• Title/Summary/Keyword: $\alpha$-thrombin

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Activation of Fibrinolytic System during Open Heart Surgery (개심술중 섬유소융해계의 활성화에 관한 연구)

  • Park, Lee-Tae;Seo, Gyeong-Pil;Lee, Jeong-Sang
    • Journal of Chest Surgery
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    • v.22 no.4
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    • pp.525-547
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    • 1989
  • Hemorrhagic tendency observed in open heart surgery patients has been attributed, among other causes, to increased fibrinolytic activity during extracorporeal circulation. But the exact mechanism of enhanced fibrinolytic activity which occurs during extracorporeal circulation is still unknown. So, we studied and compared the changes of parameters of fibrinolytic and protein C system according to time obtained from the plasma of 31 adult open heart surgery patients[EGG group] and 10 adult general thoracic surgery patients[control group], in order to confirm the hypothesis that the activated protein C system might affect the fibrinolytic system during extracorporeal circulation. In ECC group, the nature of the enhanced fibrinolytic activity that evolved during extracorporeal circulation was characterized by significant increase in fibrin degradation products[P < 0.01] and significant decrease in plasminogen and alpha2-antiplasmin[P < 0.05, P < 0.01] in spite of adequate amount of heparin administration. These changes were most pronounced in the early phase of extracorporeal circulation and normalized after termination of extracorporeal circulation. The results of these observations were the same after volume correction with the value of hematocrit. The change of volume corrected protein C ratio during extracorporeal circulation revealed similar pattern to those of plasminogen and alpha2-antiplasmin [P < 0.01], but volume corrected ratio of free protein S showed significant increase after the commencement of extracorporeal circulation then decreased after extracorporeal circulation. Although the above mentioned changes occur similarly in both bubble type oxygenator-used and membrane oxygenator-used patients groups, but the degree of decrease was more severe in membrane oxygenator-used patients group [P < 0.01] and showed much slower recovery to reach to the preextracorporeal circulation level. These results confirm the hypothesis that the enhanced fibrinolysis during extracorporeal circulation might be caused by the activation of protein C system and the activation is possibly linked to the appearance of thrombin from contact activation of blood after wide exposure to the synthetic surfaces of extracorporeal circuit. Key words: Extracorporeal circulation, Enhanced fibrinolysis, Protein C system.

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Effect of Soluble EPCR on the Anti-Inflammatory Effects by Activated Protein C (수용성 EPCR에 의한 활성화된 단백질 C의 항염증 작용에 관한 연구)

  • Bae, Jong-Sup;Park, Moon-Ki;Park, Sang-Wook
    • Korean Chemical Engineering Research
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    • v.47 no.4
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    • pp.501-505
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    • 2009
  • In this study, we evaluated the effect of soluble EPCR(Soluble Endothelial Protein C Receptor, sEPCR) on the anti-inflammatory activities by activated protein C(APC) in endothelium. We demonstrated that sEPCR inhibited the barrier protective activity, the inhibition of neutrophils adhesion toward endothelial cells and the inhibition of transendothelial migration by APC in endothelial cells. Interestingly, sEPCR also blocked the mechanism by which APC inhibited the expression of cell adhesion molecules(CAM) by TNF-alpha in endothelial cells. These results suggested that the anti-inflammatory activities of APC was inhibited by sEPCR which blocked the binding motifs of Gla domain of APC to membrane bound EPCR. This finding will provide the important evidence in the development of new medicine for the treatment of severe sepsis and inflammatory diseases and good clue for understanding unknown mechanisms by which APC showed the anti-inflammatory activities in endothelium.

Evaluation of Useful Biological Activities of Hot-Water Extracts of Raw-Red Bean and Boiled-Red Bean (Phaseolus radiatus L.) (생팥 및 삶은 팥의 열수 추출물의 유용 생리활성 평가)

  • Jung, In-Chang;Lee, Ye-Seul;Kang, Dong-Kyoon;Sohn, Ho-Yong
    • Journal of the East Asian Society of Dietary Life
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    • v.25 no.3
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    • pp.451-459
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    • 2015
  • Raw-red bean (RR) should be boiled in hot water, and only boiled-red bean (BR) has been used in the food industry. In the course of development of functional food using red- bean (Phaseolus radiatus L), hot- water extracts (HWEs) of RR and BR were prepared, respectively and their components and various biological activities were compared. The extraction yield at $100^{\circ}C$ of RR (16.2%) was higher than that of BR (14.8%), and contents of total polyphenols, total flavonoids and reducing sugars of HWE of RR were 2.5-fold, 2.1-fold and 1.5-fold higher than those of HWE of BR. In anti-oxidation activity assay, scavenging activities against DPPH anion and ABTS cation as well as reducing power of RR was higher than those of BR. The results suggest that the anti-oxidant compounds in red bean might be heat-liable or discarded during boiling in hot-water as a cooking drip. Unexpectedly, nitrite scavenging activity was stronger in HWE of BR than RR. In anti-microbial activity assay, HWE of RR ($500{\mu}g/disc$) showed growth inhibition activity against gram-positive bacteria, whereas HWE of BR did not show any activity against any tested bacteria and fungi. Assay of in-vitro anti-diabetes and anti-thrombosis activities, which were previously reported in ethanol extract of red-bean, revealed that HWEs of RR and BR did not show significant activities against ${\alpha}$-amylase, ${\alpha}$-glucosidase, thrombin, prothrombin, or blood coagulation factors. Our results suggest that the anti-oxidation, anti-diabetes and anti-thrombosis activities of HWEs of RR and BR were lower than those of ethanol extracts of red bean, and bioactive substances in RR were destroyed during boiling or discarded after boiling. Further research on suitable boiling and re-use of cooking drip of red bean is necessary.

Effects of the Dosing Regimen of Tissue-type Plasminogen Activator on Blood Coagulation System in Experimental Pulmonary Embolism (실험적 폐색전증에서 조직형플라스미노겐활성체의 투여방법이 혈액응고기전에 미치는 영향)

  • Chung, Hee-Soon;Kim, Ho-Joong;Shim, Young-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.40 no.5
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    • pp.474-482
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    • 1993
  • Background: As a physiologic plasminogen activator, tissue-type plasminogen activator (t-PA) could induce effective thrombolysis in massive pulmonary embolism, without the risk of systemic hemorrhage. However, therapeutic doses of t-PA has been associated with systemic lytic state, and fibrin selectivity may be influenced by the dosing regimen of t-PA. To investigate the effects of duration of t-PA infusion on blood coagulation system, we performed this study. Method: In a canine model of pulmonary embolism, which was induced by injection of autologous blood clots, we administered equal doses of t-PA (1 mg/kg) over 15 minutes in $t-PA_{15}$ group, over 180 minutes in $t-PA_{180}$ group, and only saline in control group. Then serial blood samplings were made to check complete blood count, prothrombin time, activated partial thromboplastin time, thrombin time, fibrin, plasminogen, ${\alpha}_2$-antiplasmin, coagulation factor V and VIII, and fibrin(ogen) degradation products. Results: 1) In all 3 groups, complete blood count showed same changes. Hemoglobin, hematocrit and platelet count decreased, but WBC count increased. 2) Prothrombin time, activated partial thromboplastin time, and thrombin time were prolonged during 15-60 minutes after t-PA administration in $t-PA_{15}$ group, and from 30 minutes through 180 minutes after administration in $t-PA_{180}$ gorup. 3) Fibrin, ${\alpha}_2$-antiplasmin, and cogulation factor V and VIII decreased in both $t-PA_{15}$ and $t-PA_{180}$ group, but returned to basal levels earlier in $t-PA_{15}$ group. 4) Fibrin(ogen) degradation products increased after pulmonary embolism in all groups, and further increased in both $t-PA_{15}$ and $t-PA_{180}$ groups after t-PA infusion. But more pronounced increment was noted in $t-PA_{180}$ gorup. Conclusion: In pulmonary embolism, the shorter (15 minutes) infusion of t-PA would have less risk of systemic hemorrhage than the longer (180 minutes) infusion when the doses is equal. And, this suggests that manipulating the duration of t-PA infusion can reduce the risk of major bleeding.

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Purification and Characterization of a New Fibrinolytic Enzyme of Bacillus licheniformis KJ-31, Isolated from Korean Traditional Jeot-gal

  • Hwang, Kyung-Ju;Choi, Kyoung-Hwa;Kim, Myo-Jeong;Park, Cheon-Seok;Cha, Jae-Ho
    • Journal of Microbiology and Biotechnology
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    • v.17 no.9
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    • pp.1469-1476
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    • 2007
  • Jeot-gal is a traditional Korean fermented seafood and has long been used for seasoning. We isolated 188 strains from shrimp, anchovy, and yellow corvina Jeot-gal, and screened sixteen strains that showed strong fibrinolytic activities on a fibrin plate. Among those strains, the strain that had the largest halo zone was chosen and identified as Bacillus licheniformis by using 16S rDNA sequencing and an API CHB kit. The fibrinolytic activity of Bacillus licheniformis was characterized and designated as bpKJ-31. The active component of bpKJ-31 was identified as a 37 kDa protein, designated bacillopeptidase F, by internal peptide mapping and N-terminal sequencing. The optimum activity of bpKJ-31 was shown at pH 9 and $40^{\circ}C$, with a chromogenic substrate for plasmin. It had high degrading activity for the $B{\beta}$-chain and $A{\alpha}$-chain of fibrin(ogen), and also acted on thrombin, but not skim milk and casein. The amidolytic activity of bpKJ-31 was inhibited by 1 mM phenylmethanesulfonyl fluoride, but 1 mM EDTA did not affect the enzyme activity, indicating that bpKJ-31 is an alkaline serine protease, like a plasmin. The bpKJ-31 showed approximately 14.3% higher fibrinolytic activity than the plasmin. These features of bpKJ-31 make it attractive as a health-promoting biomaterial.

Protective Effect of Defibrotide on Splanchnic Injury following Ischemia and Reperfusion in Rats

  • Choi, Soo-Ran;Jeong, Ji-Hoon;Song, Jin-Ho;Shin, Yong-Kyoo
    • The Korean Journal of Physiology and Pharmacology
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    • v.10 no.2
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    • pp.85-94
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    • 2006
  • A splanchic artery occlusion for 90 min followed by reperfusion of the mesenteric circulation resulted in a severe form of circulatory shock, characterized by endothelial dysfunction, severe hypotension, marked intestinal tissue injury, and a high mortality rate. The effect of defibrotide, a complex of single-stranded polydeoxyribonucleotides having antithrombotic effect, was investigated in a model of splanchnic artery occlusion (SAO) shock in urethane anesthetized rats. Occlusion of the superior mesenteric artery for 90 min produced a severe shock state, resulting in a fatal outcome within 120 min of reperfusion in many rats. Defibrotide (10 mg/kg body weight) 10 min prior to reperfusion significantly improved mean arterial blood pressure in comparison to vehicle treated rats (p<0.05). Defibrotide treatment also significantly attenuated in the increase of plasma amino nitrogen concentration, intestinal myeloperoxidase activity, intestinal lipid peroxidation, infiltration of neutrophils in intestine and thrombin induced adherence of neutrophils to superior mesentric artery segments. Superoxide anion and hydrogen peroxide production in $1{\mu}M$ formylmethionylleucylphenylalanine (fMLP)-activated PMNs was inhibited by defibrotide in a dose-dependent fashion. Defibrotide effectively scavenged hydrogen peroxide, but not hydroxyl radical. Treatment of SAO rats with defibrotide inhibited tumor necrosis factor-${\alpha}$, and interleukin-1${\beta}$ productions in blood in comparison with untreated rats. These results suggest that defibrotide partly provides beneficial effects by preserving endothelial function, attenuating neutrophil accumulation, and antioxidant in the ischemic reperfused splanchnic circulation

A Comparison of the Components and Biological Activities in Raw and Boiled Red Beans (Phaseolus radiatus L.) (생팥과 증자팥의 성분 및 생리활성 비교)

  • Lee, Ryun Kyung;Kim, Mi-Sun;Lee, Ye-Seul;Lee, Man-Hyo;Lee, Jong Hwa;Sohn, Ho-Yong
    • Microbiology and Biotechnology Letters
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    • v.42 no.2
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    • pp.162-169
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    • 2014
  • In the course of study for the development of functional food using red beans (azuki beans, Phaseolus radiatus L.), the ethanol extracts from raw-red bean (RRB) and boiled-red bean (BRB) were prepared, and the components and various biological activities of both were compared. It was observed that the extraction yield, and the total polyphenol content, of the BRB were 1.2 times higher than that of the RRB. However, the contents of total flavonoid, total sugar and reducing sugar in the BRB were 30, 27.9 and 30.8% respectively when compared with those of RRB. In relation to antioxidative activity, both RRB and BRB exhibited moderate DPPH anion, ABTS cation, and nitrite scavenging activities and reducing power, though in all cases RRB demonstrated stronger activities than BRB. The extracts of RRB and BRB did not reveal any antimicrobial activities. In a ${\alpha}$-amylase inhibitory activity assay, RRB was higher than BRB, while BRB showed higher ${\alpha}$-glucosidase inhibitory activity than RRB. A strong and particular activity was observed in an anti-thrombosis activity assay of RRB. The extract of RRB demonstrated strong inhibitions against prothrombin and blood coagulation factors, with moderate thrombin inhibition. However, the extract of BRB did not exhibit any significant anti-thrombosis activity. Our results indicate that RRB has different, but useful biological activities, and loss or elimination of the biologically active substances in RRB occurs during the production of BRB. Therefore, to develop more functional foods from red beans, a study of suitable boiling, heating and drying processes is essential, and the efficient re-use of boiled waste water from the boiling process is necessary. These results could be applied to the further development of functional red bean beverages and sweat red bean pastes.