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Toulouse, France

Charef S.,University Paris Est Creteil | Tulliez M.,Service Hematologie Biologique | Esmilaire L.,Service Biochimie | Courty J.,University Paris Est Creteil | Papy-Garcia D.,University Paris Est Creteil
Food and Chemical Toxicology | Year: 2010

Heparan sulfate mimetic polymers promotes tissue repair when injected locally in doses of 1-2. mg/kg by various routes. These biopolymers, have been extensively studied for their diverse biological activities. However, there is no detailed report investigating the toxicity of OTR4120. In this study, the acute and subchronic (30. days) toxicity of varying levels of OTR4120 was investigated in mice after intraperitoneal administration.The results showed that no significant toxicological changes were observed when 50. mg/kg body weight per day OTR4120 was administered to mice. But when the dose was increased to 60 and 70. mg/kg body weight per day, the clotting time was significantly prolonged. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities were reduced female and male at dose 70. mg/kg body weight per day. These blood biochemistry data suggest that OTR4120 have a hepatoprotective effect. Based on these results, it can be concluded that the no adverse effect level of OTR4120 is 50. mg/kg body weight per day. © 2010 Elsevier Ltd. Source

Rival T.,Service Reanimation | Cinq-Frais C.,Service Biochimie | Cinq-Frais C.,French Institute of Health and Medical Research | Silva-Sifontes S.,Service Reanimation | And 10 more authors.
Biochimie | Year: 2013

In septic shock patients, alterations of plasma phospholipid fatty acid profile have never been described. The purpose of this monocentric, non-interventional, observational prospective study was to describe this fatty acid profile in the early phase of septic shock in intensive care unit. Thirty-seven adult patients with septic shock were included after the first day of stay in intensive care unit, before any form of artificial nutritional support. Plasma phospholipid fatty acid composition was determined by gas chromatography. All biological data from patients with septic shock were compared with laboratory reference values. Patients presented hypocholesterolemia and hypertriglyceridemia. They had low concentrations of phospholipid fatty acids specifically n-6 and n-3 polyunsaturated fatty acids (PUFAs) with a high n-6/n-3 ratio. Plasma phospholipid PUFA concentrations were strongly correlated with cholesterolemia. PUFAs/SFAs (saturated fatty acids) and PUFAs/MUFAs (monounsaturated fatty acids) ratios were low because of low percentage of n-6 and n-3 PUFAs and high percentage of SFAs and MUFAs. Low levels of plasma long chain PUFAs (≥20 carbons) were significantly associated with mortality at 28th day. In conclusion, plasma phospholipid FA profile of septic patients is very characteristic, close to that of acute respiratory distress syndrome and mortality is associated with long chain PUFA decrease. This profile could be explained by numerous non-exclusive physio-pathological processes 1) an activation of hepatic de novo lipogenesis that could contribute to hepatic steatosis, 2) an elevated adipose tissue lipolysis, 3) an increased free radical attack of FA by oxidative stress, 4) an over-production of inflammatory lipid mediators. © 2013 Elsevier Masson SAS. All rights reserved. Source

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