당뇨병 환자에서 혈장 Thrombin-Antithrombin Ⅲ 및 Plasmin-α_2-Plasmin Inhibitor 복합체의 임상적 의의

김경욱,김은숙,정상수,윤수지,박우일,이준희,남수연,안철우,문병수,김경래,차봉수,송영득,임승길,이현철,허갑범 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.25 No.5

연구배경:당뇨병 환자에서 혈액응고 및 섬유소용해 체계의 이상경향이 있어 그 결과로 여러 혈관합병증의 발생위험이 높다는 사실은 널리 알려져 있다. 그 기전은 아직 확실히 밝혀지지 않았으나, 고혈당으로 인한 혈장 단백질들의 비효소성 당화작용이나 산화성 스트레스로 인한 유리 라티칼 작용으로 응고항진이나 섬유소용해 활성의 저하를 유발하는 것으로 생각되고 있다. 최근 응고 및 용해인자와 그 억제자의 복합체들의 증가가 이 상태를 비교적 예민하게 반영한다고 알려져 있다. 방법:본 연구에서는 당뇨병 환자 101명과 정상 대조군 20명에서 혈장내 thrombin­antithrombin complex(TAT)와 plasmin­α₂­plasmin inhibitor complex(PIC)를 측정하여 비교하고, 당뇨병 환자에서 미세혈관 합병증과 대혈관합병증의 유무에 따른 차이와, 이미 혈관 질환의 위험인자로 알려져 있는 인자들간의 상관성을 알아보고자 하였다. 결과:1. 환자의 분포를 살펴보면 혈관합병증이 있는 군은 85명, 혈관합병증이 없는 군은 16명이었고, 평균연령은 각각 57.9±14.1세, 49.9±16.6세로 혈관 합병증이 있는 군에서 더 나이가 많았고, 체질량지수는 23.2±3.4㎏/㎡, 24.1±3.4㎏/㎡로 두 군간 유의한 차이는 없었다. 또 두 군간의 혈압 및 HbA1c, 공복혈당 및 인슐린과 C­peptide, 총 콜레스테롤, 중성지방, HDL­콜레스테롤, Lp⒜는 유의한 차이가 없었고, 미세혈관합병증이 있는 군에서 당뇨병의 유병기간이 길었다. 2. TAT 및 PIC의 농도는 정상 대조군에서는 2.8±1.2 ng/mL, 240.4±69.7 ng/mL이었고, 당뇨병 환자군에서는 9.5±22.6 ng/mL, 472.2±258.7 ng/mL이었다. TAT와 PIC 모두 당뇨병 환자군에서 정상 대조군에 비해 유의하게 증가되어 있었고(p<0.001), TAT/PIC ratio는 두 군간 차이가 없었다. 3. 당뇨병 환자의 혈관합병증에 따른 TAT 및 PIC, fibrinogen 농도는 합병증이 없는 군은 각각 4.1±2.4ng/mL, 362.2±272.0ng/mL, 322.7±102.4mg/mL으로 PIC와 fibrinogen의 증가를 보였으나, 연령을 보정한 후에는 통계학적 유의성은 없었다. 또 대혈관 합병증군에서는 각각 6.0±4.9 ng/mL, 507.4±321.6 ng/mL, 427.1±194.7 mg/dL이었으며 미세·대혈관 합병증군에서는 10.4±6.4 ng/mL, 484.8±269.7 ng/mL, 388.4±132.4 mg/dL으로 TAT의 증가를 보였으나 역시 연령을 보정한 후에는 통계학적 유의성은 없었다. 4. 미세혈관합병증군에서 HbA1c(>8%)가 높은 군의 PIC 농도가 유의하게 높았고(p=0.049), 대혈관합병증군에서 HbA1c(>8%)가 높은 군의 총 콜레스테롤 농도가 유의하게 높았다(p=0.042). 5. 총 당뇨병 환자군에서 PIC는 fibrinogen과 HbA1c와 양의 상관관계를, BMI와 음의 상관관계를 보였으며(r=0.47, 0.31,-0.25), 혈관 합병증이 없는 당뇨병 환자군에서만 TAT는 HbA1c와 양의 상관관계를 보였다(r=0.67). 결론:이상의 결과에서 혈장 TAT 및 PIC 농도는 당뇨병 환자에서 정상 대조군에 비해 의미있게 증가되어 있었고, 당뇨병 환자군에서는 연령의 증가와 유병기간이 혈액응고항진 및 용해의 장애에 큰 역할을 함을 알 수 있었으며, 총 당뇨병 환자군에 PIC와 HbA1c와 양의 상관관계를, BMI와 음의 상관관계를 보였으며 혈관 합병증이 없는 당뇨병 환자군에서만 TAT는 HbA1c와 양의 상관관계를 보였다. 따라서 당뇨병 환자에서 혈액응고 및 용해의 장애가 동반되어 있다고 볼 수 있으며, 혈장 TAT 및 PIC는 혈관합병증으로의 진행을 예측하는 지표로서 유용하리라 생각된다. 또 혈당조절정도와 상관성이 있으므로 혈당조절후에 추적검사를 시행하여 합병증의 예방이 가능한지 추후 연구가 필요하리라 생각된다. Background : Abnormality of coagulation and fibrinolystic system is known as a predisposing factor of vascular complication in diabetes. Although the pathogenesis is not well known, non-enzymatic glycation reaction and the increase in production of free radicals due to an increased oxidative stress may be linked to the hypercoagulibility and hypofibrinolytic activity. As indices of abnormality in coagulation and firinolysis in peripheral blood, plasma thrombin-antithrombin Ⅲ complex (TAT) and plasmin-α_2-plasmin inhibitor complex (PIC) were measured. The purpose of this study was to clarify whether hypercoagulability exists in diabetic patients with or without vascular complication. Methods : In our study, we measured plasma thrombin-antithrombin Ⅲ compelx (TAT) and plasmin-α_2-plasmin inhibit or complex (PIC) in 101 diabetic subjects and 20 controls. Comparing TAT and PIC levels in diabetic microvascular complication group, diabetic macrovascular complication group and controls, we examined correlation between risk factors associated with diabetic vascular complication. Results : 1. The group with diabetic vascular complication was older than group without complication. There was no significant difference in BMI, blood pressure, HbA_ic, blood sugar level, insulin, C-peptide, serum creatinine, total cholesterol, triglyceride, HDL-cholesterol, Lp (a) between two groups. The group with diabetic microvascular complication had longer duration of diabetes. 2. Concentration of TAT and PIC were 2.8±1.2 ng/ mL, 240.4±69.7 ng/ mL in controls and 9.5±22.6 ng/ mL, 472.2±258.7 ng/ mL in diabetic patients, respectively. TAT and PIC were significantly higher in diabetic patients than in control (p<0.001). But TAT/PIC ratio was no significant difference between two groups. 3. In diabetic patients, concentration of TAT and PIC and fibrinogen were respectively 4.1±2.4 ng/ mL, 362.2±272.0 ng/ mL, 322.7±102.4 mg/ dL in group without vascular complication and 5.3±4.1 ng/ mL, 529.5±258.7 ng/ mL, 374.9±106.2 mg/ dL in group with microvascular complication, which group had increase in PIC and Fibrinogen but no significance after correction of age. Concentration of TAT and PIC and Fibrinogen were 60.±4.9 ng/ mL, 507.4±321.6 ng/ mL, 427.1±194.7 mg/ dL in macrovascular complication, and 10.4±6.7 mg/ mL, 484.8±269.7 ng/ mL, 388.4±132.4 mg/ dL in combined vascular complication which group showed increase of TAT but also had no significant increase after correction of age. 4. In diabetic microvascular complication patients, group of high HbA_1c (>8%) (p=0.049) had significant high PIC concentration. In diabetic macrovascular complication patients, group of high HbA_1c (>8%) (p=0.042) had significant high total cholesterol concentration. 5. In all diabetic patients, PIC was positively correlated with fibrinogen and HbA_1c and negatively correlated BMI (r=0.47, 0.31, -0.25). Only in daibetic patients without angiopathy, TAT was positively correlated with HbA_1c (r=0.67). Conclusion : In this study, plasma TAT and PIC concentration significantly increased in diabetic patients compared with controls, and PIC was increased in group with microvascular complication, TAT were increased in group with combined micro macrovascular complication. However, there was no significance relationship existed when correctinf for age. PIC was correlated with HbA_1c. TAT was correlated with HbA_1c only in the group without angiopathy. Abnormality of coagulation and fibrinolysis were combined in diabetes, plasma TAT and PIC can be used as an index of vascular complication. Also we found the correlation with the degree of the blood glucose control. Therefore we need follow up study for the possibility of prevention of vascular complication after controlling the blood glucose to age-matched patients (J Kor Diaabetes Asso 25:354~363, 2001).

횡문근융해증과 급성 신부전 및 범발성 혈관내 응고장애를 동반한 열사병 1예

최대은,박수진,권오경,이한규,이영모,이상주,나기량,이강욱,신영태 충남대학교 의학연구소 2003 충남의대잡지 Vol.30 No.2

Heat stroke is a life-threatening illness characterized by an elevated core body temperature that rises above 40% and central nervous system dysfunctions that results in delirium, convulsions, or coma. Heat stroke is subdivided into two forms, classic and exertional. Since strenuous exercise is one of the major exacerbating and precipitating factors, the incidence of exertional heat stroke is high among young adult, especially military personnel undergoing military training. Exertional heat stroke commonly causes rhabdomyolysis, lactic acidosis, acute renal failure, shock and pulmonary edema. We report a case of heat stroke with rhabdomyolysis, acute renal failure, disseminated intravascular coagulopathy(DIC) after strenuous exercise. A 18 year old man was admitted to the hospital because of loss of consciousness. He was a wrestler and he had tried to lose 6kg in weight by jogging and strenuous exercise on that summer day with hot temperature. The development of this illness was favoured by much clothes inappropriate for that environmental condition with a purpose to enhance sweating, and by restricted intake of water and food. On admission, the blood pressure was 80/50mmHg, and body temperature was 39.4℃ with stuporous mentality. Laboratory finding were as follows : in complete blood cell count, hemoglobin was 16.7g/dL and platelet count was 158,000/ mm³. In blood chemistry, AST 1061U/L, ALT 201U/L, BUN 30mg/dL, Cr 2.2mg/dL, LDH 941IU/L, CK 696IU/L were resulted. In arterial blood gas analysis, pH 7.39, pCO₂ 30mmHg pO₂ 86mmHg, HCO₃ 18.4mEq/L, O₂ saturation 96.7% were resulted. In urinalysis, specific gravity 1.025, protein 3+, erythrocyte 2+ were resulted. In brain imaging study, brain CT finding was normal. After appropriate treatments with rapid cooling, hydration and supportive care, he improved with alert mental status. On 2nd hospital day, in laboratory result, thrombocytopenia and coagulopathy were appeared and renal insufficiency was aggravated. So he was treated with platelet concentrate and fresh frosen plasma for DIC, and enough hydration for appropriate urine volume preservation. After all, On 22nd hospital day, he fully recovered and discharged. Nowadays, with followed for some duration, he is wellbeing with no complications.

VP-16으로 성공적으로 치료된 위 Kaposi 육종 1예

양웅석,송근암,조몽,이재승,송철수,김형욱,김영민,이수봉,김태오,이성훈 대한소화기내시경학회 1999 Clinical Endoscopy Vol.19 No.4

The skin is an uncommon site of distant metastasis from any internal malignancy, and the incidence of metastatic skin lesions as the first symptom of disease is only 0.8% in patients with all systemic malignancies. Furthermore, cutaneous metastasis from adenocarcinoma of the stomach has been found to be extremely rare. A 35-year-old female patient was admitted due to multiple cutaneous nodules in her chest, abdomen, and back. A gastroendoscopic examination and biopsy was made according to the results of skin pathologic findings. Stomach and skin biopsy results revealed a signet ring cell type of adenocarcinoma. A case of gastric adenocarcinoma in which metastatic skin nodules appeared as the first sign of disease, is here in reported with a review of related literature.

용접공들의 면역능에 관한 연구

이수일,조봉수,김영욱,고광욱,조원근,김영실,강수용,황인경,조병만,김돈균 大韓産業醫學會 1997 대한직업환경의학회지 Vol.9 No.1

The authors examined human immunity indicators such as CD4, CD8, Natural Killer(NK) cell, IgG, IgA, and IgM, and heavy metals such as Pb, Cr, Cd to evaluate the health hazard of welders. We selected total 126 male subjects, 60 welders who had more than 5 year working history as an exposure group, and 66 office workers and medical college students as a control group. This immunity evaluation approach is the first newly designed study that has never been tried in past studies on welder's heath evaluation. And the results were as follows. 1. Total lymphocyte count of peripheral blood was significantly higher in welder group, 2,615±650 ea/㎕ compared with 2,368±681 ea/㎕ in control group(p>0.05). 2. The proportion of CD4, CD8, NK cell in welder group was 37.5±9.4%, 24.0±8.8%, and 21.0±9.5%, respectively, and 35.5±6.5%, 25.0±6.9%, and 19.6±8.8% in control group. CD4 and NK cell were slightly higher, and CD8 was slightly lower in welder group. but there was no statistical significance between two groups(p≥0.05). 3. IgG, IgA, and IgM in welder group were 15.9㎎/㎗, 2.7㎎/㎗ and 1.5㎎/㎗, respectively, and 15.6㎎/㎗, 2.9㎎/㎗ and 1.7㎎/㎗ in control group. There was no statistical significance between two groups(p≥0.05). 4. Blood lead, cadmium and chromium concentrations were 4.2±1.8㎍/㎗, 0.4±0.38㎍/㎗, 1.2±0.6㎍/㎗ in welder group and 3.2±1.7㎍/㎗, 0.44±0.29㎍/㎗, 1.1±0.6㎍/㎗ in control group, respectively, and these value were within normal ranges.

여우 빙의(憑依) 1례

이병욱,김무진,이수일 大韓神經精神醫學會 1989 신경정신의학 Vol.28 No.5

The authors experienced a 50 year-old female patient who manifested so-called fox possession syndrome of 3 days duration, showing fox-like behavior, idea of being possessed and auditory hallucination. She had a recent episode of transient hysteroid dream state with automatic behavior. She was a highly suggestible shamanistic believer, and recently suffering from emotieonal crisis accompanied by frustration, helplessness, loneliness and hostility. Her symptoms were spontaneously subsided without any specific therapeutic intervention.

TV 수신 장해개선에 관한 연구

이수흠,류상욱 慶南大學校 附設 工業技術硏究所 1992 硏究論文集 Vol.10 No.-

TV 화상의 ghost 제거는 현재까지 시행착오적인 방법에 의한 안테나 조정에 의존하여 왔다. 본 연구에서는 이런 점에 착안하여 TV 수신에서의 방해파 위상을 π/2 지연시킨 신호를 합성하는 방법에 의해 이를 제거할 수 있음을 보이고, 실험을 통하여 16㏈ 정도의 방해파 제거효과를 확인함으로써 그 효용성을 입증하였다. It could suppress the undesired signals by adjust the amplitude and phase shift with π/2 of the mixed field intensity that received by the combined system with two antenna which were installed in the constant distance to cancel an undesired signals. The characteristics of the system which were designed by the author were showed that it was cancelled the undesired signal about 16㏈ than the conventional antenna.

農科大學 扶餘 演習林의 植生調査

李壽煜,金智文,宋鎬京 충남대학교 농업과학연구소 1977 農業技術硏究報告 Vol.4 No.2

The experimental forest of Chungnam National University is located in Naryung-Ri, Eunsan-Myen, Buyeo-Gun, Chungcheongnamdo. The climax vegetations of Quercus species grown in central temperate zone are supposed to be destroyed before pure pine stands as a semi-climax vegetation are established on the southern aspect and along the ridges. Variability of vegetations is rather high and dominant species are such as Pinus densiflora, Quercus acutissima, Quercus variabilis, Quercus aliena, Quercus serrata, Lindera erythrocarpa, Platycarya strobilacea, and so on. There are 203 woody plants and 128 herbal plants. According to the use of vegetations they can be classified as follows; 60 familia and 154 species for edible source, 63 familia and 143 species for medicinal, 51 familia and 140 species for forage, 32 familia and 78 species for ornamental, and 12 familia and 27 species for timber source.

리간드교환 크로마토그래피에 의한 DNP-아미노산의 고성능 액체 크로마토그래피적 분리

李善行,吳岱燮,柳在旭,尹水弘 慶北大學校 1984 論文集 Vol.37 No.-

Some derivatized DNP-amino acids can be separated by a ligand exchange chromatography, in which several libile metal chelates are added to the mobile phase of a reversed phase column. Cu^2+, Zn^2+, Cd^2+, or Ni^2+ as a central metal and L-Proline, L-Hydroxyproline, or L-Arginine as a ligand are added to the mobile phase. The DNP-amino acids separated were detected by a UV detector at 360nm. The retention times of the DNP-amino acids are different according to the use of different central metal ions. These behaviors can be explained as a ligand exchange capability. The retention time increased slightly with increase in metal chelate concentration. The separation selctivity was greatly varied with the composition of acetonitrile in the mobile phase. In DNP-amino acid separation, the variation in pH and temperature greatly affect the retention time: the increase in pH or temperature decreases the retention time. Enthalpy and entropy values for the chromatographic retention of the DNP-amino acids are calculated from the retention data by evaluation of Van’t Hoff plots. These values are dependent on the hydrophobic effect and/or ligand exchange capability.

에틸메타크릴레이트의 환경친화적인 광중합특성에 관한 연구

이내우,최재욱,설수덕 釜慶大學校 2001 釜慶大學校 論文集 Vol.6 No.-

Photopolymerization, the utilization of electromagnetic radiation(or light) as the energy source for polymerization of functional monomers, oligomers is the basis of important commercial processes with broad applicability, including photoimaging and UV curing of coatings and inks. The objective of this study is to investigate the characteristics of environmental fraternitive photopolymerization of ethyl methacrylate(EMA). This work is the second step to continue further research about alkyl methacrylate. The experiment has been carred out in aqueous solution under the influence of photo-initiator concentration(0.05∼0.25mol/H_2O_2), light intensity(5000∼9000μJ/cm^2) and monomer concentration(2∼6mol/EMA). EMA was polymerized to high conversion ratio using hydrogen peroxide (H_2O_2), and the kinetics model which we have obtained is as follows. R_P=k_p[S]^0.28[M]^0.41[L]^1.58exp^(33.30/RT) The differential method of thermogravimetric analysis(Friedman method) was used to obtain value of activation energy on decomposition reaction. The average value of it is 31.9 kcal/mol and is similiar to the activation energy of orginal polymerization.

포유동물 배양세포에서 나타나는 일본뇌염바이러스 만성감염의 분자생물학적 기전

이상용,박선희,박수영,윤성욱,정용석 慶熙大學校 1997 論文集 Vol.26 No.-

During undiluted serial passages of Japanese encephalitis virus (JEV) strains Nakayama and K94P05 in mammalian cultured cells, we were able to establish persistent infections both in Vero and BHK-21 cells. Subgenomic-sized defective interfering (DI) RNA, most possibly derived from standard viral genome, was observed by Northern hybridization. The size of the DI RNA was estimated about 3 kb smaller than that of standard JEV and the timing of the DI RNA emergence appeared preceding 1 - 2 weeks of the establishment of viral persistence. Persistently infected and cloned Vero or BHK-21 cells were strongly resistant against homotypic superinfection of JEV but both with reduced cell growth rate. We performed plaque cloning of the viruses released from the persistently infected Vero and sequence analysis of the 3' noncoding region (NCR). Plaque sizes and infectious titer of the cloned viruses were significantly reduced ranging 0.5 - 2.5 mm in diameter and averaged 10^3 pfu/ml, respectively. Sequence analysis revealed that a spectrum of diverse mutations was mainly localized within a specific region encompassing 3' end of the NS5 protein ORF and about 70 nucleotides at the veginning of the 3' NCR. Bath direct identification of the DI in conjunction with the flavivirus persistence and the localization of the specific sequence within 3' NCR as another modifiable targer for the control of virus replication efficiency of virulence are of great significance for the elucidation of the molecular mechanism of flavivirus persistent infection in mammalian and for the designing genetically engineered live-attenuated vaccine for Japanese encephalitis as well.