Navegando por Assunto "Trypanosoma cruzi"

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Anatomopathological aspects of acute Chagas myocarditis by oral transmission
(Sociedade Brasileira de Cardiologia, 2016-07) SOUZA, Dilma do Socorro Moraes de; ARAUJO, Marialva Tereza Ferreira de; SANTOS, Paulo Roberto Silva Garcez dos; FURTADO JUNIOR, Julio Cesar Branco; FIGUEIREDO, Maria Tereza Sanches; PÓVOA, Rui Manuel dos Santos
Vector transmission of Trypanosoma cruzi has declined in Latinpt_B America, which has been attributed to better epidemiological control of this form of transmission, estimated at 8 to 10 million chronic cases, in addition to reducing the number of new cases.1,2 However, there has been an increase in the incidence of acute cases, predominantly by oral transmission due to the ingestion of food contaminated with feces of triatomids, both in isolated cases and in family micro-outbreaks.3 Necropsy studies that describe myocarditis in the acute phase of Chagas' disease are scarce and the existing reports in the literature are of studies carried out in the past decades and involve vector transmission in endemic areas. Cardiac involvement in the acute phase may have varied aspects, especially in relation to myocardial lesion, from an undetectable one, to the evolution to acute heart failure with severe myocarditis and death. Cardiac involvement is present in 90% of the cases, manifesting with myocarditis and pericardial effusion.4,5 The analysis of a series of acute myocarditis cases showed a mortality of 5.6%.
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Arrabidaea chica (HBK) Verlot: phytochemical approach, antifungal and trypanocidal activities
(2008-12) BARBOSA, Wagner Luiz Ramos; PINTO, Lucianna do Nascimento; QUIGNARD, Etienne Louis Jacques; VIEIRA, José Maria dos Santos; SILVA JÚNIOR, José Otávio Carréra; ALBUQUERQUE, Sérgio de
Arrabidaea chica (HBK.) Verlot (Bignoniaceae) vernacular name "Pariri", is a climbing shrub, widespread from South Mexico to Guyana and central Brazil and is traditionally indicated to treat symptoms of inflammations and skin affections. Its ethanol extract was chemically investigated and tested against yeasts and dermatophytic fungi. The trypanocidal activity of the same extract was also evaluated. This work reports the isolation of three flavonoids, the total growth inhibition of Trichophyton mentagrophytes and a significant trypanocidal effect of the ethanol extract and its fractions. No relevant acute toxicity was detected even at a dose of 1000 mg/kg
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Estudo genotípico de Trypanosoma cruzi: epidemiologia e caracterização molecular de isolados do homem, triatomíneos e mamíferos silvestres do Pará, Amapá e Maranhão
(Universidade Federal do Pará, 2011) VALENTE, Vera da Costa; TEIXEIRA, Marta Maria Geraldes; http://lattes.cnpq.br/8067345143353691
The acute Chagas disease (ACD) is endemic in the Brazilian Amazon, and its main transmission route is oral, throughout family and multi-family outbreaks. This route is independent from the colonization of triatomine bugs in dwellings and its occurrence is regular, with mean rates of 100 cases per year and a lethality rate of 5%. The disease has a well-defined spatio-temporal distribution, which makes it a relevant public health concern in the states of Pará, Amapá and Amazonas. The existence of wild mammals and triatomine bugs naturally infected with Trypanosoma cruzi inhabiting different terrestrial and arboreal ecotopes maintains an intense enzootic cycle all over the Amazon region. Molecular profiles of T. Cruzi lineages in the region are associated with mammal reservoirs (including humans), triatomine bugs, ecotopes and clinical manifestations. We analyzed four ACD outbreaks in the municipalities of Barcarena, Belém and Cachoeira do Arari on Pará State, and Santana on Amapá State, based on epidemiologic features (laboratory, parasitological and serological diagnoses, clinical manifestations and the reservoirs and wild triatomines related to the outbreaks). We also investigated the domestic and wild transmission cycles of T. cruzi in São Luis on Maranhão State, without the occurrence of ACD cases. This study comprised molecular genotyping of T. cruzi on the mini-exon gene of the isolates associated with both transmission cycles (humans, mammals and wild triatomine vectors). Parasitological diagnosis was confirmed in 63 patients with the following sensitivity rates: 41.3% (26/63) for the thick blood film method; 58.7% (37/63) for QBC; 79.4% (50/63) for xenodiagnosis; and 61.9% (39/63) for blood culture. The serological diagnosis of 2648 individuals by indirect hemagglutination assay (IHA) was of 3.05% (81/2648), whereas the results of the indirect immunofluorescence test (IIF) were 2.49% (66/2648) for IgG and 2.37% (63/2648) for IgM. All tests carried out in São Luís were negative. A total of 24 mammals, 13 Didelphis marsupialis, 1 Marmosa cinerea, 5 Philander opossum, 3 Metachirus nudicaudatus, 1 Oryzomys macconnelli, 1 Oecomys bicolor and 433 R. rattus were captured. The infection rate for T. cruzi was of 7.14% (29/404). A total of 3279 triatomine bugs were captured: T. rubrofasciata (n=3008) and infection rate (IR) of 30.46%, (39/128) and R. robustus (n=137) IR of 76% (79/104), R. pictipes (n=94), IR of 56.9% (49/86%) E. mucronatus (n=6) and P. geniculatus (n=12) IR of 50% and the other non-infected species R. neglectus (n=5) and P. lignarius (n=6). Palm trees were the main ecotopes for the wild triatomine bugs. S. martiana was infested with 47.41% (101/213) of the triatomines; Maximiliana regia, 35,21% (75/213); Orbgnya speciosa, 5.16% (11/213); Eleas melanoccoca), 1.87% (4/213); and Oenocarpus bacaba, 10.32% (22/213). Genotyping was carried out using 46 isolates of trypanosomes obtained from humans, 31 from wild mammals and 74 from samples of triatomine bugs. All isolates were characterized as belonging to the Tcl lineage. All human cases in Pará were characterized as positive by parasitological testing. Not all the cases in Santana were tested positive because of the delay on diagnosis, but they were defined as positive. Xenodiagnosis, blood culture and QBC® were more sensitive than the thick blood film. Serological examinations by IHA and IIF (IgG and IgM) presented an optimal sensitivity to detect acute cases in different moments of infection. Mammals (D. marsupialis) and wild triatomine bugs (R. pictipes and P. geniculatus) infected with high infection rates of T. cruzi in the patients’ peridomicile area account for the importance of these reservoirs in the transmission cycle of the ACD, and are associated with its transmission. Even though several genotypes of T. cruzi circulate in the Amazon Region, only the Tcl lineage was identified in the patients, mammals and triatomines investigated in this study. In São Luís, in spite of these having no record of human cases of ACD, it has a domestic cycle associated with the black rat and the triatomine bugs of the species T. rubrofasciata, as well as a sylvatic cycle associated with didelphids. The Tcl cycles circulate in both cycles. Studies with isolates of local T. cruzi using markers with a higher definition might help clarify the transmission cycles, transmission routes and the reservoirs involved in cases of ACD in the Amazon Region.
Acesso aberto (Open Access)
Investigação computacional de bromo-ariloxi-2-acetamida etil-benzimidazólicos como inibidores não-peptídicos da proteinase cruzaína de trypanosoma cruzi
(Universidade Federal do Pará, 2017-11-17) FERREIRA, Fábio Jorge de Nazaré; ALENCAR, Nelson Alberto Nascimento de; http://lattes.cnpq.br/3035968396241810; https://orcid.org/ 0000-0002-5763-7024; CARNEIRO, Agnaldo da Silva; http://lattes.cnpq.br/8915348778787525
Chagas’ disease is an infection caused by the Trypanosoma Cruzi flagellated protozoan transmitted by insects (gnat) known in Brazil as “barbeiro” (barber). In the Amazon region, studies have shown that oral contamination has been frequent. The only available drugs for the treatment of Chagas’ disease - Benzonidazole (Rochagan R , Roche) and Nifurtimox (Lampit R , Bayer) - have shown limited efficiency and severe side effects. Cruzain is an enzyme present at all stages of the life cycle of T. cruzi and is the most abundant of the family of papain cysteine proteases found in the parasite, being a promising enzymatic target for the design and development of inhibitors against the disease. Non-peptidic non covalently bound to the enzyme were synthesized and evaluated biologically in vitro and in vivo by Ferreira et al. (2014) analogs of the 8D (or B95) leader compound (crystallographic), yielding a series of active compounds, of which the most powerful are: 8K, 8L and 8R. This work investigated the potential interactions and energies of the cruzain (PDB code: 3KKU) complexed with these four ligands by means of computational tools in order to help elucidate their potential inhibition activity in this enzyme. The computational protocol (parameters, topologies, coordinates, minimizations, thermalizations and productions) was the same for each system. In the final stage of molecular dynamics (MD) production, each system was simulated for a period of 100 ns, to which the mean square deviation (RMSD) stability values of the enzyme and the marked change in 8L ligand conformation were analyzed. The quality of the simulation was also evaluated through potential, kinetic and total energy, volume and temperature graphs. Interactions of hydrogen bonds of the ligands with some amino acid residues belonging to the catalytic site were analyzed. The interaction between the ASP161 and the 8R ligand is emphasized, being ratified by the energy decomposition by residue showing that ASP161 has the best contribution. In terms of binding free energy, the ∆Gtotal follows the experimental trend, pointing the 8R ligand as the most favorable to the reaction having a theoretical value of -30.04kcal.mol−1. This spontaneity is ratified by means of the values obtained with the SIE method, whose theoretical value was -7.54 kcal.mol−1. The results of this work should favor the optimization of compound 8R or development of a series of analogs of this molecule in order to be used as a possible drug for the treatment of Chagas’ disease.
Acesso aberto (Open Access)
Planejamento e síntese de novos derivados da associação molecular benzonidazol e metronidazol
(Universidade Federal do Pará, 2018-09-25) COSTA, Fernanda Menezes; BORGES, Rosivaldo dos Santos; http://lattes.cnpq.br/4783661132100859; https://orcid.org/0000-0003-4072-7573
Chagas disease is caused by protozoan Trypanosoma cruzi, still has high contagion rates in present days, especially in the Amazon region. After contamination, the infective cycle of Chagas disease has two phases: acute and chronic. The acute phase is, in majority of cases, asymptomatic and efficiently treated, however the chronic phase is symptomatic and has proved not efficient treatment. There is only one available medicine, the generic benznidazole or Rochagan®, distributed free of charge, and it must be administered for 60 days, approximately. However, benznidazole has low efficiency, being effective only on acute phase (asymptomatic). Besides that, the medicine use to cause severe side effects in clinical patients, producing in many times the treatment rejection. The molecular modeling has become an important tool on new drugs design, using the DFT method to evaluate of the new potent molecules. Thereby, the main goal of this work was to design new derivatives by using molecular modifications of benznidazole and metronidazole aiming to reduce their redox capacity. With this purpose, a theoretical study was performed of two benznidazole derivatives through molecular association and chain increase. From the theoretical study, this molecular association between benznidazole and metronidazole molecules can develop a less toxic new derivative of than benznidazole. Both designed derivatives were synthesized on laboratory using the classics methodologies of electrophilic and nucleophilic substitution, esterification, alkylation and nitration. According to their HOMO, LUMO, ionization potential, and electron affinity values, it was possible observe that the nibendazole 1 and nibendazole 2 compounds have a lower redox capacity when compared to benznidazole. The GAP values showed that the derivatives are less reactive than benznidazole. The HOMO and LUMO graphics, showed that the nitroimidazoles rings have high electron-withdrawing capacity as well as benzyl group has high electron-donating capacity. These properties change in accordance to methyl moiety or nitrogen positions on azolic ring of derivatives compounds.