with OR of 2.44 (95% CI 1.14-5.22, P = 0.021. The genotypes and alleles of miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608 SNPs had similar distribution between histological subtypes of GC and were not linked with the presence of diffuse or intestinal-type GC. CONCLUSIONS: Gene polymorphisms of miR-27a, miR-146a, miR-196a-2, miR-492, miR-492a and miR-608 were not associated with the presence of HRAG, GC or different histological subtypes of GC in European

  1. Tob1 induces apoptosis and inhibits proliferation, migration and invasion of gastric cancer cells by activating Smad4 and inhibiting β‑catenin signaling.

    Science.gov (United States)

    Kundu, Juthika; Wahab, S M Riajul; Kundu, Joydeb Kumar; Choi, Yoon-La; Erkin, Ozgur Cem; Lee, Hun Seok; Park, Sang Gyu; Shin, Young Kee

    2012-09-01

    Transducer of ErbB-2.1 (Tob1), a tumor suppressor protein, is inactivated in a variety of cancers including stomach cancer. However, the role of Tob1 in gastric carcinogenesis remains elusive. The present study aimed to investigate whether Tob1 could inhibit gastric cancer progression in vitro, and to elucidate its underlying molecular mechanisms. We found differential expression of Tob1 in human gastric cancer (MKN28, AGS and MKN1) cells. The overexpression of Tob1 induced apoptosis in MKN28 and AGS cells, which was associated with sub-G1 arrest, activation of caspase-3, induction of Bax, inhibition of Bcl-2 and cleavage of poly (ADP-ribose) polymerase (PARP). In addition, Tob1 inhibited proliferation, migration and invasion, which were reversed in MKN1 and AGS cells transfected with Tob1 siRNA. Overexpression of Tob1 in MKN28 and AGS cells induced the expression of Smad4, leading to the increased expression and the promoter activity of p15, which was diminished by silencing of Tob1 using specific siRNA. Tob1 decreased the phosphorylation of Akt and glycogen synthase kinase-3β (GSK3β) in MKN28 and AGS cells, resulting in the reduced protein expression and the transcriptional activity of β‑catenin, which in turn decreased the expression of cyclin D1, cyclin-dependent kinase-4 (CDK4), urokinase plasminogen activator receptor (uPAR) and peroxisome proliferator and activator receptor-δ (PPARδ). Conversely, silencing of Tob1 induced the phosphorylation of Akt and GSK-3β, and increased the expression of β‑catenin and its target genes. Collectively, our study demonstrates that the overexpression of Tob1 inhibits gastric cancer progression by activating Smad4- and inhibiting β‑catenin-mediated signaling pathways.

  2. Chrysin inhibits tumor promoter-induced MMP-9 expression by blocking AP-1 via suppression of ERK and JNK pathways in gastric cancer cells.

    Directory of Open Access Journals (Sweden)

    Yong Xia

    Full Text Available Cell invasion is a crucial mechanism of cancer metastasis and malignancy. Matrix metalloproteinase-9 (MMP-9 is an important proteolytic enzyme involved in the cancer cell invasion process. High expression levels of MMP-9 in gastric cancer positively correlate with tumor aggressiveness and have a significant negative correlation with patients' survival times. Recently, mechanisms suppressing MMP-9 by phytochemicals have become increasingly investigated. Chrysin, a naturally occurring chemical in plants, has been reported to suppress tumor metastasis. However, the effects of chrysin on MMP-9 expression in gastric cancer have not been well studied. In the present study, we tested the effects of chrysin on MMP-9 expression in gastric cancer cells, and determined its underlying mechanism. We examined the effects of chrysin on MMP-9 expression and activity via RT-PCR, zymography, promoter study, and western blotting in human gastric cancer AGS cells. Chrysin inhibited phorbol-12-myristate 13-acetate (PMA-induced MMP-9 expression in a dose-dependent manner. Using AP-1 decoy oligodeoxynucleotides, we confirmed that AP-1 was the crucial transcriptional factor for MMP-9 expression. Chrysin blocked AP-1 via suppression of the phosphorylation of c-Jun and c-Fos through blocking the JNK1/2 and ERK1/2 pathways. Furthermore, AGS cells pretreated with PMA showed markedly enhanced invasiveness, which was partially abrogated by chrysin and MMP-9 antibody. Our results suggest that chrysin may exert at least part of its anticancer effect by controlling MMP-9 expression through suppression of AP-1 activity via a block of the JNK1/2 and ERK1/2 signaling pathways in gastric cancer AGS cells.

  3. New chromatographic method for separating Omeprazole from its degradation components and the quantitatively determining it in its pharmaceutical products

    International Nuclear Information System (INIS)

    Touma, M.; Rajab, A.; Seuleiman, M.

    2007-01-01

    New chromatographic method for Quantitative Determination of Omeprazole in its Pharmaceutical Products was produced. Omeprazole and its degradation components were well separated in same chromatogram by using high perfume liquid chromatography (HPLC). The new analytical method has been validated by these characteristic tests (accuracy, precision, range, linearity, specificity/selectivity, limit of detection (LOD) and limit of quantitative (LOQ) ).(author)

  4. Gastric cancer

    International Nuclear Information System (INIS)

    Salek, T.

    2007-01-01

    Gastric cancer is still a major health problem and a leading cause of cancer mortality despite a worldwide decline in incidence. Primarily due to early detection of the disease, the results of treatment for gastric cancer have improved in Japan, Korea and several specialized Western centres. Surgery offers excellent long-term survival results for early gastric cancer (EGC). In the Western world, however more than 80 % of patients at diagnosis have an advanced gastric cancer with a poor prognosis. The aim of surgery is the complete removal of the tumour (UICC R0-resection), which is known to be the only proven, effective treatment modality and the most important treatmentrelated prognostic factor. The prognosis after surgical treatment of gastric cancer remains poor. Neoadjuvant chemotherapy is a rising option in locally advanced gastric cancer. Adjuvant chemoradiation has been shown to be beneficial in gastric cancer patients who have undergone suboptimal surgical resection. The benefits of adjuvant chemotherapy alone seem to be very small, Untreated metastatic gastric cancer is associated with a median survival of only 3 - 4 months, but this can be increased to 8 - 10 months, associated with improved quality of life, with combination chemotherapy. Currently, no standard combination chemotherapy regimen exists, although regimens utilizing both cisplatin and 5-fluorouracil, such as epirubicin/cisplatin/fluorouracil (ECF) or docetaxel/cisplatin/fluorouracil (DCF) are amongst the most active. Newer chemotherapeutic agents, including irinotecan, oxaliplatin and taxanes, show promising activity, and are currently being tested with biologics in clinical trials. (author)

  5. Auranofin induces apoptosis by ROS-mediated ER stress and mitochondrial dysfunction and displayed synergistic lethality with piperlongumine in gastric cancer.

    Science.gov (United States)

    Zou, Peng; Chen, Minxiao; Ji, Jiansong; Chen, Weiqian; Chen, Xi; Ying, Shilong; Zhang, Junru; Zhang, Ziheng; Liu, Zhiguo; Yang, Shulin; Liang, Guang

    2015-11-03

    Gastric cancer (GC) is one of the leading causes of cancer mortality in the world. In addressing the need of treatments for relapsed disease, we report the identification of an existing U.S. Food and Drug Administration-approved small-molecule drug to repurpose for GC treatment. Auranofin (AF), clinically used to treat rheumatic arthritis, but it exhibited preclinical efficacy in GC cells. By increasing intracellular reactive oxygen species (ROS) levels, AF induces a lethal endoplasmic reticulum stress response and mitochondrial dysfunction in cultured GC cells. Blockage of ROS production reversed AF-induced ER stress and mitochondrial pathways activation as well as apoptosis. In addition, AF displays synergistic lethality with an ROS-generating agent piperlongumine, which is a natural product isolated from the long pepper Piper longum L. Taken together, this work provides a novel anticancer candidate for the treatment of gastric cancer. More importantly, it reveals that increased ROS generation might be an effective strategy in treating human gastric cancer.

  6. Veronicastrum axillare Alleviates Ethanol-Induced Injury on Gastric Epithelial Cells via Downregulation of the NF-kB Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Wei-chun Zhao

    2017-01-01

    Full Text Available We used human gastric epithelial cells (GES-1 line in an ethanol-induced cell damage model to study the protective effect of Veronicastrum axillare and its modulation to NF-κB signal pathway. The goal was to probe the molecular mechanism of V. axillare decoction in the prevention of gastric ulcer and therefore provide guidance in the clinical application of V. axillare on treating injuries from chronic nephritis, pleural effusion, gastric ulcer, and other ailments. The effects of V. axillare-loaded serums on cell viability were detected by MTT assays. Enzyme-linked immunosorbent assay (ELISA and Real-Time PCR methods were used to analyze the protein and mRNA expression of TNF-α, NF-κB, IκBα, and IKKβ. The results showed that V. axillare-loaded serum partially reversed the damaging effects of ethanol and NF-κB activator (phorbol-12-myristate-13-acetate: PMA and increased cell viability. The protein and mRNA expressions of TNF-α, NF-κB, IκBα, and IKKβ were significantly upregulated by ethanol and PMA while they were downregulated by V. axillare-loaded serum. In summary, V. axillare-loaded serum has significantly protective effect on GES-1 against ethanol-induced injury. The protective effect was likely linked to downregulation of TNF-α based NF-κB signal pathway.

  7. A unique polysaccharide purified from Hericium erinaceus mycelium prevents oxidative stress induced by H2O2 in human gastric mucosa epithelium cell.

    Science.gov (United States)

    Wang, Mingxing; Kanako, Nakajima; Zhang, Yanqiu; Xiao, Xulang; Gao, Qipin; Tetsuya, Konishi

    2017-01-01

    Hericium erinaceus (HE) has been used both as a traditional Chinese medicine and home remedy for treatment of gastric and duodenal ulcers and gastritis. EP-1, a purified polysaccharide isolated from HE mycelium, has recently been identified as the active component responsible for HE anti-gastritis activity. Because oxidative stress has been implicated as a pathogenic cause of gastritis and gastric ulcers, EP-1 antioxidant properties were systematically examined in vitro using the human gastric mucosal epithelial cell line, GES-1. Results showed that EP-1 possessed higher oxygen radical absorbance capacity (ORAC) and 2-3 times higher ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide and hydroxyl radicals than a hot water extract of commercially available HE fruiting body. A crude mycelial polysaccharide (CMPS) extract of HE, from which EP-1 was purified, showed slightly stronger radical scavenging activity and ORAC than EP-1, with the exception of DPPH-scavenging activity. Antioxidant activities of these extracts were further studied using hydrogen peroxide (H2O2)-abused GES-1 cells; EP-1 dose-dependently preserved cell viability of abused cells as assessed via MTT assay. Moreover, FACS analysis revealed that EP-1 prevented H2O2-induced apoptotic cell death by inhibiting activation of apoptotic cellular signals within mitochondria-dependent apoptotic pathways. CMPS also prevented H2O2-induced oxidative stress, but to a lesser degree than did EP-1, even though CMPS exhibited comparable or stronger in vitro antioxidant activity than did EP-1.

  8. Nizatidine and omeprazole enhance the effect of metronidazole on Helicobacter pylori in vitro

    DEFF Research Database (Denmark)

    Chen, Ming; Jensen, Bente; Zhai, Lin

    2002-01-01

    to reverse antibiotic resistance do not necessarily have an antibiotic or chemotherapeutic effect in the sense of growth inhibition. Therefore, it was decided to investigate the effect of nizatidine and omeprazole on the oxidative respiratory chain, as it is known that metronidazole is able to inhibit...... the activity of fumarate reductase of H. pylori. This enzyme is a key enzyme in the alternative respiratory chain under anaerobic conditions. Nizatidine was, in these preliminary experiments, found to inhibit fumarate reductase in a dose-dependent way, like metronidazole, whereas omeprazole had almost...... no effect on fumarate reductase. No other significant effects on the enzymes of the respiratory chain were found. The synergistic effect of nizatidine on metronidazole resistant H. pylori strains could be explained by the effect on fumarate reductase, whereas the effect of omeprazole is different and could...

  9. Effects of omeprazole in improving concurrent chemoradiotherapy efficacy in rectal cancer.

    Science.gov (United States)

    Zhang, Jin-Liang; Liu, Min; Yang, Qing; Lin, Shi-Yong; Shan, Hong-Bo; Wang, Hui-Yun; Xu, Guo-Liang

    2017-04-14

    To explore the effects of omeprazole on chemoradiotherapy efficacy and tumor recurrence in rectal cancer. The medical data of 125 rectal cancer patients who received the same neoadjuvant chemoradiotherapy (CRT) followed by surgery were retrospectively collected. Patients who received omeprazole (OME) orally at a dose of 20 mg at least once daily for six days and/or intravenously at 40 mg a day were recognized as eligible OME users (EOU). Otherwise, patients were regarded as non-eligible OME users (non-EOU). Moreover, a preferred OME dose cut-off of 200 mg on tumor recurrence was obtained by receiver operating characteristic (ROC) curves. Patients were divided into two groups: the effective OME group (EOG, OME ≥ 200 mg) and the non-effective OME group (non-EOG, OME cancer treatment for relieving common side effects of chemotherapy, omeprazole has a synergetic effect in improving CRT efficacy and decreasing rectal cancer recurrence.

  10. [Endoscopic diagnosis of local chemical burn of mucous membranes of the stomach, induced with the purpose of simulation of gastric ulcer].

    Science.gov (United States)

    Byzov, N V; Plekhanov, V N

    2013-01-01

    With the purpose of improvement of diagnosis of induced gastric ulcer were examined 11 patients who took aggressive agents for simulation of gastric ulcer and 33 patients who took pseudo-aggressive agents. Observables, conduced diagnosis of local chemical burn of mucous coat of stomach during initial 6 days after taking aggressive agents. Stages of ulcerous process, resulting from local chemical burn of mucous coat of stomach, coressponds to real gactric ulcer. Gelatin capsule using as a container for delivery of aggressive agents, melts in stomach in 5-6 minutes after taking. Independent from body position, mucous coat of greater curvature of the stomach is damaged. It is impossible to simulate duodenal bulb ulcer using the gelatine capsule or ball made of breadcrumb. The last method of delivery of aggressive agent can damage the small intestine because of uncontrollability of the place of breaking the ball.

  11. Effect and mechanism of evodiamine against ethanol-induced gastric ulcer in mice by suppressing Rho/NF-кB pathway.

    Science.gov (United States)

    Zhao, Zhongyan; Gong, Shilin; Wang, Shumin; Ma, Chunhua

    2015-09-01

    Evodiamine (EVD), a major alkaloid compound extracted from the dry unripened fruit Evodia fructus (Evodia rutaecarpa Benth., Rutaceae), has various pharmacological effects. The purpose of the present study was to investigate the possible anti-ulcerogenic potential of EVD and explore the underlying mechanism against ethanol-induced gastric ulcer in mice. Administration of EVD at the doses of 20, 40mg/kg body weight prior to the ethanol ingestion could effectively protect the stomach from ulceration. The gastric lesion was significantly ameliorated in the EVD group compared with that in the model group. Pre-treatment with EVD prevented the oxidative damage and decreased the levels of prostaglandin E2 (PGE2) content, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In addition, EVD pretreatment markedly increased the serum levels of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), decreased malonaldehyde (MDA) content in serum and activity of myeloperoxidase (MPO) in stomach tissues compared with those in the model group. In the mechanistic study, significant elevation of Rho, Rho-kinase 1 (ROCK1), ROCK2, cytosolic and nucleic NF-κBp65 expressions were observed in the gastric mucosa group, whereas EVD effectively suppressed the protein expressions of Rho, Rho-kinase 1 (ROCK1), ROCK2, cytosolic and nucleic NF-κBp65 in mice. Moreover, EVD showed protective activity on ethanol-induced GES-1 cells, while the therapeutic effects were not due to its cytotoxity. Taken together, these results strongly indicated that EVD exerted a gastro-protective effect against gastric ulceration. The underlying mechanism might be associated with the improvement of antioxidant and anti-inflammatory status through Rho/NF-κB pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Comparison of outcomes twelve years after antireflux surgery or omeprazole maintenance therapy for reflux esophagitis

    DEFF Research Database (Denmark)

    Lundell, Lars; Miettinen, Pekka; Myrvold, Helge E

    2009-01-01

    with esophagitis enrolled from outpatient clinics in Nordic countries. Of the 155 patients randomly assigned to each arm of the study, 154 received omeprazole (1 withdrew before therapy began), and 144 received surgery (11 withdrew before surgery). In patients who remained in remission after treatment, post....... Heartburn and regurgitation were significantly more common in patients given omeprazole, whereas dysphagia, rectal flatulence, and the inability to belch or vomit were significantly more common in surgical patients. The therapies were otherwise well-tolerated. CONCLUSIONS: As long-term therapeutic...

  13. Hypoxia induces cyclophilin B through the activation of transcription factor 6 in gastric adenocarcinoma cells

    OpenAIRE

    JEONG, KWON; KIM, KIYOON; KIM, HUNSUNG; OH, YOOJUNG; KIM, SEONG-JIN; JO, YUNHEE; CHOE, WONCHAE

    2015-01-01

    Hypoxia is an important form of physiological stress that induces cell death, due to the resulting endoplasmic reticulum (ER) stress, particularly in solid tumors. Although previous studies have indicated that cyclophilin B (CypB) plays a role in ER stress, there is currently no direct information supporting the mechanism of CypB involvement under hypoxic conditions. However, it has previously been demonstrated that ER stress positively regulates the expression of CypB. In the present study, ...

  14. Preventive effect of Oenothera rosea on N-methyl-N-nitrosourea- (NMU induced gastric cancer in rats

    Directory of Open Access Journals (Sweden)

    Almora-Pinedo Y

    2017-12-01

    Full Text Available Yuan Almora-Pinedo,1 Jorge Arroyo-Acevedo,2 Oscar Herrera-Calderon,3 Víctor Chumpitaz-Cerrate,4 Renán Hañari-Quispe,5 Aldo Tinco-Jayo,6 Cesar Franco-Quino,4 Linder Figueroa-Salvador7 1Department of Pharmacy, Hospital Nacional Hipólito Unanue, Lima, 2Laboratory of Experimental Pharmacology, Faculty of Medicine, Universidad Nacional Mayor de San Marcos, Lima, 3Faculty of Pharmacy and Biochemistry, Universidad Nacional San Luis Gonzaga de Ica, Ica, 4Laboratory of Physiology and Pharmacology, Faculty of Dentistry, Universidad Nacional Mayor de San Marcos, Lima, 5Laboratory of Animal Physiology, Universidad Andina Néstor Cáceres Velasquez, Puno, 6Academic Department of Human Medicine, School of Pharmacy and Biochemistry, Universidad Nacional San Cristóbal de Huamanga, Ayacucho, 7School of Medicine, Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru Background: Currently, gastric cancer (GC is considered a public health problem worldwide. Using medicinal plants for the prevention of chronic diseases such as cancer constitutes new alternatives in traditional medicine. Oenothera rosea (OR could be an option, but it needs to be evaluated. Aim: The main objective of this study was to evaluate the protective effect of OR extract on N-methyl-N-nitrosourea (NMU-induced GC in rats. Methods: In total, 80 male Holtzman rats were randomized into five groups. Group A received the saline solution (5mL/kg, group B received NMU 500 μg/kg (cancer inductor by oral administration for 16 weeks, and groups C, D, and E were treated with OR extract (100, 200, and 300 mg/kg, respectively and NMU in order to evaluate the preventive effect on cancer induced by NMU for 16 weeks. Blood and histological samples of stomachs were collected to determine histopathological, biochemical, and hematological parameters between different experimental groups. Results: Groups C, D, and E presented less histopathological changes such as anaplastic and

  15. Protective effect of two extracts of Cydonia oblonga miller (Quince fruits on gastric ulcer induced by indomethacin in rats

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    Morteza Parvan

    2017-01-01

    Full Text Available Background: In various studies, Cydonia oblonga Miller (quince has been reported to have many properties such as antioxidant and anti-ulcerative effects. This study has aimed to investigate the protective effects of quince aqueous extract (QAE and quince hydroalcoholic extract (QHE on gastric ulcer caused by indomethacin and the relevant macroscopic, histopathology, and biochemical factors in rats. Methods: Ten groups of male Wistar rats, six in each, were used in this study. These groups included: normal (distilled water, control (distilled water + indomethacin, reference (ranitidine or sucralfate + indomethacin, and test groups (QAE or QHE + indomethacin treated with three increasing doses (200, 500, and 800 mg/kg. Extracts and drugs were given orally to rats 1 h before injecting the indomethacin (25 mg/kg, intraperitoneally. Six hours later, the abdomen of rats was exposed, its pylorus was legated, gastric acid content was extracted, and its pH and the amount of pepsin secreted were measured by Anson method. Then, histopathology indices, ulcer area, ulcer index, and myeloperoxidase (MPO activity were measured in gastric mucus. Results: Both extracts of quince were effective to reduce the acidity of stomach and pepsin activity. Compared to control group, the average of enzyme activity of MPO was significantly declined in all treated groups. Control group had the highest level of gastric ulcer indices including severity, area, and index while the evaluated parameters had decreased in all extract treated groups although it seems that QAE was somewhat more effective. Conclusions: Protective effect of QAE and QHE on gastric ulcer was done by undermining offensive factors including decreasing the secretion of gastric acid and pepsin activity and by strengthening the protective factors of gastric mucus including antioxidant capacity.

  16. Roux-en-Y Gastric Bypass Surgery Induces Early Plasma Metabolomic and Lipidomic Alterations in Humans Associated with Diabetes Remission.

    Directory of Open Access Journals (Sweden)

    Tulika Arora

    Full Text Available Roux-en-Y gastric bypass (RYGB is an effective method to attain sustained weight loss and diabetes remission. We aimed to elucidate early changes in the plasma metabolome and lipidome after RYGB. Plasma samples from 16 insulin-resistant morbidly obese subjects, of whom 14 had diabetes, were subjected to global metabolomics and lipidomics analysis at pre-surgery and 4 and 42 days after RYGB. Metabolites and lipid species were compared between time points and between subjects who were in remission and not in remission from diabetes 2 years after surgery. We found that the variables that were most discriminatory between time points were decanoic acid and octanoic acid, which were elevated 42 days after surgery, and sphingomyelins (18:1/21:0 and 18:1/23:3, which were at their lowest level 42 days after surgery. Insulin levels were lower at 4 and 42 days after surgery compared with pre-surgery levels. At 4 days after surgery, insulin levels correlated positively with metabolites of branched chain and aromatic amino acid metabolism and negatively with triglycerides with long-chain fatty acids. Of the 14 subjects with diabetes prior to surgery, 7 were in remission 2 years after surgery. The subjects in remission displayed higher pre-surgery levels of tricarboxylic acid cycle intermediates and triglycerides with long-chain fatty acids compared with subjects not in remission. Thus, metabolic alterations are induced soon after surgery and subjects with diabetes remission differ in the metabolic profiles at pre- and early post-surgery time points compared to patients not in remission.

  17. Biocompatible curcumin loaded PMMA-PEG/ZnO nanocomposite induce apoptosis and cytotoxicity in human gastric cancer cells.

    Science.gov (United States)

    Dhivya, Raman; Ranjani, Jothi; Bowen, Patrick K; Rajendhran, Jeyaprakash; Mayandi, Jeyanthinath; Annaraj, Jamespandi

    2017-11-01

    Although curcumin is efficient in killing cancer cells, its poor water solubility and assocaited inadequate bioavailability remain major limitations to its therapeutic application. The formulation of curcumin micellar nanoparticles (NPs) encapsulated with a biodegradable polymer promises to significantly improve curcumin's solubility, stability, and bioavailability. The past decade has witnessed the development of nanoscale curcumin delivery systems: curcumin-loaded liposomes or nanoparticles, self-microemulsifying drug delivery systems (SMEDDS), cyclodextrin inclusions, solid dispersions, nanodisks, and nanotubes. The intention of the present investigation was to enhance the bioavailability and ultimately the efficacy of curcumin by developing a curcumin loaded PMMA-PEG/ZnO bionanocomposite utilizing insoluble curcumin and poorly soluble ZnO nanoparticles. Here, the drug (curcumin) may be carry and deliver the biomolecule(s) by polymer-encapsulated ZnO NPs. Physical characteristics of these novel nanomaterials have been studied with transmission electron microscopy (TEM) and powder X-ray diffraction (XRD) in conjunction with spectral techniques. Aqueous solubility of curcumin was augmented upon conjugation with the polymer-stabilized ZnO NPs. A narrow nanocomposite particle size distribution with an average value of 40 to 90nm was found via TEM. Most importantly, the pH-responsive release of curcumin from the nano-vehicle ensures safer, more controlled delivery of the drug at physiological pH. Cytotoxic potential and cellular uptake of curcumin loaded ZnO NPs were assessed by) cell viability assay, cell cycle assays along with the cell imaging studies have been done in addition to MTT using AGS cancer cells. Hence, these studies demonstrate that the clinical potential of the Curcumin Loaded PMMA-PEG/ZnO can induce the apoptosis of cancer cells through a cell cycle mediated apoptosis corridor, which raises its probability to cure gastric cancer cells. Copyright

  18. Concanavalin A-induced and spontaneous suppressor cell activities in peripheral blood lymphocytes and spleen cells from gastric cancer patients.

    Science.gov (United States)

    Toge, T; Hamamoto, S; Itagaki, E; Yajima, K; Tanada, M; Nakane, H; Kohno, H; Nakanishi, K; Hattori, T

    1983-11-01

    In 173 gastric cancer patients, activities of Concanavalin-A-induced suppressor cells (Con-AS) and spontaneous suppressor cells (SpS) in peripheral blood lymphocytes (PBL), splenic vein lymphocytes (SVL), and spleen cells (SCs) were investigated. Suppressions by Con-AS in PBL were significantly effective in patients of Stages III and IV, while suppressions by SpS were effective in patients with recurrent tumors. Thus, in PBLs of cancer patients, suppressor precursors, which are considered to be activated in vitro by Concanavalin-A, seemed to appear with the advances of the disease, and SpS activities, which could be already activated in vivo, seemed to increase in the terminal stage. In SCs, increased activities of Con-AS, but normal activities of SpS, were observed, and these suppressor-cell populations consisted of glass nonadherent cells. Suppressor activities of SCs would be due to suppressor T-cells, not to other types of cells. Furthermore, Con-AS existed in the medium-sized lymphocytes, which were fractionated on the basis of cell size, while SpS in the large-sized lymphocytes. A higher proportion of T-cells, bearing Fc receptors for IgG, was observed in the larger-sized lymphocyte fractions. Cell numbers in the large-sized lymphocyte fraction tended to increase with the advances of tumors. From these results, it is suggested that higher presence of suppressor precursors and the increase of SpS activities may occur in cancer patients, depending on the tumor advancing.

  19. Apple Polyphenol Suppresses Indomethacin-Induced Gastric Damage in Experimental Animals by Lowering Oxidative Stress Status and Modulating the MAPK Signaling Pathway.

    Science.gov (United States)

    Lee, Yi-Chen; Cheng, Chun-Wen; Lee, Huei-Jane; Chu, Huei-Chuien

    2017-11-01

    Indomethacin is a nonsteroid anti-inflammatory drug (NSAID) that is used to alleviate pain and inflammation in clinical medicine. Previous studies indicated that NSAIDs can cause gastrointestinal mucosal complications, and it is associated with mucosal lipid peroxidation and oxidative damage. Based on the evidences, decreasing oxidative stress may be an ideal therapeutic strategy for preventing gastrointestinal ulcer. Apple (Rosaceae Malus sp.) is one of the most commonly consumed fruits worldwide. The abundant polyphenolic constituents have received increasing attention for decades. In both in vivo and in vitro studies, the reports showed that apple polyphenol (AP) seems to provide an indirect antioxidant protection by activating cellular antioxidant enzymes to defend against oxidative stress. To address this issue and develop AP into a healthy improvement supplement, we studied the effect and potential mechanisms of AP in indomethacin-treated animal. The results showed AP can decelerate the gastric lesion, significantly suppress lipid peroxidation, increase the level of glutathione and the activity of catalase, and regulate the MAPK signaling proteins. These findings imply that AP protects the gastric mucosa from indomethacin-caused lesions and the protection is at least partially attributable to its antioxidative properties. This alternative medical function of AP may be a safe and effective intervention for preventing indomethacin-induced gastric complications.

  20. Hereditary Diffuse Gastric Cancer

    Science.gov (United States)

    ... Hereditary Diffuse Gastric Cancer Request Permissions Hereditary Diffuse Gastric Cancer Approved by the Cancer.Net Editorial Board , 10/2017 What is hereditary diffuse gastric cancer? Hereditary diffuse gastric cancer (HDGC) is a rare ...

  1. Possible mechanisms of action of Caesalpinia pyramidalis against ethanol-induced gastric damage.

    Science.gov (United States)

    Diniz, Polyana B F; Ribeiro, Ana Roseli S; Estevam, Charles S; Bani, Cristiane C; Thomazzi, Sara M

    2015-06-20

    Caesalpinia pyramidalis Tul. (Fabaceae), known as "catingueira", is an endemic tree of the Northeast region of Brazil. This plant, mainly inner bark and flowers, has been used in traditional medicine to treat gastritis, heartburn, indigestion, stomachache, dysenteries, and diarrheas. The ethanol extract of C. pyramidalis inner bark was used in rats via oral route, at the doses of 30, 100, and 300 mg/kg, in the ethanol-induced ulcer model and some of the mechanisms underlying to the gastroprotective effect of this plant investigated. The ethanol extract of C. pyramidalis inner bark (100 mg/kg) produced reduction (P process with imbalance between pro-inflammatory and anti-inflammatory mediators, supporting the popular usage of this plant. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Investigating the presence of omeprazole in waters by liquid chromatography coupled to low and high resolution mass spectrometry: degradation experiments.

    Science.gov (United States)

    Boix, C; Ibáñez, M; Sancho, J V; Niessen, W M A; Hernández, F

    2013-10-01

    Omeprazole is one of the most consumed pharmaceuticals around the world. However, this compound is scarcely detected in urban wastewater and surface water. The absence of this pharmaceutical in the aquatic ecosystem might be due to its degradation in wastewater treatment plants, as well as in receiving water. In this work, different laboratory-controlled degradation experiments have been carried out on surface water in order to elucidate generated omeprazole transformation products (TPs). Surface water spiked with omeprazole was subjected to hydrolysis, photo-degradation under both sunlight and ultraviolet radiation and chlorination. Analyses by liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC-QTOF MS) permitted identification of up to 17 omeprazole TPs. In a subsequent step, the TPs identified were sought in surface water and urban wastewater by LC-QTOF MS and by LC coupled to tandem mass spectrometry with triple quadrupole. The parent omeprazole was not detected in any of the samples, but four TPs were found in several water samples. The most frequently detected compound was OTP 5 (omeprazole sulfide), which might be a reasonable candidate to be included in monitoring programs rather than the parent omeprazole. Copyright © 2013 John Wiley & Sons, Ltd.

  3. Quality of omeprazole purchased via the Internet and personally imported into Japan: comparison with products sampled in other Asian countries.

    Science.gov (United States)

    Rahman, Mohammad Sofiqur; Yoshida, Naoko; Sugiura, Sakura; Tsuboi, Hirohito; Keila, Tep; Kiet, Heng Bun; Zin, Theingi; Tanimoto, Tsuyoshi; Kimura, Kazuko

    2018-03-01

    To evaluate the quality of omeprazole personally imported into Japan via the Internet and to compare the quality of these samples with previously collected samples from two other Asian countries. The samples were evaluated by observation, authenticity investigation and pharmacopoeial quality analysis. Quality comparison of some selected samples was carried out by dissolution profiling, Raman spectroscopy and principle component analysis (PCA). Observation of the Internet sites and samples revealed some discrepancies including the delivery of a wrong sample and the selling of omeprazole without a prescription, although it is a prescription medicine. Among the 28 samples analysed, all passed the identification test, 26 (93%) passed the quantity and content uniformity tests and all passed the dissolution test. Dissolution profiling confirmed that all the personally imported omeprazole samples remained intact in the acid medium. On the other hand, six samples from two of the same manufacturers, previously collected during surveys in Cambodia and Myanmar, frequently showed premature omeprazole release in acid. Raman spectroscopy and PCA showed significant variation between omeprazole formulations in personally imported samples and the samples from Cambodia and Myanmar. Our results indicate that the pharmaceutical quality of omeprazole purchased through the Internet was sufficient, as determined by pharmacopeial tests. However, omeprazole formulations distributed in different market segments by the same manufacturers were of diverse quality. Measures are needed to ensure consistent quality of products and to prevent entry of substandard products into the legitimate supply chain. © 2018 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

  4. Prediction of Relative In Vivo Metabolite Exposure from In Vitro Data Using Two Model Drugs: Dextromethorphan and Omeprazole

    Science.gov (United States)

    Lutz, Justin D.

    2012-01-01

    Metabolites can have pharmacological or toxicological effects, inhibit metabolic enzymes, and be used as probes of drug-drug interactions or specific cytochrome P450 (P450) phenotypes. Thus, better understanding and prediction methods are needed to characterize metabolite exposures in vivo. This study aimed to test whether in vitro data could be used to predict and rationalize in vivo metabolite exposures using two model drugs and P450 probes: dextromethorphan and omeprazole with their primary metabolites dextrorphan, 5-hydroxyomeprazole (5OH-omeprazole), and omeprazole sulfone. Relative metabolite exposures were predicted using metabolite formation and elimination clearances. For dextrorphan, the formation clearances of dextrorphan glucuronide and 3-hydroxymorphinan from dextrorphan in human liver microsomes were used to predict metabolite (dextrorphan) clearance. For 5OH-omeprazole and omeprazole sulfone, the depletion rates of the metabolites in human hepatocytes were used to predict metabolite clearance. Dextrorphan/dextromethorphan in vivo metabolite/parent area under the plasma concentration versus time curve ratio (AUCm/AUCp) was overpredicted by 2.1-fold, whereas 5OH-omeprazole/omeprazole and omeprazole sulfone/omeprazole were predicted within 0.75- and 1.1-fold, respectively. The effect of inhibition or induction of the metabolite's formation and elimination on the AUCm/AUCp ratio was simulated. The simulations showed that unless metabolite clearance pathways are characterized, interpretation of the metabolic ratios is exceedingly difficult. This study shows that relative in vivo metabolite exposure can be predicted from in vitro data and characterization of secondary metabolism of probe metabolites is critical for interpretation of phenotypic data. PMID:22010218

  5. Hypoxia induces cyclophilin B through the activation of transcription factor 6 in gastric adenocarcinoma cells.

    Science.gov (United States)

    Jeong, Kwon; Kim, Kiyoon; Kim, Hunsung; Oh, Yoojung; Kim, Seong-Jin; Jo, Yunhee; Choe, Wonchae

    2015-06-01

    Hypoxia is an important form of physiological stress that induces cell death, due to the resulting endoplasmic reticulum (ER) stress, particularly in solid tumors. Although previous studies have indicated that cyclophilin B (CypB) plays a role in ER stress, there is currently no direct information supporting the mechanism of CypB involvement under hypoxic conditions. However, it has previously been demonstrated that ER stress positively regulates the expression of CypB. In the present study, it was demonstrated that CypB is transcriptionally regulated by hypoxia-mediated activation of transcription factor 6 (ATF6), an ER stress transcription factor. Subsequently, the effects of ATF6 on CypB promoter activity were investigated and an ATF6-responsive region in the promoter was identified. Hypoxia and ATF6 expression each increased CypB promoter activity. Collectively, these results demonstrate that ATF6 positively regulates the expression of CypB by binding to an ATF6-responsive region in the promoter, which may play an important role in the attenuation of apoptosis in the adaption to hypoxia. These results suggest that CypB may be a key molecule in the adaptation of cells to hypoxic conditions.

  6. Temporary percutaneous T-fastener gastropexy and continuous decompressive gastrostomy in dogs with experimentally induced gastric dilatation.

    Science.gov (United States)

    Fox-Alvarez, W Alexander; Case, J Brad; Cooke, Kirsten L; Garcia-Pereira, Fernando L; Buckley, Gareth J; Monnet, Eric; Toskich, Beau B

    2016-07-01

    OBJECTIVE To evaluate a percutaneous, continuous gastric decompression technique for dogs involving a temporary T-fastener gastropexy and self-retaining decompression catheter. ANIMALS 6 healthy male large-breed dogs. PROCEDURES Dogs were anesthetized and positioned in dorsal recumbency with slight left-lateral obliquity. The gastric lumen was insufflated endoscopically until tympany was evident. Three T-fasteners were placed percutaneously into the gastric lumen via the right lateral aspect of the abdomen, caudal to the 13th rib and lateral to the rectus abdominis muscle. Through the center of the T-fasteners, a 5F locking pigtail catheter was inserted into the gastric lumen and attached to a device measuring gas outflow and intragastric pressure. The stomach was insufflated to 23 mm Hg, air was allowed to passively drain from the catheter until intraluminal pressure reached 5 mm Hg for 3 cycles, and the catheter was removed. Dogs were hospitalized and monitored for 72 hours. RESULTS Mean ± SD catheter placement time was 3.3 ± 0.5 minutes. Mean intervals from catheter placement to a ≥ 50% decrease in intragastric pressure and to ≤ 6 mm Hg were 2.1 ± 1.3 minutes and 8.4 ± 5.1 minutes, respectively. After catheter removal, no gas or fluid leakage at the catheter site was visible laparoscopically or endoscopically. All dogs were clinically normal 72 hours after surgery. CONCLUSIONS AND CLINICAL RELEVANCE The described technique was performed rapidly and provided continuous gastric decompression with no evidence of postoperative leakage in healthy dogs. Investigation is warranted to evaluate its effectiveness in dogs with gastric dilatation-volvulus.

  7. Current evidence for a role of GLP-1 in Roux-en-Y gastric bypass-induced remission of type 2 diabetes

    DEFF Research Database (Denmark)

    Rhee, Nicolai Alexander; Vilsbøll, T; Knop, F K

    2012-01-01

    Weight-reducing surgical procedures such as Roux-en-Y gastric bypass (RYGB) have proven efficient as means of decreasing excess body weight. Furthermore, some studies report that up to 80% of patients with type 2 diabetes mellitus (T2DM) undergoing RYGB experience complete remission of their T2DM......-induced remission of T2DM are lacking. This article critically evaluates the current evidence for a role of GLP-1 in RYGB-induced remission of T2DM.......Weight-reducing surgical procedures such as Roux-en-Y gastric bypass (RYGB) have proven efficient as means of decreasing excess body weight. Furthermore, some studies report that up to 80% of patients with type 2 diabetes mellitus (T2DM) undergoing RYGB experience complete remission of their T2DM...... antidiabetic effects of GLP-1 are thought to be key mediators in RYGB-induced remission of T2DM. However, the published studies on the impact of RYGB on GLP-1 secretion are few, small and often not controlled properly. Furthermore, mechanistic studies delineating the role of endogenous GLP-1 secretion in RYGB...

  8. Protective effects of alginate–chitosan microspheres loaded with alkaloids from Coptis chinensis Franch. and Evodia rutaecarpa (Juss. Benth. (Zuojin Pill against ethanol-induced acute gastric mucosal injury in rats

    Directory of Open Access Journals (Sweden)

    Wang QS

    2015-11-01

    Full Text Available Qiang-Song Wang,1,2,* Xiao-Ning Zhu,1,* Heng-Li Jiang,1,* Gui-Fang Wang,3 Yuan-Lu Cui1 1Tianjin State Key Laboratory of Modern Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 2Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, 3Pharmacy Department, Baokang Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: Zuojin Pill (ZJP, a traditional Chinese medicine formula, consists of Coptis chinensis Franch. and Evodia rutaecarpa (Juss. Benth. in a ratio of 6:1 (w/w and was first recorded in “Danxi’s experiential therapy” for treating gastrointestinal disorders in the 15th century. However, the poor solubility of alkaloids from ZJP restricted the protective effect in treating gastritis and gastric ulcer. The aim of the study was to investigate the protective mechanism of mucoadhesive microspheres loaded with alkaloids from C. chinensis Franch. and E. rutaecarpa (Juss. Benth. on ethanol-induced acute gastric mucosal injury in rats. Surface morphology, particle size, drug loading, encapsulation efficiency, in vitro drug release, mucoadhesiveness, and fluorescent imaging of the microspheres in gastrointestinal tract were studied. The results showed that the mucoadhesive microspheres loaded with alkaloids could sustain the release of drugs beyond 12 hours and had gastric mucoadhesive property with 82.63% retention rate in vitro. The fluorescence tracer indicated high retention of mucoadhesive microspheres within 12 hours in vivo. The mucoadhesive microspheres loaded with alkaloids could reduce the gastric injury by decreasing the mucosal lesion index, increasing the percentage of inhibition and increasing the amount of mucus in the gastric mucosa in an ethanol-induced gastric mucosal injury rat model. Moreover, the

  9. IGF-1-induced MMP-11 expression promotes the proliferation and invasion of gastric cancer cells through the JAK1/STAT3 signaling pathway.

    Science.gov (United States)

    Su, Chao; Wang, Wenchang; Wang, Cunchuan

    2018-05-01

    The present study aimed to investigate the association between insulin-like growth factor-1 (IGF-1) and matrix metalloproteinase-11 (MMP-11) expression in gastric cancer (GC) and the underlying mechanisms in SGC-7901 cells. Reverse transcription-quantitative polymerase chain reaction analysis revealed that the expression of IGF-1 and MMP-11 was significantly upregulated in GC tissues compared with normal gastric tissue. Furthermore, IGF-1 significantly and dose-dependently promoted MMP-11. Western blotting revealed that the addition of IGF-1 to SGC-7901 cells led to an evident enhancement in signal transducer and activator of transcription 3 (STAT3), IGF-1R and Janus kinase 1 (JAK1) phosphorylation at 20 and 40 min. A decrease in the extent of the elevated expression of MMP-11 and the enhanced phosphorylation of STAT3, JAK1 and IGF-1 receptor (IGF-1R) induced by IGF-1 in SGC-7901 cells were observed following treatment with NT157 (an IGF-1R inhibitor). Furthermore, piceatannol (a JAK1 inhibitor) or small interfering RNA against STAT3 reduced the extent of the increased expression of MMP-11 induced by IGF-1 in SGC-7901 cells. Piceatannol treatment induced the dose-dependent decline in the enhancement of STAT3 phosphorylation induced by IGF-1, indicating that the JAK1/STAT3 pathway may be implicated in the elevated expression of MMP-11 induced by IGF-1 in SGC-7901 cells. Finally, IGF-1 treatment significantly promoted the proliferation and invasion of SGC-7901 cells, which was inhibited following NT157, piceatannol or si-STAT3 treatment. The present study therefore demonstrated that IGF-1-induced MMP-11 may have facilitated the proliferation and invasion of SGC-7901 cells via the JAK1/STAT3 pathway.

  10. Helicobacter pylori antigen HP0986 (TieA) interacts with cultured gastric epithelial cells and induces IL8 secretion via NF-κB mediated pathway.

    Science.gov (United States)

    Devi, Savita; Ansari, Suhail A; Vadivelu, Jamuna; Mégraud, Francis; Tenguria, Shivendra; Ahmed, Niyaz

    2014-02-01

    The envisaged roles and partly understood functional properties of Helicobacter pylori protein HP0986 are significant in the context of proinflammatory and or proapoptotic activities, the two important facilitators of pathogen survival and persistence. In addition, sequence analysis of this gene predicts a restriction endonuclease function which remained unknown thus far. To evaluate the role of HP0986 in gastric inflammation, we studied its expression profile using a large number of clinical isolates but a limited number of biopsies and patient sera. Also, we studied antigenic role of HP0986 in altering cytokine responses of human gastric epithelial (AGS) cells including its interaction with and localization within the AGS cells. For in vitro expression study of HP0986, 110 H. pylori clinical isolates were cultured from patients with functional dyspepsia. For expression analysis by qRT PCR of HP0986, 10 gastric biopsy specimens were studied. HP0986 was also used to detect antibodies in patient sera. AGS cells were incubated with recombinant HP0986 to determine cytokine response and NF-κB activation. Transient transfection with HP0986 cloned in pEGFPN1 was used to study its subcellular localization or homing in AGS cells. Out of 110 cultured H. pylori strains, 34 (31%) were positive for HP0986 and this observation was correlated with in vitro expression profiles. HP0986 mRNA was detected in 7 of the 10 biopsy specimens. Further, HP0986 induced IL-8 secretion in gastric epithelial cells in a dose and time-dependent manner via NF-κB pathway. Serum antibodies against HP0986 were positively associated with H. pylori positive patients. Transient transfection of AGS cells revealed both cytoplasmic and nuclear localization of HP0986. HP0986 was moderately prevalent in clinical isolates and its expression profile in cultures and gastric biopsies points to its being naturally expressed. Collective observations including the induction of IL-8 via TNFR1 and NF

  11. Role of delayed gastric emptying in the pathogenesis of cysteamine-induced duodenal ulcer in the rat

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1982-01-01

    . After 4 h this pool of undiluted gastric secretions gradually is emptied into the duodenum, where the mucosal resistance is reduced by inhibition of the secretory activity of Brunner's glands, and ulceration rapidly develops. The time relationship is supported by histopathologic findings...

  12. A unique polysaccharide purified from Hericium erinaceus mycelium prevents oxidative stress induced by H2O2 in human gastric mucosa epithelium cell.

    Directory of Open Access Journals (Sweden)

    Mingxing Wang

    Full Text Available Hericium erinaceus (HE has been used both as a traditional Chinese medicine and home remedy for treatment of gastric and duodenal ulcers and gastritis. EP-1, a purified polysaccharide isolated from HE mycelium, has recently been identified as the active component responsible for HE anti-gastritis activity. Because oxidative stress has been implicated as a pathogenic cause of gastritis and gastric ulcers, EP-1 antioxidant properties were systematically examined in vitro using the human gastric mucosal epithelial cell line, GES-1. Results showed that EP-1 possessed higher oxygen radical absorbance capacity (ORAC and 2-3 times higher ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH, superoxide and hydroxyl radicals than a hot water extract of commercially available HE fruiting body. A crude mycelial polysaccharide (CMPS extract of HE, from which EP-1 was purified, showed slightly stronger radical scavenging activity and ORAC than EP-1, with the exception of DPPH-scavenging activity. Antioxidant activities of these extracts were further studied using hydrogen peroxide (H2O2-abused GES-1 cells; EP-1 dose-dependently preserved cell viability of abused cells as assessed via MTT assay. Moreover, FACS analysis revealed that EP-1 prevented H2O2-induced apoptotic cell death by inhibiting activation of apoptotic cellular signals within mitochondria-dependent apoptotic pathways. CMPS also prevented H2O2-induced oxidative stress, but to a lesser degree than did EP-1, even though CMPS exhibited comparable or stronger in vitro antioxidant activity than did EP-1.

  13. Efecto secuestrador del D-002 sobre radicales hidroxilo en mucosa gástrica Scavenger effect of D-002 on hydroxyl radicals in the gastric mucosa

    Directory of Open Access Journals (Sweden)

    Yohani Pérez Guerra

    2012-03-01

    purified from the beeswax, cause some multiple mechanism-mediated gastroprotective effects and decrease of lipid peroxidation in the gastric mucosa. Objective: to determine whether D-002 can scavenge the in vivo added or in vivo generated hydroxyl radical in rats with indometacin-induced gastric ulcer or not. Methods: For the in vitro experiment, D-002 was added at concentrations 0.9 and 1 000 mg/mL For the in vivo experiment, the rats were randomized into 6 groups: one negative control, and five indometacin-treated groups as follows a positive excipient-treated control, three under D-002 treatment (5, 25 or 100 mg/kg, respectively, p.o., and another group treated with Omeprazole (20 mg/kg i.p.. These lines of treatment were given 1 hour (excipient and D-002 or 30 min (Omeprazole prior to inducing the ulcers. In both experiments, aliquots from the gastric mucosa were taken and the damage infringed to 2-deoxiribose by the hydroxyl radical was determined. Results: oral administration of D-002, rather than in vitro addition, significantly protected 2-desoxiribose from the oxidative damage depending on the dosage as compared to the positive control. Conclusions: these results indicate that the ability of the orally administered D-002 (25 and 100 mg/kg to scavenge the hydroxyl radical endogenously generated on the gastric mucosa by indometacin could contribute to its antioxidant and gastroprotective effects against the damage that the non-steroidal anti-inflammatory drugs carry to the gastric mucosa.

  14. Anti-Helicobacter pylori and antiulcerogenic activity of Aframomum pruinosum seeds on indomethacin-induced gastric ulcer in rats.

    Science.gov (United States)

    Kouitcheu Mabeku, Laure Brigitte; Nanfack Nana, Blandine; Eyoum Bille, Bertrand; Tchuenteu Tchuenguem, Roland; Nguepi, Eveline

    2017-12-01

    Peptic ulcer is one of the most common diseases affecting mankind. Although there are many products used for its treatment, most of these products produce severe adverse reactions requiring the search for novel compounds. Some Afromomum species are used traditionally to cure acute gastritis. To evaluate the antiulcer activity of the methanol extract of Aframomum pruinosum Gagnepain (Zingiberaceae) seeds against two major etiologic agents of peptic ulcer disease; Helicobacter pylori and non-steroidal anti-inflammatory drugs. The anti-Helicobacter activity of A. pruinosum was evaluated using the broth microdilution method. After oral administration of indomethacin (5 mg/kg) for 5 consecutive days, gastric ulcerated animals were divided into control group and five other groups: three groups that recieved respectively 125, 250 and 500 mg/kg of plant extract, the fourth group received Maalox (50 mg/kg) and the fifth group, Misoprostol (100 μg/kg), respectively, for 5 days. Ulcer areas, gastric mucus content and nitric oxide gastric levels of animals were assessed 24 h after this treatment. A. pruinosum extract shows a moderate anti-Helicobacter activity with an MIC value of 128 μg/mL. A. pruinosum extract, like Misoprostol and Maalox, markedly reduces the % of ulcerated area from 8.15 ± 0.33 to 1.71 ± 0.44% (500 mg/kg). It also increased significantly mucus and NO gastric production with respective values of 4.44 ± 1.35 and 965.81 ± 106.74 μmol/g (500 mg/kg). These findings suggest that A. pruinosum methanol extract possesses antiulcer properties as ascertained by the comparative decreases in ulcer areas, increase of mucus and NO gastric production.

  15. Effects of sucralfate, cimetidine and rabeprazole on mucosal hydroxyproline content in healing of ethanol-hcl-induced gastric lesions.

    Science.gov (United States)

    Arisawa, Tomiyasu; Shibata, Tomoyuki; Kamiya, Yoshio; Nagasaka, Mitsuo; Nakamura, Masakatsu; Fujita, Hiroshi; Hasegawa, Shin; Harata, Masao; Nakamura, Masahiko; Mizuno, Tamaki; Tahara, Tomomitsu; Ohta, Yoshiji; Nakano, Hiroshi

    2006-07-01

    1. No general consensus has been reached on the treatment of acute gastric lesions. The aims of the present study were to clarify the effects of sucralfate, cimetidine and rabeprazole monotherapies and combination therapies on acute gastric lesions from the viewpoint of connective tissue regeneration. 2. Gastric lesions were experimentally created by the oral administration of 50% ethanol-0.15 mol/L HCl to rats. After 30 min, the anti-ulcer agents sucralfate (100 mg/kg), cimetidine (20 mg/kg) and rabeprazole (2 mg/kg) were administered separately or in combination and the stomach was excised at different times to measure the level of hydroxyproline in the gastric mucosa and determine lesion index. Immunostaining against prolylhydroxylase was performed on some specimens. 3. In the control group, lesion index decreased linearly from 30 min after ethanol-HCl administration and the level of mucosal hydroxyproline peaked between 2 and 4 h later. Although sucralfate significantly promoted lesion healing, it had no effect on mucosal hydroxyproline level. Cimetidine suppressed increases in mucosal hydroxyproline and prolonged lesion healing, but these findings were reversed by combining cimetidine and sucralfate. Rabeprazole had no significant effect on lesion healing, but promoted lesion healing in combination with sucralfate. Immunohistochemical analysis showed that prolylhydroxylase was expressed in spindle cells that lined the glandular cells in a boundary area between normal and injured tissues. 4. Under conditions in which the effects of intragastric pH are minimal, sucralfate is superior to antisecretory agents in promoting the healing of acute gastric lesions.

  16. Roux-en-Y gastric bypass reverses the effects of diet-induced obesity to inhibit the responsiveness of central vagal motoneurones.

    Science.gov (United States)

    Browning, Kirsteen N; Fortna, Samuel R; Hajnal, Andras

    2013-05-01

    Diet-induced obesity (DIO) has been shown to alter the biophysical properties and pharmacological responsiveness of vagal afferent neurones and fibres, although the effects of DIO on central vagal neurones or vagal efferent functions have never been investigated. The aims of this study were to investigate whether high-fat diet-induced DIO also affects the properties of vagal efferent motoneurones, and to investigate whether these effects were reversed following weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Whole-cell patch-clamp recordings were made from rat dorsal motor nucleus of the vagus (DMV) neurones in thin brainstem slices. The DMV neurones from rats exposed to high-fat diet for 12-14 weeks were less excitable, with a decreased membrane input resistance and decreased ability to fire action potentials in response to direct current pulse injection. The DMV neurones were also less responsive to superfusion with the satiety neuropeptides cholecystokinin and glucagon-like peptide 1. Roux-en-Y gastric bypass reversed all of these DIO-induced effects. Diet-induced obesity also affected the morphological properties of DMV neurones, increasing their size and dendritic arborization; RYGB did not reverse these morphological alterations. Remarkably, independent of diet, RYGB also reversed age-related changes of membrane properties and occurrence of charybdotoxin-sensitive (BK) calcium-dependent potassium current. These results demonstrate that DIO also affects the properties of central autonomic neurones by decreasing the membrane excitability and pharmacological responsiveness of central vagal motoneurones and that these changes were reversed following RYGB. In contrast, DIO-induced changes in morphological properties of DMV neurones were not reversed following gastric bypass surgery, suggesting that they may be due to diet, rather than obesity. These findings represent the first direct evidence for the plausible effect of RYGB to improve vagal

  17. Morin protects gastric mucosa from nonsteroidal anti-inflammatory drug, indomethacin induced inflammatory damage and apoptosis by modulating NF-κB pathway.

    Science.gov (United States)

    Sinha, Krishnendu; Sadhukhan, Pritam; Saha, Sukanya; Pal, Pabitra Bikash; Sil, Parames C

    2015-04-01

    Deregulation in prostaglandin (PG) biosynthesis, severe oxidative stress, inflammation and apoptosis contribute to the pathogenesis of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. Unfortunately, most of the prescribed anti-ulcer drugs generate various side effects. In this scenario, we could consider morin as a safe herbal potential agent against IND-gastropathy and rationalize its action systematically. Rats were pretreated with morin for 30 min followed by IND (48 mgkg(-1)) administration for 4 h. The anti-ulcerogenic nature of morin was assessed by morphological and histological analysis. Its effects on the inflammatory (MPO, cytokines, adhesion molecules), ulcer-healing (COXs, PGE(2)), and signaling parameters (NF-κB and apoptotic signaling) were assessed by biochemical, RP-HPLC, immunoblots, IHC, RT-PCR, and ELISA at the time points of their maximal changes due to IND administration. IND induced NF-κB and apoptotic signaling in rat's gastric mucosa. These increased proinflammatory responses, but reduced the antioxidant enzymes and other protective factors. Morin reversed all the adverse effects to prevent IND-induced gastric ulceration in a PGE2 independent manner. Also, it did not affect the absorption and/or primary pharmacological activity of IND. The gastroprotective action of morin is primarily attributed to its potent antioxidant nature that also helps in controlling several IND-induced inflammatory responses. For the first time, the study reveals a mechanistic basis of morin mediated protective action against IND-induced gastropathy. As morin is a naturally abundant safe antioxidant, future detailed pharmacokinetic and pharmacodynamic studies are expected to establish it as a gastroprotective agent. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Gastric emptying

    International Nuclear Information System (INIS)

    Bonaz, B.; Hostein, J.; Caravel, J.P.

    1990-01-01

    Gastric emptying (GE) of nutriments is a major function of the stomach. GE disorders are observed after gastric surgery and with various diseases, either of a strictly gastroenterologic kind or interesting other specialities (especially diabetes mellitus). Scintigraphy, which has allowed a better knowledge of GE physiological and pathological mechanisms, has now become the reference method for studying the emptying of solids and liquids. In a near future, it could well have two major applications: a diagnostic approach of functional digestive disorders and an assessment of the various effects of pharmacological drugs with digestive affinity [fr

  19. Gastric cancer

    International Nuclear Information System (INIS)

    Mineur, L.; Jaegle, E.; Pointreau, Y.; Denis, F.

    2010-01-01

    Radio-chemotherapy Gastro-intestinal inter-group study have demonstrated a convincing local control and overall survival benefit. Oncologists and GI workshops have in the present not had a major interest in the radiotherapy treatment of gastric cancer due to a number of factors. Primary because toxicities may be severe, second physicians may have low experience in definition of clinical target volume and in third perioperative chemotherapy is widely used in this indication. In Summary this issue should be used as guides for defining appropriate radiation planning treatment for the adjuvant postoperative therapy of gastric cancer. (authors)

  20. Role of lipoxygenases and lipoxin A(4)/annexin-1 receptor in gastric protection induced by 20% ethanol or sodium salicylate in rats.

    Science.gov (United States)

    Peskar, Brigitta M; Ehrlich, Karlheinz; Schuligoi, Rufina; Peskar, Bernhard A

    2009-01-01

    The role of cyclooxygenases and prostaglandins in experimental models of gastroprotection is well established. We investigated the effects of the 5-lipoxygenase inhibitor A63162, the 12-lipoxygenase inhibitor baicalein and the 15-lipoxygenase inhibitor PD146176 as well as the nonspecific lipoxin A(4)/annexin-1 antagonist Boc1 on adaptive protection induced by 20% ethanol against 70% ethanol, and on protection induced by sodium salicylate against the mucosal-damage-aggravating effects of celecoxib and dexamethasone during local ischemia-reperfusion in rats. It was found that both types of gastroprotection were antagonized by the lipoxygenase inhibitors and the lipoxin A(4)/annexin-1 antagonist in doses that have no direct damaging effect on gastric mucosa. The results suggest that not only cyclooxygenases, but also active lipoxygenases and, possibly, annexin-1 are required for these types of gastroprotection to occur. Copyright 2009 S. Karger AG, Basel.

  1. Curcumin Induced Human Gastric Cancer BGC-823 Cells Apoptosis by ROS-Mediated ASK1-MKK4-JNK Stress Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Tao Liang

    2014-09-01

    Full Text Available The signaling mediated by stress-activated MAP kinases (MAPK, c-Jun N-terminal kinase (JNK has well-established importance in cancer. In the present report, we investigated the effects of curcumin on the signaling pathway in human gastric cancer BGC-823 cells. Curcumin induced reactive oxygen species (ROS production and BGC-823 cells apoptosis. Inhibition of ROS generation by antioxidant (NAC or Trion significantly prevented curcumin-mediated apoptosis. Notably, we observed that curcumin activated ASK1, a MAPKKK that is oxidative stress sensitive and responsible to phosphorylation of JNK via triggering cascades, up-regulated an upstream effector of the JNK, MKK4, and phosphorylated JNK protein expression in BGC-823 cells. However, curcumin induced ASK1-MKK4-JNK signaling was attenuated by NAC. All the findings confirm the possibility that oxidative stress-activated ASK1-MKK4-JNK signaling cascade promotes the apoptotic response in curcumin-treated BGC-823 cells.

  2. Olive (Olea europaea) leaf methanolic extract prevents HCl/ethanol-induced gastritis in rats by attenuating inflammation and augmenting antioxidant enzyme activities.

    Science.gov (United States)

    Al-Quraishy, Saleh; Othman, Mohamed S; Dkhil, Mohamed A; Abdel Moneim, Ahmed Esmat

    2017-07-01

    Gastritis is preponderantly characterized by inflammation of the lining epithelial layer and the chronic gastritis is considered as a pre-cancer lesion. For many centuries olive (Olea europaea) leaf has been used for its putative health potential, nonetheless, to date, the gastroprotective effects of olive leaves have not been studied yet. Hence, in this study we investigated whether olive leaf extract (OLE) could protect gastric mucosa against HCl/ethanol-induced gastric mucosal damage in rats. Hcl/ethanol administration caused significant damage to the gastric mucosa, as confirmed by gastric ulcer index and histological evaluation. However, this damage was largely prevented by pre-administering 20mg/kg omeprazole or 100mg/kg OLE. Interestingly, the damage was completely prevented by pre-administering 200 and 300mg/kg OLE. Moreover, OLE attenuated the inflammatory response by decreasing nuclear factor-κB (NF-κB), cycloxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) expressions, and down-regulating inducible nitric oxide synthase (iNOS) and interleukin-1β (IL-1β) in gastric mucosa. The gastroprotective mechanism of OLE involved the promotion of enzymatic and nonenzymatic molecules (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione reduced form), promoting nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression, halting lipid peroxidation and preventing the overproduction of nitric oxide. Together, our findings clearly demonstrated that OLE could prevent HCl/ethanol-induced gastritis by attenuating inflammation and oxidant/antioxidant imbalance. Indeed, OLE could potentially be useful as a natural therapy for gastritis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Regulation of the actin cytoskeleton in Helicobacter pylori-induced migration and invasive growth of gastric epithelial cells

    Directory of Open Access Journals (Sweden)

    Rieder Gabriele

    2011-11-01

    Full Text Available Abstract Dynamic rearrangement of the actin cytoskeleton is a significant hallmark of Helicobacter pylori (H. pylori infected gastric epithelial cells leading to cell migration and invasive growth. Considering the cellular mechanisms, the type IV secretion system (T4SS and the effector protein cytotoxin-associated gene A (CagA of H. pylori are well-studied initiators of distinct signal transduction pathways in host cells targeting kinases, adaptor proteins, GTPases, actin binding and other proteins involved in the regulation of the actin lattice. In this review, we summarize recent findings of how H. pylori functionally interacts with the complex signaling network that controls the actin cytoskeleton of motile and invasive gastric epithelial cells.

  4. Aprepitant plus granisetron and dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients with gastric cancer treated with S-1 plus cisplatin.

    Science.gov (United States)

    Oyama, Katsunobu; Fushida, Sachio; Kaji, Masahide; Takeda, Toshiya; Kinami, Shinichi; Hirono, Yasuo; Yoshimoto, Katsuhiro; Yabushita, Kazuhisa; Hirosawa, Hisashi; Takai, Yuki; Nakano, Tatsuo; Kimura, Hironobu; Yasui, Toshiaki; Tsuneda, Atsushi; Tsukada, Tomoya; Kinoshita, Jun; Fujimura, Takashi; Ohta, Tetsuo

    2013-11-01

    We aimed to evaluate the efficacy of a new combination antiemetic therapy comprising aprepitant, granisetron, and dexamethasone in gastric cancer patients undergoing chemotherapy with cisplatin and S-1. Gastric cancer patients scheduled to receive their first course of chemotherapy with cisplatin (60 mg/m(2)) and S-1 (80 mg/m(2)) were treated with a new combination antiemetic therapy aprepitant, granisetron, and dexamethasone on day 1; aprepitant and dexamethasone on days 2 and 3; and dexamethasone on day 4. The patients reported vomiting, nausea, use of rescue therapy, and change in the amount of diet intake, and completed the Functional Living Index-Emesis (FLIE) questionnaire. The primary endpoint was complete response (CR; no emesis and use of no rescue antiemetics) during the overall study phase (0-120 h after cisplatin administration). The secondary endpoints included complete protection (CP; CR plus no significant nausea); change in the amount of diet intake; and the impact of chemotherapy-induced nausea and vomiting (CINV) on daily life during the overall, acute (0-24 h), and delayed (24-120 h) phases. Fifty-three patients were included. CR was achieved in 88.7, 98.1, and 88.7% of patients in the overall, acute, and delayed phases, respectively. The corresponding rates of CP were 67.9, 96.2, and 67.9%. Approximately half of the patients had some degree of anorexia. FLIE results indicated that 79.5% of patients reported "minimal or no impact of CINV on daily life". Addition of aprepitant to standard antiemetic therapy was effective in gastric cancer patients undergoing treatment with cisplatin and S-1.

  5. The Middle Fragment of Helicobacter pylori CagA Induces Actin Rearrangement and Triggers Its Own Uptake into Gastric Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Abolghasem Tohidpour

    2017-07-01

    Full Text Available Cytotoxin-associated gene product A (CagA is a major virulence factor secreted by Helicobacter pylori. CagA activity in the gastric epithelium is associated with higher risk of gastric cancer development. Bacterial type IV secretion system (T4SS-mediated translocation of CagA into the cytosol of human epithelial cells occurs via a poorly understood mechanism that requires CagA interaction with the host membrane lipid phosphatidylserine (PS and host cell receptor integrin α5β1. Here we have characterized the isolated recombinant middle fragment of CagA (CagA-M that contains the positively-charged PS-binding region (aa 613–636 and a putative β1 integrin binding site, but lacks the EPIYA region, secretion signal peptide and the CagA multimerization motif. We show that CagA-M, when immobilized on latex beads, is capable of binding to, and triggering its own uptake into, gastric epithelial cells in the absence of infection with cagA-positive H. pylori. Using site-directed mutagenesis, fluorescent and electron microscopy, and highly-specific inhibitors, we demonstrate that the cell-binding and endocytosis-like internalization of CagA-M are dependent on (1 binding to PS; (2 β1 integrin activity; and (3 actin dynamics. Interaction of CagA-M with the host cells is accompanied by the development of long filopodia-like protrusions (macrospikes. This novel morphology is different from the hummingbird phenotype induced by the translocation of full-length CagA. The determinants within CagA-M and within the host that are important for endocytosis-like internalization into host cells are very similar to those observed for T4SS-mediated internalization of full-length CagA, suggesting that the latter may involve an endocytic pathway.

  6. Gastroprotective and Antioxidant Activity of Kalanchoe brasiliensis and Kalanchoe pinnata Leaf Juices against Indomethacin and Ethanol-Induced Gastric Lesions in Rats

    Directory of Open Access Journals (Sweden)

    Edilane Rodrigues Dantas de Araújo

    2018-04-01

    Full Text Available Kalanchoe brasiliensis and Kalanchoe pinnata are used interchangeably in traditional medicine for treating peptic ulcers and inflammatory problems. In this context, this study aims to characterize the chemical constituents and evaluate the gastroprotective activity of the leaf juices of the two species in acute gastric lesions models. Thin Layer Chromatography (TLC and Ultra High Performance Liquid Chromatography coupled to Mass Spectrometer (UHPLC-MS were performed for chemical characterization. Wistar rats were pre-treated orally with leaf juices (125, 250 and 500 mg/kg or ranitidine (50 mg/kg. The peaks observed in the chromatogram of K. brasiliensis showed similar mass spectra to flavonoid glycosides derived from patuletin and eupafolin, while K. pinnata showed mass spectra similar to compounds derived from quercetin, patuletin, eupafolin and kaempferol. K. brasiliensis at all doses and K. pinnata at doses of 250 mg/kg and 500 mg/kg significantly reduced the lesions in the ethanol induction model. In the indomethacin induction model, both species showed significant results at doses of 250 and 500 mg/kg. Also, the pre-treatment with leaf juices increased the antioxidant defense system, glutathione (GSH, whereas malondialdehyde (MDA, myeloperoxidase (MPO, interleukin-1β (IL-1β and tumor necrosis factor-α (TNF-α levels were significantly decreased. Treatment with leaf juices led to the upregulation of zone occludes-1 (ZO-1 and the downregulation of inducible nitric oxide synthase (iNOS and factor nuclear-κβ transcription (NF-κB-p65, while also showing a cytoprotective effect and maintaining mucus production. These findings show that the leaf juices of the two species showed gastroprotective effects on ethanol and gastric indomethacin injury which were a consequence of gastric inflammation suppression, antioxidant activity and the maintenance of cytoprotective defenses and mucosal structure architecture.

  7. Effects of omeprazole and cisapride treatment in Japanese asthmatics with reflux esophagitis

    Directory of Open Access Journals (Sweden)

    Katsuya Fujimori

    1997-01-01

    Full Text Available In the United States and Europe, gastroesophageal reflux (GER is receiving attention as a potential cause of bronchial asthma. Few Japanese case reports have described this relationship. Therefore, we investigated the effect of omeprazole and cisapride on pulmonary function tests, blood gases and home peak expiratory flow rates (PEFR in six Japanese outpatients with asthma and proven GER. After 8 weeks of treatment, reflux esophagitis had improved in all patients. However, the parameters of pulmonary function showed no change other than a significant post- treatment increase in home PEFR (4.4-27.7% in three patients. These results suggest that anti-reflux (omeprazole and cisapride treatment will produce small improvements in the PEFR in some Japanese asthmatics with GER.

  8. Effect of Jianpi Jiedu Recipe on angiogenesis and the PTEN/PI3K/AKT signaling pathway in the course of Helicobacter pylori-induced gastric cancer in C57BL/6 mice

    Directory of Open Access Journals (Sweden)

    Ning-Ning Liu

    2018-01-01

    Full Text Available Objective: To reveal the effect of Jianpi Jiedu recipe (JPJDR on angiogenesis and the PTEN (Phosphatase and tensin homolog deleted on chromosome ten/PI3K/AKT signaling pathway in the course of H. pylori infection-induced carcinogenesis of gastric mucosa in C57BL/6 mice. Methods: Two-hundred C57BL/6 mice were randomly divided into five groups (control group, model group, JPJDR low-dose group, JPJDR medium-dose group, and JPJDR high-dose group, 40 in each group. A mouse model of gastric cancer, induced by H. pylori standard strain infection, was established. The mice of JPJDR low-dose, middle-dose, and high-dose groups were intragastrically administered 250, 500, and 1000 mg/kg JPJDR per day, respectively. After 72 weeks, the H. pylori infection in gastric mucosa of the mice was analyzed by rapid urease test; the pathological changes in the gastric mucosa of mice were assessed by histopathological examination, and micro-vessel density (MVD, vascular endothelial growth factor (VEGF, and PTEN/PI3K/AKT levels were determined. Results: The incidence of gastric cancer in each group (control group, model group, JPJDR low-dose, medium-dose, high-dose group was 0%, 26.3%, 13.2%, 10%, and 7.5% respectively. The incidence of gastric cancer in the Chinese medicine group was significantly lower than that of the model group (P = 0.020, P = 0.023, P = 0.007. The expression of MVD and VEGF in the model group was significantly higher than that in the control group (P = 0.002, P < 0.001, while the expression of MVD and VEGF decreased in the Chinese medicine group. The expression of p-PTEN and p-AKT in the model group was significantly higher than that in the control group (All P < 0.001, while Chinese medicine could reduce the expression of p-PTEN and p-AKT to varying extents. Conclusion: Long-term infection of C57BL/6 mice with H. pylori induces gastric carcinogenesis, by increasing gastric mucosal MVD, promoting the expression of VEGF, inhibiting the activity of

  9. Protective effect of Calamintha officinalis Moench leaves against alcohol-induced gastric mucosa injury in rats. Macroscopic, histologic and phytochemical analysis.

    Science.gov (United States)

    Monforte, M T; Lanuzza, F; Pergolizzi, S; Mondello, F; Tzakou, O; Galati, E M

    2012-06-01

    Calamintha officinalis Moench (Lamiaceae) is an aromatic plant used since ancient times for its preservative and medicinal properties. The plant, known as 'Mentuccia' in Central Italy, is used in cooking as an aromatizant and to impart aroma and flavour to food. The methanol extract of the leaves was subjected to phytochemical and biological investigations. The extract contains polyphenols, catechic tannins and terpenes and shows radical scavenger activity. By means of HPLC analysis, eriocitrin, eriodyctiol, acacetin, linarin, benzoic acid and some phenolic acids, such as caffeic, chlorogenic, p-coumaric, were determined. The gastroprotective activity of the extract was investigated using ethanol-induced ulcer in rats, with sucralfate as a reference drug. Samples of gastric mucosa, stained by PAS and haematoxylin/eosin, were observed by light microscopy. The efficacy of the extract was comparable to that of the reference drug. Probably the gastroprotective effect depends on a synergistic action of all the compounds occurring in C. officinalis leaves, even if the antioxidant potential of the leaves plays an important role by removing damaging agents from the gastric mucosa. Copyright © 2011 John Wiley & Sons, Ltd.

  10. Gastroprotection of Suaveolol, Isolated from Hyptis suaveolens, against Ethanol-Induced Gastric Lesions in Wistar Rats: Role of Prostaglandins, Nitric Oxide and Sulfhydryls

    Directory of Open Access Journals (Sweden)

    María Elena Sánchez-Mendoza

    2012-07-01

    Full Text Available Hyptis suaveolens is a medicinal plant that is, according to traditional medicine, considered useful in the treatment of gastric ulcers. Although its gastroprotective activity was reported, the active compounds have not been identified. Therefore, the aim of the present study was to identify at least one active compound potentially responsible for the gastroprotective activity of H. suaveolens by using a bioassay guided study with an ethanol-induced gastric ulcer experimental model in rats. The results show that the hexane extract had protective activity (close to 70% when using doses between 10 and 100 mg/kg, and that the compound suaveolol, isolated from this extract, was one of the active gastroprotective agents. This is the first report about the gastroprotective activity of suaveolol. Rats treated with this compound at 3, 10, 30 and 100 mg/kg showed 12.6, 21.3, 39.6 and 70.2% gastroprotection respectively. The effect elicited by suaveolol (at 100 mg/kg was attenuated by pretreatment with either NG-nitro-L-arginine methyl ester (70 mg/kg, i.p., a nitric oxide (NO synthase inhibitor, indomethacin (10 mg/kg, s.c., a blocker of prostaglandin synthesis, or N-ethylmaleimide (10 mg/kg, s.c., a blocker of sulfhydryl groups. This suggests that the gastroprotective mechanism of action of this compound involves NO, prostaglandins and sulfhydryl groups.

  11. Biomarcadores da digestão e índice glicêmico após o uso de omeprazol em equinos sadios.

    OpenAIRE

    Stephânia Katurchi Mendes Mélo

    2013-01-01

    Objetivou-se avaliar os efeitos da administração de diferentes dosagens de omeprazol sobre biomarcadores da digestão e índice glicêmico em equinos sadios. Foram utilizadas quatro fêmeas Puro Sangue Árabe, livres de úlceras gástricas, distribuídos em quatro tratamentos, em um fatorial 4x4. Os tratamentos foram: controle (CONT), omeprazol bolus (OMPZBOLUS), omeprazol 4 mg/kg (OMPZ4MG/KG) e omeprazol 1 mg/kg (OMPZ1MG/KG). No tratamento controle e OMPZBOLUS os animais receberam 5,0 ml de água ...

  12. Gastric Sleeve Surgery

    Science.gov (United States)

    ... Videos for Educators Search English Español Gastric Sleeve Surgery KidsHealth / For Teens / Gastric Sleeve Surgery What's in ... or buying healthy food ) Preparing for Gastric Sleeve Surgery Preparing for this major operation takes months of ...

  13. Roux-en-Y Gastric Bypass and Vertical Banded Gastroplasty Induce Long-Term Changes on the Human Gut Microbiome Contributing to Fat Mass Regulation

    DEFF Research Database (Denmark)

    Tremaroli, Valentina; Karlsson, Fredrik; Werling, Malin

    2015-01-01

    Bariatric surgery is currently the most effective procedure for the treatment of obesity. Given the role of the gut microbiota in regulating host metabolism and adiposity, we investigated the long-term effects of bariatric surgery on the microbiome of patients randomized to Roux-en-Y gastric bypass...... or vertical banded gastroplasty and matched for weight and fat mass loss. The two surgical procedures induced similar and durable changes on the gut microbiome that were not dependent on body mass index and resulted in altered levels of fecal and circulating metabolites compared with obese controls....... By colonizing germ-free mice with stools from the patients, we demonstrated that the surgically altered microbiota promoted reduced fat deposition in recipient mice. These mice also had a lower respiratory quotient, indicating decreased utilization of carbohydrates as fuel. Our results suggest that the gut...

  14. Scopadulciol, Isolated from Scoparia dulcis, Induces β-Catenin Degradation and Overcomes Tumor Necrosis Factor-Related Apoptosis Ligand Resistance in AGS Human Gastric Adenocarcinoma Cells.

    Science.gov (United States)

    Fuentes, Rolly G; Toume, Kazufumi; Arai, Midori A; Sadhu, Samir K; Ahmed, Firoj; Ishibashi, Masami

    2015-04-24

    Scopadulciol (1), a scopadulan-type diterpenoid, was isolated from Scoparia dulcis along with three other compounds (2-4) by an activity-guided approach using the TCF reporter (TOP) luciferase-based assay system. A fluorometric microculture cytotoxicity assay (FMCA) revealed that compound 1 was cytotoxic to AGS human gastric adenocarcinoma cells. The treatment of AGS cells with 1 decreased β-catenin levels and also inhibited its nuclear localization. The pretreatment of AGS cells with a proteasome inhibitor, either MG132 or epoxomicin, protected against the degradation of β-catenin induced by 1. The 1-induced degradation of β-catenin was also abrogated in the presence of pifithrin-α, an inhibitor of p53 transcriptional activity. Compound 1 inhibited TOP activity in AGS cells and downregulated the protein levels of cyclin D1, c-myc, and survivin. Compound 1 also sensitized AGS cells to tumor necrosis factor-related apoptosis ligand (TRAIL)-induced apoptosis by increasing the levels of the death receptors, DR4 and DR5, and decreasing the level of the antiapoptotic protein Bcl-2. Collectively, our results demonstrated that 1 induced the p53- and proteasome-dependent degradation of β-catenin, which resulted in the inhibition of TCF/β-catenin transcription in AGS cells. Furthermore, 1 enhanced apoptosis in TRAIL-resistant AGS when combined with TRAIL.

  15. X irradiation combined with TNF alpha-related apoptosis-inducing ligand (TRAIL) reduces hypoxic regions of human gastric adenocarcinoma xenografts in SCID mice

    International Nuclear Information System (INIS)

    Takahashi, Momoko; Yasui, Hironobu; Ogura, Aki; Asanuma, Taketoshi; Inanami, Osamu; Kubota, Nobuo; Tsujitani, Michihiko; Kuwabara, Mikinori

    2008-01-01

    Our previous study showed that X irradiation induced the expression of death receptor DR5 on the cell surface in tumor cell lines under not only normoxia but also hypoxia. X irradiation combined with TNF α-related apoptosis-inducing ligand (TRAIL), which is the ligand of DR5, induced apoptosis in vitro (Takahashi et al., (2007) Journal of Radiation Research, 48: 461-468). In this report, we examined the in vivo antitumor efficacy of X irradiation combined with TRAIL treatment in tumor xenograft models derived from human gastric adenocarcinoma MKN45 and MKN28 cells in severe combined immunodeficiency (SCID) mice. X irradiation combined with TRAIL synergistically suppressed the tumor growth rates in the xenograft models derived from MKN45 and MKN28 cells, which have wild type Tp53 and mutated Tp53, respectively, indicating that the antitumor effects occurred in a Tp53-independent manner. Histological analysis showed that the combination of X irradiation and TRAIL induced caspase-3-dependent apoptotic cell death. Moreover, the immunohistochemical detection of hypoxic regions using the hypoxic marker pimonidazole revealed that caspase-3-dependent apoptosis occurred in the hypoxic regions in the tumors. These results indicated that X irradiation combined with TRAIL may be a useful treatment to reduce tumor growth in not only normoxic but also hypoxic regions. (author)

  16. Structural damage and changes in eicosanoid metabolites in the gastric mucosa of rats and pigs induced by anti-inflammatory drugs of varying ulcerogenicity.

    Science.gov (United States)

    Rainsford, K D

    1986-01-01

    The object of the studies reviewed here has been to correlate the time-course of ultrastructural changes induced by oral administration of a range of non-steroidal anti-inflammatory (NSAI) drugs with effects on eicosanoid metabolism and drug absorption, so as to discriminate what biochemical/cellular and pharmacological factors account for their varying ulcerogenicity. Oral administration of highly ulcerogenic drugs (e.g. aspirin, diclofenac, indomethacin, piroxicam) to rats causes rapid damage to surface and gastric mucous cells, selective parietal cell damage, and extensive disruption of endothelial cells of submucosal microcapillaries (especially with aspirin) with accompanying extravasation of blood cell components. These changes are coincident with depressed levels of PGE2/6-keto-PGF1 alpha (measured by GC/MS or RIA) and uptake of the drugs (measured by scintillation counting or HPLC). Low ulcerogenic NSAI drugs (e.g. azapropazone, benoxaprofen and fenclofenac) causes very little damage to the surface mucosal cells. Azapropazone has been found to be well absorbed, and benoxaprofen and fenclofenac somewhat more slowly, so for the latter two drugs their low rate of absorption might also be a factor in their reduced ulcerogenicity. Aspirin, azapropazone and benoxaprofen have been shown to reduce 5-HETE levels (RIA), although the latter two drugs were more effective than aspirin. Thus, they result in the inhibition of PG production, by cyclo-oxygenase inhibition (with potential adverse effects from excess oxyradical and/or production of HETE's) with inhibition of the lipoxygenase pathway. The time-sequence of changes induced by single oral doses of indomethacin or other NSAI drugs on the ultrastructure and the prostanoid metabolism of the pig gastric mucosa parallelled those seen in the rat. Attempts to determine whether co-administration of NSAI drugs might reduce the inhibition of PG cyclo-oxygenase by more potent inhibitors (e.g. indomethacin) have been

  17. Gastric Bezoar

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    Samer Assaf

    2017-01-01

    Full Text Available History of present illness: A 12-year-old female with no past medical history presented with abdominal pain for 3 months. The pain was intermittent, located at the epigastric region, non-radiating, fluctuating intensity up to 8/10, and had worsened over the past month. She did not have fever, nausea, vomiting, diarrhea, constipation, or blood in her stool. The patient also endorsed hair loss over the same time period and noted that her previously long hair was now short and thin. On exam, patient was noted to have shoulder-length hair, a soft, non-distended abdomen with mild tenderness to the epigastric region, and a 5cm hard mass palpated at the epigastrium. Significant findings: In the abdominal radiograph, a nonspecific and non-obstructive bowel gas pattern with no air-fluid level was noted, however the stomach was distended with soft tissue. The CT abdomen/pelvis revealed a distended stomach with undigested heterogeneous contents (presumed bezoar. Discussion: A bezoar is a mass of incompletely digested material typically originating in the stomach and consisting of vegetable fibers, hair, or drugs.1 Bezoars develop after ingested foreign material accumulates in the gastrointestinal tract due to indigestibility, gastric outlet obstruction, or intestinal stasis. Trichobezoars are comprised of hair and classically form in young females with an underlying psychiatric disorder resulting in the urge to pull one’s hair out (trichotillomania and swallow it (trichophagia.2,3 Gastric bezoars are rare with an approximate incidence of 0.3 percent of patients undergoing upper endoscopy.4 Patients tend to remain asymptomatic for long periods, but may develop abdominal pain, nausea/vomiting, early satiety, anorexia, and weight loss.5 Complications may include gastrointestinal ulcerations, perforations, intussusception, pancreatitis, obstructive jaundice, and death.6-8 The diagnosis of a gastric bezoar can be made using plain films, ultrasound, or CT, and

  18. Influence of gastric pH modifiers on development of intestinal metaplasia induced by X-irradiation in rats

    International Nuclear Information System (INIS)

    Watanabe, Hiromitsu; Okamoto, Taro; Fudaba, Yasuhiro; Ogundigie, P.S.; Ito, Akihiro

    1993-01-01

    The influence of gastric pH on intestinal metaplasia was examined in male Crj:CD(SD) rats. At the age of 5 weeks, animals were irradiated with two 10 Gy doses of X-rays to the gastric region at a 3-day interval (total 20 Gy), and 6 months after irradiation, received either secretin or histamine in silicon tubes for 2 months or had their bilateral submandibular salivary glands removed. The incidences of intestinal metaplasia in the fundus of animals after administration of secretin or histamine, or removal of the salivary glands were reduced, along with the pH values, as compared with values for rats given X-rays alone. In both the pyloric and the fundic gland mucosae, the numbers of alkaline phosphatase (ALP)-positive foci and type B metaplasias (intestinal crypts without Paneth cells) were also significantly decreased (P<0.01). In a second experiment, started six months after irradiation, rats were kept on 1% sodium chloride (NaCl) diet for 6 months. Subsequent removal of salivary glands along with histamine treatment brought about a marked drop in pH and in numbers of ALP-positive foci after three and five days. The present results thus indicated that development and maintenance of intestinal metaplasia can be influenced by a decrease of pH value. (author)

  19. Comparison of Omeprazole with Ranitidine for Treatment of Symptoms Associated with Gastroesophageal Reflux Disease and Uncomplicated Duodenal Ulcer

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    Andre P Archambault

    1996-01-01

    Full Text Available This randomized, single-blind, parallel group study was conducted to compare omeprazole with ranitidine for the treatment of symptoms associated with gastroesophageal reflux disease (GERD, uncomplicated duodenal ulcer (DU or both. After baseline assessments, patients were randomized to receive daily treatment with either 20 mg omeprazole or 300 mg ranitidine for four weeks. In total, 1481 patients (1001 omeprazole, 480 ranitidine with a diagnosis of GERD (n=904 and/or DU (n=577, confirmed by endoscopy or barium meal and reporting moderate to severe symptoms, were included in the analyses. The seventy of overall daytime symptoms reported by the omeprazole group at clinic visits was lower than that reported by the ranitidine group at week 2 for the entire patient group (P=0.0002 and at both weeks 2 and 4 for the subgroup of patients with GERD (P=0.0001 and P=0.001, respectively. The severity of overall night-time symptoms reported by the omeprazole group was lower than that reported by the ranitidine group at week 4 for all patients as a whole (P=0.042 and at both weeks 2 and 4 for the subgroup of patients with GERD (P=0.035 and P=0.010, respectively. There were no significant differences in reports of adverse events. In the omeprazole group, 19% of patients at week 2 and 15% of patients at week 4 reported adverse events, while the corresponding results from the ranitidine group were 21% and 11%. In conclusion, patients with GERD, DU or both treated with omeprazole 20 mg daily for four weeks showed statistically significant reductions in symptoms compared with patients treated with ranitidine 300 mg daily for the same period of time. The percentage of patients with any remaining daytime symptoms was 12% lower in the omeprazole group compared with the ranitidine group at week 2, and 7% lower at week 4. Five per cent fewer patients in the omeprazole group experienced night-time symptoms at either week 2 or week 4.

  20. Disposition of the anti-ulcer medications ranitidine, cimetidine, and omeprazole following administration of multiple doses to exercised Thoroughbred horses.

    Science.gov (United States)

    Knych, H K; Stanley, S D; Arthur, R M; McKemie, D S

    2017-01-01

    The use of anti-ulcer medications, such as cimetidine, ranitidine, and omeprazole, is common in performance horses. The use of these drugs is regulated in performance horses, and as such a withdrawal time is necessary prior to competition to avoid a medication violation. To the authors' knowledge, there are no reports in the literature describing repeated oral administrations of these drugs in the horse to determine a regulatory threshold and related withdrawal time recommendations. Therefore, the objective of the current study was to describe the disposition and elimination pharmacokinetics of these anti-ulcer medications following oral administration to provide data upon which appropriate regulatory recommendations can be established. Nine exercised Thoroughbred horses were administered 20 mg/kg BID of cimetidine or 8 mg/kg BID of ranitidine, both for seven doses or 2.28 g of omeprazole SID for four doses. Blood samples were collected, serum drug concentrations were determined, and elimination pharmacokinetic parameters were calculated. The serum elimination half-life was 7.05 ± 1.02, 7.43 ± 0.851 and 3.94 ± 1.04 h for cimetidine, ranitidine, and omeprazole, respectively. Serum cimetidine and ranitidine concentrations were above the LOQ and omeprazole and omeprazole sulfide below the LOQ in all horses studied upon termination of sample collection. © 2016 John Wiley & Sons Ltd.

  1. Expression of Gast, Cckbr, Reg1α genes in rat duodenal epithelial cells upon long-term gastric hypoacidity and after a multiprobiotic administration

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    Dranitsina A. S.

    2014-11-01

    Full Text Available Aim. Determination of the Cckbr, Gast and Reg1α genes expression in rat duodenal epithelial cells upon long- term hypoacidity and with the administration of the multiprobiotic Symbiter. Methods. The experiments were carried out on white non-strain male rats. The hypoacidic state was induced through intraperitoneal injection of omeprazole for 28 days. The level of genes expression was determined by semi-quantitative analysis with RT-PCR Results. The elevation of mRNA levels of the Cckbr and Gast genes in rat duodenal villus and crypt epitheliocytes, the increased expression of the Reg1A gene in crypt epithelial cells were shown as well as the appearance of the Reg1a gene expression in villus epitheliocytes upon hypoacidic conditions were shown. The content of mRNAs of the above mentioned genes decreased or remained at the control level upon the treatment of hypoacidic rats with the multiprobiotic Symbiter. Conclusions. Long-term gastric hypoacidity is accompanied by the changes in expression of the Cckbr, Gast and Reg1a genes in rat duodenum, whereas upon administration of the multiprobiotic Symbiter the pattern of studied gene expression did not changed in the most cases.

  2. The proton pump inhibitor, omeprazole, but not lansoprazole or pantoprazole, is a metabolism-dependent inhibitor of CYP2C19: implications for coadministration with clopidogrel.

    Science.gov (United States)

    Ogilvie, Brian W; Yerino, Phyllis; Kazmi, Faraz; Buckley, David B; Rostami-Hodjegan, Amin; Paris, Brandy L; Toren, Paul; Parkinson, Andrew

    2011-11-01

    As a direct-acting inhibitor of CYP2C19 in vitro, lansoprazole is more potent than omeprazole and other proton pump inhibitors (PPIs), but lansoprazole does not cause clinically significant inhibition of CYP2C19 whereas omeprazole does. To investigate this apparent paradox, we evaluated omeprazole, esomeprazole, R-omeprazole, lansoprazole, and pantoprazole for their ability to function as direct-acting and metabolism-dependent inhibitors (MDIs) of CYP2C19 in pooled human liver microsomes (HLM) as well as in cryopreserved hepatocytes and recombinant CYP2C19. In HLM, all PPIs were found to be direct-acting inhibitors of CYP2C19 with IC(50) values varying from 1.2 μM [lansoprazole; maximum plasma concentration (C(max)) = 2.2 μM] to 93 μM (pantoprazole; C(max) = 6.5 μM). In addition, we identified omeprazole, esomeprazole, R-omeprazole, and omeprazole sulfone as MDIs of CYP2C19 (they caused IC(50) shifts after a 30-min preincubation with NADPH-fortified HLM of 4.2-, 10-, 2.5-, and 3.2-fold, respectively), whereas lansoprazole and pantoprazole were not MDIs (IC(50) shifts lansoprazole, or pantoprazole, as irreversible (or quasi-irreversible) MDIs of CYP2C19. These results have important implications for the mechanism of the clinical interaction reported between omeprazole and clopidogrel, as well as other CYP2C19 substrates.

  3. Healing effects of Musa sapientum var. paradisiaca in diabetic rats with co-occurring gastric ulcer: cytokines and growth factor by PCR amplification.

    Science.gov (United States)

    Kumar, Mohan; Gautam, Manish Kumar; Singh, Amit; Goel, Raj Kumar

    2013-11-05

    The present study evaluates the effects of extract of Musa sapientum fruit (MSE) on ulcer index, blood glucose level and gastric mucosal cytokines, TNF-α and IL-1β and growth factor, TGF-α (affected in diabetes and chronic ulcer) in acetic acid (AA)-induced gastric ulcer (GU) in diabetic (DR) rat. MSE (100 mg/kg, oral), omeprazole (OMZ, 2.0 mg/kg, oral), insulin (INS, 4 U/kg, sc) or pentoxyphylline (PTX, 10 mg/kg, oral) were given once daily for 10 days in 14 days post-streptozotocin (60 mg/kg, intraperitoneal)-induced diabetic rats while, the normal/diabetic rats received CMC for the same period after induction of GU with AA. Ulcer index was calculated based upon the product of length and width (mm2/rat) of ulcers while, TNF-α, IL-1β and TGF-α were estimated in the gastric mucosal homogenate from the intact/ulcer region. Phytochemical screening and HPTLC analysis of MSE was done following standard procedures. An increase in ulcer index, TNF-α and IL-1β were observed in normal (NR)-AA rat compared to NR-normal saline rat, which were further increased in DR-AA rat while, treatments of DR-AA rat with MSE, OMZ, INS and PTX reversed them, more so with MSE and PTX. Significant increase in TGF-α was found in NR-AA rat which did not increase further in DR-AA rat. MSE and PTX tended to increase while, OMZ and INS showed little or no effect on TGF-α in AA-DR rat. Phytochemical screening of MSE showed the presence of saponins, flavonoids, glycosides, steroids and alkaloids and HPTLC analysis indicated the presence of eight active compounds. MSE showed antidiabetic and better ulcer healing effects compared with OMZ (antiulcer) or INS (antidiabetic) in diabetic rat and could be more effective in diabetes with concurrent gastric ulcer.

  4. Association of nutritional status-related indices and chemotherapy-induced adverse events in gastric cancer patients.

    Science.gov (United States)

    Seo, Seung Hee; Kim, Sung-Eun; Kang, Yoon-Koo; Ryoo, Baek-Yeol; Ryu, Min-Hee; Jeong, Jae Ho; Kang, Shin Sook; Yang, Mihi; Lee, Jung Eun; Sung, Mi-Kyung

    2016-11-18

    Malnutrition in gastrectomized patients receiving chemotherapy is associated with the susceptibility to chemotherapy-related adverse events. This study evaluated pre-operative nutritional status-related indices associated with adverse events in post-operation gastric cancer patients receiving chemotherapy. Medical records of 234 gastrectomized patients under adjuvant tegafur/gimeracil/oteracil chemotherapy with extended lymph node dissection were analyzed. Nutritional status assessment included Patient-Generated Subjective Global Assessment (PG-SGA), body weight, body mass index, serum albumin concentration, and Nutrition Risk Index (NRI). Chemotherapy-originated adverse events were determined using Common Terminology Criteria for Adverse Events. PG-SGA indicated 59% of the patients were malnourished, and 27.8% of the patients revealed serious malnutrition with PG-SGA score of ≥9. Fifteen % of patients lost ≥10% of the initial body weight, 14.5% of the patients had hypoalbuminemia (cancer patients.

  5. Mechanistic Studies of the Anti-Ulcerogenic Activity and Acute Toxicity Evaluation of Dichlorido-Copper(II-4-(2-5-Bromo-benzylideneaminoethyl Piperazin-1-ium Phenolate Complex against Ethanol-Induced Gastric Injury in Rats

    Directory of Open Access Journals (Sweden)

    A. Hamid A. Hadi

    2011-10-01

    Full Text Available The compound dichlorido-copper(II-4-(2-5-bromobenzylideneaminoethyl piperazin-1-ium phenolate (CuLBS was synthesized, characterized and screened for acute toxicity and protective activity against ethanol-induced gastric mucosal injury in rats. Gross microscopic lesions, biochemical and immunological parameters and histochemcial staining of glycogen storage were taken into consideration. Oral administration of CuLBS (30 and 60 mg/Kg for two weeks dose-dependently flattened gastric mucosa, significantly increased gastric mucus and total acidity, compared with control group (P < 0.01. Serum levels of liver enzymes aspartate (AST and alanine transaminases (ALT, pro-inflammatory (IL-6 and TNF-α and anti-inflammatory (IL-10 cytokines in the rats exposed to ethanol induced ulceration have been altered. Administration of CuLBS showed considerable (P < 0.05 protection against ulceration by modulating the acute alterations of cytokines AST, ALT and stomach glycogen. Interestingly, CuLBS did not interfere with the natural release of nitric oxide. CuLBS alone (60 mg/Kg did not exhibit any ulcerogenic effect as assessed using Adami’s scoring scale. An acute toxicity study showed that rats treated with CuLBS (1,000 and 2,000 mg/Kg manifested no abnormal signs. These findings therefore, suggested that the gastroprotective activity of CuLBS might contribute in modulating the inflammatory cytokine-mediated oxidative damage to gastric mucosa.

  6. Acidic bile salts induces mucosal barrier dysfunction through let-7a reduction during gastric carcinogenesis after Helicobacter pylori eradication

    Science.gov (United States)

    Takahashi, Yasushi; Uno, Kaname; Iijima, Katsunori; Abe, Yasuhiko; Koike, Tomoyuki; Asano, Naoki; Asanuma, Kiyotaka; Shimosegawa, Tooru

    2018-01-01

    Gastric cancer (GC) after eradication for Helicobacter pylori (H.pylori) increases, but its carcinogenesis is not elucidated. It is mainly found in acid non-secretion areas (ANA), as mucosal regeneration in acid secretory areas (AA) after eradication changes the acidity and bile toxicity of gastric juice. We aimed to clarify the role of barrier dysfunction of ANA by the stimulation of pH3 bile acid cocktail (ABC) during carcinogenesis. We collected 18 patients after curative endoscopic resection for GC, identified later than 24 months after eradication, and took biopsies by Congo-red chromoendoscopy to distinguish AA and ANA (UMIN00018967). The mucosal barrier function was investigated using a mini-Ussing chamber system and molecular biological methods. The reduction in mucosal impedance in ANA after stimulation was significantly larger than that in AA, 79.6% vs. 87.9%, respectively. The decrease of zonula occludens-1 (ZO-1) and let-7a and the increase of snail in ANA were significant compared to those in AA. In an in vitro study, the restoration of ZO-1 and let-7a as well as the induction of snail were observed after stimulation. High mobility group A2 (HMGA2)-snail activation, MTT proliferation, and cellular infiltration capacity were significantly increased in AGS transfected with let-7a inhibitor, and vice versa. Accordingly, using a mini-Ussing chamber system for human biopsy specimens followed by an in vitro study, we demonstrated for the first time that the exposure of acidic bile salts to ANA might cause serious barrier dysfunction through the let-7a reduction, promoting epithelial-mesenchymal transition during inflammation-associated carcinogenesis even after eradication. PMID:29719591

  7. 3-Bromopyruvate and sodium citrate induce apoptosis in human gastric cancer cell line MGC-803 by inhibiting glycolysis and promoting mitochondria-regulated apoptosis pathway

    International Nuclear Information System (INIS)

    Guo, Xingyu; Zhang, Xiaodong; Wang, Tingan; Xian, Shulin; Lu, Yunfei

    2016-01-01

    Cancer cells are mainly dependent on glycolysis to generate adenosine triphosphate (ATP) and intermediates required for cell growth and proliferation. Thus, inhibition of glycolysis might be of therapeutic value in antitumor treatment. Our previously studies had found that both 3-bromopyruvate (BP) and sodium citrate (SCT) can inhibit tumor growth and proliferation in vitro and in vivo. However, the mechanism involved in the BP and SCT mediated antitumor activity is not entirely clear. In this work, it is demonstrated that BP inhibits the enzyme hexokinase (HK) activity and SCT suppresses the phosphofructokinase (PFK) activity respectively, both the two agents decrease viability, ATP generation and lactate content in the human gastric cancer cell line MGC-803. These effects are directly correlated with blockage of glycolysis. Furthermore, BP and SCT can induce the characteristic manifestations of mitochondria-regulated apoptosis, such as down-regulation of anti-apoptosis proteins Bcl-2 and Survivin, up-regulation of pro-apoptosis protein Bax, activation of caspase-3, as well as leakage of cytochrome c (Cyt-c). In summary, our results provided evidences that BP and SCT inhibit the MGC-803 cells growth and proliferation might be correlated with inhibiting glycolysis and promoting mitochondria-regulated apoptosis. -- Highlights: •Blockage of glycolysis might be a novel way to anticancer. •Both 3-bromopyruvate and sodium citrate could inhibit glycolysis and regulate mitochondrial pathway in cancer cells. •Both 3-bromopyruvate and sodium citrate would be the novel agents on treatment of gastric cancer.

  8. Evidence for the involvement of peripheral β-adrenoceptors in delayed liquid gastric emptying induced by dipyrone, 4-aminoantipyrine, and antipyrine in rats

    Energy Technology Data Exchange (ETDEWEB)

    Vinagre, A.M. [Núcleo de Medicina e Cirurgia Experimental, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP (Brazil); Collares, E.F. [Departamento de Pediatria, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP (Brazil); Núcleo de Medicina e Cirurgia Experimental, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP (Brazil)

    2013-09-27

    Dipyrone (Dp), 4-aminoantipyrine (AA), and antipyrine (At) delay liquid gastric emptying (GE) in rats. We evaluated adrenergic participation in this phenomenon in a study in male Wistar rats (250-300 g) pretreated subcutaneously with guanethidine (GUA), 100 mg·kg{sup −1}·day{sup −1}, or vehicle (V) for 2 days before experimental treatments. Other groups of animals were pretreated intravenously (iv) 15 min before treatment with V, prazosin (PRA; 1 mg/kg), yohimbine (YOH; 3 mg/kg), or propranolol (PRO; 4 mg/kg), or with intracerebroventricular (icv) administration of 25 µg PRO or V. The groups were treated iv with saline or with 240 µmol/kg Dp, AA, or At. GE was determined 10 min later by measuring the percentage of gastric retention (%GR) of saline labeled with phenol red 10 min after gavage. %GR (mean±SE, n=8) indicated that GUA abolished the effect of Dp (GUA vs V=31.7±1.6 vs 47.1±2.3%) and of At (33.2±2.3 vs 54.7±3.6%) on GE and significantly reduced the effect of AA (48.1±3.2 vs 67.2±3.1%). PRA and YOH did not modify the effect of the drugs. %GR (mean±SE, n=8) indicated that iv, but not icv, PRO abolished the effect of Dp (PRO vs V=29.1±1.7 vs 46.9±2.7%) and At (30.5±1.7 vs 49±3.2%) and significantly reduced the effect of AA (48.4±2.6 vs 59.5±3.1%). These data suggest activation of peripheral β-adrenoceptors in the delayed GE induced by phenylpyrazolone derivatives.

  9. Adaptive upregulation of gastric and hypothalamic ghrelin receptors and increased plasma ghrelin in a model of cancer chemotherapy-induced dyspepsia.

    Science.gov (United States)

    Malik, N M; Moore, G B T; Kaur, R; Liu, Y-L; Wood, S L; Morrow, R W; Sanger, G J; Andrews, P L R

    2008-06-05

    Chemotherapy treatment can lead to delayed gastric emptying, early satiety, anorexia, nausea and vomiting, described collectively as the cancer-associated dyspepsia syndrome (CADS). Administration of ghrelin (GHRL), an endogenous orexigenic peptide known to stimulate gastric motility, has been shown to reduce the symptoms of CADS induced in relevant animal models with the potent chemotherapeutic agent, cisplatin. We examined the effects in the rat of cisplatin (6 mg/kg i.p.) treatment on the expression of GHRL and ghrelin receptor (GHSR) mRNAs in the hypothalamus and the stomach at a time-point (2 days) when the effects of cisplatin are pronounced. In addition, plasma levels of GHRL (acylated and total including des-acyl GHRL) were measured and the effect on these levels of treatment with the synthetic glucocorticoid dexamethasone (2 mg/kg s.c. bd.) was investigated. Cisplatin increased GHSR mRNA expression in the stomach (67%) and hypothalamus (52%) but not GHRL mRNA expression and increased the percentage of acylated GHRL (7.03+/-1.35% vs. 11.38+/-2.40%) in the plasma. Dexamethasone reduced the plasma level of acylated GHRL and the percentage of acylated GHRL to values below those in animals treated with saline alone (7.03+/-1.35% vs. 2.60+/-0.49%). Our findings support the hypothesis that an adaptive upregulation of the ghrelin receptor may occur during cancer chemotherapy-associated dyspepsia. This may have a role in defensive responses to toxic challenges to the gut. In addition, our results provide preliminary evidence for glucocorticoid modulation of plasma ghrelin levels.

  10. 3-Bromopyruvate and sodium citrate induce apoptosis in human gastric cancer cell line MGC-803 by inhibiting glycolysis and promoting mitochondria-regulated apoptosis pathway

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Xingyu; Zhang, Xiaodong; Wang, Tingan, E-mail: moonsonlife@yahoo.com; Xian, Shulin; Lu, Yunfei, E-mail: doctorlife@126.com

    2016-06-17

    Cancer cells are mainly dependent on glycolysis to generate adenosine triphosphate (ATP) and intermediates required for cell growth and proliferation. Thus, inhibition of glycolysis might be of therapeutic value in antitumor treatment. Our previously studies had found that both 3-bromopyruvate (BP) and sodium citrate (SCT) can inhibit tumor growth and proliferation in vitro and in vivo. However, the mechanism involved in the BP and SCT mediated antitumor activity is not entirely clear. In this work, it is demonstrated that BP inhibits the enzyme hexokinase (HK) activity and SCT suppresses the phosphofructokinase (PFK) activity respectively, both the two agents decrease viability, ATP generation and lactate content in the human gastric cancer cell line MGC-803. These effects are directly correlated with blockage of glycolysis. Furthermore, BP and SCT can induce the characteristic manifestations of mitochondria-regulated apoptosis, such as down-regulation of anti-apoptosis proteins Bcl-2 and Survivin, up-regulation of pro-apoptosis protein Bax, activation of caspase-3, as well as leakage of cytochrome c (Cyt-c). In summary, our results provided evidences that BP and SCT inhibit the MGC-803 cells growth and proliferation might be correlated with inhibiting glycolysis and promoting mitochondria-regulated apoptosis. -- Highlights: •Blockage of glycolysis might be a novel way to anticancer. •Both 3-bromopyruvate and sodium citrate could inhibit glycolysis and regulate mitochondrial pathway in cancer cells. •Both 3-bromopyruvate and sodium citrate would be the novel agents on treatment of gastric cancer.

  11. A Direct Comparison of Anti-ulcer Effects of Coenzyme Q10 and Vitamin C on Indomethacin-induced Gastric Ulcer in Rat: A Controlled Experimental Study

    Directory of Open Access Journals (Sweden)

    2013-08-01

    Full Text Available Introduction: Indomethacin increases generation of mitochondrial reactive oxygen species (ROS which have a crucial role in the indomethacin-induced gastric ulcer. Coenzyme Q10 has an antioxidant activity on mitochondria and cell membranes and protects lipids from oxidation and is essential for stabilizing biological membranes. Superoxide dismutase (SOD acts as one of the defense mechanisms against free radicals. When the generation of ROS overwhelms, the antioxidant defense, lipid peroxiation of cell membrane occurs and cause cell damage. Materials and Methods: Male adult Wistar rats were divided into A and B groups. The rats in group A were then further divided into three subgroups of 6 animals each and received one of the following treatments: Animals in the first subgroup received saline. Animals in the second subgroup received saline and indomethacin. Animals in the third subgroup received vitamin C and indomethacin. The rats in group B were also further divided into 3 subgroups of 6 rats each and treated with one of the following treatments: Animals in first subgroup received 1% Tween 80 as vehicle. Animals In second subgroup received 1% Tween 80 and indomethacin. Animals in third subgroup received CoQ10 and indomethacin. Four hours after the last treatment, animals were killed and the stomachs removed were cut and gastric mucosal lesions were examined. Ulcer indexes were determined and SOD activity measured in plasma                                                             Results: Pretreatment with both vitamin C and coenzyme Q10 was associated with attenuation of ulcer index and increased SOD activity compared with animals treated with indomethacin alone (P

  12. Hypoxia-inducible factor-1α and Wnt/β-catenin signaling pathways promote the invasion of hypoxic gastric cancer cells.

    Science.gov (United States)

    Liu, Hong-Lan; Liu, Dang; Ding, Guang-Rong; Liao, Peng-Fei; Zhang, Jun-Wen

    2015-09-01

    The present study aimed to examine the association between hypoxia-inducible factor (HIF)-1α and the Wnt/β-catenin signaling pathway in a hypoxic environment. The study also aimed to explore the possible mechanisms underlying the invasion of hypoxic gastric cancer cells in vitro and in vivo. The pcDNA™ 6.2‑GW/EmGFP‑miR‑β‑catenin plasmid was transfected into SGC‑7901 gastric cancer cells, resulting in cells with stable suppression of β‑catenin expression. The biological characteristics of the control, liposome, negative control, β‑catenin knockdown, hypoxia and hypoxia β‑catenin knockdown groups were tested using an invasion assay. The differences in the invasive capacity of the control, negative control and liposome groups were not statistically significant. However, the hypoxia group demonstrated a significantly enhanced invasive capacity, as compared with that in the control group (Phypoxic and control cells was high alongside increased HIF‑1α, β‑catenin, uPA and MMP‑7 levels according to western blot and immunohistochemical analyses, while growth and protein levels of tumors from hypoxic β‑catenin knockdown cells were significantly lower and those of β‑catenin knockdown cells were lowest. In conclusion, these results suggested that HIF‑1α activation was able to regulate the Wnt/β‑catenin pathway, and that HIF‑1α may be controlled by the Wnt/β‑catenin pathway. A potential mechanism underlying SGC‑7901 tumorigenicity is the activation of the Wnt/β‑catenin signaling pathway, which activates uPA and MMP‑7 expression and contributes to the enhanced invasion of hypoxic cancer cells.

  13. Características de las dispensaciones de omeprazol en una farmacia comunitaria

    Directory of Open Access Journals (Sweden)

    Ezquieta MF

    2010-06-01

    Full Text Available INTRODUCCIÓN Omeprazol es uno de los principios que más se dispensa en la farmacia comunitaria. Pertenece al grupo de los inhibidores de la bomba de protones (IBP y actúa inhibiendo la secreción de H+ al estómago, disminuyendo en consecuencia los síntomas derivados de una excesiva acidez gástrica. OBJETIVOS Estudiar las características de la utilización de omeprazol 20 mg por los pacientes en una farmacia comunitaria, tratando de investigar las causas de la elevada prevalencia de uso de este medicamento entre dicha población. RESULTADOS La primera prescripción fue del médico de familia en un 59% de los casos y del especialista en el 41%. Un 61% de los pacientes dejó de tomarlo y tuvo que volver por sentir molestias gástricas. Un 44% no sabe hasta cuándo tiene que tomarlo y un 35% cree que debe tomarlo siempre. Un 55% lo toma por estar tomando al mismo tiempo un AINE. DISCUSIÓN Este estudio se encuentra limitado por el reducido número de encuestas en una sola farmacia comunitaria. Los resultados apuntan a que las causas de la elevada utilización de omeprazol pueden ser varias: el uso de AINE durante largos periodos de tiempo en dosis elevadas, el envejecimiento de la población que necesita utilizar un AINE como antiagregante o toma varios medicamentos, el uso en indicaciones poco precisas o el empleo para afecciones gástricas menores y la gastroprotección en pacientes polimedicados sin factores de riesgo. Otro factor que también podría influir es el posible rebote ácido tras la supresión del tratamiento, que deriva en la utilización crónica del medicamento.

  14. Neutron activation analysis of chemical impurities in manipulated samples of omeprazole

    Energy Technology Data Exchange (ETDEWEB)

    Sepe, Fernanda Peixoto; Leal, Alexandre Soares; Gomes, Tatiana Cristina Bomfim; Menezes, Maria Angela de Barros Correia; Silva, Maria Aparecida, E-mail: asleal@cdtn.br [Nuclear Technology Development Centre/Brazilian Commission for Nuclear Energy (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2011-07-01

    In this work, samples of Omeprazole (C{sub 17}H{sub 19}N{sub 3}O{sub 3}S), a largely used drug in the treatment of dyspepsia and peptic ulcer, were acquired from five different pharmacies of manipulation - or retail pharmacies which prepare personalized drugs under medical recommendation - in Belo Horizonte/Brazil and investigated using the k{sub 0} - Neutron Activation Analysis (NAA). The preliminary results showed the presence of elements not foreseen in the original formula. It confirms the potential risk offered by medicines without suitable inspection. (author)

  15. Neutron activation analysis of chemical impurities in manipulated samples of omeprazole

    International Nuclear Information System (INIS)

    Sepe, Fernanda Peixoto; Leal, Alexandre Soares; Gomes, Tatiana Cristina Bomfim; Menezes, Maria Angela de Barros Correia; Silva, Maria Aparecida

    2011-01-01

    In this work, samples of Omeprazole (C 17 H 19 N 3 O 3 S), a largely used drug in the treatment of dyspepsia and peptic ulcer, were acquired from five different pharmacies of manipulation - or retail pharmacies which prepare personalized drugs under medical recommendation - in Belo Horizonte/Brazil and investigated using the k 0 - Neutron Activation Analysis (NAA). The preliminary results showed the presence of elements not foreseen in the original formula. It confirms the potential risk offered by medicines without suitable inspection. (author)

  16. Auraptene, a Major Compound of Supercritical Fluid Extract of Phalsak (Citrus Hassaku Hort ex Tanaka, Induces Apoptosis through the Suppression of mTOR Pathways in Human Gastric Cancer SNU-1 Cells

    Directory of Open Access Journals (Sweden)

    Jeong Yong Moon

    2015-01-01

    Full Text Available The supercritical extraction method is a widely used process to obtain volatile and nonvolatile compounds by avoiding thermal degradation and solvent residue in the extracts. In search of phytochemicals with potential therapeutic application in gastric cancer, the supercritical fluid extract (SFE of phalsak (Citrus hassaku Hort ex Tanaka fruits was analyzed by gas chromatography-mass spectrometry (GC-MS. Compositional analysis in comparison with the antiproliferative activities of peel and flesh suggested auraptene as the most prominent anticancer compound against gastric cancer cells. SNU-1 cells were the most susceptible to auraptene-induced toxicity among the tested gastric cancer cell lines. Auraptene induced the death of SNU-1 cells through apoptosis, as evidenced by the increased cell population in the sub-G1 phase, the appearance of fragmented nuclei, the proteolytic cleavage of caspase-3 and poly(ADP-ribose polymerase (PARP protein, and depolarization of the mitochondrial membrane. Interestingly, auraptene induces an increase in the phosphorylation of Akt, which is reminiscent of the effect of rapamycin, the mTOR inhibitor that triggers a negative feedback loop on Akt/mTOR pathway. Taken together, these findings provide valuable insights into the anticancer effects of the SFE of the phalsak peel by revealing that auraptene, the major compound of it, induced apoptosis in accompanied with the inhibition of mTOR in SNU-1 cells.

  17. PPARγ induces growth inhibition and apoptosis through upregulation of insulin-like growth factor-binding protein-3 in gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, S.Y. [Department of Pediatrics, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Biomedical Research Institute, School of Medicine, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Kim, M.S.; Lee, M.K. [Department of Pediatrics, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Kim, J.S.; Yi, H.K. [Department of Biochemistry, School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of); Nam, S.Y. [Department of Alternative Therapy, Jeonju University, Jeonju (Korea, Republic of); Lee, D.Y.; Hwang, P.H. [Department of Pediatrics, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Biomedical Research Institute, School of Medicine, Chonbuk National University Hospital, Jeonju (Korea, Republic of)

    2015-01-13

    Peroxisome proliferator activator receptor-gamma (PPARγ) is a ligand-activated transcriptional factor involved in the carcinogenesis of various cancers. Insulin-like growth factor-binding protein-3 (IGFBP-3) is a tumor suppressor gene that has anti-apoptotic activity. The purpose of this study was to investigate the anticancer mechanism of PPARγ with respect to IGFBP-3. PPARγ was overexpressed in SNU-668 gastric cancer cells using an adenovirus gene transfer system. The cells in which PPARγ was overexpressed exhibited growth inhibition, induction of apoptosis, and a significant increase in IGFBP-3 expression. We investigated the underlying molecular mechanisms of PPARγ in SNU-668 cells using an IGFBP-3 promoter/luciferase reporter system. Luciferase activity was increased up to 15-fold in PPARγ transfected cells, suggesting that PPARγ may directly interact with IGFBP-3 promoter to induce its expression. Deletion analysis of the IGFBP-3 promoter showed that luciferase activity was markedly reduced in cells without putative p53-binding sites (-Δ1755, -Δ1795). This suggests that the critical PPARγ-response region is located within the p53-binding region of the IGFBP-3 promoter. We further demonstrated an increase in PPARγ-induced luciferase activity even in cells treated with siRNA to silence p53 expression. Taken together, these data suggest that PPARγ exhibits its anticancer effect by increasing IGFBP-3 expression, and that IGFBP-3 is a significant tumor suppressor.

  18. Silkworm Pupa Protein Hydrolysate Induces Mitochondria-Dependent Apoptosis and S Phase Cell Cycle Arrest in Human Gastric Cancer SGC-7901 Cells

    Directory of Open Access Journals (Sweden)

    Xiaotong Li

    2018-03-01

    Full Text Available Silkworm pupae (Bombyx mori are a high-protein nutrition source consumed in China since more than 2 thousand years ago. Recent studies revealed that silkworm pupae have therapeutic benefits to treat many diseases. However, the ability of the compounds of silkworm pupae to inhibit tumourigenesis remains to be elucidated. Here, we separated the protein of silkworm pupae and performed alcalase hydrolysis. Silkworm pupa protein hydrolysate (SPPH can specifically inhibit the proliferation and provoke abnormal morphologic features of human gastric cancer cells SGC-7901 in a dose- and time-dependent manner. Moreover, flow cytometry indicated that SPPH can induce apoptosis and arrest the cell-cycle in S phase. Furthermore, SPPH was shown to provoke accumulation of reactive oxygen species (ROS and depolarization of mitochondrial membrane potential. Western blotting analysis indicated that SPPH inhibited Bcl-2 expression and promoted Bax expression, and subsequently induced apoptosis-inducing factor and cytochrome C release, which led to the activation of initiator caspase-9 and executioner caspase-3, cleavage of poly (ADP-ribose polymerase (PARP, eventually caused cell apoptosis. Moreover, SPPH-induced S-phase arrest was mediated by up-regulating the expression of E2F1 and down-regulating those of cyclin E, CDK2 and cyclin A2. Transcriptome sequencing and gene set enrichment analysis (GSEA also revealed that SPPH treatment could affect gene expression and pathway regulation related to tumourigenesis, apoptosis and cell cycle. In summary, our results suggest that SPPH could specifically suppress cell growth of SGC-7901 through an intrinsic apoptotic pathway, ROS accumulation and cell cycle arrest, and silkworm pupae have a potential to become a source of anticancer agents in the future.

  19. ERK inhibition enhances TSA-induced gastric cancer cell apoptosis via NF-κB-dependent and Notch-independent mechanism.

    Science.gov (United States)

    Yao, Jun; Qian, Cui-Juan; Ye, Bei; Zhang, Xin; Liang, Yong

    2012-09-04

    To analyze the combined impact of the histone deacetylase inhibitor (HDACI) Trichostatin A (TSA) and the extracellular-signal-regulated kinase 1/2 (ERK1/2) inhibitor PD98059 on gastric cancer (GC) cell line SGC7901 growth. SGC7901 cells were treated with TSA, PD98059 or with a TSA-PD98059 combination. Effects of drug treatment on tumor cell proliferation, apoptosis, cell cycle progression, and cell signaling pathways were investigated by MTS assay, flow cytometry, Western blotting, chromatin immunoprecipitation (ChIP) assay, electrophoretic mobility shift assay (EMSA), and luciferase reporter assay, respectively. PD98059 enhanced TSA-induced cell growth arrest, apoptosis and activation of p21(WAF1/CIP1), but reversed TSA-induced activation of ERK1/2 and nuclear factor-κB (NF-κB). TSA alone up-regulated Notch1 and Hes1, and down-regulated Notch2, but PD98059 did not affect the trends of Notch1 and Notch2 induced by TSA. Particularly, PD98059 did potentiate the ability of TSA to down-regulate phospho-histone H3 protein, but increased levels of the acetylated forms of histone H3 bound to the p21(WAF1/CIP1) promoter, leading to enhanced expression of p21(WAF1/CIP1) in SGC7901 cells. PD98059 synergistically potentiates TSA-induced GC growth arrest and apoptosis by manipulating NF-κB and p21(WAF1/CIP1) independent of Notch. Therefore, concomitant administration of HDACIs and ERK1/2 inhibitors may be a promising treatment strategy for individuals with GC. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Propofol inhibits hypoxia/reoxygenation-induced human gastric epithelial cell injury by suppressing the Toll-like receptor 4 pathway

    Directory of Open Access Journals (Sweden)

    Jiao-Li Zhang

    2013-06-01

    Full Text Available This study aimed to investigate the role of the Toll-like receptor 4 (TLR4 pathway in normal human gastric epithelial (GES-1 cells under hypoxia/reoxygenation (H/R in vitro, and the effect of propofol on injured GES-1 cells as well as its possible mechanism. Before H/R induction, GES-1 cells were preconditioned with fat emulsion, propofol, or epigallocatechin gallate. Then cell viability, cell apoptosis, and related molecules in the cells were analyzed under experimental conditions. We found that propofol 50 μmol/L markedly inhibited the H/R injury under hypoxia 1.5 h/reoxygenation 2 hours by promoting GES-1 cell viability and decreasing cell apoptosis. The TLR4 signal may be involved in the protective effect of propofol against H/R injury. The malondialdehyde contents and superoxide dismutase activities were recovered under propofol preconditioning. In summary, propofol preconditioning may exert a protective effect on H/R injury in GES-1 cells and the mechanism may be via inhibition of the activated TLR4 signal under H/R conditions.

  1. Aspirin and omeprazole for secondary prevention of cardiovascular disease in patients at risk for aspirin-associated gastric ulcers.

    Science.gov (United States)

    García-Rayado, Guillermo; Sostres, Carlos; Lanas, Angel

    2017-08-01

    Cardiovascular disease is the most important cause of morbidity and mortality in the world and low-dose aspirin is considered the cornerstone of the cardiovascular disease prevention. However, low-dose aspirin use is associated with gastrointestinal adverse effects in the whole gastrointestinal tract. In this setting, co-therapy with a proton pump inhibitor is the most accepted strategy to reduce aspirin related upper gastrointestinal damage. In addition, some adverse effects have been described with proton pump inhibitors long term use. Areas covered: Low-dose aspirin related beneficial and adverse effects in cardiovascular system and gastrointestinal tract are reviewed. In addition, this manuscript summarizes current data on upper gastrointestinal damage prevention and adverse events with proton pump inhibition. Finally, we discuss the benefit/risk ratio of proton pump inhibitor use in patients at risk of gastrointestinal damage taking low-dose aspirin. Expert commentary: Nowadays, with the current available evidence, the combination of low-dose aspirin with proton pump inhibitor is the most effective therapy for cardiovascular prevention in patients at high gastrointestinal risk. However, further studies are needed to discover new effective strategies with less related adverse events.

  2. Aspirin-Induced Gastric Lesions Alters EGFR and PECAM-1 Immunoreactivity in Wistar Rats: Modulatory Action of Flavonoid Fraction of Musa Paradisiaca

    Directory of Open Access Journals (Sweden)

    Margaret Olutayo Alese

    2017-07-01

    CONCLUSION: The efficacy of Musa paradisiaca in attenuating the damaging effects of aspirin on the gastric mucosa was observed as there was a significantly increased reactivity for EGFR and PECAM-1 in the gastric corpus in a dose-dependent manner.

  3. Autoimmunity and Gastric Cancer

    Science.gov (United States)

    Bizzaro, Nicola; Antico, Antonio; Villalta, Danilo

    2018-01-01

    Alterations in the immune response of patients with autoimmune diseases may predispose to malignancies, and a link between chronic autoimmune gastritis and gastric cancer has been reported in many studies. Intestinal metaplasia with dysplasia of the gastric corpus-fundus mucosa and hyperplasia of chromaffin cells, which are typical features of late-stage autoimmune gastritis, are considered precursor lesions. Autoimmune gastritis has been associated with the development of two types of gastric neoplasms: intestinal type and type I gastric carcinoid. Here, we review the association of autoimmune gastritis with gastric cancer and other autoimmune features present in gastric neoplasms. PMID:29373557

  4. Human gastric signet ring carcinoma (KATO-III) cell apoptosis induced by Vitex agnus-castus fruit extract through intracellular oxidative stress.

    Science.gov (United States)

    Ohyama, Kunio; Akaike, Takenori; Imai, Masahiko; Toyoda, Hiroo; Hirobe, Chieko; Bessho, Toshio

    2005-07-01

    We have previously reported that an ethanol extract of the dried r