Análise do efeito de polimorfismos não-sinônimos em genes de reparo de DNA da via BER na resposta inflamatória da meningite

In vitro and in animal models, APE1, OGG1, and PARP-1 have been proposed as being involved with inflammatory response. In this work, we have investigated if the SNPs APE1 Asn148Glu, OGG1 Ser326Cys, and PARP-1 Val762Ala are associated to meningitis and also developed a system to enable the functional analysis of polymorphic proteins. Patients with bacterial meningitis (BM), aseptic meningitis (AM) and controls (non-infected) genotypes were investigated by PIRA-PCR or PCR-RFLP. DNA damages were detected in genomic DNA by Fpg treatment. IgG and IgA were measured from plasma and the cytokines and chemokines were measured from cerebrospinal fluid samples using Bio-Plex assays. The levels of NF-κB and c-Jun were measured in CSF by dot blot assays. A significant (P<0.05) increase in the frequency of APE1 148Glu allele in BM and AM patients was observed. A significant increase in the genotypes Asn/Asn in control group and Asn/Glu in BM group was also found. For the SNP OGG1 Ser326Cys, the genotype Cys/Cys was more frequent (P<0.05) in BM group. The frequency of PARP-1 Val/Val genotype was higher in control group (P<0.05). The occurrence of combined SNPs increased significantly in BM patients, indicating that these SNPs may be associated to the disease. Increasing in sensitive sites to Fpg was observed in carriers of APE1 148Glu allele or OGG1 326Cys allele, suggesting that SNPs affect DNA repair activity. Alterations in IgG production were observed in the presence of SNPs APE1Asn148Glu, OGG1Ser326Cys or PARP-1Val762Ala. Reductions in the levels ofIL-6, IL-1Ra, MCP-1/CCL2and IL-8/CXCL8 were observed in the presence of APE1148Glu allele in BM patients, however no differences were observed in the levels of NF-κB and c-Jun considering genotypes and analyzed groups. Using APE1 as model, a system to enable the analysis of cellular effects and functional characterization of polymorphic proteins was developed using strategies of cloning APE1 cDNA in pIRES2-EGFP vector, cellular transfection of the construction obtained, siRNA for endogenous APE1 and cellular cultures genotyping. In conclusion, we obtained evidences of an effect of SNPs in DNA repair genes on the regulation of immune response. This is a pioneering work in the field that shows association of BER variant enzymes with an infectious disease in human patients, suggesting that the SNPs analyzed may affect immune response and damage by oxidative stress level during brain infection. Considering these data, new approaches of functional characterization must be developed to better analysis and interactions of polymorphic proteins in response to this context

Expression of the sigma35 and cry2AB genes involved in Bacillus thuringiensis virulence

Muitos genes estão envolvidos nos mecanismos de esporulação da bactéria Bacillus thuringiensis. A regulação e expressão desses genes resultam em uma produção massiva da proteína Cry, responsável pela morte das larvas de muitos insetos. Neste trabalho monitorou-se a expressão de genes de Bacillus thuringiensis, ao longo de três fases de seu desenvolvimento. Foram construídos macroarrays de DNA dos genes selecionados, cujas seqüências estão disponibilizadas no GenBank. Estes genes foram hibridizados com cDNAs obtidos de B. thuringiensis kurstaki HD-1. As sondas de cDNA foram sintetizadas a partir da transcrição reversa do RNA da bactéria, extraído durante as fases de crescimento logarítmico, estacionária e esporulativa, marcadas com 33PadCTP. A expressão diferencial encontrada foi significativa para dois genes de B.thuringiensis, um relacionado aos fatores sigma (sigma35) e outro ao gene cry (cry2Ab). Detectaram-se diferenças entre as médias de expressão do fator sigma e do gene cry2Ab. Os valores máximos de expressão diferencial foram obtidos para o gene codificador do fator sigma35 na fase log e na fase esporulativa. Na análise de médias observou-se expressão do gene cry2Ab apenas na fase log; no entanto, de forma bem mais baixa quando comparado com a expressão de sigma35, nas três fases.

Efeito de extratos da alga marinha caulerpa mexicana em modelos de inflamação em murinos

The regulation of the inflammatory response is essential to maintain homeostasis. Several studies have been performed to search new drugs that can contribute to avoiding or minimizing an excessive inflammatory process. The aim of this study was to evaluate the effect of extracts of green algae Caulerpa mexican in models of inflammation. In mice, the model of peritonitis induced inflammatory zymosan pretreatment of mice with aqueous and methanol extracts of C. mexican was able to reduce cell migration to the peritoneal cavity. Treatment of mice with extracts of C. mexican also reduced the ear edema induced by xylene and exerted inhibitory action on the migration of leukocytes in inflammation-induced zymosan the air pouch, and timedependent for the extracts tested in the model of ulcerative colitis induced by DSS 3%, the extract methanol, but not the aqueous C. mexican, significantly reduced the clinical symptoms of colitis, as well as the production of proinflammatory cytokines in the culture of mouse colon, in the histological analysis there was a slight reduction of inflammation in the intestinal mucosa. We concluded that the administration of the extracts resulted in the reduction of cell migration to different sites as well as reducing the edema formation induced by chemical irritant. This study demonstrates for the first time the antiinflammatory effect of aqueous and methanolic extracts from green marine algae Caulerpa mexican

Implementação da política de assistência social em Mossoró/RN : uma avaliação a partir dos centros de referência da assistência social

The current National Policy for Social Assistance (PNAS) is the instrument that regulates the organization and procedures of social-welfare actions. Developed and approved in 2004 since the Unified Social Assistance System (ITS) was crated in 2003, it reaffirms the democratic principles of the Social Assistance Organic Law (LOAS) focusing on the universalization of social rights and equality of rights when accessing the social-welfare system. In the SUAS point of view, the PNAS highlights the information, monitoring and evaluation fields for being the best way to assure the regulation, organization and control by the Federal Government paying attention to the principles of decentralization and participation. This political-institutional rearrangement occurs through the pact among all the three federal entities. The pact deals with the implementation of the task. It says that it has to be shared between the federal autonomous entities, established by dividing responsibilities. To the cities, considered as the smallest territorial unit of the federation and closer to the population, was given the primary responsibility, which is to feed and maintain the database of SUAS NETWORK and identify families living in situations of social vulnerability. In addition to these responsibilities, the cities that have full autonomy in the management of their actions, have the responsibility to organize the basic social protection and the special social protection, that using the Center of Social Assistance Reference (CRAS) and the Center of Specialized Social Assistance Reference (CREAS), are responsible for the provision of programs, projects and services that strengthen the family and community; that promote people who are able to enjoy the benefits of the Continuing benefit of Provisions (BPC) and transfer of incomes; that hold the infringed rights on its territory; that maximize the protective role of families and strengthen its users organization. In Mossoró/RN, city classified as autonomous in the social assistance management, has five units of CRAS that, for being public utilities, are considered the main units of basic social protection, since they are responsible for the connection between the other institutions that compose the network of local social protection. Also known as Family House, the CRAS, among other programs and services, offers the Integral Attention to Families Program (PAIF), Juvenile ProJovem Program, socio-educational coexistence services programs, as well as sending people to other public policies and social-welfare services network, provides information, among others. In this large field, social workers are highlighted as keys to implement the policy of social assistance within the city, followed by psychologists and educators. They should be effective public employees, as a solution to ensure that the provision of the services are to be continued, provided to the population living around the units. However, what we can find here is inattention to the standard rules of social assistance, which not only undermines the quality of programs and services, but also the consolidation of policy on welfare as public policy of social rights

A teoria democrática e a participação popular : as trajetórias participativas no Recife e em Módena

This work basically achieve three goals. Critically investigate the liberal democratic regime and its historical reformulation, rejecting the popular power and popular self-organization, limiting the entry of normal citizen in decision-making, believing in the market as a mediating body in regulating of the different life spheres of social. Starting from the critical liberal democracy, it discussed the concept of popular participation in the democracy, searching new democratically horizons, where the masses could have the opportunity to make decisions about their own destiny. On the basis of theoretical discussion on participation, we discuss a concrete instrument of participation, the Participatory Budgeting, comparing two participatory experiences in North and South