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1.
J Neuroinflammation ; 20(1): 61, 2023 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-36882750

RESUMEN

Zika virus (ZIKV) infection is a global public health concern linked to adult neurological disorders and congenital diseases in newborns. Host lipid metabolism, including lipid droplet (LD) biogenesis, has been associated with viral replication and pathogenesis of different viruses. However, the mechanisms of LD formation and their roles in ZIKV infection in neural cells are still unclear. Here, we demonstrate that ZIKV regulates the expression of pathways associated with lipid metabolism, including the upregulation and activation of lipogenesis-associated transcription factors and decreased expression of lipolysis-associated proteins, leading to significant LD accumulation in human neuroblastoma SH-SY5Y cells and in neural stem cells (NSCs). Pharmacological inhibition of DGAT-1 decreased LD accumulation and ZIKV replication in vitro in human cells and in an in vivo mouse model of infection. In accordance with the role of LDs in the regulation of inflammation and innate immunity, we show that blocking LD formation has major roles in inflammatory cytokine production in the brain. Moreover, we observed that inhibition of DGAT-1 inhibited the weight loss and mortality induced by ZIKV infection in vivo. Our results reveal that LD biogenesis triggered by ZIKV infection is a crucial step for ZIKV replication and pathogenesis in neural cells. Therefore, targeting lipid metabolism and LD biogenesis may represent potential strategies for anti-ZIKV treatment development.


Asunto(s)
Neuroblastoma , Infección por el Virus Zika , Virus Zika , Animales , Humanos , Ratones , Gotas Lipídicas , Replicación Viral
2.
Front Immunol ; 13: 1029213, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36569864

RESUMEN

Introduction: Dengue is an arthropod-born disease caused by dengue virus (DENV), that may manifest as a mild illness or severe form, characterized by hemorrhagic fever and shock. Nitric oxide (NO) is a vasodilator signaling molecule and an inhibitor of platelet aggregation known to be increased in platelets from dengue patients. However, the mechanisms underlying NO synthesis by platelets during dengue are not yet elucidated. IL-1ß is a pro-inflammatory cytokine able to induce iNOS expression in leukocytes and present in dengue patients at high levels. Nevertheless, the role of IL-1ß in platelet activation, especially regarding iNOS expression, are not clear. Methods: We prospectively followed a cohort of 28 dengue-infected patients to study NO synthesis in platelets and its relationship with disease outcomes. We used in vitro infection and stimulation models to gain insights on the mechanisms. Results and Discussion: We confirmed that platelets from dengue patients express iNOS and produce higher levels of NO during the acute phase compared to healthy volunteers, returning to normal levels after recovery. Platelet NO production during acute dengue infection was associated with the presence of warning signs, hypoalbuminemia and hemorrhagic manifestations, suggesting a role in dengue pathophysiology. By investigating the mechanisms, we evidenced increased iNOS expression in platelets stimulated with dengue patients´ plasma, indicating induction by circulating inflammatory mediators. We then investigated possible factors able to induce platelet iNOS expression and observed higher levels of IL-1ß in plasma from patients with dengue, which were correlated with NO production by platelets. Since platelets can synthesize and respond to IL-1ß, we investigated whether IL-1ß induces iNOS expression and NO synthesis in platelets. We observed that recombinant human IL-1ß enhanced iNOS expression and dose-dependently increased NO synthesis by platelets. Finally, platelet infection with DENV in vitro induced iNOS expression and NO production, besides the secretion of both IL-1α and IL-1ß. Importantly, treatment with IL-1 receptor antagonist or a combination of anti-IL-1α and anti-IL-1ß antibodies prevented DENV-induced iNOS expression and NO synthesis. Our data show that DENV induces iNOS expression and NO production in platelets through mechanisms depending on IL-1 receptor signaling.


Asunto(s)
Virus del Dengue , Dengue , Humanos , Óxido Nítrico/metabolismo , Plaquetas , Receptores de Interleucina-1/metabolismo
3.
Rev Panam Salud Publica ; 46: e11, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35355692

RESUMEN

Objective: To evaluate molecular tools to detect low-level parasitemia and the five species of Plasmodium that infect humans for use in control and elimination programs, and in reference laboratories. Methods: We evaluated 145 blood samples from patients who tested positive by nested polymerase chain reaction (nPCR), from asymptomatic individuals and from the WHO Global Malaria Programme/United Kingdom National External Quality Assessment Service. Samples were assayed using the genus-specific RealStar® Malaria PCR Kit 1.0 (alt-Gen; altona Diagnostics) and the RealStar® Malaria Screen & Type PCR Kit (alt-S&T; altona Diagnostics). The results from the molecular tests were compared with those from quantitative PCR (qPCR), nPCR and thick blood smear. Results: The levels of parasitemia ranged from 1 to 518 000 parasites/µL, depending on the species. Compared with nPCR, alt-S&T had a sensitivity of 100%, except for identifying P. falciparum, for which the sensitivity was 93.94%. All samples positive by alt-Gen were also positive by nPCR. When comparing alt-Gen to qPCR, the sensitivity was 100% for P. vivax, P. malariae and P. falciparum. For all Plasmodium species, the correlation between cycle threshold values of alt-S&T and alt-Gen compared with qPCR was significant (P < 0.0001, Spearman's test), with r = 0.8621 for alt-S&T and r = 0.9371 for alt-Gen. When all Plasmodium species were considered, there was a negative correlation between the level of parasitemia and real-time PCR cycle threshold values (P < 0.0001). In this study, only 2 of 28 samples from asymptomatic individuals were positive by thick blood smear; however, all 28 of these samples were positive by alt-S&T. Conclusions: The alt-Gen and alt-S&T assays are suitable for detecting submicroscopic infections for distinct epidemiological purposes, such as for use in surveys and reference laboratories, and screening in blood banks, which will contribute to global efforts to eliminate malaria.

4.
Artículo en Inglés | PAHO-IRIS | ID: phr-55854

RESUMEN

[ABSTRACT]. Objective. To evaluate molecular tools to detect low-level parasitemia and the five species of Plasmodium that infect humans for use in control and elimination programs, and in reference laboratories. Methods. We evaluated 145 blood samples from patients who tested positive by nested polymerase chain reaction (nPCR), from asymptomatic individuals and from the WHO Global Malaria Programme/United Kingdom National External Quality Assessment Service. Samples were assayed using the genus-specific RealStar® Malaria PCR Kit 1.0 (alt-Gen; altona Diagnostics) and the RealStar® Malaria Screen & Type PCR Kit (alt-S&T; altona Diagnostics). The results from the molecular tests were compared with those from quantitative PCR (qPCR), nPCR and thick blood smear. Results. The levels of parasitemia ranged from 1 to 518 000 parasites/μL, depending on the species. Compared with nPCR, alt-S&T had a sensitivity of 100%, except for identifying P. falciparum, for which the sensitivity was 93.94%. All samples positive by alt-Gen were also positive by nPCR. When comparing alt-Gen to qPCR, the sensitivity was 100% for P. vivax, P. malariae and P. falciparum. For all Plasmodium species, the correlation between cycle threshold values of alt-S&T and alt-Gen compared with qPCR was significant (P < 0.0001, Spearman’s test), with r = 0.8621 for alt-S&T and r = 0.9371 for alt-Gen. When all Plasmodium species were considered, there was a negative correlation between the level of parasitemia and real-time PCR cycle threshold values (P < 0.0001). In this study, only 2 of 28 samples from asymptomatic individuals were positive by thick blood smear; however, all 28 of these samples were positive by alt-S&T. Conclusions. The alt-Gen and alt-S&T assays are suitable for detecting submicroscopic infections for distinct epidemiological purposes, such as for use in surveys and reference laboratories, and screening in blood banks, which will contribute to global efforts to eliminate malaria.


[RESUMEN]. Objetivo. Evaluar herramientas moleculares para detectar bajos niveles de parasitemia y las cinco especies de Plasmodium que infectan a los seres humanos, a fin de emplearlas en los programas de control y eliminación y en los laboratorios de referencia. Métodos. Se evaluaron 145 muestras de sangre de pacientes positivos por reacción en cadena de la polimerasa anidada (nPCR), de individuos asintomáticos y de muestras del Programa Mundial de Malaria de la Organización Mundial de la Salud/Servicio Nacional de Evaluación Externa de Calidad del Reino Unido. Las muestras se analizaron con el kit de PCR RealStar® Malaria 1.0 (alt-Gen; altona Diagnostics), específico para cada género, y con el kit de PCR RealStar® Malaria Screen & Type (alt-S&T; altona Diagnostics). Se compararon los resultados de las pruebas moleculares con los de la PCR cuantitativa (qPCR), la nPCR y el frotis de gota gruesa. Resultados. Los niveles de parasitemia oscilaron entre 1 y 518 000 parásitos/μl, según la especie. En comparación con la nPCR, la prueba alt-S&T tuvo una sensibilidad del 100%, excepto para la identificación de P. falciparum, para el cual la sensibilidad fue del 93,94%. Todas las muestras positivas por alt-Gen lo fueron también por nPCR. Al comparar alt-Gen con la qPCR, la sensibilidad fue del 100% para P. vivax, P. malariae y P. falciparum. Para todas las especies de Plasmodium, la correlación entre los valores del umbral de ciclo de alt-S&T y alt-Gen en comparación con la qPCR fue significativa (P < 0,0001, prueba de Spearman), con r = 0,8621 para alt-S&T y r = 0,9371 para alt-Gen. Cuando se consideraron todas las especies de Plasmodium hubo una correlación negativa entre el nivel de parasitemia y los valores de umbral de ciclo de PCR en tiempo real (P < 0,0001). En este estudio, solo 2 de las 28 muestras de individuos asintomáticos fueron positivas por frotis de gota gruesa; sin embargo, las 28 muestras fueron positivas por alt-S&T. Conclusiones. Los ensayos alt-Gen y alt-S&T son adecuados para detectar infecciones submicroscópicas con distintos fines epidemiológicos, como su uso en investigaciones y laboratorios de referencia y el cribado en bancos de sangre, lo que contribuirá a los esfuerzos mundiales para eliminar la malaria.


[RESUMO]. Objectivo. Avaliar ferramentas moleculares para detectar parasitemia de baixo nível e as cinco espécies de Plasmodium que infectam humanos, para utilização em programas de controlo e eliminação e em laboratórios de referência. Métodos. Avaliámos 145 amostras de sangue de doentes que testaram positivo por reacção em cadeia da polimerase aninhada (nPCR), de indivíduos assintomáticos, e do Programa Global de Paludismo da Organização Mundial de Saúde/Serviço Nacional de Avaliação da Qualidade Externa do Reino Unido. As amostras foram ensaiadas utilizando o RealStar® Malaria PCR Kit 1.0 (alt-Gen; altona Diagnostics) e o RealStar® Malaria Screen & Type PCR Kit (alt-S&T; altona Diagnostics). Os resultados dos testes moleculares foram comparados com os resultados da PCR quantitativa (qPCR), nPCR e exame da gota espessa. Resultados. Os níveis de parasitemia variaram de 1 a 518 000 parasitas/μL, dependendo da espécie. Em comparação com a nPCR, alt-S&T tinha uma sensibilidade de 100%, excepto na identificação de P. falciparum, para a qual a sensibilidade era de 93,94%. Todas as amostras positivas por alt-Gen foram também positivas por nPCR. Ao comparar alt-Gen com qPCR, a sensibilidade foi de 100% para P. vivax, P. malariae e P. falciparum. Para todas as espécies Plasmodium, a correlação entre os valores limiares de ciclo de alt-S&T e alt-Gen comparados com qPCR foi significativa (P < 0,0001, teste de Spearman), com r = 0,8621 para alt- S&T e r = 0,9371 para alt-Gen. Quando todas as espécies de Plasmodium foram consideradas, houve uma correlação negativa entre o nível de parasitemia e os valores limiares do ciclo de PCR em tempo real (P < 0,0001). Neste estudo, apenas 2 de 28 amostras de indivíduos assintomáticos foram positivas por exame da gota espessa; no entanto, todas estas 28 amostras foram positivas por alt-S&T. Conclusões. Os ensaios alt-Gen e alt-S&T são adequados para a detecção de infecções submicroscópicas para fins epidemiológicos distintos, tais como para utilização em inquéritos e laboratórios de referência e o rastreio em bancos de sangue, o que contribuirá para os esforços globais de eliminação da malária.


Asunto(s)
Malaria , Plasmodium , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena en Tiempo Real de la Polimerasa , Malaria , Reacción en Cadena en Tiempo Real de la Polimerasa
5.
Rev. panam. salud pública ; 46: e11, 2022. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1432078

RESUMEN

ABSTRACT Objective. To evaluate molecular tools to detect low-level parasitemia and the five species of Plasmodium that infect humans for use in control and elimination programs, and in reference laboratories. Methods. We evaluated 145 blood samples from patients who tested positive by nested polymerase chain reaction (nPCR), from asymptomatic individuals and from the WHO Global Malaria Programme/United Kingdom National External Quality Assessment Service. Samples were assayed using the genus-specific RealStar® Malaria PCR Kit 1.0 (alt-Gen; altona Diagnostics) and the RealStar® Malaria Screen & Type PCR Kit (alt-S&T; altona Diagnostics). The results from the molecular tests were compared with those from quantitative PCR (qPCR), nPCR and thick blood smear. Results. The levels of parasitemia ranged from 1 to 518 000 parasites/µL, depending on the species. Compared with nPCR, alt-S&T had a sensitivity of 100%, except for identifying P. falciparum, for which the sensitivity was 93.94%. All samples positive by alt-Gen were also positive by nPCR. When comparing alt-Gen to qPCR, the sensitivity was 100% for P. vivax, P. malariae and P. falciparum. For all Plasmodium species, the correlation between cycle threshold values of alt-S&T and alt-Gen compared with qPCR was significant (P < 0.0001, Spearman's test), with r = 0.8621 for alt-S&T and r = 0.9371 for alt-Gen. When all Plasmodium species were considered, there was a negative correlation between the level of parasitemia and real-time PCR cycle threshold values (P < 0.0001). In this study, only 2 of 28 samples from asymptomatic individuals were positive by thick blood smear; however, all 28 of these samples were positive by alt-S&T. Conclusions. The alt-Gen and alt-S&T assays are suitable for detecting submicroscopic infections for distinct epidemiological purposes, such as for use in surveys and reference laboratories, and screening in blood banks, which will contribute to global efforts to eliminate malaria.


RESUMEN Objetivo. Evaluar herramientas moleculares para detectar bajos niveles de parasitemia y las cinco especies de Plasmodium que infectan a los seres humanos, a fin de emplearlas en los programas de control y eliminación y en los laboratorios de referencia. Métodos. Se evaluaron 145 muestras de sangre de pacientes positivos por reacción en cadena de la polimerasa anidada (nPCR), de individuos asintomáticos y de muestras del Programa Mundial de Malaria de la Organización Mundial de la Salud/Servicio Nacional de Evaluación Externa de Calidad del Reino Unido. Las muestras se analizaron con el kit de PCR RealStar® Malaria 1.0 (alt-Gen; altona Diagnostics), específico para cada género, y con el kit de PCR RealStar® Malaria Screen & Type (alt-S&T; altona Diagnostics). Se compararon los resultados de las pruebas moleculares con los de la PCR cuantitativa (qPCR), la nPCR y el frotis de gota gruesa. Resultados. Los niveles de parasitemia oscilaron entre 1 y 518 000 parásitos/µl, según la especie. En comparación con la nPCR, la prueba alt-S&T tuvo una sensibilidad del 100%, excepto para la identificación de P. falciparum, para el cual la sensibilidad fue del 93,94%. Todas las muestras positivas por alt-Gen lo fueron también por nPCR. Al comparar alt-Gen con la qPCR, la sensibilidad fue del 100% para P. vivax, P. malariae y P. falciparum. Para todas las especies de Plasmodium, la correlación entre los valores del umbral de ciclo de alt-S&T y alt-Gen en comparación con la qPCR fue significativa (P < 0,0001, prueba de Spearman), con r = 0,8621 para alt-S&T y r = 0,9371 para alt-Gen. Cuando se consideraron todas las especies de Plasmodium hubo una correlación negativa entre el nivel de parasitemia y los valores de umbral de ciclo de PCR en tiempo real (P < 0,0001). En este estudio, solo 2 de las 28 muestras de individuos asintomáticos fueron positivas por frotis de gota gruesa; sin embargo, las 28 muestras fueron positivas por alt-S&T. Conclusiones. Los ensayos alt-Gen y alt-S&T son adecuados para detectar infecciones submicroscópicas con distintos fines epidemiológicos, como su uso en investigaciones y laboratorios de referencia y el cribado en bancos de sangre, lo que contribuirá a los esfuerzos mundiales para eliminar la malaria.


RESUMO Objectivo. Avaliar ferramentas moleculares para detectar parasitemia de baixo nível e as cinco espécies de Plasmodium que infectam humanos, para utilização em programas de controlo e eliminação e em laboratórios de referência. Métodos. Avaliámos 145 amostras de sangue de doentes que testaram positivo por reacção em cadeia da polimerase aninhada (nPCR), de indivíduos assintomáticos, e do Programa Global de Paludismo da Organização Mundial de Saúde/Serviço Nacional de Avaliação da Qualidade Externa do Reino Unido. As amostras foram ensaiadas utilizando o RealStar® Malaria PCR Kit 1.0 (alt-Gen; altona Diagnostics) e o RealStar® Malaria Screen & Type PCR Kit (alt-S&T; altona Diagnostics). Os resultados dos testes moleculares foram comparados com os resultados da PCR quantitativa (qPCR), nPCR e exame da gota espessa. Resultados. Os níveis de parasitemia variaram de 1 a 518 000 parasitas/µL, dependendo da espécie. Em comparação com a nPCR, alt-S&T tinha uma sensibilidade de 100%, excepto na identificação de P. falciparum, para a qual a sensibilidade era de 93,94%. Todas as amostras positivas por alt-Gen foram também positivas por nPCR. Ao comparar alt-Gen com qPCR, a sensibilidade foi de 100% para P. vivax, P. malariae e P. falciparum. Para todas as espécies Plasmodium, a correlação entre os valores limiares de ciclo de alt-S&T e alt-Gen comparados com qPCR foi significativa (P < 0,0001, teste de Spearman), com r = 0,8621 para alt-S&T e r = 0,9371 para alt-Gen. Quando todas as espécies de Plasmodium foram consideradas, houve uma correlação negativa entre o nível de parasitemia e os valores limiares do ciclo de PCR em tempo real (P < 0,0001). Neste estudo, apenas 2 de 28 amostras de indivíduos assintomáticos foram positivas por exame da gota espessa; no entanto, todas estas 28 amostras foram positivas por alt-S&T. Conclusões. Os ensaios alt-Gen e alt-S&T são adequados para a detecção de infecções submicroscópicas para fins epidemiológicos distintos, tais como para utilização em inquéritos e laboratórios de referência e o rastreio em bancos de sangue, o que contribuirá para os esforços globais de eliminação da malária.

6.
Texto & contexto enferm ; 29: e20190006, Jan.-Dec. 2020. tab
Artículo en Inglés | BDENF - Enfermería, LILACS | ID: biblio-1145143

RESUMEN

ABSTRACT Objective: to analyze the sexual practices adopted by university students for the prevention of Sexually Transmitted Infections Method: a quantitative, descriptive and cross-sectional study, conducted in 2016, at a private university in the municipality of Rio de Janeiro, Brazil. A convenience sample was selected, stratified by gender, of 768 students who answered a self-administered questionnaire, structured with variables of sociodemographic characterization and related to knowledge about sexually transmitted infections, sexual practices, prevention practices and care with sexual health. In the analysis, descriptive statistics, chi-square tests and analysis of variance were used, with a significance level of 5%. Results: most of the university students ‒ 654 (85.16%) ‒ had an active sex life and 480 (62.54%) did not use condoms in all their sexual encounters. Among the participants, 509 (84.83%) said they had sexual intercourse with a steady partner, of which 224 (44.01%) used a condom. In the investigated group, 313 (47.86%) had relationships with casual partners, with 199 (63.58%) reporting having used a condom. Among the participants, 174 (26.61%) had their sexual practices classified as adequate/satisfactory. Conclusion: the findings show that the university students investigated present a risk behavior for Sexually Transmitted Infections due to inadequate/unsatisfactory sexual practices. Health education actions should consider cultural and individual aspects of the group in order to encourage reflection on practices for the prevention of sexually transmitted diseases.


RESUMEN Objetivo: analizar las prácticas sexuales adoptadas por estudiantes universitarios para prevenir Infecciones de Transmisión Sexual. Método: estudio cuantitativo, descriptivo y transversal, realizado en el año 2016 en una universidad privada del municipio de Río de Janeiro, Brasil. Ajustada por conveniencia y estratificada por sexo, la muestra estuvo compuesta por 768 estudiantes que respondieron un cuestionario autoaplicado, estructurado con variables de caracterización sociodemográfica y relacionadas con el conocimiento sobre infecciones de transmisión sexual, prácticas sexuales, prácticas de prevención y cuidados con la salud sexual. En el análisis se empleó la estadística descriptiva, pruebas de Chi-cuadrado y análisis de variancia, con un nivel de significancia del 5%. Resultados: la mayoría de los universitarios ‒ 654 (85,16%) ‒ tenía una vida sexual activa y 480 (62,54%) no usaban preservativo en todos sus encuentros sexuales. Entre los participantes, 509 (84,83%) afirmaron tener relaciones sexuales con una pareja fija y, de ellos, 224 (44,01%) utilizaban preservativo. En el grupo investigado, 313 (47,86%) tuvieron relaciones con parejas casuales, y 199 (63,58%) declararon haber usado preservativo. Entre los participantes, las prácticas sexuales de 174 (26,61%) de ellos se clasificaron como adecuadas/satisfactorias. Conclusión: las conclusiones del estudio evidencian que los universitarios investigados presentan un comportamiento de riesgo para contraer Infecciones de Transmisión Sexual como resultado de prácticas sexuales inadecuadas/insatisfactorias. Las medidas de educación en salud deben considerar aspectos culturales e individuales del grupo para favorecer la reflexión sobre las prácticas de prevención de enfermedades de transmisión sexual.


RESUMO Objetivo: analisar as práticas sexuais adotadas por estudantes universitários para prevenção de Infecções Sexualmente Transmissíveis Método: estudo quantitativo, descritivo e transversal, realizado em 2016, em uma universidade privada no município do Rio de Janeiro, Brasil. Selecionou-se amostra por conveniência, estratificada por sexo, de 768 estudantes que responderam a um questionário autoaplicado, estruturado com variáveis de caracterização sociodemográfica e relacionadas ao conhecimento sobre infecções sexualmente transmissíveis, práticas sexuais, práticas de prevenção e cuidados com a saúde sexual. Na análise, empregou-se a estatística descritiva, testes de quiquadrado e análise de variância, com nível de significância de 5%. Resultados: a maioria dos universitários ‒ 654(85,16%) ‒ tinha vida sexual ativa e 480(62,54%) não fazia uso do preservativo em todos os intercursos sexuais. Entre os participantes, 509(84,83%) afirmaram ter relação sexual com parceiro fixo, dos quais 224(44,01%) utilizaram o preservativo. No grupo investigado, 313(47,86%) tiveram relações com parceiros casuais, sendo que 199 (63,58%) informaram ter usado o preservativo. Entre os participantes, 174(26,61%) tiveram suas práticas sexuais classificadas como adequadas/satisfatórias. Conclusão: os achados evidenciam que os universitários investigados apresentam um comportamento de risco para Infecções Sexualmente Transmissíveis decorrente de práticas sexuais inadequadas/insatisfatórias. Ações de educação em saúde devem considerar aspectos culturais e individuais do grupo para favorecer a reflexão sobre as práticas de prevenção de doenças transmitidas pelo sexo.


Asunto(s)
Humanos , Adulto , Prevención Primaria , Asunción de Riesgos , Conducta Sexual , Enfermedades de Transmisión Sexual , Adulto Joven , Salud Sexual
7.
Fisioter. Bras ; 21(4): 336-342, Ago 08, 2020.
Artículo en Portugués | LILACS | ID: biblio-1283216

RESUMEN

Na postura padrão, a coluna apresenta curvaturas normais e os ossos dos membros inferiores ficam em alinhamento. Quando o componente estrutural é alterado, o corpo humano modifica-se para desempenhar tal situação da melhor forma possível, o que pode ocasionar em um desvio postural. O objetivo desta pesquisa é avaliar a postura e seus comprometimentos em discentes de um curso de Fisioterapia, traçando o perfil clínico socioeconômico, conhecendo os comprometimentos posturais dos participantes da pesquisa. Tratou-se de um estudo transversal, descritivo e quantitativo realizado entre os meses de agosto de 2015 a junho de 2016, no Centro Universitário Estácio do Ceará com 32 discentes do curso de Fisioterapia. Os dados foram coletados através de uma ficha de avaliação postural desenvolvida para o inquérito e analisada no programa Excel® 2013 e confrontados com a literatura vigente sobre o assunto. O gênero feminino foi predominante em 75% da amostra. Em relação ao estado civil dos participantes, 87,5% eram solteiros. A média de idade foi de 24,4 anos. Em relação ao Índice de Massa Corpórea, foi evidenciado que 28 participantes (87,5%) apresentaram um peso normal, de acordo com sua altura e peso. Para verificar a presença de escoliose, foi realizado o Teste de Adams. Evidenciou-se que 72% dos participantes apresentaram gibosidade, 12,50% apresentaram gibosidade lombar, 43,75% apresentaram gibosidade torácica e 15,63% apresentaram gibosidade toracolombar. A maioria dos estudantes apresentou escoliose. No entanto, estudos com uma amostra maior devem ser realizados, a fim de que resultados mais abrangentes possam ser obtidos. (AU)


In the standard posture, the spine has normal curvatures and the bones of the lower limbs are in alignment. When the structural component is changed, the human body changes to perform this situation in the best possible way, which can cause a postural deviation. The objective of this study was to evaluate the posture and its commitments in students of a Physical therapy course, tracing the socioeconomic clinical profile, knowing the postural impairments of the participants. This was a cross-sectional, descriptive and quantitative study carried out between August 2015 and June 2016, at the Estácio do Ceará University Center with 32 students. The data were collected through a postural assessment form developed for the survey and analyzed using the Excel® program and compared with the current literature. The female gender was predominant in 75% of the sample. Regarding the participants' marital status, 87.5% were single. The average age was 24.4 years. Regarding the Body Mass Index, it was evidenced that 28 participants (87.5%) had a normal weight, according to their height. To test for the presence of scoliosis, the Adams Test was performed. 72% of the participants presented gibosity, 12.50% lumbar gibosity, 43.75% thoracic gibosity and 15.63% thoraco-lumbar gibosity. Most of the students had scoliosis. However, studies with a larger sample should be carried out to obtain more accurate results. (AU)


Asunto(s)
Humanos , Postura , Escoliosis , Modalidades de Fisioterapia
8.
J Leukoc Biol ; 108(4): 1293-1306, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32663907

RESUMEN

Dengue is characterized as one of the most important arthropod-borne human viral diseases, representing a public health problem. Increased activation of immune cells is involved in the progression of infection to severe forms. Recently, our group demonstrated the contribution of platelet-monocyte interaction to inflammatory responses in dengue, adding to evolving evidence that platelets have inflammatory functions and can regulate different aspects of innate immune responses. Furthermore, stimuli-specific-activated platelets can promote phenotypic changes and metabolic reprogramming in monocytes. Thus, this study aimed to evaluate the roles of dengue virus (DENV)-activated platelets on immunometabolic reprogramming of monocytes in vitro, focusing on lipid droplet (LD) biogenesis. We demonstrated that platelets exposed to DENV in vitro form aggregates with monocytes and signal to LD formation and CXCL8/IL-8, IL-10, CCL2, and PGE2 secretion. Pharmacologic inhibition of LD biogenesis prevents PGE2 secretion, but not CXCL8/IL-8 release, by platelet-monocyte complexes. In exploring the mechanisms involved, we demonstrated that LD formation in monocytes exposed to DENV-activated platelets is partially dependent on platelet-produced MIF. Additionally, LD formation is higher in monocytes, which have platelets adhered on their surface, suggesting that beyond paracrine signaling, platelet adhesion is an important event in platelet-mediated modulation of lipid metabolism in monocytes. Together, our results demonstrate that activated platelets aggregate with monocytes during DENV infection and signal to LD biogenesis and the secretion of inflammatory mediators, which may contribute to dengue immunopathogenesis.


Asunto(s)
Plaquetas/inmunología , Citocinas/inmunología , Virus del Dengue/inmunología , Dengue/inmunología , Gotas Lipídicas/inmunología , Monocitos/inmunología , Transducción de Señal/inmunología , Plaquetas/patología , Dengue/patología , Femenino , Humanos , Gotas Lipídicas/patología , Masculino , Monocitos/patología
9.
Rev Soc Bras Med Trop ; 53: e20190526, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32578705

RESUMEN

INTRODUCTION: This study investigated the genetic environment of bla KPC-2 in Klebsiella pnemoniae multi-drug resistant clinical isolates. METHODS: Four carbapenemase gene isolates resistant to carbapenems, collected from infected patients from two hospitals in Brazil, were investigated using polymerase chain reaction and plasmid DNA sequencing. RESULTS: The bla KPC-2 gene was located between ISKpn6 and a resolvase tnpR in the non-Tn4401 element (NTEKPC-IId). It was detected on a plasmid belonging to the IncQ1 group. CONCLUSIONS: To our knowledge, this is the first report of the presence of the bla KPC-2 gene in the NTEKPC-IId element carried by plasmid IncQ1 from infections in Brazil.


Asunto(s)
Antibacterianos/farmacología , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/genética , beta-Lactamasas/genética , ADN Bacteriano/genética , Farmacorresistencia Bacteriana Múltiple , Humanos , Klebsiella pneumoniae/enzimología , Klebsiella pneumoniae/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Plásmidos/genética , Reacción en Cadena de la Polimerasa
10.
Rev. Soc. Bras. Med. Trop ; Rev. Soc. Bras. Med. Trop;53: e20190526, 2020. tab, graf
Artículo en Inglés | Sec. Est. Saúde SP, Coleciona SUS, LILACS | ID: biblio-1136834

RESUMEN

Abstract INTRODUCTION: This study investigated the genetic environment of bla KPC-2 in Klebsiella pnemoniae multi-drug resistant clinical isolates. METHODS: Four carbapenemase gene isolates resistant to carbapenems, collected from infected patients from two hospitals in Brazil, were investigated using polymerase chain reaction and plasmid DNA sequencing. RESULTS: The bla KPC-2 gene was located between ISKpn6 and a resolvase tnpR in the non-Tn4401 element (NTEKPC-IId). It was detected on a plasmid belonging to the IncQ1 group. CONCLUSIONS To our knowledge, this is the first report of the presence of the bla KPC-2 gene in the NTEKPC-IId element carried by plasmid IncQ1 from infections in Brazil.


Asunto(s)
Humanos , beta-Lactamasas/genética , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/genética , Antibacterianos/farmacología , Plásmidos/genética , ADN Bacteriano/genética , Pruebas de Sensibilidad Microbiana , Reacción en Cadena de la Polimerasa , Farmacorresistencia Bacteriana Múltiple , Klebsiella pneumoniae/aislamiento & purificación , Klebsiella pneumoniae/enzimología
11.
Sci Rep ; 9(1): 2760, 2019 02 26.
Artículo en Inglés | MEDLINE | ID: mdl-30809003

RESUMEN

Brazil, which is hyperendemic for dengue virus (DENV), has had recent Zika (ZIKV) and (CHIKV) Chikungunya virus outbreaks. Since March 2016, CHIKV is the arbovirus infection most frequently diagnosed in Rio de Janeiro. In the analysis of 1835 syndromic patients, screened by real time RT-PCR, 56.4% of the cases were attributed to CHIKV, 29.6% to ZIKV, and 14.1% to DENV-4. Sequence analyses of CHIKV from sixteen samples revealed that the East-Central-South-African (ECSA) genotype of CHIKV has been circulating in Brazil since 2013 [95% bayesian credible interval (BCI): 03/2012-10/2013], almost a year before it was detected by arbovirus surveillance program. Brazilian cases are related to Central African Republic sequences from 1980's. To the best of our knowledge, given the available sequence published here and elsewhere, the ECSA genotype was likely introduced to Rio de Janeiro early on 2014 (02/2014; BCI: 07/2013-08/2014) through a single event, after primary circulation in the Bahia state at the Northestern Brazil in the previous year. The observation that the ECSA genotype of CHIKV was circulating undetected underscores the need for improvements in molecular methods for viral surveillance.


Asunto(s)
Fiebre Chikungunya/diagnóstico , Virus Chikungunya/genética , Teorema de Bayes , Brasil/epidemiología , Fiebre Chikungunya/epidemiología , Fiebre Chikungunya/virología , Virus Chikungunya/clasificación , Virus Chikungunya/aislamiento & purificación , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Filogenia , ARN Viral/química , ARN Viral/metabolismo , Análisis de Secuencia de ARN
12.
PLoS Negl Trop Dis ; 13(1): e0007072, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30699122

RESUMEN

Yellow fever virus (YFV) is a member of the Flaviviridae family. In Brazil, yellow fever (YF) cases have increased dramatically in sylvatic areas neighboring urban zones in the last few years. Because of the high lethality rates associated with infection and absence of any antiviral treatments, it is essential to identify therapeutic options to respond to YFV outbreaks. Repurposing of clinically approved drugs represents the fastest alternative to discover antivirals for public health emergencies. Other Flaviviruses, such as Zika (ZIKV) and dengue (DENV) viruses, are susceptible to sofosbuvir, a clinically approved drug against hepatitis C virus (HCV). Our data showed that sofosbuvir docks onto YFV RNA polymerase using conserved amino acid residues for nucleotide binding. This drug inhibited the replication of both vaccine and wild-type strains of YFV on human hepatoma cells, with EC50 values around 5 µM. Sofosbuvir protected YFV-infected neonatal Swiss mice and adult type I interferon receptor knockout mice (A129-/-) from mortality and weight loss. Because of its safety profile in humans and significant antiviral effects in vitro and in mice, Sofosbuvir may represent a novel therapeutic option for the treatment of YF. Key-words: Yellow fever virus; Yellow fever, antiviral; sofosbuvir.


Asunto(s)
Antivirales/farmacología , Farmacorresistencia Viral , ARN Viral/efectos de los fármacos , Sofosbuvir/farmacología , Fiebre Amarilla/tratamiento farmacológico , Virus de la Fiebre Amarilla/efectos de los fármacos , Animales , Chlorocebus aethiops , Modelos Animales de Enfermedad , Células Hep G2 , Humanos , Ratones , Ratones Noqueados , ARN Viral/sangre , ARN Viral/genética , Células Vero , Fiebre Amarilla/sangre , Fiebre Amarilla/patología , Fiebre Amarilla/virología , Virus de la Fiebre Amarilla/genética
13.
Artículo en Inglés | MEDLINE | ID: mdl-30455237

RESUMEN

Chikungunya virus (CHIKV) causes a febrile disease associated with chronic arthralgia, which may progress to neurological impairment. Chikungunya fever (CF) is an ongoing public health problem in tropical and subtropical regions of the world, where control of the CHIKV vector, Aedes mosquitos, has failed. As there is no vaccine or specific treatment for CHIKV, patients receive only palliative care to alleviate pain and arthralgia. Thus, drug repurposing is necessary to identify antivirals against CHIKV. CHIKV RNA polymerase is similar to the orthologue enzyme of other positive-sense RNA viruses, such as members of the Flaviviridae family. Among the Flaviviridae, not only is hepatitis C virus RNA polymerase susceptible to sofosbuvir, a clinically approved nucleotide analogue, but so is dengue, Zika, and yellow fever virus replication. Here, we found that sofosbuvir was three times more selective in inhibiting CHIKV production in human hepatoma cells than ribavirin, a pan-antiviral drug. Although CHIKV replication in human induced pluripotent stem cell-derived astrocytes was less susceptible to sofosbuvir than were hepatoma cells, sofosbuvir nevertheless impaired virus production and cell death in a multiplicity of infection-dependent manner. Sofosbuvir also exhibited antiviral activity in vivo by preventing CHIKV-induced paw edema in adult mice at a dose of 20 mg/kg of body weight/day and prevented mortality in a neonate mouse model at 40- and 80-mg/kg/day doses. Our data demonstrate that a prototypic alphavirus, CHIKV, is also susceptible to sofosbuvir. As sofosbuvir is a clinically approved drug, our findings could pave the way to it becoming a therapeutic option against CF.


Asunto(s)
Antivirales/uso terapéutico , Fiebre Chikungunya/tratamiento farmacológico , Virus Chikungunya/efectos de los fármacos , Virus Chikungunya/patogenicidad , Sofosbuvir/uso terapéutico , Replicación Viral/efectos de los fármacos , Animales , Animales Recién Nacidos , Artralgia/tratamiento farmacológico , Artralgia/virología , Fiebre Chikungunya/virología , Humanos , Masculino , Ratones
14.
Rio de Janeiro; s.n; 2019. 110 p. ilus..
Tesis en Portugués | LILACS, BDENF - Enfermería | ID: biblio-1087609

RESUMEN

O estudo teve como objetivo geral: analisar comparativamente as práticas de prevenção das infecções sexualmente transmissíveis (IST) de jovens universitários do sexo masculino de duas instituições. E como objetivos específicos: identificar as práticas sexuais dos jovens universitários frente às IST; caracterizar as práticas de prevenção de IST adotadas pelos universitários; comparar as práticas sexuais e de prevenção de IST adotadas por eles. Estudo quantitativo, descritivo, transversal, desenvolvido em duas instituições de ensino superior (IES1 e IES2), no Rio de Janeiro, com amostra do tipo intencional e estratificada, de 768 jovens universitários do sexo masculino de 18 a 29 anos. Para captação das informações foi utilizado um questionário estruturado com 60 questões. A análise dos dados empregou a estatística descritiva, em frequências absolutas, relativas e análise bivariada; para a análise inferencial foi utilizado o Software Statistical Package for the Social Sciences (SPSS) e aplicado o teste qui-quadrado de Pearson. Os resultados evidenciaram que os universitários das duas instituições apresentam práticas sexuais e comportamento de risco semelhante para aquisição de IST, havendo poucas diferenças. A maioria é sexualmente ativa, tendo tido o primeiro intercurso sexual e usado o preservativo nessa ocasião. Um quantitativo expressivo de participantes não utiliza preservativo sempre e não costuma negociar o seu uso. No tocante ao emprego do preservativo com parcerias fixas, os universitários da IES1 apresentaram resultados em quantitativo maior que os participantes da IES2. Em relação ao conhecimento sobre as IST, embora os jovens tenham informado que não conhecem o suficiente, reconhecem algum método para a prevenção das infecções. As parcerias sexuais dos participantes não costumam usar o preservativo feminino. O uso de álcool e/ou drogas foi informado pela maioria dos jovens, contudo o seu emprego não precedeu à última relação sexual. Nas duas instituições, grande parte não utiliza o sistema público de assistência à saúde, nunca realizou teste para detecção do vírus da imunodeficiência humana (HIV) e não são circuncidados. Conclui-se que os participantes do estudo assumem um comportamento de risco e ficam vulneráveis às IST e, nesse contexto são oportunas ações educativas que valorizem o autocuidado de jovens e orientações relacionadas à prevenção de agravos à saúde sexual. É preciso que os profissionais envolvidos no atendimento a população jovem sejam capacitados e, estimulem a reflexão sobre a importância dos cuidados com a saúde sexual, com destaque para o público masculino que não busca com frequência os serviços de saúde, adesão às práticas de prevenção de agravos e assunção de um comportamento de risco.


The general objective of the study was to analyze sexually transmitted infections (STI) of young male college students from two institutions. And as specific objectives: to identify the sexual practices of college students against STI; to characterize the practices of prevention of STI adopted by university students; to compare the sexual practices and prevention of STI adopted by them. A quantitative, descriptive, cross-sectional study developed in two higher education institutions (IES1 and IES2), in Rio de Janeiro, with a sample of the intentional and stratified type, of 768 university students, male, aged 18 to 29 years. A questionnaire structured with 60 questions was used to gather information. Data analysis employed descriptive statistics, in absolute, relative frequencies and bivariate analysis; for the inferential analysis we used the Statistical Package for the Social Sciences (SPSS) and applied the chi- square test of Pearson. The results showed that the students of the two institutions presented sexual practices and similar risk behavior for STI acquisition, with few differences. Most are sexually active, having had their first sexual intercourse and using condoms on this occasion. An expressive number of participants does not use condoms at all and does not usually negotiate their use. Regarding the use of the condom with fixed partnerships, the students of IES1 presented results in quantitative higher than the participants of IES2. Regarding knowledge about STI, although young people have reported that they do not know enough, they recognize some method for the prevention of infections. Participant sexual partnerships do not usually use the female condom. Alcohol and / or drug use was reported by most young people, but their employment did not precede their last sexual intercourse. In both institutions, much of it does not use the public health care system, has never tested for human immunodeficiency virus (HIV) and is not circumcised. It is concluded that the participants of the study assume a risk behavior and are vulnerable to STI and, in this context, educational actions that value the self-care of young people and guidelines related to the prevention of sexual health problems are opportune. It is necessary that the professionals involved in the care of the young population be trained and stimulate the reflection on the importance of the sexual health care, with emphasis on the male audience that does not frequently seek health services, adherence to prevention practices and risk behavior.


Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Conducta Sexual , Enfermedades de Transmisión Sexual/prevención & control , Adolescente , Enfermería en Salud Comunitaria , Salud del Hombre , Salud del Estudiante , Sexualidad
15.
J Gen Virol ; 99(7): 913-916, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29771234

RESUMEN

Descriptive clinical data help to reveal factors that may provoke Zika virus (ZIKV) neuropathology. The case of a 24-year-old female with a ZIKV-associated severe acute neurological disorder was studied. The levels of ZIKV in the cerebrospinal fluid (CSF) were 50 times higher than the levels in other compartments. An acute anti-flavivirus IgG, together with enhanced TNF-alpha levels, may have contributed to ZIKV invasion in the CSF, whereas the unbiased genome sequencing [obtained by next-generation sequencing (NGS)] of the CSF revealed that no virus mutations were associated with the anatomic compartments (CSF, serum, saliva and urine).


Asunto(s)
Anticuerpos Antivirales/líquido cefalorraquídeo , Inmunoglobulina G/líquido cefalorraquídeo , Inflamación Neurogénica/diagnóstico , Factor de Necrosis Tumoral alfa/líquido cefalorraquídeo , Infección por el Virus Zika/diagnóstico , Virus Zika/genética , Femenino , Genoma Viral , Humanos , Inflamación Neurogénica/complicaciones , Inflamación Neurogénica/fisiopatología , Inflamación Neurogénica/virología , Filogenia , Secuenciación Completa del Genoma , Adulto Joven , Virus Zika/clasificación , Virus Zika/aislamiento & purificación , Virus Zika/patogenicidad , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/fisiopatología , Infección por el Virus Zika/virología
16.
Blood Transfus ; 16(1): 17-25, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-27893347

RESUMEN

BACKGROUND: Transfusion-transmitted malaria due to asymptomatic Plasmodium infections is a challenge for blood banks. There is a lack of data on the prevalence of asymptomatic infected blood donors and the incidence of transfusion-transmitted malaria in low endemicity areas worldwide. We estimated the frequency of blood donors harbouring Plasmodium in an area in which asymptomatic infections have been reported. MATERIAL AND METHODS: To estimate the frequency of blood donors harbouring Plasmodium we used microscopy and molecular tools. Serological tests were applied to measure the exposure of candidates to Plasmodium antigens. Venous blood was collected from 91 candidates attending the "Pró-Sangue" Blood Centre Foundation in São Paulo, who lived in the municipality of Juquitiba, São Paulo, Brazil, where sporadic autochthonous cases of malaria have been described. Blood samples were used for parasitological, molecular and serological studies. RESULTS: Among the 91 samples examined, rare Plasmodium forms were observed in two donors. Genus real-time polymerase chain reaction analysis demonstrated Plasmodium amplification in three candidates and species-specific nested polymerase chain reaction identified P. malariae in two. ELISA-IgG was reactive in 42.9% of samples for P. vivax (Pv-MSP119) and in 6.6% for P. falciparum (Pf-Zw). ELISA-IgM was reactive in 2.2% of samples for P. vivax and in 4.4% for P. falciparum. An indirect immunofluorescence assay was reactive for P. malariae in 15.4% of cases. DISCUSSION: Reservoirs of Plasmodium represent a challenge for blood banks, since studies have shown that high levels of submicroscopic infections can occur in low transmission areas. The risk of transfusion-transmitted malaria presented here points to the need to conduct molecular investigations of candidate donors with any positive malarial antibody test.


Asunto(s)
Antígenos de Protozoos/sangre , Donantes de Sangre , Selección de Donante/métodos , Malaria/sangre , Plasmodium , Femenino , Humanos , Malaria/transmisión , Masculino
18.
Sci Rep ; 7(1): 9409, 2017 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-28842610

RESUMEN

Zika virus (ZIKV) causes significant public health concerns because of its association with congenital malformations, neurological disorders in adults, and, more recently, death. Considering the necessity to mitigate ZIKV-associated diseases, antiviral interventions are an urgent necessity. Sofosbuvir, a drug in clinical use against hepatitis C virus (HCV), is among the FDA-approved substances endowed with anti-ZIKV activity. In this work, we further investigated the in vivo activity of sofosbuvir against ZIKV. Neonatal Swiss mice were infected with ZIKV (2 × 107 PFU) and treated with sofosbuvir at 20 mg/kg/day, a concentration compatible with pre-clinical development of this drug. We found that sofosbuvir reduced acute levels of ZIKV from 60 to 90% in different anatomical compartments, such as the blood plasma, spleen, kidney, and brain. Early treatment with sofosbuvir doubled the percentage and time of survival of ZIKV-infected animals. Sofosbuvir also prevented the acute neuromotor impairment triggered by ZIKV. In the long-term behavioural analysis of ZIKV-associated sequelae, sofosbuvir prevented loss of hippocampal- and amygdala-dependent memory. Our results indicate that sofosbuvir inhibits ZIKV replication in vivo, which is consistent with the prospective necessity of antiviral drugs to treat ZIKV-infected individuals.


Asunto(s)
Antivirales/farmacología , Sofosbuvir/farmacología , Infección por el Virus Zika/tratamiento farmacológico , Virus Zika/fisiología , Animales , Animales Recién Nacidos , Antivirales/administración & dosificación , Chlorocebus aethiops , Memoria , Ratones , ARN Viral , Reflejo de Enderezamiento , Sofosbuvir/administración & dosificación , Células Vero , Replicación Viral/efectos de los fármacos , Infección por el Virus Zika/mortalidad
19.
Nature ; 546(7658): 411-415, 2017 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-28538734

RESUMEN

Although the recent Zika virus (ZIKV) epidemic in the Americas and its link to birth defects have attracted a great deal of attention, much remains unknown about ZIKV disease epidemiology and ZIKV evolution, in part owing to a lack of genomic data. Here we address this gap in knowledge by using multiple sequencing approaches to generate 110 ZIKV genomes from clinical and mosquito samples from 10 countries and territories, greatly expanding the observed viral genetic diversity from this outbreak. We analysed the timing and patterns of introductions into distinct geographic regions; our phylogenetic evidence suggests rapid expansion of the outbreak in Brazil and multiple introductions of outbreak strains into Puerto Rico, Honduras, Colombia, other Caribbean islands, and the continental United States. We find that ZIKV circulated undetected in multiple regions for many months before the first locally transmitted cases were confirmed, highlighting the importance of surveillance of viral infections. We identify mutations with possible functional implications for ZIKV biology and pathogenesis, as well as those that might be relevant to the effectiveness of diagnostic tests.


Asunto(s)
Filogenia , Infección por el Virus Zika/transmisión , Infección por el Virus Zika/virología , Virus Zika/genética , Virus Zika/aislamiento & purificación , Animales , Brasil/epidemiología , Colombia/epidemiología , Culicidae/virología , Brotes de Enfermedades/estadística & datos numéricos , Genoma Viral/genética , Mapeo Geográfico , Honduras/epidemiología , Humanos , Metagenoma/genética , Epidemiología Molecular , Mosquitos Vectores/virología , Mutación , Vigilancia en Salud Pública , Puerto Rico/epidemiología , Estados Unidos/epidemiología , Virus Zika/clasificación , Virus Zika/patogenicidad , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/epidemiología
20.
Eur J Med Chem ; 127: 334-340, 2017 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-28068604

RESUMEN

Zika virus (ZIKV), an arthropod-born Flavivirus, has been associated with a wide range of neurological diseases in adults, foetuses and neonates. Since no vaccine is available, repurposing of antiviral drugs currently in medical use is necessary. Mefloquine has confirmed anti-ZIKV activity. We used medicinal chemistry-driven approaches to synthesize and evaluate the ability of a series of new 2,8-bis(trifluoromethyl)quinoline derivatives to inhibit ZIKV replication in vitro, in order to improve the potency of mefloquine. We found that quinoline derivatives 3a and 4 were the most potent compounds within this series, both with mean EC50 values of 0.8 µM, which represents a potency 5 times that of mefloquine. These results indicate that new 2,8-bis(trifluoromethyl)quinoline chemical structures may be promising for the development of novel anti-ZIKV drugs.


Asunto(s)
Antivirales/química , Antivirales/farmacología , Mefloquina/farmacología , Quinolinas/química , Quinolinas/farmacología , Virus Zika/efectos de los fármacos , Animales , Antivirales/síntesis química , Antivirales/toxicidad , Chlorocebus aethiops , Diseño de Fármacos , Quinolinas/síntesis química , Quinolinas/toxicidad , Relación Estructura-Actividad , Células Vero , Replicación Viral/efectos de los fármacos , Virus Zika/fisiología
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