“
“Mutations in several subgenomic regions of hepatitis C virus (HCV) have been implicated in influencing the response to interferon (IFN) therapy. Sequences within HCV NS5A (PKR binding domain [PKRBD], IFN sensitivity-determining region [ISDR], and variable region 3 [V3]) were analyzed for the pretreatment serum Bleomycin ic50 samples of 60 HCV genotype 1-infected patients treated with pegylated IFN plus ribavirin (1b, n = 47; 1a, n = 13) but with different treatment outcomes, those with sustained virologic responses (SVR; n = 36) or non-responders (NR; n = 24). Additionally, the sequence of the PKR/eIF-2 alpha phosphorylation homology domain (E2-PePHD)
region was determined for 23 patients (11 SVR and 12 NR). The presence of >4 mutations in the PKRBD region was associated with SVR (P = 0.001) and early virologic responses (EVR; 12 weeks) (P = 0.037) but not rapid virologic responses (4 weeks). In the ISDR, the difference was almost statistically significant (68% of SVR patients buy IACS-10759 with
mutations versus 45% without mutations; P = 0.07). The V3 region had a very high genetic variability, but this was not related to SVR. Finally, the E2-PePHD (n = 23) region was well conserved. The presence of >4 mutations in the PKRBD region (odds ratio [OR] = 9.9; P = 0.006) and an age of :540 years (OR = 3.2; P = 0.056) were selected in a multivariate analysis as predictive factors of SVR. NS5A sequences from serum samples taken after 1 month of treatment and posttreatment were examined for 3 SVR and 15 NR patients to select treatment-resistant viral subpopulations, and it was found that in the V3 and flanking regions, Oxymatrine the mutations increased significantly in posttreatment sera (P = 0.05). The genetic variability in the PKRBD (>4 mutations) is a predictive factor of SVR and EVR in HCV genotype 1 patients treated with pegylated IFN and ribavirin.”
“OBJECTIVE: Intracranial stenosis (IS) is associated with significant morbidity and mortality from hypoperfusion and thromboembolism. We used computational fluid dynamic methods
to analyze luminal patterns of wall shear stress (WSS), a known critical modulator of endothelial function, within patient-based IS lesions undergoing percutaneous angioplasty and stenting.
METHODS: High-resolution three-dimensional rotational angiographic data sets were reconstructed to yield a fine-resolution computational mesh allowing application of pulsatile computational fluid dynamic analysis with a non-Newtonian realistic model of blood. WSS and its gradient were analyzed spatiotemporally in five IS lesions before and after percutaneous angioplasty and stenting.
RESULTS: WSS within the stenosis reached average shear magnitudes of 1870 +/- 783 dyn/cm(2) with rapidly reversing direction to oscillating low values in the recirculation zone.