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        정신분열병에 대한 리스페리돈의 효과 및 안정성

        이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

        '스콜라' 이용 시 소속기관이 구독 중이 아닌 경우, 오후 4시부터 익일 오전 7시까지 원문보기가 가능합니다.

        연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

      • SCIESCOPUSKCI등재

        Involvement of Adenosine in Cardioprotective Effect of Catecholamine Preconditioning in Ischemia-Reperfused Heart of Rat

        Young-hoon,Kim,Chan-hyung,Kim,Gi-tae,Kim,In-kyu,Kim,Jong-wan,Park,Myung-suk,Kim 대한생리학회-대한약리학회 1998 The Korean Journal of Physiology & Pharmacology Vol.2 No.6

        '스콜라' 이용 시 소속기관이 구독 중이 아닌 경우, 오후 4시부터 익일 오전 7시까지 원문보기가 가능합니다.

        <P> Preconditioning of a heart with small doses of catecholamines induces a tolerance against the subsequent lethal ischemia. The present study was performed to find a specific receptor pathway involved with the catecholamine preconditioning and to test if adenosine plays a role in this cardioprotective effect. Isolated rat hearts, pretreated with small doses of ㄁- or ㄂-adrenergic agonists/antagonists, were subjected to 20 minutes ischemia and 20 minutes reperfusion by Langendorff perfusion method. Cardiac mechanical functions, lactate dehydrogenase and adenosine release from the hearts were measured before and after the drug treatments and ischemia. In another series of experiments, adenosine A<SUB>1</SUB> or A<SUB>2</SUB> receptor blockers were treated prior to administration of adrenergic agonists. Pretreatments of a ㄂-agonist, isoproterenol(10<SUP>⁣9</SUP>∼10<SUP>⁣7 </SUP>M) markedly improved the post-ischemic mechanical function and reduced the lactate dehydrogenase release. Similar cardioprotective effect was observed with an ㄁-agonist, phenylephrine pretreatment, but much higher concentration(10<SUP>⁣4 </SUP>M) was needed to achieve the same degree of cardioprotection. The cardioprotective effects of isoproterenol and phenylephrine pretreatments were blocked by a ㄂<SUB>1</SUB>-adrenergic receptor antagonist, atenolol, but not by an ㄁<SUB>1</SUB>-antagonist, prazosin. Adenosine release from the heart was increased by isoproterenol, and the increase was also blocked by atenolol, but not by prazosin. A selective A<SUB>1</SUB>-adenosine receptor antagonist, 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX) blocked the cardioprotection by isoproterenol pretreatment. These results suggest that catecholamine pretreatment protects rat myocardium against ischemia and reperfusion injury by mediation of ㄂<SUB>1</SUB>-adrenergic receptor pathway, and that adenosine is involved in this cardioprotective effect.

      • SCOPUSKCI등재

        Farnesyl diphosphate synthase is important for the maintenance of glioblastoma stemness

        Kim,,Hee,Yeon,Kim,,Dong,Keon,Bae,,Seung-Hyun,Gwak,,HyeRan,Jeon,,Ji,Hoon,Kim,,Jong,Kwang,Lee,,Byung,Il,You,,Hye,Jin,Shin,,Dong,Hoon,Kim,,Young-Ho,Kim,,Soo,Youl,Han,,Sung-Sik,Shim,,Jin-Kyoung,Lee,,Ji-Hy Nature Publishing Group UK 2018 Experimental and molecular medicine Vol.50 No.-

        <▼1><P>Glioblastoma is a highly malignant tumor that easily acquires resistance to treatment. The stem-cell-like character (stemness) has been thought to be closely associated with the treatment resistance of glioblastoma cells. In this study, we determined that farnesyl diphosphate synthase (FDPS), a key enzyme in isoprenoid biosynthesis, plays an important role in maintaining glioblastoma stemness. A comparison of the mRNA expression in patient-derived glioblastoma sphere cells, which maintain stemness, and their differentiated counterparts, which lose stemness, via RNA sequencing showed that most of the altered genes were networked in the cholesterol biosynthesis pathway. We screened Federal Drug Administration (FDA)-approved drugs targeting specific enzymes in the cholesterol biosynthesis pathway for their ability to inhibit glioblastoma sphere formation. Inhibitors of FDPS, such as alendronate and zoledronate, significantly reduced the formation of glioblastoma spheres, and alendronate was effective at a lower molar concentration than zoledronate. Knockdown of FDPS using short hairpin RNA also completely inhibited the formation of secondary spheres. <I>FDPS</I> mRNA in patients with glioblastoma was associated with malignancy in three independent microarray data sets. RNA sequencing showed that alendronate treatment reduced the embryonic stem cell signature and activated development- and necrosis-related pathways in glioblastoma spheres. These results suggest that FDPS is important for the maintenance of glioblastoma stemness and that alendronate, a drug widely used to treat osteoporosis, can be repositioned to treat glioblastoma.</P></▼1><▼2><P><B>Brain cancer: Enzyme target for potential therapy</B></P><P>A drug that targets a key enzyme in aggressive brain cancer tumors could help tackle resistance to existing treatments. Glioblastoma is the most aggressive form of brain cancer and remains difficult to treat because the cancer cells can survive chemotherapy and radiotherapy. Certain cells within glioblastoma tumors have ‘stemness' – unique stem cell-like metabolic characteristics that allow them to rapidly repair DNA damage and trigger relapse. Hyonchol Jang at the National Cancer Center in Goyang, South Korea and co-workers discovered that an enzyme called farnesyl diphosphate synthase (FDPS) helps maintain stemness in glioblastoma. The team then treated patient-derived glioblastoma cells with existing drugs known to inhibit FDPS. One such drug, which is already used to treat osteoporosis, inhibited the formation of secondary glioblastoma and may prove valuble in the treatment of brain cancer.</P></▼2>

      • SCIESCOPUSKCI등재

        Technical Optimization of Culture Conditions for the Production of Exopolysaccharide (EPS) by Lactobacillus rhamnosus ATCC 9595

        Kim,,Young-Hoon,Kim,,Ji-Uk,Oh,,Se-Jong,Kim,,Young-Jun,Kim,,Myung-Hee,Kim,,Sae-Hun Korean Society of Food Science and Technology 2008 Food Science and Biotechnology Vol.17 No.3

        Microbial exopolysaccharide (EPS) is a biothickener that can be added to a wide variety of food products, where it serves as a viscosifying, stabilizing, emulsifying, and gelling agent. The objective of this study was to investigate the optimum conditions of pH, incubation temperature, and whey protein concentration (WPC) for EPS production by Lactobacillus rhamnosus ATCC 9595. We found that maximal EPS production was achieved at a pH of 5.5 and temperature of $37^{\circ}C$. At the same fermentation conditions, EPS production was affected by the addition of L. rhamnosus GG (a weak-EPS producer). After growth for 24 hr, total EPS production was $583{\pm}15.4mg/L$ in the single culture system, and $865{\pm}22.6\;mg/L$ in the co-culture system with L. rhamnosus GG. Based on the presence of WPC, EPS production dramatically increased from $583{\pm}15.4$ (under no WPC supplementation) to $1,011{\pm}14.7\;mg/L$ (under supplementation with 1.0% WPC). These results suggest that WPC supplementation and the co-culture systems coupled with small portions of weak-EPS producing strain can play an important role in the enhancement of EPS production.

      • SCIESCOPUSKCI등재

        Role of Adenosine in the Activation of Myocardial Catalase Induced by Brief Regional Ischemia

        Young-hoon,Kim,Chan-hyung,Kim,Gi-tae,Kim,Hong,Choi,Jong-wan,Park,Myung-suk,Kim 대한생리학회-대한약리학회 1999 The Korean Journal of Physiology & Pharmacology Vol.3 No.1

        '스콜라' 이용 시 소속기관이 구독 중이 아닌 경우, 오후 4시부터 익일 오전 7시까지 원문보기가 가능합니다.

        <P> The activities of myocardial antioxidant enzymes are known to increase in the hearts preconditioned with the brief episodes of ischemia. This study was undertaken to elucidate the possible involvement of adenosine in the stimulation of myocardial catalase induced by the brief regional ischemia in rabbit hearts. Coronary artery descending the middle anterior wall of left ventricle was occluded for 15 min, followed by 1 hr of reperfusion. Upon reperfusion after the brief ischemia, the activity of catalase increased significantly in both ischemic and non-ischemic parts of myocardium. Pretreatment of the heart with theophylline, a non-specific adenosine receptor blocker, completely abolished the increase of catalase activity in both the ischemic and non-ischemic regions of myocardium. On the other hand, the administration of exogenous adenosine instead of the ischemia failed to increase the catalase activity in <I>in vivo</I> hearts. Moreover, adenosine infusion did not affect the catalase activity in the isolated, perfused hearts either. These results suggest that the endogenous adenosine released from the ischemic myocardium is involved in the activation of catalase induced by brief ischemia, but that adenosine may not be a final direct activator of cellular catalase in the myocardium.

      • SCISCIESCOPUS

        Risk factor analysis of the development of new neurological deficits following supplementary motor area resection

        Kim,,Young-Hoon,Kim,,Chi,Heon,Kim,,June,Sic,Lee,,Sang,Kun,Han,,Jung,Ho,Kim,,Chae-Yong,Chung,,Chun,Kee Journal of Neurosurgery Publishing Group 2013 Journal of Neurosurgery Vol.119 No.1

        <B>Object</B><P>Supplementary motor area (SMA) resection often induces postoperative contralateral hemiparesis or speech disturbance. This study was performed to assess the neurological impairments that often follow SMA resection and to assess the risk factors associated with these postoperative deficits.</P><B>Methods</B><P>The records for patients who had undergone SMA resection for pharmacologically intractable epilepsy between 1994 and 2010 were gleaned from an epilepsy surgery database and retrospectively reviewed in this study.</P><B>Results</B><P>Forty-three patients with pharmacologically intractable epilepsy underwent SMA resection with intraoperative cortical stimulation and mapping while under awake anesthesia. The mean patient age was 31.7 years (range 15-63 years), and the mean duration and frequency of seizures were 10.4 years (range 0.1-30 years) and 14.6 per month (range 0.1-150 per month), respectively. Pathological examination of the brain revealed cortical dysplasia in 18 patients (41.9%), tumors in 16 patients (37.2%), and other lesions in 9 patients (20.9%). The mean duration of the follow-up period was 84.0 months (range 24-169 months). After SMA resection, 23 patients (53.5%) experienced neurological deficits. Three patients (7.0%) experienced permanent deficits, and 20 (46.5%) experienced symptoms that were transient. All permanent deficits involved contralateral weakness, whereas the transient symptoms patients experienced were varied, including contralateral weaknesses in 15, apraxia in 1, sensory disturbances in 1, and dysphasia in 6. Thirteen patients recovered completely within 1 month. Univariate analysis revealed that resection of the SMA proper, a shorter lifetime seizure history (< 10 years), and resection of the cingulate gyrus in addition to the SMA were associated with the development of neurological deficits (p = 0.078, 0.069, and 0.023, respectively). Cingulate gyrus resection was the only risk factor identified on multivariate analysis (p = 0.027, OR 6.530, 95% CI 1.234-34.562).</P><B>Conclusions</B><P>Resection of the cingulate gyrus in addition to the SMA was significantly associated with the development of postoperative neurological impairment.</P>

      • Optimal Geometric Allocation of Ground Stations for Navigation Satellites

        Young-Hoon,Kim,Jinyoung,Suk,Young-Rok,Kim,Sang-Young,Park,Myeong-Jong,Yu,Young-Bum,Park 제어로봇시스템학회 2012 제어로봇시스템학회 국제학술대회 논문집 Vol.2012 No.10

        Precise orbit determination of navigation satellites is very important to provide accurate positioning information to the ground users. Measurement errors should be minimized to get precise orbit trajectory. A couple of ground stations are required to obtain range data using radio or SLR(Satellite Laser Ranging). However, it is very difficult to ensure observability with ground stations located inside Korean peninsula for high altitude satellites such as HEO(High Earth Orbit) or GEO(Geostationary Earth Orbit) satellites. This paper presents a comparative study on the measurement errors for the precise orbit determination of navigation satellites according to the location of the ground stations. A new method of positioning ground stations to uninhabited areas such as north or south poles and/or relevant area is proposed, and the effect of additional locations of the ground stations are investigated. Ground stations located in higher latitude are extremely useful to obtain quality range data for HEO/GEO satellites because they have high elevation angle when they are used in combination with the ones located inside the Korean peninsula. Optimal geometric locations and numbers are sought via comparative study in the pools of candidate locations. Common error sources such as troposphere errors are considered to extract best locations for ground stations.

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