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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).
Celecoxib 유도체인 PCX-계열 화합물의 항염증 및 혈관신생 억제 작용
소지현,안은경,전혜진,임은주,박은희 숙명여자대학교 약학연구소 2005 약학논문집-숙명여자대학교 Vol.22 No.-
This study aimed to evaluate the pharmacological efficacies of PCX-series compounds, which were synthesized as prodrugs of celecoxib, a COX-2 selective inhibitor. Celecoxib, PCX-1, PCX-2, PCX-3, PCX-7, PCX-15 and PCX-16 provide potent anti-angiogenic activity in chorioallantoic membrane (CAM) assay. In addition, celecoxib, PCX-2, and PCX-16 showed anti-angiogenic activity in a dose-dependent manner. PCX-2 inhibited swelling in the carrageenan-induced rat paw edema test 24 hours after the administration. In the acetic acid-induced writhing test, PCX-7 and PCX-15 were verified to provide more potent analgesic effect than celecoxib 12 hours after the administration, and PCX-2 showed potent analgesic effect 24 hours after the administration. In the carrageenan-induced rat air pouch model, PCX-2 significantly decreased exudate volume, number of leukocyte and NO level. In the ulcerogenic activity test, PCX-2, PCX-7, PCX-15, and PCX-16 showed significantly less ulcer formation than indomethacin. Especially, PCX-7 showed the highest safety in the GI safety test. These findings provide novel pharmacological knowledge on pharmacological actions of celecoxib and its PCX-series compouds.
Aspiration pneumonia caused by fentanyl-induced cough -a case report-
Kyung Jee Lim,박은영,강매화,이수경,Hyo Min Lee,Man Ho Kim,Yi Seul Kim 대한마취통증의학회 2013 Korean Journal of Anesthesiology Vol.65 No.3
Although fentanyl-induced cough is generally transient and benign, it can give rise to serious problems in patients to whom increasing intracranial, intraocular or intraabdominal pressures may create dangerous situations. This case demonstrates aspiration pneumonia as a complication, exhibiting severe cough induced by intravenous injection of fentanyl.
( Kyung Jee Lim ),( Soo Ryun Kim ),( Seung Ju Kim ),( Seon Joo Kim ),( Soo Kyung Lee ),( Hyun Soo Moon ),( Sung Wook Park ),( Hwa Ja Kang ) 경희대학교 경희의료원 2015 慶熙醫學 Vol.30 No.1
Purpose: To determine the target effect-site concentration of propofol required to substitute a ProSeal laryngeal mask airway (PLMA) for an endotracheal tube for providing suitable emergence condition in adult undergoing neurosurgery. Methods: Anaesthesia was maintained with propofol and remifentanil using target controlled infusion (TCI). After end of surgery, predetermined effect-site concentration of propofol (the starting target concentration of 3.5 μg/ml) and remifentanil 2 ng/ml was held for 10 min. A patient’s response to the endotracheal tube/ PLMA exchange was described as ‘successful’ or ‘unsuccessful’. The propofol concentration of each patient was determined by a modification of Dixon’s up-and.down method steps by 0.5 μg/ml and concentration for exchange in 50% and 95% patients were obtained by a logistic regression model. Results: The target effect-site concentration of propofol required for successful endotracheal tube/ PLMA exchange in 50% of patients was 3.86±0.21 μ g/ml and the time from an exchange till the removal of LMA was 8.4±5.8 min. Conclusions: The effect-site concentration of propofol required for endotracheal tube/PLMA exchange in 95% of patients is 4.50 μg/ml.
( Kyung Jee Lim ),( Seung Ju Kim ),( Sang Jun Lee ),( Woon Suk Hwang ),( Eun Young Park ),( Hyun Soo Moon ),( Soo Kyung Lee ),( Geon Sik Kim ) 경희대학교 경희의료원 2015 慶熙醫學 Vol.30 No.1
Purpose: Total knee arthroplasty (TKA) is associated with a considerable amount of blood loss and frequently entails allogeneic transfusion. This study was designed to evaluate the effect of perioperative intravenous iron therapy on the transfusion requirements inpatients undergoing unilateral TKA. Methods: Sixty-four patients classified as ASA physical status 1 or 2 scheduled for elective unilateral TKA were studied. Thirty-two patients scheduled for unilateral TKA were given 300 or 400 mg of intravenous iron sucrose perioperatively (iron group). A previous series of 32 patients who had undergone the same surgery without intravenous iron served as the control group. Allogeneic transfusion was indicated when the hemoglobin (Hb) level fell below 10 g/dL or patients became symptomatic of acute anemia. Results: Although no statistically meaningful difference in the allogeneic transfusion rate was noticed, the transfusion index in the iron group was lower than in the control group (1.3 vs. 1.8 units/patient, P<0.05). Hb levels measured at discharge were significantly higher in the iron group compared with the control group (11.7 vs. 10.9 g/dL, P<0.001). Conclusion: Perioperative administration of intravenous iron is a safe and effective method of reducing allogeneic blood transfusion in TKA patients.
아세틸 - 엘 - 카르니틴 정제의 생물학적 동등성 평가
박경미(Kyung Mi Park),이미경(Mi Kyung Lee),신지영(Jee Young Shin),우종수(Jong Soo Woo),임수정(Soo Jeong Lim),임윤영(Yoon Young Lim),김종국(Chong Kook Kim) 한국응용약물학회 2001 Biomolecules & Therapeutics(구 응용약물학회지) Vol.9 No.4
N/A Bioequivalence of two acetyl-l-carnitine tablets, test product (Carnitile tablet: Hanmi Pharm. Co., Ltd.) and reference product (Nicetile^? tablet: Dong-A Pharm. Co., Ltd.), was evaluated according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-six healthy volunteers were divided randomly into two groups and administered the drug orally at the dose of 500㎎ as acetyl-l-carnitine in a 2×2 crossover study. Blood samples were taken at predetermined time intervals for 12 hours and the plasma concentration of acetyl-l-carnitine was determined using HPLC by derivatization with p-bromophenacyl bromide. The pharmacokinetic parameters (AUC_(0-12h), C_max, and T_max.) were calculated and ANOVA was utilized for the statistical analysis of parameters. The apparent differences of these parameters between two drugs were less than 20% (i.e., 1.26, -5.08 and 8.59% for AUC_(0-12h), C_max, and T_max, respectively). The powers (1-β) for AUC_(0-12h), C_max and Tmax were over 0.9. Minimal detectable difference (Δ) at α=0.05, I-β=0.8 were less than 20% (i.e., 7.31, 14.88 and 11.77% for AUC_(0-12h), C_max, and T_max, respectively). The confidence intervals (δ) for these parameters were also within ± 20% (i.e., -3.03≤δ≤5.54, -13.80≤δ≤3.64 and 1.69≤δ≤15.48 for AUC_(0-12h), C_max, and T_max, respectively). These results satisfied the criteria of KFDA guideline for bioequivalence, indicating Carnitile bioequivalent to Nicetile^?