RESUMO
AIM: To investigate the role of valproic acid (VPA), a class I selective histone deacetylase inhibitor, on Michigan Cancer Foundation (MCF)-7 breast cancer cells, named and explore its possible molecular mechanism. METHODS: MCF-7 cells were cultured with sodium valproate (0. 5-4.0 mmol/L) for 24 h, 48 h, and 72 h in vitro, respectively. The cell viability, apoptosis, and cell cycle were examined. The activities and protein expressions of caspase-3, caspase-8, and caspase-9 were subsequently assayed. Finally, mRNA and protein expressions of cyclin A, cyclin D1, cyclin E, and p21 were analyzed. RESULTS: Sodium valproate suppressed MCF-7 cell growth, induced cell apoptosis, and arrested G1 phase in a time- and concentration- dependent manner, with the relative cell viabilities decreased, cell apoptosis ratios increased, and percentage of G1 phase enhanced (P<0.05). Increased activity of caspase-3 and caspase-9, but not caspase-8, and increased protein levels were found under sodium valproate (2.0 mmol/L, 48h). P21 was up-regulated and cyclin D1 was down-regulated at both mRNA and protein levels under sodium valproate (2.0 mmol/L, 48h)(P<0.05), although cyclin E and cyclin A remained changed. CONCLUSION: These results indicate that VPA can suppress the growth of breast cancer MCF-7 cells by inducing apoptosis and arresting G1 phase. Intrinsic apoptotic pathway is dominant for VPA-induced apoptosis. For G1 phase arrest, p21 up-regulation and down-regulation of cyclin D1 may be the main molecular mechanism.
Assuntos
Antineoplásicos/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Ácido Valproico/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 9/metabolismo , Proliferação de Células/efeitos dos fármacos , Ciclina D1/metabolismo , Ciclina E/metabolismo , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular , Humanos , Células MCF-7 , Proteínas Oncogênicas/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: Antibacterial therapy plays a crucial role in neonatal infections. The efficacy of antibacterial agents is closely related to the actual dose given to neonates. So we evaluated factors potentially affecting the actual dose of intravenous antibiotics during dispensing process in neonates. METHODS: Meropenem, cefoperazone/sulbactam and piperacillin/tazobactam with two strengths were used to evaluate three methods. Method A (MA) was diluted once and the volumes of 5% glucose for MA were meropenem 4.00 mL, cefoperazone/sulbactam 3.00 mL, piperacillin/tazobactam 9.00 mL. Method B (MB) differed by doubling the volume of 5% glucose. The difference in method C (MC) involved diluting with 5% glucose twice. The concentrations were measured by high-performance liquid chromatography. Relative error (RE) was used to evaluate the preparation accuracy. RESULTS: The RE values using MA/MB/MC were: (1) meropenem 0.5 g: 15.1%, 8.0%, 10.4%; 0.25 g: 7.8%, 3.1%, 6.0%; (2) cefoperazone/sulbactam 1.5 g: 13.6%, 4.2%, 3.4%; 0.75 g: 8.8%, 3.5%, 4.0%; (3) piperacillin/tazobactam 4.5 g: 18.2%, 8.7%, 6.3%; 562.5 mg: 8.1%, 2.8%, 6.1%. MB was better than MA in all three drugs. No difference in RE values was found between single and double dilution, except meropenem with 0.25 g. Using MB, meropenem and piperacillin/tazobactam with small drug strength had higher accuracy in preparation. CONCLUSIONS: MB was suitable for neonatal drug dispensing because of its high accuracy and simple operation. Drugs with small strength were promoted due to the high accuracy.
Assuntos
Antibacterianos , Cefoperazona , Recém-Nascido , Humanos , Antibacterianos/uso terapêutico , Meropeném , Cefoperazona/uso terapêutico , Sulbactam , Piperacilina , Combinação Piperacilina e Tazobactam/uso terapêutico , GlucoseRESUMO
AIM: To prepare a new oral colon-specific delivery formulation and to investigate the release profile in vitro and the colon-specific delivery property in vivo in dogs. METHODS: Sodium 4-aminosalicylic acid was selected as the model drug. The combination of Eudragit RL30D and RS30D were used as sustained-release film, and Eudragit FS30D used as enteric film, which was expected to release drug depending on pH and time. The release profile of tablets was studied in three phosphate buffers with the pH 6.5, 7.0 or 7.4 for 12 h after a simulated gastric presoak for 2 h in 0.1 mol x L(-1) HCl. The tablets were radiolabelled with 99mTc to make their release times and positions in the gastrointestinal tract be followed using a gamma camera. RESULTS: For the in vitro study, there was no drug released in 0.1 mol x L(-1) HCl for 2 h, and release occurred slowly when pH was above 6.5. Drug was released faster while pH was higher. For the in vivo study, the coated tablets remained intact in the upper gastrointestinal tract, and drug release began after the colonic arrival. The uncoated tablets, however, disintegrated in the stomach of the dogs rapidly. CONCLUSION: The coating could protect the drug until the tablets reached the ascending colon, where drug was released slowly for over 10 h.
Assuntos
Ácido Aminossalicílico/administração & dosagem , Ácido Aminossalicílico/farmacocinética , Colo/metabolismo , Sistemas de Liberação de Medicamentos , Resinas Acrílicas/química , Administração Oral , Ácido Aminossalicílico/química , Animais , Antituberculosos/administração & dosagem , Antituberculosos/química , Antituberculosos/farmacocinética , Preparações de Ação Retardada , Cães , Concentração de Íons de Hidrogênio , Masculino , Comprimidos com Revestimento EntéricoRESUMO
OBJECTIVE: To access the effect of wireless biofeedback therapy on bruxism. METHODS: Ten voluntary bruxers (seven female and three male, mean age 26.1 years) were invited to participate in this clinical research. An electric resistance strain gauge was embedded in the position of canine of a maxillary splint for monitoring the abnormal clenching or grinding movement of teeth during sleep. The relevant details of bruxism events, including value of relative force, occurring time and duration were recorded and analyzed by the receiver device and monitoring program respectively. Meanwhile, for the purpose of nerve system and muscle relaxation, a watch-style device around the patient's wrist will vibrate to alert the patient of teeth grinding or clenching if the value of biting force and duration exceed the threshold. Total average episodes of bruxism and duration was observed during eight hours sleep, and was analyzed with one-way analysis of variance in SPSS 19.0 by the end of 6th week and three months following biofeedback therapy. RESULTS: The average episodes of bruxism has declined dramatically from (9.8 ± 2.2) times to (3.0 ± 1.2) times during one night (P < 0.05), and the average duration of bruxism events was reduced from (20.7 ± 12.2) s to (10.0 ± 3.4) s (P < 0.05) after six weeks biofeedback therapy. By the end of three months, the average episodes declined to (2.9 ± 1.2) times (P < 0.05), and the average duration decline to (9.2 ± 2.9) s (P < 0.05) with contrast to preliminary night. CONCLUSIONS: The pressure-based wireless biofeedback device is able to monitoring clenching and grinding of bruxism. The results suggest that biofeedback therapy may be an effective, novel and convenient measure for treatment of bruxism according to several months therapy.