| 1. |
- Lundberg Santesson, Inger, 1959-, et al.
(författare)
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Benchmarking of the Nursing Program at Dalarna University
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Quality reviewThis report presents the result from a Benchmarking-project within the Nursing Program at Dalarna University 2012. Local team members are Jan Florin, Marie Elf, Tobias R Feldreich, Maria S Engström and Sofia Olovsson. Responsible for the project and a member of the Local team/Manager of the nursing Program; Inger L Santesson
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| 2. |
- Rudholm Feldreich, Tobias
(författare)
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Gastric acid secretion and gut peptides : mechanisms involved in inflammatory response
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The regulation of gastric acid secretion is complex and involves endocrine, paracrine, and neurocrine mechanisms. Among these, the interconnecting cross-talk between different gut peptides is an important part in the control of acid secretion. The aims of this thesis were (1) to develop a new method of measuring intragastric pH for prolonged periods of time, and (2) apply developed and in-use methods using different substances and their impact on gastric acid secretion in vivo experiments on rats. (3) To study the changes in acid output and the migrating motor complex (MMC) when subjected to different substances, and (4) to further study the alterations in expression of different gut peptides in tissue samples in vitro, and the impact of inflammation in the gut. The novel Bravo model developed gave reliable recordings compared to the chronic fistula model. The pH rose during treatment with esomeprazole and the acid output in the fistula model decreased accordingly. Gut peptides ghrelin and somatostatin increased in plasma when subjected to esomeprazole treatment, while gastrin remained unchanged. Ghrelin administered in bolus doses increased the intragastric pH in accordance with previous experiments. The gut peptides somatostatin, neurotensin, and vasoactive intestinal peptide increased during pentagastrin-stimulated infusion and challenge with hydrochloric acid and polyethylene glycol both in plasma and intestinal perfusate, though the most pronounced elevation was seen in perfusate and with somatostatin. Gastrazole gave the most extensive inhibitory effect on acid secretion compared to ranitidine and esomeprazole. The CCK2-receptor antagonist YF476 inhibited acid secretion long-term and increased concentrations of ghrelin and somatostatin in plasma, but gastrin remained low. Tissue mRNA content of the peptides and their receptors were unchanged except for the ghrelin receptor. When subdued to NSAID gastrin, CCK2-receptor and iNOS increased in mRNA expression while other peptides and receptors were unchanged. Administration of NPS evoked a response in the MMC pattern with irregular spiking and prolonged cycle length of the activity fronts, and the mRNA expression of iNOS, TNF, and IL-1ß increased in the tissue. In conclusion, The Bravo model can be used as a complement to the chronic fistula model for measurements of pH. The regulation of gastric acid secretion is not only limited to the stomach, but also present in the smaller intestine where release of somatostatin seems to be most important. Different mechanisms are involved in the blockage of acid secretion when subjected to YF476, but under NSAID treatment the expression of gastrin and its receptor CCK2 increase and COX- 2 is activated which demonstrates a novel pathway for the study of gastric ulcerations. NPS, a novel neuropeptide influences the gastric motility and could have a role in inflammatory responses seen in the changes in the migrating motor complex and inflammatory markers iNOS, TNF, and IL-1ß.
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| 3. |
- 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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