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| Author(s): |
Luís Guilherme Virgilio Fernandes
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2017-06-21 |
| Examining board members: |
Ana Lucia Tabet Oller do Nascimento;
Maria Lucia Zaidan Dagli;
Fernanda Faria;
Marilis do Valle Marques;
Rita de Cássia Ruiz
|
| Advisor: | Ana Lucia Tabet Oller do Nascimento |
| Abstract | |
The mechanisms responsible for the hemorrhagic manifestations during severe leptospirosis are still poorly understood. This work evaluated the direct and indirect effects of leptospires upon molecules of the coagulation system. It has been shown that virulent leptospires are effective in blocking the activity of the enzyme thrombin by sequestration of its substrate binding site, generating less fibrin clot formation, leading to bleeding and consequent dissemination of the pathogen to other sites of infection. It has also been shown that the inflammation caused by the immune response against the bacteria causes an activation of the coagulation, most probably via expression of Tissue Factor, which causes a consumption and consequent depletion of coagulation factors and inhibitors, culminating in hemorrhage and thrombus formation, which can lead to organ failure. These results improve the understanding of the pathogenesis of leptospirosis and may favor the development of therapies for hemorrhagic manifestations. (AU) | |
| FAPESP's process: | 12/24164-0 - Characterization of the interaction of Leptospira interrogans with prothrombin/thrombin system and possible implications in virulence |
| Grantee: | Luis Guilherme Virgílio Fernandes |
| Support Opportunities: | Scholarships in Brazil - Doctorate |