RESUMO
Life stress and mucosal inflammation may influence symptom onset and severity in certain gastrointestinal disorders, particularly irritable bowel syndrome (IBS), in connection with dysregulated intestinal barrier. However, the mechanism responsible remains unknown. Crowding is a validated animal model reproducing naturalistic psychosocial stress, whose consequences on gut physiology remain unexplored. Our aims were to prove that crowding stress induces mucosal inflammation and intestinal dysfunction, to characterize dynamics in time, and to evaluate the implication of stress-induced mast cell activation on intestinal dysfunction. Wistar-Kyoto rats were submitted to 15 days of crowding stress (8 rats/cage) or sham-crowding (2 rats/cage). We measured spontaneous and corticotropin-releasing factor-mediated release of plasma corticosterone. Stress-induced intestinal chrono-pathobiology was determined by measuring intestinal inflammation, epithelial damage, mast cell activation and infiltration, and intestinal barrier function. Corticosterone release was higher in crowded rats throughout day 15. Stress-induced mild inflammation, manifested earlier in the ileum and the colon than in the jejunum. While mast cell counts remained mostly unchanged, piecemeal degranulation increased along time, as the mucosal content and luminal release of rat mast cell protease-II. Stress-induced mitochondrial injury and increased jejunal permeability, both events strongly correlated with mast cell activation at day 15. Taken together, we have provided evidences that long-term exposure to psychosocial stress promotes mucosal inflammation and mast cell-mediated barrier dysfunction in the rat bowel. The notable resemblance of these findings with those in some IBS patients, support the potential interest and translational validity of this experimental model for the research of stress-sensitive intestinal disorders, particularly IBS.
Assuntos
Aglomeração/psicologia , Trato Gastrointestinal/imunologia , Mucosa Intestinal/imunologia , Mastócitos/imunologia , Meio Social , Estresse Psicológico/imunologia , Animais , Contagem de Células , Colo/imunologia , Corticosterona/sangue , Hormônio Liberador da Corticotropina , Modelos Animais de Doenças , Citometria de Fluxo , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/patologia , Abrigo para Animais , Íleo/imunologia , Imuno-Histoquímica , Mucosa Intestinal/metabolismo , Síndrome do Intestino Irritável/imunologia , Síndrome do Intestino Irritável/psicologia , Jejuno/imunologia , Masculino , Mitocôndrias/metabolismo , Permeabilidade , Ratos , Ratos Endogâmicos WKY , Estresse Psicológico/etiologia , Fatores de TempoRESUMO
BACKGROUND AND OBJECTIVE: The aim of this study is to assess the prevalence of peptic ulcer rebleeding by comparing patients who received omeprazole versus pantoprazole i.v. as well as to study the costs of each treatment. PATIENTS AND METHODS: Retrospective and observational study. Information was gathered on sex and age of the patients, the diagnosis of upper gastrointestinal bleeding (UGB) according to the classification of Forrest, the type of proton pump inhibitor (PPI) i.v. used and the treatment regimen, presence or absence of rebleeding, mortality and data on health costs through a pharmacoeconomic cost-effectiveness analysis. RESULTS: We included 807 patients, 490 of whom (60.7%) received pantoprazole and 317 (39.3%) omeprazole. There was no difference between the average age of both groups, 61.2 years vs 62.3, p=0.544; sex, 71% men vs 68.6%, P=.78; the percentage of patients within Forrest I was 35.1% vs 42%, P=.05, in grade II was 50.2% vs 40.4%, P=.006 and in grade III was 14.7% vs 17.7%, P=.259. The number of vials per day of treatment was significantly lower in the pantoprazole group from the third to fifth day, with no differences in the first two days and the sixth. There was rebleeding in 8.2% of patients treated with pantoprazole and 11.7% with omeprazole, P=.098. 2.2% of patients treated with pantoprazole died vs 2.6% treated with omeprazole, P=.086. The expected cost of a patient treated with pantoprazole was 2188.25 euro vs 3279.02 euro with omeprazole, P<.001. CONCLUSIONS: While the results of the administration of omeprazole vs pantoprazole i.v. in patients with UGB are similar, the latter turns out to have a better cost-effectiveness profile.