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.

Antagonizing effect of protein kinase C activation on the μ-opioid agonist-induced inhibition of high voltage-activated calcium current in rat periaqueductal gray neuron

Cho, Young-Wuk,Han, Seung-Ho,Min, Byung-Il,Rhee, Jeong-Seop,Norio Akaike 경희대학교 동서의학연구소 2001 東西醫學硏究所 論文集 Vol.2001 No.-

Opioids have been thought to induce analgesia by activating the descending pain control system, especially at the level of periaquenductal gray, and regulate the neurotransmitter release through the inhibition of calcium channel. In the present study, the modulatory effects of protein kinase C and protein kinase A on the μ-opioid agonist-induced inhibition of the high-voltage activated calcium current were examined in the acutely dissociated rat periaqueductal gray neurons with the nystatin-perforated patch-clamp technique. Among 505 neurons tested, the barium current passing through the high-voltage activated calcium channels of 172 neurons (34%) were inhibited by 32±3% with the application of an μ-opioid agonist, [D-_Ala^2, N-MePhe^4, Gly^5 -ol]-enkephalin (DAMGO, 1 μM). The barium currents itself and the DAMGO-induced inhibitory effects were not affected by the application of either an adenylate cyclase activator (forskolin, 1μM) or a protein kinase inhibitor (staurosporin, 10nM) for 2 min. The DAMGO inhibition was completely and irreversibly antagonized by the application of a protein kinase C activator, phorbol-12-myristate-13-acetate (PMA, 1μM) for 2 min without any alteration of the barium current itself. However, the antagonizing effect of PMA was completely abolished by the application of 10 nM staurosporin for 2 min. After then, PMA did not show the antagonizing effect any more. Inversely, when staurosporin was applied before PMA, the antagonizing effect of PMA was also not shown. These results demonstrate that the μ-opiod agonist-induced inhibition of the periaqueductal gray neuronal high-voltage activated calcium current can be antagonized by protein kinase C activation. This finding may provide us a significant clue to understand the action mechanism of opioid-induced analgesia in the periaqueductal gray. ⓒ 2001 Elsevier Science B.V.All rights reserved.

Comparison of Dual Probe Bipolar Mode with Monopolar and Single Probe Bipolar Modes : Comparison of Dual Probe Bipolar Mode with Monopolar and Single Probe Bipolar Modes

Lee, Jeong Min,Han, Joon Koo,Kim,Se Hyung,Lee, Jae Young,Kim, Dae Jin,Lee, Min Woo,Cho, Gyung goo,Han, Chang Jin,Choi, Byung Ihn Korean Radiological Society 2004 Korean Journal of Radiology Vol.5 No.2

피프로닐 오염도 조사를 위한 분석법 정립

조순길 ( Soon-kil Cho ),이미진 ( Mi-jin Lee ),이정민 ( Jeong-min Lee ),김호진 ( Ho-jin Kim ),박수민 ( Soo-min Park ),박혜진 ( Hye-jin Park ),이승화 ( Seung-hwa Lee ),안종성 ( Jong-sung Ahn ) 한국환경농학회 2018 한국환경농학회 학술대회집 Vol.2018 No.-

2017년 유럽에서 피프로닐에 오염된 계란이 유통된데 이어 국내에서 생산된 일부 계란에서도 살충제가 검출되었다. 피프로닐은 진드기 방제 목적으로 사용되는 살충제로 sulfide, sulfone, amide, sulfoxide의 대사산물을 생성한다. 피프로닐은 물에 1.9 mg/L 정도 용해되고, 아세톤에 545.9g/L가 용해되는 성질이 있어 시료 채취시 아세톤을 사용한다. 농장시설 등에 부착된 피프로닐을 제거하기 위해 5% 탄산나트륨(Na2CO3)과 15% 과산화수소(H2O2)를 권장하고 있다. 이는 피프로닐을 피프로닐설폰으로 산화시킨 다음 반복적으로 사용하여 제거한다. 이러한 제거 작업을 통해 피프로닐이 제거된 정도를 조사할 필요가 있고, 이를 위한 분석법 정립이 필요하다. 시료를 250 mL 용기에 넣고 1% 함유 아세토니트릴 100 mL을 주가하여 10분간 격렬하게 진탕한 후, 3500 rpm으로 원심분리를 하였다. 추출액 1 mL을 0.2 um 멤브레인필터로 여과하여 시험용액으로 하였다. 칼럼은 C18(2.0 mm I.d×50mm, 3 um)을 사용하였고, 이동상은 0.1% 포름산 함유 메탄올과 0.1% 포름산 및 5 mM 아세트산암모늄이 함유된 물을 사용하였다. 분석조건으로 피프로닐의 선구이온은 437 m/z, 생성이온은 368, 255, 290 m/z, positive 조건으로 분석하였고, 피프로닐 설폰의 선구이온은 451 m/z, 생성이온은 415, 282, 244 m/z negative 조건으로 분석하였다. 분석법의 정량한계는 피프로닐 0.92 ug/kg, 피프로닐설폰 0.70 ug/kg이었다. 피프로닐과 피프로닐 설폰을 각각 1, 5, 10, 50, 100 ug/kg 수준으로 검량선을 작성한 결과, r2는 모두 0.9999이었다. 10 ug/kg과 50 ug/kg 수준의 3반복 회수율 실험결과, 10ug/kg 수준에서 피프로닐은 74.7±0.56%, 피프로닐 설폰은 88.9± 0.27%로 나타났다. 50 ug/kg 수준에서는 피프로닐은 78.6±0.11%, 피프로닐 설폰은 95.2±0.02%로 유효회수율 범위(70~120%)에 포함되었다. 머무름 시간은 피프로닐 5.3 mim, 피프로닐 설폰은 5.7min에서 검출되었다. 교차확인 목적으로 LC/MS/MS로 분석한 시료를 GC/μ-ECD로 분석을 하였다. 분석조건은 주입구 온도 250℃, (5%-Phenyl)-methylpolysiloxane이 충진된 30 m×0.25 mm×0.25 um길이의 칼럼이다. 오븐온도는 130℃에서 300℃까지 승온 조건으로 분석하였고, 머무름시간은 피프로닐 11.64 min, 피프로닐 설폰12.79 min으로 LC/MS/MS와 GC/μ-ECD 모두 표준물질과 시료의 결과가 일치함을 알 수 있었다. 정립된 분석법은 피프로닐 오염도조사를 위한 분석법으로 활용할 수 있을 것으로 판단된다.

쌍태아에서 제 1태아의 분만 후 제 2태아의 지연분만 : 중례보고

김주환,서민정,유희정,노권일,조대현,박정규,이정헌,조성남,손영수 朝鮮大學校 附設 醫學硏究所 2005 The Medical Journal of Chosun University Vol.30 No.3

With the widespread use of fertility medications and techniques of in vitro fertilization, multiple gestation has become epidemic in modern obstetric practice. Delivery of the initial fetus in a multiple gestation usually is followed by delivery of the subsequent fetus or fetuses shortly thereafter. However in rare circumstances, the delivery is delayed for days due to disappearance of uterine contraction after delivery of the first fetus. When uterine activity ceases after the delivery of the first neonate, a policy of nonintervention may be considered in case of an immature or very premature delivery, in order to achieve a gestational age for the remaining fetus(es) more compatible with neonatal survival. We report a case of twin gestation with prolongation of the delivery interval between the twins for 46 days.

허혈 유사 조건이 심방근의 활동전위 특성에 미치는 영향

김재하,주정민,조용범,신동호,안병희,주신배,김상형 대한순환기학회 1999 Korean Circulation Journal Vol.29 No.11

Purification and Characterization of Helicobacter pylori ${\gamma}$-Glutamyltranspeptidase

Song, Jae-Young,Choi, Yeo-Jeong,Kim, Jeong-Min,Kim, Yoo-Ree,Jo, Jin-Seong,Park, Jin-Sik,Park, Hee-Jin,Song, Yun-Gyu,Lee, Kon-Ho,Kang, Hyung-Lyun,Baik, Seung-Chul,Youn, Hee-Shang,Cho, Myung-Je,Rhee, Kw The Korean Society for Microbiology 2011 Journal of Bacteriology and Virology Vol.41 No.4

Gamma-glutamyltranspeptidase (GGT) was purified to electrophoretic homogeneity from the cell extract of H. pylori. The purified enzyme consisted of heavy and light subunits with molecular weights of 38 kDa and 21 kDa, respectively. N-terminal amino acid sequence of heavy and light subunits revealed that H. pylori GGT was processed into 3 parts for a signal peptide of 27 amino acid residues, a heavy subunit of 352 residues, and a light subunit of 188 residues during translation. The reaction rate for hydrolysis of ${\gamma}$-GpNA was 84.4 ${\mu}mol/min$ per milligram of protein, and that for the ${\gamma}$-glutamyl transfer from ${\gamma}$-GpNA to gly-gly was 23.8 ${\mu}mol/min$ per milligram of protein. The apparent Km values of H. pylori GGT for ${\gamma}$-glutamyl compounds were on the order of $10^{-3}$ to $10^{-4}$ M and those for acceptor peptides and amino acids were on the order of $10^{-1}$ to $10^{-2}$ M. The GGT protein kept approximately 80% of the initial enzymatic activity on incubation at $60^{\circ}C$ for 15 min. The optimum temperature and pH for reactions of both hydrolysis and transpeptidation were $40^{\circ}C$ and 9.0, respectively. The transpeptidation and hydrolysis reactions catalyzed by H. pylori GGT were strongly inhibited by L-Gln and moderately inhibited by L-Ala, L-Ser, ${\beta}$-chloro-L-Ala, and L-Glu. These results demonstrated that the biochemical properties of H. pylori GGT are different from those of other bacterial GGTs. Further, H. pylori GGT might degrade glutathione in the gastric mucous layer of humans if the enzyme could be secreted in the bacterial niches.

Loop와 HPLC Purification 방법보다 더 높은 비방사능을 보여주는 카트리지 Methylation과 Purification을 이용한 손쉬운 [ ¹¹C]PIB 합성

이용석,조용현,이홍재,이윤상,정재민,Lee, Yong-Seok,Cho, Yong-Hyun,Lee, Hong-Jae,Lee, Yun-Sang,Jeong, Jae Min 대한핵의학기술학회 2018 핵의학 기술 Vol.22 No.2

$[^{11}C]PIB$는 베타아밀로이드($A{\beta}\;plague$)라는 변성 단백질에 결합하여 뇌의 기능과 기억력을 서서히 감퇴시키는 비가역적인 질환인 치매를 조기에 감별할 수 있는 대표적인 방사성의약품이다. 지금까지 많은 실험실에서 $[^{11}C]PIB$는 자동화합성장치에서 $[^{11}C]methyl\;iodide$나 $[^{11}C]methyl\;triflate$를 만든 다음 loop나 vial 방법을 사용하여 methylation을 한 다음 HPLC로 정제를 하는 것이다. 하지만 기존의 보고된 방법은 시간이 오래 걸리며, HPLC와 같은 복잡한 시스템을 필요로 하여 소규모 실험실에서 합성하기에 적합하지 않으며, 최종 product에서 에탄올 함량이 높다는 단점이 있었다. 이러한 단점을 보완하기 위하여 카트리지만을 사용하여 카트리지에서 methylation과 purification을 동시에 실시함으로써 합성 시간을 단축하고, 비방사능이 높고, 낮은 에탄올 함량을 가진 $[^{11}C]PIB$를 합성 가능한지 확인하고자 하였다. 가장 널리 사용하는 카트리지 6종(CM, HLB, Alumina, C18, tC18, tC18 environmental을 선택하여 screening test를 실시하였다. 6-OH-BTA-0 1 mg을 c-HXO에 녹인 다음 6개의 카트리지에 loading를 한 다음 0.5 M MSP(pH 5.1) 20 mL로 정제를 한 다음 최종 fraction을 받아서 analytical HPLC로 전구체 잔류량을 측정한 결과 hydrophobicity가 낮은 계열(CM, HLB, Alumina)의 카트리지에서는 완충액으로 정제를 하였을 때 잔류전구체의 양이 많았으나, 탄소함량이 많은 계열의 카트리지(C18, tC18, tC18 environmental)에서는 잔류전구체의 양이 CM, HLB, Alumina 카트리지에 비하여 상대적으로 적었다. 완충액의 정제 농도와 부피를 최적화 하기 위하여 screening test에서 가장 좋은 결과를 나타낸 C18 series cartridge를 가지고 추가 실험을 진행하였다. 인산완충액 농도를 10 mM, 20 mM, 30 mM, 40 mM, 50 mM, 250 mM, 500 mM로 변화시켰으며, 에탄올 함량은 20%와 30%로 하여 용출액을 분석하여서, $[^{11}C]PIB$를 카트리지로 합성하기 위한 최적의 조합은 tC18 environmental cartridge와 0.5 M MSP 20 mL인 것을 알 수 있었다. 기존에 보고된 방법과 cartridge를 비교한 결과, 합성시간에서는 각각 15 ~ 18min, 8 ~ 9 min이 소요되었으며, product activity는 각각 $4.1{\pm}1.4\;GBq$ (n=41), $3.8{\pm}0.9\;GBq$ (n=3), 방사화학적 수율(based on HPLC analysis of the crude product)에서는 $13.9{\pm}4.4%$ (n=41), $12.3{\pm}2.2%$ (n=3)로 별다른 차이가 없었으며, 비방사능에 있어서는 HPLC purification method가 $78.7{\pm}39.7\;GBq/{\mu}mol$ (n=41), cartridge method가 $420.6{\pm}20.4\;GBq/{\mu}mol$ (n=3)로 카트리지 방법이 기존 방법보다 더 좋은 결과를 나타내었다. 또한, 잔류 용매(c-HXO)도 vial or loop method와 별다른 차이가 없었으며, 에탄올 함량에 있어서는 70%(기존 방법)에서 30%(카트리지 방법)로 두 배 이상 함량이 적다는 사실을 알 수 있었다. 지금까지 알아본바와 같이 cartridge method는 reported method(HPLC purification)에 비하여 더 향상된 결과를 보여준다는 사실을 확인하였다. $[^{11}C]PIB$ synthesis has been performed by a loop-methylation and HPLC purification in our lab. However, this method is time-consuming and requires complicated systems. Thus, we developed an on-cartridge method which simplified the synthetic procedure and reduced time greatly by removing HPLC purification step. We compared 6 different cartridges and evaluated the $[^{11}C]PIB$ production yields and specific activities. $[^{11}C]MeOTf$ was synthesized by using TRACERlab FXC Pro and was transferred into the cartridge by blowing with helium gas for 3 min. To remove byproducts and impurities, cartridges were washed out by 20 mL of 30% EtOH in 0.5 M $NaH_2PO_4$ solution (pH 5.1) and 10 mL of distilled water. And then, $[^{11}C]PIB$ was eluted by 5 mL of 30% EtOH in 0.5 M $NaH_2PO_4$ into the collecting vial containing 10 mL saline. Among the 6 cartridges, only tC18 environmental cartridge could remove impurities and byproducts from $[^{11}C]PIB$ completely and showed higher specific activity than traditional HPLC purification method. This method took only 8 ~ 9 min from methylation to formulation. For the tC18 environmental cartridge and conventional HPLC loop methods, the radiochemical yields were $12.3{\pm}2.2%$ and $13.9{\pm}4.4%$, respectively, and the molar activities were $420.6{\pm}20.4GBq/{\mu}mol$ (n=3) and $78.7{\pm}39.7GBq/{\mu}mol$ (n=41), respectively. We successfully developed a facile on-cartridge methylation method for $[^{11}C]PIB$ synthesis which enabled the procedure more simple and rapid, and showed higher molar radio-activity than HPLC purification method.

벤조디아제핀 수용체 영상용 양전자 방출 핵종 표지 플루마제닐 유도체 [F-18](3-(2-Fluoro)flumazenil의 합성과 생체 내 분포

장영수,이숙자,강삼식,홍성현,이명철,이동수,정준기,정재민,조정혁 대한핵의학회 1999 핵의학 분자영상 Vol.33 No.6

Purpose: Radiotracers that bind to the central benzodiazepine receptor are useful for the investigation of various neurological and psychiatric diseases. [C-11]Flumazenil, a benzodiazepine antagonist, is the most widely used radioligand for central benzodiazepine receptor imaging by PET. We synthesized 3-(2-[F- 18]fluoro)flumazenil, a new fluorine-18 (t1/2=110 min) labeled analogue of benzodiazepine receptor imaging agent, and evaluated in vivo for biodistribution in mice. Materials and Methods: Flumazenil (Ro 15-1788) was synthesized by a modification of the reported method. Precursor of 3-(2-[F-18]fluoro)flumazenil, the tosylated flumazenil derivative was prepared by the tosylation of the ethyl ester by ditosylethane. [F-18] labeling of tosyl substitued flumazenil precursor was performed by adding F-18 ion at 85℃ in the hot cell for 20 min. The reaction mixture was trapped by C18 cartridge, washed with 10% ethanol, and eluted by 40% ethanol. Bidistribution in mice was determined after intravenous injection Results: The total chemical yield of tosylated flumazenil derivative was ∼40%. The efficiency of labeling 3-(2-[F-18]fluoro)flumazenil was 66% with a total synthesis time of 50 min. Brain uptakes of 3-(2-[F-18]fluoro)flumazenil at 10, 30, 60 min after injection, were 2.5±0.37, 2.2±0.26, 2.1±0.11 and blood activities were 3.7±0.43, 3.3±0.07, 3.3±0.09%ID/g, respectively. Conclusion: We synthesized a tosylated flumazenil derivative which was successfully labeled with no-carrier-added F-18 by nucleophilic substitution.

강직성 슬관절에서의 슬관절 전치환술

조우신,박종희,김정민,오세관 대한슬관절학회 2003 대한슬관절학회지 Vol.15 No.1

목적: 강직이 동반된 슬관절염 환자에서 슬관절 전치활술의 문제점, 결과 및 합병증을 분석하고자 하였다. 대상 및 방법: 1994년 1월부터 2000년 12월까지 슬관절 강직(운동 범위 50도이하)이 있는 환자에게 슬관절 전치환술을 시행하여 2년 이상 추시가 가능하였던 16례를 대상으로 하였다. 수술은 관절 강직이 발생한지 평균 12.2년(1~40년)에 시행하였으며, 추시기간은 평균 3.3년(2~6년)이었다. 16례 중 남자 3례, 여자 13례였고, 평균 나이는 55.8세(34세~75세)였다. 감염에 의한 후유증 6례로 가장 많았고 그 외 퇴행성 관절염 4례, 외상 후 관절염 3례, 류마티스성 관절염 3례의 순이었다. 술 후 평가는 추시기간 중의 운동 범위와 HSS score 및 합병증을 분석하였다. 결과: 관절 운동 범위는 술 전 평균 31.6도(0~50도)에서 추시시 평균 95.4도(80~120도)로 증가하였으며, 1례에서만 5도의 굴곡 구축이 있었다. HSS score는 술 전 평균 59.6점(43~76점)에서 추시시 평균 84.6점(76~92점)으로 향상되었다. 1례에서 수술 중 슬개건 부분파열이 있었으나 보조기 착용과 적극적 재활로 술 후 1년째 90°의 관절 운동이 가능했다. 표재성 감염 1례는 창상의 변연절제술 후 피부이식으로 치유되었고, 심부 감염된 3례는 추후 관절 유합술을 시행하였다. 결론: 슬관절 전지환슬은 강직된 슬관절의 기능을 회복시킬 수 있는 좋은 술기이지만 감염등의 합병증을 고려해서 시행되어야 한다. Purpose: To evlauate the results of TKRA (Total knee replacement arthroplasty) for the treatment of stiff knee. Methods & Materials : TRKA has been performed for 18 cases of stiff knee ( ROM < 50° ) between January 1994 and December 2000. 16 cases which have been followed up for more than 2 years were analysed. Average follow-up was 3.3 years(2~6 years). 3 were male and 13 female. The average age was 55.8 years(34~75 years). Sequales of infection were most with 6 cases and followed by osteoarthritis (4 cases, 2 cases had been performed arthroscopic debridement) and rheumatoid arthritis (3 cases) and traumatic arthritis (3 cases) in order. TKRA was performed on average 12.2 years (1~40 years) after knee stiffness has been developed. We evaluate the results with ROM, HSS score and complications. Results : Average ROM was increased from 31.6°(0°~50°) preoperatively to 95.4°(80°~120°) postoperatively. 5° of flexion contracture was present in only 1 cases. Average HSS score was improved from 59.6 points preoperatively to 84.6 points postoperatively. The patella tendon was partially ruptured in 1 case surgery, but by brace application and rehabilitative exercise, ROM was improved to 90°, 1 year post operatively. There were 1 superficial skin infection which was resolved by revision of wound and skin graft, and deep infection in 3 cases, which needed knee fusion finally. Conclusion : TKRA is a good method for improving function in knee stiffness although infection risk is high.