RESUMO
We recently described that a dollabelane diterpene isolated from the marine algae Dictyota pfaffii (Dolabelladienetriol) inhibits the human immunodeficiency virus type 1 (HIV-1) enzyme reverse transcriptase (RT), and HIV-1 replication in primary cells. Based on these findings, we investigated additional antiretroviral properties of Dolabelladienetriol. Here, we describe that Dolabelladienetriol blocked the synthesis and integration of HIV-1 provirus and completely abrogated viral replication in primary cells. Also, studies of kinetic mode of action revealed that the Dolabelladienetriol is a nonnucleoside RT inhibitor (NNRTI), acting as a noncompetitive inhibitor, with a K(i) value equal to 7.2 microM. To assess whether Dolabelladienetriol could potentiate the anti-HIV-1 effects of other HIV-1 inhibitors, HIV-1-infected cells were treated with Dolabelladienetriol at its EC(50) dose plus sub-optimal concentrations of classical antiretrovirals. Dolabelladienetriol provided an additive effect with the nucleoside RT inhibitor AZT, and a synergistic effect with the protease inhibitor atazanavir sulphate. There was no increment of the anti-HIV-1 effect resulting from the combination between Dolabelladienetriol and the NNRTI nevirapine. Using a large panel of HIV-1 isolates harboring NNRTI resistance mutations, we found no cross-resistance between Dolabelladienetriol and clinical available NNRTIs. Thus, Dolabelladienetriol is an NNRTI, with potent activity against HIV-1 isolates carrying common NNRTI-associated resistance mutations. Dolabelladienetriol may be considered as a potential new agent for anti-HIV-1 therapy.
Assuntos
Fármacos Anti-HIV/farmacologia , Diterpenos/farmacologia , HIV-1/efeitos dos fármacos , Leucócitos Mononucleares/virologia , Inibidores da Transcriptase Reversa/farmacologia , Combinação de Medicamentos , Farmacorresistência Viral , HIV-1/genética , HIV-1/metabolismo , Humanos , Cinética , Leucócitos Mononucleares/metabolismo , Mutação , Provírus/efeitos dos fármacos , Provírus/metabolismo , Integração Viral/efeitos dos fármacosRESUMO
The vaccine Bacillus of Calmette Guérin (BCG) was originally developed in France as an oral vaccine against tuberculosis. The oral use of this vaccine was replaced by the parenteral route in almost all countries after the Lubeck disaster. In contrast, Brazil retained the oral delivery of the vaccine until the mid-seventies when it was replaced by the intradermal route. This change in route of delivery was mainly secondary to pressure by medical practitioners based on the poor responses of oral immunized subjects to purified protein derivative (PPD) skin tests. Even after the change of route of delivery, Ataulpho de Paiva Foundation continued making the oral vaccine. Currently, BCG Moreau has been described as one of the most immunogenic and with fewer side effects than other BCGs. The genomics, proteomics and vaccine trials for oral BCG Moreau Rio de Janeiro are currently under investigation. In this review, we intend to describe the history of BCG Moreau Rio de Janeiro in Brazil.
Assuntos
Vacina BCG/administração & dosagem , Tuberculose Pulmonar/prevenção & controle , Vacinação/história , Vacina BCG/história , Brasil , História do Século XIX , História do Século XX , Tuberculose Pulmonar/históriaRESUMO
We evaluated, for the first time in Latin America, the performance of a commercial enzyme immunoassay (EIA) (Calypte Biomedical Corporation, Berkeley, Calif.) that detects human immunodeficiency virus type 1 (HIV-1)-specific antibodies in urine in comparison to standard serological assays (two commercial EIAs and a commercial Western blot [WB] assay). Paired serum and urine specimens were collected from two different groups of Brazilian patients: 225 drug users with unknown HIV status who attended drug treatment centers in Rio de Janeiro, Brazil, and 135 subjects with known HIV status. Patients showing positive results in the serum EIAs and/or in the urine EIA were serologically confirmed by WB assay. For 135 individuals with known HIV status, the urine EIA showed 100% sensitivity (74 positive samples) and 95.1% specificity (58 of 61 negative specimens). For 225 drug users, the test showed 100% sensitivity (2 positive samples) and 98.7% specificity (220 of 223 negative samples) compared to WB-confirmed serological EIA results. Thus, in a total of 360 samples, the urine EIA correctly identified all 76 HIV-positive samples and 278 of 284 negative samples (100% sensitivity and 97.9% specificity). Detailed analysis of the urine EIA results indicates that an increase of the recommended cutoff value might raise the specificity of the assay without affecting its sensitivity. Our results suggest that the HIV-1 urine EIA is a good screening test suitable for developing countries like Brazil. However, as for all other HIV screening tests on the market, it is not specific enough to be used as a one-step test and therefore requires confirmation.
Assuntos
Anticorpos Anti-HIV/urina , HIV-1/imunologia , Sorodiagnóstico da AIDS , Brasil , Humanos , Técnicas Imunoenzimáticas , Sensibilidade e EspecificidadeAssuntos
Infecções por HIV , Vacinas contra a AIDS/uso terapêutico , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Brasil/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/prevenção & controle , HIV-1/genética , HIV-1/imunologia , HumanosRESUMO
The vaccine Bacillus of Calmette Guérin (BCG) was originally developed in France as an oral vaccine against tuberculosis. The oral use of this vaccine was replaced by the parenteral route in almost all countries after the Lubeck disaster. In contrast, Brazil retained the oral delivery of the vaccine until the mid-seventies when it was replaced by the intradermal route. This change in route of delivery was mainly secondary to pressure by medical practitioners based on the poor responses of oral immunized subjects to purified protein derivative (PPD) skin tests. Even after the change of route of delivery, Ataulpho de Paiva Foundation continued making the oral vaccine. Currently, BCG Moreau has been described as one of the most immunogenic and with fewer side effects than other BCGs. The genomics, proteomics and vaccine trials for oral BCG Moreau Rio de Janeiro are currently under investigation. In this review, we intend to describe the history of BCG Moreau Rio de Janeiro in Brazil.
Assuntos
Humanos , Recém-Nascido , Lactente , História do Século XIX , História do Século XX , Vacina BCG/administração & dosagem , Tuberculose Pulmonar/prevenção & controle , Vacinação/história , Vacina BCG/história , Brasil , Tuberculose Pulmonar/históriaAssuntos
Humanos , Infecções por HIV , Vacinas contra a AIDS , Brasil/epidemiologia , HIV-1 , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Infecções por HIV/prevenção & controle , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome da Imunodeficiência Adquirida/prevenção & controleRESUMO
Em exames médicos de rotina realizados em um centro de integração social que abriga, em regime de internato, cerca de 160 homens, ex-moradores de rua, na faixa etária de 20 a 74 anos foram detectados sinais e sintomas de tuberculose pulmonar em alguns comunitários, sendo confirmado o diagnóstico em cinco deles. Foram investigados os aspectos nutricionais e os fatores de risco que poderiam estar associados ao surto infeccioso. Realizamos avaliações dietéticas, antropométricas e laboratoriais em todos os indivíduos. Na análise dietética verificou-se que esta é superestimada com relação ao valor energético e deficitária na oferta dos micronutrientes associados à imunocompetência. Quando avaliamos os compartimentos corporais observamos que grande parte da população estudada (47%) encontrava-se com a reserva gordurosa acima dos valores de normalidade e a massa protéica somática com valores abaixo do normal. Ao compararmos o grupo de tuberculosos com os não doentes somente os valores para hemoglobina foram significativos, sendo inferiores nos indivíduos doentes. Esta alteração pode estar associada a parasitoses intestinais, já que a ingestão de ferro foi similar em todos os indivíduos investigados. Ancilostomíase, amebíase, giardíase e ascaridíase estavam presentes em 40% da amostra de albergados investigada. A correlação entre os achados da avaliação antropométrica e dietética nos sugere que fatores envolvidos com a qualidade da dieta, tal qual o teor de alguns micronutrientes, possam estar envolvidos com o maior risco para o desenvolvimento de tuberculose