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Dijon, France

Gautier T.,French Institute of Health and Medical Research | Gautier T.,University of Burgundy | Gautier T.,LipSTIC LabEx | Masson D.,French Institute of Health and Medical Research | And 7 more authors.
Expert Opinion on Therapeutic Targets | Year: 2016

Introduction: Over recent decades, attempts to ascertain the pro-atherogenic nature of plasma cholesteryl ester transfer protein (CETP) and to establish the relevance of its pharmacological blockade as a promising high density lipoproteins-raising and anti-atherogenic therapy have been disappointing.Areas covered: The current review focuses on CETP as a multifaceted protein, on genetic variations at the CETP gene and on their possible consequences for cardiovascular risk in human populations. Specific attention is given to physiological modulation of endogenous CETP activity by the apoC1 inhibitor. Finally, the rationale behind the need for selection of patients to treat is discussed in the light of recent studies.Expert opinion: At this stage one can only speculate on the clinical outcome of pharmacological CETP inhibitors in high-risk populations, but recent advances give cause to adjust the expectations from now on. The CETP effect is probably largely influenced by the overall metabolic state, and whether CETP blockade may be relevant or not in promoting cholesterol disposal is still questioned. The possible need for a careful stratification of patients to treat with CETP inhibitors is outlined. Finally, manipulation of CETP activity should be considered with caution in the context of sepsis and infectious diseases. © 2015 Taylor & Francis.

De Barros J.-P.P.,French Institute of Health and Medical Research | De Barros J.-P.P.,University of Burgundy | De Barros J.-P.P.,LipSTIC LabEx | Gautier T.,French Institute of Health and Medical Research | And 24 more authors.
Journal of Lipid Research | Year: 2015

Quantitation of plasma lipopolysaccharides (LPSs) might be used to document Gram-negative bacterial infection. In the present work, LPS-derived 3-hydroxymyristate was extracted from plasma samples with an organic solvent, separated by reversed phase HPLC, and quantitated by MS/MS. This mass assay was combined with the limulus amebocyte lysate (LAL) bioassay to monitor neutralization of LPS activity in biological samples. The described HPLC/MS/MS method is a reliable, practical, accurate, and sensitive tool to quantitate LPS. The combination of the LAL and HPLC/MS/MS analyses provided new evidence for the intrinsic capacity of plasma lipoproteins and phospholipid transfer protein to neutralize the activity of LPS. In a subset of patients with systemic inflammatory response syndrome, with documented infection but with a negative plasma LAL test, significant amounts of LPS were measured by the HPLC/MS/MS method. Patients with the highest plasma LPS concentration were more severely ill. HPLC/MS/MS is a relevant method to quantitate endotoxin in a sample, to assess the efficacy of LPS neutralization, and to evaluate the proinflammatory potential of LPS in vivo. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

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