This study showed that LA is protective against sulfite-induced VEP alterations and oxidative stress in the brain and retina. (C) 2008 Elsevier Inc. All rights reserved.”
“Several arenaviruses, including Lassa virus (LASV), are causative agents of hemorrhagic fever, for which effective therapeutic options are lacking. The LASV envelope glycoprotein (GP) gene was used to generate lentiviral pseudotypes to identify small-molecule inhibitors of viral entry. A benzimidazole derivative with potent antiviral activity was identified from a high-throughput screen utilizing this strategy. Subsequent lead optimization for antiviral EPZ004777 solubility dmso activity identified a modified structure, ST-193, with

a 50% inhibitory concentration (IC50) of 1.6 nM against LASV pseudotypes. ST-193 inhibited pseudotypes generated with other arenavirus envelopes

as well, including the remaining four commonly associated with hemorrhagic fever (IC(50)s for Junin, Machupo, Guanarito, and Sabia were in the 0.2 to 12 nM range) but exhibited no antiviral activity against pseudotypes incorporating either the GP from the LASV-related arenavirus lymphocytic choriomeningitis virus (LCMV) or the unrelated G protein from vesicular stomatitis virus, at concentrations of up to 10 mu M. Determinants of Chk inhibitor ST-193 sensitivity were mapped through a combination of LASV-LCMV domain-swapping experiments, genetic selection of viral variants, and site-directed mutagenesis. Taken together, these studies demonstrate that sensitivity to ST-193 is dictated by a segment of about 30 amino acids within the GP2 subunit. This region includes the carboxy-terminal region of the ectodomain and the predicted transmembrane domain of the envelope protein, revealing a novel antiviral target within the arenavirus envelope GP.”
“Prenatal alcohol exposure can affect brain

development, leading to behavioral problems, including overactivity, motor dysfunction and learning deficits. Despite warnings about the effects of drinking during pregnancy, rates of fetal alcohol syndrome remain unchanged and thus, there not is an urgent need to identify interventions that reduce the severity of alcohol’s teratogenic effects. Insulin-like growth factor-I (IGF-I) is neuroprotective against ethanol-related toxicity and promotes white matter production following a number of insults. Given that prenatal alcohol leads to cell death and white matter deficits, the present study examined whether IGF-I could reduce the severity of behavioral deficits associated with developmental alcohol exposure. Sprague-Dawley rat pups received ethanol intubations (5.25 g/kg/day) or sham intubations on postnatal days (PD) 4-9, a period of brain development equivalent to the third trimester. On PD 10-13, subjects from each treatment received 0 or 10 mu g IGF-I intranasally each day.