• 대한임상독성학회지
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• 제12권2호
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• pp.92-96
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• 2014

Dabigatran is the first oral direct thrombin inhibitor approved by the US Food and Drug Administration (FDA) for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Because dabigatran is excreted mainly by the kidneys, serum levels of dabigatran can be elevated to a supratherapeutic range in patients with renal failure, predisposing to emergent bleeding. We describe the case of a 66-year-old man taking dabigatran 150 mg twice daily for atrial fibrillation and cerebral infarction who presented with hematochezia and disseminated intravascular coagulation. Laboratory evaluation showed a hemoglobin level of 6.3 g/dL, platelets of $138,000/mm^3$, activated partial thromboplastin time (aPTT) of 10 s, and an international normalized ratio (INR) of 8.17. Colonoscopy showed a bleeding anal fissure. Hemostasis was provided by hemoclips and packed red blood cells and fresh frozen plasma were transfused. Since then, there was no further hematochezia, however, bleeding including oral mucosal bleeding, hematuria, and intravenous site bleeding persisted. At presentation, his serum creatinine was 4.96 mg/dL (baseline creatinine, 0.9 mg/dL). Dabigatran toxicity secondary to acute kidney injury was presumed. Because acute kidney injury of unknown cause was progressing after admission, he was treated with hemodialysis. Fresh frozen plasma transfusion was provided with hemodialysis. At 15 days from admission, there was no further bleeding, and laboratory values, including hemoglobin, partial thromboplastin time, and prothrombin time were normalized. He was discharged without bleeding. After 2 months, he undergoes dialysis three times per week and no recurrence of bleeding has been observed.

• Journal of Chest Surgery
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• 제31권10호
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• pp.952-963
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• 1998

연구배경 : 체외 순환으로 인한 지혈 기전의 심각한 손상은 술후 과다 출혈을 일으켜 환자의 생명을 위협하고, 대량 수혈에 따른 부작용과 재수술의 우려마저 증가시킬 수 있다. 특히, 심장 수술동안 섬유소 용해계의 활성화와 혈소판의 숫적, 기능적 변화가 술후 상당 시간동안 출혈의 원인이 된다고 보고하고 있다 대상 및 방법 : 본 연구는 체외 순환 동안 및 그 후에 있어, 체외 순환에 의한 섬유소 용해계의 활성화를 포함한 다양한 혈액학적 변화를 조사하고, 이러한 변화들이 술후 비외과적 출혈의 정도와 어떤 상관성이 있는가를 규명하기위해 체외 순환을 실시할 성인 환자 20명을 대상으로 전향적으로 계획되었다. 혈소판 수, 섬유소원 및 plasminogen 농도, FDP, D-dimer, BT, aPTT, PT와 같은 혈액학적 변수의 측정을 위해 수술동안 또는 술후 시기에 혈액을 연속적으로 채취하였다. 출혈량은 흉부 삽관을 통한 배출량을 술후 3, 6, 12, 24, 48시간의 양과 총혈액량을 각각 측정하였다. 결과 : 연구 결과를 요약하면 다음과 같다:혈소판 수는 체외 순환으로 인해 급격히 감소되었다 (p<0.01). 총 체외 순환 시간이 길수록 혈소판 수의 감소률은 더 높았으며 (r=0.55, p=0.01) 술후 7일이 되어서야 비로소 술전치에 근접하였다. 체외 순환동안 FDP와 D-dimer의 농도가 의미있게 증가하였고 (p<0.0001), 섬유소원 및 plasminogen 농도 둘 다 서로간에 상관성을 보이면서 감소하였다 (r=0.57, p<0.01). 술후 2hr-BT, 2hr-PT, 2hr-aPTT 모두 술전치에 비해 유의하게 연장되었다(각각 p<0.05, p<0.0001, p<0.0001). 술후 총 출혈량과 환자의 연령, 대동맥 차단 시간, 체외 순환 시간은 각각 양의 상관관계 (positive correlation)가 있었다. 술전 기준치 혈소판 수와 술후 3시간 출혈량, 체외 순환 종료시의 혈소판 수와 술후 3시간, 6시간 및 총 출혈량 그리고 술후 1일의 혈소판 수와 48시간 출혈량 사이에는 각각 음의 상관관계 (negative correlation)가 있었다. 술후 2hr-aPTT는 술후 6시간 및 48시간대의 출혈량에 상관성이 있었고 (r=0.53, p=0.02) 술후 2hr-PT는 48시간 출혈량과 각각 양의 상관성이 있었으나 (r=0.43, p=0.05). 이 두가지 변수와 총 출혈량 간에는 상관성이 없었고, 술후 2hr-BT와 술후 출혈량 사이에도 유의한 상관성을 발견하지 못하였다. 결론 : 이상의 관찰 결과들은 체외 순환이 섬유소 용해계의 활성화와 혈소판 수의 심한 감소를 포함한 다양한 혈액학적 변화를 유도하고 환자의 연령, 혈소판 수, 대동맥 차단 시간, 체외 순환 시간, 술후 PT 및 aPTT와 같은 다인적 상황들이 술후 출혈에 영향을 미친다는 점들을 시사하고 있다. 본 연구 결과들은 체외 순환에 따른 지혈적 손상에 관한 이해와 술후 출혈을 감소시키기 위한 기초 자료로 활용 가능하리라 사료된다.

• 대한본초학회지
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• 제26권4호
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• pp.139-147
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• 2011

Objectives : The aim of this study is to research an anti-thrombus effect by Diospyros Kaki Calyx. Methods : The healthy human plasma were gained and used in vitro study such as factor X activity (FXa) inhibition, prothrombinase inhibition, prothrombin time (PT) and activated partial thromboplastin time. Fifteen SD rats were divided into three groups ; intact control group (orally administrated with distilled water 5ml/kg) and two experimental group treated with extract of diospyros kaki calyx (EKC). Experimental rats were orally 600 mg/kg concentration of EKC and 200 mg/kg concentration of EKC. After an hour from administration, we anesthetized rats and made arteriovenous (AV) shunt rat models to study weight of thrombus, took whole blood to study content of thromboxane B2 and blood clotting time. Results : In vitro, EKC significantly increased inhibitory activity of FXa, prothrombinase compared with intact control group ($^*P$ <0.05). PT and aPTT were increased in EKC treated (600 mg/kg) group compared with intact control group ($^*P$ <0.05). In vivo, blood clotting time of experiment group treated with EKC 600 mg/kg were significantly increased compare with that of intact control group (p<0.05) and content of thromboxane B2 was significantly decreased in group treated with EKC 600 mg/kg in serum. The weight of thrombus were significantly reduced in group treated with EKC 600 mg/kg compared with intact control group (p<0.05). But in vivo experiment study, those parameters of group treated with EKC 200 mg/kg were relatively decreased compared with those of intact control group without statistical significance. Conclusions : EKC has an antithrombic activity because of inhibition internal course such as FXa and prothrombin. And EKC inhibited a hole blood clotting in vivo experiment by low content of thromboxane B2.

• 한국미생물·생명공학회지
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• 제42권3호
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• pp.302-306
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• 2014

이화누룩은 증자하지 않은 쌀을 물에 불린 후 분쇄하고, 이를 솔잎으로 띄워 발효시킨 한국 전통누룩이다. 이화누룩의 기능성을 평가하기 위해 이화누룩의 에탄올 추출물과 이의 순차적 유기용매 분획물을 조제하고 항혈전 활성을 평가하였다. 그 결과, ethylacetate 분획물은 강력한 thrombin time, prothrombin time, aPTT 연장효과를 나타내었으며, 유기용매 분획후의 물 잔류물에서는 강력한 혈소판 응집저해능이 확인되었다. 본 연구결과는 이화누룩의 ethylacetate 분획이 신규의 항혈전제로 사용 가능함을 나타내며, 이는 이화누룩의 항혈전 활성에 대한 최초의 보고이다.

• Biomolecules & Therapeutics
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• 제7권3호
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• pp.271-277
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• 1999

Safety evaluation of LB71350, a new HIV-1 protease inhibitor, was performed in mice, rats and dogs. For the general behavior of mice, LB71350 at an oral dose of 200 mg/kg did not show any significant effects on muscle tone and locomotor activity. In terms of central nervous system, at oral doses of 200 mg/kg and 1000 mg/kg, LB71350 inhibited acetic acid-induced pain response approximately 41% and 83% of control. respectively. At oral doses of 200 mg/kg and 500 mg/kg, it reduced the rectal body temperature in rats. Pentylenetetrazole-induced seizure in mice was slightly potentiated by oral administration of LB71350 at doses ranging from 200 mg/kg to 1000 mg/Ag. Single or five day treatment of LB71350 doubled the hexobarbital- induced sleeping time in mice at oral doses ranging from 50 mg/kg to 500 mg/kg. It did not cause any effects on gastric secretion and acidity in rat at oral doses of 200 mg/kg and 1000 mg/kg and also it did not change intestinal motility in mice up to 1000 mg/kg. Blood coagulation indices such as prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT) in rats were not affected by the treatment of LB71350 up to 500 mg/kg. LB71350 caused no significant effects on the cardiac output, stroke volume, heart rate, and mean blood pressure when infused intravenously to the anesthetized rats and dogs. Taken together, LB71350 at high oral doses caused significant pharmacological effects on the central nervous system and the hexobarbital-induced sleeping time.

• 대한약침학회지
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• 제18권4호
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• pp.7-11
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• 2015

Objectives: Bee venom (BV) is a complex mixture of proteins and contains proteins such as phospholipase and melittin, which have an effect on blood clotting and blood clots. The mechanism of action of honey bee venom (HBV, Apis mellifera) on human plasma proteins and its anti-thrombotic effect were studied. The purpose of this study was to investigate the anti-coagulation effect of BV and its effects on blood coagulation and purification. Methods: Crude venom obtained from Apis mellifera was selected. The anti-coagulation factor of the crude venom from this species was purified by using gel filtration chromatography (sephadex G-50), and the molecular weights of the anti-coagulants in this venom estimated by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Blood samples were obtained from 10 rabbits, and the prothrombin time (PT) and the partial thromboplastin time (PTT) tests were conducted. The approximate lethal dose (LD) values of BV were determined. Results: Crude BV increased the blood clotting time. For BV concentrations from 1 to 4 mg/mL, clotting was not observed even at more than 300 seconds, standard deviations $(SDs)={\pm}0.71$; however, clotting was observed in the control group 13.8 s, $SDs={\pm}0.52$. Thus, BV can be considered as containing anti-coagulation factors. Crude BV is composed 4 protein bands with molecular weights of 3, 15, 20 and 41 kilodalton (kDa), respectively. The $LD_{50}$ of the crude BV was found to be $177.8{\mu}g/mouse$. Conclusion: BV contains anti-coagulation factors. The fraction extracted from the Iranian bees contains proteins that are similar to anti-coagulation proteins, such as phospholipase $A_2(PLA_2)$ and melittin, and that can increase the blood clotting times in vitro.

• 대한임상독성학회지
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• 제7권2호
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• pp.90-96
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• 2009

Purpose: This study explored and evaluated the systemic complications resulting from the bite of Korean venomous snake, focussing on hematologic and neurologic features. Methods: Medical records (demographic data, clinical measurements including laboratory results, severity score, and amount of antidote administration, and hospitalization course) of consecutive patients who presented with snakebites to two university teaching hospital during a 10-year period were retrospectively reviewed. Subgroup analysis was conducted for evaluations of anti-acetylcholine esterase administration in complicated victims. Results: The 170 patients displayed occurrence rates of hematologic and neurologic complications of 12.9% and 20.6%, respectively. Among 22 patients with hematologic complications, isolated thrombocytopenia was evident in eight patients (36.4%), prothrombin time (PT) / activated partial thromboplastin time (aPTT) prolongation in 11 patients (50.0%), and both in three patients (13.6%). The mean time to recovery was $4.5{\pm}1.8$ days for isolated thrombocytopenia, and $5.1{\pm}1.8$ days for PT and aPTT prolongation. Hematologic complications could occur suddenly 1?4 days after hospitalization. Among 35 patients with neurologic complications, dizziness was evident in 16 patients (45.7%), and diplopia / blurred vision in 19 patients (54.3%). The mean time to recovery was $3.4{\pm}0.6$ days in patients receiving anti-acetylcholine esterase and $6.9{\pm}1.8$ days in those not receiving anti-acetylcholine esterase (p=0.00). Conclusion: Occurrence rates of hematologic and neurologic complications following venomous snake bite differed as compared to other studies conducted in Korea. Onset of hematologic complications can occur rapidly days after admittance. Anti-acetylcholine esterase administration may be effective in treating neurologic complications.

• Journal of Trauma and Injury
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• 제29권4호
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• pp.99-104
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• 2016

Purpose: There are many patients visited to ED in an alcohol intoxicated state. For these patients, it is difficult to predict by only clinical examination whether he/she would have brain lesion. The purpose of this study is to research whether it is possible to predict brain lesion by only clinical examination findings, with comparing patients with/without actual brain lesions. Methods: A retrospective study was performed at a university hospital for the period 11 months with the medical records. As for the inclusion group, head trauma patients with objectively proved drunk, judging by their blood ethanol concentration, and performed the brain CT were selected. In terms of medical record, Glasgow coma scale (GCS), the presence of neurologic abnormalities, the presence of lesion on brain CT of the patients, were examined. From laboratory results, blood ethanol concentration, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT) and glucose concentration were identified. Results: For this study, there were total 80 patients of inclusion group. There was no statistically significant difference in terms of GCS score and neurological examination abnormalities, between the group with brain lesion and the group without brain lesion on brain CT. Conclusion: Alcohol intoxicated patient with head trauma visits the ED, it is not possible to distinguish or determine whether brain lesion exists or not by only clinical findings. In order to check the lesion existence, the image examination, therefore, should be considered and performed.

• 대한의생명과학회지
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• 제14권4호
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• pp.219-223
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• 2008

The present study was designed to clarify whether scuba diving at 5 meters of seawater influences cerebral hemodynamics, hematological and biochemical variables. Twenty healthy young men well trained scuba diving participated in this study. The blood flow velocity in the right and left middle cerebral arteries (L-MCAV and R-MCAV), blood pressure (BP), heart rate (HR), CBC and differential count, prothrombin time (PT), activated partial thromboplastin time (aPTT), biochemical variables, D-dimer and interleukin-8 (IL-8) levels were determined before, immediately after scuba diving for 30 min, and after 30 min of rest (Pre-scuba, Scuba and R-30m, respectively). L-MCAV and R-MCAV tended to increase, but the only significant increase was in L-MCAV in Scuba. SBP and HR significantly declined in R-30m compared with those of Pre-scuba and the Scuba. IL-8 levels were elevated in Scuba and R-30m compared with that of Pre-scuba. In Scuba and R-30m, hematological variables except PT and biochemical parameters excluding glucose and lactic acid did not significantly changed in comparison with those of Pre-scuba. PT level at Scuba and glucose level at R-30m significantly declined in Scuba, while lactate level at R-30m increased compared with each in Pre-scuba. However, PT level at Scuba was within a normal range. These results suggest that scuba diving at 5 m of seawater for 30 min has no adverse effects, is safe and useful for improving health. However, further study must be performed to clarify the mechanism of elevated IL-8 level following scuba diving.

• 대한예방한의학회지
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• 제2권1호
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• pp.193-208
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• 1998

In order to study the effects of emitted-qi therapy, Youngyeonondamtang and Jeokyeonondamtang on the mice bearing ascites cancer caused by Sarcoma 180, the author divided the mice into normal group, control group, EQ group, YO group, JO group, CTX+QE group, CTX+YO group, CTX+JO group, and treated with emitted -qi therapy and administrated Youngyeonondamtang, Jeokyeononondaintang and Cyclophosphamide (CTX). After collecting blood from the mice, measured the values of Prothrombin Time(PT), Partial Thromboplastin Time(PTT), Fibrinogen, White Blood Cell(WBC) and Platelet. The results were as follows, 1. PT was not showed any significant change in ever)r group, being compared with the control group. 2. H increased significantly in YO group, being compared with the control group. 3. Fibrinogen decreased significantly in EQ group, YO group, CTX+EQ group, CTX+YO group, CTX+JO group, being compared with the control group. 4. WBC increased significantly in CTX+EQ group, CTX+YO group, CTX+JO group, being compared with the CTX group. 5. Platelet decreased significantly in every group, being compared with the control group. These results suggest that emitted-qi therapy, Youngyeonondamtang and Jeokyeonondamtang had the effects that could heal the hematopoiesis system in the mice bearing ascites cancer, and especially had the better effects in the case that hematopoiesis system has been impaired by CTX.