A tens??o na defini????o de compet??ncias entre Judici??rio e Executivo: a coleta de lixo

O estudo de caso analisa o fen??meno de judicializa????o de pol??ticas p??blicas, o qual se d?? quando se transfere quest??es de cunho pol??tico, t??picas do Poder Executivo e do Legislativo, para serem analisadas pelo Poder Judici??rio. Considerando-se o extenso leque de direitos sociais, o Poder Judici??rio passa a ser tamb??m demandado em quest??es pol??ticas mais espec??ficas, previstas ou n??o em pol??ticas p??blicas, o que gera in??meras possibilidades de atua????o para esta esfera de poder. O presente caso analisa, portanto, a tens??o na defini????o de compet??ncias entre os Poderes Judici??rio e Executivo, no que se refere ?? coleta de lixo no munic??pio de Cambuquira, Minas Gerais. Ele aborda dois direitos sociais: o direito ?? sa??de e ao meio ambiente saud??vel. O estudo suscita, portanto, o debate sobre a exist??ncia de uma pol??tica p??blica, que passa a ser questionada no Poder Judici??rio, debatendo-se quais seriam os reais limites da democracia

A defini????o do conte??do do prontu??rio essencial

Este projeto refere-se ?? experi??ncia realizada pelo Hospital de Cl??nicas de Porto Alegre que visa organizar as informa????es armazenadas nos prontu??rios, melhorando a qualidade da informa????o necess??ria para a tomada de decis??o cl??nica, administrativa e legal. Al??m da diminui????o do volume de papel e da ??rea necess??ria para seu armazenamento, foi obtida tamb??m melhoria na qualidade e no acesso ?? informa????o, ap??s a ado????o dos relat??rios consolidados de exames e prescri????es e da cria????o da nota de alta informatizada

Biópsia percutânea de lesões ósseas guiada por tomografia computadorizada: taxas de definição diagnóstica e complicações

Objetivo: Determinar taxas de definição diagnóstica e complicações da biópsia percutânea guiada por tomografia computadorizada (TC) de lesões ósseas suspeitas de malignidade. Materiais e Métodos: Estudo retrospectivo que incluiu 186 casos de biópsia percutânea guiada por TC de lesões ósseas no período de janeiro de 2010 a dezembro de 2012. Todas as amostras foram obtidas usando agulhas de 8 a 10 gauge. Foram coletados dados demográficos, história de neoplasia maligna prévia, dados relacionados à lesão, ao procedimento e ao resultado histológico. Resultados: A maioria dos pacientes era do sexo feminino (57%) e a idade média foi 53,0 ± 16,4 anos. Em 139 casos (74,6%) a suspeita diagnóstica era metástase e os tumores primários mais comuns foram de mama (32,1%) e próstata (11,8%). Os ossos mais envolvidos foram coluna vertebral (36,0%), bacia (32,8%) e ossos longos (18,3%). Houve complicações em apenas três pacientes (1,6%), incluindo uma fratura, um caso de parestesia com comprometimento funcional e uma quebra da agulha necessitando remoção cirúrgica. Amostras de 183 lesões (98,4%) foram consideradas adequadas para diagnóstico. Resultados malignos foram mais frequentes nos pacientes com suspeita de lesão secundária e história de neoplasia maligna conhecida (p < 0,001) e nos procedimentos orientados pela PET/CT (p = 0,011). Conclusão: A biópsia percutânea guiada por TC é segura e eficaz no diagnóstico de lesões ósseas suspeitas.

Design, Synthesis And Biological Evaluation Of Hybrid Bioisoster Derivatives Of N-acylhydrazone And Furoxan Groups With Potential And Selective Anti-trypanosoma Cruzi Activity.

Hybrid bioisoster derivatives from N-acylhydrazones and furoxan groups were designed with the objective of obtaining at least a dual mechanism of action: cruzain inhibition and nitric oxide (NO) releasing activity. Fifteen designed compounds were synthesized varying the substitution in N-acylhydrazone and in furoxan group as well. They had its anti-Trypanosoma cruzi activity in amastigotes forms, NO releasing potential and inhibitory cruzain activity evaluated. The two most active compounds (6, 14) both in the parasite amastigotes and in the enzyme contain the nitro group in para position of the aromatic ring. The permeability screening in Caco-2 cell and cytotoxicity assay in human cells were performed for those most active compounds and both showed to be less cytotoxic than the reference drug, benznidazole. Compound 6 was the most promising, since besides activity it showed good permeability and selectivity index, higher than the reference drug. Thereby the compound 6 was considered as a possible candidate for additional studies.

Descriptor-and fragment-based QSAR models for a series of Schistosoma mansoni purine nucleoside inhibitors

The enzyme purine nucleoside phosphorylase from Schistosoma mansoni (SmPNP) is an attractive molecular target for the treatment of major parasitic infectious diseases, with special emphasis on its role in the discovery of new drugs against schistosomiasis, a tropical disease that affects millions of people worldwide. In the present work, we have determined the inhibitory potency and developed descriptor- and fragment-based quantitative structure-activity relationships (QSAR) for a series of 9-deazaguanine analogs as inhibitors of SmPNP. Significant statistical parameters (descriptor-based model: r² = 0.79, q² = 0.62, r²pred = 0.52; and fragment-based model: r² = 0.95, q² = 0.81, r²pred = 0.80) were obtained, indicating the potential of the models for untested compounds. The fragment-based model was then used to predict the inhibitory potency of a test set of compounds, and the predicted values are in good agreement with the experimental results

Enzyme kinetics, structural analysis and molecular modeling studies on a series of Schistosoma mansoni PNP inhibitors

The enzyme purine nucleoside phosphorylase from Schistosoma mansoni (SmPNP) is an attractive molecular target for the development of novel drugs against schistosomiasis, a neglected tropical disease that affects about 200 million people worldwide. In the present work, enzyme kinetic studies were carried out in order to determine the potency and mechanism of inhibition of a series of SmPNP inhibitors. In addition to the biochemical investigations, crystallographic and molecular modeling studies revealed important molecular features for binding affinity towards the target enzyme, leading to the development of structure-activity relationships (SAR).

A new bianthron glycoside as inhibitor of Trypanosoma cruzi glyceraldehyde 3-phosphate dehydrogenase activity

A phytochemical investigation of the ethanolic extract of stalks of Senna martiana Benth. (Leguminoseae), native specie of northeast Brazil, resulted in the isolation and spectroscopic characterization of a new bianthrone glycoside, martianine 1 (10,10'-il-chrysophanol-10-oxi10,10'-bi-glucosyl). Its identification was established by HRMS, IR and 2D NMR experiments. The evaluation of martianine trypanocidal activity was carried out against gliceraldehyde 3-phosphate dehydrogenase enzyme from Trypanosoma cruzi. Its inhibitory constant (Ki) is in the low micromolar concentration and it was determined by isothermal titration calorimetry to be 27.3 ± 2.47 µmol L-1. The non-competitive mechanism is asserted to be putative of the mode of action martianine displays against T. cruzi GAPDH. Results show that martianine has a great potential to become new lead molecule by inhibiting this key enzyme and for the development of new drugs against Chagas disease.

Structural and chemical basis for anticancer activity of a series of 'beta'-tubulin ligands: molecular modeling and 3D QSAR studies

An important approach to cancer therapy is the design of small molecule modulators that interfere with microtubule dynamics through their specific binding to the ²-subunit of tubulin. In the present work, comparative molecular field analysis (CoMFA) studies were conducted on a series of discodermolide analogs with antimitotic properties. Significant correlation coefficients were obtained (CoMFA(i), q² =0.68, r²=0.94; CoMFA(ii), q² = 0.63, r²= 0.91), indicating the good internal and external consistency of the models generated using two independent structural alignment strategies. The models were externally validated employing a test set, and the predicted values were in good agreement with the experimental results. The final QSAR models and the 3D contour maps provided important insights into the chemical and structural basis involved in the molecular recognition process of this family of discodermolide analogs, and should be useful for the design of new specific ²-tubulin modulators with potent anticancer activity.

Synthesis, screening for antiacetylcholinesterase activity and binding mode prediction of a new series of [3-(disubstituted-phosphate)-4,4,4-trifluoro-butyl]-carbamic acid ethyl esters

A series of nine new [3-(disubstituted-phosphate)-4,4,4-trifluoro-butyl]-carbamic acid ethyl esters (phosphate-carbamate compounds) was obtained through the reaction of (4,4,4-trifluoro-3-hydroxybut-1-yl)-carbamic acid ethyl esters with phosphorus oxychloride followed by the addition of alcohols. The products were characterized by ¹H, 13C, 31P, and 19F NMR spectroscopy, GC-MS, and elemental analysis. All the synthesized compounds were screened for acetylcholinesterase (AChE) inhibitory activity using the Ellman method. All compounds containing phosphate and carbamate pharmacophores in their structures showed enzyme inhibition, being the compound bearing the diethoxy phosphate group (2b) the most active compound. Molecular modeling studies were performed to investigate the detailed interactions between AChE active site and small-molecule inhibitor candidates, providing valuable structural insights into AChE inhibition.

Quimioterapia da doença de Chagas: estado da arte e perspectivas no desenvolvimento de novos fármacos

Neglected diseases are a major global cause of illness, long-term disability and death. Chagas' disease is a parasitic infection widely distributed throughout Latin America, with devastating consequences in terms of human morbidity and mortality. The existing drug therapy suffers from a combination of drawbacks including poor efficacy, resistance and serious side effects. In 2009, we celebrate the 100th anniversary of the discovery of Chagas' disease, facing the challenges of developing new, safe and effective drugs for the treatment of this disease. This brief review attempts to highlight the state of the art, limitations and perspectives of Chagas' disease drug development.

The development of an immobilized enzyme reactor containing glyceraldehyde-3-phosphate dehydrogenase from Trypanosoma cruzi: the effect of species' specific differences on the immobilization

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays an important role in the life cycle of the Trypanosoma cruzi, and an immobilized enzyme reactor (IMER) has been developed for use in the on-line screening for GAPDH inhibitors. An IMER containing human GAPDH has been previously reported; however, these conditions produced a T. cruzi GAPDH-IMER with poor activity and stability. The factors affecting the stability of the human and T. cruzi GAPDHs in the immobilization process and the influence of pH and buffer type on the stability and activity of the IMERs have been investigated. The resulting T. cruzi GAPDH-IMER was coupled to an analytical octyl column, which was used to achieve chromatographic separation of NAD+ from NADH. The production of NADH stimulated by D-glyceraldehyde-3-phosphate was used to investigate the activity and kinetic parameters of the immobilized T. cruzi GAPDH. The Michaelis-Menten constant (K-m) values determined for D-glyceraldehyde-3-phosphate and NAD(+) were K-m = 0.5 +/- 0.05 mM and 0.648 +/- 0.08 mM, respectively, which were consistent with the values obtained using the non-immobilized enzyme.

Sulfonyl-hydrazones of cyclic imides derivatives as potent inhibitors of the Mycobacterium tuberculosis protein tyrosine phosphatase B (PtpB)

Searching lead compounds for new antituberculosis drugs, the activity of synthetic sulfonamides and sulfonyl-hydrazones were assayed for their potential inhibitory activity towards a protein tyrosine phosphatase from Mycobacterium tuberculosis - PtpB. Four sulfonyl-hydrazones N-phenylmaleimide derivatives were active (compounds 14, 15, 19 and 21), and the inhibition of PtpB was found to be competitive with respect to the substrate p-nitrophenyl phosphate. Structure-based molecular docking simulations were performed and indicated that the new inhibitor candidates showed similar binding modes, filling the hydrophobic pocket of the protein by the establishment of van der Waals contacts, thereby contributing significantly to the complex stability.

Boletim eletr??nico de bibliografias especializadas: igualdade de g??nero

A 2?? edi????o de 2013 do Boletim Eletr??nico de Bibliografias Especializadas destaca o tema Igualdade de G??nero. O documento traz indica????es de pu-blica????es do acervo da Biblioteca Graciliano Ramos/ENAP com reflex??es acerca das desi-gualdades entre homens e mulheres e suas consequ??ncias ?? sociedade. O objetivo ?? dar publicidade a esses materiais, visando a con-tribuir para uma melhor compreens??o do com-plexo cen??rio de defini????o das prioridades p??blicas e da formula????o de pol??ticas p??blicas governamentais comprometidas com a pers-pectiva de g??nero, em seus diversos aspectos. De acordo com a Organiza????o das Na????es Unidas para a Educa????o, a Ci??ncia e a Cultura (Unesco), os direitos das mulheres devem ser entendidos como direitos humanos e cultu-rais fundamentais. J?? a Pol??tica Nacional para as Mulheres, coordenada pela Secre-taria Especial de Pol??ticas para as Mulhe-res (SPM), da Presid??ncia da Rep??blica, tem como pressupostos e princ??pios a equi-dade, a autonomia das mulheres, a laicida-de do Estado, a universalidade das pol??ti-cas, a justi??a social, a transpar??ncia dos atos p??blicos, a participa????o e o controle social.

Melhoria de gest??o com foco no trin??mio: pessoas, processos e tecnologia de informa????o

O trabalho iniciou-se em junho de 2005, na GMEFH1, cuja metodologia se pautava na revis??o dos processos de trabalho, levantados a partir de reuni??es semanais com um grupo representativo, na defini????o de pap??is e responsabilidades dos colaboradores da ??rea, no desenvolvimento de um sistema de informa????o que possibilitasse a consolida????o dos procedimentos e uniformiza????o de condutas e, por fim, no treinamento de uma pr??tica gestora, com estabelecimento de metas, registro e revis??o de procedimentos, bem como o monitoramento de prazos e resultados. O cen??rio anterior apresentava grande descontrole do fluxo do processo de trabalho, aus??ncia de padr??o nos procedimentos, n??mero desconhecido das peti????es sem an??lise (passivo), infraestrutura impr??pria, subjetividade na an??lise t??cnica, inexist??ncia de planejamento estrat??gico, entre outros. Ap??s a realiza????o do trabalho, foram observados os seguintes resultados: acr??scimo significativo da produtividade, apesar da redu????o do quadro-geral de pessoas (de 38 para 30) e do n??mero de t??cnicos (de 34 para 23) desempenhando a atividade-fim (an??lise 100 t??cnica para concess??o de registro de medicamentos); tratamento do passivo com redu????o de 89% das peti????es que iriam para a an??lise; grande diminui????o do tempo de resposta ao setor regulado; e padroniza????o nos procedimentos de an??lise t??cnica, trazendo uniformidade na conduta t??cnica, tema recorrentemente requisitado pelo setor regulado