지연성 운동장애(Tardive Dyskinesia)의 최근 견해

김용식,강웅구,주연호,Kim, Yong-Sik,Kang, Ung-Gu,Joo, Yeon-Ho 대한생물정신의학회 1996 생물정신의학 Vol.3 No.1

Tardive dyskinesia is a syndrome of involuntary hyperkinetic abnormal movements that occurs during or shortly after the cessation of neuroleptic drug treatment. Typically, the movements are choreoatheoid. Other movements such as tics and dystonia may be present. Nonetheless, any dyskinesia seen in a neuroleptic-treated patient is not always neuroleptic-induced tardive dyskinesia. The prevalence of tardive dyskinesia varies widely, which reflects many methodological problems, such as differential diagnosis. symptom fluctuation, masking effect of neuroleptics, validated diagnostic criteria. Of suggested risk factors, only old age has been consistently found to be associated with an increased frequency of tardive dyskinesia. Many hypotheses about the pathophysiolgy of tardive kinesia are proposeed, but time-honored ones are not present. No consistently safe and effective treatments are found. Various treatment modalities signifies the general ineffectiveness of these agents for most patients. In general, reduction or cessation of neuroleptics, if possible, is recommended. Remission or improvemets of tardive dyskinesia after neuroleptics withdrawal usually occurs among most patients within three months.

MPTP와 대사물인 $MPP^+$의 도파민 신경세포에 대한 독성효과에 관한 연구

김용식,박찬웅,윤영란,윤용하,Kim, Yong-Sik,Park, Chan-Woong,Yoon, Young-Ran,Youn, Yong-Ha 대한약리학회 1995 대한약리학잡지 Vol.31 No.2

Dissociated cell cultures from rat embryonic ventral mesencephalon were used to evaluate the mechanisms of $MPP^+$ neurotoxicity. The cells were treated with MPTP or $MPP^+$ and the viability of the cells was assessed biochemically; tyrosine hydroxylase (TH) immunoreactivity, protein, intracellular ATP and lactate content and lipid peroxidation. Also the generation of the intracellular oxidants was measured after loading 2', 7‘-dichlorofluorescin diacetate to the cells. When cultures were exposed to 0.1 mM $MPP^+$, at 2 hour incubation lactate was significantly accumulated in the cells and then the intracellular ATP content and TH immunoreactivity were decreased dose- and time-dependently. But, malondialdehyde as an index for lipid peroxidation was not changed even though the generation of the intracellular oxidants was stimulated by the addition of $MPP^+$. On the other hand, 1 mM MPTP significantly reduced the TH immunoreactivity at 24 hour exposure without any change in the intracellular A TP, lactate and MDA content until 6 hour exposure. And also MPTP inhibited the generation of the intracellular oxidants from control cells and $MPP^+$ exposed cells. These results indicate that cytotoxicity of $MPP^+$ is mediated by inhibiting the mitochondrial energy metabolism rather than generating the intracellular oxidants. And MPTP would have direct action in addition to conveting to the toxic metabolite, $MPP^+$ to exert the toxicity on the dopaminergic neurons.

Protective Effects of Calcium Antagonists and Vitamine E on the Ischemia-induced Neuronal Damage in Rat Brain Slices

김용식,윤영란,박찬웅,Kim, Yong-Sik,Yoon, Young-Ran,Park, Chan-Woong The Korean Society of Pharmacology 1993 대한약리학잡지 Vol.29 No.1

허혈성 뇌손상시 칼슘길항제, 항산화제와 산소라디칼 제거제 그리고 흥분성 아미노산 수용체 길항제의 보호효과를 검토하기 위해 본 연구에서는 랫트 뇌 해마조직 절편을 산소와 포도당을 제거한 반응액에 노출시켜 실험적 허혈상태를 유도하였다. 그리고 여러 약물을 처리한 상태에서 허혈시의 뇌세포 손상정도를 생화학적 지표들(절편내 ATP와 반응액내 lactate 및 malondialdehyde (MDA)유리량)을 측정하여 검토하였다. 60분까지 허혈상태를 유발시킨 경우 시간에 따라 절편내 ATP 함량이 감소하였고 lactate 유리량이 증가하였다. 그 후 산소와 포도당이 든 반응액으로 바꿔주니 이들 생화학적 변화들이 회복되는 양상을 보였다. 그러나 본 실험조건에서 허혈상태로부터 완전히 회복되지는 않았다. 동일한 허혈조건에서 verapamil과 비타민 E는 ATP 함량 감소와 절편으로부터의 lactate 유리량의 증가에 대해 보고효과를 보였다. 그리고 verapamil과 diltiazem은 반응액내로의 MDA유리를 감소시켰다. Superoxide dismutase (SOD), glutathione과 MK-801 (NMDA 수용체 길항제)은 20분 허혈조건에서 ATP 함량을 증가시켰으나 그외 다른 조건에서 보호효과를 보이지 않았다. 허혈 후 20분간 산소와 포도당을 재공급한 경우 verapamil은 ATP 함량과 lactate 유리에 보호효과를 보였다. 한편 비타민 E는 20분 허혈 조건에서의 lactate 유리와 60분 허혈시의 MDA 유리 증가에 대해 감소효과를 보였다. 이상의 결과는 칼슘길항제와 비타민 E가 랫트 뇌절편에서의 허혈성 생화학적 손상을 방지함으로 나타난 결과로 해석되며, 칼슘갈항제의 효과가 비타민 E보다 우수함으로 미루어 칼슘길항제는 허혈성 뇌손상에 예방 및 보고효과를 보일 것으로 믿어졌다. To evaluate the protective effects of calcium antagonists, oxygen radical scavengers and excitatory amino acid (EAA) antagonist on the ischemic brain damage, we induced in vitro ischemic condition (namely, lack of oxygen and glucose) to rat hippocampal slices. And the degree of ischemic damage was determined by assaying changes in biochemical parameters such as ATP content and lactate ralease, MDA production in the presence or absence of the various drugs. During experimental ischemia for up to 60 min, ATP content was decreased and the amount of lactate release was markedly increased time-dependently. By changing the reaction medium which contained oxygen and glucose those biochemical parameters were recovered. But the recovery was not complete in this experimental condition. In the same ischemic conditions verapamil and vitamine E prevented the decrease of ATP content and the increase of lactate release from the slices. And verapamil and diltiazem decreased MDA release to the reaction medium. Superoxide dismutase (SOD) and MK-801 (as EAA receptor antagonist) protected the decrease of ATP content and reduced MDA release in 20 min ischemic condition, but glutathione affected ATP content and lactate release at the same condition. When oxygen and glucose were resupplied for 20 min after ischemic condition, verapamil showed the protective effect on the changes of ATP content and lactate release, and vitamine E decreased lactate release (at 20 min ischemia) and MDA release (at 60 min ischemia). These results showed that calcium antagonist and vitamine E protect the ischemic biochemical changes from rat hippocampal slices and calcium antagonist is more potent than vitamine E to protect the ischemical brain damege.

Transforming growth factor ${\beta}_1$이 배양랫트 신경교세포의 성장 및 생화학적 변화에 미치는 영향

김용식,윤용하,박난향,박찬웅,Kim, Yong-Sik,Youn, Yong-Ha,Park, Nan-Hyang,Park, Chan-Woong 대한약리학회 1994 대한약리학잡지 Vol.30 No.2

Recent evidence indicates that glial cells have a wide range of funtions which are critical for maintaining a balanced homeostatic environment in the central nervous system(CNS) peripheral nervous system(PNS). Morever, astrocytes are known to participate in the tissue repair and neuroimmunologic events within the CNS through many kinds of growth factors and cytokines. We investigated the effect of $TGF\;{\beta}_1$, on the growth and biochemical changes of rat glial cells in culture. The proliferative effect was determined by $^3H-thymidine$ uptake and the double immunostain with anti-cell-specific marker and anti-Bromodeoxyuridine(BrdU) antibody. To check the effect of biochemical changes we compared the amounts of glial fibrillar acidic protein(GFAP) and the activity of glutamine synthetase(GS) in astrocyte. And the amounts of myelin basic protein and the activity of 2',3'-cyclic nucleotide phosphohydrolase(CNPase) were measured in oligodendrocyte and the amounts of peripheral myelin in Schwann cell. When $TGF\;{\beta}_1$, was treated for 2 days with cultured glial cell, $TGF\;{\beta}_1$, decreased the $^3H-thymidine$ uptake and proliferation index of double immunostain of astrocytes, which indicates the inhibition of astroglial DNA synthesis, but stimulated the growth of Schwann cell. Also, $TGF\;{\beta}_1$, decrease the GS activity and increased the amounts of GFAP in astrocyte. In the case of Schwann cells the amounts of peripheral myelin was increased when treated with $TGF\;{\beta}_1$. However, $TGF\;{\beta}_1$, didn't show any effect on the proliferation and biochemical changes in oligodendrocyte. These results suggest that $TGF\;{\beta}_1$, might have a critical action in the regulation of proliferation and biochemical changes in glial cells, especially astrocyte.

연구논문 - 펄프 , 제지 , 피혁분과 : 라이너지 제조공정의 폐쇄화율 향상을 위한 보류시스템 선정 및 적용 결과 (Ⅱ) - 현장적용에 따른 공정 및 제품 품질 변화 -

김용식,안국헌,오종익,이학래,성용주,박철웅,윤혜정 ( Yong Sik Kim,Kuk Hun Ahn,Jong Ik Oh,Hak Lae Lee,Yong Joo Sung,Chul Woong Park,Hye Jung Youn ) 한국공업화학회 1997 한국공업화학회 연구논문 초록집 Vol.1994 No.1

3개월간의 일본 연수

김용식,Kim, Yong-Sik 대한산업보건협회 1993 산업보건 Vol.64 No.-

한국윤활유공업협회 회장 취임사

김용식,Kim, Yong-Sik 한국윤활유공업협회 2007 윤활유협회보 Vol.123 No.-

새로운 항정신병약물의 약물상호작용

김용식,강웅구,노명선,Kim, Yong Sik,Kang, Ung Gu,Roh, Myoung Sun 대한생물정신의학회 2000 생물정신의학 Vol.7 No.1

Recently atypical antipsychotics have been used as first line agent in the treatment of schizophrenia, and also played a significant role in the treatment of many kinds of psychiatric disorders. The pharmacokinetic and pharmacodynamic properties of these newer antipsychotics are well known through preclinical and early clinical trials. However, it is important to note the limitations of the results due to its relatively short experience. Clozapine is eliminated principally by the hepatic P450 1A2 and 3A4 cytochrome enzymes. 1A2 inducers such as carbamazepine and smoking can reduce its half-life, while 1A2 inhibitors such as SSRIs, especially fluvoxamine can increase its duration of action. Carbamazepine should be avoided in a patient on clozapine because of carbamazepine's potential effects on bone marrow. Benzodiazepines tend to increase the chances of sedation, delirium and respiratory depression. Risperidone is metabolized to 9-hydroxyriperidone by the hepatic P450 2D6 cytochrome enzymes. Fluoxetine and paroxetine, 2D6 inhibitors interfere with metabolism, but 9-hydroxyrisperidone has similar biological activity as parental drug, so it has little affect on the outcome. Olanzapine shows minimal capacity to inhibit cytochrome P450 isoenzymes and shows minimal chance of drug interaction. It is eliminated principally by the hepatic P450 1A2 and 2D6 cytochrome enzymes.

Ascorbic acid가 에탄올 대사효소에 미치는 영향

김용식,Kim Yong-Sik 대한약리학회 1984 대한약리학잡지 Vol.20 No.1

Effect of ascorbic acid on various hepatic ethanol metabolizing enzymes including alcohol dehydrogenase(ADH), the microsomal . ethanol oxidizing system(MEOS), and catalase was quantitatively evaluated in liver microsomal and cytosolic preparation from Sprague-Dowley rats. In present study, ADH activities were no changed significantly by ascorbic acid. The MEOS activity, dependent on NADPH and $O_2$, was affected by azide (inhibitor of catalase) or exogenous catalase. In the presence of ascorbic acid, ethanol oxidation by rat liver microsomal preparation reacted with NADPH-generating system was increased by up to 22.5%, but decreased when liver microsome was reacted with $H_2O_2$ generated by xanthine and xanthine oxidase. Increase in the activity of the MEOS in the presence of ascorbic acid was greater in liver microsomal preparation pretreated with azide. Also ascorbic acid oxidized ethanol nonenzymatically. This ethanol oxidation induced by ascorbic acid was inhibited by OH radical scavengers (thiourea, sodium benzoate), but was not much affected by superoxide dismutase. From these results it was suggested that ascorbic acidcould interact directly with the MEOS, then promote the oxidation of ethanol. And, to some extent, ${\cdot}OH$-radicals or other radicals generated during the spontaneous autooxidation of ascorbic acid may be responsible for the production of acetaldehyde from ethanol.

2008 신년사

김용식,Kim, Yong-Sik 한국윤활유공업협회 2007 윤활유협회보 Vol.125 No.-