IPTSP - Instituto de Patologia Tropical e Saúde Pública

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    Epidemiologia molecular do HIV-1, resistência aos antirretrovirais em gestantes e transmissão vertical no estado de Goiás
    (Universidade Federal de Goiás, 2010-10-31) ALCÂNTARA, Keila Correia de; STEFANI, Mariane Martins de Araújo; http://lattes.cnpq.br/5581414958714905
    Introduction: The spread of the aids epidemic among young women and HIV-1 mother-tochild transmission (MTCT) represent important public health issues. In this context, prenatal care represents a unique opportunity for the early diagnosis of young women and for the implementation of full preventive strategies to HIV-1MTCT. Objectives: To study immunological, virological, clinical and epidemiological characteristics and to identify factors associated with HIV-1MTCT among HIV-1 pregnant women/infants recruited in Goias State. Material and methods: Cohort 1: 41 pregnant HIV/AIDS: infant pairs (April/2000-August/2001) were recruited and prospectively followed up at two regional reference centers-Mother-Infant Hospital (HMI/SUS) and Hospital Dr. Anuar Auad (HAA/HDT/SUS). Cohort 2: 172 HIV/AIDS pregnant women and 149 exposed children were recruited at the Institute of diagnosis and prevention (IDP/APAE) and prospectively followed up at HAA/HDT/SUS. The following tests were performed: maternal viral load, CD4+ T cell counts, HIV-1env/gag subtypes by heteroduplex mobility assay/HMA (cohort 1) and pol (protease and reverse transcriptase-PR/RT) sequencing for resistance profile, subtypes identification and phylogeography analysis for subtype C (cohort 2). Infants born to HIV-1/aids mothers were evaluated by plasma viral RNA and CD4+ T cell counts. Seroreversion of exposed- uninfected children was followed by sequential ELISA tests for IgG anti HIV-1. Results: Patients from cohorts 1 and 2 presented similar social-demographic and clinical profiles. The median age was 26 years; 15-41 years), lower educational level predominated and most were diagnosed during pregnancy (90%). Over 80% received ARV prophylaxis. One case of MTCT was observed in cohort 1 which was associated with short prophylaxis and long labor period. Exposed-uninfected infants born to symptomatic mothers seroreverted earlier. Cohort 2 included 80% of all HIV-1 infected pregnant women from Goias state in that period. The early prophylaxis and undetectable viral load predominated among previously diagnosed patients (p<0.05). One ARV naive patient presented transmitted drug resistance; 10 ARV experienced patients presented secondary drug resistance: 6 under MTCT prophylaxis, 4 under HAART. MTCT was observed in 3/149 (2.01%) cases and late diagnosis, vaginal delivery, brastfeeding and lack of oral ZDV were observed. Among MTCT cases resistance mutations were not detected. HMA env/gag (cohort 1) and pol sequencing (cohort 2) results showed mostly subtype B followed by subtypes F1, C and recombinants, mainly BF1. HIV-1 subtype C was identified only among pregnant women from cohort 2 which together with recombinants BC represented around 20% of the isolates. Subtype C and BC recombinants were isolated in interior municipalities of Goias state located close to the main highways that connect south/southern to north (BR153), northeast (BR020) and South/west (BR369/BR070). Phylogenetic/ phylogeographic analysis showed a subtype C clado, clusters (aLTR ≥ 0.85) with sequences from Southern states and from Sao Paulo and evidences of multiple introductions. Conclusion: Our results indicate the importance of prenatal care for the early diagnosis/prevention of HIV-1 vertical transmission. However late diagnosis and missed opportunities to fully prevent transmission were associated with vertical transmission. Multiple introductions and the dissemination of HIV-1 subtype C by heterosexual contact in interior cities highlight the importance of monitoring the genetic diversity and the impact of subtype C dissemination in the interior of Brazil. Note: superscript + is where it appears and the program does not copy.
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    Estratégias na identificação e caracterização de potenciais antifúngicos e seus alvos em Paracoccidioides brasiliensis
    (Universidade Federal de Goiás, 2010-09-10) CARVALHO, Patrícia Fernanda Zambuzzi; PEREIRA, Maristela; http://lattes.cnpq.br/1345781867765758
    The termodimorphic fungus Paracoccidioides brasiliensis is the etiological agent of paracoccidioidomycosis (PCM), a systemic human mycosis geographically distributed in Latin America, being the eighth most common cause of death among chronic infections. PCM is acquired by inhalation of fungal propagules, which reach the lungs and is disseminate through the bloodstream and/or lymph to all parts of the body. The treatment of PCM is long, starting with a dosage of aggressive antifungal agents, extending for months or years. Resistance to antimicrobial drugs may limit the ability of effective treatment of patients, interfering with therapeutic efficacy. Thus, it is necessary to discover and develop new antifungal agents. Plants compounds have a great structural diversity, many of which are models for the synthesis of a vast number of drugs. The action of the oenothein B compound, purified from leaves of Eugenia uniflora, a plant from the Brazilian Savannah, was evaluated on growth, viability and expression of P. brasiliensis genes. The compound interfered with cell morphology and inhibited the transcripts of β-1- 3-glucan synthase. The synergistic effect between oenothein B and drugs used to treat PCM (amphotericin B, itraconazole, Sulfamethoxazole and Trimethoprim-Sulfamethoxazole Combination) was evaluated in this study by the method of sensitivity on plates. The highest inhibition of the fungal growth was observed in association of oenothein B with Trimethoprim-Sulfamethoxazole Combination, followed by amphotericin B, itraconazole and sulfamethoxazole, respectively. Representational Difference Analysis (RDA) was also performed to elucidate the mechanism of action of oenothein B in P. brasiliensis. We identified 463 ESTs up regulated and 121 ESTs down regulated after 90 min of incubation of P. brasiliensis yeast cells with the compound. After 180 min incubation 301 ESTs up regulated and 143 down regulated were identified. The ESTs were classified according to their functional categories using the program Blast2GO. The analysis indicated the presence of transcripts with functions related to cell wall and membrane, transcription factors and hypothetical proteins. In this study, we evaluated also the characteristics of the malate synthase (Pbmls) cDNA, regulation of Pbmls gene expression, and enzymatic activity of the MLS protein of P. brasiliensis (PbMLS), isolate Pb01. The cDNA contains 1617 bp, which encodes a protein of 539 amino acids. The protein has the signature of the MLSs, residues essential for catalytic activity and addressing signal for peroxisomes, PTS1. The high level of Pbmls transcript observed in the presence of 2C sources suggests that in P. brasiliensis, the primary regulation of carbon flux into glyoxylate cycle was at the level of the Pbmls transcript. Transcript analysis, protein levels and enzymatic activity in the presence of different carbon and nitrogen sources suggest that PbMLS acts in both pathways: in glyoxylate cycle, when 2C sources are used, and in alantoin degradation pathway, when proline is used as nitrogen source, or when oxalurate is used to induces genes from pathway.
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    Estudo do metabolismo energético de Leishmania spp utilizando cromatografia líquida de alta eficiência e ressonância magnética nuclear
    (Universidade Federal de Goiás, 2011-09-16) COSTA, Tatiane Luiza da; VINAUD, Marina Clare; http://lattes.cnpq.br/1921551651088660; BEZERRA, José Clecildo Barreto; http://lattes.cnpq.br/9491755585617846
    Leishmaniasis is a disease of the endothelial reticulum system and is caused by protozoans form the Leishmania genus. The promastigote forms of Leishmania sp degradate carbohydrates through the glycolityc pathway and its first reaction occurs inside the glicosome. As they use as energy source glucose, aminoacids and lipids from the culture media the excreted/secreted (E/S) products may be useful as indicative of the energetic and metabolis profile of the parasite and of its biological disturbances. The biochemical analysis of Leishmania metabolism is important to upgrade the parasitological studies with techniques which are adequate to the evaluation of the biochemical profile of the host-parasite relationship towards a better understanding of how these organisms are able to survive in such diverse environments such as the digestory tract of the insect or inside vertebrate hosts tissues. The aim of this study was to perform a study of the energetic metabolism of species and isolates of Leishmania spp. Therefore the in vitro analysis of E/S metabolic products from the parasite within the culture media during logarithmic and stationary growth phases was performed through chromatographic (HPLC) methods. The spectrophometry was used to glucose measurement and the nuclear magnetic resonance (NMR) was implanted aiming the study of the parasite‟s metabolism. Through HPLC it was possible to verify a significant difference in the E/S of organic acids from the carbohydrates metabolism (pyruvate and lactate), intermediary metabolism (citrate, α-ketoglutarate, succinate, fumarate, malate and oxaloacetate) and from the fatty acids oxidation (β-hydroxibutyrate) between differents species and isolates of Leishmania spp. Through the enzymatic spectrophotometric analysis we verified the different concentrations of glucose. The NMR through 13C and 1H detected the following metabolites in pellet and supernatant: alanine, lactate, acetate, oxalate, pyruvate, succinate, glicerol, CO2, ureia and aminoacids (glutamine, valine and arginine). Therefore, through the several methods it was possible to observe that there is difference of E/S metabolites between the isolates and strains of Leishmania spp that utilize several biochemical pathways to energy production and the identification of these pathways may be used to identify each isolate and also establish metabolic differences in the host-parasite relationship.
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    Mortalidade por causas violentas em jovens de Goiânia
    (Universidade Federal de Goiás, 2010-05-19) MINAMISAVA, Ruth; ANDRADE, Ana Lúcia Sampaio Sgambatti de; http://lattes.cnpq.br/7770363683068899
    Background: Deaths due to homicides and traffic accidents among youth are a public health issue worldwide. Studies of the complex network of cause and effect on this topic point to both poverty and health inequalities. Different investigational approaches to intentional and unintentional deaths combined with socioeconomic variables can help create a better understanding of the association between violence and socioeconomic conditions. This study analyzed the spatial distribution and potential clusters of risk for intentional and unintentional deaths among youths aged 15-24 years in Goiânia, a newly urbanized city in central Brazil. Methods: Death data and residential addresses were extracted from the national Mortality Information System and validated by household visits. To detect all potential cases, we prospectively investigated every death classified as a transport accident, assault, legal intervention,intentional self-harm, unknown underlying cause, and undetermined intent according to the ICD-10. The Geographical Information System was used to plot residential addresses, and cases were interactively geocoded to the residential address level using a digital map of the municipality. Spatial scan statistic was applied (Poisson model) to identify clusters of census tracts with high mortality due to intentional injuries and traffic accidents. The socioeconomic variables obtained using census data were compared between the most likely cluster and other areas of the municipality. Results: The most violent deaths among young people were due to intentional injuries. Between August 2005 and August 2006, 145 addresses for cases of intentional injuries and traffic accidents were located and geocoded. No significant clusters for deaths due to traffic accidents were found within the municipality. One significant cluster (RR = 4.65; p = 0.029) composed of 14 cases of intentional deaths, mostly homicides, was detected in an emergent, populated, and very poor area on the outskirts of the town. This cluster had a significantly higher proportion of people with the lowest educational status, lowest income, and poor housing conditions in comparison to the remainder of the municipality. Conclusion: Our findings highlight the link between social inequalities and intentional deaths, clearly showing the need for urgent social interventions to reduce violence and premature mortality.