고혈당 쥐의 췌장 효소활성에 미치는 Nicotinamide의 영향

손기호(Kie-Ho Sohn),김석환(Seok-Hwan Kim),최종원(Jong-Won Choi) 한국식품영양과학회 1992 한국식품영양과학회지 Vol.21 No.2

Nicotinamide의 항 당뇨작용을 연구할 목적으로 streptozotocin으로 당뇨병을 유발시킨 흰 쥐를 모델동물로 하여 수분섭취량과 체중, 혈당, 뇨당 및 혈중 insulin함량과 췌장중 효소변동을 형태학적인 측면과 함께 상호 비교 관찰하였다. Nicotinamide의 전처리로 STZ에 의해 유발되는 당뇨병시 나타나는 생리적 현상의 감소 및 혈당증가가 유의성있게 감소되었으며 혈중 insulin농도도 STZ에 의해 현저히 억제되던 것이 nicotinamide의 전처리로 정상수준으로 회복되었다. 혈청중 lipase 및 trypsin활성은 STZ투여에 의해 증가되었으며, amylase활성은 대조군에 비해서 억제되었으나 nicotinamide의 전처리로 lipase, trypsin 및 amylase활성이 회복되었다. 췌장의 형태학적인 변화에서는 STZ 투여로 췌장 소엽세포 및 췌관을 포함하는 외분비계의 조직에는 변화가 없으나 Langerhans's islet β세포가 심하게 파괴되었고 nicotinamide의 전처리로 β세포의 파괴가 현저하게 감소되었다. The present study was undertaken in order to elucidate the effects of pretreatment with nicotinamide on changes in serum glucose level, body weight, water consumption, serum insulin concentration, and the activity of pancreatic enzyme in rats treated with streptozotocin (STZ). Histological studies were also carried out to evaluate the effects on pancreatic tissues and langerhans' s islet cells. Nicotinamide pretreatment in STZ diabetic rats inhibited the rise of fasting serum glucose concentration and water consumption. Pretreatment with nicotinamide significantly increased the concentration of serum insulin and body weight changes compared to the STZ-treated group. Pancreatic lipase and trypsin activites were increased, but amylase activity was decreased and pancreatic β-cell was destroyed by STZ. Pretreatment with nicotinamide prevented these STZ-induced changes. These results suggest that nicotinamide pretreatment supresses STZ-induced changes in pancreatic enzymes by preventing β-cell destruction and therefore maintaining a normal serum insulin level.

Nicotinamide가 Streptozotocin 당뇨성 쥐의 혈중 지질 성분에 미치는 영향

최종원(Jong-Won Choi),손기호(Kie-Ho Sohn),김석환(Seok-Hwan Kim) 한국식품영양과학회 1991 한국식품영양과학회지 Vol.20 No.4

Streptozotocin(STZ)에 의해서 유도된 당뇨성 쥐에서 nicotinamide의 영향을 알아보기 위하여 혈중 당의 농도, 지질함량 변동과 동맥경화 지표와의 상관관계를 관찰하였다. STZ 투여로서 혈중당의 농도가 증가되던 것이 nicotinamide의 전처리로 정상상태로 억제되었고 total lipid 및 triglyceride 함량에서도 STZ 투여로 증가되던 것이 nicotinamide 전처리로 억제되었으나 phospholipid 함량에는 별다른 영향이 없었다. 혈중 total cholesterol, VLDL, LDL-cholesterol 함량 및 동맥경화 지표는 STZ에 의해 증가되었으나 nicotinamide 전처리로 저지되었으며 HDL-cholesterol 함량에서는 STZ 투여에 의해 감소되던 것이 nicotinamide의 전처리로 회복되었다. 혈중 lipase의 활성은 STZ 투여로서 억제되던 것이 nicotinamide의 전처리로 회복되었다. s-ALT 및 s-AST의 활성은 STZ 투여군이나 nicotinamide 전처리 군에서나 별다른 영향이 없었다.<br/> 이상의 실험 결과에서 nicotinamide의 전처리는 STZ에 의하여 유도되는 당뇨병을 예방할 것이라는 사실이 다른 측면에서 뒷받침하는 것으로 본 연구에서는 당뇨성 고지혈증의 예방에 nicotinamide가 유용하게 응용될 수 있는 가능성을 제시하고 있다. The purpose of this study was to investigate the effect of pretreatment with nicotinamide on the serum lipid composition and atherosclerotic index in streptozotocin(STZ)-induced diabetic rats. Nicotinamide pretreatment in STZ-induced diabetic rats inhibited the rise of serum glucose concentration. Serum total lipids and triglyceride levels in the STZ-induced diabetic rats were significantly higher than those in the control group. But in the group pretreated with nicotinamide, triglyceride and lipid levels were significantly lower compared with those of STZ-induced diabetic rat group without nicotinamide. However, the serum phospholipid levels were not statistically different among treatment groups. In the STZ-induced diabetic group, the serum total cholesterol, VLDL, LDL-cholesterol levels and atherosclerotic index were higher and HDL-cholesterol level was lower compared to the control group. However, these changes were prevented by nicotinamide pretreatment. Pretreatment with nicotinamide significantly increased the activities of serum lipase compared to the STZ-treated group. Aminotranferase (ALT, AST) activities were not significantly different in any of the groups.

Effect of Pretreatment with Nicotinamide on Changes in the Hepatic Metabolizing Enzyme System Induced by Streptozotocin

최종원(Jong-Won Choi),손기호(Kie-Ho Sohn),김석환(Seok-Hwan Kim) 한국식품영양과학회 1991 한국식품영양과학회지 Vol.20 No.3

Streptozotocin(STZ)에 의해 야기되는 대사효소활성의 변동에 nicotinamide의 전처리가 어떠한 영향을 주는가를 알아보기 위하여 aniline hydroxylase, aminopyrine N-demethylase, cytochrome P-450 및 포합 반응에 관여하는 UDP-glucuronyl transferase, sulfotransferase, glutathione S-transferase에 미치는 활성변동을 관찰하였다. STZ투여로서 간 microsomal aniline hydroxylase 및 cytochrome P-450의 활성이 증가되던 것이 nicotinamide 전처리로 대조군 수준으로 억제되었으며 aminopyrine N-demethylase의 활성은 STZ 투여로 억제되던 것이 nicotinamide전처리로 도리어 대조군 수준으로 증가되었다. Microsomal UDP-glucuronyl transferase 및 cytosolic sulfotransferase의 활성에서는 STZ투여군에서나 nicotinamide전처리군에서도 대조군과 비교하여 별다른 영향이 없었다. Cytosolic glutathione S-transferase의 활성은 STZ투여로 증가되던 것이 nicotinamide전처리로 억제되었다. The present study was undertaken in order to elucidate the effect of pretreatment with nicotinamide on changes in the hepatic metabolizing enzyme system induced by streptozotocin (STZ). In rats, STZ(50㎎/㎏) administered by tail vein caused a significant rise in hepatic aniline hydroxylase and a decrease in aminopyrine N-demethylase when compared to control (p<0.05). Pretreatment with nicotinamide inhibited these effects (p<0.05). Similarly, STZ induced changes in hepatic microsomal cytochrome P-450 activity were inhibited by pretreatment with nicotinamide(p<0.05). However, changes in UDP-glucuronyl transferase and sulfotransferase activity were not significantly different(p>0.05). Pretreatment with nicotinamide also prevented STZ induced increases in glutathione S-transferase activity when compared to the control(p<0.05). These results suggest that nicotinamide pretreatment suppresses STZ-induced changes in the hepatic metabolizing enzyme system.

삼채 추출물의 인슐린 저항성 개선 효과 및 기전 탐색

김지수(Ji-Soo Kim),허진선(Jin-Sun Heo),최종원(Jong-Won Choi),김군도(Gun-Do Kim),손기호(Kie-Ho Sohn) 한국생명과학회 2015 생명과학회지 Vol.25 No.10

본 연구는 우리나라에서 재배한 삼채 추출물의 주요생리활성 물질을 2형 당뇨 쥐에 투여하였을 때 인슐린 저항성 개선효과와 췌장에서 β-cell의 형태 및 간 조직의 2형 당뇨 관련 단백질의 발현을 확인 함으로써 그 메카니즘을 확인코자 하였다. 특히 TZDS당뇨약 계열로 현재 시판중인 actoz와 활성을 비교 함으로써 그 유효성 정도를 살펴보고자 본 실험을 디자인하였다. 먼저 식이섭취량, 물 섭취량의 경우, Control군은 2형 당뇨 특징인 다식, 다뇨, 다갈의 형태로 증가하였으나, 삼채 추출물 투여로 식이 및 물 섭취량이 감소하는 경향을 보였다. 식이 투여 2시간 후 혈당변화와 OGTT 검사결과, 2형 당뇨인 Control군에서 혈당의 농도가 가장 높았으나 삼채 추출물 8주 경구 투여로 인해 안정화되는 것을 확인할 수 있었으며, serum의 glucose농도 또한 삼채 추출물 투여로 2형당뇨 control군에 비해 혈당이 감소한 것을 확인할 수 있었다. HbA1c (당화혈색소)는 2형 당뇨군(control)에서 9% 수치 범위로 고혈당 범위였으나, 삼채 추출물 섭취로 인하여 Positive control군(actoz 투여군) 7% 수준으로 감소하는 경향을 확인할 수 있었으며, insulin농도는 2형 당뇨인 Control군에서 insulin 농도가 1 ng/ml로 가장 낮은 농도였으며, 삼채 추출물 및 SAC 1.5 ng/ml수준으로 insulin수치가 상승하는 것을 확인할 수 있었다. 혈중 triglyceride, total cholesterol 및 LDL-cholesterol 수치 모두 시료 투여군에서 혈중 지질관련 인자의 농도가 감소하는 것을 확인할 수 있었으며, 특히 AH 400군의 경우 triglyceride, total cholesterol 및 LDL-cholesterol 농도가 각각 482.86±13.40 mg/dl, 163.56±13.24 mg/dl, 142.04±3.24 mg/dl로 대조군에 비해 약 50% 감소한 결과를 나타내었다. 간장 조직 중 지질 과산화의 함량의 경우, 2형 당뇨인 Control군에서 467.74±1.12 MDA nmole/g of tissue로 삼채 추출물 투여(AH 400)로 319.61±26.98 MDA nmole/g of tissue 로 Normal군과 비슷한 수준으로 혈중 lipid peroxide의 함량이 감소하는 것을 확인할 수 있었다. 간장조직을 H&E염색한 결과, Normal군에 비하여 2형 당뇨인 Control군의 간 조직에서 많은 지방적이 나타나 지방간이 확인되었으나, Positive control 및 삼채 추출물 투여에 의해 지방적의 크기와 수가 많이 줄어드는 결과를 얻어 조직학적 검사상 지방간의 소견이 현저히 호전되었으며, 췌장에서 insulin 면역화학 염색 결과 2형 당뇨로 췌도 세포가 거의 손상된 것과는 대조적으로, 삼채 추출물을 투여한 결과 정상군과 유사한 형태의 췌도 세포가 확인되었으며 췌도 세포의 형태가 다양한 정도의 과 형성을 보이는 것이 확인되었다. 또한 간장 조직의 PPARγ, PDK4, SREBP-1, FOX0 1의 발현을 확인한 결과, 발현이 2형 당뇨인 Control군에서 모두 발현이 증가하였으나, 삼채 추출물 투여로 인해 발현 정도가 낮게 나타나 앞서 확인하였던 glucose 및 HbA1c 및 insulin농도의 결과와 상통함을 확인하였다. 이들의 결과로 미루어 볼 때, 삼채 메탄올 추출물의 8주간 경구 투여로 인하여 2형 당뇨에 관여하는 PPARγ 단백질 및 비만 관련 단백질 인자를 조절하였으며, insulin농도 및 식후 혈당조절에도 도움을 주는 것을 확인할 수 있었다. 또한, 췌장의 insulin 면역화학염색 결과, 췌도 세포 형태 및 insulin 합성에도 긍정적인 역할을 하는 것으로 미루어 보아 2형 당뇨에 대한 치료효과가 큰 것으로 사료 된다. Diabetes has been one of major health risks in industrialized countries. Allium hookeri is a wild herb distributed in India and Myanmar. The root of the plant has been used as food and medicine in Southeast Asia. We investigated Allium hookeri extract improves type 2 diabetes mellitus in C57BL/KSJ db/db obese mouse. C57BL/KSJ db/db obese mouse arise out of Type 2 diabetes and we treated Allium hookeri methanol extract 400 mg/kg (AH 400), 800 mg/kg (AH 800), positive control group (thiazolidinedine;TZDs) were administered orally for 8weeks. AH treated group normalized lipid enzyme system (triglyceride, total cholesterol, HDL-cholesterol and LDL-cholesterol) and serum glucose, HbA1c and plasma insulin level. AH treated group recovered β-cell damage by hyperglycemia and fatty liver disease. AH treated group significantly up regulated expression of Peroxisome proliferatoractivated receptor gamma (PPAR-γ), pyruvate dehydrogenase kinase4 (PDK4), Sterol regulatory element-binding protein 1c (SREBP 1) and fork head box O1 (FOX 01) proteins in C57BL/KSJ db/db obese mouse liver. And we found that AH treated group decreased hepatic malondialdehyde formation in C57BL/KSJ db/db obese mouse liver. These results indicate that Allium hookeri methanol extract might be a potential anti-diabetic agent and could be useful in the treatment of type 2 diabetes mellitus.

무균조제 항암제 취급의 안전관리

이수미(Su Mi Lee),정선영(Seon Young Chung),임현정(Hyun Jeong Im),박효정(Hyo Jung Park),이수연(Su Yun Lee),전은용(Eun Yong Jeon),손기호(Kie Ho Sohn) 대한약학회 2011 약학회지 Vol.55 No.2

Most antineoplastic agents are nonselective in their mechanism of action, affecting noncancerous as well as cancerous cells, and resulting in acute effects such as irritation of mucous membranes and chronic effects such as genotoxicity, teratogenicity, and carcinogenicity. Healthcare workers occupationally exposed to antineoplastic agents are at risk. The present study aimed to develop and apply methods to monitor occupational exposure to antineoplastic agents, using cyclophosphamide (CP) as the model compound. To monitor environmental and biological exposure, potentially contaminated surfaces were wiped and 24 hour urine samples were collected from workers. Liquid chromatography combined with tandem mass spectrometry was performed, with a limit of detection of 0.05 ng/ml. Measurable amounts of CP were detected on 92% of the sampled surfaces, with a geometric mean of 175.22 ng/m2. Despite the environmental contamination of the model compound, CP was below the detection limit in all urine samples. If workplace contamination cannot be completely avoided, it is importance to reduce exposure to the lowest possible levels. To this aim, efforts to minimize occupational exposure along with biological and environmental monitoring are required. The standardized sampling techniques, and specific and sensitive analytical methods reported in this study may be helpful in assessing occupational exposure and devising strategies to reduce exposure.

한국 소아 기관지 천식 환아에서 연령에 따른 Theophylline 의 대사 변화에 관한 연구

이희정(Hee Jeong Lee),조혜영(Hye Young Cho),윤운기(Un Ki Youn),오지섭(Ji Sub Oh),류환선(Hwan Seon Ryu),손기호(Kie Ho Sohn),(Charles D . Sands) 대한소아알레르기호흡기학회(구 대한소아알레르기 및 호흡기학회) 1995 소아알레르기 및 호흡기학회지 Vol.5 No.1

N/A Theophylline is widely used in Korean pediatric patients in the treatment of asthma. To achieve adequate bronchodilation and avoid side effects , it is generally accepted that the serum theophylline concentration should be maintained between 10 and 20mcg/ml . Concentrations greater than 20mcg/ml are associated with an increased incidence of toxicity . Clinical effectiveness and toxicity are clearly related to understand factors which might altel theophylline pharmacokinetics . Age has been reported as a factor which might alter theophylline clearance. Thus we studied 287 asthmatic children who were admitted to our hospital and received intravenous aminophylline and oral theophylline. The average total clearance of theophylline was 30.00ml/kg/h in the infants under 6 months old and 53.14ml/kg/h in the infants between the age of 6 and 12 months . The average total clearance of theophylline was significantly increased in infants above 6 months old(p<0.001) . The average total clearance of theophylline of the children aged between 1 to 12 years was 65.77ml/kg/h and no significant difference according to age was noticed in this group . These suggest that age may be a factor which affects clearance of theophylline under 12 months old .

소아 기관지 천식 환아에서 Prednisolone 이 Theophylline 의 대사에 미치는 영향에 관한 연구

정혜영(Hyea Yeong Chung),이희정(Hee Jung Lee),윤운기(Un Ki Youn),오지섭(Ji Sub Oh),류환선(Hwan Seon Ryu),손기호(Kie Ho Sohn),(Charies D . Sands) 대한소아알레르기호흡기학회(구 대한소아알레르기 및 호흡기학회) 1993 소아알레르기 및 호흡기학회지 Vol.3 No.1

N/A Theophylline is widely used in pediatric patients for the treatment of asthma and neonatal apnea. To achieve adequate bronchodilation and avoid toxicity, it is generally accepted that the serum theophylline concentration should be maintained between 10 and 20㎍/ml. Concentrations greater than 20㎍/ml are associated with an increased incidence of toxicity. Clinical effectiveness and toxicity are clearly related to the serum concentrations. Thus, it is important to understand factors which might alter theophylline pharmacokinetics. Prednisolone has been reported to both increase and decrease theophylline serum concentrations. Clinical experience at our hospital (one case) suggested that there might be an interaction between prednisolone and theophylline that can potentially results in clinically significant changes in theophylline serum concentrations. Thus, we studied eleven asthmatic children, who were admitted to our hospital and received oral sustained release theophylline and prednisolone. The mean serum theophylline concentration of single therapy group (phase 1) was 8.10㎍/ml and of concomitant administered prednisolone group (phase 2) was 8.39㎍/ml. On basis of serum theophylline concentrations, we had taken the volume of distribution (Vd), half life (t1/2) and calculated clearance (Cl), in each of phase 1 and 2. The mean clearance of phase 1 was 67.37ml/㎏/hr and of phase 2 was 67.85ml/㎏/hr. The difference between mean serum theophylline concentration and clearance in the single therapy group (phase 1) compared with concomitant administered prednisolone therapy group (phase 2) was not statistically significant. (p>0.05) This suggests that prednisolone does not affect the metabolism of theophylline and does not alter serum concentration of theophylline.

Stability of Glutamine-Suppiemented Total Parenteral Nutrition

조민희 ( Min Hee Cho ),김선미 ( Sun Mi Kim ),이은경 ( Eun Kyung Lee ),민명숙 ( Myung Sook Min ),인용원 ( Yong Won In ),손기호 ( Kie Ho Sohn ),최경업 ( Kyung Eob Choi ),최윤식 ( Yun Sik Choi ),( Jeong Meen Seo ) 한국정맥경장영양학회 2004 한국정맥경장영양학회 학술대회집 Vol.2004 No.-

정맥영양요법을 시행한 조혈모세포이식 소아의 재원기간에 영향을 미치는 인자

박효정 ( Hyo Jung Park ),윤정아 ( Jung A Yoon ),김도영 ( Do Young Kim ),허윤정 ( Yoon Jung Huh ),정선영 ( Seon Young Chung ),인용원 ( Yong Won In ),이영미 ( Young Mee Lee ),서정민 ( Jeong Meen Seo ),손기호 ( Kie Ho Sohn ) 한국정맥경장영양학회 2011 한국정맥경장영양학회지 Vol.4 No.1

Purpose: Parenteral nutrition (PN) is a standard supportive care for pediatric patients undergoing hematopoietic stem cell transplantation (HSCT) in Samsung Medical Center. The objective of this study was to identify the factors associated with the length of hospital stay (LOS) in pediatric HSCT patients administrating PN routinely. Methods: This was a retrospective study for 128 pediatric HSCT patients from Aug. 2008 to Dec. 2009. Demographics, nutrition status on the first report in the nutrition support team, calories and nutrients supplied, PN duration, LOS, PN-induced complications, and laboratory data were collected from electronic medical records. Multivariate analyses were conducted to identify factors associated with LOS. Results: The median age of registered patients was 70 months (range 6∼239 months). Twenty-three patients (18.0%) were malnourished moderately to severely when PN was started. Number of autologous HSCT was larger than allogeneic HSCT (87 vs 41). In children undergoing HSCT, LOS was significantly correlated with PN duration (P<0.001) and graft type (P<0.001). Especially, in autologous peripheral blood stem cell transplantation (PBSCT), malnourished patients at the beginning of PN were shown the tendency to increase LOS (P=0.024) and PN duration (P=0.043). Conclusion: In pediatric HSCT patients administrating PN routinely, LOS was associated with a graft type of HSCT and PN duration. Especially for autologous PBSCT patients, the nutrition status at the beginning of PN had the influence on LOS and PN duration. During the peri-HSCT period, careful nutrition monitoring can prevent malnutrition, decrease PN duration, and shorten LOS. (JKSPEN 2011;4(1):1-6)

지방식이가 Rat 간 Epoxide Hydrolase 활성에 미치는 영향

김은주,손기호,최종원 慶星大學校 環境問題硏究所 1991 環境硏報 Vol.1 No.1

간 microsomal epoxide hydrolase 활성과 bromobenzene에 의해 유도된 간 독성에 미치는 지방식이의 영향에 대한 실험을 통하여 다음과 같은 결과를 얻었다. 간 microsomal cytochrome p-450 및 aniline hydroxylase 활성에 지방식이 (20%)를 섭취케 한 군에서는 본 효소의 활성이 다소 증가되었으나 bromobenzene을 동시에 투여함으로 두 효소의 활성이 유의성 있게 증가되었다. Bromobenzene 단독 투여에서는 두 효소의 활성에 별다른 영향이 없었다. Epoxide hydrolase 활성에서는 bromobenzene 투여로서 감소 되었으며 지방식이를 섭취게 하고 bromobenzene을 투여함으로 bromobenzene 단독 투여보다 약 25% 현저하게 감소하였다. 지방식이를 섭취게 하고 bromobenzene을 투여한 군에서의 간 손상의 지표를 생화학적 측면(s-AST,sALT) 및 간 조직의 과산화 지질 함량에 미치는 영향에서 bromobenzene 단독 투여보다 지방식이를 섭취케 하고 bromobenzene을 투여함으로 현저하게 증가되었다. We have the mecdied the mechanism by examining the effect of fat diet on the epoxide hydrolase activity and bromobenzene-induced hepatotoxicity. Activities of anivities of aniline hydroxylase and cytochrome p-450 as epoxide generating enzymes were singificantly increased by the treatment with fat diet and bromobenzene treatment with fat diet and bromobenzene decreased show any changes on the activities of the epoxide scavenging enzyme such as epoxide hydrolase Furthermore, fat diet elevated against bromobenzene-inducible hepatotoxicity in rats as evidenced by the increased formation of lipid peroxidation, highered serum alanine and aspartate aminotrnsferase activities. Therfore, it can be concluded that the mechanism for the observed elevative effect of fat diet against bromobenzene-induced hepatotoxicity was due to the inhibition of epoxide hydrolase which related with metabolism of these materials.