162 research outputs found
Anticorpos líticos induzidos por infecção pelo Trypanosoma cruzi reconhecem epitopos presentes nas formas tripomastigotas e epimastigotas do parasita
Sera of Chaga's disease patients containing anti-T. cruzi lytic antibodies were submitted to affinity chromatography using Sepharose 4B conjugated with antigen extracted from epimasiigote or trypomasiigote forms of the parasite. Epimastigotes were obtained from culture at the exponential growth phase and the trypomastigotes from blood of infected and immunosuppressed mice. Antigen of both parasite forms was obtained by sonication of the parasites followed by centrifugation. Both antigens were then conjugated to activated Sepharose 4B. Affinity chromatography was performed by passing sera from chagasic patients through an immunoadsorbent column containing either epimasiigote or trypomasiigote antigens. Antibodies bound to the column were eluted with cold 0,2 M glycine buffer pH 2,8. The eluted antibodies were analysed regarding their isotype and lytic activity. The results showed that anti-T. cruzi lytic antibodies present in sera from chagasic patients are mainly located in the IgG isotype and recognize epitopes present in both trypomasiigote and epimastigote forms. A brief report of this work has already been published12.Soro de pacientes com doença de Chagas na fase crônica foram submetidos a cromatografia de afinidade com Sepharose 4B conjugada com um extrato antigênico obtido de formas epimastigotas ou tripomastigotas de T. cruzi: os epimastigotas foram obtidos de cultura na fase exponencial de crescimento e os tripomastigotas de sangue de camundongos infectados e imunossuprimidos. Os antígenos de ambas formas parasitárias foram obtidos por tratamento dos parasitas por ultra-som, seguido de centrifugação. A cromatografia de afinidade foi feita passando-se os soros chagásicos através de uma coluna de imunoadsorvente contendo antígenos de epimastigotas ou tripomastigotas. Os anticorpos foram eluídos da coluna com tampão glicina 0,2 M pH 2,8 a 4°C. Os anticorpos eluidos foram analisados quanto ao seu isotipo e atividade lítica. Os resultados mostraram que os anticorpos anti-T. cruzi com atividade lítica presentes em soros chagásicos estão localizados no isotipo IgG e reconhecem epitopos presentes tanto nos tripomastigotas quanto nos epimastigotas
Avaliação da técnica de lise mediada por complemento em pacientes chagásicos crônicos tratados com drogas tripanosomicidas
Levels of lytic antibodies were determined by complement mediated lysis (CoML) in chronic chagasic patients treated with nifurtimox orbenznidazole. Two groups of patients were studied: one who had been treated more than six years ago and another with less than six years since treatment, although serologic reactions remained positive. CoML was carried out in two samples obtained from patients on different occasions, in test groups as well as in positive controls. In view of results observed sensitivity of reaction (83.3%) and its specifity (100.0%) were calculated. It was observed that about half of the patients presented lysis up to 20% and this result may corroborate "parasitological cure". It was noted that 43.6% of patients treated more than six years ago and 20.0% of patients with less than six years since treatment presented variable results, either positive or negative, differing for each sample from the same individual. Such results were thus considered as inconclusive, since parasitological tests remain negative. A prolonged follow-up may shed light over such results.Os níveis de anticorpos líticos foram determinados em pacientes chagásicos crônicos, tratados com nifurtimox ou benzonidazol, através da Lise Mediada por Complemento (LMCo). Dois grupos de pacientes foram estudados: um grupo tratado há mais de seis anos e outro há menos de seis anos. Ambos os grupos, após o tratamento, apresentaram xenodiagnósticos negativos, embora as provas sorológicas permanecessem reagentes. Foram incluídos um grupo controle negativo com provas sorológicas não reagentes e um grupo controle positivo com provas sorológicas e parasitológicas positivas. Para a LMCo foram utilizadas duas amostras de cada paciente, obtidas em ocasiões diferentes, tanto dos grupos estudados quanto do grupo controle positivo. Em vista dos resultados foi calculada a sensibilidade da reaçáo (83.3%) e a especificidade (100,0%). Nos grupos estudados observou-se que cerca da metade dos pacientes apresentaram lise menor do que 20%, podendo, este resultado, corroborar a "cura parasitológica". Notou-se que 43,6% dos pacientes tratados há mais de seis anos apresentaram resultados contraditórios, ora negativos, ora positivos, dependendo da amostra. Tais resultados foram considerados inconclusivos, em virtude das provas parasitológicas permanecerem negativas. Um seguimento a longo prazo poderá esclarecer o significado desses resultados
Xenodiagnostico, hemocultura e teste de lise mediada pelo complemento, como critérios de seleção de pacientes chagásicos crônicos para quimioterapia
Synthesis, antimalarial activity in vitro, and docking studies of novel neolignan derivatives
CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESThe absence of effective vaccines against malaria and the difficulties associated with controlling mosquito vectors have left chemotherapy as the primary control measure against malaria. However, the emergence and spread of parasite resistance to conventi903464472CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESSEM INFORMAÇÃOSEM INFORMAÇÃOSEM INFORMAÇÃOThe authors thank Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES (CAPES) for financial suppor
Antimalarial Activity of Potential Inhibitors of Plasmodium falciparum Lactate Dehydrogenase Enzyme Selected by Docking Studies
The Plasmodium falciparum lactate dehydrogenase enzyme (PfLDH) has been considered as a potential molecular target for antimalarials due to this parasite's dependence on glycolysis for energy production. Because the LDH enzymes found in P. vivax, P. malariae and P. ovale (pLDH) all exhibit ∼90% identity to PfLDH, it would be desirable to have new anti-pLDH drugs, particularly ones that are effective against P. falciparum, the most virulent species of human malaria. Our present work used docking studies to select potential inhibitors of pLDH, which were then tested for antimalarial activity against P. falciparum in vitro and P. berghei malaria in mice. A virtual screening in DrugBank for analogs of NADH (an essential cofactor to pLDH) and computational studies were undertaken, and the potential binding of the selected compounds to the PfLDH active site was analyzed using Molegro Virtual Docker software. Fifty compounds were selected based on their similarity to NADH. The compounds with the best binding energies (itraconazole, atorvastatin and posaconazole) were tested against P. falciparum chloroquine-resistant blood parasites. All three compounds proved to be active in two immunoenzymatic assays performed in parallel using monoclonals specific to PfLDH or a histidine rich protein (HRP2). The IC50 values for each drug in both tests were similar, were lowest for posaconazole (<5 µM) and were 40- and 100-fold less active than chloroquine. The compounds reduced P. berghei parasitemia in treated mice, in comparison to untreated controls; itraconazole was the least active compound. The results of these activity trials confirmed that molecular docking studies are an important strategy for discovering new antimalarial drugs. This approach is more practical and less expensive than discovering novel compounds that require studies on human toxicology, since these compounds are already commercially available and thus approved for human use
Differential Serodiagnosis of Human Infections Caused by Trypanosoma cruzi and Leishmania spp. Using ELISA with a Recombinant Antigen (rTc24)
The utility of anti-trypomastigote lytic antibodies for determining cure of Trypanosoma cruzi infections in treated patients: an overview and perspectives
Antimalarial Activity and Mechanisms of Action of Two Novel 4-Aminoquinolines against Chloroquine-Resistant Parasites
Chloroquine (CQ) is a cost effective antimalarial drug with a relatively good safety profile (or therapeutic index). However, CQ is no longer used alone to treat patients with Plasmodium falciparum due to the emergence and spread of CQ-resistant strains, also reported for P. vivax. Despite CQ resistance, novel drug candidates based on the structure of CQ continue to be considered, as in the present work. One CQ analog was synthesized as monoquinoline (MAQ) and compared with a previously synthesized bisquinoline (BAQ), both tested against P. falciparum in vitro and against P. berghei in mice, then evaluated in vitro for their cytotoxicity and ability to inhibit hemozoin formation. Their interactions with residues present in the NADH binding site of P falciparum lactate dehydrogenase were evaluated using docking analysis software. Both compounds were active in the nanomolar range evaluated through the HRPII and hypoxanthine tests. MAQ and BAQ derivatives were not toxic, and both compounds significantly inhibited hemozoin formation, in a dose-dependent manner. MAQ had a higher selectivity index than BAQ and both compounds were weak PfLDH inhibitors, a result previously reported also for CQ. Taken together, the two CQ analogues represent promising molecules which seem to act in a crucial point for the parasite, inhibiting hemozoin formation
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