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1.
PLoS Comput Biol ; 11(12): e1004665, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26709961

RESUMEN

The progressive loss of CD4+ T cell population is the hallmark of HIV-1 infection but the mechanism underlying the slow T cell decline remains unclear. Some recent studies suggested that pyroptosis, a form of programmed cell death triggered during abortive HIV infection, is associated with the release of inflammatory cytokines, which can attract more CD4+ T cells to be infected. In this paper, we developed mathematical models to study whether this mechanism can explain the time scale of CD4+ T cell decline during HIV infection. Simulations of the models showed that cytokine induced T cell movement can explain the very slow decline of CD4+ T cells within untreated patients. The long-term CD4+ T cell dynamics predicted by the models were shown to be consistent with available data from patients in Rio de Janeiro, Brazil. Highly active antiretroviral therapy has the potential to restore the CD4+ T cell population but CD4+ response depends on the effectiveness of the therapy, when the therapy is initiated, and whether there are drug sanctuary sites. The model also showed that chronic inflammation induced by pyroptosis may facilitate persistence of the HIV latent reservoir by promoting homeostatic proliferation of memory CD4+ cells. These results improve our understanding of the long-term T cell dynamics in HIV-1 infection, and support that new treatment strategies, such as the use of caspase-1 inhibitors that inhibit pyroptosis, may maintain the CD4+ T cell population and reduce the latent reservoir size.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/patología , Infecciones por VIH/inmunología , Infecciones por VIH/patología , Memoria Inmunológica/inmunología , Modelos Inmunológicos , Recuento de Linfocito CD4 , Proliferación Celular , Simulación por Computador , Citocinas/inmunología , Progresión de la Enfermedad , Humanos
2.
Artículo en Inglés | MEDLINE | ID: mdl-37610941

RESUMEN

Histoplasmosis is a systemic mycosis prevalent in the Americas. Humans become infected via the respiratory route by inhaling aerosols from soil contaminated with bird and bat excretions. Acute pulmonary histoplasmosis is usually asymptomatic and is more often a self-limiting illness. We report a series of seven acute pulmonary cases in adults during an outbreak in Nova Friburgo city, Rio de Janeiro State, Brazil, in a group of volunteers who were cleaning an old, abandoned house without using personal protective equipment. The patients had a favorable evolution after suitable treatment, but all required hospitalization.


Asunto(s)
Histoplasmosis , Adulto , Humanos , Histoplasmosis/diagnóstico , Histoplasmosis/epidemiología , Brasil/epidemiología , Brotes de Enfermedades , Suelo
3.
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1507400

RESUMEN

ABSTRACT Histoplasmosis is a systemic mycosis prevalent in the Americas. Humans become infected via the respiratory route by inhaling aerosols from soil contaminated with bird and bat excretions. Acute pulmonary histoplasmosis is usually asymptomatic and is more often a self-limiting illness. We report a series of seven acute pulmonary cases in adults during an outbreak in Nova Friburgo city, Rio de Janeiro State, Brazil, in a group of volunteers who were cleaning an old, abandoned house without using personal protective equipment. The patients had a favorable evolution after suitable treatment, but all required hospitalization.

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