METHODS: Adult nonhuman primates underwent saline infusion/T2 acquisition, immediately followed by gadoteridol

infusion/T1 acquisition in the putamen and brainstem. Distribution volumes and spatial patterns were analyzed. Gadoteridol and adeno-associated virus encoding human aromatic l-amino acid decarboxylase (AAV2-hAADC) were co-infused under alternating T2/T1 acquisition in the thalamus, and hyperintense areas were compared with areas of subsequent transgene expression.

RESULTS: Ratios of distribution volume to infusion volume were similar between saline and gadoteridol RCD. Spatial overlap correlated well between T2 and T1 images. The second infusate followed BMS-754807 a spatiotemporal pattern similar to that of the first, filling the target area before developing extra-target distribution. Areas of human L-amino acid decarboxylase

expression correlated well with areas of both T1 and T2 hyperintensity observed during RCD.

CONCLUSION: Accuracy find more of cannula placement and initial infusate distribution may be safely determined by saline infusion without significantly altering the subsequent distribution of the tracer agent. T2 RCD provides detection of intraparenchymal convection-enhanced delivery in the uninjured brain and may predict subsequent distribution of a transgene after viral vector infusion.”
“Arenaviruses merit interest as clinically important human pathogens and include several causative agents, chiefly Lassa virus (LASV), of hemorrhagic fever disease in humans. There are no licensed LASV vaccines, and current antiarenavirus therapy is limited Stem Cells inhibitor to the use of ribavirin, which is only partially effective and is associated with significant side effects. The arenavirus glycoprotein (GP) precursor GPC is processed by the

cellular site 1 protease (S1P) to generate the peripheral virion attachment protein GP1 and the fusion-active transmembrane protein GP2, which is critical for production of infectious progeny and virus propagation. Therefore, S1P-mediated processing of arenavirus GPC is a promising target for therapeutic intervention. To this end, we have evaluated the antiarenaviral activity of PF-429242, a recently described small-molecule inhibitor of S1P. PF-429242 efficiently prevented the processing of GPC from the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) and LASV, which correlated with the compound’s potent antiviral activity against LCMV and LASV in cultured cells. In contrast, a recombinant LCMV expressing a GPC whose processing into GP1 and GP2 was mediated by furin, instead of S1P, was highly resistant to PF-429242 treatment.