RESUMO
BACKGROUND: Methamphetamine (Meth) abuse is a major health problem linked to the aggravation of HIV- associated complications, especially within the Central Nervous System (CNS). Within the CNS, Meth has the ability to modify the activity/function of innate immune cells and increase brain viral loads. Here, we examined changes in the gene expression profile of neuron-free microglial cell preparations isolated from the brain of macaques infected with the Simian Immunodeficiency Virus (SIV), a model of neuroAIDS, and exposed to Meth. We aimed to identify molecular patterns triggered by Meth that could explain the detection of higher brain viral loads and the development of a pro-inflammatory CNS environment in the brain of infected drug abusers. RESULTS: We found that Meth alone has a strong effect on the transcription of genes associated with immune pathways, particularly inflammation and chemotaxis. Systems analysis led to a strong correlation between Meth exposure and enhancement of molecules associated with chemokines and chemokine receptors, especially CXCR4 and CCR5, which function as co-receptors for viral entry. The increase in CCR5 expression was confirmed in the brain in correlation with increased brain viral load. CONCLUSIONS: Meth enhances the availability of CCR5-expressing cells for SIV in the brain, in correlation with increased viral load. This suggests that Meth is an important factor in the susceptibility to the infection and to the aggravated CNS inflammatory pathology associated with SIV in macaques and HIV in humans.
Assuntos
Encéfalo/imunologia , Inflamação/imunologia , Metanfetamina/administração & dosagem , Microglia/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia/fisiologia , Transtornos Relacionados ao Uso de Substâncias/imunologia , Animais , Encéfalo/virologia , Células Cultivadas , Quimiotaxia , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Infecções por HIV/imunologia , HIV-1/fisiologia , Humanos , Macaca , Microglia/virologia , Receptores CCR5/genética , Receptores CCR5/metabolismo , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Transtornos Relacionados ao Uso de Substâncias/virologia , Carga ViralRESUMO
Photoluminescent mechanisms in erbium-doped barium titanate nanoparticle systems were studied. Er3+ ions were introduced into the BaTiO3 lattice by the sol-gel method. The resulting Er3+ concentration was between 0% and 5%, with Ba/Ti ratios of 1.008 and 0.993. The stoichiometry of Ba and Ti concentrations in the lattice influenced the doping mechanism and placement of erbium ions in the lattice structure. Our research shows the existence of a strong correlation between Ba/Ti ratios, erbium concentration, phase structure and doping site location on the upconversion photoluminescence mechanisms. Competing upconversion emissions ²H11/2/4S3/2â4I15/2 at 523 and 548 nm respectively and other photoluminescent mechanisms as 4I9/2â4I11/2 around 4000 nm (2500 cm-1) were studied using Raman and emission spectroscopy. The upconversion process is predominant over other photoluminescent decay when the material presents high distortion in the surrounding activator.