DEFAR - Departamento de Farmácia

URI permanente desta comunidadehttp://www.hml.repositorio.ufop.br/handle/123456789/530

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2004 - 200932010 - 20151

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Autor: search.filters.author.Martins, Helen Rodrigues

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    Effects of specific treatment on parasitological and histopathological parameters in mice infected with different Trypanosoma cruzi clonal genotypes.
    (2004) Toledo, Max Jean de Ornelas; Bahia, Maria Terezinha; Veloso, Vanja Maria; Carneiro, Cláudia Martins; Coelho, George Luiz Lins Machado; Alves, Cíntia Fontes; Martins, Helen Rodrigues; Cruz, Ruth Elizabeth; Tafuri, Washington Luiz; Lana, Marta de
    The goal of this study was to verify the effect of specific treatment on parasitological and histopathological parameters in mice experimentally infected with different Trypanosoma cruzi clonal genotypes. Twenty cloned stocks were selected, representative of the whole phylogenetic diversity of the protozoan and belonging to the clonal genotypes 19 and 20 (T. cruzi I) and 39 and 32 (T. cruzi II). The stocks were inoculated in 40 BALB/c mice divided into four groups: (i) treated with benznidazole, (ii) treated with itraconazole and (iii and iv) untreated control groups (NT) for each drug, respectively. Seven parameters related to parasitaemia curves and histopathological lesions were analysed. Four during the acute phase (AP) and three during both the AP and chronic phase (CP) of infection. Statistical comparison between benznidazole-treated and NT groups for the biological parameters showed significant differences for all genotypes. Benznidazole treatment led to lower patent period, maximum of parasitaemia, day of maximum parasitaemia and area under the parasitaemia curve for all genotypes analysed. Percentage of positive haemoculture during AP and CP was lower for genotypes 19 and 32. Tissue parasitism (TP) and inflammatory process (IP) during AP were lower for genotypes 19 and 32, respectively. In general, itraconazole treatment induced a smaller reduction in these same parameters between treated and NT animals in relation to benznidazole treatment. Our results indicate that phylogenetic divergence among T. cruzi clonal genotypes must be taken in account in chemotherapy and studies dealing with all aspects of the parasite and the disease.
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    Impact of dual infections on chemotherapeutic efficacy in balb/c mice infected with major genotypes of trypanosoma cruzi.
    (2007) Martins, Helen Rodrigues; Silva, Rodrigo Moreira da; Valadares, Helder Magno Silva; Toledo, Max Jean de Ornelas; Veloso, Vanja Maria; Avelar, Danielle Marchetti Vitelli; Carneiro, Cláudia Martins; Coelho, George Luiz Lins Machado; Bahia, Maria Terezinha; Martins Filho, Olindo Assis; Macedo, Andréa Mara; Lana, Marta de
    The aim of this work was to investigate the impact of dual infections with stocks of Trypanosoma cruzi major genotypes on benznidazole (BZ) treatment efficacy. For this purpose, T. cruzi stocks representative of the genetic T. cruzi lineages, displaying different susceptibilities to BZ, belonging to the major T. cruzi genotypes broadly dispersed in North and South America and important in Chagas’ disease epidemiology were used. Therapeutic efficacy was observed in 27.8% of the animals treated. Following BZ susceptibility classification, significant differences were observed in dual infections on the major genotype level, demonstrating that combinations of genotypes 19 39 and genotypes 19 32 led to a shift in the expected BZ susceptibility profile toward the resistance pattern. Analysis on the T. cruzi stock level demonstrated that 9 out of 24 dual infections shifted the expected BZ susceptibility profile compared with the respective single infections, including shifts toward lower and higher BZ susceptibilities. Microsatellite identification was able to identify a mixture of T. cruzi stocks in 7.7% of the T. cruzi isolates from infected and untreated mice (6.9%) and infected and treated but not cured mice (9.0%), revealing in some mixtures of BZ-susceptible and -resistant stocks that the T. cruzi stock identified after BZ treatment was previously susceptible in single infections. Considering the clonal structure and evolution of T. cruzi, an unexpected result was the identification of parasite subpopulations with distinct microsatellite alleles in relation to the original stocks observed in 12.2% of the isolates. Taken together, the data suggest that mixed infections, already verified in nature, may have an important impact on the efficacy of chemotherapy.
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    Persistence of PCR-positive tissue in benznidazole-treated mice with negative blood parasitological and serological tests in dual infections with Trypanosoma cruzi stocks from different genotypes.
    (2008) Martins, Helen Rodrigues; Moreira, Lílian Figueiredo; Silva, Jaquelline Carla Valamiel de Oliveira e; Carneiro, Cláudia Martins; Coelho, George Luiz Lins Machado; Avelar, Danielle Marchetti Vitelli; Bahia, Maria Terezinha; Martins Filho, Olindo Assis; Macedo, Andréa Mara; Lana, Marta de
    Objectives: To assess different methodologies to better define an early post-therapeutic cure criterion after benznidazole treatment in BALB/c mice following mixed infection with dual Trypanosoma cruzi genotypes. Methods: According to the classical cure criteria, animals were classified as treated not cured (TNC 5 76.4%), treated cured (TC 5 12.5%) and dissociated (DIS 5 11.1%) using parasitological [fresh blood examination (FBE), blood culture (BC) and blood PCR] and serological methods [conventional serology (CS-ELISA) and non-conventional serology (NCS-FC-ALTA)]. Tissues were also evaluated by PCR. Results: FBE was able to detect patent parasitaemia in only 18.1% of TNC and therapeutic failure was detected in 79.1% and 97.2% of TNC by BC and blood PCR, respectively. CS-ELISA should not be used before 3 months after treatment since it may lead to false-negative results. At 3 months after treatment with benznidazole, NCS-FC-ALTA was more efficient for categorizing the groups of treated mice. In the TNC group, although a decreased frequency of PCR-positive tissue was observed in several host tissues, increased positivity was also observed, despite the T. cruzi genotype combination. All TC animals presented at least two positive tissue-PCR results. Conclusions: Our results confirm that NSC-FC-ALTA and blood PCR are the most suitable methods to early detect therapeutic failure in acute murine T. cruzi infection. Additionally, our data show that BC positivity is highly dependent upon the T. cruzi genotype combination. Moreover, our findings demonstrated that PCR tests performed on tissues from animals considered cured after benznidazole treatment still detected T. cruzi DNA, most probably indicating residual infection.
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    Trypanosoma cruzi Discret Typing Units (TcII and TcVI) in samples of patients from two municipalities of the Jequitinhonha Valley, MG, Brazil, using two molecular typing strategies.
    (2015) Oliveira, Maykon Tavares de; Assis, Girley Francisco Machado de; Silva, Jaquelline Carla Valamiel de Oliveira e; Machado, Evandro Marques de Menezes; Silva, Glenda Nicioli da; Veloso, Vanja Maria; Macedo, Andréa Mara; Martins, Helen Rodrigues; Lana, Marta de
    Background: Trypanosoma cruzi is classified into six discrete taxonomic units (DTUs). For this classification, different biological markers and classification criteria have been used. The objective was to identify the genetic profile of T. cruzi samples isolated from patients of two municipalities of Jequitinhonha Valley, MG, Brazil. Methods: Molecular characterization was performed using two different criteria for T. cruzi typing to characterize 63 T. cruzi samples isolated from chronic Chagas disease patients. The characterizations followed two distinct methodologies. Additionally, the RAPD technique was used to evaluate the existence of genetic intragroup variability. Results: The first methodology identified 89 % of the samples as TcII, but it was not possible to define the genetic identity of seven isolates. The results obtained with the second methodology corroborated the classification as TcII of the same samples and defined the classification of the other seven as TcVI. RAPD analysis showed lower intra-group variability in TcII. Conclusions: The results confirmed the preliminary data obtained in other municipalities of the Jequitinhonha Valley, showing a predominance of TcII, similar to that verified in northeast/south axis of Brazil and the first detection of TcVI in the study region. The second protocol was more simple and reliable to identify samples of hybrid character.