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류승렬(Seung Rel Ryu),김혜진(Hye Jin Kim),홍진태(Jin Tae Hong),이종권(Jong Kwon Lee),이선희(Sun Hee Lee),이병무(Byung Mu Lee),김부영(Pu Young Kim) 대한약학회 1999 약학회지 Vol.43 No.5
Abuse liability of ephedrine was investigated by measurement of locomotor activity and self-administration in Sprague-Dawley rats. Locomotor activity was determined in rats treated with 3, 10 and 30mg/kg ephedrine for 14 days. Self-administration by ephedrine (0.23, 1 and 2.3mg/kg) was examined in food-trained rats. We also examined effect of dopamine receptor antagonist (spiperone, 30mcg/kg) on the ephedrine-induced response of self-administration. Body weight was not statistically difference between control and ephedrine treatment group, but locomotor activity was dose-dependently increased. Self-administration for ephedrine was decreased in the early response (day 1 and 2) but the response was increased by higher dose of ephedrine. Self-administration was decreased by dopamine receptor antagonist (spiperone). These data showed that ephedrine increased locomotor activity and induced response of self-administration, and the effects of ephedrine were partially related to the dopaminergic system, which suggest that ephedrine may have abuse liability.
In vitro Alternatives to Skin Irritation Test
Kim, Dai Byung,Ryu, Seung Rel,Kim, Pu Young,Shin, Dae Sup,Lee, Sun Hee,Koh, Jae Sook,Park, Won Sae 한국응용약물학회 1995 Biomolecules & Therapeutics(구 응용약물학회지) Vol.3 No.3
In vitro cell culture system has been proposed as a promising alternative model to in vivo skin irritation test. These studies were performed to screen the cytotoxicity effects of surfactants using normal human skin fibroblasts. Cell membrane integrity assessed by the leakage of lactate dehydrogenase (LDH) and mitochondrial integrity by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] reduction test were affected in a dose dependent manner. The irritation potential of surfactants to human skin patch test, and the changes of capillary permeability by rabbit intradermal safety test were assessed as in vivo methods. Our results suggest that LDH leakage assay and MTT reduction test using cultured human fibroblasts could be predictive for the irritancy of various surfactants in human, and LDH assay is superior correlated with in vivo test (r=0.886) to MTT test with in vivo test (r=0.757).
Involvement of Cortical Damage in the Ischemia/Reperfusion-Induced Memory Impairment of Wistar Rats
Hong, Jin-Tae,Ryu, Seung-Rel,Kim, Hye-Jin,Lee, Sun-Hee,Lee, Byung-Moo,Kim, Pu-Young The Pharmaceutical Society of Korea 2000 Archives of Pharmacal Research Vol.23 No.4
The effect of ischemia/reperfusion-induced neuronal damage on the memory impairment were investigated using active avoidance and Morris water maze tasks in Wistar rats. Focal ischemia was induced by 1 h occlusion of the right middle cerebral artery (MCA) of Wistar male rats. Reperfusion was induced by releasing the occlusion and restoring the blood circulation for 24 h. The acquisition and preservation memory tested by active avoidance showed a significant difference between the sham and ischemia/reperfusion group. The water maze acquisition performance was also significant difference between sham and ischemia/repefusion groups in both latency and moving distance. The infarction volume was increased by the ischemia/reperfusion. Furthermore, the cresyl violet staining of the ischemia/reperfusion brain showed severe neuronal damage (pyramidal cell loss) in the cortex in addition to the striatum lesion of brain. This study shows that pyramidal cell damage in the cortex lesion may be partially related to memorial disturbance in the ischemia/reperfusion brain injury.
민경일,백선영,신진호,김재옥,류승렬,민복순,김병국,김도근,김훈,이석호,박순희 식품의약품안전청 2001 식품의약품안전청 연보 Vol.5 No.-
수두(chicltenpo즈) 및 대상포진(shingles)의 예방을 위해 사용되는 수두 생 바이러스 백근은 현재 국내 -외 제조사들이 정상사람 2배체 폐 태아 세포 주들을 이용하여 바이러스를 배양 · 증식시켜 생산하고 있으나, 품질관리를 쒸한 역가 시험에는 t·fRC튼 띤 LB딘EL 세포 주외에 제조사가 설정한 세포 주를 이용하고 있으며, 역파신험 방법인 fH Ui'rFO Plaque 3SSaIT에도 조사별로 다소 차이가 있는 시헌법을 사용하고 있다. 그러므로 일반적으로 세포 주간우 감수성 차이, 계대력(passa딩e level)간의 차이,varicelta-zoster virus(4'2V) diluent medium 등에 의한 차이에 의해 역가시힘 결과에 많은 차이를 나타낼 수 있다. 이에 본 연구에서는 역가 시험 결과꼭 편차를 촉소화 할 수 있는 시헌방법을 극힙하고자 Ok퍼 백신 주와 세로 주간 및 기타 요인에 따른 차이를 비교 분석하고 이를 표준확하여 일관겅있는 국가 및 제조사의 품질관리예 활용하고 나아가 수두 생 바이러스 백신 역가시헌 국가 표준품 거달에 활용하고자 하는데 목적이 운.다. 수두 생 바이러스 빅신의 역가 시험에 영향을 띠칠 수 꿀.는 모민으로 우선 바이러스 흡착에 사용되는 1#Z)·'diluent medium이 가장 큰 오인으로 확인되.고. 현개까기 최종적으로 if4 sucrose, 10% FBS, 0.1% sodiun) rrlonog)utamate in PBS(-), fIH 7.2가 가당 두수글 L'z).「 린luent medium 조성으로 확인되었단. 또한 '·:~l포 주별로 다소의 차이는 잇.으나 최대 바이러스 흡착시간은 90분으론:÷잰착인 되었다. 다른 negati)Fe effect를 보일 수 있는 요인으로 항생물질 및 항츤 제인 fuugiBone이 곡이러스의 역가에 영향을 미치는 것으로 확인되었다 따라서 이러한 항생물 띤 항균제를 standard solid agarose overla?·(5.tO) 시헌방법에는 사용하지 않는 것이 역가 시험의 편차를 줄일 수 있는 요인이라 판단된다. 최적의 조건하데서 Oka 수두 백신 주의 j 종의 세포 쭈에 대한 역가시험 수행 결과 각 세포 주의 감수성의 차이는 크지 않았으나, 반복시헌에 대한 표준편차는 다소 차이를 나타났다. Until now in Korea, the international and domestic vaccine maufacturers produce and sale live attenuated daricella vaccines, used to prevent chickenpox and shinglees, which are propagated in and done the potency test with various originated human diploid embryonic lung cells. Also manufacturers perform in vitro plaque assay with a little different methods to their quality control tests. Therefore, in general, there is slight or big difference among in vitro plaque assay results because of the difference in susceptibility of various originated human diploid embryonic lung cells and in assay methods. The purpose of this study is to confirm what factors occurring deviation to establish the standardized method which minimize deviation intracellularly and intercellularly. Eventually the standadized method will be used in consistent national and manufacturer's quality control and moreover intra and inter laboratory's validation assay of national standard for live varicella vaccine candidate. We confirmed VZV diluent medium was the biggest factor influencing in vitor plaque assay and the excellent composition of VZV diluent medium was final 5% sucrose, 10% FBS, 0.1% sodium monoglutamate in PBS(-), pH 7.2. We confirmed 90 minutes was maximum and optimum VZV adsorption time, but a little different among cells Also we recommended not use antibiotics and antimycotic, fungizone in standard solid agarose overlay assay in varicella potency test. Eventually 5 different originated human diploid embryonic lung cells showed little difference in susceptibility to Oka vaccine strain, but showed a lot of difference in reproducibility.
이종권,김대병,이은희,이선희,류승렬,최기환,김윤정,김부영 식품의약품안전청 1997 식품의약품안전청 연보 Vol.1 No.-
신제형개발시 기초자료제공비 목적으로 5종의 소염진통제 약물에 대한 피부자극시험을 id oifroassay로 실시하여 비교하고자 하였파. 시험물질로는 경근 및 주사꾹로 시판중인 소염진통제 diclofenac, naproxen, meclofenamicacid, ibuprofen, fenoprofen등 5종을 선정하여 in oifro cytotoxicity를 비교분석하였다. 사람의 foreskin으로부터 fibroblast를 배양하고 투여딸물의 노출시간을 24, 48시간으로 하여 노출시간에 대한 차이를 비교하였으며 세포독성은 비교적 많이 쓰이는 neutr,al red uptake assay 및 최근게 소개된 .a.lamar Blueassay를 실시하여 microplatereader로 측정하였으며 시험방법에 따른 cytotoxicity결과를 비교하였다. ,111포의 성장을 50% 감소시키는 TCiL느로비교해 볼 때 meclofenamic acid)diclofenac>fenoprofen>ibuprefen>naproxen순으로 나타났으며 5종의 소염진통제틀 대한 세포독성시험방법으로 alamarblue방법이 MTT나 고RV방법보다 세포독성이 민감하게 나타났다. This study vras carried out to investigate the cytotoricitf was assayed with human skin fibroblasts on 5 anti-infl.ammatorr drugs(Oiclofenac, Naprexen, Merlefenamic acid, rbuprofen andFenoprofen) which are commercially used as oral preparations cr injections. The cytotoxicity of 5 chem-icals was evaluated by using MTT assay, neutral red uptake assay and Atamar Blue assay after theCells had beeu exposed tO Chemicals fOr 24 hours Of 48 hours. The CDmPartiVe Cytotoxicity followed thegeneral order of nleclofenamic acid>diclofenae>fenoprefen>ibuprofen>naproxen as results of Icso de-termined by Alamar Blue assar were lower than those of MTT and NRU assay. These data providealarnar blue assay can be useful method for the assessment of in vitro skin irritation test for anti- in-flammatory drugs.