Functional characterization of MATE2-K genetic variants and their effects on metformin pharmacokinetics

Chung, Jae-Yong,Cho, Sung Kweon,Kim, Tae Hee,Kim, Kyoung Hee,Jang, Geun Hye,Kim, Choon Ok,Park, Eun-Mi,Cho, Joo-Youn,Jang, In-Jin,Choi, Ji Ha Wolters Kluwer Health | Lippincott Williams Wilkin 2013 Pharmacogenetics and genomics Vol.23 No.7

OBJECTIVE: Human multidrug and toxin extrusion member 2 (MATE2-K, SLC47A2) plays an important role in the renal elimination of various clinical drugs including the antidiabetic drug metformin. The goal of this study was to characterize genetic variants of MATE2-K and determine their association with the pharmacokinetics of metformin. METHODS: We screened DNA samples from 48 healthy Koreans for variants in the promoter and coding regions of MATE2-K and examined the function of common haplotypes in the promoter region using in-vitro luciferase assays. Then, the metformin pharmacokinetic study was carried out to determine the association between MATE2-K promoter haplotypes and metformin pharmacokinetics. RESULTS: Nine variants in the promoter region of MATE2-K and one nonsynonymous variant, p.G211V, were identified. The MATE2-K promoter haplotype 1 containing a known functional polymorphism, g.−130G>A and haplotype 2 containing two polymorphisms, g.−609G>A and g.−396G>A showed a significant increase in reporter activity. Among the 45 individuals who participated in the metformin pharmacokinetic study, 12 healthy Koreans who were homozygous for haplotype 1 or 2 showed a significant increase in renal clearance [539±76 (reference group) vs. 633±102 (variant group) ml/min; P=0.006] and secretion clearance [439±81 (reference group) vs. 531±102 (variant group) ml/min; P=0.007] of metformin compared with that shown by the reference group. CONCLUSION: Our study suggests that common promoter haplotypes of MATE2-K are associated with the pharmacokinetics of metformin.

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

진공압밀공법의 적용에 관한 해석적 연구

정연인 啓明大學校 産業技術硏究所 1997 産業技術硏究所 論文報告集 Vol.19 No.2

Laboratory testings, consisting of soil properties testing and vacuum consolidation testing with and without vertical wick drain, were carried out on CL soil to determine soil properties and relationship between settlement and time. In vacuum consolidation, strategic placement of wick drain ensures moisture content and the value of the density are similar throughout the soil sample. Inside of soil. the density of the portion close to vacuum source, with wick drain and without wick drain, increase much faster than that of the portion further from vacuum source. Therefore, the coefficient of permeability adjacent to the drain in particular(called, hardening zone), is altered significantly. The analytical study was carried out how hardening zone will affect to the consolidation. The results predicted by the developed method of analysis are compared with this from the experimental test. The comparison shows in general good agreement in term of settlement with repect to time.

Back Analysis of Displacements Measured During Excavation of Underground Storage Caverns

Lee, Chung-In,Lee, Youn-Kyou,Kim, Chee-Hwan 한국지반공학회 1996 지반 : 한국지반공학회지 Vol.12 No.3

In this paper, the results of back analysis based on, the inverse method are presented. Using the field measurements obtained from the two different underground storage caverns in Korea during their construction, the deformation modulus and the initial in-situ stresses of the rock masses around the access tunnels are calculated. The finite element analysis is carried out by usinB these results as input parameters. The calculated displacements are compared with the measured ones. 이 논문에서는 역순법 원리를 이용한 역해석 결과를 제시하였다. 국내에서 건설된 두 곳의 지하비축기지 공사 중에 계측한 자료를 이용하여 비축기지 진입터널 주위 암반의 변형계수와 초기 지압을 계산하였다. 역해석에서 얻어진 결과를 입력자를로 하여 유한요소해석을 수행하였으며 그 결과를 계측치와 비교, 검토하였다.

ICR계 마우스에서 홍화씨 에탄올 추출물의 급성독성시험

황윤환,박병권,임종환,김명석,송인배,명노일,정상일,윤효인 忠南大學校 獸醫科大學 附設 動物醫科學硏究所 2008 動物醫科學硏究誌 Vol.15 No.1

The present study was carried out to investigate the potential acute toxicity of safflower seed by a single oral dose in ICR mice. Twenty animals of each sex were randomly assigned to four groups of 5 rats each and were administered singly by gavage at dose levels of 0, and 2,500 mg/kg bodyweight. Mortalities, clinical findings, and body weight changes were found and complete gross postmortem examinations were performed. Throughout the study period, no treatment-related deaths were observed. There were no adverse effects in clinical signs, body weight, and gross findings at any dose tested. The results showed that the single oral administration of safflower seed did not cause any toxic effect at the dose levels of 2,500 mg/kg in rats and the minimal lethal dose was considered to be over 2,500 mg/kg body weight for both sexes.

隔板에 의해 分離된 四角密閉空間內의 自然對流

金壽淵,鄭仁基,金重燁,朴日均 영남대학교 공업기술연구소 1984 연구보고 Vol.12 No.1

Natural convection heat transfer in a two-dimensional, square enclosure fitted with a partial vertical partition was investigated numerically using ADI and SOR methods. The vertical walls of the enclosure were maintained isothermal at different temperatures, while the horizontal walls and the partition were insulated. The computation were carried out with air, Pr=0.733, in the Grashof numbers range 1.25×10³≤Gr≤2×10⁴, for seven cases as the lengths and positions of the partition were varied. The partition were found to significantly effect on the heat transfer and the flow pattern within an enclosure.

토끼에서 Etofenprox와 Spinosad 합제의 국소자극성 시험

황윤환,김명석,송인배,박병권,양승호,임용현,송치용,안성한,남현수,임정교,정상일,명노일,윤효인 忠南大學校 獸醫科大學 附設 動物醫科學硏究所 2008 動物醫科學硏究誌 Vol.15 No.1

This study was performed to evaluation the skin and eye irritation of etofenprox 8% and spinosad 4% combination in male New Zealand White rabbits. In skin irritation test, the combination of etofenprox and spinosad did not showed any change of body weight but caused slight skin irritation with the P.I.I. (primary irritation index) value 0.25. The etofenprox and spinosad combination showed severe eye irritation 1 h, 24 h, 48 h, and 72 h after ocular treatment, having the A.O.I. (acute ocular irritation) value of 37.3. Therefore, these result indicated that the combination of etofenprox and spinosad might be irritant formulation on eye and skin.

지반침하예방 최적 모니터링 기술 개발을 위한 기술수준 분석

정연인(Chung, Youn-In),박원주(Park, Won-Joo),최병일(Choi, Byoung-Il) 한국방재학회 2020 한국방재학회논문집 Vol.20 No.1

최근 지반침하 현상이 이슈화되고, 매년 증가함에 따라 정부 및 지자체에서는 지반침하 예방을 위해 여러 가지 대책을 발표하고있다. 특히, 국토부에서는 주요내용에 ‘불안요소에 대한 선제적 모니터링 및 관리’를 제시하는 등 지반침하 관련 지하시설물모니터링 기술개발의 중요성이 부각되고 있다. 도심지 지반침하 발생 원인으로 노후 상하수도관로 파손이 가장 크게 지목받고있으며, 여기에 적용할 수 있는 모니터링기술은 크게 2가지 선제적 및 긴급 대응 기술로 나눌 수 있다. 정확한 관로상태진단을 위해 관련기술 개발이 국내·외에서 활발히 진행되고 있지만 지반침하가 일어날 수 있는 환경과 직접적으로 연계한기술개발은 이뤄지지 않고 있는 실정이다. 따라서 최근 이슈화되고 있는 도심지 지반침하 예방을 위해 상하수도관로를 계측및 탐사 할 수 있는 새로운 기술개발이 필요할 것으로 판단된다. 본 연구에서는 상하수도관로 파손에 의한 지반침하 대응을위한 계측 및 탐사 기술 개발 전 계측기준 분석 및 기술사양 분석연구를 수행하고자 한다. 이를 통해 개발기술의 효율성, 기술도입 가능성 등을 분석한 후 최적의 기술 사양을 제안하고자 한다. As ground subsidence has recently been gaining public attention, the government (the Ministry of Land, Infrastructure and Transport) as well as local autonomous bodies have recommended preemptive monitoring and have announced a variety of preventive measures against this catastrophic phenomenon. Furthermore, risk factors associated with ground subsidence were identified in a bid to raise awareness regarding the importance of developing preemptive and energy-response technologies (for checking and monitoring underground facilities). Despite the ongoing efforts to reliably detect and identify the condition of buried pipes at home and abroad, very little has been accomplished when it comes to developing technologies for preventing ground subsidence. Therefore, developing new and innovative technologies to (1) inspect and explore water pipes, sewage pipes, and ducts, and (2) to prevent ground subsidence (which has recently become a major threat) in urban areas is crucial. To this end, this study aims to conduct an in-depth analysis on the measurement and exploration criteria and on technical specifications, prior to developing measurement and exploration technologies (as preventive measures against ground subsidence due to damage to water and sewage pipelines). Based on these, the applicability, efficiency, and feasibility of the technologies will be evaluated, and optimal technical specifications will be suggested.

Determination of metabolic enzymes involved in biotransformation of IN-1130, an ALK5 inhibitor

Yeo Woon KIM(김여운),Kyung Nan MIN(민경난),Jung In JEE(지정인),Kyoung Jin KWON(권경진),Seo Youn GO(고서운),Yong Kook KIM(김용국),Il Young CHO(조일영),Youn Jee CHUNG(정연지),Dae-kee KIM(김대희),Yhun Yhong SHEEN(신윤용) 환경독성보건학회 2007 한국독성학회 심포지움 및 학술발표회 Vol.- No.-

가스交煥過程을 包含하는 4行程 CI 機關의 Cycle Simulation

金重燁,金壽淵,權俊博,鄭仁基 嶺南大學校 工業技術硏究所 1985 연구보고 Vol.13 No.1

A comprehensive cycle simulation was developed to predict the performance of CI engine including intake and exhaust systems with variation of operating conditions and design factors. In this work, the gas-exchange model, compression and expansion model, single-zone combustion model and heat transfer model were used. In order to confirm the feasibility of the simulation program, the calculated results were compared with the experimental results. Pressure diagram, I.M.E.P. and S.F.C. by means of calculations showed acceptable quantitative agreement with the experimental data. A parametric study of the effect of variations in injection timing and inlet pressure was carried out. Therefore, the optimal design of CI engine will be possible by the cycle simulation using this program.