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1.
Pharm Res ; 40(11): 2597-2606, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37704895

RESUMEN

BACKGROUND: Dose modification of renally secreted drugs in patients with chronic kidney disease (CKD) has relied on serum creatinine concentration as a biomarker to estimate glomerular filtration (GFR) under the assumption that filtration and secretion decline in parallel. A discrepancy between actual renal clearance and predicted renal clearance based on GFR alone is observed in severe CKD patients with tenofovir, a compound secreted by renal OAT1/3. Uremic solutes that inhibit OAT1/3 may play a role in this divergence. METHODS: To examine the impact of transporter inhibition by uremic solutes on tenofovir renal clearance, we determined the inhibitory potential of uremic solutes hippuric acid, indoxyl sulfate, and p-cresol sulfate. The inhibition parameters (IC50) were incorporated into a previously validated mechanistic kidney model; simulated renal clearance and plasma PK profile were compared to data from clinical studies. RESULTS: Without the incorporation of uremic solute inhibition, the PBPK model failed to capture the observed data with an absolute average fold error (AAFE) > 2. However, when the inhibition of renal uptake transporters and uptake transporters in the slow distribution tissues were included, the AAFE value was within the pre-defined twofold model acceptance criterion, demonstrating successful model extrapolation to CKD patients. CONCLUSION: A PBPK model that incorporates inhibition by uremic solutes has potential to better predict renal clearance and systemic disposition of secreted drugs in patients with CKD. Ongoing research is warranted to determine if the model can be expanded to include other OAT1/3 substrate drugs and to evaluate how these findings can be translated to clinical guidance for drug selection and dose optimization in patients with CKD.


Asunto(s)
Riñón , Insuficiencia Renal Crónica , Humanos , Riñón/metabolismo , Insuficiencia Renal Crónica/tratamiento farmacológico , Transporte Biológico , Proteínas de Transporte de Membrana/metabolismo
2.
Sensors (Basel) ; 22(20)2022 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-36298060

RESUMEN

With the continuous progress of renewable energy technology and the large-scale construction of microgrids, the architecture of power systems is becoming increasingly complex and huge. In order to achieve efficient and low-delay data processing and meet the needs of smart grid users, emerging smart energy systems are often deployed at the edge of the power grid, and edge computing modules are integrated into the microgrids system, so as to realize the cost-optimal control decision of the microgrids under the condition of load balancing. Therefore, this paper presents a bilevel optimization control model, which is divided into an upper-level optimal control module and a lower-level optimal control module. The purpose of the two-layer optimization modules is to optimize the cost of the power distribution of microgrids. The function of the upper-level optimal control module is to set decision variables for the lower-level module, while the function of the lower-level module is to find the optimal solution by mathematical methods on the basis of the upper-level and then feed back the optimal solution to the upper-layer. The upper-level and lower-level modules affect system decisions together. Finally, the feasibility of the bilevel optimization model is demonstrated by experiments.

3.
Arch Toxicol ; 89(1): 57-72, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25069801

RESUMEN

Antagonizing the action of the pregnane X receptor (PXR) may have important clinical implications for preventing inducer-drug interactions and improving therapeutic efficacy. We identified a widely distributed isothiocyanate, allyl isothiocyanate (AITC), which acts as an effective antagonist of the nuclear receptor pregnane X receptor (PXR, NR1I2) and constitutive androstane receptor (CAR, NR1I3). HepG2 cells were used to assay reporter function, mRNA levels, and protein expression. Catalytic activities of the PXR and CAR target genes, CYP3A4 and CYP2B6, respectively, were also assessed in differentiated HepaRG cells. Protective effects of AITC on rifampin-induced cytotoxicity were observed, and transient transfection assays showed that AITC was able to effectively attenuate the agonist effects of rifampin and CITCO on human PXR and CAR activity, respectively. AITC-mediated reduction in the transcriptional activity of PXR and CAR correlated well with the suppression of CYP3A4 and CYP2B6 expression in HepG2 cells, which reflected the reduced catalytic activities of both of these genes following AITC treatment in differentiated HepaRG cells. Furthermore, AITC disrupts the co-regulations of PXR with several important co-regulators. Furthermore, the antagonist effect of AITC against PXR was found in HepaRG cells upon addition of acetaminophen (APAP) and amiodarone, indicating that AITC protects cells from drug-induced cytotoxicity. Taken together, our results show that AITC inhibits the transactivation effects of PXR and CAR and reduces the expression and function of CYP3A4 and CYP2B6. Additionally, AITC reversed the cytotoxic effects of APAP and amiodarone induced by PXR ligand. Results from this study suggest that AITC could be a powerful agent for reducing potentially dangerous interactions between transcriptional inducers of CYP enzymes and therapeutic drugs.


Asunto(s)
Acetaminofén/toxicidad , Amiodarona/toxicidad , Isotiocianatos/farmacología , Receptores Citoplasmáticos y Nucleares/antagonistas & inhibidores , Receptores de Esteroides/antagonistas & inhibidores , Acetaminofén/metabolismo , Amiodarona/metabolismo , Animales , Western Blotting , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Receptor de Androstano Constitutivo , Citocromo P-450 CYP2B6/genética , Citocromo P-450 CYP2B6/metabolismo , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Humanos , Ratones , Receptor X de Pregnano , Receptores Citoplasmáticos y Nucleares/genética , Receptores de Esteroides/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Activación Transcripcional , Transfección
4.
IEEE Trans Cybern ; 54(5): 2852-2865, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37074888

RESUMEN

The approach of least squares (LSs) has been quite popular and widely adopted for the common linear regression analysis, which can give rise to the solution to an arbitrary critically-, over-, or under-determined system. Such a linear regression analysis can be easily applied for linear estimation and equalization in signal processing for cybernetics. Nonetheless, the current LS approach for linear regression is unfortunately limited to the dimensionality of data, that is, the exact LS solution can involve only a data matrix. As the dimension of data increases and such data need to be represented by a tensor, the corresponding exact tensor-based LS (TLS) solution does not exist due to the lack of a pertinent mathematical framework. Lately, some alternatives such as tensor decomposition and tensor unfolding were proposed to approximate the TLS solutions to the linear regression problems involving tensor data, but these techniques cannot provide the exact or true TLS solution. In this work, we would like to make the first-ever attempt to present a new mathematical framework for facilitating the exact TLS solutions involving tensor data. To demonstrate the applicability of our proposed new scheme, numerical experiments regarding machine learning and robust speech recognition are illustrated and the associated memory and computational complexities are also studied.

5.
J Neurosci ; 32(12): 4118-32, 2012 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-22442076

RESUMEN

ERK5 MAP kinase is highly expressed in the developing nervous system and has been implicated in promoting the survival of immature neurons in culture. However, its role in the development and function of the mammalian nervous system has not been established in vivo. Here, we report that conditional deletion of the erk5 gene in mouse neural stem cells during development reduces the number of GABAergic interneurons in the main olfactory bulb (OB). Our data suggest that this is due to a decrease in proliferation and an increase in apoptosis in the subventricular zone and rostral migratory stream of ERK5 mutant mice. Interestingly, ERK5 mutant mice have smaller OB and are impaired in odor discrimination between structurally similar odorants. We conclude that ERK5 is a novel signaling pathway regulating developmental OB neurogenesis and olfactory behavior.


Asunto(s)
Neuronas GABAérgicas/fisiología , Proteína Quinasa 7 Activada por Mitógenos/deficiencia , Odorantes , Bulbo Olfatorio , Trastornos de la Percepción/genética , Trastornos de la Percepción/patología , Factores de Edad , Análisis de Varianza , Animales , Animales Recién Nacidos , Apoptosis/genética , Bromodesoxiuridina/metabolismo , Movimiento Celular , Modelos Animales de Enfermedad , Electrooculografía/métodos , Embrión de Mamíferos , Regulación del Desarrollo de la Expresión Génica/genética , Glutamato Descarboxilasa/metabolismo , Etiquetado Corte-Fin in Situ , Ventrículos Laterales/embriología , Ventrículos Laterales/crecimiento & desarrollo , Ventrículos Laterales/patología , Ratones , Ratones Transgénicos , Proteína Quinasa 7 Activada por Mitógenos/genética , Molécula L1 de Adhesión de Célula Nerviosa/metabolismo , Células-Madre Neurales/fisiología , Neurogénesis/genética , Bulbo Olfatorio/embriología , Bulbo Olfatorio/crecimiento & desarrollo , Bulbo Olfatorio/patología , Fosfopiruvato Hidratasa/metabolismo , Factores de Transcripción SOXB1/metabolismo , Ácidos Siálicos/metabolismo , Transducción de Señal , Olfato/genética
6.
J Med Virol ; 85(7): 1206-14, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23918539

RESUMEN

This study aimed to evaluate whether genetic polymorphisms of the inducible nitric oxide synthase (iNOS) gene NOS2A could be associated with a sustained virological response (SVR) among patients infected with hepatitis C virus genotypes 1 and 2 (HCV-1 and HCV-2) who were treated with peginterferon plus ribavirin (PEG-IFNα-RBV). We analyzed the associations between SVR to PEG-IFNα-RBV therapy and two single nucleotide polymorphisms (SNPs) in NOS2A. This study included Taiwanese Chinese patients infected with either HCV-1 (n = 265) or HCV-2 (n = 195) with or without a SVR. Among the NOS2A SNPs examined, the combination of genotypes A/A and A/G of rs2248814 was inversely correlated with SVR in patients infected with HCV-1 (P = 0.0048), particularly in males (P = 0.0281). This effect was not observed in patients infected with HCV-2. The AC NOS2A haplotype comprising two SNPs (rs2248814 and rs2072324) was found to be associated with SVR, and its presence may decrease the chances for a successful outcome of treatment of patients infected with HCV-1 (P = 0.0053). HCV-1 infected patients who carried the A-C diplotype will have a lower success rate of achieving a SVR (P = 0.0117). In addition, a multivariate logistic regression model for predicting a SVR revealed that the presence of the A-C diplotype interactively affected the outcome of PEG-IFNα-RBV treatment. The presence of NOS2A SNPs and the association with SVR showed that NOS2A polymorphisms may influence the therapeutic outcomes of patients infected with HCV-1 under standard of care treatment.


Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Óxido Nítrico Sintasa de Tipo II/genética , Polietilenglicoles/uso terapéutico , Polimorfismo de Nucleótido Simple , Ribavirina/uso terapéutico , Adulto , Anciano , Quimioterapia Combinada/métodos , Femenino , Genotipo , Hepatitis C Crónica/virología , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Taiwán , Resultado del Tratamiento
7.
J Air Waste Manag Assoc ; 63(4): 433-41, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23687728

RESUMEN

UNLABELLED: There are four types of PM10 (particulate matter with an aerodynamic diameter <10 microm) episodes that occur frequently in central Taiwan: long-range transport with dust storms (DS), long-range transport with frontal pollution (FP), river dust (RD), and stagnant weather (SW). During the periods of the four episodes, poor visibility usually results. Multiple linear regression was applied to visibility using eight potential influential variables (temperature, relative humidity, wind speed, PM2.5, PM2.5-10, SO2, NO2, and NO) as independent variables. Of the eight variables, PM2.5 showed the greatest explainable percentage of about 48.6% and 58.1% for Taichung and Wuchi stations, respectively. This suggested that PM2.5 was the most important contributor to reduced visibility. Compared with other type of episodes, the aerosols tended to be offine size during the SWepisodes. This is the main reason that the poorest visibility occurred during the SWepisodes. Good correlation between visibility and secondary inorganic salts (NH4+, NO3, and SO4(2-)) were found at Taichung station (r = 0.71) and Wuchi station (r = 0.81), suggesting that secondary inorganic salts did contribute significantly to the degradation ofvisibility. The visibility degradation due to the effects ofNO3- was much higher than that due to SO4(2-) and NH4+ in the urban area, whereas the visibility degradation due to the effects of NO3 , SO42-, and NH4+ did not show significant diference in the rural area. IMPLICATIONS: Of the eight potential influential variables, PM2.5 showed the greatest effects on reduced visibility. Compared with other type of episodes, the aerosols tend to be fine size during the episodes of stagnant weather. This is the main reason why the poorest visibility occurred during the SW episodes. Good correlations between visibility and secondary inorganic salts (NH4+, NO3-, and SO4(2-)) suggested that secondary inorganic salts did contribute significantly to the degradation of visibility. Among the three inorganic salts, nitrates played a leading role for visibility degradation in urban areas in central Taiwan.


Asunto(s)
Contaminantes Atmosféricos/química , Monitoreo del Ambiente/métodos , Tamaño de la Partícula , Material Particulado , Taiwán
8.
Environ Monit Assess ; 185(12): 9777-87, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23761164

RESUMEN

Daily and hourly average data from nine air-quality monitoring stations distributed across central Taiwan, which include ten items (i.e., PM10, PM2.5, wind direction, wind speed, temperature, relative humidity, SO2, NO2, NO, and CO), were collected from 2005 to 2009. Four episode types: long-range transport with dust storms (DS), long-range transport with frontal pollution (FP), river dust (RD), and stagnant weather (SW), and one mixed type of episode were identified. Of these four episode types, the SW was the dominant type, averaging about 70%. The mean ratio of PM2.5/PM10 was the lowest during the RD episodes (0.42), while the mean ratio of PM2.5/PM10 was the highest during the SW episodes (0.64). Fine aerosol (PM2.5) and coarse aerosol (PM10-2.5) samples were collected by high-volume samplers for chemical composition analysis, from only three stations (Douliou, Lunbei, and Siansi) during the days of SW, RD, DS, and FP. The concentrations of PM2.5 and three ionic species (NH4⁺, NO3⁻, and SO4²â») all showed significant differences among the four episode types. The highest levels of NO3⁻ (12.1 µg/m(3)) and SO4²â» (20.5 µg/m(3)) were found during the SW and FP episodes, respectively. A comparison on the spatial similarity of aerosol compositions among the episodes and/or non-episodes (control) was characterized by the coefficient of divergence (CD). The results showed higher CD values in PM10-2.5 than in PM2.5, and the CD values between RD episodes and the other three episodes were higher than those between two types of episode for the other three episodes. The ratios of SOR (sulfur oxidation ratio), SO4²â»/EC (elemental carbon), NOR (nitrogen oxidation ratio), and NO3⁻/EC showed that sulfate formation was most rapid during the FP, while nitrate formation was most rapid during the SW.


Asunto(s)
Aerosoles/análisis , Contaminantes Atmosféricos/análisis , Contaminación del Aire/estadística & datos numéricos , Monitoreo del Ambiente , Material Particulado/análisis , Estaciones del Año , Taiwán , Tiempo (Meteorología)
9.
Sci Total Environ ; 904: 166849, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37673250

RESUMEN

Variations in the height of the boundary layer have a critical impact on the vertical transport of near-surface aerosols. Variations can affect the interactions between aerosols and clouds/fog by altering the scattering and absorption of solar radiation, significantly changing radiative forcing, convective precipitation, and regional climate. In this study, we simultaneously monitored air pollution and meteorological factors in a flat urban area (YunTech site, 50 m asl) and its peripheral mountainous region (MeiShan site, 980 m asl), analyzed the characteristics of pollutants under different atmospheric conditions, and explored the differences in the chemical reaction mechanisms of aerosols at various altitudes, aiming to clarify the evolution of the boundary layer in urban and suburban areas and its impact on the transport of pollutants. The results show that even without anthropogenic emissions, urban ground-level pollutants could be transported to peripheral mountainous areas through boundary layer height variations and local circulations, such as mountain-valley breezes. The PM2.5 concentration was higher at the urban site (average 31.14 ± 14.82µgm-3) and could be transported aloft by valley winds, leading to the gradual accumulation of daytime PM2.5 with an afternoon peak at the mountain site. Moreover, the nitrogen oxidation rate (NOR = [NO3-]/[NO3-] + [NO2]) exhibited clear site variations, the mountain site (average 0.41 ± 0.20) was higher than the urban site (average 0.19 ± 0.07), likely due to the atmospheric environment with thick clouds/fog and strong oxidation capacity in the mountain area. Our study has verified that aerosol characteristics, origins, formation pathways and transport mechanisms at the two measurement sites are significantly different under different conditions, which provides a theoretical basis for future air pollution prevention and regional climate research.

11.
Sci Rep ; 12(1): 4343, 2022 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-35288600

RESUMEN

Particulate lead (Pb) is a primary air pollutant that affects society because of its health impacts. This study investigates the source sectors of Pb associated with ambient fine particulate matter (PM2.5) over central-western Taiwan (CWT) with new constraints on the Pb-isotopic composition. We demonstrate that the contribution of coal-fired facilities is overwhelming, which is estimated to reach 35 ± 16% in the summertime and is enhanced to 57 ± 24% during the winter monsoon seasons. Moreover, fossil-fuel vehicles remain a major source of atmospheric Pb, which accounts for 12 ± 5%, despite the current absence of a leaded gasoline supply. Significant seasonal and geographical variations in the Pb-isotopic composition are revealed, which suggest that the impact of East Asian (EA) pollution outflows is important in north CWT and drastically declines toward the south. We estimate the average contribution of EA outflows as accounting for 35 ± 15% (3.6 ± 1.5 ng/m3) of the atmospheric Pb loading in CWT during the winter monsoon seasons.


Asunto(s)
Contaminantes Atmosféricos , Plomo , Contaminantes Atmosféricos/análisis , Carbón Mineral , Monitoreo del Ambiente , Material Particulado/análisis , Estaciones del Año
12.
Toxicol Appl Pharmacol ; 257(1): 59-66, 2011 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-21889949

RESUMEN

The efficacy of arsenic trioxide (ATO) against acute promyelocytic leukemia (APL) and relapsed APL has been well documented. ATO may cause DNA damage by generating reactive oxygen intermediates. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, modulates gene and protein expression via histone-dependent or -independent pathways that may result in chromatin decondensation, cell cycle arrest, differentiation, and apoptosis. We investigated whether ATO and SAHA act synergistically to enhance the death of cancer cells. Our current findings showed that combined treatment with ATO and SAHA resulted in enhanced suppression of non-small-cell lung carcinoma in vitro in H1299 cells and in vivo in a xenograft mouse model. Flow cytometric analysis of annexin V+ cells showed that apoptotic cell death was significantly enhanced after combined treatment with ATO and SAHA. At the doses used, ATO did not interfere with cell cycle progression, but SAHA induced p21 expression and led to G1 arrest. A Comet assay demonstrated that ATO, but not SAHA, induced DNA strand breaks in H1299 cells; however, co-treatment with SAHA significantly increased ATO-induced DNA damage. Moreover, SAHA enhanced acetylation of histone H3 and sensitized genomic DNA to DNase I digestion. Our results suggest that SAHA may cause chromatin relaxation and increase cellular susceptibility to ATO-induced DNA damage. Combined administration of SAHA and ATO may be an effective approach to the treatment of lung cancer.


Asunto(s)
Antineoplásicos/uso terapéutico , Arsenicales/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Ácidos Hidroxámicos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Óxidos/uso terapéutico , Animales , Antineoplásicos/administración & dosificación , Apoptosis/efectos de los fármacos , Trióxido de Arsénico , Arsenicales/administración & dosificación , Western Blotting , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Ensayo Cometa , Daño del ADN/efectos de los fármacos , Sinergismo Farmacológico , Quimioterapia Combinada , Citometría de Flujo , Humanos , Ácidos Hidroxámicos/administración & dosificación , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Óxidos/administración & dosificación , Vorinostat
13.
J Environ Manage ; 92(6): 1520-7, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21320743

RESUMEN

In autumn of 2008, the chemical characteristics of major secondary ionic aerosols at a suburban site in central Taiwan were measured during an annually occurring season of high pollution. The semicontinuous measurement system measured major soluble inorganic species, including NH(4)(+), NO(3)(-), and SO(4)(2-), in PM(10) with a 15 min resolution time. The atmospheric conditions, except for the influences of typhoons, were dominated by the local sea-land breeze with clear diurnal variations of meteorological parameters and air pollutant concentrations. To evaluate secondary aerosol formation at different ozone levels, daily ozone maximum concentration (O(3,daily max)) was used as an index of photochemical activity for dividing between the heavily polluted period (O(3,daily max) ≧80 ppb) and the lightly polluted period (O(3,daily max)<80 ppb). The concentrations of PM(10), NO(3)(-), SO(4)(2-), NH(4)(+) and total major ions during the heavily polluted period were 1.6, 1.9, 2.4, 2.7 and 2.3 times the concentrations during the lightly polluted period, respectively. Results showed that the daily maximum concentrations of PM(10) occurred around midnight and the daily maximum ozone concentration occurred during daytime. The average concentration of SO(2) was higher during daytime, which could be explained by the transportation of coastal industry emissions to the sampling site. In contrast, the high concentration of NO(2) at night was due to the land breeze flow that transport inland urban air masses toward this site. The simulations of breeze circulations and transitions were reflected in transports and distributions of these pollutants. During heavily polluted periods, NO(3)(-) and NH(4)(+) showed a clear diurnal variations with lower concentrations after midday, possibly due to the thermal volatilization of NH(4)NO(3) during daytime and transport of inland urban plume at night. The diurnal variation of PM(10) showed the similar pattern to that of NO(3)(-) and NH(4)(+) aerosols. This indicated that the formatted secondary aerosols in the inland urban area could be transported to the coastal area by the weak land breeze and deteriorated the air quality in the coastal area at night.


Asunto(s)
Aerosoles/análisis , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/estadística & datos numéricos , Iones/análisis , Estaciones del Año , Ozono/análisis , Taiwán , Viento
14.
Sci Rep ; 11(1): 21356, 2021 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-34725352

RESUMEN

Opioid overdose, dependence, and addiction are a major public health crisis. Patients with chronic kidney disease (CKD) are at high risk of opioid overdose, therefore novel methods that provide accurate prediction of renal clearance (CLr) and systemic disposition of opioids in CKD patients can facilitate the optimization of therapeutic regimens. The present study aimed to predict renal clearance and systemic disposition of morphine and its active metabolite morphine-6-glucuronide (M6G) in CKD patients using a vascularized human proximal tubule microphysiological system (VPT-MPS) coupled with a parent-metabolite full body physiologically-based pharmacokinetic (PBPK) model. The VPT-MPS, populated with a human umbilical vein endothelial cell (HUVEC) channel and an adjacent human primary proximal tubular epithelial cells (PTEC) channel, successfully demonstrated secretory transport of morphine and M6G from the HUVEC channel into the PTEC channel. The in vitro data generated by VPT-MPS were incorporated into a mechanistic kidney model and parent-metabolite full body PBPK model to predict CLr and systemic disposition of morphine and M6G, resulting in successful prediction of CLr and the plasma concentration-time profiles in both healthy subjects and CKD patients. A microphysiological system together with mathematical modeling successfully predicted renal clearance and systemic disposition of opioids in CKD patients and healthy subjects.


Asunto(s)
Analgésicos Opioides/farmacocinética , Túbulos Renales Proximales/metabolismo , Transporte Biológico , Línea Celular , Simulación por Computador , Células Endoteliales de la Vena Umbilical Humana , Humanos , Modelos Biológicos , Insuficiencia Renal Crónica/metabolismo
15.
ACS Pharmacol Transl Sci ; 3(3): 496-508, 2020 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-32566915

RESUMEN

A vascularized human proximal tubule model in a dual-channel microphysiological system (VPT-MPS) was developed, representing an advance over previous, single-cell-type kidney microphysiological systems. Human proximal tubule epithelial cells (PTECs) and human umbilical vein endothelial cells (HUVECs) were cocultured in side-by-side channels. Over 24 h of coculturing, PTECs maintained polarized expression of Na+/K+ ATPase, tight junctions (ZO-1), and OAT1. HUVECs showed the absence of ZO-1 but expressed endothelial cell marker (CD-31). In time-lapse imaging studies, fluorescein isothiocyanate (FITC)-dextran passed freely from the HUVEC vessel into the supporting extracellular matrix, confirming the leakiness of the endothelium (at 80 min, matrix/intravessel fluorescence ratio = 0.2). Dextran-associated fluorescence accumulated in the matrix adjacent to the basolateral aspect of the PTEC tubule with minimal passage of the compound into the tubule lumen observed (at 80 min, tubule lumen/matrix fluorescence ratio = 0.01). This demonstrates that the proximal tubule compartment is the rate-limiting step in the secretion of compounds in VPT-MPS. In kinetic studies with radiolabeled markers, p-aminohippuric acid (PAH) exhibited greater output into the tubule lumen than did paracellular markers mannitol and FITC-dextran (tubule outflow/vessel outflow concentration ratio of 7.7% vs 0.5 and 0.4%, respectively). A trend toward reduced PAH secretion by 45% was observed upon coadministration of probenecid. This signifies functional expression of renal transporters in PTECs that normally mediate the renal secretion of PAH. The VPT-MPS holds the promise of providing an in vitro platform for evaluating the renal secretion of new drug candidates and investigating the dysregulation of tubular drug secretion in chronic kidney disease.

16.
Environ Pollut ; 265(Pt B): 114813, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32504975

RESUMEN

This study examined the long-term trends in chemical components in PM2.5 (particulate matter with aerodynamic diameter ≤2.5 µm) samples collected at Lulin Atmospheric Background Station (LABS) located on the summit of Mt. Lulin (2862 m above mean sea level) in Taiwan in the western North Pacific during 2003-2018. High ambient concentrations of PM2.5 and its chemical components were observed during March and April every year. This enhancement was primarily associated with the long-range transport of biomass burning (BB) smoke emissions from Indochina, as revealed from cluster analysis of backward air mass trajectories. The decreasing trends in ambient concentrations of organic carbon (-0.67% yr-1; p = 0.01), elemental carbon (-0.48% yr-1; p = 0.18), and non-sea-salt (nss) K+ (-0.71% yr-1; p = 0.04) during 2003-2018 indicated a declining effect of transported BB aerosol over the western North Pacific. These findings were supported by the decreasing trend in levoglucosan (-0.26% yr-1; p = 0.20) during the period affected by the long-range transport of BB aerosol. However, NO3- displayed an increasing trend (0.71% yr-1; p = 0.003) with considerable enhancement resulting from the air masses transported from the Asian continent. Given that the decreasing trends were for the majority of the chemical components, the columnar aerosol optical depth (AOD) also demonstrated a decreasing trend (-1.04% yr-1; p = 0.0001) during 2006-2018. Overall decreasing trends in ambient (carbonaceous aerosol and nss-K+) as well as columnar (e.g., AOD) aerosol loadings at the LABS may influence the regional climate, which warrants further investigations. This study provides an improved understanding of the long-term trends in PM2.5 chemical components over the western North Pacific, and the results would be highly useful in model simulations for evaluating the effects of BB transport on an area.


Asunto(s)
Contaminantes Atmosféricos/análisis , Aerosoles/análisis , Altitud , Asia , Monitoreo del Ambiente , Material Particulado/análisis , Estaciones del Año , Taiwán
17.
Cytokine ; 45(1): 32-8, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19026558

RESUMEN

Expression of interleukin-1 receptor type II (IL1R2), a decoy receptor for pro-inflammatory interleukin 1 (IL-1), is enhanced by chronic exposure of the human uroepithelial cell line HUC-1 to arsenite. To explore the function of IL1R2, we ectopically expressed IL1R2 in HUC-1 cells. IL1R2 overexpression results in changes in cell morphology, actin rearrangement, and promoted cell migration. Ectopic expression of IL1R2 specifically blocked exogenous IL-1beta signaling but increased expression of the precursor form of IL-1alpha (pIL-1alpha) and its downstream targets, including interleukin 6 (IL-6), interleukin 8 (IL-8), and type I collagen alpha1 (COL1A1). However, depleting gene expression using small RNA interference specific to either pIL-1alpha or COL1A1, but not IL-6 or IL-8, significantly attenuated the migration of IL1R2-overexpressing cells. Furthermore, IL1R2 overexpression was associated with enhanced expression of Smad-interacting protein 1 (SIP-1) and reduced expression of E-cadherin. Because SIP-1 is a repressor of COL1A1-induced E-cadherin expression, the present results suggest that IL1R2 overexpression is likely through activation of the pIL-1alpha pathway to enhance cell migration.


Asunto(s)
Movimiento Celular/fisiología , Interleucina-1alfa/metabolismo , Precursores de Proteínas/metabolismo , Receptores Tipo II de Interleucina-1/metabolismo , Cadherinas/genética , Cadherinas/metabolismo , Línea Celular , Forma de la Célula , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Cadena alfa 1 del Colágeno Tipo I , Humanos , Interleucina-1alfa/genética , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , FN-kappa B/metabolismo , Precursores de Proteínas/genética , Interferencia de ARN , Receptores Tipo II de Interleucina-1/genética , Urotelio/citología , Urotelio/metabolismo
18.
J Hazard Mater ; 161(1): 344-50, 2009 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-18448250

RESUMEN

The purpose of this study was to explore the feasibility of removing silica particles and reducing turbidity from oxide chemical mechanical polishing (oxide-CMP) wastewater. Based on the dynamic characteristics of batch electrocoagulation, three operating stages (lag, reactive, and stabilizing) are proposed to identify the relationships among the zeta potential of the silica particles, solution turbidity, and the corresponding mean particle size of the silica. Experimental results show that the silica particles were destabilized and settled at the critical mean particle size, which was estimated to be above 520nm after 10min, and the corresponding turbidity removal mostly occurred during the reactive stage. Furthermore, the corresponding mean particle size varied from 520 to 1900nm as the treatment time progressed from 10 to 20min, which also occurred during the reactive stage. Several parameters, including different electrode pairs, electrolyte concentration, applied voltage, and the optimum condition of power input were investigated. Experimental results indicate that a Fe/Al electrode pair is the most efficient choice of the four electrode pair combinations in terms of energy consumption. The optimum electrolyte concentration and applied voltage were found to be 200ppm NaCl and 30V, respectively.


Asunto(s)
Electrocoagulación/instrumentación , Electrocoagulación/métodos , Óxidos/química , Óxidos/aislamiento & purificación , Dióxido de Silicio/química , Eliminación de Residuos Líquidos/instrumentación , Eliminación de Residuos Líquidos/métodos , Electrodos , Concentración de Iones de Hidrógeno , Tamaño de la Partícula
19.
Environ Pollut ; 243(Pt B): 1360-1367, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30273862

RESUMEN

This study developed a lightweight air composition measuring equipment (ACME) mounted in unmanned aerial vehicles (UAVs) to measure the vertical distribution characteristics of PM2.5 chemical species in the micro-scale urban environment for the first time. 212 samples collected from 0 to 350 m above ground level were analyzed for water-soluble ions. The concentrations of most ions on the above ground level were higher than that on the ground surface during the sampling period. The measurements of the total ion concentrations were approximately 54 to 26% of the PM2.5 mass concentrations on the ground surface. The concentrations of NH4+ and NO3- decreased with increases in the height from the ground, which may be related to the influence of the vehicle emissions and human activities. NO2- and SO42- both had a peak concentration on the higher vertical altitude at night in the sea-land wind system. In the southern wind system, the emissions of sea salts, dust, and stationary pollution, might be transported by the regional prevailing airflow from the southern coastal area, were the major pollutant sources above the boundary layer. The vertical distribution of ionic concentrations and wind field provided information concerning changes in pollutant transport and source regions that affect the local air quality. The ACME mounted in UAVs is the feasible and convenient method to fast understand the vertical distributions of aerosol chemical species. It provides important information about the accumulation and diffusion effects by the boundary layer variation to aerosol characteristics, which is difficulty observed from the conventional ground-based measurements. In future, this technology is the useful application for investigating the pollutant species emitted from the smokestack and the sudden pollution accident.


Asunto(s)
Aerosoles/análisis , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente , Contaminación del Aire/análisis , Polvo , Humanos , Iones/análisis , Material Particulado/análisis , Emisiones de Vehículos/análisis
20.
Chemosphere ; 67(5): 966-74, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17166552

RESUMEN

For reasonable and convenient assessments of the characteristics of the dry deposition velocities between Taichung harbor site and Wuchi town site in central Taiwan, the overall dry deposition velocities of several metallic elements were calculated as the particulate diameter (D(p)) distributions of large particles (D(p) > 10 microm), coarse particles (10 microm < D(p) < 2.5 microm), and fine particles (D(p) < 2.5 microm) based on the ambient measurements during March-December of 2004. In this work, the dry deposition fluxes showed the higher correlation with coarse particle concentrations than large particle concentrations; however, the least well correlation was observed between the dry deposition fluxes and the fine particle concentrations. The calculated best-fit overall dry deposition velocities obtained using coarse particle concentrations varied from approximately 0.2 cm s(-1) for Cr to 1.5 cm s(-1) for Pb and 0.2 cm s(-1) for Fe to 2.6 cm s(-1) for Pb at Taichung harbor and Wuchi town site, respectively. In general, the crustal elements had higher deposition velocities than anthropogenic elements. In addition, overall dry deposition velocities for crustal elements were higher in Wuchi town site than in Taichung harbor site. The results identified the dry deposition flux was mainly contributed from large and coarse particles due to their high deposition velocities. The results also indicated that the best approach to estimate overall dry deposition was by depending on the characteristics of particles with diameters larger than 2.5 microm.


Asunto(s)
Contaminantes Atmosféricos/análisis , Metales Pesados/análisis , Material Particulado/análisis , Monitoreo del Ambiente , Vehículos a Motor , Tamaño de la Partícula , Taiwán
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