EFAR - Escola de Farmácia

URI permanente desta comunidadehttp://www.hml.repositorio.ufop.br/handle/123456789/451

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O curso de Farmácia em Ouro Preto foi criado em 1839, sendo a mais antiga Escola de Farmácia da América Latina.

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Synthesis, in vitro and in vivo anti-Trypanosoma cruzi and toxicological activities of nitroaromatic Schiff bases.
(2018) Almeida, Tamires Cunha; Ribeiro, Luis Henrique Gonzaga; Santos, Luiza Braga Ferreira dos; Silva, Cleiton Moreira da; Branquinho, Renata Tupinambá; Lana, Marta de; Gadelha, Fernanda Ramos; Fátima, Angelo de
Chagas disease is a major health problem not only in Latin America but also in Europe and North America due to the spread of this disease into nonendemic areas. In terms of global burden, this major tropical infection is considered to be one of the most neglected diseases, and there are currently only two available chemotherapies: benznidazole and nifurtimox. Unfortunately, although these chemotherapies are beneficial in the acute phase of the disease, benznidazole and nifurtimox lead to significant side effects, including hepatitis and neurotoxicity. Therefore, the search for and development of more effective, safe and inexpensive anti-Trypanosoma cruzi drugs are required. In this work, a series of 10 nitroaromatic Schiff bases bearing different (nitro) aromatic rings-was synthesized. Subsequently, the in vitro and in vivo anti-T. cruzi activities of the Schiff bases were investigated, as well as the in vivo toxicity and the biological effects. The basic structure of the most promising in vivo Schiff base, 10 would be useful in the synthesis of new compounds for Chagas disease treatment.
Trypanosoma cruzi high infectivity in vitro is related to cardiac lesions during long-term infection in beagle dogs.
(2007) Guedes, Paulo Marcos da Matta; Veloso, Vanja Maria; Caliari, Marcelo Vidigal; Carneiro, Cláudia Martins; Souza, Sheler Martins de; Lana, Marta de; Chiari, Egler; Bahia, Maria Terezinha; Galvão, Lúcia Maria da Cunha
Trypanosoma cruzi is a hemoflagelate parasite associated with heart dysfunctions causing serious problems in Central and South America. Beagle dogs develop the symptoms of Chagas disease in humans, and could be an important experimental model for better understanding the immunopathogenic mechanisms involved in the chagasic infection. In the present study we investigated the relation among biological factors inherent to the parasite (trypomastigote polymorphism and in vitro infectivity) and immunoglobulin production, inflammation, and fibrosis in the heart of Beagle dogs infected with either T. cruzi Y or Berenice-78 strains. In vitro infectivity of Vero cells as well as the extension of cardiac lesions in infected Beagle was higher for Y strain when compared to Berenice-78 strain. These data suggested that in vitro infectivity assays may correlate with pathogenicity in vivo. In fact, animals infected with Y strain, which shows prevalence of slender forms and high infectivity in vitro, presented cardiomegaly, inflammation, and fibrosis in heart area. Concerning the immunoglobulin production, no statistically significant difference was observed for IgA, IgM or IgG levels among T. cruzi infected animals. However, IgA together IgM levels have shown to be a good marker for the acute phase of Chagas disease.
A serological, parasitological and clinical evaluation of untreated Chagas disease patients and those treated with benznidazole before and thirteen years after intervention.
(2013) Assis, Girley Francisco Machado de; Diniz, Glaucia Alessio; Montoya, Roberto Araújo; Dias, João Carlos Pinto; Coura, José Rodrigues; Coelho, George Luiz Lins Machado; Viñas, Pedro Albajar; Torres, Rosália Morais; Lana, Marta de
The etiological treatment of Chagas disease is recommended for all patients with acute or recent chronic infection, but controversies remain regarding the benefit of chemotherapy and interpretations of the parasitological cure after etiological treatment. This study compares the laboratory and clinical evaluations of Chagas disease patients who were diagnosed 13 years earlier. Fifty-eight Chagas disease patients (29 treated with benznidazole and 29 untreated) were matched at the time of treatment based on several variables. Conventional serology revealed the absence of seroconversion in all patients. However, lower serological titres were verified in the treated group, pri¬marily among patients who had the indeterminate form of the disease. Haemoculture performed 13 years after the intervention was positive for 6.9% and 27.6% of the treated and untreated patients, respectively. Polymerase chain reaction tests were positive for 44.8% and 13.8% of the treated and untreated patients, respectively. Patients who presented with the indeterminate form of the disease at the beginning of the study exhibited less clinical progression (17.4%) compared with the untreated group (56.5%). Therefore, this global analysis revealed that etiological treatment with benznidazole may benefit patients with respect to the clinical progression of Chagas disease and the prognosis, particularly when administered to patients with the indeterminate form of the disease.
Entomological surveillance of Chagas disease in Berilo municipality, Jequitinhonha Valley, State of Minas Gerais, Brazil.
(2009) Assis, Girley Francisco Machado de; Azeredo, Bernardino Vaz de Mello; Gorla, David; Diotaiuti, Liléia Gonçalves; Lana, Marta de
O objetivo deste estudo foi avaliar o Programa de Controle de doença de Chagas instalado desde 1982 no município de Berilo, Vale do Jequitinhonha, MG, Brasil, baseado na avaliação de 5.242 unidades domiciliares e 7.807 anexos após oito anos de implantação da vigilância epidemiológica que ocorreu em 1997. Um total de 391 triatomíneos (280 Panstrongylus megistus e 111 Triatoma pseudomaculata) foram capturados, indicando o contínuo predomínio da primeira espécie. No entanto, Triatoma pseudomaculata está claramente se tornando mais importante nesta região, com colônias intradomiciliares sendo detectadas recentemente. Parâmetros entomológicos, como os índices de dispersão (17%) e infestação intradomiciliar (0,15%), são compatíveis com a fase de vigilância epidemiológica. A maioria das UDs apresenta padrão de construção tipo A (tijolo com reboco) e A maioria das UDs apresenta padrão de construção tipo A (tijolo com reboco) e C (adobe com reboco). Dentre os habitantes das unidades domiciliares infestadas por triatomíneos, 25% apresentavam testes reativos na ELISA, HAI e IFI para antígenos de Trypanosoma cruzi.
Seroprevalence of chagas disease in schoolchildren from two municipalities of jequitinhonha valley, Minas Gerais, Brazil; six years following the onset of epidemiological surveillance.
(2006) Borges, Jaila Dias; Assis, Girley Francisco Machado de; Gomes, Lizziani de Vasconcelos; Dias, João Carlos Pinto; Pinto, Ildikô Delkim Miranda; Martins Filho, Olindo Assis; Torres, Rosália Morais; Viñas, Pedro Albajar; Bahia, Maria Terezinha; Coelho, George Luiz Lins Machado; Lana, Marta de
Six years after the beginning of the epidemiological surveillance of Chagas disease in Berilo and José Gonçalves de Minas, Jequitinhonha Valley, MG, Brazil, a serological inquiry was performed to observe whether the transmission of this endemy was occurring in this area. A randomized sample of 1,412 children seven to 14 years old, was screened. Six asymptomatic children were found to be positive, leading to 0.4% of prevalence. Hemoculture confirmed infection in five out of the six positive cases. Additional epidemiological investigation revealed important antecedents, such as disease reports in relatives and predisposing ecological and housing conditions. Our results demonstrated similar seroprevalence (0.4%) in schoolchildren, ranging from seven to 14 years old, and that were observed six years ago (0.2%) for children 0-9 year-old. Thus, considering the constant presence of Panstrogylus megistus in the peridomicile these findings emphasize the need of continuous improved epidemiological surveillance of Chagas disease in this region.
Experimental Trypanosoma cruzi biclonal infection in Triatoma infestans : detection of distinct clonal genotypes using kinetoplast DNA probes.
(2000) Pinto, Artur da Silveira; Lana, Marta de; Britto, Constança; Bastrenta, Brigitte; Tibayrenc, Michel
Monitored biclonal densities of parasites were offered to third-stage larvae of Triatoma infestans via an arti®cial feeding device and 30 days later, the gut contents of the insects were processed for microscopic examination and polymerase chain reaction (PCR) detection of Trypanosoma cruzi kinetoplast DNA [kDNA]). A total of 15 mixtures involving nine different stocks attributed to the 19/20, 32 and 39 major clonal genotypes of Trypanosoma cruzi were used. The presence of each T. cruzi clonal genotype after completion of the cycle through the insects was investigated by hybridising the PCR ampli®cation products with genotype-speci®c minicircle kDNA probes. Sixty-®ve out of 90 examined insects (72.2%) were positive for parasites by microscopic examination and 85 (94.4%) were positive by PCR. The results show that almost half of the biclonal infections are not detectable after completion of the cycle, and that there are important differences in detection of such biclonal infections according to the clonal genotypes considered. Moreover, elimination of a clonal genotype by another is a frequent, but not constant, pattern in biclonal infections of T. infestans. The use of PCR and kDNA probes makes it possible to avoid the culture phase, which makes detection of mixed infections much easier in epidemiological surveys. Moreover, the fact that T. infestansdoes not transmit different T. cruzi clonal genotypes with the same ef®ciency has strong implications for the reliability of xenogiagnosis. q 2000 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved.
Clinical and laboratory status of patients with chronic Chagas disease living in a vector controlled area in Minas Gerais, Brazil, before and nine years after aetiological treatment.
(2009) Lana, Marta de; Lopes, Leonardo de Araújo; Martins, Helen Rodrigues; Bahia, Maria Terezinha; Assis, Girley Francisco Machado de; Wendling, Ana Paula Barbosa; Martins Filho, Olindo Assis; Montoya, Roberto Araújo; Dias, João Carlos Pinto; Viñas, Pedro Albajar; Coura, José Rodrigues
Twenty-eight Chagas disease patients (CD), 22 with the indeterminate clinical form (IND) and six with the cardiac or digestive form (CARD/DIG), were treated with benznidazole and underwent clinical and laboratorial analysis before (IND and CARD/DIG) and nine years after [patients after treatment (CDt), patients with the indeterminate clinical form at treatment onset (INDt) and with the cardiac or digestive form at treatment onset (CARD/DIGt)] treatment. The data demonstrate that 82.1% of CDt patients (23/28) remained clinically stable and 95.4% of the INDt (21/22) and 33.3% of the CARD/DIGt (2/6) patients showed unaltered physical and laboratorial examinations. The clinical evolution rate was 2%/year and was especially low in INDt patients (0.5%/year) relative to CARD/DIGt patients (7.4%/year). Positive haemoculture in treated patients was observed in 7.1% of the cases. None of the INDt (0/21) and 33.3% of the CARD/DIGt (2/6) patients displayed positive cultures. The PCR presented a positive rate significantly higher (85.2%, 23/27) than haemoculture and two samples from the same patient revealed the same result 57.7% of the patients. Conventional serology-ELISA on 16 paired samples remained positive in all individuals. Semi-quantitative ELISA highlighted significant decreases in reactivity, particularly in INDt relative to IND. Non-conventional serology- FC-ALTA-IgG, after treatment, showed positive results in all sera and 22 paired samples examined at seven and nine years after treatment, demonstrated significantly lower reactivity, particularly in INDt patients. This study was retrospective in nature, had a low number of samples and lacked an intrinsic control group, but the data corroborate other results found in the literature. The data also demonstrate that, even though a cure has not been detected in the none-treated patients, the benefits for clinical evolution were selectively observed in the group of INDt patients and did not occur for CARD/DIGt patients.
Etiological treatment during early chronic indeterminate Chagas disease incites an activated status on innate and adaptive immunity associated with a type 1-modulated cytokine pattern.
(2008) Avelar, Renato Sathler; Avelar, Danielle Marchetti Vitelli; Massara, Rodrigo Lima; Lana, Marta de; Dias, João Carlos Pinto; Carvalho, Andréa Teixeira de; Santos, Silvana Maria Elói; Martins Filho, Olindo Assis
Pro-inflammatory immune response is usually associated with Chagas disease pathogenesis, but is also relevant to treatment effectiveness. Cross-sectional studies have suggested that this activated state may persist for years after therapeutic intervention. However, short-term longitudinal investigation has suggested that the Benznidazole treatment (Bz-treatment) leads to decreased immunological activation. In order to elucidate this issue, we performed a longitudinal study to evaluate the immunological status following Bz-treatment during early indeterminate Chagas disease. Our results demonstrated that Bz-treatment led to higher activation status of circulating monocytes but was negatively associated with the number of IL-12þCD14þ cells. Moreover, Bz-treatment triggered a high frequency of circulating CD3_CD16þCD56_ NK cells, in addition to elevated activation status associated with a type 1-modulated cytokine pattern. Bz-treatment induced substantial T and B-cell activation status associated with an overall IL-10 modulated type 1 cytokine profile. In summary, these findings provide new information regarding immune activation status following the etiological treatment of Chagas disease. These results suggest that in addition to the increased number of activated leukocytes in the peripheral blood, Bz-treatment may also involve a qualitative change in their functional capacity that drives their activation state toward a modulated cytokine profile. These changes may account for the benefits of etiological treatment of Chagas disease.
Domiciliation of Triatoma pseudomaculata (Corrêa e Espínola 1964) in the Jequitinhonha Valley, State of Minas Gerais.
(2007) Assis, Girley Francisco Machado de; Azeredo, Bernardino Vaz de Mello; Fuente, Ana Laura Carbajal de la; Diotaiuti, Liléia Gonçalves; Lana, Marta de
Oito anos após a implantação da vigilância epidemiológica para doença de Chagas em Berilo, Vale do Jequitinhonha, MG, Brasil, foi realizada uma pesquisa para verificar o impacto do Programa de Controle Vetorial. Neste trabalho, 5.242 (96%) unidades domiciliares foram vistoriadas. Dez estavam infestadas por Triatoma pseudomaculata. Em nove delas os insetos estavam infestando o peridomicílio e em uma casa foi constatado um foco intradomiciliar associado a morcegos. Foram capturados 111 insetos da espécie Triatoma pseudomaculata e nenhum exemplar estava infectado por Trypanosoma cruzi. Na casa infestada e em torno dela foram instaladas respectivamente 8 e 100 armadilhas de Noireau et al16 e nenhum triatomíneo foi capturado. Oitenta morcegos capturados e examinados também estavam negativos para Trypanosoma cruzi bem como três gambás (Didelphis albiventris) e um roedor, todos capturados no peridomicílio. Um porcentual de 24% dos moradores das casas infestadas por Triatoma pseudomaculata foi sororeativo (ELISA, HAI e IFI) para Tripanosoma cruzi.
Evaluation of the Chagas disease control program in Açucena Municipality, Rio Doce Valley, State of Minas Gerais, Brazil.
(2014) Santos, Adriana dos; Letro, Rejane Balmant; Bem, Vitor Antônio Lemos do; Azeredo, Bernardino Vaz de Mello; Coelho, George Luiz Lins Machado; Diotaiuti, Liléia Gonçalves; Assis, Girley Francisco Machado de; Lana, Marta de
Açucena Municipality, Rio Doce Valley, State of Minas Gerais, Brazil temporarily (2001-2005) interrupted epidemiological surveillance for Chagas disease. The objective of this work was to evaluate the Chagas Disease Control Program (CDCP) in Açucena and to offer suggestions for improving local epidemiological surveillance. Methods: This study was conducted in three phases: I) a serological investigation of schoolchildren aged 5 to 15 years using an enzyme-linked immunosorbent assay (ELISA) test performed on blood collected on fi lter paper followed by ELISA, indirect immunofl uorescence (IIF) and indirect hemaglutination (IHA) on venous blood for borderline cases and those in the gray zone of reactivity; II) vector evaluation using the data obtained by local health agents during 2006-2010; and III) examination by ELISA, IIF and IHA of serum samples from the inhabitants of houses where infected Triatoma vitticeps was found and evaluation of their knowledge about Chagas disease. Results: Five individuals had inconclusive results in the ELISA screening but were seronegative for Chagas disease. The triatomine evaluation revealed the presence of three species: Triatoma vitticeps, Panstrongylus megistus and Panstrongylus diasi. Triatoma vitticeps was the most prevalent and widespread, with a higher (67%) index of Trypanosoma cruzi fl agellates and evidence of colonization. Most of the inhabitants of the infested houses recognized triatomines and had basic knowledge about Chagas disease. Conclusions: Although T. vitticeps is not clearly associated with Chagas disease transmission, these results highlight the importance of maintaining CDCP in endemic areas and the need for greater emphasis on epidemiological surveillance, especially in areas with important vectorial changes or that have been modifi ed by human intervention.

EFAR - Escola de Farmácia

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