Federal University of São Paulo

About: Federal University of São Paulo is a education organization based out in São Paulo, Brazil. It is known for research contribution in the topics: Population & Transplantation. The organization has 27971 authors who have published 49365 publications receiving 935536 citations. The organization is also known as: Universidade Federal de São Paulo & Universidade Federal de Sao Paulo.

The ergosterol biosynthesis pathway, transporter genes, and azole resistance in Aspergillus fumigatus

Abstract: The continuous use of triazoles can result in the development of drug resistance. Azole-resistant clinical isolates, spontaneous and induced mutants of Aspergillus fumigatus have been documented. The azoles block the ergosterol biosynthesis pathway by inhibiting the enzyme 14-α-demethylase, product of the CYP51. Fungal azole resistance involves both amino acid changes in the target site that alter drug-target interactions and those that decrease net azole accumulation. The reduced intracellular accumulation has also been correlated with overexpression of multidrug resistance (MDR) efflux transporter genes of the ATP-binding cassette (ABC) and the major facilitator superfamily (MFS) classes. About 20 genes are involved in the A. fumigatus ergosterol biosynthesis pathway. There are several duplicated genes in this pathway. Interestingly, erg3 and erg11 showed two copies in A. fumigatus. In general, Aspergillus spp. have proportionally more MFS transporter encoding genes than Saccharomyces cerevisiae, S. pom...

Number Needed to Treat With Rosuvastatin to Prevent First Cardiovascular Events and Death Among Men and Women With Low Low-Density Lipoprotein Cholesterol and Elevated High-Sensitivity C-Reactive Protein: Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER)

Abstract: Background— As recently demonstrated, random allocation to rosuvastatin results in large relative risk reductions for first cardiovascular events among apparently healthy men and women with low levels of low-density lipoprotein cholesterol but elevated levels of high-sensitivity C-reactive protein. However, whether the absolute risk reduction among such individuals justifies wide application of statin therapy in primary prevention is a controversial issue with broad policy and public health implications. Methods and Results— Absolute risk reductions and consequent number needed to treat (NNT) values were calculated across a range of end points, timeframes, and subgroups using data from Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), a randomized evaluation of rosuvastatin 20 mg versus placebo conducted among 17 802 apparently healthy men and women with low-density lipoprotein cholesterol <130 mg/dL and high-sensitivity C-reactive protein ≥2 mg/L...

Strong HIV-1-specific T cell responses in HIV-1-exposed uninfected infants and neonates revealed after regulatory T cell removal.

Abstract: Background In utero transmission of HIV-1 occurs on average in only 3%-15% of HIV-1-exposed neonates born to mothers not on antiretroviral drug therapy. Thus, despite potential exposure, the majority of infants remain uninfected. Weak HIV-1-specific T-cell responses have been detected in children exposed to HIV-1, and potentially contribute to protection against infection. We, and others, have recently shown that the removal of CD4(+) CD25(+) T-regulatory (Treg) cells can reveal strong HIV-1 specific T-cell responses in some HIV-1 infected adults. Here, we hypothesized that Treg cells could suppress HIV-1-specific immune responses in young children. Methodology/principal findings We studied two cohorts of children. The first group included HIV-1-exposed-uninfected (EU) as well as unexposed (UNEX) neonates. The second group comprised HIV-1-infected and HIV-1-EU children. We quantified the frequency of Treg cells, T-cell activation, and cell-mediated immune responses. We detected high levels of CD4(+) CD25(+) CD127(-) Treg cells and low levels of CD4(+) and CD8(+) T cell activation in the cord blood of the EU neonates. We observed HIV-1-specific T cell immune responses in all of the children exposed to the virus. These T-cell responses were not seen in the cord blood of control HIV-1 unexposed neonates. Moreover, the depletion of CD4(+) CD25(+) Treg cells from the cord blood of EU newborns strikingly augmented both CD4(+) and CD8(+) HIV-1-specific immune responses. Conclusions/significance This study provides new evidence that EU infants can mount strong HIV-1-specific T cell responses, and that in utero CD4(+) CD25(+) T-regulatory cells may be contributing to the lack of vertical transmission by reducing T cell activation.