Protection against recurrent stroke with resveratrol: endothelial protection.

Despite increased risk of a recurrent stroke following a minor stroke, information is minimal regarding the interaction between injurious mild cerebral ischemic episodes and the possible treatments which might be effective. The aim of the current study was to investigate recurrent ischemic stroke and whether resveratrol, a nutritive polyphenol with promising cardio- and neuro- protective properties, could ameliorate the associated brain damage. Experiments in adult rats demonstrated that a mild ischemic stroke followed by a second mild cerebral ischemia exacerbated brain damage, and, daily oral resveratrol treatment after the first ischemic insult reduced ischemic cell death with the recurrent insult (P<0.002). Further investigation demonstrated reduction of both inflammatory changes and markers of oxidative stress in resveratrol treated animals. The protection observed with resveratrol treatment could not be explained by systemic effects of resveratrol treatment including effects either on blood pressure or body temperature measured telemetrically. Investigation of resveratrol effects on the blood-brain barrier in vivo demonstrated that resveratrol treatment reduced blood-brain barrier disruption and edema following recurrent stroke without affecting regional cerebral blood flow. Investigation of the mechanism in primary cell culture studies demonstrated that resveratrol treatment significantly protected endothelial cells against an in vitro 'ischemia' resulting in improved viability against oxygen and glucose deprivation (39.6 ± 6.6% and 81.3 ± 9.5% in vehicle and resveratrol treated cells, respectively). An inhibition of nitric oxide synthesis did not prevent the improved cell viability following oxygen glucose deprivation but SIRT-1 inhibition with sirtinol partially blocked the protection (P<0.001) suggesting endothelial protection is to some extent SIRT-1 dependent. Collectively, the results support that oral resveratrol treatment provides a low risk strategy to protect the brain from enhanced damage produced by recurrent stroke which is mediated in part by a protective effect of resveratrol on the endothelium of the cerebrovasculature.

Discovery and SAR of benzyl phenyl ethers as inhibitors of bacterial phenylalanyl-tRNA synthetase.

A series of benzyl phenyl ethers (BPEs) is described that displays potent inhibition of bacterial phenylalanyl-tRNA synthetase. The synthesis, SAR, and select ADMET data are provided.

Intercalation of alcohols in Ag sulfonates: topotactic behavior despite flexible layers.

This article presents the inaugural intercalation study of a layered metal sulfonate network. Silver triflate forms intercalation complexes with straight chain primary alcohols from ethanol (C(2)H(5)OH) to eicosanol (C(20)H(41)OH). Single-crystal data for the EtOH adduct, 1, are presented which show that the intercalation is coordinative to Ag. In contrast to many other layered hosts, no preheating of Ag triflate is required to liberate a coordination site for intercalation to take place, owing to the ability of the triflate ion to reorient. Crystal structure parameters for 1: C(4)H(6)F(6)S(2)O(7)Ag(2), a = 5.345(7) A, b = 11.310(2) A, c = 12.004(2) A, alpha = 116.87(1) degrees, beta = 90.46(1) degrees, gamma = 99.59(1) degrees, triclinic, space group P, Z = 2. Intercalate 1 presents the triflate ion in an unprecedented mu(5)-coordination mode. PXRD data on the family of complexes show that the intercalation is topotactic, as verified by the linear increase in d-spacing and calculated c-axis lengths for the intercalates, with increasing chain length. The data also show that the alcohol intercalates adopt an interdigitated rather than bilayer arrangement.