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.

출생후 성숙에 따라 나타나는 흰쥐 십이지장 및 공장 점막의 alkaline phosphatase 활성에 대한 연구

백두진 한양대학교 의과대학 1994 한양의대 학술지 Vol.14 No.2

The alkaline phosphatase, which is the hydrolytic enzyme of the phosphate salt in alkaline solution, acts on differentiation and maturation of cells and tissues, absorption and metabolism of nucleic acid and proteins. The author has investigated the change in the activity of alkaline phosphatase of the duodenal and jejunal mucosa of the rats according to biochemical and physiological maturation during early postnatal life. The experimental animals, which were obtained from litters deliveried, normally and randomly sampled adults, were sacrificed at the 1st, 5th, 10th, 20th, and 30th day after birth. The specimens of duodenum and jejunum were fixed in 10%-neutral formalin at 4℃ and sectioned 10㎛ thickness in cryostat. The activity of the alkaline phosphatase was evaluated histochemically by Gomori's method and the incubation time of sliced specimens was 30 minutes. The results were as follows. 1. In the neonatal rats of the 1st day after birth, the activities of the alkaline phosphatase were moderately positive in the epithelium and lamina propria of villi and weakly positive in the intestinal glands and its surrounding lamina propria of the duodenal mucosa. ANd the activities of alkaline phosphatase in the mucosa of the jejunum were moderately positive in the epithelium of the villi and weakly positive in the intestinal glands and lamina propria. 2. In the neonatal rats of the 5th day after birth, the activities of the alkaline phosphatase were moderately positive in the epithelium of apical and middle portion of villi. traceablely positive in the epithelium of basal portion and lamina propria of the mucosa of the duodenum. And the activities of alkaline phosphatase were moderately positive in the epithelium of apical and basal portion of the villi and weakly positive in the epithelium of middle portion of the villi. the intestinal glands and lamina propria of the jejumum. 3. In the neonatal rats of the 10th day after birth, the activities of alkline phosphatase were moderately or strong positive in the epithelium of the villi and weakly positive in the epithelium of the villi and weakly positive in the intestinal gland and lamina propria of jejunal mucosa. 4. In the rats of the 20th day after birth, the activities of alkaline phosphatase were strong or moderately positive in the epithelium of the villi, moderately positive in lamina propria of the core of the villi and the weakly positive in the intestinal glands and its surrunding lamina propria of duodenum. And the activities of alkaline phosphatase in the mucosa of the jejunum were strong positive in the epithelium of basal portion of the villi, intestinal gland and lamina propria of the villi and weakly positive in the lamina propria surrounding intestinal glands. 5. In the rats of the 30th day after birth, the activities of alkaline phosphatase were moderately or strong positive in the epithelium of the villi, modereate positive in the lamina propria of the villi and weakly positive in the intestinal glands and its surrounding lamina propria of the duodenal mucosa. And the activity of alkaline phosphatase was strong positive in the epithelium of apical portion of villi of the mucosa of the jejunum. Activity was decreased gradually and in the epithelium of basal portion of the villi activity was weakly positive. The activities were moderately positive in the intestinal glands and weakly positive in surrounding lamina propria of the glands and weakly positive in surrounding lamina propria of the glands of the jejunal mucosa. 6. In the rats of the adulthood, the activities of the alkaline phosphatase were strong positive in the epithelium of the villi and weakly positive in the intestinal glands and lamina propria of the duodenum. And the activities of alkaline phosphatase were moderately positive in the epithelium of the villi and weakly positive in the intestinal glands and lamina propria of the mucosa of the jejunum. Consequently, it is suggested that the activities of the alkaline phosphatase in the mucosa of duodenum and jejunum were increased by differentiation, growth, maturation and the changes of diet during early postnatal life, of the rats.

Methotrexate가 Mouse 간장의 Acid 및 Alkaline Phosphatase 활성에 미치는 영향

백두진,조태봉,정호삼 한양대학교 의과대학 1987 한양의대 학술지 Vol.7 No.2

Methotrxate (MTX), a folic acid analog, so effectively inhibits the synthesis of thymidine nucleotide that the synthesis of DNA is subsequently interrupted. It is widely used as an anticancer drug for the therapy of psoriasis and acute lymphatic leukemia. It inhibits not only DNA synthesis but also the protein synthesis and glycolysis, and general and cytotoxic toxicity are, therefore, observed during the therapy. Therefore the author undertook the present study to pursue the effect of methotrexate on the alkaline phosphatase and acid phosphatases in the liver. Albino mice, ICR strain, weighing 20g were used as experimental animals. The experimental animals were killed at 12, 24, 48, 72 and 96 hours after administration of 12 mg/kg of methotrexate. The specimens obtained from the liver were fixed and sectioned with 16㎛ thickness in a frozen cryostat. The activities of alkaline phosphatase and acid phosphatase were observed by the Gomori's method for histochemical study. The results obtained were as follows. 1. The activity of alkaline phosphatase was negative in the intermediate zone and trace positive in the periportal zone of the hepatic lobule in the 12 hours-MTX treated group. The activity of alkaline phosphatase was restored toward normal with time, moderate positive activity being in the intermediate zone and strong positive activity being in the peroportal zone of the 96 hours-MTX treated group. 2. The activities of acid phosphatase were increased with time, a moderate positive activity being in the central zone of the hepatic lobule of the 24 hours-MTX treated group and a strong positive activity being in the central zone of the hepatic lobule of the 48 hours-MTX treated group. A Moderate positive activity was observed in the central zone of the hepatic lobule of the 72 hours and 96 hours-MTX treated group. Consequently, it is suggested that methorexate decreases alkaline phosphatase activity and increase the acid phosphatase activity in the liver due to its cytotoxic effects.

허혈 및 재관류후 흰쥐 앞정강근과 가자미근에서 나타나는 미세구조와 SOD 활성의 변화

백두진,안동춘,황규성,김혜주,박철홍,정호삼,조근열 대한체질인류학회 1999 해부·생물인류학 (Anat Biol Anthropol) Vol.12 No.2

에너지 획득방법, 당원의 분포, 모세혈관의 분포 및 미세구조의 차이가 나는 백색근육섬유와 적색근육섬유에서 허혈시간에 따라 나타나는 미세구조의 변화와 SOD의 활성변동을 비교 관찰하여 다음과 같은 결과를 얻었다. 1. 앞정강근에서는 2시간 허혈시 사립체에서 바탕질의 전자밀도가 감소하고 사립체능선이 팽대하였고, 재관류 24시간 경과시에는 근육원섬유사이의 거리가 멀어지고 근육세포질세망의 수조와 종말수조가 팽대하였으며 재관류 72시간 경과시에는 정상대조군과 유사한 소견이 나타났다. 2. 가자미근에서 2시간 허혈시 사립체에서는 사렵체바탕질의 전자밀도가 감소하였으며, 재관류 24 시간 경과시는 근육세포질세망의 수조가 팽대하였고, 재관류 72시간 경과시에는 정상대조군과 유사하였다. 3. 4시간 및 6시간 허혈시 미세구조의 변화는 허혈시간과 재관류 시간경과에 따라 심해져 앞정강근에서는 사립체에서 바탕질의 전자밀도가 감소하고 사렵체능선은 불분명하고 소용돌이소체가 나타났으며 근육원섬유 용해와 곤육원섬유괴사가 관찰되었다. 가자미근에서는 근육원섬유에서 근육미세섬유의 배열과 끝가로막이 불규칙해지고 근육세포질세망의 수조가 팽대하였으며 근육원섬유용해가 나타났다. 4. 앞정강근에서 Cu, Zn-및 Mn-SOD 활성은 미약한 흑은 약한 양성반응을 나타내었고, 가자미근에서는 Cu, Zn-SOD는 미약한 양성반응을, Mn-SOD 는 미약한 혹은 약한 양성반응을 나타내었다. 허혈후 Cu, Zn- 및 Mn-SOD 의 활성은 허혈시간이 길수록 더욱 증가하였다. 5. Cu, Zn- 및 Mn-SOD 활성은 2시간 허혈 및 재관류 24 시간 경과시 약간 증가하였으며 72시간 경과시에는 앞정강근과 가자미근에서 정상대조군과 유사하게 나타났다. 6. 4시간 및 6시간 허혈 및 재관류후 두 근육에서 Cu, Zn- 및 Mn-SOD활성은 증가하였다. 두 근육에서 Mn-SOD의 활성변동은 유사하였으나 Cu, Zn- Mn-SOD의 활성증가는 앞정강근보다 가자미근에서 크게 나타났다. 이상의 결과를 종합하면 허혈 및 재관류 손상은 허혈시간과 재관류시간 경과에 따라 심하게 나타났고 가자미근보다 앞정강근에서 심하게 나타났으며, 손상의 차이는 두 근육에서 나타나는 SOD활성변동과 깊은 연관이 있는 것으로 생각된다. Skeletal muscles are known to have tolerance to ischemia, but a prolonged ischemia can cause damage to muscular tissues. The ischemia-reperfusion injury results from the oxygen free radicals released by leucocytes and formed by the reaction of hypoxanthine and xanthine oxidase. Superoxide dismutase (SOD), one of major antioxidant enzymes occurring in the various tissues of the body metabolizes or scarvanges the oxygen free radicals. Although many studies reported difference in tolerance to ischemia and reperfusion between white and red muscles, some other investigators failed in finding such difference. The present study was performed to examine effects of graded periods of ischemia and reperfusion on the cellular ultrastructure and activity of SOD in white and red muscles. The Sprague-Dawley rats (200~250 g) were used as experimental animals. Under pentobarbita] (50 mg/kg IP) anesthesia, incision was made on lower abdomen and left common iliac artery was occluded by means of a vascular clamp for 2, 4 and 6 hour (hrs). Thereafter, the superficial portion of mid-belly of anterior tibial muscle and soleus muscles were excised at 0, 24 and 72 hrs after onset of reperfusion. The specimens were sectioned into slices, 2 mm in length, 1 mm in width and thickness. Some specimens were prepared for electron microscopic observation and others for determination of SOD activity by using antihuman CU, Zn- and Mn-SOD antibodies. The results obtained were as follows. 1. In anterior tibial muscle, areas with loose electron-density and dilated cristae were observed in the mitochondria immediately after 2 hrs of ischemia, while widened intermyofibrillar spaces and dilated cisternae of sarcoplasmic reticulum were seen after 2 hrs and 24 hrs reperfusion. When subjected to 2 hrs ischemia and 72 hrs reperfusion, no significant change was found in the cellular ultrastructure. 2. In soleus muscle, electron density was loose in the matrix of mitochondria immediately after 2 hrs of ischemia, while cisternae of sarcoplasmic reticulum were dilalated after 2 hrs of ischemia and 24 hrs reperfusion. Following 2 hrs of ischemia and 72 hrs repeifusion, the electron microscopic findings were similar to those of normal rats. 3. The changes in cellular ultrastructure were more prominent in both the 4 hrs and 6 hrs ischemia groups, in which degree of ultrastructural changes were proportional to duration of reperfusion. 4. In anterior tibial muscle, trace or weak immunoreactivities of Cu, Zn- and Mn-SOD were seen, whereas trace immunoreactivity of Cu, Zn-SOD and trace or weak immunoreactivity of Mn-SOD were observed in soleus muscle. 5. The immunoreactivities of CU, Zn- and Mn-SOD were not altered in 2 hrs ischemic and 72 hrs reperfused group, while they were increased slightly in 2 hrs ischemic and 24 hrs reperfused group. 6. In both muscles, the activity of SOD increased following 4 hrs or 6 hrs ischemia and 24 hrs or 72 hrs reperfusion. The changes in immunoreactivity of Mn-SOD were not different between two muscles, whereas immunoreactivity of Cu, Zn-SOD were higher in anterior tibial muscle. Consequently, it is suggested that significant ischemia reperfusion injuries are produced after 4 ~ 6 hrs ishemia followed by 24 hrs or 72 hrs reperfusion, that anterior tibial muscle is more susceptible to ischemic reperfusion injury and that the ischemic-reperfusion injury is closely related with activity of SOD.

일산화탄소 및 고압산소의 폭로가 흰쥐의 제2형 폐포세포와 사구체에 미치는 영향에 관한 연구

백두진,정호삼,이계훈,황세진,전영호,전영희 한양대학교 의과대학 1997 한양의대 학술지 Vol.17 No.2

The present study was performed to investigate the ultrastructural changes of the type Ⅱ pneumocyte in the lung and that of the glomerulus in the kidney after carbon monoxide(CO) or hyperbaric oxygen (HBO) exposure. The male Sprague-Dawley rats, weighing about 200gm, were used as experimental animals. The animals were divided into CO exposure group, air exposure after CO exposure group, HBO exposure group and HBO exposure after CO exposure group. After single CO and HBO exposure (3790ppm), the specimen of lung and kidney were obtained. According to routine method, EM preparations were made and observed with electron microscope. The results obtained were as follows ; 1. Slight disruption of the mitochondrial membrane was observed in alveolar type Ⅱ pneumocyte, after single CO exposure. 2. In all experimental groups except CO exposure group, decrease in number and atropy of rough endoplasmic reticulum, disruption of double membrane and crista of mitochondria and vacuolar degeneration of lamellar bodies in alveolar type Ⅱ pneumocytes were observed. 3. In all experimental groups, fusion of the pedicles of podocytes, and obliterations of the endothelial fenestrations were observed. These results suggested that CO and HBO exposure may induced the ultrastructural damages in the alveolar type Ⅱ pneumocyte and the glomerulus.

청년기 한국인 얼굴에 대한 계측적 연구 Ⅱ

백두진,안동춘,고기석 대한췌담도연구회 2000 대한췌담도연구회지 Vol.5 No.4

허혈양상화, Adenosine 및 Pinacidil이 허혈 및 재관류후 흰쥐넙다리곧은근에서 Superoxide dismutase발현에 미치는 영향

백두진,유영미,황규성,안동춘,정호삼,강봉균 대한체질인류학회 2000 해부·생물인류학 (Anat Biol Anthropol) Vol.13 No.1

본 실험은 흰쥐에서 나타나는 허혈양상화의 효과와 그 발생기전을 규명하고자 하였다. 실험동물로는 300-350g 내외의 숫흰쥐를 사용하였으며 온엉덩동맥을 2시간 결찰한 후, 3시간, 6시간, 12시간, 24시간 및 72시간 재관류시켰으며, 온엉덩동맥을 5분간 결찰하고 5분간 재관류시키는 과정을 3회 반복하여 허혈양상화시키거나 시술적전 adenosine 혹은 pinacidil을 투여하고 같은 방법으로 허혈 및 재관류시켰다. 8-cyclopentyl-1,3-dipropylxanthine 혹은 glibenclmide 투여하고 허혈양상화시킨 다음 허혈 및 재관류시키고 넙다리곧은근을 적출하여 파라핀절편을 제작하고 in situ hybridization 조직화학법으로 Cu, Zn 및 Mn-SOD mRNA의 발현을 비교관찰하여 다음과 같은 결과를 얻었다. 1. 모든 실험군 넙다리곧은근에서 Cu, Zn 및 Mn-SOD mRNA는 단면적이 작은 근육섬유에서만 발현되었다. 2. 정상대조군 넙다리곧은근에서 Cu, Zn- 및 Mn -SOD mRNA는 약하게 발현되였다. 3. 허혈 및 재관류군에서는 재관류 시간경과에 따라 넙다리곧은근에서 CU, Zn-SOD mRNA는 중등도로 발현되었고, Mn-SOD mRNA는 재관류 3시간 및 6시간 경과시 약하게 혹은 중등도로 발현되었으며 재관류 12시간 경과시 약하게 혹은 미약하게 발현되었고, 24시간 경과시에는 중등도로 발현되었으며 72시간 경과시에는 약하게 혹은 중등도로 발현되었다. 4. 허혈양상화 처치로 넙다리곧은근에서는 Cu, Zn-SOD mRNA의 발현이 증가하여 12시간 경과시 중등도로 발현되었고 24시간 경과시 약하게 혹은 중등도로 발현되었으며 72시간 경과시에는 약하게 발현되었다. Mn-SOD mRNA 는 처치후 12시간 경과시 중등도로 발현되였고 24시간 경과시 중등도 혹은 강하게 발현되었으며 72시간 경과시 약하게 발현되었다. 5. 허혈양상화 허혈 및 재관류군에서 Cu, Zn-SOD mRNA는 재관류 6시간까지 중등도로 발현되었으며 재관류 12시간 및 24시간 경과시에는 약하게 혹은 중등도로 발현되였고 72시간 경과시에는 약하게 발현되였다. Mn-SOD mRNA는 재관류 12시간까지 중등도로 발현되었고 24시간 경과시 중등도 혹은 강하게 발현되었으며 72시간 경과시에는 약하게 발현되었다. 6. Adenosine 투여후 허혈 및 재관류시에는 넙다리곧은근에서 Cu, Zn-SOD mRNA는 재관류 12시간 경과시까지 중등도로 발현되었고 재관류 24시간 경과시에는 약하게 혹은 중등도로 발현되였으며 재관류 72시간 경과시에는 약하게 발현되었다. 7. Pinacidil 투여후 허혈 및 재관류시에는 넙다리곧은근에서 Cu, Zn-SOD mRNA는 재관류 6시간까지 중등도로 발현되었고 재관류 12시간 경과시에는 약하게 혹은 중등도로 발현되었으며 재관류 24시간 및 72시간 경과시에는 약하게 발현되었다. 8. 8-cyclopentyl-1,3-dipropylxanthine 투여후 허혈양상화 허혈 및 재관류시 넙다리곧은곤에서 Cu, Zn-SOD mRNA는 재관류 3시간까지 중등도로 발현되였고 재관류 6시간 및 12시간에는 약하게 흑은 중등도로 발현되었으며 재관류 24시간 및 72시간 경과시에는 약하게 발현되였다. Mn-SOD mRNA를 재관류 3시간까지 약하게 발현되었고 재관류 12시간까지 중등도 혹은 약하게 발현되였으며, 재관류 24시간 경과시에는 약하게 발현되었고 재관류 72시간 경과시에는 중등도로 발현되었다. 9. Glibenclamide 투여후 허혈양상화 허혈 및 재관류시에는 넙다리곧은근에서 Cu, Zn-SOD mRNA는 재관류 24시간까지 중등도로 발현되었고, 재관류 72시간 경과시까지는 약하게 혹은 중등도로 발현되었다. Mn-SOD mRNA는 재관류 기간을 통하여 중등도로 발현되었다. 이상의 소견을 종합하면 허혈 및 재관류시 Cu, Zn- 및 SOD mRNA의 발현은 증가하였고 허혈양상화로 특히 Mn-SOD mRNA의 발현이 증가하였으며, 허혈양상화의 효과는 adenosine A_(1) 수용체와 K_(ATP) 통로의 자극과 밀접한 연관이 있는 것으로 결론 지을 수 있다. A brief episode of ischemia and reperfusion termed 'ischemic preconditioning' has been established as rendering muscle tolerance to damage during a subsequent prolonged ischemia. The effects of ischemic preconditioning in the cardiac muscle are related to the stimulation of adenosine A, receptor and the opening of KATP channel. The effect and mechanisms of ischemic preconditioning in the skeletal muscle are not known clearly. The superoxide radical injures the skeletal muscle during the ischemia and reperfusion. There are two types of SOD, which metabolizes the superoxide radicals to H_(2)O_(2) and O_(2), in the cell. One of them is Cu, Zn-SOD in the cytoplasm and the other is Mn-SOD in the mitochondria. The activities of SOD are increased against the formation of superoxide radical during the reperfusion. The author performed the present study to investigate the effect and the mechanisms of ischemic preconditioning by measuring the expression of SOD mRNA on timely reperfused ischemic muscles. The healthy Sprague-Dawley rats weighing from 300g to 350g were used as experimental animals. Under pentobarbital(50 mg/kg) anesthesia, lower abdominal incision was done and left common iliac artery was occluded by vascular clamp for 2 hours. Rectus femoris muscles were obtained respectively at 3, 6, 12, 24 and 72 hours after reperfusion. The ischemic preconditioning group underwent three episodes of 5minute occlusion and 5minute reperfusion of common iliac artery followed by 2hours of ischemia and timely reperfusion. Adenosine (50 ㎍/kg) or pinacidil(1 mg/kg) was administered intravenously before ischemia. 8-cyclopentyl-1,3-dipropylxanthine(15 mg/kg) or glibenclamide(0.5 mg/g) was administered intravenously before ischemic preconditioning. Paraffin sections with 4 ㎛ thickness in all groups were obtained. The expression of Cu, Zn- and Mn-SOD mRNA was observed by use of in situ hybridization. The results obtained were as follows. I. The expression of SOD mRNA was seen only in small muscle fibers of the rectus femoris muscle of the rat. 2. Weak expressions of Cu, Zn- and Mn-SOD mRNA were observed in the normal control rat. 3. After 2 hours of ischemia, moderate expression of Cu, Zn-SOD mRNA was observed until 72 hours of reperfusion. Weak or moderate expression of Mn-SOD mRNA at 3 hours and 6 hours of reperfusion, weak or trace expression at 12 hours of reperfusion, moderate expression at 24hours of reperfusion and weak or moderate expression at 72hours of reperfusion were observed. 4. After ischemic preconditioning, moderate expressions of Cu, Zn-SOD mRNA were seen in the groups of 3, 6, 12 and 24 hours of reperfusion. Moderate expressions of Mn -SOD mRNA were seen in the group of 0, 3, 6 and 12hours of reperfusion and strong expression was seen in the group of 24hours of reperfusion after ischemic preconditioning. 5. After 2 hours of ischemia with ischemic preconditoining, moderate expressions of Cu, Zn-SOD mRNA were seen in the groups of 0, 3, 6, 12, 24 hours of reperfusion. Moderate expressions of Mn-SOD mRNA were observed in the groups of 0, 3, 6, and 12 hours of reperfusion and moderate or strong expression was seen in the group of 24 hours of reperfusion. 6. After 2 hours of ischemia with the pretreatment of adenosine, moderate expressions of Cu, Zn-SOD mRN A were seen in the group of 0, 3, 6, 12 and 24hours of reperfusion. Moderate expression of Mn-SOD mRNA in the groups and 3 hours of reperfusion, strong expression in the group of 6 and 12 hours of reperfusion and moderate expression in the group of 24hours of reperfusion were seen. 7. After 2 hours of ischemia with the pretreatment of pinacidil, moderate expressions of Cu, Zn-SOD mRNA were seen in the groups of 0, 3, 6 and 12 hours of reperfusion and those of Mn-SOD mRNA were seen in the groups of 3, 6, 12 and 24 hours ofreperfusion. 8. After 2hours of ischemia with ischemic preconditioning and the pretreatment of 8 -cyclopentyl- l,3dipropylxanthine, moderate expression of Cu, Zn-SOD mRNA were observed in the groups of 0, 3, 6. and 12hours of reperfusion and those of Mn-SOD were seen in the groups of 6, 12 and 72hours of reperfusion. 9. After 2hours of ischemia with ischemic preconditioning and the pretreatment of glibenclamide, moderate expressions of CU, Zn-and Mn-SOD mRNA were seen in all groups of reperfusion. Consequently, these results suggest that the expression of Cu, Zn and Mn-SOD mRNA increases during 2hours ischemia and reperfusion with or without ischemic preconditioning. The effects of ischemic preconditioning are closely related to the stimulation of adenosine A₁receptor and K.ATP channel.

Daunomycin이 Mouse 간장의 Alkaline Phosphatase 활성에 미치는 영향

백두진,김훈기,정호삼 한양대학교 의과대학 1987 한양의대 학술지 Vol.7 No.2

Daunomycin is a member of the anthracycline class of antitumor antibiotics. And it was isolated from cultures of Streptomyces peucetius in 1963. Cemically, it was found to consist of a pigmented aglycone (daunomycinone) bound to an aminosugar, daunosamine. The biochemical mode of cytotoxic action of daunomycin results from its binding to DNA possibly by intercalation between the base pairs, thereby inhibiting the DNA polymerases. The author has investigated the effect of daunomycin on the mouse liver histochemically observing the change in the activity of alkaline phosphatase. The animals treated with 16 mg per kg of daunomycin wee sacrified at 6, 12, 24 and 36 hours after drug administration. The animals of control group were administered only water for injection. The liver specimens were fixed in 10% neutral formalin at 4℃ and sectioned at 16? In thickness in a frozen cryostat. The activity of alkaline phosphatase was evaluated histochemically by Gomori's method. The results were as follows. 1. The activity of alkaline phosphatase was moderate positive at the periportal and intermediate zones and trace positive at the centrilobular zone of the hepatic lobule in 6 hours daunomycin treated group. Ad the time goes by, the activity of alkaline phosphatase was decreased in the hepatic lobule. At 24 hours after administraton of daunomycin, negative reaction at the centrilobular zone, trace positive at the intermediate zone and weak positive at the periportal zone of the hepatic lobule were seen. Consequently, it is suggested that daunomycin decreases the activity of alkaline phoshatase in the liver, due probably to its cytotoxic effect on the hepatocyte.

Dactinomycin이 Hamster 위점막에 미치는 영향

백두진 한양대학교 의과대학 1992 한양의대 학술지 Vol.12 No.2

Dactinomycin, an anticancer drug, has been widely used in the therapies of Wilm's tumor, Kaposi's sarcoma, Ewing's tumor and soft tissue cancers. Dactinomycin inhibits not only nucleic acid synthesis but also protein synthesis. It has been reported that during the therapies, its cytotoxicities lead to bone marrow depression, alopecia and ulceraion. The author has invertigated the effect of dactinomycin on the gastric mucosa of the hamster histologically observing the morpholohycal changes of the cells. The animals treated with 1mg per kg of dactionmycin were sacrificed at 24 and 48hours after the drug administration and fasted for 12 hours before sacrificing animals of the control and experimental groups. The animals of the control group were administered only water for injection. 1. Dilatation of the lumen of the gastric gland associated with atrophied and vacuolated parietal cells and chief cells are observed in the gastric mucosa at 24 hours after aministration of dactinomycin. 2. Cystic dilatation associated with severely atrophied parietal cells and cheif cells in the fundus of the gastric glands and pasammoma bodies, corpuscles of lamellated calcification, in the mouth of the glasnds are observed. Arterioles, capillries and venules in the mucosa are dilated and congested. Consequently, it is suggested that dactinomycin would induced the damages of the epithelial cells of the gastric glands and vessels in the mucosa of the stomach in hamster.

탈지작업 근로자의 트리클로로에틸렌 폭로에 관한 조사

박두용,김형아,김창엽,백남원,조정진,김양호,이광묵 가톨릭대학 산업의학 쎈타 산업의학연구소 1989 韓國의 産業醫學 Vol.28 No.4

Trichloroethylene(TCE) is a widely used organic solvent, especially in degreasing process of metal manufacturing, however few data concerning its exposure and poisoning were obt-ainable. This survey was performed for more information of TCE exposure in this country. Urine sanmples were collected from 144 TCE handling workers and 46 non-TCE-exposed workers. TCE concentrations of four workshops in working environment were analyzed. The results were as follows; 1. TCE exposed workers were 48 male and 96 female employees. Average total duration of employment of these workers was 39.0 months, average duration of works per day was 10.7 hours, and average duation of TCE handling was 469.7 minutes. 2. The average concentration of urine total trichloro-compounds was 156.32㎎/ g crea-tinine, and that of trichloroacetic acid was 69.2㎎/g creatinine. Of those workers, 78 workers had the concentrations of urine trichloroacetic acid over 75㎎/g, which is the biological exposure index (BEI) of urine trichloroaxetic acid in Korea. Duration of work per day and duration of TCE- related work were significantly longer in the group of workers whose urine trichloroacetic acid concentration was over the criteria level of BEI. 3. TCE concentrations of three workshops were over the level of ACGIH TLV(threshold limit value), 50ppm in TWA (time -weighted average). In remaining one workshop, duration of TCE related works was only one hour per day. There was statistically significant correl-ation between the concentration of TCE in working environment and the proportion of workers in a workshop whose urinary trichloroacetic acid concentration was over the criteria level of BEI. 4. Responses to self-administered questionnaire were not meaningful for differentiation of psychoneurologica symptoms due to chronic TCE exposure from othres.