Navegando por Autor "Cunha, Eleonora Lima Alves"
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Item Avaliação do tratamento com benznidazol, itraconazol e sua associação na fase aguda da doença de Chagas experimental no modelo cão.(2017) Cunha, Eleonora Lima Alves; Lana, Marta de; Lana, Marta de; Silva, André Talvani Pedrosa da; Murta, Silvane Maria FonsecaA doença de Chagas (DCh) e seu tratamento permanecem negligenciados e ainda constitui um sério problema de saúde pública na América Latina. O benznidazol (BZ) é atualmente o único fármaco disponível no Brasil para o tratamento da DCh, apresentando efeitos colaterais graves, limitada e variável eficácia terapêutica, especialmente na fase crônica da doença. Após os ensaios clínicos feitos no Brasil demonstrarem que os derivados azólicos de primeira geração não promoveram cura parasitológica e nem impediram a progressão da DCh em humanos, os estudos de associação de fármacos desta classe de compostos com BZ passaram a ser estimulados. Nesse sentido, o objetivo do presente estudo foi avaliar a ação terapêutica do BZ, itraconazol (ITRA) e de sua associação (BZ+ITRA), em cães infectados com cepa VL-10 do Trypanosoma cruzi (T. cruzi) tratados durante a fase aguda da infecção e seu impacto na evolução clínica da doença. O modelo cão foi utilizado por ser considerado ideal para o estudo da DCh e seu tratamento, pois reproduzem as fases aguda e crônica da doença e a manifestação clínica mais importante, a cardiopatia chagásica crônica. Para tal, 20 cães jovens sem raça definida foram inoculados via IP com 2000 tripomastigotas sanguíneas de T. cruzi/kg, e divididos em 4 grupos: I – tratados com BZ: 7 mg/kg em duas doses diárias; II – tratados com ITRA: 6 mg/kg/dia; III – tratados com BZ+ITRA na mesma posologia da monoterapia; IV – grupo controle infectado não tratado. Os animais foram tratados a partir do primeiro dia de parasitemia patente por 60 dias consecutivos. Foram realizados exames de sangue a fresco, hemocultura, reação em cadeia da polimerase (PCR) em eluato de sangue, sorologia convencional (ELISA), PCR quantitativa e histopatologia de tecido cardíaco. Após 18 meses das repetidas avaliações dos animais, foi possível observar uma melhor atividade terapêutica da associação de BZ+ITRA do que nos grupos tratados com ITRA e BZ em monoterapia. De acordo com o critério de cura estabelecido pelo Ministério da Saúde (2016), o cão B8, tratado com BZ+ITRA, apresentou na sua última avaliação resultados negativos nos testes parasitológicos e na ELISA, sugerindo estar curado. Já o cão B4 tratado com ITRA e o cão B7 tratados com BZ+ITRA, apresentaram avaliações parasitológicas negativas, exceto sorologia convencional. Contudo, para a melhor compreensão da cura efetiva dos animais ainda seriam necessárias mais avaliações a longo prazo ou técnicas alternativas.Item 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 deChagas 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.Item Benznidazole, itraconazole, and their combination for the treatment of chronic experimental Chagas disease in dogs.(2022) Cunha, Eleonora Lima Alves; Torchelsen, Fernanda Karoline Vieira da Silva; Fonseca, Kátia da Silva; Sousa, Lucas Resende Dutra; Vieira, Paula Melo de Abreu; Carneiro, Cláudia Martins; Pinto, Kelerson Mauro de Castro; Torres, Rosália Morais; Lana, Marta deTreatment for Chagas disease has limited efficacy in the chronic phase. We evaluated benznidazole (BZ) and itraconazole (ITZ) individually and in association in dogs 16 months after infection with a BZ-resistant Trypa- nosoma cruzi strain. Four study groups (20 animals) were evaluated and treated for 60 days with BZ, ITZ, or BZ + ITZ, and maintained in parallel to control group infected and not treated (INT). All dogs were evaluated in the first, sixth, 12th, 18th and 24th months of study. Polymerase chain reaction (PCR) was negative in 2 of 3 animals in the BZ + ITZ group, 2 of 5 in the BZ group, and 4 of 5 in the ITZ group. Hemoculture performed in the 24th month was negative in all groups. Enzyme-linked immunoassay remained reactive in all treated animals. Echocardiography differentiated treated animals from control animals. Quantitative PCR analysis of cardiac tissue was negative in the BZ + ITZ and BZ groups, positive in 2 of 5 dogs in the ITZ group and in 2 of 3 dogs in the control group, but negative in colon tissue in all groups. Inflammation was significantly reduced in the right atrium and left ventricle of dogs treated with BZ + ITZ and BZ compared with those receiving ITZ alone. Fibrosis was absent in most dogs treated with BZ + ITZ, mild in those treated with BZ or ITZ alone, and intense in the control group. Parasitological and histopathological evaluations showed that BZ + ITZ treatment improved or stabilized the clinical condition of the dogs.