Chlorpropamide 2-hydroxylation is catalysed by CYP2C9 and CYP2C19 <i>in vitro</i>: chlorpropamide disposition is influenced by CYP2C9, but not by CYP2C19 genetic polymorphism

Shon, Ji-Hong,Yoon, Young-Ran,Kim, Min-Jung,Kim, Kyoung-Ah,Lim, Young-Chae,Liu, Kwang-Hyeon,Shin, Dong-Hoon,Lee, Chung Han,Cha, In-June,Shin, Jae-Gook Blackwell Science Ltd 2005 British journal of clinical pharmacology Vol.59 No.5

<P>Aims</P><P>We evaluated the involvement of cytochrome P450 (CYP) isoforms 2C9 and 2C19 in chlorpropamide 2-hydroxylation <I>in vitro</I> and in chlorpropamide disposition <I>in vivo</I>.</P><P>Methods</P><P>To identify CYP isoforms(s) that catalyse 2-hydroxylation of chlorpropamide, the incubation studies were conducted using human liver microsomes and recombinant CYP isoforms. To evaluate whether genetic polymorphisms of CYP2C9 and/or CYP2C19 influence the disposition of chlorpropamide, a single oral dose of 250 mg chlorpropamide was administered to 21 healthy subjects pregenotyped for CYP2C9 and CYP2C19.</P><P>Results</P><P>In human liver microsomal incubation studies, the formation of 2-hydroxychlorpropamide (2-OH-chlorpropamide), a major chlorpropamide metabolite in human, has been best described by a one-enzyme model with estimated <I>K</I><SUB><I>m</I></SUB> and <I>V</I><SUB>max</SUB> of 121.7 ± 19.9 µ<SMALL>M</SMALL> and 16.1 ± 5.0 pmol min<SUP>−1</SUP> mg<SUP>−1</SUP> protein, respectively. In incubation studies using human recombinant CYP isoforms, however, 2-OH-chlorpropamide was formed by both CYP2C9 and CYP2C19 with similar intrinsic clearances (CYP2C9 <I>vs.</I> CYP2C19: 0.26 <I>vs.</I> 0.22 µl min<SUP>−1</SUP> nmol<SUP>−1</SUP> protein). Formation of 2-OH-chlorpropamide in human liver microsomes was significantly inhibited by sulfaphenazole, but not by <I>S</I>-mephenytoin, ketoconazole, quinidine, or furafylline. In <I>in vivo</I> clinical trials, eight subjects with the <I>CYP2C9</I>*<I>1/</I>*<I>3</I> genotype exhibited significantly lower nonrenal clearance [*<I>1/</I>*<I>3 vs.</I>*<I>1/</I>*<I>1</I>: 1.8 ± 0.2 <I>vs.</I> 2.4 ± 0.1 ml h<SUP>−1</SUP> kg<SUP>−1</SUP>, <I>P</I> < 0.05; 95% confidence interval (CI) on the difference 0.2, 1.0] and higher metabolic ratios (of chlorpropamide/2-OH-chlorpropamide in urine: *<I>1/</I>*<I>3 vs.</I>*<I>1/</I>*<I>1</I>: 1.01 ± 0.19 <I>vs.</I> 0.56 ± 0.08, <I>P</I> < 0.05; 95% CI on the difference − 0.9, − 0.1) than did 13 subjects with <I>CYP2C9</I>*<I>1/</I>*<I>1</I> genotype. In contrast, no differences in chlorpropamide pharmacokinetics were observed for subjects with the <I>CYP2C19</I> extensive metabolizer <I>vs.</I> poor metabolizer genotypes.</P><P>Conclusions</P><P>These results suggest that chlorpropamide disposition is principally determined by CYP2C9 activity <I>in vivo</I>, although both CYP2C9 and CYP2C19 have a catalysing activity of chlorpropamide 2-hydroxylation pathway.</P>

연구 논문 : 전기화학적 마이크로머시닝 기술을 이용한 균일한 니오븀 표면 에칭 연구

김경민 ( Kyung Min Kim ),유현석 ( Hyeon Seok Yoo ),박지영 ( Ji Young Park ),신소운 ( So Woon Shin ),최진섭 ( Jin Sub Choi ) 한국공업화학회 2014 공업화학 Vol.25 No.1

본 연구에서는 micro-contact printing을 통하여 니오븀 호일 표면 위에 균일한 에칭 pits를 형성하였다. 균일한 보호층을 형성하고자 전해연마의 효과를 확인하였으며, 기존의 O2 플라즈마 공정 없이 손쉽게 균일한 에칭 pits를 형성시킬 수 있는 조건을 확인하였다. 메탄올 혼합 전해질을 사용하여 10 min 동안 에칭을 진행한 결과 니오븀 호일 표면 위에 지름과 간격이 각각 10 μm와 5 μm로 잘 정렬된 에칭 pits를 관찰하였다. We describe the preparation of highly-ordered etching pits on the Nb foil through a micromachining. The effects of electro-chemical polishing on the formation of uniformly-patterned protective epoxy layer was investigated. Unlike the previous proc-ess using O2 plasma, well-ordered etched pits were prepared without any dry processes. As a result, the Nb foil with the well-ordered pits of 10 μm × 5 μm could be obtained by electrochemical etching in methanolic electrolytes for 10 min.

어류 알의 Protease Inhibitor 활성 분포

지성준 ( Seong Jun Ji ),이지선 ( Ji Sun Lee ),신준호 ( Joon Ho Shin ),박권현 ( Kwon Hyun Park ),김진수 ( Jin Soo Kim ),김경섭 ( Kyoung Sub Kim ),허민수 ( Min Soo Heu ) 한국수산과학회(구 한국수산학회) 2011 한국수산과학회지 Vol.44 No.1

To identify and examine the distribution of proteolytic inhibitory activity in crude extracts from fish eggs, and to determine the applicability of these protease inhibitors as anti-degradation agents in surimi-based products and fish meat, we compared the inhibitory activities of various extracts from fish eggs to those of commercial proteases, such as trypsin and papain. We used the optimal conditions for the screening of trypsin activity: 30 ug/uL of 0.1 % trypsin and 0.6 mM Na-benzoyl-L-arginine-p-nitroanilide (BAPNA) with a pH of 8.0 at 40℃ for 60 min. The activities of papain and four commercial proteases were investigated after mixing with 100 ug/uL enzymes and 0.3% casein with a pH of 8.0 at 40℃ for 60 min. We performed a screening assay to detect the inhibitory activity (%) of crude extracts from eight species of fish eggs against the target proteases trypsin and papain. The assay revealed a wide distribution of trypsin and papain inhibitors in fish eggs. The specific inhibitory activities (11.6-28.6 U/mg) of crude extracts from fish eggs against trypsin and BAPNA substrate were higher than that (0.64 U/mg) of egg whites, used as a commercial inhibitor. The inhibitory activities of crude extracts from fish eggs against trypsin, and of egg whites against casein substrate (1.94-4.51 U/mg), were higher than those of papain (0.24-1.57 U/mg) and commercial protease (0.04-0.32 U/mg). The extracts from fish eggs were rich in protease inhibitors that exhibited strong inhibitory activity against trypsin, a serine protease, and papain, a cysteine protease.

헬스케어용 가다랑어(Katsuwonus pelamis) 통조림의 제조 및 특성

김현정 ( Hyeon Jeong Kim ),김민지 ( Min Ji Kim ),김기현 ( Ki Hyun Kim ),지성준 ( Seung Jun Ji ),임경훈 ( Kyung Hun Lim ),박권현 ( Kwon Hyun Park ),신준호 ( Joon Ho Shin ),허민수 ( Min Soo Heu ),김진수 ( Jin Soo Kim ) 한국수산과학회 2012 한국수산과학회지 Vol.45 No.3

This study was conducted to prepare canned skipjack tuna Katsuwonus pelamis in the mixture of isotonic beverage and tomato paste (ST-S) for use as a health food. An analysis of the time-temperature profile and viable cells showed that a reasonable F0 value for ST-S preparation was 4 min. The proximate composition of ST-S was 76.8% moisture, 20.2% crude protein, 0.8% crude lipid, 1.7% ash and 0.5% carbohydrate. The calorie content of ST-S was 94.8 kcal, which is 47.4% lower than that of commercial canned skipjack tuna in oil (ST-O) and 2.2% lower than that of commercial chicken breast in water (CB-B). The total amino acid content of ST-S was 18.54 g/100 g, which is 31.4% lower than that of ST-O and 7.9% lower than that of CB-B. The major amino acids in ST-S were aspartic acid and glutamic acid. An enrichment effect due to such minerals as phosphorus, potassium and iron would be expected on consuming 100 g of ST-S. The major fatty acids in ST-S were 16:0 (27.4%), 18:1n-9 (14.3%) and 22:6n-3 (27.8%), which are different from those in ST-O and CB-B. The major free amino acids in ST-S were glutamic acid (8.1%), histidine (38.6%) and its related dipeptide, such as anserine (15.7%). In an evaluation of taste, flavor and color, ST-S was found to be superior to ST-O and CB-B.

의과대학생과 일반대학생의 삶의 질 비교

민성길,신원철,김광일,정지인,김동기 대한신경정신의학회 2000 신경정신의학 Vol.39 No.6

연구목적 : 미래에 환자들의 신체적, 정신적 건강을 책임지게 될 의과 대학생 집단이 의학을 공부하는 과정에서 어떤 신체적, 정신적 및 사회적 문제들에 의해 고통받는지 알아보고 이의 개선방향을 발견하기 위해, 의과대학생들이 느끼고 있는 삶의 질에 대한 연구를 실시하였다. 방 법 : 1999년도에 연세대학교 의과 대학에 재학중인 본과 학생 317명과, 연세대학교 재학중인 일반 대학 150명을 대상으로 설문조사를 하였다. 조사도구는 세계보건기구 삶의 질 간편형 척도(WHOQOL-BREF)였다. 의과대학생과 일반대학생의 삶의 질을 각 항목(item)별, 영역(domain)별, 그리고 총점의 평균값을 비교하여, T-test로 검정하였고, 각 영역의 기여도를 다중회귀 분석으로 평가하였다. 결 과 : 전체점수에서는 차이를 보이지 않았다. 그러나 항목별점수에서는, 수면과 휴식, 성적 활동, 레저와 여가활동에 대한 참여와 기회에서는 의과대학생의 삶의 질이 유의하게 낮게 보고되었으며, 약물과 치료에 대한 의존도, 경제적 자원, 새로운 정보와 기술을 얻을수 있는 기회, 교통수단에서는 의과대학생의 삶의질이 유의하게 높게 보고되었다. 영역점수에서는, 사회적 관계 영역에서 의과대학생의 삶의 질이 낮게, 환경 영역에서는 높게 보고되었다. 그리고 의대생에서 신체적 건강, 환경, 그리고 사회적 관계 영역들이 삶의 질에 크게 기여하였고, 반면 일반대생에서는 심리적 영역과 환경 영역이 크게 기여하였다. 결 론 : 이와 같은 결과는 주로 의대생들의 사회적 관계 영역, 그리고 기타 하부척도에서는 수면과 휴식, 성적활동, 레저와 여가 활동에 대한 참여와 기회 등의 항목에서 삶의 질을 높이는 것이 필요하다는 것을 시사한다. Objectives : The quality of life of medical students was investigated and compared with that of general college students to identify what kind of problems medical students are suffering from. Method : Korean version of WHOQOL-BREF was administered to 317 medical students and 150 general college students of Yonsei University in 1999. Collected data were analyzed with t-test and multiple regression analysis Results: There was no significant difference in the total scores of WHOQOL-BREF between medical students and general college students. However, the scores of facets of sleep and rest, sexual activity, and participation and opportunities for recreation/leisure were significantly lower in medical students than in general colleges for recreation/leisure were significantly lower in medical students than in general college students, while the scores of facets of dependency on medication and treatment, financial resources, opportunities for acquiring new information and skills, and transport were significantly higher in medical students than in general college students. The score of social relationships domain was significantly lower in medical students than in general college students, while, the score of environmental domain was significantly higher in medical students than in general college students. Physical, environmental and social relationships domains contributed more to the quality of life of medical students than psychological domain while psychological and environmental domains contributed more to the quality of life of general college students than physical and social relationships domains. Conclusion : The result suggests that it is necessary to improve the quality of life of medical students in social relationships domain and in the facets of sleep and rest, sexual activity, participation and opportunities for recreation/leisure.

화병척도와 연구용 화병진단기준 개발

민성길,서신영,조윤경,허지은,송기준 大韓神經精神醫學會 2009 신경정신의학 Vol.48 No.2

Objectives The aim of this study was to identify the characteristic symptoms for diagnosis of Hwabyung (HB), a culture-related anger syndrome in Korea; to construct a rating scale for HB and test its validity and reliability; and propose diagnostic criteria for HB. Methods Subjects were male and female Korean patients, who were diagnosed following Structured Clinical Interview (SCID) as having depressive disorders, anxiety disorders and somatoform disorders and who reported as having self-labeled HB. A HB Scale was constructed with 22 of the most common symptoms of HB as identified by previous studies. The HB scale's inter-rated reliability was tested with 60 subjects. Its validity was tested by comparison between a HB only group(n=47) and depressive disorder only group (n=44). Logistic regression analysis was conducted to make a predictive model of HB. Based on these results diagnostic criteria for HB was proposed. Results Inter-rated reliability in each of all the items and the total score of the HB Scale were statistically significant. The HB scale differentiated HB from depressive disorder with statistical significance. In logistic regression analysis, the ability of the HB model to predict symptoms of heat sensation, ukwool/boon (feeling of unfairness), and subjective anger was high with sensitivity of 80.0%, specificity of 88.4% accuracy of 84.1% and area under ROC of 0.92. Based on these results and information from previous research, diagnostic criteria of HB were formulated. Conclusion The HB Scale was found to be reliable and valid. Consequently, diagnostic criteria of HB were proposed, to include subject anger, "kwool/boon" (Feeling of unfairness), expressed anger, heat sensation, hostility, "haan", pushing-up in the chest, epigastric mass, respiratory stuffiness, palpitation, dry mouth, sighing, racing thoughts, and lamentation.

난원공 개존을 통한 우심방에서 좌심방으로의 단락 진단에 있어 경흉부 심초음파 하모닉 영상의 유용성

신미승,강석민,장길진,변기현,하종원,정남식,허지회,이병인 대한순환기학회 2000 Korean Circulation Journal Vol.30 No.4

석면함유 슬레이트 지붕 물받이 퇴적물 중 석면 섬유 함유율

임지현,한솔민,김현석,신유민,박시은,허정윤,김민영,장봉기 순천향대학교 기초과학연구소 2022 순천향자연과학연구 논문집 Vol.28 No.1,2

This study attempted to determine the degree of asbestos release from the aging slate roof by comparing the asbestos content in the slate roof rain gutter with a colored steel plate (tin plate) over the slate roof. Four slate roof houses located in Haengmok-ri, Asan-si, Chungcheongnam-do, and one house constructed with a colored steel plate on the slate roof were selected to collect the sediment of the roof rain gutter. The asbestos fiber content was calculated by a point counting method using a polarization microscope after pretreatment with conversion treatment and hydrochloric acid treatment. The average asbestos content of the four slate roof rain gutter were 1.89%. However, asbestos was not detected in the Slate covering roof rain gutter, which were constructed on the slate roof. Asbestos fiber content was the highest at 2.89% in the slate roof rain gutter installed in 1976, followed by 2.44% in 1953. From the above results, it is necessary to minimize secondary damage as asbestos fibers released from slate roof houses to the surrounding atmosphere or leaked from slate roofs as rainwater may cause soil pollution and seriously affect residents' health. Although covering with colored steel plates (tin plates) has been shown to prevent the leakage of asbestos fibers to some extent, it is believed that a policy alternative to remove the slate roof as soon as possible is needed to solve the fundamental problem.

라우팅 브로커링에 기초한 분산 데이터베이스 액세스 메커니즘의 설계

신혜균,장지훈,김정선,최중민,우훈식 漢陽大學校 工學技術硏究所 1998 工學技術論文集 Vol.7 No.1

현재의 클라이언트 서버 환경에서는 수많은 이질적인 데이터베이스 서버들이 LAN과 WAN상에 분산되어 있다. 따라서 이들 서버의 위치에 관계없이 일관되고 확장성 있는 액세스 메커니즘을 클라이언트에게 제공하는 것이 필요하다. 본 논문에서는 라우팅 브로커링에 기초하여 분산되고 이질적인 데이터베이스에 대한 일관되고 위치 투명성과 확장성 있는 액세스 매커니즘을 제시한다. 본 고에서 제안한 메커니즘은 클라이언트와 다수의 서버사이의 중간계층으로서 작동되도록 java와 CORBA 그리고 JDBC의 최신 기술을 적용시켜 설계되었다. In current client/server environments, it is not uncommon to have multiple, heterogeneous database servers scattered on LAN or WAN. Therefore, it is desirable to provide clients with uniform and scalable access mechanism to connect to those servers in a location-transparent way. In this paper, we propose a uniform, location-transparent, and scalable access mechanism based on routing brokering scheme to access distributed, heterogeneous databases on LAN. The proposed mechanism is designed to act as a middle tier between clients and multiple servers, and adopts Java, CORBA and JDBC as its state -of-the -art techniques.

광주광역시 치매의 유병률과 위험인자의 도시-농촌 지역 비교

신일선,김재민,윤진상,김석재,양수진,김웅장,이승현,강순아,곽지영,이형영 大韓神經精神醫學會 2002 신경정신의학 Vol.41 No.6

연구목적 : 본 연구의 목적은 광주광역시의 도시 및 농촌 지역에 거주하는 노인에서 치매의 유병률과 위험인자를 조사하고자 하였다. 부가적으로 이 두 지역간에 치매의 유병률과 위험인자를 비교하고자 하였다. 방 법 : 광주광역시의 전형적인 도시와 농촌지역의 65세 이상의 노인(N=1,598)을 대상으로, 2단계의 역학연구를 수행하였다. 1차 선별 단계에서는 38명의 훈련된 연구보조원이 대상노인을 면담하여, 사회인구학적 특징을 조사하고 한국판 간이정신상태검사(Korean version of Mini-Mental State Examination ; MMSE-K)로 평가하였다. 2차 임상 진단 단계에서는 1차 단계에서 MMSE-K 점수가 24점 이하인 노인(N=431)을 대상으로, 전문연구팀의 임상적 평가를 통해 치매를 진단하고 원인질환별로 알쯔하이머병(Alzheimer's disease ; AD), 혈관성 치매(vascular dementia ; VaD) 및 기타 치매로 분류하였다. 대상노인에서 치매의 유병률을 측정한 후, 광주광역시 전체 노인의 연령보정 유병률을 산출하였다. 전체 대상에서 AD의 위험인자를 조사한 후, 도시와 농촌군으로 나누어 분석을 다시 시행하였다. 결 과 : 1차 및 2차 단계의 참가율은 각각 71.0%(N=1,134) 및 83.2%(N=410) 였다. 연구 참여 노인(N=1,134)에서 전체 치매, AD 및 VaD의 유병률은 최소 각각 9.7%, 5.2%, 1.8%였다. 광주광역시 전체 노인의 연령 보정 유병률은 각각 10.7%, 5.7%, 1.9%인 것으로 산출되었다. AD의 독립 위험인자는 고령, 여성, 무학이었다. 도시와 농촌에 따른 유병률의 차이는 파악되지 않았다. 그러나 AD의 위험인자는 지역에 따라 차이가 있었다. 도시 노인에게는 무학만이, 농촌 노인에게는 고령과 여성인 경우가 독립 위험인자였다. 결 론 : 광주광역시 노인에서 치매의 유병률은 높았고, 이는 국내 다른 지역에서 수행된 선행연구 결과와 유사하였다. 알쯔하이머형 치매의 위험인자는 도시와 농촌에 따라 다른 결과를 보였다. 본 연구 결과는 한국에서의 치매의 실태를 반영하며, 치매의 적절한 관리와 예방을 위해서는 지역성 특성이 고려되어야 함을 시사한다. Objectives : The purpose of this study was to investigate the prevalence rate and risk factors of dementia in an urban and a rural sample of older persons in the metropolitan Kwangju area, Republic of Korea. In addition, the prevalence rate and risk factors of dementia between the two samples were compared. Methods : A two-phase epidemiological study of residents aged 65 or over(N=1,598) was conducted in a highly developed, urban and a non-contiguous, poorly developed, rural area of metropolitan Kwangju. In the first(screening) phase, 38 trained research assistants collectively peformed in-home interviews for all participants. Detailed sociodemographic characteristics were gathered and the Korean version of Mini-Mental State Examination (MMSE-K) was administered. In the second (diagnosing) phase, diagnosis of dementia was established for those scoring 24 or less on the MMSE-K in the screening phase(N=431), and etiological types of dementia were classified to Alzheimer's disease(AD), vascular dementia(VaD) or miscellanous type by two teams of experts. Prevalence rate of dementia was determined in the participants, and age-standardized prevalence rate adjusted by age distribution in metropolitan Kwangju was estimated. For AD, the risk factors were investigated in all participants, and analyses were repeated for the urban and rural samples separately. Results : The participating rates in the first and second phases were 71.0%(N=1,134) and 83.2%(N=410), respectively. In the participants, the prevalence rates of dementia(all types), AD and VaD were 9.7%, 5.2% and 1.8%, respectively. The age-standardized prevalence rates were 10.7%, 5.7% and 1.9%, respectively. Aging, female gender and no education(complete lack of formal education) were identified as independent risk factors for AD. No difference between the urban and rural samples was observed in the prevalence rates of dementia(all types), AD and YaD. However, risk factors for AD differed between these areas. In the urban sample, no education was the only significant factor ; whereas, aging and female gender were identified as risk factors in the rural sample. Conclusion : A high prevalence rate of dementia was observed among old persons in metropolitan Kwangju, consistent with previous studies conducted in other Korean areas. The risk factor profi1es for AD differed between urban and rural settings. The results of this study reflect the current status of dementia in Korea and suggests that appropriate management and prevention strategies for dementia should be tailored toward the geographic settings.