• Title/Summary/Keyword: Fibrinolytic agent

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Studies on the Development of a Thrombolytic Agent from Korean Snake Venom II. Characterization and Thrombolytic Activity of a Pretense from the Venom of a Protease from the Venom of A. bromhoffi brevicaudus (한국 독사독으로부터의 혈전 용해제 개발에 관한 연구 II. 살모사(A. bromhoffi brevicaudus) 사독 Protease의 특성과 혈전 용해능에 관한 연구)

  • Kim, Byoung-Jae;Lee, Mun-Han;Rim, Jong-Seop;Lee, Hang;Lee, Hye-Suk;Kim, Jong-Ho;Chai, Chang-Su
    • Biomolecules & Therapeutics
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    • v.3 no.2
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    • pp.165-170
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    • 1995
  • The biochemical properties of the fibrinolytic protease of 50,800 Da isolated from the venom of Kgdistrodon blomhoffi brevicaudus were characterized. The enzyme hydrolyzed the carboxyl side of arginine in the synthetic chromogenic peptides, N-Benzoyl-Phe-Val-Arg-pNA and N-p-Tosyl-Gly-Pro-Arg-pNA, and the enzyme activity was inhibited by phenylmethylsulfonylfluoride indicating that the enzyme belongs to the serine protease family. The pretense showed maximum activity at pH 7.5 and inhibited by ZnCl$_2$, CuSO$_4$, but not by soybean trypsin inhibitor, pepstatin A, 2-mercaptoethanol and EDTA. The fm value determined with N-p-Tosyl-Gly-Pro-Arg-pNA was 0.2 mM. The thrombolytic activity of the purified enzyme was evaluated by platelet aggregation test in rabbits. While the platelet count ratio in blood of the rabbits injected with thrombin alone declined from 1.0 to 0.6 within 7 min and maintained around 0.6 for 24 hours thereafter, the ratio rapidly recovered from around 0.6 to 0.8 in 1 hr, to 1.0 in 24 hrs when the rabbits were sequentially treated with thrombin and the purified enzyme. The result showed that the serine protease from A. blomhoffi brevicoudus of 50,800 Da had a thrombolytic activity in vivo and the enzyme might be developed as a therapuetic agent for the treatment of thrombic disease.

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Screening of Thrombin Inhibitors from Medicinal and Wild Plants (약용 및 야생식물로부터 트롬빈 저해물질의 탐색)

  • Kwon, Yun-Sook;Kim, Young-Sook;Kwon, Ha-Young;Kwon, Gi-Seok;Kim, Kyung-Jae;Kwon, Chong-Suk;Son, Kun-Ho;Sohn, Ho-Yong
    • Korean Journal of Pharmacognosy
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    • v.35 no.1 s.136
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    • pp.52-61
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    • 2004
  • Inhibitory activities of 264 methanol extracts, which were prepared from different parts of 210 kinds of wild and medicinal plants, against human thrombin were evaluated. Based on the anti-coagulation activity determined by thrombin time and activated partial thromboplastin time, the 14 extracts were screened. The fibrinolytic activity, heat stability and inhibition of other proteolytic digestive enzymes, such as pepsin, papain, trypsin and chymotrypsin, of the 14 extracts were further determined, and Ginko biloba (herba), Ephedra sinica (radix), Reynoutria elliptica (herba), Amomum tsao-ko Crevost (fructus), and Magnolia officinalis Rehd. et Wils (bark) were finally selected as possible plant sources for anti-thrombosis agent. These results suggested that medicinal and wild plants could be the potential source of thrombin inhibitor.

Treatment of Severe Henoch-Schoenlein Purpura Nephritis in Children (소아의 심한 헤노흐-쇤라인 자반증의 치료)

  • Shin, Jae-Il;Lee, Jae-Seung
    • Childhood Kidney Diseases
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    • v.14 no.1
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    • pp.10-21
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    • 2010
  • The overall prognosis of Henoch-Schoenlein purpura (HSP) is favorable, but severe nephritis has a high risk of progression to end stage renal failure. Recent studies emphasize the importance of early treatment in children with severe HSP nephritis, but the treatment of severe HSP nephritis still remains controversial due to the rarity of randomized controlled studies in this field. Nevertheless, several intensive therapies, such as intravenous high-dose methylprednisolone pulse, immunosuppressive/cytotoxic drugs, fibrinolytic therapy, anticoagulants, antiplatelet agent and plasma exchange, have been used in children with severe HSP nephritis. In this review, we focus on the treatment of severe HSP nephritis in children.

Effect of VEGF on the Secretion of MMP-2 and Plasmin from Human Keratinocyte Cells (Keratinocytes 세포의 MMP-2 및 plasmin 분비에 미치는 VEGF의 영향)

  • 김환규;오인숙;소상섭;박종완
    • KSBB Journal
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    • v.16 no.3
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    • pp.237-240
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    • 2001
  • Epithelial cell migration plays an important role in many physiological processes such as morphogenesis and wound healing, and cell mobility requires the release of the cell from its adhesion site. This is directed, at least in part, by limited proteolysis of matrix molecules by matrix metalloproteinases (MMPs). MMPs are zinc-dependent proteases produced by a variety of cell types, and have a fundamental role in tissue remodelling, tumour invasion and metastasis. In addition, the ability of cells to mediate fibrinolytic agent, plasmin. The purpose of this study was to test if vascular endothlial growth factor (VEGF) can regulate the production of MMPs and plasmin by keratinocyte cells. Supernatants from a human keratinocyte cell line grown in the presence or absence of VEGF (10ng/mL) produced ?2.5 fold increases in cell proliferation, and ?3.0 fold increses in MMP-2 and plasmin levels. Our results suggest that VEGF may modulate keratinocyte cell proliferating activity by increasing the abundance of MMP-2 and plasmin, and indicates a role for VEGF in the regulation of keratinocyte behaviour in wound healing and tissue remodelling.

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EFFECT OF ARTERIAL REPAIR AND PATENCY AFTER MICROVASCULAR ANASTOMOSIS WITH TOPICAL IRRIGATION OF VARIOUS ANTI-THROMBUS DRUGS (수종의 항혈전제의 국소 세척이 미세혈관문합의 동맥 치유 및 개존에 미치는 영향)

  • Choi, Yong-Chul;Kim, Kyung-Wook;Kim, Chul-Hwan
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.32 no.2
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    • pp.117-128
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    • 2006
  • Free flap transplantation with microvascular anastomosis has been successfully performed by development of surgical technique, materials and postoperative monitoring equipments of flap. But success rate of microvascular anastomosis is influenced by various factors, and failure rate is about 5-10%. The most influential factor for success rate is surgical technique and other factors that influence failure of microvascular anastomosis are ischemic time of free flap, thrombus formation of anastomosis region and vascular spasm. Many studies has been published in microvascular anastomosis with histologic effect for irrigating solution. But local irrigation solution has been used clinically in microvascular anastomosis, the comparison with each solution, microhistological study for endothelial cell repair and vascular patency has not been reported. The heparin which is anti-thrombotic agent, and urokinase which is fibrinolytic agent are used for this study. Vascular patency and thrombus formation in experimental micro-arterial anastomosis, and endothelial repair were observed with histologic analysis, scanning electron microscopy, transmission electron microscopic examination. The results were obtained as follows: 1. In vascular patency test in 30 minute and 7 days after micro-arterial anastomosis, equal effects of good vascular patency were obtained in group of local irrigation with heparin and urokinase. 2. In thrombus formation in 7 days after micro-arterial anastomosis, equal effects of minimal thrombus formation were obtained in group of local irrigation with heparin and urokinase. 3. In toluidin blue staining in 7 days after micro-arterial anastomosis, local destruction of endothelial cell and inner elastic lamina were seen and endothelial repair was not seen. 4. In scanning electron microscope examination in 7 days after micro-arterial anastomosis, endothelial cell was not seen in peripheral to suture materials, thrombus associated fibrin network was observed. 5. In transmission electron microscope examination in 7 days after micro-arterial anastomosis, inflammatory cell was seen within smooth muscle cells in site of endothelial cell destruction, smooth muscle cell around suture material were arranged irregularly, some collagenous change were seen. From the results obtained in this study, same results of good vascular patency and anti-thrombotic effect of heparin and urokinase were obtained as a local irrigation solution, and repair of endothelial cell was not seen in 7 days after micro-arterial anastomosis.

Evaluation of the Antioxidant Activity and Physiological Functionality of Baegilju (백일주의 항산화 활성 및 생리기능성 평가)

  • Cho, Young Ho;Byun, Tae Kang;Lee, Jong-Hwa;Lee, Gye Won
    • Journal of Life Science
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    • v.23 no.12
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    • pp.1525-1531
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    • 2013
  • Baegilju is a famous traditional Korean wine made over the course of 100 days. The physiological functionalities of Baegilju were evaluated using different tests. The spectrophotometric method was used to determine the total concentration of polyphenolics and flavonoids and DPPH and ABTS radicals. A nitrite scavenging assay was used to evaluate antioxidant activity. The fibrin plate method was used for fibrinolysis and to evaluate angiotensin I converting enzyme (ACE) inhibitory activity; finally, the colorimetric determination method was used to evaluate acetylcholinesterase (AChE) inhibitory activity. The total polyphenolic content of non-sterilized Baegilju and sterilized Baegilju were 391.59 ${\mu}g$ and 401.33 ${\mu}g$ tannic acid equivalents/ml, respectively; and the flavonoids contents were 284.75 ${\mu}g$ and 308.35 ${\mu}g$ quercetin equivalents/ml, respectively. Baegilju exhibited more excellent antioxidant activities (DPPH and ABTS radicals, nitrite scavenging activity) than did Cheongju. In addition, the fibrinolytic activity and AChE inhibitory activity were found to be higher in Baegilju than they were in Cheongju. The ACE inhibitory activity of non-sterilized Baegilju, sterilized Baegilju, and Cheongju were 23.62%, 19.99%, and 38.91%, respectively. Therefore, these results suggest that Baegilju has potential as an antioxidant agent and anti-thrombosis agent.

The Effect of Tissue Plasminogen Activator on TGF-${\beta}1$ Pre-Treated Human Mesothelial Cell Line (TGF-${\beta}1$으로 자극한 사람중피세포주에서 조직플라스미노겐 활성제가 미치는 영향)

  • Lee, Jung-Lim;Jeon, Soo-Jin;Yoo, Young-Choon;Kim, Ji-Hye;Lee, Yu-Mi;Kwon, Sun-Jung;Son, Ji-Woong;Choi, Eu-Gene;Na, Moon-Jun
    • Tuberculosis and Respiratory Diseases
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    • v.70 no.5
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    • pp.405-415
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    • 2011
  • Background: In an effort to find alternative therapeutic agents to prevent excessive fibrosis as a sequela to complicated parapneumonic effusion or empyema, we examined the effect of tissue plasminogen activator (tPA) as a fibrinolytic agent combined with talc or transforming growth factor (TGF)-${\beta}1$ in a human pleural mesothelial cell line, MeT-5A. Methods: MeT-5A cells were stimulated with various doses of talc, doxycycline or TGF-${\beta}1$ for 24 h and then were treated with tPA for an additional 24 h. Cell viability was measured by MTT assay. The production of interleukin (IL)-8 and vascular endothelial growth factor (VEGF) in the culture supernatants was measured by ELISA. Real-time PCR was carried out for measurement of type I collagen mRNA. Results: MeT-5A cells treated with talc showed a dose-dependent increase in production of IL-8. Talc also increased production of type I collagen mRNA at low doses, but talc did not influence the induction of VEGF. Addition of tPA to talc-stimulated cells showed further increases in the production of IL-8, but tPA did not influence the production of VEGF or type I collagen mRNA. TGF-${\beta}1$ increased the production of both VEGF and collagen type I mRNA, both of which were effectively inhibited by additional tPA treatment in MeT-5A cells. Conclusion: TGF-${\beta}1$ is a potent inducer of collagen synthesis without induction of IL-8 in MeT-5A cells. Addition of tPA after TGF-${\beta}1$ stimulation inhibited further fibrosis by direct inhibition of collagen mRNA synthesis as well as by inhibition of VEGF production.

Intrapleural Fibrinolysis with Urokinase versus Alteplase in Complicated Pleural Effusions and Empyema: A Prospective Randomized Controlled Trial

  • Sudipt Adhikari;Vikas Marwah;Robin Choudhary;Indermani Pandey;Tentu Ajai Kumar;Virender Malik;Arpita Pemmaraju;Shrinath Vasudevan;Suraj Kapoor
    • Tuberculosis and Respiratory Diseases
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    • v.87 no.3
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    • pp.378-385
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    • 2024
  • Background: Intrapleural fibrinolytic therapy (IPFT) has been used as an effective agent since 1949 for managing complicated pleural effusion and empyema. Several agents, such as streptokinase, urokinase (UK), and recombinant tissue plasminogen activator (rt-PA), have been found to be effective with variable effectiveness. However, a head-tohead controlled trial comparing the efficacy of the most frequently used agents, i.e., UK and rt-PA (alteplase) for managing complicated pleural effusion has rarely been reported. Methods: A total of 50 patients were randomized in two intervention groups, i.e., UK and rt-PA. The dose of rt-PA was 10 mg, and that of UK was 1.0 lac units. UK was given thrice daily for 2 days, followed by clamping to allow the retainment of drugs in the pleural space for 2 hours. rt-PA was instilled into the pleural space twice daily for 2 days, and intercostal drainage was clamped for 1 hour. Results: A total of 50 patients were enrolled into the study, of which 84% (n=42) were males and 16% (n=8) were females. Among them, 30 (60%) patients received UK, and 20 (40%) patients received alteplase as IPFT agents. The percentage of mean±standard deviation changes in pleural opacity was -33.0%±9.9% in the UK group and -41.0%±14.9% in the alteplase group, respectively (p=0.014). Pain was the most common adverse side effect, occurring in 60% (n=18) of the patients in the UK group and in 40% (n=8) of the patients in the alteplase group (p=0.24), while fever was the second most common side effect. Patients who reported early (within 6 weeks of onset of symptoms) showed a greater response than those who reported late for the intervention. Conclusion: IPFT is a safe and effective option for managing complicated pleural effusion or empyema, and newer agents, such as alteplase, have greater efficacy and a similar adverse effect profile when compared with conventional agents, such as UK.

Video-Assisted Thoracoscopic Surgery for Fibrinopurulent Empyema (섬유농성 농흉의 비디오 흉강경을 이용한 치료)

  • 손정환;모은경;지현근;김응중;신호승;신윤철
    • Journal of Chest Surgery
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    • v.36 no.6
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    • pp.404-410
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    • 2003
  • Different treatment options are available according to the stage and duration of the empyema. Stage I empyema (exudate stage) is treated concurrently by the administration of appropriate antibiotics and chest tube drainage. Stage III empyema (organized stage) is considered for decortication through an open thoracotomy. However, the treatment of fibrinopurulent, stage II empyema remains controversial. Recently, debridement with the use of Video-Assisted Thoracoscopic Surgery (VATS) has been proposed for the treatment of stage II empyema. We analyzed and report our initial experience of 5 cases of stage II empyema, treated with the use of VATS. Material and Method: Between June 2001 and February 2002, 5 patients with fibrinopurulent empyema that did not respond to antibiotics, chest tube drainage or Percutaneous Catheter drainage (PCD), and instillation of fibrinolytic agent were treated by debridement and irrigation with the use of VATS. A CT scan was performed in all patients before the operation to confirm the diagnosis of loculated empyema and to detect additional lung parenchymal diseases. Result: All 5 patients underwent successful debridement and irrigation with the use of VATS and the chest tube was inserted properly. And no patients needed conversion to open thoracotomy. The ratio of sex was 4 : 1 (male : female), the mean age was 53 years old (range, 26~73 years), the mean operative time was 73.4 minutes (range, 52~95 minutes), the mean duration of postoperative chest tube placement was 12.4 days (range, 6~19 days), and the mean duration of postoperative hospital stay was 20.8 days (range, 10~36 days). In all patients, clinical symptoms such as pain and fever subsided and simple chest PA view revealed satisfactory lung expansion. No major postoperative complication was observed during the hospital course and no patient suffered from the recurrence of empyema in the follow-up period. Conclusion: We think that early operation with the use of VATS is safe and efficient for stage II empyema which did not respond to medical treatment(antibiotics and chest tube drainage), therefore, it can prevent stage II empyema from advancing to stage III, organized empyema.

Effect of Chitosan-Trimer on the Prevention of Postoperative Intraperitoneal Adhesion Formation in Rats (랫트에서 Chitosan-Trimer가 복강유착에 미치는 영향)

  • Kwon, Eun-ju;Jang, Kwang-ho;Jang, In-ho
    • Journal of Veterinary Clinics
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    • v.18 no.3
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    • pp.257-264
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    • 2001
  • This study was performed to investigate the effects of chitosan-trimer (CT) on the prevention of postoperative adhesion formation in the rate model. All animals divided into PBS (control), 1% CT, 3% CT, and chitin treated group. The mean adhesion score in 1% CT group (1.03$\pm$0.63), 3% CT group (0.64$\pm$0.53) and chitin group (1.67$\pm$0.71) was found to be lower than that in control group (2.07$\pm$0.81). More favorable adhesion prevention was achieved in 3% CT group (0.64$\pm$0.53) in comparison with the control group, 1% CT group, and chitin group without any hemorrhagic complications. A statistically significant difference was observed in adhesion formation between control group and 3% CT group (p<0.001). In control group, 44 of 45 sites (97.7%) formed adhesions between the intestine defects. In contrast, 3% CT was effective in reducing the incidence of adhesion formation to 17 to 45 sites (62.2%) (p<0.05). The locations of adhesions were observed in serosa-serosa (60%), serosa-mesentery (13.3%), serosa-connective tissue of testis (10%), omentum-liver (10%), serosa-omentum (3.3%), serosa-cecum (3.3%), and serosa-incision (0%). On the results of histological analysis, grade of inflammation and fibrosis at the sites of postoperative peritoneal adhesion formation were not significantly different in all groups. But, 3% CT showed the lowest score of inflammation and fibrosis. In 3% CT group, the rate of increase of plasma fibrinogen was significantly lower compared with that in control group from pre-operation to 10 days later (p<0.05). There were no appreciable difference in the CBC, leukocyte differential counts and total protein concentrations among four groups. In conclusion, our data suggested that CT should be effective on reducing adhesion formation in experimental rat models. The results also showed that 3% CT does not adversely affect normal wound healing and healthy recovery after operation.

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