In this study the effect of eight DNA topoisomerase inhibitors on the growth Trypanosoma rangeli epimastigotes in cell culture was investigated. Among the eight compounds tested, idarubicin was the only compound that displayed promising trypanocidal activity with a half-maximal growth inhibition (GI50) value in the sub-micromolar range. Fluorescence-activated cell sorting analysis showed a reduction in DNA content in T. rangeli epimastigotes when treated with idarubicin. In contrast to T. rangeli, against Trypanosoma cruzi epimastigotes idarubicin was much less effective exhibiting a GI50 value in the mid-micromolar range. This result indicates that idarubicin displays differential toxic effects in T. rangeli and T. cruzi. Compared with African trypanosomes, it seems that American trypanosomes are generally less susceptible to DNA topoisomerase inhibitors.

Markets for life-saving vaccines do not often generate the most desired outcomes from a public health perspective in terms of product quantity, quality, affordability, programmatic suitability and/or sustainability for use in the lowest income countries. The perceived risks and uncertainties about sustainably funded demand from developing countries often leads to underinvestment in development and manufacturing of appropriate products. The pilot initiative Advance Market Commitment (AMC) for pneumococcal vaccines, launched in 2009, aims to remove some of these market risks by providing a legally binding forward commitment to purchase vaccines according to predetermined terms. To date, 14 countries have already introduced pneumococcal vaccines through the AMC with a further 39 countries expected to introduce before the end of 2013. This paper describes early lessons learnt on the selection of a target disease and the core design choices for the pilot AMC. It highlights the challenges faced with tailoring the AMC design to the specific supply situation of pneumococcal vaccines. It points to the difficulty - and the AMC's apparent early success - in establishing a long-term, credible commitment in a constantly changing unpredictable environment. It highlights one of the inherent challenges of the AMC: its dependence on continuous donor funding to ensure long-term purchases of products. The paper examines alternative design choices and aims to provide a starting point to inform discussions and encourage debate about the potential application of the AMC concept to other fields.

Los mercados de vacunas que salvan vidas no suelen generar los resultados más deseados desde una perspectiva de salud pública, en términos de cantidad, calidad, viabilidad del producto, así como de idoneidad y/o sostenibilidad programática para su uso en los países con menores ingresos. Es frecuente que los riesgos e incertidumbres percibidos sobre la demanda financiada sostenible de países en desarrollo conlleven a la desinversión en el desarrollo y fabricación de los productos adecuados. La iniciativa piloto Compromiso de mercado anticipado (CAM) para vacunas neumocócicas, que se lanzó en 2009, pretende eliminar algunos de estos riesgos de mercado mediante la creación de un compromiso legalmente vinculante para la compra de vacunas de acuerdo con condiciones predeterminadas. Hasta la fecha, ya son 14 los países que han introducido vacunas neumocócicas a través del CAM y se espera que otros 39 países las introduzcan antes de finales del 2013. Este documento describe las lecciones anteriormente aprendidas sobre la selección de una enfermedad objetivo y las elecciones de diseño principales para el CAM piloto. Destaca los retos a los que hay que enfrentarse para adaptar el diseño CAM a la situación de suministro de vacunas neumocócicas específica. Señala la dificultad - y al aparentemente temprano éxito del CAM - de establecer un compromiso creíble, a largo plazo, en un entorno impredecible y constantemente cambiante. Destaca uno de los desafíos inherentes del CAM: su dependencia de la financiación donante continua para asegurar compras de productos a largo plazo. El documento examina las opciones de diseño alternativas y pretende proporcionar un punto inicial para informar las discusiones y promover los debates sobre la aplicación potencial del concepto CAM a otros campos.

Les marchés des vaccins salvateurs ne génèrent souvent pas les résultats désirés du point de vue de la santé publique, en termes de quantité, de qualité et de fiabilité des produits, mais aussi d'adéquation et/ou de durabilité des programmes pour l'utilisation dans les pays aux plus faibles revenus. Les risques perçus et les incertitudes concernant une demande durablement financée, de la part des pays en voie de développement, conduisent souvent à un sous-investissement dans le développement et la fabrication des produits appropriés. L'initiative pilote Garantie de marché (AMC) pour le vaccin antipneumococcique, lancée en 2009, vise à éliminer certains de ces risques du marché en offrant un engagement préalable, juridiquement contraignant, d'acheter des vaccins selon des conditions prédéfinies. À ce jour, 14 pays ont déjà introduit les vaccins contre le pneumocoque par le biais de l'AMC. Il est prévu que 39 autres pays les introduisent avant la fin de 2013. Cet article décrit les premières leçons tirées de la sélection d'une maladie cible et des choix du concept de base de l'AMC pilote. Il souligne les défis que suppose l'adaptation du concept d'AMC à la situation spécifique d'approvisionnement des vaccins contre le pneumocoque. Il met en exergue la difficulté - et l'apparent succès initial de l'AMC - d'établir un engagement crédible à long terme dans un environnement imprévisible, en constante évolution. Il met l'accent sur l'un des défis inhérents de l'AMC: sa dépendance vis-à-vis du financement continu des donateurs pour garantir les achats à long terme de produits. L'article examine les choix de concept alternatifs et vise à fournir un point de départ pour préparer les discussions et encourager le débat sur l'application potentielle du concept AMC à d'autres domaines.

Gas emissions discovered on the Brazo Rincon sector of Lake Nahuel Huapi in Patagonia, are described and characterized through analysis of hydroacoustic targets rising from the bottom. Echograms target analysis allowed for the identification of two possible sources. The first one corresponding to multiple gas vents in a seep field in 30 m to 100 m water depths. The second consisting of gas, fluids, resuspended bottom debris, and sediments in near-shore shallow waters. The hydroacoustic characteristics of these plumes are described, and possible origins of gas emissions are considered in relation to geological characteristics associated to local volcanism and/or biological phenomena.

Emisiones de gas en el brazo Rincón del lago Nahuel Huapi, Patagonia, son descriptas y caracterizadas en función del análisis de señales blancos ecoicos que migran desde el fondo hacia la superficie. Dichos blancos identificados como burbujas de gas, provienen en apariencia de dos fuentes distintas. Una de las señales resulta consistente con emanaciones de gases de múltiples fuentes de emisión, las cuales conforman un campo sumergido que se extiende entre los 30 y 100 m de profundidad. La otra consistente en el surgimiento de burbujas, arrastre de fluidos restos orgánicos resuspendidos y sedimentos de fondo en zonas litorales someras. Para ambos casos se analiza el posible origen de las emisiones en relación con condiciones geológicas asociadas a procesos volcánicos locales y/o a procesos biológicos.

The aim of this work was the study a trickling biofilter, where water was circulated throughout the bed. In the first steady state experiment, the packing materials used were 25mm Pall rings. The airflow rate was increased gradually and the concentration of styrene in the air stream was held constant. In the second experiment, 15mm Pall rings were used. In this case, the feed contained both styrene and a small amount of acetone. The concentration of acetone and the air flow rate were kept constant, but the styrene inlet concentration was increased. The concentrations were measured at the input, and also at an intermediate and the outlet position in the biotrickling filter to determine the concentration profile along the reactor. Using the values of coefficient of determination (R²) and the coefficient of variation of the fitted constant as criteria, a zero order model with diffusional limitation was chosen as the best representation of the data. Then a further, third, set of experiments were done at unsteady state, using step changes of the inlet concentration levels of both styrene and acetone at a steady air flow-rate . Inlet and outlet concentrations were measured as a function of time and the results were adequately described using a simple first order model.

ANTECEDENTES: A excreção urinária de albumina indica lesão nos rins e é reconhecida como fator de risco para a progressão das doenças renal e cardiovascular. A dosagem da albumina urinária chama a atenção sobre a necessidade clínica de relatos de resultados precisos e claramente descritos. O National Kidney Disease Education Program e a Federação Internacional de Química Clínica e Medicina Laboratorial (IFCC) reuniram-se para avaliar o estado atual das questões pré-analíticas, analíticas e pós-analíticas que afetam as dosagens da albumina na urina e para identificar as áreas que necessitam de melhorias. CONTEÚDO: A química da albumina na urina não é completamente compreendida. Diretrizes atuais recomendam a utilização da relação albumina/creatinina (RAC) como substituta para a coleta de amostras cronometradas de urina, frequentemente inadequadas. Os resultados da RAC são afetados pela preparação do paciente, pela hora do dia da coleta das amostras e não é padronizada. Foram relatadas consideráveis diferenças intermétodos para a dosagem tanto de albumina quanto de creatinina, mas a verdade é desconhecida, porque não existem procedimentos de referência para a dosagem de albumina e não há materiais de referência para qualquer um desses analitos na urina. Os intervalos de referência recomendados para a RAC não consideram as grandes diferenças intergrupos na excreção da creatinina (por exemplo, relacionadas com diferenças em idade, sexo e etnia), nem o aumento contínuo no risco relacionado com a excreção de albumina. DISCUSSÃO: Necessidades clínicas foram identificadas para a padronização de (a) métodos de coleta da urina, (b) dosagens de albumina e de creatinina na urina com base em um sistema de referência completo, (c) relatórios dos resultados dos testes e (d) intervalos de referência para a RAC.

BACKGROUND: Urinary excretion of albumin indicates kidney damage and is recognized as a risk factor for progression of kidney disease and cardiovascular disease. The role of urinary albumin measurements has focused attention on the clinical need for accurate and clearly reported results. The National Kidney Disease Education Program and the IFCC convened a conference to assess the current state of preanalytical, analytical, and postanalytical issues affecting urine albumin measurements and to identify areas needing improvement. CONTENT: The chemistry of albumin in urine is incompletely understood. Current guidelines recommend the use of the albumin/creatinine ratio (ACR) as a surrogate for the error-prone collection of timed urine samples. Although ACR results are affected by patient preparation and time of day of sample collection, neither is standardized. Considerable intermethod differences have been reported for both albumin and creatinine measurement, but trueness is unknown because there are no reference measurement procedures for albumin and no reference materials for either analyte in urine. The recommended reference intervals for the ACR do not take into account the large intergroup differences in creatinine excretion (e.g., related to differences in age, sex, and ethnicity) nor the continuous increase in risk related to albumin excretion. DISCUSSION: Clinical needs have been identified for standardization of (a) urine collection methods, (b) urine albumin and creatinine measurements based on a complete reference system, (c) reporting of test results, and (d) reference intervals for the ACR.

El Norte de Potosí es una de las partes más pobres de Bolivia, contiene los indicadores más altos de pobreza rural desnutrición e inseguridad alimentaria de los Andes bolivianos. El propósito fue caracterizar los niveles de desnutrición y las prácticas de alimentación de infantes para desarrollar un programa de intervenciones efectivas, sensibles al género y culturalmente relevantes, fomentando las buenas prácticas de alimentación infantil. Para la toma de los datos antropométricos se usó métodos estándares. Se tomaron el peso y la talla de 400 niños/as menores de cinco años de 30 comunidades. En seis de estas comunidades, se usaron entrevistas y discusiones con grupos focales con 33 madres y otros familiares, además de observaciones en los hogares para describir las prácticas de alimentación de los infantes. Casi el 20% de los niños/as son de bajo peso; además los niños/as tienen altos niveles de retraso en la talla. El 38% de las mamás empezaron la lactancia materna después de 12 horas. El 39% inició la alimentación complementaria, en los primeros tres meses. El tipo de alimento complementario que se da al infante en general fue inadecuado. Con este estudio se pudo ver que las deficiencias nutricionales a menudo empiezan cuando la madre inicia la lactancia materna y cuando introduce por primera vez la alimentación complementaria. Para las intervenciones que estén destinadas a mejorar la nutrición materno-infantil se requerirá cambios en el comportamiento personal, un mayor reconocimiento y apoyo comunitario; estrategias para llegar a la gente joven, hacer participar a los hombres y una mayor disponibilidad de servicios de calidad.

Northern Potosí is one of the poorest parts of Bolivia with the highest indicators of rural poverty, malnutrition and food insecurity in the Bolivian Andes. The objective of this research was to characterize the levels of malnutrition and describe infant feeding practices in Potosi, Bolivia and use this information to develop an effective, gender sensitive and culturally relevant intervention encouraging good infant feeding practices. Standard methods were used to collect anthropometric data. Weight and height data were collected for 400 children under five years of age from 30 communities. In six of these communities, interviews and focus group discussions were conducted with 33 mothers and other families in addition to household observational data that were collected to describe infant feeding practices. Nearly 20% of children were underweight; stunting was widespread as well. 38% of mothers initiated breastfeeding 12 hours or more after birth. 39% of mothers initiated complementary feeding in the first three months following birth. The type of complementary food given to children was usually inadequate. With this research we could see that nutritional deficiencies often begin when the mother starts breastfeeding and when first introduced complementary feeding. Interventions aimed at improving maternal and child nutrition will require changes in parents’ behavior, greater recognition and community support of the importance of child feeding, and the inclusion of strategies to reach young people, involve men, and make high quality nutrition promotion more widely available in the communities.