Pharmacokinetic analysis for the development of new potent anti-HIV-1 agents, the KR-V series

이영미,김진석,한상섭,신호철,Lee, Young-mi,Kim, Jin-suk,Han, Sang-seop,Shin, Ho-chul The Korean Society of Veterinary Science 2000 大韓獸醫學會誌 Vol.40 No.3

새로운 항HIV 후보물질인 19개의 KR-V 경구제제의 생체이용률을 평가하기 위해 랫드에서 정맥 및 경구투여후 약물동태를 연구하였다. 혈장내 KR-V 화합물들의 검출은 HPLC-UVD 법을 이용하여 분석하였다. 19개 KR-V series 중 KR-V 3, 10, 14, 16 및 18-1만이 랫드에서 경구로 흡수되어 생체이용성을 나타내었다. 10mg/kg의 정맥투여후 약물 통태 연구에 있어서는 5개물질, KR-V3, 10, 14, 16 및 18-1의 소실 반감기는 서로 비슷하였으나 KR-V 3, 10, 14 및 16의 총청소율($CL_{total}$, >4L/hr/kg)은 KR-V 18-1(1.1L/hr/kg) 보다 유의성있게 높았다. KR-V 3, 10, 14 및 16에 비해 KR-V3 18-1이 혈중곡선하면적(AUC, $8.97{\mu}g{\cdot}hr/ml$)은 크고 겉보기분포용적(Vd, 0.58L/kg)은 적었다. 50mg/kg의 경구투여후 약물동태 연구에 있어서는 KR-V 18-1의 반감기가 다른 4개의 물질에 비해 비록 짧았지만 경구 AUC($3.659{\mu}g{\cdot}hr/ml$), 최고혈중농도($C_{max}$, $1.891{\mu}g/ml$) 는 현저히 높았다. 또한 별도의 in virus 실험결과 생체이용률을 나타낸 이들 5개의 물질들 중 KR-V 18-1만이 HIV-1 돌연변이종(mutants)에 대한 억제효과를 나타내었다. 따라서 KR-V 18-1이 항에이즈(AIDS)제의 새로운 후보물질 혹은 선도물질로서 가능성이 기대되었다. The pharmacokinetic properties of KR-V compounds, recently developed as new anti-HIV agents, were studied after i.v. and p.o. administration in rats. The concentrations of the KR-V series were determined in rat plasma using an high-performance liquid chromatography (HPLC)-UV detection system. Of the 19 KR-V compounds investigated in the present study, only KR-V 3, 10, 14, 16 and 18-1 showed oral bioavailability. The plasma concentration-time data could be adequately described by an one-compartment open model. In the i.v. kinetic study (10mg/kg), the CLt of KR-V 3, 10, 14 and 16 (>4L/hr/kg) were significantly higher than that of KR-V 18-1 (1.1 L/hr/kg). The AUC of KR-V 18-1 was greater ($8.97{\mu}g{\cdot}hr/ml$) than that of the other compounds, but the Vd (0.58 L/kg) was lower. In the p.o. kinetic study (50mg/kg), although the t-1/2 of KR-V 18-1 was shorter than that of the other compounds, the AUC ($3.659{\mu}g{\cdot}hr/ml)$ and $C_{max}(1.891{\mu}g/ml$) were markedly higher. In a seperated in vitro experiment, only KR-V 18-1, of the 5 compounds with bioavailibility, exhibits potent activity against HIV-1 mutant strains. Therefore, KR-V 18-1 is expected to become a new potent anti-AIDS drug candidate/lead compound.

논문편 : 한국 농촌여성의 경제적 역할 변화에 대한 사례연구 - 충청북도 청원군 산마을을 중심으로 -

이영미,김주희 ( Young Mi Lee,Joo Hee Kim ) 대한가정학회 1991 Human Ecology Research(HER) Vol.29 No.3

들뢰즈의 "주름 : Le Pli"을 통해 본 바로크 건축의 특성

이영미,천득염,Lee, Young-Mi,Cheon, Deuk-Youm 한국건축역사학회 2008 건축역사연구 Vol.17 No.6

The primary object of this study lies in reilluminating the meaning of the Baroque, through studying arts and architecture by means of the features of Baroque aesthetics suggested by Deleuze in his writing 'Le Pli' on the basis of Leibniz's 'Pli' concept. Through this study we can see the following. In the first place, the six features - pli, separation between the inner and the exterior, highs and lows, unfolding, texture and paradigm presented as the features of Baroque aesthetics - have to be understood not as being independent features but as those derived from a series of continuous process of folding and unfolding. In the second place, Deleuze's thinking ranging from the 'Pli' of the Baroque to the paradigm derived on the ground of Leibniz thinking is a dynamic world of folding and unfolding, ultimately seeking unity through the topological changes and succession repeating deterritorization and reterritorization. In the third place, most architectural trends claiming 'Fold Architect' or the 'Pli' of Deleuze as their architectural philosophy are committing errors of mass-producing standardized designs by confining the meaning of Deleuze's 'Pli' concept into a simple reproduction of plied superficial things. With this finding in mind, the concept of folding and unfolding examined through reilluminating the Baroque Architecture where the 'Pli' concept is embodied, suggests to us that the problems of contemporary architecture should be rightened, and shows us that it can become an architectural philosophy which can be concretely realized in architecture.

전도성 고분자의 전기화학적 합성과 특성분석

이영미,여태환 ( Young Mi Lee,Tae Whan Yeu ) 한국화학공학회 1996 화학공학의이론과응용 Vol.2 No.2

Determination of new anti-HIV agents, the KR-V series, in rat plasma using microbore high-performance liquid chromatography

이영미,박명진,김진석,신호철,Lee, Young-mi,Park, Myung-jin,Kim, Jin-suk,Shin, Ho-chul The Korean Society of Veterinary Science 2000 大韓獸醫學會誌 Vol.40 No.4

최근 새로 개발중인 항AIDS치료제 KR-V 시리즈를 대상으로 HPLC-UV 검출법을 이용해 랫드 혈장중에서 분석법을 검토하였다. 분석컬럼은 $C_{18}$($5{\mu}m$, $250{\times}2.0mm$ I.D.)을 이용하였으며 이동상은 물과 ACN의 혼합액(40/60, v/v)으로 하였다. 이상의 조건에서 모든 KR-V 물질들은 용출시간 4-12분에 비교적 신속하게 잘 분리되었으며 정량한계는 15-30 ng/ml, 혈장중 회수율은 KR-V 2, 7 및 15를 제외하고는 85%(C.V. <10%) 이상으로 나타내었다. Ester 구조를 포함하고 있는 KR-V 2, 7 및 15는 혈장중에서 극히 불안정하여 유도체 개발의 분자설계상 제외시키는 것이 좋을 것으로 사료되었다. 결론적으로 본 HPLC-UV 검출법온 KR-V 시리즈 물질들의 약물동태연구를 위한 약물 분석법의 유효한 방법으로 검토되었다. We have developed a rapid, simple and precise high-performance liquid chromatographic (HPLC) method using an UV detection system for the determination of new anti-HIV candidates, nineteen KR-V compounds, in rat plasma. We used a analytical columnn of $C_{18}$ ($5{\mu}m$, $250{\times}2.0mm$ I.D.) and a mobile phase of water and ACN mixture (40/60, v/v). Under these conditions, all the KR-V compounds were readily separated from plasma with retention times of 4-12 min. The limits of quantitation for the 19 KR-V compounds were 15-30 ng/ml. The recoveries from the plasma were higher than 85% (C.V.<10%) with exception of KR-V 2, 7 and 15. The compounds KR-V 2, 7 and 15, containing ester moieties, were found to be unstable in plasma. This result suggests that esters, like KR -V 2, 7 and 15, should be excluded from future structure design studies of anti-HIV KR-V agents. In conclusion, the current HPLC method is a valuable analytical tool for investigating the pharmacokinetics of the KR-V series in rats.

한국 전통건축과 랜드스케이프 건축에 나타난 생태학적 특성

이영미,천득염,Lee, Young-Mi,Cheon, Deuk-Youm 한국건축역사학회 2005 건축역사연구 Vol.14 No.4

The main aim of this research is centered on the relation between nature and humans, and is to study the ecological characteristics appearing both in Landscape Architecture, one of the currents of ecological architecture as the architectural solution on the relation between humans and nature, and in our traditional architecture. Through this study, we were able to see that our traditional architecture was influenced by our ancestor's view of nature, and that the foremost feature of our ancestor's view of nature on our traditional architecture is not conflicting with nature, but, instead it is complying with it through seeking harmony with nature. Also we could see that our ancestor's view of nature is similar to Landscape Architecture having come to the fore toward the tendency of modern ecological paradigm in that it is the representation seeking the organic view of nature pursuing the oneness among artificial structure, humans, and nature. That is, we could figure out that various ecological features appearing in modem Landscape Architecture had been represented for a long long time, in a natural fashion, In the manner of space makeup in our traditional architecture. This is the characteristic of our ecological thinking system understanding nature and humans at the same context, and it has come down not only to our everyday living but to the manner of architectural solutions as well. Through this research, we could reconsider the modern value of ecological architecture inherent in our traditional architecture.

여대생의 체중조절에 대한 관심도와 섭식 행동

이영미,이기완 ( Young Mee Lee,Ki Wan Lee ) 대한가정학회 1994 Human Ecology Research(HER) Vol.32 No.2

대장균 rnpA 돌연변이를 보완작용할 수 있는 Brevibacterium albidum 염색체 부위의 특성

이영미,채건상,박충웅,이영훈 ( Young Mi Lee,Keon Sang Chae,Chung Ung Park,Young Hoon Lee ) 생화학분자생물학회 1990 BMB Reports Vol.23 No.4

The chromosomal region containing the gene capable of complementing the E. coli rnpA mutation was obtained from genomic DNA of Brevibacterium albidum. The selection procedure was based on the formation of an enzymatically functional hybrid RNase P enzyme by heterologous gene products in E. coli. Unlike the E. coli rnpB gene, the B. albidum DNA region on a multicopy plasmid did not complement the E. coli rnpB mutation. The deletion analysis indicates that the rnpA-complementing activity resides in the 2.75 kb region.

발반사 요법이 탄광부 진폐증 환자의 우울과 불안에 미치는 영향

이영미,Lee, Young-Mee 한국재활간호학회 2005 재활간호학회지 Vol.8 No.1

Purpose: This study was to evaluate the effects of foot reflexology on depression and anxiety in coal workers' pneumoconiosis. Method: The research design used was a non-equivalent control group pretest-posttest design. The foot reflexology was performed for 60 minutes twice a week through five weeks in the experimental group, not in the control group. The subjects of this study consisted of both the experimental group of twenty-nine and the control group of thirty coal workers' pneumoconiosis. The data were collected from December 10, 2002 to February 15, 2003. To evaluate the effects of foot reflexology the scores of depression and anxiety were measured before and after the experiment in both groups. Data of this experiment were analyzed by Chi-square test, t-test, unpaired t-test, ANCOVA and Repeated Measures ANOVA with the SAS Program. Results: The score of depression decreased in the experimental group, not in the control group. There was a significant difference of depression between the two groups. The score of anxiety decreased in the experimental group, not in the control group. There was a significant difference of anxiety between the two groups. Conclusion: As a summary of the study results, foot reflexology was regarded that it attributed to the emotional promotion of coal workers' pneumoconiosis. Therefore the foot reflexology is considered that might be used as an effective skill of nursing intervention program for coal workers' pneumoconiosis.

Escherichia coli M1 RNA 유전자의 전사 종결

이영미,이영훈,박충웅 ( Young Mi Lee,Young Hoon Lee,Chung Ung Park ) 생화학분자생물학회 1989 BMB Reports Vol.22 No.3

The deletion experiment at the 3` flanking sequences of the gene for M1 RNA, the RNA component of Escherichia coli ribonuclease P, was carried out to estimate the efficiency of tandem terminators, T1, T2, and T3. The serially deleted sequences of the M1 RNA gene were cloned into GalK expression vector pK0100 and relative galactokinase activities were measured. The major termination occurred at the first terminator, T1, and three terminators all together functioned with almost 100% efficiency. Biosynthesis of the polypeptides encoded by readthrough transcripts from the terminators was also discussed.