Brain Vitamin E Deficiency During Development Is Associated With Increased Glutamate Levels and Anxiety in Adult Mice

Vitamin E, the most important lipophilic radical scavenging antioxidant in vivo, has a pivotal role in brain. In an earlier study, we observed that adult mice with a defect in the gene encoding plasma phospholipid transfer protein (PLTP) display a moderate reduction in cerebral vitamin E levels, and exacerbated anxiety despite normal locomotion and memory functions. Here we sought to determine whether dietary vitamin E supplementation can modulate neurotransmitter levels and alleviate the increased anxiety phenotype of PLTP-deficient (PLTP−/−) mice. To address this question, a vitamin E-enriched diet was used, and two complementary approches were implemented: (i) “early supplementation”: neurotransmitter levels and anxiety were assessed in 6 months old PLTP−/− mice born from vitamin E-supplemented parents; and (ii) “late supplementation”: neurotransmitter levels and anxiety were assessed in 6 months old PLTP−/− mice fed a vitamin E-enriched diet from weaning. Our results show for the first time that an inadequate supply of vitamin E during development, due to moderate maternal vitamin E deficiency, is associated with reduced brain vitamin E levels at birth and irreversible alterations in brain glutamate levels. They also suggest this deficiency is associated with increased anxiety at adulthood. Thus, the present study leads to conclude on the importance of the micronutrient vitamin E during pregnancy

Up to 425 GHz All Optical Frequency Down‐Conversion Clock Recovery Based on Quantum Dash Fabry‐Perot Mode‐Locked Laser

Postdeadline Session C " OFDM and OTDM "International audienceWe demonstrate that quantum‐dash mode‐locked laser can perform all optical frequency down‐conversion clock recovery up to 425 GHz. We measured 0.3 dB penalty on the optical recovered clock for 170 Gbit/s signal

Cytotoxic dendritic cells generated from cancer patients.

International audienceKnown for years as professional APCs, dendritic cells (DCs) are also endowed with tumoricidal activity. This dual role of DC as killers and messengers may have important implications for tumor immunotherapy. However, the tumoricidal activity of DCs has mainly been investigated in animal models. Cancer cells inhibit antitumor immune responses using numerous mechanisms, including the induction of immunosuppressive/ tolerogenic DCs that have lost their ability to present Ags in an immunogenic manner. In this study, we evaluated the possibility of generating tumor killer DCs from patients with advanced-stage cancers. We demonstrate that human monocyte-derived DCs are endowed with significant cytotoxic activity against tumor cells following activation with LPS. The mechanism of DC-mediated tumor cell killing primarily involves peroxynitrites. This observed cytotoxic activity is restricted to immature DCs. Additionally, after killing, these cytotoxic DCs are able to activate tumor Ag-specific T cells. These observations may open important new perspectives for the use of autologous cytotoxic DCs in cancer immunotherapy strategies

Possible mediators of metabolic endotoxemia in women with obesity and women with obesity-diabetes in The Gambia.

AIMS/HYPOTHESIS: Translocation of bacterial debris from the gut causes metabolic endotoxemia (ME) that results in insulin resistance, and may be on the causal pathway to obesity-related type 2 diabetes. To guide interventions against ME we tested two hypothesised mechanisms for lipopolysaccharide (LPS) ingress: a leaky gut and chylomicron-associated transfer following a high-fat meal. METHODS: In lean women (n = 48; fat mass index (FMI) 9.6 kg/m2), women with obesity (n = 62; FMI 23.6 kg/m2) and women with obesity-diabetes (n = 38; FMI 24.9 kg/m2) we used the lactulose-mannitol dual-sugar permeability test (LM ratio) to assess gut integrity. Markers of ME (LPS, EndoCAb IgG and IgM, IL-6, CD14 and lipoprotein binding protein) were assessed at baseline, 2 h and 5 h after a standardised 49 g fat-containing mixed meal. mRNA expression of markers of inflammation, macrophage activation and lipid metabolism were measured in peri-umbilical adipose tissue (AT) biopsies. RESULTS: The LM ratio did not differ between groups. LPS levels were 57% higher in the obesity-diabetes group (P < 0.001), but, contrary to the chylomicron transfer hypothesis, levels significantly declined following the high-fat challenge. EndoCAb IgM was markedly lower in women with obesity and women with obesity-diabetes. mRNA levels of inflammatory markers in adipose tissue were consistent with the prior concept that fat soluble LPS in AT attracts and activates macrophages. CONCLUSIONS/INTERPRETATION: Raised levels of LPS and IL-6 in women with obesity-diabetes and evidence of macrophage activation in adipose tissue support the concept of metabolic endotoxemia-mediated inflammation, but we found no evidence for abnormal gut permeability or chylomicron-associated post-prandial translocation of LPS. Instead, the markedly lower EndoCAb IgM levels indicate a failure in sequestration and detoxification

Distribution et role metabolique de l'apolipoproteine A-4 serique humaine

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Rôle de la protéine de transfert des phospholipides (PLTP) dans l'athérogénèse (modifications phénotypiques des lymphocytes et des macrophages)

DIJON-BU Médecine Pharmacie (212312103) / SudocSudocFranceF

Identification et caractérisation de l'inhibiteur physiologique de la protéine de transfert des esters de cholestérol (CETP) chez l'homme

DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Implication de la protéine de transfert des phospholipides (PLTP) dans la thrombose et le choc endotoxique

DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Rôle de la protéine de transfert des phospholipides (PLTP) dans le métabolisme de la vitamine E in vivo

DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF