35 resultados para 337.9
8-Methoxy-naphtho[2,3-b]thiophen-4,9-quinone, a non-competitive inhibitor of trypanothione reductase
Resumo:
The enzyme trypanothione reductase is a recognised drug target in trypanosomatids and has been used in the search of new compounds with potential activity against diseases such as leishmaniasis, Chagas disease and African trypanosomiasis. 8-Methoxy-naphtho [2,3-b] thiophen-4,9-quinone was selected in a screening of natural and synthetic compounds using an in vitro assay with the recombinant enzyme from Trypanosoma cruzi. Its mode of inhibition fits a non-competitive model with respect to the substrate (trypanothione) and to the co-factor (NADPH), with Ki-values of 5 and 3.6 µM, respectively. When tested against human glutathione reductase, this compound did not display any significant inhibition at 100 µM, indicating a good selectivity against the parasite enzyme.
Resumo:
Toxoplasma gondii infection is an important mediator of ocular disease in Brazil more frequently than reported from elsewhere. Infection and pathology are characterized by a strong proinflammatory response which in mice is triggered by interaction of the parasite with the toll-like receptor (TLR)/MyD88 pathway. A powerful way to identify the role of TLRs in humans is to determine whether polymorphisms at these loci influence susceptibility to T. gondii-mediated pathologies. Here we report on a small family-based study (60 families; 68 affected offspring) undertaken in Brazil which was powered for large effect sizes using single nucleotide polymorphisms with minor alleles frequencies > 0.3. Of markers in TLR2, TLR5 and TLR9 that met these criteria, we found an association Family Based Association Tests [(FBAT) Z score = 4.232; p = 1.5 x 10-5; p corrected = 1.2 x 10-4] between the C allele (frequency = 0.424; odds ratio = 7; 95% confidence interval 1.6-30.8) of rs352140 at TLR9 and toxoplasmic retinochoroiditis in Brazil. This supports the hypothesis that direct interaction between T. gondii and TLR9 may trigger proinflammatory responses that lead to severe pathologies such as the ocular disease that is associated with this infection in Brazil.
Resumo:
Abstract OBJECTIVE Determining which is the most effective solution (heparin flush compared to 0.9% saline flush) for reducing the risk of occlusions in central venous catheters (CVC) in adults. METHOD The systematic review followed the principles proposed by the Cochrane Handbook; critical analysis, extraction and synthesis of data were performed by two independent researchers; statistical analysis was performed using the RevMan program 5.2.8. RESULTS Eight randomized controlled trials and one cohort study were included and the results of the meta-analysis showed no difference (RR=0.68, 95% CI=0.41-1.10; p=0.12). Analysis by subgroups showed that there was no difference in fully deployed CVC (RR=1.09, CI 95%=0.53-2.22;p=0.82); Multi-Lumen CVC showed beneficial effects in the heparin group (RR=0.53, CI 95%=0.29-0.95; p=0.03); in Double-Lumen CVC for hemodialysis (RR=1.18, CI 95%=0.08-17.82;p=0.90) and Peripherally inserted CVC (RR=0.14, CI 95%=0.01-2.60; p=0.19) also showed no difference. CONCLUSION Saline solution is sufficient for maintaining patency of the central venous catheter, preventing the risks associated with heparin administration.