대뇌 피질 신경 세포 일차 배양에서 6-hydroxydopamine에 의한 신경세포사멸의 특성

정재훈,강효정,손성향,정영기,곽병주,노재성 大韓神經精神醫學會 2000 신경정신의학 Vol.39 No.3

연구목적 : 본 연구는 생쥐 태자 대뇌 피질 세포 일차 배양에서 파킨슨씨병의 동물 모델을 만드는데 사용되는 신경독성 물질인 6-hydroxydopamine(6-OHDA)에 의한 신경세포 사멸의 특성을 관찰한 것이다. 방 법 : 생쥐태자의 신경세포를 배양하여 6-OHDA를 처리하고 이와 더불어 여러가지 신경세포 사멸에 영향을 주는 물질을 투여하여 신경세포의 사멸을 정량적으로 분석하고 형태학적 분석을 전자현미경을 통하여 관찰하였다. 결 과 : 배양한 신경세포에 6-OHDA를 처리하면 투여 양에 비례하여 신경세포의 사멸이 증가하여 50μM 66-OHDA를 24시간 투여하여 일으킨 신경세포 사멸의 형태학적 특징은 세포질의 수축 및 염색질의 응축(nuclear chromatin condensation) 및 핵질의 fragmentation을 동반하는 고사(apoptosis) 형태이다. 이 때의 신경세포의 사멸은 항고사 물질인, 1㎍/ml cycloheximide와 caspase 억제제인 10μMzVAD-fmk에 의해 약화되었으나 글루타메이트 길항제(10μM MK-801 혹은 50μM CNQX)나 항산화제 (100μM trolox 혹은 100μM N-acetyl-cysteine)는 6-OHDA에 의한 신경세포의 사멸을 막지 못했다. 결 론 : 이상의 형태학적 및 약물학적 특징은 6-OHDA가 고사성 신경세포 사멸을 유도한다는 것을 의미하고, 항산화제들이 효과가 없다는 것과 caspase 억제제가 보호효과가 있다는 것은 6-OHDA에 의한 고사성 신경세포 사멸에는 산화적 스트레스보다는 caspase cascade와 관여된 기전이 기여한다는 것을 시사한다. 또한 6-OHDA에 의한 신경세포의 사며른 도파민성 신경세포에 선택적이지 않으며, 일차 대뇌피질 신경세포 배양 시스템이 6-OHDA에 의한 신경세포사멸인구에 사용될 수 있음을 보여준다 Objectives : We examined the patterns of cell death induced by the 6-hydroxydopamine, a selective dopaminergic toxin that used to produce Parkinson's disease model. Method : Neocortices from 14 - or 15-day-old fetal mice for neuron-glia co-cultures were used for this experiments. Results : Cortical cell cultures exposed to 10-100μM 6-hydroxydopamine for 24 hr underwent neuronal death without injuring glia. The degenerating neurons showed hallmark of apoptosis featuring cell body shrinkage, nuclear chromatin condensation and aggregation, nuclear membrane disintegration with intact plasma membrane, and prominent internucle- osomal DNA fragmentation. Neither the glutamate antagonists (10μM MK-801 and 50μM CNQX) nor antioxidants(trolox, 100μM, N-acetyl-cysteine, 100μM prevented the 6-OHDA induced neuronal injury. The death was attenuated by addition of two different anti-apoptotic agents, 1㎍/ml cycloheximide and caspase inhibitor(100μM zVAD-fmk). Conclusion : These features suggest that 6-OHDA induced apoptotic type of neuronal death in cortical neuronal culture. Considering the protective effect of caspase inhibitors, a mechanism involing caspase cascade rather than oxidative stress is responsible for the 6-OHDA-induced neuronal apoptosis. In addition, our results showed that 6-OHDA-induced apoptosis is not confined to dopaminergic neurons and the primary cortical culture system so this system is suitable for the study of 6-OHDA-induced neuronal apoptosis.

진행성 비호지킨 림프종 환자에서 ICE 구제 요법에 의한 조혈모세포 가동화 후 자가 말초혈액 조혈모세포이식

이제중,이병환,김여경,변정래,이일권,박무림,정익주,김형준 대한조혈모세포이식학회 2003 대한조혈모세포이식학회지 Vol.8 No.1

연구배경: 비호지킨 림프종에서 자가 말초혈액 조혈모세포이식술이 폭넓게 이용됨으로 인해서, 높은 치료효과뿐만 아니라 조혈모세포의 가동화 효율이 높은 구제 요법이 요구되었다. 방법: 본 연구에서는 진행성 비호지킨 림프종에서 ICE 요법을 이용하여 조혈모세포를 가동화시킨 후 자가 말초혈액 조혈모세포이식이 시행하였던 환자를 후향적으로 분석하였다. 결과: 대상 환자의 중앙 연령은 38세(범위, 16~61)였으며, ICE 요법은 환자당 4주기(범위, 1~6주기)가 투여되었고, 투여 간격은 중앙값이 24일(범위, 16~36일)이었다. 고위험도 관해군을 제외한 13예의 환자 중 완전반응은 7예(53.8%), 부분반응은 4예(30.8%), 진행성질환은 2예(15.4%)를 보였다. 치료에 따른 3~4등급의 혈액학적 독성은 중성구감소증이 13예(81.3%), 혈소판감소증이 7예(42.8%)에서 관찰되었다. 조혈모세포 채집은 ICE 요법 후 중앙값이 12일(범위, 6~20일)에 시행되었고, 각 ICE 요법당 채집한 단핵구치는 중앙값이 5.75× 10^(8)/체중, CD34^(+) 세포는 중앙값이 1.25× 10^(6)/체중, CFU-GM치는 중앙값이 1.19× 10^(5)/체중이었다. 조혈모세포이식은 11예에서 시행되었고, 중앙 추적기간 401일에 평가한 2년 전체생존율은 70.1±14.7%, 1년 및 2년 무사건생존율은 각각 60.7±15.4%와 32.3±17.1%를 보였다. 결론: ICE 요법은 재발성/불응성 비호지킨 림프종 환자에서 높은 치료 반응률과 만족할 만한 조혈모세포 가동화를 보여 주었지만, 치료에 대한 순응도가 낮아서 투여 간격이 연장되는 문제점을 안고 있어서, 우리나라 환자의 실정에 적합한 구제요법에 대한 연구가 필요할 것으로 생각된다. Background: Due to the extensive application of high-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT), a salvage chemotherapeutic regimen with high response rate as well as effective capacity of PBSC mobilization is needed in non-Hodgkin's lymphoma (NHL). Methods: We analyzed the applicability of ICE (ifosphamide, carboplatin, and etoposide) regimen in NHL patients who underewent autologous PBSCT. Results: The median age was 38 years (range, 16~61 years), the patients received median 4 cycles (range, 1~6 cycles) of ICE regimen, and the median interval between each chemotherapeutic cycle was 24 days (range, 16~36 days). There were 7 (53.8%) complete responses, 4 (30.8%) partial responses, and 2 (15.4%) progressive diseases after ICE regimen. Toxicity included grade 3/4 neutropenia and throm bocytopenia in 13 (81.3%) and 7 (42.8%) patients, respectively. PBSC collection began on median day 12 (range, 6~20 days) after ICE therapy. The median number of mononuclear cells, CD34+ cells, and CFU-GM was 5.75× 10^(8)/kg, 1.25× 10^(6)/kg, and 1.19× 10^(5)/kg, respectively. With a median follow- up of 401 days, the patients who underwent autologous PBSCT had overall survival with 70.1±14.7% at 2 year and event free survival with 60.7±15.4% and 32.3±17.1% at 1 year and 2 years, respectively. Conclusion: ICE chemotherapy is an effective cytoreduction and mobilization regimen in patients with NHL, but profound myelosuppression with delayed recovery might pose difficulties in applying for Korean patients. Further evaluation for appropriate salvage regimens in Korean patients should be needed.

할로페리돌로 유도한 신경세포 고사에 대한 신경성장인자 및 인슐린 유사 성장인자의 억제효과

강효정,강지윤,곽병주,정영기,노재성 大韓神經精神醫學會 2000 신경정신의학 Vol.39 No.5

연구목적: 본 연구는 생쥐 태자의 대뇌피질 세포 일차 배양을 이용하여 할로페리돌로 유도한 신경세포의 사멸에 대해 신경 성장인자인 brain-dervied neurtrophic factor(BDNF), Neurotrophin 4/5(NT 4/5)와 인슐린 유사 성장인자인 insulin-like growth factor Ⅰ(IGF-Ⅰ)및 IGF-Ⅱ의 조절효과를 실험한 것이다. 방법: 생쥐 태자의 신경세포를 배양한 후 할로페리돌을 처리하여 신경세포의 사멸을 유도하고 이에 대한 성장인자의 효과를 정량적으로 분석하였다. 결과: 30M의 할로페리돌을 배양한 일차 대뇌 신경세포에 24시간 처리하면 광범위한 신경세포의 사멸이 유도된다. 이때 신경세포는 세포의 응축, DNA의 단편화와 응집, 세포막보다 핵막의 이른 붕괴 등 고사 형태의 신경세포 사멸 특성을 보인다. 할로페리돌과 더불어 신경성장인자인 BDNF, NT 4/5 및 인슐린 유사 성장 인자인 IGF-Ⅰ 혹은 IGF-Ⅱ를 동시에 처리할 경우 용량 의존적으로 신경세포의 사멸을 억제한다. 결론: 본 연구의 결과는 할로페리돌에 의한 신경독성이 성장인다들에 의해 억제될 수 있음을 보여주는 것이며, 장기적인 항정신병약물의 사용 후에 발생하는 부작용인 지발성 운동장애의 한가지 원인 가설로 대두되고 있는 항정신병 약물에 의한 신경독성을 신경성장인자에 의해 억제할 수 있을 가능성을 제시하는 것이다. 중심단어:할로페리돌·고사·세포사멸·고사·BDNF·NT-4/5·IGF-Ⅰ·IGF-Ⅱ. Objectives: We examined the effects of neurotrophins and insulin-like growth factors on cell death induced by haloperidol, a typical anti-psychotic agent. Method: Neocortices from 14- or 5-daysold fetal mice for neuron-glia co-cultures were used for this experiment. Result: Twenty-four hours treatment of mouse cortical cell cultures with 30 M haloperidol-induced wide spread neuronal apoptosis characterized by cell body shrinkage, DNA frag-mentation and condensation. Concurrent treatment with growth factors, BDNF, NT4/5, IGF-Ⅰand IGF-Ⅱ, protect the neurons from the haloperidol-induced neuronal apoptosis(HINA) in a dose dependent manner(10-100ng/ml). Conclusion: The present study suggests the possibility that haloperidol toxicity can be hampered with growth factors. Further study about the mechanism underlying the protective capacity of the growth factors on HINA may lead to the development of the new protective strategy for tardive dyskinesia. KEY WORDS:Haloperidol·Apoptosis·Neuronal death·BDNF·NT4/5·IGF-Ⅰ·IGF-Ⅱ.

동종 골수이식을 시행받은 환자에서 폐색성 세기관지염에 의하여 발생한 자발성 기종격동과 피하 기종

이병환,이제중,이연경,안재숙,김여경,황호인,박무림,조상희,정익주,김형준 대한조혈모세포이식학회 2002 대한조혈모세포이식학회지 Vol.7 No.2

저자들은 만성골수성백혈병으로 동종 골수이식과 이식편 부전으로 인하여 추가적인 말초혈액 조혈모세포이식을 시행 받은 환자에서 만성 이식편대숙주질환과 그 폐 합병증인 폐색성 세기관지염에 동반된 자발성 기종격동과 피하 기종이 병발한 1예를 경험하였기에 이를 보고하는 바이다. Obstructive lung disorders following after allogeneic bone marrow transplantation (BMT) in association with graft- versus-host disease (GVHD) contribute significant morbidity and mortality. We report a case of a 28-year-old man who developed spontaneous pneumomediatinum and subcutaneous emphysema complicating bronchiolitis obliterans after allogeneic BMT. He received an allogeneic BMT for chronic phase of chronic myeloid leukemia. Five months after BMT, he was boostered by allogeneic peripheral blood stem cells from the same donor due to graft failure. One month after the boostering, chronic GVHD developed and were treated with cyclosporine and steroid. The patients developed spontaneous pneumomediatinum and subcutaneous emphysema secondary to severe bronchiolitis obliterans 4 months after boostering donor cells. The air-leak syndromes were recovered by conservative management, including high-flow oxygen.

건일로딘 정(미결정에토돌락 200 ㎎)에 대한 에토돌 정의 생물학적동등성

이정애,이윤영,조태섭,박영준,문병석,김호현,이예리,이희주,이경률 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.4

A bioequivalence of Etodol™ tablets (Yuhan corporation) and Kuhnillodine™ tablets (Kuhnil Pharm, Co., Ltd.) was evaluated according to the guideline of Korea Food and Drug Administration (KFDA). Single 200 ㎎ dose of etodolac of each medicine was administered orally to 24 healthy male volunteers. This study was performed in a 2×2 cross-over design. Concentrations of etodolac in human plasma were monitored by a high-performance liquid chromatography. AUCt (the area under the plasma concentration-time curve from time zero to 24 hr) was calculated by the linear trapezoidal rule method. C_(max) (maximum plasma drug concentration) and T_(max) (time to reach C_(max)) were compiled from the plasma concentration-time data. Analysis of variance was performed using logarithmically transformed AUCt and C_(max). No significant sequence effect was found for all of the bioavailability parameters. The 90% confidence intervals of the AUCt ratio and the C_(max) ratio for Etodol™/Kuhnillodine™ were 1.01 - 1.10 and 0.87 - 1.06, respectively. This study demonstrated a bioequivalence of Etodol™ and Kuhnillodine™ with respect to the rate and extent of absorption.

스포츠센터 운영을 위한 마케팅전략 분석 : 성인여성회원을 중심으로

김미정,김병주,정철규,박충일 龍仁大學校 2000 용인대학교 논문집 Vol.18 No.-

Administrative plan and execution should be premised exact analysis of customer background and customer behavior. This means profits of customer are promoted by satisfying their need and desire, and that results in development and success of this business. The purpose of this study was to investigate the satisfaction of adult women members who are useful for making marketing strategy of commercial sports center. We had conclusions as follows : 1.The main motivation of using the sports facilities is advertising paper(54.3%) and frequency of using them is swimming pool(38.4%), aerobic(36.4%), fitness center(36.4%). It is revealed necessary facilities are swimming pool(17.3%), exercise prescription room(16.4%), resting room(12.7%) by the subjects of this study. 2.The results of correlation efficiency between choosing factors and individual tendency are the old prefer facility level and highly educated prefer location and excellent instructor. 3.The users satisfied with facility, equipment, exercise implement, parking lot, shower and locker room but dissatisfied with resting room, restaurant and store. Provided incident facilities to these, it would bring about efficiency and profit. 4.In terms of facilities satisfaction, the results of regression showed significant difference in equipment, exercise implement, shower and locker room. 5.In terms of program satisfaction, the results of regression showed significant difference in diversity of the program and properly instruction time. 6.In terms of staffs and instructors satisfaction, the results of regression showed significant difference in ability, attitude, method and responsibility of instructor and kindness of staffs.

STI571 (Glivec^(�))에 의하여 빠른 치료 반응을 보인 불응성 Gastrointestinal stromal tumor

윤경원,이제중,김여경,황호인,이병환,조상희,정익주,김형준 全南大醫大 2001 전남의대학술지 Vol.37 No.4

필라델피아 염색체 양성 급성골수성백혈병에서 Imatinib Mesylate로 분자학적 관해를 유도한 후 성공적인 자가 말초혈액 조혈모세포이식이 시행되었던 1예

김여경,이제중,이병환,변정래,조덕,이일권,정익주,양동욱,김형준 대한조혈모세포이식학회 2003 대한조혈모세포이식학회지 Vol.8 No.1

저자들은 필라델피아 염색체 양성 급성골수성백혈병 환자에서 복합항암화학요법으로 혈액학적 완전관해를 유도하고, imatinib mesylate를 이용하여 분자학적 관해를 유도한 후, 성공적으로 자가 말초혈액조혈모세포이식을 시행하였던 1예를 경험하였기에 이를 보고하는 바이다. Philadelphia chromosome (Ph¹)-positive acute myeloid leukemia (AML) is very rare disease, comprising 3~4% of the AML, and is a clinically distinct entity with poor clinical outcome with conventional chemotherapy. We report a case of Ph¹-positive AML who underwent successful autologous peripheral blood stem cell transplantation after achieving a molecular remission with imatinib mesylate.

주요우울증에 대한 Milnacipran의 효과 및 안정성 : Fluoxetine과의 비교

이민수,함병주,기백석,김정범,연병길,오강섭,오병훈,이철,정한용,지익성,최병무,백인호 大韓神經精神醫學會 2004 신경정신의학 Vol.43 No.4

Objectives : This 6-week, open label randomized, multicenter study was conducted to evaluate the antidepressant effect and safety of milnacipran and fluoxetine in patients with major depression. Methods : The study was done in patients with major depression diagnosed by DSM-IV who score ≥17 in 17 items Hamilton Rating Scale for Depression (17-item HAM-D) and score ≥25 in Montgomery and Asberg Depression Rating Scale (MADRS). A total of 87 patients were randomized to milnacipran group and fluoxetine group. In cases of the patients taking other antidepressants, 6 weeks of each medication was administered after 7 days of drug excretion period. The evaluation was done using 17 item HAM-D, MADRS, Clinical Global Impression Scale (CGI), and COVI scale after baseline, 1 week, 2 weeks, 4 weeks, and 6 weeks. The side effects that had occurred during the period of our study were put in records by developed/disappeared time, severities, incidences, managements and results. Results : A total of 87 patients were enrolled. 70 (mitnacipran group 39 ; fluoxetine group 31) of them were included for the 6 weeks of research and 17 of them dropped out with in the first week, not due to adverse reactions or deficiency of effects. Total 17 item HAM-D scores, total points of MADRS, and CGI showed significant decrease after 1 week in each treatment group and continued decrease after 2 weeks and 4, 6 weeks. But there was no difference between milnacipran group and fluoxetine group in the antidepressant effect. There were no significant changes in vital sign, CBC, chemistry, and EKG in each treatment group. The commonly reported side elfects of minlacipran were nausea (25.0%), headache (10.7%), vomiting (7.1%),constipation (7.1%), dizziness (7.1%) and those of fluoxetne were GI trouble (11.1%), diarrhea (11.1%), insomnia (11.1%),agitation (5.6%), and dizziness (5.6%). Conclusion : Milnacipran was effective for the improvement of depressive symptoms and was well tolerated and safe in patients with depression.

多樣한 黃芩藥鍼製劑의 安全性 및 效能에 關한 硏究

김호경,마진열,전원경,윤수영,강은정,주혜정,고병섭 한국한의학연구원 1997 한국한의학연구원논문집 Vol.3 No.1

In order to detect the safety and effect of various aqua-acupunctures from Scutellariae Radix, the modifications of boiling, filtration and dilution were employed for the manufacture of aqua-acupunctures. We injected 0.2cc of aqua-acupunctures into Joksamri(足三里) of rat, repeatedly. we compared subacute toxicity of them with saline group, distilled water(D.W.) group, acupuncture group and control group. The results were summarized as follows: 1. The groups were all healthy and alive, and there was no special abnormality in physical condition and autopsy. And there were not any toxic symptoms in repeating application of aqua-acupunctures to the rat, including changes of body weight, organ weight, haematological examination and serum biochemical test. 2. There was slight change of body weight in acupuncture group : We could see significance after 3 days (p<0.05) and after 7 days (p<0.001) in body weight loss. After 9 days, all tested groups were suppressed in body weight increment. 3. Result of organ weight: In Palking aqua-acupuncture(D-2 group), saline group and acupuncture group there were some statistical significance. Especially, acupuncture group revealed significant result in liver and spleen than aqua-acupunctures. From this result, we could suggest that the efficacy of acupuncture was preceded herbal medicine. 4. In serum biochemical test, we examined glucose(GLU), triglyceride(TG) and cholesterol(CHOL). In comparison with control group, the diluted 10 times of hwanggum aqua-acupuncture (× 10 group) was recognized significant decrease of glucose, but the diluted 100 times of Hwanggum aqua-acupuncture (× 100 group), D-2 group, saline group were confirmed significant increment. There was not any meaningful change of CHOL in all of tested group, excepting the acupuncture group was exhibited statistically significant decrease(p<0.05). In TG level all tested group except complex injection of standard compound (CPA group) and HG, there were significant value in statistically. The diluted solution was more significant decrease than Hwanggaum aqua-acupuncture(HG). The mutual relationship of components of aqua-acupuncture tended to decrease level of TG, regardless of its concentration. In acupuncture group, we gained some interesting result in meaningful decrease in TG. 5. Haematological examination showed significant increment of gramulocytes(GR) in all tested groups except Hwanggum aqua-acupuncture. And the diluted solutions of HG expressed very high increment of them(p<0.001). The GR and Mean Corpuscular Volume(MCV) of acupuncture group showed statistical significance.