18 research outputs found

    In Vitro and In Vivo High-Throughput Assays for the Testing of Anti-Trypanosoma cruzi Compounds

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    The treatment of Trypanosoma cruzi infection (the cause of human Chagas disease) remains a significant challenge. Only two drugs, both with substantial toxicity, are available and the efficacy of these dugs is often questioned – in many cases due to the limitations of the methods for assessing efficacy rather than to true lack of efficacy. For these reasons relatively few individuals infected with T. cruzi actually have their infections treated. In this study, we report on innovative methods that will facilitate the discovery of new compounds for the treatment of T. cruzi infection and Chagas disease. Utilizing fluorescent and bioluminescent parasite lines, we have developed in vitro tests that are reproducible and facile and can be scaled for high-throughput screening of large compound libraries. We also validate an in vivo screening test that monitors parasite replication at the site of infection and determines the effectiveness of drug treatment in less than two weeks. More importantly, results in this rapid in vivo test show strong correlations with those obtained in long-term (e.g. 40 day or more) treatment assays. The results of this study remove one of the obstacles for identification of effective and safe compounds to treat Chagas disease

    Type-Specific HPV Prevalence in Cervical Cancer and High-Grade Lesions in Latin America and the Caribbean: Systematic Review and Meta-Analysis

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    BACKGROUND: Cervical cancer is a major public health problem in Latin America and the Caribbean (LA&C), showing some of the highest incidence and mortality rates worldwide. Information on HPV type distribution in high-grade cervical lesions (HSIL) and invasive cervical cancer (ICC) is crucial to predict the future impact of HPV16/18 vaccines and screening programmes, and to establish an appropriate post-vaccinal virologic surveillance. The aim was to assess the prevalence of HPV types in HSIL and ICC in studies in LA&C. METHODS AND FINDINGS: We performed a systematic review, following the MOOSE guidelines for systematic reviews of observational studies, and the PRISMA statement for reporting systematic reviews and meta-analyses. Inclusion criteria were at least ten cases of HSIL/ICC, and HPV-type elicitation. The search, without language restrictions, was performed in MEDLINE, Cochrane Library, EMBASE, LILACS from inception date to December 2009, proceedings, reference lists and consulting experts. A meta-analysis was performed using arc-sine transformations to stabilize the variance of simple proportions. Seventy-nine studies from 18 countries were identified, including 2446 cases of HSIL and 5540 of ICC. Overall, 46.5% of HSIL cases harbored HPV 16 and 8.9% HPV18; in ICC, 53.2% of cases harbored HPV 16 and 13.2% HPV 18. The next five most common types, in decreasing frequency, were HPV 31, 58, 33, 45, and 52. Study's limitations comprise the cross-sectional design of most included studies and their inherent risk of bias, the lack of representativeness, and variations in the HPV type-specific sensitivity of different PCR protocols. CONCLUSIONS: This study is the broadest summary of HPV type distribution in HSIL and ICC in LA&C to date. These data are essential for local decision makers regarding HPV screening and vaccination policies. Continued HPV surveillance would be useful, to assess the potential for changing type-specific HPV prevalence in the post-vaccination era in Latin America

    Patterns on the Fish Skins Induced by Anisotropy in Diffusion (Interfaces, Pulses and Waves in Nonlinear Dissipative Systems : RIMS Project 2000 "Reaction-diffusion systems : theory and applications")

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    The EURECA (European Underground Rare Event Calorimeter Array) project is aimed at searching for dark matter particles using cryogenic bolometers. The proponents of the present project have decided to pool their strengths and expertise to build a facility to house up to 1000 kg of detectors, EURECA, consisting in the first instance of germanium and CaWO 4 crystals. The shielding will be provided through a large water tank in which the cryostat with detectors will be immersed. The EURECA infrastructure will be an essential tool for the community interested in using cryogenic detectors for dark matter searches. Beyond European detectors, it will be designed to host other types of similar cryogenic detectors, requiring millikelvin operating temperatures. In particular, this includes the germanium detectors currently in use by the SuperCDMS team, following the current collaborative work performed by the EURECA and SuperCDMS collaborations. EURECA will have two stages. The first phase aims at a sensitivity of 3 . 10 −10  pb and will involve building the infrastructure, cryostat and shielding, and operating 150 kg of detectors. The second phase will be completed with 850 kg of additional detectors, the relative weight between the different detectors being decided by the collaboration according to the physics reach. A sensitivity of 2 . 10 −11 pb is aimed for at the second stage. EURECA will ideally benefit from the planned extension of the deepest underground laboratory in Europe  – LSM. With a site-independent design, it can also be hosted in other locations at similar or deeper sites such as SNOLAB

    Temporal variation of biomass and nutrient status of azolla filiculoides lam: (sal viniaceae) in a small shallow dystrophic lake

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    This study determined the temporal variation of the biomass and the concentrations of carbon, nitrogen and phosphorus in Azolla filiculoides Lam. in a small (0.5 ha) shallow dystrophic lake located in the city of Rio Grande (Rio Grande do Sul State, Brazil). Method: Sampling was conducted monthly between November 2000 and October 2001. The macrophytes were collected randomly in three replicates with a circular collector 0.3 m in diameter and subsequently washed with tap water and oven-dried at 60 °C for determination of the dry weight and the nutrient status (i.e., carbon, nitrogen and phosphorus). Primary productivity was estimated by the variation in biomass among successive samples. Results: A. filiculoides was present in the lake throughout the year and occupied between 50 and 80% of the surface area. The biomass values ranged from 34.2 g DW.m–2, recorded in May (autumn), to 170.9 g DW.m–2 in January (summer). The highest rate of primary productivity was 3.3 g DW.m–2.d–1, observed in June. The concentrations of carbon, nitrogen and phosphorus in the plant ranged between 403 and 551 g.kg–1, 13.4 and 25.7 g.kg–1 and 0.5 and 1.9 g.kg–1, respectively. The water N:P ratio ranged between 19:1 and 368:1. Conclusion: The coverage of the surface of the lake by A. filiculoides throughout the study period and the nutritional status of the plant demonstrate the importance of the cycling of nutrients by macrophytes in this aquatic environment. The higher N:P ratio in the water column, compared with other neighboring environments without macrophytes, shows that the enrichment of the lake may result from the biological N-fixation activity produced by A. filiculoides.Este estudo determinou a variação temporal da biomassa e as concentrações de carbono, nitrogênio e fósforo de Azolla filiculoides Lam., em um pequeno lago raso distrófico situado no município do Rio Grande (Rio Grande do Sul, Brasil). Método: As amostragens foram realizadas mensalmente no período entre novembro de 2000 e outubro de 2001. As macrófitas foram coletadas aleatoriamente em três repetições, utilizando-se coletor circular de 0,3 m de diâmetro e posteriormente lavadas com água corrente e secas em estufa 60 °C para determinação do peso seco e dos nutrientes: carbono, nitrogênio e fósforo. A produção primária foi estimada pela variação de biomassa entre coletas sucessivas. Resultados: A. filiculoides esteve presente no lago durante todo o ano, ocupando sempre entre 50 e 80% da superfície do lago. Os valores de biomassa variaram entre 34,2 g PS.m–2, registrado em maio (outono) e 170,9 g PS.m–2 em janeiro (verão). A maior taxa de produtividade primária foi 3,3 g PS.m–2.d–1 foi registrada em Junho. As concentrações de carbono, nitrogênio e fósforo na planta variaram entre: 403 e 551 g. kg–1, 13,4 e 25,7 g.kg–1 e 0,5 e 1,9 g.kg–1, respectivamente. Os valores da relação N:P na coluna de água variou entre 19:1 e 368:1. Conclusão: A cobertura da superfície do lago por A. filiculoides durante todo o período do estudo e o seu estado nutricional demonstram sua importância na ciclagem dos nutrientes neste ambiente aquático. A maior relação N:P na coluna de água quando comparada a outro ambiente próximo sem a presença desta macrófita, apoia a ideia de que A. filiculoides pode ser a responsável pelo enriquecimento do lago por meio da atividade de fixação biológica de nitrogênio
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