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원저 : 제2형 당뇨병 동물모델에서 항 혈관내피세포 성장인자(Anti-Vascular Endothelial Growth Factor (VEGF)) 투여 시 췌장에 대한 효과
김지원 ( Ji Won Kim ),함동식 ( Dong Sik Ham ),박헌석 ( Heon Seok Park ),안유배 ( Yu Bai Ahn ),송기호 ( Ki Ho Song ),윤건호 ( Kun Ho Yoon ),유기동 ( Ki Dong Yoo ),김명준 ( Myung Jun Kim ),정인경 ( In Kyung Jeong ),고승현 ( Seung Hy 대한당뇨병학회 2009 Diabetes and Metabolism Journal Vol.33 No.3
연구배경: 대표적인 당뇨병성 합병증인 당뇨병성 신증과 망막병증은 공통적으로 혈관내피세포성장인자(Vascular endothelial growth factor, VEGF)가 합병증의 발생에 중요한 역할을 하는 것이 알려져 있으나 항 VEGF 치료가 췌도나 베타세포에 직접적으로 어떠한 영향을 주는지는 거의 알려진 바가 없다. 이에 당뇨병성 합병증 치료를 목적으로 하는 항 VEGF 치료가 췌장과 당뇨병의 경과에 미치는 영향을 관찰하고, 당뇨병이 진행되면서 나타나는 췌도 및 베타세포의 변화에 있어서 VEGF의 역할을 규명하고 치료에 응용하고자 하였다. 방법: 이에 당뇨병 동물모델인 db/db mouse에 12주간 VEGF 수용체 type 2 antagonist (ATWLPPR, 5 mg/kg)를 복강 내 투여하여 혈당의 변화와 함께 췌장의 면역염색을 통하여 베타세포 질량 및 췌도의 형태적인 변화를 관찰하고 VEGF의 췌도 내 발현 및 혈관신생 정도를 평가하였다. 결과: 12주간 항 VEGF peptide를 투여한 결과, 복강 내당부하검사 시 db/db mouse에 비해 항 VEGF 투여군에서 현저한 고혈당을 보였으며 고혈당이 심해지면서 항 VEGF 투여군에서 체중의 증가가 적었다. 췌장의 무게(db/dm vs. db/db vs. anti-VEGF group, 0.321±0.05 vs. 0.206±0.13 vs. 0.158±0.12 g) 및 베타세포 질량(db/dm vs. db/db vs. anti-VEGF group, 4.08±0.1 vs. 3.77±0.2 vs. 2.89±0.2 mg, P<0.05) 역시 db/db군에 비해 항 VEGF군에서 더 감소되었다. 또한 정상 췌도에 비해 당뇨병이 발생한 군에서 췌도 내 VEGF 발현이 증가되었으나, 항 VEGF 투여시 췌도 내 VEGF 단백의 발현이 감소하였고(db/dm vs. db/db vs. anti-VEGF group, 3.63±2.86 vs. 6.60±3.56 vs. 2.74±1.55%, * P<0.05) 췌도의 크기가 감소하였으며, 췌도 내 섬유화 진행이 더 심하게 관찰되었고(db/dm vs. db/db vs. anti-VEGF group, 3.37±1.51 vs. 13.96±3.20 vs. 16.99±4.96%, * P<0.05) 췌도 내 내피세포의 증식이 더 감소되어 있었다. 결론: 제2형 당뇨병 동물모델에서 혈관내피세포 성장인자(VEGF)는 정상 췌도보다 당뇨병이 발생한 췌도에서 발현이 증가되므로 당뇨병의 발병 기전과 관련이 있을 것이며, 베타세포의 증식 및 췌도 변형에 중요한 역할을 하므로 당뇨병의 치료에도 응용할 수 있을 것으로 생각되고, 당뇨병성 미세혈관 합병증의 치료나 예방을 목적으로 제2형 당뇨병모델에 항 VEGF를 투여할 경우 고혈당 상태를 더 악화시키고 베타세포 증식을 억제하며 췌도 파괴를 가속화 시키므로, 항 VEGF 치료 시 이에 대한 충분한 고려가 필요할 것이다. Background: Vascular endothelial growth factor (VEGF) is associated with the development of diabetic complications. However, it is unknown whether systemic VEGF treatment has any effects on the pancreatic islets in an animal model of type 2 diabetes mellitus. Methods: Anti-VEGF peptide (synthetic ATWLPPR, VEGF receptor type 2antagonist) was injected into db/db mice for 12 weeks. We analyzed pancreatic islet morphology and quantified beta-cell mass. Endothelial cell proliferation and the severity of islet fibrosis were also measured. VEGF expression in isolated islets was determined using Western blot analysis. Results: When anti-VEGF was administered, db/db mice exhibited more severe hyperglycemia and associated delayed weight gain than non-treated db/db mice. Pancreas weight and pancreatic beta-cell mass were also significantly decreased in the anti-VEGF-treated group. VEGF and VEGF receptor proteins (types 1 and 2) were expressed in the pancreatic islets, and their expression was significantly increased in the db/db group compared with the db/dm group. However, the elevated VEGF expression was significantly reduced by anti-VEGF treatment compared with the db/db group. The anti-VEGF-treated group had more prominent islet fibrosis and islet destruction than db/db mice. Intra-islet endothelial cell proliferation was also remarkably reduced by the anti-VEGF peptide. Conclusion: Inhibition of VEGF action by the VEGF receptor 2antagonist not only suppressed the proliferation of intra-islet endothelial cells but also accelerated pancreatic islet destruction and aggravated hyperglycemia in a type 2 diabetes mouse model. Therefore, the potential effects of anti-VEGF treatment on pancreatic beta cell damage should be considered. (Korean Diabetes J 33:185-197, 2009)
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김형욱 ( Hyung Wook Kim ),김영옥 ( Young Ok Kim ),윤선애 ( Sun Ae Yoon ),황현석 ( Hyeon Seok Hwang ),장세나 ( Se Na Jang ),박미연 ( Mi Youn Park ),윤혜은 ( Hye Ene You ),유기동 ( Ki Dong Yoo ),김용수 ( Yong Soo Kim ),김영수 ( Youn 대한신장학회 2009 Kidney Research and Clinical Practice Vol.28 No.1
목적: 심혈관계 질환은 말기 신부전 환자에서 가장 흔한 사망 원인으로, 전체의 33.7%를 차지하며, 이 중 27%가 급성 심근 경색증에 의한 것으로 보고되었다. 투석 환자에서 급성 심근 경색증의 중요성에도 불구하고 투석 환자에서 발생한 급성 심근 경색증의 임상적 특징에 대한 연구는 많지 않다. 방법: 본 연구는 2004년 1월부터 2007년 12월까지 급성 심근 경색증으로 입원한 투석 환자 32명을 대상으로 하였으며 대상 환자와 연령 및 성별이 유사한 급성 심근 경색 환자 123명을 비투석군으로 정하였다. 본 연구는 투석 환자와 비투석군에서 급성 심근 경색증의 임상적 특징을 비교하기 위해 임상소견 및 검사실 소견을 후향적으로 조사하였다. 결과: 투석환자는 비투석군에 비해 전형적인 흉통의 빈도가 낮고 (18.8% vs. 62.6%, p<0.001), 심전도에서 전형적인 STEMI의 빈도가 낮았다 (28.1% vs. 82.9%, p<0.001). 또한 심근 손상을 반영하는 CPK, CK-MB, Troponin T의 상승 정도가 비투석군에 비해 유의하게 낮았다 (p<0.001). 그러나 이와는 반대로 심혈관 조영술 검사 결과, 다혈관 관상동맥 질환의 비율이 높았고 (63.0% vs. 43.3%, p=0.045), 좌심실비대가 심하였으며 (78.9±20.9 g/m2.7 vs. 61.0±15.8 g/m2.7, p<0.001), 입원 사망률이 유의하게 높았다 (25.0% vs. 5.7%, p=0.003). 결론: 본 연구결과 투석환자는 일반인에 비해 심근 경색증의 전형적인 임상증세나 심전도 소견을 보이지 않고, 낮은 심근 손상 효소 수준을 보이나 오히려 관상동맥 병변이 더 심하고 사망률도 높았다. 그리므로 호흡곤란 등의 비특이적인 임상증세를 호소하는 투석환자에서 심근경색증을 조기에 진단하려는 적극적인 노력이 필요할 것으로 사료된다. Purpose: Cardiovascular disease is the predominant cause of death in patients with end stage renal disease. Approximately 33.7% of overall mortality is due to cardiovascular disease, and about 27% of these cardiovascular deaths are attributed to acute myocardial infarction (AMI). Despite the significance of AMI, there are little data on the clinical characteristics of AMI in dialysis patients. Methods: Thirty-two dialysis patients admitted for AMI from January 2004 to December 2007 were retrospectively analyzed. One hundred twenty-three AMI patients were included as a control. The clinical and laboratory findings of AMI were compared between dialysis patients and non-dialysis patients. Results: The frequency of typical chest pain was significantly lower in dialysis patients than in non-dialysis patients (18.8% vs. 62.6%, p<0.001), and typical ECG findings of STEMI were significantly less noted (28.1% vs. 82.9%, p<0.001). Increases in CPK, CK-MB, and troponin T levels were significantly lower in dialysis patients than in non-dialysis patients (p<0.001). In contrast, dialysis patients revealed more multi-vessel diseases on coronary angiography and more left ventricular hypertrophy and were associated with higher mortality during admission than non-dialysis patients. Conclusion: Although dialysis patients with AMI had less typical chest pain and typical ECG findings, and had lower increases in cardiac enzyme levels, they revealed more severe coronary vessel diseases than non-dialysis patients. Therefore, efforts for early and accurate diagnosis of AMI are needed in dialysis patients with nonspecific complaints of AMI.
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최현숙 ( Hyun Sook Choi ),김은선 ( Eun Sun Kim ),민정요 ( Jeong Yo Min ),강경미 ( Kyung Mi Kang ),김지훈 ( Ji Hoon Kim ),유기동 ( Ki Dong Yoo ),김철민 ( Chul Min Kim ) 대한내과학회 2008 대한내과학회지 Vol.75 No.1
본 증례는 흡연 이외에는 심혈관 질환의 위험인자가 없는 젊은 환자에서 급성 심근경색이 발생한 경우로 자가면역질환, 다른 응고성 질환, 종양 등의 원인 없이 lupus anticoagulant 항체 양성 소견으로 원발성 항인지질 증후군에 의한 심근경색을 진단하였기에 문헌고찰과 함께 보고하는 바이다. Antiphospholipid syndrome is a multi-system disorder characterized by arterial or venous thromboses and antiphospholipid antibodies, such as lupus anticoagulant or anticardiolipin antibodies. Most common clinical manifestations are recurrent pregnancy losses and deep vein thromboses. Cardiac manifestations in antiphospholipid syndrome include valve abnormalities, occlusive arterial disease, intracardiac emboli, and ventricular dysfunction. Acute myocardial infarction is a rare manifestation of the primary antiphospholipid syndrome. We have experienced a case of myocardial infarction with antiphospholipid syndrome. A 35-year-old man with no cardiovascular risk factors, other than smoking, presented with chest pain. He was diagnosed with an acute myocardial infarction. Our evaluation for coagulapathy revealed elevated lupus anticoagulant antibody. The antiphospholipid syndrome should be considered early in the differential diagnosis as an important cause of unexplained thrombosis in young patients. (Korean J Med 75:108-111, 2008)
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손현화,유기동,서영선,김태균,김양수,정재용,박유환,정춘해,홍승민,전제열,이상운 조선대학교 부설 의학연구소 1999 The Medical Journal of Chosun University Vol.24 No.2
Background: Cancer has become the major cause of death in Korea. Doctors who treat terminal cancer come across problems which are too difficult to solve. These problems are related with religious, moral and legal problems. These problems are easy death, patients' or family' s refuse of treatment, practice of cardiopulmonary resuscitation(CPR) in terminal cancer, definition of death and so forth. In Korea, studies related with terminal cancer patients and the doctors who treat them are very rare and the hospice system for terminal cancer patients is not organized yet. Objectives: The aim of this study was to identify the opinions of doctors who treat terminal cancer about these problems. Materials ðod: This study was performed on 90 doctors working at Chosun university hospital, who are divided in to three parts as staff, residents and interns. We used questionares related with the above problems, composed of 19 items and six general characteristics. We could confirm 75 questionaires. Results &onclusion: For the question "ve terminal cancer patients was announced their diagnosis and prognosis?"hat was most important to doctors was patients' opinions and the second was their family' s. For the question "eatment which could prolong the life of terminal cancer patients who are unnconscious is performed?"doctors showed a negative opinion. About the easy death of terminal cancer patients, more than half the doctors showed agreement. The prohibition of CPR in terminal cancer patients was agreed by 40%. For the question about the definition of death in terminal cancer patients 76.1% doctors agreed it was brain death. 85.7% subjects answered that they felt moral enmity in treatment of terminal cancer patients. In Korea, the programs for these problems are very poor, and the results of this study can affect the formation of systems and laws about the terminal cancer patients and the doctor's treatment. National support for terminal cancer patients and the hospice care system is required.
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이만재,유기동,손현화,정재용,김양수,김태균,서영선,박유환,정춘해,이미자,박종,오윤경 조선대학교 부설 의학연구소 1999 The Medical Journal of Chosun University Vol.24 No.2
Purpose: Even though the entire resection is only option for primary cure in case of the localized colorectal cancer. However, recurrence rate is relatively high(30%). The evaluation for chromosome 18 long arm status in the patients who have stage II colon cancer gives a important information about a prognosis and evaluation of the patients. This study was undertaken to evaluate the possible prognostic role of the expression of deleted in colorectal cancer (DCC) protein in the patients with stage II colon cancer. Materials and Methods: The present study analysed 22 patients with stage II &II (AJC TNM 1992 classification) colorectal adenocarcinoma who were admitted to the Chosun University Hospital between March 1989 and February 1992. Clinicopathologic parameters including age, sex, TNM stage, adjuvant chemotherapy, location and tumor differentiation and DCC status were examined. Results: The survival rate of the patients expressing DCC was found to be significantly higher in the patients in whom the DCC was expressed, while 4 (18%) in the other who had not the expression of DCC(P= 0.044). Although the patients with the stage II of the TNM stage have a better prognosis than those with stage III (P=0.046), no significant difference was found between these two groups in terms of the eastern cooperative oncology group (ECOG) performance status of patients (P= 0.525). Conclusion: when the expression of DCC protein is negative in patients with colon cancer staged II need a more aggressive treatments like in the patients with staged III colon cancer and thereafter the more exact operative method is required identifying the expression of DCC protein using the frozen biopsy during operation and thereafter the consideration for the chemotherapy and radiation therapy will be possible.
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