N-acetyl cysteine inhibits H2O2-mediated reduction in the mineralization of MC3T3-E1 cells by down-regulating Nrf2/HO-1 pathway

( Daewoo Lee ),( Sung Ho Kook ),( Hyeok Ji ),( Seung Ah Lee ),( Ki Choon Choi ),( Kyung Yeol Lee ),( Jeong Chae Lee ) 생화학분자생물학회(구 한국생화학분자생물학회) 2015 BMB Reports Vol.48 No.11

There are controversial findings regarding the roles of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway on bone metabolism under oxidative stress. We investigated how Nrf2/HO-1 pathway affects osteoblast differentiation of MC3T3-E1 cells in response to hydrogen peroxide (H2O2), N-acetyl cysteine (NAC), or both. Exposing the cells to H2O2 decreased the alkaline phosphatase activity, calcium accumulation, and expression of osteoblast markers, such as osteocalcin and runt-related transcription factor-2. In contrast, H2O2 treatment increased the expression of Nrf2 and HO-1 in the cells. Treatment with hemin, a chemical HO-1 inducer, mimicked the inhibitory effect of H2O2 on osteoblast differentiation by increasing the HO-1 expression and decreasing the osteogenic marker genes. Pretreatment with NAC restored all changes induced by H2O2 to near normal levels in the cells. Collectively, our findings suggest that H2O2-mediated activation of Nrf2/HO-1 pathway negatively regulates the osteoblast differentiation, which is inhibited by NAC. [BMB Reports 2015; 48(11): 636-641]

한국인 직무 스트레스 측정도구의 개발 및 표준화

장세진,고상백,강동묵,김성아,강명근,이철갑,정진주,조정진,손미아,채창호,김정원,김정일,김형수,노상철,박재범,우종민,김수영,김정연,하미나,박정선,이경용,김형렬,공정옥,김인아,김정수,박준호,현숙정,손동국 大韓産業醫學會 2005 대한직업환경의학회지 Vol.17 No.4

Background and Purposes: Over the past three decades, numerous studies performed in Korea have reported that job stress is a determinant risk factor for chronic diseases and work disability. Every society has its own culture and occupational climate particular to their organizations, and hence experiences different occupational stress. An occupational stress measurement tool therefore needs to be developed to estimate it objectively. The purpose of this study is to develop and standardize the Korean Occupational Stress Scale (KOSS) which is considered to be unique and specific occupational stressors in Korean employees. Subjects and Methods: Data were obtained from the National Study for Development and Standardization of Occupational Stress (NSDSOS Project: 2002-2004). A total of 12,631 employees from a nationwide sample proportional to the Korean Standard Industrial Classification and the Korean Standard Occupational Classification were administered. The KOSS was developed for 2 years (2002-2004). In the first year, we collected 255 items from the most popular job stress measurement tools such as JCQ, ERI, NIOSH and OSI, and 44 items derived from the a qualitative study (depth interview). Forty-three items of KOSS, in the second year, were retained for use in the final version of the KOSS by using Delphi and factor analysis. Items were scored using conventional 1-2-3-4 Likert scores for the response categories. Results: We developed eight subscales by using factor analysis and validation process: physical environment (3 items), job demand (8 items), insufficient job control (5 items), interpersonal conflict (4 items), job insecurity (6 items), organizational system (7 items), lack of reward (6 items), and occupational climate (4 items). Together they explained 50.0% of total variance. Internal consistency alpha scores were ranged from 0.51 to 0.82. Twenty-four items of the short form of the KOSS (KOSS-SF) were also developed to estimate job stress in the work setting. Because the levels of the subscales of occupational stress were gender dependent, gender-specific standard norms for both the 43-item full version and the 24-item short form using a quartile for the subscales of KOSS were presented. Conclusion: The results of this study suggest that KOSS might be an appropriate measurement scale to estimate occupational stress of Korean employees. Further and more detailed study needs to be conducted to improve the validity of this scale.

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.

정신분열병의 양성 및 음성증상 개념의 역사 및 문제점

채정호 대한정신분열병학회 2000 정신분열병 클리닉 Vol.2 No.-

항정신병 약물 비폭로, 치료 중 및 만성 시설화 정신분열증 환자에서의 연성 신경학적 징후의 비교

채정호,이규항,백인호,이정균 大韓神經精神醫學會 1997 신경정신의학 Vol.36 No.2

Objects : Many studies have demonstrated greater frequency of soft neurologic signs in patients with schizophrenia than in controls. However, factors associated with chronicity,institutionalization, individual differences and neuroleptic medication make it difficult to interpret these results. We report on our ongoing study of soft neurologic signs and their relationship to neuroleptics and institutionalization in schizophrenia. Methods : Soft neurologic signs were examined with a standardized instrument, Neurological Evaluation Scale- Korean Version(NES-K) in 11 neuroleptic-naive patients with schizophrenia, 17 neuroleptic-treated patients and 14 chronically institutionalized patients. Results : Scores of total items(p<0.05), sensory integration(p<0.05), sequencing of complex motor acts(p<0.05) and others(p<0.01) functional areas of NES-K were significantly different among three groups. There was no difference in the area of motor coordination. Posthoc analysis showed that scores of total items(p<0.005) and sensory integration areas(p<0.01) of NES-K were significantly higher in the institutionalized patients than those of neurolepticnaive group. However scores of sequencing of complex motor act and others categories were not different in the institutionalized and neuroleptic-naive patients. Conclusion : These findings suggested that neuroleptic treatment or chronic institutionalization might partially affect soft neurologic signs, especially sensory integration area, in patients with schizophrenia. However, the soft neurologic signs of motor coordination area could be a biological trait marker of schizophrenia independent of confounding variables.

알쯔하이머 치매·혈관성 치매·아밀로이드·면역·IL-1β·TNF-α, Alzheimer's discase·Vascular dementia·Amyloid·Immunity·IL-1β·Tnf-α.

채정호,백인호 대한신경정신의학회 1999 신경정신의학 Vol.38 No.1

연구목적 : 알쯔하이머 치매의 병인론에 면역성 기전이 개입된다는 가설을 확인하고자 본 연구를 행하였다. 방 법 : 알쯔하이머 치매 19명, 혈관성 치매 22명, 정상노인 19명에서 말초 혈액 단핵세포를 분리하여 phyohemagglutinin-P(PHA-P) 및 1-40의 β-아밀로이드(Aβ)로 자극하여 세포 증식 정도를 비교하였으며, 배양 상청액에서 interleukin-1β(IL-1β)와 tumor necrosis factor-α(TNF-α)를 효소결합면역흡착분석법으로 측정하였다. 결 과 : 1) PHA-P 자극에 의한 단핵 세포의 증식은 세 군에서 차이가 없었다. 2) Aβ 자극은 단핵세포의 증식에 현저한 영향이 없었으나, 알쯔하이머 치매군이 혈관성 치매군과 대조군에 비하여 유의하게 많이 증식되었다. 3) 배양한 단핵세포 알쯔하이머 치매상청액의 IL-1β는 혈관성 치매군이 가장 높았으며, Aβ자극 후에도 혈관성 치매군에서 가장 높았으나 자극 전후를 비교할 때, 알쯔하이머 치매군에서 가장 현저하게 자극 후 IL-1β 생성이 증가되었다. 4) 배양한 단핵세포 상청액의 TNF-α는 알쯔하이머 치매군이 대조군보다 유의하게 높았으며, Aβ 자극 후에도 알쯔하이머 치매군이 대조군보다 유의하게 높았다. 결 론 : 이상의 실험을 통하여 알쯔하이머 치매군의 말초 혈액 단핵세포가 Aβ 자극에 따라 나타내는 과도한 면역 반응을 관찰하였다. 이는 알쯔하이머 치매의 병태생리에서 Aβ침착에 따른 면역성 반응이 중요한 역할을 한다는 것을 시사한다. Objectives : Deposition of the β-amyloid(Aβ) peptide in the senile plaque has been thought as a major etiologic factor for the development of Alzheimer's disease. Among the hypotheses suggested to explain the mechanism by which Aβ causes Alzheimer's disease, the immune processes have been considered as crucial events in the pathophysiology of the Alzheimer's disease. This study examined the effects of Aβ on the proliferation and production of IL-1β(interleukin-1β) and TNF-α(tumor necrosis factor-α) in peripheral blood mononuclear cells isolated from the patients with Alzheimer's disease, vascular dementia, and normal elderly control subjects. Method : Nineteen patient with Alzheimer's disease, 22 patients with vascular dementia, and 19 controls were participated in this study. Peripheral blood mononuclear cells were obtained from each donors, and subjected to the proliferation assays in response to the stimulation of phytohemagglutinin-P(PHA-P) and Aβ. The levels of IL-1β and TNF-α from the culture supernatant of the cells before and after the stimulation of Aβ were also determined by enzyme linked immunosorbent assay. Results : The results were as follows : 1) The proliferation of mononuclear cells in response to PHA-P were not different among three groups. 2) When compared to PHA-P, the proliferation responses of mononuclear cells to Aβ were insignificant in all experimental groups. However Alzheimer's disease group showed greater stimulation index than vascular dementia and controls. 3) IL-1β production was higher in the vascular dementia group than Alzheimer's disease and control groups both before and after the stimulation of Aβ. However the stimulation ratio of before and after Aβ stimulation was highest in Alzheimer's disease group. 4) TNF-α production was higher in Alzheimer's disease group than controls both before and after the stimulation of Aβ. Conclusion : These finding suggest that the immune responses to the stimulation of Aβ may be enhanced in patients with Alzheimer's disease compared to vascular dementia and control groups, supporting the immune hypothesis for th epathophysiology of Alzheimer's disease.

한 정신병원에서의 강박 처치에 대한 입원 환자 및 병원 직원의 지각의 차이

채정호,차성조,함웅,이규항,이정균 大韓神經精神醫學會 1996 신경정신의학 Vol.35 No.5

한 정신병원에서 강박처치의 적응증, 합병증, 대체법, 감정적 영향, 적당한 처치 시간, 처치의 효능과 필요성등을 병원에 입원 중인 환자들과 직원들에게 설문조사를 하여 양 집단간에 차이가 있는 지를 알아봄으로써 환자들과 직원들간에 있는 강박처치에 대한 지각 차이를 조사하고 나아가 강박처치 시행의 규준을 확립하기 위한 기본 자를 제시하기 위하여 본 연구를 시행하였다. 강박처치의 적응증에 대해서 입원환자들은 대부분의 항목에 대해 부정적으로 보았고 단지 타환자에 대한 신체적 공격에 대해서만 다소 긍정적인 반응을 보인 반면 직원들의 경우 자해, 타환자에 대한 신체적 공격, 치료진에 대한 공격 등에 높은 응답율을 보였다. 강박처치의 부작용에 대한 지각은 입원환자의 경우 정신상태의 악화, 자해의 증가 등에 대해 보다 민감하게 반응 하였고, 실제로 경험한 부작용에 있어서는 직원들의 경우 피부박탈을 더 강조한 반면 환자군에서는 호흡곤란, 정신 상태의 악화 등을 강조하였다. 강제 처치에 대한 대체치료 방법으로는 환자군에서 면담을 중요시한 반면 직원군에서는 격리실의 이용을 강조하였다. 신체억제와 고용량의 정온화를 비교한 것은 환자군에서 신체억제가 더 효과적이라고 하였다. 신체억제 동안 느끼는 감정에 대한 지각에서 환자군은 슬픔을 가장 많이 보고하였고, 직원군은 적개심을 가장 많이 느낄 것으로 추정하였다. 신체억제의 시간에 대해서는 환자군이 긴 것으로 지각하고 있으며, 이상적인 신체억제의 시간은 환자군이 짧은 것이 좋다고 생각하고 있었다. 본 연구 결과 정신과 입원환자들과 병원직원들은 강박처치에 대하여 유의한 지각의 차이가 있다는 것을 알았으며 정신병원내에서 강제처치를 실시할 때에는 명확한 강박처치 시행에 대한 규준에 따라야 할 것임을 확인할 수 있었다. Objectives : The purpose of this study was to examine different perceptions of physical restraint and their nature between psychiatric inpatients and hospital staffs in a mental hospital and to provide baseline data for establishing the practicing standard of this therapeutic maneuver. Methods : Two hundred and two psychiatric inpatients who experienced physical restraint and 103 hospital staffs who frequently used this maneurer were surveyed with a questionnaire regarding indications, complications, alternative methods, emotional influences, duration of treatment and subjective effects of restraint. Results : Regarding indications of physical restraint, the inpatient group had negative viewpoint on the most items except "physical assault to other patients". Regarding the perception about possible complications of this treatment, the inpatient group had more concerns about "deterioration of mental status" and "increasing risk of self-injury". For experienced complications, staffs stressed "skin abrasion " while inpatients believed of "respiratory difficulties" and "deterioration of mental status" more frequently. As alternative methods of physical restraint, "increasing frequency of interview" was suggested by the inpatient group and "using seclusion room" was favored by the staff group. The inpatient group had an impression that physical restraint was more effective than high-dose neuroleptic tranquilization. For suspected emotion during this procedure, the inpatient group reported "sorrow" most frequently while the staff group presumed that "hostility" might be most frequent. Inpatients estimated that the average duration of physical restraint was longer than staffs did. Ideal duration of physical restraint was shorter in the inpatient group. Conclusion : These results suggest that there are definite differences in the perception of physical restraint between psychiatric inpatients and hospital staffs. Formal practing guideline for restraint should be set up with careful attention for these differences to maximize the therapeutic effect of this maneuver.

얼굴 인식의 발달학적 관점

채정호,양대현,이경욱,박원명 한국의학사 2004 診斷과治療 Vol.24 No.2

미주신경자극술(Vagus Nerve Stimulation)의 신경정신과적 응용

채정호,배치운,박원명,전태연,김광수,Mark S. George 大韓神經精神醫學會 2001 신경정신의학 Vol.40 No.3

연구목적: 최근 신경생물학과 두뇌 조영술 발달에 따라 두뇌에 비침습적 자극을 줌으로써 신경회로를 변화시킬수 있는 새로운 신경정신과적 치료방법의 개발이 태동하고 있다. 그 중 두뇌와 다양한 연결을 구축하고 있는 제 10번 두개신경인 미주신경을 직접 자극할 수 있는 미주신경자극술(Vagus Nerve Stimulation:이하푼)이 개발되어 간질 및 일부 신경정신과적 질환에서 시술되고 있다. 본 논문의 목적은 VNS의 발달과정, 시술방법, 신경정신과적 응용, 및 부작용 등에 대하여 개괄하고 그 현황과 미래를 고찰하는데에 있다. 방 법 : 광범위한 문헌 검색과 현재 VNS를 시술하고 있는 기관의 세계적 전문가와의 논의를 통하여 조사 및 정리하였다. 결 과 : 현재 VNS는 치료 저항성 간질의 치료 방법의 하나로 공인되어 있으며 일부 신경정신과적 질환에서 치료적으로 사용될수 있는 가능성이 제시되고 있다. 결 론 : 두뇌를 자극할 수 있는 새로운 방법인 VNS는 우울증을 비롯한 일부 신경정신과적 질환에서 유의한 치료효과를 거둘 가능성이 있으며, 두뇌-행동 관계를 이해하는데에 매우 흥미있는 방법으로 향후 많은 관심을 끌게 된 것이다. Objectives : Several novel and minimally invasive techniques to stimulate the brain have recently developed. Among these newer somatic interventions, vagus nerve stimulation(VNS) is regarded as a promising tool in the treatment of various neuropsychiatric disorders. This article reviews the history, methodology, and the future of VNS technique and its emerging research and therapeutic applications in the field on neuropsychiatry. Methods : Wide ranged literature reviews and discussion with pioneering researchers were performed. Results : VNS has been used in the treatment of refractory seizure disorder and depression. There are some reasons to hope that VNS might have other therapeutic applications in neuro-psychiatric disorders, as well as advanced understanding about the pathophysiology of these disorders. Conclusion : Regardless of its clinical role as a new therapeutic technique, the capacity of VNS as a research tool to alter brain activity should lead to important advances in the understanding of brain-behavior relationships.

수면 무호흡과 불안장애의 불면증에 대한 다원수면기록

채정호,박원명,채영래,김제헌 大韓神經精神醫學會 1994 신경정신의학 Vol.33 No.2

Objects : The authors studied polysomnographic findings of patients with sleep apnea DIMS (disorders of initiating and maintainig sleep) syndrome and anxiety disorders with insomnia related to another mental disorders. Methods : Eight patients with sleep apnea DIMS syndrome and fourteen patients with anxiety disorder with insomnia related to another mental disorder(nonorganic) were studied using computerized polysomnography. Results : 1) The sleep period time were significantly decreased in anxiety disorder group and the sleep latency was prolonged in these patients. 2) The changes in sleep stage and the number of arousals during sleep period time were more frequent in sleep apneic patients group. And using these variables we could discriminate sleep apneic patients group from subjects with anxiety disorder. 3) The stage 1 sleep was significantly increased in sleep apneic patients. 4) The apnea index in sleep apnea patients was 28.1±25.7. Conclusion : These results suggested that even though there were similiar clinical presentaion such as insomnia, the sleep features of sleep apnea DIMS syndrome and anxiety disorder with insomnia were different. And though there were no instruments to check respiratory flow or movement, it would be possible to discriminate the sleep apnea DIMS syndrome from the anxiety disorder with insomnia by recording the changes in sleep stage and the number of arousals in overnight electroencephalographic procedure.