흰쥐에서의 CYCLOSPORIN A-유발 간독성에 대한 THROMBOXANE A₂-수용체 길항제인 KT2-962의 효과

신인철,강주섭,서대규,김정희 한양대학교 의과대학 1993 한양의대 학술지 Vol.13 No.1

Cyclosporine (CsA) is now widely used as immunosuppressive agents which has the unique capacity to prolong graft survival by a selective inhibitory effect on antigen-reactive T-lymphocytes. But, its renal toxicity is a major limiting factor for clinical use of CsA and is partially related to renal hemodynamic alteration. It has been suggested that thromboxane (TX) A₂would be one of the critical mediators of altered renal meondynamics. Therefore, various factors and effects can be participated in the toxic effect of CsA on liver function. In this study, the effect of KT2-962 (KT), an azulene derivative of recently synthesized selective TXA₂receptor antagonist on preventing acute hephtoxicity in CsA -treated rats was examined and blood glucose level. COT and CPT activity, and body weight were measured. Ultrastructural changes of the hephtocyte were evaluated by electron microscopy. Male Wistar rats were administered of CsA (25mg/kg, i.p) or KT2-962(30mg/kg,p.o) with CsA (25mg/kg, i.p) once a day for 20 consecutive days. The pretreatment of extra KT2 for 3 days was done before coadministration of CsA+KT2. The results (values are means±SE) obtained can be summarized as follows: 1) Body Weight (gm): Body weight was progressively increased and gained about 66.06±3.1(251.1 vs 318.7) on 3rd week of treatment in the control group. In contrast, there was weight loss of 37.1±2.8 (259.5 vs 220.9) in the CsA group. KT2 cotreatment with CsA inhibited weight loss by CsA and gained 40.2±1.9 (250.2 vs 290.4). 2) Blood glucose concentration (mg/dl): Blood glucose level was significantly increased to 2.3 times compared with control group (92.5 vs 210.0) in the CsA group. But, in the KT2+CsA group the blood glucose level within normal range preserved. 3) Serum GPT activity(U/L) : Serum GPT activity was significantly increased to 4.1 times compared with control group (24.4 vs 100.3) in the CsA group. But, in the KT2+CsA group, it was slighty increased to 1.9 times as control group and corresponded to below half of CsA group. 4) Serum GOT activity (U/L): Serum GOT activity was markedly increased to 4.6 times compared with control group (46.5 vs 215.7) in the CsA group. But, in the KT2+CsA group, it was slightly increased to 1.4 times compared with control group and correspond to below 70% of CsA group. 5) In the electron microscopic finding of a hepatocyte in CsA group. Nucleus is deformed. Mitochondria are swollen and cisternae of the rough endoplasmicis reticulum are dilated and sacculated. Autophagic vacuoles are seen, Golgi complex is slightly hypertrophied and amount of glycogen particles is reduced. But in the KT2+CsA group. Nucleus is round and rough endoplasmic reticula are evenly distributed and consist of paralelled cidternae with ribosomegranules. Mitochondria and Golgi complex are seen. Glycogen particles are distributed in large number. Consequently, it is suggested that endogenous TXA₂may be related with CsAhepatotoxicity and cotreatment of selective TXA₂receptor antagonist, TXA₂-962 can suppress CsA-induced hepatotoxicity in rats.

Streptomyces 속 균주 HA-40이 생산하는 내열성 α-Amylase의 효소학적 성질

신운섭,이동희,이현우,권태종,정호권 建國大學校 附設 産業技術硏究所 1988 논문집 Vol.13 No.-

토양으로부터 분리한 Streptomyces 속 균주 HA-40이 생산하는 내열성 α-amylase의 효소학적 성질을 조사한 결과는 다음과 같다. 효소의 작용 최적 온도는 65℃였으며 activation energy 는 16.9Kcal/mole이었고 60℃에서는 안정하였으나 70℃에서는 30분 처리로 약 50%, 1시간 처리로 약 75%가 실활하였다. 그러나 ??를 0.1mM농도로 첨가한 경우엔 70℃ 에서 1시간 처리하여도 잔존활성도가 55%이상으로 열변성에 대한 ??의 보호효과가 있었다. 본 효소는 pH7에서 활성이 가장 강하였으며 안정성도 가장 높았다. 그리고 금속이온 중에서 ??의 첨가로 효소활성이 증대되었으며 ??, ??, ??등에 의해서 활성이 저해되었다. 각종 효소저해제는 대부분 영향을 미치지 못하였으나 EDTA가 반응액 중에 공존하면 효소활성이 강하게 저해되었다 본 효소는 maltotriose이하의 당류에 대해서는 분해력이 없었으며 amylose에 대한 환원당 생성력을 100으로 하였을때 soluble starch 108, amylopectin 94, glycogen 87, dextrin 48, potato starch 25, corn starch 18로 생전분에 대한 분해력은 soluble starch에 비해서 1/4∼1/5 정도밖에 되지 않았다. 그리고 soluble starch에 대한 Km 치는 1.9㎎/㎖였다. The properties of a thermostale α-amylase produced from Streptomyces sp. strain HA-40, isolated from soil, were investigated. The optimal temperature of the enzyme was 65℃ and the enzyme was stable below 60℃. However, at 70℃ about 75% of the activity was lost after 1hr treatment, but by the addition of ?? in the concentration of 0.1mM only 45% of the activity was lost. The enzyme was most active and stable at around pH 7. The activity of the enzyme was increased by the addition of ??, but depressed by ??, ??, and EDTA. The enzyme could be hydrolyze soluble starch, amylose, amylopectin and glycogen well, and could also digest dextrin and raw starch. The Km value for soluble starch was 1.9㎎/㎖.

흰쥐에서의 Puromycin Aminonucleoside-유발 단백뇨에 대한 선택적 Thromboxane A₂수용체길항제, KT2-962의 효과

서대규,신인철,고현철,하경란,강주섭 한양대학교 의과대학 1994 한양의대 학술지 Vol.14 No.1

The administration of puromycin aminonucleoside(PAN) to rats caused to nephrotic syndrome which characterized ascites, proteinurisa, hypoalbuminemia, and hyperlipidemia similar to those observed in human minimal change disease. Recently, several studies indicate that renal endogenous thromboxane(Tx) A₂may have an important role in pathophysiology of various renal disease. In this sutdy, we hafve examined the protective effct of a selective TxA₂receptor antagonist, KT2-962(KT2) on PAN-induced proteinuria in rats. Thus, male Wistar rats were given either daily subsutaneous injection of PAN, 20mg/kg, for 10 consecutive days from 3 days before to 7 days with PAN treatment. Urine was collectd, and body weight was measured in interval of 2 days during 2 weeks and urinary N-acetyl-β-Dglucosaminidase(NAG) activity as an index of renal tubular cell damage and urine protein were measured. In addition to measuring BUN, serum creatinine and creatinine clearance were measured to assess the degree of renal functional damage in 14th day. The results(Means SE) otained can be summarized as follows: 1)Body weight(gm) was progressively increased and gained about 46.4gm and 39.2gm on 2 weeks of treatment in the control and KT2 groups respectively. In constrast, there was weight loss about 27.4gm in the PAN group. But, it was increased about 23.2 gm in KT2+PAN grou and means that KT2 has significantly(p<0.05) suppressed weight loss by PAN. 2)Urine flow (ml/24 hours) was slightly increased in both control and KT2 groups during 2 weeks. But, it was significantly(p<0.05) increased after 7th groups during 2 weeks. But, it was significantly(p<0.05) increased after 7th day. But, concurrent administration of KT2 significantly(P<0.05) suppressed PAN-induced polyuria in KT2+PAN group. 3)Urinary protein(mg/24 hours0 was slightly increased in both control and KT2 groups. But, it was progressively increased and reached at the maximal level, 3.2 folds of initial level to 11th day and thereafter slightly reduced proteinuria to 14th day in the PAN group. In contrast, KT2 cotreatment with PAN was significantly(P<0.05) suppressed PAN-induced proteinuria in the KT2+PAN group. 4)Urinary NAG activity was markedly increased and reached to maximal level, 122.03 18.53 U/mg of urine creatinine, 12.7 folds of initial by day 9 and thenafter progressively decreased to 5.4 folds of initial level by day 14 in the PAN group. But, when KT2 was administered with PAN, it was significantly depressed its increment to day 13. But, it was reached to maximal level, 99.05 42.55, 12.7 folds of inital level much than PAN group. This result indicated that KT2 had a partial preventive effect on PAn-induced renal tubular cell damage. 5)The BUN and serum creatinine level(mg/dl) were significantly(p<0.05) increased from initial level, 18.48 1.28 and 0.50 0.03 to 118.42 41.34 and 1.66 0.27 respectively, and creatinine clearance(ml/min) was significantly(P<0.05) decreased from initial level, 0.44 0.02 to 0.28 0.07 by day 14 by PAN treatment. But, when PAN was given together with KT2, the increment of BUN and serum creatinine except for creatinine clearance were significantly(P<0.05) inhibited in the KT2+PAN group. Based on all these results obtained in this study, it is concluded that the coadministration of KT2-962 with PAN can be ingibited protein excretion in urine and suggested that endogenous TxA₂would take part in PAN-induced proteinuria in rats.

경주지역 여고생의 초경과 체성장간의 관계

김준섭,권오구,박진석,오종수,박정현,박제식,안세한,이용환,서정호,신태섭,최영배,김덕수,이관,박수경 東國大學校醫學硏究所 2002 東國醫學 Vol.9 No.1

본 연구는 경주지역 1개 고등학교 3학년 여고생을 대상으로 초경 시작 전인 초등학교 4학년부터 고등학교 2학년까지의 키, 몸무게, 가슴둘레 수치와 초경 연령을 파악하여 여성의 초경이 빠를수록 체성장 속도의 변화가 있을 것이라는 가설을 기초로 두 요인간의 관련성을 파악하고자 시행되었다. 경주시 1개 여자고등학교 3학년생 총 317명에 대해 ㅊ경 나이, 초경시 심리 상태, 초경이 시작되었을 때의 상담 여부와 상담하였던 사람, 부모 신장과 초경전후의 식사 규칙성, 다이어트 경험, 수면시간, 스트레스, 음주/흡연 여부, 질병력 등에 대한 설문 조사를 시행하였고, 초등학교 4학년부터 고등학교 2학년까지의 키, 몸무게, 가슴둘레에 대한 정보는 건강기록부에서 확보하였다. 상기 대상자 중 건강기록부가 분실된 39명, 초경나이에 대해 응답하지 않았던 29명 및 결석 등으로 조사를 하지 못하였던 42명을 제외한 조사 대상자는 206명으로 선정하였다. 대상자들의 초경연령 평균값(Mean±SD)은 13.0±1.11이었고, 초등학교 4학년부터 고등학교 2학년까지의 초경 이후 신장 성장률은 감소하였으며, 초경연령이 빠른 군이 초등학교 때는 신장에 있어서 우위를 차지하나 고등학교에 오면서 신장은 비슷한 수준이 되었다. 초경후 1-2년 사이에 체중과 흉위의 증가율은 감소하였고, 초경연령이 빠른 군이 초등학교와 고등학교 사이에 체중과 흉위에서 모두 우위를 차지하였다. 본 연구의 결과는, 흔히 이차 성징의 시작 시점 혹은 사춘기의 시작 시점으로 보고있는 초경 연령이 청소년기의 성장과 밀접한 관련성이 있고, 특히 체중과 흉위의 성장 속도와 밀접한 관련성이 있음을 시사한다. To understand the onset of menarche in relation to changes in physical growth that take place during female adolescence, especially the changes in height and weight velocity. The 207 senior in one women high school of Kyongju were investigated in April 3 to 8, 2001. We collected the information, relation in the age at menarche, height & weight of parents, regularity of eating, and obesity diet, duration of sleeping, sickness & stress near age at menarche, by self-recording. The status of height, weight & chest circumference between the 4th grade of primary school and the junior of high school was collected by individual Health Record. The results were followed; The average age at menarche was 12.95±1.11 years old and the most frequent age of menarche is 13 years. After menarche, the velocity of height, weight and chest circumference were decreased. The most rapid group of menarche hold dominant position in height during elementary school. As time passed, they dont hold dominant position in height. The most rapid group of menarche get an advantage in the weight and the girth of chest after elementary school. The height of subjects is directly proportional to the height of their parents. These results suggest that the starting age at menestuation can be closely associated with physical growth and development.

2단 선회류 유동층 소각로에서 비산유출에 대한 상단 공탑속도의 영향

이태언,신용섭 慶星大學校 環境問題硏究所 1992 環境硏報 Vol.2 No.1

The effect of the secondary superficial air velocity on the elutriation rate of fines were investigated ina cold model of two-stage swirl-flow fluidized bed. The elutriation rates of fluidized particles were measured. And entrainment rates of particles were measured along the freeboard height in the single stage fluidized bed. As a result, the initial entrainment rates of the particles at the bed surface were calulated. The entrainment rate of the particles exponentially decreased as the height of freeboard was increased. The decay constant was almost inversly proportional to the superficial air velocity. The initial entrainment rate of particles depended on the excess air velocity to the power of 1.6. As the secondary air superficial velocity increased the elutriation rates of the particles maintained low values until the secondary air superficial velocity reached to 0.3m/s. When the secoandry air superficial velocity exceeded 0.3m/s, the elutriation rate of the particles increased sharply. By the increment of the secondary air superficial velocity, solid loading was increased and swirl intensity was decreased in the upper stage freeboard. Due to this combined effects, the elutriation rate of the particles increased sharply. However, the trapping rate of the particles in the upper stage freeboard showed high values above 97% in whole rage of the secondary air superficial velocity.

Gymnemic acid의 간장 및 신장의 조직에 미치는 영향에 대한 실험적 연구

박순록,신인철,강주섭,서대규 漢陽大學校 環境科學硏究所 1994 環境科學論文集 Vol.15 No.-

생체에 투여된 물질은 생체내에서 아무 변화없이 체외로 배설되는 경우도 있지만, 대부분은 체내에서 여러가지 생화학적 변화를 거쳐 배설된다. 이런 체내에서의 생화학적 변화는 주로 간장에서 일어나고, 이런 물질과 그 대산사물의 배설은 주로 신장에서 이루어지며, 일부는 다른 경로를 통하기도 한다. 그러므로, 약물의 대사 및 배설장기인 간장과 신장에 이런 물질이 축적되면 그 장기가 손상되는 악순환을 거치게 된다. 이에, 본 실험은 2000여년 전부터 오늘에 이르기까지도 인도지방에서 비만이나 당뇨병에 대한 민간요법제로 이용되어 온 Gymnema sylvestre 잎의 유효성분인 gymnemic acid의 신장과 간장의 조직에 미치는 영향을 검토하고자 실시하였다. 실험동물은 정상 Wistar계 웅성 흰쥐(체중 200gm 내외)를 사용하였고, 실험기간중에 먹이와 물은 자유로이 공급하였다. 실험군은 정상대조군과 동일한 조건하에서 15일동안 gymnema산을 각각 500㎎/㎏, 800㎎/㎏의 용량으로 하루 3회, 즉 오전 7시, 오후 2시, 오후 7시에 각각 경구투여하고, gymnema산 투여 15일째 24시간동안 절식시킨 후 경동맥사혈로 희생시킨 다음 개복하여 간우측 전엽과 우측 신장을 적출하여 일반 육안적 소견과 Hematoxylin 및 eosin 이중염색상의 광학 현미경적 소견을 관찰하여 다음과 같은 결과를 얻었다. 1. 흰쥐 신장의 육안적 소견과 Hematoxylin 및 eosin 이중염색 소견에서는 정상 대조군과 GA투여군에서 특기할 만한 소견이 관찰되지 않았다.(Fig 1-a, 1-b, 1-c). 2. GA(500㎎/㎏)투여군 흰쥐 간장에서 Hematoxylin 및 eosin 이중염색 소견상 간소엽의 중심대와 일부 중간대에서 동양혈관이 확장되었고, 간세포대의 배열이 불규칙해졌으며, 간세포내의 간세포배열이 불규칙해졌고, 공포변성이 초래된 간세포도 관찰도었다(Fig. 3-a,3-b). 3. GA(800㎎/㎏) 투여군 흰쥐 간장에서 Hematoxylin 및 eosin 이중염색 소견상 간소염 전반에 걸쳐 동양혈관이 확장되었고, 간세포대배열이 불규칙해졌으며, 간세포대내의 간세포 배열이 불규칙해졌고, 공포변성이 초래된 간세포도 관찰되었다(Fig. 4-a, 4-b). The majority of the chemicals that enter a living system is taken to elimination by hepatic biotransformation and renal excretion of its metabolites and unchanged form. But, some chemicals are also excreted into feces or through other routes. Therefore, the accumulation of the chemicals in the liver and kidney have damaged the organs. It was more than 3000 yours ago that Gymnema sylvestre. Asclepaidaceae piant indegenous to certain regionss of the tropical and subtropical countries, began to be used a popular folk medicine among native population in India in order to treat obesity and "Madhumeha(DM)" and its use still continues to today in India. Theorefore, this study has the purpose to investigate the effect of gymnemic acid(GA) Which is an effective ingredient of Gymnema sylvestre on the liver and the kidney. In the study, Wistar albino male rats weighing around 200gm were divided into three groups, basic diet group(control), GA(500㎎/㎏)group, GA(800㎎/㎏)group, and administered orally the gymnemic acid for 15 days in dose of 500㎎ and 800㎎ per ㎏ of body weight triple a day. All animals were sacrificed at 15 days after the daministration of gymnemic acid and starved for 24 hours sacrificing them, the specimens and eosin. The specimens have been examined grossly and light microscopically. The results were as follows. 1. In the gross and light microscopic observations of the kidney, the control and all experimental groups were not observed pathologic findings. 2. The gross observations of the liver of the of the control and all experimental groups wrer not observed pathologic findings. 3. The sinusoidal dilation, hepatic cord irregularity and disarrangement of hepatocyte were observed in the central zone and a part of intermediate zone of the hepatic lobule of the 15 days GA(500㎎/㎏) administered group. 4. The sinusoidal dilatation, hepatic cord irregularity, disarrangement of hepatocyte and abnormal shaped hepatocytes were observed in all zonesof the hepatic lobule of the 15 days GA(800㎎/㎏) administered gruop. Consequently, it is suggested that administration of large dose of gymnemic acid in the normal rats induces hepatic cellular damages.

만화 과제를 이용한 정신분열병 환자의 사회인지 능력의 측정

오정은,나명현,하태현,신용욱,노규식,홍순범,이경진,신민섭,이영호,권준수 大韓神經精神醫學會 2005 신경정신의학 Vol.44 No.3

Objectives : This study is to investigate the hypothesis that schizophrenic patients have difficulty in inferring mental state of others. Methods : Twenty schizophrenic patients and twenty normal subjects were administered to the Cartoon Task required inferring the character's intention in a given context. Results : The schizophrenic patients showed a statistically significant impairment in the Cartoon Task. Both groups chose the card depicting a frequent everyday action significantly more rather than the similar card to the last picture in each story for wrong answers. Conclusion : These preliminary results suggest that schizophrenia is associated with a specific deficit of the cognitive ability referred to as social cognition, and this deficit can be detected not only in the acute phase as found in previous research studies, but also in remission. Also when subjects fail to appreciate what is going on in the minds of other people, they seem to rely on a socially familiar experience.

Cancer Immunotherapy Using Bacteria-Derived Metabolites

Tae-Seop Shin 대한외과학회 2019 대한외과학회 학술대회 초록집 Vol.2019 No.10

Role of inducible nitric oxide synthase on the development of virus-associated asthma exacerbation which is dependent on Th1 and Th17 cell responses

Tae-Seop Shin,이병재,You-Me Tae,김유선,전성규,고용송,Dong-Chull Choi,김윤근 생화학분자생물학회 2010 Experimental and molecular medicine Vol.42 No.10

Asthma is characterized by airway inflammation induced by immune dysfunction to inhaled antigens. Although respiratory viral infections are the most common cause of asthma exacerbation, immunologic mechanisms underlying virus-associated asthma exacerbation are controversial. Clinical evidence indicates that nitric oxide (NO) levels in exhaled air are increased in exacerbated asthma patients compared to stable patients. Here, we evaluated the immunologic mechanisms and the role of NO synthases (NOSs) in the development of virus-associated asthma exacerbation. A murine model of virus-associated asthma exacerbation was established using intranasal challenge with ovalbumin (OVA) plus dsRNA for 4weeks in mice sensitized with OVA plus dsRNA. Lung infiltration of inflammatory cells, especially neutrophils,was increased by repeated challenge with OVA plus dsRNA, as compared to OVA alone. The neutrophilic inflammation enhanced by dsRNA was partly abolished in the absence of IFN-gamma or IL-17 gene expression, whereas unaffected in the absence of IL-13. In terms of the roles of NOSs, dsRNA-enhanced neutrophilic inflammation was significantly decreased in inducible NOS (iNOS)-deficient mice compared to wild type controls; in addition, this phenotype was inhibited by treatment with a non-specific NOS inhibitor (L-NAME) or an specific inhibitor (1400 W), but not with a specific endothelial NOS inhibitor (AP-CAV peptide). Taken together, these findings suggest that iNOS pathway is important in the development of virus-associated exacerbation of neutrophilic inflammation,which is dependent on both Th1 and Th17 cell responses.

Role of inducible nitric oxide synthase on the development of virus-associated asthma exacerbation which is dependent on Th1 and Th17 cell responses

Shin, Tae-Seop,Lee, Byung-Jae,Tae, You-Me,Kim, You-Sun,Jeon, Seong-Gyu,Gho, Yong-Song,Choi, Dong-Chull,Kim, Yoon-Keun Korean Society for Biochemistry and Molecular Bion 2010 Experimental and molecular medicine Vol.42 No.10

Asthma is characterized by airway inflammation induced by immune dysfunction to inhaled antigens. Although respiratory viral infections are the most common cause of asthma exacerbation, immunologic mechanisms underlying virus-associated asthma exacerbation are controversial. Clinical evidence indicates that nitric oxide (NO) levels in exhaled air are increased in exacerbated asthma patients compared to stable patients. Here, we evaluated the immunologic mechanisms and the role of NO synthases (NOSs) in the development of virus-associated asthma exacerbation. A murine model of virus-associated asthma exacerbation was established using intranasal challenge with ovalbumin (OVA) plus dsRNA for 4 weeks in mice sensitized with OVA plus dsRNA. Lung infiltration of inflammatory cells, especially neutrophils, was increased by repeated challenge with OVA plus dsRNA, as compared to OVA alone. The neutrophilic inflammation enhanced by dsRNA was partly abolished in the absence of IFN-gamma or IL-17 gene expression, whereas unaffected in the absence of IL-13. In terms of the roles of NOSs, dsRNA-enhanced neutrophilic inflammation was significantly decreased in inducible NOS (iNOS)-deficient mice compared to wild type controls; in addition, this phenotype was inhibited by treatment with a non-specific NOS inhibitor (L-NAME) or an specific inhibitor (1400 W), but not with a specific endothelial NOS inhibitor (AP-CAV peptide). Taken together, these findings suggest that iNOS pathway is important in the development of virus-associated exacerbation of neutrophilic inflammation, which is dependent on both Th1 and Th17 cell responses.