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Le Touquet – Paris-Plage, France

Aubert J.,University of Rennes 1 | Begriche K.,University of Rennes 1 | Delannoy M.,University of Rennes 1 | Morel I.,University of Rennes 1 | And 10 more authors.
Journal of Pharmacology and Experimental Therapeutics | Year: 2012

Clinical investigations suggest that hepatotoxicity after acetaminophen (APAP) overdose could be more severe in the context of obesity and nonalcoholic fatty liver disease. The preexistence of fat accumulation and CYP2E1 induction could be major mechanisms accounting for such hepatic susceptibility. To explore this issue, experiments were performed in obese diabetic ob/ob and db/db mice. Preliminary investigations performed in male and female wild-type, ob/ob, and db/db mice showed a selective increase in hepatic CYP2E1 activity in female db/db mice. However, liver triglycerides in these animals were significantly lower compared with ob/ob mice. Next, APAP (500 mg/kg) was administered in female wild-type, ob/ob, and db/db mice, and investigations were carried out 0.5, 2, 4, and 8 h after APAP intoxication. Liver injury 8 h after APAP intoxication was higher in db/db mice, as assessed by plasma transaminases, liver histology, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. In db/db mice, however, the extent of hepatic glutathione depletion, levels of APAP-protein adducts, c-Jun N-terminal kinase activation, changes in gene expression, and mitochondrial DNA levels were not greater compared with the other genotypes. Furthermore, in the db/db genotype plasma lactate and β-hydroxybutyrate were not specifically altered, whereas the plasma levels of APAP-glucuronide were intermediary between wild-type and ob/ob mice. Thus, early APAP-induced hepato-toxicity was greater in db/db than ob/ob mice, despite less severe fatty liver and similar basal levels of transaminases. Hepatic CYP2E1 induction could have an important pathogenic role when APAP-induced liver injury occurs in the context of obesity and related metabolic disorders. Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics.

Jday-Daly I.,Laboratoire Of Biochimie Generale | Augereau-Vacher C.,Laboratoire Of Biochimie | De Curraize C.,Laboratoire Of Biochimie Metabolique | Fonfrede M.,Laboratoire Of Biochimie Metabolique | And 3 more authors.
Annales de Biologie Clinique | Year: 2011

As part of a tender AP-HP Paris Hospitals, an assessment of the reliability record of five blood glucose monitoring systems (BGMSs) (Optium Xceed (Abbott), Contour TS (Bayer), One Touch Ultra (Lifescan), Stat Strip Xpress (Nova) and Accu Check (Roche) and an evaluation of their sensitivity to changes in hematocrit were conducted in 4 hospitals of Paris. In terms of inaccuracy, all BGMSs have submitted CV repetability under the limits of acceptability. One BGMS (Lifescan) presented a CV of reproducibility outside limit of acceptability (13.1%). The inaccuracy was measured by a comparison method on multiparameter analyser relative to the hexokinase method for two sites, the glucose oxidase for the two others. The coefficients of correlation varied from 0.8405 to 0.9303. However, according to both defined acceptability criteria (absolute value difference between the result acquired on analyzer and those determined with the BGMS), the percentage of results outside acceptability was above 20% for two BGMSs (Abbott and Lifescan). Similarly, a net effect of changes in hematocrit was observed on the results of those two BGMSs.BGMSNovawas the most reliable, because of the correction device for hematocrit and blank substractions owed to interferences. In terms of expertise, BGMSs Nova and Roche have been selected with the best analytical performance and practicability satisfactory. In the future, accreditation with standard NF/EN 22870 requested for point of care testing, will require a close collaboration between biologists and clinicians to establish a system of strict quality control to detect deviations of these BGMSs.

Hauck F.,French Institute of Health and Medical Research | Hauck F.,University of Paris Descartes | Hauck F.,University Childrens Hospital Carl Gustav Carus | Hauck F.,Ludwig Maximilians University of Munich | And 8 more authors.
Clinical Immunology | Year: 2013

We describe a family with 12 members carrying a heterozygous germline FAS c.3G > T start codon mutation leading to FAS haploinsufficiency. One patient had autoimmune lymphoproliferative syndrome (ALPS), one had recovered from ALPS, and ten mutation-positive relatives (MPRs) were healthy. FAS-mediated apoptosis and surface expression of FAS in single-positive T cells were lower for MPRs but did not discriminate between them and the ALPS patient. However, double-negative (DN) T cells of the ALPS patient had no FAS expression due to somatic loss of heterozygosity. Our results in this kindred suggest that FAS haploinsufficiency does not cause ALPS-FAS, but that modifying genetic events are crucial for its pathogenesis. FAS surface expression on DN T cells should be assessed routinely and FAS haploinsufficient patients should be followed as its potential for lymphomagenesis is not well defined and a second hit might occur later on. © 2013 Elsevier Inc.

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