한국의 당뇨병성 신증 및 대혈관 합병증의 발생에서 Angiotensin Converting Enzyme Gene 과 Plasminogen Activator Inhibitor-1 Gene Polymorphism 에 관한 연구

윤종우(Jong Woo Yoon),조상경(Sang Kyung Jo),한상엽(Sang Yup Han),차대룡(Dae Ryong Cha),조원용(Won Yong Cho),김형규(Hyung Kyu Kim) 대한신장학회 2001 Kidney Research and Clinical Practice Vol.20 No.4

Background: Although development of DM nephropathy in NIDDM patients is associated with poorly controlled blood sugar level and hypertension, relationship of genetic factor is also emphasized. Recent studies showed that an insertion or deletion (I/D) polymorphism in the ACE gene and a 4/5- guanine tract polymorphism in the promotor region of the PAI-1 gene are associated with the myocardial infarction. The aim of this study were to determine the relationships of these polymorphism and substance activities to DM nephropathy and macroangiopathy. Methods 72 NIDDM patients who suffered from DM more than 6 years and 62 non-diabetic healthy control were evaluated. After extraction of DNA from peripheral blood, ACE and PAI-1 gene polymorphisrns were determined by polymerase chain reaction, SSCP electrophoresis and silver stain. Serum PAI-1 level was dctected by Immulyse PAI-1 ELISA kit(Bipool Sweden). Results: Total 134 samples were evaluated and ACE genotype were DD 27(20%), ID 88(66%), and II 19(14%). PAI-1 genotype were 4G4G 26(19%), 4G5G 73(55%), and 4G5G 35(26%). The distribution of ACE and PAI-1 polymorphism according to presence or absence of nephropathy were DD 10, ID 32, II 8, 4G4G 9, 4G5G 31, and 5G5G 10 in DM nephropathy group and DD 3, ID 17, II 2, 4G4G 5, 4G5G 12, and 5G5G 5 in non-nephropathy group. There were no significant differences in the distribution of ACE and PAI-1 gene between the two groups. The distribution of ACE and PAI-1 polymorphism according to macroangiopathy were DD 6, ID 16, II 3, 4G4G 5, 4G5G 15, and 5G5G 5 in macroangiopathy group and DD 7, ID 33, II 7, 4G4G 9, 4G5G 28, and 5(;5(i 10 in non-macroangiopathy group. There were no significant differences in the distribution of ACE and PAI- 1 gene between macroangiopathy and non-macroangiopathy groups. Serum PAI-1 level according to PAI-1 gene and ACE gene polymorphism were 4G4G 47.9919.73, 4G5G 40.1918.49, 5G5G 40.37±20.99ng/mL, DD 37.99±16.64, ID 44.80 20.:35, and II:31.92 12.% and had a tendency that is higher in 4G4G genotype. Conclusion: From the above results, we cannot define the relationships of ACE and PAI-1 gene polymorphism and PAI-1 activities to DM nephropathy and macrovascular complications of NIDDh1 patients, but prospective studies including more patients population will be required.

여성 무기수형자의 특성에 대한 기초적 연구 - 범죄특성, 수용생활과 가족접촉을 중심으로 -

윤옥경(Okkyung Yoon),윤종우(Jong-Woo Yoon) 한국가족학회 2005 가족과 문화 Vol.17 No.2

이 연구는 여성무기수형자들의 범죄특성과 수용생활의 특성, 그리고 수용생활 중 가족과의 접촉실태를 알아보고자 하였다. 이를 위해 청주교도소에 수감되어 있는 무기수형자 34명을 대상으로 설문조사를 하였으며 이 중 7명을 선정하여 심층면접을 시행하였다. 여성무기수형자의 대부분은 가족 살인의 범주에 속하는 범죄행위로 무기형을 선고받거나, 사형을 선고받은 후 무기로 감형되어 생활하고 있는 이들이다. 이들의 구금생활은 초기에는 상당한 고통을 감수해야 하지만 차차 적응을 하게 되면서 단기수보다 오히려 순응적이고 모범적인 생활을 하는 경향을 보인다. 물론 이것은 무기수형자 대부분이 전과가 없고, 따라서 범죄성향이 없는 이유도 있겠으나, 그것보다는 시설 내 교정처우의 완화기준이 수용생활을 얼마나 잘하고 있느냐에 달려 있으므로 처우개선의 기회를 위해 노력하는 것으로 이해될 수 있다. 왜냐하면 무기수형자의 지위 상, 처우 중 제한받는 것이 많으며, 가족과의 관계유지를 위한 전화통화, 가족접견, 가족만남의 집, 귀휴의 기회 등이 모두 그 처우의 내용에 포함되어 있기 때문이다. 무기수형자들은 일반적인 인식과는 달리 가족과의 접촉이 이어지고 있었지만, 어린 자녀들이 있는 경우에는 자녀와의 관계가 단절되는 사례들도 있었다. 여성무기수형자들이 가장 바라는 것도 가족과의 접촉을 더 자주 할 수 있는 프로그램의 시행이었다. 이런 결과를 볼 때 무기수형자들의 수용생활의 안정에 가족과의 관계유지가 주는 긍정적인 역할을 생각해 무기수라는 이유로 가족과의 접촉을 제한 할 것이 아니라 더 확대하는 것이 필요하다 점을 제안하였다. This article aimed at describing who the female life-time prisoners are, why they were locked up in prison for a long time, and how they managed their prison life, focusing on their relationship with family. To meet these aims, a total of 34 female life-timers was surveyed and 7 out of 34 women prisoners were interviewed. Based on the survey and interview results, it was found that 1) most of these female life-timers were convicted with intra-familial homicide, especially killing their husbands. They committed spouse murder with a male partner and this fact seemed to play a role to increase their sentence length in court. In this process, double standard of sexual norms was borrowed to validate harsh punishment for female murderer. 2) Female life-timers struggled to adjust prison environment at first, but gradually turned to the 'model' prisoners. Things that made them "good" prisoners were in some sense related to their desires to get more contacts with family members-family visits, furlough, telephone use etc. Even though some life-time prisoners kept contact with their children and other family members, still many other prisoners wanted to have the opportunities. Based on the fact that family connection and committment are the most important factor in rehabilitating criminals, we should think how to preserve family relationship between criminals behind the walls and their children and relatives outside world. And life-time prisouers should not be excluded from the effort to strengthen the relationship between inmater and their family members.

급성 허혈성 신손상 백서에서 α-melanocyte stimulating hormone이 intercellular adhesion molecule-1의 발현 및 신기능에 미치는 영향에 관한 연구

조상경(Sang Kyung Jo),윤종우(Jong Woo Yoon),차대룡(Dae Ryong Cha),조원용(Won Yong Cho),김형규(Hyoung Kyu Kim),원남희(Nam Hee Won),윤수영(Soo Young Yoon),장경현(Kyung Hyun Chang) 대한내과학회 2000 대한내과학회지 Vol.59 No.6

N/A Background : Acute renal failure is a reversible process in majority of cases but mechanisms of renal injury or recovery are poorly understood. Recently neutrophil infiltration is reported to potentiate inflammatory and cytotoxic cascade in ischemic renal injury and α-melanocyte stimulating hormone has been reported to have a potent anti-inflammatory properties in a variety of animal models. We examined the beneficial effects of α-MSH in acute ischemic renal injury in rats and tried to clarify its action mechanism. Methods : After unilateral nephrectomy, renal artery of contralateral kidney was clamped for 40 minutes and reperfused in female Sprague-Dawley rats. α-MSH (50μg) and vehicle was injected intraperitoneally immediately after and 6, 24 hours after reperfusion. Biochemical, histological data, ICAM-1 mRNA, protein expressions and polymorphonuclear cell infiltration were examined. Results : α-MSH significantly attenuated the renal injury, measured by plasma BUN and creatinine level and also the degree of severity of histological injury (BUN 125.2±14.6 mg/dL : 46±19.6 mg/dL (p=0.004), creatinine 3.65±0.81 mg/dL : 1.47±0.5 mg/dL (p=0.005) at 24 hours after reperfusion, BUN 88±12.5 mg/dL : 25.5±15.8mg/dl (p=0.002), creatinine 2.76±0.5 mg/dL : 0.93±0.2 mg/dL (p=0.002) at 72 hours after reperfusion and 5.4±1.94/ 2.6±0.77 (p=0.006) at 24 hours after reperfusion in histilogical grading system). In the α-MSH treated groups, ICAM-1 mRNA expression decreased significantly compared to the vehicle treated ischemic group in 72 hours after reperfusion (0.49±0.01/0.31±0.2, p<0.008). ICAM-1 protein expression also decreased in α-MSH treated group, but it was not statistically significant. Polymorphonuclear cell infiltration showed a significant decrease in the α-MSH treated group at 24 hours after reperfusion (5.05±1.8/1.59±0.4, p=0.009). Conclusion : α-MSH attenuates ischemic renal injury by inhibiting the expression of ICAM-1 and subsequent polymorphonuclear cell infiltration. These results provide a rationale of α-MSH as a potential therapeutic drug in acute renal failure.(Korean J Med 59:641-650, 2000)

유지 혈액투석환자에서의 우울증 발생의 위험인자 및 우울증이 영양지표에 미치는 영향

김진철(Jin Cheol Kim),조성태(Sung Tae Jo),윤종우(Jong Yoo Yoon),김근호(Gheun Ho Kim),전노원(Rho Won Jeon),김형직(Hyung Jig Kim),채동완(Dong Wan Chae),노정우(Jung Woo Noh),손봉기(Bong Ki Son),구자룡(Ja Roung Koo) 대한내과학회 2002 대한내과학회지 Vol.62 No.1

N/A Background: Depression is common in chronic renal failure patients and usually associated with poor appetite. Malnutrition with poor appetite is known to be associated with increased mortality in chronic hemodialysis (HD) patients. So we evaluated the prevalence, risk factors of depression and effects of depression to nutritional status in chronic HD patients. Methods: Sixty two HD patients (age 48.8±11.1 years, diabetes 29%) were investigated. Each patients were interviewed and completed the Beck depression inventory (BDI, 21 items, 0-3 point). To exclude the possible confounding effects of illness and treatment symptoms, cognitive depression index (CDI, a cognitive subset of 15 items selected from BDI) was used as a measure of depression. KT/V and nutritional parameters such as serum albumin, normalized protein catabolic rate (nPCR), subjective global assesment (SGA), body mass index (BMI), triceps skinfold thickness (TSF) and midarm muscle circumference (MAMC) were also measured. Results: Corrected BDI score (CDI score multiplied by 21/15) was 24.9±12.7 and the prevalence of depression (corrected BDI score≥21) was 64.5%. DM patient s had higher CDI score than non DM patient (22.9±7.2 vs 15.6±9.0). In univariate analysis, CDI score was correlated with age (r =0.39, p <0.01), serum albumin (r =- 0.37, p <0.005), nPCR (r =- 0.30, p <0.05), SGA (r =- 0.42, p <0.05), BMI (r =- 0.28, p <0.05), TSF (r =- 0.41, p <0.05) and MAMC (r =- 0.50, p <0.01). In multivariate analysis, CDI score was the strongest correlate of nPCR, SGA, BMI, TSF and MAMC. But KT/V, hematocrit, erythropoietin usage, plasma bicarbonate, serum parathyroid hormone, c-reactive protein concentration and HD duration had no relationship with CDI score. Conclusion: The prevalence of depression in chronic HD patients was high. Diabetes and old age were import ant risk factors for depression. It was also concluded that severity of depression was correlated with markers of malnutrition and depression could be a independent risk factors of malnutrition in chronic HD patients.(Korean J Med 62:77-82, 2002)

싸이클로포린에 의한 흰쥐 신손상에서 아포토시스의 역할

이영호(Young Ho Lee),김난희(Nam Hee Kim),윤종우(Jong Woo Yoon),이영기(Young Ki Lee),조상경(Sang Kyung Jo),김용섭(Yong Sup Kim),차대룡(Dae Ryong Cha),조원용(Won Yong Cho),김애리(Ae Ree Kim),원남희(Nam Hee Won),구자룡(Ja Ryong Ku),김형규( 대한내과학회 1997 대한내과학회지 Vol.52 No.6

N/A Objectives: Apoptosis is a physiologic or programmed cell death in contrast with necrotic cell death. Recently it has been known that apoptosis are concerned in the effects of chemotherapeutic agents or radiation therapy on tumor cells. Cyclosporine a(CsA), a potent immunosuppressant, has been effectively used in organ transplantaion, but it also has a significant toxicity in the kidneys. However the exact mechanism of CsA nephrotoxicity has not been ellucidated yet. This study was performed to investigate whether apoptosis particiates in CsA nephrotoxicity or not. Methods: Twenty seven Sprague-Dawley rats were divided into 5 groups. 1) Vehicle group(n=7) as a control: Cremopbor 50mg/kg/day/subcutaneously (sc) for 7 days, 2) CsA4 groupin=5): CsA 50mg/kg/ day/sc for 4 days, 3) CsA7 group(n=5): CsA 50mg/ kg/day/sc for 7 days, 4) R4 group(n=5): 4 days after CsA 50mg/kg/day/se for 7 days, and 5) R8 group (n=5): 8 days after CsA 50mg/kg/day/sc for 6 days, Biochemical parameters including blood pressure were measured in each group and the cell count of apoptosis in rat kidney was evaluated by in situ end labelling(ISEL) method. Results: 1) The increase of serum creatinine, blood pressure and decrease of creatinine clearance appeared in CsA4 and CsA7 groups. 2) The ce11 counts of apoptosis on tubular cells in CsA4 and CsA7 groups were significantly increased more than in control group(79.0±16.9, 98.4±11.4 vs 35.4±8.8, p<0.05), and the cell counts of apoptosis on tubular cells in R4 and R8 groups were not significantly different from that in control group(53.8±12.5, 65.2±7.1 vs 35.4±8.8, p>0.05), 3) The cell count of apoptosis on the interstitium in each group was not significantly different from that in control group(p>0.05). 4) The cell count of apaptosis on tubular cells was increased more than that on the interstitium in all groups. 5) The cell count of apoptosis on cortex only in CsA7 group was significantly increased more than that io control group(57.8±11.5 vs 21.8±2.6, p<0.05), 6) The cell count of apoptosis on medulla only in CsA4 group was significantly increased more than that in control group(636. ±17.9 vs 22.6±9.7, p<0.05). 7) Total cell counts of apoptosis only in CsA4 and CsA7 groups were significantly increased more than in contral group(96.0±21.1, 99.8±11.8 vs 46.6±11.4, p<0.05). Conclusion: CsA caused apoptosis mainly on tubular cells rather than the interstitial cells and apoptotic cells in CsA nephrotoxicity were not in- creased during the recovery phase. With the results apoptosis may play an important role in CsA nephrotoxicity.

혈액투석 : 지속적 정정맥 여과술에서 헤파린과 생리식염수 주사 및 Nafamostat mesilate의 항응고 효과에 대한 전향적 비교 연구

박인일 ( In Il Park ),구자룡 ( Ja Ryong Koo ),윤종우 ( Jong Woo Yoon ),김수진 ( Soo Jin Kim ),송영수 ( Young Soo Song ),박태진 ( Tae Jin Park ),서장원 ( Jang Won Seo ),오지은 ( Ji Eun Oh ),이영기 ( Young Ki Lee ),김성균 ( Seong Gy 대한신장학회 2008 춘계학술대회 초록집 Vol.28 No.1

출혈 위험성이 있는 환자에서 지속적 정정맥 여과술 시행 시 생리식염수 주사와 nafamostat mesilate의 항응고 효과의 전향적 비교 연구

박인일 ( In Il Park ),최명진 ( Myung Jin Choi ),윤종우 ( Jong Woo Yoon ),오지은 ( Ji Eun Oh ),서장원 ( Jang Won Seo ),김성균 ( Sung Gyun Kim ),이영기 ( Young Ki Lee ),김형직 ( Hyung Jik Kim ),노정우 ( Jung Woo Noh ),구자룡 ( Ja Ry 대한신장학회 2009 Kidney Research and Clinical Practice Vol.28 No.3

목적: 출혈의 위험성이 있는 급성 신부전 환자에서 CVVH 치료 시 항응고 요법으로 생리 식염수 주사가 주로 사용되어 왔으나 필터의 응고를 증가시킬 수 있으며 응고장애 유무에 따라 항응고제의 효과가 다를 수 있어 그 효과가 제한적이다. 이에 비해 국소 항응고제인 nafamostat mesilate 주사는 짧은 반감기로 인해 혈액투석 환자에서 효과적이고 안전한 항응고제로 보고되고 있다. 이에 저자들은 CVVH 치료 시 혈액응고 장애 유무에 따른 nafamostat mesilate의 항응고 효과를 생리식염수 항응고 요법과 전향적으로 비교하고자 하였다. 방법: CVVH를 필요로 하는 환자들 중 (1) 수술 직전 및 직후, 뇌출혈, 위장관 출혈 등이 동반되어 항응고제로 헤파린을 사용할 수 없거나 (2) 검사실 검사상 응고 장애의 기준인 INR>2 혹은 aPTT>60 sec, 혈소판<50,000/mm3 중 한 개 이상이 존재 하는 43명의 환자들을 각각 생리식염수 주사군 (n=23)과 nafamostat mesilate 주사군 (n=20)으로 나누어 필터의 평균 사용시간으로 의 항응고 효과를 비교하였다. 결과: 필터의 평균 사용 시간은 nafamostat mesilate 군에서 생리식염수 군에 비해 12 시간 정도 유의하게 증가되었으며 (28.73±12.67 versus 16.34±7.86, p=0.001) 이러한 효과는 응고장애 존재 유무와 무관하게 지속되었다. 치료 기간 동안 양군 모두에서 임상적으로 유의한 출혈 합병증은 발생하지 않았다. 결론: Nafamostat mesilate는 CVVH를 필요로 하면서 출혈 위험성이 있는 급성 신부전 환자들에게서 응고 장애 유무와 상관없이 사용될 수 있는 효과적이고 안전한 항응고제로 생각 된다. Purpose: In patients with a higherrisk of bleeding, performing CVVH with heparin or saline anticoagulation is associated with increased bleeding or thrombotic risk. Nafamostat mesilate (NM), a serine proteinase inhibitor, while inhibiting various clotting factors in filter circuit, is characterized by short half life resulting in little systemic anticoagulation effect. Accordingly, we prospectively evaluated the anticoagulant effect and safety of NM in patients with a higher risk of bleeding who underwent CVVH. Methods: Among 43 patients with high risk of bleeding [defined by (1) INR>2, aPTT>20 sec, platelet<50,000/mm3 or (2) ongoing bleeding, major hemorrhage/surgery in the last 48 hrs], 20 patients were treated with continuous nafamostat mesilate infusion (10-20 mg/hr) and remaining 23 patients were treated with saline bolus infusion (100 mLq 1 hr) for CVVH anticoagulation. Results: As compared with saline bolus group, mean circuit life was significantly longer in NM infusion group (28.73±12.67 versus 16.34±7.86, p=0.001). There was no significant bleeding complication in either saline bolus or NMinfusion group. In subgroup analysis according to the presence of abnormal coagulation status (defined by INR>2, aPTT>20 sec, platelet<50,000/mm3), the positive effect of NM on circuit lifespan persisted irrespective of the coagulation status. Conclusion: As compared with saline bolus, nafamostat mesilate infusion was associated with higher CVVH filter life. In patients with high risk of bleeding, nafamostat mesilate can be used as a safe and effective anticoagulant for CVVH with acceptable filter life.

혈액투석 개수 후 단핵구배양 상청액에 의한 사람 근위 세뇨관 상피세포의 Fas 유전자 발현에 대한 연구

차대룡(Dae Ryong Cha),조원용(Won Yong Cho),윤종우(Jong Woo Yoon),조상경(Sang Kyung Jo),김형규(Hyung Kyu Kim),장경현(Kyung Hyun Chang) 대한신장학회 2000 Kidney Research and Clinical Practice Vol.19 No.3

N/A Residual renal function rapidly declines after the initiation of hemodialysis and its mechanisms are supposed to be associated with frequent hypotensive episodes during hemodialysis and subsequent ischemic injury to remnant nephron, but blood-membrane interaction might play an important role because of its ability to activate complement system and other various humoral and cellular mechanisms. Blood monocytes are activated by complements, bacterial conta- minants and activated monocytes are known to secrete multiple proinflammatory cytokines such as TNF-α, IL-1β. The expression of TNF-αand IL-1β in mRNA and protein level were examined by RT-PCR and ELISA respectively in patients with ESRD after the initiation of hemodialysis. Author also investigated the mRNA expression of Fas in human proximal tubular cell culture in the presence of TNF-a and PBMC culture supernatant before and after the ini-tiation of hemodialysis. Compared to PBMC separated before the initiation of HD, the amount of cytokine mRNA from PBMC separated after the initiation of HD showed increased tendency from 0.97±0.2 to 1.12±0.28 for TNF-α(p=0.29), from 1.03±0.18 to 1.10±027 for IL-1β (p=0.54). TNF-αand IL-lβ protein level in PBMC culture supernatant also showed increased tendency from 2.25±0.5 to 4.254±3.77 for TNF- α(p=0.10), from 3.5±2.08 to 4.0±4.3 for IL-1β(p=0,25). TNF-a in-creased Fas mRNA expression dose-dependently com-pared to control but it was not stat.istically significant(p=0,37, 0.22). Compared to the the level of Fas expression in HPTC cultured in the presence of pre HD PBMC supernatant, the level of Fas expression increased significantly in the presence of post HD PBMC supernatant(0.64±057 vs 1.05±0.12, p=0.01). As a conclusion, cytokine gene expression and secretion can increase as a result of blood-membrane interaction and these might have some influence on the loss of residual renal function in CRF patients maintained on hemodialysis.

Vflo™ 모형의 초기함수조건에 따른 유출 해석

김진성(Kim Jin Sung),김원일(Kim Won il),윤종우(Yoon Jong Woo),안원식(Ahn Won Sik) 대한토목학회 2007 대한토목학회 학술대회 Vol.2007 No.10

Sulodexide 유발 고칼륨 혈증: 증례 보고

박인일 ( In Il Park ),최명진 ( Myung Jin Choi ),윤종우 ( Jong Woo Yoon ),김수진 ( Soo Jin Kim ),박태진 ( Tae Jin Park ),송영수 ( Young Soo Song ),이영기 ( Young Ki Lee ),김형직 ( Hyung Jik Kim ),노정우 ( Jung Woo Noh ),구자룡 ( Ja 대한신장학회 2009 Kidney Research and Clinical Practice Vol.28 No.3

Sulodexide is composed of two glycosaminoglycans (fast-moving heparin 80%, dermatan sulfate 20%) that are capable of preventing diabetic nephropathy by correcting abnormal glycosaminoglycan metabolism. Considering heparin-like propertyof sulodexide, side effect profiles of sulodexide are expected to be similar with those of heparin. Among those side effects, we remarked on heparin-induced hyperkalemia and hereby report a case of severe hyperkalemia during the use of sulodexide. A 52-year-old man with diabetic nephroapthy and hypertension was admitted to our hospital because of severe hyperkalemia up to 7.5 meq/L. His clinical condition was stable and medications including losartan and furosemide had not been changed for last 6 months except the addition of sulodexide, which was started 30 days prior to admission. Despite intensive use of Kayexalate and immediate discontinuation of losartan, hyperkalemia aggravated up to 8.0 meq/L. After recognition of possible sulodexide-induced hyperkalemia, sulodexide was discontinued, which resulted in rapid correction of hyperkalemia. In view of the above discussed clinical consideration, we suspect sulodexide as a major cause of hyperkalmia and report this case with a review of literature.