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- Rudholm, Tobias, et al.
(författare)
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Bravo capsule system optimizes intragastric pH monitoring over prolonged time : Effects of ghrelin on gastric acid and hormone secretion in the rat
- 2008
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 14:40, s. 6180-6187
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To evaluate measurements of intragastric pH with the Bravo capsule system over a prolonged time. Methods: A Bravo capsule was placed inside the rat gastric body and pH was studied for periods up to five consecutive. days. For comparison, a gastric fistula model was used. Effects of ghrelin and esomeprazole, with or without pentagastrin, on gastric pH were studied. In addition, effects of esomeprazole on plasma ghrelin, gastrin and somatostatin were analyzed. Results: All rats recovered after surgery. The average 24-h pH during free feeding was 2.3 +/- 0.1 (n = 20) with a variation of 18% +/- 6% over 5 d. Ghrelin, 2400 pmol/kg, t.i.d. increased pH from 1.7 +/- 0.1 to 3.1 +/- 0.3 (P < 0.01) as recorded with the Bravo system. After esomeprazole (1 mg/kg, 3 mg/kg and 5 mg/kg) there was a dose-dependent pH increase of maximally 3.4 +/- 0.1, with day-to-day variation over the entire period of 8% +/- 3%. The fistula and pH studies generated similar results. Acid inhibition with esomeprazole increased plasma ghrelin from 10 +/- 2 pmol/L to 65 +/- 26 pmol/L (P < 0.001), and somatostatin from 10 +/- 2 pmol/L to 67 +/- 18 pmol/L (P < 0.001). Conclusion: pH measurements with the Bravo capsule are reliable, and comparable to those of the gastric fistula model. The Bravo system optimizes accurate intragastric pH monitoring over prolonged periods and allows both short- and long-term evaluation of effects of drugs and hormones.
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| 2. |
- Webb, Dominic-Luc, et al.
(författare)
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The type 2 CCK/gastrin receptor antagonist YF476 acutely prevents NSAID-induced gastric ulceration while increasing iNOS expression
- 2013
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Ingår i: Naunyn-Schmiedeberg's Archives of Pharmacology. - : Springer Verlag (Germany). - 0028-1298 .- 1432-1912. ; 386:1, s. 41-49
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Tidskriftsartikel (refereegranskat)abstract
- YF476 differs from the proton pump inhibitor (PPI) esomeprazole in mode of action by antagonizing the type 2 receptor of cholecystokinin/gastrin (CCK-2R). YF476 protection against diclofenac-induced gastric ulcers was compared to esomeprazole and correlated with plasma levels of hormones related to gastric pH (gastrin, ghrelin, and somatostatin), gastric gene expression of these hormones, their receptors, and inducible nitric oxide synthase (iNOS). YF476 or esomeprazole pretreatments were followed by diclofenac. Four hours later, gastric tissue was excised and analyzed for ulcer index. An intragastrically implanted Bravo capsule measured pH for 5 days during YF476 plus pentagastrin treatment. Changes in gene expression were assayed for gastrin, ghrelin, and somatostatin; their receptors; and iNOS. YF476 acutely (within 4 h) protected against diclofenac-induced gastric ulcers equivalent to esomeprazole. Gastric pH recorded during 5 days in the presence of pentagastrin was 1.83 (+/- 0.06). YF476 raised pH to 3.67 (+/- 0.09) and plasma ghrelin, gastrin, and somatostatin increased. YF476 increased gene expression of somatostatin receptor and gastrin, while ghrelin receptor decreased; transcripts coding ghrelin, somatostatin, and CCK-2R remained unchanged. In the presence of diclofenac, esomeprazole increased expression of all these transcripts and that of iNOS, while YF476 yielded only decreased CCK-2R and increased iNOS transcripts. YF476 is a potential new preventative treatment for patients at risk of nonsteroidal antiinflammatory drug (NSAID)-induced ulceration. Gastric gene expressions of ghrelin, gastrin, and somatostatin and their receptors differ between esomeprazole and YF476. Despite these differences and different modes of action to raise gastric pH, both drugs acutely increase iNOS, suggesting iNOS expression parallels pH.
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