• Title/Summary/Keyword: 혈전용해치료

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Study on tPA-mediated MMP Regulation in Rat Neuronal Cells. (뇌신경세포에서 tPA에 의한 MMP의 발현 조절에 관한 연구)

  • Ko, Woon-Chul;Lee, Sun-Ryung
    • Journal of Life Science
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    • v.19 no.6
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    • pp.836-838
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    • 2009
  • Tissue plasminogen activator (tPA) is very useful for dissolving the clots of blood, however, the use of tPA is limited to only 3-5% of ischemic stroke patients because of the narrow therapeutic time windows and negative side effects. Previous evidences suggest that limitation of tPA in thrombolytic therapy may be related to the upregulation of MMPs. However, little is known about the regulatory mechanism. In this study, we examined the role of tPA on MMP upregulation in rat neuronal cells. tPA (5 ${\mu}g$/ml) increased MMP-9 levels of neuronal cells in a time dependent manner. Hypoxia/reoxygenation amplified tPA-induced MMP-9 levels significantly. Pretreatment with JNK inhibitor SP600125 reduced the MMP-9 response. These results suggest that tPA can upregulate MMPs in neuronal cells and that JNK kinase may be involved.

Detection of Biological Activities of Wild Mushroom Methanol Extracts (야생버섯 메탄올추출물의 생리활성 검색)

  • Kim, Jun-Ho;Yoo, Kwan-Hee;Kim, Yang-Sup;Seok, Soon-Ja
    • The Korean Journal of Mycology
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    • v.40 no.4
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    • pp.296-298
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    • 2012
  • In this study, the biological activities of 33 kinds of wild mushroom methanol extracts were investigated. Boletellus elatus showed the greatest fibrinolytic activity (1.08 plasmin units/mL) in a fibrin plate assay, and the activity of Heterobasidion insulasis was 0.89 plasmin units. The thrombin inhibitory activities of Boletellus elatus and Heterobasidion insulasis were 93.32% and 93.69%, respectively. In a ${\alpha}$-glucosidase inhibitory activity test, Laccaria amethystina showed the greatest inhibitory activity at 81.25%. The antioxidative activities of Gomphus sp. and Geastrum lageniforme were 91.37% and 90.42%, respectively. Since Boletellus elatus and Heterobasidion insulasis have strong fibrinolytic and thrombin inhibitory and antioxidative activities, the two mushrooms can be used as material for the development of biofunctional foods for cardiovascular diseases.

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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Effects of Intracavitary Urokinase Instillation in Complicated Pleural Effusion (합병성 흉막 삼출에 대한 국소적 Urokinase 주입치료 효과에 관한 연구)

  • Sohn, Dong-Hyun;Yoon, Su-Mi;Kim, Chung-Mi;Park, Ik-Soo;Sohn, Jang-Won;Yang, Seok-Chul;Yoon, Ho-Joo;Shin, Dong-Ho;Park, Sung-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.3
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    • pp.357-364
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    • 2000
  • Background : Complicated exudative pleural fluid collections have traditionally been treated by either closed tube thoracostomy drainage or by open surgical drainage. Complete drainage is important in order to control pleural sepsis, restore pulmonary function, and entrapment. Recently intracavitary fibrinolytic therapy has been advocated as a method to facillitate drainage of complicated exudative pleural effusion and to allow enzymatic debridemant of the restrictive fibrinous sheets covering the pleural surface. The purpose of this study is to prospectively evaluate the effects of image-guided catheter drainage with high dose urokinase(UK) instillation in the treatment of complicated pleural effusions. Patients : Twenty complicated pleural effusion patients that poorly respond to image-guided drainage were allocated to receive UK. There were 8 pneumonia and 12 tuberculosis. Methods : Drugs were diluted in 250 mL normal saline and were infused intrapleurally through the chest tube or pig-tail catheter in a daily dose of 250,000 IU of UK. Response was assessed by clinical outcome, fluid drainage, chest radiography, pleural ultrasound and/or computed tomography. Results : The mean UK instillation time was $1.63{\pm}0.10$. The mean volume drained UK instillation was $381.3{\pm}314.4\;mL$, and post-UK was $321.6{\pm}489.5\;mL$. The follow up duration after UK therapy was mean $212.9{\pm}194.5$ days. We had successful results in 19 cases (95.0%). There were 12 pleural thickenings (60.0%), 2 markedly decreased effusions (10.0%) and 5 cases of no thickening or effusion. There was recurrence after treatment in only one patient(5%) with complicated pleural effusiondue to tuberculosis. Conclusions : Image-guided drainage with high dose UK instillation (250,000 U/day) in complicated pleural effusion is a safe and more effective method than closed thoracostomy drainage. And this management, in turn, can obviate surgery in most cases.

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The Effect of Early IASP and Reperfusion Therapy in Patient of Post MI Cardiogenic Shock (Post MI Cardiogenic Shock 환자에서 조기 IABP 및 Reperfusion Therapy의 효과)

  • Lee, Jong-Suk;Kim, Min-Kyeung;Kim, Woong;Kim, Hyung-Jun;Bae, Jun-Ho;Park, Jong-Sean;Sin, Dong-Gu;Kim, Young-Jo;Shim, Bong-Sup
    • Journal of Yeungnam Medical Science
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    • v.17 no.1
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    • pp.31-38
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    • 2000
  • Background: We sought to examine the use and outcomes of early intraaortic balloon counterpulsation(IABP) combined with early reperfusion therapy in patients presenting cardiogenic shock complicated acute myocardial infarction. The usc of IABP in patients with cardiogenic shock is widely accepted. However there is not ample information on the use of this technique in patients with cardiogenic shock who arc treated with reperfusion therapy in Korea. Materials and Methods: Twenty-eight patients presented with cardiogenic shock were classified into two groups: the early IABP group (insertion within 12 hours after AMI onset time) and the late IABP group (insertion after 12 hours). We compared In-hospital mortality between the two groups (early IABP group vs late IABP group). Results: Two groups showed no significant difference in clinical feature and coronary angiographic results. Among total 28 patients, 7 patients were treated with thrombolytic therapy and 21 patients with PTCA. Insertion site bleeding, fever, thrombocytopenia were reported as some of the complications of IABP insertion. In-hospital mortalities in the early IABP group and late IABP group were 4 patients(25%) and 8 patients(66%), respectively(p<0.05). Early IABP insertion and early PTCA showed lower hospital mortality rates. There was significant difference in the time to PTCA after AMI onset between the two groups(p<0.05). Conclusion: IABP appears to be useful in patients presenting cardiogenic shock unresponsive medical therapy. Early IABP insertion and early reperfusion therapy may reduce in-hospital mortality rates of post-MI cardiogenic shock patients.

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Effect of Reperfusion after 20 min Ligation of the Left Coronary Artery in Open-chest Bovine Heart: An Ultrastructural Study (재관류가 허혈 심근세포의 미세구조에 미치는 영향 : 재관류 손상에 관한 연구)

  • 이종욱;조대윤;손동섭;양기민;라봉진;김호덕
    • Journal of Chest Surgery
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    • v.31 no.8
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    • pp.739-748
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    • 1998
  • Background: It has been well documented that transient occlusion of the coronary artery causes myocardial ischemia and finally cell death when ischemia is sustained for more than 20 minutes. Extensive studies have revealed that ischemic myocardium cannot recover without reperfusion by adequate restoration of blood flow, however, reperfusion can cause long-lasting cardiac dysfunction and aggravation of structural damage. The author therefore attempted to examine the effect of postischemic reperfusion on myocardial ultrastructure and to determine the rationales for recanalization therapy to salvage ischemic myocardium. Materials and methods: Young Holstein-Friesian cows(130∼140 Kg body weight; n=40) of both sexes, maintained with nutritionally balanced diet and under constant conditions, were used. The left anterior descending coronary artery(LAD) was occluded by ligation with 4-0 silk snare for 20 minutes and recanalized by release of the ligation under continuous intravenous drip anesthesia with sodium pentobarbital(0.15 mg/Kg/min). Drill biopsies of the risk area (antero-lateral wall) were performed at just on reperfusion(5 minutes), 1-, 2-, 3-, 6-, 12-hours after recanalization, and at 1-hour assist(only with mechanical respiration and fluid replacement) after 12-hour recanalization. The materials were subdivided into subepicardial and subendocardial tissues. Tissue samples were examined with a transmission electron microscope (Philips EM 300) at the accelerating voltage of 60 KeV. Results: After a 20-minute ligation of the LAD, myocytes showed slight to moderate degree of ultrastructural changes including subsarcolemmal bleb formation, loss of nuclear matrix, clumping of chromatin and margination, mitochondrial destruction, and contracture of sarcomeres. However, microvascular structures were relatively well preserved. After 1-hour reperfusion, nuclear and mitochondrial matrices reappeared and intravascular plugging by polymorphonuclear leukocytes or platelets was observed. However, nucleoli and intramitochondrial granules reappeared within 3 hours of reperfusion and a large number of myocytes were recovered progressively within 6 hours of reperfusion. Recovery was apparent in the subepicardial myocytes and there were no distinct changes in the ultrastructure except narrowed lumen of the microvessels in the later period of reperfusion. Conclusions: It is likely that the ischemic myocardium could not be salvaged without adequate restoration of coronary flow and that the microvasculature is more resistant to reversible period of ischemia than subendocardium and subepicardium. Therefore, thrombolysis and/or angioplasty may be a rational method of therapy for coronarogenic myocardial ischemia. However, it may take a relatively longer period of time to recover from ischemic insult and reperfusion injury should be considered.

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Usefulness of $^{201}Tl$ Myocardial Perfusion SPECT in Prediction of Left Ventricular Remodeling following an Acute Myocardial Infarction (급성심근경색 후 발생하는 좌심실 재구도 예측에 대한 $^{201}Tl$ 심근관류 SPECT의 운용성)

  • Yoon, Seok-Nam;Park, C.H.;Hwang, Kyung-Hoon
    • The Korean Journal of Nuclear Medicine
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    • v.34 no.1
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    • pp.30-38
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    • 2000
  • Purpose: We investigated the role of myocardial perfusion SPECT in prediction of ventricular dilatation and the role of revascularization including thrombolytic therapy and PTCA in prevention of ventricular dilatation after an acute myocardial infarction (AMI). Materials and Methods: We performed dipyridamole stress, 4 hour redistribution, and 24 hour reinjection Tl-201 SPECT in 16 patients with AMI two to nine days after attack. Perfusion and wall motion abnormalities were quantified by perfusion index (PI) and wall motion index (WMI). Left ventricular ejection fraction (LVEF), WMI and ventricular volume were measured within 1 week of AMI and after average of 6 months. According to serial changes of left ventricular end-diastolic volume (LVEDV), patients were divided into two groups. We compared WMI, PI and LVEF between the two groups. Relationships among degree of volume, stress-rest PI, WMI, CKMB, Q wave, LVEF and revascularization were analysed using multivariate analysis. Results: Only initial rest perfusion index was significantly different between the two groups (p<0.05). While initial LVEF, stress PI, CKMB, trial of revascularization procedure, presence of Q wave and WMI were not significantly different between the two groups. Eight of 16 patients (50%) showed LV dilatation on follow-up echocardiography. Three of 3 patients (100%) who did not undergo revascualrization procedure documented LV dilatation. And only 5 (38%) of the remaining 13 patients who underwent revascularization revealed LV dilatation. There was no difference in infarct location between the two groups. By multivariate linear regression analysis in patients only undergoing revascularization, rest perfusion index was the only significant factor. Conclusion: Myocardial perfusion SPECT performed prior to revascularization was useful in prediction of LV dilatation after an AMI. Rest perfusion index on myocardial perfusion plays as a significant predictor of left ventricular dilatation after AMI. And revascularization appears to be a valuable procedure in alleviating LV dilatation after AMI with or without viable myocardium in a limited number of patients studied retrospectively.

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Physiological Activity of Sarcodon aspratus Extracts (능이버섯(Sarcodon aspratus) 추출물의 생리활성)

  • 송재환;이현숙;황진국;한정환;노정근;금동혁;박기문
    • Food Science of Animal Resources
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    • v.23 no.2
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    • pp.172-179
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    • 2003
  • This study was carried out to find the preventive medical and therapeutic effects of Sarcodon asparatus on adult disease by employing several biological and biochemical assays. Nitrate scavenging ability(NSA) of Sarcodan asparatus extracts was displayed up to 99.9% at pH 1.2 in a dose-dependent manner. They also had 90.4% electron donating ability(EDA) at the concentration of 0.1 mg/mL. Extracts of Sarcodon asparatus were also able to function as a powerful antioxidant at all concentrations(0.01∼l.0 mg/mL). Furthermore, we observed that 1 mg/mL concentration of the extracts was more powerful than BHT, With respect to fibrolytic activity, Sarcodon asparatus showed 1,843.8 unit/g, which was higher than streptokinase(1,189 unit/g). The inhibitory effects of the extracts on angiotensin converting enzyme, measured by the normal and pretreatment methods, were 53 and 58%, respectively. We also performed cytotoxicity effect of Sarcodon asparatus extracts on a various cancer cell lines. The growth inhibitory effects of the extracts(5.0 mg/mL) on A549, HeLa, AGS, and SK-Hep-1 cells were 78.9, 55.3, 69.0, and 42.5 %, respectively. Interestingly, Sarcodon asparatusextracts induced mutation on Salmonella typhimurium TA98 and TA100 when Ames test was done.