• Title/Summary/Keyword: Thrombolytic

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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.

The Therapeutic Efficacy and the Bleeding Complications of Urokinase and Alteplase in Patients with Massive Pulmonary Thromboembolism (중증 폐혈전색전증 환자에서 Urokinase와 Alteplase의 효과 및 출혈 합병증 비교)

  • Yoo, Jung-Wan;Kim, Wongyoung;Choi, Chang Min;Hong, Sang-Bum;Oh, Yeon Mok;Shim, Tae Sun;Lim, Chae-Man;Lee, Sang Do;Kim, Woo Sung;Kim, Dong Soon;Kim, Won Dong;Koh, Younsuck
    • Tuberculosis and Respiratory Diseases
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    • v.66 no.1
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    • pp.6-12
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    • 2009
  • Background: The efficacy of several thrombolytic agents for treating massive pulmonary thromboembolism (PTE) has been reported to be similar. However, the difference of the bleeding complications caused by two commonly used thrombolytic agents in PTE patients is not well known. The aim of this study was to compare the therapeutic efficacy and the bleeding complications between urokinase and recombinant tissue-type plasminogen activatior (rt-PA, alteplase) in a Korean medical center. Methods: We retrospectively reviewed the clinical data of the patients who were treated with thrombolytic agents (urokinase and alteplase) because of massive PTE. Results: A total of 40 patients were included: 16 (40%) treated with urokinase and 24 (60%) with alteplase. The patients treated with alteplase showed a shorter duration of using vasopressor agents than did the patients who were given urokinase, but the duration of mechanical ventilation, the length of the ICU stay and the hospital stay were not different between the thrombolytic agents. Five patients treated with urokinase and eight patients treated with alteplase died (p=0.565): One patient in the urokinase group and four patients in the alteplase group died due to pulmonary thromboembolism. Bleeding complications after thrombolysis were observed in 3 patients (7.5%) treated with urokinase and in 11 (27.5%) patients treated with alteplase (p=0.079). Major bleeding complication occurred in 2 patients who were treated with alteplase. Conclusion: Urokinase seems to have fewer bleeding complications with an equivalent efficacy, as compared to alteplase, in Korean patients who suffer with massive pulmonary thromboembolism.

Surgical Management of Chronic Pulmonary Embolism - Surgical treatment and perioperative problems - (만성 페색전증의 외과적 요법수술 및 수술 전후 문제)

  • 김응수
    • Journal of Chest Surgery
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    • v.20 no.1
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    • pp.139-147
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    • 1987
  • in general rapid and complete resolution of pulmonary emboli, even massive, is the natural history. However, rarely, the emboli do not resolve but rather became fibrotic organization and densely adherent to the arterial wall, therefore, may lead to significant clinical disability. In patients with chronic pulmonary embolism, medical management usually has little effect and only surgical treatment can offer improvement. The case was 30-year-old man who had admission to the Hanyang University Hospital due to fall-down from 11th floor 407 days before operation and then transferred to our department for surgical management under the diagnosis of chronic pulmonary embolism, Pulmonary angiogram demonstrated multifocal thromboembolism with infarction and lung scans showed no improvement in spite of anticoagulant and thrombolytic therapy. At median sternotomy for pulmonary artery thromboembolectomy, the well organized and multiple septic emboli could be removed by gallstone forceps. But reoperation of left upper lobectomy was performed because of the repeated hemoptysis and suspicious pulmonary arterio-bronchial fistula 19 days postoperatively. Despite of ventilatory support and drug treatment, the patient died due to right heart failure associated with cor pulmonale 27 days after first operation. Discussion of the operative and perioperative problems are offered.

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Cardiovascular complications after Kawasaki disease and its management (가와사끼병의 심혈관계 합병증 및 치료)

  • Jang, Gi Young
    • Clinical and Experimental Pediatrics
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    • v.51 no.5
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    • pp.462-467
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    • 2008
  • Kawasaki disease is a systemic vasculitis of unknown etiology, usually occurring in infants and young children. Although the etiology of Kawasaki disease remains uncertain, its serious complicationssuch as giant aneurysm formation, coronary arterial stenotic lesions, and thrombotic occlusionhave been proven to cause myocardial ischemia or infarction in patients with Kawasaki disease. To prevent and treat these complications, several modes of therapyincluding long-term anticoagulation, interventional catheterization, and surgical treatmenthave been gradually developed. In this article, we review the cardiovascular complications following Kawasaki disease and the management thereof, which includes thrombolytic therapy, catheter intervention, and coronary artery bypass graft.

Soluble Expression and Purification of Human Tissue-type Plasminogen Activator Protease Domain

  • Lee, Hak-Joo;Im, Ha-Na
    • Bulletin of the Korean Chemical Society
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    • v.31 no.9
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    • pp.2607-2612
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    • 2010
  • Human tissue-type plasminogen activator (tPA) is a valuable thrombolytic agent used to successfully treat acute myocardial infarction, thromboembolic stroke, peripheral arterial occlusion, and venous thromboembolism. Recombinant tPA is accumulated as an inactive form in inclusion bodies of E. coli and is refolded in vitro, which is accompanied by extensive aggregation. In the present study, a tPA protease domain was expressed in an active soluble form in the cytosol of E. coli Rosetta-gami cells, which allowed disulfide bond formation and supplied the tRNA molecules required for six rarely used codons in E. coli. This strategy increased the amount of soluble protease domain protein and avoided the cumbersome refolding process. The purified protease domain not only degraded tPA substrate peptides but also formed a covalently bound complex with plasminogen activator inhibitor-1, as does full-length tPA. Soluble expression and purification of tPA domains may aid in functional analyses of this multi-domain protein, which has been implicated in many physiological and pathological processes.

The Clinical Efficacy of Chungpyesagan-tang on Acute Stroke (급성기 중풍 환자에 대한 청폐사간탕의 임상적 효능)

  • 최동준;정우상;문상관;조기호;김영석;배형섭
    • The Journal of Korean Medicine
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    • v.23 no.4
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    • pp.9-14
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    • 2002
  • To assess the clinical efficacy of Chungpyesagan-tang on acute stroke, we prescribed this medicine to 88 acute stroke patients without thrombolytic treatment. The rate of progressive stroke type was 2.3%, remarkably lower than in previous reports. 1.1 % felt an itching sensation, and 17.0% complaxined of loose stool and diarrhea. Chungpyesagan-tang decreased Stroke-Pattern Identification and National Institute of Health Stroke Scale (NIHSS), and increased Modified Barthel Index (MBI). Thus, we could suggest that this medicine has a desirable effect to reduce the severity of stroke and improve functional recovery. As to the laboratory findings, ALT had anupward tendency and increased over normal value in 16 cases (18.2%). However, the mean serum level 2 weeks later was within the normal value and the other hepatic enzymes did not increase.

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The Clinical Efficacy of Yangkyuksanwha-tang on Acute Stroke (급성기 중풍 환자에 대한 양격산화탕의 임상적 효능)

  • 최동준;류순현;정우상;문상관;조기호;김영석;배형섭
    • The Journal of Korean Medicine
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    • v.25 no.1
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    • pp.111-116
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    • 2004
  • Objective : To assess the clinical efficacy of Yangkyuksanwha-tang on acute stroke Methods : We prescribed Yangkyuksanwha-tang to 83 acute stroke patients without thrombolytic treatment. Results : The rate of progressive stroke type was 1.2%, it was remarkably lower than previous reports. 3.6% felt an itching sensation, 3.6% complained headache, dizziness and powerless, 2.4% complained indigestion and diarrhea, 1.2% appeared hematuria and G-I bleeding. Yangkyuksanwha-tang decreased Stroke-Pattern Identification and National Institute of Health Stroke Scale(NIHSS), and increased Modified Barthel Index(MBI). So we could suggest that this medicine have desirable effect to reduce the severity of stroke and improve functional recovery. As to the laboratory findings, all results were within the normal value, which showed no hepatic or renal toxicity. Conclusion : We could suggest that Yangkyuksanwha-tang is a useful medicine which has clinical efficacy for acute stroke, but further investigation for an administration of more than 2 weeks is necessary.

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Cerebral Postischemic Hyperperfusion in PET and SPECT (PET과 SPECT에서 나타나는 뇌허혈후 과관류)

  • Cho, Ihn-Ho
    • The Korean Journal of Nuclear Medicine
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    • v.35 no.6
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    • pp.343-351
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    • 2001
  • Cerebral post-ischemic hyperperfusion has been observed at the acute and subacute periods of ischemic stroke. In the animal stroke model, early post-ischemic hyperperfusion is the mark of recanalization of the occluded artery with reperfusion. In the PET studios of both humans and experimental animals, early post-ischemic hyperperfusion is not a key factor in the development of tissue infarction and indicates the spontaneous reperfusion of the ischemic brain tissue without late infarction or with small infarction. But late post-ischemic hyperperfusion shows the worse prognosis with reperfusion injury associated with brain tissue necrosis. Early post-ischemic hyperperfusion defined by PET and SPECT may be useful in predicting the prognosis of ischemic stroke and the effect of thrombolytic therapy.

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Respiratory Review of 2014: Pulmonary Thromboembolism

  • Lee, Jae Seung
    • Tuberculosis and Respiratory Diseases
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    • v.77 no.3
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    • pp.105-110
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    • 2014
  • Venous thromboembolism (VTE), which includes pulmonary embolism and deep vein thrombosis, is an important cause of morbidity and mortality. The aim of this review is to summarize the findings from clinically important publications over the last year in the area of VTE. In this review, we discuss 11 randomized controlled trials published from March 2013 to April 2014. The COAG and the EU-PACT trials indicate that pharmacogenetic testing has either no usefulness in the initial dosing of vitamin K antagonists or marginal usefulness in the Caucasian population. Recent clinical trials with novel oral anticoagulants (NOACs) have demonstrated that the efficacy and safety of rivaroxaban, apixaban, edoxaban, and dabigatran are not inferior to those of conventional anticoagulants for the treatment of VTE. The PEITHO and ULTIMA trials suggested that rescue thrombolysis or catheter-directed thrombolysis may maximize the clinical benefits and minimize the bleeding risk. Lastly, riociguat has a proven efficacy in treating chronic thromboembolic pulmonary hypertension. In the future, NOACs, riociguat, and catheter-directed thrombolysis have the potential to revolutionize the management of patients with VTE.

Neurovascular Mechanisms in Stroke, Neurodegeneration and Recovery

  • Lo, Eng-H.
    • The Korean Journal of Physiology and Pharmacology
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    • v.10 no.5
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    • pp.223-229
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    • 2006
  • The emerging concept of the 'neurovascular unit' may enable a powerful paradigm shift for neuroscience. Instead of a pure focus on the 'neurobiology' of disease, an opportunity now exists to return to a more integrative approach. The neurovascular unit emphasizes that signaling between vascular and neuronal compartments comprise the basis for both function and dysfunction in brain. Hence, brain disorders are not just due to death of neurons, but instead manifested as cell signaling perturbations at the neurovascular interface. In this mini-review, we will examine 3 examples of this hypothesis: neurovascular mechanisms involved in the thrombolytic therapy of stroke, the crosstalk between neurogenesis and angiogenesis, and the link between vascular dysfunction and amyloid pathology in Alzheimer's disease. An understanding of cell-cell and cell-matrix signaling at the neurovascular interface may yield new approaches for targeting CNS disorders.