On the mechanisms of phenothiazine-induced mitochondrial permeability transition: Thiol oxidation, strict Ca(2+) dependence, and cyt c release

Phenothiazines (PTZ) are drugs widely used in the treatment of schizophrenia. Trifluoperazine, a piperazinic PTZ derivative, has been described as inhibitor of the mitochondrial permeability transition (MPT). We reported previously the antioxidant activity of thioridazine at relatively low concentrations associated to the inhibition of the MPT (Brit. J. Pharmacol., 2002;136:136-142). In this study, it was investigated the induction of MPT by PTZ derivatives at concentrations higher than 10 mu M focusing on the molecular mechanism involved. PTZ promoted a dose-response mitochondrial swelling accompanied by mitochondrial transmembrane potential dissipation and calcium release, being thioridazine the most potent derivative. PTZ-induced MPT was partially inhibited by CsA or Mg(2+) and completely abolished by the abstraction of calcium. The oxidation of reduced thiol group of mitochondrial membrane proteins by PTZ was upstream the VIP opening and it was not sufficient to promote the opening of PTP that only occurred when calcium was present in the mitochondrial matrix. EPR experiments using DMPO as spin trapping excluded the participation of reactive oxygen species on the PTZ-induced MPT. Since 117 give rise to cation radicals chemically by the action of peroxidases and cyanide inhibited the PTZ-induced swelling, we propose that VIZ bury in the inner mitochondrial membrane and the chemically generated 117 cation radicals modify specific thiol groups that in the presence of Ca(2+) result in MPT associated to cytochrome c release. These findings contribute for the understanding of mechanisms of MET induction and may have implications for the cell death induced by PTZ. (C) 2010 Elsevier Inc. All rights reserved.

Antiviral and antiparasite properties of an L-amino acid oxidase from the Snake Bothrops jararaca: Cloning and identification of a complete cDNA sequence (Retracted article. See vol. 80, pg. 288, 2010)

L-Amino acid oxidases (LAAOs, EC 1.4.3.2) are flavoenzymes that catalyze the stereospecific oxidative deamination of an L-amino acid substrate to the corresponding a-ketoacid with hydrogen peroxide and ammonia production. The present work describes the first report on the antiviral (Dengue virus) and antiprotozoal (trypanocidal and leishmanicide) activities of a Bothrops jararaca L-amino acid oxidase (BjarLAAO-I) and identify its cDNA sequence. Antiparasite effects were inhibited by catalase, suggesting that they are mediated by H(2)O(2) production. Cells infected with DENV-3 virus previously treated with BjarLAAO-I, showed a decrease in viral titer (13-83-fold) when compared with cells infected with untreated viruses. Untreated and treated promastigotes (T. cruzi and L. amazonensis) were observed by transmission electron microscopy with different degrees of damage. Its complete cDNA sequence, with 1452 bp, encoded an open reading frame of 484 amino acid residues with a theoretical molecular weight and pl of 54,771.8 and 5.7, respectively. The cDNA-deduced amino acid sequence of BjarLAAO shows high identity to LAAOs from other snake venoms. Further investigations will be focused on the related molecular and functional correlation of these enzymes. Such a study should provide valuable information for the therapeutic development of new generations of microbicidal drugs. (C) 2008 Elsevier Inc. All rights reserved.

Highlights from the III International Symposium of Thrombosis and Anticoagulation (ISTA), October 14-16, 2010, Sao Paulo, Brazil

To discuss and share knowledge around advances in the care of patients with thrombotic disorders, the Third International Symposium of Thrombosis and Anticoagulation was held in So Paulo, Brazil, from October 14-16, 2010. This scientific program was developed by clinicians for clinicians, and was promoted by four major clinical research institutes: the Brazilian Clinical Research Institute, the Duke Clinical Research Institute of the Duke University School of Medicine, the Canadian VIGOUR Centre, and the Uppsala Clinical Research Center. Comprising 3 days of academic presentations and open discussion, the symposium had as its primary goal to educate, motivate, and inspire internists, cardiologists, hematologists, and other physicians by convening national and international visionaries, thought-leaders, and dedicated clinician-scientists. This paper summarizes the symposium proceedings.

Cognitive impairment and dementia in neurocysticercosis A cross-sectional controlled study

Objectives: Neurocysticercosis (NCYST) is the most frequent CNS parasitic disease worldwide, affecting more than 50 million people. However, some of its clinical findings, such as cognitive impairment and dementia, remain poorly characterized, with no controlled studies conducted so far. We investigated the frequency and the clinical profile of cognitive impairment and dementia in a sample of patients with NCYST in comparison with cognitively healthy controls (HC) and patients with cryptogenic epilepsy (CE). Methods: Forty treatment-naive patients with NCYST, aged 39.25 +/- 10.50 years and fulfilling absolute criteria for definitive active NCYST on MRI, were submitted to a comprehensive cognitive and functional evaluation and were compared with 49 HC and 28 patients with CE of similar age, educational level, and seizure frequency. Results: Patients with NCYST displayed significant impairment in executive functions, verbal and nonverbal memory, constructive praxis, and verbal fluency when compared with HC (p < 0.05). Dementia was diagnosed in 12.5% patients with NCYST according to DSM-IV criteria. When compared with patients with CE, patients with NCYST presented altered working and episodic verbal memory, executive functions, naming, verbal fluency, constructive praxis, and visual-spatial orientation. No correlation emerged between cognitive scores and number, localization, or type of NCYST lesions on MRI. Conclusions: Cognitive impairment was ubiquitous in this sample of patients with active neurocysticercosis (NCYST). Antiepileptic drug use and seizure frequency could not account for these features. Dementia was present in a significant proportion of patients. These data broaden our knowledge on the clinical presentations of NCYST and its impact in world public health. Neurology (R) 2010;74:1288-1295

A????es premiadas no 15?? Concurso Inova????o na Gest??o P??blica Federal 2010

Nesta publica????o, referente ao 15?? Concurso Inova????o na Gest??o P??blica Federal, o leitor encontrar?? iniciativas inovadoras nas seguintes ??reas: Arranjos institucionais para coordena????o e/ou implementa????o de pol??ticas p??blicas (intra e inter-governamental); atendimento ao cidad??o; gest??o da informa????o; melhoria dos processos de trabalho

Evolu????o e distribui????o dos precat??rios da Uni??o de 2010 ?? 2013

Este trabalho pretende tra??ar a evolu????o dos recursos alocados para o pagamento das d??vidas da Administra????o P??blica Federal direta, desde 2010 at?? 2013, bem como identificar a origem desses d??bitos quanto ao Tribunal julgador e a Regi??o geogr??fica. Trata-se de pesquisa quantitativa realizada com base nos dados anualmente encaminhados pelo Poder Judici??rio ao Executivo, e que se destinam a quantificar, na Lei Or??ament??ria Anual do exerc??cio subsequente, a dota????o necess??ria para realizar os pagamentos devidos. Seus principais resultados foram: distinguir o volume de recursos referentes a parcelamentos anteriores ou a novos precat??rios; classificar os Tribunais da Justi??a da Uni??o por precat??rios autuados; esbo??ar um mapa dos Estados brasileiros por precat??rios emitidos; apontar as varia????es anuais dos valores de precat??rios, por Tribunal e por Estado; possibilitar a constru????o de uma metodologia de acompanhamento da emiss??o de precat??rios; e constituir um ponto de partida para pesquisas futuras sobre o tema, notadamente, as que pretendam relacionar os n??meros apresentados ??s causas de expedi????o de precat??rios e aos ??rg??os executados

Relat??rio de gest??o 2008

A Escola Nacional de Administra????o P??blica - ENAP ratificou sua miss??o de desenvolver compet??ncias de servidores p??blicos para aumentar a capacidade de governo na gest??o das pol??ticas p??blicas, buscando o enfrentamento dos desafios previstos at?? 2010, quais sejam: consolidar-se como refer??ncia na forma????o de dirigentes; implementar de forma estrat??gica e inovadora a Pol??tica Nacional de Desenvolvimento de Pessoal - PNDP; prospectar e disseminar conceitos e tecnologias inovadoras de gest??o de pol??ticas p??blicas; prospectar, construir e disseminar, interna e externamente tecnologias educacionais inovadoras; tornar-se escola de governo refer??ncia nacional e internacional; e consolidar-se como uma organiza????o de aprendizagem. A relev??ncia da capacita????o ?? destacada pelo Decreto n?? 5.707/06, que criou a PNDP. Em 2008 a ENAP destacou-se no processo de implementa????o desta Pol??tica, por integrar seu Comit?? Gestor e coordenar o sistema de escolas de governo da Uni??o

Presta????o de contas ordin??ria anual: relat??rio de gest??o do exerc??cio de 2010

Relat??rio de Gest??o do exerc??cio de 2010 apresentado aos ??rg??os de controle interno e externo como presta????o de contas anual que a ENAP est?? obrigada nos termos do art. 70 da Constitui????o Federal, elaborado de acordo com as disposi????es da IN TCU n?? 63/2010, da DN TCU n?? 107/2010, da Portaria TCU n?? 277/2010 e das orienta????es do ??rg??o de controle interno (Portaria CGU n?? 2546/2010)

Orienta????es b??sicas para a gest??o consorciada de res??duos s??lidos

O s??timo volume da s??rie Inova????o na Gest??o P??blica apresenta orienta????es b??sicas para a gest??o consorciada de res??duos s??lidos. Este ???guia??? surgiu de uma a????o conjunta entre a coopera????o espanhola e o Projeto Brasil Munic??pios, realizada entre setembro de 2010 maio de 2011, com o intuito de apoiar a implementa????o de uma experi??ncia de cons??rcio p??blico na Regi??o Metropolitana da Grande Aracaju para a gest??o integrada dos res??duos s??lidos nos moldes da Lei de Cons??rcios (Lei 11.107/2005) e seu decreto regulamentador, bem como na Lei de Saneamento B??sico (Lei 11.445/2007) e em sintonia com a Pol??tica Nacional de Res??duos S??lidos. O cap??tulo 1 traz informa????es sobre a Pol??tica Nacional de Res??duos S??lidos (PNRS), a ado????o de solu????es intermunicipais para a destina????o final de rejeitos e sobre as novas responsabilidades dos munic??pios para gest??o e manejo de res??duo s??lidos previstas na PNRS. O segundo cap??tulo, por sua vez, discorre sobre o instituto do cons??rcio p??blico dando ??nfase ?? gest??o consorciada intermunicipal dos res??duos s??lidos. Por fim, o terceiro cap??tulo apresenta informa????es t??cnicas para apoiar esse arranjo institucional, como ??ndices de gera????o per capita de res??duos s??lidos domiciliares e p??blicos, dimensionamento de pessoal para cons??rcio, e respectivos custos e diretrizes para a fiscaliza????o do operador de aterro sanit??rios

Cat??logo de cursos ENAP - 2010

O cat??logo de cursos da Escola Nacional de Administra????o P??blica (ENAP) tem como objetivo apoiar a escolha de a????es de desenvolvimento de compet??ncias de dirigentes p??blicos brasileiros

Fortalecimento da gest??o de pol??ticas p??blicas da inclus??o social do governo federal brasileiro: projeto de coopera????o t??cnica Brasil-Espanha 2007-2010

O Projeto de Fortalecimento da Gest??o de Pol??ticas P??blicas de Inclus??o Social do Governo Federal Brasileiro, apresentado pela ENAP ?? AECI em 2006, visa promover processos de inclus??o social de grupos que vivem em situa????o de extrema vulnerabilidade. Nos 36 meses de dura????o do projeto a qualidade dos servi??os prestados pelas redes de atendimento p??blica e privada aos idosos, pessoas com defici??ncia e benefici??rios do sistema de previd??ncia social, dever?? ser incrementada. Para isso, pretende-se melhorar a regulamenta????o dos servi??os de aten????o a estes grupos sociais, melhorar a forma????o dos gestores e operadores p??blicos e privados destes servi??os, melhorar o acesso ??s informa????es, aumentar o compromisso dos estados e munic??pios e da rede de aten????o a estes grupos sociais, agilizar a resposta da administra????o perante as solicita????es dos cidad??os e melhorar a rede de atendimento

Balan??o de gest??o 2003-2010 Escola Nacional de Administra????o P??blica

O balan??o destes oito anos de trabalho da ENAP durante os dois mandatos do Presidente Luiz In??cio Lula da Silva busca descrever a a????o desta Escola para o fortalecimento da fun????o capacita????o de servidores na administra????o p??blica federal

Relat??rio de gest??o do exerc??cio de 2013

Relat??rio de Gest??o do exerc??cio de 2013 apresentado aos ??rg??os de controle interno e externo como presta????o de contas anual a que esta Unidade est?? obrigada nos termos do art. 70 da Constitui????o Federal, elaborado de acordo com as disposi????es da IN TCU n?? 63/2010, da DN TCU n?? 127/2013, da Portaria TCU n?? 175/2013 e das orienta????es do ??rg??o de controle interno (Portaria CGU n?? 133/2013)

Decreto n?? 6.563, de 11 de setembro de 2008: Aprova o Estatuto e o Quadro Demonstrativo dos Cargos em Comiss??o e das Fun????es Gratificadas da ENAP

Decreto n?? 6.563, de 11 de setembro de 2008 aprova o Estatuto e o Quadro Demonstrativo dos Cargos em Comiss??o e das Fun????es Gratificadas da Funda????o Escola Nacional de Administra????o P??blica - ENAP, e d?? outras provid??ncias.

Decreto n?? 8.091, de 3 de setembro de 2013: Altera o Decreto n?? 6.563, de 11 de setembro de 2008, que aprova o Estatuto e o Quadro Demonstrativo dos Cargos em Comiss??o e das Fun????es Gratificadas da Funda????o Escola Nacional de Administra????o P??blica - ENAP, e remaneja cargos em comiss??o

Decreto n?? 8.091, de 3 de setembro de 2013 altera o Decreto n?? 6.563, de 11 de setembro de 2008, que aprova o Estatuto e o Quadro Demonstrativo dos Cargos em Comiss??o e das Fun????es Gratificadas da Funda????o Escola Nacional de Administra????o P??blica - ENAP, e remaneja cargos em comiss??o.