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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.
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.
마우스복강비만세포에서 프로테아제 발현 표현형의 조직 의존적 변화
이영미,Lee, Young-Mi 대한수의학회 2001 大韓獸醫學會誌 Vol.41 No.4
To examine the fate of the injected peritoneal mast cells (PMCs), we injected PMCs (500 or $10^5$) derived from WBB6F1-green fluorescent protein(GFP) mice into stomach wall of $WBB6F1-W/W^v$ mice. When 500 PMCs were injected, the proportion of alcian blue $(AB)^+$ mast cells to $GFP^+$ mast cells in the muscle was 25.0% on day 1, but decreased to 0.9% on day 7. Then, it increased to 98.2% on day 35. In contrast,$GFP^+$ mast cells in the mucosa were not detectable on day 1, 3, and 7 after injection. On day 35, the proportion of $AB^+$ mast cells to $GFP^+$ mast cells in the mucosa was 97.0%. When $10^5$ PMCs were injected, the proportion of $AB^+$ mast cells to $GFP^+$ mast cells in the muscle was more than 88.2%, and that in the mucosa was more than 86.3% from day 1 through 35 after injection. These results indicated that percentage of degranulation on day 1, 3, 7, 14 after injection of 500 PMCs was significantly higher than that after injection of $10^5$ PMCs. Futhermore, when 500 PMCs were injected, protease expression phenotypes of PMCs changed from day 14 after injection. When $10^5$ PMCs were injected, protease expression phenotype of PMCs did not change after injection. Such degranulated PMCs may acquire the new phenotype and adapt the new tissue.
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.
이영미,이성희,김재백,손동환,Lee, Young-Mi,Lee, Sung-Hee,Kim, Jae-Baek,Sohn, Dong-Hwan 한국약제학회 1995 Journal of Pharmaceutical Investigation Vol.25 No.4
Antisense phosphorothioate oligodeoxynucleotide(PS-ODN) against $TGF-{\beta}$ was developed as scar formation inhibitor. The scar was caused collagen deposition due to overexpression of $TGF-{\beta}$ in wounded skin. The percutaneous absorption of partially modified PS-ODN(25 mer) was investigated for the purpose of its effective delivery. Though PS-ODN has high molecular weight (MW=8,000) and polyanionic charge, it was permeated through skin. The skin permeation of PS-ODN was markedly increased by the removal of stratum corneum and dermis. Moreover, the skin permeation of PS-ODN was decreased in the following order; hairless mouse skin>rat skin>human cadaver skin. Thus, PS-ODN represents a logical candidate for further evalution due to the potential for delivery into the wounded skin.
이영미,조경희,황규인,김은혜,김민철,홍순규,이홍금,Lee, Yung Mi,Cho, Kyung Hee,Hwang, Kyuin,Kim, Eun Hye,Kim, Mincheol,Hong, Soon Gyu,Lee, Hong Kum The Microbiological Society of Korea 2016 미생물학회지 Vol.52 No.1
부유 세균의 군집과 구별되는 생물막내 세균 군집은 다양한 수생태계에서 중요한 생태학적 역할을 수행한다. 자연계에서 생물막이 생태학적으로 중요함에도 불구하고, 남극 해양 환경에서 생물막 형성 과정 동안의 세균 군집 구조와 그들의 변화에 대한 연구는 수행되지 않았다. 본 연구에서, 남극 해양 환경에서 생물막 형성 초기 단계에서의 세균 군집 구조 변화를 16S rRNA 유전자의 pyrosequencing을 통해 수행하였다. 생물막내 전반적인 세균 군집은 주변의 해수의 군집과 매우 달랐다. 전체 세균 군집의 78.8%에서 88.3%를 차지한 Gammaproteobacteria와 Bacteroidetes의 상대적 풍부도는 생물막의 형성에 따라 급격하게 변하였다. Gammaproteobacteria는 생물막 형성 진행에 따라 증가하다가 (4일째에 75.7%), 7일째에 46.1%로 감소하였다. 반면, Bacteroidetes는 초기에서 중기로 갈수록 감소하다가 다시 증가하는 양상을 보이며, Gammaproteobacteria와 반대의 변화 양상을 나타내었다. 생물막 형성의 초기 과정에 우점 하는 OTU (>1%)들의 변화 양상은 시기에 따라 뚜렷한 차이를 보였다. Gammaproteobacteria에 속하는 종의 경우, 4일째까지 증가한 반면, 첫째날 가장 우점 하였던 문인 Bacteroidetes에 속하는 종은 4일째까지 감소한 후, 다시 증가하는 양상을 보였다. 흥미롭게, Pseudoalteromonas prydzensis가 67.4%를 차지하며 우점 하였는데, 이는 생물막 형성에 이 종이 중요한 역할을 수행함을 시사하는 것으로 보인다. Compared to planktonic bacterial populations, biofilms have distinct bacterial community structures and play important ecological roles in various aquatic environments. Despite their ecological importance in nature, bacterial community structure and its succession during biofilm development in the Antarctic marine environment have not been elucidated. In this study, the succession of bacterial community, particularly during the early stage of biofilm development, in the Antarctic marine environment was investigated by pyrosequencing of the 16S rRNA gene. Overall bacterial distribution in biofilms differed considerably from surrounding seawater. Relative abundance of Gammaproteobacteria and Bacteroidetes which accounted for 78.9-88.3% of bacterial community changed drastically during biofilm succession. Gammaproteobacteria became more abundant with proceeding succession (75.7% on day 4) and decreased to 46.1% on day 7. The relative abundance of Bacteroidetes showed opposite trend to Gammaproteobacteria, decreasing from the early days to the intermediate days and becoming more abundant in the later days. There were striking differences in the composition of major OTUs (${\geq}1%$) among samples during the early stages of biofilm formation. Gammaproteobacterial species increased until day 4, while members of Bacteroidetes, the most dominant group on day 1, decreased until day 4 and then increased again. Interestingly, Pseudoalteromonas prydzensis was predominant, accounting for up to 67.4% of the biofilm bacterial community and indicating its important roles in the biofilm development.
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.