Populações de minhocas em diferentes sistemas de uso do solo na região leste do Estado de Santa Catarina.

Resumo. FERTBIO 2014

Primary hepatocytes as targets for hepatitis C virus replication

Much of our current understanding of hepatitis C virus (HCV) replication has hailed from the use of a small number of cloned viral genomes and transformed hepatoma cell lines. Recent evidence suggests that lipoproteins play a key role in the HCV life cycle and virus particles derived from the sera of infected patients exist in association with host lipoproteins. This report will review the literature on HCV replication in primary hepatocytes and transformed cell lines, focusing largely on host factors defining particle entry

Objective response by mRECIST as a predictor and potential surrogate end point of overall survival in advanced HCC

Background & Aims: The Modified Response Evaluation Criteria in Solid Tumors (mRECIST) was developed to overcome the limitations of standard RECIST criteria in response assessment of hepatocellular carcinoma (HCC). We aimed to investigate whether objective response by mRECIST accurately predicted overall survival (OS) in patients with advanced HCC treated with systemic targeted therapies and also to preliminarily assess this endpoint as a potential surrogate of OS.Methods: Individual patient data from the BRISK-PS randomized phase III trial comparing brivanib vs. placebo (the first to prospectively incorporate mRECIST) were used to analyze objective response as a predictor of OS in a time-dependent covariate analysis. Patients with available imaging scans during follow-up were included (n = 334; 85% of those randomized). Moreover, a correlation of the survival probability in deciles vs. the observed objective response was performed to evaluate its suitability as a surrogate end-point.Results: Objective response was observed in 11.5% and 1.9% of patients treated with brivanib and placebo respectively, and was associated with a better survival (median OS 15.0 vs. 9.4 months, p < 0.001). In addition, objective response had an independent prognostic value (HR = 0.48; 95% confidence interval [CI], 0.26-0.91, p = 0.025) along with known prognostic factors. Finally, objective response showed promising results as a surrogate of OS in this trial (R = -0.92; 95% CI, -1 to -0.73, p < 0.001). It was an early indicator of the treatment effect (median time to objective response was 1.4 months).Conclusions: Objective response by mRECIST in advanced HCC predicts OS and thus can be considered as a candidate surrogate end-point. Further studies are needed to support this finding.Lay summary: There is a need to identify surrogate end-points for overall survival in advanced hepatocellular carcinoma. We studied patients from the phase III BRISK trial, comparing brivanib treatment with placebo after sorafenib progression. We demonstrate that objective response is an independent predictor of survival and qualifies as a potential surrogate end-point for overall survival in this patient population.Clinical trial number: NCT00825955

Taming of Furfurylidenes by Chiral Bismuth-Rhodium Paddlewheel Catalysts. Preparation and Functionalization of Optically Active 1,1-Disubstituted (Trifluoromethyl)cyclopropanes

Although 2-furyl-carbenes (furfurylidenes) are prone to instantaneous electrocyclic ring opening, chiral [BiRh]-paddlewheel complexes empowered by London dispersion allow (trifluoromethyl)furfurylidene metal complexes to be generated from a bench-stable triftosylhydrazone precursor. These reactive intermediates engage in asymmetric [2+1] cycloadditions and hence open entry into valuable trifluoromethylated cyclopropane or −cyclopropene in optically active form, which are important building blocks for medicinal chemistry but difficult to make otherwise

Chiral Bismuth-Rhodium Paddlewheel Complexes Empowered by London Dispersion: The C-H Functionalization Nexus

Heterobimetallic [BiRh] tetracarboxylate catalysts endowed with 1,3-disilylated phenylglycine paddlewheels benefit from interligand London dispersion. They were originally designed for asymmetric cyclopropanation but are now shown to perform very well in asymmetric C−H functionalization reactions too. Because of the confined ligand sphere about the derived donor/acceptor carbenes, insertions into unhindered methyl groups are kinetically favored, although methylene units also react with excellent levels of asymmetric induction; even gaseous ethane is a suitable substrate. Moreover, many functional groups in both partners are tolerated. The resulting products are synthetically equivalent to the outcome of traditional asymmetric ester alkylation, allylation, benzylation, propargylation and aldol reactions and therefore constitute a valuable nexus to more conventional chemical logic