항정신병약물 사용 중인 정신분열병 환자에서 올란자판으로의 교체 방법에 관한 연구(II) : Comparison of Safety 안전성 비교

안용민,권용실,권준수,민성호,박두병,양문정,소형석,송종호,신윤식,우행원,유범희,이홍석,정한용,한창환,김용식 大韓神經精神醫學會 2002 신경정신의학 Vol.41 No.5

연구목적: 이 다기관 공동임상연구는 사용 중인 항정신병약물을 ’직접 교체 방법’또는 ’시작-감량 교체 방법’중 한 가지 방법으로 올란자핀으로 교체한 후, 안정성 측면에서 두 교체 방법 간의 비교와 교체후의 변화를 관찰하기 위한 것이다. 방법: 국내 13개 병원의 입원 및 외래에 내원한 환자들 중 ICD-10 지단기준으로 정신분열병에 해당되며, 임상적으로 항정신병약물 교체가 필요한 환자를 대상으로 하였다. 두 가지 교체 방법 중 한 가지를 무작위로 피험자에 적용하였으며, ’직접 교체 방법’에 배정된 경우에는 사용중인 항정신병약물을 일시에 중단하고 10㎎의 올란자핀을 바로 투여하였고, ’시작-감량 교체 방법’에 배정된 경우는 10㎎의 올란자핀 투여하고 2주에 걸쳐서 기존 약물을 감량하여 중단하였다. 올란자핀 사용기간은 총 6주이며, 용량은 5∼20㎎ 범위로 제한하였다. 한정성 평가를 위해서 체중, 생명징후, 자발적인 이상반응 복, 실험실 검사 그리고 Simpson-Angus Scale(SAS), Barnes akathisia rating scale(BARS), Abnormal involuntary movement scale(AIMS). Liverpool University neuroleptic side effect rating scale(LUNSERS)등을 이용하였다. 결과: 총 103명의 정신분열병 환자를 대상으로 하였다. 사용한 올란자핀의 용량, 벤조디아제핀의 병용률, 탈락률과 탈락 사유, 자발적인 이상반응 보고, 생명징후, 실험실 검사 그리고 대부분의 부작용 척도 상에서 임상적으로 의미 있는 차이를 두 교체 방법간에 발견하지 못하였다. 다만 AIMS의 감소는 ’직접 교체 방법’군에서 보다 적었고, 항콜린제의 병용률은 ’시작-감량 교체 방법’군에서 보다 많았다. 기저 상태에서 전체 피험자의 SAS와 BARS 점수는 각각 3.5점과 1.8점이었으며 70% 이상의 피험자가 고프로락틴 혈증을 보였다. 올란자핀으로 교체한 후, SAS, BARS, AIMS 점수의 유의한 감소가 있었으며 고프로락틴 혈증을 보인 피험자 분율도 약 30%이하로 감소하였다. 그러나 교체 방법과 상관없이 올란자핀 교체 후 유의한 체중 증가가 있었다. 결론: 이 연구를 통해 교체 방법에 관계없이 비교적 안전하고 용이하게 올란자핀으로 교체 할 수 있음을 알 수 있었다. 그리고 기존 항정신병약물을 올란자핀으로 교체함으로써 일부 부작용들을 줄일 수 있음을 간접적으로 관찰할 수 있었다. 하지만 이 연구는 여러 제한점과 문제점을 지니고 있기 때문에 보다 체계적인 연구를 통해 검정이 필요하리라 생각된다. Objectives: This multicenter clinical trial involving 13 hospital sites compared the safely of switching to olanzapine between ’direct switching method’ and ’start-tapering switching method’. Method: This study included both inpatients and outpatients who fulfilled the criteria for schizophrenia as defined in the ICD-10, and were in need to be appropriate for switching antipsychotics. Subjects were randomly assigned to one of the two switching methods. For ’direct switching method’group, previous antipsychotics were abruptly discontinued and 10㎎ of olanzapine was administered, and previous antipsychotics was gradually tapered for 2 weeks. Olanzapine was used for 6 weeks and the dose was adjusted within the range of 5-20㎎. The safety of switching to olanzapine was measured with vital sings including body weight, adverse events reported spontaneously, laboratory tests, and various scales such as Simpson-Angus Scale(SAS), Barnes Akathisia Rating Scale(BARS). Abnormal Involuntary Movement Scale(AIMS), and Liverpool University Neuroleptic Side Effect Rating Scale(LUNSERS). Results: 103 patients were switched to olanzapine in this study. The comparison between two switching methods did not show any significant difference in the dosage of olanzapine used, the concomitant use of benzodiazepine, the rate and reasons of drop-out, the adverse events, vital signs, laboratory tests, and most scales for measuring side-effects. However, the decrease in AIMS scores was significantly lower in ’direct switching method’ group, and the concomitant use of anticholinergics was comparatively greater in ’start-tapering switching method’ group. At baseline, SAS and BARS scores were 3.5 and 1.8 points respectively, and more than 70% of the subjects showed hyperprolactinemia. After switching to olanzapine, SAS, BARS, and AIMS scores were significantly decreased and the proportion of the patients with hyperprolactinemia was also decreased to less than 30%. However significant weight gain after the treatment of olanzapine was observed regardless of switching method. Conclusion: This study may suggest that switching to olanzapine can be done with relatively high safety regardless of switching methods and olanzapine can significantly decrease some side-effects induced by other antipsychotics.

ERK1/2 activation in quercetin-treated BEAS-2B cell plays a role in Nrf2-driven HO-1 expression

이윤진,Jun-Hwan Song,Myung-Ho Oh,Yong-Jin Lee,김용배,Jae-Hyuk Im,이상한 대한독성 유전단백체 학회 2011 Molecular & cellular toxicology Vol.7 No.4

Quercetin, a member of the flavonoids,has been heralded as chemopreventive agent, generally because of its free radical-scavenging and antiproliferative activities. In this process, NF-E2-related factor-2 (Nrf2) plays a role in protecting cells from oxidative damage; however, the exact mechanisms in which bronchial epithelial cells respond to quercetin by activating Nrf2 are not fully understood. Here, we report the role of extracellular signal-regulated kinase (ERK) activation in response to quercetin. Quercetin treatment decreased the viability of human bronchial epithelial BEAS-2B cells in a dose- and time-dependent manner. ERK1/2 was activated within 10 min of quercetin addition and then remained increased above control level throughout 48 h, whereas AKT phosphorylation was suppressed from the first 1 h of quercetin treatment. Inhibition of Erk1/2 phosphorylation attenuated quercetin-induced loss of cell viability. Nrf2levels in both nuclear and whole cell lysates increased after quercetin treatment and was accompanied by the increase of heme oxygenase-1 (HO-1) protein level,indicating that increased HO-1 expression is Nrf2-mediated. Activation of the Nrf2/HO-1 system after quercetin treatment was suppressed by the pretreatment with MEK inhibitor, PD98059. Also, silencing Nrf2 with siRNA decreased cell viability and augmented cytotoxic effect of anticancer drug LBH589. Overall, our results indicate that quercetin induces the up-regulation of Nrf2-mediated HO-1 expression, at least in part, via MEK/ERK1/2 signaling, as an adaptive mechanism which may provide advantages for cell proliferation and enhance survival despite endogenous and/or exogenous oxidative insults.

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

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.

3,4,5-Trihydroxycinnamic Acid Inhibits Lipopolysaccharide-Induced Inflammatory Response through the Activation of Nrf2 Pathway in BV2 Microglial Cells

( Jae Won Lee ),( Yong Jun Choi ),( Jun Ho Park ),( Jae Young Sim ),( Yong Soo Kwon ),( Hee Jae Lee ),( Sung Soo Kim ),( Wan Joo Chun ) 한국응용약물학회 2013 Biomolecules & Therapeutics(구 응용약물학회지) Vol.21 No.1

3,4,5-Trihydroxycinnamic acid (THC) is a derivative of hydroxycinnamic acids, which have been reported to possess a variety of biological properties such as anti-inflammatory, anti-tumor, and neuroprotective activities. However, biological activity of THC has not been extensively examined. Recently, we reported that THC possesses anti-inflammatory activity in LPS-stimulated BV2 microglial cells. However, its precise mechanism by which THC exerts anti-inflammatory action has not been clearly identified. Therefore, the present study was carried out to understand the anti-inflammatory mechanism of THC in BV2 microglial cells. THC effectively suppressed the LPS-induced induction of pro-inflammatory mediators such as NO, TNF-a, and IL-1b. THC also suppressed expression of MCP-1, which plays a key role in the migration of activated microglia. To understand the underlying mechanism by which THC exerts these anti-inflammatory properties, involvement of Nrf2, which is a cytoprotective transcription factor, was examined. THC resulted in increased phosphorylation of Nrf2 with consequent expression of HO-1 in a concentration-dependent manner. THC-induced phosphorylation of Nrf2 was blocked with SB203580, a p38 MAPK inhibitor, indicating that p38 MAPK is the responsible kinase for the phosphorylation of Nrf2. Taken together, the present study for the first time demonstrates that THC exerts anti-inflammatory properties through the activation of Nrf2 in BV2 microglial cells, suggesting that THC might be a valuable therapeutic adjuvant for the treatment of inflammation-related disorders in the CNS.

Gliotoxin ameliorates TNBS-induced colitis through regulation of NF-kB, and up-regulation of HO-1

김상욱 ( Kim Sang Ug ),( Jay Min Oh ),( Yeon Hwa Kim ),( Jung Moo Hur ),( Kyo Sang Yoo ),( Yong Sung Kim ),( Joo Jin Yeom ),( Tae Hyeon Kim ),( Suck Chei Choi ),( Chang Duk Jun ),( Yong Ho Nah ) 대한소화기학회 2003 대한소화기학회 추계학술대회 Vol.2003 No.-

<Background & aims> During inflammation in colon, cells of the gut mucosa produce or express various inflammatory mediators, including IL-8, TNF-a and IL-1b, and intercellular adhesion molecule 1 (ICAM-1). These cytokines and chemokines have recently been

우심방을 침범한 거대 비호지킨씨 림프종 1예

강상범,진승원,이은경,박용현,최용호,김용주,박준철,김재형,홍순조,최규보,권종범,원용순,박건,이은희 대한순환기학회 2000 Korean Circulation Journal Vol.30 No.4

吸氣管 內에 空氣噴射가 터보過給디젤機關의 過渡性能改善에 미치는 影響

용호택,전봉준,최낙정 서울産業大學校 産業大學院 1995 大學院論文集 Vol.3 No.-

This study investigates the characteristics of transient response in a turbocharged diesel engine by using the computer simulation with experiments. Experimental study on the engine system is carried out to examine the validity of numerical analysis, and the predicted results are compared with experimental data at various conditions. Further, experiment for improving the low speed torque and acceleration performance is also performed by means of injecting air in the inlet manifold. The effects of air injection on the response performance are investigated at various conditions such as injection pressure, injection period, accelerating time, accelerating rate, load and engine speed.

공조시스템을 적용한 석실 고분내 온ㆍ습도 분포

전용두,이금배,박진양,고석보,전희호 公州大學校 工學硏究院 生産技術硏究所 2005 論文集 Vol.13 No.-

Although the importance of good conservation of historic sites including ancient royal tombs is well aware, still not much attention has been paid for the facilities and systems to preserve those historic sites, which includes precious artifacts as wall paints and carved works, etc. Even the general understanding about the environment of the underground space of tombs is not satisfactory. In Korea, researchers have recently begun addressing the above issue and are making efforts to develop suitable HVAC(heating, ventilating and air-conditioning) systems for conservation of tombs. An experimental investigation was carried out to study the behavior of the HVAC system installed for a tomb. This tomb resembles in size and shape the original stone built tomb of Baek-je Dynasty, which dates back to 6th Century in southwest part of Korean peninsula. In this study, an HVAC system for a tomb(D×W×H=1.3m×3.0m×1.2m) was installed to maintain sui표 indoor conditions for conservation of tomb. The temperature and humidity inside the tomb were measured different of the setting. Finally, performance of the HVAC system is presented and discussed.

PE배관의 융착 강도에 관한 연구

전흥원,김용수,태순호 한국산업안전학회 2002 한국안전학회지 Vol.17 No.2

At present, the Polyethylene piping, on supporting LNG is widely used because of it's disposition which are anti-corrosion, flexible and so on. However, it has a few kinds of risk which are the possibility of piping leak, the character of easily corroded and so on. For giving solution, this study is intended to experiment the intension of the PE pipe after melted and when it is melting, the condition which are temperature and pressure is changed. the melting condition in temperature and pressure is adapted identically. After melting, it's joint is tested as intension. The result is that the effect of temperature in intension is more effective than pressure. In 210℃, 20㎏/㎠ condition, the melting intension has the highest. Compare to the Butt melting joint and the Saddle melting joint, the former was 214㎏/㎠ and the latter was 50㎏/㎠(bead 2~3㎜) and 73㎏/㎠(bead 5~7㎜). It means that the Butt melting method has more intensive than saddle. Consequently, the result shows that the liability and safety when PE pipe melting method is used will improve in pipe installation.

정신과 입원환자의 공격행동 특성

전태연,권용실,도규영,장계호 大韓神經精神醫學會 1997 신경정신의학 Vol.36 No.3

저자들은 1994년 1월 1일부터 1995년 6월 31일까지 가톨릭대학교 의과대학 의정부성모병원 정신과에 입원했던 환자들 중세서 공격행동을 보인 환자(공격군) 72명과 공격행동이 없었던 환자(비공격군) 215명의 임상적 특성에 관한 조사를 하여 다음과 같은 결과를 얻었다. 1) 공격행동을 보인 환자는 72명으로 전체 조사 환자의 25.1%이었다. 2) 성별, 연령, 종교, 결혼 상태와 정신과 질환의 가족력 등에 따른 공격행동의 발생비율의 차이는 유의하지 않았다. 3) 교육 정도와 직업에 따른 공격군의 비육에 유의한 차이가 있었다(p<.05). 4) 진단별로는 공격군에서 조증, 기질성 정신장애, 정신분열증의 빈도가 높았으나 진단에 따른 의미 있는 차이는 없었다. 5) 공격행동의 기왕력은 공격군에서 더 많았고 비공격군과 비교시 의미 있는 차이를 보였으며(p<.001), 입원 형태는 공격군에서 타의 입원의 빈도가 유의하게 높았다(p<.005). 7) 입원시 정신병리는 초조-흥분과 적대감-의심에서 공격군의 빈도가 높았으며 정신병리에 따른 의미 있는 차이를 보였다(p<.001). 8) 총 재원 일수는 공격군에서 평균 59.3일이었고 비공격군이 평균 38.4일로 유의한 차이를 보였다(p<.001). 9) 공격행동의 유형은 말로한 경우가 가장 많았고 물건을 대상으로한 행동, 타인을 대상으로 하는 행동의 순으로 나타났다. 10) 공격행동 직전 행동 특징은 활동증가, 시끄러움, 욕설, 분노, 적대적이었던 경우가 가장 많았다. 11) 공격행동은 정오에서 오후 6시 사이, 휴식시간에 가장 많이 나타났다. 12) 입원 후 1주일 이내에 공격행동의 62.3%가 나타났다. 13) 총공격 점수에 의미 있게 영향을 주었던 변인들로는 종교(p<.05), 교육 정도(p<.05), 직업(p<.05), 입원형태(p<.005), 진단(p<.001), 입원시 정신 병리(p<.001), 공격행동의 기왕력(p<.001) 등으로 나타났다. To evaluate the characteristics of violent behavior of psychiatric inpatients the authors reviewed clinical records of psychiatric patients who had admitted at UiJong Bu St. Mary's Hospital from January 1994 to June 1995. We divided the 287 subjects into violent and nonviolent group according to the presence of violent behaviors in psychiatric ward. We assessed demographic variables, clinical characteristics and violent behaviors using Overt Aggression Scale and compared these variables of violent group with nonviolent group. The results were as follows : 1) The number of violent patients was 72(25.1% of the total). 2) In terms of demographic variables, the differences between two groups in education and occupation were significant(p<.05). 3) In psychiatric diagnoses, violent group were more likely to have mania, schizophrenia and organic mental disorder in sequence but there were no differences between violent and nonviolent group. 4) The history of violent behavior was greater in violent group(p<.001) and the mode of admission was significantly different between two groups(p<.005). 5) In cluster of psychopathology on admission, more frequently found clusters of psychopathology in violent group were agitation-excitement and hostile- suspiciousness and there were significant differences between two groups(p<.001). 6) The length of stay in violent group(59.3 days)was significantly longer than nonviolent group(38.4 days)(p<.001). 7) The types of violent behavior were verbal aggression, physical aggression against objects and physical aggression against other people in frequency sequence. 8) The most frequent type of behavioral clue before violent behavior was hyperactive, loud, verbally abusive, angry, hostile(68.1%). 9) Most of violent behaviors were presented between midday and 6 pm. in resting time. 10) 62.3% of total violent behaviors were occurred within first week following admission. 11) The variables which showed significant effects on total aggression score were religion, educational status, occupation, mode of admission, psychiatric diagnosis, psychopathology on admission and history of violent behavior before admission. In summary, these results showed similar trends compared to previous studies on characteristics of psychiatric inpatients. And we found that more important predictors of violent behavior in practice were likely to be history of violent behavior, psychopathology on admission and behavioral cue before violent behavior.