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        Clozapine이 백서의 억제된 자발적 교대 행동에 미치는 영향

        천강훈,이기철,이정호,최영민,전성일,정홍경,류정환,최미 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.5

        연구목적 : 강박장애의 생물학적 원인론중 세로토닌-도파민 상호작용 가설에 적합한 5-HT₂ 수용체와 도파민 D₂수용체를 동시에 차단하는 약물의 일종인 cloazpine과 세라토닌 재흡수 차단약물인 clomipramine, 그리고 도파민 D₂수용체 차단 약물인 haloperidol을 실험백서의 강박장애 동물모형에 투여하여 자발적 교대 행동에 미치는 영향을 비교, 측정하였다. 그 결과로서 1) 세라토닌 수용체와 도파민 수용체를 동시에 차단하는 약물의 효과를 확인하고, 2) 세라토닌과 도파민 수용체 동시차단 약물의 효과가 확인되면 임상적으로 기존의 세라토닌 재흡수 차단약물에 반응을 보이지 않는 강박장애 환자 치료에 세라토닌 수용체와 도파민 수용체를 동시에 차단하는 비전형적인 항정신병 약물들이 강박장애의 치료에 유용하게 사용될 수 있는 가능성을 제시하고자 하였다. 실험재료 및 연구방법 : 실험동물은 동일한 배에서 출생한 수컷 Spraque-Dawley 백서를 사용하였다. 자발적 교대 행동(spontaneous alternation behaviour : 이하 SAB)을 시험하기 위해 SAB의 기준치를 구하고 난 후, SAB을 차단하기 위한 방법으로 비선택적 세라토닌 순응제인 5-MeODMT(5-methoxy-N, N-dimethyltrytamine)를 투여하였다. 실험백서들을 clomipramine(5㎎/㎏), clozapine(10㎎/㎏), clozapine(20㎎/㎏), haloperidol(0.1㎎/㎏), 그리고 saline(0.2cc) 투여군으로 나누고 21일에 걸쳐서 복강내 주사하였다. 실험약물 투여가 끝난 다음날인 22일째에 5-MeODMT(5-methoxy-N, N-dimethyltryptamine : 1.25㎎/㎏/IP)를 각각의 실험동물군에게 투여하고 실험약물의 만성투여가 5-MeODMT 투여로 억제되는 SAB을 얼마나 호전시키는 지를 측정하였다. 모든 자료는 SPSS for window 7.5으로 통계처리 하였다. SAB의 기준치 5-MeODMT 투여로 억제되는 SAB의 효과, 실험약물의 만성투여에 따른 SAB의 변화는 일원분산분석을 사용하였으며, 사후검증은 Scheffe 검증을 적용하였다. 각 군내에서 기준치와 5-MeODMT 투여로 억제되는 SAB의 변화, 그리고 실험약물의 만성투여에 따른 SAB의 변화는 다중변량분석을 시행하였다. 결과 및 결론 : 역구결과 실험동물은 T-형 미로의 SAB에서 평균 1.33±0.36회의 훈련 기준치를 보였다. 5-MeODMT 주사후 , 실험동물의 SAB치는 3.12±0.63회를 보여 강박행동이 유발하였다. 21일간의 실험약물 투여후, 22일째에 5-MeODMT 주사에 대한 SAB의 반응은 clozapine 투여군과 clomipramine 투여군이 halo-peridol 투여군과 saline 투여군에 비하여 유의하게 낮은 수치를 보여 5-MeODMT투여로 억제된 SAB을 호전시키는 소견을 나타냈다. 각 실험동물군 내에서 각각의 SAB 훈련 기준치와 실험약물 투여 전후에 5-MeODMT 투여로 인한 SAB을 비교한 바, clomipramine 투여군은 약물투여 전에 5-MeODMT로 억제된 SAB이 약물투여후 의미있게 호전되었다. 한편, clozapine 투여군도 약물 투여전에 5-MeODMT로 억제된 SAB가 약물투여후 의미있게 호전되었으며, 이런 SAB의 호전은 clomipramine 투여군보다 우수하였다. 이상의 연구결과로 보아, 강박장애의 생물학적 병리론을 이해하는데 있어 세라토닌-도파민 상호작용 가설이 의미가 있음을 추정할 수 있었다. 향후, 강박장애의 임상치료에서 전형적인 SSRIs 치료에 반응치 않는 환자들에게 세라토닌-도파민 동시차단제인 비전형적인 약물의 단독투여를 시행하는 후속연구를 기대해 본다. Objectives : This study was designed to evaluate the role of the 5-HT₂and dopamine D₂antagonist on spontaneous alteration behaviour which is an animal modal of obsessive-compulsive disorder in rat. On the basis of serotonin-dopamine interaction hypothesis, the effect of clozapine was evaluated by applying the suppressed spontaneous alternation behaviour model. Methods : The apparatus for spontaneous alternation behaviour was a black plexiglas T-maze with distinctive black and white goal boxes. Black guillotine doors separated the start box and the goal boxes from the main body of the T-maze. Small cups of chocolate milk were placed in the corners of both goal boxes. At 24 hours prior to experiment, rats(Spraque-Dawley) food-deprived. The food-deprived rats were put into T-maze, in which both goal boxes were baited with small amounts of chocolate milk. Each rat was given 2 set of 7 trials during which it was placed in the start box and allowed to choose one of the goal boxes for each time. The mean number of choices until the occurrence of spontaneous alternation behaviour were checked. After baseline of the number of choices of spontaneous alternation behaviour was stabilized, the spontaneous alternation was disrupted by nonselective 5-HT agonist, 5-MeODMT(1.25mg/Kg/IP), The experimental animals were stratified into 5 groups :clomipramine(5mg/Kg/IP), clozapine(10mg/Kg/IP), clozapine(20mg/Kg/IP), haloperidol(0.1mg/Kg /IP), and saline(0.2cc/IP) control groups. They all went through 21 days fo treatment(intraperitoneal). The protective effects against the 5-MeODMT-induced disruption of spontaneous alternation behaviour were evaluated on the next day of drug treatment in each group. Results : 1) SAB was suppressed by 5-MeODMT injection. 2) After 21 days of the drug treatment, the clozapine and the clomipramine groups showed significant difference from the haloperidol and the saline control groups in the reversal of 5-MeODMT-induced suppression of spontaneous alternation behaviour. 3) The clozapine (20mg/kg/IP) group was superior to the clomipramine group in the protective effect of 5-MeODMT-induced suppression of spontaneous alternation behaviour. Conclusion : In clinical situation, the we think that atypical antipsychotic drugs those acting as serotonin and dopamine receptor antagonist with no extrapyramidal side effect can be beneficial to improve the symptoms of obsessive-compulsive disorder.

      • 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.

      • KCI등재
      • KCI등재

        흉부외상 없이 발생한 흉부대동맥 절단증의 조기 진단 : 2례 보고 Two Cases Report

        한승백,전영진,백광제,김준식,김정택,김광호,선경 大韓應急醫學會 1998 대한응급의학회지 Vol.9 No.4

        Aortic transection or interruption is a rare condition which developed after an acute deceleration injury. Its occurrence depends on the location and direction of the force applied and is usually from motor vehicle accident or falling down. The exact incidence of aortic transection in trauma is not known but, when develops, only about 10-15% of the victims can survive and be transported to the hospital. Even in the survivors, majority of them will be fatal within a few days if a prompt diagnosis and surgical treatments are not made. Aggressive diagnostic work-up is recommended for the patients with high suspicious index, which would salvage the victims with this fatal condition. We report the experience of two cases of aortic transection or interruption following motor vehicle accidents.

      • Risperidone이 백서의 억제된 자발적 교대행동에 미치는 영향

        이기철,이정호,김진규,정홍경,천강훈,류정환,최영민,전성일 대한생물치료정신의학회 1998 생물치료정신의학 Vol.4 No.2

        Objectives : Recently, some case reports have shown that risperidone is effective to refractory obsessive-compulsive disorder. Possible explanations for efficacy of risperidone in refractory obsessive-compulsive disorder maybe due to that it is both serolonin and dopamine receptor antagonist. On the basis of serotonin-dopamine interaction hypothesis, a biological etiology of obsessive-compulsive disorder, the effect of risperidone was evaluated to the suppressed spontaneous alternation behaviour of animal model of obsessive-compulsive disorder in rats. Methods : The apparatus for spontaneous alternation behaviour was a black plexiglas T-maze with distinctive black and white goal boxes. Black gullotine doors separated the start box and the goal boxes from the main body of the T-maze Small cups were placed in the corners of both goal boxes(all arms measured 50×10cm) 24 hours prior to experiment, rats(Spraque-Dawley) were food-deprived. The food-deprived rats were put into T-maze, in which both goal boxes were baited with small amounts of chocolate milk. Each rat was given 2 set of 7 trials during which it was placed in the start box and allowed to choose the one of the goal boxes for checked. After baseline of the number of choices of spontaneous alternation behaviour was stabilized, the pontaneous alternation disrupted by nonselective 5-HT agonist, 5-MeODMT (1.25mg/kg/IP). The experimental animals were stratified into 5 groups, fluoxetine(10mg/kg/IP), risperidone(0.1mg/Kg/IP), haloperidol(0.1㎎/Kg/IP), fluoxetine(10mg/Kg) with haloperidol(0.1 mg/Kg), and saline(0.5cc/IP) control group. Each drugs were injected for 21 days as a chronic treatment. The protective effects were evaluated on the nest day of discontinuation of the each drugs among 5 groups. Results : 1) After 21 days of the drug treatment, the risperidone group and the fluoxetine group showed significant difference from the haloperidol group and the saline control group on the protection of the 5-MeODMT induced suppression of spontaneous alternation behaviour. 2) The fluoxetine group and fluoxetine with haloperidol group showed significant difference between before and after treatment in the protection of 5-MeODMT induced suppression of spontaneous alternation behaviour. The risperidone group also showed significant difference between before and after treatment in the protection of 5-MeODMT induced suppression of spontaneous alternation behaviour, but the protective effect of risperidone was superior to fluoxetine. Conclusion : These findings suggest that both risperidone and fluoxetine have a favorable effect in the protection of 5-MeODMT induced suppression of spontaneous alternation behaviour. We think that risperidone can be possible alternatives to SSRIs in the treatment of refractory obsessive-compulsive disorder in clinical situation.

      • 반복치료로 호전된 호산구성 폐렴 유사 폐흡충증 1예

        박세진,김희규,김봉준,이천우,옥철호,정만홍 고신대학교 의과대학 2010 고신대학교 의과대학 학술지 Vol.25 No.2

        우리나라에서 인기 있는 게장등의 섭취로2) 성인뿐만 아니라 소아에서도 지속적으로 보고되고 있는 폐흡충증은 다양한 임상양상을 보일 수 있다. 저자들은 방사선 소견상 만성 호산구성 폐렴과 유사하였고, 반복적인 치료로 호전된 폐흡충증 1예를 경험하였기에 보고하는 바이다. Paragonimiasis mostly occurs by ingestion of raw or undercooked freshwater crabs or crayfish. Recently, re-emergence of paragonimiasis is reported because of ingestion of raw food such as freshwater fish and Gejang (marinated raw crabs). As the radiological features as well as the laboratory findings are similar to those of chronic eosinophilic pneumonia, the diagnosis of pulmonary paragonimiasis is often difficult and delayed. A 43 year-old female was visited our hospital for migrating and new developing consolidative lung lesions and peripheral blood eosinophilia. The eosinophil profile of leukocyte was 32% (absolute count 2,690 /mm3). Histologic finding was organizing pneumonia pattern with severe infiltration of eosinophils. Parasite specific antibody IgG forParagonimus westermani was positive (titer:0.61, normal range<0.20). After treatment with praziquantel (75mg/Kg once a day for 2days), the chest x-ray was clearly resolved. Follow-up study showed right pleural effusion, newly developed focal infiltration, and several nodules. After retreatment, we couldn't find any recurrent evidence.

      • SCOPUSKCI등재

        한국 정상인에서 연령에 따른 뇌혈류분포와 혈류예비능의 변화 : Tc-99m HMPAO SPECT 에 의한 연구

        문대혁,이희경,송호천,이재태,범희승,손혜경,정환정,민정준,김지열 대한핵의학회 1999 핵의학 분자영상 Vol.33 No.3

        Purpose: The aim of this study was to evaluate the normal values of regional cerebral blood flow (rCBF) and cerebrovascular reserve (CVR) in normal children to aged volunteers using Tc-99m HMPAO. Materials and Methods: Thirty four right-handed normal volunteers (20 males, 14 females, mean age 40.3±24.9 years, range 4 to 82 years) were underwent rest/acetazolamide (ACZ) brain SPECT using Tc-99m HMPAO and the sequential injection and subtraction method. rCBF was estimated on the basis of a semiquantitative approach by means of right/left ratio, region/cerebellum and region to whole brain ratios in frontal, parietal, temporal, and occipital lobes, basal ganglia, thalami, and cerebellum. CVR was measured by means of % perfusion increase calculated as % mean count change compared to rest rCBF in each regions. Results: Mean values of right to left ratios range from 1.004 to 1.018. rCBF was highest in cerebellum and lowest in basal ganglia and thalami. Frontal and temporal rCBF decreased while occipital and thalami rCBF increased according to age. No sexual difference of rCBF was noted. Mean CVR was 29.9±12.9%. Mean CVR significantly increased to late teens, and declined thereafter. After 6th decade, CVR in both frontal lobes, left parietal lobe and right basal ganglia decreased significantly with advancing age. There was no sexual difference of CVR. Conclusion: Quantitative assessment of CVR was possible by ACZ Tc-99m HMPAO brain SPECT. It revealed that rCBF and CVR changed according to age in normal Korean volunteers. There was no sexual difference.

      • KCI등재
      • SCOPUSKCI등재

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