Representaciones sociales de la violencia contra la mujer entre mujeres habitantes de la comunidad de Paranoá/Itapoã de Brasilia-DF

O estudo investiga as representações sociais de mulheres com relação à violência doméstica, e, particularmente, da violência contra mulher. O objetivo geral é identificar os significados atribuídos pelas mulheres ao fenômeno da violência de gênero, buscando compreender categorias próprias de interpretação do fenômeno da violência doméstica, assim como os recursos disponíveis para apoiar às mulheres em situação de violência. Metodologicamente, o estudo lança mão de uma abordagem triangulada entre a Teoria das Representações Sociais e a Etnografia. Foram realizadas entrevistas com 30 mulheres que concordaram em participar do estudo. As entrevistas foram processadas pelo software AlCESTE, que distribuiu as falas das entrevistadas em quatro classes, onde a 1 e a 4 remetem, respectivamente, à prática da violência e à forma como ela se perpetua, seu conceito e representação social, enquanto que as categorias classificadas como 2 e 3 dizem respeito à fragilidade da lei Maria da Penha e a falta de credibilidade na sua aplicação. ______________________________________________________________________________________________________ ABSTRACTThe study investigates the social representations of women in regard to domestic violence, and, particularly, of intimate violence against woman. The main purpose is to identify the meanings attributed by these women to the gender violence phenomenon, aiming the identification of native categories of the domestic violence event, as well as to recognize available resources for supporting women in a violence situation. It was applied a triangulation methodological approach between the Theory of Social Representations and Ethnography. Interviews were carried out with 30 women who voluntarily agreed to participate in the study. The interviews were processed by the Alceste software, which distributed women’s narratives in four different classes. Fist and fourth relate, respectively, to the practice of violence and to the way it is perpetuated, its concept and social representation. Categories classified as 2 and 3 concern to the fragility of the national law Maria da Penha and the lack of credibility in its application. ______________________________________________________________________________________________________ RESUMENEl estudio investiga las representaciones sociales con relación a la violencia doméstica y, particularmente, de la violencia contra la mujer entre mujeres habitantes de esas comunidades El objetivo general es identificar los significados atribuidos por las mujeres al fenómeno de la violencia de género, tratando de comprender categorías propias de interpretación del fenómeno de la violencia doméstica, así como los recursos disponibles para apoyar a las mujeres en situación de violencia. Metodológicamente, el estudio se basa en un enfoque triangulado entre la Teoría de las Representaciones Sociales y la Etnografía. Fueron llevadas a cabo 30 entrevistas con mujeres que estuvieron de acuerdo en participar del estudio. las entrevistas se procesaron por medio del software Alceste, que distribuyó las narrativas de las entrevistadas en cuatro clases. Las clases 1 y 4 se refieren, respectivamente, a la práctica de la violencia y a la forma como ésta se perpetúa, su concepto y representación social. Las categorías clasificadas como 2 y 3 indican la fragilidad de la ley Maria da Penha y a la falta de credibilidad en su aplicación

Anti-Prion Activity of a Panel of Aromatic Chemical Compounds: <i>In Vitro</i> and <i>In Silico</i> Approaches

<div><p>The prion protein (PrP) is implicated in the Transmissible Spongiform Encephalopathies (TSEs), which comprise a group of fatal neurodegenerative diseases affecting humans and other mammals. Conversion of cellular PrP (PrP^C) into the scrapie form (PrP^Sc) is the hallmark of TSEs. Once formed, PrP^Sc aggregates and catalyzes PrP^C misfolding into new PrP^Sc molecules. Although many compounds have been shown to inhibit the conversion process, so far there is no effective therapy for TSEs. Besides, most of the previously evaluated compounds failed <i>in vivo</i> due to poor pharmacokinetic profiles. In this work we propose a combined <i>in vitro</i>/<i>in silico</i> approach to screen for active anti-prion compounds presenting acceptable drugability and pharmacokinetic parameters. A diverse panel of aromatic compounds was screened in neuroblastoma cells persistently infected with PrP^Sc (ScN2a) for their ability to inhibit PK-resistant PrP (PrP^Res) accumulation. From ∼200 compounds, 47 were effective in decreasing the accumulation of PrP^Res in ScN2a cells. Pharmacokinetic and physicochemical properties were predicted <i>in silico</i>, allowing us to obtain estimates of relative blood brain barrier permeation and mutagenicity. MTT reduction assays showed that most of the active compounds were non cytotoxic. Compounds that cleared PrP^Res from ScN2a cells, were non-toxic in the MTT assay, and presented a good pharmacokinetic profile were investigated for their ability to inhibit aggregation of an amyloidogenic PrP peptide fragment (PrP^109–149). Molecular docking results provided structural models and binding affinities for the interaction between PrP and the most promising compounds. In summary, using this combined <i>in vitro</i>/<i>in silico</i> approach we have identified new small organic anti-scrapie compounds that decrease the accumulation of PrP^Res in ScN2a cells, inhibit the aggregation of a PrP peptide, and possess pharmacokinetic characteristics that support their drugability. These compounds are attractive candidates for prion disease therapy.</p></div

Representative dot-blot showing PK-resistant PrP (PrP^Res) accumulated in ScN2a cells grown in the presence of compounds.

<p>ScN2a cells were grown for 4-well plates in the presence of compounds from the R series at 1, 5, and 10 μM final concentrations. Cell lysates were subjected to PK treatment and dot-blotting with antiserum R30. Control wells (C) show untreated cells.</p

<i>In silico</i> prediction of physicochemical and pharmacokinetic properties.

<p><i>In silico</i> prediction of physicochemical and pharmacokinetic properties.</p

Energies and stoichiometry ratios for binding of recombinant murine PrP (1AG2) to compounds from D, G, J, L, R and Y series obtained from molecular docking.

<p>Energies and stoichiometry ratios for binding of recombinant murine PrP (1AG2) to compounds from D, G, J, L, R and Y series obtained from molecular docking.</p

Evaluation of the compounds' capacity to delay PrP^Sen conversion into PrP^Res by RT-QuIC assay seeded with 263 K scrapie.

<p>RT-QuIC reactions were seeded with 10fg of 263 K infected hamster brain or the equivalent amount of normal brain homogenates (NBH). The substrate for the reaction was recombinant hamster PrP^90–231. NaCl was used at 300 mM final concentration. Compounds Y13 and Y17 were assayed at 25 and 50 μM. The assay was followed by ThT fluorescence (excitation 450 nm; emission 480 nm) emission over time (average of 4 replicate wells).</p

Dose-response curves showing PrP^Res accumulated in ScN2a cells grown in the presence of selected compounds.

<p>ScN2a cells were treated with compounds from the R and R' (panel A); G (panel B); D, J and Y (panel C); and C series (panel D) at 1, 5, or 10 µM. Control bar (medium) represents intensity density of the blot from wells without compound addition, corresponding to 100% of PrP^Res content. Quantification of the assay was done by integration of the density of each dot using ImageJ software considering as control the final DMSO concentration in each well. All bars had <b>*</b><i>P</i><0.05 in relation to control except those labeled as NS (non-significant).</p

Decrease of PrP^Res levels in ScN2a cells.

<p>ScN2a cells were treated with the compounds belonging to the L (panels A and B), G, R', R and Y (panel C) series at 10 µM. After four days of incubation with the compounds, cells were lysed, treated with PK and PrP^Res was detected in the dot-blot assay with anti-PrP antibody (R30). Control bar (medium) represents intensity density of the blot from wells without compound addition, corresponding to 100% of PrP^Res content. Quantification of the assay was done by integration of the density of each dot using ImageJ software. All bars had <b>*</b><i>P</i><0.05 in relation to control.</p

Dose-response curves for compounds from the J and Y series.

<p>Lysates of ScN2a cells grown in the presence of the compounds for 4-blotted as described in the Methods section. Quantification of the relative dot-blot signal intensities were done with ImageJ considering as the control the final DMSO concentration in each well. The curves were fitted by a sigmoidal curve with SigmaPlot software v. 10.0.</p