Programa de Pós-graduação em Medicina Tropical e Saúde Pública
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Navegando Programa de Pós-graduação em Medicina Tropical e Saúde Pública por Por Orientador "Bezerra, José Clecildo Barreto"
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Item Reposicionamento in silico de novos fármacos contra o schistosoma mansoni(Universidade Federal de Goiás, 2016-03-14) Arantes, Morgana Elias; Andrade, Carolina Horta; http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4745602P1; Bezerra, José Clecildo Barreto; http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4781675U6; Andrade, Carolina Horta de; Cravo, Pedro Vitor Lemos; Braga, Rodolpho CamposSchistosomiasis is a neglected tropical disease caused by parasites of the genus Schistosoma. In Brazil only Schistosoma mansoni transmits this disease. The World Health Organization estimated in 2012 approximately 249 million people at risk of acquiring this disease around the world. The main strategy to control this disease is the treatment of individuals living in endemic areas with Praziquantel. The drug praziquantel is used on a large scale in the treatment of schistosomiasis and currently there are reported cases of resistance, indicating the need to discover new drugs. In silico drug repositioning is a strategy that reduces the time and cost in the search of anti-schistosomal agents. This work used bioinformatics tools and methodology based on previous studies, as a means to identify potential new S. mansoni targets and drug homologs, consequently identifying potential new schistosomal drugs. A list was compiled with S. mansoni potential targets that are part of essential processes in the database TDR and the targets that are part of the tegument were obtained in the scientific literature. The file with S. mansoni targets contained 1376 targets, and of these only 61 targets associated with 399 drugs had homology with drug targets. After removal of duplicate drugs, drugs found in previous studies and after the analysis of the conservation of the active site only 28 S. mansoni targets associated with 102 drugs had 60% or more of the active site conserved. Some of the drugs had activity and are interesting to validate this study such as: artemether, lumefantrine, meloxicam. Among the drugs found 18 drugs were selected to be tested using the following criteria: low toxicity in vivo, expired patent and a value of log P interesting for oral administration.Item Reposicionamento in silico de fármacos para doenças negligenciadas com ênfase no metabolismo energético de Leishmania spp e apicoplasto de Plasmodium falciparum(Universidade Federal de Goiás, 2015-02-27) Silva, Lourival de Almeida; Cravo, Pedro Vítor Lemos; Castro, Ana Maria de; Bezerra, José Clecildo Barreto; http://lattes.cnpq.br/9491755585617846; Bezerra, José Clecildo Barreto; Silva, Cláudio Carlos da; Andrade, Carolina Horta; Lacerda, Elisângela de Paula Silveira; Borges, Clayton LuizLeishmaniasis is a neglected tropical disease responsible for physical, economic and social damages. Even though malaria is not classified as a neglected tropical disease, is responsible for high morbidity and mortality, especially in African countries. Current treatments for both diseases face several drawbacks, including the evolution of drugresistant parasites, the high cost of major drugs and the high toxicity of others. For these reasons, there is an urgent need to develop new drugs that minimize these downsides and, consequently, help eradicate these diseases. To overcome these difficulties, both academics and pharmaceutical companies are increasingly employing the so-called “drug repositioning strategy”. Drug repositioning aims to find new applications for drugs approved for other indications, and has proven valuable for decreasing research costs as well as to decrease the time required to market the "new" drug. In the present study, we used bioinformatics to identify and analyze molecular targets of the energy metabolism of Leishmania spp and of the P. falciparum apicoplast. The energy metabolism of Leishmania and the apicoplast metabolism have various enzymes that can be targeted by specific drugs, leading to lower toxicity and more promising therapies for humans. Using the TDR Targets database, we were able to identify 94 genes and 93 Leishmania energy metabolism targets. We identified 44 positive targets in these databases, and for 11 of these targets we found drugs already approved for use in humans. We used a similar strategy to identify antimalarial drugs that acted specifically against the apicoplast metabolism. The GeneDB database of the P. falciparum genome was used to compile a list of 600 proteins with apicoplast signal peptides. Each of these proteins was treated as a potential drug target and its predicted sequence was used to interrogate three different open access databases (DB TTD, DrugBank and STITCH ). We identified many drugs with the potential to interact with 47 peptides allegedly involved in apicoplast biology in P. falciparum. Fifteen of these hypothetical targets are predicted to interact with drugs are already approved for clinical use, but were never evaluated against malaria parasites. Our results suggest that the drugs identified here show potential activity against leishmania parasite and malaria, but need experimental validation to confirm their effectiveness.Item Influência da exposição ao carbonato de cálcio no metabolismo de compostos orgânicos e inorgânicos em biomphalaria glabrata, hospedeiro de schistosoma mansoni(Universidade Federal de Goiás, 2014-03-26) Silva, Luciana Damacena; Castro, Ana Maria de; Mello-Silva, Clélia Christina Corrê de; Bezerra, José Clecildo Barreto; http://lattes.cnpq.br/9491755585617846; Bezerra, José Clecildo Barreto; Castro, Ana maria de; Mello-Silva, Clélia Christina Corrêa de; Vinaud, Mariana Clare; Barcelos, Rejane da Silva SenaBiomphalaria snails act as intermediate hosts that harbor the Schistosoma mansoni parasite, the causative agent of schistosomiasis. As population increases, snails have their geographical distribution conditioned to the presence of calcium in the environment, which is essential for their energetic metabolism. The objective of this study was the assessment on the influence of exposure to different concentrations of CaCO3 (20, 40, 60, 80 and 100 mg/L) at different intervals (1, 14, 21 and 30 days) forthe concentrations of glucose, calcium, total proteins, urea, uric acid and creatinine in hemolymph B. glabrata. All substances were dosed using specific kits with a spectrophotometer reading at 545 nm. High performance liquid chromatography (HPLC) was the technique applied to quantify the presence of organic acids: pyruvate, oxaloacetate, citrate, succinate, fumarate, propionate, acetoacetate and βhydroxybutyrate in the hemolymph of mollusks exposed to CaCO3. Results revealed that the calcium concentration in the hemolymph did not present significant difference (p>0.05) with regard to control as well as to the concentrations assessed. The glucose concentration decreased (p<0.05) in exposures to 20mg and 40mg and increased in exposures to 80mg and 100mg of CaCO3 with regard to control. The organic acids pyruvate, oxaloacetate, citrate, succinate fumarate and lactate had their concentrations increased; propionate in turn had its concentration decreased set against control in exposure to CaCO3. In the exposures to the concentrations assessed, acetoacetate decreased and β-hidroxibutirato increased. Total proteins and urea presented decrease. The uric acid concentration increased in the exposure to 20mg of CaCO3; the creatinine concentration increased in the exposures to 40mg and 100mg of CaCO3. It was possible to conclude that snails exposed to different concentrations of CaCO3 had their major metabolic alterations occurring from the 14th day of exposure.Item Caracterização histológica de vermes adultos machos de Lagochilascaris minor(Universidade Federal de Goiás, 2012-02-27) Vieira, Ana Paula de Toledo; Barbosa, Alverne Passos; Bezerra, José Clecildo Barreto; http://lattes.cnpq.br/9491755585617846; Bezerra, José Clecildo Barreto; Oliveira, Jayrson Araújo de; Campos, Dulcinéa Maria BarbosaNematoda Lagochilascaris minor is the etiologic agent of lagochilascaríase in human beings. Until today, no one knows the natural host of this helminth and Brazil registers about 90% of the cases of lagochilascaríase world-wide human being. The life cycle of L. minor was described using an experimental model in mice and domestic cat, behaving as an intermediate host and definitive host respectively. The objective of this study was to evaluate the histology of the adult males of this helminth worms, using light microscopy. These specimens were removed after necropsy of cats kept in their cages cataloged in male and female worms, and the adult male specimens were fixed in formalin solution 10 % hot, AFA and 4% paraformaldehyde in sodium cacodylate buffer 0 1 M, pH 7.2. After the different fixations, the samples were dehydrated in a gradual series of ethanol in different concentrations of alcohol levels, and included in historesin cut with 3μm –thick microtome, with horizontal and transverse serial sections. The sections were stained with Hematoxylin & Eosin (HE), Carmin, Giemsa and Toluidine Blue. The best fixation was achieved with the use of AFA and 4% paraformaldehyde in 0.1 M sodium cacodylate buffer pH 7.2 and the best staining was obtained from the use of the dye HE, which showed histological structures of adult male worms L. minor loop as testicular, seminal vesicle, ejaculatory duct, sperm and spicule. It was also observed structures of the digestive system, muscular system, cuticle, wing side and lateral line. The sections were photomicrographed using photomicroscope with the help of the program Motic Images Plus 2.0, selected and analyzed.