RESUMO
Estudos apontam maior ocorrência de complicações cardiovasculares na população com HIV/aids. Sabe-se que as alterações iniciais que posteriormente evoluem para doenças cardíacas estão relacionadas às mudanças no perfil inflamatório e oxidativo. Diversas pesquisas, utilizando diferentes populações, demonstraram que os flavonoides presentes no cacau (Theobroma cacao) e na erva mate (Ilex paraguaensis) podem melhorar a função anti-inflamatória e antioxidante do organismo. Objetivo: Avaliar o efeito da ingestão de chocolate e chá mate no perfil inflamatório e oxidativo de pessoas vivendo com HIV/aids (PVHIV/aids) em terapia antirretroviral (TARV). Metodologia: Ensaio clínico do tipo crossover, aleatorizado, cego e controlado por placebo envolvendo 92 voluntários, de 28-59 anos de idade, em tratamento regular com TARV por, no mínimo, 6 meses e com carga viral...
There has been an increase on cardiovascular diseases occurrence in the HIV/AIDS population. It is know that initial alterations that after evolve to cardiovascular diseases are related with changes in inflammatory and oxidative disorders. Several studies in other populations demonstrated that flavonoids in cocoa (Theobroma cacao) and yerba mate (Ilex paraguaensis) may improve cardiovascular function due to its antioxidant and anti-inflammatory properties. Objective: To evaluated the effect of chocolate and yerba mate intake on the inflammatory and oxidative profile of people living with HIV/AIDS in antiretroviral therapy (ART). Methodology: Randomized, placebo-controlled, blinded cross-over trial involving 92 volunteers ages 28-59 years, in ART for at least six months and with viral load...
Assuntos
Humanos , Antioxidantes/metabolismo , Cacau/metabolismo , Ilex paraguariensis/metabolismo , Lipídeos/sangue , Síndrome da Imunodeficiência Adquirida/metabolismo , Soropositividade para HIV/metabolismo , Ensaio Clínico , Inflamação/fisiopatologiaRESUMO
OBJECTIVE: HIV-1-associated neurocognitive disorders (HAND) is triggered by immune activation of brain cells and remain prevalent during progressive viral infection despite antiretroviral therapy. Cathepsins and cystatins are lysosomal proteins secreted by macrophages and microglia, and may play important roles in neuroregulatory responses. Our laboratory has shown increased secretion and neurotoxicity of cathepsin B from in-vitro HIV-infected monocyte-derived macrophages, and increased expression in postmortem brain tissue with HIV encephalitis and HAND. We hypothesized that cystatin B and cathepsin B could represent potential biomarkers for HAND. METHODS: Monocytes, plasma, and cerebrospinal fluid (CSF) from retrospective samples from 63 HIV-seropositive Hispanic women were selected for this study. These were stratified as 27 normal, 14 asymptomatic, and 22 HIV dementia, and as 14 progressors and 17 nonprogressors. Samples were evaluated for cystatins B and C and cathepsin B expression and activity. RESULTS: Increased cathepsin B and cystatins B and C were found in plasma of HIV-seropositive women. Higher intracellular expression of cathepsin B and cystatin B were found in monocytes from women with HIV-associated dementia (P < 0.05). Significant increase in cystatin B concentration in CSF was found in women with dementia compared with HIV-seropositive asymptomatic women. CONCLUSION: These results demonstrate that dysregulation of cystatin B-cathepsin B system is operative in HIV-associated neurocognitive impairment and suggests that intracellular expression of cystatin B and cathepsin B in monocytes could be potential candidate biomarkers for HIV dementia, whereas increased cathepsin B and cystatins B and C in plasma are potential candidate markers of chronic HIV-1 activation.
Assuntos
Complexo AIDS Demência/metabolismo , Catepsina B , Cistatina B , Soropositividade para HIV/metabolismo , HIV-1/metabolismo , Hispânico ou Latino/estatística & dados numéricos , Complexo AIDS Demência/epidemiologia , Complexo AIDS Demência/fisiopatologia , Adulto , Biomarcadores/metabolismo , Barreira Hematoencefálica/metabolismo , Catepsina B/metabolismo , Cistatina B/metabolismo , Progressão da Doença , Feminino , Citometria de Fluxo , Soropositividade para HIV/epidemiologia , Soropositividade para HIV/fisiopatologia , Humanos , Estudos Longitudinais , Monócitos/metabolismo , Testes Neuropsicológicos , Estados Unidos/epidemiologia , Regulação para Cima , Carga ViralRESUMO
BACKGROUND: Blood sugar metabolism abnormalities have been identified in HIV-infected individuals and associated with HIV-associated neurocognitive disorders (HAND). These abnormalities may occur as a result of chronic HIV infection, long-term use of combined antiretroviral treatment (CART), aging, genetic predisposition, or a combination of these factors, and may increase morbidity and mortality in this population. OBJECTIVE: To determine if changes in soluble and cell-associated insulin receptor (IR) levels, IR substrate-1 (IRS-1) levels, and IRS-1 tyrosine phosphorylation are associated with the presence and severity of HAND in a cohort of HIV-seropositive women. METHODS AND RESULTS: This is a retrospective cross-sectional study using patient database information and stored samples from 34 HIV-seropositive women and 10 controls without history of diabetes from the Hispanic-Latino Longitudinal Cohort of Women. Soluble IR subunits [sIR, ectodomain (α) and full-length or intact (αß)] were assayed in plasma and CSF samples by ELISA. Membrane IR levels, IRS-1 levels, and IRS-1 tyrosine phosphorylation were analyzed in CSF white cell pellets (WCP) using flow cytometry. HIV-seropositive women had significantly increased levels of intact or full-length sIR in plasma (p<0.001) and CSF (p<0.005) relative to controls. Stratified by HAND, increased levels of full-length sIR in plasma were associated with the presence (p<0.001) and severity (p<0.005) of HAND. A significant decrease in IRS-1 tyrosine-phosphorylation in the WCP was also associated with the presence (p<0.02) and severity (p<0.02) of HAND. CONCLUSIONS: This study provides evidence that IR secretion is increased in HIV-seropositive women, and increased IR secretion is associated with cognitive impairment in these women. Thus, IR dysfunction may have a role in the progression of HAND and could represent a biomarker for the presence and severity of HAND.
Assuntos
Complexo AIDS Demência/metabolismo , Infecções por HIV/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Receptor de Insulina/metabolismo , Complexo AIDS Demência/sangue , Complexo AIDS Demência/líquido cefalorraquidiano , Adulto , Estudos Transversais , Bases de Dados Factuais , Progressão da Doença , Feminino , Infecções por HIV/sangue , Infecções por HIV/líquido cefalorraquidiano , Soropositividade para HIV/metabolismo , Humanos , Proteínas Substratos do Receptor de Insulina/sangue , Proteínas Substratos do Receptor de Insulina/líquido cefalorraquidiano , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fosforilação , Receptor de Insulina/sangue , Receptor de Insulina/líquido cefalorraquidiano , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
CCR5 and CXCR4 play an important role in the establishment of HIV infection and disease progression. Caucasian people exposed to HIV but uninfected (EU) present a deletion of 32bp in CCR5 that has not been reported in EU Hispanics from Latin America. Therefore, other factors besides mutations should be involved in this phenomenon. Studies in healthy women have shown that sex hormones such as progesterone (P) can modulate CCR5/CXCR4 expression through an unknown mechanism. The aim of this paper was to determine the role of P in the regulation of CCR5 and CXCR4 in peripheral blood mononuclear cells (PBMCs) of HIV-1 infected and EU women. We analyzed HIV-1-infected women with stable highly active antiretroviral therapy (HAART) with CD4+ cell counts <400/mm(3) or diminution of 20%, EU and HIV-1 seronegative healthy controls. 5×10(6) PBMCs, from HIV-1 infected women, EU women and HIV-1 seronegative healthy controls were cultured and incubated with P (10 or 100 nM), RU486 (P antagonist, 1 µM) or P (100 nM)+RU486 (1 µM). CCR5/CXCR4 content was determined by Western blot. Densitometry data were analyzed using Mann-Whitney test. We found that CCR5 content was reduced by P in all groups. In contrast, CXCR4 content was increased by P in healthy controls and in HIV-1 infected women. Interestingly, CXCR4 content was reduced by P in EU. RU486 did not block P effects in any group. These findings suggest that P should participate in the acquisition and progression of HIV-1 infection by modulating CCR5 and CXCR4 expression. P could contribute to the resistance acquisition of HIV by EU through the down-regulation of both coreceptors.
Assuntos
Infecções por HIV/metabolismo , Soropositividade para HIV/metabolismo , Progesterona/farmacologia , Receptores CCR5/metabolismo , Receptores CXCR4/metabolismo , Adulto , Células Cultivadas , Estradiol/sangue , Etnicidade , Feminino , HIV-1 , Antagonistas de Hormônios/farmacologia , Humanos , Leucócitos Mononucleares , Pessoa de Meia-Idade , Mifepristona/farmacologia , Progesterona/sangue , Receptores de Progesterona/antagonistas & inibidoresRESUMO
INTRODUCTION: Low infection rates in neonates born to HIV-1-seropositive mothers highlight the existence of natural defense mechanisms in the maternal-fetal interface. Human beta defensins (HBDs) inhibit HIV-1 replication in vitro and their variants are associated with HIV-1 resistance/susceptibility. OBJECTIVE: Levels of HBD mRNA expression in placentas were obtained from seropositive and healthy mothers to determine whether HIV-1 infection induces anti-viral factors. Materials and methods. HBD-1, -2 and -3 transcripts were quantified by real time RT-PCR, and A692G/G1654A/A1836G variants in the DEFB1 gene were evaluated by sequencing. RESULTS: Transcript levels of HBD-1 were significantly higher, and those of HBD-3 were lower in placenta from seropositive mothers compared to controls. Additionally, simultaneous presence of the A692G A/G and A1836G G/G genotypes was associated with high expression of HBD-1 in all populations and the A692G variant in babies born to seropositive mothers was in Hardy-Weinberg disequilibrium. CONCLUSION: Contrasting results in levels of HBDs were probably due to viral stimuli and suggest that HIV-1 induce a differential expression of HBDs in placenta and these proteins could be involved in protecting against HIV-1 at least early in pregnancy. However, it was not possible to associate these findings directly with protection against HIV-1 vertical transmission since none of the newborn infants became infected.
Assuntos
Anti-Infecciosos/metabolismo , Soropositividade para HIV/metabolismo , HIV-1/imunologia , Placenta/metabolismo , Polimorfismo Genético , beta-Defensinas/genética , beta-Defensinas/metabolismo , Adolescente , Adulto , Alelos , Feminino , Genótipo , Antígenos HLA/imunologia , Humanos , Recém-Nascido/imunologia , Transmissão Vertical de Doenças Infecciosas , Gravidez , Complicações Infecciosas na Gravidez/genética , Complicações Infecciosas na Gravidez/metabolismo , Adulto JovemRESUMO
The prevalence of mutations that confer resistance to protease inhibitors and to nucleoside and nonnucleoside reverse transcriptase inhibitors in 49 blood samples from drug-naïve human immunodeficiency virus type 1-infected blood donors living in Rio de Janeiro state, Brazil, in 1998 was evaluated genotypically and phenotypically.
Assuntos
Inibidores da Protease de HIV/farmacologia , HIV-1/efeitos dos fármacos , Inibidores da Transcriptase Reversa/farmacologia , Substituição de Aminoácidos , Brasil/epidemiologia , Farmacorresistência Viral , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Protease de HIV/metabolismo , Transcriptase Reversa do HIV/metabolismo , Soropositividade para HIV/enzimologia , Soropositividade para HIV/metabolismo , HIV-1/enzimologia , Humanos , Dados de Sequência Molecular , Mutação/genética , Fenótipo , FilogeniaRESUMO
PURPOSE: The objective of the present study was to evaluate the expression of the p27 protein in the normal epithelium and vulvar condylomas in human immunodeficiency (HIV) positive and negative patients. METHODS: Eight samples of normal vulvar epithelium were evaluated (Group A), ten of the HIV negative vulvar condyloma patients (Group B) and another eight of the vulvar condyloma HIV positive patients (Group C). The DNA of human papillomavirus (HPV) was identified by means of polymerase chain reaction (PCR). Immunohistochemistry was the method used to evaluate the expression of p27 using monoclonal mouse antibody (Monoclonal Mouse, anti-human p27, Clone Sx 53 G8). The immunoexpression was evaluated at a magnification of 400x, counting a minimum of 1,000 cells per slide. RESULTS: The results obtained were the following: a) comparing groups A and B and groups A and C there was a significant difference in relation to the expression of the p27 protein which was 63.32% in group A and only 13.35% and 18.89% in groups B and C, respectively; b) comparing groups B and C among them, there was no significant difference. CONCLUSION: We concluded that in normal vulvar tissue the p27 protein is present in a large number of cells and that in vulval condylomas its expression is very much lowered both in HIV positive and negative cases.
Assuntos
Proteínas do Capsídeo , Condiloma Acuminado/metabolismo , Soropositividade para HIV/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Doenças da Vulva/metabolismo , Capsídeo/metabolismo , Epitélio/metabolismo , Feminino , Produtos do Gene gag/metabolismo , HIV-1 , Humanos , Imuno-Histoquímica , Produtos do Gene gag do Vírus da Imunodeficiência HumanaRESUMO
A child with perinatally acquired human immunodeficiency virus infection had rapidly progressive hepatic dysfunction, as had her older sibling who died. Urinary organic acid studies revealed 3-hydroxydicarboxylic aciduria, and cultured skin fibroblasts had reduced activity of 3-hydroxy-coenzyme A dehydrogenase. The introduction of a low fat diet resulted in marked improvement in clinical status and reversal of the liver disease. This case illustrates the necessity of metabolic evaluation in patients with liver dysfunction, even when other causes of liver dysfunction are present.