RESUMEN
Na,K-ATPase (NKA) and cardiotonic steroids (CTS) have shown potent cytotoxic and anticancer effects. Here, we have synthesized a series of CTS digoxin derivatives (γ-benzylidene) with substitutions in the lactone ring and evaluated the cytotoxicity caused by digoxin derivatives in tumor and non-tumor cells lines, as well as their effects on NKA. The cytotoxicity assay was determined in HeLa, A549, and WI-26 VA4 after they were treated for 48 h with increased concentrations of CTS. The effects of CTS on NKA activity and immunoblotting of α1 and ß1 isoforms were evaluated at IC50 concentrations in A549 cell membrane. NKA activity from mouse brain cortex was also measured. The majority of CTS exhibited low cytotoxicity in tumor and non-tumor cells, presenting IC50 values at micromolar concentrations, while digoxin showed cytotoxicity at nanomolar concentrations. BD-15 presented the lowest IC50 value (8 µM) in A549 and reduced its NKA activity in 28%. In contrast, BD-7 was the compound that most inhibited NKA (56% inhibition) and presented high IC50 value for A549. In mouse cortex, only BD-15 modulated the enzyme activity in a concentration-dependent inhibition curve. These results demonstrate that the cytotoxicity of these compounds is not related to NKA inhibition. The substitutions in the lactone ring of digoxin led to an increase in the cytotoxic concentration in tumor cells, which may not be interesting for cancer, but it has the advantage of increasing the therapeutic margin of these molecules when compared to classic CTS, and can be used safely in research for other diseases.
Asunto(s)
Glicósidos Cardíacos/toxicidad , Animales , Digoxina , Lactonas , Ratones , Sodio , ATPasa Intercambiadora de Sodio-PotasioRESUMEN
Estudo transversal de abordagem avaliativa do grau de implantação da cadeia de frio durante o transporte de vacina do nível regional para municípios. Avaliamos 53 rotas de transporte de vacina de municípios de Minas Gerais. Para a coleta de dados, utilizamos um questionário estruturado e o monitoramento das temperaturas das caixas de vacina encaminhadas aos municípios atraveÌs do data logger. O grau de implantação foi definido por meio de um sistema de escores, com pesos diferenciados para indicadores em cada dimensão avaliada. Os escores obtidos a partir da soma dos pontos dos indicadores foram transformados em percentuais, com referência à pontuação máxima possível. A seguir, foram definidas as categorias para o grau de qualidade: "adequado", "parcialmente adequado" e "não adequado". Os dados foram digitados no programa Epidata 3,0 e analisados no EPI-INFO 7.0, GraphPad Prism 5 e BioEstat 5.0, Excel. Realizamos análise univariada com cálculo das frequências, medidas de aferição e dispersão. A cadeia de frio durante o transporte de vacina não está adequadamente implantada na maioria dos municípios avaliados. Em vinte e dois municípios as vacinas foram expostas a temperaturas abaixo de +2°C, sendo que em seis destes a temperatura variou de 0°C a +0,5°C. O transporte de vacina apresenta falhas que podem comprometer a qualidade dos imunobiológicos.
Cross-sectional study aimed to evaluate the degree of cold chain implementation during vaccine transport from regions to municipalities. We evaluated 53 vaccine delivery routes in municipalities from the state of Minas Gerais. For data collection, we utilized a structured questionnaire and data logger in order to monitor the temperature inside the vaccine coldboxesthatwere distributed to thesemunicipalities through the data logger device. The degree of implementation was defined by means of a scoring system, with differentscores of different weights attributed to indicators for each rated dimension. The scores obtained from the sum of indicator points were transformed into percentages and referenced to the maximum possible score. The categories for quality grades were then defined as: "adequate", "partially adequate" and "not adequate". The data were entered in the Epidata 3.0 program and analyzed with EPI-INFO 7.0, GraphPad Prism 5 and BioEstat 5.0, Excel. We conducted univariate analysis to calculate frequencies,standardized measures and dispersion. Cold chain implementation during vaccine transport was found to be inadequate in the majority of the municipalities evaluated. In twenty-two municipalities, vaccines were exposed to temperatures below +2ºC and in six of these twenty-two,temperatures varied from 0oC to +0.5ºC. The vaccine transportation reveals shortcomings that could potentially compromise the immunobiologicals quality.
Asunto(s)
Refrigeración , VacunasRESUMEN
RESUMO A falta de integração entre os serviços que compõem a rede de atenção à saúde, além da incapacidade de muitos profissionais, são apontadas como causas da problemática para o controle da tuberculose no Brasil. Este estudo avaliou o grau de implantação do Programa de Controle de Tuberculose (PCT) em Divinópolis (MG). Trata-se de uma pesquisa avaliativa na perspectiva de análise de implantação. O PCT encontra-se parcialmente implantado. Como limitações, destacam-se a deficiência de gestão e planejamento, e a insuficiência de profissionais capacitados e insumos. Sugere-se a descentralização das ações do PCT e o aumento das ações de vigilância como possíveis soluções para a melhoria da assistência e da prevenção.
ABSTRACT The lack of integration between health care services network, in addition to the inefficiency of health professionals, are some of the identified problems for the control of Tuberculosis in Brazil. This study evaluated the level of implementation of the Tuberculosis Control Program (PCT) in Divinopolis (MG). The results signalize that PCT is partially implemented, due mostly to deficiencies related to management and planning, the insufficiency of trained professionals and insufficient resources. The decentralization of PCT actions and the enhancement of surveillance activities are signalized as possible solutions for the improvement of TB health care and prevention.
