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1.
Clin Infect Dis ; 70(10): 2143-2151, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-31314073

RESUMO

BACKGROUND: Direct measurement of tenofovir (TFV) in urine could be an objective measure to monitor adherence to preexposure prophylaxis (PrEP) or TFV-based antiretroviral therapy (ART). METHODS: We conducted a 3-arm randomized, pharmacokinetic study of tenofovir disoproxil fumarate (TDF) 300 mg/emtricitabine (FTC) 200 mg among adults living with human immunodeficiency virus. Participants were randomized to receive controlled TDF/FTC dosing as (1) "perfect" adherence (daily); (2) "moderate" adherence (4 doses/week); or (3) "low" adherence (2 doses/week). We obtained trough spot urine and plasma samples during a 6-week directly observed therapy period and a 4-week washout period. TFV concentrations were compared between adherence arms using 1-way analysis of variance. RESULTS: Among 28 participants, the median age was 33 years and 16 (57%) were male. Correlation between TFV plasma and urine concentrations was strong (ρ = 0.78; P < .0001). Median (interquartile range) steady-state trough TFV concentrations (ng/mL) for perfect, moderate, and low TDF adherence were 41 (26-52), 16 (14-19), and 4 (3-5) in plasma; and 6480 (3940-14 300), 3405 (2210-5020), and 448 (228-675) in urine. Trough TFV concentrations at steady state were significantly different between the 3 adherence arms for plasma (P < .0001) and urine (P = .0002). Following drug cessation, TFV concentrations persisted longer in urine than plasma samples. Washout urine TFV concentrations and time to undetectable concentrations did not differ between the 3 randomized adherence groups. CONCLUSIONS: Urine TFV concentrations can inform interpretation of novel point-of-care urine-based TFV assays to assess recent TDF adherence. CLINICAL TRIALS REGISTRATION: NCT03012607


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Preparações Farmacêuticas , Profilaxia Pré-Exposição , Tenofovir , Adulto , Fármacos Anti-HIV/uso terapêutico , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Plasma , Tenofovir/uso terapêutico
2.
Asian Pac J Cancer Prev ; 12(3): 593-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21627350

RESUMO

Rhizomes of Alpinia galanga (Linn.) or 'Kha' in Thai are used in food and as folk medicine in South and Southeast Asia. The aims of this study were to identify the mechanism of cell death of human leukemic HL-60 and U937 cells induced by 4'-hydroxycinnamaldehyde (4'-HCA) isolated from A. galanga. 4'-HCA was cytotoxic to both cell lines in a dose-dependent manner (p<0.05) as demonstrated by MTT assay. Apoptosis induced by 4'-HCA was demonstrated by a variety of methods: visualization of propidium iodide (PI)-stained cells under fluorescence microscope, detection of subdiploid cells by PI-staining and flow cytometry, and assay of active caspase-3 using a specific fluorogenic substrate. 4'-HCA-treated cells (10 and 50 µg/ml for 4 h) showed significant increase in reactive oxygen species production and decreased mitochondrial transmembrane potential as detected by dichlorohydrofluorescein diacetate and 3,3'-dihexyloxacarbocyanine iodide respectively, together with flow cytometry. The apoptotic death involved cytochrome c release, increase in Bax level and concomitant decreases in levels of Bcl-2 and Bcl-xL (using Western blotting), and elevation in cytosolic and mitochondrial Ca²âº contents (using compartment-specific fluorescent Ca2+ dyes). These results indicate that 4'-HCA induces apoptosis of human leukemic cell through a combination of mitochondrial and ER stress pathways.


Assuntos
Alpinia/química , Apoptose/efeitos dos fármacos , Cinamatos/farmacologia , Retículo Endoplasmático/efeitos dos fármacos , Leucemia/patologia , Mitocôndrias/efeitos dos fármacos , Western Blotting , Caspases/metabolismo , Proliferação de Células/efeitos dos fármacos , Citocromos c/metabolismo , Retículo Endoplasmático/metabolismo , Humanos , Leucemia/tratamento farmacológico , Leucemia/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio , Células Tumorais Cultivadas , Proteína X Associada a bcl-2/metabolismo , Proteína bcl-X/metabolismo
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