Browsing by Author "Cunha, Lucas Maciel"

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    Benznidazole, itraconazole and their combination in the treatment of acute experimental chagas disease in dogs.
    (2019) Cunha, Eleonora Lima Alves; Torchelsen, Fernanda Karoline Vieira da Silva; Cunha, Lucas Maciel; Oliveira, Maykon Tavares de; Fonseca, Kátia da Silva; Vieira, Paula Melo de Abreu; Carneiro, Cláudia Martins; Lana, Marta de
    Chagas disease (CD) is a serious public health problem in Latin America and its treatment remains neglected. Benznidazole (BZ), the only drug available in Brazil, presents serious side effects and low therapeutic efficacy, especially at the chronic phase. The last clinical trials demonstrated that the first generation of azole compounds were less successful than BZ in CD chemotherapy, which stimulated studies of these compounds associated to BZ and nifurtimox (NF). This study evaluated the therapeutic efficacy of BZ, itraconazole (ITZ) and their combination (BZ + ITZ) in dogs infected with the VL-10 T. cruzi strain in the acute phase of the disease. Twenty young mongrel dogs were inoculated with 2.0 × 103 blood trypomastigotes/kg and divided into four groups: treated with BZ, ITZ and BZ + ITZ for 60 days, and control group (INT). The parasitemia of the BZ + ITZ and BZ groups were similar and showed significant reduction compared to the INT group. The group treated with ITZ also showed significant parasitemia reduction compared to the INT group. The global analysis of hemoculture (HC), blood PCR, conventional serology (CS-ELISA), heart qPCR and histopathology techniques, used in the post-treatment evaluation, revealed that BZ + ITZ combination lead to a more reduction of parasitemia during the acute phase and heart qPCR positivity, less cardiac damage (inflammation and fibrosis in the left ventricle) and total survival. According to the classical cure criteria one animal treated with BZ + ITZ can be considered cured in its final evaluation and two other dogs, one of this group and one treated with ITZ were in process of cure. At least for BZ-resistant T. cruzi strains such as VL-10, BZ + ITZ was not effective to induce parasitological cure or a profound and sustained reduction of the parasite burden in blood and infected organs.
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    Cães sentinelas no monitoramento de contaminantes inorgânicos ambientais.
    (2019) Neves, Luana Clarice das; Silva, André Talvani Pedrosa da; Bezerra, Olívia Maria de Paula Alves; Cunha, Lucas Maciel; Silva, André Talvani Pedrosa da; Fontenelle, Júlio Cesar Rodrigues; Souza, Vanner Boere
    Bioindicadores sentinelas, como podem ser os cães domésticos (Canis lupus familiaris), são organismos vivos que indicam alterações num determinado ecossistema, já que compartilham características fisiológicas semelhantes aos humanos, podendo ser intoxicados pelos mesmos contaminantes, e consequentemente, produzirem a mesma resposta à exposição. Faz-se necessário um aprofundamento do estudo dos riscos de contaminação, usando bioindicadores, especialmente em áreas de intenso extrativismo mineral. Assim, o objetivo do trabalho é avaliar a exposição aos contaminantes inorgânicos nessas áreas de risco iminente de contaminação, usando cães domésticos como potenciais bioindicadores. Avaliaram-se os exames semiológicos nos cães e amostras de sangue foram coletadas para análises de identificação e concentração dos contaminantes inorgânicos chumbo e cádmio. Durante a realização da pesquisa, a análise de dados, verificou-se correlações entre os níveis de cádmio e chumbo e sua correção com enzimas hepáticas (TGO, TGP), parâmetros hematológicos, clínicos e socioambientais dos animais. Observou-se que todos os cães de Antônio Pereira apresentaram presença de cádmio e chumbo no sangue, sendo de 1.30 a 1.57 para cádmio e 3.33 a 4.26 para chumbo. Identificou-se maior correlação entre o tipo de alimentação (comida caseira + ração), o tipo de solo (terra e calçamento da residência), o gênero (fêmea) e a maior idade com os contaminantes inorgânicos nos animais do distrito de Antônio Pereira. Além disso, observou-se maior atividade da enzima TGP associada aos elementos inorgânicos. Estes dados sugerem que, mesmo com níveis não tão elevados de cádmio e chumbo, ainda assim os cães domésticos atuam como importantes bioindicadores sentinelas para contaminantes inorgânicos em áreas de atividade de mineração.
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    The effect of benznidazole dose among the efficacy outcome in the murine animal model. A quantitative integration of the literature.
    (2020) Molina, Israel; Melo, Luísa Helena Perin de; Aviles, Augusto Sao; Vieira, Paula Melo de Abreu; Fonseca, Kátia da Silva; Cunha, Lucas Maciel; Carneiro, Cláudia Martins
    Despite more than 100 years since it was firstly described Chagas disease, only two drugs are available to treat Chagas disease: Nifurtimox launched by Bayer in 1965 and benznidazole launched by Roche in 1971. Drug discovery initiatives have been looking for new compounds as an alternative to these old drugs. Although new platforms have been used with the latest technologies, a critical step on that process still relies on the in vivo model. Unfortunately, to date, available animal models have limited predictive value and there is no standardization. With the aim to better understand the role of benznidazole, the current standard of care of Chagas disease, we performed this review. We intend to analyze the influence of the experimental design of the most used animal model, the murine model, in the assessment of the efficacy endpoint.
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    Visceral leishmaniasis : a practical strategy for quantitative molecular diagnosis in naturally infected dogs.
    (2020) Caldas, Sérgio; Marcelino, Andreza Pain; Faria, Gilson; Silva, Fernanda de Oliveira; Ataide, Ana Caroline Zampiroli; Cunha, Lucas Maciel; Bahia, Maria Terezinha; Paz, Gustavo Fontes; Gontijo, Célia Maria Ferreira
    The diagnosis of canine visceral leishmaniasis (CVL) has been a problem for public health services due to the variety of clinical signs similar to other diseases and low sensitivity and specificity of available tests. In this sense, our main objective was to develop a simple, rapid, and accurate quantitative real-time PCR (qPCR) diagnosis for CVL. Thus, low-invasive samples from bone marrow (BM), popliteal lymph nodes (PLN), and conjunctival swabs (CS) were selected from negative and VL-positive dogs, using as gold standard, immunological and parasitological tests performed with different tissues. Oligonucleotides for Leishmania infantum kDNA were designed and the limit of quantification and amplification efficiency of the qPCR were determined using tissue-specific standards produced with DNA from those different tissues, mixed with DNA from a known amount of L. infantum promastigotes. Endogenous control was used to validate a comparative Ct method, and tissue parasite concentrations were estimated by comparison with tissue-specific reference standard samples. The overall analysis of the qPCR data suggests the following ranking for tissue choice: PLN > BM > CS. Finally, we have concluded that this molecular approach simplifies and accelerates the quantitative diagnostic process because it is easy to perform, requiring no DNA dosing or standard curve application, and it shows good diagnostic parameters, especially when using popliteal lymph node samples.