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Previous issue date: 2016-03-07 / FACEPE / As Doencas Prionicas, tambem conhecidas como Encefalopatias Espongiformes Transmissiveis (EET), fazem parte de um grupo de doencas raras e invariavelmente fatais e incidem em diversos animais, incluindo o homem, e sao ocasionadas pelo acumulo de uma proteina insoluvel denominada PríonScrapie (PrPsc). Fazem parte deste grupo a Encefalopatia Espongiforme Bovina (EEB), CronicWastingDisease (CWD) nos cervideos, Scrapie em ovinos e nos humanos Doenca de Creutzfeldt-Jakob(DCJ), Kuru, Gerstmann-Straussler-ScheinkerDisease (GSS) e Insonia Familiar Fatal. Uma forte caracteristica das EET e a altaheterogeneidade clinica e histopatologica, tendo como o codon 129 da proteina príon o maior fator para esta variabilidade. Por conta desta variabilidade e a falta de biomarcadores determinantes para as Doencas Prionicas, o estudo clinico dos casos se torna crucial para o diagnostico diferencial. Nesta tese, criamos um banco de dados online, o epiCJD, para
centralizar informacoes epidemiologicas a fim de orientar medicos e servir como apoio aos gestores de saude. Utilizamos os registros dos casos ate entao coletados pelo Centro de Doencas Prionicas da Alemanha. Alem disso, foram analisados Aβ42 e a proteina Tau atraves de eletroquimioluminiescencia (MSD) como possiveis biomarcadores para diagnostico diferencial. Apos a analise dos dados, observamos que a distribuicao geografica dos registros nao indicam clusters ou hotspots, obedecendo basicamente o tamanho populacional. A distribuicao de acordo com o genero nao difere de outras populacoes descritas na literatura e os primeiros sintomas sao compativeis com os descritos previamente, bem como a idade media do inicio da doenca. A distribuicao genotipica do codon 129 esta de acordo com a literatura. Quanto ao MSD, observamos que a quantificacao foi ligeiramente superior nos niveis de TAU e significativamente superior Aβ42 em relacao aos controles, DA e DCJ. Baixos niveis de Aβ42 e alto nivel de TAU se mostraram caracteristicas em DA e DCJ, comparado aos controles. Como perspectivas futuras, o banco de dados sera alimentado por outros dados, alem dos provenientes da Alemanha, a fim de observar se ha ou nao variacoes entre outras populacoes. A tecnica MSD se mostrou promissora podendo, depois de melhoramentos, ser uma ferramenta de diagnostico molecular. / Prion diseases, or Transmissible Spongiform Encephalopathies (TSEs), are part of a group of rare diseases and invariably fatal and focus on various animals, including humans, and are caused by the accumulation of insoluble protein called Prion Scrapie (PrPsc). Bovine Spongiform Encephalopathy (BSE), CronicWastingDisease (CWD) in deer, scrapie in sheep and Creutzfeldt-Jakob disease (CJD), Kuru, Gerstmann-Straussler-ScheinkerDisease (GSS) and Fatal Familial Insomnia, in humans, are example of TSEs. A strong feature of the TSE is the high heterogeneity clinical and histopathological, with the codon 129 of the prion protein the biggest factor for this variability. Because of this variability and lack of biomarkers to determine the prion diseases, the clinical study of cases becomes crucial for the differential diagnosis. In this thesis, we have created an online database, epiCJD, to centralize epidemiological information in order to guide physicians and serve as support for public health managers. We use records from German Prion Disease Center. Furthermore, Ab42 were analyzed and Tau protein by electrochemiluminescence-based detection system (MSD) as biomarkers for the differential diagnosis. The distribution according to gender does not differ from other populations described in the literature and the first symptoms are consistent with those described previously, as well as the average age of onset of the disease. The genotype distribution of the 129 codon is in agreement with the literature. As for the MSD,we noted that the quantification was slightly higher levels of TAU and Ab42 significantly higher compared to controls, AD and CJD. Low levels of Ab42 and high TAU proved characteristics in AD and CJD, compared to controls. As future prospects, the database will be fed by other data, in addition to from Germany, in order to observe whether there are variations among other populations. MSD technique proved promising and may, afterimprovements, to be a molecular diagnostic tool.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufpe.br:123456789/22399 |
| Date | 07 March 2016 |
| Creators | CUNHA, José Eriton Gomes da |
| Contributors | http://lattes.cnpq.br/6651024132073862, OLIVEIRA, Joao Ricardo Mendes de |
| Publisher | Universidade Federal de Pernambuco, Programa de Pos Graduacao em Biologia Aplicada a Saude, UFPE, Brasil |
| Source Sets | IBICT Brazilian ETDs |
| Language | Breton |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Source | reponame:Repositório Institucional da UFPE, instname:Universidade Federal de Pernambuco, instacron:UFPE |
| Rights | Attribution-NonCommercial-NoDerivs 3.0 Brazil, http://creativecommons.org/licenses/by-nc-nd/3.0/br/, info:eu-repo/semantics/openAccess |
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