• Molecules and Cells
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• v.19 no.3
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• pp.350-355
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• 2005

Selectins are carbohydrate-binding cell adhesion molecules that play a major role in the initiation of inflammatory responses. Heparin can bind to P-selectin, and its anti-inflammatory property is mainly due to inhibition of P-selectin. However, the strong anticoagulant activity of heparin limits its clinical use. We prepared periodate-oxidized, borohydride-reduced heparin (RO-heparin) by chemical modification and tested its anticoagulant and anti-inflammatory activities. Activated partial thromboplastin time (aPTT) assays showed that, compared with heparin, RO-heparin had greatly reduced anticoagulant activity. Intravenous administration of this compound led to reduction in the peritoneal infiltration of neutrophils in a mouse acute inflammation model. In vitro cell adhesion experiments demonstrated that the effect of RO-heparin on inflammatory responses was mainly due to inhibiting the interaction of P-selectin with its ligands. These results indicate that RO-heparin may be a safer treatment for inflammation than heparin, especially when selectin is targeted.

• Journal of Yeungnam Medical Science
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• v.40 no.3
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• pp.276-282
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• 2023

Background: Bleeding and thrombosis are major complications associated with high mortality in extracorporeal membrane oxygenation (ECMO) management. Anticoagulant therapy should be adequate to reduce thrombosis. However, related studies are limited. Methods: We retrospectively reviewed all patients supported with ECMO at a single institution between January 2014 and July 2022 and included those on all types of ECMO using the Permanent Life Support System. Patients were classified into two groups according to their measured mean activated partial thromboplastin time (aPTT) during ECMO management: a high-anticoagulation (AC) group (aPTT, ≥55 seconds; n=52) and a low-AC group (aPTT, <55 seconds; n=79). The primary outcome was thrombotic or bleeding events during ECMO. Results: We identified 10 patients with bleeding; significantly more of these patients were in the high-AC group (n=8) than in the low-AC group (15.4% vs. 2.5%, p=0.01). However, thrombus events and oxygenator change-free times were not significantly different between the two groups. Four patients in the high-AC group died of bleeding complications (brain hemorrhage, two; hemopericardium, one; and gastrointestinal bleeding, one). One patient in the low-AC group developed a thrombus and died of ECMO dysfunction due to circuit thrombosis. Conclusion: Heparin did not significantly improve thrombotic outcomes. However, maintaining an aPTT of ≥55 seconds was a significant risk factor for bleeding events, especially those associated with mortality.

• The Korea Journal of Herbology
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• v.26 no.4
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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.

• Microbiology and Biotechnology Letters
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• v.42 no.3
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• pp.302-306
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• 2014

Ehwa nuruk (EN), a traditional Korean alcoholic rice beverage, is manufactured from pulverized wet rice and the needles of pine trees. In this study, the ethanol extract of EN and its subsequent organic solvent fractions were prepared, and their in-vitro anti-thrombosis activity evaluated. In an anti-coagulation assay, only the ethylacetate (EA) fraction of the ethanol extract showed significant extensions of thrombin time, prothrombin time and activated partial thromboplastin time. In a platelet aggregation assay, the water residue of the ethanol extract exhibited aggregation inhibitory activity. Our results suggest that the EA fraction has potential as a new anticoagulation agent and EN could be used as a novel resource for anti-thrombosis agents. This report provides the first evidence of the anti-thrombosis activity of EN.

• Biomolecules & Therapeutics
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• v.7 no.3
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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.

• The Journal of Internal Korean Medicine
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• v.17 no.1
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• pp.34-50
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• 1996

The present experiment was desinged to investigate the effects of Tongdosan water extracts on the Cardiovascular System in the Experimental Animals. Thus, the changes of blood pressure and heart rate were measured after oral admini- stration. Measurment of Mortality rate was observed for measuring the effect of Tongdosan water extract. Tongdosan water extract against pulmonary thrombo- embolism induced by collagen the mixture(0.1ml/10g, 2mg/kg B.W) plus serotonin(5mg/kg B.W) in mouse. The effect of Tongdosan water extract was examined by observing the change of collagen-induced platelet aggregation, coagulation activity, ex vivo and in vitro fibrinolytic activity of euglobulin fraction in rats. The results were summarized as followings. 1. Tongdosan dropped the blood pressure in spontaneous hypertensive rat. 2. The drug increased the auricular blood flow in rabbit. 3. The drug relaxed the artery contraction by pretreated norepinephrine in rat. 4. The drug inhibited the death rate of mouse which was led to thromboembo- lism by serotonin and collagen. 5. The drug inhibited the platelet aggregation in rat. 6. The drug prolonged the prothrombin time and activated partial thromboplastin time on the test of plasma coagulation factor activity in rat, but was not valuable. 7. The drug reduced the fibrinogen lyses time of rat ex vivo assay and lyses area was increased. 8. Tongdosan reduced fibrinogen lyses time of rat in vitro assay. According to the above mentioned results, Tongdosan increased the blood flow and dropped the blood pressure by the dilation of blood vessel. And the drug presented the antithrombin acivity, inhibited the platelet aggregation.

• The Journal of Internal Korean Medicine
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• v.18 no.1
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• pp.69-85
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• 1997

This study was designed to elucidate the anti-inflammatory, cardiovascular, anti-thrombotic and analgesic effects of Shintongchugeotang. The anti-inflammatory effect was measured by the method of carragenin induced edema, protein leakage test using CMC-pouch, and the analgesic effect was measured by the acetic acid method and hot plate method, and the effect of Shintongchugeotang on the cardiovascular system was observed by the change of flow rate of Ringer solution in the vascular system in the ear of rabbit, and the contraction and dilatation of rat tail artery. Death rate, platelet aggregation, plasma coagulation activity was observed for the measurement of the anti-coagurative effect of Shintongchugeotang. The result was as follows : 1. After the administration of Shintongchugeotang extract, Carragenin induced edema and CMC-pouch protein leakage were significantly decreased. 2. The slight analgesic effect of Shintongchugeotang extract was confirmed by the observation of writhing syndrome, paw licking time, and escape time. 3. The drug increased the auricular blood flow in rabbit. 4. The drug relaxed the artery contraction by pretreated norepinephrine in rat. 5. The drug inhibited the death rate of mouse which was led to thromboembolism by serotonin and collagen. 6. The drug inhibited the platelet aggregation in rat. 7. The drug prolonged the prothrombin time and activated partial thromboplastin time on the test of plasma coagulation factor activity in rat, but was not valuable.

• The Journal of Internal Korean Medicine
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• v.18 no.1
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• pp.97-113
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• 1997

The present experiment was designed to investigate the effects of Sambutang water extracts on the serum cholesterol levels and the cardiovascular system in the experimental animals. Thus, the changes of blood pressure and heart rate were measured after oral administration. Measurment of Mortality rate was observed for measuring the effect of Sambutang water extract. Sambutang water extract against pulmonary thromboembolism induced by collagen the mixture(0.1 ml/10 g, 2 mg/kg) plus serotonin(5 mg/kg) in mouse. The effect of Sambutang water extract was examined by observing the change of collagen-induced platelet aggregation, coagulation activity, ex vivo and in vitro fibrinolytic activity of euglobulin fraction in rats. The results were summarized as follows. 1. Sambutang decreased the serum cholesterol levels in rats. 2. Sambutang dropped the blood pressure in spontaneous hypertensive rat. 3. The drug increased the auricular blood flow in rabbit. 4. The drug relaxed the artery contraction by pretreated norepinephrine in rat. 5. The drug inhibited the death rate of mouse which was led to thromboembolism by serotonin and collagen. 6. The drug inhibited the platelet aggregation in rat. 7. The drug prolonged the prothrombin time and activated partial thromboplastin time on the test of plasma coagulation factor activity in rat, but was not valuable. 8. The drug increased the antithrombin activity in rat and the fibrinogen lysis time was reduced and lysis area was increased. 9. Sambutang reduced fibrinogen lysis time of rat in vitro assay. According to the above mentioned results. Sambutang increased the blood flow and dropped the blood pressure by the dilation of blood vessel. And the drug presented the antithrombin activity, inhibited the platelet aggregation.

• Journal of Pharmacopuncture
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• v.18 no.4
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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.

• The Journal of Internal Korean Medicine
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• v.16 no.1
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• pp.197-213
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• 1995

The present experiment was desinged to investigate the effects of Sopungtang water extracts on the Cardiovascular System in the Experimental Animals. Thus, the changes of blood pressure and heart rate were measured after oral administration. Measurments of Mortality rate were observed for measuring the effect of Sopungtang water extract. Sopungtang water extract against pulmonary thromboembolism induced by collagen the mixture(0.1ml/10g, 2mg/kg B.W) plus serotonin(5mg/kg B.W) in mouse. The effects of Sopungtang water extract were examined by observing the change of collagen-induced platelet aggregation, coagulation activity, ex vivo and in vitro fibrinolytic activity of euglobulin fraction in rats. The results were summarized as followings. 1. Sopungtang dropped the blood pressure in spontaneous hypertensive rat. 2. The drug increased the auricular blood flow in rabbit. 3. The drug relaxed the artery contraction by pretreated norepinephrine in rat. 4. The drug inhibited the death rate of mouse which was led to thromboembolism by serotonin and collagen. 5. The drug inhibited the platelet aggregation in rat. 6. The drug prolonged the prothrombin time and activated partial thromboplastin time on the test of plasma coagulation factor activity in rat, but was not valuable. 7. The drug increased the antithrombin activity in rat and the fibrinogen lyses time was reduced and lyses area was increased. 8. Sopungtang reduced fibrinogen lyses time of rat in vitro assay. According to the above mentioned results, Sopungtang increased the blood flow and dropped the blood pressure by the dilation of blood vessel. And the drug presented the antithrombin acivity, inhibited the platelet aggregation.