LCT showed tissue-specific damage to gill, heart, liver and kidney tissues of goldfish. NMR profiling combined with statistical methods such as orthogonal partial least squares discriminant analysis (OPLS-DA) and two-dimensional statistical total correlation spectroscopy (2D-STOCSY) was developed to discern metabolite changes occurring after one week LCT exposure in brain, heart and kidney tissues of goldfish. LCT exposure influenced levels of many metabolites

(e.g., leucine, isoleucine and valine in brain and kidney; lactate in brain, heart and kidney; alanine in brain and kidney; choline in brain, heart and kidney; taurine in brain, heart and kidney; N-acetylaspartate in brain; myo-inositol in brain; phosphocreatine in brain and heart; 2-oxoglutarate in brain; cis-aconitate LDN-193189 in brain, and etc.), and broke the balance of neurotransmitters and osmoregulators, evoked oxidative stress, disturbed metabolisms of energy and amino acids. The implication of glutamate-glutamine-gamma-aminobutyric axis in LCT induced toxicity was demonstrated for the first time. Our findings demonstrated the applicability and potential of metabolomics approach for the elucidation of toxicological effects of pesticides and the underlying mechanisms, and the discovery of biomarkers for pesticide pollution in aquatic environment. (C) 2013 Elsevier

B.V. All rights reserved.”
“OBJECTIVE: The purpose of this study was to explore the mechanism and utility of everolimus Stem Cells & Wnt inhibitor as a single-agent therapy

in preventing mouse laryngeal allograft rejection.\n\nSTUDY A1155463 DESIGN: Prospective animal study.\n\nSETTING: Academic research at a tertiary medical center.\n\nSUBJECTS AND METHODS: Fifteen recipient mice (five per group) were injected with everolimus (1 mg/kg/d) until euthanized at 15, 30, and 60 days posttransplantation. Five mice received transplants without immunosuppression and were euthanized at day 15. Larynges were graded for rejection severity. Draining lymph nodes and spleens were evaluated by flow cytometry to assess the systemic immunological environment.\n\nRESULTS: Each time group demonstrated minor allograft rejection (rejection severity scores: 2.51, 2.46, 2.78; no rejection, I; severe, 6). This was not significantly different between groups. Everolimus-treated mice had significantly less rejection at all time points compared with non-immunosuppressed mice. Flow cytometry showed a blunted cytotoxic T-cell response, differentiation favoring regulatory T-cells, and decreased number and function of dendritic cells.\n\nCONCLUSIONS: Everolimus successfully prevents laryngeal allograft rejection up to 60 days posttransplantation. It appears to increase the production of regulatory T-cells while decreasing cytotoxic T-cell and dendritic cell response.