Serum Predose Metabolic Profiling for Prediction of Rosuvastatin Pharmacokinetic Parameters in Healthy Volunteers.

Rosuvastatin is a well-known lipid-lowering agent generally used for hypercholesterolemia treatment and coronary artery disease prevention. There is a substantial inter-individual variability in the absorption of statins usually caused by genetic polymorphisms leading to a variation in the corresponding pharmacokinetic parameters, which may affect drug therapy safety and efficacy. Therefore, the investigation of metabolic markers associated with rosuvastatin inter-individual variability is exceedingly relevant for drug therapy optimization and minimizing side effects. This work describes the application of pharmacometabolomic strategies using liquid chromatography coupled to mass spectrometry to investigate endogenous plasma metabolites capable of predicting pharmacokinetic parameters in predose samples. First, a targeted method for the determination of plasma concentration levels of rosuvastatin was validated and applied to obtain the pharmacokinetic parameters from 40 enrolled individuals; then, predose samples were analyzed using a metabolomic approach to search for associations between endogenous metabolites and the corresponding pharmacokinetic parameters. Data processing using machine learning revealed some candidates including sterols and bile acids, carboxylated metabolites, and lipids, suggesting the approach herein described as promising for personalized drug therapy.

Water provisioning improvement through payment for ecosystem services.

We assess whether a Payments for Ecosystem Services (PES) programme met its objectives of reducing soil erosion and yielding water in an environmental protected area, the Guariroba River Basin, Midwestern Brazil. We measured rainfall and water discharge throughout 2012 and 2016. During the same period, soil and water conservation practices were performed in the basin, such as: building level terraces and riparian vegetation recovery. We separated streamflow into baseflow and direct runoff, then we evaluted the baseflow index that indicated that groundwater significantly contributes to total flow. Therefore, to investigate the effects on streamflow, we performed a trend analysis in the baseflow time series using the Mann-Kendall test. In addition, we analysed the efficiency of soil erosion regulation practices over time, considering the total payment and the trends found in the baseflow. Whereas precipitation records present a decreasing trend (1 mm month-1), baseflow tends to increase by 0.018 m3 s-1 in the same period. Our findings show that soil conservation practices performed in the basin increase baseflow and also provide a better resilience to endure extreme events such as drought based on an increase in forest areas and soil conservation practices such as level terrace.

O Pacto pela Saúde e a gestão da força de trabalho na Atenção Básica do SUS: um retrato da situação de alguns municípios no Estado de São Paulo / The Health Pact and workforce management within the Unified Health System's Primary Care: a portrait of the situation in some municipalities in São Paulo state, Brazil

Este artigo aborda o cumprimento, em oito municípios do Estado de São Paulo, dos compromissos concernentes à gestão do trabalho inscritos no Pacto de Gestão, assinado em 2006 por gestores dos três níveis do SUS. Entre os municípios estudados, três são polos de regiões metropolitanas; e cinco tinham, em 2008, população acima de 500 mil habitantes. Foram realizadas coletas de dados e análise documental, particularmente dos Planos de Carreira, Cargos e Salários (PCCS) de três municípios e entrevistas com gestores e representantes de trabalhadores e usuários nos Conselhos Municipais de Saúde. As categorias analisadas derivaram do Pacto de Gestão: democratização das relações de trabalho, direitos sociais e previdenciários, regime jurídico e vínculo, carreira, progressão funcional e educação permanente. Os resultados mostraram repercussão pouco relevante das decisões das mesas de negociação na política de gestão do trabalho; incorporação parcial das diretrizes do PCCS-SUS apenas em três municípios; política de formação de pessoal caracterizada por iniciativas pontuais dissociadas da progressão funcional. Foram também identificados: visão restrita dos conselheiros sobre sua participação na discussão do tema gestão do trabalho, expressa numa abordagem periférica pelos Conselhos Municipais de Saúde dos temas relativos à gestão da força de trabalho; deficiências na descentralização da gestão dos cargos no SUS municipal; tendência ao tratamento privado, pelos gestores, dos dados relativos ao quadro de pessoal. Embora seja incipiente a implementação dos compromissos formulados no Termo de Compromisso de Gestão, cabe destacar o ineditismo da inclusão no Pacto de Gestão das questões relativas à gestão do trabalho como uma política definida.

This paper discusses the implementation in eight municipalities in Sao Paulo state of the commitments concerning the management of work composing the Management Pact, signed in 2006 by the three levels of the Unified Health System (SUS). Among the municipalities studied, three are centers of metropolitan areas and five had in 2008 population over 500,000 inhabitants. Data were collected, particularly concerning the Career, Positions and Wages Plan (PCCS) and interviews were accomplished with managers and representatives of workers and users in Municipal Health Councils. The categories analyzed were derived from the Management Pact: democratization of labor relations, social rights and social security, juridical regime and working arrangements, career progression and permanent training. The results showed irrelevant repercussion of the collective-bargaining mechanisms' decisions on personnel policy; partial incorporation of the guidelines of PCCS-SUS in only three municipalities, staff training policy characterized by specific initiatives decoupled from career progression. It was also possible to identify a restricted view by the counselors interviewed about their participation in the work management discussion; Municipal Health Councils' peripheral approach of the issues related to the management of the workforce; deficiencies in the decentralization of management positions for municipal SUS; tendency for private treatment by managers of the data concerning staff. In spite of the incipient implementation of the commitments stated in the Management Pact, we highlight the innovative inclusion of the work management on the Public Health System managers' agenda as a definite policy.

[Quality of life, work management, and career planning as a primary care technology in the Unified National Health System in São Paulo State, Brazil]. / Qualidade de vida, gestão do trabalho e plano de carreira como tecnologia (corrected) na atenção básica do Sistema Unico de Saúde em São Paulo, Brasil.

This article discusses the concept of quality of life in and at work, linked to health work management based on the evaluation of a work management instrument: the Career, Job, and Wage Plan. The aim was to analyze the plan as a work management technology in primary care in the Unified National Health System (SUS). The article discusses the plan in three municipalities in São Paulo State, Brazil: São Paulo, Guarulhos, and Campinas, in compliance with guidelines issued by the National Health Council in 2006, and using a qualitative survey conducted in 2007-2008. The study presents the findings from research in eight municipalities, based on interviews with managers, users (represented by Health Councils), and health workers and health sector trade unionists. The article concludes that this is still an incipient public management policy issue, with limited command by users, trade unionists, and health workers in the target municipalities, heavily populated 'hub cities' in the health regions.

Qualidade de vida, gestão do trabalho e plano de carreira como tecnologista em saúde na atenção básica do Sistema Único de Saúde em São Paulo, Brasil / Quality of life, work management, and career planning as a primary care technology in the Unified National Health System in São Paulo State, Brazil

O artigo trata do conceito de qualidade de vida no/do trabalho, articulando-o com a gestão do trabalho em saúde com base na avaliação de um instrumento de gestão do trabalho: o Plano de Carreiras, Cargos e Salários (PCCS). Objetiva-se analisá-lo como tecnologia de gestão do trabalho na atenção básica do Sistema Único de Saúde (SUS). São discutidos os PCCS de três municípios de São Paulo, Brasil: São Paulo, Guarulhos e Campinas, conforme diretriz emanada do Conselho Nacional de Saúde em 2006, mediante pesquisa de caráter qualitativo desenvolvida em 2007-2008. Retrata resultados de investigação realizada em oito municípios, considerando a visão do gestor, dos usuários representados nos Conselhos de Saúde e de sindicalistas e trabalhadores representantes dos trabalhadores de saúde que foram entrevistados. Conclui-se que a temática é incipiente como política pública de gestão, sendo matéria de pouco domínio seja dos usuários, seja dos sindicalistas e trabalhadores do setor saúde nos municípios estudados, situados dentre os mais populosos e "municípios-polo" de regiões de saúde.

This article discusses the concept of quality of life in and at work, linked to health work management based on the evaluation of a work management instrument: the Career, Job, and Wage Plan. The aim was to analyze the plan as a work management technology in primary care in the Unified National Health System (SUS). The article discusses the plan in three municipalities in São Paulo State, Brazil: São Paulo, Guarulhos, and Campinas, in compliance with guidelines issued by the National Health Council in 2006, and using a qualitative survey conducted in 2007-2008. The study presents the findings from research in eight municipalities, based on interviews with managers, users (represented by Health Councils), and health workers and health sector trade unionists. The article concludes that this is still an incipient public management policy issue, with limited command by users, trade unionists, and health workers in the target municipalities, heavily populated "hub cities" in the health regions.

Bioequivalence of two enteric coated formulations of pantoprazole in healthy volunteers under fasting and fed conditions.

PURPOSE: To compare the bioavailability of two pantoprazole (CAS 102625-70-7) formulations (40 mg pantoprazole enteric coated tablets) under fasted and fed conditions as well as to evaluate the dissolution profile in biorelevant media. METHODS: The subjects received either 40 mg of the reference or of test formulation in fasting (n = 28) and fed (n=70) condition. The studies were conducted according to a single dose and randomized crossover design. Blood samples were collected up to 12 h after drug administration in fasting condition and up to 48 h in fed condition. Plasma concentrations of pantoprazole were determined by LC-MS/MS. Pharmacokinetic parameters were calculated from the observed plasma concentration-time profiles. Bioequivalence between the formulations in fasting and fed condition was assessed considering 90% confidence intervals for the ratio of means for lnCmax and lnAUC(0-t) within 0.8-1.25. Dissolution profiles were evaluated in biorelevant media [Fasting State Simulating Intestinal Fluid (FaSSIF) and Fed State Simulating Intestinal Fluid (FeSSIF)]. The sameness of the dissolution curves was assessed by f2 values between 50 and 100. RESULTS: Under fasting condition the 90% confidence interval for the ratio of means for the lnCmax, (0.94-1.03) and lnAUC(0-t) (0.89-0.99) was within the guideline range of bioequivalence (0.80-1.25). However, the data for lnCmax (0.51-0.76) and lnAUC(0-t) (0.68-0.90) under fed condition were not within the bioequivalence range. The postprandial study demonstrated a high intra-subject variability and in some subjects pantoprazole could not be detected for up to 24 h, although the dissolution profile of reference and test formulations presented a similar disposition in FaSSIF and FeSSIF as confirmed by the values of f2 higher than 50. CONCLUSION: The results demonstrated that the test formulation was bioequivalent to the reference in fasting condition but not in postprandial state. The dissolution profile in FaSSIF indicates that this biorelevant medium was more adequate to discriminate the in vivo disposition of pantoprazole than FeSSIF. Furthermore, the fed condition study had shown a pronounced influence of food in the absorption of pantoprazole after single oral dose administration.

Indo mais rápido: para onde?: Um estudo do Projeto de Classes de Aceleração da Secretaria de Estado da Educação de São Paulo / Going faster: where to? A research of the Acceleration Classrooms Program of the São Paulo State Department of Education

A pesquisa situa o Projeto Classes de Aceleração no contexto das políticas neoliberais em educação. O economicismo presente nas ações da Secretaria de Estado da Educação transforma as possibilidades 'democratizantes' do Projeto em artifício para reduzir as despesas com o ensino público. Como mostram as pesquisas analisadas, se por um lado o Projeto preconiza uma relação de ensino-aprendizagem menos autoritária e proporciona melhores condições para o trabalho docente, por outro instala descontinuidades entre as condições oferecidas para a rede, em geral, e para o Projeto, em particular. O depoimento de um ex-aluno de uma Classe de Aceleração ilustra essa situação ao mostrar frustração e mágoa diante da oportunidade de aprendizagem que 'veio tarde', da curta carreira escolar após a saída do Projeto, da impotência diante de um mercado de trabalho cada vez mais restrito e exigente, e da ambigüidade frente ao papel redentor da escola na atualidade. O fluxo escolar foi desobstruído e esses alunos jogados de volta em uma escola que não se transformou, continuando a violentá-los, e em um mercado de trabalho que deles prescinde (AU)

Correçäo cirúrgica da persistência do canal arterial em crianças de baixo peso e neonatos / Surgical treatment of patent ductus arteriosus in low-weight child and neonates

A persistência do canal arterial ocorre com freqüência em neonatos prematuros, provocando um grave quadro de disfunçao cardiopulmonar. O tratamento envolve duas abordagens, sendo uma clínica e outra cirúrgica. A operaçao para a ligadura do canal arterial é praticada desde 1938. O enfoque clínico preconiza o uso da indometacina, com o intuito de promover a oclusao do canal arterial. O presente trabalho tem por objetivo avaliar os resultados obtidos com o tratamento cirúrgico da persistência do canal arterial, através de toracotomia e ligadura em 14 pacientes, incluindo crianças de baixo peso e neonatos prematuros com quadro clínico instável. A principal indicaçao cirúrgica, nestes casos, foi a presença de insuficiência respiratória aguda e insuficiência cardíaca. A técnica empregada foi a tripla ligadura do canal arterial. Nos 14 casos nao obtivemos nenhum tipo de complicaçao e sem mortalidade. A presença de uma Unidade de Tratamento Intensivo Neonatal (U.T.I) no Hospital foi de extremo valor no preparo dos pacientes e na evoluçao no período de pós-operatório. Este trabalho comprova a eficácia do método cirúrgico empregado, com baixas taxas de morbidade e mortalidade e a importância da U.T.I neonatal no acompanhamento dos pacientes.