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Hospital de Órbigo, Spain

Pereda J.,University of Valencia | Perez S.,University of Valencia | Escobar J.,University of Valencia | Arduini A.,University of Valencia | And 5 more authors.
PLoS ONE | Year: 2012

Background: Obesity is a prognostic factor for severity in acute pancreatitis in humans. Our aim was to assess the role of oxidative stress and abdominal fat in the increased severity of acute pancreatitis in obese rats. Methodology: Taurocholate-induced acute pancreatitis was performed in lean and obese Zucker rats. Levels of reduced glutathione, oxidized glutathione, L-cysteine, cystine, and S-adenosylmethionine were measured in pancreas as well as the activities of serine/threonine protein phosphatases PP1 and PP2A and tyrosin phosphatases. Isoprostane, malondialdehyde, triglyceride, and free fatty acid levels and lipase activity were measured in plasma and ascites. Lipase activity was measured in white adipose tissue with and without necrosis and confirmed by western blotting. Findings: Under basal conditions obese rats exhibited lower reduced glutathione levels in pancreas and higher triglyceride and free fatty acid levels in plasma than lean rats. S-adenosyl methionine levels were markedly increased in pancreas of obese rats. Acute pancreatitis in obese rats led to glutathione oxidation and lower reduced glutathione levels in pancreas together with decreased activities of redox-sensitive phosphatases PP1, and PP2A. S-adenosyl methionine levels decreased but cystine levels increased markedly in pancreas upon pancreatitis. Acute pancreatitis triggered an increase in isoprostane levels in plasma and ascites in obese rats. Free fatty acid levels were extremely high in pancreatitis-associated ascitic fluid from obese rats and lipase was bound with great affinity to white adipose tissue, especially to areas of necrosis. Conclusions: Our results show that oxidative stress occurs locally and systemically in obese rats with pancreatitis favouring inactivation of protein phosphatases in pancreas, which would promote up-regulation of pro-inflammatory cytokines, and the increase of isoprostanes which might cause powerful pulmonary and renal vasoconstriction. Future studies are needed to confirm the translational relevance of the present findings obtained in a rat model of taurocholate-induced pancreatic damage and necrosis. © 2012 Pereda et al. Source


Herranz Bachiller M.T.,Rio Hortega Hospital | Barrio Andres J.,Rio Hortega Hospital | Fernandez Salazar L.,Universitary Clinic Hospital | Ruiz-Zorrilla R.,Rio Hortega Hospital | And 2 more authors.
Scandinavian Journal of Gastroenterology | Year: 2016

Objective: Endoscopic recurrence in Crohn's disease occurs in up to 80% of patients during the first year after surgery. Due to this, these patients need close monitoring. Faecal calprotectin has been proposed to be used as a non-invasive marker to monitor inflammatory activity. Up to now the use of faecal markers in endoscopic recurrence has been scarcely studied and with contradictory results. Material and methods: This was a cross-sectional observational study of diagnostic validity. It included all patients with Crohn's disease (CD) and ileocolic resection retrospectively who had had an ileocolonoscopy and a determination of faecal calprotectin before this colonoscopy, from 2007 to 2015. Results: Ninety-seven patients were included. We observed that the mean value of faecal calprotectin increased as the Rutgeerts score increased. The variable of that most statistical significance obtained in bivariate analysis was faecal calprotectin (p < 0.0001). Area under curve (AUC) of faecal calprotectin in endoscopic recurrence was 0.74 (95% CI: 0.644-0.842), and an optimal cut-off of 60 mcrgr/gr, obtained a score of 0.45 using Youden test. This indicated that calprotectin would have 88% Sensitivity and 58% Specificity in detecting any recurrence, the NPV was approximately 83,9%. None of the other variables studied had a significant correlation. Conclusion: Faecal calprotectin predicts endoscopic recurrence in CD patients who have gone through surgery, however the cut-off point is still a problem so we cannot recommend calprotectin as a substitute of colonoscopy for CD monitoring and treatment adjustment. © 2016 Taylor & Francis. Source


Escobar J.,University of Valencia | Pereda J.,University of Valencia | Arduini A.,University of Valencia | Sandoval J.,University of Valencia | And 10 more authors.
Biochemical Pharmacology | Year: 2012

Reactive oxygen species are considered mediators of the inflammatory response and tissue damage in acute pancreatitis. We previously found that the combined treatment with oxypurinol-as inhibitor of xanthine oxidase-and pentoxifylline-as inhibitor of TNF-α production-restrained local and systemic inflammatory response and decreased mortality in experimental acute pancreatitis. Our aims were (1) to determine the time-course of glutathione depletion and oxidation in necrotizing pancreatitis in rats and its modulation by oxypurinol and pentoxifylline; (2) to determine whether TNF-α is responsible for glutathione depletion in acute pancreatitis; and (3) to elucidate the role of oxidative stress in the inflammatory cascade in pancreatic AR42J acinar cells. We report here that oxidative stress and nitrosative stress occur in pancreas and lung in acute pancreatitis and the co-treatment with oxypurinol and pentoxifylline prevents oxidative stress in both tissues. Oxypurinol was effective in preventing glutathione oxidation, whereas pentoxifylline abrogated glutathione depletion. This latter effect was independent of TNF-α since glutathione depletion occurred in mice deficient in TNF-α or its receptors after induction of pancreatitis. The beneficial effects of oxypurinol in the inflammatory response may also be ascribed to a partial inhibition of MEK1/2 activity. Pentoxifylline markedly reduced the expression of Icam1 and iNos induced by TNF-α in vitro in AR42J cells. Oxidative stress significantly contributes to the TNF-α-induced up-regulation of Icam and iNos in AR42J cells. These results provide new insights into the mechanism of action of oxypurinol and pentoxifylline as anti-inflammatory agents in acute pancreatitis. © 2011 Elsevier Inc. Source

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