• Journal of Microbiology and Biotechnology
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• v.12 no.2
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• pp.196-203
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• 2002

A novel process for urokinase purification was studied using p-aminobenzamidine as the ligand and sepharose 4B as the matrix. The adsorption, washing, and elution conditions were optimized by an unusual method. An adsorption buffer containing 2.5 M NaCl and $1\%$ Tween 80 facilitated the adsorption of urokinase on the affinity media and prevented contaminants from binding to the p-aminobenzamidine affinity gel. It was found that $5\%$ Tween 80 removed most of the contaminants from the affinity column. A 0.2 M glycine elution buffer containing 0.5 M NaCl (pH 3.0) was found to have a strong elution ability with a high recovery and purity of urokinase. A crude urokinase material of231 IU/mg protein from human urine was purified to 124,300 IU/mg protein with a purification factor of 538 and yield of $86.7\%$. As a result, a high purity urokinase was obtained with only a single affinity chromatography step. The purification process was successfully scaled-up to a 2-1 chromatography column. The resulting urokinase eluate could be directly lyophilized, thereby complying with Chinese pharmacopoeia (1995 version) standards.

• 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.

• Journal of Chest Surgery
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• v.19 no.2
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• pp.225-231
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• 1986

Pericardial adhesions following open heart surgery pose a special problems, increasing the risk of cardiac reoperation because of the danger of damaging the heart, coronary artery and veins, or grafts and also the fibrous tissue may obliterate the pericardial space and eventually constrict the heart. This study was undertaken to evaluate the effect of intrapericardial urokinase and dextran 40 on the formation of pericardial adhesions in an animal model. latrogenic traumas on the pericardium were surgically induced in 30 rabbits, simulating injuries possible during actual surgery. In all rabbits, blood [1 ml] was obtained from an ear vessel and injected into the pericardium. Control group of ten rabbits did not receive any further medication, urokinase group of ten received 15, 000-20, 000 IU of urokinase, and remained ten received 1 ml of 10% dextran 40. All rabbits were sacrificed at 4 weeks. At autopsy, the development of adhesions were graded as none [Grade I], minimal [Grade II], moderate [Grade III], and severe [Grade IV]. Histological studies of the parietal pericardium and epicardium were performed. The results were as follows: 1. Group 1[Control group] showed minimal adhesion in 40%, moderate in 50%, and severe in 10% of the group. Sharp dissections were necessary in 60% of adhesions. 2. Group II [Dextran group] showed no adhesions in 20%, minimal in 60%, and moderate in 20% of the group. 3. Group III [Urokinase group] showed no adhesions in 40%, minimal in 40%, and moderate in 20% of the group. Considering in this group, the adhesion activity was significantly suppressed [60% adhesions] compared to the control group [100% adhesions] [P < 0.05]. 4. Histological findings revealed mild serosal fibrosis in none adherent group, loose fibrous connections between two layers of pericardium in minimal adhesion group, tight fibrous connections in moderate adhesion group, and marked fibrous thickening and close attachment of two surfaces were noted in severe adhesion group. These data have revealed the decreased incidence of pericardial adhesions with urokinase and dextran 40.

• 순환기질환의공학회:학술대회논문집
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• 2005.12a
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• pp.17-20
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• 2005

• Journal of Yeungnam Medical Science
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• v.1 no.1
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• pp.35-39
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• 1984

Since opening of the Yeungnam University Hospital in June 1983 till end of 1984, total 30 cases of cerebral thrombosis were analysed clinically. Among the 30, 17 cases were given Urokinase from 60,000 to 240,000 units daily for 2-46 days. The interval from the onset to the inititiation of therapy varied from 1 hour to 17 days. Ten cases showed marked recovery and 6 cases moderate improvement. One case, in which only 120,000 units daily were administered, showed stationary course. The interval of the Urokinase untreated 13 cases was from 3 days to 18 months. Six cases were stationary, whereas 7 cases showed mild improvement. Age, sex, past history, associated diseases, and the laboratory findings are shown in the tables. Conclusion is that the earlier the therapy started, the higher the dosage used, the better of the results is obtained.

• The Journal of the Society of Stroke on Korean Medicine
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• v.10 no.1
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• pp.1-7
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• 2009

Objectives : This Study was prepared for investigating the safety of oriental medicine and continuous intravenous urokinase combined therapy in acute cerebral infarction. Methods : We prospectively estimate safety of hemorrhagic transformation occurred in oriental medical therapy and continuous intravenous urokinase combined therapy. We estimate National Institute of Health Stroke Scale Score and Modified Barthel Index. Results : Hemorrhagic transformation was not noted. and Others are not fatal complication. Conclusions : oriental medical therapy and continuous intravenous urokinase combined therapy are safety method in treatment of acute cerebral infarction. We think this can be a good model of Oriental and western cooperative therapy.

• 대한미세수술학회:학술대회논문집
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• 1994.11a
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• pp.102.2-103
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• 1994

• 한국생물공학회:학술대회논문집
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• 2001.11a
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• pp.85-88
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• 2001

We scaled up a covalent immobilization system of urokinase to the activated Sepharose and used it repeatedly to cleave a fusion protein consisting of human growth hormone and GST fragment. After scale up from 6 ml to 250 ml, the column system still demonstrated basically the same performance in terms of urokinase immobilization and fusion protein cleavage. When the column was washed with 6M guanidine HCl after the cleavage reaction. the immobilized urokinase showed no activity probably because it was fully unfolded. However. as the denaturant was gradually removed from the column the immobilized urokinase fully regained its bioactivity. which indicated it was properly refolded into its native conformation as covalently attached to the solid matrix. After 20 cycles of this 'solid-phase unfolding/refolding', the immobilized urokinase maintained approx. 80% of the initial bioactivity. This method provides an efficient protocol to apply the solid-phase refolding technique to improve the longevity of immobilized enzyme columns.

• Tuberculosis and Respiratory Diseases
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• v.57 no.5
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• pp.465-469
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• 2004

Exudative pleural effusion can arise from pneumonia, tuberculosis, cancer, etc. Early drainage is needed for prevention of complications such as pleural fibrosis, thickening, bronchopleural fistulae and decline of lung function. Intrapleural Instillation of fibrinolytic enzymes has been used for 50years as an adjunct in the removal of fibrous material, hematoma and pus from the thoracic cavity. By the local fibrinolytic effect on fibrinous exudates within the pleural space, fibrinolytic agent has improved results of chest tube or pig tail drainage. But there were no controlled randomized studies, so significant controversy exists concerning the efficacy of this therpy, especially tuberculous pleurisy. Furthermore about complication, severe spontaneous bleeding has not been reported with intrapleural urokinase. Intrapleural fibrinolytic enzymes has shows no systemic complication. When it is administrated intravenously, not into intrpleural space, major bleeding is reported about 1-3% of patient, especially they had systemic disease, such as coagulation abnormalities. This case report presents a patient who suffered major hemothorax induced hypovolemic shock following the administration of 100,000 units of urokinase intrapleurally. He was 25-year old male with tuberculosis pleurisy without systemic illness demonstraion.

• The Journal of Internal Korean Medicine
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• v.22 no.4
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• pp.633-638
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• 2001

Objective : Stroke is the most frequent cause of death in Korea. Because it remains severe disablities disturbing normal life, it is important to carry out intervention preventing from progression of condition in patients with acute ischemic stroke within therapeutic time window. Thus early thrombolysis is beneficial for patients with acute ischemic stroke. However its therapeutic efficacy is not known in combination with oriental medical therapy. In this study, we investigated the safety and the clinical effect of continous intravenous urokinase therapy and oriental medical therapy. Methods : Twenty eight patients with acute onset of ischemic stroke no later than three days received continous infusion of urokinase and oriental medical therapy. We estimated the subjects's neurological deficit and functional status with National institute of Neurologic Disorders and Stroke Scale(NIHSS) and Europian Stroke Scale (ESS) prior to therapy, on day 3, 7, 14 after the starting urokinase therapy and on day at discharge. Results: After day 7, the scores of NIHSS and ESS were improved significantly. There are no differences in therapeutic effects of the interval between onset of stroke and initiation of therapy. Complication were noted in four(14%) patients, but these are not fatal complication and make no neurological deficiency. Conclusion : The results of these investment suggest that continuous intravenous urokinase with oriental medical therapy could be a safe and effective intervention to prevent from progression in acute ischemic stroke. But this findings should be confirmed in multicenter double blind controlled trial.