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Biomed Chromatogr ; 33(2): e4388, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30238481


In this study, we developed a method for the determination of Penicillium griseofulvum-oriented pyripyropene A (PPPA), a selective inhibitor of acyl-coenzyme A:cholesterol acyltransferase 2, in mouse and human plasma and validated it using liquid chromatography-tandem mass spectrometry. Pyripyropene A (PPPA) and an internal standard, carbamazepine, were separated using a Xterra MS C18 column with a mixture of acetonitrile and 0.1% formic acid as the mobile phase. The ion transitions monitored in positive-ion mode [M + H]+ of multiple-reaction monitoring (MRM) were m/z 148.0 from m/z 584.0 for PPPA and m/z 194.0 from m/z 237.0 for the internal standard. The detector response was specific and linear for PPPA at concentrations within the range from 1 to 5,000 ng/mL. The intra-/inter-day precision and accuracy of the method was acceptable by the criteria for assay validation. The matrix effects of PPPA ranged from 97.6 to 104.2% and from 93.3 to 105.3% in post-preparative mouse and human plasma samples, respectively. PPPA was also stable under various processing and/or handling conditions. Finally, PPPA concentrations in the mouse plasma samples could be measured after intravenous, intraperitoneal, or oral administration of PPPA, suggesting that the assay is useful for pharmacokinetic studies on mice and applicable to human studies.

Cromatografia Líquida/métodos , Penicillium/química , Piridinas/sangue , Piridinas/farmacocinética , Sesquiterpenos/sangue , Sesquiterpenos/farmacocinética , Espectrometria de Massas em Tandem/métodos , Animais , Estabilidade de Medicamentos , Modelos Lineares , Masculino , Camundongos , Camundongos Endogâmicos ICR , Piridinas/química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Sesquiterpenos/química , Esterol O-Aciltransferase/antagonistas & inibidores
Integr Biol (Camb) ; 9(5): 436-443, 2017 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-28386617


Blue light has high photochemical energy and induces cell apoptosis in retinal pigment epithelial cells. Due to its phototoxicity, retinal hazard by blue light stimulation has been well demonstrated using high intensity light sources. However, it has not been studied whether blue light in the displays, emitting low intensity light, such as those used in today's smartphones, monitors, and TVs, also causes apoptosis in retinal pigment epithelial cells. We attempted to examine the blue light effect on human adult retinal epithelial cells using display devices with different blue light wavelength ranges, the peaks of which specifically appear at 449 nm, 458 nm, and 470 nm. When blue light was illuminated on A2E-loaded ARPE-19 cells using these displays, the display with a blue light peak at a shorter wavelength resulted in an increased production of reactive oxygen species (ROS). Moreover, the reduction of cell viability and induction of caspase-3/7 activity were more evident in A2E-loaded ARPE-19 cells after illumination by the display with a blue light peak at a shorter wavelength, especially at 449 nm. Additionally, white light was tested to examine the effect of blue light in a mixed color illumination with red and green lights. Consistent with the results obtained using only blue light, white light illuminated by display devices with a blue light peak at a shorter wavelength also triggered increased cell death and apoptosis compared to that illuminated by display devices with a blue light peak at longer wavelength. These results show that even at the low intensity utilized in the display devices, blue light can induce ROS production and apoptosis in retinal cells. Our results also suggest that the blue light hazard of display devices might be highly reduced if the display devices contain less short wavelength blue light.

Luz/efeitos adversos , Epitélio Pigmentado da Retina/patologia , Epitélio Pigmentado da Retina/efeitos da radiação , Apoptose/efeitos da radiação , Linhagem Celular , Sobrevivência Celular/efeitos da radiação , Terminais de Computador , Humanos , Estimulação Luminosa/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Retinoides/metabolismo , Televisão , Dispositivos Eletrônicos Vestíveis/efeitos adversos
Bioresour Technol ; 100(11): 2816-22, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19217774


The objective of the study was to examine the application of the Anaerobic Digestion Model No. 1 (ADM1) developed by the IWA task group for mathematical modelling of anaerobic process. Lab-scale temperature-phased anaerobic digestion (TPAD) process were operated continuously, and were fed with co-substrate composed of dog food and flour. The model platform implemented in the simulation was a derivative of the ADM1. Sensitivity analysis showed that k(m.process) (maximum specific uptake rate) and K(S.process) (half saturation value) had high sensitivities to model components. Important parameters including maximum uptake rate for propionate utilisers (k( and half saturation constant for acetate utilisers (K( in the thermophilic digester and maximum uptake rate for acetate utilisers (k( in the mesophilic digester were estimated using iterative methods, which optimized the parameters with experimental results. Simulation with estimated parameters showed good agreement with experimental results in the case of methane production, uptake of acetate, soluble chemical oxygen demand (SCOD) and total chemical oxygen demand (TCOD). Under these conditions, the model predicted reasonably well the dynamic behavior of the TPAD process for verifying the model.

Bactérias Anaeróbias/metabolismo , Reatores Biológicos/microbiologia , Microbiologia de Alimentos , Resíduos Industriais/prevenção & controle , Modelos Biológicos , Oxigênio/metabolismo , Eliminação de Resíduos/métodos , Simulação por Computador , Transição de Fase , Temperatura