고혈압환자에서 도플러 심초음파를 이용한 좌우심실 이완기능에 관한 연구

강덕희(Duk Hee Kang),신길자(Gil Ja Shin) 대한내과학회 1993 대한내과학회지 Vol.45 No.3

N/A Background: It is well known that the diastolic dysfunction of the left ventricle plays an important role in pathophysiology of heart failure in the various cardiac diseases. And many hypertensive patients manifest diastolic dysfunction of the left ventricle in its early stage. But, there are very few studies of right ventricular diastolic dysfunction reported, and effects of systemic hypertension on right ventricular function are not well understood. Thus, left ventricular diastolic dysfunction and its effects to right ventricular function need to be evaluated in hypertensive patients. Method: For the evaluation of the left and right ventricuiar diastolic function in the hypertensive patients, 20 normotensive control subjects and 30 untreated essential hypertensive patients were studied by pulsed doppler echocardiography at the left and right ventricular inflow, and then E/A velocity ratio [E/A (v)], acceleration time (AT), deceleration time (DT), and diastolic filling period (DFP) were measured after confirming normal ejection fraction by M-mode echocardiography. Results: 1) In the 20 normal control group, ejection fraction was 63.7±11.8% and in the 30 hypertensive patient group, it was 60.3±10.8%. There was no significant differences between the normal control and the hypertensive patient group. 2) In the normal control group, E/A (v) of left ventricle was 1. 48±0.32, E/A (v) of LV was 0.88±1.07, mean E/A (v) of RV was 0.91±0.73. E/A (v) of LV & RV was significantly decreased (p<0.01), compared with those of normal control group. 3) DT of left ventricle was significantly prolonged in hypertensive group (p<0.05), but there was no significant difference in DT of right ventricle. 4) AT and DFP were signficantly prolonged in right ventricle, compared with left ventricle, but there was no significant correlation between normal control group and hypertensive patient group. 5) Among the factors influencing the RV E/A ratio, LV E/A ratio was only significantly correlated (r=0. 538, p<0.05). Age of subject, left ventricular ejection fraction and severity of hypertension have no significant correlation with right and left ventricular E/A ratio. Conclusion: The E/A ratio and deceleration time measured from pulsed doppler echocardiogram seem to be useful parameters for evaluation of left and right ventricular diastolic function in hypertensive patients with normal systolic function. And, right ventricular diastolic dysfunction is closely related with left ventricular diastolic function.

혈액 투석 환자에서 Recombinant Human Erythropoietin ( rHuEpo ) 치료가 혈중 Lipoprotein ( a ) [ Lp ( a ) ] 를 포함한 지질 농도에 미치는 영향

강덕희(Duk Hee Kang),윤견일(Kyun Il Yoon) 대한내과학회 1996 대한내과학회지 Vol.51 No.5

N/A Objectives: The efficacy of rHuEpo in the correction of renal anemia has been well established resulting in theoretical benefits on cardiac function with the regression of left ventricular dilatation. However, hypertension and thrombogenic complications can be developed with rHuEpo therapy, which impose the deleterious effects on cardiovascular system. Moreover there has been no study into the effects of rHuEpo on uremic dyslipidemia which may also contribute to an increased cardiovascular mortality in dialysis patients. Methods: The present prospective study was undertaken to evaluate the effects of rHuEpo on lipid profiles including Lp (a) in 22 (M:F 12:10) maintenance HD patients. rHuEpo was started at a dose of 2000 unit, given subcutaneously two or three times a week, at the end of each dialysis session. Lp (a) and other lipid profiles including total cholesterol (TC), triglyceride (Tg), HDL-cholesterol (HDL-C), and LDL-cholesterol (LDL-C) were measured before treatment, and at two week intervals during the first eight weeks of rHuEpo. Results: Hct started to increase significantly 4 weeks after rHuEpo therapy. The concentrations of TC, Tg and LDL-cholesterol did not significantly change during rHuEpo. The median value of Lp (a) before rHuEpo therapy was 20.4㎎/dl with a distribution from 1.4 to 113.6㎎/dl. Five out of 22 patients (22.7%) had Lp (a) concentrations above 30㎎/dl, which value has been shown to be a high risk for atherosclerosis. The Lp (a) concentration also showed no statistically significant changes in spite of a tendency to decrease with rHuEpo. However, it was interesting that Lp (a) levels in all of the five patients whose Lp (a) was above 30㎎/dl decreased significantly 8 weeks after rHuEpo therapy (58.8±4.5 vs. 32.5±7.9㎎/dl, p<0.05). Conclusions: rHuEpo may decrease the serum Lp (a) level, especially in the high Lp (a) subjects. Although the exact mechanism of this favorable effect on Lp (a) during rHuEpo administration is uncertain, it may contribute to a decrease in cardiovascular morbidity, independent of the effects of anemia correction itself.

인슐린이 혈관 내피 성장 인자(Vascular Endothelial Growth Factor)의 합성에 미치는 영향: 복강내 인슐린 사용이 복막기능에 미치는 영향을 중심으로

강덕희 ( Duk Hee Kang ) 대한내과학회 2006 대한내과학회지 Vol.71 No.5

목적: 장기적으로 복막 투석을 하고 있는 환자에서 발생되는 복막 혈관의 변화는 복막 기능의 소실과 밀접한 연관이 있다. 최근 복강내의 혈관내피 세포 성장 인자(vascular endothelial growth factor, 이하 VEGF)의 형성이 복막의 기능의 변화에 중요한 역할을 한다는 실험 결과가 보고된 바 있고 이러한 VEGF의 합성 조절에 관여하는 여러 인자들에 대한 관심이 증가되고 있다. 말기 신부전의 가장 흔한 원인인 당뇨병성 신증 환자에서는 복막 투석을 시작한 후 주로 복강내 인슐린 투여를 받게 되는데 이러한 복강내로의 인슐린 투여가 장기적으로 복막의 기능과 복강에서의 VEGF 합성과 어떤 연관이 있는지의 여부에 관해서는 아직 연구된 바 없는 상태이다. 방법: 일차분리한 인간의 복막 중피세포를 인슐린(0.1~100 nM)에 노출시키면서 세포 증식, VEGF mRNA 및 단백질의 합성을 조사하였다. 관여하는 세포 신호전달 체계를 알기 위하여 p42/44 MAPK 및 p38 MAPK의 활성도를 조사하였고, MAPK 특이 억제제, PI3K 억제제 및 protein kinase C (PKC) 억제제가 인슐린에 의해 유도된 VEGF 합성에 미치는 영향을 조사하였다. 인슐린의 효과는 고포도당에 의한 VEGF 합성 유도 효과와 비교하여 조사하였다. 결과: 인슐린은 1 nM 이상의 농도에서 VEGF mRNA 발현을 증가시켰다. 10 nM의 인슐린에 의해 유도된 VEGF mRNA의 발현은 3시간부터 증가되기 시작하여 24시간 후까지도 증가된 소견을 보였다. 인슐린은 노출 24시간에 VEGF 단백질의 발현도 의의 있게 증가시켰다. 인슐린의 VEGF 유도는 고포도당(30 nM)에 의한 VEGF mRNA의 발현 증가와 유사한 정도로 출현하였으나 인슐린과 고포도당으로 동시에 자극한 경우 VEGF 발현에 additive effect는 없었다. 인슐린은 복막 중피세포의 p38 및 p42/44의 활성화를 자극 5분 후부터 유도하였고, 인슐린에 의해 유도된 VEGF의 발현은 p38와 p42/44의 특이 억제제로 전처치한 경우 의의 있게 억제되었다. 인슐린과 연관된 유전자 발현에 중요한 역할을 하는 것으로 알려진 PI3K 억제제 역시 VEGF의 발현을 억제하였으나 PKC 억제제는 아무런 영향이 없었다. 하지만 고포도당에 의해 유도된 VEGF 발현의 증가는 ERK와 p38의 특이 억제제의 전처치로 의의 있게 억제된 반면 PI3K 억제제에 처리로는 변화되지 않았다. 결론: 결론적으로 인슐린 자체는 복막 중피 세포의 VEGF 발현을 직접적으로 자극하였고, PI3K 및 MAPK 활성 경로가 중요한 역할을 할 것으로 생각되었다. 복막투석 환자에서 복강내 인슐린의 사용이 장기적으로 복막의 기능 및 형태학적 변화에 미치는 영향에 관해서는 추가적인 임상 필요할 것으로 사료된다. Background: Intraperitoneal (IP) insulin administration in peritoneal dialysis (PD) patients has several advantages, including the prevention of major fluctuations of blood glucose and hyperinsulinemia and the formation of insulin antibodies. However, the effects of IP insulin on dialysis efficacy, ultrafiltration and the ultimate peritoneal function have not been investigated. Ultrafiltration failure is the most important functional abnormality during PD, which is now known to be associated with increased peritoneal vascular remodeling and vascular endothelial growth factor (VEGF) synthesis. There are also some evidences of insulin-induced vascular remodeling in other organs. Therefore, we investigated whether insulin regulates VEGF synthesis in human peritoneal mesothelial cells (HPMC), and also compared its signaling pathway to the glucose-induced signaling for VEGF synthesis. Methods: The expression of VEGF mRNA and protein was evaluated in HPMC stimulated with insulin (0.1-100 mM) and high glucose (30 mM); the evaluation was done by RT-PCR and ELISA with an examination of related signal transduction system, including p38, p42/44 MAPkinase, protein kinase C (PKC) and PI3 kinase (PI3K). Results: Insulin (10 nM) increased VEGF mRNA and protein synthesis of the HPMCs from 3 and 24 hours, respectively. Pretreatment with inhibitors of p38 MAPK (SB203580, 10 μM), p42/p44 MAPK (PD98059, 50 μM) or PI3K (wortmannin, 50 nM) suppressed the insulin-induced VEGF synthesis, whereas there was no effect with PKC inhibition. High glucose (D-glucose, 30 mM)-induced increase in VEGF synthesis was inhibited by pretreatment with inhibitors of p38, p42/p44 MAPK or PKC. Conclusions: Insulin per se can induce VEGF synthesis from HPMC via differential mechanisms and signaling pathways from high glucose, which may be related to the later development of peritoneal angiogenesis and ultrafiltration failure. The long-term effects of IP insulin on peritoneal function need to be evaluated in relevant animal models and human subjects.(Korean J Med 71:518-526, 2006)

혈액투석 환자에서 항인지질 항체와 동정맥루 폐쇄의 상관관계에 대한 연구

강덕희(Duk Hee Kang),유승기(Seung Ki Ryu),김성남(Sung Nam Kim),최규복,윤견일(Kyun Il Yoon),이윤하(Yoon Ha Lee) 대한내과학회 1997 대한내과학회지 Vol.53 No.5

N/A Objectives: Anticardiolipin antibody (ACA) and lupus anticoagulant (LA) are acquired antiphospholipid antibodies (APAs), which are regarded as important risk factors far vascular thrombosis and recurrent fetal loss. Although the clinical relevance of APAs in dialysis patients is uncertain, recent studies have suggested that APAs are involved in bioincompatibility and thrombogenic complications in hemadialysis (HD) patients. Method : We performed a cross sectional study of ACA and LA in 50 stable HD patients and their 68 vascular accesses (52 native arteriovenous fistulae and 16 synthetic arterovenous grafts), with the analysis of factors associated with the presence of APAs and the retrospective evaluation of vascular access occlusion (VAO). LA was assessed by platelet neutralization method whereas IgG-ACA was measured by a solid phase ELISA. Values higher than 23GPLU/ml (IgG phospholipid units) were considered to be positive for IgG-ACA and positive values for LA was more than 8 seconds in prolongation of the clotting time with human platelet lysate. Vascular access survival was assessed by Kaplan- Meier method, Results: The mean age of the subject (M:F 21:29) was 46 years and the mean duration of hemodialysis was 49 months. The frequency of VAO in entire subjects was 0.45±0.98 episodes/patient year. The median value of IgG-ACA was 16.0 GPLU/ml with a distribution from 2.7 to 46.1GPLU/ ml. The median titer of I.A was 4.5 (3.1-45.6) seconds. Fourteen patients (28%) were found to have at least one episode of VAO. In spite of comparable clinical and biochemical data according to the presence of VAO, the titers of IgG-ACA (13.6±7.7 vs, 20.3±8.7GPLIJ/ml, P<0.05) and LA (4.5±2.9 vs. 11.7 ±12.6sec, P<0.05) were significantly higher in VAO group. Six out of 50 patients(12%) had an increased titer of IgG-ACA and LA was found in 11 patients(22%). No patients were positive for ACA and LA simultaneously. There was no significant difference in sex, etiology of ESRD, diabetic status, the dosage of heparin during HD or the amount of erythropoietin administered according to the presence of APAs. We could not find any significant correlation between the titer of APAs and age, duration of dialysis, blood pressure, platelet count and biochemical parameters. In the patients with positive ACA, the frequency of VAO was 1.05±0.12 episodes/patient · year, which was significantly higher than patients without ACA (0.33±0.17 episodes/ patient year, P<0.05). In the patients with the presence of LA(1.06±0.43 vs. 0.12±0.06 episodes/ patients · year, P<0.01). The median vascular access survival time in IgG-ACA positive patients (32.7 months) was significantly decreased compared to 66.8 months in IgG-ACA negative group. Conclusion: Our data suggest that the presence of APAs (ACA and/or LA) affects the event-free vascular access survival in HD patients. Therefore the evaluation of APAs status have to be included in the diagnostic strategies for the patients with recurrent VAO. Further studies are necessary to explore the pharmacologic intervention method to decrease APAs and prevent VAO in HD patients.

요산이 말초혈액 단핵세포의 C-반응 단백 (C-reactive protein)의 합성에 미치는 영향

강덕희 ( Duk Hee Kang ),유민아 ( Mi Na Yu ),류정화 ( Jung Hwa Ryu ) 대한신장학회 2007 Kidney Research and Clinical Practice Vol.26 No.6

Purpose : Systemic inflammatory reaction (SIR) is an important determinant of cardiovascular (CV) mortality in CRF patients. UA is an end-product of purine metabolism, and recent studies have demonstrated that an elevated serum UA level is associated with an increased level of inflammatory mediators. Since hyperuricemia is one of the most prevalent complications in CRF and is linked to CV disease, we hypothesized hyperuricemia in CRF may play an important role in the development of CV disease by inducing SIR. Methods : PBMCs were isolated by density gradient centrifugation in 21 CRF patients and age and sex-matched 20 healthy adults. CRP expression was evaluated by real time PCR and ELISA in PBMC stimulated with UA (0.3-12 mg/dL). Results : There was no difference in constitutional CRP expression in PBMC from control and CRF patients. UA induced CRP mRNA (RT-PCR) and protein (ELISA) expression in PBMC, which was blocked by the organic anion transport inhibitor, probenecid (1 mM), suggesting entry of uric acid into cells was responsible for CRP expression. PBMC from CRF patients showed a significantly higher CRP production by UA compared to healthy control. There was no correlation between serum UA level and % increase in CRP production by UA. Conclusion : The exaggerated CRP expression by UA can be another mechanism of SIR and increased CV morbidity in CRF patients. Prospective studies with uric acid-lowering therapy are necessary to confirm clinical significance of these interesting in-vitro findings.

동화를 활용한 홀리스틱 심상활동이 유아의 창의성에 미치는 효과

강덕희 ( Duk-hee Kang ) 한국독서치료학회 2015 독서치료연구 Vol.7 No.1

본 연구는 동화를 활용한 홀리스틱 심상활동이 유아의 창의성에 어떤 효과를 미치는지 알아보기 위한 목적으로 실시하였다. 홀리스틱 심상활동은 유아 자신이 생각한 것을 머릿속에 그려 봄으로서 다양한 경험을 표현 할 수 있는 기회가 주어질 수 있다는 것, 그리고 이에 동화를 활용한다는 것은 유아의 창의적 사고와 문제해결력을 기르는데 효과적일 것이라 예측되었다. 본 연구의 결과 동화를 활용한 홀리스틱 심상활동을 적용한 실험집단이 통제집단에 비해 창의성 하위영역(상상력, 유창성, 융통성, 독창성)과 창의성 분야별(언어, 도형, 신체)에서 모두 향상되었으며, 통계적으로도 유의미한 차이가 있는 것으로 나타났다. 즉, 동화를 활용한 홀리스틱 심상활동은 유아의 창의성 향상에 긍정적 영향을 미쳤음을 알 수 있었다. 논의에서는 유아교육 현장에서 동화를 활용한 홀리스틱 심상활동을 활용한 지도방법에 대한 적극적 모색을 논이 하였다. This study focuses on the effect of the holistic images on children's creativity through children's books. Children's picturebooks are very useful to evoke vivid imaginations as well as to enhance the ability of problem solving in various situations. According to the individual objective of the study, the two questions have been established. By combining all the results of the study, it can be said that the influence of the holistic images on children's creativity through children's stories also influences the overall creativity for each standard and category in a positive way. There were significant increase in terms of subarea of creativity. There were discussed some implications and prospects for applying holistic image activity in the field of early childhood education.

Heparin 백서 사구체 메산지움 배양세포의 중식에 미치는 영향

강덕희(Duk Hee Kang),윤견일(Kyun Il yoon),강신욱(Shin Wook Kang),최규헌(Kyu Hun Choi),이호영(Ho Yung Lee),한대석(Dae Suk Han) 대한내과학회 1996 대한내과학회지 Vol.51 No.3

N/A Objectives: Glomerular mesangial cells are the main component of human glomerulus, and exist as a quiescent state in normal healthy kidney. It is now apparent that mesangial cells do not act as a mere framework within the glomerular tuft, but that these cells can undergo striking phenotypic transformation after an exposure to a variety of such as platelet derived growth factor(PDGF) and epidermal growth factor(EGF). Proliferation of mesangial cells is a prominant histologic feature of various glomerular diseases in human as well as in experimental animal. Because glomerular mesangial cells have direct relation with glomerular function through their contractility and proliferation, the inhibitory effects on cell proliferation can result in preventing or delaying the progression of renal disease into end stage renal failure. Heparin is a highly sulfated glycosaminoglycan with anticoagulant activity. It has also been shown that heparin exhibits antiproliferative effects in cultured vascular smooth muscle cells and can ameliorate glomerular injury in some animal model. Methods: The present study was undertaken to characterize the inhibitory effects of heparin on PDGF- and EGF-induced proliferation of mesangial cells isolated from male Sprague-Dawley rat in vitro. Also to examine whether this antiproliferative effects of heparin is related with anticoagulant activity, the effect on the PDGF-induced mesangial cell proliferation was assessed using N-desulfated and N-desulfated N-acetylated heparin which showes no anticoagulant effects. Results: 1) PDGF stimulated the DNA synthesis of glomerular mesangial cell assessed by 3H-thymidine uptake in a dose-dependent manner. At a concentration of 10ng/ml, 3H-thymidine uptake was significantly increased compared to the control value (512,0±38.6 vs. 3300.0±432,5cpm, p<0.05) 2) EGF also induced a significant increase of DNA synthesis of cultured mesangial cell, and at the concentrations of 5ng,ml or higher, the increases in DNA synthesis assessed by 3H-thymidine uptake were statistically significant compared to the control value(428.0±50.4 vs. 1618.0±219.7cpm, p<0.05). 3) Intact heparin caused a dose-dependent inhibition of PDGF-induced DNA synthesis of mesangial cells. At a concentration of 1 ㎍/ml of heparin, 36.7% of inhibition in DNA synthesis of mesangial cell was found. At a concentration of 25, 100 and 500㎍ /ml of heparin, PDGF-induced 3H-thymidine uptake of mesangial cell was reduced by 44.4%, 56.2% and 69.8%, respectively. Chondroitin sulfate and N-desulfated N-acetylated heparin also caused a significant inhibition of PDGF-induced DNA synthesis at the concentraion of 25㎍/ml or higher. However, N-desulfated heparin showed no significant inhibitory effects on PDGF-induced proliferation of mesangial cell at all concentrations. 4) Intact heparin, N-desulfated N-acetylated he- parin and chondroitin sulfate caused a significant inhibition of EGF-induced DNA synthesis only at the highest concentration of 500o㎍/ml. 5) Cell count assessment by hemocytometer revealed the similar results with 3H-thymidine uptake. Conclusion : Heparin had an inhibitory effect on the PDGF-induced DNA synthesis and proliferation of mesangial cell. These antiproliferative effects appear to be unrelated to the anticoagulant effects of heparin, and mediated by selective inhibition of protein kinase C-dependent pathway of mesangial cell proliferation. Further studies utilizing in-vivo glomerulonephritis model are warranted to clarify the potential benefit of heparin in the treatment of glomerulonephritis and to document expected effects of heparin in delaying the progression of glomerulonephritis into end stage renal failure.

종설 : 고요산혈증은 신장, 심혈관 및 대사 질환의 발생/악화 인자인가?

강덕희 ( Duk Hee Kang ) 대한내과학회 2011 대한내과학회지 Vol.80 No.5

Although an elevation of serum uric acid level is often associated with kidney disease, cardiovascular disease and metabolic syndrome, it remains controversial whether hyperuricemia per se is a true risk factor for the development or aggravation of these diseases. Recent studies have demonstrated the independent role of uric acid in progression of renal disease and the development of new-onset hypertension and diabetes. Furthermore, lowering uric acid in these patients is found to stabilize renal function and decrease cardiovascular morbidity, suggesting the causative role of uric acid in renal, cardiovascular and metabolic disease, rather than an incidental association. In this manuscript, recent understanding about the role of uric acid in the development and/or aggravation of renal, cardiovascular and metabolic diseases will be reviewed based on the results from epidemiologic, clinical and experimental studies.

만성 신부전증에서 고요산혈증의 치료

강덕희 ( Duk Hee Kang ),이지수 ( Ji Soo Lee ) 대한신장학회 2008 Kidney Research and Clinical Practice Vol.27 No.2

1. 급성 통풍 발작이 있는 경우 요산강하제 처방은 금기이며, 일단 염증을 완화시킨 후에 요산강하 치료를 시작해야 한다. 2. Colchicine은 사구체여과율이 50 mL/min 이하인 경우 용량 감소가 필요하고 10 mL/min 이하인 경우는 금기이다. Colchicine 투여시 같이 복용하고 있는 약물에 따라 치명적인 합병증이 발생할 수 있다. 3. 요산 농도를 높일 수 있는 약물을 복용하고 있는 경우는 약물의 중단이나 교체를 고려하여야 한다. 4. Allopurinol 처방은 신기능에 따라 용량 조절이 필요하고, AHS을 포함한 부작용의 발생 가능성에 관하여 환자에게 주지시켜 조기 증상이 출현할 때 즉시 치료하는 것이 중요하다. 5. 요산 배설 촉진제 사용이 필요한 경우 bezbromarone이 probenecid보다 사구체저하율 감소가 진행된 경우에도 사용 가능하나 간기능 모니터링이 필요하다. 6. 무증상 고요산혈증은 요산 농도가 아주 높지 않은 한 (남성 13 mg/dL 이상, 여성 10 mg/dL 이상) 치료하지 않은 것이 현재까지의 원칙이지만, 향후 치료의 가이드라인이 바뀔 것으로 예측된다.

섬유유연제의 사용실태와 유연제 처리된 면직물의 연소특성

이정순 ( Jung Soon Lee ),강덕희 ( Duk Hee Kang ),이윤정 ( Youn Jung Lee ),최혜영 ( Hae Young Choi ) 충남대학교 생활과학연구소 2005 忠南生活科學硏究誌 Vol.18 No.-