Blunting the response to endotoxin in healthy subjects: effects of various doses of intravenous fish oil

Objective: To test the dose response effect of infused fish oil (FO) rich in n-3 PUFAs on the inflammatory response to endotoxin (LPS) and on membrane incorporation of fatty acids in healthy subjects. Design: Prospective, sequential investigation comparing three different FO doses. Subjects: Three groups of male subjects aged 26.8±3.2years (BMI 22.5±2.1). Intervention: One of three FO doses (Omegaven®10%) as a slow infusion before LPS: 0.5g/kg 1day before LPS, 0.2g/kg 1day before, or 0.2g/kg 2h before. Measurements and results: Temperature, hemodynamic variables, indirect calorimetry and blood samples (TNF-α, stress hormones) were collected. After LPS temperature, ACTH and TNF-α concentrations increased in the three groups: the responses were significantly blunted (p<0.0001) compared with the control group of the Pluess et al. trial. Cortisol was unchanged. Lowest plasma ACTH, TNF-α and temperature AUC values were observed after a single 0.2g/kg dose of FO. EPA incorporation into platelet membranes was dose-dependent. Conclusions: Having previously shown that the response to LPS was reproducible, this study shows that three FO doses blunted it to various degrees. The 0.2g/kg perfusion immediately before LPS was the most efficient in blunting the responses, suggesting LPS capture in addition to the systemic and membrane effect

Mol Vis

PURPOSE: To analyze in vivo the function of chicken acidic leucine-rich epidermal growth factor-like domain containing brain protein/Neuroglycan C (gene symbol: Cspg5) during retinal degeneration in the Rpe65(-)/(-) mouse model of Leber congenital amaurosis. METHODS: We resorted to mice with targeted deletions in the Cspg5 and retinal pigment epithelium protein of 65 kDa (Rpe65) genes (Cspg5(-)/(-)/Rpe65(-)/(-)). Cone degeneration was assessed with cone-specific peanut agglutinin staining. Transcriptional expression of rhodopsin (Rho), S-opsin (Opn1sw), M-opsin (Opn1mw), rod transducin alpha subunit (Gnat1), and cone transducin alpha subunit (Gnat2) genes was assessed with quantitative PCR from 2 weeks to 12 months. The retinal pigment epithelium (RPE) was analyzed at P14 with immunodetection of the retinol-binding protein membrane receptor Stra6. RESULTS: No differences in the progression of retinal degeneration were observed between the Rpe65(-)/(-) and Cspg5(-)/(-)/Rpe65(-)/(-) mice. No retinal phenotype was detected in the late postnatal and adult Cspg5(-)/(-) mice, when compared to the wild-type mice. CONCLUSIONS: Despite the previously reported upregulation of Cspg5 during retinal degeneration in Rpe65(-)/(-) mice, no protective effect or any involvement of Cspg5 in disease progression was identified

The Fetal Hypothalamus Has the Potential to Generate Cells with a Gonadotropin Releasing Hormone (GnRH) Phenotype

Neurospheres (NS) are colonies of neural stem and precursor cells capable of differentiating into the central nervous system (CNS) cell lineages upon appropriate culture conditions: neurons, and glial cells. NS were originally derived from the embryonic and adult mouse striatum subventricular zone. More recently, experimental evidence substantiated the isolation of NS from almost any region of the CNS, including the hypothalamus. Here we report a protocol that enables to generate large quantities of NS from both fetal and adult rat hypothalami. We found that either FGF-2 or EGF were capable of inducing NS formation from fetal hypothalamic cultures, but that only FGF-2 is effective in the adult cultures. The hypothalamic-derived NS are capable of differentiating into neurons and glial cells and most notably, as demonstrated by immunocytochemical detection with a specific anti-GnRH antibody, the fetal cultures contain cells that exhibit a GnRH phenotype upon differentiation. This in vitro model should be useful to study the molecular mechanisms involved in GnRH neuronal differentiation