Publications (81) View all
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Article: Time-course proteomic analysis of taurocholate-induced necrotizing acute pancreatitis.
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ABSTRACT: Acute pancreatitis is an inflammatory disease of the pancreas, which varies greatly in course and severity. Severe forms are associated with serious local and/or systemic complications, and eventually death. The pathobiology of acute pancreatitis is complex. Animal models have been developed to investigate pathobiological processes and identify factors determining disease course. We performed a time-course proteomic analysis using a rat model of severe necrotizing acute pancreatitis induced by taurocholate perfusion in the pancreatic ducts. Results showed that levels of proteins associated to a given biological process changed in a coordinated fashion after disease onset. It was possible to follow the response of a particular pathobiological process to pancreatitis induction and to compare the course of protein pathways. Proteins involved in acinar cell secretion were found to follow a different kinetics than other cellular processes. After an initial decrease, secretory pathway-associated proteins raised again at 18 hours post-induction. This phenomenon coincided with a burst in the expression of pancreatitis-associated protein (REG3A), an acute phase protein produced by the exocrine pancreas, and with the decrease of classical markers of pancreatic injury, suggesting that the expression of proteins associated to the secretory pathway may be a modulating factor of pancreas injury. BIOLOGICAL SIGNIFICANCE: Acute pancreatitis (AP) is a complex inflammatory disease, the pathobiology of which is not yet fully understood. Various animal models, relying on different mechanisms of disease induction, have been developed in order to investigate pathobiological processes of AP. In this study, we performed a time-course proteomic analysis to investigate changes of the pancreas proteome occurring in an experimental model of AP induced by perfusion of taurocholate, a bile acid, into the pancreatic duct. This experimental model is characterized by a severe disease with pancreatic necrosis and systemic inflammation. The objectives of this study were to determine the kinetics of functionally related proteins in the early steps of the experimental disease in order to identify protein pathways playing key roles in AP pathobiology and to correlate these data with parameters classically used to assess disease severity. The present work provides for the first time an overview of protein expression in the pancreas during the course of taurocholate-induced necrotizing AP. We believe that correlation of these results with data obtained using proteomic or biochemical approaches in various experimental models of AP will help highlighting new features, generating hypotheses and constitute therefore a strong and reliable basis for further targeted investigations.Journal of proteomics 04/2013; · 5.07 Impact Factor -
Article: The role of transient elastography in the detection of liver disease in patients with chronic pancreatitis.
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ABSTRACT: BACKGROUND & AIMS: Quantification of liver stiffness with transient elastography (TE) is validated for staging hepatic fibrosis in chronic hepatitis C infection. The current study was aimed to assess the diagnostic performance of liver stiffness measurement for the determination of fibrosis stage in patients with chronic pancreatitis. METHODS: Thirty consecutive patients with chronic pancreatitis and increased liver enzyme were enrolled over a 2.5-year period. Eight liver living donor candidates were recruited to serve as internal controls. The TE values were compared with non-invasive fibrosis scoring systems including aspartate transaminase (AST)/alanine aminotransferase (ALT) ratio, APRI, non-alcoholic fatty liver disease NAFLD score, FIB-4 index and to liver histology. RESULTS: TE was successful in all patients. Stiffness values ranged from 3.1 to 69 kPa (mean 16.9). Liver stiffness was correlated with fibrosis stage (Spearman's correlation 0.73, P < 0.0001). Areas under receiver operator characteristics curves for fibrosis F = 4 were 0.92 for TE, 0.87 for FIB-4 index, 0.81 for APRI, 0.73 for NAFLD score and 0.71 for AST/ALT ratio. Optimal stiffness cut-off values for diagnosis fibrosis F = 4 was 10.9 kPa, with 90% sensitivity, 85% specificity and 86% accuracy. CONCLUSION: Our study provides for the first time evidence that liver stiffness in patients with chronic pancreatitis and concomitant cholestasis can be measured by TE.Liver international: official journal of the International Association for the Study of the Liver 03/2013; · 3.82 Impact Factor -
Article: Autologous bone marrow mononuclear cell transplantation in patients with decompensated alcoholic liver disease: a randomized controlled trial.
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ABSTRACT: Impaired liver regeneration is associated with a poor outcome in patients with decompensated alcoholic liver disease (ALD). We assessed whether autologous bone marrow mononuclear cell transplantation (BMMCT) improved liver function in decompensated ALD. 58 patients (mean age 54 yrs; mean MELD score 19, all with cirrhosis, 81% with alcoholic steatohepatitis at baseline liver biopsy) were randomized early after hospital admission to standard medical therapy (SMT) alone (n = 30), including steroids in patients with a Maddrey's score ≥32, or combined with G-CSF injections and autologous BMMCT into the hepatic artery (n = 28). Bone marrow cells were harvested, isolated and reinfused the same day. The primary endpoint was a ≥3 points decrease in the MELD score at 3 months, corresponding to a clinically relevant improvement in liver function. Liver biopsy was repeated at week 4 to assess changes in Ki67+/CK7+ hepatic progenitor cells (HPC) compartment. Both study groups were comparable at baseline. After 3 months, 2 and 4 patients died in the BMMCT and SMT groups, respectively. Adverse events were equally distributed between groups. Moderate alcohol relapse occurred in 31% of patients. The MELD score improved in parallel in both groups during follow-up with 18 patients (64%) from the BMMCT group and 18 patients (53%) from the SMT group reaching the primary endpoint (p = 0.43 (OR 1.6, CI 0.49-5.4) in an intention to treat analysis. Comparing liver biopsy at 4 weeks to baseline, steatosis improved (p<0.001), and proliferating HPC tended to decrease in both groups (-35 and -33%, respectively). Autologous BMMCT, compared to SMT is a safe procedure but did not result in an expanded HPC compartment or improved liver function. These data suggest either insufficient regenerative stimulation after BMMCT or resistance to liver regenerative drive in patients with decompensated alcoholic cirrhosis. Controlled-Trials.com ISRCTN83972743.PLoS ONE 01/2013; 8(1):e53719. · 4.09 Impact Factor -
Article: An Unusual Cause of Cholecystitis.
Gastroenterology 10/2012; · 11.68 Impact Factor -
Article: Clopidogrel and proton pump inhibitors--where do we stand in 2012?
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ABSTRACT: Clopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic events. Concomitant treatment with proton pump inhibitors in order to prevent gastrointestinal side effects is recommended by clinical guidelines. Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme Cytochrome 2C19 (CYP2C19) and proton pump inhibitors (PPIs) are extensively metabolized by the CYP2C19 isoenzyme as well. Several pharmacodynamic studies investigating a potential clopidogrel-PPI interaction found a significant decrease of the clopidogrel platelet antiaggregation effect for omeprazole, but not for pantoprazole. Initial clinical cohort studies in 2009 reported an increased risk for adverse cardiovascular events, when under clopidogrel and PPI treatment at the same time. These observations led the United States Food and Drug Administration and the European Medecines Agency to discourage the combination of clopidogrel and PPI (especially omeprazole) in the same year. In contrast, more recent retrospective cohort studies including propensity score matching and the only existing randomized trial have not shown any difference concerning adverse cardiovascular events when concomitantly on clopidogrel and PPI or only on clopidogrel. Three meta-analyses report an inverse correlation between clopidogrel-PPI interaction and study quality, with high and moderate quality studies not reporting any association, rising concern about unmeasured confounders biasing the low quality studies. Thus, no definite evidence exists for an effect on mortality. Because PPI induced risk reduction clearly overweighs the possible adverse cardiovascular risk in patients with high risk of gastrointestinal bleeding, combination of clopidogrel with the less CYP2C19 inhibiting pantoprazole should be recommended.World Journal of Gastroenterology 05/2012; 18(18):2161-71. · 2.47 Impact Factor
