Navegando por Palavras-chave "dengue"
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- ItemAcesso aberto (Open Access)An Approach for a Synthetic CTL Vaccine Design against Zika Flavivrus Using Class I and Class II Epitopes Identified by Computer Modeling(Frontiers Media Sa, 2017) Cunha-Neto, Edecio; Rosa, Daniela S. [UNIFESP]; Harris, Paul E.; Olson, Tim; Morrow, Alex; Ciotlos, Serban; Herst, Charles V.; Rubsamen, Reid MartinThe threat posed by severe congenital abnormalities related to Zika virus (ZKV) infection during pregnancy has turned development of a ZKV vaccine into an emergency. Recent work suggests that the cytotoxic T lymphocyte (CTL) response to infection is an important defense mechanism in response to ZKV. Here, we develop the rationale and strategy for a new approach to developing cytotoxic T lymphocyte (CTL) vaccines for ZKV flavivirus infection. The proposed approach is based on recent studies using a protein structure computer model for HIV epitope selection designed to select epitopes for CTL attack optimized for viruses that exhibit antigenic drift. Because naturally processed and presented human ZKV T cell epitopes have not yet been described, we identified predicted class I peptide sequences on ZKV matching previously identified DNV (Dengue) class I epitopes and by using a Major Histocompatibility Complex (MHC) binding prediction tool. A subset of those met the criteria for optimal CD8+ attack based on physical chemistry parameters determined by analysis of the ZKV protein structure encoded in open source Protein Data File (PDB) format files. We also identified candidate ZKV epitopes predicted to bind promiscuously to multiple HLA class II molecules that could provide help to the CTL responses. This work suggests that a CTL vaccine for ZKV may be possible even if ZKV exhibits significant antigenic drift. We have previously described a microsphere-based CTL vaccine platform capable of eliciting an immune response for class I epitopes in mice and are currently working toward in vivo testing of class I and class II epitope delivery directed against ZKV epitopes using the same microsphere-based vaccine.
- ItemAcesso aberto (Open Access)Dengue: muscle biopsy findings in 15 patients(Academia Brasileira de Neurologia - ABNEURO, 1993-06-01) Malheiros, Suzana Maria Fleury [UNIFESP]; Oliveira, Acary Souza Bulle [UNIFESP]; Schmidt, Beny [UNIFESP]; Lima, J.g. Camargo [UNIFESP]; Gabbai, Alberto Alain [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Dengue is known to produce a syndrome involving muscles, tendons and joints. The hallmark of this syndrome is severe myalgia but includes fever, cutaneous rash, and headache. The neuromuscular aspects of this infection are outlined only in isolated reports, and the muscle histopathological features during myalgia have not been described. In order to ascertain the actual neuromuscular involvement in dengue and better comprehend the histological nature of myalgia, we performed a clinical and neurological evaluation, a serum CPK level and a muscle biopsy (with histochemistry) in 15 patients (4 males), median age 23 years (range 14-47) with classic dengue fever, serologically confirmed, during the bra-zilian dengue epidemics from September 1986 to March 1987. All patients had a history of fever, headache and severe myalgia. Upon examination 4 had a cutaneous rash, 3 had fever, and 3 a small hepatomegaly. The neurological examination was unremarkable in all and included a manual muscle test. CPK was mildly elevated in only 3 patients. Muscle biopsy revealed a light to moderate perivascular mononuclear infiltrate in 12 patients and lipid accumulation in 11. Mild mitochondrial proliferation was seen in 3, few central nuclei in 3, rare foci of myonecrosis in 3, and 2 patients had type grouping. Dengue in our patients, produced myalgia but no detectable muscle weakness or other neuromuscular involvement. The main histopathological correlation with myalgia seems to be a perivascular mononuclear infiltrate and lipid accumulation.
- ItemAcesso aberto (Open Access)Environmental factors can influence dengue reported cases(Assoc Medica Brasileira, 2017) Carneiro, Marco Antonio F.; Alves, Beatriz da C. A.; Gehrke, Flavia de Sousa; Domingues, Jose Nuno; Sa, Nelson; Paixao, Susana; Figueiredo, Joao; Ferreira, Ana; Almeida, Cleonice; Machi, Amaury; Savoia, Eriane; Nascimento, Vania; Fonseca, Fernando [UNIFESP]Introduction: Global climate changes directly affect the natural environment and contribute to an increase in the transmission of diseases by vectors. Among these diseases, dengue is at the top of the list. The aim of our study was to understand the consequences of temporal variability of air temperature in the occurrence of dengue in an area comprising seven municipalities of the Greater Sao Paulo. Method: Characterization of a temporal trend of the disease in the region between 2010 and 2013 was performed through analysis of the notified number of dengue cases over this period. Our analysis was complemented with meteorological (temperature) and pollutant concentration data (PM10). Results: We observed that the months of January, February, March, April and May (from 2010 to 2013) were the ones with the highest number of notified cases. We also found that there is a statistical association of moisture and PM10 with the reported cases of dengue. Conclusion: Although the temperature does not statistically display an association with recorded cases of dengue, we were able to verify that temperature peaks coincide with dengue outbreak peaks. Future studies on environmental pollution and its influence on the development of Aedes aegypti mosquito during all stages of its life cycle, and the definition of strategies for better monitoring, including campaigns and surveillance, would be compelling.
- ItemSomente MetadadadosEstudo molecular e funcional de um inibidor de cisteínoproteases identificado no genoma do mosquito aedes aegypti(Universidade Federal de São Paulo (UNIFESP), 2013-11-27) Oliveira, Felipe Araujo de Alcantara [UNIFESP]; Tanaka, Aparecida Sadae Tanaka [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Objetivo: Caracterizar um inibidor de protease da família das cistatinas no mosquito Aedes aegypti, abordando parâmetros bioquímicos e verificar seus possível papel na infecção do mosquito com vírus da DENV. Métodos: A proteína foi expressa em E. colí para a produção de anticorpos, afim de confirmar a presença da proteína nativa, e para a realização de testes enzirnáticos. Reações de cadeia da polimerase quantitativos (qPCRs) foram realizadas afim de verificar quais tecidos o transcrito está expresso e sua modulação com a infecção por DENV. Resultados: A proteína pertence à família das estefinas (125B) e inibe diversas cisteinopeptases como as cathepsias humanas B, L1, L2, S e a papaína. O anticorpo produzido apresentou afinidade por uma proteína de tamanho similar ao esperado. A cistatina se encontrada majoritariamente no intestino e a quantidade de transcritos apresenta redução durante a infecção.
- ItemAcesso aberto (Open Access)Risk of symptomatic dengue for foreign visitors to the 2014 FIFA World Cup in Brazil(Fundaco Oswaldo Cruz, 2014-05-01) Massad, Eduardo; Wilder-Smith, Annelies; Ximenes, Raphael; Amaku, Marcos; Lopez, Luis Fernandez; Bezerra Coutinho, Francisco Antonio; Coelho, Giovanini Evelim; Silva, Jarbas Barbosa da; Struchiner, Claudio Jose; Burattini, Marcelo Nascimento [UNIFESP]; Universidade de São Paulo (USP); London Sch Hyg & Trop Med; Nanyang Univ; Florida Int Univ; Minist Saude; Fiocruz MS; Universidade Federal de São Paulo (UNIFESP)Brazil will host the FIFA World Cup T, the biggest single-event competition in the world, from June 12-July 13 2014 in 12 cities. This event will draw an estimated 600,000 international visitors. Brazil is endemic for dengue. Hence, attendees of the 2014 event are theoretically at risk for dengue. We calculated the risk of dengue acquisition to non-immune international travellers to Brazil, depending on the football match schedules, considering locations and dates of such matches for June and July 2014. We estimated the average per-capita risk and expected number of dengue cases for each host-city and each game schedule chosen based on reported dengue cases to the Brazilian Ministry of Health for the period between 2010-2013. On the average, the expected number of cases among the 600,000 foreigner tourists during the World Cup is 33, varying from 3-59. Such risk estimates will not only benefit individual travellers for adequate pre-travel preparations, but also provide valuable information for public health professionals and policy makers worldwide. Furthermore, estimates of dengue cases in international travellers during the World Cup can help to anticipate the theoretical risk for exportation of dengue into currently non-infected areas.
- ItemSomente MetadadadosSubstrate specificity of recombinant dengue 2 virus NS2B-NS3 protease: Influence of natural and unnatural basic amino acids on hydrolysis of synthetic fluorescent substrates(Elsevier B.V., 2007-01-15) Gouvea, I. E.; Izidoro, M. A.; Judice, W. A. S.; Cezari, M. H. S.; Caliendo, G.; Santagada, V.; Santos, C. N. D. dos; Queiroz, M. H.; Juliano, M. A.; Young, P. R.; Fairlie, D. P.; Juliano, L.; Universidade Federal de São Paulo (UNIFESP); Univ Naples Federico II; Inst Biol Mol Parana; Univ QueenslandA recombinant dengue 2 virus NS2B-NS3 protease (NS means non-structural virus protein) was compared with human furin for the capacity to process short peptide substrates corresponding to seven native Substrate cleavage sites in the dengue viral polyprotein. Using fluorescence resonance energy transfer peptides to measure kinetics, the processing of these substrates was found to be selective for the Dengue protease. Substrates containing two or three basic amino acids (Arg or Lys) in tandem were found to be the best, with Abz-AKRRSQ-EDDnp being the most efficiently cleaved. the hydrolysis of dipeptide substrates Bz-X-Arg-MCA where X is a non-natural basic amino acid were also kinetically examined, the best substrates containing aliphatic basic amino acids. Our results indicated that proteolytic processing by dengue NS3 protease, tethered to its activating NS2B co-factor, was strongly inhibited by Ca2+ and kosmotropic salts of the Hofmeister's series, and significantly influenced by substrate modifications between S-4 and S'. Incorporation of basic non-natural amino acids in short peptide substrates had significant but differential effects on K-m and k(cat) suggesting that further dissection of their influences on substrate affinity might enable the development of effective dengue protease inhibitors. (c) 2006 Elsevier Inc. All rights reserved.