SERPINB3 inibisce il poro di transizione della permeabilità mitocondriale attraverso la regolazione della produzione di ROS mitocondriali e incrementa la resistenza ai trattamenti chemioterapici

Resistance to chemotherapeutic agents is well known in patients with hepatocarcinoma. Inhibition of the mitochondrial permeability transition pore (PTP) is a crucial step in tumor cell resistance to apoptosis induced by anticancer drugs. Since SERPINB3 is overexpressed in hepatocellular carcinoma and has an anti-apoptotic activity, aim of the study was to assess the role of this serpin on PTP modulation during treatment with chemotherapeutic agents. HepG2 cells stably transfected with SERPINB3 where assayed for cell death induced by Cisplatin, Doxorubicin, Etoposide and 5-Fluorine Uracil. Reactive Oxygen Species (ROS) were detected with dichlorofluorescein. Threshold of PTP opening was evaluated by CRC assay and Complex I activity was determined by spectrophotometric assay. After cell death induction by Cisplatin and Doxorubicin, HepG2 cells expressing SERPINB3 showed a significant increase in viability compared to controls, while there was no difference in cell death after Etoposide and 5-FU treatments. The addition of the antioxidant N-acetyl cysteine abrogated cell death induction by Cisplatin and Doxorubicin, suggesting that SERPINB3 protects from death through an antioxidant activity. Since Cisplatin and Doxorubicin induce mitochondrial oxidative stress and favor PTP opening, cells were treated with the PTP inducer EM20-25 that acts at mitochondrial level. In presence of SERPINB3 the effect of EM20-25 resulted in PTP opening inhibition and decreased ROS formation. Subcellular localization analysis revealed that a fraction of SERPINB3 was located in mitochondria and that it increased after death-promoting treatments. Mitochondrial SERPINB3 was found associated to respiratory chain Complex I by immunoprecipitation experiments. In vitro analysis confirmed the inhibition by SERPINB3 of Complex I activity, known as one of the main sources of mitochondrial ROS. In conclusion, SERPINB3 acts at mitochondrial level protecting cells from chemotherapeutic-induced oxidative stress and consequent cell death. This antioxidant function could represent a relevant advantage for a transformed cell to balance its ROS equilibrium and for SB3-expressing cells exposed to anticancer treatments

Gold(III)-pyrrolidinedithiocarbamato Derivatives as Antineoplastic Agents

Transition metals offer many possibilities in developing potent chemotherapeutic agents. They are endowed with a variety of oxidation states, allowing for the selection of their coordination numbers and geometries via the choice of proper ligands, leading to the tuning of their final biological properties. We report here on the synthesis, physico-chemical characterization, and solution behavior of two gold(III) pyrrolidinedithiocarbamates (PDT), namely [AuIIIBr2(PDT)] and [AuIIICl2(PDT)]. We found that the bromide derivative was more effective than the chloride one in inducing cell death for several cancer cell lines. [AuIIIBr2(PDT)] elicited oxidative stress with effects on the permeability transition pore, a mitochondrial channel whose opening leads to cell death. More efficient antineoplastic strategies are required for the widespread burden that is cancer. In line with this, our results indicate that [AuIIIBr2(PDT)] is a promising antineoplastic agent that targets cellular components with crucial functions for the survival of tumor cells

Baruch Spinoza. Natura, Diritto, Potentia

Nel tentativo di inquadrare il pensiero di Baruch Spinoza nel secolo XVII, il saggio delinea un confronto con lo sviluppo dottrinale del giusnaturalismo moderno, e indaga le implicazioni della premessa immanentistica in particolare alle luce del problema della secolarizzazione, chiave interpretativa precisa per rintracciare la ragione delle discontinuit\ue0 che emergono tra la prospettiva del filosofo olandese e il paradigma elaborato dalla scuola del diritto naturale laico

Estudos sobre aplicação do pó da casca de pinhão para remoção de violeta genciana em solução aquosa

TCC (graduação) - Universidade Federal de Santa Catarina. Centro de Ciências Físicas e Matemáticas. Curso de Química.Devido a crescente problemática de contaminação ambiental por efluentes da indústria têxtil contendo altos níveis de concentração de corantes, encontrar meios eficazes e sustentáveis de tratamentos para esses resíduos se torna cada vez mais necessário. A adsorção é um método muito empregado na remoção de substâncias e adsorventes naturais são estudados com o objetivo de verificar as suas capacidades de adsorção e, assim, encontrar alternativas versáteis e de baixo custo para a remoção de corantes em resíduos aquosos. O pinhão, semente da Araucaria angustifólia, é muito popular na região sul do Brasil no período do inverno, principalmente no estado de Santa Catarina. Seu consumo gera as cascas como resíduos, que são descartados. Referências na literatura apontam que o emprego da casca do pinhão como adsorvente se mostra eficaz na remoção de corantes de efluentes. Este trabalho tem como objetivo verificar a aplicabilidade desse biossorvente, em forma de pó, na remoção do corante violeta genciana de soluções aquosas. O estudo do efeito do pH na adsorção revelou que pH entre 3 e 7 são as melhores faixas para remoção do corante. Estudos cinéticos evidenciaram que o processo de adsorção acontece por meio do modelo de pseudo-segunda ordem. Os dados obtidos pelas isotermas de adsorção foram tratados pelos modelos de Langmuir e Freundlich, determinando-se a capacidade máxima de adsorção em 11,20 mg g-1. O estudo completo de adsorção revelou que o pó da casca do pinhão tem eficácia na tratativa de remoção do corante violeta genciana de soluções aquosas

Estratégias para a vinculação das gestantes no pré-natal odontológico, em uma UBS de Curitiba

Orientador : Cristhiane Aparecida Mariot.Projeto Técnico (especialização) - Universidade Federal do Paraná, Setor de Ciências Sociais Aplicadas. Curso de Especialização em Gestão da SaúdeInclui referênciasResumo: Este trabalho é uma proposta de Projeto Técnico a ser realizada em uma Unidade Básica de Saúde do Município de Curitiba. Observa-se que nesta UBS um número reduzido de gestantes realiza a consulta odontológica durante o pré-natal, sendo que a realização destas consultas é importante para a orientação sobre os cuidados com a saúde bucal da mãe e do bebê, além do atendimento odontológico básico da gestante, evitando inflamações e infecções, as quais podem acarretar parto prematuro e bebê de baixo peso. Este projeto tem como objetivo a elaboração de propostas que visem a melhoria no acesso e no fluxo de atendimento das gestantes vinculadas nesta UBS, de uma forma que tenham um cuidado integral por toda a equipe de saúde. A metodologia utilizada para a comprovação da situação observada foi a busca por dados através de relatórios no sistema de saúde informatizado de Curitiba, o e-saúde. O resultado da análise destes dados indicou que apenas 9,2% das gestantes que foram vinculadas nesta UBS de fevereiro a outubro de 2013 realizaram pelo menos uma avaliação odontológica durante seu pré-natal. As propostas de melhoria incluíram o estabelecimento de um fluxo de assistência médico-odontológico no pré-natal, o fortalecimento da educação em saúde durante o pré-natal e a elaboração de um sistema de informação da gestante integrado com a odontologia

Inverse electron transfer in peroxyoxalate chemiexcitation using easily reducible activators

Chemiluminescence properties of the peroxyoxalate reaction in the presence of activators bearing electron withdrawing substituents were studied, to evaluate the possible occurrence of an inverse electron transfer, from the peroxide intermediate to the activator, in its chemiexcitation step. Relative catalytic rate constants and singlet quantum yields were obtained for the peroxyoxalate reaction, using 9-chloro, 9,10-dichloro, 9-cyano and 9,10-dicyanoanthracenes as activators. The linear free-energy correlation of the relative rate constants with the activators' reduction potentials and the dependence of the quantum yields on the released energy confirm, for the first time, the occurrence of this inverse electron transfer.À Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

PESTICIDE RESIDUES EVALUATION IN BRAZILIAN BASIC DIET: RICE AND BEAN

Rice and bean constitute the basic diet in underdeveloped countries. In Brazil, the acquisition per capita of these aliments is around 182.9 g/day (beans) and 160.3 g/day (rice). In the present work were evaluated the pesticide residue contamination on these aliments, and possible risks for the consumer health. Pesticide residues were evaluated in 364 bean samples and 143 rice samples commercialized in Sao Paulo City (BRAZIL). A multi-residue method (DFG S19) was employed with gas and liquid chromatography identification and quantification. Dietary intake estimation was processed using the Acute Dietary Ingestion (ADI) based on national data regarding food consumption. Residues of pesticides that, according to the Brazilian legislation, are not allowed for this culture were detected respectively in 4.5% and 3.6% of the bean and rice samples. However, none of the samples had pesticide residues above the Maximum Residue Level (MRL). The European Union (EU) database showed that 7.3% of the bean sample and 85.7% of rice presented pesticide residues above the MRL. The toxicological parameter used for assessing the risk of contamination (ADI <100%) was not exceeded in none of the commodities. The results do not pose a hazard for the consumer’s health. Nevertheless, the presence of multiple residues indicates that continuous studies and monitoring of these commodities are required.

Like Attract Like? A Structural Comparison of Homogamy Across Same-Sex and Different-Sex Households

In this paper, we extend the marriage market theory of Gary Becker to same-sex couples. Beckers's theory rationalizes the well-known phenomenon of homogamy among heterosexual couples: individuals mate with their likes because of complementarities in the household production function. However, asymmetries in the distributions of male and female characteristics set theoretical limits to assortativeness among heterosexual couples: men and women have to marry "up" or "down" according to the relative shortage of their characteristics among the populations of men and women. Yet, among homosexual couples, this limit does not exist as partners are drawn from the same population, and thus the theory of assortative mating boldly predicts that individuals will choose a partner with nearly identical characteristics. Empirical evidence suggests a very different picture: a robust stylized fact is that the correlation of characteristics is in fact weaker among the homosexual couples. In this paper, we build an equilibrium model of the same-sex marriage market which allows for straightforward identification of the gains to marriage. We estimate the model with recent ACS data on California and show that preferences for similar partners are much less relevant for homosexuals than for heterosexuals with respect to age, education and race. As regards labor market outcomes such as hourly wages and working hours, our results highlight that the process of specialization within the household mainly applies to heterosexual couples. Finally, we discuss a number of interesting estimated interactions, like the one between education and wage, and the one between education and Hispanic origins

Ecotoxicological effects and bioaccumulation of BPA analogues and their mixture in the clam Ruditapes philippinarum

Bisphenol A is recognized as an endocrine disruptor that can affect several biological processes in marine species. Consequently, its use has been restricted and it has been replaced with other similar compounds named bisphenol A analogues (BPA analogues). BPA analogues are speculatively considered safer compounds than BPA and their usage is increasing with a consequent higher environmental release. In this study, specimens of the clam Ruditapes philippinarum were exposed to three main BPA analogues, namely BPAF, BPF, BPS and their mixture at an environmentally relevant concentration of 300 ng/L for 7 and 14 days. Effects on biomarkers indicative of cytotoxicity, oxidative stress and damage and neurotoxicity were evaluated. In addition, bioaccumulation of the compound tested was analysed in clam soft tissues. Results showed that BPA analogues at an environment concentration affected cellular parameters and antioxidant system causing also oxidative damage, suggesting that BPA analogues can be harmful compounds for clams