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.

정신분열증과 주요 우울장애에서 Natural Killer Cell 수와 백분율 변화NK cell

윤장봉,이재우,박두병 大韓神經精神醫學會 1996 신경정신의학 Vol.35 No.5

The purpose of this study was to compare the number and percentage of natural killer cell in schizophrenic and major depressive patients with those in normal healthy subjects 15 Schizophrenic patients, 15 major depressive patients and 16 healthy subjects were included in this study There was no statistical difference in the age and sex between patients and control subjects. All of these patients were drug-free for at lest two weeks before this study. The results of this study were as follows : 1) In schizophrenic patients, the number and percentage of natural killer cell of the group with below-mean score of general psychopathology were significantly lower than those of the group with above-mean score(p<.05). The number but not the percentage of natural killer cell of the group with below-mean BPRS score was significantly lower than that of the group with above-mean BPRS score(p<.05). 2) The number of natural killer cell showed statistically negative correlation with generalpsychopathology score or BPRS score(p<0.05). In conclusion, these findings suggest that the number and percentage of natural killer cell is not significantly changed in schizophrenia and major depressive disorder, but in schizophrenic patients, severe psychopathology in the rating scales is associated with suppression of the number and percentage of natural killer cell.

HM7 세포 표면 점액이 국소침윤 및 전이에 미치는 영향에 관한 연구

윤완희,박혜덕,임규,황병두 충남대학교 생물공학연구소 1998 생물공학연구지 Vol.6 No.-

Mucinous colorectal cancers have a poorer prognosis than which colorectal cancer produce low amount of mucin, but the exact mechanism is not well understood. The present study was undertaken to elucidate the exact mechanism of invasion and metastasis of high mucin producing colon cancer cells using mucin glycosylation inhibitor, benzyl-a-N-acetylgalactosamine. Materials and Methods: To evaluate the effect of glycosylated mucin on invasion and metastasis, in vitro invasion, metalloproteinases(MMPs) activity, cell-matrix protein binding, cell-cell aggregation, as well as endothelial leukocyte adhesion molecule(ELAM-1) binding and cell surface expression of various mucin related antigens were analyzed. Results: MMPs activity in conditioned medium and invasion of ECM-coated porous filters by benzyl-a-GalNAc treated HM7 cells were decreased. There was no difference between control and treated HM7 cells in terms of matrix protein binding assay, but treated HM7 cells showed higher homotypic cell adhesion. The binding activity of treated HM7 cells to ELAM-1 was significantly decreased and fixed cell binding of MoAb SNH-3, 19-9(specific for sialyl-Lewis X and sialy-Lewis A) were also significantly decreased. Conclusion: These results suggest that glycosylated mucin modulates ELAM-1 binding, MMPs activity and homotypic cell adhesion, therefore enhance invasive and metastatic properties of human colon cancer cells.

韓國産 鳥類의 重金屬 蓄積

李斗杓,元炳旿,閔丙允,本田克久,立川凉 경희대학교 한국조류연구소 1988 연구보고 Vol.2 No.-

Five different tissues taken from 13 Korean bird species were analyzed for seven heavy metals, iron, manganese, zinc, copper, lead, cadmium and mercury. The main purpose was to make clear the background levels of the metal concentrations. The metal levels were generally low and could be considered as the background levels. But some markedly elevated levels of toxic metals were found in estuarine and urban birds, suggesting that there may be heavily polluted areas in Korea. Furthermore, it was found that the avian feather is useful as an “indicator” tissue for monitoring heavy metal pollution in birds.

電流 制御形 共振形 컨버터를 위한 大信號 및 小信號 모델

金倫鎬,尹炳道,尙枓換 중앙대학교 기술과학연구소 1990 기술과학연구소 논문집 Vol.20 No.-

Recently resonant converter is being widely used and studied throughout the industrial applications. However, it is too difficult to understand the general conception of resonant converter because of the analysis of power circuits and various output control methods. This paper gives the general conception of resonant converter power circuits and describes the various output control methods. In this paper the pulse width modulation using discontinuous conduction mode is applied to a fullbridge series resonant converter to regulate the output from no load to full load with low switching loss and with a narrow range of frequency variation. Finally, a simple nonlinear discrete-time dynamic model for this converter is derived using approximation. This discrete time model is linearized and a general input - output transfer function for the converter is derived.

경남 마산시 및 전남 승주군 일대에서 채집된 관박쥐의 중금속 오염에 관한 연구

손성원,민병윤,이두표 경남대학교 환경문제연구소 1989 환경연구 Vol.11 No.-

Investigation of heavy metals (Fe, Mn, Zn, Cu, Pb, Cd, and Hg) content accumulated in the greater horseshoe bat, Rhinolophus ferrumequinum, was carried out on samples collected from urban (Masan city) and rural (Sungju-gun) habitats. Toxic metals, Pb, Cd and Hg, were detected in all the samples analyzed, suggesting that both urban and rural populations were contaminated with these metals. However, differences of heavy metal concentation in the bats captured in urban and rural area were not found. This result may come from that bats have a long range(about 20~30 ㎞) of feeding habitats.

백서 간재생중 H2B Histone 유전자 발현에 대한 Octamer Binding Transcription Factor의 역할

임규,방재웅,최두식,손미영,이영철,박청,김태동,김영래,박종일,윤완희,박승길,황병두 한국노화학회 2001 한국노화학회지 Vol.11 No.1

철서 지역에서 채집한 양서류의 중금속 오염에 관한 연구

이호원,손성원,이두표,민병윤 경남대학교 환경문제연구소 1991 환경연구 Vol.13 No.-

본 연구는 비오염 지역에서 참개구리의 성장 단계벨로 증금속의 축적 변동을 조사한 것이다. 일반적으로 올챙이 시기의 증금속 농도는 Fe > Mn > Zn > Cu > Ni > Pb > Cd,Hg의 순이었으며 성체 시기에는 Zn > Fe, Mn > Cu > Pb > Ni > Cd, Hg의 순으로 나타났다. Fe, Mn, Cu, Ni 농도는 성장이 진행됨에 따라 점차 낮아지는 경향을 보였고 Zn은 전기간을 통해 큰 변동이 없는것으로 나타났다. 대부분의 원소는 뒷다리 형성 시기에 체중 증가에 따른 농도 회석 현상이 발견 되었으며 이러한 현상은 Fe, Mn, Ni에 대하여 성체가 되는 시기에 특히 현저하였다. Heavy metal accumulations and their age-related changes were investigated in the tadpole and adult frog (Rana nigromaculata) inhabiting non-polluted area. A rank of metal concentrations was Fe > Mn > Zn > Cu > Ni > Pb > Cd. Hg in tadpole stage, and Zn > Fe, Mn > Cu > Pb > Ni > Cd, Hg in frog stage. The concentration of Fe, Mn, Cu and Ni decreased with age, and Zn concentration did not change much. A dilution effect of metal concentration by increased body weight was observed in the stage of tadpole with hind limb for most of metals, and it was marked in the stage of adult frog for Fe, Mn and Ni.

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.

RAW264.7 세포에서 interferon-r 및 LPS에 의해 유도되는 NO생성에 미치는 TALT-35의 영향

박종일,박경석,김종석,박지훈,윤은진,송경섭,서강식,김훈,윤완희,박승길,임규,황병두 충남대학교 생물공학연구소 2006 생물공학연구지 Vol.12 No.-

TALP-35 purified from human term placenta is known to increase microtubule polymerization and stabilize the polymerized microtubule. To examine the effect of TALP-35 on immune system this study was performed. MTT assay was performed to investigate the effect of TALP-35 on the proliferation of RAW264.7 cells. TALP-35 dose dependently suppress the proliferation of RAW264.7 cells at high concentration (above 1 μM) in unstimulated cells, in case of 10 μM TALP-35 treated cells the suppression was 25% but in stimulated cells it was only 15%. Cosedimentation assay was carried out to investigate whether TALP-35 can bind to tubulin of RAW264.7, monocyte/macrophage lineage of mouse, and polymerize it. TALP-35 polymerize the tubulin of RAW264.7 cells and sedimented in dose-dependent manner. To investigate the effect of TALP-35 on the expression of iNOS protein western blotting was performed. The expression level of iNOS was decreased dose dependently in high concentration of TALP-35 treatment. To examine the activity of iNOS, secreted NO was determined by method based on Griess reaction. Interferon-γ and LPS-stimulated production of NO from RAW264.7 cells was decreased dose dependently above 0.1 μM concentration of TALP-35 and 50% is decreased at 10μM of it. This study shows TALP-35 can control cytokine induced-iNOS expression therefore it might control inflammatory diseases.