Anticancer compound ABT-263 accelerates apoptosis in virus-infected cells and imbalances cytokine production and lowers survival rates of infected mice.

ABT-263 and its structural analogues ABT-199 and ABT-737 inhibit B-cell lymphoma 2 (Bcl-2), BCL2L1 long isoform (Bcl-xL) and BCL2L2 (Bcl-w) proteins and promote cancer cell death. Here, we show that at non-cytotoxic concentrations, these small molecules accelerate the deaths of non-cancerous cells infected with influenza A virus (IAV) or other viruses. In particular, we demonstrate that ABT-263 altered Bcl-xL interactions with Bcl-2 antagonist of cell death (Bad), Bcl-2-associated X protein (Bax), uveal autoantigen with coiled-coil domains and ankyrin repeats protein (UACA). ABT-263 thereby activated the caspase-9-mediated mitochondria-initiated apoptosis pathway, which, together with the IAV-initiated caspase-8-mediated apoptosis pathway, triggered the deaths of IAV-infected cells. Our results also indicate that Bcl-xL, Bcl-2 and Bcl-w interact with pattern recognition receptors (PRRs) that sense virus constituents to regulate cellular apoptosis. Importantly, premature killing of IAV-infected cells by ABT-263 attenuated the production of key pro-inflammatory and antiviral cytokines. The imbalance in cytokine production was also observed in ABT-263-treated IAV-infected mice, which resulted in an inability of the immune system to clear the virus and eventually lowered the survival rates of infected animals. Thus, the results suggest that the chemical inhibition of Bcl-xL, Bcl-2 and Bcl-w could potentially be hazardous for cancer patients with viral infections.

Toxicity of chromated copper arsenate: a study in mice.

Chromated copper arsenate (CCA) was widespread used as a chemical wood preservative with application in the construction of playground equipment, fences, jetties, and naval. Environmental protection agency (EPA) had limited the use of CCA-treated wood on 2002, due to probable implications on both human and environmental health. Although this fact, several industries pursue the use of this product within their manufactories. In addition, the durability of this wood for 60 years, makes these treated products an hazard to the public health. In the present work, studies were explored exposing mice to CCA, during 14, 24, 48, and 96 h for the assessment of acute toxicity of CCA. Kidney and liver were removed, prepared for histology and for metalloid, and copper content evaluation by high resolution inductively coupled plasma mass spectroscopy. The histological results evidenced apparently normal structures for control animals and group exposed to As2O5. On the contrary, the renal sections of the animals treated with CCA revealed epithelium cells desquamation, hyaline, and granular casts in renal tubules lumen. Furthermore, high levels of arsenic were detected in the kidney of animals treated with CCA over 14 and 48 h, being significantly greater than controls. Although this approach underlines the potential hazard of CCA on some vital organs, further testing may be required to establish the impacts on other functions.

Improved superovulatory response in beef cattle following ovarian follicular ablation using a simplified transvaginal device.

The influence of the timing for the ablation of dominant follicle(s) prior to superovulatory treatment, and its effect on ovarian follicular growth and embryo yield, still remain elusive in cattle. The present study was designed to evaluate the effects of: (1) the day of the estrous cycle, at mid-diestrus, for the onset of superstimulation of follicular development, (2) the presence or absence of large ovarian follicles (ovary status) and (3) the time of follicular ablation, in hours, prior to the superovulatory treatment, on the superovulatory response in cattle. From a total of 244 superovulatory treatments and embryo collections in nulliparous and multiparous females, 76 were conducted after follicular ablation using a simplified transvaginal puncture cannula. Results from the present study indicated that the presence of large palpable follicle(s) at the onset of superstimulation of follicular development markedly reduced the superovulatory response. In addition, follicular ablation at 0 h or at 24 h prior to the onset of the superstimulation treatment significantly increased the number of total viable embryos. However, superovulatory responses were not affected by the day of the estrous cycle for the onset of follicular superstimulation and by the animal category (heifers or cows). In conclusion, the ablation of palpable follicle(s) 24 h or immediately prior to the onset of gonadotropin treatment, from days 8 to 12 of the estrous cycle (day 0, behavioral estrus), increased the total number of transferable embryos per flushing in cattle.

Amperometric determination of dipyrone in pharmaceutical formulations with a flow cell containing gold electrodes from recordable compact discs.

A simple, rapid, and precise amperometric method for quantification of dipyrone in pharmaceutical formulations is presented. The proposed method permits determinations in the 10(-7) mol L(-1) of the analyte and enables 90 determinations h(-1), employing only 100 microL of sample per determination. This method is based on the direct quantification of dipyrone in many pharmaceutical products, avoiding cumbersome processes such as previous separations, solvent extraction, or sample filtration. This new procedure was applied to commercial pharmaceutical tablets, and the results obtained were in excellent agreement with the ones obtained by the classical iodometric method.

Gold electrodes from compact discs modified with platinum for amperometric determination of ascorbic acid in pharmaceutical formulations.

A simple, rapid and precise amperometric method has been developed for quantification of ascorbic acid (AA) in pharmaceutical formulations using flow-injection analysis (FIA). A slice of recordable compact disc (CD) modified by electrodeposition of platinum was employed as the working electrode. The proposed flow system allows determinations in the 1 mumol l(-1) of the analyte and enables 90 determinations per h, employing only 150-mul sample. The method permits the direct quantification of ascorbic acid in many pharmaceutical products, avoiding cumbersome processes as previous separations, solvent extraction or sample filtration. This new procedure was applied to commercial pharmaceutical tablets and the results obtained were identical than the ones obtained by the classical iodometric method. The calibration plots for freshly prepared ascorbic acid standards were highly linear in the concentration range of 1-10 mumol l(-1) with a relative standard deviation (R.S.D.) <1%. For all real samples studied, the deviations were situated between 0.5 and 8.7%.

Modified microelectrodes and multivariate calibration for flow injection amperometric simultaneous determination of ascorbic acid, dopamine, epinephrine and dipyrone.

Flow injection amperometric quantification of ascorbic acid (AA), dopamine (DA), epinephrine (EP) and dipyrone (DI) in mixtures (in the microgram g-1 range) was successfully performed by using an array of microelectrodes with units modified by the electrodeposition of different noble metals, together with multivariate calibration analysis. The four groups of microelectrodes utilized included a pure gold electrode and electrodes modified by electrodeposition of platinum, palladium or a mixture of platinum + palladium. The array of microelectrodes was inserted in a flow cell and the amperometric data acquisition was performed with a four-channel potentiostat. The analysis of the resulting signals was carried out by a multivariate calibration method, using a group of 16 standard mixtures selected by a two-level factorial design. The analysis of synthetic samples and pharmaceutical compounds containing AA and DI led to very similar values to those obtained by the classical iodimetric analysis. The average absolute errors (in microgram g-1) calculated for each analyte were 0.3, 0.2, 0.4 and 0.4 for AA, DA, EP and DI, respectively.