Analysis of the procedures used to evaluate suicide crime scenes in Brazil: a statistical approach to interpret reports.

This study uses statistical techniques to evaluate reports on suicide scenes; it utilizes 80 reports from different locations in Brazil, randomly collected from both federal and state jurisdictions. We aimed to assess a heterogeneous group of cases in order to obtain an overall perspective of the problem. We evaluated variables regarding the characteristics of the crime scene, such as the detected traces (blood, instruments and clothes) that were found and we addressed the methodology employed by the experts. A qualitative approach using basic statistics revealed a wide distribution as to how the issue was addressed in the documents. We examined a quantitative approach involving an empirical equation and we used multivariate procedures to validate the quantitative methodology proposed for this empirical equation. The methodology successfully identified the main differences in the information presented in the reports, showing that there is no standardized method of analyzing evidences.

Mangiferin, a natural occurring glucosyl xanthone, increases susceptibility of rat liver mitochondria to calcium-induced permeability transition.

Mitochondrial permeability transition (MPT) is a Ca(2+)-dependent, cyclosporine A-sensitive, non-selective inner membrane permeabilization induced by a wide range of agents or conditions, which has often been associated with necrotic or apoptotic cell death. When mitochondria isolated from livers of rats treated with the natural occurring glucosyl xanthone mangiferin (40 mg/kg body weight) were exposed in vitro to Ca(2+), they underwent CsA, NEM, and ADP-sensitive high amplitude swelling and associated membrane potential dissipation, release of pre-accumulated Ca(2+), oxidation of thiol groups, and depletion of GSH, without changes in the NAD(P)H redox state. The same treatment reduced the phosphorylation rate of mitochondria and the resting respiration by around 4 and 11%, respectively, as well as generation of reactive oxygen species (ROS) by organelle. The in vitro exposure of untreated mitochondria to mangiferin plus Ca(2+) also resulted in oxidation of thiol groups, in the same way that the compound inhibited the Ca(2+)-induced peroxidation of mitochondrial membrane lipids. The spectrum of mangiferin during its oxidation by the H(2)O(2)/HRP system showed a characteristic absorption peak at 380 nm, which decreased immediately after reaction was started; two isosbestic points at around 336 and 412 nm, with a blue shift in the position of the maxima absorption of mangiferin were observed, suggesting their conversion into one oxidation product. Glutathione abolished this decrease of absorbance, suggesting that the oxidation product of mangiferin forms adducts with GSH. We propose that Ca(2+) increases levels of mitochondria-generated ROS, which reacts with mangiferin producing quinoid derivatives, which in turn react with the most accessible mitochondrial thiol groups, thus triggering MPT. It seems probable that the free radical scavenging activity of mangiferin shifts its anti-oxidant protection to the thiol arylation. An interesting proposition is that accumulation of mangiferin quinoid products would take place in cells exposed to an overproduction of ROS, such as cancer cells, where the occurrence of MPT-mediated apoptosis may be a cellular defence mechanism against excessive ROS formation.

High performance liquid chromatography analysis of a 4-anilinoquinazoline derivative (PD153035), a specific inhibitor of the epidermal growth factor receptor tyrosine kinase, in rat plasma.

The quinazoline derivative, 4-N-(3'-bromo-phenyl)amino-6,7-dimethoxyquinazoline (PD153035), has recently been identified as a potential drug for the treatment of proliferative disease. Here, we report a sensitive high performance liquid chromatography (HPLC)-based quantitative detection method for measurement of PD153035 levels in rat plasma. Sample pretreatment involved a two-step extraction with chloroform. The analytes were separated on a column packed with OmniSpher C18 material and eluted with acetonitrile-0.1 M ammonium acetate, pH 7.2 (70:30, v/v). The column effluent was monitored by UV detection at 330 nm. A linear response was achieved over the concentration range 0.50-100.00 microM using multilevel calibration with an internal standard. The analytical method inter- and intra-run accuracy and precision were better than +/-15%. The lower limit of quantification was 0.50 microM. The method has been applied to study the preclinical pharmacokinetics of this compound in rats.