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( Chi-dung Nguyen ),( Hyun-kyung Lee ),( Hyun Kuk Kim ),( Hye Kyeong Park ),( Hyuk Pyo Lee ),( Ho-kee Yum ),( Yong-soon Cho ),( Jae-gook Shin ) 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.-
Background Prothionamide (PTO) is a pro-drug in thionamides group widely used for treatment multidrug-resistant tuberculosis (MDR-TB) and meningitis TB. PTO is extensively metabolized mainly by flavin-containing monooxygenases (FMOs), to form major active metabolite - prothionamide sulfoxide. Our in-house data showed that PTO is a substrate of multiple transporters: OCT1, P-gp, MRP1, MRP2. In this research, we aimed to develop a physiologically based pharmacokinetic (PBPK) model integrating those finding to understand more about PTO disposition process and predict PTO exposure in individual patients. Methods The formation of prothionamide sulfoxide from PTO was estimated using pooled human liver and human lung microsomes. A PTO PBPK model was developed in Simcyp (V.19) and validated based on published clinical data. The validated model was used to predict PTO exposure in TB patients using virtual twin approach. The predicted concentration was compared with clinical data from TB patients using PTO. Results The Results for Km and Vmax from in vitro metabolism study using pooled human liver microsomes were 275.8 μM and 2976 pmol/min/mg protein, respectively. The Results for Km and Vmax of prothionamide sulfoxide formation using pooled human lung microsomes 25.9 μM and 4260 pmol/min/mg protein, respectively. PTO plasma concentration predicted by PTO PBPK model described well published data. All predicted pharmacokinetic parameters were within 2 fold range of observed Results. The model predicted quite well observed PTO drug concentration from tuberculosis patients. Conclusion To the best of our knowledge, this is the first PTO PBPK model integrating metaboli PTO exposure in real-world patients, providing roadmap towards personalized dose estimation.sm and transporter kinetic data to predict
Spectrum of Lysosomal Storage Disease Targeted for Newborn Screening in Vietnam
Dung, Vu Chi,Ngoc, Can Thi Bich,Khanh, Nguyen Ngoc,Mai, Do Thi Thanh,Thao, Bui Phuong,Mai, Tran Thi Chi,Ha, Nguyen Thu,Huong, Nguyen Thi Mai,Nam, Nguyen Hoang,Hai, Le Thanh,Tomatsu, Shunji,Yoo, Han-Wo Association for Research of MPS and Rare Diseases 2017 Journal of mucopolysaccharidosis and rare disease Vol.3 No.1
( Chi-dung Nguyen ),( Md Masud Parvez ),( Nazia Kaisar ),( Yong-soon Cho ),( Jae-gook Shin ) 대한결핵 및 호흡기학회 2020 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.128 No.-
Background Ethambutol (EMB) is a first-line antituberculosis drug of which renal elimination is the primary route of elimination. EMB has been proven to be a substrate of OCT2. The EMB concentration significantly increases in renal failure patients. It is of importance to evaluate renal function, OCT2 genotypes as well as the interplay among them on EMB pharmacokinetics. Therefore, we aimed to develop a physiologically based pharmacokinetic (PBPK) model implying those variables to understand more in detail and predict EMB exposure in individual patients. Methods The effect of OCT2 genetic variants on OCT2-mediated uptake of EMB was estimated using in vitro stably transfected HEK293 cells with OCT2 wild type and variants. A PBPK model for EMB was constructed in Simcyp (V.17) and validated against clinical data. The validated model was used to predict the effect of OCT2 genotypes and renal impairment on EMB disposition. The predicted EMB exposure in “virtual twins” tuberculosis patients was compared with clinical data. Results OCT2-genetic variants showed a significant decrease in OCT2-mediated uptake of EMB in vitro compared to wild type. EMB plasma concentration predicted by EMB PBPK model compared well with published clinical data. OCT2-T199I increases EMB AUCinf by 42% and decreases renal clearance (CLr) by 46% compared to that of wild type. An increased AUCinf ratio of 1.3 and 1.5 among GFR 30-60 and GFR 15-30 groups is predicted, with significantly reduced CLr than healthy. Most importantly, terminally impaired GFR and OCT2-T199I combined caused approximately 2 fold increase of EMB AUCinf, reduced about 4.5 fold CLr than healthy subjects. The model predicted quite good observed data in "virtual twin" tuberculosis patients. Conclusion To the best of our knowledge, this is the first PBPK model showing a significant effect of renal impairment and transporter genotypes on EMB pharmacokinetics, a roadmap towards personalized dose estimation.
Audit Quality and Stock Return Co-Movement: Evidence from Vietnam
PHAM, Chi Bich Thi,VU, Thu Minh Thi,NGUYEN, Linh Ha,NGUYEN, Dung Duc Korea Distribution Science Association 2020 The Journal of Asian Finance, Economics and Busine Vol.7 No.7
This paper aims to explore the relationship between the quality of the audit and the level of stock return co-movement in the context of the Vietnamese emerging market. The empirical study is designed based on the quatitative method and deductive approach. The panel dataset includes 256 listed firms from different industries,with 1115 firm-year observations on Ho Chi Minh City Stock Exchange for the period from 2014 to 2018. In the research, we built the econometric regression model, using stock return synchronicity and audit quality as the dependent and independent variable, respectively. Some control variables are also added to the econometric regression models as they are well-documented in prior research to have an effect on stock price synchronicity. To improve the accuracy of the regression coefficients, beside the Ordinary Least Squares, we employ the Random Effects Model and the Fixed Effects Model for better statistical analysis of panel data set. The results show that the quality of the audit is positively correlated to stock price synchronicity. This finding suggests that stock returns of companies with higher quality of the audit are more synchronous with the market. Results for other control variables also support our reasoning for the main findings.
Mucolipidosis Type II in Vietnam
Vu, Chi Dung Association for Research of MPS and Rare Diseases 2016 Journal of mucopolysaccharidosis and rare disease Vol.2 No.1
Purpose: To describle clinical features and enzyme activity of Vietnamese patients with Mucolipidosis type II. Methods: Clinical features, laboratory and plasma lysosom enzyme activity by 4 MU-Fluorometric assay was studied from 2014-2015 at the Northern referral center of Pediatrics - National Children's Hospital. Results: 16 cases (7 girls and 9 boys) were diagnosed with I-cell bases on clinical symptoms and enzyme activities studies. Diagnosis age was $5.93{\pm}4.28$ years, onset age was recognised from birth to 4 years (median 1.25) with the feature of joint stiffness and bone deformation. All cases presented with the feature of joint stiffness, chest deformation and kyphoscoliosis; Fifteen cases (93.7%) had coarse facial features. No patients had hepatosplenomegaly on abdominal ultrasound, 5/15 patients had heart valves disease. Enzyme assay showed ${\alpha}$-Hexosaminidase of $1,885.9{\pm}338.7$ (nmol/mg plasma/17 hrs), ${\alpha}$-Iduronate sulfatase of $4,534.8{\pm}1,062.9nmol/mg$ plasma/4 hrs). Conclusion: Mucolipidosis II seriously affected the life of the patients with skeletal deformities, contractures develop in all joints and cardiac involvement.
3R Policy Development in Vietnam and Study on Biomass Waste to Energy
( Chi Kim Ngo ),( Nguyen Xuan Dung ),( Dang Ngoc Phuong ),( Chu Thao Khanh ) 한국폐기물자원순환학회(구 한국폐기물학회) 2015 한국폐기물자원순환학회 3RINCs초록집 Vol.2015 No.-
The 3R policy development in Vietnam has been analyzed and updated including the new stipulated regulation on home electronic applicants and ELV waste. Facing to the climate change, lacking sustainable energy sources the need the cooperation on R-D projects and planning response for coming targeted years to explore and utilization of biomass for energy. For this purpose, INPC is one of the leading institutes has experiences on baseline studied on Solid Waste Generation, Landfill gas and biomass fuels. The achievements in BMP testing, SMA assessment and technical skill on operation of biomass methane production and utilization and studies on GHG emission reduction of biomass conversion technologies have presented with the recommendation on feasible and economical model on conversion biomass to energy.