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.

성상세포종의 MIB-1, AgNORs 및 PCNA 발현에 대한 비교연구

최양문,김태영,김종문,윤기중,문형배 대한신경외과학회 1997 Journal of Korean neurosurgical society Vol.26 No.4

아리스톨로크산 함유 생약제에 대한 안전성평가연구 : 3개월간 반복투여독성시험을 통한 신장독성평가

황명실,박미선,문지영,이지선,염영나,이효민,신동환,강진석,윤은경,최미나,육미영,장동덕,길광섭,김승희,양기화 식품의약품안전청 2001 식품의약품안전청 연보 Vol.5 No.-

본 실험에서는 아리스톨로크산을 함운하고 있는 생약제중 하나인 마두령(.4risfoforfioe JTurruf)의 90일 반복투여독성시헌을 실f,」하였다. 마두령에서 아리스톨로크산을 정량분석한 결과 마두령 단일 건조븐말의 경운 2.112mg/g, 잉상에서 처방되고 있는 마든령복방 (마두령외 9가지 생약제 복합처방) 건조분말꼭 경무에는 0.066m9/5으로 각각 검출되었다. 본 실험에서 용량설정은 마두령 처리군 (저용량 군; 21.3m9/k9/day (임상용량), 중용량군; 2t3mgfg/day, 고용량군; 2430mg딘g b.w./day), 마두령복방 처리군 (427mg/kg b.w./da?; 임상용량) 및 positive control (아리스톨로크산) 처리군 (저용량군;0.05mgag/da17, 중용량군; 0.Smg/kg/day, 고용량군; 5mg./kg/dal·1으료 하여 랫드에게 경구투여하였다. 마두령단방 처궈근 및 마두령복방 처리군에서 저용량군과 중응량군에서는 잉상관찰 및 생화학적 분석에서 패조군과 유의적인 차이가 없었다. 그러나 마두령단방 고용량근에서는 간, 신장의 상대적인 무계가 증가되었고, 신장의 유두이행상피증식 및 암종이 관찰되었으며, 위에서는 편평세포암종이 관찰되었다. 하자만 간손상이나 간암은 유발하지는 않는 것으로 판단되었다. 결론끌으로 본 실험의 결과에서는 아리스톨로크산 함유 생약제인 마두령이 임상용량인 저응량 처리군에서는 독성을 나타내지 않았으나, 고용쏭으로 장기 복용시켰을 깅우 설치류의 전위부위 및 신장에서 독성이 있음을 알 수 있었다. Chines herbs nephropathy (CHN) has been described in young women who had taken a slimming pills containing some chines herbs. Aristolochic acid (AA), suspected substance as the causal factor of CHN, is known a carcinogen. The Aristolochiae fructus (fruit of Aristolochia contorta) was used in Korean Traditional Medicine consists of appropriate amounts of mixed natural products. Subchronic toxicity of A. furctus containing aristolochic acid was investigated in SD rats. The body weight and clinical signs were observed after orally administration of A. futctus at doses of 21.2, 213, and 2130 mg/kg/day; mixture (including 9 other herbs) at dose of 427 mg/kg/day; aristolochic aicd (Ⅰ+Ⅱ) at doses of 0.05, 0.5, and 5 mg/kg/day for 3 months. At the end of the treatment, high dose treated animals revealed a deficit in final body weight about 25% compared with that of control. Organ weights of kidney, liver, testis, or ovary were increased with dose dependent manner. No changes considered to be due to the administration of A. furctus, mixture or aristolochic acid were in hematological and clinical study. However, significant changes at histopathological study of kidney and stomach were boserved in high-dose treated groups. In conclusion, for human health safety it needs appropriate regulatory actions regarding the use of natural herbal medicines known or suspected of containing aristolochic acid.

뇌 해마의 복측 또는 배측 부분이 제거된 흰쥐 중격핵의 신경전달물질

양훈모,김종규,한영길,민영기 순천향의학연구소 1999 Journal of Soonchunhyang Medical Science Vol.5 No.1

This study was planned to analyze amino acids in the septal nucleus of dorsal and ventral hippocampectomized rats by high performance liquid chromatography (HPLC). Male albino rats were used. Under chloral hydrate anesthesia (20%, 2 ml/kg body weight), a hole was made in each parietal bone about 4 mm lateral to the sagittal suture, and 4 mm rostral to the lambda suture. The cortical tissue on each side was removed and, through this opening, the hippocampal tissue anterodorsal and posteroventral to the hippocampal flexures on both sides was removed by aspiration. This preparation served as the dorsal and the ventral hippocampal animals, respectively. The cortical control animal received the same surgery short of hippocampectomy. The normal rats served as normal control animal. One day later, the animals were sacrificed by decapitation in the cold room. Two to three milligrams of tissue was obtained form the septal nucleus in one side of the brain. The tissue samples were homogenized and centrifuged. Then content of each amino acid was measured by HPLC form the brain tissue. The contents of aspartate and glutamate were decreased significantly more in the dorsal and ventral hippocampal groups than in the normal and the cortical control groups. The contents of glutamate were decreased significantly more in the ventral hippocampal group than in the dorsal hippocampal, while there were no significant differences between the two control groups. It is inferred form the above mentioned results that glutamate and aspartate may be used as excitatory transmitters in septal nucleus, and that the dorsal hippocampus may be facilitatory to the septal nucleus, but the ventral hippocampus would be inhibitory/facilitatory to the cortex.

악교정 수술후 자가통증조절장치(Patient-Controlled Analgesia)의 사용 효과에 관한 연구

양병은,유준영,송상훈,엄기훈 大韓顎顔面成形再建外科學會 1999 Maxillofacial Plastic Reconstructive Surgery Vol.21 No.4

The concept of PCA(Patient Controlled Analgesia) was first described in 1968, by Sechzer. The earliest descriptions of actual self-administered PCA machines were by Forrest et al. In gastric bypass surgery, cesarian section, orthopedic surgery etc, PCA is widely used in the control of postoperative pain. Previous Studies have shown that PCA provides effective pain-control for the postoperative patient. The postoperative pain-control is a problem that should be solved in surgery. Especially in orthognathic surgery, it is not same as in the case of maxillofacial trauma surgery or of tumor surgery : most orthognathic surgery patients are under operation not accustomed to pains, and difficulties in pain-complaint due to IMF(Intermaxillary fixation), postoperative nausea, and vomiting are additional problem. In this study, we have compared PCA and IM analgesics with respect not only to time request but also to the quality of postoperative pain control.

핵전이에 의한 Aspergillus oryzae var. oryzae와 Aspergillus nidulans 514의 잡종으로 부터 생산된 Xylanase의 특성

양영기,문명님,박형남,임채영 한국미생물생명공학회 ( 구 한국산업미생물학회 ) 1996 한국미생물·생명공학회지 Vol.24 No.1

Aspergillus oryzae var oryzae 와 Aspergillus nidulans 514간의 xylanase 우수 생성 종간 형질전환체를 획득하고, 유전분석과 정제를 통하여 다음과 같은 결과를 얻었다. 1. 핵전이를 위한 원형질체 형성 및 재생 조건에서는 Novozym 234의 농도 1%, 삼투안정제는 0.6M (NH_4)_2 SO_4, 효소의 처리 시간은 90분 그리고 최적 pH는 5.8로 나타났다. 2. 핵전이에 의한 형질전환의 빈도는 3×10 exp (-5)~1×10 exp (-5)으로 비교적 낮은 편이었다. 3. 유전적 안정성, conidia의 크기, DNA 함량의 측정 그리고 핵염색의 결과 형질전환체의 핵형은 aneuploid로 추정되었다. 4. 형질전환체의 xylanase 활성은 모균주와 비교하여 1.1~1.4배 증가하였다. 5. 형질전환체중 xylanase 활성이 가장 높은 TAVD514-3을 정제하고 몇가지 특성을 조사하였는데 전체적인 회수율이 17%, 분자량은 32,000 그리고 효소 활성에 미치는 기질의 영향을 올 조사하였다. 6. 정제된 효소의 최적 pH와 온도는 각각 pH 9.0과 80℃로 나타났으며, 효소활성은 Mg^2+ 와 Mn^2+의 존재시에 증가하는 경향을 나타내었다. Inerspecific hybrids between Aspergillus oryzae var oryzae and A. nidulans 514 were obtained by nuclear transfer technique. Several auxotrophic mutants isolated from conidiospores of the two strains were mutagenized with ultraviolet and N-methyl-N-nitrosoguanidine. Optimal conditions for formation of intergeneric hybrids were investigated. Frequencies of hybrid formation by nuclear transfer were 3×10 exp (-5)~1×10 exp (-5). From observation of genetic stability, conidial size, DNA content, and nuclear stain, it was suggested that their karyptypes are aneuploid. The hybrids showed 1.1~1.4 fold higher xylanase activities than parental strains did. The xylanase of Aspergiilus sp. TAVD514-3 was purified and some of it's enzymatc characteristics were investigated. The enzyme was purified about 85 fold with an overall yield of 17% from the culture medium by ammonium sulfate fractionation, Sephadex G-75 gel permeation chromatography, and CM-sephadex A-50 ion exchange chromatography. The purified enzyme functions optimally at pH 9.0 and 80℃. The enzymatic activity was increased by the presence of Mg^2+ and Mn^2 ions.

光州市場의 高等蔬菜類에 對한 細菌學的 硏究

梁永基,金英珠,朴悅 조선의대 1985 The Medical Journal of Chosun University Vol.10 No.1

개에서 17-ODYA가 신혈류량 자동 조절에 미치는 영향

양훈모,민영기,박중섭 순천향의학연구소 1999 Journal of Soonchunhyang Medical Science Vol.5 No.1

17-ODYA is a potent inhibitor of the formation of 20-hydroxyeicosatetraenoic acid, epoxyeicosatrienoic acids and dihydroeicosatetraenoic acids by renal cortical microsomes. This study characterized the effects of intrarenal infusion of 17-ODYA on renal blood flow (RBF) and autoregulation of RBF. Seven dogs were prepared for the measurements of RBF, mean systemic and renal perfusion pressure. The renal perfusion pressure was able to be adjusted to desired levels by an inflatable supra-aortic occluder. Intrarenal infusion of 17-ODYA produced a diuresis and a natriuresis but no change in RBF. 17-ODYA had no effect on autoregulation of RBF: Both the plateau and steep portrions. of the autoregulatory curves were identical to control. Thesholds for lower limit of autoregulation were 72±4 and 72±5 mmHg during control and 17-ODYA and not significantly different from each other. These results suggest that endogenous cytochrome P-450 metabolites of AA do not influence RBF autoregulatory capacity in dogs.

Aspergillus nidulans 에서의 핵전이에 의한 종내잡종 형성

양영기,박열,이영하,맹필재 충남대학교부설 생명공학연구소 1991 생물공학연구지 Vol.1 No.-

The nuclear transfer technique was employed to obtain intraspecific hybrids in Aspergillus nidulans. Nuclei isolated from either a wild type or an auxotrophic mutant strain (FGSC 475) were transferred into the protoplasts of a recipient strain (FGSC 514). The frequency of hybrid formation (4.8% and 10.1%, respectively) by nuclear transfer was higher than the frequency (0.6%) by protoplast fusion. Furthermore, most of the hybrids formed showed increased activity of some components of cellulase system, xylanase system, and mannanase. The hybrids were analyzed to be either diploid or aneuploid. These results suggest that nuclear transfer technique is more efficient in the formation of intraspecific hybrids than protoplast fusion method and is useful for the improvement of Aspergillus strains.

핵전이에 의한 Aspergillus속과 Penicillium 속의 잡종으로부터 생산된 esterase특성

양영기,문명님,임채영 조선대학교 부설 유전생물공학연구소 1994 유전생물공학연구지 Vol.4 No.-

핵전이에 의해 Aspergillus oryzae var oryzae와 MPV 31 사이의 잡종을 획득하였고, 그특성과 esterase 활성 및 동위효소 양상을 조사한 결과는 다음과 같다. UV와 MNNG의 이중처리에 의해 A. oryzae var oryzae와 P. verruculosum F-3의 영양요구성 돌연변이를 각각 3주, 6주를 획득하였으며, 핵전이를 위한 원형질체 형성의 최적조건은 PH 5.8, 1.0% Novozym 234, 0.6 M KCl 그리고 효소의 처리시간은 2 시간으로 하였다. 또한 원형질체 재생을 위한 삼투안정제도 역시 0.6 M KCl이었으며, 재생율은 각각 56.4%, 52.3%로 나타났다. 핵전이에 의한 형질전환율은 3.0 x 10<윗첨자>-5</윗첨자>~1.0 x 1<윗첨자>-5</윗첨자>으로 나타났으며, 형질전환체의 유전적 안정성과 conidial size, 핵염색, 그리고 DNA 함량의 측정결과핵형은 aneuploid로 추정되었고 효소 활성의 측정결과 형질전환체가 모균주에 비해 1.3~2.2배 가량 증가하였으며, 동위효소 양상은 형질전환체와 모균주에서 유사하게 나타났으나 효소활성에 차이가 있음을 알수 있었다. Intergeneric hybrids formed between Aspergillus oryzae var oryzae and Penicillium verruculosum F-3 were obtained by nuclear transfer technique. Several auxotrophic mutants isolated from conidiospores of the two strains mutagenized with ultraviolet and N-methyl-N-nitrosoguani-dine. Optimal conditions for formation of intergeneric hybrids were investigated. Frequencies of hybrid formation by nuclear transfer were 1 x 10<윗첨자>-5</윗첨자>~3 x 10<윗첨자>-5</윗첨자>. From observation of genetic stability, conidial size, DNA content, nuclear stain, it was suggested that their karyptypes are aneuploid. The hybrid posses the 1.2~l.8 fold higher esterase activities than those of parental strains. It was also revealed that some hybrids had different isozyme patterns compared with those of parental strains by esterase activity assays.