Fluoxetine이 Schedule-Induced Polydipsia가 유발된 백서 뇌에서 Tyrosine Hydroxylase 발현에 미치는 영향

이기철,이정호,최영민,정주호,정홍경,이용민,김도형,이대환 大韓神經精神醫學會 2001 신경정신의학 Vol.40 No.2

연구목적: Fluoxetine은 serotonin을 매개하여 간접적으로 dopamine 신경전달기능을 억제한다고 추정되고 있다. 또한 운동장애에서 운동기능의 악화를 유발한다고 알려져 있다. 그러나 신경세포체에서 fluoxetine이 dopamine에 어떠한 영향을 주는지는 아직까지 확실치 않다. 저자들은 schedule-induced polydipsia를 유발시킨 백서 뇌의 흑질, 복부피개영역, 미상핵에서 tyrosine hydroxylase(TH) 발현이 저하됨을 발견하였다. 이를 통해서 fluoxetine이 백서 뇌의 dopamine 기능에 긍정적인지 혹은 부정적인지를 규명하고자 하였다. 방법: 4주간의 schedule-induced polydipsia 과정을 거친 백서에서 면역죄치화학적인 방법으로 흑질, 복부피개영역, 미상핵의 tyrosine hydroxylase 발현이 저하됨을 확인한 후, 실험동물들에게 fluoxetine 10mg/kg를 3주간 복강내 주사하였다. 실험백서들을 희생시켜 뇌 조직을 적출하여, TH 면역조직화학 염색법을 이용하여 흑질, 복부피개영역, 그리고 미상핵의 TH 면역반응세포를 관찰하고 이를 정상백서와 비교하였다. 결과: 1) 다갈증이 유발된 백서의 흑질, 복부피개영역, 미상핵에서 tyrosine hydroxylase 발현이 정상백서 보다 저하됨을 관찰하였다. 2) 3주간에 걸친 fluoxetine 투여후 흑질, 복부피개영역, 미상핵의 tyrosin hydroxylase 발현이 다시 증가하는 소견을 보였다. 결론: Fluoxetine 만성투여가 흑질, 복부피개영역 그리고 미상핵의 tyrosin hydroxylase를 증가시키는 소견을 얻었다. 이러한 결과는 임상에서 dopamine 결핍과 연관된 질환들에서 fluoxetine을 만성투여하면 운동기능을 포함한 증상들의 개선을 가져올 수도 있다고 추정된다. Objective: It has been suggested that fluoxetine inhibits the dopaminergic neurotransmission by serotonergic mediation. And also, it has been shown to inhibit synthesis of DOPA in dopamine-rich areas of the rat forebrain. These dopamine-antagonistic capacity of fluoxetine is only supported by anecdotal report that the increased amount of motor disability in patients with idiopathic Parkinson's disease after exposure to fluoxetine. However, there is still no evidence of the direct effect of fluoxetine on dopaminergic neuronal cell body in the substantia nigra, VTA, caudate & putamen. This study was designed to evaluate the effects of fluoxetine in rat brain which showed decreased numbers of dopaminergic neuronal cell body induced by schedule-induced polydipsia(SIP). Method: We incidentally found that 4 weeks of schedule-induced polydipsic rats revealed the suppression of tyrosine hydroxylase expression in the substantia nigra, VTA, caudate & putamen with the immunohistochemistric measures. After 3 weeks of intraperitoneal injection of 10mg/kg of fluoxetine to the schedule induced polydipsic rats, the tyrosine hydroxylase expression was also measured with immunohistochemistry. We compared the tyrosine hydroxylase expression among the normal control, the polydipsic rats, and the rats with fluoxetine treatment. Results: 1) By contrast with the control, the polydipsic rats revealed the evidence of decreased tyrosine hydroxylase expression in the substantia nigra, VTA, caudate & putamen. 2)After daily injection of fluoxetine for 3 weeks, the polydipsic rats showed increment of tyrosine hydroxyase expression in those areas. Conclusions: In previous studies, a great deal of results suggest that fluoxetine negatively influence the dopaminergic systems indirectly via serotonergic activation such as inhibition of dopamine synthesis or transport system. Although our results are obtained from rodents, we suggest that fluoxetine directly and positively enhance the dopamine system in the substantia nigra, VTA, caudate & putamen. The chronic adminstration of fluoxetine may be helpful to dopamine-depleted condition in clinical situations. We anticipate the replication studies of our findings and well-controlled clinical trial.

에탄올을 장기간 섭취한 백서에서 Acamprosate 투여가 Nitric Oxide Synthase 발현에 미치는 영향

정홍경,이기철,이정호,이승휘,이희제,정주호 대한생물치료정신의학회 2002 생물치료정신의학 Vol.8 No.1

에탄올이 백서의 해마에서 Neuropeptide Y 발현에 미치는 영향

정홍경,이기철,이정호,이희제,정주호,이주영 대한생물치료정신의학회 2002 생물치료정신의학 Vol.8 No.1

고품질 복숭아 만생종 ‘진백’ 육성

이기우(Gi-Woo Lee1),박원흠(Won-Heum Park),권오흔(Oh-Heun Kwon),정경미(Kyung-Mi Jung),이형일(Hyung-Il Lee) 한국원예학회 2018 한국원예학회 학술발표요지 Vol.2018 No.10

Risperidone이 백서의 Schedule-Induced Polydipsia에 미치는 영향

이기철,이정호,윤도준,최영민,전성일,김태수,정홍경,하준명,정재현 大韓神經精神醫學會 2000 신경정신의학 Vol.39 No.3

연구목적 : 강박장애의 원인론중 세로토닌-도파민 가설에 기초하여 강박장애 동물모형으로 고려되는 고정된 시간 간격으로 평소의 먹이섭취량보다 작은 양의 음식물을 백서에게 장기간 공급하여 다음중(schedule-induced polydipsia : SIP)을 유발시켰다. SIP모형에 강박장애에 효과적이라고 알려진 선택적 세로토닌 재흡수 차단제로서 fluoxetine을 장기 투여하고, 신경절후 5-HT²와 도파민 D² 수용체를 동시에 차단하는 risperidone을 투여하고, 신경절후 도파민 수용체 차단제인 haloperidol을 투여하였다. 그결과로서 risperidone이 강박장애 동물모형으로 고려되는 SIP에서 어떤 영향을 미치는지 알아보았다. 방 법 : SIP를 유발하기 위해 각각의 사육상자에 1정당 90㎎의 사료를 자동급이장치 (automatic dispenser)에서 60초당 1정씩 고정된 시간 간격으로 하루에 150분씩 공급하였다. 4주간 고정된 시간 간격으로 머기를 공급하고 매주 음수량과 체중을 측정한 실험 동물과 동등한 사료의 양을 한번에 덩어리로 공급받은 통제 집단의 체중과 음수량을 비교하였다. SIP 행동변화를 보인 실험 동물들을 fluoxetine 5㎎/㎏(N=8), risperidone 0.1㎎/㎏(N=8), haloperidol 0.1㎎/㎏(N=8), 그리고 vehicle 대조군 1㏄/㎏(N=8)으로 나누고 각각의 실험 동물군에서 3주간에 걸쳐서 실험 약물을 매일 복강내 주사하였다. 매주 실험 동물의 음수량과 체중을 측정, 비교하였다. 결 과 : 1) 고정된 시간 간격으로 제한된 먹이를 공급한 실험 동물군은 1주부터 4주에 걸쳐서 기저치보다 유의한 음수량의 증가를 보였다. 반면 통제 집단은 2주째 음수량이 일시적으로 증가한 소견 이외에 4주간의 실험 기간중 유의한 변화는 보이지 않았다. 실험 동물과 통제 집단간의 음수량에서 3주와 4주째에 실험 동물이 통제 집단보다 유의하게 높은 음수량을 보였지만 양군간에 체중의 차이는 보이지 않았다. 2) 각각의 실험 동물군 내에서 risperidone 0.1㎎ 투여군은 약물 투여 2주부터 3주까지 기저치 음수량과 비교하여 유의한 저하를 보였다. Risperidone 0.5㎎ 투여군은 약물터여 3주에서 기저치의 음수량과 비교하여 유의한 저하를 보였다. Fluoxetine 투여군은 약물 투여 시작 1주부터 3주에서 기저치의 음수량과 비교하여 유의한 저하를 보였다. 한편, haloperidol 투여군과, vehicle은 3주간에 걸친 약물 투여에서 각각의 기저치 음수량과 비교하여 차이를 보이지 않았다. 3) 실험 동물 각 군간에 약물 투여 시간 경과에 따른 음수량을 비교한 바, 약물투여 1주에서 각 군간에 유의한 차이는 없었다. 약물 토여 2주에서 fluoxetine 투여군, risperidone 0.1㎎ 투여군, 그리고 risperidone 0.5㎎투여군이 haloperidol 투여군과 비교하여 유의한 차이를 보였다. 약물투여 3주째에 fluoxetine투여군, risperidone 0.1㎎ 투여군, 그리고 risperidone 0.5㎎투여군이 haloperidol 투여군, vehicle과 비교하여 유의한 음수량의 저하를 보였다. 결 론 : 백서의 강박 행동은 fluoxetine, risperidone에 의해 효과적으로 억제되었으나 haloperidol에는 반응이 없었으므로, 임상에서 난치성 강박장애의 치료에 비정형 항정신병 약물 투여를 고려해 볼 수 있다고 제안한다. Objectives : This study was designed to evaluate the effects of risperidone on the schedule-induced polydipsia(SIP) which is one of animal model of obsessive-compulsive disorder in rats. We administered risperidone as a serotonin and dopamine blocking agent, fluoxetine as a selective serotonin reuptake inhibitor, and haloperidol as a dopamine antagonist to rats which showed schedule-induced polydipsic behaviour. Methods : Sprage-Dawley rats weighing 200∼250gm were individually housed and maintained and allowed free access to water. The rats were placed on a restricted diet. To induce polydipsia, rats were placed in the cage where a pellet dispenser automatically dispensed 90㎎ pellets on a fixed-time 60 seconds(FT 60s) feeding schedule over 150 minute test session per day. Water was available at all times in the cage. After 4 weeks of daily exposure to the FT 60s feeding schedule, experimental rats met a predetermined criterion for polydipsic behavior(greater than 3 times of water per session on average). 5 groups of rats were administered risperidone(0.1㎎/㎏, i.p), risperidone(0.5㎎/㎏, i.p), fluoxetine(5㎎/㎏, i.p), haloperidol(0.1㎎/㎏, i.p), and vehicle(1㏄/㎏, i.p) for 3 weeks. The rats were tested once a week to access schedule induced polydipsic behavior. Water bottles were weighed before and after the 150-minute test session. The chronic effects of administration of experimental drugs on schedule induced polydipsic behavior were analyzed with ANOVA and Scheffe test as a post-hoc comparison. In order to measure water consumption in non-polydipsic food-deprived rats, a separate group of rats(N=8) was individually housed and given a single bolus(14.5gm) of food per day which maintained them at their average body weight. Results : The results were as follows ; 1) After 4 weeks of scheduled feeding procedure, the experimental group showed significant differences than the bolus control in the amount of water consumption as compared with their average water intakes for 4 weeks. At the same periods, there were no differences between the experimental group and the bolus control in the body weight. 2) The fluoxetine group showed significant decrease in the amount of water intake at 1st, 2nd, and 3rd weeks of drug treatment as compared with their average amount of polydipsic water intakes. The risperidone 0.1㎎ group and the risperidone 0.5㎎ group showed significant decrease in the amount of water intake at the 3rd weeks of drug treatment as compared with their baseline of polydipsic water intakes. However, the haloperidol group and the vehicle control group showed no changes of amounts of water intake for 3 weeks of treatment as compared with their baseline of polydipsic water intakes. 3) The fluoxetine group(22.5±10.4ml) showed significantly lower amounts of water intake than haloperidol group(41.3±7.1ml) at 2nd weeks of drug treatment. And also the fluoxetine group(18.8±3.5ml) showed significantly lower amounts of water intake than the haloperidol group(35.0±11.7ml) and the vehicle control(34.4±6.8ml) at 3rd weeks of drug treatment. The risperidone 0.1㎎ group and the risperidone 0.5㎎ group showed significantly lower amounts of water intake than the haloperidol group(35±11.7ml) at 2nd weeks and the vehicle control(37.5±12.5, 34.4±6.8ml) at 2nd and 3rd weeks of drug treatment. Conclusions : Above findings suggest that the fixed time feeding procedure for schedule induced polydipsia could be applied as an effective animal model of obsessive compulsive disorder for the evaluation of pharmacological challenge study. We confirmed that chronic treatment with risperidone revealed antipolydipsic effect as effective as fluoxetine on the schedule-induced polydipsic behaviour but the onset of effect was later than fluoxetine.

소아 여성 요도탈출증

이경섭,최병기,배한익 東國大學校 1993 東國論叢 Vol.32 No.-

Urethral prolapse in female patients is a characterized by the protrusion of the urethral mucosa through the external urethral meatus. It is a rare pathological condition that generally occurs in prepubertal black girls and in postmenopausal white women. We experienced a case of urethral prolapse in a 12-year-old girl at Pohang hospital of Dongguk University. The clinical characteristics and treatment of the urethral prolapse are discussed with references.

구리와 철분말의 사출성형 및 소결

이혁기,이동희,장경옥 연세대학교 산업기술연구소 1991 논문집 Vol.23 No.2

The mixtures of Cu or Fe powders and microcrystalline wax as binder were extruded into the long wire by metal injection molding method and sintered after debinding at different conditions. In the case of coarse(33㎛) and irregular Cu powders, the mixture containing 50 vol% wax was suitable for the uniform mixing and forming when injected at 70℃. Binder in coarse Cu powder mixtures was removed at 300℃ for 10 hours. On the other hand, for the spherical and fine Fe powders(4㎛) 30 vol% wax was appropriate and 78% of wax was removed at 400℃ for 1 hour. The density of sintered Cu specimens reached up to 73% of full density when sintered at 1000℃ for 1 hour, but that of Fe specimens was observed to be as high as 97% when sintered at 1200℃ for 1 hour after the optimum debinding.

Clozapine 투여로 유발된 무과립구증 1례

이기철,정홍경,이정호,최영민,전성일,최수전 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

저자들은 clozapine 투여 29일이 경과한 시점에서 무과립구증을 보인 20세 여자환자 1례를 치험하였기에 문헌고찰과 함께 보고하였다. 무과립구증은 무균처치와 항생제투여 및 G-CSF와 GM-CSF를 투여하여 무과립구증 상태는 8일만에 회복되었다. Clozapine에 의해 유발된 무과립구증의 원인은 아직까지 확실치 않다. 현재까지 알려진 원인으로는 MHC(major histocompatibility complex region)의 우성인자가 원인이라는 제안과 대사산물이 자유기근으로서 골수세포를 억제한다는 설이 제안되고 있다. 저자들은 clozapine을 투여함에 있어서 환자의 선정, 위험인자들의 고려 및 철저한 CPMS 관리를 제안하고, 일단 무과립구증이 발생하면 즉각적으로 내과적인 도움을 받을 것을 권장한다. We report a 20-year-old female patient who developed clozapine-induced agranulocytosis on the 29th day of clozapine treatment. She recovered from the agranulocytosis on the 8th day of progression after treatment with G-CSF, GM-CSF, antibiotics and associated aseptic procedures. The cause of clozapine-induced agranulocytosis is still un known and it is proposed that the dominant gene of major histocompatibility complex region and the reactive metabolites which suppress the myeloid system may be responsible. We recommend that careful attentions such as the selection of patient, evaluation of the risk factors, and the thorough control of CPMS should be paid. If the agranulocytosis happens, it is helpful to consult to the department of medicine immediately.

식물체의 활성 물질연구(Ⅰ) : 소나무잎의 지방산 조성 Fatty acid composition in the needle of Genus Pinus

이미경,노기환 광주보건대학 1993 論文集 Vol.18 No.-

In order to investigate of the fatty acid composition in the needle of Genus Pinus, this study was carried out. The raw materials used in this study were the green needle of Pinus densiflora, Pinus rigida and Pinus thunbergii. The results obtained are as follows : 1. Three samples such as Pinus densiflora, Pinus rigida and Pinus thunbergii, moisture, Crude protein, Crude Lipid and ash was 61.6%, 5.95% and 6.10% ; 7.46%, 6.95% and 7.63% ; 11.61%, 10.53% and 11.85% ; 2.66%, 2.45% and 2.57% respectively. 2. In the Pinus densiflora, 11 kinds of fatty acids were analyzed and one unknown peak comes out. There are 10 kinds of fatty acid were analyzed in the needle of Pinus rigida and Pinus thunbergii. 3. There are favorable contents of essential fatty acid in the needle of Genus Pinus. Especially the contents of linoleic acid were 51~55%, alpha linolenic acid were 8.7~9.9% and arachidonic were 2~2.28%. 4. P/S ratio for Pinus densiflora, Pinus rigida and Pinus thunbergii was 6.23, 6.01 and 5.28 respectively. Therfore, there are a lot of polyunsaturated fatty acid in the needle of Ginus Pinus what we obtained. 5. W-6/W-3 ratio for Pinus densiflora, Pinus rigida and Pinus thunbergii was 6.24, 5.64 and 6.37, respectively. Especially C_(18:2)/C_(18:3) was 5.9, 5.4 and 6.2 respectively.

추출시간에 따른 돼지 족(足)의 지방산과 칼슘·마그네슘 함량 변화에 관한 연구

이미경,노기환 광주보건대학 1989 論文集 Vol.14 No.-

The concent of fatty acid, calcium and magnesium of pig's shank according to be extracted hour was examined. The results what investigated are follows ; 1. There were 9 kinds of different fatty acids in water extract of pig's shank by GLC. The composition was not very different between each other. Linolenic acid was increased as much as 276% when extracted f o r 12hrs. but the amount of monounsaturated fatty acid was decreased as much as 30% by extracting hours. The amount of polyunsaturated fatty acid was decreased also by extracting hours. Therefore, p/s ratio was also decreased by extracting hours. 2. The amount of calcium, magnesium was analyzed by chelatemetry. The amount of calcium was 124.7mg% in raw materials, but water extract sample and bone powder showed higher value. In case of magnesium, it was 138.4 mg % in raw materials, but e xtract sample showed less amount and bone powder indicated higher value. Therefore, the amount of calcium and magnesium were the highest value in S_(B1) and T_(B2), respectively.