Dose-linear pharmacokinetics of oleanolic acid after intravenous and oral administration in rats

Jeong, Dong Won,Kim, Young Hoon,Kim, Hui Hyun,Ji, Hye Young,Yoo, Sun Dong,Choi, Won Rack,Lee, Soo Min,Han, Chang-Kyun,Lee, Hye Suk WILEY PUBLISHERS 2007 BIOPHARMACEUTICS AND DRUG DISPOSITION Vol.28 No.2

<P>The pharmacokinetics of oleanolic acid was evaluated in vitro and in vivo. From Caco-2 cell permeation studies, oleanolic acid was a low permeability compound with no directional effects, suggesting a low in vivo absorption mediated by a passive diffusion. Oleanolic acid was metabolically unstable following incubation with rat liver microsomes in the presence of NADPH. After intravenous injection at doses of 0.5, 1 and 2 mg/kg doses, oleanolic acid showed dose-linear pharmacokinetics as evidenced by unaltered CL (28.6–33.0 ml/min/kg), V<SUB>ss</SUB> (437–583 ml/kg), dose-normalized AUC (16.0–17.9 µg min/ml based on 1 mg/kg) and t<SUB>1/2</SUB> (41.9–52.7 min). Following oral administration of oleanolic acid at doses of 10, 25 and 50 mg/kg, T<SUB>max</SUB>, t<SUB>1/2</SUB>, dose-normalized C<SUB>max</SUB> (66–74 ng/ml based on 25 mg/kg) and dose-normalized AUC (5.4–5.9 µg min/ml based on 25 mg/kg) were comparable between 25 and 50 mg/kg dose, but the plasma concentrations at 10 mg/kg dose were not measurable as they were below the limit of quantitation (2 ng/ml). The absolute oral bioavailability was 0.7% for oral doses of 25 and 50 mg/kg. The extent of urinary excretion was minimal for both i.v. and oral doses. The very low oral bioavailability of oleanolic acid could be due to a poor absorption and extensive metabolic clearance. Copyright © 2007 John Wiley & Sons, Ltd.</P>

혈액 투석 환자에서 중심정맥 협착에 대한 스텐트 삽입술 : Wallstent Placement

임대승,노상필,이유선,정승현,김보영,이정우,강정아,김정희,이민수,정준용,최시완,정진옥,성인환,이강욱,신영태 충남대학교 의과대학 의학연구소 2002 충남의대잡지 Vol.29 No.1

Stenosis of central vein is a common complication arising after percutaneous subclavian vein catheter insertion performed for temporary vascular access in chronic renal failure patients undergoing hemodialysis. There are several treatment methods for the condition like percutaneous angioplasty(PTA), stent insertion, and surgery, but recent trend is toward PTA and stents. Among the patients diagnosed with chronic renal failure from March 1993 to May 2002 and undergoing hemodialysis through AV fistula, the 14 Patients in whom central vein stenosis arose were selected for the study. A total of 28 percutaneous interventions(5 PTA and 23 stent placement) were performed, and restenosis rate and the time taken till the restenosis in de novo lesions and instant lesions were compared. All 28 cases were operated successfully. The 14 cases that received both anigioplasty and stent placement initially. (de novo lesion : 14 cases), Among the 10 cases with de novo lesion that followed up more than 1 year, 3 cases are currently undergoing hemodialysis without restenosis, and the remaining 7 cases have recurred stenosis with the mean time to restenosis of 10.9 months. In the 7 cases in whom stenosis recurred, 11 interventions were done(instent lesion: 11 cases). 4 of these were using only ballon angioplasty with 100% restenosis rate and the mean time of 3 months until restenosis. The remaining 7 cases were using both balloon angioplasty and stent placement, also with 100% restenosis rate but with the mean time of 12 months until restenosis, which was later than the group receiving only balloon angioplasty. In treating the patients with central vein stenosis, stent placement seems to be more advantageous over PTA in terms of restenosis rate and the mean duration of patency. In the case of instent lesion, inserting the stent for the second time after stenosis recurred lengthened the duration of patency compared to performing balloon angioplasty alone.

신장기능영상용 방사성의약품 Bz - MAG3 ( Benzoylmercaptoacetylglycylglycylglycine ) 의 키트화 및 체내분포

고창순(Chang Soon Koh),이명철(Myung Chul Lee),정준기(June Key Chung),이동수(Dong Soo Lee),김영주(Young Ju Kim),정재민(Jae Min Jeong),장영수(Young Soo Chang),조정혁(Jung Hyuk Cho) 대한핵의학회 1996 핵의학 분자영상 Vol.30 No.3

N/A The MAG3 is a tubular excreting radiopharmaceutical for renal image. We synthe-sized benzoyl MAG3 (Bz-MAG3) and made a kit for labeling with Tc-99m. We checked the labeling effeciency of Tc-99m labeled MAG3 and biodistribution. Labeling efficiency was checked by TLC- SG (acetonitrile/H2O=2/1). After injecting of 1 mCi of Tc-99M-MAG3 to ICR-mice, Tmax(min), T1/2(min) were obtained in the renogram. Sequencial images (30sec, 2min, 5min, 10min, 15min, 20min) of TC-99m-MAG3 were compared with those of commercial Tc-99m-DTPA (Du Pont Merck Pharmaceutical Co.) kit. 1) The Rf value of synthesized Tc-99m-MAG3 was 0.78 and labeling efficiency was 97.5±1.9% (n=10). 2) The dynamic images of the Tc-99m-MAG3 were better than those of the Tc-99m-DTPA. 3) The Tmax(min.) and T1/2(min.) of Tc-99m-MAG3 (n=10) were 1.5±0.5 (left), 1.4±0.4(right), and 4.3±1.4 (left), 4.8±2.0 (right), respectivel. The Tmax(min.) and T1/2(min.) of Tc-99m-DTPA (n=7) were 2.7±1.6 (left), 2.7±1.6 right), and 3.8±1.7 (left), 4.5±2.7 (right), respectively. The quaility of image and labeling efficiency of the synthesized Bz-MAG3 kit were excellent, that it was supposed to be used in routine clinical work.

Soft, adhesive and conductive composite for electroencephalogram signal quality improvement

Jeong E Jin,Seohyeon Kim,Hyeji Yu,Keyong Nam Lee,Young Rag Do,Seung Min Lee 대한의용생체공학회 2023 Biomedical Engineering Letters (BMEL) Vol.13 No.3

Since electroencephalogram (EEG) is a very small electrical signal from the brain, it is very vulnerable to external noise ormotion artifact, making it difficult to measure. Therefore, despite the excellent convenience of dry electrodes, wet electrodeshave been used. To solve this problem, self-adhesive and conductive composites using carbon nanotubes (CNTs) in adhesivepolydimethylsiloxane (aPDMS), which can have the advantages of both dry and wet electrodes, have been developed bymixing them uniformly with methyl group-terminated PDMS. The CNT/aPDMS composite has a low Young's modulus,penetrates the skin well, has a high contact area, and excellent adhesion and conductivity, so the signal quality is enhanced. As a result of the EEG measurement test, although it was a dry electrode, results comparable to those of a wet electrode wereobtained in terms of impedance and motion noise. It also shows excellent biocompatibility in a human fibroblast cell test anda week-long skin reaction test, so it can measure EEG with high signal quality for a long period of time.

식용유지의 誘電특성에 관한 연구

민용규,정헌상 충북대학교 농업과학기술연구소 1991 農業科學硏究 Vol.9 No.2

In order to predict the quality of edible oils with electric properties the dielectric properties of the fresh and the thermally oxidized soybean and corn oil were determined at room temperature in the frequency from 0.2 to 100kHz, and also physical and chemical properties of these oils were determined by AOAC methods and the correlationship among these properties was investigated. Thermal oxidation was carried out at 180℃ for 12 hrs. The dielectric constant of edible oils showed the characteristic of Debye's dispersion with frequency and remarkable decrease around 1kHz. Dielectic loss tangent showed the peek around 4kHz frequency. These phenomena could be thought as the result from the frequency properties of dipole orientational polarization. Due to the increase of polar materials, free fatty acid value, peroxide value, density, dielectric constant, and dielectric loss tangent increased in proportion to the thermal oxidation time. Accordingly, the index of rancidity of edible oils could be predicted by measurement of the dielectnc properties. Key Words : Soybean oil, Corn oil, Dielectric constant, Thermal oxidation, Dielectric loss tangent.

대장암종에서 암관련 유전자들의 Promoter Methylation과 암종 발생 및 진행과의 관게에 대한 연구

정동준,이정은,민영기,조성우,백무준,양승하,김의한,김창진 순천향대학교 교수학습개발센터 2004 Journal of Soonchunhyang Medical Science Vol.10 No.3

The colorectal corcinoma is one of the most common malignant tumor in Korea and its carcinogenic mechanism has not been elucidated exactly yet. So far, the most common carcinogenic mechanism has been known to be multiple genetic changes. But, the CpG island hypermethylation has been revealed to be one of the most important carcinogenic mechanism second to the genetic changes. The epigenetic changes characteristically imprint and transfer to the next generation without changes of nucleotide sequences. When the CpG island of promoter or 5'- exon 1 of a specific gene is methylated by DNA methyltrasferases (DNMTs), the gene expression is inhibited. Carcinogenic mechansisms by promoter methylation has been well known, but the progression of the cancer has not been elucidated yet. The molecular researches on the carcinogenic mechanisms largely depended on the tumor tissue containing various components of cell, due to difficulties in harvesting pure homogeneous tumor cells. Promoter methylatonof the cancer related genes as APc, hMLH2, p16, DAP-K and MGMT in 50 cases of sporadic colorectal carcinoma was studied. The pure normal colorectal epithelial cells, and cancer cells from superficial and deep invasive portion were harvested respectively by laser captured microdissection(LCM), and DNA was extracted from them. The promoter methylation was studied by methylation specific poymerase reaction (MSP) after bisulfite modification of the DNA and the expression of the genes by immunohistochemistry. The results suggests that promoter methylation of the cancer related genes are closely related with the colorectal carcinogenesis and it occurrs from early phase of carcinogenesis, progressing constantly to the late stage. And the promoter methylation of normal epithelial cells increased by age. The p15, known to be the genes related to hematologic malignancy, was closely related to the colorectal carcinoma as well.

향나무와 그 變種들의 類綠關係에 關한 核學的 硏究

鄭宇珪,孫玲杰,成敏雄,金鼎錫 慶尙大學校 기초과학연구소 1992 基礎科學硏究所報 Vol.8 No.-

In this study the relationship among Juniperus chinensis and its seven varieties-J. chinensis var. procumbens, J. chinensis var. horizontalis, J. chinensis var sargentii, J. chinensis var, kaizuka, J. chinensis var. aureo-variegata, J. chinensis var. globosa, J. chinensis var. aureo-globosa-and J. rigida was studied by using the karyological methods. The results obtained from this study were as follows : In the karyotype analysis, J. chinensis, J. chinensis var. horizontalis, J. chinensis var. sargentii, J. chinensis var. globosa, J. chinensis var. aureo-globosa, and J. rigida were diploid with 2n=22, although J. chinensis var. procumbens, J. chinensis var. kaizuka and J. chinensis var. aureo-variegata were tetraploid with 2n=44. According to descending order of the total length of the chromosomes and the length of short and long arms, from the arrangement order of chromosomes and the position of centromeres, J. chinensis var. procumbens and J. chinensis var. horizontalis were categorized into the first group J. chinensis var. kaizuka and J. chinensis var. aureo-variegata were into the second group, and J. chinensis var, globosa and J. chinensis var. aureo-globosa were into the third group, respectively. Aneuploid(2n=26) in the C-band staining of J. chinensis var. aureo-variegata was identified, although it normally showed 2n=44 as karyotype. Because light was emitted from all chromatids of the samples by fluorescent light staining with DAPI, A-T rich regions would be located all over the chromatids.

하수에서 분리한 합성세제 분해균의 특성

정민선,전진경,정영건,이해경,권오진,지원대,김관배 嶺南大學校 環境問題硏究所 1993 環境硏究 Vol.13 No.1

대구시와 경산시의 하수에서 음이온계 합성세제인 sodium dodecyl sulfate(SDS)와 sodium dodecylbenzene sulfonate(SDBS)를 유일한 탄소원으로 이용하는 균주 289종을 분리하고 이중 합성세제 분해력이 강한, 그람음성 간균으로 운동성인 8균주를 선정하여 그 선정균들의 특성을 조사하였다. 선정균은 40℃ 이상에서는 생육하지 못하였으며 생육 최적 pH는 균주간에 다소 차이가 있었으며 pH 4.0 이하에서는 선정균 모두 생육치 못하였다. 질소원으로는 SDS분해균의 생육에는 potassium nitrate가, SDBS 분해균의 생육에는 soytone이 좋았다. SDS 분해균인 DS-3, 6, 8, 24 및 SDBS 분해균인 BS-7, 8은 세제농도가 5.0% 이상에서도 생육이 가능하였다. 선정균들은 tetracycline에 감수성이 강한 것으로 나타났지만 penicillin에는 강한 내성을 띠는 것으로 나타났고, ??와 ??금속이온은 모든 선정균들의 생육을 억제하는 것으로 나타났다. On purpose to isolate the organisms, which would utilize detergents(sodium dodecyl sulfate, SDS and sodium dodecylbenzene sulfonate, SDBS) as a sole carbon source, from the waste water of Kyungsan and Taegu city 289 strains were isolated. Among them 8 strains, which are gram negative rods with motility and produce strong enzyme to biodegrade the synthetic detergents, were selected. The characteristics of them were investigated as follows, 8 strains were failed to grow above the temperature of 40℃ and below the pH 4.0 even though they have variable optimum pH. Potassium nitrate was very effective for the growth of SDS-biodegradable strains and soytone was effective for the growth of SDBS-biodegradable strains as a sole nitrogen source. Among 8 strains especially DS-3, DS-6, DS-8 and DS-24(SDS-biodegradation strains) and BS-7 and BS-8(SDBS-biodegradation strains) could grow above 5.0% of detergent concentration. All of 8 strains were very sensitive to tetracycline but resistant to penicillin. Selected 8 strains were inhibited by metal ions of ??(0.156mg/㎖) and ??(0.156mg/㎖).

Dimethylnitrosamine 유발 급성 간 손상 흰쥐에서 ^(99m)Tc-Lactosylated Serum Albumin을 이용한 간 기능의 평가

정신영,이재태,서명랑,유정아,배진호,안병철,황재석,정재민,하정희,이규보 대한핵의학회 2003 핵의학 분자영상 Vol.37 No.6

목적: ^(99m)Tc-lactosylated serum albumin (^(99m)Tc-LSA)은 간세포에 특이적으로 결합하는 간수용체 영상용 방사성의약품으로 새로이 합성되었다. 간섬유화를 유발하는 dimethylnitrosamine (DMN)을 투여한 간 손상 휜쥐 모델에서 ^(99m)Tc-LSa의 역동학적인 간섭취를 조사하고 간효소치의 변화와 조직학적 소견을 비교하여, LSA의 간섭취가 간기능의 변화를 반영하는지를 연구하였다. 대상 및 방법: SD계 흰쥐에 DMN를 27 mg/kg으로 복강 내 주사하여 급성 간손상을 유도하고 대조군과 비교하였다. DMN을 주사한 흰쥐를 3일(DMN-3), 8일(DMN-8), 21일(DMN-21)에 ^(99m)Tc=LSA (1,665 mg/kg) 29 MBq를 정맥 주사하여, 30분 동안 동적 영상을 획득하고 간과 신장부위에 관심영역을 설정하여 간과 심장부위의 시간방사능 곡선을 얻었다. 간기능 평가를 위해 시간방사능 곡선을 이용하여 간섭취지수와 혈중제거지수를 구하였고 곡선 최적화를 시행하였다. DMN 투여군과 대조군의 간효소치의 변화와 간조직의 광학현미경 소견을 비교하였다. 결과: 대조군에서는 ^(99m)Tc-LSA가 빠르게 간에 섭취되고 혈중에서 제거되었으나 DMN을 처리한 군에서는 간섭취가 낮았다. 간섭취지수의 비교에서 대조군에 비해 DMN 처리군에서 유의하게 간섭취지수가 낮았다(DMN-3: 0.842, DMN-8: 0.898, DMN-21: 0.91, 대조군: 0.96, p<0.05). 혈중제거지수의 비교에서도 대조군에 비해 DMN 처리군에서 혈중제거지수가 유의하게 높았다(DMN-3: 0.731, DMN-8: 0.654, DMN-21: 0.604, 대조군: 0.473, p<0.05). 비선형 회귀분석에서 R_(2) 값은 0.9이상으로 좋은 일치를 보였고, 대조군에ㅓ K값이 DMN처리군에 비해 크고(DMN-3: 0.28, DMN-8: 0.41, DMN-21: 0.46, 대조군: 0.97, p<0.05), T_(1/2)값은 작았다(DMN-3: 2.5, DMN-8: 1.7, DMN-21: 1.5, 대조군: 0.7, p<0.05). 간효소치의 변화는 DMN-3군에서는 대조군에 비해 상승하였으나 DMN-8, DMN-21군에서는 간효소치의 상승이 관찰되지 않았다. 간조직 소견의 경우 DMN-3군에서 중심정맥 주위에 괴사가 관찰되었으나 DMN-8군, DMN-21군에서는 미약한 정도의 염증세포 침윤만이 관찰되었다. 결론: ^(99m)Tc-LSA 간신티그래피의 간섭취 정도는 간손상과 반비례하였으며 간섭취의 변화는 조직학적 손상이 심한 정도와 간손상후 회복되는 과정을 반영하여 주었다. ^(99m)Tc-LSA 간신티그래피가 간손상을 평가하고 간손상후 회복되는 과정을 추적하는 간수용체 영상용 방사성 의약품으로 사용될 수 있을 것으로 생각된다. Objects: ^(99m)Tc-lactosylated human serum albumin(LSA) is a newly synthesized radiopharmaceutical that binds to asialoglycoprotein receptors, which are specifically presented on the hepatocyte membrane. Hepatic uptake and blood clearance of LSA were evaluated in rat with acute hepatic injury induced by dimethylnitrosamine(DMN) and results were compared with corresponding findings of liver enzyme profile and these of histologic changes. Materials and Methods: DMN (27 mg/kg) was injected intraperitoneally in Sprague-Dawley rat to induce acute hepatic injury. At 3(DMN-3), 8(DMN-8), and 21(DMN-21) days after injection of DMN, LSA injected intravenously, and dynamic images of the liver and heart were recorded for 30 minutes. Time-activity curves of the heart and liver were generated from regions of interest drawn over liver and heart area. Degree of hepatic uptake and blood clearance of LSA were evaluated with visual interpretation and semiquantitative analysis using parameters (receptor index : LHL3 and index of blood clearance : HH3), analysis of time-activity curve was also performed with curve fitting using Prism program. Results: Visual assessment of LSA images revealed decreased hepatic uptake in DMN treated rat, compared to control group. In semiquantitative analysis, LHL3 was significantly lower in DMN treated rat group than control rat group (DMN-3:0.842, DMN-8: 0.898, DMN-21: 0.91, Control: 0.96, p<0.05), whereas HH3 was significantly higher than control rat group (DMN-3: 0.731, DMN-8: 0.654, DMN-21: 0.604, Control: 0.473, p<0.05). AST and ALT were significantly higher in DMN-3 group than those of control group. Centrilobular necrosis and infiltration of inflammatory cells were most prominent in DMN-3 group, and were decreased over time. Conclusion: The degree of hepatic uptake of LSA was inversely correlated with liver transaminase and degree of histologic liver injury in rat with acute hepatic injury.

Resin infiltration을 시행한 법랑질 초기 우식 병소의 특성

김은영,권민석,김신,정태성 大韓小兒齒科學會 2012 大韓小兒齒科學會誌 Vol.39 No.1

The concept of resin infiltration which was born in an innovative philosophy to arrest the incipient caries. However, the structural changes of resin infiltrated lesions have not yet explained completely. The liquid resin might contribute not only to maximizing the penetration but to deteriorating physical stability. This study was performed to examine some physical and histological features of resin infiltrated incipient carious lesions. With the specimen of resin infiltrated lesions, microhardness by nanoindentation in depth profile, morphology of resin tags were revealed after HCl dissolution, and degree of microleakage were assessed. The percentage of microhardness of surface layer and lesion body of untreated specimen to sound enamel was 64.6% and 24.6% respectively, while that of resin-infiltrated lesions was 72.1%, showing significant difference (p<0.05). The resin tags observed under SEM had relatively homogeneous length of 433(282~501) ㎛ on the average. Among 20 specimens for microleakage assessment, 13 specimens showed no leakage while 5 and 2 showed leakage into outer and inner half of lesion respectively. It was thought the infiltrant resin penetrates deeply and homogeneously into lesion body and improves its hardness with relatively good physical stability. 본 연구는 infiltrant resin을 침투시킨 초기 우식 병소의 특성을 평가하기 위해 법랑질의 깊이에 따른 경도를 측정하고, 병 소 내로의 레진 침투양상을 분석하며, 미세누출 정도를 관찰하여 다음의 결과를 얻었다. 건전 법랑질에 대한 초기 우식 법랑질의 경도 백분율은 표층(5~40 ㎛) 64.6%, 병소본체(60~350 ㎛) 24.6%였으며, infiltrant resin을 침투시킨 병소의 경도 백분율은 72.1%로 나타났다. 5~350 ㎛의 전 깊이에서, infiltrant resin을 침투시 킨 병소는 비처치 우식 병소보다 경도가 유의하게 높았지만 정상 법랑질에 비해서는 경도가 유의하게 낮았다(p<0.05). FESEM 관찰 결과 탈회된 법랑질 내부로 비교적 균일하게 침투한 레진 테그가 관찰되었으며, 침투깊이는 433 ㎛(282-501)로 측정되었다. 열순환 처리 후 13개의 치아에서 미세누출이 관찰되지 않았고, 5개에서 병소 외측 절반, 2개에서 병소 내측 절 반까지 미세누출이 관찰되었다.