WorldWideScience

Sample records for intra-carotid urokinase thrombolytic

  1. Thrombolytic treatment for acute ischemic cerebral stroke: intraarterial urokinase infusion vs. intravenous heparin and urokinase infusion

    International Nuclear Information System (INIS)

    Ko, Gi Young; Suh, Dae Chul; Lee, Jae Hong; Kim, Jun Hyoung; Choi, Choong Gon; Lee, Ho Kyu; Lee, Myoung Chong

    1996-01-01

    To evaluate the efficacy and limitation of intra-arterial urokinase (IAUK) infusion for treatment of acute cerebral stroke. Twenty-seven acute cerebral stroke patients treated with IAUK infusion within six hours of stroke onset were reviewed. All patients showed normal initial brain findings on CT. In 21 patients, urokinase(5-15 x 10 5 IU) was administered through a microcatheter placed into or proximal to occluded segment. Mechanical disruption of thrombus by guidewire was performed in 17 patients. Angiographic and clinical responses and complications after IAUK infusion, were evaluated and the results were compared with those of intravenous heparin(N=19) and urokinase infusion(N=19). Complete or partial angiographic recanalization of occluded segment was found in 18 patients (67%), and neurologic improvement was followed in 14 patients(52%). The degree of improvement on the stroke scale score after IAUK infusion was statistically more significant(p<0.05) than that shown after intravenous heparin and urokinase infusion. Complications after IAUK infusion were large(15%) and small amount intracerebral hemorrhage(15%), contrast leakage into brain parenchyma(11%), and gastrointestinal bleeding(4%). Between the IAVK and the intravenous urokinase infusion group, differences in extent and types of complications were statistically insignificant, but were significantly higher in those two groups than in the intravenous heparin infusion group. IAUK infusion may be effective for the treatment of acute cerebral stroke

  2. Urokinase vs Tissue-Type Plasminogen Activator for Thrombolytic Evacuation of Spontaneous Intracerebral Hemorrhage in Basal Ganglia

    Directory of Open Access Journals (Sweden)

    Yuqian Li

    2017-08-01

    Full Text Available Spontaneous intracerebral hemorrhage (ICH is a devastating form of stroke, which leads to a high rate of mortality and poor neurological outcomes worldwide. Thrombolytic evacuation with urokinase-type plasminogen activator (uPA or tissue-type plasminogen activator (tPA has been showed to be a hopeful treatment for ICH. However, to the best of our knowledge, no clinical trials were reported to compare the efficacy and safety of these two fibrinolytics administrated following minimally invasive stereotactic puncture (MISP in patients with spontaneous basal ganglia ICH. Therefore, the authors intended here to evaluate the differential impact of uPA and tPA in a retrospective study. In the present study, a total of 86 patients with spontaneous ICH in basal ganglia using MISP received either uPA (uPA group, n = 45 or tPA (tPA group, n = 41, respectively. The clinical baseline characteristics prior to the operation were collected. In addition, therapeutic responses were assessed by the short-term outcomes within 30 days postoperation, as well as long-term outcomes at 1 year postoperation. Our findings showed that, in comparison with tPA, uPA was able to better promote hematoma evacuation and ameliorate perihematomal edema, but the differences were not statistically significant. Moreover, the long-term functional outcomes of both groups were similar, with no statistical difference. In conclusion, these results provide evidence supporting that uPA and tPA are similar in the efficacy and safety for thrombolytic evacuation in combination with MISP in patients with spontaneous basal ganglia ICH.

  3. Managing dysfunctional central venous access devices: a practical approach to urokinase thrombolysis.

    Science.gov (United States)

    Kumwenda, Mick; Dougherty, Lisa; Spooner, Helen; Jackson, Victoria; Mitra, Sandip; Inston, Nicholas

    2018-01-25

    Tunnelled central venous access devices (CVADs) are defined as any intravenous multipurpose catheters placed within the central veins for use in haemodialysis and administration of blood products or chemotherapy in oncology and haematological conditions. Frequent complications include thrombosis and catheter-related infection, which may lead to significant adverse patient outcomes. Once thrombosis is suspected correction should be attempted empirically with thrombolytic agents. Commonly available thrombolytic agents in the UK include urokinase (Syner-Kinase) and alteplase (Cathflo). It is well recognised that urokinase usage differs widely and concerns were raised by clinicians about the variation of dose regimens nationally. The objective of the CVAD Focus Group was to address this issue and offer guidance in the management of suspected thrombosis of CVAD with urokinase using two algorithms for renal and non-renal dysfunctional CVAD and to audit prospectively the outcomes of intervention.

  4. Intracranial hemorrhage complicating thrombolytic therapy for acute myocardial infarction

    International Nuclear Information System (INIS)

    Uglietta, J.P.; Boyko, O.B.; O'Connor, C.M.; Aldrich, H.; Massey, E.W.; Heinz, E.R.

    1990-01-01

    This paper determines the incidence and types of intracranial hemorrhage (ICH) in 1,696 patients treated with thrombolytic therapy for acute myocardial infarction (AMI). Thirteen of 1,696 patients experienced ICH, and their nonenhanced brain CT scans were reviewed. Their mean age was 62 years (range, 53-74 years), and nine of 13 were male. Six patients received tissue plasminogen activator (tPA), four streptokinase, two urokinase, and one tPA and urokinase. The hemorrhages were classified according to CT location: intraparenchymal (IPH), subarachnoid (SAH), subdural (SDH), and intraventricular (IVH). The incidence of ICH was 0.76%. There were 31 hemorrhages in 13 patients. Twelve hemorrhages were IPH, 10 were SDH, seven were SAH, and two were IVH. Excluding IVH, 24 of 29 hemorrhages (83%) were supratentorial

  5. Alteplase vs. urokinase for occluded hemodialysis catheter: A randomized trial.

    Science.gov (United States)

    Pollo, Viviane; Dionízio, Danielle; Bucuvic, Edwa Maria; Castro, João Henrique; Ponce, Daniela

    2016-07-01

    Introduction Thrombosis of tunneled central venous catheters (CVC) in hemodialysis (HD) patients is common and it can lead to the elimination of vascular sites. To compare the efficacy of alteplase vs. urokinase in reestablishing adequate blood flow through completely occluded vascular catheters. Methods In this randomized study, patients with completely occluded tunneled HD catheters received 40 minutes intracatheter dwell with alteplase (1 mg/mL) or urokinase (5000 IU/mL). Primary endpoint was the proportion of patients with occluded catheters achieving post-thrombolytic blood flow of ≥250 mL/min. Safety endpoints included the incidence of hemorrhagic and infectious complications. Findings Eligible adult patients (n = 100) were treated with alteplase (n = 44) or urokinase (n = 56). The two groups were similar in gender (male: 51.8% vs. 56.8%, P = 0.35), age (60 ± 12 vs. 59 ± 13 years, P = 0.71), time on dialysis (678 ± 203 vs. 548 ± 189 days, P = 0.77), diabetes and cardiovascular disease (55.6% vs. 70.4%, P = 0.08 and 17.8% vs. 22.7%, P = 0.38, respectively), jugular vein as main vascular access (54.8% vs. 62.5%, P = 0.57), and time of CVC (278 ± 63 vs. 218 ± 59 days, P = 0.67). Primary success with alteplase and urokinase occurred in 42/44 (95%) vs. 46/56 (82%), P = 0.06. Success was not achieved after the second dose of alteplase and urokinase in 1 and 7 cases, respectively (2% vs. 12%, P = 0.075). Serious adverse effects were not observed in both groups. There was no difference between the two groups in infectious complications (P = 0.94). Discussion Alteplase and urokinase are effective thrombolytic agents for restoring HD catheter patency. Our study has revealed a likely slight superiority of alteplase over urokinase for unblocking central lines, but which has enrolled too few patients to be able to detect a difference of this size. © 2016 International Society for

  6. Tailored thrombolytic therapy. A perspective

    NARCIS (Netherlands)

    M.L. Simoons (Maarten); A.E.R. Arnold (Alfred)

    1993-01-01

    textabstractBACKGROUND. In contrast with current standard regimens, it seems more appropriate to tailor thrombolytic therapy to individual patient characteristics. A proposed model for such tailored therapy is based on individual assessment of benefits and risks of thrombolytic therapy, taking into

  7. Thrombolytic drugs for heart attack

    Science.gov (United States)

    ... gov/ency/article/007488.htm Thrombolytic drugs for heart attack To use the sharing features on this page, ... supply blood and oxygen to the heart. A heart attack can occur if a blood clot stops the ...

  8. Thrombolytic therapy in pulmonary embolism.

    LENUS (Irish Health Repository)

    Nagi, D

    2010-01-01

    Massive pulmonary embolism carries a high mortality. Potential treatment includes anticoagulation, thrombolytic therapy and embolectomy. We report a case of deep vein thrombosis leading to progressive massive pulmonary embolism despite appropriate anticoagulation, where thrombolysis with IVC filter placement resulted in a successful outcome.

  9. Selective arterial thrombolysis with urokinase

    International Nuclear Information System (INIS)

    Park, Jae Hyung; Park, Kil Sun; Chung, Jin Wook; Han, Joon Koo; Kim, Sang Joon; Kim, Dae Young

    1991-01-01

    Seven patients with thrombotic occlusions of the peripheral arteries or grafts were treated with urokinase by direct intraarterial selective infusion. During the infusion, simultaneous heparin infusion was used to reduce the frequency of thrombus formation on the infusion catheter or recurrent thrombosis. In 4 patients in whom a complete thrombolysis occurred, urokinase was infused by a high-dose transthrombus bolus technique followed by continuous infusion. There other patients, in whom thrombolysis was partially accomplished and then surgical thrombectomy was performed, were treated only by continuous urokinase infusion. Small hematomas developed at the infusion catheter entry site in 2 patients, but transfusion or operation was not required. Other significant complications were not found. Our results suggest that selective arterial infusion of urokinase with a transthrombus bolus technique can accomplish a complete arterial thrombolysis without any significant complications

  10. Role of the low density lipoprotein receptorrelated protein (lrp) in the clearance and liver uptake of recombinant single chain urokinase-type plasminogen activator (rscu-pa) in rats

    NARCIS (Netherlands)

    Kaaden, M.E. van der; Riiken, D.C.; Kruiit, J.K.; Berkel, T. van; Kuiper, J.

    1996-01-01

    Urokinase-type plasminogen activator (u-PA) is used as a thrombolytic agent in the treatment of acute myocardial infarction. In vitro, E.coli produced rscu-PA is recognized by LRP on parenchyma! liver cells. In this study we investigated the role of LRP in the liver uptake and plasma clearance of

  11. The method of thrombolytic radioassay in vitro

    International Nuclear Information System (INIS)

    Yang Yi; Zhao Zhuanyou; Liu Houxiao; Niu Huisheng; Li Huaifen; Wang Yinlan

    1998-01-01

    The similar nature thrombus is made of 125 I-fibrinogen with platelet-rich or antithrombotic blood to culture together with platelet-rich plasma and thrombolytic agent. The thrombolytic rate is calculated depending on the radioactivity of plasma. At the same time, some relative factors with thrombus and thrombolytic effects of recombinant staphylokinase (STAR) is discussed. These results show that radioassay technology is sensitive, stable, specific and wonderful method

  12. Local intracranial intraarterial thrombolytic therapy in acute cerebral infarction

    International Nuclear Information System (INIS)

    Kim, Sun Yong; Suh, Jung Ho

    1996-01-01

    To evaluate the efficacy of direct intracranial intraarterial thrombolytic therapy in patients with acute atherothrombotic and embolic stroke. Forth-one patients with cerebral thromboembolic disease, all in the area of the middle cerebral artery and including two cases of internal carotid artry occlusion, were treated with microcatheter-directed local intraarterial thrombolysis, using 180,000 to 1,000,000 unit urokinase and 15 to 50 mg of tissue plasminogen activator (tPA). The time elapsed before treatment ranged from 260 to 470 minute (mean : 380 minutes). The effect of treatment was assessed by cerebral angiography, by the clinical outcome. For 25 patients (61%), complete vessel recanalization was successful. In eight and three cases, respectively, the result was partial recanalization and residual stenosis. In 21 patients (51%), both acute neurologic and functional outcomes improved significantly within 24 hours and in 92% of patients, within one month. Hemorrhagic transformations occurred in five patients (12.2%), and in five others there were high density lesions around the basal ganglia and temporal lobe, which was cleared on CT within 24 hours. This suggested transient extrapolation of the contrast media rather than true hemorrhage. tPA showed better results than urokinase in terms of the rate of recanalization (68.7% vs 56.7%) and the occurrence of hemorrhagic infarction(6.3% vs 16.0%). Local intraarterial cerebral thrombolysis is thought be an effective method in the treatment of acute brain infarction, but in some patients may cause intracerebral hemorrhage in some patients

  13. Local intracranial intraarterial thrombolytic therapy in acute cerebral infarction

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sun Yong; Suh, Jung Ho [Ajou Univ. College of Medicine, Suwon (Korea, Republic of)

    1996-06-01

    To evaluate the efficacy of direct intracranial intraarterial thrombolytic therapy in patients with acute atherothrombotic and embolic stroke. Forth-one patients with cerebral thromboembolic disease, all in the area of the middle cerebral artery and including two cases of internal carotid artry occlusion, were treated with microcatheter-directed local intraarterial thrombolysis, using 180,000 to 1,000,000 unit urokinase and 15 to 50 mg of tissue plasminogen activator (tPA). The time elapsed before treatment ranged from 260 to 470 minute (mean : 380 minutes). The effect of treatment was assessed by cerebral angiography, by the clinical outcome. For 25 patients (61%), complete vessel recanalization was successful. In eight and three cases, respectively, the result was partial recanalization and residual stenosis. In 21 patients (51%), both acute neurologic and functional outcomes improved significantly within 24 hours and in 92% of patients, within one month. Hemorrhagic transformations occurred in five patients (12.2%), and in five others there were high density lesions around the basal ganglia and temporal lobe, which was cleared on CT within 24 hours. This suggested transient extrapolation of the contrast media rather than true hemorrhage. tPA showed better results than urokinase in terms of the rate of recanalization (68.7% vs 56.7%) and the occurrence of hemorrhagic infarction(6.3% vs 16.0%). Local intraarterial cerebral thrombolysis is thought be an effective method in the treatment of acute brain infarction, but in some patients may cause intracerebral hemorrhage in some patients.

  14. Intra-artery thrombolytic therapy for acute ischemic cerebral infarction

    International Nuclear Information System (INIS)

    Du Wei; Shao Chengmin; Wang Jianlin; Lei Jin; Jia Fan; Cao Lanfang; Chai Ruchang; Su Wei; Gu Jinchuan

    2004-01-01

    Objective: To evaluate the clinical effects of intra-arterial thrombolytic therapy for acute ischemic cerebral infarction and analyze the factors influencing the clinical prognosis. Methods: 32 patients were treated with intra-arterial thrombolysis using urokinase (median dose, 65 x 10 4 U) within 2-20 hours, after the onset. The patient's condition was assessed by neurologists using National Institutes of Health Stroke Scale (NIHSS) score right at the admission. Clinical outcome was assessed after 3 months and graded as good for Modified Rankin Scale (MRS) scores of 0 to 3 and poor for MRS scores of 4 or 5 and death. Results: Follow up cerebral angiography of 14 cases treated within 6 hours after onset showed complete/partial recanalization in 13 cases. Other 18 patients whose treatment started beyond 6 hours after onset out-came with complete/partial in 7. 20 (62.5%) of the 32 patients had good out-come, 12(37.5%) had poor outcome and two patients(9.4%) died. Cerebral hemorrhage occurred in 2 of the 32 patients. Good outcome was associated with an initial NIHSS score of <20 (P<0.01) and vascular recanalization (P<0.025). Recanalization was more likely to be obtained if thrombolysis began within 6 hours (P<0.05). Conclusion: Intra-arterial thrombolysis is a safe and effective therapy for acute ischemic cerebral infarction. (authors)

  15. Cerebral Venous Congestion as Indication for Thrombolytic Treatment

    International Nuclear Information System (INIS)

    Tsai, Fong Y.; Kostanian, Varoujan; Rivera, Monica; Lee, Kwo-Whie; Chen, Clayton C.; Nguyen, Thong H.

    2007-01-01

    Purpose. To carry out a retrospective analysis of patients with acute dural sinus thrombosis, and the role of cerebral venous congestion in patient management. Methods. Twenty-five patients were identified with the clinical and imaging diagnosis of acute dural sinus thrombosis. The imaging diagnosis was by magnetic resonance (MR) and/or computed tomography (CT) venography. There was a female predominance with a female to male ratio of 1.5 to 1 (16 women, 9 men). The age range was from 19 to 64 years old with an average age of 37 years. The first 10 patients, who ranged in age from 21 to 64 years old (average 37 years), received only anticoagulation therapy with heparin and warfarin for periods ranging from 5 days to 2 months. The remaining 15 patients ranged in age from 19 to 57 years old (average 38 years). They either underwent subsequent thrombectomy after a trial of anticoagulation therapy, or went straight to thrombectomy. These latter 15 patients had initial evidence of cerebral venous congestion, either clinically by severe or worsening symptoms despite anticoagulation therapy, or on initial or subsequent CT or MR imaging. In our experience, the cerebral venous congestion imaging findings included intracranial hemorrhage, a hematoma, or edema. The thrombolytic treatment technique consisted of the advancement of a 6 Fr guiding catheter to the jugular bulb or sigmoid sinus from a transfemoral approach. A microcatheter was then advanced to the proximal portion of the thrombus and then either tissue plasminogen activator (tPA) or urokinase was injected to prevent clot propagation. A balloon catheter was used to perform thrombectomy since the thrombolytic agents can be injected via the inner lumen with an inflated balloon. The inflated balloon helped to keep the venous flow from washing out the thrombolytic agent, thus facilitating the agent's effect. Results. The first 10 patients received only anticoagulation therapy with heparin and warfarin for periods

  16. Simple canine model of arterial thrombosis with endothelial injury suitable for investigation of thrombolytic agents

    International Nuclear Information System (INIS)

    Badylak, S.F.; Poehlman, E.; Williams, C.; Klabunde, R.E.; Turek, J.; Schoenlein, W.

    1988-01-01

    Three separate studies were done to evaluate a new canine model of arterial thrombosis with endothelial injury. Endothelial injury was produced by exposing the luminal surface of a 2-cm segment of femoral artery to 100 degrees C saline for 5 min. There was no disruption of proximal or distal blood flow with this model, and thrombolysis was continuously monitored by measuring 125 I-labelled fibrin gamma emissions from the thrombus. Study No. 1 showed that complete endothelial denudation was achieved with this model. Study No. 2 demonstrated 1) adherence of the experimentally induced thrombus to subendothelial connective tissue, and 2) endogenous thrombolysis of approximately 9% during the initial 2 h after thrombus formation. Study No. 3 tested the usefulness of the model for evaluating the thrombolytic efficacy of urokinase. Urokinase (30,000 U/Kg, bolus IV injection) caused 38 +/- 5.4% thrombolysis within 90 min of drug administration versus 5.9 +/- 2.4% for a saline-treated control group. We conclude that this model provides a technically simple and reproducible method for the laboratory investigation of thrombosis and thrombolysis in arteries with endothelial injury

  17. Phytochemical Screening and Thrombolytic Activity of Chloroform ...

    African Journals Online (AJOL)

    The present study was designed to investigate thrombolytic properties of chloroform extract of Urena sinuata along with phytochemical study for the presence of phytochemical constituents. The concentrated extracts were collected and allow to air dry for complete evaporation of chloroform. Phytochemical analyses were ...

  18. Local thrombolytic treatment for renal arterial embolism.

    Science.gov (United States)

    Glück, G; Croitoru, M; Deleanu, D; Platon, P

    2000-09-01

    To determine the utility of local thrombolysis in the treatment of acute renal arterial occlusion. We used local thrombolytic treatment in a female patient, aged 76, with 72 h of anuria, right lumbar and flank pain. She had a 3-year history of ischemic heart disease and atrial fibrillation controlled with digital treatment. Also, she was nephrectomized on the left side 33 years ago for lithiasic pyonephrosis. A normal right urinary tract was demonstrated with ultrasound examination, KUB radiography and retrograde pyelography. The next step was diagnostic abdominal angiography and local thrombolytic treatment with streptokinase. Thrombolysis with streptokinase was successful following 72 h of renal artery occlusion. After 24 months the patient is doing well. Local intra-arterial thrombolysis is the treatment of choice in renal artery occlusion.

  19. [Intra-arterial thrombolytic therapy of lower limb ischemia].

    Science.gov (United States)

    Juhan, C; Haupert, S; Miltgen, G; Dulac, P; Girard, N; Barthélémy, P; Raybaud, C

    1990-02-01

    Between 1984 and 1989, 35 patients with recent arterial or graft occlusions have been treated with intra-arterial infusion using sequential association of Urokinase (U.K.) and Lys-Plasminogen. Occlusion was thrombotic in 68.5% of the cases ans embolic in 31.5%, involving 28 native arteries and 7 bypass grafts. The mean duration was 16 days (2 to 90). Continuous infusion of U.K.: 84,000 U.I./H and bolus of Lys-Plasminogen 15 microKatals every 30 minutes were delivered through a catheter embedded into the clot. Intra-venous heparin was always associated. The mean duration of lytic drug infusion was 8 H. Complementary arterial reconstruction by vascular surgery of percutaneous transluminal angioplasty was performed in 23% of the patients. Patients with recent alimentary tract bleeding, hemorragic stroke in the last six months or severe high blood pressures were contra-indicated. Complete lysis was obtained in 23 cases (66%), partial lysis in 7 (20%) and no lysis in 5 (14%). The clinical result was excellent in 24 cases (68.5%), good in 3 (8.5%) and bad in 8 (23%) in which amputation was always necessary. 5 local hematoma (14%) treated by surgery or transfusion and one death (3%) due to neurological complication occurring 24 hours after the end of the procedure were observed. The literature survey has shown that the results of low doses of Streptokinase (S.K.) local infusions were not better, and that higher doses of S.K. or U.K. delivered during a shorter infusion time increased the efficacy of lysis and decreased the rate of hemorragic complications. We have proposed the local thrombolytic treatment to the limb threatening ischemic cases when the traditional medical or surgical techniques where thought to be associated to a high risk of failure or complication. The specific indications are the acute or sub-acute ischemic situation due to atheromatous artery thrombosis, distal or old embolism where the Fogarty catheter is inefficient, and graft thrombosis. Severe

  20. Efficacy of femoral vascular closure devices in patients treated with anticoagulant, abciximab or thrombolytics during percutaneous endovascular procedures

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ha Young; Choo, Sung Wook [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Roh, Hong Gee [Konkuk University School of Medicine, Seoul (Korea, Republic of)] (and others)

    2006-03-15

    This study assessed the outcomes of using vascular closure devices following percutaneous transfemoral endovascular procedures in the patients who were treated with heparin, abciximab thrombolytics (urokinase or t-PA) during the procedures. From March 28, 2003 to August 31, 2004, we conducted a prospective and randomized study in which 1,676 cases of 1.180 patients were treated with one of the two different closure devices (the collagen plug device was Angio-Seal{sup TM.}, the suture-mediated closure device was The Closer S{sup TM}) at the femoral access site after instituting percutaneous endovascular procedures. Among the 1,676 cases, 108 cases (the drug group) were treated with heparin only (n=94), thrombolytics only (n=10), heparin and thrombolytics (n=3), or abciximab and thrombolytics (n=1) during the procedures; 1,568 cases (the no-drug group) were treated without any medication. We compared the efficacy and complications between the two groups. Of the drug group, 42 cases underwent arterial closures with the collagen plug devices and 66 cases underwent arterial closures with the suture-mediated closure devices. We also compared the efficacy and complications between these two group. The immediate hemostasis rates were 92.9% (1,456/1,568) in the no drug group and 91.7% (99/108) in the drug group. Early complications occurred in four cases of the drug group. These included two episodes of rebleeding with using the Closer S, which required manual compression for at least 10 minutes, and two episodes of minor oozing with using one Angio-Seal and one Closer S, which required two hours of additional bed rest. There was no late complication. So, the total success rates were 90.8% (1,423/1,568) in the no-drug group and 88.0% (95/108) in the drug group. These results were not significantly different between the two groups ({rho}=0.34). In the drug group, the difference of the successful hemostasis rate between the collagen plug devices and the suture

  1. Efficacy of femoral vascular closure devices in patients treated with anticoagulant, abciximab or thrombolytics during percutaneous endovascular procedures

    International Nuclear Information System (INIS)

    Kim, Ha Young; Choo, Sung Wook; Roh, Hong Gee

    2006-01-01

    This study assessed the outcomes of using vascular closure devices following percutaneous transfemoral endovascular procedures in the patients who were treated with heparin, abciximab thrombolytics (urokinase or t-PA) during the procedures. From March 28, 2003 to August 31, 2004, we conducted a prospective and randomized study in which 1,676 cases of 1.180 patients were treated with one of the two different closure devices (the collagen plug device was Angio-Seal TM. , the suture-mediated closure device was The Closer S TM ) at the femoral access site after instituting percutaneous endovascular procedures. Among the 1,676 cases, 108 cases (the drug group) were treated with heparin only (n=94), thrombolytics only (n=10), heparin and thrombolytics (n=3), or abciximab and thrombolytics (n=1) during the procedures; 1,568 cases (the no-drug group) were treated without any medication. We compared the efficacy and complications between the two groups. Of the drug group, 42 cases underwent arterial closures with the collagen plug devices and 66 cases underwent arterial closures with the suture-mediated closure devices. We also compared the efficacy and complications between these two group. The immediate hemostasis rates were 92.9% (1,456/1,568) in the no drug group and 91.7% (99/108) in the drug group. Early complications occurred in four cases of the drug group. These included two episodes of rebleeding with using the Closer S, which required manual compression for at least 10 minutes, and two episodes of minor oozing with using one Angio-Seal and one Closer S, which required two hours of additional bed rest. There was no late complication. So, the total success rates were 90.8% (1,423/1,568) in the no-drug group and 88.0% (95/108) in the drug group. These results were not significantly different between the two groups (ρ=0.34). In the drug group, the difference of the successful hemostasis rate between the collagen plug devices and the suture-mediated devices was also

  2. Antimicrobial, hemolytic and thrombolytic activities of some new N ...

    African Journals Online (AJOL)

    Triton X-100 and phosphate buffer saline (PBS) were employed as references. Thrombolytic activity assay. Thrombolytic activity was assayed according to. Mannan et al [16] using a bovine blood sample. PBS and streptokinase were employed as references. Activity was determined by the following equation, where X ...

  3. The effect of thrombolytic therapy on QT dispersion in acute ...

    African Journals Online (AJOL)

    Purpose: We aimed to determine the effect of intravenous thrombolytic therapy on QT dispersion (QTd) and its role in the prediction of reperfusion arrhythmias. Materials and Methods: Twenty patients with acute myocardial infarction (MI) were enrolled in the study. Measurements of QTd were carried out prior to thrombolytic ...

  4. [Urokinase in the management of occluded PICC lines].

    Science.gov (United States)

    Muller, C; Jacquier, A; Varoquaux, A; Cohen, F; Louis, G; Gaubert, J Y; Moulin, G; Bartoli, J M; Vidal, V

    2010-03-01

    To determine the efficacy and safety of urokinase in the management of occluded PICC lines. A total of 587 PICC lines were placed over an 11 month period. During this period, 28 PICC lines (4.8%) became occluded: 12 occluded PICC lines were successfully managed by simple flushing with normal saline while 16 PICC lines were thrombolyzed with urokinase. After urokinase, 93.8% (15/16) of occluded PICC lines were completely patent. A single infusion of urokinase, 20,000 IU over 30 minutes, was used in all cases. No secondary occlusion or complication was noted after urokinase. Urokinase is effective and safe to restore patency to occluded PICC lines. The procedure is simple, and could be performed at the bedside by nursing staff after medical prescription. It is an alternative to over the wire PICC line exchange, that could reduce the risk of complication related to manipulations, patient discomfort and cost.

  5. Pharmaceutical Sponsorship Bias Influences Thrombolytic Literature in Acute Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Ryan P Radecki

    2011-05-01

    Full Text Available Background: The efficacy of thrombolytic therapy for acute ischemic stroke remains controversial in Emergency Medicine and has not been fully endorsed by either the American College of Emergency Physicians or the American Academy of emergency medicine. A growing recognition exists of the influence of pharmaceutical sponsorship on the reported findings of published clinical trials. Sponsorship bias has been suggested as a potential criticism of the literature and guidelines favoring thrombolytic therapy. Objective: The objective of this study is to review the most influential literature regarding thrombolytic therapy for acute ischemic stroke and document the presence or absence of pharmaceutical sponsorship. Methods: A publication-citation analysis was performed to identify the most frequently cited articles pertaining to thrombolytic therapy for acute ischemic stroke. Identified articles were reviewed for disclosures of pharmaceutical funding. Results: Of the 20 most-cited articles pertaining to thrombolytic therapy for acute stroke, 17 (85% disclosed pharmaceutical sponsorship. These disclosures range from general sponsorship to direct employment of authors by pharmaceutical companies. Conclusion: An overwhelming predominance of the most influential literature regarding thrombolytic therapy for acute ischemic stroke is susceptible to sponsorship bias. This potential bias may provide a basis for physician concern regarding the efficacy and safety of thrombolytic therapy. Further, large, independent, placebo-controlled studies may be required to guide therapy and professional guidelines definitively for acute ischemic stroke. [West J Emerg Med. 2011;12(4:435–441.

  6. Antimicrobial, hemolytic and thrombolytic activities of some new N ...

    African Journals Online (AJOL)

    . Hemolytic and thrombolytic activities were determined by measuring absorbance before and after incubation of blood cells with test compound. Results: Compound 9d strongly inhibited Bacillus subtilis and Escherichia coli with zone of ...

  7. Pre-hospital Obstacles in Thrombolytic Therapy and Suggested Solutions

    Directory of Open Access Journals (Sweden)

    Betül Tekin Güveli

    2015-12-01

    Full Text Available INTRODUCTION: Acute ischemic stroke is frequently encountered in emergency neurology clinics. Especially when administered within 3 hours of symptom onset, thrombolytic therapy is important in reducing ischemic injury and neurological disability. In this study, we aimed to investigate the demographic and clinical characteristics according to application time, to identify situations which pose an obstacle to thrombolytic therapy and to review the thrombolytic therapy results in patients diagnosed with acute ischemic stroke. METHODS: The patients diagnosed with acute ischemic stroke were evaluated and their age, gender, complaints, risk factors, previous history of stroke, with whom they live, how they arrived at the hospital and their application time information were recorded. Those who were admitted within 3 hours of symptom onset were assessed as early, those admitted after 3 hours were assessed as late admission. Then the rate of thrombolytic therapy, final results and the clinical status in early admission patients and the reasons for delay in late admission patients were discussed. RESULTS: Among 361 acute ischemic stroke patients, the mean age was 66±14,1. 111 patients were admitted within 3 hours of symptom onset, 246 patients were admitted after three hours. Patients arriving to emergency room with 112 Ambulance Service were admitted earlier than those brought in by family, and this difference was statistically significant. The most common causes of time loss in late admissions were the patients being referred from other centers and the unawareness of family about the importance of the disease. There were 13 patients treated with thrombolytic therapy, and complications occurred in one patient. DISCUSSION AND CONCLUSION: Thrombolytic therapy is important in acute ischemic stroke for suitable patients.Our study suggested that the most important factors in spreading of performing the thrombolytic therapy are informing the public about

  8. Debate: Should the elderly receive thrombolytic therapy or primary angioplasty?

    Directory of Open Access Journals (Sweden)

    White Harvey D

    2000-12-01

    Full Text Available Abstract Thrombolysis and primary angioplasty are both recommended reperfusion strategies for elderly patients presenting with myocardial infarction (MI. Primary angioplasty is most beneficial in high-risk patients. While the elderly have a high absolute risk of dying or developing complications after MI, they also have an increased risk of intracranial haemorrhage if they are given thrombolytic therapy. It could therefore be reasonably argued that primary angioplasty is the reperfusion strategy of choice in the elderly. However, primary angioplasty has not been shown to have a greater relative benefit than thrombolytic therapy in the elderly. Recent data from the Fibrinolytic Therapy Trialists' (FTT Collaborative Group show that thrombolytic therapy significantly reduces mortality compared with control treatment in patients over 75 years of age presenting within 12 h of symptom onset, with ST-segment elevation or bundle branch block. Future advances in adjunctive therapies may improve myocyte perfusion and hence the outcomes achieved by both invasive and noninvasive reperfusion strategies. Better thrombolytic regimens incorporating adjunctive agents such as bivalirudin may reduce the risk of intracranial haemorrhage. Few hospitals can provide a 24-h primary angioplasty service with door-to-balloon times consistently less than 90 min, and thrombolytic therapy is therefore a far more practical option in most instances.

  9. Effect of thrombolytic therapy on postinfarction myocardial ischemia

    DEFF Research Database (Denmark)

    Mickley, H; Junker, A; Møller, M

    1994-01-01

    be responsible for the reduction in cardiac death. So far it has not been clearly established how thrombolytic therapy affects postinfarction myocardial ischemia. From studies evaluating ST segment changes on exercise testing or ambulatory monitoring it is concluded that thrombolysis probably results......In patients with acute myocardial infarction a substantial reduction in mortality can be achieved by early intravenous thrombolytic therapy. The beneficial effect of thrombolysis on left ventricular function is relatively small, and it seems unlikely that this minor improvement alone can...... in a reduction of residual ischemia. The reduced ischemic burden is proposed to be one important pathophysiological mechanism underlying the frequently observed improvement in hemodynamic stress test variables following thrombolytic treatment....

  10. MANAGEMENT OF THROMBOLYTIC TREATMENT IN PATIENTS WTH MASSIVE PULMONARY THROMBOEMBOLISM

    Directory of Open Access Journals (Sweden)

    Turan Aktas

    2013-09-01

    In total, whose age change between 27 and 90, who got mPTE diagnosis and received thrombolytic treatment were included in the study. Male vs. female rate was 2/3. Mortality developed in 2 patients, who were included in the study. Intracranial hemorrhage which is one of the major complications occurred in only one patient . Recurrence thromboembolism was not followed in none of the patients after the thrombolytic treatment. In mPTE, early diagnosis and rapid treatment are life saving. With the help of the diagnostic methods developing and becoming widespread lately, diagnosis of the mPTE can be made more rapidly and the treatment can be started without losing time. Moreover, it can be said that thrombolytic treatment is definitely a life saving treatment way in mPTE when it is made with close follow-up. [J Contemp Med 2013; 3(3.000: 166-172

  11. Thrombolytic therapy of acute myocardial infarction alters collagen metabolism

    DEFF Research Database (Denmark)

    Høst, N B; Hansen, S S; Jensen, L T

    1994-01-01

    infarction and receiving thrombolytic therapy. Regardless of whether acute myocardial infarction was confirmed or not, S-PIIINP increased (94-120%) 4 h after streptokinase therapy (p ....02). With confirmed acute myocardial infarction, S-PIIINP increased from 24 h towards a plateau reached at day 2-3 (p acute myocardial infarction had S-PICP above baseline at 1, 2, and 6 months (p ....05). A less pronounced S-PIIINP increase was noted with tissue-plasminogen activator than with streptokinase. Thrombolytic therapy induces collagen breakdown regardless of whether acute myocardial infarction is confirmed or not. With confirmed acute myocardial infarction collagen metabolism is altered...

  12. Thrombolytic therapy of acute myocardial infarction alters collagen metabolism

    DEFF Research Database (Denmark)

    Høst, N B; Hansen, S S; Jensen, L T

    1994-01-01

    The objective of the study was to monitor collagen metabolism after thrombolytic therapy. Sequential measurements of serum aminoterminal type-III procollagen propeptide (S-PIIINP) and carboxyterminal type-I procollagen propeptide (S-PICP) were made in 62 patients suspected of acute myocardial...

  13. Thrombolytic therapy preserves vagal activity early after acute myocardial infarction

    DEFF Research Database (Denmark)

    Lind, P; Hintze, U; Møller, M

    2001-01-01

    to the pattern observed in thrombolysed patients early after AMI. In thrombolysed patients pNN50 values, particularly at night, were further improved 6 weeks after AMI (p = 0.037). CONCLUSION: These observations indicate that thrombolytic therapy, given for a first AMI, preserves vagal activity when compared...

  14. The effect of thrombolytic therapy on QT dispersion in acute ...

    African Journals Online (AJOL)

    2013-07-02

    Jul 2, 2013 ... heart failure. Simple linear regression analysis revealed no correlation between the ejection fraction and peak creatine kinase levels, and QTcd values in the late phase of MI in all patients. Reperfusion arrhythmias. Ventricular arrhythmias after thrombolytic therapies were analyzed by a 24‑h Holter ECG.

  15. Interaction of urokinase A chain with the receptor of human keratinocytes stimulates release of urokinase-like plasminogen activator

    Energy Technology Data Exchange (ETDEWEB)

    Fibbi, G.; Magnelli, L.; Pucci, M.; Del Rosso, M. (Florence Univ. (Italy))

    1990-03-01

    On the basis of a fibrinolytic assay with {sup 125}I-fibrin, zymography, and immunoprobing with anti-human urokinase antibody, the authors have observed that the in vitro established NCTC human keratinocyte cell line releases into the culture medium a 54,000-Da plasminogen activator which is indistinguishable from human urokinase. Only the early release following the washing of keratinocyte monolayers is accounted for by secretion of preformed enzyme, while late secretory events require the de novo synthesis of urokinase. The released enzyme can interact by autocriny with its own receptor present on keratinocytes. The addition to the keratinocyte culture medium of the urokinase A chain can stimulate a concentration-dependent urokinase oversecretion, which is not paralleled by oversecretion of plasminogen activator inhibitor-1. Since stimulation of urokinase production can be obtained by an A chain concentration which was previously shown to be efficient in inducing keratinocyte mobilization in an in vitro migration model system, they hypothesize that this mechanism may be important in vivo during the process of wound repair.

  16. Thrombolytic treatment for stroke in the Scandinavian countries

    DEFF Research Database (Denmark)

    Slot, K.B.; Murray, V.; Boysen, G.

    2009-01-01

    Objective - We wanted to describe the use of thrombolytic treatment for stroke in Scandinavia, to assess stroke doctors' opinions on this treatment, to identify barriers against treatment, and to suggest improvements to overcome these barriers. Methods - We sent questionnaires to 493 Scandinavian...... treatment for stroke as beneficial, yet its implementation in clinical practice has so far been poor. Our survey identified important barriers and potential measures that could increase its future use Udgivelsesdato: 2009/10...

  17. Limitations in thrombolytic therapy in acute ischemic stroke

    International Nuclear Information System (INIS)

    Kocak, S.; Kokcam, M.; Girisgin, A.S.; Dogan, E.; Bodur, S.

    2012-01-01

    Objective: The eligibility for thrombolytic therapy for patients who present to the emergency department with Acute Ischaemic Stroke (AIS) has been researched in this study. Methodology: Patients who had presented to the emergency department of our hospital between March 2008-2009 and diagnosed as AIS clinically and radiologically were included in the study prospectively. Results: One hundred and twelve patients were included in the study. Forty nine (43.8 %) were female and the mean age was 68.7+- 12.2 (median 71.5). The mean time from the onset of symptom to hospital admission was 12.2 +- 12.9 hours (median 6 hours). Two (1.8%) patients did not have any contraindication for thrombolytic therapy. Arrival time at the hospital of three hours and higher was the single contraindication in 40 (35.7%) patients. The most common four contraindications were delayed admission, multilobar infarct or hypo density of more than 1/3 of the hemisphere, hypertension and mild neurological symptoms respectively. Conclusions: Our data suggest that the primary barrier to the delivery of thrombolytic therapy for AIS is delayed arrival of the patient to a hospital, and up to 1/3 of our patients, the percentage arriving within 4 hours of the onset of stroke symptoms, might be eligible for attempted re-perfusion. (author)

  18. The urokinase receptor associated protein (uPARAP/endo180)

    DEFF Research Database (Denmark)

    Engelholm, L H; Nielsen, B S; Danø, K

    2001-01-01

    of this proteolytic system. uPARAP is a high molecular weight type-1 membrane protein, belonging to the macrophage mannose receptor protein family. On the surface of certain cells, uPARAP forms a ternary complex with the pro-form of the urokinase-type plasminogen activator (uPA) and its primary receptor (uPAR). While......The urokinase-mediated plasminogen activation system plays a central role in the extracellular proteolytic degradation reactions in cancer invasion. In this review article we discuss a number of recent findings identifying a new cellular receptor protein, uPARAP, that interacts with components...

  19. Differential binding of urokinase and peptide antagonists to the urokinase receptor

    DEFF Research Database (Denmark)

    Engelholm, L H; Behrendt, N

    2001-01-01

    for the invasion of cancer cells, thus making uPAR a potential target for anti-invasive therapy based on binding antagonists. A remarkable property of the uPA-uPAR system is a pronounced species specificity in ligand recognition. We have now cloned and studied uPAR from four primate species and show that even......The urokinase plasminogen activator receptor (uPAR) is a membrane protein active in localizing the plasminogen activation cascade system on the cell surface. The resulting pericellular proteolytic activity is responsible for degradation reactions in the extracellular matrix that are needed....... These findings aid the elucidation of the structure/function relationship of uPAR and, unexpectedly, identify a structural distinction governing the binding of uPA and a very similar peptide antagonist....

  20. Combined intravenous and intra-arterial thrombolytic therapy for acute ischemic stroke: a comparative study with simple intra-arterial thrombolytic therapy

    International Nuclear Information System (INIS)

    Xu Haowen; Li Minghua; Guan Sheng; Song Bo; Wang Jianbo; Gu Binxian

    2011-01-01

    Objective: to evaluate the feasibility, efficacy, safety and risk of combined intravenous and local intra-arterial thrombolytic therapy (IV + IA) for ischemic stroke and to compare the results with those obtained by simple intra-arterial thrombolytic therapy (IA). Methods: A total of 46 consecutive patients with ischemic strokes, who were suitable candidates for thrombolytic therapy, were randomly divided into (IV + IA) group (n=24) and IA group (n=22). After the treatment, the arterial recanalization rates, the early clinical improvement, the occurrence of symptomatic intracerebral hemorrhage, the favourable outcome rate and the mortality were evaluated, and the results were compared between the two groups. Results: The average interval between the onset of symptoms and the start of thrombolytic therapy in (IV + IA) group was 255 minutes, which was remarkably lower than that in IA group (310 minutes) with P=0.012. After the thrombolytic therapy, the arterial recanalization rate for (IV + IA) group and IA group was 54.1% and 40.9% respectively (P=0.226). The occurrence of symptomatic intracerebral hemorrhage for (IV + IA) group and IA group was 16.7% and 22.7% respectively (P=0.361). There months after the treatment the favourable outcome rate (modified Rankin Scale, 0 to 2) of (IV + IA) group was 54.2%, which was higher than that of IA group (36.4%), and the mortality in (IV + IA) group and IA group was 8.3% and 9.1% (P=0.927) respectively. No statistically significant difference in recanalization rate and mortality existed between the two groups. Conclusion: This pilot indicates that both (IV + IA) thrombolytic therapy and simple IA thrombolytic therapy are clinically feasible and safe in treating acute ischemic stroke. Compared to simple IA thrombolytic therapy, (IV + IA) thrombolytic therapy is more effective with rather minimal risks. The conclusion of this study needs to be further proved by double-blind and controlled studies with large sample. (authors)

  1. Urokinase production by electrophoretically separated cultured human embryonic kidney cells

    Science.gov (United States)

    Kunze, M. E.; Plank, L. D.; Giranda, V.; Sedor, K.; Todd, P. W.

    1985-01-01

    Urokinase is a plasminogen activator found in urine. Relatively pure preparations have been tested in Europe, Japan and the United States for the treatment of deep vein thrombosis and other dangerous blood clots. Human embryonic kidney cell cultures have been found to produce urokinase at much higher concentrations, but less than 5% of the cells in typical cultures are producers. Since human diploid cells become senescent in culture the selection of clones derived from single cells will not provide enough material to be useful, so a bulk purification method is needed for the isolation of urokinase producing cell populations. Preparative cell electrophoresis was chosen as the method, since evidence exists that human embryonic cell cultures are richly heterogeneous with respect to electrophoretic mobility, and preliminary electrophoretic separations on the Apollo-Soyuz space flight produced cell populations that were rich in urokinase production. Similarly, erythropoietin is useful in the treatment of certain anemias and is a kidney cell duct, and electrophoretically enriched cell populations producing this product have been reported. Thus, there is a clear need for diploid human cells that produce these products, and there is evidence that such cells should be separable by free-flow cell electrophoresis.

  2. The urokinase receptor as a potential target in cancer therapy

    DEFF Research Database (Denmark)

    Romer, John; Nielsen, Boye Schnack; Ploug, Michael

    2004-01-01

    The glycolipid-anchored receptor for urokinase-type plasminogen activator (uPAR) is essential for cell-surface associated plasminogen activation and is overexpressed at the invasive tumor-stromal microenvironment in many human cancers. In line with this, uPAR and uPA levels in both resected tumor...

  3. The urokinase plasminogen activator receptor-associated protein/endo180 is coexpressed with its interaction partners urokinase plasminogen activator receptor and matrix metalloprotease-13 during osteogenesis

    DEFF Research Database (Denmark)

    Engelholm, L H; Nielsen, B S; Netzel-Arnett, Sarah

    2001-01-01

    The urokinase plasminogen activator receptor-associated protein/Endo180 (uPARAP/Endo180) is a newly discovered member of the macrophage mannose receptor family that was reported to interact with ligand-bound urokinase plasminogen activator receptor (uPAR), matrix metalloprotease-13 (MMP-13), and ...

  4. Drip-and-ship thrombolytic treatment paradigm among acute ischemic stroke patients in the United States.

    Science.gov (United States)

    Tekle, Wondwossen G; Chaudhry, Saqib A; Hassan, Ameer E; Rodriguez, Gustavo J; Suri, M Fareed K; Qureshi, Adnan I

    2012-07-01

    To provide a national assessment of thrombolytic administration using drip-and-ship treatment paradigm. Patients treated with the drip-and-ship paradigm among all acute ischemic stroke patients treated with thrombolytic treatment were identified within the Nationwide Inpatient Sample. Thrombolytic utilization, patterns of referral, comparative in-hospital outcomes, and hospitalization charges related to drip-and-ship paradigm were determined. All the in-hospital outcomes were analyzed after adjusting for potential confounders using multivariate analysis. Of the 22 243 ischemic stroke patients who received thrombolytic treatment, 4474 patients (17%) were treated using drip-and-ship paradigm. Of these 4474 patients, 81% were referred to urban teaching hospitals for additional care, and 7% of them received follow-up endovascular treatment. States with a higher proportion of patients treated using the drip-and-ship paradigm had higher rates of overall thrombolytic utilization (5.4% versus 3.3%; Pcare was significantly higher in patients treated with drip-and-ship paradigm compared with those who received thrombolytics through primary emergency department arrival in the multivariate analysis (OR, 1.198; 95% CI, 1.019-1.409; P=0.0286). One of every 6 thrombolytic-treated patients in United States is treated using drip-and-ship paradigm. States with the highest proportion of drip-and-ship cases were also the states with the highest thrombolytic utilization.

  5. Thrombolytic therapy in prosthetic valve thrombosis during early pregnancy

    Directory of Open Access Journals (Sweden)

    B.C. Srinivas

    2012-01-01

    Full Text Available Regardless of the improvements in the design of prosthetic heart valves and the use of anticoagulation, systemic embolism and valve thrombosis remains the most dreaded complications of mechanical heart valve replacement. A course of thrombolytic therapy may be considered as a first-line therapy for prosthetic heart valve thrombosis. The safety of thrombolysis in early pregnancy is not known. We describe a primigravida with mitral valve replacement status presenting with acute prosthetic valve thrombosis and treated successfully with intravenous streptokinase.

  6. Complete dysphagia after thrombolytic treatment for myocardial infarction.

    Science.gov (United States)

    Mosimann, T; Terracciano, L; Sieber, C; Rappo, F

    2000-12-01

    An 82 year old man was admitted to hospital with unstable angina pectoris. There was a long history of minor symptoms suggesting reflux disease, with a small diaphragmatic hernia. One day after admission the patient complained of severe chest pain. An acute inferior-posterior myocardial infarction was diagnosed on ECG, and thrombolytic treatment with alteplase (rt-PA) was initiated. Within a few hours total dysphagia occurred, caused by haemorrhagic oesophagitis. The haematoma resolved spontaneously within about 10 days. The patient was discharged three weeks later after full resolution of the dysphagia.

  7. Annual thrombolytic treatment experience in an education and research hospital

    Directory of Open Access Journals (Sweden)

    Cemile Haki

    2018-04-01

    Full Text Available INTRODUCTION: In this study, we aimed to discuss the data of patients with acute ischemic stroke with intravenous thrombolytic therapy (IV-tPA in our clinic in the light of the literature. METHODS: Seventy patients with acute ischemic stroke diagnosed between April 2016 and 2017 who received IV-tPA were included in the study. Demographic, radiological and clinical data of the patients were recorded. The intracranial hemorrhages and neurological status at the end of the third month were evaluated with the modified MRS score and the National Stroke Health Scale (NIHSS scores within 3 months after discharge. The values of the symptom-needle time, the Alberta stroke program, the early computerized tomography score (ASPECT and the NIHSS scores at the first application and follow-up were analyzed. RESULTS: 28 of the patients were female and 42 were male and the mean age was 66.44 ± 13.47. Thirty-nine (55.7% of the patients were referred to emergency services and 31 (44.3% were directed to thrombolytic therapy from the emergency department of other hospitals. The initial NIHSS scores at the time of admission were 14.27 ± 4.26, while the NIHSS scores at the 24th hour were 11.47 ± 5.85. The ASPECT score at the time of admission was 9.61 ± 0.81. The median symptom-to-needle time was 89.5 minutes (0-245. The median door-to-needle time was 77 minutes (20-187. During thrombolytic application, edema occurred in 4 patients and intrahepatic hemorrhage occurred in 1 patient. At the end of the third month, 20 patients (28.5% had complete recovery of neurological disability and 9 (12.9% were exiting. DISCUSSION AND CONCLUSION: The results of this study show that IV-tPA treatment is a safe and effective treatment for acute ischemic stroke, similar to past studies, and that this treatment reduces the disability at the end of the third month.

  8. A composite role of vitronectin and urokinase in the modulation of cell morphology upon expression of the urokinase receptor

    DEFF Research Database (Denmark)

    Hillig, Thore; Engelholm, Lars H; Ingvarsen, Signe

    2008-01-01

    The urokinase receptor, urokinase receptor (uPAR), is a glycosylphosphatidylinositol-anchored membrane protein engaged in pericellular proteolysis and cellular adhesion, migration, and modulation of cell morphology. A direct matrix adhesion is mediated through the binding of uPAR to vitronectin...... induce the same response. In this report, we show that both of these triggering mechanisms can be operative and that uPAR-dependent modulation of cell morphology can indeed occur independently of a direct vitronectin binding. Expression of wild-type uPAR on HEK293 cells led to pronounced vitronectin...... was restored, although this did not rescue the uPAR-vitronectin binding and adhesion capability. On the other hand, using other uPAR variants, we could show that uPAR-vitronectin adhesion is indeed capable and sufficient to induce the same morphological rearrangements. This was shown with cells expressing...

  9. Urokinase receptor forms in serum from non-small cell lung cancer patients

    DEFF Research Database (Denmark)

    Almasi, Charlotte Elberling; Christensen, Ib Jarle; Høyer-Hansen, Gunilla

    2011-01-01

    To study the prognostic impact of the different forms of the receptor for urokinase plasminogen activator (uPAR) in serum from 171 non-small cell lung cancer (NSCLC) patients.......To study the prognostic impact of the different forms of the receptor for urokinase plasminogen activator (uPAR) in serum from 171 non-small cell lung cancer (NSCLC) patients....

  10. Plasma soluble urokinase plasminogen activator receptor in children with urinary tract infection

    DEFF Research Database (Denmark)

    Wittenhagen, Per; Andersen, Jesper Brandt; Hansen, Anita

    2011-01-01

    In this prospective study we investigated the role of plasma levels of soluble urokinase plasminogen activator receptor (suPAR) in children with urinary tract infection.......In this prospective study we investigated the role of plasma levels of soluble urokinase plasminogen activator receptor (suPAR) in children with urinary tract infection....

  11. Urokinase plasminogen activator cleaves its cell surface receptor releasing the ligand-binding domain

    DEFF Research Database (Denmark)

    Høyer-Hansen, G; Rønne, E; Solberg, H.

    1992-01-01

    The cellular receptor for urokinase-type plasminogen activator (uPAR) is a glycolipid-anchored three-domain membrane protein playing a central role in pericellular plasminogen activation. We have found that urokinase (uPA) can cleave its receptor between domains 1 and 2 generating a cell-associat...

  12. Commonly asked questions: thrombolytic therapy in the management of acute stroke.

    Science.gov (United States)

    Block, H Steven; Biller, José

    2013-02-01

    Questions about thrombolytic management arise frequently, often with the intent of ascertaining safety and efficacy in specific situations. Thrombolytic therapy is generally safe, even if a nonruptured intracranial aneurysm is present. The risk of cardiac rupture with tamponade is low, except for the first 7 weeks following myocardial infarction. Over this duration, there is an increased risk of intravenous thrombolytic therapy in specific patient groups. Stroke infrequently occurs during cardiac catheterization. Its infrequent occurrence has limited large treatment trials. Basilar artery occlusion management will be reviewed. Thrombolytic therapy is generally safe in the context of pre-existing cerebral microhemorrhages and cervical artery dissections. Additionally, the role of multimodal penumbral imaging in planning stroke therapy will be reviewed.

  13. Arteriovenous Fistula Complicated by Popliteal Venous Access for Endovascular Thrombolytic Therapy of Deep Vein Thrombosis

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Sung Su; Kim, Jeong Ho; Park, Chul Hi; Hwang, Hee Young; Kim, Hyung SiK [Gacheon University Gil Medical Center, Gacheon (Korea, Republic of); Jeon, Young Sun; Kim, Won Hong [Inha University College of Medicine, Incheon (Korea, Republic of)

    2008-10-15

    We report a case of an iatrogenic arteriovenous fistula complicated by catheter- directed thrombolytic therapy in a patient with acute deep vein thrombosis of a lower extremity. To the best of our knowledge, this is the first report of an arteriovenous fistula between the sural artery and popliteal vein in that situation. As the vessels have a close anatomical relationship, the arteriovenous fistula seems to be a potential complication after endovascular thrombolytic therapy of acute deep vein thrombosis.

  14. Use of Intra-arterial Thrombolytic Therapy for Acute Treatment of Frostbite in 62 Patients with Review of Thrombolytic Therapy in Frostbite.

    Science.gov (United States)

    Gonzaga, Teresa; Jenabzadeh, Kamrun; Anderson, Christopher P; Mohr, William J; Endorf, Frederick W; Ahrenholz, David H

    2016-01-01

    Amputations are common after severe frostbite injuries, often mediated by postinjury arterial thrombosis. Since 1994, the authors have performed angiography to identify perfusion deficits in severely frostbitten digits and treated these lesions with intraarterial infusion of thrombolytic agents, usually combined with papaverine to reduce vasospasm. A retrospective review was performed of patients admitted to the regional burn center with frostbite injury from 1994 to 2007. Patients with severe frostbite, without contraindications to thrombolytic therapy, underwent diagnostic angiography of the affected extremities. Limbs with perfusion defects received intraarterial thrombolytic therapy according to protocol and the response was documented. Delayed amputation was performed for mummified digits. Angiogram results and amputation rates were tabulated. In this 14-year review, 114 patients were admitted for frostbite injuries. There was a male predominance (84%) and the mean age was 40.4 years. Of this group, 69 patients with severe frostbite underwent angiography; 66 were treated with intraarterial thrombolytic therapy. Four treated were excluded due to incomplete data. In the remaining 62 patients, angiography identified 472 digits with frostbite injury and impaired arterial perfusion. At the termination of thrombolytic infusion, a completion angiogram was performed. Partial or complete amputations were performed on only four of 198 digits (2.0%) with distal vascular blush, and in 71 of 75 digits (94.7%) with no improvement. Amputations occurred in 73 of 199 digits (36.7%) with partially restored flow. Overall complete digit salvage rate was 68.6%. Angiography after severe frostbite is a sensitive method to detect impaired arterial blood flow and permits catheter-directed treatment with thrombolytic agents. Improved perfusion after such treatment decreases late amputations following frostbite injury.

  15. Soluble urokinase plasminogen activator receptor during allogeneic stem cell transplantation

    DEFF Research Database (Denmark)

    Haastrup, E; Andersen, J; Ostrowski, S R

    2011-01-01

    Previous studies have found that soluble urokinase plasminogen activation receptor (suPAR) increases during inflammatory and malignant illness and elevated suPAR levels may be associated with poor clinical outcome. The purpose of this study was to investigate plasma levels of suPAR during...... to pretreatment levels. High suPAR levels at day 0 were associated with increased mortality (P = 0.011). The present study found increased suPAR levels during the conditioning in SCT patients. Further, the data indicated that increased suPAR levels may be associated with increased mortality, suggesting su...

  16. The pro-urokinase plasminogen-activation system in the presence of serpin-type inhibitors and the urokinase receptor

    DEFF Research Database (Denmark)

    Behrendt, Niels; List, Karin; Andreasen, Peter A

    2003-01-01

    The reciprocal pro-enzyme activation system of plasmin, urokinase-type plasminogen activator (uPA) and their respective zymogens is a potent mechanism in the generation of extracellular proteolytic activity. Plasminogen activator inhibitor type 1 (PAI-1) acts as a negative regulator. This system...... is complicated by a poorly understood intrinsic reactivity of the uPA pro-enzyme (pro-uPA) before proteolytic activation, directed against both plasminogen and PAI-1. We have studied the integrated activation mechanism under the repression of PAI-1 in a purified system. A covalent reaction between pro...

  17. Expression of urokinase receptors by human trophoblast. A histochemical and ultrastructural analysis.

    Science.gov (United States)

    Multhaupt, H A; Mazar, A; Cines, D B; Warhol, M J; McCrae, K R

    1994-09-01

    Through their ability to invade endometrium, remodel the uterine spiral arteries, and sustain placental blood fluidity, trophoblast cells play a central role in establishing and maintaining the integrity of the uteroplacental vasculature. The expression of urokinase receptors by trophoblast may facilitate these processes by focusing plasminogen activator activity to discrete sites on the cell surface and promoting the activation of cell-bound plasminogen. However, although urokinase receptors are expressed by cultured trophoblast, the expression of these receptors by trophoblast in vivo has not been examined. Immunohistochemistry and immunoelectron microscopy were used to characterize the expression of urokinase receptors by villous and extravillous trophoblast at several points in gestation. Urokinase receptors were expressed in a polarized fashion at the leading edge of migrating extravillous trophoblast cells. Receptors were also abundantly expressed during the first and second trimesters of gestation by villous trophoblast, where they were located on apical villous projections and within intracellular vacuoles, a subset of which were lysosomes. The polarized expression of urokinase receptors by invasive extravillous trophoblast cells is consistent with a role for these receptors in mediating the extent and directionality of trophoblast migration. In contrast, the expression of urokinase receptors by villous trophoblast, which are not actively invasive in vivo, may serve to facilitate the generation of plasmin at the interface of these cells with maternal plasma, thereby limiting the deposition of fibrin within the placental intervillous spaces. Diminished urokinase receptor expression by villous trophoblast at term may represent a physiologic adaptation to diminish local fibrinolysis and limit hemorrhage at parturition.

  18. Long-term effects of invasive treatment in patients with a post-thrombolytic Q-wave myocardial infarction

    DEFF Research Database (Denmark)

    Kofoed, Klaus F; Madsen, Jan Kyst; Grande, Peer

    2010-01-01

    Abstract Objectives. The aim of the present study was to assess the effect of a deferred invasive treatment strategy on long-term outcome in patients with a post-thrombolytic Q-wave myocardial infarction and inducible myocardial ischemia. Design. Patients (N=751) with post-thrombolytic Q-wave myo......Abstract Objectives. The aim of the present study was to assess the effect of a deferred invasive treatment strategy on long-term outcome in patients with a post-thrombolytic Q-wave myocardial infarction and inducible myocardial ischemia. Design. Patients (N=751) with post-thrombolytic Q...

  19. Dependence of the effectiveness of thrombolytic therapy at ischemic stroke from clinical and paraclinical predictors

    Directory of Open Access Journals (Sweden)

    Іванна Михайлівна Мельнічек

    2015-12-01

    Full Text Available The aim of the work. The aim of the work is an assessment of informativeness of several clinical and paraclinical predictors in prognostics of the results of effectiveness of thrombolytic therapy at the most acute period of ishemic stroke with the further definition of the most significant ones for achieving the least neurologic deficiency.Methods of research: There were retrospectively considered 61 patients 60,5±7,8 years old with ishemic stroket who sucsessfully underwent thrombolytic therapy as an intravenous administration of Actilyse. These patients demonstrated the next factors of gemostasis: prothrombin time, prothrombin index, fibrinogen. For the research there were also used the scales of neurological deficiency activisation (Rankin and NIHSS; ultrasound of the magistral arteries and extracranial CT of brain; methods of mathematical statistics (the definition of chances and confidence intervals ratio, Pirson and Student criteria, verification of hypothesis about the law of distribution and equality of the mean values in the both samplings.Results. There were defined the most informative factors in prognostication of the good result after thrombolytic therapy. There was formed the list of output factors that the results of actilyse thrombolytic therapy effectiveness in Lviv region are depending on. There was grounded the necessity of laboratory data monitoring in patients with stroke for receiving the best results of thrombolytic therapy.There was established that thrombolytic therapy of ishemic stroke must begin as early as possible (in computed tomography department if possible for receiving the maximal effectiveness. There was detected that ultrasound of magistral vessels that supply brain with blood is necessary for all patients who are candidates for thrombolytic therapy because the stenosis of the vessel lumen more than 60 % significantly worsens an effectiveness of treatment

  20. A targeted ferritin-microplasmin based thrombolytic nanocage selectively dissolves blood clots.

    Science.gov (United States)

    Seo, Junyoung; Al-Hilal, Taslim A; Jee, Jun-Goo; Kim, Yong-Lim; Kim, Ha-Jeong; Lee, Byung-Heon; Kim, Soyoun; Kim, In-San

    2018-04-01

    The use of thrombolytic therapies is limited by an increased risk of systemic hemorrhage due to lysis of hemostatic clots. We sought to develop a plasmin-based thrombolytic nanocage that efficiently dissolves the clot without causing systemic fibrinolysis or disrupting hemostatic clots. Here, we generated a double chambered short-length ferritin (sFt) construct that has an N-terminal region fused to multivalent clot targeting peptides (CLT: CNAGESSKNC) and a C-terminal end fused to a microplasmin (μPn); CLT recognizes fibrin-fibronectin complexes in clots, μPn efficiently dissolves clots, and the assembly of double chambered sFt (CLT-sFt-μPn) into nanocage structure protects the activated-μPn from its circulating inhibitors. Importantly, activated CLT-sFt-μPn thrombolytic nanocage showed a prolonged circulatory life over activated-μPn and efficiently lysed the preexisting clots in both arterial and venous thromboses models. Thus, CLT-sFt-μPn thrombolytic nanocage platform represents the prototype of a targeted clot-busting agent with high efficacy and safety over existing thrombolytic therapies. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Dialysis Access Graft Thrombolysis: Randomized Study of Pulse-Spray Versus Continuous Urokinase Infusion

    International Nuclear Information System (INIS)

    Goodwin, Scott C.; Arora, Lokesh C.; Razavi, Mahmood K.; Sayre, James; McNamara, Thomas O.; Yoon, Chun

    1998-01-01

    Purpose: To compare pulse-spray to continuous-infusion thrombolysis with high-dose urokinase in thrombosed dialysis access grafts. Methods: A prospective randomized controlled trial was performed. From August 1992 to September 1993, 30 thrombosed polytetrafluoroethylene (PTFE) grafts in 24 patients were included, 15 grafts in each group. The success of thrombolysis, mean time to thrombolysis, mean urokinase dose, and 60-day patency rate were evaluated. Results: In the pulse-spray group, the mean time to thrombolysis was 72 min with a mean urokinase dose of 560,000 U. The 60-day patency rate was 71%. In the continuous-infusion group, the mean infusion time to thrombolysis was 55 min with a mean dose of 479,000 U. The 60-day patency rate was 73%. Conclusion: No statistically significant difference was found between the two techniques in the mean time to thrombolysis, the mean urokinase dose used, or the 60-day patency rate

  2. Expression of urokinase receptors by human trophoblast. A histochemical and ultrastructural analysis

    DEFF Research Database (Denmark)

    Multhaupt, H A; Mazar, A; Cines, D B

    1994-01-01

    BACKGROUND: Through their ability to invade endometrium, remodel the uterine spiral arteries, and sustain placental blood fluidity, trophoblast cells play a central role in establishing and maintaining the integrity of the uteroplacental vasculature. The expression of urokinase receptors by troph...

  3. Temporary vena cava filter for the thrombolytic treatment of venous thrombosis

    International Nuclear Information System (INIS)

    Chen Huanjun; Li Liyun; Wan Liren; Zhao Jinqi; Jiang Wei

    2001-01-01

    Objective: To study the value of the temporary vena cava filter in the prevention of ectopic embolism formation in cases with thrombolytic therapy of venous thrombosis. Methods: Of 11 patients, 10 suffered from venous thrombosis of lower limb and 1 from thrombosis of right internal jugular vein with persistent truncus arteriosus were treated by inserting permanent or temporary vena cava filter via median vein. Results: In all 11 case control of symptoms followed this treatment occurred 7 to 15 days, thrombi were completely or partly dissolute, the blood vessels re-canalized, and finally removed the temporary vena cava filter. There were no complication and ectopic emboli related to thrombolytic therapy. Conclusions: The observation indicated that temporary vena cava filter insertion is safe and effective to prevent ectopic embolism in thrombolytic therapy of venous thrombosis

  4. Molecular docking for thrombolytic activity of some isolated compounds from Clausena lansium.

    Directory of Open Access Journals (Sweden)

    Arkajyoti Paul

    2017-03-01

    Full Text Available Clausena lansium (Family- Rutaceae is commonly known as wampee, is found in fallow lands throughout Bangladesh. Our aim of the study to performed molecular docking studies to identify potential binding affinities of the phytocompounds from Clausena lansium, namely Clausemarin B, Clausenaline C, Clausenaline E, Murrayanine, vanillic acid and Xanthotoxol for searching of lead molecule for thrombolytic activity. A wide range of docking score found during molecular docking by Schrodinger. Clausemarin B , Clausenaline C , Clausenaline E, Murrayanine , vanillic acid and Xanthotoxol showed the docking score -6.926, -4.041, -4.889 , -4.356, -3.007 and -5.816 respectively. Among all the compounds Clausemarin B showed the best docking score. So, Clausemarin B is the best compounds for thrombolytic activity, as it possessed the best value in Molecular docking. Further in vivo investigation need to identify the thrombolytic activity of isolated compounds from Clausena lansium.

  5. Effectiveness of Thrombolytic Therapy in Acute Embolic Stroke due to Infective Endocarditis

    Directory of Open Access Journals (Sweden)

    Siva P. Sontineni

    2010-01-01

    Full Text Available Objective. To identify the role of thrombolytic therapy in acute embolic stroke due to infective endocarditis. Design. Case report. Setting. University hospital. Patient. A 70-year-old male presented with acute onset aphasia and hemiparesis due to infective endocarditis. His head computerized tomographic scan revealed left parietal sulcal effacement. He was given intravenous tissue plasminogen activator with significant resolution of the neurologic deficits without complications. Main Outcome Measures. Physical examination, National Institute of Health Stroke Scale, radiologic examination results. Conclusions. Thrombolytic therapy in selected cases of stroke due to infective endocarditis manifesting as major neurologic deficits can be considered as an option after careful consideration of risks and benefits. The basis for such favorable response rests in the presence of fibrin as a major constituent of the vegetation. The risk of precipitating hemorrhage with thrombolytic therapy especially with large infarcts and mycotic aneurysms should be weighed against the benefits of averting a major neurologic deficit.

  6. Thrombolytic therapeutic effect monitoring based on functional near-infrared spectroscopy

    Science.gov (United States)

    Pan, Boan; Wang, Pengbo; Li, Yaoxian; Gao, Yuan; Li, Ting

    2017-02-01

    Deep vein thrombosis (DVT) is of serious mortality and morbidity, which often happens in inpatients and especially with the postoperative population [1]. The golden standard to diagnose DVT is venography, which relies on complicated imaging modalities requiring to be injected in a vein below the clot invasively and ionizing procedures that employing xray imaging to show where and how the DVT blocks. The near-infrared spectroscopy (NIRS) is recently found to be an intriguing and potential method detecting DVT in clinics. It has been reported recently that employing NIRS to diagnose DVT. Arteriosclerosis obliterans (ASO), local extremities manifestations of systemic atherosclerosis, usually cause thrombosis and the reduction of distal blood flow. Thrombolytic therapy is to use exogenous activator to activate the dissolution system, which can dissolve intracoronary thrombus. Here we attempt to monitor the DVT and ASO patients during the whole procedure of thrombolytic treatment, then compare the data with those DVT and ASO patients did not take treatments and normal population. 8 DVT and 9 ASO patients and 12 normal subjects were recruited to take the measurements of concentration variation of oxy- and deoxy-hemoglobins (Δ[HbO2] and Δ[Hb]) by NIRS-based thrombosis monitor. Thereinto, 5 DVT and 6 ASO patients has taken the thrombolytic treatment, and the data for the periods before treatment, during treatment, and after treatment were extracted for analysis. We found that Δ[HbO2] fluctuates and even decreases in DVT and ASO patients. After the thrombolytic therapy, Δ[HbO2] increases about 45% and converge to the curves of normal subjects. And the Δ[Hb] emerges the similar trends, except for the rising trend in the beginning and the downtrend after thrombolytic therapy. The findings indicated NIRS has big potential in clinical monitoring of DVT and ASO patients and offering reliable and quantitative evaluation of thrombolytic therapy outcomes.

  7. Preparation, characterization and in vitro thrombolytic activity of a novel streptokinase foam.

    Science.gov (United States)

    Farret, Abdo N; Azevedo, Eduardo P; Raffin, Fernanda N

    2014-01-01

    Vascular thrombosis is a potentially fatal disease. Thrombolysis represents an efficient therapeutic option, although it still presents intrinsic bleeding risks. In order to minimize this problem, intra-thrombus injections, alone or associated with some kind of mechanical thrombectomy, have been used. In this work, a new approach to thrombolysis is presented, where the preparation, characterization and in vitro thrombolytic activity of a novel streptokinase foam are reported. Foams were prepared by mixing albumin solution with CO2 at different volume ratios. Foam stability and apparent viscosity were the parameters used to characterize the foams. The volume ratio between CO2 and albumin solution that yielded the samples with the best properties was used to prepare the thrombolytic foams, where streptokinase was used as the thrombolytic agent. The thrombolytic effect of this foam was assessed in vitro by delivering it intra-thrombus and the results were compared with those of the foam without streptokinase as well as those of a regular streptokinase solution. Both foam stability and viscosity increased as the ratio of CO2:albumin solution increased and the 3:1 ratio was used to incorporate streptokinase. The in vitro thrombolytic activity study revealed that the streptokinase foam caused a 46.6 % of thrombus lysis after 30 min of experiment against 21 and 31 % of those of the foam without streptokinase and the regular streptokinase liquid solution, respectively. Thus, the use of CO2:albumin foam enhanced the in vitro thrombolytic effect of streptokinase, which indicates its potential as a novel vehicle for carrying and delivering streptokinase to targeted thrombi.

  8. Thrombolytic treatment in a patient with antiphospholipid syndrome : APS developing renal infarction.

    Science.gov (United States)

    Ugan, Y; Dogru, A; Sahin, M; Tunc, S E

    2016-10-01

    Antiphospholipid syndrome (APS), a leading entity in acquired thrombophilia, is characterized by recurrent thrombosis, morbidity in pregnancy and presence of antiphospholipid antibodies (APA). Although the etiopathogenesis is unclear, APA against negatively charged phospholipids and phospholipid-protein complexes are held responsible for the clinical picture. In case of acute thrombosis due to APS, thrombolytic therapy is not a commonly administered treatment option. Here, we present a case with acute thrombosis in the left renal artery showing partial response to thrombolytic therapy.

  9. Thrombolytic Treatment of Thrombosis on the Aortic Valvular Prosthesis Complicated by Brain Embolism

    Directory of Open Access Journals (Sweden)

    Lucie Horáková

    2008-01-01

    Full Text Available The authors present a case of thrombosis on the St. Jude Medical 19 aortic valve prosthesis. The diagnosis was confirmed by transthoracic and transoesofageal echocardiography, cardiac fluoroscopy revealed restricted movement of the aortic valve prosthesis leaflet. Thrombolytic therapy was complicated with brain embolism that was successfully percutaneously removed from the cerebral artery by the mechanical device. The patient has fully recovered without any neurological residual symptoms. This case report should be instructive to other clinicians who encounter the same complications after thrombolytic treatment.

  10. Thrombolytic potential of Ocimum sanctum L., Curcuma longa L., Azadirachta indica L. and Anacardium occidentale L.

    Science.gov (United States)

    Khan, Irfan Newaz; Habib, Md Razibul; Rahman, Md Mominur; Mannan, Adnan; Sarker, Md Mominul Islam; Hawlader, Sourav

    2011-06-01

    Atherothrombotic diseases such as myocardial or cerebral infarction are serious consequences of the thrombus formed xin blood vessels. Thrombolytic agents are used to dissolve the already formed clots in the blood vessels; however, these drugs have certain limitations which cause serious and sometimes fatal consequences. Herbal preparations have been used since ancient times for the treatment of several diseases. The aim of this study was to investigate whether herbal preparations possess thrombolytic activity or not. An in vitro thrombolytic model was used to check the clot lysis effect of four aqueous herbal extracts viz., O. sanctum, C. longa, A. indica, A. occidentale along with Streptokinase as a positive control and water as a negative control. The percentage (%) clot lysis was statistically significant (poccidentale showed moderate clot lysis activity (30.01 ± 6.168%, 32.94 ± 3.663%, 27.47 ± 6.943%, 33.79 ± 2.926% respectively) whereas standard streptokinase showed 86.2 ± 10.7 % clot lysis effect. From our study we found that all the herbs showed reasonable % of clot lysis. These herbal extracts possess thrombolytic properties that could lyse blood clots in vitro; however, in vivo clot dissolving properties and active component(s) of these extracts for clot lysis are yet to be discovered.

  11. Effect of thrombolytic therapy on exercise response during early recovery from acute myocardial infarction

    DEFF Research Database (Denmark)

    Svendsen, J H; Madsen, J K; Saunamäki, K I

    1992-01-01

    Several studies have shown that infarct size is reduced following thrombolytic treatment in patients with acute myocardial infarction. Exercise test variables, such as an impaired heart rate response during exercise, are known to be related to left ventricular function and patient prognosis follo...

  12. Production of recombinant streptokinase from Streptococcus pyogenes isolate and its potential for thrombolytic therapy.

    Science.gov (United States)

    Assiri, Abdullah S; El-Gamal, Basiouny A; Hafez, Elsayed E; Haidara, Mohamed A

    2014-12-01

    To produce an effective recombinant streptokinase (rSK) from pathogenic Streptococcus pyogenes isolate in yeast, and evaluate its potential for thrombolytic therapy. This study was conducted from November 2012 to December 2013 at King Khalid University, Abha, Kingdom of Saudi Arabia (KSA). Throat swabs collected from 45 pharyngitis patients in Asser Central Hospital, Abha, KSA were used to isolate Streptococcus pyogenes. The bacterial DNA was used for amplification of the streptokinase gene (1200 bp). The gene was cloned and in vitro transcribed in an eukaryotic expression vector that was transformed into yeast Pichia pastoris SMD1168, and the rSK protein was purified and tested for its thrombolytic activity. The Streptococcus pyogenes strain was isolated and its DNA nucleotide sequence revealed similarity to other Streptococcus pyogenes in the Gene bank. Sequencing of the amplified gene based on DNA nucleotide sequence revealed a SK gene closely related to other SK genes in the Gene bank. However, based on deduced amino acids sequence, the gene formed a separate cluster different from clusters formed by other examined genes, suggesting a new bacterial isolate and accordingly a new gene. The purified protein showed 82% clot lysis compared to a commercial SK (81%) at an enzyme concentration of 2000 U/ml. The present yeast rSK showed similar thrombolytic activity in vitro as that of a commercial SK, suggesting its potential for thrombolytic therapy and large scale production. 

  13. Production of recombinant streptokinase from Streptococcus pyogenes isolate and its potential for thrombolytic therapy

    Science.gov (United States)

    Assiri, Abdullah S.; El-Gamal, Basiouny A.; Hafez, Elsayed E.; Haidara, Mohamed A.

    2014-01-01

    Objectives: To produce an effective recombinant streptokinase (rSK) from pathogenic Streptococcus pyogenes isolate in yeast, and evaluate its potential for thrombolytic therapy. Methods: This study was conducted from November 2012 to December 2013 at King Khalid University, Abha, Kingdom of Saudi Arabia (KSA). Throat swabs collected from 45 pharyngitis patients in Asser Central Hospital, Abha, KSA were used to isolate Streptococcus pyogenes. The bacterial DNA was used for amplification of the streptokinase gene (1200 bp). The gene was cloned and in vitro transcribed in an eukaryotic expression vector that was transformed into yeast Pichia pastoris SMD1168, and the rSK protein was purified and tested for its thrombolytic activity. Results: The Streptococcus pyogenes strain was isolated and its DNA nucleotide sequence revealed similarity to other Streptococcus pyogenes in the Gene bank. Sequencing of the amplified gene based on DNA nucleotide sequence revealed a SK gene closely related to other SK genes in the Gene bank. However, based on deduced amino acids sequence, the gene formed a separate cluster different from clusters formed by other examined genes, suggesting a new bacterial isolate and accordingly a new gene. The purified protein showed 82% clot lysis compared to a commercial SK (81%) at an enzyme concentration of 2000 U/ml. Conclusion: The present yeast rSK showed similar thrombolytic activity in vitro as that of a commercial SK, suggesting its potential for thrombolytic therapy and large scale production. PMID:25491213

  14. Thrombolytic Therapy for Right-Sided Mechanical Pulmonic and Tricuspid Valves: The Largest Survival Analysis to Date.

    Science.gov (United States)

    Taherkhani, Maryam; Hashemi, Seyed Reza; Hekmat, Manouchehr; Safi, Morteza; Taherkhani, Adineh; Movahed, Mohammad Reza

    2015-12-01

    Data regarding thrombolytic treatment of right-sided mechanical valve thrombosis are almost nonexistent, and all current guidelines arise from very small case series. We retrospectively studied the in-hospital and long-term outcome data of a larger series of patients who had received, from September 2005 through June 2012, thrombolytic therapy for right-sided mechanical pulmonary valve or tricuspid valve thrombosis. We identified 16 patients aged 8-67 years who had undergone thrombolytic therapy for definite thrombotic mechanical valve obstruction in the tricuspid or pulmonary valve position (8 in each position). All study patients except one had subtherapeutic international normalized ratios. The 8 patients with pulmonary mechanical valve thrombosis had a 100% response rate to thrombolytic therapy, and their in-hospital survival rate was also 100%. The 8 patients with tricuspid mechanical valve thrombosis had a 75% response rate to thrombolytic therapy, with an in-hospital survival rate of 87.5%. The one-year survival rate for mechanical valve thrombosis treated with thrombolytic therapy (whether pulmonary or tricuspid) was 87.5%. On the basis of our data, we recommend that thrombolytic therapy remain the first-line therapy for right-sided mechanical valve thrombosis in adults or children-including children with complex congenital heart disease and patients with mechanical pulmonary valve thrombosis. Surgery should be reserved for patients in whom this treatment fails.

  15. In vitro thrombolytic potential of root extracts of four medicinal plants available in Bangladesh.

    Science.gov (United States)

    Hussain, Fahad; Islam, Ariful; Bulbul, Latifa; Moghal, Mizanur Rahman; Hossain, Mohammad Salim

    2014-01-01

    Thrombus formation inside the blood vessels obstructs blood flow through the circulatory system leading hypertension, stroke to the heart, anoxia, and so on. Thrombolytic drugs are widely used for the management of cerebral venous sinus thrombosis patients, but they have certain limitations. Medicinal plants and their components possessing antithrombotic activity have been reported before. However, plants that could be used for thrombolysis has not been reported so far. This study's aim was to evaluate the thrombolytic potential of selected plants' root extracts. Plants were collected, dried, powdered and extracted by methanol and then fractionated by n-hexane for getting the sample root extracts. Venous blood samples were drawn from 10 healthy volunteers for the purposes of investigation. An in vitro thrombolytic model was used to check the clot lysis potential of four n-hexane soluble roots extracts viz., Acacia nilotica, Justicia adhatoda, Azadirachta indica, and Lagerstroemia speciosa along with streptokinase as a positive control and saline water as a negative control. Dunnett t-test analysis was performed using SPSS is a statistical analysis program developed by IBM Corporation, USA. on Windows. Using an in vitro thrombolytic model, A. nilotica, L. speciosa, A. indica, and J. adhatoda at 5 mg extract/ml NaCl solution concentration showed 15.1%, 15.49%, 21.26%, and 19.63% clot lysis activity respectively. The reference streptokinase showed 47.21%, and 24.73% clot lysis for 30,000 IU and 15,000 IU concentrations, respectively whereas 0.9% normal saline showed 5.35% clot lysis. The selected extracts of the plant roots possess marked thrombolytic properties that could lyse blood clots in vitro; however, in vivo clot dissolving properties and active components responsible for clot lysis are yet to be discovered.

  16. Systemic thrombolytic therapy alone and in combination with mechanical revascularization in acute ischemic stroke in two children

    DEFF Research Database (Denmark)

    Modrau, B; Sørensen, L; Bartholdy, N J

    2011-01-01

    Thrombolytic therapy is not recommended for acute ischemic stroke (AIS) in patients under the age of 18 and published experience is limited. In this case report, we describe two children treated with systemic thrombolytic therapy. One child received additional mechanical revascularization...... and achieved a good clinical outcome. The differences in the fibrinolytic system and the different etiology of AIS in childhood may limit a simple extrapolation of the adult guidelines for systemic thrombolytic therapy. Acute multimodal imaging to clarify the etiology of AIS might help to select the most...... appropriate treatment modality....

  17. Prolonged radiation damage in rat colon and urokinase expression in epithelium

    Energy Technology Data Exchange (ETDEWEB)

    Hayashida, Masayuki; Minami, Kazunori; Okimoto, Tomoaki [Nagasaki Univ. (Japan). School of Medicine; Shichijo, Kazuko; Matsuu, Mutsumi; Nakayama, Toshiyuki; Sekine, Ichiro

    2001-12-01

    Although radiation therapy plays important role in the treatment of gynecological tumors, it may cause radiation injury as a late effect. Several recent reports show that urokinase such as urokinase type plasminogen activator (uPA) contributes to the repair of ulcerative lesions of the colon epithelium. We studied radiation induced enterocolitis using rat animal models. Seventy-two female Wistar rats were irradiated by a single fraction dose of 36 Gy at laparotomy. Histological changes and activity of urokinase system were investigated after irradiation. Ulcers were observed in irradiated field in 12 of 19 animals (63%) even at 60th week after irradiation. Urokinase expressions were observed in the margins of active ulcer. Urokinase was thought to play important role in exacerbation of ulcer formation. Expression of uPA was also observed in submucosal glands. Ischaemic changes were not observed in irradiated colon despite sclerosing vasculitis. It is suggested that uPA played reciprocal roles in radiation induced enterocolitis: healing and aggravation of ulcer. (author)

  18. Interleukin-6 infusion during human endotoxaemia inhibits in vitro release of the urokinase receptor from peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Ostrowski, S R; Plomgaard, P; Fischer, C P

    2005-01-01

    Leucocyte expression of the urokinase receptor [urokinase-type plasminogen activator receptor (uPAR)] is regulated by inflammatory mediators. This study investigated the in vivo effect of endotoxin, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha on uPAR-release in vivo and in vitro in ...

  19. Application of Molecular Modeling to Urokinase Inhibitors Development

    Directory of Open Access Journals (Sweden)

    V. B. Sulimov

    2014-01-01

    Full Text Available Urokinase-type plasminogen activator (uPA plays an important role in the regulation of diverse physiologic and pathologic processes. Experimental research has shown that elevated uPA expression is associated with cancer progression, metastasis, and shortened survival in patients, whereas suppression of proteolytic activity of uPA leads to evident decrease of metastasis. Therefore, uPA has been considered as a promising molecular target for development of anticancer drugs. The present study sets out to develop the new selective uPA inhibitors using computer-aided structural based drug design methods. Investigation involves the following stages: computer modeling of the protein active site, development and validation of computer molecular modeling methods: docking (SOL program, postprocessing (DISCORE program, direct generalized docking (FLM program, and the application of the quantum chemical calculations (MOPAC package, search of uPA inhibitors among molecules from databases of ready-made compounds to find new uPA inhibitors, and design of new chemical structures and their optimization and experimental examination. On the basis of known uPA inhibitors and modeling results, 18 new compounds have been designed, calculated using programs mentioned above, synthesized, and tested in vitro. Eight of them display inhibitory activity and two of them display activity about 10 μM.

  20. Studies on urokinase (UK) therapy of thromboembolic diseases

    International Nuclear Information System (INIS)

    Wakayama, Ryuji; Satake, Kisaburo; Hisamatsu, Tokugoro; Fukase, Masaichi

    1974-01-01

    In order to determine the urokinase (UK) concentration in blood, a radioimmunoassay method was developed, in which a radioactive material labeled with 125 I-Na was used. In this method, the movement of UK in blood and the relationship between the UK concentration and fibrinolytic activity were studied with the following results: 1) The concentration of UK in normal human blood was found to be 6.84 +- 2.53 PKU early in the morning with an apparent daily rythmic fluctuation in concentration. 2) With an intravenous drip of 20,000 to 30,000 PKU, the UK concentration increased 6 to 8 PKU/ml above the early morning value, then in one to two hours it returned to the previous value once again. In some of the cases, a slight, transient decrease occurred. 3) Following the UK drip, UK concentration in the blood and fibrinolytic activity varied in a parallel fashion. Plasminogen and antiplasmin levels were not altered by administration of only 20,000 to 30,000 PKU of UK. Fibrinogen was lowered, but the fluctuation was within the physiological range. (S. Oyama)

  1. Analysis of related factors of orolingual angioedema after rt-PA intravenous thrombolytic therapy.

    Science.gov (United States)

    Wang, Y-X; Li, Y-Q; Chen, Y; Zhang, C-H; Dong, Z; Wang, Z; Zhao, S-N; Li, C-H; Zhang, P-L

    2018-03-01

    Orolingual angioedema (OA) is a rare clinical complication with a potentially fatal risk that occurs after the intravenous application of alteplase (rt-PA) in patients with acute ischemic stroke. The purpose of this work is to investigate the related factors of OA in patients with acute ischemic stroke after the administration of intravenous thrombolytic therapy, to improve the predictive ability of OA during intravenous thrombolytic therapy, and to reduce the prevalence of complications. We recruited 1223 cases of patients with acute ischemic stroke that were treated in the Department of Neurology No. 4 of the Tianjin Huanhu Hospital from June 2014 to April 2015. The clinical manifestations of rt-PA related OA were recorded, the clinical prevalence was counted, related factors of OA after intravenous thrombolytic therapy were analyzed, and the risk assessment of rt-PA related OA was conducted. 14 cases of patients developed OA, with a prevalence rate of 1.14%. Among them, 5 had a history of urticaria, 4 of drug allergy, and 3 of food allergy. Among the 14 cases of patients, 10 developed OA in the process of intravenous thrombolysis and 4 after intravenous thrombolysis, 12 showed lip edema, 9 showed extensive swelling of tongue, 3 showed swelling of lateral tongue, 3 were complicated by respiratory distress, 10 showed infarction in the middle cerebral artery territory, and 6 had previously been given oral ACEI drugs. Orolingual angioedema is a rare complication that occurs after rt-PA intravenous thrombolytic therapy; when serious, it may endanger a patient's life. If patients take an oral hypotension such as ACEI drugs before the onset of OA, they have a history of allergies, or the lesion is an infraction in the dominated area of the middle cerebral artery, the risk of OA after rt-PA intravenous thrombolytic therapy will be increased. The prevalence of OA should be monitored during the rt-PA intravenous thrombolytic therapy process; timely detection and early

  2. A modified thromboembolic stroke model of rat suitable for the delayed thrombolytic therapy

    International Nuclear Information System (INIS)

    You Xiaofang; Li Minghua; Zhao Jungong; Li Yongdong; Cheng Yingsheng

    2007-01-01

    Objective: To develop a modified focal thromboembolic stroke model of rat suitable for the delayed thrombolytic therapy. Methods: Ten fibrin-rich autologous blood clots (0.8-1.0 mm in length, 0.35 mm in width) were injected into the internal carotid artery to establish a focal thromboembolic stroke model. 138 embolized rats were divided randomly into ischemic group (n=68) and delayed thrombolytic therapeutic group (n=70). At 3 h, 6 h and 9 h after embolization, the rats in delayed thrombolytic therapeutic group were treated with 10 mg/kg recombinant tissue plasminogen activator respectively, while no treatment was performed on ischemic group. Lesion size, location, relative cerebral blood flow volume at different time, and intracranial hemorrhage after treatment were evaluated by MRI. After the last MRI examination, the rats were decapitated and their brain tissue were fixed with formalin for further pathology study. Results: Embolization with a preformed clot resulted in a focal infarction in the territory supplied by the MCA branch or anterior choroid artery, including 79.4% (104/131) of infarction located in ipsilateral parietal cortex or /and audoputamen, with infarction volume of (23.12 ± 6.04)% in embolized hemisphere. At 3 h, 6 h, and 9 h after embolization, the relative cerebral blood flow volumes were (36.86 ± 16.02)%, (40.67 ± 25.91)% and (44.72 ± 26.51)% respectively, with no statistical difference between them (3 h vs 6 h, Z=- 0.958, P=0.338, 3 h vs 9 h, Z=- 1.147, P=0.251). Hemorrhage was observed in 12 rats, all of that were in delayed thrombolytic therapeutic group. 13 rats died within 24 hours and 3 died within 12 days after delayed thrombolytic therapy. Conclusion: The modified rat thromboembolic brain model is reliable and repeaducible closely mimicking that of the human middle cerebral arterial branch thrombosis, suitable for investigating the delayed thrombolytic therapy in rats. (authors)

  3. Two distinct expression patterns of urokinase, urokinase receptor and plasminogen activator inhibitor-1 in colon cancer liver metastases

    DEFF Research Database (Denmark)

    Illemann, Martin; Bird, Nigel; Majeed, Ali

    2009-01-01

    Metastatic growth and invasion by colon cancer cells in the liver requires the ability of the cancer cells to interact with the new tissue environment. Plasmin(ogen) is activated on cell surfaces by urokinase-type PA (uPA), and is regulated by uPAR and plasminogen activator inhibitor-1 (PAI-1......). To compare the expression patterns of uPA, uPAR and PAI-1 in colon cancer with that in their liver metastases, we analysed matched samples from 14 patients. In all 14 primary colon cancers, we found upregulation of uPAR, uPA mRNA and PAI-1 in primarily stromal cells at the invasive front. In 5 of the 14......, whereas 8 of the remaining 9 showed direct contact between the cancer cells and the liver parenchyma. We conclude that there are 2 distinct patterns of expression of uPAR, uPA and PAI-1 in colon cancer liver metastases and that these correlate closely with 2 morphological growth patterns. These findings...

  4. Comparative proteomic analysis of the sun- and freeze-dried earthworm Eisenia fetida with differentially thrombolytic activities.

    Science.gov (United States)

    Fu, Zhirong; Zhang, Lin; Liu, Xiaobao; Zhang, Yanzhen; Zhang, Qianlan; Li, Ximin; Zheng, Wen; Sun, Lianli; Tian, Jingkui

    2013-05-27

    The dried earthworm is a traditional thrombolytic medicine in East Asia. Its thrombolytic mechanism has been extensively studied. However, the effects of drying process on thrombolysis were rarely investigated. Herein, we compared the thrombolytic activity of earthworm Eisenia fetida processed by sun-drying to that by freeze-drying. Fibrin plate and blood clot lysis assays showed that freeze-dried earthworms gave dramatically higher fibrinolytic and thrombolytic activities than the sun-dried earthworms. To address the thrombolytic difference, comparative proteomic analysis was carried out using fibrin zymography and two-dimensional gel electrophoresis (2-DE). The freeze- and sun-dried earthworms generated remarkably different 2-DE protein spot patterns. A total of 126 differential protein spots were detected, 83 of them were identified by matrix-assisted laser desorption/ionization-tandem time-of-flight mass spectrometry and database searching with 13 quantitative changes and 70 qualitative changes. Five of these differential proteins were identified as fibrinolytic proteases (lumbrokinases), responsible for dissolving fibrin, the main protein component of thrombus. The total abundance of these fibrinolytic proteases in the freeze-dried earthworms was significantly higher, consistent with the results of fibrin zymography. Therefore, the higher concentration of fibrinolytic enzymes along with their broad substrate specificity explained the stronger fibrinolytic and thrombolytic activities of the freeze-dried earthworms. This study suggests that freeze-drying represents an improved processing method for earthworm as the thrombolytic therapy in the future. Thrombosis has become one of the biggest concerns all over the world. The dried earthworms have been intensively used as thrombolytic agents. Its thrombotic mechanism has been studied by the modern pharmacological researches. However, the drying procedure of the earthworm and its effects on the thrombolysis were

  5. Theophylline as an add-on to thrombolytic therapy in acute ischaemic stroke (TEA-Stroke)

    DEFF Research Database (Denmark)

    Modrau, Boris; Hjort, Niels; Østergaard, Leif

    2016-01-01

    IntroductionEarly reperfusion of brain tissue at risk of injury (penumbra salvage) is crucial in treating acute ischaemic stroke. Neuroprotective agents may extend the time window for the reperfusion. The vasoactive agent theophylline redistributes the perfusion to ischaemic brain tissue and thus...... the collateral supply in acute ischaemic brain tissue and thus facilitate reperfusion despite proximal vessel occlusion. The primary study objective is to evaluate whether theophylline is safe and efficient in acute ischaemic stroke patients as an add-on to thrombolytic therapy.MethodsThe TEA-Stroke Trial...... theophylline as an add-on to standard thrombolytic therapy improves penumbra salvage with a reduced risk of reperfusion damage, reduced final infarct size, and improved clinical outcome....

  6. Purification and characterization of mutant miniPlasmin for thrombolytic therapy

    Directory of Open Access Journals (Sweden)

    Lin Xiaotao

    2013-01-01

    Full Text Available Abstract Background Previous animal studies by us and others have indicated that catheter-administered plasmin or its des-kringle derivatives may be more appropriate alternatives to plasminogen activators for treating thrombolytic diseases, since it has a very short serum half-life and therefore does not result in hemorrhaging. We have previously produced recombinant miniPlasmin (mPlasmin that was proven suitable for treating peripheral arterial occlusion in animal models. However, our previous results showed that non-specific cleavage at position K698 of mPlasmin during activation hindered the further development of this promising therapeutic candidate. In order to minimize or eliminate the non-specific cleavage problem, we performed saturation mutagenesis at the K698 position to develop a mutant form of mPlasmin for thrombolytic therapy. Methods We changed K698 to 16 other amino acids, with preferred E. coli codons. Each of these mutants were expressed in E. coli as inclusion bodies and then refolded, purified, and subsequently characterized by detailed kinetic assays/experiments/studies which identified highly active mutants devoid of non-specific cleavage. Results Activation studies indicated that at those conditions in which the wild type enzyme is cut at the non-specific position K698, the active mutants can be activated without being cleaved at this position. Conclusions From the above results, we selected two mutants, K698Q and K698N, as our lead candidates for further thrombolytic drug developments. The selected mutants are potentially better therapeutic candidates for thrombolytic therapy.

  7. Danhong Injection Combined With t-PA Improves Thrombolytic Therapy in Focal Embolic Stroke

    OpenAIRE

    Min Li; Jing Zhou; Weifeng Jin; Xiaohong Li; Yuyan Zhang

    2018-01-01

    Background: Hemorrhagic transformation, neurotoxicity, short treatment time windows, and other defects are considered as the major limitations for the thrombolytic therapy. This study is devoted to figure out whether Danhong injection (DHI) combined with tissue-plasminogen activator (t-PA) could extend the treatment time windows and ameliorate brain injury, hemorrhagic complication and BBB disruption after focal embolic stroke.Methods:In vitro, the combined concentrations of DHI and t-PA were...

  8. A case of carotid dissection having significant benefit from thrombolytic treatment

    Directory of Open Access Journals (Sweden)

    Sibel Güler

    2016-01-01

    Full Text Available Ischemic stroke due to carotid artery dissection is more common among young people and it accounts about 2-5% of all strokes. A 56 year old left landed male patient was evaluated for left-sided hemiparesis and aphasia in the emergency department. His cranial CT was assessed normal and NIH score was assessed 24 then he undergone thrombolytic therapy. His NIH score was decreased to 14 after 24 hours. At extracranial dupplex USG, cranial MRI and MR-Angiography, done the same day there were findings for carotid dissection. At MR-anjio repeated 5 days later, partial recanalization were seen. At control cranial CT only striocapsüler infarct was seen. There was no any evidence of bleeding as complication. Here we present a rare case of extracranial carotid artery dissection case undergone IV thrombolytic therapy and want to take attention that in carotid dissection IV thrombolytic therapy is quiet safe and there is no difference of complication such as hemorrhage and the prognosis is no different then those with no carotid dissection.

  9. Impact of metabolic syndrome on ST segment resolution after thrombolytic therapy for acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Ayşe Saatçı Yaşar

    2010-09-01

    Full Text Available Objectives: It has been shown that metabolic syndrome is associated with poor short-term outcome and poor long-term survival in patients with acute myocardial infarction. We aimed to investigate the effect of metabolic syndrome on ST segment resolution in patients received thrombolytic therapy for acute myocardial infarction.Materials and methods: We retrospectively analyzed 161 patients, who were admitted to our clinics with acute ST-elevated-myocardial infarction and received thrombolytic therapy within 12 hours of chest pain. Metabolic syndrome was diagnosed according to National Cholesterol Education Program Adult Treatment Panel III criteria. Resolution of ST segment elevation was assessed on the baseline and 90-minute electrocardiograms. ST segment resolution ≥70% was defined as complete resolution.Results: Metabolic syndrome was found in 56.5% of patients. The proportion of patients with metabolic syndrome who achieved complete ST segment resolution after thrombolysis was significantly lower than that of patients without metabolic syndrome (32.9% versus 58.6%, p=0.001. On multivariate analysis metabolic syndrome was the only independent predictor of ST segment resolution (p=0.01, Odds ratio=2.543, %95 CI:1.248-5.179Conclusion: The patients with metabolic syndrome had lower rates of complete ST segment resolution after thrombolytic therapy for acute myocardial infarction. This finding may contribute to the higher morbidity and mortality of patients with metabolic syndrome.

  10. The soluble urokinase plasminogen activator receptor and its fragments in venous ulcers

    DEFF Research Database (Denmark)

    Ahmad, Anwar; Saha, Prakash; Evans, Colin

    2015-01-01

    OBJECTIVE: Activation of proteolytic mechanisms at the cell surface through the activity of urokinase-type plasminogen activator (uPA) bound to its receptor, uPAR, is an important process in wound healing. The soluble forms of uPAR (suPAR and its fragments I, II, and III) have nonproteolytic...

  11. Soluble Urokinase-Type Plasminogen Activator Receptor Levels in Patients With Schizophrenia

    DEFF Research Database (Denmark)

    Nielsen, Jimmi; Røge, Rasmus; Pristed, Sofie Gry

    2015-01-01

    BACKGROUND: The etiology of schizophrenia remains largely unknown but alterations in the immune system may be involved. In addition to the psychiatric symptoms, schizophrenia is also associated with up to 20 years reduction in life span. Soluble urokinase-type plasminogen activator receptor (suPA...

  12. A sensitive bioimmunoassay for thrombin-cleaved two-chain urokinase-type plasminogen activator (abstract)

    NARCIS (Netherlands)

    Braat, E.A.M.; Nauland, U.; Dooijewaard, G.; Rijken, P.C.

    1996-01-01

    Thrombin cleaves single-chain urokinase-type plasminogen activator (scu-PA) into a virtually inactive two-chain form (tcu-PA/T). Little is known about the physiological importance of tcu-PA/T. To examine the occurrence of tcu-PA/T in vivo, we developed a sensitive and specific bioimmunoassay (BIA)

  13. Physical exercise induces enhancement of urokinase-type plasminogen activator (u-PA) levels in plasma

    NARCIS (Netherlands)

    Dooijewaard, G.; Boer, A.de; Turion, P.N.C.; Cohen, A.F.; Breimer, D.D.; Kluft, C.

    1991-01-01

    The enhancement of the blood fibrinolytic potential by physical exercise is generally attributed to the release of tissue-type plasminogen activator (t-PA) from the vessel wall. In this study we have investigated the possible contribution of urokinase-type plasminogen activator (u-PA). Six healthy

  14. Adsorption behavior of Urokinase by the polypropylene film with amine, hydroxylamine and polyol groups

    International Nuclear Information System (INIS)

    Lee, Kwang-Pill; Kang, Hae-Jeong; Joo, Duck-Lae; Choi, Seong-Ho

    2001-01-01

    For the purpose of the recovery of urokinase, the polypropylene (PP) films were modified by radiation-induced grafting of glycidylmethacrylate (GMA) and subsequent chemical modification of epoxy group of poly-GMA graft chains. The physical and chemical properties of the irradiated PP film, GMA-grafted PP film and the PP films modified with trimethylamine (TMA), hydroxylamine (HA), diethanolamine (DEA), and tri(hydroxymethyl)aminomethane (THMAM) were investigated by IR, SEM, and XPS. The adsorption of urokinase for the PP films modified with TMA, HA, DEA, and THMAM group were examined under various conditions of the functional group content, pH value and salt. It increased with increasing the content of functional group. The adsorption behavior of the PP films modified for different functional groups was in the following order: TMA>DEA>THMAM>HA. The adsorption of urokinase by the PP films with various functional groups at pH=7.4 were higher than that at pH=9.0. In TMA, DEA, and THMAM groups, the adsorption of urokinase without salts was also higher than those with salts. (author)

  15. Peptide antagonists of the human urokinase receptor and method for selecting them

    DEFF Research Database (Denmark)

    2006-01-01

    A novel set of inhibitors of the binding interaction between human urokinase plasminogen activator (uPA) and its cell surface receptor (uPAR) has been developed. The inhibitors comprise of peptide fragments, monomeric or in multiple copies attached to a common scaffold, in which the amino acid se...... are antagonistic....

  16. Expression of urokinase receptors by human trophoblast. A histochemical and ultrastructural analysis

    DEFF Research Database (Denmark)

    Multhaupt, H A; Mazar, A; Cines, D B

    1994-01-01

    are not actively invasive in vivo, may serve to facilitate the generation of plasmin at the interface of these cells with maternal plasma, thereby limiting the deposition of fibrin within the placental intervillous spaces. Diminished urokinase receptor expression by villous trophoblast at term may represent...

  17. Inactivation of single-chain urokinase-type plasminogen activator by thrombin in human subjects

    NARCIS (Netherlands)

    Braat, E. A.; Levi, M. [=Marcel M.; Bos, R.; Haverkate, F.; Lassen, M. R.; de Maat, M. P.; Rijken, D. C.

    1999-01-01

    Thrombin cleaves single-chain urokinase-type plasminogen activator (scu-PA) into a virtually inactive two-chain form (tcu-PA/T), a process that may protect a blood clot from early fibrinolysis. It is not known under what circumstances tcu-PA/T can be generated in vivo. We have studied the occurrence

  18. Characterization of human endothelial cell urokinase-type plasminogen activator receptor protein and messenger RNA

    DEFF Research Database (Denmark)

    Barnathan, E S; Kuo, A; Karikó, K

    1990-01-01

    Human umbilical vein endothelial cells in culture (HUVEC) express receptors for urokinase-type plasminogen activators (u-PA). The immunochemical nature of this receptor and its relationship to u-PA receptors expressed by other cell types is unknown. Cross-linking active site-blocked u-PA to HUVEC...

  19. Structure and ligand interactions of the urokinase receptor (uPAR)

    DEFF Research Database (Denmark)

    Kjaergaard, Magnus; Hansen, Line V.; Jacobsen, Benedikte

    2008-01-01

    The urokinase-type plasminogen activator receptor (uPAR or CD87) is a glycolipid-anchored membrane glycoprotein, which is responsible for focalizing plasminogen activation to the cell surface through its high-affinity binding to the serine protease uPA. This tight interaction (KD less than 1 nM) ...

  20. Soluble Urokinase Plasminogen Activator Receptor for Risk Prediction in Patients Admitted with Acute Chest Pain

    DEFF Research Database (Denmark)

    Lyngbæk, Stig; Andersson, Charlotte; Marott, Jacob L

    2013-01-01

    Plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) predict mortality in several clinical settings, but the long-term prognostic importance of suPAR in chest pain patients admitted on suspicion of non-ST-segment elevation acute coronary syndrome (NSTEACS) is uncertain....

  1. Quantitation of the receptor for urokinase plasminogen activator by enzyme-linked immunosorbent assay

    DEFF Research Database (Denmark)

    Rønne, E; Behrendt, N; Ploug, M

    1994-01-01

    Binding of the urokinase plasminogen activator (uPA) to a specific cell surface receptor (uPAR) plays a crucial role in proteolysis during tissue remodelling and cancer invasion. An immunosorbent assay for the quantitation of uPAR has now been developed. This assay is based on two monoclonal anti...

  2. Activity of Nanobins Targeted to the Urokinase Plasminogen Activator System

    Science.gov (United States)

    Hankins, Patrick Leon

    While innovations in nanotechnology have resulted in numerous medical advancements for the treatment of cancer, there remains an urgent unmet need for safe and efficient molecular platforms that facilitate the delivery of potent therapeutics to solid tumors. Nanoscale formulations help to overcome the poor bioavailability and systemic organ toxicity associated with many small molecule drugs. Of these nanoparticle drug delivery systems, the greatest clinical successes to date have employed simple nanoscale lipid bilayer assemblies which encase large payloads of chemotherapeutic. While the nanobin platform we have developed has seen initial success through the passive accumulation into tumors, actively targeting nanobins to tumor specific antigens has the potential to increase the therapeutic index of these nanoparticle drugs. We have identified the urokinase plasminogen activator (uPA) and its cell surface bound receptor (uPAR) as ideal targets for drug delivery due to their selective overexpression in metastatic cancers and their important role in tumor progression. From a panel of monoclonal antibodies targeted to uPA and uPAR, we have selected ATN291 and ATN658 as lead candidates for nanobin targeting based on their tumor cell binding and ability to be internalized by cells. A novel method of conjugating antibodies to liposomes was developed for our nanobin platform that preserves the high binding affinity and specificity of these antibodies. We evaluated these uPA- and uPAR-targeted nanobins in several xenograft tumor models and found that they were well-tolerated over a wide range of doses and demonstrated significantly increased antitumor efficacy over untargeted nanobins in multiple tumor types. Preliminary studies suggest that uPA-targeted nanobins are readily internalized by tumor cells, and we believe this is the mechanism for their increased antitumor effect. A method for radiolabeling nanobins with gallium-67 was developed, and preliminary SPECT

  3. Half-life of single-chain urokinase-type plasminogen activator (scu-PA) and two-chain urokinase-type plasminogen activator (tcu-PA) in patients with acute myocardial infarction.

    Science.gov (United States)

    Köhler, M; Sen, S; Miyashita, C; Hermes, R; Pindur, G; Heiden, M; Berg, G; Mörsdorf, S; Leipnitz, G; Zeppezauer, M

    1991-04-01

    The pharmacokinetics of urokinase (two-chain urokinase-type plasminogen activator, tcu-PA) and single-chain urokinase-type plasminogen activator (scu-PA) were studied in 20 patients with acute myocardial infarction (AMI). Ten consecutive patients received 2.5 million units tcu-PA by bolus injection within 5 min during the first 6 h after AMI (group I). Ten further consecutive patients received 250,000 U tcu-PA within 5 min, followed by 4.5 million U scu-PA by intravenous infusion over 40 min (group II). An enzyme immunoassay was developed for urokinase antigen determinations, and a fibrin plate assay for determinations of fibrinolytic activity was applied. Using a 3-compartment model, in group I 98% of urokinase antigen were cleared with a half-life of 60.8 min. After scu-PA, urokinase antigen was cleared with half-lives (area under the curve in parentheses) of 6.9 min (74.8%), 26.5 min (23.6%), and 329.7 min (2.2%). The half-disappearance times of fibrinolytic activity were 18 and 8 min in group I and II, respectively. A more pronounced decrease of plasminogen was observed after tcu-PA.

  4. Regions involved in binding of urokinase-type-1 inhibitor complex and pro-urokinase to the endocytic alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein. Evidence that the urokinase receptor protects pro-urokinase against binding to the endocytic receptor.

    Science.gov (United States)

    Nykjaer, A; Kjøller, L; Cohen, R L; Lawrence, D A; Garni-Wagner, B A; Todd, R F; van Zonneveld, A J; Gliemann, J; Andreasen, P A

    1994-10-14

    The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2MR/LRP) binds several ligands, including complex between the two chain urokinase-type plasminogen activator (uPA) and type-1 plasminogen activator inhibitor (PAI-1), and the single chain zymogen pro-urokinase (pro-uPA). We have used truncated variants of uPA and PAI-1 as well as Fab fragments of monoclonal antibodies with known epitopes to identify regions in the uPA.PAI-1 complex and in pro-uPA involved in binding to alpha 2MR/LRP.uPA.PAI-1 complex bound with high affinity (EC50 about 0.4 nM) via contacts in the PAI-1 moiety as well as the uPA serine proteinase domain and the uPAA chain. Pro-uPA bound with lower affinity (EC50 about 10 nM), and efficient binding to alpha 2MR/LRP was dependent on contact with both the A chain and the serine proteinase domain. We analyzed the effect of complex formation with the urokinase receptor since this is the primary target for binding of uPA.PAI-1 and pro-uPA at the cell surface, and since it has been demonstrated that urokinase receptor-bound uPA.PAI-1 complex is internalized following interaction with alpha 2 MR/LRP (Nykjaer, A., Petersen, C. M., Møller, B., Jensen, P.H., Moestrup, S.K., Holtet, T.L., Etzerodt M., Thøgersen, H.C., Munch, M., Andreasen, P.A., and Gliemann, J. (1992) J. Biol. Chem. 267, 14543-14546). Soluble recombinant urokinase receptor blocked the binding of pro-uPA to alpha 2MR/LRP but caused only a slight reduction in the affinity for binding of uPA.PAI-1. Moreover, pro-uPA bound to the urokinase receptor at the cell surface was not internalized and degraded unless activated to uPA and complexed with PAI-1. We conclude that pro-uPA is protected against degradation via alpha 2MR/LRP when bound to uPAR due to shielding of a binding contact in the A chain, whereas the affinity of uPAR-bound uPA.PAI-1 complex for binding to alpha 2MR/LRP remains sufficient to allow rapid internalization and degradation.

  5. Obstructive Thrombosis of Left-Sided Mechanical Heart Valves: Clinical Profile and Thrombolytic Therapy.

    Science.gov (United States)

    Chandrakasu, Arumugam; Jayachandran, Avinash; Gopinath Nayar, Pradeep; Meyyappan, Chokkalingam; Narayan, Ganesh; Basha Abdul Bari, Ahamed; Johnson Samuel, Prince

    2017-05-01

    Thrombosis of a mechanical prosthetic heart valve is a potentially life-threatening complication associated with a high mortality. Although thrombolytic therapy has been considered highly beneficial in this situation, very few studies have been conducted to monitor the effectiveness of such thrombolytic therapy among Asian populations. Hence, the study aim was to evaluate the clinical profile, efficacy and safety of the thrombolytic agent streptokinase (SK) in patients with obstructive thrombosis of a left-sided mechanical heart valve. Patients (n = 30) with left-sided mechanical heart valve thrombosis (LSMHVT) who had been managed with SK during the past four years were included in this retrospective study. Clinical features such as presenting symptoms based on NYHA functional class, prosthetic valve position, oral anticoagulant compliance, International Normalized Ratio (INR) and imaging methods including fluoroscopy, transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) were evaluated. In addition, the effectiveness and complications of SK were analyzed. The majority of patients presented with advanced NYHA class (III and IV, each 40%). Obstructive thromboses were observed at the mitral prosthesis in 70% of cases, at the aortic prosthesis in 27%, and at both valves in 3%. All patients underwent TTE, but fluoroscopy was used more often than TEE. Despite compliance with oral anticoagulation therapy, a sub-therapeutic INR was observed in 40% of cases at the time of presentation. Overall, thrombolysis was successful in 80% of patients using intravenous SK, with 100% success in patients in NYHA classes I-III and 42% for NYHA class IV. Moreover, embolic complications occurred in only a small number of patients. In patients with obstructive thrombosis of LSMHVT, intravenous SK was effective and should be considered as first choice in patients in NYHA classes I-III, and as an acceptable alternative in those in NYHA class IV.

  6. Spontaneous coronary thrombosis following thrombolytic therapy for acute cardiovascular accident and stroke: a case study.

    Science.gov (United States)

    Wallace, Eric L; Smyth, Susan S

    2012-11-01

    Cardiac complications following stroke or acute cerebrovascular accidents (CVA) are common; however, many of these complications are asymptomatic and do not cause adverse cardiac effects. Symptomatic events (such as acute myocardial infarction after CVA) rarely occur and are often the result of an underlying cardiac embolic source, such as a left ventricular thrombus. We report a case of spontaneous coronary thrombosis following thrombolytic therapy for acute CVA, and discuss the implication that an underlying systemic pro-thrombotic state may predispose individuals to thrombosis in disparate vascular beds.

  7. The 100 Most Influential Papers in the Field of Thrombolytic Therapy: A Bibliometric Analysis.

    Science.gov (United States)

    Siddiqi, Tariq Jamal; Usman, Muhammad Shariq; Khan, Muhammad Shahzeb; Fatima, Kaneez; Norbash, Alexander; Qureshi, Adnan Iqbal; Khan, Abdur Rahman; Khosa, Faisal

    2017-08-01

    Bibliometric analyses are used by researchers and research funding agencies to help determine areas of greatest interest, and consequently which topics and domains warrant increased research attention. Bibliometric analyses have similarly been published in a number of clinical subspecialties concerning areas of specific medical interest; however, a thorough literature search revealed that such a study has been absent in the field of thrombolytics to date. To bridge this gap, we conducted a citation analysis of the 100 most influential articles on thrombolytics. Scopus was selected as the database of choice. Two independent researchers explored the database to extract relevant articles. The articles were ranked according to the number of citations, and a sequential list of the top 100 original articles was prepared in descending order. A detailed analysis was carried out to identify trends and uncover significant discriminators. A second list containing the top 10 review articles was also separately prepared. The 100 most-cited articles regarding thrombolytics were published between 1973 and 2015, with the most articles (n = 29) published in the 5-year period extending from 1996 to 2000. The total number of citations of these 100 most-cited articles ranged from a low of 389 to a high of 6971, with a median of 612.5 citations. These 100 most-cited articles originated from 26 different countries, with more than half from the USA (n = 54), followed by the next most popular countries of origin Germany (n = 20) and France (n = 15). The New England Journal of Medicine (n = 26) and The Lancet (n = 26) contributed the majority of the articles. Our analysis provides insight into the span of research activity and the nature of inquiry dealing with 'thrombolytic therapy,' with the hope that such analysis may help to effectively guide future research. Our analysis also yielded a list of the most highly cited and presumably most impactful guideline articles within

  8. Plasma iron status and lipid peroxidation following thrombolytic therapy for acute myocardial infarction.

    Science.gov (United States)

    Cottin, Y; Doise, J M; Maupoil, V; Tannière-Zeller, M; Dalloz, F; Maynadié, M; Walker, M K; Louis, P; Carli, P M; Wolf, J E; Rochette, L

    1998-01-01

    Free radical species have been implicated as important agents involved in myocardial ischemic and reperfusion injuries. Superoxide is capable of mobilizing iron from ferritin and the released iron can cause hydroxyl formation from H2O2. The aim of this study was to evaluate the time-dependent increase in lipid peroxidation assessed by plasma thiobarbituric acid reactive substances (TBARS) and the relationship between lipid-peroxidation and the iron status. Peripheral venous blood samples were obtained from 17 men with acute myocardial infarction (AMI) before thrombolytic treatment (T0) and 1, 2, 3, 4, 8, 12, 16, 20, 24 and 48 hours after commencing fibrinolytic treatment. The concentration of TBARS, the parameters of iron metabolism, serum myoglobin, creatine kinase, and creatine kinase-MB were measured. Early reperfusion was judged by regression of sinus tachycardia (ST) elevation and reduction of chest pain. Recanalization of coronary artery was evaluated by a late coronary angiography 24-96 hours after thrombolysis. After thrombolytic therapy, the TBARS level was raised from 2.98 +/- 0.80 (T0) to 4.57 +/- 1.24 (peak), and decreased to 2.96 +/- 0.40 nmol/mL plasma at T48 (T0 vs peak: P < 0.001, peak vs T48: P < 0.001, T0 vs T48: NS). The mean time of the peak was observed at 9.7 +/- 7.5 hours. The iron increased significantly from 0.67 +/- 0.34 (T0) to 1.15 +/- 0.52 mg/L (peak), and returned to the pre-reperfusion to levels: 0.53 +/- 0.28 UI/L at T48 (TO vs peak: P < 0.001, peak vs T48: P < 0.001, T0 vs T48: NS). The mean time of the peak was observed at 9.4 +/- 7.3 hours. In return, no correlation was found between the increase of plasma creatine-kinase activity, myoglobin and iron or between the biochemical markers and time of fibrinolytic therapy. The results confirmed the importance of the temporal relationship between lipid peroxidation and iron status after thrombolytic therapy. Our results are in agreement with the concept that antioxidant agents used in

  9. Urokinase mediates endothelial cell survival via induction of the X-linked inhibitor of apoptosis protein

    DEFF Research Database (Denmark)

    Prager, Gerald W; Mihaly, Judit; Brunner, Patrick M

    2008-01-01

    Urokinase-type plasminogen activator (uPA) additionally elicits a whole array of pro-angiogenic responses, such as differentiation, proliferation, and migration. In this study, we demonstrate that in endothelial cells uPA also protects against apoptosis by transcriptional up-regulation and partia......Urokinase-type plasminogen activator (uPA) additionally elicits a whole array of pro-angiogenic responses, such as differentiation, proliferation, and migration. In this study, we demonstrate that in endothelial cells uPA also protects against apoptosis by transcriptional up......-regulation and partially by mRNA stabilization of inhibitor of apoptosis proteins, most prominently the X-linked inhibitor of apoptosis protein (XIAP). The antiapoptotic activity of uPA was dependent on its protease activity, the presence of uPA receptor (uPAR) and low-density lipoprotein receptor-related protein (LRP...

  10. Effect of purified, soluble urokinase receptor on the plasminogen-prourokinase activation system

    DEFF Research Database (Denmark)

    Behrendt, N; Danø, K

    1996-01-01

    The extracellular proteolytic pathway mediated by the urokinase plasminogen activator (uPA) is a cascade system, initiated by activation of the zymogen, pro-uPA. Pro-uPA as well as uPA binds to the cellular uPA receptor (uPAR) which has a central function in cell-dependent acceleration of the cas......The extracellular proteolytic pathway mediated by the urokinase plasminogen activator (uPA) is a cascade system, initiated by activation of the zymogen, pro-uPA. Pro-uPA as well as uPA binds to the cellular uPA receptor (uPAR) which has a central function in cell-dependent acceleration...

  11. Anterograde Intra-Arterial Urokinase Injection for Salvaging Fibular Free Flap

    Directory of Open Access Journals (Sweden)

    Dae-Sung Lee

    2013-05-01

    Full Text Available We present a case of a 57-year-old male patient who presented with squamous cell carcinoma on his mouth floor with cervical and mandibular metastases. Wide glossectomy with intergonial mandibular ostectomy, and sequential reconstruction using fibular osteomyocutaneous free flap were planned. When the anastomosis between the peroneal artery of the fibular free flap and the right lingual artery was performed, no venous flow was observed at the vena comitans. Then re-anastomosis followed by topical application of papaverine and lidocaine was attempted. However, the blood supply was not recovered. Warm saline irrigation over 30 minutes was also useless. Microvascular thromboses of donor vessels were clinically suspected, so a solution of 100,000 units of urokinase was infused once through a 26-gauge angiocatheter inserted into the recipient artery just at the arterial anastomotic site, until the solution gushed out through the flap vena comitans. Immediately after the application of urokinase, arterial flow and venous return were restored. There were no complications during the follow-up period of 11 months. We believe that vibrating injuries from the reciprocating saw during osteotomies and flap insetting might be the cause of microvascular thromboses. The use of urokinase may provide a viable option for the treatment of suspicious intraoperative arterial thrombosis.

  12. Effect of thrombolytic therapy on exercise response during early recovery from acute myocardial infarction: a placebo controlled study

    DEFF Research Database (Denmark)

    Svendsen, Jesper Hastrup; Madsen, J K; Saunamäki, K I

    1992-01-01

    Several studies have shown that infarct size is reduced following thrombolytic treatment in patients with acute myocardial infarction. Exercise test variables, such as an impaired heart rate response during exercise, are known to be related to left ventricular function and patient prognosis follo...

  13. Thrombolytic treatment in the oldest-old patient with acute ischemic stroke: an update on current evidence

    Directory of Open Access Journals (Sweden)

    Fabiola Maioli

    2013-09-01

    Full Text Available The incidence of ischemic stroke rises exponentially with age, with a steep increase in the age interval between 75 and 85 years. Thrombolytic therapy restores cerebral blood flow in patients with acute ischemic stroke of any etiology by using drugs that dissolve blood clots. Infusion for 1 h of alteplase at the dose of 0.9 mg/kg within 3 h of the start of the symptoms is associated to a 30% increase in the likelihood of gaining a favorable outcome with respect to placebo. There is strong evidence that selected patients with ischemic stroke may benefit from intravenous thrombolysis when treated within 3 h. The aim of the study was to evaluate available evidence for the efficacy and safety of thrombolytic therapy in patients with ischemic stroke aged 80 years and over. Compared to younger stroke patients treated with thrombolytic therapy, those aged 80 years and over have higher acute mortality due to symptomatic intracranial hemorrhage. However, functional outcome at six months is significantly better for over-80-year-olds than younger patients. There is a need for screening tools that take into account pre-stroke functional and cognitive status that are able to identify those over-80-year-old patients with ischemic stroke who can most benefit from thrombolytic treatment. Available evidence supports further recruitment of oldest-old patients into ongoing trials of thrombolysis.

  14. Evaluation of the analgesic, sedative-anxiolytic, cytotoxic and thrombolytic potentials of the different extracts of Kalanchoe pinnata leaves

    Directory of Open Access Journals (Sweden)

    Md. Razibul Habib

    2015-12-01

    Full Text Available Objective: To evaluate the analgesic, neuropharmacological, cytotoxic and thrombolytic potentials of the aqueous, ethanol and ethyl acetate extracts of Kalanchoe pinnata leaves. Methods: At the dose of 400 mg/kg body weight, the analgesic activity of the extracts were evaluated by the acetic acid-induced writhing and formalin-induced persistent pain tests while neuropharmacological activity was evaluated by the open field, hole cross and elevated plus maze tests. The cytotoxic potential was observed by brine shrimp lethality bioassay and the thrombolytic potential was investigated by clot lysis test. Results: The aqueous extract significantly suppressed the number of writhing (96.78% as well as the formalin-induced persistent pain on the early phase (46.92% and on the late phase (40.98%. Again in case of hole cross and open field tests, the locomotor activity was decreased significantly (P < 0.001 mostly by the ethyl acetate extract. Furthermore, the sedative-anxiolytic activity was supported by the increased percent (P < 0.01 of frequency into the open arm on elevated plus maze test. Besides, the extracts showed moderate lethality and thrombolytic activity. Conclusions: The findings showed that activities are comparable to the standards and in some cases are stronger than the standards. Therefore, based on the results, it is evident that it has great analgesic and sedative-anxiolytic activity with moderate cytotoxic and thrombolytic potential.

  15. Thrombolytic therapy

    Science.gov (United States)

    ... is the most common risk. It can be life threatening. Minor bleeding from the gums or nose can occur in approximately 25% of people who receive the drug. Bleeding into the brain occurs approximately 1% of the time. This risk is the same for both stroke ...

  16. Analysis of multi-factors affecting symptomatic intracranial hemorrhage in intraarterial thrombolysis with urokinase for acute ischemic stroke

    International Nuclear Information System (INIS)

    Qiao Qianlin; Zhou Shi; Wang Xuejian; Wu Qinghua; Song Jie

    2005-01-01

    Objective: To explore the causes and preventive measures of symptomatic intracranial hemorrhage in 217 patients with acute cerebral ischemic stroke treated with local intra-arterial urokinase. Methods: From February 1999 to June 2004, 217 patients were treated for acute ischemic stroke with local intra-arterial urokinase in our hospital. Factors associated with symptomatic intracranial hemorrhage of intra-arterial thrombolysis were analyzed by Stepwise logistic regression to identify some factors relating the prediction symptomatic intracranial hemorrhage. Results: Symptomatic intracranial hemorrhage occurred in 8 cases (3.7%). Predictors of the symptomatic intracranial hemorrhage were the elevated systolic blood pressure before therapy (odds ratio, 1.096; 95% CI, 1.006 to 1.194) and urokinase (UK) treatment (odds ratio, 1.068 ; 95% CL, 1.053 to 1.247). Risk of secondary symptomatic intracranial hemorrhage was increased with elevated systolic blood pressure. Other factors like age, initial treating time, NIHSS, diabetes and collateral circulation did not predict the symptomatic intracranial hemorrhage respectively. Conclusions: Predictors of symptomatic intracranial hemorrhage after local intra-arterial infusion of urokinase for acute ischemic stroke were the elevated systolic blood pressure before therapy and urokinase (UK) treatment. (authors)

  17. Pharmacokinetics and pharmacodynamics of saruplase, an unglycosylated single-chain urokinase-type plasminogen activator, in patients with acute myocardial infarction

    NARCIS (Netherlands)

    Koster, R. W.; Cohen, A. F.; Hopkins, G. R.; Beier, H.; Günzler, W. A.; van der Wouw, P. A.

    1994-01-01

    We examined in patients with acute myocardial infarction (AMI) the pharmacokinetics of saruplase, an unglycosylated, single chain, urokinase-type plasminogen activator (rscu-PA) by measuring urokinase-type plasminogen activator (u-PA) antigen and total u-PA activity, its conversion to active

  18. Citation bias favoring positive clinical trials of thrombolytics for acute ischemic stroke: a cross-sectional analysis.

    Science.gov (United States)

    Misemer, Benjamin S; Platts-Mills, Timothy F; Jones, Christopher W

    2016-09-28

    Citation bias occurs when positive trials involving a medical intervention receive more citations than neutral or negative trials of similar quality. Several large clinical trials have studied the use of thrombolytic agents for the treatment of acute ischemic stroke with differing results, thereby presenting an opportunity to assess these trials for evidence of citation bias. We compared citation rates among positive, neutral, and negative trials of alteplase (tPA) and other thrombolytic agents for stroke. We used a 2014 Cochrane Review of thrombolytic therapy for the treatment of acute stroke to identify non-pilot, English-language stroke trials published in MEDLINE-indexed journals comparing thrombolytic therapy with control. We classified trials as positive if there was a statistically significant primary outcome difference favoring the intervention, neutral if there was no difference in primary outcome, or negative for a significant primary outcome difference favoring the control group. Trials were also considered negative if safety concerns supported stopping the trial early. Using Scopus, we collected citation counts through 2015 and compared citation rates according to trial outcomes. Eight tPA trials met inclusion criteria: two were positive, four were neutral, and two were negative. The two positive trials received 9080 total citations, the four neutral trials received 4847 citations, and the two negative trials received 1096 citations. The mean annual per-trial citation rates were 333 citations per year for positive trials, 96 citations per year for neutral trials, and 35 citations per year for negative trials. Trials involving other thrombolytic agents were not cited as often, though as with tPA, positive trials were cited more frequently than neutral or negative trials. Positive trials of tPA for ischemic stroke are cited approximately three times as often as neutral trials, and nearly 10 times as often as negative trials, indicating the presence of

  19. Late Thrombolytic Treatment In A Patient With Ischemic Stroke Caused By Biatrial Thrombus

    Directory of Open Access Journals (Sweden)

    Halit CINARKA

    2015-07-01

    Full Text Available Venous thromboembolism is a preventable disease when necessary precautions are taken and it occurs along with deep vein thrombosis and pulmonary embolism. Mortality related to venous thromboembolism may be high in the acute phase of the disease and it may become chronic. Intracardiac thrombus may be detected in some venous thromboemboli cases. Cardiac embolism is responsible for most of the ischemic strokes which can be very mortal or may cause serious morbidity when they are not treated in time. In this report, we aimed to present the results of late antithrombolytic treatment in a 77-year old patient who developed deep vein thrombosis, biatrial thrombosis and ischemic stroke following hydrocephalus shunt operation.   Key words: Venous thromboembolism; ischemic stroke; thrombolytic therapy

  20. Computed Tomography--Verified Leukoaraiosis Is a Risk Factor for Post-thrombolytic Hemorrhage

    DEFF Research Database (Denmark)

    Willer, Lasse; Havsteen, Inger; Ovesen, Christian

    2015-01-01

    BACKGROUND: Is computed tomography (CT)-verified leukoaraiosis (LA) a risk factor for post-thrombolytic hemorrhagic transformation and symptomatic hemorrhage? METHODS: (1) Retrospective analysis based on a prospectively planned single-center registry of consecutive tissue plasminogen activator (t......PA)-treated patients within 4.5 hours from symptom onset. Standard work-up included baseline noncontrast CT and CT angiography and next day follow-up noncontrast CT. Baseline noncontrast CT LA was graded using Fazekas' score and dichotomized as the absence (Fazekas, 0) or the presence (Fazekas, 1-3). Hemorrhagic...... transformation was rated using European Cooperative Acute Stroke Study (ECASS) criteria. Symptomatic intracerebral hemorrhage was defined as hemorrhage and deterioration of National Institutes of Health Stroke Scale (NIHSS) of 4 or greater within 36 hours from symptom onset. Endovascularly treated patients were...

  1. CLINICAL CASE OF RUSSIAN THROMBOLYTIC AGENT FORTELYZIN® USE IN PATIENTS WITH ACUTE CORONARY ARTERY DISEASE

    Directory of Open Access Journals (Sweden)

    K. A. Kireev

    2015-01-01

    Full Text Available One of the three clinical examples of hospital thrombolysis using Russian thrombolytic agent recombinant protein comprising an amino acid sequence of staphylokinase is described. The trial was held in Chelyabinsk Regional Vascular Centre of specialized medical care for patients with acute coronary syndromes. Each of the three patients had similar reasons for systemic intravenous thrombolysis: hospitalization with ST-segment elevation myocardial infarction, unavailability of coronary interventions due to the X-ray operating room occupancy, high need for the reperfusion therapy in the setting of significant acute myocardial ischemia. In all the cases the pharmacologic reperfusion with recombinant protein comprising an amino acid sequence of staphylokinase was successful, hereafter percutaneous coronary interventions were performed. There were no complications registered.

  2. Effective management of patients with acute ischemic stroke based on lean production on thrombolytic flow optimization.

    Science.gov (United States)

    Liang, Zhuoyuan; Ren, Lijie; Wang, Ting; Hu, Huoyou; Li, Weiping; Wang, Yaping; Liu, Dehong; Lie, Yi

    2016-12-01

    The efficacy of thrombolytic therapy for acute ischemic stroke (AIS) decreases when the administration of tissue plasminogen activator (tPA) is delayed. Derived from Toyota Production System, lean production aims to create top-quality products with high-efficiency procedures, a concept that easily applies to emergency medicine. In this study, we aimed to determine whether applying lean principles to flow optimization could hasten the initiation of thrombolysis. A multidisciplinary team (Stroke Team) was organized to implement an ongoing, continuous loop of lean production that contained the following steps: decomposition, recognition, intervention, reengineering and assessment. The door-to-needle time (DNT) and the percentage of patients with DNT ≤ 60 min before and after the adoption of lean principles were used to evaluate the efficiency of our flow optimization. Thirteen patients with AIS in the pre-lean period and 43 patients with AIS in the lean period (23 in lean period I and 20 patients in lean period II) were consecutively enrolled in our study. After flow optimization, we reduced DNT from 90 to 47 min (p < 0.001 ¤ ). In addition, the percentage of patients treated ≤60 min after hospital arrival increased from 38.46 to 75.0 % (p = 0.015 ¤ ). Adjusted analysis of covariance confirmed a significant influence of optimization on delay of tPA administration (p < 0.001). The patients were more likely to have a good prognosis (mRS ≤ 2 at 90 days) after the flow optimization (30.77-75.00 %, p = 0.012 ¤ ). Our study may offer an effective approach for optimizing the thrombolytic flow in the management of AIS.

  3. INDUCTION AND/OR MAINTENANCE OF TUMOR DORMANCY BY DISRUPTION OF UROKINASE PLASMINOGEN ACTIVATOR RECEPTOR-INTEGRIN INTERACTION

    DEFF Research Database (Denmark)

    2010-01-01

    The present invention relates to a method of inducing cancer cells into dormancy and treating cancer in a subject. This method involves administering to a subject an effective amount of a compound that disrupts interaction between urokinase plasminogen activator receptor and integrin, thereby...... including cancer cells into dormancy and treating cancer in the subject. Also disclosed is a method of disrupting interaction between integrin and urokinase plasminogen activator receptor on cancer cells. The present invention also relates to a method of screening for compounds effective in inducing tumor...... dormancy and treating cancer in a subject....

  4. Rational targeting of the urokinase receptor (uPAR): development of antagonists and non-invasive imaging probes

    DEFF Research Database (Denmark)

    Kriegbaum, Mette Camilla; Persson, Morten; Haldager, L

    2011-01-01

    In the last two decades, the urokinase-type plasminogen activator receptor (uPAR) has been implicated in a number of human pathologies such as cancer, bacterial infections, and paroxysmal nocturnal hemoglobinuria. The primary function of this glycolipid-anchored receptor is to focalize uPA-mediat......In the last two decades, the urokinase-type plasminogen activator receptor (uPAR) has been implicated in a number of human pathologies such as cancer, bacterial infections, and paroxysmal nocturnal hemoglobinuria. The primary function of this glycolipid-anchored receptor is to focalize u...

  5. Association between polymorphism at 3 ׳UTR of urokinase gene and risk of calcium

    Directory of Open Access Journals (Sweden)

    S. Morovvati

    2016-06-01

    Full Text Available Background: Kidney stone is a common multifactorial disease in Iran. Environmental and genetic factors including single nucleotide polymorphism (SNP affect the incidence of kidney stones. Objective: The aim of this study was to determine the association of +4065 T/C polymorphism at 3′untranslated region (3'UTR of urokinase gene and calcium kidney stones. Methods: This case-control study was conducted on 70 patients with history of calcium kidney stones as case group and 70 healthy subjects as control group in the Baqiyatallah hospital in 2013. The polymorphism was assessed using the Allele Specific PCR (AS-PCR method. Allele and genotype frequencies of the two groups were compared using 2x2 contingency tables. Hardy-Weinberg equilibrium was compared between the two groups using Chi-square test. Findings: Of 70 cases, 10 (15% were heterozygous and 24 (34% were homozygous for the polymorphism. Of 70 controls, 25 (35% were heterozygous for the polymorphism. The frequency of mutant T allele was 41% in the case group and 18% in the control group. The frequency of mutant C allele was 59% in the case group and 82% in the control group. The risk of calcium kidney stones in carriers of the mutant allele was 1.7 times higher than non-carriers (OR: 1.7. Conclusion: With regards to the results, it seems that there is a significant association between the polymorphism at 3 ׳UTR of urokinase gene and formation of calcium kidney stones. Urokinase gene polymorphism may be introduced as a candidate gene involved in calcium stone formation.

  6. EARLY INTERVENTION WITH ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS DURING THROMBOLYTIC THERAPY IN ACUTE MYOCARDIAL-INFARCTION - RATIONALE AND DESIGN OF CAPTOPRIL AND THROMBOLYSIS STUDY

    NARCIS (Netherlands)

    VANGILST, WH; KINGMA, JH

    1991-01-01

    The adjunctive use of angiotensin-converting enzyme (ACE) inhibitors with thrombolytic therapy early during acute myocardial infarction offers theoretic advantages. In the acute phase, captopril may scavenge free radicals, blunt the catecholamine response, elicit coronary vasodilation, and increase

  7. The ligand-binding domain of the cell surface receptor for urokinase-type plasminogen activator

    DEFF Research Database (Denmark)

    Behrendt, N; Ploug, M; Patthy, L

    1991-01-01

    The purified urokinase plasminogen activator receptor (u-PAR) was cleaved into two fragments by mild chymotrypsin treatment. The smaller fragment (apparent Mr 16,000) possessed the ligand-binding capability, as shown by chemical cross-linking analysis. This fragment constituted the NH2-terminal...... part of the intact receptor, probably including the whole sequence 1-87, and contained N-linked carbohydrate. After detergent phase separation in the Triton X-114 system, the fragment was present in the water phase where its binding activity could be demonstrated in the absence of the rest...

  8. Jet and ultrasonic nebulization of single chain urokinase plasminogen activator (scu-PA)

    DEFF Research Database (Denmark)

    Münster, Anna-Marie; Bendstrup, E; Jensen, J.I.

    2000-01-01

    locally by nebulization in a recombinant zymogen form as single chain urokinase plasminogen activator (scu-PA). We aimed to characterize the particle size distribution, drug output, and enzymatic activity of scu-PA after nebulization with a Ventstream jet nebulizer (Medic-Aid, Bognor Regis, UK) and a Syst......'AM DP-100 ultrasonic nebulizer (Pulmolink, Kent, UK). The particle size distribution was measured with a laser diffraction method and the drug output was determined by collection on filters. The amount of protein on the filters was determined with the Lowry method, and the enzymatic activity after...... in terms of particle size distribution and preservation of fibrinolytic activity....

  9. Structure and ligand interactions of the urokinase receptor (uPAR)

    DEFF Research Database (Denmark)

    Kjaergaard, Magnus; Hansen, Line V.; Jacobsen, Benedikte

    2008-01-01

    The urokinase-type plasminogen activator receptor (uPAR or CD87) is a glycolipid-anchored membrane glycoprotein, which is responsible for focalizing plasminogen activation to the cell surface through its high-affinity binding to the serine protease uPA. This tight interaction (KD less than 1 n...... on disulfide connectivities, and they adopt a characteristic three-finger fold. Interestingly, the gene for uPAR is localized in a cluster of 6 homologous genes encoding proteins with multiple LU-domains. The structural biology of uPAR will be reviewed with special emphasis on its multidomain composition...

  10. The urokinase receptor and its structural homologue C4.4A in human cancer

    DEFF Research Database (Denmark)

    Jacobsen, B; Ploug, M

    2008-01-01

    The urokinase-type plasminogen activator receptor (uPAR) and its structural homologue C4.4A are multidomain members of the Ly6/uPAR/alpha-neurotoxin protein domain family. Both are glycosylphosphatidylinositol-anchored membrane glycoproteins encoded by neighbouring genes located on chromosome 19q13...... in a number of human cancers including colon adenocarcinoma and pulmonary squamous cell carcinoma. Targeting uPAR in experimental animal models has also provided promising results regarding the interference with pathogenic plasminogen activation. In the case of C4.4A, very recent data have demonstrated...

  11. Soluble Urokinase Plasminogen Activator Receptor as a Marker for Use of Antidepressants

    DEFF Research Database (Denmark)

    Haastrup, Eva; Grau, Katrine; Eugen-Olsen, Jesper

    2014-01-01

    OBJECTIVES: Inflammation is involved in the pathogenesis of depression. A few cross-sectional population-based studies have found that depression is associated with increased levels of inflammatory markers. Soluble urokinase plasminogen activation receptor (suPAR) is known to be a stable marker...... for inflammation. We investigated the bidirectional association between suPAR levels and use of antidepressants. METHODS: suPAR level was measured in 9305 blood donors and analysed in relation to 5-years follow-up data on purchase of antidepressants and hospital diagnoses of depression from a nationwide Danish...

  12. Combination Low Dose Tissue Type-Plasminogen Activator plus Annexin A2 for Improving Thrombolytic Stroke Therapy

    Directory of Open Access Journals (Sweden)

    Yinghua eJiang

    2015-10-01

    Full Text Available Risk of hemorrhagic transformation, incomplete reperfusion, neurotoxicity and a short treatment time window comprise major challenges for tissue plasminogen activator (tPA thrombolytic stroke therapy. Improving tPA therapy has become one of the highest priorities in the stroke field. This mini review article focuses on our recent efforts aimed at evaluating a novel combination approach of low-dose tPA plus recombinant annexin A2 (rA2, a tPA and plasminogen co-receptor, that might enhance tPA thrombolytic efficacy, while reducing its associated complications related to intracerebral hemorrhagic (ICH transformation. Results of our experimental studies using a focal embolic stroke model in rats support the feasibility of the combination approach and suggest the potential for successful clinical translation.

  13. Cross Mapping Between the Priority Nursing Care for Stroke Patients Treated With Thrombolytic Therapy and the Nursing Interventions Classification (NIC).

    Science.gov (United States)

    Nonnenmacher, Carine Lais; Ávila, Christiane Wahast; Mantovani, Vanessa Monteiro; de Oliveira Vargas, Mara Ambrosina; Echer, Isabel Cristina; de Fátima Lucena, Amália

    2017-10-01

    To verify the correspondence between the priority nursing care for stroke patients treated with thrombolytic therapy and the Nursing Interventions Classification (NIC). A cross-mapping study with a semi-structured interview was conducted with 11 expert nurses who described priority nursing care in clinical practice, and mapped it to the NIC. Eleven nursing care priorities cited by the nurses were mapped to eight NICs, including Thrombolytic Therapy Management (4270). There was correspondence between all priority nursing care interventions for stroke patients treated with thrombolytic therapy and the NIC. The nursing care cited by the nurses was corroborated by the NIC, providing evidence for the clinical practice. Verificar a correspondência entre os cuidados de enfermagem prioritários a pacientes com acidente vascular encefálico tratados com terapia trombolítica e a Classificação das Intervenções de Enfermagem (NIC). MÉTODOS: Estudo de mapeamento cruzado com uma entrevista semi-estruturada aplicada a 11 enfermeiros especialistas que descreveram os cuidados de enfermagem prioritários na prática clínica, e mapeados para a NIC. Onze cuidados de enfermagem prioritários foram citados pelos enfermeiros e mapeados em oito intervenções de enfermagem NIC, incluindo a Thrombolytic Therapy Management (4270). CONCLUSÕES: Houve correspondência entre todos os cuidados de enfermagem prioritários para pacientes com acidente vascular encefálico tratados com a terapia trombolítica e as intervençães de enfermagem NIC. IMPLICAÇÕES PARA A PRÁTICA DE ENFERMAGEM: Os cuidados de enfermagem citados pelos enfermeiros foram corroborados pela NIC, produzindo evidências para a prática clínica. © 2016 NANDA International, Inc.

  14. ST-segment elevation myocardial infarction treated with thrombolytic therapy in a patient with thrombotic thrombocytopenic purpura.

    Science.gov (United States)

    Doll, Jacob A; Kelly, Jacob P

    2014-07-01

    Acute myocardial infarction is a common complication of thrombotic thrombocytopenic purpura (TTP), but rarely the presenting manifestation. Anti-thrombotic therapy for myocardial infarction is rarely utilized in the setting of TTP because of elevated bleeding risk. We report a case of TTP presenting with ST-segment elevation myocardial infarction and treated with thrombolytic therapy. The resultant cardiac and neurological complications highlight the challenges of using evidence-based therapy for myocardial infarction in the setting of TTP.

  15. Urokinase plasminogen activator receptor affects bone homeostasis by regulating osteoblast and osteoclast function

    DEFF Research Database (Denmark)

    Furlan, Federico; Galbiati, Clara; Jørgensen, Niklas R

    2007-01-01

    The uPAR and its ligand uPA are expressed by both osteoblasts and osteoclasts. Their function in bone remodeling is unknown. We report that uPAR-lacking mice display increased BMD, increased osteogenic potential of osteoblasts, decreased osteoclasts formation, and altered cytoskeletal reorganizat......The uPAR and its ligand uPA are expressed by both osteoblasts and osteoclasts. Their function in bone remodeling is unknown. We report that uPAR-lacking mice display increased BMD, increased osteogenic potential of osteoblasts, decreased osteoclasts formation, and altered cytoskeletal...... reorganization in mature osteoclasts. INTRODUCTION: Urokinase receptor (uPAR) is actively involved in the regulation of important cell functions, such as proliferation, adhesion, and migration. It was previously shown that the major players in bone remodeling, osteoblasts and osteoclasts, express u......PAR and produce urokinase (uPA). The purpose of this study was to investigate the role of uPAR in bone remodeling. MATERIALS AND METHODS: In vivo studies were performed in uPAR knockout (KO) and wildtype (WT) mice on a C57Bl6/SV129 (75:25) background. Bone mass was analyzed by pQCT. Excised tibias were subjected...

  16. Regulation of urokinase receptors in monocytelike U937 cells by phorbol ester phorbol myristate acetate

    DEFF Research Database (Denmark)

    Picone, R; Kajtaniak, E L; Nielsen, Lars Søegaard

    1989-01-01

    A specific surface receptor for urokinase plasminogen activator (uPA) recognizes the amino-terminal growth factor-like sequence of uPA, a region independent from and not required for the catalytic activity of this enzyme. The properties of the uPA receptor (uPAR) and the localization and distribu......A specific surface receptor for urokinase plasminogen activator (uPA) recognizes the amino-terminal growth factor-like sequence of uPA, a region independent from and not required for the catalytic activity of this enzyme. The properties of the uPA receptor (uPAR) and the localization...... and distribution of uPA in tumor cells and tissues suggest that the uPA/uPAR interaction may be important in regulating extracellular proteolysis-dependent processes (e.g., invasion, tissue destruction). Phorbol myristate acetate (PMA), an inducer of U937 cell differentiation to macrophage-like cells, elicits...... in the affinity of the uPAR for uPA, thus uncovering another way of regulating the interaction between uPA and uPAR. In addition, the PMA treatment causes a modification of migration of the cross-linked receptor in mono- and bidimensional gel electrophoresis....

  17. Does thrombolytic therapy harm or help in ST elevation myocardial infarction (STEMI caused by the spontaneous coronary dissection?

    Directory of Open Access Journals (Sweden)

    Jović Zoran

    2015-01-01

    Full Text Available Introduction. Spontaneous coronary artery dissection (SCAD is a very rare disease with poor prognosis. It mainly affects young women free of risk factors for coronary artery disease (CAD and women during the peripartum period. The prognosis for myocardial infarction caused by SCAD is poor, management is often difficult and guidelines still missing. Case report. We presented a woman with acute myocardial infarction of anterior wall of the left ventricle, caused by spontaneous dissection of medial segment of the left anterior descending coronary artery. We treated the patient with thrombolytic therapy and performed coronary angiography after that. Finally we decided to do nothing more. Two years later we performed coronary angiography again and founded the coronary artery normal. We also analyzed 19 cases publiched from 1996 to 2012 when coronary artery dissection had been treated with thrombolytic agent. Analysis revealed only one case of 19, with complication after treating SCAD with thrombolysis. Conclusion. Sometimes, regarding myocardial infarction in young women with no risk factors for CAD, especially in young women in peripartum, we should think about SCAD. The presented case, like eight others, demonstrates that good clinical outcomes can be achieved with thrombolysis. In spite of all this, we still need more data to verify that thrombolysis does not have to harm the therapy for SCAD. For the time being thrombolytic therapy could be an option.

  18. GC-MS analysis, evaluation of phytochemicals, anti-oxidant, thrombolytic and anti-inflammatory activities of Exacum bicolor

    Directory of Open Access Journals (Sweden)

    Appaji Mahesh Ashwini

    2015-12-01

    Full Text Available The aim of the present study was to investigate the GC-MS analysis, phytochemical screening, anti-oxidant, thrombolytic and anti-inflammatory activities of methanol extract of leaves of Exacum bicolor. FTIR analysis confirmed the presence of alcohol, phenols, alkanes, aromatic compounds, aldehyde and ethers. GC-MS analysis revealed the presence of eight phyto-constituents. The total phenol, flavonoid and alkaloid contents were 18.0 ± 0.2 mg/GAE/g, 13.1 ± 0.4 mg QE/g and 108.0 ± 1.2 mg AE/g respectively. The DPPH assay exhibited potent anti-oxidant abilities with IC50 8.8 µg/mL. Significant thrombolytic activity was demonstrated by clot lysis method (45.1 ± 0.8%. The methanol extract showed significant membrane stabilization on human red blood cell with IC50 value of 37.4 µg/mL. There was a significant correlation (R2>0.98 with total phenolic content versus anti-oxidant and anti-inflammatory activity. The above results confirmed that E. bicolor could be a promising anti-oxidant, thrombolytic and anti-inflammatory agent.

  19. Plasma levels of intact and cleaved urokinase receptor decrease in HIV-1-infected patients initiating highly active antiretroviral therapy

    DEFF Research Database (Denmark)

    Ostrowski, S R; Katzenstein, T L; Pedersen, M

    2006-01-01

    Elevated blood levels of soluble urokinase receptor (suPAR) measured by ELISA decrease in human immunodeficiency virus-1 (HIV-1)-infected patients initiating highly active antiretroviral therapy (HAART). As the suPAR ELISA measures both three- and two-domain suPAR [suPAR(I-III), suPAR(II-III)] an...

  20. Serum levels of soluble urokinase plasminogen activator receptor is associated with parasitemia in children with acute Plasmodium falciparum malaria infection

    DEFF Research Database (Denmark)

    Perch, M; Kofoed, P; Fischer, TK

    2004-01-01

    Serum levels of soluble urokinase plasminogen activator receptor (suPAR) are significantly elevated and of prognostic value in patients suffering from serious infectious diseases such as HIV and tuberculosis. Our objective was to investigate suPAR levels during symptomatic malaria infection and 7...... an important association between suPAR and acute malaria infection in humans....

  1. Rational targeting of the urokinase receptor (uPAR): development of antagonists and non-invasive imaging probes

    DEFF Research Database (Denmark)

    Kriegbaum, M C; Persson, M; Haldager, L

    2011-01-01

    In the last two decades, the urokinase-type plasminogen activator receptor (uPAR) has been implicated in a number of human pathologies such as cancer, bacterial infections, and paroxysmal nocturnal hemoglobinuria. The primary function of this glycolipid-anchored receptor is to focalize uPA-mediat...

  2. A sensitive bioimmunoassay for thrombin-cleaved two-chain urokinase-type plasminogen activator in human body fluids

    NARCIS (Netherlands)

    Braat, E.A.M.; Nauland, U.; Dooijewaard, G.; Rijken, D.C.

    1996-01-01

    Thrombin cleaves single-chain urokinase-type plasminogen activator (scu-PA) into a two-chain form (tcu-PA/T), which is virtually inactive in plasminogen activator assays. Little is known about the physiological importance of tcu-PA/T. To examine the occurrence of tcu-PA/T in vivo, we developed a

  3. The inactivation of single-chain urokinase-type plasminogen activator by thrombin in a plasma milieu : effect of thrombomodulin

    NARCIS (Netherlands)

    Braat, E.A.M.; Los, P.; Rijken, D.C.

    1998-01-01

    Thrombin cleaves single-chain urokinase-type plasminogen activator (scu- PA) into a virtually inactive two-chain form (tcu-PA/T), a process which may contribute to the maintenance of a fresh blood clot. We have examined the inactivation of scu-PA by thrombin in a plasma milieu to get more insight in

  4. The liberated domain I of urokinase plasminogen activator receptor--a new tumour marker in small cell lung cancer

    DEFF Research Database (Denmark)

    Almasi, Charlotte E; Drivsholm, Lars; Pappot, Helle

    2013-01-01

    The prognosis of small cell lung cancer (SCLC) remains poor with a 5-year survival rate of 4-6%. In non-small cell lung cancer (NSCLC), high levels of intact and cleaved forms of the receptor for urokinase plasminogen activator (uPAR) are significantly associated with short overall survival. Our...

  5. Danhong Injection Combined With t-PA Improves Thrombolytic Therapy in Focal Embolic Stroke

    Directory of Open Access Journals (Sweden)

    Min Li

    2018-04-01

    Full Text Available Background: Hemorrhagic transformation, neurotoxicity, short treatment time windows, and other defects are considered as the major limitations for the thrombolytic therapy. This study is devoted to figure out whether Danhong injection (DHI combined with tissue-plasminogen activator (t-PA could extend the treatment time windows and ameliorate brain injury, hemorrhagic complication and BBB disruption after focal embolic stroke.Methods:In vitro, the combined concentrations of DHI and t-PA were added to wells reacted with plasminogen and D-Val-Leu-Lys-AMC. The optimum ratio of the combination of DHI plus t-PA was explored by detecting relative fluorescent. In vivo experiments, we firstly investigated the optimal dose of t-PA and Danhong injection for focal embolic stroke. The neurological deficit score, infarct volume and brain edema were assessed. Secondly, we proved that the combination group extended the thrombolytic window for treatment of focal embolic stroke. The neurological deficit score, infarct volume, brain edema and hemorrhagic complication were assessed, while levels of BAX, Bcl-2 and caspase-3 in brain tissue were analyzed by real-time polymerase chain reaction. Finally, to ask whether combination therapy with DHI plus t-PA protected the blood–brain barrier in a rat model of focal embolic stroke, neurological deficit score, ELISA, RT-PCR, western blot and fluorescence were used to detect the indicators of blood–brain barrier, such as tight junction protein, blood–brain barrier permeability and related gene expression.Results:In vitro, plasmin activity assays showed that the combination of t-PA with DHI at about 1:1.6 w/v ratio increased by almost 1.4-fold the plasmin-generating capability of t-PA. In vivo experiments, the results showed that the combination of Danhong injection (4 mL/kg and t-PA (2.5 mg/kg could extend the t-PA treatment time windows to 4.5 h. And the combination t-PA (2.5 mg/kg with DHI (4 mL/kg ameliorated

  6. Microencapsulation of anti-tumor, antibiotic and thrombolytic drugs in microgravity

    Science.gov (United States)

    Morrison, Dennis R.; Mosier, Benjamin; Cassanto, John

    1994-01-01

    Encapsulation of cytotoxic or labile drugs enables targeted delivery and sustained release kinetics that are not available with intravenous injection. A new liquid-liquid diffusion process has been developed for forming unique microcapsules that contain both aqueous and hydrocarbon soluble drugs. Microgravity experiments, on sounding rockets (1989-92) and Shuttle missions STS-52 (1992) and STS-56 (1993) using an automated Materials Dispersion Apparatus, produced multi-lamellar microcapsules containing both Cis-platinum (anti-tumor drug) and iodinated poppy seed oil (a radiocontrast medium), surrounded by a polyglyceride skin. Microcapsules formed with amoxicillin (antibiotic) or urokinase (a clot dissolving enzyme), co-encapsulated with IPO, are still intact after two years. Microcapsules were formed with the drug so concentrated that crystals formed inside. Multi-layered microspheres, with both hydrophobic drug compartments, can enable diffusion of complementary drugs from the same microcapsule, e.g. antibiotics and immuno-stimulants to treat resistant infections or multiple fibrinolytic drugs to dissolve emboli. Co-encapsulation of enough radio-contrast medium enables oncologists to monitor the delivery of anti-tumor microcapsules to target tumors using computerized tomography and radiography that would track the distribution of microcapsules after release from the intra-arterial catheter. These microcapsules could have important applications in chemotheraphy of certain liver, kidney, brain and other tumors.

  7. Thrombolytic Therapy for Cerebral Vein Thrombosis in Antiphospholipid Syndrome Secondary to Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Mehrzad Hajialilo

    2012-03-01

    Full Text Available A 20-year-old woman was admitted to a Gynecology Hospital in her 6th month of pregnancy for high blood pressure and tonic-clonic seizure. Primary diagnosis was eclampsia, and for that reason she underwent cesarean section. She also had headache on frontal and parietal areas without nausea or vomiting. There was not a focal neurological sign. Rheumatology consultation was requested. Sys-temic lupus erythematosus and secondary antiphospholipid (APS was confirmed. The patient had headache that continued several days after cesarean section, therefore, brain magnetic resonance im-aging (MRI and magnetic resonance venography (MRV were performed, and cerebral vein thrombosis was documented. Distal segment of right lateral sinus and sigmoid sinus were not ap-peared in brain MRV. Abnormal hypersignal intensity of right lateral sinus/coronal T2 was detected. Thrombolytic therapy with 20 mg tissue plasminogen activator on right sigmoid and transverse sinus was performed by an interventional neurologist. After this procedure, the patient's headache healed and she was discharged in a good condition.

  8. In vitro activity of probiotic Lactobacillus reuteri against gastric cancer progression by downregulation of urokinase plasminogen activator/urokinase plasminogen activator receptor gene expression.

    Science.gov (United States)

    Rasouli, Bahareh Sadat; Ghadimi-Darsajini, Ali; Nekouian, Reza; Iragian, Gholam-Reza

    2017-01-01

    Gastric cancer (GC) is the third leading cause of cancer death, and most patients represent metastatic phenotype at the time of diagnosis. Urokinase plasminogen activator (uPA) system is well known for its critical roles in cancer cells invasion since uPA/uPA receptor (uPAR) overexpresses in several cancers. Subsequently, suppression of uPA/uPAR gene expression improves patients overall survival and prevents cancer progression. The aim of the current study was to investigate possible effects of live Lactobacillus reuteri as a probiotic in inhibition of GC cells proliferation and invasion. Human gastric adenocarcinoma epithelial cell line (AGS) cells were treated with different ratios of live L. reuteri and were incubated for 24, 48, and 72 h. Viability of cancer cells was measured with 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay, and the effects of L. reuteri on uPA/uPAR gene expression were assessed by real-time polymerase chain reaction. Our results showed that L. reuteri inhibits cell proliferation significantly in dose-dependent manner. Expressions of uPA and uPAR were downregulated followed by co-incubation of AGS cells and live L. reuteri compared to untreated-based line level. This study provides strong support in the role of L. reuteri in suppression of GC cell invasion by downregulation of pathways which is involved in extracellular matrix degradation such as uPA and uPAR.

  9. Soluble urokinase-type plasminogen activator receptor forms in plasma as markers of atherosclerotic plaque vulnerability

    DEFF Research Database (Denmark)

    Olson, Fredrik J; Thurison, Tine; Ryndel, Mikael

    2009-01-01

    OBJECTIVES:: To test if circulating forms of the soluble urokinase-type plasminogen activator receptor (suPAR) are potential biomarkers of plaque vulnerability. DESIGN AND METHODS:: Plasma concentrations of suPAR(I-III), suPAR(II-III) and uPAR(I) were measured by time-resolved fluorescence...... immunoassays in Caucasian patients operated for symptomatic carotid atherosclerosis (n=255). Local suPAR release from plaques into the circulation was assessed in plasma passing retrogradely over the plaque in the carotid artery, collected during surgery (n=7). RESULTS:: The suPAR(I-III) (P=0.03) and su......PAR(II-III) (P=0.006) concentrations were higher after ischemic strokes and transient ischemic attacks, i.e., clinical subgroups associated with poorer prognosis and a less stable plaque phenotype, than after amaurosis fugax. Slightly elevated suPAR(I-III) levels were found in plasma from the carotid lesion...

  10. Dynamics of urokinase receptor interaction with Peptide antagonists studied by amide hydrogen exchange and mass spectrometry

    DEFF Research Database (Denmark)

    Jørgensen, Thomas J D; Gårdsvoll, Henrik; Danø, Keld

    2004-01-01

    Using amide hydrogen exchange combined with electrospray ionization mass spectrometry, we have in this study determined the number of amide hydrogens on several peptides that become solvent-inaccessible as a result of their high-affinity interaction with the urokinase-type plasminogen activator...... receptor (uPAR). These experiments reveal that at least six out of eight amide hydrogens in a synthetic nine-mer peptide antagonist (AE105) become sequestered upon engagement in uPAR binding. Various uPAR mutants with decreased affinity for this peptide antagonist gave similar results, thereby indicating...... that deletion of the favorable interactions involving the side chains of these residues in uPAR does not affect the number of hydrogen bonds established by the main chain of the peptide ligand. The isolated growth factor-like domain (GFD) of the cognate serine protease ligand for uPAR showed 11 protected amide...

  11. Targeting of peptide conjugated magnetic nanoparticles to urokinase plasminogen activator receptor (uPAR) expressing cells

    DEFF Research Database (Denmark)

    Hansen, Line; Larsen, Esben Kjær Unmack; Nielsen, Erik Holm

    2013-01-01

    Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are currently being used as a magnetic resonance imaging (MRI) contrast agent in vivo, mainly by their passive accumulation in tissues of interest. However, a higher specificity can ideally be achieved when the nanoparticles are targeted...... towards cell specific receptors and this may also facilitate specific drug delivery by an enhanced target-mediated endocytosis. We report efficient peptide-mediated targeting of magnetic nanoparticles to cells expressing the urokinase plasminogen activator receptor (uPAR), a surface biomarker for poor...... patient prognosis shared by several cancers including breast, colorectal, and gastric cancers. Conjugation of a uPAR specific targeting peptide onto polyethylene glycol (PEG) coated USPIO nanoparticles by click chemistry resulted in a five times higher uptake in vitro in a uPAR positive cell line compared...

  12. The superoxide scavenger TEMPOL induces urokinase receptor (uPAR expression in human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Francis Joseph

    2006-06-01

    Full Text Available Abstract There is little understanding of the effect that reactive oxygen metabolites have on cellular behavior during the processes of invasion and metastasis. These oxygen metabolites could interact with a number of targets modulating their function such as enzymes involved in basement membrane dissolution, adhesion molecules involved in motility or receptors involved in proliferation. We investigated the effect of increased scavenging of superoxide anions on the expression of the urokinase receptor (uPAR in PC-3M human prostate cancer cells. Urokinase receptor is a GPI-linked cell surface molecule which mediates multiple functions including adhesion, proliferation and pericellular proteolysis. Addition of the superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (TEMPOL to PC-3M cultures stimulated expression of uPAR protein peaking between 48 and 72 hours. Cell surface expression of the uPAR was also increased. Surprisingly, uPAR transcript levels increased only slightly and this mild increase did not coincide with the striking degree of protein increase. This disparity indicates that the TEMPOL effect on uPAR occurs through a post-transcriptional mechanism. TEMPOL presence in PC-3M cultures reduced intracellular superoxide-type species by 75% as assayed by NBT dye conversion; however this reduction significantly diminished within hours following TEMPOL removal. The time gap between TEMPOL treatment and peak uPAR protein expression suggests that reduction of reactive oxygen metabolites in prostate cancer cells initiates a multistep pathway which requires several hours to culminate in uPAR induction. These findings reveal a novel pathway for uPAR regulation involving reactive oxygens such as superoxide anion.

  13. Activity and expression of urokinase-type plasminogen activator and matrix metalloproteinases in human colorectal cancer

    International Nuclear Information System (INIS)

    Kim, Tae-Dong; Song, Kyoung-Sub; Li, Ge; Choi, Hoon; Park, Hae-Duck; Lim, Kyu; Hwang, Byung-Doo; Yoon, Wan-Hee

    2006-01-01

    Matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-type plasminogen activator (uPA) are involved in colorectal cancer invasion and metastasis. There is still debate whether the activity of MMP-2 and MMP-9 differs between tumors located in the colon and rectum. We designed this study to determine any differences in the expression of MMP-2, MMP-9 and uPA system between colon and rectal cancer tissues. Cancer tissue samples were obtained from colon carcinoma (n = 12) and rectal carcinomas (n = 10). MMP-2 and MMP-9 levels were examined using gelatin zymography and Western blotting; their endogenous inhibitors, tissue inhibitor of metalloproteinase-2 (TIMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1), were assessed by Western blotting. uPA, uPAR and PAI-1 were examined using enzyme-linked immunosorbent assay (ELISA). The activity of uPA was assessed by casein-plasminogen zymography. In both colon and rectal tumors, MMP-2, MMP-9 and TIMP-1 protein levels were higher than in corresponding paired normal mucosa, while TIMP-2 level in tumors was significantly lower than in normal mucosa. The enzyme activities or protein levels of MMP-2, MMP-9 and their endogenous inhibitors did not reach a statistically significant difference between colon and rectal cancer compared with their normal mucosa. In rectal tumors, there was an increased activity of uPA compared with the activity in colon tumors (P = 0.0266), however urokinase-type plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) showed no significant difference between colon and rectal cancer tissues. These findings suggest that uPA may be expressed differentially in colon and rectal cancers, however, the activities or protein levels of MMP-2, MMP-9, TIMP-1, TIMP-2, PAI-1 and uPAR are not affected by tumor location in the colon or the rectum

  14. Soluble urokinase plasminogen activator receptor: a risk factor for carotid plaque, stroke, and coronary artery disease.

    Science.gov (United States)

    Persson, Margaretha; Östling, Gerd; Smith, Gustav; Hamrefors, Viktor; Melander, Olle; Hedblad, Bo; Engström, Gunnar

    2014-01-01

    Recent studies indicate that the urokinase system could have an important role in atherogenesis and plaque rupture. The relationships among the soluble urokinase plasminogen activator receptor (suPAR), carotid plaque, and incidence of ischemic stroke and coronary artery disease (CAD) events were studied in a prospective cohort. Occurrence of carotid plaque and plasma levels of suPAR were assessed in 5166 men and women, aged 45 to 68 years, participating in the Malmö Diet and Cancer study. Incidences of ischemic stroke and CAD were monitored during a mean follow-up of 15 years. Subjects with carotid plaque had significantly higher levels of suPAR compared with those without carotid plaque. suPAR was associated with increased incidence of ischemic stroke (hazard ratio [HR] for third versus first tertile, 1.50; 95% confidence interval [CI], 1.06-2.11) and CAD (HR, 1.55; 95% CI, 1.13-2.13) after adjustment for risk factors. The risk factor-adjusted HR for ischemic stroke was 2.21 (95% CI, 1.52-3.22) in subjects with carotid plaque and high suPAR (ie, third tertile) and 1.51 (95% CI, 1.05-2.17) in subjects with carotid plaque and low suPAR compared with those without carotid plaque and low suPAR (reference). High levels of suPAR significantly increased the risk of ischemic stroke and CAD in subjects with carotid plaque. suPAR is associated with increased occurrence of carotid plaque and increased incidence of ischemic stroke and CAD. Presence of both elevated levels of suPAR and carotid plaque increases the risk of ischemic stroke in an additive way.

  15. Outcome evaluation of intra-arterial infusion of urokinase for acute ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Hai Bin [First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Suh, Dae Chul; Lim, Soo Mee [Asan Medical Center, College of Medicine, University of Ulsan, Seoul (Korea, Republic of); And Others

    2000-06-01

    To evaluate the results of intra-arterial urokinase thrombolysis in cases of acute ischemic stroke and to define the factors affecting prognosis. Forty-eight patients with angiographically proven occlusion of the intracranial arteries were treated with local intra-arterial infusion of urokinase within six hours of the onset of symptoms. Neurologic status was evaluated on admission and on discharge using the NIH (National Institute of Health) stroke scale score (SSS). When the SSS decreased by at least four points, this was considered indicative of an improved clinical outcome. Complete recanalization was achieved in 17/48 patients (35%), including 8 of 13 (62%) with occlusion of the vertebrobasilar artery (VBA), 9 of 20 (45%) with occlusion of the middle cerebral artery (MCA), and none of 15 with occlusion of the internal carotid artery (ICA). Neurologic status improved in 12 (60%) of patients with MCA occlusion, in five (38%) of those with VBA occlusion and in three (20%) of those with ICA occlusion (p less than 0.005). Patients in whom occluded MCA was completely recanalized showed greater clinical improvement than those with partial or no recanalization (p less than 0.05). The overall mortality rate was 21%, 43% (9/21) in patients in whom CT revealed signs of early infarct, but only 4% (1/27) in those without this sign (p less than 0.05). The mortality rate of patients with parenchymal hematoma (4/5) was higher than that of those with hemorrhagic infarct (3/9) or without hemorrhage (3/34) (p less than 0.005). In patients in whom occluded MCA was completely recanalized, the clinical outcome was better, while patients with VBA occlusion did not benefit from recanalization. The presence on CT scans of signs of early infarct and of parenchymal hematoma after thrombolysis correlated with a high mortality rate. (author)

  16. Labeling of the Recombinant Streptokinase Using Iodine-131 as a New Thrombolytic Agent

    Directory of Open Access Journals (Sweden)

    I. Daruwati

    2012-12-01

    Full Text Available Stroke and acute myocardial infarction is a disease with the highest mortality in the world. WHO has estimated in 2008, 30% of deaths from heart disease and more than 80% of this cases have been occurred in developing countries. Streptokinase (SK as an effective thrombolytic agent has been used as a drug of choice for about forty years ago. SK is plasminogen (PG activator that converts plasminogen to active protease, called plasmin (PN which degrades fibrin to soluble products. Recombinant streptokinase (SKA from genetic engineering has been developed at School of Pharmacy ITB to reduce or eliminate immunogenicity of SK. However, scientific disclosures relating to dynamic and its kinetic studies in the body have still to be proven. One method that can explain this phenomenon is the pharmacological studies using radionuclide labeled compounds. Radioiodine labeled compound is used extensively and most suitable for biological studies. This paper describes the preparation of 131I-SKA and its characterization. The labeling conditions of SKA, such as chloramine-T as an oxidizing agent, amount of SKA, incubation time, and size of resin to purify the labeling yield have been observed. The result showed that the optimum condition of labeling (35.11% was obtained using 10 µg of chloramine-T and 60 seconds of incubation time. The highest radiochemical purity (97.46 ± 1.14% has also been obtained by passing through the resin chromatography column using 100 mg Dowex 1x8, size 50-100 mesh. The characterization of 131I-SKA with SDS PAGE method and autoradiography showed the similar performance with unlabeled-SKA

  17. "Clinical-CT mismatch" and the response to systemic thrombolytic therapy in acute ischemic stroke.

    Science.gov (United States)

    Kent, David M; Hill, Michael D; Ruthazer, Robin; Coutts, Shelagh B; Demchuk, Andrew M; Dzialowski, Imanuel; Wunderlich, Olaf; von Kummer, Rudiger

    2005-08-01

    Mismatch between clinical deficits and imaging lesions in acute stroke has been proposed as a method of identifying patients who have hypoperfused but still have viable brain, and may be especially apt to respond to reperfusion therapy. We explored this hypothesis using a combined database including 4 major clinical trials of intravenous (IV) thrombolytic therapy. To determine what the radiological correlates of a "matched" functional deficit are, we calculated the relationship between the ASPECT score of the 24-hour (follow-up) CT scan and the 24-hour National Institutes of Health Stroke Scale (NIHSS) score on the subsample with ASPECT scores performed at this time (n=820). Based on this empirical relationship, we computed the absolute difference between the observed baseline ASPECT score and the "expected" score (ie, matched) based on baseline NIHSS for all patients (n=2131). We tested whether patients with better than expected baseline ASPECTS were more likely to benefit from IV recombinant tissue plasminogen activation (rtPA). At 24 hours, there was a strong, linear, negative correlation between NIHSS and ASPECTS (r2=0.33, P<0.0001); on average, an increase of 10 points on NIHSS corresponded to a decrease of approximately 3 points on ASPECTS. At baseline, the average degree of mismatch between the observed and "expected" ASPECTS was 2.1 points (interquartile range, 1.0 to 3.4). However, multiple analyses failed to reveal a consistent relationship between the degree of clinical-CT mismatch at baseline and a patient's likelihood of benefiting from IV rtPA. Clinical-CT mismatch using ASPECT scoring does not reliably identify patients more or less likely to benefit from IV rtPA.

  18. The stroke-thrombolytic predictive instrument: a predictive instrument for intravenous thrombolysis in acute ischemic stroke.

    Science.gov (United States)

    Kent, David M; Selker, Harry P; Ruthazer, Robin; Bluhmki, Erich; Hacke, Werner

    2006-12-01

    Many patients with ischemic stroke eligible for recombinant tissue plasminogen activator (rt-PA) are not treated in part because of the risks and benefits perceived by treating physicians. Therefore, we aimed to develop a Stroke-Thrombolytic Predictive Instrument (TPI) to aid physicians considering thrombolysis for stroke. Using data from 5 major randomized clinical trials (n=2184) testing rt-PA in the 0- to 6-hour window, we developed logistic regression equations using clinical variables as potential predictors of a good outcome (modified Rankin Scale score or =5), with and without rt-PA. The models were internally validated using bootstrap re-sampling. To predict good outcome, in addition to rt-PA treatment, 7 variables significantly affected prognosis and/or the treatment-effect of rt-PA: age, diabetes, stroke severity, sex, previous stroke, systolic blood pressure, and time from symptom onset. To predict catastrophic outcome, only age, stroke severity, and serum glucose were significant; rt-PA treatment was not. For patients treated within 3 hours, the median predicted probability of a good outcome with rt-PA was 42.9% (interquartile range [IQR]=18.6% to 64.7%) versus 25.3% (IQR=9.8% to 46.2%) without rt-PA; the median predicted absolute benefit was 12.5% (IQR=5.1% to 21.0%). The median probability for a catastrophic outcome, with or without, rt-PA was 15.2% (IQR=8.0% to 31.2%). The area under the receiver-operator characteristic curve was 0.788 for the model predicting good outcome and 0.775 for the model predicting bad outcome. The Stroke-TPI predicts good and bad functional outcomes with and without thrombolysis. Incorporated into a usable tool, it may assist in decision-making.

  19. Thrombolytic utilization for ischemic stroke in US hospitals with neurology residency program.

    Science.gov (United States)

    Moradiya, Yogesh; Crystal, Howard; Valsamis, Helen; Levine, Steven R

    2013-12-03

    We aimed to compare the rates of thrombolysis utilization for acute ischemic stroke in hospitals with neurology residency (NR) to those of other teaching (OT) and nonteaching (NT) hospitals. A retrospective serial cross-sectional cohort study of a nationally representative sample of stroke patients was conducted. Accreditation Council for Graduate Medical Education-accredited NR program-affiliated hospitals in the United States were cross-matched to the hospitals in the Nationwide Inpatient Sample from 2000 to 2010. ICD-9-CM codes were used for case ascertainment. A total of 712,433 adult ischemic stroke patients from 6,839 hospital samples were included, of whom 10.1%, 29.1%, and 60.8% were treated in NR, OT, and NT hospitals, respectively. Stroke patients in NR received thrombolysis more frequently (3.74% ± 0.24% [standard error]) than in OT (2.28% ± 0.11%, p < 0.001) and NT hospitals (1.44% ± 0.06%, p < 0.001). The adjusted odds ratios (ORs) of thrombolysis rates in NR vs OT and NR vs NT increased with each decade increment in age. In multivariate analysis, NR was independently predictive of higher thrombolysis rate (adjusted OR 1.51; 95% confidence interval [CI] 1.44-1.59 [NR vs OT], and adjusted OR 1.82; 95% CI 1.73-1.91 [NR vs NT]). Acute stroke care in NR hospitals is associated with an increased thrombolytic utilization. The disparities between the thrombolysis rate in NR and that in OT and NT hospitals are greater among elderly patients.

  20. GC-MS analysis, evaluation of phytochemicals, anti-oxidant, thrombolytic and anti-inflammatory activities of Exacum bicolor

    OpenAIRE

    Appaji Mahesh Ashwini; Latha Puttarudrappa; Belagumba Vijaykumar Ravi; Mala Majumdar

    2015-01-01

    The aim of the present study was to investigate the GC-MS analysis, phytochemical screening, anti-oxidant, thrombolytic and anti-inflammatory activities of methanol extract of leaves of Exacum bicolor. FTIR analysis confirmed the presence of alcohol, phenols, alkanes, aromatic compounds, aldehyde and ethers. GC-MS analysis revealed the presence of eight phyto-constituents. The total phenol, flavonoid and alkaloid contents were 18.0 ± 0.2 mg/GAE/g, 13.1 ± 0.4 mg QE/g and 108.0 ± 1.2 mg AE/g re...

  1. Soluble urokinase plasminogen activator receptor is a marker of dysmetabolism in HIV-infected patients receiving highly active antiretroviral therapy

    DEFF Research Database (Denmark)

    Andersen, Ove; Eugen-Olsen, Jesper; Kofoed, Kristian

    2008-01-01

    Circulating soluble urokinase plasminogen activator receptor (suPAR) reflects the immune and pro-inflammatory status of the HIV-infected patient. Highly active antiretroviral therapy (HAART) suppresses suPAR. Independent of the immune response to HAART, suPAR remains elevated in some HIV-infected......Circulating soluble urokinase plasminogen activator receptor (suPAR) reflects the immune and pro-inflammatory status of the HIV-infected patient. Highly active antiretroviral therapy (HAART) suppresses suPAR. Independent of the immune response to HAART, suPAR remains elevated in some HIV...... fluctuate. In conclusion, suPAR may reflect the metabolic status of the HIV-infected patient on HAART, thus linking low-grade inflammation, immune constitution, lipid and glucose metabolism, and fat redistribution. Circadian suPAR concentration appeared stable, suggesting that sampling schedule does...

  2. Soluble urokinase plasminogen activator receptor as a prognostic marker of all-cause and cardiovascular mortality in a black population

    DEFF Research Database (Denmark)

    Botha, Shani; Fourie, Carla M T; Schutte, Rudolph

    2015-01-01

    BACKGROUND: Elevated inflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) are well-known risk factors for cardiovascular mortality. The less familiar marker, soluble urokinase plasminogen activator receptor (suPAR), is known to predict cancer, infections and all-cause mo......BACKGROUND: Elevated inflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) are well-known risk factors for cardiovascular mortality. The less familiar marker, soluble urokinase plasminogen activator receptor (suPAR), is known to predict cancer, infections and all......-cause mortality. We determined whether suPAR, CRP and IL-6 are predictive of both all-cause and cardiovascular mortality in a black population, highly burdened by cardiovascular disease and HIV infection. METHODS: We included 1425 black South Africans, of which 208 died within five years after baseline data...

  3. Quantitative PET of human urokinase-type plasminogen activator receptor with 64Cu-DOTA-AE105

    DEFF Research Database (Denmark)

    Persson, Morten; Madsen, Jacob; Østergaard, Søren

    2012-01-01

    Expression levels of the urokinase-type plasminogen activator receptor (uPAR) represent an established biomarker for poor prognosis in a variety of human cancers. The objective of the present study was to explore whether noninvasive PET can be used to perform a quantitative assessment of expressi...... levels of uPAR across different human cancer xenograft models in mice and to illustrate the clinical potential of uPAR PET in future settings for individualized therapy....

  4. Dead Space Ventilation Parallels Changes in Scintigraphic Vascular Obstruction at Recurrence of Pulmonary Embolism and after Thrombolytic Therapy: A Case Report

    Directory of Open Access Journals (Sweden)

    Marc A Rodger

    1998-01-01

    Full Text Available Physiological and alveolar dead space ventilation both increase in pulmonary embolism (PE in proportion to the severity of vascular obstruction. The case of a patient with recurrent PE while on heparin therapy is presented. The recurrence was characterized clinically by severe pulmonary vascular obstruction and right heart dysfunction. The patient was treated with thrombolytic therapy, with excellent clinical and scintigraphic resolution. Dead space ventilation measurements at baseline, at the time of recurrence and after thrombolytic therapy are presented. The potential utility of dead space ventilation measurements for PE diagnosis and management are discussed.

  5. Two-color cytofluorometry and cellular properties of the urokinase receptor associated with a human metastatic carcinomatous cell line

    International Nuclear Information System (INIS)

    Takahashi, K.; Gojobori, T.; Tanifuji, M.

    1991-01-01

    Purified human urokinase was labeled with either fluorescein isothiocyanate or iodine-125 and used as a probe for binding to the human metastatic carcinomatous cell line, Detroit 562. Cytofluorometry showed that the ligand bound preferentially to cells that had been exposed to acidic pH. The binding was competitive and decreased after mild tryptic digestion. The bound ligand could be removed by restoration of the cells to a low pH. Therefore, the cells had specific binding sites. The bound urokinase was involved in the breakdown of fibrin. Two-color cytofluorometric maps were constructed by counterstaining with propidium iodide. Results suggested that there were different cell populations that had different numbers of receptors and amounts of DNA. We cloned cells and found that single clones had homogeneous levels of receptors with different dissociation constants (from 10(-13) to 10(-11) mol/mg protein) for different clones. Cells of one clone, C5, which had high levels of receptor production, moved characteristically on a glass substratum coated with gold particles and reacted with wheat germ agglutinin, but not with concanavalin A. The receptors were found together with adhesion proteins at the sites where the cells adhered to the substrate. These results and the data obtained by zymography of the cellular proteins suggested that the urokinase-type plasminogen activators were bound to the receptors. The membrane-associated activator may stimulate local proteolysis, facilitating the migration of the tumor cell across the substrate

  6. Two-color cytofluorometry and cellular properties of the urokinase receptor associated with a human metastatic carcinomatous cell line

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, K.; Gojobori, T.; Tanifuji, M. (Shimane Medical Univ., Izumo (Japan))

    1991-02-01

    Purified human urokinase was labeled with either fluorescein isothiocyanate or iodine-125 and used as a probe for binding to the human metastatic carcinomatous cell line, Detroit 562. Cytofluorometry showed that the ligand bound preferentially to cells that had been exposed to acidic pH. The binding was competitive and decreased after mild tryptic digestion. The bound ligand could be removed by restoration of the cells to a low pH. Therefore, the cells had specific binding sites. The bound urokinase was involved in the breakdown of fibrin. Two-color cytofluorometric maps were constructed by counterstaining with propidium iodide. Results suggested that there were different cell populations that had different numbers of receptors and amounts of DNA. We cloned cells and found that single clones had homogeneous levels of receptors with different dissociation constants (from 10(-13) to 10(-11) mol/mg protein) for different clones. Cells of one clone, C5, which had high levels of receptor production, moved characteristically on a glass substratum coated with gold particles and reacted with wheat germ agglutinin, but not with concanavalin A. The receptors were found together with adhesion proteins at the sites where the cells adhered to the substrate. These results and the data obtained by zymography of the cellular proteins suggested that the urokinase-type plasminogen activators were bound to the receptors. The membrane-associated activator may stimulate local proteolysis, facilitating the migration of the tumor cell across the substrate.

  7. In vitro thrombolytic, anthelmintic, anti-oxidant and cytotoxic activity with phytochemical screening of methanolic extract of Xanthium indicum leaves

    Directory of Open Access Journals (Sweden)

    Antara Ghosh

    2015-12-01

    Full Text Available Xanthium indicum is an important medicinal plant traditionally used in Bangladesh as a folkloric treatment. The current study was undertaken to evaluate thrombolytic, anthelmintic, anti-oxidant, cytotoxic properties with phytochemical screening of methanolic extract of X. indicum leaves. The analysis of phytochemical screening confirmed the existence of phytosetrols and diterpenes. In thrombolytic assay, a significant clot lysis was observed at four concentrations of plant extract compare to the positive control streptokinase (30,000 IU, 15,000 IU and negative control normal saline. The extract revealed potent anthelmintic activity at different concentrations. In anti-oxidant activity evaluation by two potential experiments namely total phenolic content determination and free radical scavenging assay by 2, 2-diphenylpicrylhydrazyl (DPPH, the leaves extract possess good anti-oxidant property. In the brine shrimp lethality bioassay, the crude extract showed potent (LC50 1.3 μg/mL cytotoxic activity compare to the vincristine sulfate as a positive control (LC50 0.8 μg/mL.

  8. Capabilities of perfusion ASPECTS in predicting the efficiency of intravenous thrombolytic therapy

    Directory of Open Access Journals (Sweden)

    A. A. Kulesh

    2017-01-01

    Full Text Available Perfusion computed tomography (PCT is increasingly used to diagnose ischemic stroke (IS, as well as to identify candidates for thrombolytic therapy (TLT. The feasibility of using this technique in all patients within the therapeutic window has not yet been established. Objective: to investigate cerebral blood flow according to PCT findings and its relationship to clinical and instrumental indicators and functional status of patients who had received TLT in the acute period of IS.Patients and methods. 62 patients with acute IS who had received TLT were examined. All the patients underwent clinical, laboratory, and instrumental examinations and PCT, by assessing cerebral blood volume (CBV, cerebral blood flow (CBF, and mean transit time (MTT in 10 brain regions in accordance with the Alberta Score Program Early CT Score (ASPECTS. The total result of perfusion ASPECTS was calculated separately for CBV, CBF and MTT, as well as combinations of these parameters. The penumbra size was calculated as CBV minus MTT (CBV - MTT ASPECTS, the infarct core size was measured as CBV + MTT ASPECTS.Results. There was an increase in MTT in most regions of interest of the affected hemisphere as compared to the intact one and a predominance of reversible perfusion disorders. The averaged penumbra size constituted three zones according to ASPECTS. No relationship was found between ASPECTS scores and time after the onset of symptoms prior to hospital admission. Perfusion parameters, particularly penumbra size (CBV - MTT, were associated with the degree of stenosis in the contralateral common carotid artery, body mass index, and blood triglyceride level. Cerebral blood flow indices were also influenced by red blood cell counts and heart ejection fraction. The scores of the perfusion scales were correlated with those of the non-contrast scale. The data of the investigated ASPECTS variants correlated with the level of neurological deficit in patients, its course, and the

  9. Pre-hospital thrombolytic therapy with either alteplase or streptokinase. : Practical applications, complications and long-term results in 529 patients.

    NARCIS (Netherlands)

    E.W.M. Grijseels (Els); M.J.M. Bouten; J.W. Deckers (Jaap); A.W. Hoes (Arno); J.A.M. Hartman; E. van der Does (Emiel); M.L. Simoons (Maarten); T. Lenderink (Timo)

    1995-01-01

    markdownabstractOBJECTIVE: To assess the practical application, safety and long-term outcome of pre-hospital thrombolytic intervention with either alteplase or streptokinase in patients with extensive myocardial infarction. DESIGN: Prospective study. SUBJECTS: Patients with chest pain of more

  10. Identification and characterization of the murine cell surface receptor for the urokinase-type plasminogen activator

    DEFF Research Database (Denmark)

    Solberg, H; Løber, D; Eriksen, J

    1992-01-01

    Cell-binding experiments have indicated that murine cells on their surface have specific binding sites for mouse urokinase-type plasminogen activator (u-PA). In contrast to the human system, chemical cross-linking studies with an iodinated ligand did not yield any covalent adducts in the murine...... system, but in ligand-blotting analysis, two mouse u-PA-binding proteins could be visualized. To confirm that these proteins are the murine counterpart of the human u-PA receptor (u-PAR), a peptide was derived from the murine cDNA clone assigned to represent the murine u-PAR due to cross......-blotting analysis. Binding of mouse u-PA to its receptor showed species specificity in ligand-blotting analysis, since mouse u-PA did not bind to human u-PAR and human u-PA did not bind to mouse u-PAR. The apparent M(r) of mouse u-PAR varied between different mouse cell lines and ranged over M(r) 45...

  11. Urokinase-type plasminogen activator: a new target for male contraception?

    Science.gov (United States)

    Qin, Ying; Han, Yan; Xiong, Cheng-Liang; Li, Hong-Gang; Hu, Lian; Zhang, Ling

    2015-01-01

    Urokinase-type plasminogen activator (uPA) is closely related to male reproduction. With the aim of investigating the possibility for uPA as a potential contraceptive target, in the present work, Kunming male mice were immunized by human uPA subcutaneous injection at three separate doses for 3 times. Then the potency of the anti-human uPA antibody in serum was analyzed, and mouse fertility was evaluated. Serum antibody titers for human uPA in immunized groups all reached 1:10,240 or higher levels by enzyme linked immunosorbent assay, and mating experiments revealed that pregnancy rates and the mean number of embryos implanted after mating declined obviously (P male mice. Sperm function tests suggested that the sperm concentration, sperm viability, sperm motility, and in vitro fertilization rate for the cauda epididymis sperm in uPA-immunized groups were lower than those in the controls (P male mice could effectively reduce their fertility, and uPA could become a new target for immunocontraception in male contraceptive development.

  12. Endovascular Treatment of Left Iliofemoral Deep Vein Thrombosis Using Urokinase Thrombolysis and Adjunctive Aspiration Thrombectomy

    Energy Technology Data Exchange (ETDEWEB)

    Suh, Sang Hyun; Lee, Do Yun; Won, Jong Yun [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2010-02-15

    To evaluate the efficacy of adjunctive aspiration thrombectomy for the treatment of iliofemoral deep vein thrombosis (DVT). 24 patients (9 males and 15 females; mean age, 53 years), treated by aspiration thrombectomy were enrolled in this study. The day after undergoing urokinase (UK) thrombolysis, any residual thrombus over a long segment was treated by aspiration thrombectomy using a 12 Fr long sheath. Residual short-segment (< 10 cm) iliac vein thrombus and/or stenosis were treated with a stent. The evaluation of venous patency was conducted by color Doppler ultrasonography, venography and/or computed tomography. The technical and clinical success rates were 100% and 92%, respectively. Twenty-three patients were treated by UK thrombolysis and iliac stent. The overall patency rate at 1, 2 and 3 years was 85%, 82% and 81%, respectively. Over the course of the follow-up period, occlusion was observed in 4 cases (1 acute and 3 chronic cases). Periprocedural complication occurred in 4 cases (17%) in the form of a minimal hematoma or pain on the puncture site as well as a case of pulmonary embolism at one month after treatment. The adjunctive aspiration thrombectomy with conventional thrombolysis and stent placement can be an effective and safe method in the treatment of left iliofemoral DVT

  13. Tyk2 mediates effects of urokinase on human vascular smooth muscle cell growth

    International Nuclear Information System (INIS)

    Patecki, Margret; Schaewen, Markus von; Tkachuk, Sergey; Jerke, Uwe; Dietz, Rainer; Dumler, Inna; Kusch, Angelika

    2007-01-01

    The urokinase (uPA)/uPA receptor (uPAR) system plays a role in the response of the vessel wall to injury, presumably by modulating vascular smooth muscle cell (VSMC) functional behaviour. The Jak/Stat signaling pathway has been implicated to mediate the uPA/uPAR-directed cell migration and proliferation in VSMC. We have therefore investigated the underlying molecular mechanisms, which remained not completely understood. In particular, we aimed at identification of the kinase involved in the signaling cascade leading to Stat1 phosphorylation by uPA and its impact on VSMC growth. We performed expression in VSMC of kinase-deficient mutant forms of the Janus kinases Jak1 and Tyk2 and used different cell culture models imitating the response to vascular injury. We provide evidence that Tyk2, but not Jak1, mediates uPA-induced Stat1 phosphorylation and VSMC growth inhibition and suggest a novel function for Tyk2 as an important modulator of the uPA-directed VSMC functional behaviour at the place of injury

  14. Terminalia catappa attenuates urokinase-type plasminogen activator expression through Erk pathways in Hepatocellular carcinoma.

    Science.gov (United States)

    Yeh, Chao-Bin; Yu, Yung-Luen; Lin, Chiao-Wen; Chiou, Hui-Ling; Hsieh, Ming-Ju; Yang, Shun-Fa

    2014-04-30

    The survival rate of malignant tumors, and especially hepatocellular carcinoma (HCC), has not improved primarily because of uncontrolled metastasis. In our previous studies, we have reported that Terminalia catappa leaf extract (TCE) exerts antimetastasis effects on HCC cells. However, the molecular mechanisms of urokinase-type plasminogen activator (u-PA) in HCC metastasis have not been thoroughly investigated, and remain poorly understood. The activities and protein levels of u-PA were determined by casein zymography and western blotting. Transcriptional levels of u-PA were detected by real-time PCR and promoter assays. We found that treatment of Huh7 cells with TCE significantly reduced the activities, protein levels and mRNA levels of u-PA. A chromatin immunoprecipitation (ChIP) assay showed that TCE inhibited the transcription protein of nuclear factors SP-1 and NF-κB. TCE also did inhibit the effects of u-PA by reducing the phosphorylation of ERK1/2 pathway. These results show that u-PA expression may be a potent therapeutic target in the TCE-mediated suppression of HCC metastasis.

  15. Urokinase receptor cleavage correlates with tumor volume in a transgenic mouse model of breast cancer

    DEFF Research Database (Denmark)

    Thurison, Tine; Almholt, Kasper; Gårdsvoll, Henrik

    2015-01-01

    PAR(I)]. The level of muPAR(I) is significantly increased in mammary tumor-bearing mice compared to controls and, notably, there is a strong correlation to tumor volume. In contrast, the tumor volume is only weakly correlated to the level of intact muPAR(I-III), indicating that cleavage of muPAR is a more specific...... marker for cancer than increased expression of muPAR per se. The levels of the muPAR forms are dramatically affected by in vivo challenge with a urokinase -blocking antibody, demonstrating a functional role of uPA in uPAR cleavage. The levels of the muPAR forms are, however, unaffected by u......PA-deficiency, suggesting that redundant proteases maintains the task of cleaving uPAR(I-III) when uPA is absent. Our findings emphasize the significance of the cleaved uPAR forms as cancer biomarkers. The strong correlation between muPAR(I) and the tumor volume in our experimental setup may motivate investigations...

  16. Soluble Urokinase Plasminogen Activator Receptor as a Marker for Use of Antidepressants

    Science.gov (United States)

    Haastrup, Eva; Grau, Katrine; Eugen-Olsen, Jesper; Thorball, Christian; Kessing, Lars Vedel; Ullum, Henrik

    2014-01-01

    Objectives Inflammation is involved in the pathogenesis of depression. A few cross-sectional population-based studies have found that depression is associated with increased levels of inflammatory markers. Soluble urokinase plasminogen activation receptor (suPAR) is known to be a stable marker for inflammation. We investigated the bidirectional association between suPAR levels and use of antidepressants. Methods suPAR level was measured in 9305 blood donors and analysed in relation to 5-years follow-up data on purchase of antidepressants and hospital diagnoses of depression from a nationwide Danish register. Results For men and women without prior use of antidepressants we found a significantly higher risk for incident use of antidepressants with higher suPAR values. For men, the risk of first use of antidepressants increased by 72% from the 1st to the 4th quartile (HR = 1.72, 95% CI: 1.11–2.69). For women, it increased by 108% from the 1st to the 4th quartile (HR = 2.08, 95% CI: 1.45–2.98). Previous use of antidepressants was also significantly associated with higher suPAR levels (p = 0.002). Conclusions High suPAR levels are associated with an increased risk for both previous and future use of antidepressants in healthy men and women. High suPAR are also associated with increased risk for a hospital diagnosis of depression. PMID:25329298

  17. Inhibition of receptor-bound urokinase by plasminogen-activator inhibitors

    DEFF Research Database (Denmark)

    Ellis, Vincent John; Wun, T C; Behrendt, N

    1990-01-01

    Urokinase-type plasminogen activator (uPA) binds to a specific receptor on various cell types, the bound molecule retaining its enzymatic activity against plasminogen. We have now investigated whether receptor-bound uPA also retains the ability to react with and be inhibited by plasminogen...... activator inhibitors (PAI-1 and PAI-2). uPA bound to its receptor on human U937 monocyte-like cells was inhibited by PAI-1 (in its active form in the presence of vitronectin fragments) with an association rate constant of 4.5 x 10(6) M-1 s-1, which was 40% lower than that obtained for uPA in solution (7.9 x...... 10(6) M-1 s-1). The inhibition of uPA by PAI-2 was decreased to a similar extent by receptor binding, falling from 5.3 x 10(5) to 3.3 x 10(5) M-1 s-1. Stimulation of U937 cells with phorbol 12-myristate 13-acetate was accompanied by a further reduction in receptor-bound uPA inhibition by PAI-1...

  18. Urokinase plasminogen activator receptor affects bone homeostasis by regulating osteoblast and osteoclast function

    DEFF Research Database (Denmark)

    Furlan, Federico; Galbiati, Clara; Jørgensen, Niklas R

    2007-01-01

    PAR and produce urokinase (uPA). The purpose of this study was to investigate the role of uPAR in bone remodeling. MATERIALS AND METHODS: In vivo studies were performed in uPAR knockout (KO) and wildtype (WT) mice on a C57Bl6/SV129 (75:25) background. Bone mass was analyzed by pQCT. Excised tibias were subjected......The uPAR and its ligand uPA are expressed by both osteoblasts and osteoclasts. Their function in bone remodeling is unknown. We report that uPAR-lacking mice display increased BMD, increased osteogenic potential of osteoblasts, decreased osteoclasts formation, and altered cytoskeletal...... of macrophage-colony stimulating factor (M-CSF) and RANKL. Phalloidin staining in osteoclasts served to study actin ring and podosome formation. RESULTS: pQCT revealed increased bone mass in uPAR-null mice. Mechanical tests showed reduced load-sustaining capability in uPAR KO tibias. uPAR KO osteoblasts showed...

  19. Soluble Urokinase Receptors in Focal Segmental Glomerulosclerosis: A Review on the Scientific Point of View

    Directory of Open Access Journals (Sweden)

    Andreas Kronbichler

    2016-01-01

    Full Text Available Focal segmental glomerulosclerosis (FSGS is one of the primary glomerular disorders in both children and adults which can progress to end-stage renal failure. Although there are genetic and secondary causes, circulating factors have also been regarded as an important factor in the pathogenesis of FSGS, because about 40% of the patients with FSGS have recurrence after renal transplantation. Soluble urokinase-type plasminogen activator receptor (suPAR is a soluble form of uPAR, which is a membrane-bound protein linked to GPI in various immunologically active cells, including podocytes. It has recently been suggested as a potential circulating factor in FSGS by in vitro podocyte experiments, in vivo mice models, and human studies. However, there have also been controversies on this issue, because subsequent studies showed conflicting results. suPAR levels were also increased in patients with other glomerular diseases and were inversely correlated with estimated glomerular filtration rate. Nevertheless, there has been no balanced review on this issue. In this review, we compare the conflicting data on the involvement of suPAR in the pathogenesis of FSGS and shed light on interpretation by taking into account many points and the potential variables and confounders influencing serum suPAR levels.

  20. Data on the regulation of moesin and merlin by the urokinase receptor (uPAR: Model explaining distal activation of integrins by uPAR

    Directory of Open Access Journals (Sweden)

    Bernard Degryse

    2017-12-01

    Full Text Available The data presented herein are connected to our research article (doi: 10.1016/j.biocel.2017.04.012 [1], in which we investigated the functional connections between the urokinase receptor (uPAR, and the ezrin/radixin/moesin (ERM proteins, moesin and merlin [1]. Firstly, a model of action is proposed that enlightens how uPAR regulates distal integrins. In addition, data show the effects of expressing wild-type moesin or permanently active T558D mutant of moesin on angiogenesis and morphology of human aortic endothelial cells (HAEC. Additional data compare the effects of urokinase (uPA, the main ligand of uPAR on the same cells. Lastly, we provide technical data demonstrating the effects of specific siRNA for moesin and merlin on moesin and merlin expression, respectively. Keywords: Urokinase receptor, Moesin, Merlin, Angiogenesis, siRNA

  1. Plasminogen-independent initiation of the pro-urokinase activation cascade in vivo. Activation of pro-urokinase by glandular kallikrein (mGK-6) in plasminogen-deficient mice

    DEFF Research Database (Denmark)

    List, K; Jensen, Ole Nørregaard; Bugge, T H

    2000-01-01

    The plasminogen activation (PA) system is involved in the degradation of fibrin and various extracellular matrix proteins, taking part in a number of physiological and pathological tissue remodeling processes including cancer invasion. This system is organized as a classical proteolytic cascade......, and as for other cascade systems, understanding the physiological initiation mechanism is of central importance. The attempts to identify initiation routes for activation of the proform of the key enzyme urokinase-type plasminogen activator (pro-uPA) in vivo have been hampered by the strong activator potency...

  2. [Thrombolytic therapy of acute myocardial infarct in a district hospital. Analysis of a group of patients treated with streptokinase].

    Science.gov (United States)

    Baraniková, D; Renker, B; Augustín, E; Brunclík, P

    1993-03-01

    At the intensive care unit of the hospital and policlinical department in Zilina the authors treated between May 29, 1985 and Dec. 31, 1990, 87 patients with AIM by systemic administration of streptokinase which was injected after an average period of 2.5 hours following the onset of stenocardia. As to the selection of patients for thrombolysis and tactics of treatment, the authors proceeded according to an elaborated protocol. The upper borderline of the age range is not limited. Non-invasive markers of reperfusion of the heart muscle (regression of stenocardia, regression of ECG changes, reperfusion arrhythmias) were observed in 25-80% of the patients. There was only a small number of complications in the patients of the described group; they were not serious and did not call for therapeutic intervention. Thrombolytic treatment of AIM by streptokinase is a safe and effective method which can be successfully used also in intensive care units of district hospitals.

  3. Use of streptokinase for the salvage of a free flap: case report and review of the use of thrombolytic therapy.

    Science.gov (United States)

    Schubert, W; Hunter, D W; Guzman-Stein, G; Ahrenholz, D H; Solem, L D; Dressel, T D; Cunningham, B L

    1987-01-01

    This is the first case report of the clinical use of intraoperative streptokinase to promote free flap salvage. A latissimus dorsi free flap was mobilized to cover a scalping type injury. After 4 1/2 hours of ischemia and recurrent thrombosis, streptokinase was perfused into the thoracodorsal artery (7,500 units of streptokinase in 30 cc of normal saline). The free flap was exposed to this concentration of streptokinase for 10 minutes followed by drainage of the venous effluent in order to avoid possible deleterious systemic effects of the streptokinase. Good flow throughout the free flap resulted, and the flap remained viable, providing good coverage for the patient's skull. Controversies regarding the no-reflow phenomena and the use of various thrombolytic agents are discussed.

  4. Factors associated with rapid neurological improvement 24 h following intra-arterial thrombolytic treatment for acute ischemic stroke.

    Science.gov (United States)

    Christoforidis, Gregorgy; Mohammad, Yousef M; Khadir, Mohammed; Yang, Ming; Slivka, Andrew P

    2013-01-01

    Significant 24 h improvement is the strongest indicator of functional recovery following thrombolytic treatment for acute ischemic stroke. This study sought to analyze factors contributing to rapid neurological improvement (RNI) following intra-arterial thrombolytic treatment (IATT). Angiograms and clinical information derived from consecutive patients receiving treatment initiated within 6 h of stroke onset were retrospectively reviewed. RNI was defined as at least 50% 24 h improvement on the National Institutes of Health Stroke Scale score. Logistic regression analysis identified factors associated with RNI. Variables tested included: age, gender, serum glucose, platelet count, pial collateral formation, presenting National Institutes of Health Stroke Scale score, time to treatment, extent of reperfusion, site and location of occlusion, treatment agent and systolic blood pressure. Greater than 50% reperfusion of the involved territory, time to treatment within 270 min and good pial collateral formation (large penumbra zone) significantly predicted RNI. RNI occurred in 31% of the 112 patients studied. RNI occurred in 21/26 (80.8%) patients exhibiting all three favorable variables whereas patients with only one favorable variable had a 6.5% chance of RNI. 94% of patients displaying RNI had a modified Rankin Scale score of 2 or less at 3 months compared with 28.6% without RNI. RNI following IATT for stroke is more likely when at least two of the following are present: good reperfusion, good pial collateral formation and treatment within 4.5 h of symptom onset, and is strongly predictive of 3 month outcomes. Important to clinical management, IATT may need to be reconsidered in patients with poor pial collateral formation if time to treatment exceeds 4.5 h.

  5. Comparison of coronary angiography and early oral dipyridamole thallium-201 scintigraphy in patients receiving thrombolytic therapy for acute myocardial infarction

    International Nuclear Information System (INIS)

    Jain, A.; Hicks, R.R.; Myers, G.H.; McCarthy, J.J.; Perry, J.R.; Adams, K.F.

    1990-01-01

    We evaluated 50 consecutive patients who received thrombolytic therapy for acute myocardial infarction using thallium-201 single photon emission computed tomography in combination with oral dipyridamole to assess the frequency of residual myocardial ischemia. Thallium studies were performed early after myocardial infarction at a mean of 4.6 days. The time from the onset of chest pain to the administration of thrombolytic therapy was 2.6 hours (range 0.5 to 5.5). Q wave myocardial infarction was evident in 46 patients; four patients had a non-Q wave infarction (anterior infarction in 31 patients and inferior infarction in 19 patients). The serum mean peak creatinine kinase was 1503 IU/L (range 127 to 6500). Coronary angiography was performed in all patients at a mean of 3.1 days (range 2 to 10) and revealed the infarct-related vessel to be patent in 36 patients (72%). The ejection fraction was 48% (range 26% to 67%). After dipyridamole administration, 13 patients (26%) developed angina that was easily reversed with the administration of intravenous aminophylline. Systolic blood pressure decreased from 122 to 115 mm Hg (p less than 0.05) and the heart rate increased from 76 to 85 beats/min (p less than 0.05). None of the patients had significant hypotension, arrhythmias, or evidence of infarct extension. Perfusion abnormalities were present on the initial thallium images in 48 patients. Redistribution suggestive of ischemia was present in 36 patients (72%). Ischemia confined to the vascular distribution of the infarct vessel was evident in 22 patients. Seven patients had ischemia in the infarct zone as well as in a remote myocardial segment. Thus 29 patients (58%) had ischemia in the distribution of the infarct vessel. Ischemia in the infarct zone was evident in 19 of 36 patients with open infarct vessels and in 10 of 14 patients with occluded infarct vessels

  6. A region in urokinase plasminogen receptor domain III controlling a functional association with alpha5beta1 integrin and tumor growth

    DEFF Research Database (Denmark)

    Chaurasia, Pratima; Aguirre-Ghiso, Julio; Liang, Olin D

    2006-01-01

    Highly expressed urokinase plasminogen activator receptor (uPAR) can interact with alpha5beta1 integrin leading to persistent ERK activation and tumorigenicity. Disrupting this interaction reduces ERK activity, forcing cancer cells into dormancy. We identified a site in uPAR domain III that is in......Highly expressed urokinase plasminogen activator receptor (uPAR) can interact with alpha5beta1 integrin leading to persistent ERK activation and tumorigenicity. Disrupting this interaction reduces ERK activity, forcing cancer cells into dormancy. We identified a site in uPAR domain III...

  7. Aberrant glomerular filtration of urokinase-plasminogen activator in nephrotic syndrome leads to amiloride-sensitive plasminogen activation in urine

    DEFF Research Database (Denmark)

    Stæhr, Mette; Buhl, Kristian Bergholt; Andersen, René F

    2015-01-01

    In nephrotic syndrome, aberrant glomerular filtration of plasminogen and conversion to active plasmin in pre-urine is thought to activate proteolytically ENaC and contribute to sodium retention and edema. The ENaC blocker amiloride is an off-target inhibitor of urokinase-type plasminogen activator...... with aberrant filtration of uPA across the injured glomerular barrier. Amiloride inhibits urine uPA activity which attenuates plasminogen activation and urine protease activity in vivo. Urine uPA is a relevant target for amiloride in vivo....

  8. Risk Factors Associated with Serum Levels of the Inflammatory Biomarker Soluble Urokinase Plasminogen Activator Receptor in a General Population

    DEFF Research Database (Denmark)

    Haupt, Thomas H; Kallemose, Thomas; Ladelund, Steen

    2014-01-01

    The soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of mortality risk in various patient populations. However, little is known about the implications of lifestyle for suPAR levels in the general population. Lifestyle, demographic, and cardiovascular disease (CVD) risk factor...... data were collected from 5,538 participants in the Danish population-based Inter99 study. Their suPAR levels were measured using a sandwich enzyme-linked immunosorbent assay. In the final adjusted model, smoking and morbid obesity were strongly associated with higher suPAR levels (P

  9. The urokinase receptor (uPAR) and the uPAR-associated protein (uPARAP/Endo180)

    DEFF Research Database (Denmark)

    Behrendt, Niels

    2004-01-01

    processes involve a highly organized interplay between proteases and their cellular binding sites as well as specific substrates and internalization receptors. This review article is focused on two components, the urokinase plasminogen activator receptor (uPAR) and the uPAR-associated protein (uPARAP, also...... designated Endo180), that are considered crucially engaged in matrix degradation. uPAR and uPARAP have highly diverse functions, but on certain cell types they interact with each other in a process that is still incompletely understood. uPAR is a glycosyl-phosphatidylinositol-anchored glycoprotein...

  10. Expression and activity of the urokinase plasminogen activator system in canine primary brain tumors

    Directory of Open Access Journals (Sweden)

    Rossmeisl JH

    2017-04-01

    Full Text Available John H Rossmeisl,1–3 Kelli Hall-Manning,4 John L Robertson,1,3,5 Jamie N King,1,2 Rafael V Davalos,3,5 Waldemar Debinski,3 Subbiah Elankumaran6,† 1Veterinary and Comparative Neuro-Oncology Laboratory, 2Department of Small Animal Clinical Sciences, 3The Brain Tumor Center of Excellence, Wake Forest Baptist Medical Center Comprehensive Cancer Center, Winston-Salem, NC, 4Virginia Tech Animal Laboratory Services, Virginia-Maryland College of Veterinary Medicine, 5Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Virginia Tech, 6Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, USA†The authors regret to advise of the passing of Dr Subbiah Elankumaran prior to publicationBackground: The expression of the urokinase plasminogen activator receptor (uPAR, a glycosylphosphatidylinositol-anchored protein family member, and the activity of its ligand, urokinase-type plasminogen activator (uPA, have been associated with the invasive and metastatic potentials of a variety of human brain tumors through their regulation of extracellular matrix degradation. Domesticated dogs develop naturally occurring brain tumors that share many clinical, phenotypic, molecular, and genetic features with their human counterparts, which has prompted the use of the dogs with spontaneous brain tumors as models to expedite the translation of novel brain tumor therapeutics to humans. There is currently little known regarding the role of the uPA system in canine brain tumorigenesis. The objective of this study was to characterize the expression of uPAR and the activity of uPA in canine brain tumors as justification for the development of uPAR-targeted brain tumor therapeutics in dogs.Methods: We investigated the expression of uPAR in 37 primary canine brain tumors using immunohistochemistry, Western blotting, real

  11. The urokinase-system in tumor tissue stroma of the breast and breast cancer cell invasion.

    Science.gov (United States)

    Hildenbrand, Ralf; Schaaf, Antonela

    2009-01-01

    The urokinase-system has been implicated in tumor spread. The serine protease urokinase-type plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI-1) are involved in the control of extracellular turnover, cell migration, invasion, cell signalling, proliferation, apoptosis and angiogenesis leading to a variety of different responses, under both physiological and pathological conditions. uPA and PAI-1 were the first novel tumor biological factors to be validated at the highest level of evidence regarding their clinical utility in breast cancer. However, it is unclear whether it is their (relative) levels in the tumor stroma or in the tumor cells themselves that is the most relevant to patients outcome. This is the first study in which tumor cells and stromal tissue of invasive breast carcinomas were separated by laser capture microdissection followed by ELISA-based determination of the uPA, uPAR and PAI-1 levels. In addition, we localized uPA, uPAR and PAI-1 distribution in invasive breast cancer (n=30) and in ductal carcinoma in situ (DCIS, n=30) by immunohistochemistry and in situ hybridization. We have demonstrated that no significant differences between uPA, uPAR and PAI-1 levels in tumor stroma only, tumor cells only and not separated breast cancer tissue exist (p>0.05). Our results suggest that similar expression levels of these factors in both compartments and in not separated breast cancer tissue may have the same impact on the clinical behavior of breast cancer. These results are an important issue for practical use of tissue sampling. For using uPA and PAI-1 levels as prognostic and predictive factors in breast cancer the quantity of tumor stroma in the tumor tissue specimen is not relevant for assessment patients outcome. Our results were confirmed by immunohistochemistry and in situ hybridization analysis showing that in nearly all cases of invasive carcinomas and DCIS fibroblasts as well as macrophages strongly express uPA, uPAR and PAI

  12. The urokinase receptor (uPAR facilitates clearance of Borrelia burgdorferi.

    Directory of Open Access Journals (Sweden)

    Joppe W R Hovius

    2009-05-01

    Full Text Available The causative agent of Lyme borreliosis, the spirochete Borrelia burgdorferi, has been shown to induce expression of the urokinase receptor (uPAR; however, the role of uPAR in the immune response against Borrelia has never been investigated. uPAR not only acts as a proteinase receptor, but can also, dependently or independently of ligation to uPA, directly affect leukocyte function. We here demonstrate that uPAR is upregulated on murine and human leukocytes upon exposure to B. burgdorferi both in vitro as well as in vivo. Notably, B. burgdorferi-inoculated C57BL/6 uPAR knock-out mice harbored significantly higher Borrelia numbers compared to WT controls. This was associated with impaired phagocytotic capacity of B. burgdorferi by uPAR knock-out leukocytes in vitro. B. burgdorferi numbers in vivo, and phagocytotic capacity in vitro, were unaltered in uPA, tPA (low fibrinolytic activity and PAI-1 (high fibrinolytic activity knock-out mice compared to WT controls. Strikingly, in uPAR knock-out mice partially backcrossed to a B. burgdorferi susceptible C3H/HeN background, higher B. burgdorferi numbers were associated with more severe carditis and increased local TLR2 and IL-1beta mRNA expression. In conclusion, in B. burgdorferi infection, uPAR is required for phagocytosis and adequate eradication of the spirochete from the heart by a mechanism that is independent of binding of uPAR to uPA or its role in the fibrinolytic system.

  13. Interleukin-33 induces urokinase in human endothelial cells--possible impact on angiogenesis.

    Science.gov (United States)

    Stojkovic, S; Kaun, C; Heinz, M; Krychtiuk, K A; Rauscher, S; Lemberger, C E; de Martin, R; Gröger, M; Petzelbauer, P; Huk, I; Huber, K; Wojta, J; Demyanets, S

    2014-06-01

    Urokinase-type plasminogen activator (u-PA) plays a pivotal role in extracellular proteolysis and is thought to be critically involved in the modulation of angiogenesis. Interleukin (IL)-33 is a member of the IL-1 cytokine family, which is thought to act as danger signal that is released from cells after injury. IL-33 is involved in the pathogenesis of various inflammatory diseases and previously was shown to induce angiogenesis and inflammatory activation of endothelial cells. We investigated the impact of IL-33 on u-PA in endothelial cells as a new possible function for IL-33. We could demonstrate that IL-33 upregulated u-PA mRNA expression and protein production in human coronary artery and human umbilical vein endothelial cells in a time- and concentration-dependent manner via interaction with its receptor ST2 and activation of the nuclear factor-κB pathway but independent of autocrine IL-1-induced effects. The hydroxymethylglutaryl-coenzyme A reductase inhibitor simvastatin abrogated the IL-33-induced increase in u-PA, thus providing further evidence for pleiotropic effects of statins. IL-33 induced u-PA-dependent capillary-like tube formation and vessel sprouting. In human carotid atherosclerotic plaques (n = 16), u-PA mRNA positively correlated with IL-33 mRNA expression (r = 0.780, P < 0.001). Furthermore, IL-33 and u-PA protein were detected in endothelial cells in these samples using fluorescence immunohistochemistry. We hypothesize that IL-33, representing a danger signal that is released after tissue damage, in addition to its role in the inflammatory activation of endothelial cells, is involved in u-PA-driven angiogenesis, a process that has been shown before to be linked to inflammation in various pathologies. © 2014 International Society on Thrombosis and Haemostasis.

  14. Imaging the urokinase plasminongen activator receptor in preclinical breast cancer models of acquired drug resistance.

    Science.gov (United States)

    LeBeau, Aaron M; Sevillano, Natalia; King, Mandy L; Duriseti, Sai; Murphy, Stephanie T; Craik, Charles S; Murphy, Laura L; VanBrocklin, Henry F

    2014-01-01

    Subtype-targeted therapies can have a dramatic impact on improving the quality and quantity of life for women suffering from breast cancer. Despite an initial therapeutic response, cancer recurrence and acquired drug-resistance are commonplace. Non-invasive imaging probes that identify drug-resistant lesions are urgently needed to aid in the development of novel drugs and the effective utilization of established therapies for breast cancer. The protease receptor urokinase plasminogen activator receptor (uPAR) is a target that can be exploited for non-invasive imaging. The expression of uPAR has been associated with phenotypically aggressive breast cancer and acquired drug-resistance. Acquired drug-resistance was modeled in cell lines from two different breast cancer subtypes, the uPAR negative luminal A subtype and the uPAR positive triple negative subtype cell line MDA-MB-231. MCF-7 cells, cultured to be resistant to tamoxifen (MCF-7 TamR), were found to significantly over-express uPAR compared to the parental cell line. uPAR expression was maintained when resistance was modeled in triple-negative breast cancer by generating doxorubicin and paclitaxel resistant MDA-MB-231 cells (MDA-MB-231 DoxR and MDA-MB-231 TaxR). Using the antagonistic uPAR antibody 2G10, uPAR was imaged in vivo by near-infrared (NIR) optical imaging and (111)In-single photon emission computed tomography (SPECT). Tumor uptake of the (111)In-SPECT probe was high in the three drug-resistant xenografts (> 46 %ID/g) and minimal in uPAR negative xenografts at 72 hours post-injection. This preclinical study demonstrates that uPAR can be targeted for imaging breast cancer models of acquired resistance leading to potential clinical applications.

  15. Targeting the autolysis loop of urokinase-type plasminogen activator with conformation-specific monoclonal antibodies.

    Science.gov (United States)

    Botkjaer, Kenneth A; Fogh, Sarah; Bekes, Erin C; Chen, Zhuo; Blouse, Grant E; Jensen, Janni M; Mortensen, Kim K; Huang, Mingdong; Deryugina, Elena; Quigley, James P; Declerck, Paul J; Andreasen, Peter A

    2011-08-15

    Tight regulation of serine proteases is essential for their physiological function, and unbalanced states of protease activity have been implicated in a variety of human diseases. One key example is the presence of uPA (urokinase-type plasminogen activator) in different human cancer types, with high levels correlating with a poor prognosis. This observation has stimulated efforts into finding new principles for intervening with uPA's activity. In the present study we characterize the so-called autolysis loop in the catalytic domain of uPA as a potential inhibitory target. This loop was found to harbour the epitopes for three conformation-specific monoclonal antibodies, two with a preference for the zymogen form pro-uPA, and one with a preference for active uPA. All three antibodies were shown to have overlapping epitopes, with three common residues being crucial for all three antibodies, demonstrating a direct link between conformational changes of the autolysis loop and the creation of a catalytically mature active site. All three antibodies are potent inhibitors of uPA activity, the two pro-uPA-specific ones by inhibiting conversion of pro-uPA to active uPA and the active uPA-specific antibody by shielding the access of plasminogen to the active site. Furthermore, using immunofluorescence, the conformation-specific antibodies mAb-112 and mAb-12E6B10 enabled us to selectively stain pro-uPA or active uPA on the surface of cultured cells. Moreover, in various independent model systems, the antibodies inhibited tumour cell invasion and dissemination, providing evidence for the feasibility of pharmaceutical intervention with serine protease activity by targeting surface loops that undergo conformational changes during zymogen activation. © The Authors Journal compilation © 2011 Biochemical Society

  16. Role of the urokinase-fibrinolytic system in epithelial-mesenchymal transition during lung injury.

    Science.gov (United States)

    Marudamuthu, Amarnath Satheesh; Bhandary, Yashodhar Prabhakar; Shetty, Shwetha Kumari; Fu, Jian; Sathish, Venkatachalem; Prakash, Ys; Shetty, Sreerama

    2015-01-01

    Alveolar type II epithelial (ATII) cell injury precedes development of pulmonary fibrosis. Mice lacking urokinase-type plasminogen activator (uPA) are highly susceptible, whereas those deficient in plasminogen activator inhibitor (PAI-1) are resistant to lung injury and pulmonary fibrosis. Epithelial-mesenchymal transition (EMT) has been considered, at least in part, as a source of myofibroblast formation during fibrogenesis. However, the contribution of altered expression of major components of the uPA system on ATII cell EMT during lung injury is not well understood. To investigate whether changes in uPA and PAI-1 by ATII cells contribute to EMT, ATII cells from patients with idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease, and mice with bleomycin-, transforming growth factor β-, or passive cigarette smoke-induced lung injury were analyzed for uPA, PAI-1, and EMT markers. We found reduced expression of E-cadherin and zona occludens-1, whereas collagen-I and α-smooth muscle actin were increased in ATII cells isolated from injured lungs. These changes were associated with a parallel increase in PAI-1 and reduced uPA expression. Further, inhibition of Src kinase activity using caveolin-1 scaffolding domain peptide suppressed bleomycin-, transforming growth factor β-, or passive cigarette smoke-induced EMT and restored uPA expression while suppressing PAI-1. These studies show that induction of PAI-1 and inhibition of uPA during fibrosing lung injury lead to EMT in ATII cells. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  17. Comparison of the inhibition of urokinase-type plasminogen activator (u-PA) activity by monoclonal antibodies specific for u-PA as assessed by different assays

    NARCIS (Netherlands)

    Boheemen, P.A. van; Hoogen, N.M. van den; Koolwijk, N.

    1995-01-01

    Six murine monoclonal antibodies (MAbs) specific for urokinase-type plasminogen activator (u-PA) were tested for their ability to inhibit u-PA activity in three different assays with respect to amidolytic activity, plasminogen activation and fibrinolytic activity. Two of the MAbs were able to

  18. A new assay for measurement of the liberated domain I of the urokinase receptor in plasma improves the prediction of survival in colorectal cancer

    DEFF Research Database (Denmark)

    Thurison, Tine; Lomholt, Anne F; Rasch, Morten G

    2010-01-01

    The liberated domain I of the urokinase plasminogen activator receptor [uPAR(I)] is a significant prognostic marker in lung and ovarian cancer, although the uPAR(I) concentration is below the limit of quantification (LOQ) in a substantial proportion of patient samples (Lung Cancer 2005;48:349-55;...

  19. Distinctive binding modes and inhibitory mechanisms of two peptidic inhibitors of urokinase-type plasminogen activator with isomeric P1 residues

    DEFF Research Database (Denmark)

    Jiang, Longguang; Zhao, Baoyu; Xu, Peng

    2015-01-01

    Abstract Two isomeric piperidine derivatives (meta and para isomers) were used as arginine mimics in the P1 position of a cyclic peptidic inhibitor (CPAYSRYLDC) of urokinase-type plasminogen activator. The two resulting cyclic peptides showed vastly different affinities (∼70 fold) to the target...

  20. Prognostic value of plasma soluble urokinase plasminogen activator receptor (suPAR) in Danish patients with recurrent epithelial ovarian cancer (REOC)

    DEFF Research Database (Denmark)

    Begum, Farah Diba; Høgdall, Estrid V S; Riisbo, Rikke

    2006-01-01

    The level of the soluble urokinase plasminogen activator receptor (suPAR) is elevated in tumour tissue from several types of cancer. This is the first study aiming to predict the prognosis for survival by the use of a pre-chemotherapeutic plasma suPAR value in 71 patients with recurrent epithelial...

  1. Targeting tumor cell invasion and dissemination in vivo by an aptamer that inhibits urokinase-type plasminogen activator through a novel multifunctional mechanism

    DEFF Research Database (Denmark)

    Botkjaer, Kenneth A; Deryugina, Elena I; Dupont, Daniel Miotto

    2012-01-01

    Data accumulated over the latest two decades have established that the serine protease urokinase-type plasminogen activator (uPA) is a potential therapeutic target in cancer. When designing inhibitors of the proteolytic activity of serine proteases, obtaining sufficient specificity is problematic...

  2. Domain interplay in the urokinase receptor. Requirement for the third domain in high affinity ligand binding and demonstration of ligand contact sites in distinct receptor domains

    DEFF Research Database (Denmark)

    Behrendt, N; Ronne, E; Dano, K

    1996-01-01

    The urokinase plasminogen activator receptor (uPAR) is a membrane protein comprised of three extracellular domains. In order to study the importance of this domain organization in the ligand-binding process of the receptor we subjected a recombinant, soluble uPAR (suPAR) to specific proteolytic...

  3. Cell-induced potentiation of the plasminogen activation system is abolished by a monoclonal antibody that recognizes the NH2-terminal domain of the urokinase receptor

    DEFF Research Database (Denmark)

    Rønne, E; Behrendt, N; Ellis, V

    1991-01-01

    We have raised four monoclonal antibodies recognizing different epitopes within the human cell-surface receptor for urokinase-type plasminogen activator (u-PA). One of these antibodies completely abolishes the potentiation of plasmin generation observed upon incubation of the zymogens pro...

  4. The serum level of soluble urokinase receptor is elevated in tuberculosis patients and predicts mortality during treatment: a community study from Guinea-Bissau

    DEFF Research Database (Denmark)

    Eugen-Olsen, Jesper; Gustafson, P; Sidenius, N

    2002-01-01

    OBJECTIVE: To investigate whether the serum level of soluble urokinase plasminogen activator receptor (suPAR) carries prognostic information in individuals infected with Mycobacterium tuberculosis. DESIGN: suPAR was measured by ELISA in 262 individuals at the time of enrolment into a cohort based...

  5. Urokinase-type plasminogen activator receptor plays a role in neutrophil migration during lipopolysaccharide-induced peritoneal inflammation but not during Escherichia coli-induced peritonitis

    NARCIS (Netherlands)

    Renckens, Rosemarijn; Roelofs, Joris J. T. H.; Florquin, Sandrine; van der Poll, Tom

    2006-01-01

    BACKGROUND: Urokinase-type plasminogen activator receptor (uPAR) is expressed on many different cells, including leukocytes. uPAR has been implicated to play a role in neutrophil migration to sites of inflammation. METHODS: To determine the role that uPAR plays in neutrophil recruitment in response

  6. Dead Space Ventilation Parallels Changes in Scintigraphic Vascular Obstruction at Recurrence of Pulmonary Embolism and after Thrombolytic Therapy: A Case Report

    OpenAIRE

    Marc A Rodger; Gwynne Jones; Francois Raymond; Daniel Lalonde; Mike Proulx; Lothar Huebsch; Christopher Bredeson

    1998-01-01

    Physiological and alveolar dead space ventilation both increase in pulmonary embolism (PE) in proportion to the severity of vascular obstruction. The case of a patient with recurrent PE while on heparin therapy is presented. The recurrence was characterized clinically by severe pulmonary vascular obstruction and right heart dysfunction. The patient was treated with thrombolytic therapy, with excellent clinical and scintigraphic resolution. Dead space ventilation measurements at baseline, at t...

  7. Comparison of the efficacy and safety of thrombolytic therapy for st-elevation myocardial infarction in patients with and without diabetes mellitus

    International Nuclear Information System (INIS)

    Shah, I.; Hafizullah, M.; Shah, S.T.; Gul, A.M.; Iqbal, A.

    2012-01-01

    Objective: This study compared the efficacy and safety of streptokinase as thrombolytic agent for ST-elevation myocardial infarction (STEMI) in patients with and without diabetes mellitus. Methodology: This prospective interventional study was carried out in the department of Cardiology, Postgraduate Medical Institute Govt. Lady Reading Hospital Peshawar. A total of 444 patients admitted to coronary care unit with STEMI and eligible for thrombolytic therapy (no contraindications per AHA/ACC guidelines) were studied from December 2009 to December 2010. Among these half of patients were diabetic while rests were non-diabetic. Streptokinase was administered to all patients. Resolution (reduction) of elevated ST segment was evaluated after 90 min of streptokinase administration. Complications of streptokinase infusion including hypotension, shock and hemorrhage was noted. Results: Failed reperfusion (<30% ST resolution) was significantly higher in diabetic as compared to non-diabetic patients (21.6% vs. 9.5%; p<0.0003) while successful reperfusion (=70% ST-resolution) was significantly higher in non-diabetic than diabetic patients (66.7% vs. 49.1%; p<0.0001). Complication rates between the two groups were statistically similar. Hypotension occurred in 45 (20.3%) and 51 (23%); p=0.458 patients in non-diabetic and diabetic group respectively while shock occurred in 10 (4.5%) and 13 (5.9%); p= 0.506 and hemorrhagic manifestations in 13 (5.9%) and 10 (4.5%); p=0.294 patients respectively. Conclusion: The outcome of thrombolytic therapy is adversely affected by Diabetes mellitus in patients with ST-elevation myocardial infarction. Secondly the risk of hazards associated with thrombolytic therapy is same in both diabetic and non-diabetic patients. (author)

  8. Circulating soluble urokinase plasminogen activator receptor levels and peripheral arterial disease outcomes.

    Science.gov (United States)

    Samman Tahhan, Ayman; Hayek, Salim S; Sandesara, Pratik; Hajjari, Jamal; Hammadah, Muhammad; O'Neal, Wesley T; Kelli, Heval M; Alkhoder, Ayman; Ghasemzadeh, Nima; Ko, Yi-An; Aida, Hiroshi; Gafeer, Mohamad Mazen; Abdelhadi, Naser; Mohammed, Kareem Hosny; Patel, Keyur; Arya, Shipra; Reiser, Jochen; Vaccarino, Viola; Sperling, Laurence; Quyyumi, Arshed

    2017-09-01

    Circulating soluble urokinase plasminogen activator receptor (suPAR) is a marker of immune activation associated with atherosclerosis. Whether suPAR levels are associated with prevalent peripheral arterial disease (PAD) and its adverse outcomes remains unknown and is the aim of the study. SuPAR levels were measured in 5810 patients (mean age 63 years, 63% male, 77% with obstructive coronary artery disease [CAD]) undergoing cardiac catheterization. The presence of PAD (n = 967, 17%) was classified as carotid (36%), lower/upper extremities (30%), aortic (15%) and multisite disease (19%). Multivariable logistic and Cox regression models were used to determine independent predictors of prevalent PAD and outcomes including all-cause death, cardiovascular death and PAD-related events after adjustment for age, gender, race, body mass index, smoking, diabetes, hypertension, hyperlipidemia, renal function, heart failure history, and obstructive CAD. Plasma suPAR levels were 22.5% (p < 0.001) higher in patients with PAD compared to those without PAD. Plasma suPAR was higher in patients with more extensive PAD (≥2 compared to single site) p < 0.001. After multivariable adjustment, suPAR was associated with prevalent PAD; odds ratio (OR) for highest compared to lowest tertile of 2.0, 95% CI (1.6-2.5) p < 0.001. In Cox survival analyses adjusted for clinical characteristics and medication regimen, suPAR (in the highest vs. lowest tertile) remained an independent predictor of all-cause death [HR 3.1, 95% CI (1.9-5.3)], cardiovascular death [HR 3.5, 95% CI (1.8-7.0)] and PAD-related events [HR = 1.8, 95% CI (1.3-2.6) p < 0.001 for all]. Plasma suPAR level is predictive of prevalent PAD and of incident cardiovascular and PAD-related events. Whether SuPAR measurement can help screen, risk stratify, or monitor therapeutic responses in PAD requires further investigation. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Soluble urokinase-type plasminogen activator receptor is a novel biomarker predicting acute exacerbation in COPD

    Directory of Open Access Journals (Sweden)

    Gumus A

    2015-02-01

    Full Text Available Aziz Gumus,1 Nejat Altintas,2 Halit Cinarka,1 Aynur Kirbas,3 Muge Haziroglu,1 Mevlut Karatas,1 Unal Sahin1 1Department of Pulmonary Medicine, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey; 2Department of Pulmonary Medicine, School of Medicine, Namik Kemal University, Tekirdag, Turkey; 3Department of Clinical Biochemistry, School of Medicine, Recep Tayyip Erdogan University, Rize, Turkey Background: Chronic obstructive pulmonary disease (COPD is a chronic inflammatory condition, and progresses with acute exacerbations. (AE. During AE, levels of acute phase reactants such as C-reactive protein (CRP and inflammatory cells in the circulation increase. Soluble urokinase-type plasminogen activator receptor (suPAR levels increase in acute viral and bacterial infections and in diseases involving chronic inflammation. The purpose of this study was to investigate the effectiveness of suPAR in predicting diagnosis of AE of COPD (AE-COPD and response to treatment. Methods: The study population consisted of 43 patients diagnosed with AE-COPD and 30 healthy controls. suPAR, CRP, and fibrinogen levels were measured on the first day of hospitalization and on the seventh day of treatment. Results: We found that fibrinogen (P<0.001, CRP (P<0.001, and suPAR (P<0.001 were significantly higher in patients with AE-COPD than in healthy controls. Fibrinogen (P<0.001, CRP (P=0.001, and suPAR (P<0.001 were significantly decreased by the seventh day of treatment. However, the area under receiver operator characteristic curve showed that suPAR is superior to CRP and fibrinogen in distinguishing AE-COPD. There was a correlation between fibrinogen, CRP, and suPAR. However, only fibrinogen was a powerful predictor of suPAR in multiple linear regression. In multiple logistic regression, only suPAR and fibrinogen were strong predictors of AE-COPD (P=0.002 and P=0.014, respectively. Serum suPAR was negatively correlated with forced expiratory volume in 1

  10. Reasons for not receiving thrombolytic therapy in patients with acute myocardial infarction admitted to Bu-Ali Sina Hospital in Qazvin (2013-14

    Directory of Open Access Journals (Sweden)

    MM. Daei

    2017-04-01

    Full Text Available This hospital-based cross-sectional study was conducted in 2013-14 in Qazvin Bu-Ali Sina Hospital. 170 patients with acute myocardial infarction who not receiving thrombolytic therapy entered the study and were analyzed. Medical history, physical examination, twelve lead ECG and cardiac biomarkers were obtained. The mean age of the patients was 63.4±14.4 years (from 19 to 90 years. 110 (64.7% of the patients were male and 48 (28.2% were diabetic. 86 (50% of patients due to late presentation and 47 (28% due to lack of diagnosis and 29 (17% due to contraindication and 8 (5% due to autolysis or coronary spam were not received thrombolytic therapy. We could reduce failure of receiving thrombolytic therapy more than seventy five percent with increasing people's awareness about the symptoms of myocardial infarction and skills of health staff in relation to the proper and timely diagnosis of myocardial infarction.

  11. Thrombolytic therapy with rt-PA and transcranial color Doppler ultrasound (TCCS) combined with microbubbles for embolic thrombus.

    Science.gov (United States)

    Ren, Xinping; Wang, Yong; Wang, Yi; Chen, Hong; Chen, Li; Liu, Yi; Xue, Chengshi

    2015-11-01

    To investigate the efficacy of transcranial color Doppler ultrasound (TCCS) combined with microbubbles (MBs) and rt-PA (recombinant tissue plasminogen activator) for thrombolysis in vivo. An arterial embolization model was established in Sprague-Dawley rats by retrograde placement of autologous thrombi into the common carotid artery followed by ligation of external carotid artery and temporary occlusion of the carotid artery and internal carotid artery by clamping. The animals were divided into 5 groups with 6 rats in each group: ① untreated control group, ② rt-PA group, ③ TCCS+MBs group, ④ TCCS+MBs+rt-PA group, ⑤ TCCS+MBs+1/2 rt-PA+group. Thrombolytic effects including recanalization rate and recanalization grade were evaluated with grayscale and color Doppler ultrasound post treatment. Examination of histological change in the involved vessel was performed at the end of the experiments. Thrombolysis in terms of recanalization rate and recanalization grade was observed in the treated groups in a time-dependent manner, except the TCCS+MBs group. Addition of rt-PA remarkably enhanced the therapeutic lysis in TCCS+MBs group. However, no difference of therapeutic effects existed between TCCS+MBs+rt-PA group and TCCS+MBs+1/2 rt-PA group. TCCS+MBs combined with rt-PA is a relatively effective approach for ischemic arterial thrombosis with an additive or synergistic effect. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Thrombolytics for late superior caval vein thrombus in a patient with tricuspid atresia and single-lung Glenn anastomosis.

    Science.gov (United States)

    Bonnel, Alexander R; Paruchuri, Vijayapraveena; Franklin, Wayne J

    2016-01-01

    Those with cyanotic heart disease have an elevated bleeding risk but also are hypercoaguable. Treating haemodynamically significant thrombi in this unique cohort poses a monumental challenge. Case A 29-year-old women with tricuspid atresia and left pulmonary artery atresia presented with superior caval vein syndrome. She had a right modified Blalock-Taussig shunt as a neonate. A left modified Blalock-Taussig shunt performed later failed to establish flow to her left lung. At age 5, she had a Fontan procedure to the right lung but could not tolerate the physiology and had a low cardiac output syndrome. The Fontan was taken down and she was left with a Glenn anastamosis to the right pulmonary artery. She did well for years until she had dyspnea, upper extremity oedema and "facial fullness". On examination she was tachycardic, hypotensive, and more desaturated than baseline. She also had facial plethora. Decision-making Echocardiogram showed a large 9 × 3 mm nearly occlusive thrombus in the superior caval vein at the bifurcation of the left and right innominate veins. An emergent venogram confirmed the location and size of the thrombus. Given the thrombus burden and potential for distal embolisation through the Glenn to the single functional lung, we chose to treat the patient with thrombolytics. She had uncomplicated ICU course and was sent home on warfarin. Follow-up echocardiogram showed complete resolution of clot. This case shows the importance of history and physical exam in caring for this complex cohort of adult patients with CHD.

  13. [Use of coronary angioplasty in acute myocardial infarction without previous use of thrombolytic agents. Analysis of 201 patients].

    Science.gov (United States)

    Mattos, L A; Cano, M N; Maldonado, G; Feres, F; Pinto, I M; Tanajura, L F; Piegas, L S; Barbosa, M; Timerman, A; Paulista, P P

    1990-11-01

    To evaluate the experience with the use of primary PTCA in the set of acute myocardial infarction (AMI) without the previous administration of thrombolytic agents. Two hundred and one patients with AMI, aged 35 to 86 years (mean = 57.2). There were 83.5% men. Twenty patients were older than 70 years and 48.2% had an anterior AMI. PTCA was performed early in the AMI, with a delay no longer than 12 hours. In 95%, it was done solely to the infarct related artery. Seventy percent patients were in Killip class I, 21% in class II, and 8% in classes III and IV (more than 50% of this subset of patients were in cardiogenic shock). Primary success was achieved in 84.5%. In hospital mortality was 5.9%, and there were 7% reinfarctions. Among the 84 patients who underwent a late cinecoronariography study, there were 19% restenosis and 8.3% reocclusions. In the long term follow up 75% were asymptomatic. Repeat PTCA was required in 10.2% of the cases, late coronary surgery was performed on 10.8% of the patients, and post-hospital cardiac mortality was 8.8% during an average follow up of 28 months (range 2-72 months). Primary PTCA is a effective way of reperfusion in the AMI, with a high primary success, low complications rate and without any major contraindications.

  14. Plasminogen activation by receptor-bound urokinase. A kinetic study with both cell-associated and isolated receptor

    DEFF Research Database (Denmark)

    Ellis, V; Behrendt, N; Danø, K

    1991-01-01

    importance for the efficient activation of Plg by receptor-bound uPA. Plasmin generated in the cell-surface Plg activation system described here was also observed to be protected from its principal physiological inhibitor alpha-2-antiplasmin. Together, these data demonstrate that the cell surface constitutes......The specific cellular receptor for urokinase-type plasminogen activator (uPA) is found on a variety of cell types and has been postulated to play a central role in the mediation of pericellular proteolytic activity. We have studied the kinetics of plasminogen (Plg) activation catalyzed by u.......67 microM, below the physiological Plg concentration of 2 microM. A concomitant 6-fold reduction in kcat resulted in an increase in the overall catalytic efficiency, kcat/Km, of 5.7-fold. This high affinity Plg activation was abolished in the presence of a Plg-binding antagonist. In contrast to intact...

  15. Soluble urokinase plasminogen activator receptor levels are elevated and associated with complications in patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Theilade, S; Lyngbaek, S; Hansen, T W

    2015-01-01

    OBJECTIVES: Soluble urokinase plasminogen activator receptor (suPAR) is a marker of inflammation and endothelial dysfunction. We investigated the associations between suPAR and diabetes, including diabetes duration and complications, in patients with type 1 diabetes. DESIGN, SETTING AND SUBJECTS......: From 2009 to 2011, 667 patients with type 1 diabetes and 51 nondiabetic control subjects were included in a cross-sectional study at Steno Diabetes Center, Gentofte, Denmark. suPAR levels were measured with an enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: The investigated diabetic...... of arterial stiffness (pulse wave velocity ≥10 m s(-1) ). Analyses were adjusted for gender, age, systolic blood pressure, estimated glomerular filtration rate, UAER, glycated haemoglobin (HbA1c ), total cholesterol, body mass index, C-reactive protein, antihypertensive treatment and smoking. RESULTS: Soluble...

  16. Soluble urokinase receptor levels in plasma during 5 years of highly active antiretroviral therapy in HIV-1-infected patients

    DEFF Research Database (Denmark)

    Ostrowski, Sisse R; Katzenstein, Terese L; Piironen, Timo

    2004-01-01

    High blood levels of the soluble urokinase receptor (suPAR) strongly predict increased mortality in human immunodeficiency virus-1 (HIV-1)-infected patients. This study investigated the plasma concentration of suPAR in 29 treatment-naive HIV-1-infected patients during 5 years treatment with highly...... active antiretroviral therapy (HAART). Plasma suPAR decreased after introducing HAART, most pronounced during the first treatment year. The change in plasma suPAR was independent of changes in viral replication and CD4+ cells but it was strongly correlated with plasma levels of the soluble TNF receptor...... II. Compared with healthy individuals, plasma suPAR and sTN-FrII was increased in untreated patients. After initiating HAART, plasma sTNFrII remained increased whereas plasma suPAR decreased to a level comparable with healthy individuals. The present data indicate that the circulating suPAR level...

  17. Soluble urokinase receptor is elevated in cerebrospinal fluid from patients with purulent meningitis and is associated with fatal outcome

    DEFF Research Database (Denmark)

    Ostergaard, Christian; Benfield, Thomas; Lundgren, Jens D

    2004-01-01

    The urokinase-type plasminogen activator system has been suggested to play a pathophysiological role in brain damage. The aim of this study was to evaluate CSF levels of suPAR in 183 patients clinically suspected of having meningitis on admission. Of these, 54 patients were found to have purulent...... meningitis, 63 had lymphocytic meningitis, 12 had encephalitis, and 54 patients were suspected of, but had no evidence of, meningitis. There was a significant difference in suPAR levels among patient groups (Kruskal Wallis test, p ... infection (purulent meningitis: median suPAR 2.41 microg/l (range 0.12-35), lymphocytic meningitis: 1.10 microg/l (0.15-5.31), and encephalitis (1.77 microg/l (0.17-11.7)) than in patients without meningitis (0.64 microg/l (0-5.34) (Dunn's multiple comparison test, p

  18. Involvement of urokinase receptor in the cross-talk between human hematopoietic stem cells and bone marrow microenvironment

    DEFF Research Database (Denmark)

    Selleri, Carmine; Montuori, Nunzia; Salvati, Annamaria

    2016-01-01

    Hematopoietic stem cells (HSCs) reside in bone marrow (BM) and can be induced to mobilize into the circulation for transplantation. Homing and lodgement into BM of transplanted HSCs are the first critical steps in their engraftment and involve multiple interactions between HSCs and the BM...... Culture (LTC)-Initiating Cells (ICs) and in the release of clonogenic progenitors from LTCs of CD34+ HSCs. Further, suPAR increases adhesion and survival of CD34+ KG1 AML cells, whereas uPAR84-95 increases their proliferation.Thus, circulating DIIDIII-suPAR, strongly increased in HSC mobilization...... microenvironment.uPAR is a three domain receptor (DIDIIDIII) which binds urokinase, vitronectin, integrins. uPAR can be cleaved and shed from the cell surface generating full-length and cleaved soluble forms (suPAR and DIIDIII-suPAR). DIIDIII-suPAR can bind fMLF receptors through the SRSRY sequence (residues 88...

  19. Influential factors of clinical outcome of local intra-arterial thrombolysis using urokinase in patients with hyperacute ischemic stroke

    International Nuclear Information System (INIS)

    Song, Jae Min; Yoon, Woong; Kim, Jae Kyu; Seo, Jeong Jin; Heo, Sook Hee; Park, Jin Gyoon; Jeong, Yoon Yeon; Kang, Heoung Keun

    2002-01-01

    To evaluate the clinical outcome and other relevant factors in cases where local intra-arterial thrombolysis (LIT) is used for the treatment of hyperacute ischemic stroke. Forty-eight hyperacute ischemic stroke patients were treated by LIT, using urokinase, within six hours of ictus, and for evaluation of their neurological status, the national institutes of health stroke scale (NIHSS) score was used. Angiography recanalization was classified according to Mori recanalization grades. Three months after LIT, the outcome was assessed by clinical examination using the modified rankin scale (good outcome: RS=0-3; poor outcome: RS=4-6). In all patients, the findings of pre- and post- LIT CT, and angiography, as well as neurological status and hemorrhagic complications, were also analysed. Thirty-three patients had occlusions of the middle cerebral artery (MCA), and 15, of the internal carotid artery (ICA). The NIHSS score averaged 16.9 at the onset of therapy and 13.5 at 24 hours later. Successful recanalization (Mori grade 3,4) was achieved in 28 (58.3%) of 48 patients, but in 20 (41.7%) the attempt failed. Twenty-two (45.8%) of the 48 patients had a good outcome, but in (54.2%) the outcome was poor. Thirteen (40.6%) of 32 patients with MCA occlusions and 13 (81.2%) of 16 with ICA occlusions had a poor outcome. Eight patients (16.7%) died. Overall, hemorrhages occured in 20 (41.7%) of 48 patients, with symptomatic hemorrhage in ten. Five (50%) of these ten died. LIT using urokinase for hyperacute ischemic stroke is feasible; patients with MCA occlusions had better outcomes than those with ICA occlusions. Hemorrhagic complications of LIT were frequent, and in cases of symptomatic hemorrhage a fatal outcome may be expected

  20. Influential factors of clinical outcome of local intra-arterial thrombolysis using urokinase in patients with hyperacute ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Song, Jae Min; Yoon, Woong; Kim, Jae Kyu; Seo, Jeong Jin; Heo, Sook Hee; Park, Jin Gyoon; Jeong, Yoon Yeon; Kang, Heoung Keun [Chonam University Hospital, Kwangju (Korea, Republic of)

    2002-10-01

    To evaluate the clinical outcome and other relevant factors in cases where local intra-arterial thrombolysis (LIT) is used for the treatment of hyperacute ischemic stroke. Forty-eight hyperacute ischemic stroke patients were treated by LIT, using urokinase, within six hours of ictus, and for evaluation of their neurological status, the national institutes of health stroke scale (NIHSS) score was used. Angiography recanalization was classified according to Mori recanalization grades. Three months after LIT, the outcome was assessed by clinical examination using the modified rankin scale (good outcome: RS=0-3; poor outcome: RS=4-6). In all patients, the findings of pre- and post- LIT CT, and angiography, as well as neurological status and hemorrhagic complications, were also analysed. Thirty-three patients had occlusions of the middle cerebral artery (MCA), and 15, of the internal carotid artery (ICA). The NIHSS score averaged 16.9 at the onset of therapy and 13.5 at 24 hours later. Successful recanalization (Mori grade 3,4) was achieved in 28 (58.3%) of 48 patients, but in 20 (41.7%) the attempt failed. Twenty-two (45.8%) of the 48 patients had a good outcome, but in (54.2%) the outcome was poor. Thirteen (40.6%) of 32 patients with MCA occlusions and 13 (81.2%) of 16 with ICA occlusions had a poor outcome. Eight patients (16.7%) died. Overall, hemorrhages occured in 20 (41.7%) of 48 patients, with symptomatic hemorrhage in ten. Five (50%) of these ten died. LIT using urokinase for hyperacute ischemic stroke is feasible; patients with MCA occlusions had better outcomes than those with ICA occlusions. Hemorrhagic complications of LIT were frequent, and in cases of symptomatic hemorrhage a fatal outcome may be expected.

  1. [Transradial approach for transcatheter selective superior mesenteric artery urokinase infusion therapy in patients with acute extensive portal and superior mesenteric vein thrombosis].

    Science.gov (United States)

    Wang, Yan; Wang, Mao-qiang; Liu, Feng-yong; Wang, Zhi-jun; Duan, Feng; Song, Peng

    2012-06-05

    To evaluate the feasibility and efficacy of urokinase infusion therapy via a transradial approach for transcatheter superior mesenteric artery (SMA) in patients with acute extensive portal and superior mesenteric venous thrombosis. During a period of 8 years, 47 patients with acute extensive thrombosis of portal vein (PV) and superior mesenteric veins (SMV) received urokinase infusion therapy by transcatheter selective SMA via radial artery. Their mean age was 44 ± 13 years (range: 19 - 65). Through radial sheath, a 5F catheter was placed into SMA and subsequently the infusion of urokinase was given for 5 - 11 days (mean: 7.1 ± 2.5). Adequate anticoagulation was initiated during treatment, throughout hospitalization and post-discharge. Follow-up contrast-enhanced computed tomography (CT) was performed in each patient every 3 days and before the removal of infusion catheter. Termination of urokinase infusion therapy was decided on the basis of clinical and radiographic findings. Technical success was achieved in all patients. Two patients had worsening abdominal pain, developed the signs of peritonitis at 24 hours after interventional treatment and underwent eventual laparotomy with the resection of necrotic bowel. Substantial clinical improvement was observed in 45 (95.7%) of them after the procedure. Minor complications at the radial puncture site were observed in 7 patients (14.9%) and infusion therapy continued. Follow-up CT scans at pre-discharge demonstrated a nearly complete disappearance of PV-SMV thrombosis in 29 patients (64.4%) and partial recanalization of PV-SMV thrombosis in 16 patients (35.6%). They were discharged at 9 - 20 days (mean: 12 ± 6) post-admission. The mean post-discharge duration of follow-up was 48 ± 20 months. Recurrent episodes of PV and SMV thrombosis were observed in 2 (4.4%) patients at 6 months and 5 years respectively post-discharge and they were treated successfully with urokinase infusion. The transcatheter SMA urokinase

  2. Preclinical evaluation of a urokinase plasminogen activator receptor-targeted nanoprobe in rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Chen Y

    2015-10-01

    Full Text Available Yushu Chen,1 Li Gong,2 Ning Gao,3 Jichun Liao,1 Jiayu Sun,1 Yuqing Wang,1 Lei Wang,1 Pengjin Zhu,1 Qing Fan,1 Yongqiang Andrew Wang,4 Wen Zeng,2 Hui Mao,3 Lily Yang,5 Fabao Gao11Molecular Imaging Center, Department of Radiology, West China Hospital, Sichuan University, Chengdu, 2Sichuan Primed Bio-Tech Group Co, Ltd, Chengdu, People’s Republic of China; 3Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, 4Ocean NanoTech, LLC, San Diego, CA, 5Department of Surgery, Emory University School of Medicine, Atlanta, GA, USAPurpose: To translate a recombinant peptide containing the amino-terminal fragment (ATF of urokinase plasminogen activator receptor-targeted magnetic iron oxide (IO nanoparticles (uPAR-targeted human ATF-IONPs into clinical applications, we conducted a pilot study to evaluate the toxicity and pharmacokinetics of this nanoparticle in normal rhesus monkeys.Methods: We assessed the changes in the following: magnetic resonance imaging (MRI signals from pretreatment stage to 14 days posttreatment, serum iron concentrations from 5 minutes posttreatment to 12 weeks posttreatment, routine blood examination and serum chemistry analysis results from pretreatment stage to 12 weeks after administration, and results of staining of the liver with Perls’ Prussian Blue and hematoxylin–eosin at 24 hours and 3 months posttreatment in two rhesus monkeys following an intravenous administration of the targeted nanoparticles either with a polyethylene glycol (ATF-PEG-IONP or without a PEG (ATF-IONP coating.Results: The levels of alkaline phosphatase, alanine transaminase, and direct bilirubin in the two monkeys increased immediately after the administration of the IONPs but returned to normal within 20 days and stayed within the normal reference range 3 months after the injection. The creatinine levels of the two monkeys stayed within the normal range during the study. In addition, red blood cells

  3. Association of Serum Soluble Urokinase Receptor Levels With Progression of Kidney Disease in Children.

    Science.gov (United States)

    Schaefer, Franz; Trachtman, Howard; Wühl, Elke; Kirchner, Marietta; Hayek, Salim S; Anarat, Ali; Duzova, Ali; Mir, Sevgi; Paripovic, Dusan; Yilmaz, Alev; Lugani, Francesca; Arbeiter, Klaus; Litwin, Mieczyslaw; Oh, Jun; Matteucci, Maria Chiara; Gellermann, Jutta; Wygoda, Simone; Jankauskiene, Augustina; Klaus, Günter; Dusek, Jiri; Testa, Sara; Zurowska, Aleksandra; Caldas Afonso, Alberto; Tracy, Melissa; Wei, Changli; Sever, Sanja; Smoyer, William; Reiser, Jochen

    2017-11-06

    Conventional methods to diagnose and monitor chronic kidney disease (CKD) in children, such as creatinine level and cystatin C-derived estimated glomerular filtration rate (eGFR) and assessment of proteinuria in spot or timed urine samples, are of limited value in identifying patients at risk of progressive kidney function loss. Serum soluble urokinase receptor (suPAR) levels strongly predict incident CKD stage 3 in adults. To determine whether elevated suPAR levels are associated with renal disease progression in children with CKD. Post hoc analysis of 2 prospectively followed up pediatric CKD cohorts, ie, the ESCAPE Trial (1999-2007) and the 4C Study (2010-2016), with serum suPAR level measured at enrollment and longitudinal eGFR measured prospectively. In the 2 trials, a total of 898 children were observed at 30 (ESCAPE Trial; n = 256) and 55 (4C Study; n = 642) tertiary care hospitals in 13 European countries. Renal diagnoses included congenital anomalies of the kidneys and urinary tract (n = 637 [70.9%]), tubulointerstitial nephropathies (n = 92 [10.2%]), glomerulopathies (n = 69 [7.7%]), postischemic CKD (n = 42 [4.7%]), and other CKD (n = 58 [6.5%]). Total follow-up duration was up to 7.9 years, and median follow-up was 3.1 years. Analyses were conducted from October 2016 to December 2016. Serum suPAR level was measured at enrollment, and eGFR was measured every 2 months in the ESCAPE Trial and every 6 months in the 4C Study. The primary end point of CKD progression was a composite of 50% eGFR loss, eGFR less than 10 mL/min/1.73 m2, or initiation of renal replacement therapy. The primary end point in this study was renal survival, defined as a composite of 50% loss of GFR that persisted for at least 1 month, the start of renal replacement therapy, or an eGFR less than 10 mL/min/1.73 m2. Of the 898 included children, 560 (62.4%) were male, and the mean (SD) patient age at enrollment was 11.9 (3.5) years. The mean (SD) eGFR was 34

  4. Factors influencing nonadministration of thrombolytic therapy in early arrival strokes in a university hospital in Hyderabad, India

    Directory of Open Access Journals (Sweden)

    Lalitha Pidaparthi

    2016-01-01

    Full Text Available Background: It is a well-known fact that very few patients of stroke arrive at the hospital within the window period of thrombolysis. Even among those who do, not all receive thrombolytic therapy. Objective: The objectives of this study were to determine the proportion of early arrival ischemic strokes (within 6 h of stroke onset in our hospital and to evaluate the causes of nonadministration of intravenous and/or intraarterial thrombolysis in them. Materials and Methods: Data of all early arrival acute stroke patients between January 2010 and January 2015 were included. Factors determining nonadministration of intravenous and/or intraarterial thrombolysis in early arrival strokes were analyzed. Results: Out of 2,593 stroke patients, only 145 (5.6% patients presented within 6 h of stroke onset and among them 118 (81.4% patients had ischemic stroke and 27 (18.6% patients had hemorrhagic stroke. A total of 89/118 (75.4% patients were thrombolyzed. The reasons for nonadministration of thrombolysis in the remaining 29 patients were analyzed, which included unavoidable factors in 8/29 patients [massive infarct (N = 4, hemorrhagic infarct (N = 1, gastrointestinal bleed (N = 1, oral anticoagulant usage with prolonged international normalized ratio (INR (N = 1, and recent cataract surgery (N = 1]. Avoidable factors were found for 21/29 patients, include nonaffordability (N = 7, fear of bleed (N = 4, rapidly improving symptoms (N = 4, mild stroke (N = 2, delayed neurologist referral within the hospital (N = 2, and logistic difficulty in organizing endovascular treatment (N = 2. Conclusion: One-fourth of early ischemic stroke patients in our study were not thrombolyzed even though they arrived within the window period. The majority of the reasons for nonadministration of thrombolysis were potentially preventable, such as nonaffordability, intrahospital delay, and nonavailability of newer endovascular interventions.

  5. Soluble urokinase-type plasminogen activator receptor levels in patients with burn injuries and inhalation trauma requiring mechanical ventilation: an observational cohort study

    OpenAIRE

    Backes, Yara; van der Sluijs, Koenraad F; Tuip de Boer, Anita M; Hofstra, Jorrit Jan; Vlaar, Alexander PJ; Determann, Rogier M; Knape, Paul; Mackie, David P; Schultz, Marcus J

    2011-01-01

    Introduction Soluble urokinase-type plasminogen activator receptor (suPAR) has been proposed as a biologic marker of fibrinolysis and inflammation. The aim of this study was to investigate the diagnostic and prognostic value of systemic and pulmonary levels of suPAR in burn patients with inhalation trauma who need mechanical ventilation. Methods suPAR was measured in plasma and nondirected lung-lavage fluid of mechanically ventilated burn patients with inhalation trauma. The samples were obta...

  6. Transradial Approach for Transcatheter Selective Superior Mesenteric Artery Urokinase Infusion Therapy in Patients with Acute Extensive Portal and Superior Mesenteric Vein Thrombosis

    International Nuclear Information System (INIS)

    Wang Maoqiang; Guo Liping; Lin Hanying; Liu Fengyong; Duan Feng; Wang Zhijun

    2010-01-01

    The purpose of this investigation was to assess the feasibility and effectiveness of transradial approach for transcatheter superior mesenteric artery (SMA) urokinase infusion therapy in patients with acute extensive portal and superior mesenteric venous thrombosis. During a period of 7 years, 16 patients with acute extensive thrombosis of the portal (PV) and superior mesenteric veins (SMV) were treated by transcatheter selective SMA urokinase infusion therapy by way of the radial artery. The mean age of the patients was 39.5 years. Through the radial sheath, a 5F Cobra catheter was inserted into the SMA, and continuous infusion of urokinase was performed for 5-11 days (7.1 ± 2.5 days). Adequate anticoagulation was given during treatment, throughout hospitalization, and after discharge. Technical success was achieved in all 16 patients. Substantial clinical improvement was seen in these 16 patients after the procedure. Minor complications at the radial puncture site were observed in 5 patients, but trans-SMA infusion therapy was not interrupted. Follow-up computed tomography scan before discharge demonstrated nearly complete disappearance of PV-SMV thrombosis in 9 patients and partial recanalization of PV-SMV thrombosis in 7 patients. The 16 patients were discharged 9-19 days (12 ± 6.0 days) after admission. Mean duration of follow-up after hospital discharge was 44 ± 18.5 months, and no recurrent episodes of PV-SMV thrombosis developed during that time period. Transradial approach for transcatheter selective SMA urokinase infusion therapy in addition to anticoagulation is a safe and effective therapy for the management of patients with acute extensive PV-SMV thrombosis.

  7. Urokinase plasminogen activator (uPA and plasminogen activator inhibitor type-1 (PAI-1 in breast cancer - correlation with traditional prognostic factors

    Directory of Open Access Journals (Sweden)

    Lampelj Maja

    2015-12-01

    Full Text Available Background. Urokinase plasminogen activator (uPA and plasminogen activator inhibitor type-1 (PAI-1 play a key role in tumour invasion and metastasis. High levels of both proteolytic enzymes are associated with poor prognosis in breast cancer patients. The purpose of this study was to evaluate the correlation between traditional prognostic factors and uPA and PAI-1 expression in primary tumour of breast cancer patients.

  8. Thrombolytic Effects of the Snake Venom Disintegrin Saxatilin Determined by Novel Assessment Methods: A FeCl3-Induced Thrombosis Model in Mice

    Science.gov (United States)

    Kim, Young Dae; Nam, Hyo Suk; Kang, Sungsoo; Yang, Seung-Hee; Heo, Ji Hoe

    2013-01-01

    Saxatilin, a novel disintegrin purified and cloned from the venom of the Korean snake Gloydius saxatilis, strongly inhibits activation and aggregation of platelets. Glycoprotein (GP) IIb/IIIa receptor antagonists can resolve thrombus, so saxatilin might also have thrombolytic effects. We investigated the thrombolytic effects of saxatilin in mice using a ferric chloride-induced carotid arterial thrombosis model. Thrombotic occlusion and thrombus resolution were evaluated quantitatively by measuring blood flow in the carotid artery with an ultrasonic flow meter and calculating the degree of flow restoration on a minute-by-minute basis; results were confirmed by histological examination. Saxatilin dissolved thrombi in a dose-dependent manner. Saxatilin at 5 mg/kg restored blood flow to baseline levels. As saxatilin dose increased, time to recanalization decreased. A bolus injection of 10% of a complete dose with continuous infusion of the remaining dose for 60 minutes resulted in effective recanalization without reocclusion. The thrombolytic effect of saxatilin was also demonstrated in vitro using platelet aggregometry by administering saxatilin in preformed thrombi. Bleeding complications were observed in 2 of 71 mice that received saxatilin. Fibrin/fibrinogen zymography and platelet aggregometry studies indicated that saxatilin does not have fibrinolytic activity, but exerted its action on platelets. Integrin-binding assays showed that saxatilin inhibited multiple integrins, specifically α2bβ3 (GP IIb/IIIa), α5β1, αvβ3, αvβ1, and αvβ5, which act on platelet adhesion/aggregation. Saxatilin inhibited multiple integrins by acting on platelets, and was safe and effective in resolving thrombi in mice. PMID:24260554

  9. A comparison of the enzymatic properties of three recombinant isoforms of thrombolytic and antibacterial protein--Destabilase-Lysozyme from medicinal leech.

    Science.gov (United States)

    Kurdyumov, Alexey S; Manuvera, Valentin A; Baskova, Isolda P; Lazarev, Vassili N

    2015-11-21

    Destabilase-Lysozyme (mlDL) is a multifunctional i-type enzyme that has been found in the secretions from the salivary glands of medicinal leeches. mlDL has been shown to exhibit isopeptidase, muramidase and antibacterial activity. This enzyme attracts interest because it expresses thrombolytic activity through isopeptidolysis of the ε-(γ-Glu)-Lys bonds that cross-link polypeptide chains in stabilised fibrin. To date, three isoforms of mlDL have been identified. The enzymatic properties of pure mlDL isoforms have not yet been described because only destabilase complexes containing other proteins could be isolated from the salivary gland secretion and because low product yield from the generation of recombinant proteins has made comprehensive testing difficult. In the present study, we optimised the procedures related to the expression, isolation and purification of active mlDL isoforms (mlDL-Ds1, mlDL-Ds2, mlDL-Ds3) using an Escherichia coli expression system, and we detected and compared their muramidase, lytic, isopeptidase and antimicrobial activities. After optimisation, the product yield was 30 mg per litre of culture. The data obtained in our study led to the suggestion that the recombinant mlDL isoforms isolated from inclusion bodies form stable oligomeric complexes. Analyses of the tested activities revealed that all isoforms exhibited almost identical patterns of pH and ionic strength effects on the activities. We determined that mlDL-Ds1, 2, 3 possessed non-enzymatic antibacterial activity independent of their muramidase activity. For the first time, we demonstrated the fibrinolytic activity of the recombinant mlDL and showed that only intact proteins possessed this activity, suggesting their enzymatic nature. The recombinant Destabilase-Lysozyme isoforms obtained in our study may be considered potential thrombolytic agents that act through a mechanism different from that of common thrombolytics.

  10. PAI-1 4G/5G gene polymorphism is associated with angiographic patency in ST-elevation myocardial infarction patients treated with thrombolytic therapy.

    Science.gov (United States)

    Ozkan, Bugra; Cagliyan, Caglar E; Elbasan, Zafer; Uysal, Onur K; Kalkan, Gulhan Y; Bozkurt, Mehmet; Tekin, Kamuran; Bozdogan, Sevcan T; Ozalp, Ozge; Duran, Mustafa; Sahin, Durmus Y; Cayli, Murat

    2012-09-01

    In this study, we examined the relationship between PAI-1 4G/5G polymorphism and patency of the infarct-related artery after thrombolysis in patients with ST-elevation myocardial infarction (STEMI). Acute STEMI patients who received thrombolytic therapy within first 12 h were included in our study. The PAI-1 4G/5G promoter region insertion/deletion polymorphism was studied from venous blood samples. Patients with the PAI-1 4G/5G gene polymorphism were included in group 1 and the others were included in group 2. Coronary angiography was performed in all patients in the first 24 h after receiving thrombolytic therapy. Thrombolysis in myocardial infarction (TIMI) 0-1 flow in the infarct-related artery was considered as 'no flow', TIMI 2 flow as 'slow flow', and TIMI 3 flow as 'normal flow'. A total of 61 patients were included in our study. Thirty patients (49.2%) were positive for the PAI-1 4G/5G gene polymorphism, whereas 31 of them (50.8%) were in the control group. There were significantly more patients with 'no flow' (14 vs. 6; P=0.02) and less patients with 'normal flow' (8 vs. 19; P=0.02) in group 1. In addition, time to thrombolytic therapy (TTT) was maximum in the 'no flow' group and minimum in the 'normal flow' group (P=0.005). In the logistic regression analysis, TTT (odds ratio: 0.9898; 95% confidence interval: 0.982-0.997; P=0.004) and the PAI-1 4G/5G gene polymorphism (odds ratio: 4.621; 95% confidence interval: 1.399-15.268; P5G gene polymorphism and TTT are associated independently with 'no flow' after thrombolysis in patients with STEMI.

  11. Monitoring of chemotherapy successfulness of Platina/Taxol chemotherapy protocol by using determination of serum urokinase plasminogen activator (uPA and soluble urokinase plasminogen activator receptor (suPAR in patients with ovarian carcinoma FIGO II

    Directory of Open Access Journals (Sweden)

    Dženita Ljuca

    2007-05-01

    Full Text Available In about 70% of cases, ovarian carcinoma has been diagnosed at an advanced stage. Invasion and metastasis of solid tumors request protease activity resulting in basal membrane destruction and surrounding matrix. In that process, urokinase plasminogen activator (uPA and its receptor, urokinase plasminogen activator receptor (suPAR play a key role, that via plasmin activation lead to basal membrane and matrix degradation in surrounding of the tumor, enable to its invasion and metastasis. Determination of serum concentration of those tumor markers can be useful in preoperative as well as in postoperative period. Their serum concentrations in ovarian cancer patients may help in good monitoring of remission or progression during chemotherapy treatment. In late 1950s and eariy 1960s, when it was found out that malignant ovarian tumors were chemosensitive, their chemotherapy treatment has begun. In the beginning it was used only mono-therapy, and by discovering new cytostatics it was replaced by poly-chemotherapy. Now days, in the therapy of advanced stages of ovarian carcinoma combination of cisplatine or carboplatine with paclitaxel is considering as standard treatment. Aim of this study was to determine serum uPA, suPAR and CEA in FIGO II and III patients with different histo-logical type (serous, mucinous, clear cell tumor before and after PT chemotherapy protocol during following three cycles. In this prospective study we have analyzed 17 patients with ovarian carcinoma, those have been after surgery treated by chemotherapy. Serum levels of uPA and suPAR have been determined by ELISA-test (Imubind uPA, Imubind uPAR, American Diagnostica, and CEA by OPUS Imunoassay method. Results of this study have shown that uPA, suPAR and CEA met criteria for prognostic markers for monitoring of successful-ness of platina/taxol chemotherapy protocol for serous, mucinous and clear cell tumor FIGO II and III stage of ovarian carcinoma. In case of PT chemotherapy

  12. Cadmium exposure is associated with soluble urokinase plasminogen activator receptor, a circulating marker of inflammation and future cardiovascular disease

    International Nuclear Information System (INIS)

    Fagerberg, Björn; Borné, Yan; Barregard, Lars; Sallsten, Gerd; Forsgard, Niklas; Hedblad, Bo; Persson, Margaretha; Engström, Gunnar

    2017-01-01

    Background: Diet and smoking are the main sources of cadmium exposure in the general population. Cadmium increases the risk of cardiovascular diseases, and experimental studies show that it induces inflammation. Blood cadmium levels are associated with macrophages in human atherosclerotic plaques. Soluble urokinase-type plasminogen activator receptor (suPAR) is an emerging biomarker for cardiovascular events related to inflammation and atherosclerotic plaques. The aim was to examine whether blood cadmium levels are associated with circulating suPAR and other markers of inflammation. Methods: A population sample of 4648 Swedish middle-aged women and men was examined cross-sectionally in 1991–1994. Plasma suPAR was assessed by ELISA, leukocytes were measured by standard methods, and blood cadmium was analysed by inductively coupled plasma mass spectrometry. Prevalent cardiovascular disease, ultrasound-assessed carotid plaque occurrence, and several possible confounding factors were recorded. Results: After full adjustment for risk factors and confounding variables, a 3-fold increase in blood cadmium was associated with an 10.9% increase in suPAR concentration (p<0.001). In never-smokers, a 3-fold increase in blood cadmium was associated with a 3.7% increase in suPAR concentration (p<0.01) after full adjustment. Blood cadmium was not associated with C-reactive protein, white blood cell count and Lp-PLA2 but with neutrophil/lymphocyte ratio in one of two statistical models. Conclusions: Exposure to cadmium was associated with increased plasma suPAR in the general population, independently of smoking and cardiovascular disease. These results imply that cadmium is a possible cause for raised levels of this inflammatory marker. - Highlights: • Cadmium is a toxic proinflammatory, proatherosclerotic metal. • Soluble urokinase-type plasminogen activator receptor (suPAR) in plasma is a promising proinflammatory marker of atherosclerosis. • Blood cadmium and plasma su

  13. Intravenous thrombolytic treatment experiences in patients with acute ischemic stroke at the University of Kocatepe, Neurology Clinics

    Directory of Open Access Journals (Sweden)

    Serdar Oruç

    2015-12-01

    Full Text Available INTRODUCTION: This study aimed to discuss the results of the intravenous thrombolytic treatment (IV-tPA to acute ischemic stroke patients, in the light of the literature. METHODS: We performed our study with forty acute ischemic stroke patients who were receiving the IV-tPA in the intensive care unit of our neurology clinic between 2011 and 2015.. The demographic, clinical and radiological data were collected retrospectively. The intracranial hemorrhage detected within 3 months after discharge and neurological status at the end of the 3rd month were evaluated by using modified Rankin scale (MRS and National Institutes of Health Stroke Scale (NIHSS scores. The symptom-to-needle time, Alberta stroke programe early computed tomography score (ASPECT and initial and follow-up scores of NIHSS were analyzed. RESULTS: Fifteen patients were female, twenty-five were male, and the mean age was 66.45±10.56. The initial mean NIHSS score was 13±4.33, whereas it was 4,10±3,37at 3rd month. The initial mean ASPECT score was 8.23±1.20. Symptomatic intracranial hemorrhage was detected in 1 patient and asymptomatic intracranial hemorrhage was detected in 6. The mean symptom-to-needle time was 139,0±48,1 minutes. The neurological disability of 13 patients ( %32.5 were fully recovered at the end of the 3rd month, while 7 patients were died. (% 17,5 The initial NIHSS and ASPECT scores were significantly different between group of patients with a MRS score between 0-2 and between 3-6 (p=0.03 and p=0.006; respectively, while the symptom-to-needle time was not different (p=0.79. DISCUSSION AND CONCLUSION: The results of the current study are in accordance with previous studies in the literature. These results have shown that the IV-tPA treatment is efficient and safe treatment modality in acute ischemic stroke, and reduces disability at the end of the 3rd month.

  14. ELISA for complexes between urokinase-type plasminogen activator and its receptor in lung cancer tissue extracts

    DEFF Research Database (Denmark)

    de Witte, H; Pappot, H; Brünner, N

    1997-01-01

    A sandwich-type ELISA has been developed for the assessment of complexes between urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in extracts of squamous cell lung carcinomas. The assay is based on a combination of rabbit polyclonal anti-uPA antibodies and a biotinylated mouse...... anti-uPAR monoclonal antibody (MAb). The detection limit of the assay is approximately 0.5 fmol/ml. A linear dose-response is obtained with up to 40 fmol/ml of uPA:uPAR complexes, while uPA and uPAR separately do not cause any response in the ELISA. A buffer which has been used previously for optimal...... extraction of uPAR yields the highest amounts of uPA:uPAR complexes. Absorption of tumor extracts with anti-uPA or anti-uPAR MAbs results in a complete disappearance of the ELISA signal, demonstrating the specificity of the ELISA. The recovery of chemically cross-linked uPA:uPAR complexes added to tumor...

  15. Inhibition of plasmin, urokinase, tissue plasminogen activator, and C1S by a myxoma virus serine proteinase inhibitor.

    Science.gov (United States)

    Lomas, D A; Evans, D L; Upton, C; McFadden, G; Carrell, R W

    1993-01-05

    The myxoma and malignant rabbit fibroma poxviruses are lethal tumorigenic viruses of rabbits whose virulence is modulated by the production of a virus-encoded secreted serine proteinase inhibitor, SERP-1. This viral protein was detected in medium harvested from myxoma and malignant rabbit fibroma virus-infected cells, and its inhibitory profile has been characterized by gel and kinetic analysis. SERP-1 forms complexes with and inhibits the human fibrinolytic enzymes plasmin, urokinase, and two-chain tissue-type plasminogen activator (association rate constants 3.4 x 10(4), 4.3 x 10(4), and 3.6 x 10(4) M-1 s-1 respectively). It is also able to inhibit C1S, the first enzyme in the complement cascade with an association rate constant which was unaffected by the addition of heparin (1.3 x 10(3) M-1 s-1). SERP-1 acts as a substrate for and is cleaved by thrombin, porcine trypsin, human neutrophil elastase, porcine pancreatic elastase, thermolysin, subtilisin, bovine alpha-chymotrypsin, and factor Xa. Incubation with kallikrein and cathepsin G had no effect. The structure of SERP-1 has been modeled on other members of the serpin family which revealed the characteristic serpin architecture apart from the absence of the D-helix. Structural analysis and kinetic assays demonstrate that the absence of this region does not prevent inhibitory activity and furthermore allow the identification of cysteine residues involved in internal and intermolecular disulfide bonding.

  16. Interventional recanalization of artificial arteriovenous fistula and graft for hemodialysis: angioplasty and pulsed-spray thrombolysis with Urokinase

    International Nuclear Information System (INIS)

    Shin, Sung Wook; Do, Young Soo; Park, Hong Seok and others

    1998-01-01

    To evaluate the effectiveness of percutaneous transluminal angioplasty (PTA) and pul-sed-spray pharmaco-mechanical thrombolysis (PSPMT) using urokinase for the management of insufficient hemodialysis access. Between September 1996 and May 1998, 21 insufficient hemodialysis accesses were treated in 16 patients(3 artificial arteriovenous fistulae, AVF; and 13 arteriovenous graft, AVG). PTA and PSPMT were performed in 6 and 15 cases, respectively, and success and long-term patency rates were evaluated. The overall success rate of PTA and PSPMT for insufficient hemodialysis access was 76. 2%(16/21). The success rates of PTA and PSPMT were 83.3%(5/6) and 73.3%(11/15), respectively. The primary patency rates of PSPMT were 69±12.8% at 6 months and 38±18.6% at 12 months. One of the two initially successful PTAs had been patent for 7 months, and the second PTA was performed at that time due to venous stenosis. The other was patent for 15 months throughout the follow-up period. PTA and PSPMT are effective primary methods for the treatment of insufficient hemodialysis access;success and patency rates were high, and the procedures can be performed repeatedly.=20

  17. Soluble urokinase-type plasminogen activator receptor (suPAR) and interleukin-6 levels in hyperemesis gravidarum.

    Science.gov (United States)

    Desdicioglu, Raziye; Yildirim, Melahat; Kocaoglu, Gulcan; Demir Cendek, Busra; Avcioglu, Gamze; Tas, Emre Erdem; Sengul, Ozlem; Erel, Ozcan; Yavuz, Ayse Filiz

    2017-10-09

    The aim was to compare serum soluble urokinase-type plasminogen activator receptor (suPAR) levels as well as interleukin-6 levels (IL-6) in pregnant women with hyperemesis gravidarum (HG) and asymptomatic pregnant women. Our study population consists of voluntary first trimester-pregnant women who applied to the outpatient clinic of the department of obstetrics and gynecology of Ankara Ataturk Training and Research Hospital. Between February and May 2016, 60 pregnant women were included in our prospective study. Serum suPAR and IL-6 levels were evaluated with the ELISA method. Twenty-nine pregnant women with HG and 31 asymptomatic pregnant women were included in the study. Serum suPAR level in the HG group was measured as 0.36 ± 0.56 ng/ml, whereas this level in the healthy pregnant control group was measured as 0.15 ± 0.15 ng/ml (p hyperemesis gravidarum. Copyright © 2017. Published by Elsevier Taiwan LLC.

  18. Urokinase-Type Plasminogen Activator Receptor Transcriptionally Controlled Adenoviruses Eradicate Pancreatic Tumors and Liver Metastasis in Mouse Models12

    Science.gov (United States)

    Huch, Meritxell; Gros, Alena; José, Anabel; González, Juan Ramon; Alemany, Ramon; Fillat, Cristina

    2009-01-01

    Treatment options for pancreatic cancer have shown limited success mainly owing to poor selectivity for pancreatic tumor tissue and to a lack of activity in the tumor. In this study, we describe the ability of the urokinase-type plasminogen activator receptor (uPAR) promoter to efficiently and selectively target pancreatic tumors and metastases, which enables the successful management of pancreatic cancer. We have generated a replication-defective reporter adenovirus, AduPARLuc, and a conditionally replicating adenovirus, AduPARE1A, and we have studied the selectivity and antitumoral efficacy in pancreatic tumors and metastases. Toxicity was studied on intravascular delivery. We demonstrate that the uPAR promoter is highly active in pancreatic tumors but very weak in normal tissues. Tumor specificity is evidenced by a 100-fold increase in the tumor-to-liver ratio and by selective targeting of liver metastases (P < .001). Importantly, the AduPARE1A maintains the oncolytic activity of the wild-type virus, with reduced toxicity, and exhibits significant antitumoral activity (25% tumor eradication) and prolonged survival in pancreatic xenograft models (P < .0001). Furthermore, upon intravascular delivery, we demonstrate complete eradication of liver metastasis in 33% of mice, improving median survival (P = 5.43 x 10-5). The antitumoral selective activity of AduPARE1A shows the potential of uPAR promoter-based therapies in pancreatic cancer treatment. PMID:19484141

  19. The plasma level of soluble urokinase receptor is elevated in patients with Streptococcus pneumoniae bacteraemia and predicts mortality

    DEFF Research Database (Denmark)

    Wittenhagen, P; Kronborg, G; Weis, N

    2004-01-01

    .05). In multivariate analysis, only suPAR remained a significant predictor of death (mortality rate of 13 for suPAR levels of > 10 ng/mL; 95% CI: 1.1-158). The increase in suPAR levels may reflect increased expression by vascular or inflammatory cells in the setting of pneumococcal sepsis. This plasma protein may......This multicentre prospective study was conducted to investigate whether the level of the soluble form of urokinase-type plasminogen activator receptor (suPAR) is elevated during pneumococcal bacteraemia and is of predictive value in the early stage of the disease. Plasma levels of suPAR were...... increased significantly (median 5.5; range 2.4-21.0 ng/mL) in 141 patients with pneumococcal bacteraemia, compared to 31 healthy controls (median 2.6, range 1.5-4.0 ng/mL, p 0.001). Furthermore, suPAR levels were elevated significantly in patients who died from the infection (n = 24) compared to survivors...

  20. Urokinase receptor derived peptides as potent inhibitors of the formyl peptide receptor type 1-triggered cell migration.

    Science.gov (United States)

    Yousif, Ali Munaim; Ingangi, Vincenzo; Merlino, Francesco; Brancaccio, Diego; Minopoli, Michele; Bellavita, Rosa; Novellino, Ettore; Carriero, Maria Vincenza; Carotenuto, Alfonso; Grieco, Paolo

    2018-01-01

    The receptor for the urokinase-type plasminogen activator (uPAR) is a widely recognized master regulator of cell migration. We and others have previously documented that the uPAR(84-95) sequence, interacts with the formyl peptide receptors (FPR)s, henceforth inducing cell migration of several cell lines, including leukocytes, and the synthetic shorter peptide (Ser 88 -Arg-Ser-Arg-Tyr 92 , SRSRY) retains chemotactic activity in vitro and in vivo. Recently, we have developed the head-to-tail cyclic analog [SRSRY], a new potent and stable inhibitor of monocyte trafficking. This prompted us to develop novel cyclic and linear analogs of [SRSRY] with the aim to broaden the knowledge about structure-activity relationships of peptide [SRSRY]. Herein we report their synthesis, effects on cell migration, conformational and docking analyses which served to envisage a new pharmacophore model for inhibitors of FPR1-triggered cell migration. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Enhanced discrimination of benign from malignant prostatic disease by selective measurements of cleaved forms of urokinase receptor in serum

    DEFF Research Database (Denmark)

    Piironen, Timo; Haese, Alexander; Huland, Hartwig

    2006-01-01

    BACKGROUND: Early detection of prostate cancer (PCa) centers on measurements of prostate-specific antigen (PSA), but current testing practices suffer from lack of specificity and generate many unnecessary prostate biopsies. Soluble urokinase plasminogen activator receptor (uPAR) is present in blood...... total PSA (tPSA), free PSA (fPSA), intact uPAR [uPAR(I-III)], intact uPAR + cleaved uPAR domains II+III [uPAR(I-III) + uPAR(II-III)], and cleaved uPAR domain I [uPAR(I)] in sera from 224 men with and 166 men without PCa. We assessed differences in serum concentrations between the PCa and noncancer...... groups within the entire cohort and in men with tPSA concentrations of 2-10 microg/L. The diagnostic accuracy of individual analytes and analyte combinations was explored by logistic regression and ROC analyses and evaluations of sensitivity and specificity pairs. RESULTS: Serum uPAR(I) and u...

  2. Variations in pre-hospital fibrinolysis process of care: insights from the Assessment of the Safety and Efficacy of a New Thrombolytic 3 Plus international acute myocardial infarction pre-hospital care survey.

    NARCIS (Netherlands)

    Welsh, R.C.; Goldstein, P.; Adgey, J.; Verheugt, F.W.A.; Bestilny, S.A.; Wallentin, L.; Werf, F. van de; Armstrong, P.W.

    2004-01-01

    The Assessment of the Safety and Efficacy of a New Thrombolytic 3 (ASSENT 3 PLUS) Plus trial (n=1639) was an international trial of pre-hospital fibrinolysis with tenecteplase randomly assigned to enoxaparin or unfractionated heparin, involving 106 sites in 12 countries. Given the potential impact

  3. Clinical outcomes of transcatheter selective superior mesenteric artery urokinase infusion therapy vs transjugular intrahepatic portosystemic shunt in patients with cirrhosis and acute portal vein thrombosis.

    Science.gov (United States)

    Jiang, Ting-Ting; Luo, Xiao-Ping; Sun, Jian-Ming; Gao, Jian

    2017-11-07

    To compare the outcomes of transcatheter superior mesenteric artery (SMA) urokinase infusion and transjugular intrahepatic portosystemic shunt (TIPS) for acute portal vein thrombosis (PVT) in cirrhosis. From January 2013 to December 2014, patients with liver cirrhosis and acute symptomatic PVT who met the inclusion criteria were randomly assigned to either an SMA group or a TIPS group. The two groups accepted transcatheter selective SMA urokinase infusion therapy and TIPS, respectively. The total follow-up time was 24 mo. The primary outcome measure was the change in portal vein patency status which was evaluated by angio-computed tomography or Doppler ultrasound. Secondary outcomes were rebleeding and hepatic encephalopathy. A total of 40 patients were enrolled, with 20 assigned to the SMA group and 20 to the TIPS group. The symptoms of all patients in the two groups improved within 48 h. PVT was improved in 17 (85%) patients in the SMA group and 14 (70%) patients in the TIPS group. The main portal vein (MPV) thrombosis was significantly reduced in both groups ( P mesenteric vein (SMV) thrombosis and splenic vein (SV) thrombosis were significantly reduced ( P = 0.048 and P = 0.02), which did not occur in the TIPS group. At 6-, 12-, and 24-mo follow-up, in the SMA group and the TIPS group, the cumulative rates free of the first episode of rebleeding were 80%, 65%, and 45% vs 90%, 80%, and 60%, respectively ( P = 0.320); the cumulative rates free of the first episode of hepatic encephalopathy were 85%, 80%, and 65% vs 50%, 40%, and 35%, respectively ( P = 0.022). Transcatheter selective SMA urokinase infusion and TIPS are safe and effective for acute symptomatic PVT in cirrhosis.

  4. Catheter-Directed Thrombolysis with a Continuous Infusion of Low-Dose Urokinase for Non-Acute Deep Venous Thrombosis of the Lower Extremity

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Binbin; Zhang, Jingyong; Wu, Xuejun; Han, Zonglin; Zhou, Hua; Dong, Dianning; Jin, Xing [Shandong Provincial Hospital, Shandong University, Ji' nan (China)

    2011-02-15

    We wanted to evaluate the feasibility of catheter-directed thrombolysis with a continuous infusion of low-dose urokinase for treating non-acute (less than 14 days) deep venous thrombosis of the lower extremity. The clinical data of 110 patients who were treated by catheter-directed thrombolysis with a continuous infusion of low-dose urokinase for lower extremity deep venous thrombosis was analysed. Adjunctive angioplasty or/and stenting was performed for the residual stenosis. Venous recanalization was graded by pre- and posttreatment venography. Follow-up was performed by clinical evaluation and Doppler ultrasound. A total of 112 limbs with deep venous thrombosis with a mean symptom duration of 22.7 days (range: 15-38 days) were treated with a urokinase infusion (mean: 3.5 million IU) for a mean of 196 hours. After thrombolysis, stent placement was performed in 25 iliac vein lesions and percutaneous angioplasty (PTA) alone was done in fi ve iliac veins. Clinically significant recanalization was achieved in 81% (90 of 112) of the treated limbs: complete recanalization was achieved in 28% (31 of 112) and partial recanalization was achieved in 53% (59 of 112). Minor bleeding occurred in 14 (13%) patients, but none of the patients suffered from major bleeding or symptomatic pulmonary embolism. During followup (mean: 15.2 months, range: 3-24 months), the veins were patent in 74 (67%) limbs. Thirty seven limbs (32%) showed progression of the stenosis with luminal narrowing more than 50%, including three with rethrombosis, while one revealed an asymptomatic iliac vein occlusion: 25 limbs (22%) developed mild post-thrombotic syndrome, and none had severe post-thrombotic syndrome. Valvular reflux occurred in 24 (21%) limbs. Catheter-directed thrombolysis with a continuous infusion of low-dose urokinase combined with adjunctive iliac vein stenting is safe and effective for removal of the clot burden and for restoration of the venous flow in patients with non-acute lower

  5. Serum level of soluble urokinase-type plasminogen activator receptor is a strong and independent predictor of survival in human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Sidenius, N; Sier, CFM; Ullum, H

    2000-01-01

    Human immunodeficiency virus-1 (HIV-1) infection has been shown to result in up-regulation of the urokinase-type plasminogen activator receptor (uPAR/CD87) on leukocytes in vitro and in vivo. The objective of this study was to investigate whether this up-regulation is paralleled by higher serum...... that the serum suPAR level is a novel, strong, and independent predictor of survival in HIV-1 infection. This report is the first to demonstrate an important association between the plasminogen activator system and disease progression in HIV-1 infection....

  6. The immune marker soluble urokinase plasminogen activator receptor is associated with new-onset diabetes in non-smoking women and men

    DEFF Research Database (Denmark)

    Haugaard, S B; Andersen, O; Hansen, T W

    2012-01-01

    Aim: To explore the putative association of new-onset diabetes and the soluble urokinase plasminogen activator receptor (suPAR), which is a new and stable plasma marker of immune function and low-grade inflammation. This association has been previously suggested by using the less sensitive...... International Classification of Disease system to detect incident diabetes in the Danish MONICA 10 cohort. Methods: The Danish National Diabetes Register enabled more accurate identification of incident diabetes during a median follow-up of 13.8 years in the Danish MONICA 10 cohort (n = 2353 generally healthy......-onset diabetes (P...

  7. Prognostic value of intact and cleaved forms of the urokinase plasminogen activator receptor in a retrospective study of 518 colorectal cancer patients

    DEFF Research Database (Denmark)

    Lomholt, Anne Fog; Christensen, Ib J; Høyer-Hansen, Gunilla

    2010-01-01

    The levels of the soluble urokinase plasminogen activator receptor (suPAR) in blood have been shown to correlate with prognosis in various cancers. Plasma levels of the combined suPAR forms have previously shown to be a strong prognostic marker in the present cohort of CRC patients and could...... potentially identify high-risk patients among those with early stage disease. In order to investigate whether the individual suPAR forms are stronger prognostic markers than the combined amount we measured the different uPAR forms in serum from the same cohort and evaluated their prognostic significance....

  8. In vivo evaluation of urokinase-loaded hollow nanogels for sonothrombolysis on suture embolization-induced acute ischemic stroke rat model

    OpenAIRE

    Yuming Teng; Haiqiang Jin; Ding Nan; Mengnan Li; Chenghe Fan; Yuanyuan Liu; Pu Lv; Wei Cui; Yongan Sun; Hongjun Hao; Xiaozhong Qu; Zhenzhong Yang; Yining Huang

    2018-01-01

    The urokinase-type plasminogen activator (uPA) loaded hollow nanogels (nUK) were synthesized by a one-step reaction of glycol chitosan and aldehyde capped poly (ethylene oxide). The resultant formulation is sensitive to diagnostic ultrasound (US) of 2 MHz. Herein, we evaluated the in vivo sonothrombolysis performance of the nUK on acute ischemic stroke rat model which was established by suture embolization of middle cerebral artery (MCA). Via intravenous (i.v.) administration, the experimenta...

  9. Plasminogen activator inhibitor-1 (PAI-1 and urokinase plasminogen activator (uPA in sputum of allergic asthma patients.

    Directory of Open Access Journals (Sweden)

    Sebastian Zukowski

    2008-06-01

    Full Text Available Urokinase plasminogen activator (uPA and its inhibitor (PAI-1 have been associated with asthma. The aim of this study was to evaluate concentration of uPA and PAI-1 in induced sputum of house dust mite allergic asthmatics (HDM-AAs. The study was performed on 19 HDM-AAs and 8 healthy nonatopic controls (HCs. Concentration of uPA and PAI-1 was evaluated in induced sputum supernatants using ELISA method. In HDM-AAs the median sputum concentration of uPA (128 pg/ml; 95% CI 99 to 183 pg/ml and PAI-1 (4063 pg/ml; 95%CI 3319 to 4784 pg/ml were significantly greater than in HCs (17 pg/ml; 95%CI 12 to 32 pg/ml; p<0.001 and 626 pg/ml; 95%CI 357 to 961 pg/ml; p<0.001 for uPA and PAI-1 respectively. The sputum concentration of uPA correlated with sputum total cell count (r=0.781; p=0.0001 and with logarithmically transformed exhaled nitric oxide concentration (eNO (r=0.486; p=0.035 but not with FEV1 or bronchial reactivity to histamine. On the contrary, the sputum PAI-1 concentration correlated with FEV1 (r=-0,718; p=0.0005 and bronchial reactivity to histamine expressed as log(PC20 (r=-0.824; p<0.0001 but did not correlate with sputum total cell count or eNO. The results of this study support previous observations linking PAI-1 with airway remodeling and uPA with cellular inflammation. Moreover, the observed effect of uPA seems to be independent of its fibrynolytic activity.

  10. Proteomic Identification of LASP-1 Down-regulation After RNAi Urokinase Silencing in Human Hepatocellular Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Alessandro Salvi

    2009-02-01

    Full Text Available In human hepatocellular carcinoma (HCC, the high expression of urokinase-type plasminogen activator (uPA is an unfavorable prognostic factor and a therapeutic target. To identify the downstream effects of uPA silencing by RNA interference, we studied proteome modifications of uPA-inhibited SKHep1C3 cells, an HCC-derived cell line. The study with two-dimensional difference gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight-mass spectrometry showed Lim and SH3 protein 1 (LASP-1, cytokeratin 1 (CK-1, cytokeratin 10 (CK-10, and heterogeneous nuclear ribonucleoprotein H1 down-modulation after uPA inhibition. LASP-1, CK-1, and CK-10 are involved in cytoskeleton dynamics as heterogeneous nuclear ribonucleoprotein H1 takes part in the mRNA processing and stability. We first confirmed the proteomic data by Western blot and immunoflorescence and then explored the link between uPA and LASP-1. The ectopic expression of uPA and LASP-1 supported the proteomic results and showed that uPA up-regulation increased LASP-1 expression and that both were implicated in SKHep1C3 motility. siRNA LASP-1 inhibition showed that LASP-1 was involved in actin microfilaments organization of SKHep1C3 cells. The disruption of the actin microfilaments after LASP-1 depletion increased uPA secretion and SKHep1C3 motility. Our results would suggest the hypothesis that uPA and LASP-1 expression may be coordinated in HCC-derived cells. In summary, the proteomic identification of a set of uPA downstream proteins provides new insight into the function of uPA in HCC cells.

  11. Ligand binding modulates the structural dynamics and activity of urokinase-type plasminogen activator: A possible mechanism of plasminogen activation.

    Directory of Open Access Journals (Sweden)

    Tobias Kromann-Hansen

    Full Text Available The catalytic activity of trypsin-like serine proteases is in many cases regulated by conformational changes initiated by binding of physiological modulators to exosites located distantly from the active site. A trypsin-like serine protease of particular interest is urokinase-type plasminogen activator (uPA, which is involved in extracellular tissue remodeling processes. Herein, we used hydrogen/deuterium exchange mass spectrometry (HDXMS to study regulation of activity in the catalytic domain of the murine version of uPA (muPA by two muPA specific monoclonal antibodies. Using a truncated muPA variant (muPA16-243, containing the catalytic domain only, we show that the two monoclonal antibodies, despite binding to an overlapping epitope in the 37s and 70s loops of muPA16-243, stabilize distinct muPA16-243 conformations. Whereas the inhibitory antibody, mU1 was found to increase the conformational flexibility of muPA16-243, the stimulatory antibody, mU3, decreased muPA16-243 conformational flexibility. Furthermore, the HDXMS data unveil the existence of a pathway connecting the 70s loop to the active site region. Using alanine scanning mutagenesis, we further identify the 70s loop as an important exosite for the activation of the physiological uPA substrate plasminogen. Thus, the data presented here reveal important information about dynamics in uPA by demonstrating how various ligands can modulate uPA activity by mediating long-range conformational changes. Moreover, the results provide a possible mechanism of plasminogen activation.

  12. Prognostic value analysis of urokinase-type plasminogen activator receptor in oral squamous cell carcinoma: an immunohistochemical study

    International Nuclear Information System (INIS)

    Bacchiocchi, Roberta; Lo Muzio, Lorenzo; Fazioli, Francesca; Rubini, Corrado; Pierpaoli, Elisa; Borghetti, Giulia; Procacci, Pasquale; Nocini, Pier Francesco; Santarelli, Andrea; Rocchetti, Romina; Ciavarella, Domenico

    2008-01-01

    Oral squamous cell carcinoma (OSCC) represents the most common oral malignancy. Despite recent advances in therapy, up to 50% of the cases have relapse and/or metastasis. There is therefore a strong need for the identification of new biological markers able to predict the clinical behaviour of these lesions in order to improve quality of life and overall survival. Among tumour progression biomarkers, already known for their involvement in other neoplasia, a crucial role is ascribed to the urokinase-type plasminogen activator receptor (uPAR), which plays a multiple role in extracellular proteolysis, cell migration and tissue remodelling not only as a receptor for the zymogen pro-uPA but also as a component for cell adhesion and as a chemoattractant. The purpose of this study was to gain information on the expression of uPAR in OSCC and to verify whether this molecule can have a role as a prognostic/predictive marker for this neoplasia. In a retrospective study, a cohort of 189 OSCC patients was investigated for uPAR expression and its cellular localization by immunohistochemistry. As standard controls, 8 normal oral mucosal tissues free of malignancy, obtained from patients with no evidence or history of oral cavity tumours, were similarly investigated. After grouping for uPAR expression, OSCCs were statistically analyzed for the variables age, gender, histological grading (G), tumour size, recurrence, TNM staging and overall survival rate. In our immunohistochemical study, 74 cases (39.1%) of OSCC showed a mostly cytoplasmic positivity for uPAR, whereas 115 were negative. uPAR expression correlated with tumour differentiation grade and prognosis: percentage of positive cases was the greatest in G3 (70.4%) and patients positives for uPAR expression had an expectation of life lower than those for uPAR negatives. The results obtained in this study suggest a role of uPAR as a potential biomarker useful to identify higher risk subgroups of OSCC patients

  13. Safety of thrombolytic therapy with rt-PA and transcranial color Doppler ultrasound (TCCS) combined with microbubbles: a histopathologic study on rabbit brain tissues.

    Science.gov (United States)

    Ren, Xinping; Wang, Yong; Wang, Yi; Chen, Hong; Chen, Li; Liu, Yi; Xu, Chengshi

    2015-04-01

    To evaluate effect of thrombolytic therapy with rt-PA (recombinant tissue plasminogen activator) and transcranial color Doppler ultrasound (TCCS) combined with microbubbles on histology of brain tissue. New Zealand rabbits were subjected to TCCS based thrombolytic therapy, in 8 groups depending on dose of rt-PA, exposure duration of TCCS and presence of attenuation by skull bone window, 2 animals/group: (1) skull+1/2 rt-PA+TCCS+MBs, 10 min, (2) skull+rt-PA+TCCS+MBs, 10 min, (3) skull+1/2 rt-PA+TCCS+MBs, 20 min, (4) skull+rt-PA+TCCS+MBs, 20 min, (5) skull+1/2 rt-PA+TCCS+MBs, 30 min, (6) skull+rt-PA+TCCS+MBs, 30 min, (7) 1/2 rt-PA+TCCS+MBs, 10 min, (8) 1/2 rt-PA+TCCS+MBs, 20 min. The brain tissues were harvested after therapies and submitted for microscopic, electronic microscope and immunohistochemical examination. The histological changes were scored. TCCS caused exposure duration dependent brain tissue damage. With attenuation by bone window, TCCS based therapies for 10-20 min caused minimal tissue damage. However, significant tissue damage was observed upon TCCS for 30 min in presence of skull bone window, presenting as hemorrhage, misdistribution of organelles, demyelination of nerve fibers, and thinning of basement membrane in blood-brain barrier, which was milder than that after 20 min of exposure to TCCS in absence of bone window. Dose of rt-PA did not affect brain histology in all groups. Short treatment of brain tissue with TCCS through a bone window is relative safe. And skull bone window protected brain tissue from TCCS induced damage. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Lysosomal degradation of receptor-bound urokinase-type plasminogen activator is enhanced by its inhibitors in human trophoblastic choriocarcinoma cells

    DEFF Research Database (Denmark)

    Jensen, Poul Henning; Christensen, Erik Ilsø; Ebbesen, P.

    1990-01-01

    We have studied the effect of plasminogen activator inhibitors PAI-1 and PAI-2 on the binding of urokinase-type plasminogen activator (u-PA) to its receptor in the human choriocarcinoma cell line JAR. With 125I-labeled ligands in whole-cell binding assays, both uncomplexed u-PA and u-PA-inhibitor......We have studied the effect of plasminogen activator inhibitors PAI-1 and PAI-2 on the binding of urokinase-type plasminogen activator (u-PA) to its receptor in the human choriocarcinoma cell line JAR. With 125I-labeled ligands in whole-cell binding assays, both uncomplexed u-PA and u...... in an apparently intact form in the medium or was still cell associated. The degradation could be inhibited by inhibitors of vesicle transport and lysosomal hydrolases. By electron microscopic autoradiography, both 125I-u-PA and 125I-u-PA-inhibitor complexes were located over the cell membrane at 4 degrees C...

  15. Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2

    International Nuclear Information System (INIS)

    Peng, P.-L.; Hsieh, Y.-S.; Wang, C.-J.; Hsu, J.-L.; Chou, F.-P.

    2006-01-01

    Berberine, a compound isolated from medicinal herbs, has been reported with many pharmacological effects related to anti-cancer and anti-inflammation capabilities. In this study, we observed that berberine exerted a dose- and time-dependent inhibitory effect on the motility and invasion ability of a highly metastatic A549 cells under non-cytotoxic concentrations. In cancer cell migration and invasion process, matrix-degrading proteinases are required. A549 cell treated with berberine at various concentrations showed reduced ECM proteinases including matrix metalloproteinase-2 (MMP2) and urokinase-plasminogen activator (u-PA) by gelatin and casein zymography analysis. The inhibitory effect is likely to be at the transcriptional level, since the reduction in the transcripts levels was corresponding to the proteins. Moreover, berberine also exerted its action via regulating tissue inhibitor of metalloproteinase-2 (TIMP-2) and urokinase-plasminogen activator inhibitor (PAI). The upstream mediators of the effect involved c-jun, c-fos and NF-κB, as evidenced by reduced phosphorylation of the proteins. These findings suggest that berberine possesses an anti-metastatic effect in non-small lung cancer cell and may, therefore, be helpful in clinical treatment

  16. Artificial exon shuffling between tissue-type plasminogen activator (t-PA) and urokinase (u-PA): a comparative study on the fibrinolytic properties of t-PA/u-PA hybrid proteins

    NARCIS (Netherlands)

    de Vries, C. [=Carlie J. M.; Veerman, H.; Blasi, F.; Pannekoek, H.

    1988-01-01

    We constructed two human tissue-type plasminogen activator/urokinase (t-PA/u-PA) hybrid cDNAs which were expressed by transfection of mouse Ltk- cells. The properties of the secreted proteins were compared with those of recombinant t-PA (rt-PA) and high molecular weight (HMW) u-PA. The hybrid

  17. Urokinase receptor-associated protein (uPARAP) is expressed in connection with malignant as well as benign lesions of the human breast and occurs in specific populations of stromal cells

    DEFF Research Database (Denmark)

    Schnack Nielsen, Boye; Rank, Fritz; Engelholm, Lars H

    2002-01-01

    The urokinase-type plasminogen activator (uPA) and the uPA receptor (uPAR) are key components in the plasminogen activation system, serving to promote specific events of extracellular matrix degradation in connection with tissue remodeling and cancer invasion. We recently described a new u...

  18. Tumour microenvironments induce expression of urokinase plasminogen activator receptor (uPAR and concomitant activation of gelatinolytic enzymes.

    Directory of Open Access Journals (Sweden)

    Synnøve Magnussen

    Full Text Available The urokinase plasminogen activator receptor (uPAR is associated with poor prognosis in oral squamous cell carcinoma (OSCC, and increased expression of uPAR is often found at the invasive tumour front. The aim of the current study was to elucidate the role of uPAR in invasion and metastasis of OSCC, and the effects of various tumour microenvironments in these processes. Furthermore, we wanted to study whether the cells' expression level of uPAR affected the activity of gelatinolytic enzymes.The Plaur gene was both overexpressed and knocked-down in the murine OSCC cell line AT84. Tongue and skin tumours were established in syngeneic mice, and cells were also studied in an ex vivo leiomyoma invasion model. Soluble factors derived from leiomyoma tissue, as well as purified extracellular matrix (ECM proteins, were assessed for their ability to affect uPAR expression, glycosylation and cleavage. Activity of gelatinolytic enzymes in the tissues were assessed by in situ zymography.We found that increased levels of uPAR did not induce tumour invasion or metastasis. However, cells expressing low endogenous levels of uPAR in vitro up-regulated uPAR expression both in tongue, skin and leiomyoma tissue. Various ECM proteins had no effect on uPAR expression, while soluble factors originating from the leiomyoma tissue increased both the expression and glycosylation of uPAR, and possibly also affected the proteolytic processing of uPAR. Tumours with high levels of uPAR, as well as cells invading leiomyoma tissue with up-regulated uPAR expression, all displayed enhanced activity of gelatinolytic enzymes.Although high levels of uPAR are not sufficient to induce invasion and metastasis, the activity of gelatinolytic enzymes was increased. Furthermore, several tumour microenvironments have the capacity to induce up-regulation of uPAR expression, and soluble factors in the tumour microenvironment may have an important role in the regulation of posttranslational

  19. Tumour Microenvironments Induce Expression of Urokinase Plasminogen Activator Receptor (uPAR) and Concomitant Activation of Gelatinolytic Enzymes

    Science.gov (United States)

    Magnussen, Synnøve; Hadler-Olsen, Elin; Latysheva, Nadezhda; Pirila, Emma; Steigen, Sonja E.; Hanes, Robert; Salo, Tuula; Winberg, Jan-Olof; Uhlin-Hansen, Lars; Svineng, Gunbjørg

    2014-01-01

    Background The urokinase plasminogen activator receptor (uPAR) is associated with poor prognosis in oral squamous cell carcinoma (OSCC), and increased expression of uPAR is often found at the invasive tumour front. The aim of the current study was to elucidate the role of uPAR in invasion and metastasis of OSCC, and the effects of various tumour microenvironments in these processes. Furthermore, we wanted to study whether the cells’ expression level of uPAR affected the activity of gelatinolytic enzymes. Methods The Plaur gene was both overexpressed and knocked-down in the murine OSCC cell line AT84. Tongue and skin tumours were established in syngeneic mice, and cells were also studied in an ex vivo leiomyoma invasion model. Soluble factors derived from leiomyoma tissue, as well as purified extracellular matrix (ECM) proteins, were assessed for their ability to affect uPAR expression, glycosylation and cleavage. Activity of gelatinolytic enzymes in the tissues were assessed by in situ zymography. Results We found that increased levels of uPAR did not induce tumour invasion or metastasis. However, cells expressing low endogenous levels of uPAR in vitro up-regulated uPAR expression both in tongue, skin and leiomyoma tissue. Various ECM proteins had no effect on uPAR expression, while soluble factors originating from the leiomyoma tissue increased both the expression and glycosylation of uPAR, and possibly also affected the proteolytic processing of uPAR. Tumours with high levels of uPAR, as well as cells invading leiomyoma tissue with up-regulated uPAR expression, all displayed enhanced activity of gelatinolytic enzymes. Conclusions Although high levels of uPAR are not sufficient to induce invasion and metastasis, the activity of gelatinolytic enzymes was increased. Furthermore, several tumour microenvironments have the capacity to induce up-regulation of uPAR expression, and soluble factors in the tumour microenvironment may have an important role in the

  20. Comparison of early exercise treadmill test and oral dipyridamole thallium-201 tomography for the identification of jeopardized myocardium in patients receiving thrombolytic therapy for acute Q-wave myocardial infarction

    International Nuclear Information System (INIS)

    Jain, A.; Hicks, R.R.; Frantz, D.M.; Myers, G.H.; Rowe, M.W.

    1990-01-01

    Thrombolytic therapy has become the treatment of choice for patients with acute myocardial infarction. Researchers are not yet able to identify patients with salvage of myocardium who are at risk for recurrent coronary events. Thus, a prospective trial was performed in 46 patients with myocardial infarction (28 anterior and 18 inferior) who received thrombolytic therapy to determine if early thallium tomography (4.7 days) using oral dipyridamole would identify more patients with residual ischemia than early symptom-limited exercise treadmill tests (5.5 days). There were no complications during the exercise treadmill tests or oral dipyridamole thallium tomography. Mean duration of exercise was 11 +/- 3 minutes and the peak heart rate was 126 beats/min. Thirteen patients had positive test results. After oral dipyridamole all patients had abnormal thallium uptake on the early images. Positive scans with partial filling in of the initial perfusion defects were evident in 34 patients. Angina developed in 13 patients and was easily reversed with intravenous aminophylline. Both symptom-limited exercise treadmill tests and thallium tomography using oral dipyridamole were safely performed early after myocardial infarction in patients receiving thrombolytic therapy. Thallium tomography identified more patients with residual ischemia than exercise treadmill tests (74 vs 28%). Further studies are required to determine whether the results of thallium tomography after oral dipyridamole can be used to optimize patient management and eliminate the need for coronary angiography in some patients

  1. Catheter-directed thrombolytic therapy for thoracic deep vein thrombosis is safe and effective in selected patients with and without cancer

    Energy Technology Data Exchange (ETDEWEB)

    Maleux, Geert; Marchal, Pieter; Heye, Sam; Vaninbroukx, Johan [University Hospitals Leuven, Department of Radiology, Leuven (Belgium); Palmers, Marleen [Sint-Trudo Hospital, Department of Radiology, Sint-Truiden (Belgium); Verhamme, Peter; Verhaeghe, Raymond [University Hospitals Leuven, Department of Vascular Medicine, Leuven (Belgium)

    2010-09-15

    To assess the safety, feasibility and efficacy of catheter-directed thrombolysis for thoracic central venous thrombosis in both cancer and non-cancer patients. A retrospective case series of 68 patients, including 35 with active cancer and 33 without cancer, was analysed. They all received catheter-directed thrombolysis with alteplase or urokinase for symptomatic acute major thoracic vein thrombosis. Substantial clot lysis was obtained in 62 out of 68 patients (91%), the results being 88.6 and 93.8% for cancer and non-cancer patients respectively (P = 0.68). The mean infusion time in patients with and without cancer was 2.11 and 1.84 days respectively (P = 0.3259). Procedure-related complications occurred in two cancer patients (8.6%) and in seven non-cancer patients (21%) (P = 0.18). One cancer patient developed a fatal intracranial bleeding. Additional intervention after successful lysis was performed in cancer (n = 18; 51%) as well as in non-cancer patients (n = 29; 88%). Catheter-directed thrombolysis is a feasible and highly effective interventional procedure with an acceptable safety profile in selected patients with and without cancer for the treatment of symptomatic thoracic central venous thrombosis. In most cases, additional endovascular or surgical procedures are required to restore and maintain vessel patency after successful thrombolysis. (orig.)

  2. Catheter-directed thrombolytic therapy for thoracic deep vein thrombosis is safe and effective in selected patients with and without cancer

    International Nuclear Information System (INIS)

    Maleux, Geert; Marchal, Pieter; Heye, Sam; Vaninbroukx, Johan; Palmers, Marleen; Verhamme, Peter; Verhaeghe, Raymond

    2010-01-01

    To assess the safety, feasibility and efficacy of catheter-directed thrombolysis for thoracic central venous thrombosis in both cancer and non-cancer patients. A retrospective case series of 68 patients, including 35 with active cancer and 33 without cancer, was analysed. They all received catheter-directed thrombolysis with alteplase or urokinase for symptomatic acute major thoracic vein thrombosis. Substantial clot lysis was obtained in 62 out of 68 patients (91%), the results being 88.6 and 93.8% for cancer and non-cancer patients respectively (P = 0.68). The mean infusion time in patients with and without cancer was 2.11 and 1.84 days respectively (P = 0.3259). Procedure-related complications occurred in two cancer patients (8.6%) and in seven non-cancer patients (21%) (P = 0.18). One cancer patient developed a fatal intracranial bleeding. Additional intervention after successful lysis was performed in cancer (n = 18; 51%) as well as in non-cancer patients (n = 29; 88%). Catheter-directed thrombolysis is a feasible and highly effective interventional procedure with an acceptable safety profile in selected patients with and without cancer for the treatment of symptomatic thoracic central venous thrombosis. In most cases, additional endovascular or surgical procedures are required to restore and maintain vessel patency after successful thrombolysis. (orig.)

  3. A new tagging system for production of recombinant proteins in Drosophila S2 cells using the third domain of the urokinase receptor

    DEFF Research Database (Denmark)

    Gårdsvoll, Henrik; Hansen, Line V; Jørgensen, Thomas J D

    2007-01-01

    The use of protein fusion tag technology greatly facilitates detection, expression and purification of recombinant proteins, and the demands for new and more effective systems are therefore expanding. We have used a soluble truncated form of the third domain of the urokinase receptor...... as a convenient C-terminal fusion partner for various recombinant extracellular human proteins used in basic cancer research. The stability of this cystein-rich domain, which structure adopts a three-finger fold, provides an important asset for its applicability as a fusion tag for expression of recombinant...... proteins. Up to 20mg of intact fusion protein were expressed by stably transfected Drosophila S2 cells per liter of culture using this strategy. Purification of these secreted fusion proteins from the conditioned serum free medium of S2 cells was accompanied by an efficient one-step immunoaffinity...

  4. Presence of urokinase plasminogen activator, its inhibitor and receptor in small cell lung cancer and non-small cell lung cancer

    DEFF Research Database (Denmark)

    Pappot, H.; Pfeiffer, P.; Grøndahl Hansen, J.

    1997-01-01

    Spreading of cancer cells is dependent on the combined action of several proteolytic enzymes, such as serine proteases, comprising the urokinase pathway of plasminogen activation. Previous studies of lung cancer indicate that expression, localization and prognostic impact of the components...... of the plasminogen activation system differ in the different non-small cell lung cancer (NSCLC) types, whereas the expression of the components in small cell lung cancer (SCLC) has only sparingly been investigated. In the present study we investigate the presence of the components of the plasminogen activation...... and the clinical parameters. This is the first report of a study using a quantitative method to compare levels of the components of the plasminogen activation system in tissue extracts from the two major lung cancer groups. The study shows that uPA, PAI-1 and uPAR are present in SCLC-tissue, suggesting...

  5. A 55,000-60,000 Mr receptor protein for urokinase-type plasminogen activator. Identification in human tumor cell lines and partial purification

    DEFF Research Database (Denmark)

    Nielsen, Lars Søegaard; Kellerman, G M; Behrendt, N

    1988-01-01

    a bifunctional amino-reactive reagent followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography revealed with the four cell lines studied the occurrence of a single band migrating with an Mr of 70,000-75,000, indicating complex formation with an Mr of 55,000-60,000 u-PA receptor...... protein (u-PA-R). In the human monocyte cell line U937 cultivated in the presence of phorbol ester, the amount of complex was strongly increased, and a fraction of the complex had a slower electrophoretic mobility. Comparison between autoradiograms of reduced and unreduced samples suggests that u......The iodinated Mr approximately equal to 15,000 amino-terminal fragment (ATF) of the urokinase-type plasminogen activator (u-PA) molecule bound specifically to the cell surface of all of seven cultured human tumor cell lines studied. Cross-linking of iodinated ATF to the cell surface using...

  6. Mapping the topographic epitope landscape on the urokinase plasminogen activator receptor (uPAR) by surface plasmon resonance and X-ray crystallography

    DEFF Research Database (Denmark)

    Zhao, Baoyu; Gandhi, Sonu; Yuan, Cai

    2015-01-01

    as a dynamic modular protein structure composed of three homologous Ly6/uPAR domains (LU).This internally flexible protein structure of uPAR enables an allosteric regulation of the interactions with its two principal ligands: the serine protease urokinase-type plasminogen activator (uPA) and the provisional...... matrix protein vitronectin (Vn) (Mertens et al., 2012; Gårdsvoll et al., 2011; Madsen et al., 2007 [2-4]). The data presented here relates to the non-covalent trapping of one of these biologically relevant uPAR-conformations by a novel class of monoclonal antibodies (Zhao et al., 2015 [5......]) and to the general mapping of the topographic epitope landscape on uPAR. The methods required to achieve these data include: (1) recombinant expression and purification of a uPAR-hybrid protein trapped in the desired conformation [patent; WO 2013/020898 A12013]; (2) developing monoclonal antibodies with unique...

  7. Elevated soluble urokinase receptor values in CSF, age and bacterial meningitis infection are independent and additive risk factors of fatal outcome

    DEFF Research Database (Denmark)

    Tzanakaki, G; Paparoupa, M; Kyprianou, M

    2012-01-01

    The aim of the present study was to evaluate the potential role of cerebrospinal fluid soluble urokinase receptor (suPAR) level, infection and age as risk factors for fatal outcome in patients suspected of having meningitis and/or bacteraemia on admission to hospital. A total of 545 cerebrospinal...... fluid samples from patients with clinically suspected meningitis were sent to the Hellenic National Meningitis Reference Laboratory. Ten of 545 (1.83%) patients died. Analysis by receiver operating characteristics (ROC) curve revealed that both suPAR and age were significant for prediction of fatal...... outcome. Patients with levels of suPAR above the cut-off values and age ≥51 years, or patients in which either Neisseria meningitis or Streptococcus pneumoniae were detected were categorized as high risk patients. The combination of the above three predictors (suPAR, age and infectious agent...

  8. Presence of urokinase plasminogen activator, its inhibitor and receptor in small cell lung cancer and non-small cell lung cancer

    DEFF Research Database (Denmark)

    Pappot, H.; Pfeiffer, P.; Grøndahl Hansen, J.

    1997-01-01

    Spreading of cancer cells is dependent on the combined action of several proteolytic enzymes, such as serine proteases, comprising the urokinase pathway of plasminogen activation. Previous studies of lung cancer indicate that expression, localization and prognostic impact of the components...... of the plasminogen activation system differ in the different non-small cell lung cancer (NSCLC) types, whereas the expression of the components in small cell lung cancer (SCLC) has only sparingly been investigated. In the present study we investigate the presence of the components of the plasminogen activation...... that the plasminogen activation system could play a role in this type of cancer during invasion. In addition a difference in the levels of the components of the plasminogen activation system in NSCLC and SCLC is found, which could contribute to the differences in biology....

  9. Anti-Urokinase Receptor Antisense Oligonucleotide (uPAR-aODN) to Prevent and Cure Long-Term Space Exploration-Related Retinal Pathological Angiogenesis

    Science.gov (United States)

    Lazzarano, Stefano; Lulli, Matteo; Fibbi, Gabriella; Margheri, Francesca; Papucci, Laura; Serrati, Simona; Witort, Ewa; Chilla, Anastasia; Lapucci, Andrea; Donnini, Martino; Quaglierini, Paolo; Romiti, Alice; Specogna, Rebecca; Del Rosso, Mario; Capaccioli, Sergio

    2008-06-01

    Angiogenesis underlies a variety of physiological processes and its possible deregulation during long term space exploration needs to be investigated. Angiogenesis is a multistep process of new blood capillary formation, where degradation of the extracellular matrix (ECM) by proteolytic enzymes, including uPA (urokinase plasminogen activator) and opening the way to migration of endothelial cells (EC), is critical. Plasminogen activation system regulates angiogenesis by both uPA-driven ECM degradation and uPA receptor (uPAR). Microgravity and low dose irradiations promote tissue neoangiogeenesis and neovascularization is often common occurence in ophthalmologic pathologies. We have designed and patented the uPAR antisense oligonucleotide (aODN) and evaluated its antiangiogenetic activity by EC cellular migration and capillary morphogenesis assays. The uPAR aODN treatment caused a 75% inhibition of human microvascular EC migration and a complete inhibition of capillary morphogenesis, suggesting its therapeutic application to prevent neoangiogenesis-related ophthalmologic pathologies during space exploration.

  10. A high-protein diet during hospitalization is associated with an accelerated decrease in soluble urokinase plasminogen activator receptor levels in acutely ill elderly medical patients with SIRS

    DEFF Research Database (Denmark)

    Tavenier, Juliette; Haupt, Thomas Huneck; Andersen, Aino L

    2017-01-01

    inflammation in healthy elderly. We hypothesized that nutritional support and resistance training would accelerate the resolution of inflammation in hospitalized elderly patients with SIRS. Acutely admitted patients aged >65 years with SIRS were randomized to an intervention consisting of a high-protein diet......Acute illness and hospitalization in elderly individuals are often accompanied by the systemic inflammatory response syndrome (SIRS) and malnutrition, both associated with wasting and mortality. Nutritional support and resistance training were shown to increase muscle anabolism and reduce...... (1.7 g/kg per day) during hospitalization, and daily protein supplement (18.8 g) and 3 weekly resistance training sessions for 12 weeks after discharge (Intervention, n=14), or to standard-care (Control, n=15). Plasma levels of the inflammatory biomarkers soluble urokinase plasminogen activator...

  11. Hemorragia alveolar como complicación del uso de trombolíticos Alveolar hemorrhage as a complication of thrombolytic therapy

    Directory of Open Access Journals (Sweden)

    Alejandra González

    2011-12-01

    Full Text Available La trombolisis se usa como estrategia de reperfusión coronaria en el infarto agudo de miocardio. El sangrado es su principal complicación; la mayoría ocurre en los sitios de accesos venosos y es leve, pero también pueden presentarse hemorragia gastrointestinal, retroperitoneal, genitourinaria, pulmonar y a nivel del sistema nervioso central, episodios estos generalmente de mayor gravedad y a veces fatales. Se describe aquí el caso de un paciente que recibió terapia trombolítica con estreptoquinasa como tratamiento por un infarto de miocardio, y que posteriormente desarrolló insuficiencia respiratoria aguda, infiltrados pulmonares bilaterales, caída del hematocrito y aumento de la difusión de monóxido de carbono, cuadro compatible con diagnóstico de hemorragia alveolar.Coronary thrombolysis is used as a strategy for coronary reperfusion for acute myocardial infarction. Bleeding is the main complication described. Although most of these events occur at sites of vascular access and are mild, in some cases gastrointestinal, retroperitoneal, genitourinary, lung and central nervous system bleeding may occur. These episodes are usually serious and sometimes fatal. The following report describes the case of a patient who received thrombolytic therapy with streptokinase as a treatment for myocardial infarction. Subsequently he developed acute respiratory failure, bilateral pulmonary infiltrates and fall of hematocrit compatible with diagnosis of alveolar hemorrhage.

  12. Bacterial endotoxin enhances colorectal cancer cell adhesion and invasion through TLR-4 and NF-kappaB-dependent activation of the urokinase plasminogen activator system.

    LENUS (Irish Health Repository)

    Killeen, S D

    2009-05-19

    Perioperative exposure to lipopolysaccharide (LPS) is associated with accelerated metastatic colorectal tumour growth. LPS directly affects cells through Toll-like receptor 4 (TLR-4) and the transcription factor NF-kappaB. The urokinase plasminogen activator (u-PA) system is intimately implicated in tumour cell extracellular matrix (ECM) interactions fundamental to tumour progression. Thus we sought to determine if LPS directly induces accelerated tumour cell ECM adhesion and invasion through activation of the u-PA system and to elucidate the cellular pathways involved. Human colorectal tumour cell lines were stimulated with LPS. u-PA concentration, u-PA activity, active u-PA, surface urokinase plasminogen activator receptor (u-PAR) and TLR-4 expression were assessed by ELISA, colorimetric assay, western blot analysis and flow cytometry respectively. In vitro tumour cell vitronectin adhesion and ECM invasion were analysed by vitronectin adhesion assay and ECM invasion chambers. u-PA and u-PAR function was inhibited with anti u-PA antibodies or the selective u-PA inhibitors amiloride or WXC-340, TLR-4 by TLR-4-blocking antibodies and NF-kappaB by the selective NF-kappaB inhibitor SN-50. LPS upregulates u-PA and u-PAR in a dose-dependent manner, enhancing in vitro tumour cell vitronectin adhesion and ECM invasion by >40% (P<0.01). These effects were ameliorated by u-PA and u-PAR inhibition. LPS activates NF-kappaB through TLR-4. TLR-4 and NF-kappaB inhibition ameliorated LPS-enhanced u-PA and u-PAR expression, tumour cell vitronectin adhesion and ECM invasion. LPS promotes tumour cell ECM adhesion and invasion through activation of the u-PA system in a TLR-4- and NF-kappaB-dependent manner.

  13. Randomized comparison of intracoronary tirofiban versus urokinase as an adjunct to primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: results of the ICTUS-AMI trial.

    Science.gov (United States)

    Zhu, Tian-qi; Zhang, Qi; Ding, Feng-hua; Qiu, Jian-ping; Jin, Hui-geng; Jiang, Li; Lu, Lin; Zhang, Rui-yan; Hu, Jian; Yang, Zhen-kun; Shen, Ying; Shen, Wei-feng

    2013-08-01

    No randomized trial has been performed to compare the efficacy of an intracoronary bolus of tirofiban versus urokinase during primary percutaneous coronary intervention (PCI). We investigated whether the effects of adjunctive therapy with an intracoronary bolus of urokinase was noninferior to the effects of an intracoronary bolus of tirofiban in patients with ST-elevation myocardial infarction (STEMI) undergoing PCI. A total of 490 patients with acute STEMI undergoing primary PCI were randomized to an intracoronary bolus of tirofiban (10 µg/kg; n = 247) or urokinase (250 kU/20 ml; n = 243). Serum levels of P-selectin, von Willebrand factor (vWF), CD40 ligand (CD40L), and serum amyloid A (SAA) in the coronary sinus were measured before and after intracoronary drug administration. The primary endpoint was the rate of complete ( ≥ 70%) ST-segment resolution (STR) at 90 minutes after intervention, and the noninferiority margin was set to 15%. In the intention-to-treat analysis, complete STR was achieved in 54.4% of patients treated with an intracoronary bolus of urokinase and in 60.6% of those treated with an intracoronary bolus of tirofiban (adjusted difference: -7.0%; 95% confidence interval: -15.7% to 1.8%). The corrected TIMI frame count of the infarct-related artery was lower, left ventricular ejection fraction was higher, and the 6-month major adverse cardiac event-free survival tended to be better in the intracoronary tirofiban group. An intracoronary bolus of tirofiban resulted in lower levels of P-selectin, vWF, CD40L, and SAA in the coronary sinus compared with an intracoronary bolus of urokinase after primary PCI (P < 0.05). An intracoronary bolus of urokinase as an adjunct to primary PCI for acute STEMI is not equally effective to an intracoronary bolus of tirofiban with respect to improvement in myocardial reperfusion assessed by STR. This may be caused by less reduction in coronary circulatory platelet activation and inflammation.

  14. Use of a Diagnostic Score to Prioritize Computed Tomographic (CT) Imaging for Patients Suspected of Ischemic Stroke Who May Benefit from Thrombolytic Therapy

    Science.gov (United States)

    Bots, Michiel L.; Selvarajah, Sharmini; Kappelle, L. Jaap; Abdul Aziz, Zariah; Sidek, Norsima Nazifah; Vaartjes, Ilonca

    2016-01-01

    Background A shortage of computed tomographic (CT) machines in low and middle income countries often results in delayed CT imaging for patients suspected of a stroke. Yet, time constraint is one of the most important aspects for patients with an ischemic stroke to benefit from thrombolytic therapy. We set out to assess whether application of the Siriraj Stroke Score is able to assist physicians in prioritizing patients with a high probability of having an ischemic stroke for urgent CT imaging. Methods From the Malaysian National Neurology Registry, we selected patients aged 18 years and over with clinical features suggesting of a stroke, who arrived in the hospital 4.5 hours or less from ictus. The prioritization of receiving CT imaging was left to the discretion of the treating physician. We applied the Siriraj Stroke Score to all patients, refitted the score and defined a cut-off value to best distinguish an ischemic stroke from a hemorrhagic stroke. Results Of the 2176 patients included, 73% had an ischemic stroke. Only 33% of the ischemic stroke patients had CT imaging within 4.5 hours. The median door-to-scan time for these patients was 4 hours (IQR: 1;16). With the recalibrated score, it would have been possible to prioritize 95% (95% CI: 94%–96%) of patients with an ischemic stroke for urgent CT imaging. Conclusions In settings where CT imaging capacity is limited, we propose the use of the Siriraj Stroke Score to prioritize patients with a probable ischemic stroke for urgent CT imaging. PMID:27768752

  15. Use of a Diagnostic Score to Prioritize Computed Tomographic (CT Imaging for Patients Suspected of Ischemic Stroke Who May Benefit from Thrombolytic Therapy.

    Directory of Open Access Journals (Sweden)

    Wen Yea Hwong

    Full Text Available A shortage of computed tomographic (CT machines in low and middle income countries often results in delayed CT imaging for patients suspected of a stroke. Yet, time constraint is one of the most important aspects for patients with an ischemic stroke to benefit from thrombolytic therapy. We set out to assess whether application of the Siriraj Stroke Score is able to assist physicians in prioritizing patients with a high probability of having an ischemic stroke for urgent CT imaging.From the Malaysian National Neurology Registry, we selected patients aged 18 years and over with clinical features suggesting of a stroke, who arrived in the hospital 4.5 hours or less from ictus. The prioritization of receiving CT imaging was left to the discretion of the treating physician. We applied the Siriraj Stroke Score to all patients, refitted the score and defined a cut-off value to best distinguish an ischemic stroke from a hemorrhagic stroke.Of the 2176 patients included, 73% had an ischemic stroke. Only 33% of the ischemic stroke patients had CT imaging within 4.5 hours. The median door-to-scan time for these patients was 4 hours (IQR: 1;16. With the recalibrated score, it would have been possible to prioritize 95% (95% CI: 94%-96% of patients with an ischemic stroke for urgent CT imaging.In settings where CT imaging capacity is limited, we propose the use of the Siriraj Stroke Score to prioritize patients with a probable ischemic stroke for urgent CT imaging.

  16. TISSUE INHIBITOR OF METALLOPROTEINASE 1, MATRIX METALLOPROTEINASE 9, ALPHA-1 ANTITRYPSIN, METALLOTHIONEIN AND UROKINASE TYPE PLASMINOGEN ACTIVATOR RECEPTOR IN SKIN BIOPSIES FROM PATIENTS AFFECTED BY AUTOIMMUNE BLISTERING DISEASES

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2013-07-01

    Full Text Available Introduction: Proteinases and proteinase inhibitors have been described to play a role in autoimmune skin blistering diseases. We studied skin lesional biopsies from patients affected by several autoimmune skin blistering diseases for proteinases and proteinase inhibitors. Methods: We utilized immunohistochemistry to evaluate biopsies for alpha-1-antitrypsin, human matrix metalloproteinase 9 (MMP9, human tissue inhibitor of metalloproteinases 1 (TIMP-1, metallothionein and urokinase type plasminogen activator receptor (uPAR. We tested 30 patients affected by endemic pemphigus, 30 controls from the endemic area, and 15 normal controls. We also tested 30 biopsies from patients with bullous pemphigoid (BP, 20 with pemphigus vulgaris (PV, 8 with pemphigus foliaceus, and 14 with dermatitis herpetiformis (DH. Results: Contrary to findings in the current literature, most autoimmune skin blistering disease biopsies were negative for uPAR and MMP9. Only some chronic patients with El Bagre-EPF were positive to MMP9 in the dermis, in proximity to telocytes. TIMP-1 and metallothionein were positive in half of the biopsies from BP patients at the basement membrane of the skin, within several skin appendices, in areas of dermal blood vessel inflammation and within dermal mesenchymal-epithelial cell junctions.

  17. Short-Term Catheter-Directed Thrombolysis with Low-Dose Urokinase Followed by Aspiration Thrombectomy for Treatment of Symptomatic Lower Extremity Deep Venous Thrombosis

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Se Hee; Lim, Nam Yeul; Song, Jang Hyeon [Dept. of Radiology, Chonnam National University Hospital, Gwangju (Korea, Republic of); Kim, Jae Kyu; Lim, Jae Hoon [Dept. of Radiology, Hospital, Ulsan University School of Medicine, Gweangju (Korea, Republic of); Chang, Nam Kyu [Dept. of Radiology, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of); Choi, Soo Jin Na; Chung, Sang Young [Dept. of Radiology, Chonnam National University Hospital, Chonnam National University School of Medicine, Gwangju (Korea, Republic of)

    2011-10-15

    To evaluate the venous patency in patients treated by catheter-directed thrombolysis with low-dose urokinase (UK) for symptomatic lower extremity deep venous thrombosis (DVT). Eighty-nine consecutive patients (46 women and 43 men; mean age, 58.1 years), treated by catheter-directed thrombolysis with low-dose UK were included in this study. Immediate venous patency was evaluated in terms of technical success (successful restoration of antegrade in-line flow in the treated vein with residual stenosis rate of less than 30%) and clinical success (significant reduction of clinical symptoms before hospital discharge). Late venous patency was evaluated in terms of primary patency rate and clinical success. Immediate technical success was achieved in all patients and immediate clinical success in 80 (90%) patients. There was no major systemic bleeding complication. The primary patency rate at 6 months and 12 months was 84% and 79%, respectively. Fifty-six (63%) patients were asymptomatic after a median clinical follow-up of 18 months, eleven (12%) patients improved moderately, seven (8%) patients remained unchanged, and fifteen (17%) patients had no clinical follow-up. Short-term catheter-directed thrombolysis with low-dose UK can be an effective, safe method to manage DVT of the lower extremities.

  18. Renin angiotensin system blockade reduces urinary levels of soluble urokinase plasminogen activator receptor (suPAR) in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Persson, Frederik; Theilade, Simone; Eugen-Olsen, Jesper

    2016-01-01

    treatment periods were compared to placebo. Patients (n = 22) were treated for 2-month periods with either placebo, irbesartan 300 mg once daily, aliskiren 300 mg once daily or irbesartan/aliskiren combination in random order. Placebo geometric mean plasma (SEM) levels of suPAR were 3.3 ng/mL (1.1......) and urine levels were 4.0 ng/mL (1.1). None of the treatments had significant effects on plasma levels of suPAR compared to placebo. Compared to placebo, irbesartan and combination treatment decreased urinary levels of suPAR significantly (-1.3 ng/mL), while aliskiren did not. In patients with type 2......Soluble urokinase plasminogen activator receptor (suPAR) is associated with faster decline in kidney function and the pathogenesis of diabetic nephropathy. However, little is known about the impact of treatment on plasma and urinary levels of suPAR. We aimed to investigate the impact of renin...

  19. In vivo evaluation of urokinase-loaded hollow nanogels for sonothrombolysis on suture embolization-induced acute ischemic stroke rat model

    Directory of Open Access Journals (Sweden)

    Yuming Teng

    2018-03-01

    Full Text Available The urokinase-type plasminogen activator (uPA loaded hollow nanogels (nUK were synthesized by a one-step reaction of glycol chitosan and aldehyde capped poly (ethylene oxide. The resultant formulation is sensitive to diagnostic ultrasound (US of 2 MHz. Herein, we evaluated the in vivo sonothrombolysis performance of the nUK on acute ischemic stroke rat model which was established by suture embolization of middle cerebral artery (MCA. Via intravenous (i.v. administration, the experimental data prove a controlled release of the therapeutic protein around the clots under ultrasound stimulation, leading to enhanced thrombolysis efficiency of the nUK, evidenced from smaller infarct volume and better clinical scores when compared to the i.v. dose of free uPA no matter with or without US intervention. Meanwhile, the preservation ability of the nanogels not only prolonged the circulation duration of the protein, but also resulted in the better blood-brain barrier protection of the nUK formulation, showing no increased risk on the hemorrhagic transformation than the controls. This work suggests that the nUK is a safe sonothrombolytic formulation for the treatment of acute ischemic stroke.

  20. Soluble Urokinase Plasminogen Activator Receptor Level Is an Independent Predictor of the Presence and Severity of Coronary Artery Disease and of Future Adverse Events

    DEFF Research Database (Denmark)

    Eapen, Danny J; Manocha, Pankaj; Ghasemzedah, Nima

    2014-01-01

    -statistic for a model based on traditional risk factors was improved from 0.72 to 0.74 (P=0.008) with the addition of suPAR. CONCLUSION: Elevated levels of plasma suPAR are associated with the presence and severity of CAD and are independent predictors of death and MI in patients with suspected or known CAD.......INTRODUCTION: Soluble urokinase plasminogen activator receptor (suPAR) is an emerging inflammatory and immune biomarker. Whether suPAR level predicts the presence and the severity of coronary artery disease (CAD), and of incident death and myocardial infarction (MI) in subjects with suspected CAD......, is unknown. METHODS AND RESULTS: We measured plasma suPAR levels in 3367 subjects (67% with CAD) recruited in the Emory Cardiovascular Biobank and followed them for adverse cardiovascular (CV) outcomes of death and MI over a mean 2.1±1.1 years. Presence of angiographic CAD (≥50% stenosis in ≥1 coronary...

  1. Extracellular collagenases and the endocytic receptor, urokinase plasminogen activator receptor-associated protein/Endo180, cooperate in fibroblast-mediated collagen degradation

    DEFF Research Database (Denmark)

    Madsen, Daniel H; Engelholm, Lars H; Ingvarsen, Signe

    2007-01-01

    The collagens of the extracellular matrix are the most abundant structural proteins in the mammalian body. In tissue remodeling and in the invasive growth of malignant tumors, collagens constitute an important barrier, and consequently, the turnover of collagen is a rate-limiting process in these......The collagens of the extracellular matrix are the most abundant structural proteins in the mammalian body. In tissue remodeling and in the invasive growth of malignant tumors, collagens constitute an important barrier, and consequently, the turnover of collagen is a rate-limiting process...... in these events. A recently discovered turnover route with importance for tumor growth involves intracellular collagen degradation and is governed by the collagen receptor, urokinase plasminogen activator receptor-associated protein (uPARAP or Endo180). The interplay between this mechanism and extracellular...... of large collagen fragments. First, we show that collagen that has been pre-cleaved by a mammalian collagenase is taken up much more efficiently than intact, native collagen by uPARAP/Endo180-positive cells. Second, we demonstrate that this preference is governed by the acquisition of a gelatin...

  2. PHYTOCHEMICAL SCREENING AND THROMBOLYTIC ACTIVITY ...

    African Journals Online (AJOL)

    2014-12-31

    Dec 31, 2014 ... S. Dibyajyoti et al. J Fundam Appl Sci. 2014, 6(2), 208-219. 215. Independent Samples Test. % of Clot lysis. Equal variances assumed. Equal variances not assumed. Levene's Test for. Equality of. Variances. F. 5.950. Sig. 0.025 t-test for Equality of Means. T. -197.372. -197.372. Df. 18. 14.444. Sig. (2-tailed).

  3. Thrombolytic therapy for acute extra-cranial artery dissection: report of two cases Terapia trombolítica em dissecções arteriais cérvico-cefálicas agudas: relato de dois casos

    Directory of Open Access Journals (Sweden)

    Osama O. Zaidat

    2001-12-01

    Full Text Available Extra-cranial arterial dissection accounts for 10% of strokes in young people. Information on safety of thrombolytic administration in this group is limited. The literature, however, does not favor use of thrombolytics for myocardial ischemia when peripheral arterial dissection coexists. Based on the clinical and radiological features, two patients who presented with acute stroke secondary to arterial dissection were considered for thrombolysis. One of them received intra-venous recombinant tissue plasminogen activator (rtPA, and the other patient received intra-arterial rtPA. There were no post thrombolysis complications. This report supports feasibility of administering thrombolytics in acute ischemic strokes resulting from extra-cranial arterial dissection. Future larger studies are necessary to determine the efficacy, safety and long-term outcome in this patient population.Dissecção arterial cérvico-cefálica corresponde a 10 % dos acidentes vasculares cerebrais (AVC em jovens. Informação sobre a segurança da administração de trombolíticos neste grupo é limitada. A literatura médica, entretanto, não favorece o uso de trombolíticos em isquemia miocárdica na coexistência de dissecção arterial periférica. Baseado nas características clínicas e radiológicas, dois pacientes com AVC agudo secundário a dissecção arterial foram considerados para terapia trombolítica. Um deles recebeu rtPA intravenoso e o outro paciente recebeu rtPA intra-arterial. Não houve complicações pós-trombólise. Este relato suporta a possibilidade do tratamento destes pacientes com terapia trombolítica. Estudos maiores são necessários para determinar a eficácia, segurança e resultados a longo prazo nesta população de pacientes.

  4. Protection and repair of post-thrombolytic brain tissue with high-dose human albumin and magnesium sulfate: an experimental study

    International Nuclear Information System (INIS)

    Li Yongdong; Zhao Jungong; Li Minghua; You Xiaofang; Chen Yingsheng

    2008-01-01

    Objective: To evaluate the neuroprotective effects of high-dose human albumin and magnesium sulfate combined with recombinant tissue plasminogen activator (rt-PA) thrombolysis in a SD rat model of embolic stroke, with the aim to explore the possibility of extention for thrombolytic window. Methods: A thromboembolic stroke model performed on male SD rats (n=40) was randomly assigned into four groups: group A (n=10): rats received an intravenous infusion of 10 mg/kg rt-PA over a period of one hour at 3 h after onset of MCAO; group B (n=10): rats received an intravenous infusion of 10 mg/kg rt-PA over a period of one hour at 6 h after onset of MCAO; group C(n=10): rats received an intravenous infusion of human albumin (2.5 g/kg) and rt-PA(10 mg/kg) at 3 h and 6 h after onset of MCAO; group D(n=10): rats received same dose human albumin and rt-PA as that in group C, in addition, magnesium salfate (500 mg/ kg) was given intraperitoneally 3 h and 18 h after onset of MCAO. MRI was performed in each animal at preischemia, 24 h, 7 d and 14 d after treatment. After the last MR examination, all animals were killed under anesthesia, pathologic study (including electron microscope, light microscope, immuno-histochemistry) was performed in each animal, and LSCM were performed in two animals of each group. Results: The infarct volumes in four groups at 14 d after thrombolysis reduced 5.07% , 2.58%, 10.18% and 35.40% respectively compared with the infarct volume at 3 h after MCAO, with a predominant reduction in group D (P<0.05); increase of rCBV was confirmed at the marginal area of the cerebral infarction from the onset of stroke to 14 d, with significant increase between group A and C from 1 d to 7 d (P<0.05), while no significant difference was found in group B and C. The longest survival exhibited in group D and the shortest in group B, and no significant difference occurred concerning about survival among the four groups (P=0.763, P=0.636). In addition, LSCM showed a slight

  5. Aspirin Inhibits IKK-β-mediated Prostate Cancer Cell Invasion by Targeting Matrix Metalloproteinase-9 and Urokinase-Type Plasminogen Activator.

    Science.gov (United States)

    Shi, Chongjun; Zhang, Nini; Feng, Yang; Cao, Jiewei; Chen, Xuyi; Liu, Bin

    2017-01-01

    Aspirin has been demonstrated to possess potent chemopreventive and anticancer effects on prostate cancer. However, the more detailed molecular mechanisms of aspirin to suppress prostate cancer cell invasion have not been clearly elucidated. Transwell assays were performed to evaluate the effects of aspirin on cell invasion. Matrix metalloproteinases (MMPs) and serine proteinases activities in cell media were examined by gelatin zymography and ELISA. In addition, inhibitor of κB (IκB) kinase-β (IKK-β) phosphorylation and IKK-β kinase activity were measured to assess the effects of aspirin on IKK-β activation. We found that aspirin suppressed the invasion and attachment in human prostate cancer cells. Aspirin treatment significantly resulted in reduction of matrix metalloproteinase-9 (MMP-9) and upregulation of tissue inhibitors of metalloproteinase-1 (TIMP-1) activity, which are the proteolytic enzymes contributing to the degradation of extracellular matrix and basement membrane in cell invasion and metastasis. Our data further showed that aspirin was able to inhibit both urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) expression in the cells. In addition, aspirin treatment caused a strong decrease in nuclear factor-kappa B (NF-κB) activation, inhibitor of κB (IκB)-α phosphorylation together with translocation of NF-κB p65 to nucleus and IκB kinase (IKK)- β activation. Moreover, the inhibitory effects of aspirin on cell invasion were reversed by IKK-β overexpression, while the IKK inhibitor sensitizes the anti-invasive effect of aspirin in prostate cancer cells. The present research concluded that aspirin suppressed prostate cancer cell invasion by reducing MMP-9 activity and uPA expression through decreasing of IKK-β-mediated NF-κB activation, indicating that the ability of aspirin to inhibit cell invasion might be useful in the chemoprevention of metastatic prostate cancer. © 2017 The Author(s)Published by

  6. Aspirin Inhibits IKK-β-mediated Prostate Cancer Cell Invasion by Targeting Matrix Metalloproteinase-9 and Urokinase-Type Plasminogen Activator

    Directory of Open Access Journals (Sweden)

    Chongjun Shi

    2017-03-01

    Full Text Available Background/Aims: Aspirin has been demonstrated to possess potent chemopreventive and anticancer effects on prostate cancer. However, the more detailed molecular mechanisms of aspirin to suppress prostate cancer cell invasion have not been clearly elucidated. Methods: Transwell assays were performed to evaluate the effects of aspirin on cell invasion. Matrix metalloproteinases (MMPs and serine proteinases activities in cell media were examined by gelatin zymography and ELISA. In addition, inhibitor of κB (IκB kinase-β (IKK-β phosphorylation and IKK-β kinase activity were measured to assess the effects of aspirin on IKK-β activation. Results: We found that aspirin suppressed the invasion and attachment in human prostate cancer cells. Aspirin treatment significantly resulted in reduction of matrix metalloproteinase-9 (MMP-9 and upregulation of tissue inhibitors of metalloproteinase-1 (TIMP-1 activity, which are the proteolytic enzymes contributing to the degradation of extracellular matrix and basement membrane in cell invasion and metastasis. Our data further showed that aspirin was able to inhibit both urokinase-type plasminogen activator (uPA and plasminogen activator inhibitor-1 (PAI-1 expression in the cells. In addition, aspirin treatment caused a strong decrease in nuclear factor-kappa B (NF-κB activation, inhibitor of κB (IκB-α phosphorylation together with translocation of NF-κB p65 to nucleus and IκB kinase (IKK- β activation. Moreover, the inhibitory effects of aspirin on cell invasion were reversed by IKK-β overexpression, while the IKK inhibitor sensitizes the anti-invasive effect of aspirin in prostate cancer cells. Conclusion: The present research concluded that aspirin suppressed prostate cancer cell invasion by reducing MMP-9 activity and uPA expression through decreasing of IKK-β-mediated NF-κB activation, indicating that the ability of aspirin to inhibit cell invasion might be useful in the chemoprevention of

  7. Plasma levels of soluble urokinase-type plasminogen activator receptor (suPAR and early mortality risk among patients enrolling for antiretroviral treatment in South Africa

    Directory of Open Access Journals (Sweden)

    Bangani Nonzwakazi

    2007-05-01

    Full Text Available Abstract Background Serum concentrations of soluble urokinase-type plasminogen activator receptor (suPAR have a strong independent association with HIV-1-related mortality. The practical utility of plasma suPAR in assessing short-term all-cause mortality risk was evaluated in patients with advanced immunodeficiency enrolling in an antiretroviral treatment (ART programme in South Africa. Methods An enzyme-linked immunosorbent assay (ELISA was used to measure plasma concentrations of suPAR in patients at the time of enrolment to the ART programme. The association between plasma suPAR concentrations, baseline patient characteristics and cohort outcomes after 4 months of ART were determined. Results Patients (n = 293, 70% female had a median age of 33 years and were followed up for a median of 5 months from enrolment. The median CD4 cell count was 47 cells/μl (IQR = 22–72 and 38% of patients had WHO stage 4 disease. 218 (74% patients remained alive after 4 months of ART; 39 (13% died and 36 (12% were lost to the programme for other reasons. Patients who died had significantly higher plasma suPAR concentrations compared to those who either survived (P 10 suPAR concentrations were significantly associated with lower CD4 cell counts, WHO clinical stage 4 disease and male sex. In multivariate analysis to identify factors associated with death, log10 suPAR concentration was the most strongly associated variable (P Conclusion Plasma suPAR concentration was the strongest independent predictor of short-term mortality risk among patients with advanced immunodeficiency enrolling in this ART programme. However, lack of a discriminatory threshold did not permit this marker to be used to triage patients according to short-term mortality risk.

  8. Circulating intact and cleaved forms of the urokinase-type plasminogen activator receptor: biological variation, reference intervals and clinical useful cut-points.

    Science.gov (United States)

    Thurison, Tine; Christensen, Ib J; Lund, Ida K; Nielsen, Hans J; Høyer-Hansen, Gunilla

    2015-01-15

    High levels of circulating forms of the urokinase-type plasminogen activator receptor (uPAR) are significantly associated to poor prognosis in cancer patients. Our aim was to determine biological variations and reference intervals of the uPAR forms in blood, and in addition, to test the clinical relevance of using these as cut-points in colorectal cancer (CRC) prognosis. uPAR forms were measured in citrated and EDTA plasma samples using time-resolved fluorescence immunoassays. Diurnal, intra- and inter-individual variations were assessed in plasma samples from cohorts of healthy individuals. Reference intervals were determined in plasma from healthy individuals randomly selected from a Danish multi-center cross-sectional study. A cohort of CRC patients was selected from the same cross-sectional study. The reference intervals showed a slight increase with age and women had ~20% higher levels. The intra- and inter-individual variations were ~10% and ~20-30%, respectively and the measured levels of the uPAR forms were within the determined 95% reference intervals. No diurnal variation was found. Applying the normal upper limit of the reference intervals as cut-point for dichotomizing CRC patients revealed significantly decreased overall survival of patients with levels above this cut-point of any uPAR form. The reference intervals for the different uPAR forms are valid and the upper normal limits are clinically relevant cut-points for CRC prognosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. An Anti-Urokinase Plasminogen Activator Receptor Antibody (ATN-658 Blocks Prostate Cancer Invasion, Migration, Growth, and Experimental Skeletal Metastasis In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Shafaat A. Rabbani

    2010-10-01

    Full Text Available Urokinase plasminogen activator receptor (uPAR is a multidomain protein that plays important roles in the growth, invasion, and metastasis of a number of cancers. In the present study, we examined the effects of administration of a monoclonal anti-uPAR antibody (ATN-658 on prostate cancer progression in vitro and in vivo. We examined the effect of treatment of ATN-658 on human prostate cancer cell invasion, migration, proliferation, and regulation of intracellular signaling pathways. For in vivo studies, PC-3 cells (1 x 106 were inoculated into the right flank of male Balb C nu/nu mice through subcutaneous or through intratibial route (2 x 105 of male Fox Chase severe combined immunodeficient mice to monitor the effect on tumor growth and skeletal metastasis. Treatment with ATN-658 resulted in a significant dose-dependent decrease in PC-3 cell invasion and migration without affecting cell doubling time. Western blot analysis showed that ATN-658 treatment decreased the phosphorylation of serine/threonine protein kinase B (AKT, mitogen-activated protein kinase (MAPK, and focal adhesion kinase (FAK without affecting AKT, MAPK, and FAK total protein expression. In in vivo studies, ATN-658 caused a significant decrease in tumor volume and a marked reduction in skeletal lesions as determined by Faxitron x-ray and micro-computed tomography. Immunohistochemical analysis of subcutaneous and tibial tumors showed a marked decrease in the levels of expression of pAKT, pMAPK, and pFAK, consistent with the in vitro observations. Results from these studies provide compelling evidence for the continued development of ATN-658 as a potential therapeutic agent for the treatment of prostate and other cancers expressing uPAR.

  10. Soluble urokinase-type plasminogen activator receptor (suPAR) in patients with acute pancreatitis (AP) - Progress in prediction of AP severity.

    Science.gov (United States)

    Lipinski, Michal; Rydzewska-Rosolowska, Alicja; Rydzewski, Andrzej; Cicha, Malgorzata; Rydzewska, Grazyna

    Soluble urokinase-type plasminogen activator receptor (suPAR) is a glycoprotein secreted during inflammation and infections. Moreover, increased levels of suPAR are observed after hypoxia and ischaemia. The aim of the study was to assess whether suPAR could represent a useful marker of acute pancreatitis (AP) severity. We have observed a cohort of 126 prospectively enrolled patients. Based on the presence of persistent organ failure (more than 48 h) and local complications (diagnosis of moderate AP [MSAP]), patients were classified into three groups: mild AP (MAP), moderate and severe AP (SAP). The blood samples were taken on admission for detecting suPAR concentrations. AP was considered severe in 33 patients (26.2%), MSAP was found in 37 patients (29.4%), and MAP was found in 56 patients (44,4%). The AUC for SAP predicted by suPAR was 0.993. The calculated cut-off point for prognosis SAP is 4.75 ng/mL. The BISAP score of ≥3 for detection of SAP had sensitivity and specificity of 94.6% and 63.6%, respectively. The AUC for severity predicted by BISAP amounted to 0.916. Additionally, suPAR turned out to be a good predictor of fatal AP: for the cut-off point 7.05 ng/mL, the AUC was 0.917. The AUC for death prediction in AP patients based on the BISAP score ≥3 was 0.894. suPAR concentration is a promising new diagnostic and prognostic indicator in SAP obtainable in the early stage of disease. Larger studies are recommended to evaluate this role further. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  11. A high-protein diet during hospitalization is associated with an accelerated decrease in soluble urokinase plasminogen activator receptor levels in acutely ill elderly medical patients with SIRS.

    Science.gov (United States)

    Tavenier, Juliette; Haupt, Thomas H; Andersen, Aino L; Buhl, Sussi F; Langkilde, Anne; Andersen, Jens R; Jensen, Jens-Erik B; Pedersen, Mette M; Petersen, Janne; Andersen, Ove

    2017-05-01

    Acute illness and hospitalization in elderly individuals are often accompanied by the systemic inflammatory response syndrome (SIRS) and malnutrition, both associated with wasting and mortality. Nutritional support and resistance training were shown to increase muscle anabolism and reduce inflammation in healthy elderly. We hypothesized that nutritional support and resistance training would accelerate the resolution of inflammation in hospitalized elderly patients with SIRS. Acutely admitted patients aged >65 years with SIRS were randomized to an intervention consisting of a high-protein diet (1.7 g/kg per day) during hospitalization, and daily protein supplement (18.8 g) and 3 weekly resistance training sessions for 12 weeks after discharge (Intervention, n=14), or to standard-care (Control, n=15). Plasma levels of the inflammatory biomarkers soluble urokinase plasminogen activator receptor (suPAR), interleukin-6, C-reactive protein (CRP), and albumin were measured at admission, discharge, and 4 and 13 weeks after discharge. The Intervention group had an earlier decrease in suPAR levels than the Control group: -15.4% vs. +14.5%, P=.007 during hospitalization, and -2.4% vs. -28.6%, P=.007 between discharge and 4 weeks. There were no significant effects of the intervention on the other biomarkers. All biomarkers improved significantly between admission and 13 weeks, although with different kinetics (suPAR: -22%, interleukin-6: -86%, CRP: -89%, albumin: +11%). Nutritional support during hospitalization was associated with an accelerated decrease in suPAR levels, whereas the combined nutrition and resistance training intervention after discharge did not appear to affect the inflammatory state. Our results indicate that improved nutritional care during hospitalization may accelerate recovery in acutely ill elderly medical patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Hemangiosarcoma and its cancer stem cell subpopulation are effectively killed by a toxin targeted through epidermal growth factor and urokinase receptors.

    Science.gov (United States)

    Schappa, Jill T; Frantz, Aric M; Gorden, Brandi H; Dickerson, Erin B; Vallera, Daniel A; Modiano, Jaime F

    2013-10-15

    Targeted toxins have the potential to overcome intrinsic or acquired resistance of cancer cells to conventional cytotoxic agents. Here, we hypothesized that EGFuPA-toxin, a bispecific ligand-targeted toxin (BLT) consisting of a deimmunized Pseudomonas exotoxin (PE) conjugated to epidermal growth factor and urokinase, would efficiently target and kill cells derived from canine hemangiosarcoma (HSA), a highly chemotherapy resistant tumor, as well as cultured hemangiospheres, used as a surrogate for cancer stem cells (CSC). EGFuPA-toxin showed cytotoxicity in four HSA cell lines (Emma, Frog, DD-1 and SB) at a concentration of ≤100 nM, and the cytotoxicity was dependent on specific ligand-receptor interactions. Monospecific targeted toxins also killed these chemoresistant cells; in this case, a "threshold" level of EGFR expression appeared to be required to make cells sensitive to the monospecific EGF-toxin, but not to the monospecific uPA-toxin. The IC₅₀ of CSCs was higher by approximately two orders of magnitude as compared to non-CSCs, but these cells were still sensitive to EGFuPA-toxin at nanomolar (i.e., pharmacologically relevant) concentrations, and when targeted by EGFuPA-toxin, resulted in death of the entire cell population. Taken together, our results support the use of these toxins to treat chemoresistant tumors such as sarcomas, including those that conform to the CSC model. Our results also support the use of companion animals with cancer for further translational development of these cytotoxic molecules. Copyright © 2013 UICC.

  13. Staurosporine induces ganglion cell differentiation in part by stimulating urokinase-type plasminogen activator expression and activation in the developing chick retina

    International Nuclear Information System (INIS)

    Kim, Yeoun-Hee; Chang, Yongmin; Jung, Jae-Chang

    2012-01-01

    Highlights: ► Staurosporine mediates stimulation of RGC differentiation in vitro cultured retinal neuroblasts. ► Staurosporine mediates uPA activation during RGC differentiation in vitro. ► Inhibition of uPA blocks the staurosporine mediated RGC differentiation both in vitro and in ovo. ► Thus, uPA may play a role in the staurosporine-mediated stimulation of RGC differentiation. -- Abstract: Here, we investigated whether staurosporine-mediated urokinase-type plasminogen activator (uPA) activation is involved in retinal ganglion cell (RGC) differentiation. Retinal cells were isolated from developing chick retinas at embryonic day 6 (E6). Relatively few control cells grown in serum-free medium started to form processes by 12 h. In contrast, staurosporine-treated cells had processes within 3 h, and processes were evident at 8 h. Immunofluorescence staining showed that Tuj-1-positive cells with shorter neurites could be detected in control cultures at 18 h, whereas numerous Tuj-1 positive ganglion cells with longer neuritic extensions were seen in staurosporine-treated cultures. BrdU-positive proliferating cells were more numerous in control cultures than in staurosporine-treated cultures, and the BrdU staining was not detected in post-mitotic Tuj-1 positive ganglion cells. Western blotting of cell lysates showed that staurosporine induced high levels of the active form of uPA. The staurosporine-induced uPA signal was localized predominantly in the soma, neurites and axons of Tuj-1-positive ganglion cells. Amiloride, an inhibitor of uPA, markedly reduced staurosporine-induced Tuj-1 staining, neurite length, neurite number, and uPA staining versus controls. In developing retinas in ovo, amiloride administration remarkably reduced the staurosporine-induced uPA staining and RGC differentiation. Taken together, our in vitro and in vivo data collectively indicate that uPA plays a role in the staurosporine-mediated stimulation of RGC differentiation.

  14. Diagnostic accuracy of soluble urokinase plasminogen activator receptor (suPAR) for prediction of bacteremia in patients with systemic inflammatory response syndrome.

    Science.gov (United States)

    Hoenigl, Martin; Raggam, Reinhard B; Wagner, Jasmin; Valentin, Thomas; Leitner, Eva; Seeber, Katharina; Zollner-Schwetz, Ines; Krammer, Werner; Prüller, Florian; Grisold, Andrea J; Krause, Robert

    2013-02-01

    Soluble urokinase plasminogen activator receptor (suPAR) serum concentrations have recently been described to reflect the severity status of systemic inflammation. In this study, the diagnostic accuracy of suPAR, C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) to predict bacteremia in patients with systemic inflammatory response syndrome (SIRS) was compared. A total of 132 patients with SIRS were included. In 55 patients blood cultures had resulted positive (study group 1, Gram positive bacteria: Staphylococcus aureus and Streptococcus spp., n=15; study group 2, Gram-negative bacteria, n=40) and 77 patients had negative blood culture results (control group, n=77). Simultaneously with blood cultures suPAR, CRP, PCT, IL-6 and white blood count (WBC) were determined. SuPAR values were significantly higher in study group 1 (median 8.11; IQR 5.78-15.53; p=0.006) and study group 2 (median 9.62; IQR 6.52-11.74; p<0.001) when compared with the control group (median 5.65; IQR 4.30-7.83). ROC curve analysis revealed an AUC of 0.726 for suPAR in differentiating SIRS patients with bacteremia from those without. The biomarkers PCT and IL-6 showed comparable results. Regarding combinations of biomarkers multiplying suPAR, PCT and IL-6 was most promising and resulted in an AUC value of 0.804. Initial suPAR serum concentrations were significantly higher (p=0.028) in patients who died within 28 days than in those who survived. No significant difference was seen for PCT, IL-6 and CRP. In conclusion, suPAR, IL-6 and PCT may contribute to predicting bacteremia in SIRS patients. Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  15. Urokinase-type plasminogen activator (uPA) stimulates triglyceride synthesis in Huh7 hepatoma cells via p38-dependent upregulation of DGAT2.

    Science.gov (United States)

    Paland, Nicole; Gamliel-Lazarovich, Aviva; Coleman, Raymond; Fuhrman, Bianca

    2014-11-01

    The liver is the central organ of fatty acid and triglyceride metabolism. Oxidation and synthesis of fatty acids and triglycerides is under the control of peroxisome-proliferator-activated receptors (PPAR) α. Impairment of these receptors' function contributes to the accumulation of triglycerides in the liver resulting in non-alcoholic fatty liver disease. Urokinase-type plasminogen activator (uPA) was shown to regulate gene expression in the liver involving PPARγ transcriptional activity. In this study we questioned whether uPA modulates triglyceride metabolism in the liver, and investigated the mechanisms involved in the observed processes. Huh7 hepatoma cells were incubated with increasing concentrations of uPA for 24 h uPA dose-dependently increased the cellular triglyceride mass, and this effect resulted from increased de novo triglyceride synthesis mediated by the enzyme diglyceride acyltransferase 2 (DGAT2). Also, the amount of free fatty acids was highly up regulated by uPA through activation of the transcription factor SREBP-1. Chemical activation of PPARα further increased uPA-stimulated triglyceride synthesis, whereas inhibition of p38, an upstream activator of PPARα, completely abolished the stimulatory effect of uPA on both triglyceride synthesis and DGAT2 upregulation. The effect of uPA on triglyceride synthesis in Huh7 cells was mediated via binding to its receptor, the uPAR. In vivo studies in uPAR(-/-) mice demonstrated that no lipid droplets were observed in their livers compared to C57BL/6 mice and the triglyceride levels were significantly lower. This study presents a new biological function of the uPA/uPAR system in the metabolism of triglycerides and might present a new target for an early therapeutic intervention for NAFLD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. A combination of desmopressin and docetaxel inhibit cell proliferation and invasion mediated by urokinase-type plasminogen activator (uPA) in human prostate cancer cells

    International Nuclear Information System (INIS)

    Sasaki, Hiroshi; Klotz, Laurence H.; Sugar, Linda M.; Kiss, Alexander; Venkateswaran, Vasundara

    2015-01-01

    Background: This study was designed to assess the effectiveness of a combination treatment using both desmopressin and docetaxel in prostate cancer treatment. Desmopressin is a well-known synthetic analogue of the antidiuretic hormone vasopressin. It has recently been demonstrated to inhibit tumor progression and metastasis in in vivo models. Docetaxel is widely used for the treatment of castration resistant prostate cancer (CRPC) patients. However, durable responses have been uncommon to date. In this study, we investigated the anti-tumor effect of desmopressin in combination with docetaxel in vitro and in vivo. Methods: Two prostate cancer cells (PC3, LNCaP) were treated with different concentrations of desmopressin alone, docetaxel alone, and a combination of desmopressin and docetaxel. Cell proliferation was determined by MTS assay. The anti-invasive and anti-migration potential of desmopressin and in combination with docetaxel were examined by wound healing assay, migration chamber assay, and matrigel invasion assay. Results: The combination of desmopressin and docetaxel resulted in a significant inhibition of PC3 and LNCaP cell proliferation (p < 0.01). Additionally, cell migration and invasion were also inhibited by the combination when compared to that of either treatment alone in PC3 cells (p < 0.01). The anti-tumor effect of this combination treatment was associated with down-regulation of both urokinase-type plasminogen activator (uPA) and matrix metalloproteinase (MMP-2 and MMP-9) in PC3 cells. Conclusions: We are the first to elucidate the anti-tumor and anti-metastatic potential of desmopressin in combination with docetaxel in a prostate cancer model via the uPA-MMP pathway. Our finding could potentially contribute to the therapeutic profile of desmopressin and enhance the efficacy of docetaxel based treatment for CRPC. - Highlights: • Desmopressin inhibits cell proliferation in prostate cancer cells. • The expression of cyclin A and CDK2

  17. Nicotine stimulates urokinase-type plasminogen activator receptor expression and cell invasiveness through mitogen-activated protein kinase and reactive oxygen species signaling in ECV304 endothelial cells

    International Nuclear Information System (INIS)

    Khoi, Pham Ngoc; Park, Jung Sun; Kim, Nam Ho; Jung, Young Do

    2012-01-01

    Urokinase-type plasminogen activator receptor (uPAR) expression is elevated during inflammation, tissue remodeling and in many human cancers. This study investigated the effect of nicotine, a major alkaloid in tobacco, on uPAR expression and cell invasiveness in ECV304 endothelial cells. Nicotine stimulated uPAR expression in a dose-dependent manner and activated extracellular signal-regulated kinases-1/2 (Erk-1/2), c-Jun amino-terminal kinase (JNK) and p38 mitogen activated protein kinase (MAPK). Specific inhibitors of MEK-1 (PD98059) and JNK (SP600125) inhibited the nicotine-induced uPAR expression, while the p38 MAPK inhibitor SB203580 did not. Expression vectors encoding dominant negative MEK-1 (pMCL-K97M) and JNK (TAM67) also prevented nicotine-induced uPAR promoter activity. The intracellular hydrogen peroxide (H 2 O 2 ) content was increased by nicotine treatment. The antioxidant N-acetylcysteine prevented nicotine-activated production of reactive oxygen species (ROS) and uPAR expression. Furthermore, exogenous H 2 O 2 increased uPAR mRNA expression. Deleted and site-directed mutagenesis demonstrated the involvement of the binding sites of transcription factor nuclear factor-kappaB (NF-κB) and activator protein (AP)-1 in the nicotine-induced uPAR expression. Studies with expression vectors encoding mutated NF-κB signaling molecules and AP-1 decoy confirmed that NF-κB and AP-1 were essential for the nicotine-stimulated uPAR expression. MAPK (Erk-1/2 and JNK) and ROS functioned as upstream signaling molecules in the activation of AP-1 and NF-κB, respectively. In addition, ECV304 endothelial cells treated with nicotine displayed markedly enhanced invasiveness, which was partially abrogated by uPAR neutralizing antibodies. The data indicate that nicotine induces uPAR expression via the MAPK/AP-1 and ROS/NF-κB signaling pathways and, in turn, stimulates invasiveness in human ECV304 endothelial cells. -- Highlights: ► Endothelial cells treated with nicotine

  18. Nicotine stimulates urokinase-type plasminogen activator receptor expression and cell invasiveness through mitogen-activated protein kinase and reactive oxygen species signaling in ECV304 endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Khoi, Pham Ngoc; Park, Jung Sun; Kim, Nam Ho; Jung, Young Do, E-mail: ydjung@chonnam.ac.kr

    2012-03-01

    Urokinase-type plasminogen activator receptor (uPAR) expression is elevated during inflammation, tissue remodeling and in many human cancers. This study investigated the effect of nicotine, a major alkaloid in tobacco, on uPAR expression and cell invasiveness in ECV304 endothelial cells. Nicotine stimulated uPAR expression in a dose-dependent manner and activated extracellular signal-regulated kinases-1/2 (Erk-1/2), c-Jun amino-terminal kinase (JNK) and p38 mitogen activated protein kinase (MAPK). Specific inhibitors of MEK-1 (PD98059) and JNK (SP600125) inhibited the nicotine-induced uPAR expression, while the p38 MAPK inhibitor SB203580 did not. Expression vectors encoding dominant negative MEK-1 (pMCL-K97M) and JNK (TAM67) also prevented nicotine-induced uPAR promoter activity. The intracellular hydrogen peroxide (H{sub 2}O{sub 2}) content was increased by nicotine treatment. The antioxidant N-acetylcysteine prevented nicotine-activated production of reactive oxygen species (ROS) and uPAR expression. Furthermore, exogenous H{sub 2}O{sub 2} increased uPAR mRNA expression. Deleted and site-directed mutagenesis demonstrated the involvement of the binding sites of transcription factor nuclear factor-kappaB (NF-κB) and activator protein (AP)-1 in the nicotine-induced uPAR expression. Studies with expression vectors encoding mutated NF-κB signaling molecules and AP-1 decoy confirmed that NF-κB and AP-1 were essential for the nicotine-stimulated uPAR expression. MAPK (Erk-1/2 and JNK) and ROS functioned as upstream signaling molecules in the activation of AP-1 and NF-κB, respectively. In addition, ECV304 endothelial cells treated with nicotine displayed markedly enhanced invasiveness, which was partially abrogated by uPAR neutralizing antibodies. The data indicate that nicotine induces uPAR expression via the MAPK/AP-1 and ROS/NF-κB signaling pathways and, in turn, stimulates invasiveness in human ECV304 endothelial cells. -- Highlights: ► Endothelial cells

  19. In IgA Nephropathy, Glomerulosclerosis Is Associated with Increased Urinary CD80 Excretion and Urokinase-Type Plasminogen Activator Receptor-Positive Podocyturia

    Directory of Open Access Journals (Sweden)

    Hernán Trimarchi

    2017-05-01

    Full Text Available Background: Podocyturia may determine the evolution to podocytopenia, glomerulosclerosis, and renal failure. According to the Oxford classification of IgA nephropathy (IgAN, the S1 lesion describes glomerulosclerosis. Urokinase-type plasminogen activator receptor (uPAR participates in podocyte attachment, while CD80 increases in glomerulosclerosis. We measured uPAR-positive urinary podocytes and urinary CD80 (uCD80 in controls and in IgAN subjects with M1E0S0T0 and M1E0S1T0 Oxford scores to assess a potential association between podocyturia, inflammation, and glomerulosclerosis. Methods: The groups were as follows: controls (G1, n = 20 and IgAN group (G2, n = 39, subdivided into M1E0S0T0 (G2A, n = 21 and M1E0S1T0 (G2B, n = 18. Among the included variables, we determined uPAR-positive podocytes/gram of urinary creatinine (gUrCr and uCD80 ng/gUrCr. Biopsies with interstitial fibrosis and tubular atrophy <10% were included. Results: Groups were not different in age and gender; urinary protein-creatinine (uP/C ratio, Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI equation, uPAR-positive podocytes/gUrCr, and uCD80 were significantly increased in G2 versus G1. G2A and G2B were not different in age, gender, hypertension, and follow-up. G2B displayed significantly higher uP/C, uPAR-positive podocytes, uCD80, and lower CKD-EPI versus G2A. Strong significant correlations were encountered between uCD80 and podocyturia in G2A and G2B. However, when G1 was compared to G2A and G2B separately, the differences with respect to uP/C, uPAR-positive podocytes, and podocyturia were significantly stronger versus G2B than versus G2A. Conclusions: IgAN presents elevated uCD80 excretion and uPAR-positive podocyturia, while CD80 correlates with podocyturia. Glomerulosclerosis (S1 at the time of biopsy is associated with higher uP/C, lower renal function, increased uPAR-positive podocyturia, and CD80 excretion, and is independent of M1. In IgAN, uPAR may

  20. Intact and cleaved forms of the urokinase receptor enhance discrimination of cancer from non-malignant conditions in patients presenting with symptoms related to colorectal cancer.

    Science.gov (United States)

    Lomholt, A F; Høyer-Hansen, G; Nielsen, H J; Christensen, I J

    2009-09-15

    Colorectal cancer (CRC) is a leading cause of cancer-related morbidity and mortality in developed countries. It is known that early detection results in improved survival, and consequently there is a need for improved diagnostic tools in CRC. The plasma level of soluble urokinase plasminogen activator receptor (suPAR) was proposed as a marker in CRC patients. This study was undertaken to evaluate the individual molecular forms of suPAR as discriminators in a group of patients undergoing endoscopical examination following symptoms related to colorectal cancer. In a case-control study comprising 308 patients undergoing endoscopical examination following CRC-related symptoms, 77 CRC patients with adenocarcinoma were age and gender matched to: 77 patients with adenomas; 77 with other non-malignant findings, and 77 with no findings. The different uPAR forms were measured in citrate plasma collected before endoscopical examination, using three different Time Resolved - Fluorescence Immuno Assays (TR-FIA's). All soluble uPAR forms were found to be significantly higher in cancer patients than in patients presenting with other non-malignant findings; uPAR(I) P=0.0006, suPAR(I-III) P<0.0001 and suPAR(I-III)+(II-III) P<0.0001, whereas no significant difference was found when performing similar comparisons for patients presenting with adenomas. The odds ratio (OR) for the comparison of uPAR(I) in patients with CRC to subjects with other non-malignant findings was 3.44 (95% CI:1.86-6.37). CRC patients had a mean elevated level of 20.9% (95% CI:10.2-32.6) for suPAR(I-III) and 18.5% (95% CI:9.0-28.8) for suPAR(I-III)+(II-III) compared with subjects with non-malignant findings. The findings confirm reports on increased uPAR expression in cancer patients and in particular elevated levels of suPAR in blood from CRC patients and indicate that suPAR levels in blood are increasing during carcinogenesis. Although none of the measured uPAR forms were cancer specific, our findings suggest

  1. Staurosporine induces ganglion cell differentiation in part by stimulating urokinase-type plasminogen activator expression and activation in the developing chick retina

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yeoun-Hee [Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Chang, Yongmin [Department of Molecular Medicine, Kyungpook National University College of Medicine, Kyungpook National University, 200 Dongduk-Ro Jung-Gu, Daegu 700-714 (Korea, Republic of); Jung, Jae-Chang, E-mail: jcjung@knu.ac.kr [Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu 702-701 (Korea, Republic of)

    2012-06-22

    Highlights: Black-Right-Pointing-Pointer Staurosporine mediates stimulation of RGC differentiation in vitro cultured retinal neuroblasts. Black-Right-Pointing-Pointer Staurosporine mediates uPA activation during RGC differentiation in vitro. Black-Right-Pointing-Pointer Inhibition of uPA blocks the staurosporine mediated RGC differentiation both in vitro and in ovo. Black-Right-Pointing-Pointer Thus, uPA may play a role in the staurosporine-mediated stimulation of RGC differentiation. -- Abstract: Here, we investigated whether staurosporine-mediated urokinase-type plasminogen activator (uPA) activation is involved in retinal ganglion cell (RGC) differentiation. Retinal cells were isolated from developing chick retinas at embryonic day 6 (E6). Relatively few control cells grown in serum-free medium started to form processes by 12 h. In contrast, staurosporine-treated cells had processes within 3 h, and processes were evident at 8 h. Immunofluorescence staining showed that Tuj-1-positive cells with shorter neurites could be detected in control cultures at 18 h, whereas numerous Tuj-1 positive ganglion cells with longer neuritic extensions were seen in staurosporine-treated cultures. BrdU-positive proliferating cells were more numerous in control cultures than in staurosporine-treated cultures, and the BrdU staining was not detected in post-mitotic Tuj-1 positive ganglion cells. Western blotting of cell lysates showed that staurosporine induced high levels of the active form of uPA. The staurosporine-induced uPA signal was localized predominantly in the soma, neurites and axons of Tuj-1-positive ganglion cells. Amiloride, an inhibitor of uPA, markedly reduced staurosporine-induced Tuj-1 staining, neurite length, neurite number, and uPA staining versus controls. In developing retinas in ovo, amiloride administration remarkably reduced the staurosporine-induced uPA staining and RGC differentiation. Taken together, our in vitro and in vivo data collectively indicate that

  2. Regulation of DNA methylation in human breast cancer. Effect on the urokinase-type plasminogen activator gene production and tumor invasion.

    Science.gov (United States)

    Guo, Yongjing; Pakneshan, Pouya; Gladu, Julienne; Slack, Andrew; Szyf, Moshe; Rabbani, Shafaat A

    2002-11-01

    Urokinase-type plasminogen activator (uPA) is a member of the serine protease family and can break down various components of the extracellular matrix to promote growth, invasion, and metastasis of several malignancies including breast cancer. In the current study we examined the role that the DNA methylation machinery might be playing in regulating differential uPA gene expression in breast cancer cell lines. uPA mRNA is expressed in the highly invasive, hormone-insensitive human breast cancer cell line MDA-MB-231 but not in hormone-responsive cell line MCF-7. Using methylation-sensitive PCR, we show that 90% of CpG dinucleotides in the uPA promoter are methylated in MCF-7 cells, whereas fully demethylated CpGs were detected in MDA-MB-231 cells. uPA promoter activity, which is directly regulated by the Ets-1 transcription factor, is inhibited by methylation as determined by uPA promoter-luciferase reporter assays. We then tested whether the state of expression and methylation of the uPA promoter correlates with the global level of DNA methyltransferase and demethylase activities in these cell lines. We show that maintenance DNA methyltransferase activity is significantly higher in MCF-7 cells than in MDA-MB-231 cells, whereas demethylase activity is higher in MDA-MB-231 cells. We suggest that the combination of increased DNA methyltransferase activity with reduced demethylase activity contributes to the methylation and silencing of uPA expression in MCF-7 cells. The converse is true in MDA-MB-231 cells, which represents a late stage highly invasive breast cancer. The histone deacetylase inhibitor, Trichostatin A, induces the expression of the uPA gene in MDA-MB-231 cells but not in MCF-7 cells. This supports the hypothesis that DNA methylation is the dominant mechanism involved in the silencing of uPA gene expression. Taken together, these results provide insight into the mechanism regulating the transcription of the uPA gene in the complex multistep process of

  3. Exploiting subsite S1 of trypsin-like serine proteases for selectivity: potent and selective inhibitors of urokinase-type plasminogen activator.

    Science.gov (United States)

    Mackman, R L; Katz, B A; Breitenbucher, J G; Hui, H C; Verner, E; Luong, C; Liu, L; Sprengeler, P A

    2001-11-08

    A nonselective inhibitor of trypsin-like serine proteases, 2-(2-hydroxybiphenyl-3-yl)-1H-indole-5-carboxamidine (1) (Verner, E.; Katz, B. A.; Spencer, J.; Allen, D.; Hataye, J.; Hruzewicz, W.; Hui, H. C.; Kolesnikov, A.; Li, Y.; Luong, C.; Martelli, A.; Radika. K.; Rai, R.; She, M.; Shrader, W.; Sprengeler, P. A.; Trapp, S.; Wang, J.; Young, W. B.; Mackman, R. L. J. Med. Chem. 2001, 44, 2753-2771) has been optimized through minor structural changes on the S1 binding group to afford remarkably selective and potent inhibitors of urokinase-type plasminogen activator (uPA). The trypsin-like serine proteases(1) that comprise drug targets can be broadly categorized into two subfamilies, those with Ser190 and those with Ala190. A single-atom modification, for example, replacement of hydrogen for chlorine at the 6-position of the 5-amidinoindole P1 group on 1, generated up to 6700-fold selectivity toward the Ser190 enzymes and against the Ala190 enzymes. The larger chlorine atom displaces a water molecule (H(2)O1(S1)) that binds near residue 190 in all the complexes of 1, and related inhibitors, in uPA, thrombin, and trypsin. The water molecule, H(2)O1(S1), in both the Ser190 or Ala190 enzymes, hydrogen bonds with the amidine N1 nitrogen of the inhibitor. When it is displaced, a reduction in affinity toward the Ala190 enzymes is observed due to the amidine N1 nitrogen of the bound inhibitor being deprived of a key hydrogen-bonding partner. In the Ser190 enzymes the affinity is maintained since the serine hydroxyl oxygen O gamma(Ser190) compensates for the displaced water molecule. High-resolution crystallography provided evidence for the displacement of the water molecule and validated the design rationale. In summation, a novel and powerful method for engineering selectivity toward Ser190 proteases and against Ala190 proteases without substantially increasing molecular weight is described.

  4. A combination of desmopressin and docetaxel inhibit cell proliferation and invasion mediated by urokinase-type plasminogen activator (uPA) in human prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Hiroshi; Klotz, Laurence H. [Division of Urology, Sunnybrook Health Sciences Center, Toronto, ON (Canada); Sugar, Linda M. [Department of Pathology, Sunnybrook Health Sciences Center, Toronto, ON (Canada); Kiss, Alexander [Department of Research Design and Biostatistics, Institute for Clinical Evaluative Sciences, Sunnybrook Health Sciences Center, Toronto, ON (Canada); Venkateswaran, Vasundara, E-mail: vasundara.venkateswaran@sunnybrook.ca [Division of Urology, Sunnybrook Health Sciences Center, Toronto, ON (Canada)

    2015-08-28

    Background: This study was designed to assess the effectiveness of a combination treatment using both desmopressin and docetaxel in prostate cancer treatment. Desmopressin is a well-known synthetic analogue of the antidiuretic hormone vasopressin. It has recently been demonstrated to inhibit tumor progression and metastasis in in vivo models. Docetaxel is widely used for the treatment of castration resistant prostate cancer (CRPC) patients. However, durable responses have been uncommon to date. In this study, we investigated the anti-tumor effect of desmopressin in combination with docetaxel in vitro and in vivo. Methods: Two prostate cancer cells (PC3, LNCaP) were treated with different concentrations of desmopressin alone, docetaxel alone, and a combination of desmopressin and docetaxel. Cell proliferation was determined by MTS assay. The anti-invasive and anti-migration potential of desmopressin and in combination with docetaxel were examined by wound healing assay, migration chamber assay, and matrigel invasion assay. Results: The combination of desmopressin and docetaxel resulted in a significant inhibition of PC3 and LNCaP cell proliferation (p < 0.01). Additionally, cell migration and invasion were also inhibited by the combination when compared to that of either treatment alone in PC3 cells (p < 0.01). The anti-tumor effect of this combination treatment was associated with down-regulation of both urokinase-type plasminogen activator (uPA) and matrix metalloproteinase (MMP-2 and MMP-9) in PC3 cells. Conclusions: We are the first to elucidate the anti-tumor and anti-metastatic potential of desmopressin in combination with docetaxel in a prostate cancer model via the uPA-MMP pathway. Our finding could potentially contribute to the therapeutic profile of desmopressin and enhance the efficacy of docetaxel based treatment for CRPC. - Highlights: • Desmopressin inhibits cell proliferation in prostate cancer cells. • The expression of cyclin A and CDK2

  5. Prognostic significance of urokinase plasminogen activator and plasminogen activator inhibitor-1 mRNA expression in lymph node- and hormone receptor-positive breast cancer

    Directory of Open Access Journals (Sweden)

    Krause Alexander

    2006-08-01

    Full Text Available Abstract Background One of the most thoroughly studied systems in relation to its prognostic relevance in patients with breast cancer, is the plasminogen activation system that comprises of, among others, the urokinase Plasminogen Activator (uPA and its main inhibitor, the Plasminogen Activator Inhibitor-1 (PAI-1. In this study, we investigated the prognostic value of uPA and PAI-1 at the mRNA level in lymph node- and hormone receptor-positive breast cancer. Methods The study included a retrospective series of 87 patients with hormone-receptor positive and axillary lymph node-positive breast cancer. All patients received radiotherapy, adjuvant anthracycline-based chemotherapy and five years of tamoxifen treatment. The median patient age was 54 and the median follow-up time was 79 months. Distant relapse occurred in 30 patients and 22 patients died from breast cancer during follow-up. We investigated the prognostic value of uPA and PAI-1 at the mRNA level as measured by real-time quantitative RT-PCR. Results uPA and PAI-1 gene expression was not found to be correlated with any of the established clinical and pathological factors. Metastasis-free Survival (MFS and Breast Cancer specific Survival (BCS were significantly shorter in patients expressing high levels of PAI-1 mRNA (p PAI-1 mRNA appeared to be the strongest prognostic factor for MFS (Hazard Ratio (HR = 10.12; p = 0.0002 and for BCS (HR = 13.17; p = 0.0003. Furthermore, uPA gene expression was not significantly associated neither with MFS (p = 0.41 nor with BCS (p = 0.19. In a Cox-multivariate regression analysis, uPA expression did not demonstrate significant independent prognostic value. Conclusion These findings indicate that high PAI-1 mRNA expression represents a strong and independent unfavorable prognostic factor for the development of metastases and for breast cancer specific survival in a population of hormone receptor- and lymph node-positive breast cancer patients.

  6. Prognostic significance of urokinase plasminogen activator and plasminogen activator inhibitor-1 mRNA expression in lymph node- and hormone receptor-positive breast cancer

    International Nuclear Information System (INIS)

    Leissner, Philippe; Verjat, Thibault; Bachelot, Thomas; Paye, Malick; Krause, Alexander; Puisieux, Alain; Mougin, Bruno

    2006-01-01

    One of the most thoroughly studied systems in relation to its prognostic relevance in patients with breast cancer, is the plasminogen activation system that comprises of, among others, the urokinase Plasminogen Activator (uPA) and its main inhibitor, the Plasminogen Activator Inhibitor-1 (PAI-1). In this study, we investigated the prognostic value of uPA and PAI-1 at the mRNA level in lymph node- and hormone receptor-positive breast cancer. The study included a retrospective series of 87 patients with hormone-receptor positive and axillary lymph node-positive breast cancer. All patients received radiotherapy, adjuvant anthracycline-based chemotherapy and five years of tamoxifen treatment. The median patient age was 54 and the median follow-up time was 79 months. Distant relapse occurred in 30 patients and 22 patients died from breast cancer during follow-up. We investigated the prognostic value of uPA and PAI-1 at the mRNA level as measured by real-time quantitative RT-PCR. uPA and PAI-1 gene expression was not found to be correlated with any of the established clinical and pathological factors. Metastasis-free Survival (MFS) and Breast Cancer specific Survival (BCS) were significantly shorter in patients expressing high levels of PAI-1 mRNA (p < 0.0001; p < 0.0001; respectively). In Cox multivariate analysis, the level of PAI-1 mRNA appeared to be the strongest prognostic factor for MFS (Hazard Ratio (HR) = 10.12; p = 0.0002) and for BCS (HR = 13.17; p = 0.0003). Furthermore, uPA gene expression was not significantly associated neither with MFS (p = 0.41) nor with BCS (p = 0.19). In a Cox-multivariate regression analysis, uPA expression did not demonstrate significant independent prognostic value. These findings indicate that high PAI-1 mRNA expression represents a strong and independent unfavorable prognostic factor for the development of metastases and for breast cancer specific survival in a population of hormone receptor- and lymph node-positive breast cancer

  7. The pro-inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is associated with incident type 2 diabetes among overweight but not obese individuals with impaired glucose regulation

    DEFF Research Database (Denmark)

    Heraclides, A; Jensen, T M; Rasmussen, S S

    2013-01-01

    Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION) and for whom data on suPAR, BMI and smoking were available. Logistic regression analysis was used to estimate the odds for incident type 2 diabetes per twofold increase in suPAR levels. Interactions between both smoking and body......Recent evidence links the soluble urokinase plasminogen activator receptor (suPAR), a stable biomarker of systemic immune activation, to several chronic diseases, including type 2 diabetes. suPAR is also associated with adiposity and smoking. We hypothesised that this biomarker would be linked...... to incident type 2 diabetes in individuals with impaired glucose regulation and that this association would be modified by smoking and body weight status. The study included 1,933 participants with impaired glucose regulation, who were drawn from the Danish arm of the Anglo-Danish-Dutch Study of Intensive...

  8. Flavonol-enriched fraction from Vaccinium macrocarpon fruit inhibits matrix metalloproteinase-2, matrix metalloproteinase-9 and urokinase-type plasminogen activator expression in human prostate cancer cells in vitro

    Directory of Open Access Journals (Sweden)

    James MacPhee

    2014-11-01

    Full Text Available Background: Prostate cancer, amongst other cancer types has a genetic and environmental component, which can contribute to prostate cancer development and progression. Vaccinum macrocarpon (American cranberry is a botanical that contains several phytochemicals which have been suggested to play a role in preventing cardiovascular disease, cancer, and urinary tract infections as well as in the maintenance of oral health. Context and purpose of this study: This investigation evaluated the effects of a flavonolenriched fraction (FL from the American cranberry (Vaccinium macrocarpon containing quercetin and myricetin glycosides on matrix metalloproteinase (MMP and urokinase-type plasminogen activator (uPA activities and their associated regulatory proteins in DU145 human prostate cancer cells in vitro. Results: A flavonol-enriched fraction (FL was prepared from Vaccinium macrocarpon berries and the effect of this fraction on prostate cancer cell behaviour was assessed using biochemical and molecular approaches including cytotoxicity assays and Western blot analysis to determine protein expression. Cranberry FL decreased cellular viability of DU145 cells at a concentration of 25 ug/ml by 20% after 6 hours of treatment. Further investigations determined that associated with this cytotoxicity, cranberry FL decreases matrix metalloproteinase (MMP ( specifically MMP-2 and MMP-9 activity and urokinase plasminogen activator (uPA activity through effects on specific temporal MMP regulators and uPA regulators and by affecting either the phosphorylation status and/or expression of specific MAP kinase, PI-3 kinase, NF-kB and AP-1 pathway associated proteins. Conclusion: This study demonstrates, for the first time, the ability of Vaccinium macrocarpon flavonols to modulate cellular pathways associated with migration, invasion, and proliferation, suggesting that cranberry (Vaccinium macrocarpon is a viable candidate for further research as a natural product that

  9. Recanalization rate and clinical outcome of intravenous tissue plasminogen activator at 0.6 mg/kg and intra-arterial urokinase in acute ischemic stroke with large vessel occlusion

    International Nuclear Information System (INIS)

    Nakashima, Kazuya; Ohnishi, Hideyuki; Taomoto, Katsushi

    2008-01-01

    We evaluated the recanalization rate and clinical outcome of intravenous tissue plasminogen activator (t-PA) and intra-arterial urokinase (PTA) in acute ischemic stroke with large vessel occlusion. The recanalization of the occlusion site and the ischemic change were evaluated with pre-and post-treated MRI and MR angiography (MRA). Total recanalization rates after the intravenous (IV) t-PA and the PTA therapy were 35.6 and 21.9%, respectively. These rates were 50.0 and 16.7% in the distal middle cerebral artery (MCA), 52.6 and 25.0% in the proximal MCA, 6.3 and 5.3% in the internal carotid artery (ICA), 25.0 and 26.3% in the basilar artery (BA), respectively. The rates of the symptomatic intracerebral hemorrhage after IV t-PA and PTA were 0 and 5.2%, respectively. The proportion of modified Rankin Scale (mRS) of 0 to 1 at 3 months after treatments were 17.4% in IV t-PA and 12.5% in PTA. Our results indicated better recanalization rate and outcome of MCA with t-PA than that of PTA. However, the recanalization rate of ICA and BA were very poor in both t-PA and PTA as yet. It is necessary to investigate newly strategies and/or modality for ICA and BA occlusion. (author)

  10. Vasodilator-Stimulated Phosphoprotein (VASP) depletion from breast cancer MDA-MB-231 cells inhibits tumor spheroid invasion through downregulation of Migfilin, β-catenin and urokinase-plasminogen activator (uPA).

    Science.gov (United States)

    Gkretsi, Vasiliki; Stylianou, Andreas; Stylianopoulos, Triantafyllos

    2017-03-15

    A hallmark of cancer cells is their ability to invade surrounding tissues and form metastases. Cell-extracellular matrix (ECM)-adhesion proteins are crucial in metastasis, connecting tumor ECM with actin cytoskeleton thus enabling cells to respond to mechanical cues. Vasodilator-stimulated phosphoprotein (VASP) is an actin-polymerization regulator which interacts with cell-ECM adhesion protein Migfilin, and regulates cell migration. We compared VASP expression in MCF-7 and MDA-MB-231 breast cancer (BC) cells and found that more invasive MDA-MB-231 cells overexpress VASP. We then utilized a 3-dimensional (3D) approach to study metastasis in MDA-MB-231 cells using a system that considers mechanical forces exerted by the ECM. We prepared 3D collagen I gels of increasing concentration, imaged them by atomic force microscopy, and used them to either embed cells or tumor spheroids, in the presence or absence of VASP. We show, for the first time, that VASP silencing downregulated Migfilin, β-catenin and urokinase plasminogen activator both in 2D and 3D, suggesting a matrix-independent mechanism. Tumor spheroids lacking VASP demonstrated impaired invasion, indicating VASP's involvement in metastasis, which was corroborated by Kaplan-Meier plotter showing high VASP expression to be associated with poor remission-free survival in lymph node-positive BC patients. Hence, VASP may be a novel BC metastasis biomarker. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Vasodilator-Stimulated Phosphoprotein (VASP) depletion from breast cancer MDA-MB-231 cells inhibits tumor spheroid invasion through downregulation of Migfilin, β-catenin and urokinase-plasminogen activator (uPA)

    Energy Technology Data Exchange (ETDEWEB)

    Gkretsi, Vasiliki; Stylianou, Andreas; Stylianopoulos, Triantafyllos, E-mail: tstylian@ucy.ac.cy

    2017-03-15

    A hallmark of cancer cells is their ability to invade surrounding tissues and form metastases. Cell-extracellular matrix (ECM)-adhesion proteins are crucial in metastasis, connecting tumor ECM with actin cytoskeleton thus enabling cells to respond to mechanical cues. Vasodilator-stimulated phosphoprotein (VASP) is an actin-polymerization regulator which interacts with cell-ECM adhesion protein Migfilin, and regulates cell migration. We compared VASP expression in MCF-7 and MDA-MB-231 breast cancer (BC) cells and found that more invasive MDA-MB-231 cells overexpress VASP. We then utilized a 3-dimensional (3D) approach to study metastasis in MDA-MB-231 cells using a system that considers mechanical forces exerted by the ECM. We prepared 3D collagen I gels of increasing concentration, imaged them by atomic force microscopy, and used them to either embed cells or tumor spheroids, in the presence or absence of VASP. We show, for the first time, that VASP silencing downregulated Migfilin, β-catenin and urokinase plasminogen activator both in 2D and 3D, suggesting a matrix-independent mechanism. Tumor spheroids lacking VASP demonstrated impaired invasion, indicating VASP’s involvement in metastasis, which was corroborated by Kaplan-Meier plotter showing high VASP expression to be associated with poor remission-free survival in lymph node-positive BC patients. Hence, VASP may be a novel BC metastasis biomarker. - Highlights: • More invasive MDA-MB-231 overexpress VASP compared to MCF-7 breast cancer cells. • We prepared 3D collagen I gels of increasing concentration and characterized them. • VASP silencing downregulated Migfilin, β-catenin and uPA both in 2D and 3D culture. • Tumor spheroids lacking VASP demonstrated impaired invasion. • Kaplan-Meier plotter shows association of high VASP expression with poor survival.

  12. Tumor marker utility and prognostic relevance of cathepsin B, cathepsin L, urokinase-type plasminogen activator, plasminogen activator inhibitor type-1, CEA and CA 19-9 in colorectal cancer

    International Nuclear Information System (INIS)

    Herszényi, László; Farinati, Fabio; Cardin, Romilda; István, Gábor; Molnár, László D; Hritz, István; De Paoli, Massimo; Plebani, Mario; Tulassay, Zsolt

    2008-01-01

    Cathepsin B and L (CATB, CATL), urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 play an important role in colorectal cancer invasion. The tumor marker utility and prognostic relevance of these proteases have not been evaluated in the same experimental setting and compared with that of CEA and CA-19-9. Protease, CEA and CA 19-9 serum or plasma levels were determined in 56 patients with colorectal cancer, 25 patients with ulcerative colitis, 26 patients with colorectal adenomas and 35 tumor-free control patients. Protease, CEA, CA 19-9 levels have been determined by ELISA and electrochemiluminescence immunoassay, respectively; their sensitivity, specificity, diagnostic accuracy have been calculated and correlated with clinicopathological staging. The protease antigen levels were significantly higher in colorectal cancer compared with other groups. Sensitivity of PAI-1 (94%), CATB (82%), uPA (69%), CATL (41%) were higher than those of CEA or CA 19-9 (30% and 18%, respectively). PAI-1, CATB and uPA demonstrated a better accuracy than CEA or CA 19-9. A combination of PAI-1 with CATB or uPA exhibited the highest sensitivity value (98%). High CATB, PAI-1, CEA and CA 19-9 levels correlated with advanced Dukes stages. CATB (P = 0.0004), CATL (P = 0.02), PAI-1 (P = 0.01) and CA 19-9 (P = 0.004) had a significant prognostic impact. PAI-1 (P = 0.001), CATB (P = 0.04) and CA 19-9 (P = 0.02) proved as independent prognostic variables. At the time of clinical detection proteases are more sensitive indicators for colorectal cancer than the commonly used tumor markers. Determinations of CATB, CATL and PAI-1 have a major prognostic impact in patients with colorectal cancer

  13. Dioscorea nipponica Attenuates Migration and Invasion by Inhibition of Urokinase-Type Plasminogen Activator through Involving PI3K/Akt and Transcriptional Inhibition of NF-[Formula: see text]B and SP-1 in Hepatocellular Carcinoma.

    Science.gov (United States)

    Hsieh, Ming-Ju; Yeh, Chao-Bin; Chiou, Hui-Ling; Hsieh, Ming-Chang; Yang, Shun-Fa

    2016-01-01

    High mortality and morbidity rates for hepatocellular carcinoma (HCC) in Taiwan primarily result from uncontrolled tumor metastasis. In our previous studies, we have reported that Dioscorea nipponica Makino extract (DNE) has anti-metastasis effects on human oral cancer cells. However, the effect of DNE on hepatoma metastasis have not been thoroughly investigated and remains poorly understood. To determine the effects of DNE on the migration and invasion in HCC cells we used a wound healing model, Boyden chamber assays, gelatin/casein zymography and Western blotting. Transcriptional levels of matrix metalloproteinase-9 (MMP-9) and urokinase-type plasminogen activator (u-PA) were detected by real-time PCR and promoter assays. In this study, DNE treatment significantly inhibited the migration/invasion capacities of Huh7 cell lines. The results of gelatin/casein zymography and Western blotting revealed that the activities and protein levels of the MMP-9 and u-PA were inhibited by DNE. Tests of the mRNA levels, real-time PCR, and promoter assays evaluated the inhibitory effects of DNE on u-PA expression in human hepatoma cells. A chromatin immunoprecipitation (ChIP) assay showed not only that DNE inhibits u-PA expression, but also the inhibitory effects were associated with the down-regulation of the transcription factors of NF-[Formula: see text]B and SP-1 signaling pathways. Western blot analysis also showed that DNE inhibits PI3K and phosphorylation of Akt. In conclusion, these results show that u-PA expression may be a potent therapeutic target in the DNE-mediated suppression of HCC invasion/migration. DNE may have potential use as a chemo-preventive agent against liver cancer metastasis.

  14. Antithrombotic and Thrombolytic Therapy for Ischemic Stroke

    Science.gov (United States)

    Lansberg, Maarten G.; O’Donnell, Martin J.; Khatri, Pooja; Lang, Eddy S.; Nguyen-Huynh, Mai N.; Schwartz, Neil E.; Sonnenberg, Frank A.; Schulman, Sam; Vandvik, Per Olav; Spencer, Frederick A.; Alonso-Coello, Pablo; Guyatt, Gordon H.

    2012-01-01

    Objectives: This article provides recommendations on the use of antithrombotic therapy in patients with stroke or transient ischemic attack (TIA). Methods: We generated treatment recommendations (Grade 1) and suggestions (Grade 2) based on high (A), moderate (B), and low (C) quality evidence. Results: In patients with acute ischemic stroke, we recommend IV recombinant tissue plasminogen activator (r-tPA) if treatment can be initiated within 3 h (Grade 1A) or 4.5 h (Grade 2C) of symptom onset; we suggest intraarterial r-tPA in patients ineligible for IV tPA if treatment can be initiated within 6 h (Grade 2C); we suggest against the use of mechanical thrombectomy (Grade 2C) although carefully selected patients may choose this intervention; and we recommend early aspirin therapy at a dose of 160 to 325 mg (Grade 1A). In patients with acute stroke and restricted mobility, we suggest the use of prophylactic-dose heparin or intermittent pneumatic compression devices (Grade 2B) and suggest against the use of elastic compression stockings (Grade 2B). In patients with a history of noncardioembolic ischemic stroke or TIA, we recommend long-term treatment with aspirin (75-100 mg once daily), clopidogrel (75 mg once daily), aspirin/extended release dipyridamole (25 mg/200 mg bid), or cilostazol (100 mg bid) over no antiplatelet therapy (Grade 1A), oral anticoagulants (Grade 1B), the combination of clopidogrel plus aspirin (Grade 1B), or triflusal (Grade 2B). Of the recommended antiplatelet regimens, we suggest clopidogrel or aspirin/extended-release dipyridamole over aspirin (Grade 2B) or cilostazol (Grade 2C). In patients with a history of stroke or TIA and atrial fibrillation we recommend oral anticoagulation over no antithrombotic therapy, aspirin, and combination therapy with aspirin and clopidogrel (Grade 1B). Conclusions: These recommendations can help clinicians make evidence-based treatment decisions with their patients who have had strokes. PMID:22315273

  15. Analysis of a two-domain binding site for the urokinase-type plasminogen activator-plasminogen activator inhibitor-1 complex in low-density-lipoprotein-receptor-related protein.

    Science.gov (United States)

    Andersen, O M; Petersen, H H; Jacobsen, C; Moestrup, S K; Etzerodt, M; Andreasen, P A; Thøgersen, H C

    2001-07-01

    The low-density-lipoprotein-receptor (LDLR)-related protein (LRP) is composed of several classes of domains, including complement-type repeats (CR), which occur in clusters that contain binding sites for a multitude of different ligands. Each approximately 40-residue CR domain contains three conserved disulphide linkages and an octahedral Ca(2+) cage. LRP is a scavenging receptor for ligands from extracellular fluids, e.g. alpha(2)-macroglobulin (alpha(2)M)-proteinase complexes, lipoprotein-containing particles and serine proteinase-inhibitor complexes, like the complex between urokinase-type plasminogen activator (uPA) and the plasminogen activator inhibitor-1 (PAI-1). In the present study we analysed the interaction of the uPA-PAI-1 complex with an ensemble of fragments representing a complete overlapping set of two-domain fragments accounting for the ligand-binding cluster II (CR3-CR10) of LRP. By ligand blotting, solid-state competition analysis and surface-plasmon-resonance analysis, we demonstrate binding to multiple CR domains, but show a preferential interaction between the uPA-PAI-1 complex and a two-domain fragment comprising CR domains 5 and 6 of LRP. We demonstrate that surface-exposed aspartic acid and tryptophan residues at identical positions in the two homologous domains, CR5 and CR6 (Asp(958,CR5), Asp(999,CR6), Trp(953,CR5) and Trp(994,CR6)), are critical for the binding of the complex as well as for the binding of the receptor-associated protein (RAP) - the folding chaperone/escort protein required for transport of LRP to the cell surface. Accordingly, the present work provides (1) an identification of a preferred binding site within LRP CR cluster II; (2) evidence that the uPA-PAI-1 binding site involves residues from two adjacent protein domains; and (3) direct evidence identifying specific residues as important for the binding of uPA-PAI-1 as well as for the binding of RAP.

  16. Conformational regulation of urokinase receptor function

    DEFF Research Database (Denmark)

    Gårdsvoll, Henrik; Jacobsen, Benedikte; Kriegbaum, Mette C

    2011-01-01

    PA per se into the hydrophobic ligand binding cavity of uPAR that modulates the function of this receptor. Based on these data, we now propose a model in which the inherent interdomain mobility in uPAR plays a major role in modulating its function. Particularly one uPAR conformation, which is stabilized...

  17. Urokinase plasminogen activator receptor, plasminogen activator ...

    African Journals Online (AJOL)

    Breast cancer is one of the most important leading causes of cancer deathin the less developed countries.The identification of markers that could assist in diagnosis, evaluation of therapeutic response, detection of recurrence and metastasis is a useful tool. The present study is undertaken to provide insights about the role of ...

  18. Outcome in hyperglycemic stroke with ultrasound-augmented thrombolytic therapy.

    Science.gov (United States)

    Martini, S R; Hill, M D; Alexandrov, A V; Molina, C A; Kent, T A

    2006-08-22

    Hyperglycemia independently predicts poor outcome after acute ischemic stroke. CLOTBUST (Combined Lysis Of Thrombus in Brain ischemia using transcranial Ultrasound and Systemic tPA) demonstrated that ultrasound-augmented thrombolysis improves recanalization and 24-hour outcome in patients with acute ischemic stroke. We hypothesized that ultrasound would preferentially benefit hyperglycemic patients, and reviewed CLOTBUST with respect to admission glucose and good outcome. We found that ultrasound's benefit on 90-day outcome was primarily apparent at higher glucose levels, suggesting that ultrasound therapy may improve outcome following hyperglycemic stroke.

  19. Thrombolytic therapy for patients who wake-up with stroke.

    Science.gov (United States)

    Barreto, Andrew D; Martin-Schild, Sheryl; Hallevi, Hen; Morales, Miriam M; Abraham, Anitha T; Gonzales, Nicole R; Illoh, Kachi; Grotta, James C; Savitz, Sean I

    2009-03-01

    Approximately 25% of ischemic stroke patients awaken with their deficits. The last-seen-normal time is defined as the time the patient went to sleep, which places these patients outside the window for thrombolysis. The purpose of this study was to describe our center's experience with off-label, compassionate thrombolysis for wake-up stroke (WUS) patients. A retrospective review of our database identified 3 groups of ischemic stroke patients: (1) WUS treated with thrombolysis; (2) nontreated WUS; and (3) 0- to 3-hour intravenous tissue plasminogen activator-treated patients. Safety and clinical outcome measures were symptomatic intracerebral hemorrhage, excellent outcome (discharge modified Rankin score, 0-1), favorable outcome (modified Rankin score, 0-2), and mortality. Outcome measures were controlled for baseline NIHSS using logistic regression. Forty-six thrombolysed and 34 nonthrombolysed WUS patients were identified. Sixty-one percent (28/46) of the treated WUS patients underwent intravenous thrombolysis alone whereas 30% (14/46) were given only intra-arterial thrombolysis. Four patients received both intravenous and intra-arterial thrombolysis (9%). Two symptomatic intracerebral hemorrhages occurred in treated WUS (4.3%). Controlling for NIHSS imbalance, treated WUS had higher rates of excellent (14% vs 6%; P=0.06) and favorable outcome (28% vs 13%; P=0.006), but higher mortality (15% vs 0%) compared to nontreated WUS. A second comparison controlling for baseline NIHSS between treated WUS and 174 intravenous tissue plasminogen activator patients treated within 3 hours of symptoms showed no significant differences in safety and clinical outcomes. Thrombolysis may be safe in WUS patients. Our center's experience supports considering a prospective, randomized trial to assess the safety and outcome of thrombolysis for this specific patient population.

  20. Thrombolytic and anticoagulation treatment in a rat embolic stroke model

    DEFF Research Database (Denmark)

    Rasmussen, Rune Skovgaard; Overgaard, K; Meden, P

    2003-01-01

    and assigned to: (i). controls, (ii). rt-PA 6 mg/kg, (iii). PENTA 0.5 mg/kg, (iv). PENTA 0.5 mg/kg and rt-PA 6 mg/kg. After 2 days animals were killed, the brains removed and evaluated microscopically. RESULTS: The median infarct size measured in percentage of the affected hemisphere was 25% in the control...

  1. Thrombolytic and anticoagulation treatment in a rat embolic stroke model

    DEFF Research Database (Denmark)

    Rasmussen, Rune Skovgaard; Overgaard, K; Meden, P

    2003-01-01

    OBJECTIVES: The effects of pentasaccharide (PENTA), given alone or combined with thrombolysis using recombinant tissue plasminogen activator (rt-PA), on infarct size and clinical outcome were evaluated in a rat embolic stroke model. MATERIALS AND METHODS: Ninety-two rats were embolized unilaterally...... group, 4% (P treatment. Compared with rt-PA treatment alone, 0.5 mg/kg PENTA...... alone or combined with rt-PA did not significantly increase mortality or tendency for hemorrhage....

  2. Cell-surface acceleration of urokinase-catalyzed receptor cleavage

    DEFF Research Database (Denmark)

    Høyer-Hansen, G; Ploug, M; Behrendt, N

    1997-01-01

    relative to the reaction in solution. The time course of uPA-catalyzed cleavage of cell-bound uPAR was studied using U937 cells stimulated with phorbol 12-myristate 13-acetate. Only 30 min was required for 10 nM uPA to cleave 50% of the cell-bound uPAR. This uPA-catalyzed cleavage reaction was inhibited...

  3. Bicyclic peptide inhibitor of urokinase-type plasminogen activator

    DEFF Research Database (Denmark)

    Roodbeen, Renée; Jensen, Berit Paaske; Jiang, Longguang

    2013-01-01

    burden upon binding. Two bicyclic peptides were synthesised with affinities similar to that of upain-2, and their binding energetics were evaluated by isothermal titration calorimetry. Indeed, compared to upain-2, the bicyclic peptides showed reduced loss of entropy upon binding to uPA. We also...

  4. The urokinase receptor associated protein (uPARAP/endo180)

    DEFF Research Database (Denmark)

    Engelholm, L H; Nielsen, B S; Danø, K

    2001-01-01

    the biological consequences of this reaction have not yet been verified experimentally, a likely event is ligand internalization because uPARAP is a constitutively recycling internalization receptor. uPARAP also binds at least one component, collagen type V, in the extracellular matrix meshwork, pointing...

  5. Nephrotic syndrome complicated with portal, splenic, and superior mesenteric vein thrombosis

    Directory of Open Access Journals (Sweden)

    Bong Soo Park

    2014-09-01

    Full Text Available Thromboembolism is a major complication of nephrotic syndrome. Renal vein thrombosis and deep vein thrombosis are relatively common, especially in membranous nephropathy. However, the incidence of portal vein and superior mesenteric vein (SMV thrombosis in patients with nephrotic syndrome is very rare. To date, several cases of portal vein thrombosis treated by anticoagulation therapy, not by thrombolytic therapy, have been reported as a complication of nephrotic syndrome. Here, we report a case of portal, splenic, and SMV thrombosis in a patient with a relapsed steroid dependent minimal change disease who was treated successfully with anticoagulation and thrombolytic therapy using urokinase. Radiologic findings and his clinical conditions gradually improved. Six months later, a complete remission of the nephrotic syndrome was observed and the follow-up computed tomography scan showed the disappearance of all portal vein, splenic vein, and SMV thrombi.

  6. Delay factors on the administration of thrombolytic therapy in patients diagnosed with acute myocardial infarction in a general hospital Factores que atrasan la administración de trombolítico en pacientes con diagnóstico de infarto agudo del miocardio atendidos en un hospital general Fatores que retardam a administração de trombolítico em pacientes com diagnóstico de infarto agudo do miocárdio atendidos em um hospital geral

    Directory of Open Access Journals (Sweden)

    Luis Antônio Muller

    2008-02-01

    Full Text Available OBJECTIVE: To identify factors that delay the onset of thrombolysis in patients with acute myocardial infarction (AMI. METHODS: A cohort study was carried out with 146 patients, each diagnosed with AMI and subjected to thrombolytic therapy. The data was extracted from medical records between January 2002 and December 2004. RESULTS: The average age of the studied population was 57.5 ± 9 years, 64.4% were male. The average time between the onset of pain and arrival at the hospital was 254.7 ± 126.6 minutes, 28.1% used an ambulance for the trip to the hospital, the door-to-electrocardiogram time averaged 19.4 ± 7.3 minutes and the door-to-needle time was 51.1 ± 14.9 minutes. There was no significant difference between the time of arrival to the hospital and the method of transportation used (P= 0.81, and those seen by cardiologists and during the nightshift had a reduction in the door-to-needle time, respectively (P=0.014 and (P=0.034. CONCLUSIONS: Study results show that the delay in the search for medical service, and the long time taken from door-to-electrocardiogram and to reach the AMI diagnosis were the factors involved in the delay of thrombolytic treatment.OBJETIVO: Identificar los factores que retardan el inicio de la trombolisis en pacientes con IAM. MÉTODOS: Estudio de coorte, en 146 pacientes, con diagnóstico de IAM sometidos a la terapéutica trombolitica. Los datos fueron extraídos de prontuarios, entre enero de 2002 y diciembre de 2004. RESULTADOS: El promedio de edad fue de 57,5 ± 9 años y 64% eran del sexo masculino. El tiempo promedio transcurrido entre el inicio del dolor y la entrada al hospital fue de 254,7 ± 126,6 minutos; 28% utilizaron la ambulancia como medio de transporte; el tiempo promedio porta ECG (tiempo porta ECG: intervalo entre el ingreso del paciente al hospital y la realización del electrocardiograma fue de 19,4 ± 7,3 minutos y el tiempo porta aguja de 51,1 ± 14,9 minutos (tiempo porta aguja

  7. Discussion on the treatment of cerebral ischemia-reperfusion injuries following intra-arterial thrombolysis

    International Nuclear Information System (INIS)

    Tian Hong; Song Chuan; Fan Ruxiong; Zhou Huchuan; Zhang Yubo; Zang Qiaoli; Zhang Yunquan; Liu Lei

    2011-01-01

    Objective: To investigate the therapeutic method of cerebral ischemia-reperfusion injuries occurred after arterial thrombolytic therapy for acute cerebral infarction. Methods: Thirty-five patients, encountered in authors' Department since Oct. 2005, with cerebral ischemia-reperfusion injuries, which occurred after thrombolytic therapy by using arterial perfusion of urokinase for acute cerebral infarction, were enrolled in this study. The clinical data were retrospectively analyzed. Results: After the thrombolytic therapy, completer or partial recanalization of the occluded cerebral arteries was obtained in 33 cases, while secondary cerebral hemorrhage occurred in 13 cases, of whom cerebral parenchyma bleeding was seen in 2 and hemorrhagic infarction in 11. Different degrees of cerebral edema were found in all 33 cases. Among them significant shift of the midline structures was detected in 18 (54.5%), which was manifested clinically as the worsening of disturbance of consciousness. Strict control of blood pressure, prompt adjustment of dehydration medication, strengthening the cerebral protection measures, cerebral decompression by fenestration, etc. were carried out. All the patients took a turn for the better and were out of danger with remarkable improvement of neurological functions except one patient who died from massive intracerebral hemorrhage. Conclusion: Usually, different degrees of reperfusion injuries will develop after thrombolytic therapy for cerebral arterial infarction. Strictly controlling blood pressure, promptly adjusting dehydration medication and strengthening cerebral protection are the keys to reduce the severity of cerebral reperfusion injuries. (authors)

  8. Central venous catheter associated thrombosis of major veins: thrombolytic treatment with recombinant tissue plasminogen activator

    NARCIS (Netherlands)

    Rodenhuis, S.; van't Hek, L. G.; Vlasveld, L. T.; Kröger, R.; Dubbelman, R.; van Tol, R. G.

    1993-01-01

    Major thromboses can occur in the venous system in association with central venous catheters. This usually necessitates removal of the catheter. The effectiveness of low dose recombinant tissue type plasminogen activator (rt-PA) in combination with heparin was assessed in patients with central

  9. Evaluation of pre-hospital transport time of stroke patients to thrombolytic treatment

    DEFF Research Database (Denmark)

    Simonsen, Sofie; Andresen, Morten; Michelsen, Lene

    2014-01-01

    BackgroundEffective treatment of stroke is time dependent. Pre-hospital management is an important link in reducing the time from occurrence of stroke symptoms to effective treatment. The aim of this study was to evaluate time used by emergency medical services (EMS) for stroke patients during...

  10. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction

    NARCIS (Netherlands)

    M.L. Simoons (Maarten); E.J. Topol (Eric); R.M. Califf (Robert); F.J.J. van de Werf (Frans); P.W. Armstrong (Paul); P.E. Aylward (Philip Edmund); G.I. Barbash; E.R. Bates (Eric); A. Betriu; J.H. Chesebro (James); J.J. Col (Jacques); D.P. de Bono (David); J.M. Gore (Joel); A.D. Guerci (Alan); J.R. Hampton (John)

    1993-01-01

    textabstractBACKGROUND: The relative efficacy of streptokinase and tissue plasminogen activator and the roles of intravenous as compared with subcutaneous heparin as adjunctive therapy in acute myocardial infarction are unresolved questions. The current trial was designed to compare new, aggressive

  11. Purification and characterization of a fibrinolytic enzyme from tempeh bongkrek as an alternative of thrombolytic agents

    Science.gov (United States)

    Sasmita, I. R. A.; Sutrisno, A.; Zubaidah, E.; Wardani, A. K.

    2018-03-01

    Tempeh is one of Indonesia’s traditional foods that contain fibrinolytic enzymes. Tempeh bongkrek shows very strong activity among various tempeh. The fibrinolytic enzymes of bongkrek tempeh are obtained by steps of purification i.e, ammonium sulphate precipitation, ion exchange chromatography and gel filtration chromatography. The fibrinolytic enzymes has been successfully purified with a yield of 4.37%, specific activity of 3,361 U / mg and purification fold of 44.02. SDS PAGE analysis showed that the enzyme was purified in to single band with estimated molecular mass of 75.82 kDa. The purified enzyme has optimum pH of 7 and optimum temperature of 50°C and pH stability between pH 4 - 7 with temperature stability from 30°-50°C. The fibrinolytic activity is increased with addition of CaCl2 but inhibited with CuSO4, phenylmethylsulfonyl fluoride (PMSF), sodium dodecyl sulfate (SDS), and ethylenediaminetetraacetic acid (EDTA).

  12. Coulomb nanoradiator-mediated, site-specific thrombolytic proton treatment with a traversing pristine Bragg peak

    Science.gov (United States)

    Jeon, Jae-Kun; Han, Sung-Mi; Min, Soon-Ki; Seo, Seung-Jun; Ihm, Kyuwook; Chang, Won-Seok; Kim, Jong-Ki

    2016-11-01

    Traversing proton beam-irradiated, mid/high-Z nanoparticles produce site-specific enhancement of X-ray photon-electron emission via the Coulomb nanoradiator (CNR) effect, resulting in a nano- to micro-scale therapeutic effect at the nanoparticle-uptake target site. Here, we demonstrate the uptake of iron oxide nanoparticles (IONs) and nanoradiator-mediated, site-specific thrombolysis without damaging the vascular endothelium in an arterial thrombosis mouse model. The enhancement of low-energy electron (LEE) emission and reactive oxygen species (ROS) production from traversing proton beam-irradiated IONs was examined. Flow recovery was only observed in CNR-treated mice, and greater than 50% removal of the thrombus was achieved. A 2.5-fold greater reduction in the thrombus-enabled flow recovery was observed in the CNR group compared with that observed in the untreated ION-only and proton-only control groups (p ROS by the proton-irradiated IONs, which suggests chemical degradation of the thrombus without potent emboli.

  13. Process improvement to enhance existing stroke team activity toward more timely thrombolytic treatment.

    Science.gov (United States)

    Cho, Han-Jin; Lee, Kyung Yul; Nam, Hyo Suk; Kim, Young Dae; Song, Tae-Jin; Jung, Yo Han; Choi, Hye-Yeon; Heo, Ji Hoe

    2014-10-01

    Process improvement (PI) is an approach for enhancing the existing quality improvement process by making changes while keeping the existing process. We have shown that implementation of a stroke code program using a computerized physician order entry system is effective in reducing the in-hospital time delay to thrombolysis in acute stroke patients. We investigated whether implementation of this PI could further reduce the time delays by continuous improvement of the existing process. After determining a key indicator [time interval from emergency department (ED) arrival to intravenous (IV) thrombolysis] and conducting data analysis, the target time from ED arrival to IV thrombolysis in acute stroke patients was set at 40 min. The key indicator was monitored continuously at a weekly stroke conference. The possible reasons for the delay were determined in cases for which IV thrombolysis was not administered within the target time and, where possible, the problems were corrected. The time intervals from ED arrival to the various evaluation steps and treatment before and after implementation of the PI were compared. The median time interval from ED arrival to IV thrombolysis in acute stroke patients was significantly reduced after implementation of the PI (from 63.5 to 45 min, p=0.001). The variation in the time interval was also reduced. A reduction in the evaluation time intervals was achieved after the PI [from 23 to 17 min for computed tomography scanning (p=0.003) and from 35 to 29 min for complete blood counts (p=0.006)]. PI is effective for continuous improvement of the existing process by reducing the time delays between ED arrival and IV thrombolysis in acute stroke patients.

  14. EVALUATION OF EARLY ISCHEMIC CHANGES IN STROKE PATIENTS TREATED WITH THROMBOLYTIC THERAPY

    Directory of Open Access Journals (Sweden)

    Kolevski Goran

    2016-07-01

    Full Text Available Introduction:The aim of this study is to evaluate early brain ischemic changes on CT scan in stroke patients in correlation with the clinical outcome, as well as to evaluate if there is prognostic and predictive features that can be used. Patients and methods: We examined 20 patients with acute ischemic stroke, from which 12 were male and 8 were female, at the age from 47 to 76 years. Results: The hyperdense medial artery (HMA sign was present in 10 (50% patients. Concerning the ASPECTS score, 5 patients (25% had normal score of 10 points, while 7 patients (35% had score of 7 points. 12 patients (60% had unfavorable outcome, while 8 patients (40% had favorable outcome. Our statistical analysis shows that age of more than 65 years, presence of 2 or more risk-factors, ASPECTS score of 7 and presence of HMA sign were all statistically significant predictors of unfavorable outcome in examined patients (p<0.05 each. The presence of the hyperdense medial artery sign was the most significant single predictor for unfavorable clinical outcome (p=0.0042, p<0.05. Conclusion:The presence of HMA sign is the most significant single predictor for unfavorable clinical outcome.

  15. Exploring hemostatic and thrombolytic potential of heynein - A cysteine protease from Ervatamia heyneana latex.

    Science.gov (United States)

    Uday, Priyanka; Maheshwari, M; Sharanappa, P; Nafeesa, Zohara; Kameshwar, Vivek Hamse; Priya, B S; Nanjunda Swamy, S

    2017-03-06

    The latex of Ervatamia heyneana (Wall.) T. Cooke plant has been used for wound healing and various skin diseases by Indian tribes and folklore. To validate the scientific basis of heynein - a key protease of Ervatamia heyneana, in hemostasis and wound healing process. The latex from E. heyneana was processed and subjected to two step purification. The purified heynein was assayed for proteolytic activity using casein as substrate and also attested by zymography. The inhibition studies confirmed the nature of heynein. Pure fibrinogen was used for fibrinogenolytic activity and citrated plasma was used for coagulant and fibrinolytic activities. The edema inducing action and hemorrhagic activity of heynein were assessed on mice model. The purified heynein exhibited proteolytic activity, which was confirmed by caseinolytic assay and zymography. The inhibition studies confirmed heynein to be a cysteine protease. Heynein showed complete hydrolysis of all the three subunits of human fibrinogen (Aα, Bβ, γ). It exhibited strong pro-coagulant activity by reducing plasma clotting time from 248 to 39s at 40µg concentration. Heynein cleaved α polymer subunit in fibrin clot and did not induce edema and hemorrhage in mice models. The non-hemorrhagic nature was supported with histopathological studies of skin samples. Heynein displays strong pro-coagulant action associated with fibrin(ogen)olytic activity. This provides basis for the observed pharmacological action of Ervatamia heyneana and thereby justifies its use in folk medicine. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  16. Anti-thrombolytic effect of Salvia miltiorrhiza Bge extract in rats | Tian ...

    African Journals Online (AJOL)

    Purpose: To study the effects of Salvia miltiorrhiza Bge. extract (SMBE) on thrombosis in rats. Methods: SMBE was obtained in water at 60 oC in an oven and then freeze-drying. Rats were divided into 6 groups of ten rats each: normal group, control group, reference group (aspirin 5 mg/kg) as well as three groups of SMBE ...

  17. Anti-thrombolytic effect of Salvia miltiorrhiza Bge extract in rats

    African Journals Online (AJOL)

    Purpose: To study the effects of Salvia miltiorrhiza Bge. extract (SMBE) on thrombosis in rats. Methods: SMBE was obtained in water at 60 oC in an oven and then freeze-drying. Rats were divided into 6 groups of ten rats each: normal group, control group, reference group (aspirin 5 mg/kg) as well as three groups of SMBE ...

  18. Acute Superior Mesenteric Venous Thrombosis: Transcatheter Thrombolysis and Aspiration Thrombectomy Therapy by Combined Route of Superior Mesenteric Vein and Artery in Eight Patients

    International Nuclear Information System (INIS)

    Yang, Shuofei; Liu, Baochen; Ding, Weiwei; He, Changsheng; Wu, Xingjiang; Li, Jieshou

    2015-01-01

    PurposeTo assess the feasibility, effectiveness, and safety of catheter-directed thrombolysis and aspiration thrombectomy therapy by combined route of superior mesenteric vein and artery (SMV+SMA) for acute superior mesenteric venous thrombosis (ASMVT).MethodsThis retrospective study reviewed eight ASMVT patients with transcatheter direct thrombolysis and aspiration thrombectomy therapy via SMV and indirect thrombolysis via SMA during a period of 14 months. The demographics, etiology, risk factors, therapeutic effect, complications, mortality, and follow-up of the study population were assessed. Anatomic and imaging classification of location and extent of thrombus at diagnosis and degree of thrombus lysis were described.ResultsTechnical success was achieved with substantial improvement in symptoms and thrombus resolution after thrombolytic therapy in all patients. The local urokinase infusion by SMA and SMV was performed for 5–7 (6.13 ± 0.83) and 7–15 (12 ± 2.51) days. Anticoagulation was performed catheter-directed and then orally throughout hospitalization and after discharge. Four patients required delayed localized bowel resection after thrombolytic therapy with no death. Thrombolytic therapy was not interrupted despite minor bleeding at the puncture site in two patients and sepsis in another two postoperatively. Nearly complete removal of thrombus was demonstrated by contrast-enhanced CT scan and portography before discharge. Patients were discharged in 10–27 (19.25 ± 4.89) days after admission. No recurrence developed during the follow-up of 10–13 (12.13 ± 0.99) months.ConclusionsCatheter-directed thrombolytic and aspiration therapy via SMV+SMA is beneficial for ASMVT in avoiding patient death, efficient resolving thrombus, rapid improving symptoms, reversing extensive intestinal ischemia, averting bowel resection, or localizing infarcted bowel segment and preventing short bowel syndrome

  19. Acute superior mesenteric venous thrombosis: transcatheter thrombolysis and aspiration thrombectomy therapy by combined route of superior mesenteric vein and artery in eight patients.

    Science.gov (United States)

    Yang, Shuofei; Liu, Baochen; Ding, Weiwei; He, Changsheng; Wu, Xingjiang; Li, Jieshou

    2015-02-01

    To assess the feasibility, effectiveness, and safety of catheter-directed thrombolysis and aspiration thrombectomy therapy by combined route of superior mesenteric vein and artery (SMV+SMA) for acute superior mesenteric venous thrombosis (ASMVT). This retrospective study reviewed eight ASMVT patients with transcatheter direct thrombolysis and aspiration thrombectomy therapy via SMV and indirect thrombolysis via SMA during a period of 14 months. The demographics, etiology, risk factors, therapeutic effect, complications, mortality, and follow-up of the study population were assessed. Anatomic and imaging classification of location and extent of thrombus at diagnosis and degree of thrombus lysis were described. Technical success was achieved with substantial improvement in symptoms and thrombus resolution after thrombolytic therapy in all patients. The local urokinase infusion by SMA and SMV was performed for 5-7 (6.13 ± 0.83) and 7-15 (12 ± 2.51) days. Anticoagulation was performed catheter-directed and then orally throughout hospitalization and after discharge. Four patients required delayed localized bowel resection after thrombolytic therapy with no death. Thrombolytic therapy was not interrupted despite minor bleeding at the puncture site in two patients and sepsis in another two postoperatively. Nearly complete removal of thrombus was demonstrated by contrast-enhanced CT scan and portography before discharge. Patients were discharged in 10-27 (19.25 ± 4.89) days after admission. No recurrence developed during the follow-up of 10-13 (12.13 ± 0.99) months. Catheter-directed thrombolytic and aspiration therapy via SMV+SMA is beneficial for ASMVT in avoiding patient death, efficient resolving thrombus, rapid improving symptoms, reversing extensive intestinal ischemia, averting bowel resection, or localizing infarcted bowel segment and preventing short bowel syndrome.

  20. Acute Superior Mesenteric Venous Thrombosis: Transcatheter Thrombolysis and Aspiration Thrombectomy Therapy by Combined Route of Superior Mesenteric Vein and Artery in Eight Patients

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Shuofei, E-mail: yangshuofei@gmail.com; Liu, Baochen, E-mail: 306446264@qq.com; Ding, Weiwei, E-mail: dingwei-nju@hotmail.com; He, Changsheng, E-mail: hechsh@163.com; Wu, Xingjiang, E-mail: wuxingjiang@sohu.com; Li, Jieshou, E-mail: lijieshou2013@sohu.com [Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University (China)

    2015-02-15

    PurposeTo assess the feasibility, effectiveness, and safety of catheter-directed thrombolysis and aspiration thrombectomy therapy by combined route of superior mesenteric vein and artery (SMV+SMA) for acute superior mesenteric venous thrombosis (ASMVT).MethodsThis retrospective study reviewed eight ASMVT patients with transcatheter direct thrombolysis and aspiration thrombectomy therapy via SMV and indirect thrombolysis via SMA during a period of 14 months. The demographics, etiology, risk factors, therapeutic effect, complications, mortality, and follow-up of the study population were assessed. Anatomic and imaging classification of location and extent of thrombus at diagnosis and degree of thrombus lysis were described.ResultsTechnical success was achieved with substantial improvement in symptoms and thrombus resolution after thrombolytic therapy in all patients. The local urokinase infusion by SMA and SMV was performed for 5–7 (6.13 ± 0.83) and 7–15 (12 ± 2.51) days. Anticoagulation was performed catheter-directed and then orally throughout hospitalization and after discharge. Four patients required delayed localized bowel resection after thrombolytic therapy with no death. Thrombolytic therapy was not interrupted despite minor bleeding at the puncture site in two patients and sepsis in another two postoperatively. Nearly complete removal of thrombus was demonstrated by contrast-enhanced CT scan and portography before discharge. Patients were discharged in 10–27 (19.25 ± 4.89) days after admission. No recurrence developed during the follow-up of 10–13 (12.13 ± 0.99) months.ConclusionsCatheter-directed thrombolytic and aspiration therapy via SMV+SMA is beneficial for ASMVT in avoiding patient death, efficient resolving thrombus, rapid improving symptoms, reversing extensive intestinal ischemia, averting bowel resection, or localizing infarcted bowel segment and preventing short bowel syndrome.

  1. In vitro activity of probiotic Lactobacillus reuteri against gastric cancer progression by downregulation of urokinase plasminogen activator/urokinase plasminogen activator receptor gene expression

    Directory of Open Access Journals (Sweden)

    Bahareh Sadat Rasouli

    2017-01-01

    Conclusion: This study provides strong support in the role of L. reuteri in suppression of GC cell invasion by downregulation of pathways which is involved in extracellular matrix degradation such as uPA and uPAR.

  2. Clinical study of interventional therapy for acute cerebral infarction

    International Nuclear Information System (INIS)

    Xiang Guangze; Xiao Yiming; Wen Zhilin

    2004-01-01

    Objective: To evaluate the clinical efficacy and safety of interventional therapy for acute cerebral infarction. Method: Using urokinase, 35 patients with acute cerebral infarction within 24 hours were treated by intra-artery thrombolytic therapy. Europe stroke scale (ESS), Barthel index (BI) were used to evaluate the recovery of neurological functions. Result: ESS score increase rapidly after thrombolytisis, and there were significant difference between the two teams. Thirteen of 13 cases treated within 6 hours from onset showed complete/partial recanalization in cerebral angiography and intraparenchymal hemorrhagic rate were 0%, twenty-six of 35 cases treated within 24 hours showed complete/partial recanalization and intraparenchymal hemorrhagic rate were 5.71%. Conclusion: Interventional therapy for acute cerebral infarction within 6h were safe and effective. (authors)

  3. Superior mesenteric venous thrombosis treated by direct aspiration thrombectomy.

    Science.gov (United States)

    Nakayama, Satoshi; Murashima, Naoya; Isobe, Yoshinori

    2008-01-01

    A 69-year-old man, with hepatits C virus-related liver cirrhosis and hemophilia B, developed massive ascites and watery diarrhea after endoscopic injection sclerotherapy for esophageal varices. A multi detector row computed tomography revealed a superior mesenteric venous thrombus without bowel infarction. It was assumed that the thrombus was caused by transient congestion of the portal system after retrograde propagation of the sclerosant agent, in a condition where anticoagulation proteins, such as proteins C and S, had decreased. Because long systemic thrombolytic therapy was hazardous for the patient with hemorrhagic diathesis due to impaired coagulation, a direct thrombolysis was performed with urokinase followed by aspiration thrombectomy, with cannulation of the portal venous system using a transjugular intrahepatic approach. The patient had no complications in this procedure and subsequently diarrhea and refractory ascites were resolved. Direct thrombectomy via the transjugular intrahepatic route may be a useful therapy for mesenteric venous thrombus in the cirrhotic patient.

  4. Thromboembolism Induced by Umbilical Cord Mesenchymal Stem Cell Infusion: A Report of Two Cases and Literature Review.

    Science.gov (United States)

    Wu, Z; Zhang, S; Zhou, L; Cai, J; Tan, J; Gao, X; Zeng, Z; Li, D

    2017-09-01

    To investigate the thromboembolism induced by blood-mediated inflammatory reactions against infused cells during the clinical application of stem cells. Two patients with renal transplantation and chronic kidney disease, respectively, experienced thromboembolism after umbilical cord mesenchymal stem cell (UCMSC) infusion. The clinical manifestations and the laboratory test results were collected and analyzed. The patients received stem cell infusion through the peripheral veins and presented with a swollen and painful forearm postinfusion. Doppler ultrasound showed venous clots at the proximal end of the puncture site. Urokinase and warfarin were used for thrombolytic therapy. The swelling and pain were relieved and cured. Safety concerns are still a primary hurdle for stem cell therapy, and thromboembolism as a critical complication should be prevented appropriately. Copyright © 2017. Published by Elsevier Inc.

  5. Fibrinolytic Treatment after Transient Ischaemic Attack Caused by Prosthetic Mitral Valve Thrombosis.

    Science.gov (United States)

    Koban, Cornel; Neuß, Michael; Tambor, Grit; Hölschermann, Frank; Butter, Christian

    2016-01-01

    Prosthetic valve thrombosis is one of the most severe complications after surgical valve replacement. There are many possible presentations: from asymptomatic to life-threatening complications. We report on a 61-year-old female patient with prosthetic replacement of the aortic and mitral valve in the in-house department of cardiac surgery 3 months ago. The patient was suffering from aphasia during 5 minutes in domesticity. After her presentation in the emergency room, the echocardiographic examination revealed a thrombotic formation of the prosthetic mitral valve. At presentation, the anticoagulation was outside the effective range (INR: 1.7). A successful thrombolytic therapy with the plasminogen activator urokinase was begun with complete resolution of the thrombus.

  6. Fibrinolytic Treatment after Transient Ischaemic Attack Caused by Prosthetic Mitral Valve Thrombosis

    Directory of Open Access Journals (Sweden)

    Cornel Koban

    2016-01-01

    Full Text Available Prosthetic valve thrombosis is one of the most severe complications after surgical valve replacement. There are many possible presentations: from asymptomatic to life-threatening complications. We report on a 61-year-old female patient with prosthetic replacement of the aortic and mitral valve in the in-house department of cardiac surgery 3 months ago. The patient was suffering from aphasia during 5 minutes in domesticity. After her presentation in the emergency room, the echocardiographic examination revealed a thrombotic formation of the prosthetic mitral valve. At presentation, the anticoagulation was outside the effective range (INR: 1.7. A successful thrombolytic therapy with the plasminogen activator urokinase was begun with complete resolution of the thrombus.

  7. Radiological interventional procedures for the acute abdomen; Radiologisch-interventionelle Massnahmen beim akuten Abdomen

    Energy Technology Data Exchange (ETDEWEB)

    Trumm, C.; Hoffmann, R.T.; Reiser, M.F. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer Klinische Radiologie, Muenchen (Germany)

    2010-03-15

    In patients with acute thrombo-embolic occlusion of the superior mesenteric artery, catheter-assisted thrombolytic therapy represents a procedure of increasing importance in addition to surgery and intensive care treatment. The thrombolytic drugs utilized for this purpose are urokinase, streptokinase and recombinant tissue plasminogen activator (rtPA). Therapeutic embolization is predominantly used in the treatment of arterial bleeding from the gastro-intestinal tract, the liver, the intestines (due to an aneurysm or vascular malformation) and in bleeding from intestinal anastomoses. Polyvinyl alcohol particles, embospheres, gelfoam and microcoils can be utilized as embolic agents. Percutaneous transhepatic cholangiodrainage and stent implantation are applied in patients with biliary obstructions caused by inoperable tumors of the gall bladder or bile ducts, of the pancreatic head or duodenum and by metastases located in the liver parenchyma or hepatic hilum. Image-guided percutaneous drainage is a valuable option in the management of abscesses in the peritoneal cavity; less common indications are lymphoceles, biliomas, urinomas, hematomas, necrosis and pseudocysts. (orig.) [German] Die kathetergestuetzte thrombolytische Therapie stellt im Kontext einer chirurgischen und intensivmedizinischen Versorgung von Patienten mit thrombembolisch bedingter mesenterialer Ischaemie ein unterstuetzendes Behandlungsverfahren von zunehmender Bedeutung dar. Als thrombolytische Agenzien werden Urokinase, Streptokinase und der rekombinante Gewebeplasminogenaktivator (rtPA) verwendet. Die therapeutische Embolisation kommt neben der endoskopischen und chirurgischen Blutungsstillung bei arteriellen Blutungen im Gastrointestinaltrakt, aus der Leber, im Darm (als Folge eines Aneurysmas oder einer vaskulaeren Malformation) sowie bei blutenden intestinalen Anastomosen zum Einsatz. Zur Embolisation koennen Polyvinylalkoholpartikel, Embosphaeren, Gelfoam oder Mikrocoils verwendet werden. Die

  8. Reduction of mouse atherosclerosis by urokinase inhibition or with a limited-spectrum matrix metalloproteinase inhibitor

    DEFF Research Database (Denmark)

    Hu, Jie Hong; Touch, Phanith; Zhang, Jingwan

    2015-01-01

    ) or a control antibody. mU1-treated mice were also compared with PBS-treated non-uPA-overexpressing Apoe-null mice. Other SR-uPA mice were treated with one of three doses of a limited-spectrum synthetic MMP inhibitor (XL784) or vehicle. mU1 reduced aortic root intimal lesion area (20%; P = 0.05) and aortic root...... circumference (12%; P = 0.01). All XL784 doses reduced aortic root intimal lesion area (22-29%) and oil-red-O-positive lesion area (36-42%; P

  9. Tumor necrosis factor induces the production of urokinase-type plasminogen activator by human endothelial cells

    NARCIS (Netherlands)

    Hinsbergh, V.W.M. van; Berg, E.A. van den; Fiers, W.; Dooijewaard, G.

    1990-01-01

    Endothelial cells play an important role in the regulation of fibrinolysis by the production of several key regulatory proteins. The cytokines tumor necrosis factor (TNF), lymphotoxin, and interleukin-1 (IL-1), but not interleukin-6, increase the production of plasminogen activator inhibitor-1

  10. Association between serum soluble urokinase-type plasminogen activator receptor and atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Noboru Ichihara

    2017-10-01

    Conclusions: Serum suPAR was associated with AF, particularly NPAF, as demonstrated by multivariate logistic regression analysis. Whether suPAR promotes or maintains AF should be investigated in further studies.

  11. Reduced metastasis of transgenic mammary cancer in urokinase-deficient mice

    DEFF Research Database (Denmark)

    Almholt, Kasper; Lund, L.R.; Rygaard, Jørgen

    2005-01-01

    >7-fold in the MMTV-PymT model. We studied a cohort of 55 MMTV-PymT transgenic mice, either uPA-deficient or wild-type controls. Tumor incidence, latency, growth rate and final primary tumor burden were not significantly affected by uPA deficiency. In contrast, average lung metastasis volume...... was reduced from 1.58 mm3 in wild-type controls to 0.21 mm3 in uPA-deficient mice (p = 0.023). Tumor cell dissemination to brachial lymph nodes was also reduced from 53% (28/53) in wild-type controls to 31% (17/54) in uPA-deficient mice (p = 0.032). Mice without plasminogen display a severe pleiotropic...

  12. Substrate specificity of tissue-type and urokinase-type plasminogen activators

    NARCIS (Netherlands)

    Rijken, D.C.; Groeneveld, E.

    1991-01-01

    Recent studies suggest that plasminogen activators not only hydrolyse a specific arginine-valine bond in plasminogen, but may also cleave other proteins such as fibronectin. We studied the substrate specificity, particularly the preference for arginyl over lysyl peptide bonds, of tissue-type

  13. Elevated plasma urokinase receptor predicts low birth weight in maternal malaria

    DEFF Research Database (Denmark)

    Ostrowski, S R; Shulman, C E; Peshu, N

    2007-01-01

    -suPAR and gestational age were the only independent predictors of birth weight in multivariate linear regression adjusted for maternal-suPAR, HIV-1 infection, age, BMI, haemoglobin, peripheral parasitaemia, parity and gestational age; 1 ng/mL higher maternal-suPAR predicted -56 g (95% CI -100 to -12, P = 0.016) reduced...... birth weight. Cord-suPAR could not predict birth weight after adjusting for gestational age. Future studies are warranted to investigate whether the maternal suPAR level is increased earlier in pregnancy in women with active placental malaria infection and whether early maternal suPAR measurements can...... predict birth weight. If so, measurements of maternal suPAR early in pregnancy might then potentially identify women with increased needs for antenatal care and intervention....

  14. A urokinase receptor-associated protein with specific collagen binding properties

    DEFF Research Database (Denmark)

    Behrendt, N; Jensen, O N; Engelholm, L H

    2000-01-01

    membrane-bound lectin with hitherto unknown function. The human cDNA was cloned and sequenced. The protein, designated uPARAP, is a member of the macrophage mannose receptor protein family and contains a putative collagen-binding (fibronectin type II) domain in addition to 8 C-type carbohydrate recognition...... domains. It proved capable of binding strongly to a single type of collagen, collagen V. This collagen binding reaction at the exact site of plasminogen activation on the cell may lead to adhesive functions as well as a contribution to cellular degradation of collagen matrices....

  15. Urokinase plasminogen activator receptor on invasive cancer cells: A prognostic factor in distal gastric adenocarcinoma

    DEFF Research Database (Denmark)

    Alpizar, Warner Enrique Alpizar; Christensen, Ib Jarle; Santoni-Rugiu, Eric

    2012-01-01

    association between the expression of uPAR on tumor cells in the peripheral invasion zone and overall survival of gastric cancer patients (HR = 2.16; 95% CI: 1.13-4.14; p = 0.02). Multivariate analysis showed that uPAR immunoreactivity in cancer cells at the invasive front is an independent prognostic factor...

  16. Urokinase-type plasminogen activator receptor (uPAR) as a promising new imaging target

    DEFF Research Database (Denmark)

    Persson, Morten; Kjaer, Andreas

    2013-01-01

    modalities such as optical imaging, magnetic resonance imaging, single photon emission computer tomography (SPECT) and positron emission topography (PET). In this review, we will discuss recent advances in the development of uPAR-targeted imaging ligands according to imaging modality. In addition, we...... will discuss the potential future clinical application for uPAR imaging as a new imaging biomarker....

  17. PET imaging of urokinase-type plasminogen activator receptor (uPAR) in prostate cancer

    DEFF Research Database (Denmark)

    Skovgaard, Dorthe; Persson, Morten; Kjaer, Andreas

    2016-01-01

    , which can provide the required quantitative information on the uPAR expression profile, without the need for invasive procedures and the risk of missing the target due to tumor heterogeneity. These observations support non-invasive PET imaging of uPAR in PC as a clinically relevant diagnostic...

  18. Different mechanisms are involved in the antibody mediated inhibition of ligand binding to the urokinase receptor

    DEFF Research Database (Denmark)

    List, K; Høyer-Hansen, G; Rønne, E

    1999-01-01

    or interference with conformational properties of the receptor critical for ligand binding. This distinction is central when employing the antibodies as tools in the elucidation of the structure-function relationship of the protein in question. We have studied the effect of monoclonal antibodies against......PA/uPAR complex. The continuous recording of binding and dissociation, obtained in BIA, is central in characterizing these phenomena. The identification of a non-competitive inhibitory mechanism against this receptor reveals the presence of a determinant which influences the binding properties of a remote site...

  19. A novel urokinase receptor-targeted inhibitor for plasmin and matrix metalloproteinases suppresses vein graft disease

    NARCIS (Netherlands)

    Eefting, D.; Seghers, L.; Grimbergen, J.M.; Vries, M.R. de; Boer, H.C. de; Lardenoye, J.W.H.P.; Jukema, J.W.; Bockel, J.H. van; Quax, P.H.A.

    2010-01-01

    Aims Matrix metalloproteinases (MMP) and plasminogen activator (PA)/plasmin-mediated proteolysis, especially at the cell surface, play important roles in matrix degeneration and smooth muscle cell migration, which largely contributes to vein graft failure. In this study, a novel hybrid protein was

  20. Urokinase-plasminogen activator from bovine plasma obtained by cellulose sulfate precipitation

    Directory of Open Access Journals (Sweden)

    Maria Regina Torqueti Toloi

    1997-02-01

    Full Text Available Plasma bovino tratado com sulfato de celulose produz, em placas de fibrina, múltiplas formas de ativadores de plasminogênio. A fração fibrinoliticamente mais ativa foi isolada por eletroforese preparativa. Testes amidolíticos com substratos cromogênicos e testes de imunodifusão radial com anticorpos monoclonais revelaram que o ativador de plasminogênio isolado neste trabalho possui propriedades semelhantes às da uroquinase.

  1. The human receptor for urokinase plasminogen activator. NH2-terminal amino acid sequence and glycosylation variants

    DEFF Research Database (Denmark)

    Behrendt, N; Rønne, E; Ploug, M

    1990-01-01

    , but no N-acetyl-D-galactosamine. Glycosylation is responsible for substantial heterogeneity in the receptor on phorbol ester-stimulated U937 cells, and also for molecular weight variations among various cell lines. The amino acid composition and the NH2-terminal amino acid sequence are reported...... amino-terminal fragment; 2) the identical electrophoretic mobilities observed for cross-linked conjugates, formed between either the purified protein or the u-PA receptor on intact U937 cells and the above ligands; 3) the identity of the apparent molecular weight of the purified protein...

  2. Crystal structure of the urokinase receptor in a ligand-free form

    DEFF Research Database (Denmark)

    Xu, Xiang; Gårdsvoll, Henrik; Yuan, Cai

    2012-01-01

    . The crystal structure of human uPAR in its ligand-free state would clarify this issue, but such information remains unfortunately elusive. We now report the crystal structures of a stabilized, human uPAR (H47C/N259C) in its ligand-free form to 2.4 Å and in complex with amino-terminal fragment (ATF) to 3.2 Å...... represents one of the biologically active conformations of uPAR as defined by extensive biochemical studies. The domain boundary between uPAR DI-DII domains is more flexible than the DII-DIII domain boundary. Two important structural features are highlighted by the present uPAR structure. First, the DI......-DIII domain boundary may face the cell membrane. Second, loop 130-140 of uPAR plays a dynamic role during ligand loading/unloading. Together, these studies provide new insights into uPAR structure-function relationships, emphasizing the importance of the inter-domain dynamics of this modular receptor....

  3. Targeting the autolysis loop of urokinase-type plasminogen activator with conformation-specific monoclonal antibodies

    DEFF Research Database (Denmark)

    Bøtkjær, Kenneth Alrø; Fogh, Sarah; Bekes, Erin C

    2011-01-01

    , with high levels correlating with a poor prognosis. This observation has stimulated efforts into finding new principles for intervening with uPA's activity. In the present study we characterize the so-called autolysis loop in the catalytic domain of uPA as a potential inhibitory target. This loop was found......, demonstrating a direct link between conformational changes of the autolysis loop and the creation of a catalytically mature active site. All three antibodies are potent inhibitors of uPA activity, the two pro-uPA-specific ones by inhibiting conversion of pro-uPA to active uPA and the active u...

  4. Enhancement of Skeletal Muscle Repair by the Urokinase Type Plasminogen Activator System

    National Research Council Canada - National Science Library

    Koh, Timothy J

    2008-01-01

    .... In this progress report, we present data indicating that satellite cell fusion during muscle regeneration is impaired in uPA null mice, and accelerated in mice deficient in the inhibitor of uPA...

  5. Inhibition of receptor-bound urokinase by plasminogen-activator inhibitors

    DEFF Research Database (Denmark)

    Ellis, Vincent John; Wun, T C; Behrendt, N

    1990-01-01

    activator inhibitors (PAI-1 and PAI-2). uPA bound to its receptor on human U937 monocyte-like cells was inhibited by PAI-1 (in its active form in the presence of vitronectin fragments) with an association rate constant of 4.5 x 10(6) M-1 s-1, which was 40% lower than that obtained for uPA in solution (7.9 x...

  6. Soluble urokinase plasminogen activator receptor as a prognostic marker in men participating in prostate cancer screening

    DEFF Research Database (Denmark)

    Kjellman, A; Akre, O; Gustafsson, O

    2011-01-01

    in a prostate cancer screening trial. A total of 312 men were free of prostate cancer and 63 men had prostate cancer diagnosed at the time of screening. The cohort was followed for 15 years. We assessed survival using Kaplan-Meier estimation and Cox proportional hazards regression. RESULTS: The mean age...... with prostate cancer and cardiovascular disease mortality. METHODS: Using time-resolved fluorescence immunoassays, we measured intact suPAR [suPAR(I-III)] and intact plus cleaved suPAR [suPAR(I-III) + suPAR(II-III)] and thus calculated the amount of suPAR(II-III) in serum samples from 375 men participating......PAR(I-III) and suPAR(II-III) by 1-unit (ln-scale) was associated with a hazard ratio (HR) of 2.26 [95% confidence interval (CI) 1.17-4.35] and 2.53 (95% CI 1.56-4.10), respectively. There was a trend towards an increased risk of death from prostate cancer in screening-detected prostate cancer patients...

  7. The urokinase receptor homolog Haldisin is a novel differentiation marker of stratum granulosum in squamous epithelia

    DEFF Research Database (Denmark)

    Gårdsvoll, Henrik; Kriegbaum, Mette C; Hertz, Emil P

    2013-01-01

    Several members of the Ly-6/uPAR (LU)-protein domain family are differentially expressed in human squamous epithelia. In some cases, they even play important roles in maintaining skin homeostasis, as exemplified by the secreted single domain member, SLURP-1, the deficiency of which is associated ...

  8. Urokinase-Type Plasminogen Activator Receptor as a Potential PET Biomarker in Glioblastoma

    DEFF Research Database (Denmark)

    Persson, Morten; Nedergaard, Mette K; Brandt-Larsen, Malene

    2016-01-01

    -fluoroethyl)-l-tyrosine ((18)F-FET). One MRI scan was obtained for each mouse to confirm tumor location. The uPAR specificity of (64)Cu-NOTA-AE105 was confirmed by alignment of hematoxylin- and eosin-stained and uPAR immunohistochemistry-stained slides of the brain with the activity distribution as determined using....../μmol and a radiochemical purity of more than 98% for (64)Cu-NOTA-AE105 and more than 97% for (68)Ga-NOTA-AE105. High image contrast resulting in clear tumor delineation was found for both (68)Ga-NOTA-AE105 and (64)Cu-NOTA-AE105. Absolute uptake in tumor was higher for (18)F-FET (3.5 ± 0.8 percentage injected dose [%ID...

  9. Interconversion of active and inactive conformations of urokinase-type plasminogen activator

    DEFF Research Database (Denmark)

    Liu, Zhuo; Kromann-Hansen, Tobias; Lund, Ida K.

    2012-01-01

    The catalytic activity of serine proteases depends on a salt-bridge between the amino group of residue 16 and the side chain of Asp194. The salt-bridge stabilizes the oxyanion hole and the S1 specificity pocket of the protease. Some serine proteases exist in only partially active forms, in which...... active state. Both a monoclonal antibody (mU3) and a peptidic inhibitor (mupain-1--16) stabilize the active state. The epitope of mU3 is located in the 37- and 70-loops at a site homologous to exosite I of thrombin. The N-terminus((Ile16)) of muPA((16--243)) was less exposed upon binding of mU3 or mupain......-1--16. In contrast, introduction of the mutations F40Y or E137A into muPA((16--243)) increased exposure of the N-terminus((Ile16)) and resulted in large changes in the thermodynamic parameters for mupain-1--16 binding. We conclude that the distorted state of muPA((16--243)) is conformationally...

  10. Decreased urokinase receptor expression on granulocytes in HIV-infected patients

    DEFF Research Database (Denmark)

    Storgaard, M; Obel, N; Black, F T

    2002-01-01

    PAR) expression in granulocytes (3.9 x 104 +/- 0.9 x 104 sites/cell). Modulation of uPAR expression was assessed in the presence of chemoattractant gradients. Our findings demonstrate that interleukin (IL)-8, leukotriene B4(LTB4) and formyl-methionyl-leucyl-phenylalanine (f MLP) caused a dose...

  11. Selection and characterization of camelid nanobodies towards urokinase-type plasminogen activator

    DEFF Research Database (Denmark)

    Kaczmarek, Jakub; Skottrup, Peter Durand

    2015-01-01

    , increased cancer malignancy and poor survival prognosis. For these reasons uPA is considered an important target for anticancer drug therapy. In this study we isolated two camel single domain antibodies (nanobodies) from a naïve library by phage display. The nanobody sequences were sequence......-optimized for Escherichia coli expression, cloned into the pET22-B(+) vector system, expressed in BL-21 cells and purified from the periplasmic fraction by IMAC. ELISA tests demonstrated that the purified nanobodies were specific for uPA when tested towards other trypsin-like serine proteases. The apparent affinities...... of the nanobodies were determined by competitive ELISA to 80 nM and 522 nM, respectively. The best binder did not inhibit uPA (nAb-C3), however the lowest affinity binder (nAb-C8) was able to inhibit the uPA-mediated cleavage of the substrate S-2444. The results validate the naïve library as a resource...

  12. Activation of the zymogen to urokinase-type plasminogen activator is associated with increased interdomain flexibility

    DEFF Research Database (Denmark)

    Behrens, Manja A; Bøtkjær, Kenneth Alrø; Goswami, Sumit

    2011-01-01

    A key regulatory step for serine proteases of the trypsin clan is activation of the initially secreted zymogens, leading to an increase in activity by orders of magnitude. Zymogen activation occurs by cleavage of a single peptide bond near the N-terminus of the catalytic domain. Besides the catal...

  13. The ligand-binding domain of the cell surface receptor for urokinase-type plasminogen activator

    DEFF Research Database (Denmark)

    Behrendt, N; Ploug, M; Patthy, L

    1991-01-01

    with the internal repeats of u-PAR constitute the extracellular part of Ly-6 antigens and of the squid glycoprotein Sgp-2. Like u-PAR, these proteins are attached to the membrane by a glycosyl-phosphatidylinositol anchor. The hydrophilic, ligand-binding u-PAR domain identified in the present study has potential...

  14. Mapping of the vitronectin-binding site on the urokinase receptor

    DEFF Research Database (Denmark)

    Gårdsvoll, Henrik; Ploug, Michael

    2007-01-01

    a comprehensive alanine-scanning library of purified single-site uPAR mutants (244 positions tested). Interestingly, the five residues identified as "hot spots" for vitronectin binding form a contiguous epitope consisting of two exposed loops connecting the central fourstranded beta-sheet in uPAR domain I (Trp(32...... the intriguing possibility that the canonical receptor and inhibitor for uPA (uPAR and PAI-1) may have reached a convergent solution for binding to the somatomedin B domain of vitronectin....

  15. Different mechanisms are involved in the antibody mediated inhibition of ligand binding to the urokinase receptor

    DEFF Research Database (Denmark)

    List, K; Høyer-Hansen, G; Rønne, E

    1999-01-01

    Certain monoclonal antibodies are capable of inhibiting the biological binding reactions of their target proteins. At the molecular level, this type of effect may be brought about by completely different mechanisms, such as competition for common binding determinants, steric hindrance or interfer...

  16. Activation of pro-urokinase and plasminogen on human sarcoma cells

    DEFF Research Database (Denmark)

    Stephens, R W; Pöllänen, J; Tapiovaara, H

    1989-01-01

    by an anticatalytic monoclonal antibody to u-PA, indicating that this enzyme was responsible for the activation. Preincubation of the cells with diisopropyl fluorophosphate-inhibited u-PA led to a decrease in surface-bound plasmin, indicating that a large part, if not all, of the cell surface plasminogen activation...

  17. Thrombolysoangioplasty in chronic, long segmental occlusive arterial disease

    International Nuclear Information System (INIS)

    Chung, Tae Woong; Kim, Jae Kyu; Koh, Byung Kwan; Kim, Jin Yup; Seo, Jeoung Jin; Kang, Hyeoung Keun

    1993-01-01

    From July 1988 to September 1992, we experienced 15 cases of thrombolysoangioplasty (TLA) at Chonnam University Hospital. Among 15 cases, 5 had claudication (Clinical stage II according to Modified Fontaine Classification), pain at rest (III),and gangrene (IV). Duration of symptoms was 1-7 months except patients of clinical stage IV unable to guess occlusion age. The occlusion length was 5-10 cm in 8 cases, 10-20 cm in 4 cases, and above 30 cm in 2 cases. In all cases, thrombolytic therapy was performed with intraarterial urokinase infusion. The total amount of urokinase ranged from 300,000 IU to 2,000,000 IU and infusion time ranged from 2 to 50 hours except three cases infused bolus dose only. Complete successful TLA was defined as technical (less than 50% of residual stenosis) and clinical success. Partial success was defined as technical success but clinical failure. Follow-up angiography could be performed in 8 cases. Overall initial success rate was 86.6% (13/15). Among them, complete success was in 11 cases and partial success was in 2 cases. Recurrence of disease was not noted on all cases(n=8). Severe complications, such as hemorrhage, did not occurred. TLA was considered to be effective and safe way to recanalized chronic long artery occlusion in lower extremity

  18. Radiological interventional procedures for the acute abdomen

    International Nuclear Information System (INIS)

    Trumm, C.; Hoffmann, R.T.; Reiser, M.F.

    2010-01-01

    In patients with acute thrombo-embolic occlusion of the superior mesenteric artery, catheter-assisted thrombolytic therapy represents a procedure of increasing importance in addition to surgery and intensive care treatment. The thrombolytic drugs utilized for this purpose are urokinase, streptokinase and recombinant tissue plasminogen activator (rtPA). Therapeutic embolization is predominantly used in the treatment of arterial bleeding from the gastro-intestinal tract, the liver, the intestines (due to an aneurysm or vascular malformation) and in bleeding from intestinal anastomoses. Polyvinyl alcohol particles, embospheres, gelfoam and microcoils can be utilized as embolic agents. Percutaneous transhepatic cholangiodrainage and stent implantation are applied in patients with biliary obstructions caused by inoperable tumors of the gall bladder or bile ducts, of the pancreatic head or duodenum and by metastases located in the liver parenchyma or hepatic hilum. Image-guided percutaneous drainage is a valuable option in the management of abscesses in the peritoneal cavity; less common indications are lymphoceles, biliomas, urinomas, hematomas, necrosis and pseudocysts. (orig.) [de

  19. [Application of percutaneous AngioJet thrombectomy in patients with acute symptomatic portal and superior mesenteric venous thrombosis].

    Science.gov (United States)

    Song, J H; He, X; Lou, W S; Chen, L; Chen, G P; Su, H B; Shi, W Y; Wang, T; Zhao, B X; Gu, J P

    2017-04-04

    Objective: To evaluate the clinical value of percutaneous AngioJet thrombectomy in treatment of acute symptomatic portal and superior mesenteric venous thrombosis venous thrombosis (PVMVT) . Method: From January 2014 to January 2016, a total of 8 patients in Nanjing First Hospital with PVMVT verified by color Doppler ultrasound and computed tomographic angiography (CTA) were analyzed retrospectively. Under ultrasound guidance , the branch of the right portal vein(PV) was punctured with a micropuncture set and a 4-F infusion catheter was advanced to the superior mesenteric vein(SMV). The venogram demonstrated the thrombosis in the PV/SMV and a 6-F AngioJet Xpeeedior catheter was advanced over the guidewire and positioned in the distal SMV. Percutaneous thrombectomy was performed after a mixture of 250 000 U of urokinase in 100 ml of normal saline for mechanical pulse spray of thrombus in all patients for approximately 15 minutes. 2 patients underwent PTA and stent implantation after the thrombectomy procedure, 1 of them and the others 6 patients received continuous transcatheter infusion of urokinase (500 000 U/d) for 24 or 48 hours until the thrombosis was completely dissolved confirmed by angiography at 24 and 48 hours.After procedure and the thrombolytic therapy was discontinued, removal of the infusion catheter and the sheath from the liver, the transhepatic tract was embolized with coils or gelfoam to reduce the risk of bleeding. The patency rate of PV /SMV was assessed by CTA at 1 and 6 months after the procedure. Patients were discharged with oral anticoagulation regimen for at least 6 months.The following criteria were used in evaluation of thrombolysis: grade Ⅰ90% thrombus removal. Results: All 8 patients with PVMVT were treated by AngioJet thrombectomy. Angiography after the thrombectomy procedure showed complete thrombus removal (>90%) was in 3 cases, substantial thrombus removal (50%~90%) in 5 cases. Grade Ⅲ (complete) thrombolysis was achieved in 7

  20. Angiographic Findings and Outcome in Diabetec Patients Treated With Thrombolytic Therapy for Acute Myocardial Infarction: The GUSTO-I Experience

    NARCIS (Netherlands)

    S.L. Woodfield (Scott); C.F. Lundergan (Conor); J.S. Reiner (Jonathan); S.W. Greenhouse (Samuel); M.A. Thompson (Mark); S.C. Rohrbeck (Steven); Y. Deychak (Yuri); M.L. Simoons (Maarten); R.M. Califf (Robert); E.J. Topol (Eric); A.M. Ross (Allan)

    1997-01-01

    textabstractOBJECTIVES: This study sought to determine whether diabetes mellitus, in the setting of thrombolysis for acute myocardial infarction, affects 1) early infarct-related artery patency and reocclusion rates; and 2) global and regional ventricular function indexes. We also sought to assess

  1. Implementation of Telemedicine and Stroke Network in thrombolytic administration: comparison between walk-in and referred patients.

    Science.gov (United States)

    Dharmasaroja, Pornpatr A; Muengtaweepongsa, Sombat; Kommarkg, Urai

    2010-08-01

    The purpose of this study was to evaluate the efficacy and safety of implementation of telemedicine and the Thammasat Stroke Network model in treating acute ischemic stroke patients with intravenous thrombolysis. Telemedicine (telephone consultation and tele-radiology) has been used in acute ischemic stroke management since June, 2007. The Thammasat Stroke Network (TSN) was effectively organized in March, 2008. Thammasat Hospital served as a "hub" hospital, with 25 "spoke" hospitals in the TSN. The main outcome measures included favorable outcome of the patients treated with intravenous tissue plasminogen activator (tPA) at 3 months and symptomatic intracerebral hemorrhage by comparison between walk-in patients and the patients who were referred by the TSN. There were 14 patients (14 out of 170 acute ischemic stroke patients, 8%) and 110 patients (110 out of 406 patients, 27%) receiving tPA, before and after implementation of TSN, respectively. Walk-in patients (66 patients) had significant shorter onset-to-treatment duration as compared with referred patients (58 patients) (130 vs. 170 min, P TSN markedly increased tPA administrations, without compromising favorable and safety outcomes.

  2. Importance of plasminogen activator inhibitor type 1 (PAI-1) for preventing single chain urokinase plasminogen activator (scu-PA) conversion into two chain urokinase plasminogen activator (tcu-PA) in plasma in vitro.

    Science.gov (United States)

    Dosne, A M; Dubor, F; Samama, M

    1991-09-01

    We have studied the effects of PAI-1 on the conversion of scu-PA into tcu-PA in vitro in plasma containing or not a 125I-fibrin clot by determining tcu-PA activity on S2444. Two preparations of PAI-1 have been used, a fraction of medium conditioned with the monkey Vero cells (Vero-Prep), the antiurokinase activity of which is inhibited at 83% by anti PAI-1 IgG, or purified human PAI-1 from HT 1080 fibrosarcoma cells. Scu-PA purified from human kidney cells has been treated with diisopropylfluorophosphate before use. In plasma, conversion of scu-PA into the tc form is accelerated by addition of anti PAI-1 IgG. In plasma containing a clot, generation of tcu-PA, is considerably delayed after addition of the Vero-Prep or human PAI-1. Clot lysis is also decreased but to a lesser extent than it would be expected from the level of tcu-PA activity. Addition of anti PAI-1 antibodies shortens the lag phase before tcu-PA appears and moderatly accelerates clot lysis. These results demonstrate the importance of PAI-1 for the stability of scu-PA in plasma in vitro by delaying its conversion into tcu-PA.

  3. Urokinase-type plasminogen activator (u-PA) and the risk of coronary events in patients with angina pectoris (AP)

    NARCIS (Netherlands)

    Dooijewaard, G.D.; Maat Mpm, E.; Meijer, P.; Kluft, C.; Binder, B.R.; Jespersen, J.; Keber, D.; Risberg, B.

    1998-01-01

    Introduction. This study addresses the rote of circulatory u-PA in the prevention and precipitation of arterial thrombosis. u-PA occurs in three forms: the inactive zymogen scu-PA, the active enzyme tcu-PA and u-PA#, the inactive complex of tcu-PA with inhibitors. In apparently healthy individuals

  4. The structure and function of the urokinase receptor, a membrane protein governing plasminogen activation on the cell surface

    DEFF Research Database (Denmark)

    Behrendt, N; Rønne, E; Danø, K

    1995-01-01

    PA receptor, uPAR, is a cell-surface protein which plays an important role in the localization and regulation of these processes. In the present article a number of established conclusions concerning the structure and function of uPAR are presented, and in addition various models are discussed which might...... domain is directly involved in the molecular contact with uPA. The receptor binds uPA as well as its proenzyme, pro-uPA, in such a manner that the activation cascade can occur directly on the cell surface. Furthermore, the activation rates are enhanced relative to the situation in solution, probably due...... between uPAR and uPA. The growing knowledge on the structure and function of uPAR which is a result of protein chemical analyses, functional studies and analyses of other, interacting components, should help to obtain a better understanding of the regulation of extracellular proteolysis. In conjunction...

  5. A conserved TATA-less proximal promoter drives basal transcription from the urokinase-type plasminogen activator receptor gene

    DEFF Research Database (Denmark)

    Soravia, E; Grebe, A; De Luca, P

    1995-01-01

    have cloned an uPAR DNA segment containing upstream regulatory sequences from both the human and murine genomes. We report that a proximal promoter, contained within 180 bp from the major transcription start sites of the human uPAR gene, drives basal transcription. This region lacks TATA and CAAT boxes...... and contains relatively GC-rich proximal sequences. A subregion of this sequence, highly conserved between human and murine genes, contains most of the promoter activity and is specifically bound by HeLa nuclear proteins, one of which belongs to the SP1 class....

  6. Plasma levels of intact and cleaved urokinase plasminogen activator receptor (uPAR) in men with clinically localised prostate cancer

    DEFF Research Database (Denmark)

    Kristensen, Gitte; Berg, Kasper Drimer; Lippert, Solvej

    2017-01-01

    1 disease. Soluble uPAR forms were measured using three time-resolved fluorescence immunoassays. The prognostic value of the different uPAR forms together with clinicopathological parameters for N1 disease were analysed using logistic regression, receiver operating characteristic (ROC) regression...

  7. Characterization of the functional epitope on the urokinase receptor. Complete alanine scanning mutagenesis supplemented by chemical cross-linking

    DEFF Research Database (Denmark)

    Gårdsvoll, Henrik; Gilquin, Bernard; Le Du, Marie Hélène

    2006-01-01

    a comprehensive alanine scanning mutagenesis of uPAR combined with low resolution distance constraints defined within the complex using chemical cross-linkers as molecular rulers. The kinetic rate constants for the interaction between pro-uPA and 244 purified uPAR mutants with single-site replacements were...... determined by surface plasmon resonance. This complete alanine scanning of uPAR highlighted the involvement of 20 surface-exposed side chains in this interaction. Mutations causing delta deltaG > or = 1 kcal/mol for the uPA interaction are all located within or at the rim of the central cavity uniquely...

  8. Structure-function relationships in the interaction between the urokinase-type plasminogen activator and its receptor

    DEFF Research Database (Denmark)

    Ploug, Michael

    2003-01-01

    Degradation of the extracellular matrix plays an important role in a number of normal and pathological conditions involving active tissue remodeling such as postlactational mammary gland involution, wound healing and tumor invasion and metastasis. The expression of a high-affinity, glycolipid...

  9. ELISA for complexes between urokinase-type plasminogen activator and its receptor in lung cancer tissue extracts

    DEFF Research Database (Denmark)

    de Witte, H; Pappot, H; Brünner, N

    1997-01-01

    indicate that de novo complex formation is a major factor to consider and that complexes analyzed in the presence of this antagonist represent original uPA:uPAR complexes present prior to tumor tissue processing. The present ELISA appears suitable for studying the potential prognostic impact of u...

  10. Studies on functional and structural role of urokinase receptor and other components of the plasminogen activation system in malignancy

    DEFF Research Database (Denmark)

    Weidle, U H; Wöllisch, E; Rønne, E

    1994-01-01

    Using immunohistochemistry and in-situ hybridization, we studied the expression of the components of the plasminogen activation system during progression to malignant melanoma with fresh melanocytic lesions. Expression of these components is confined to late stages of melanoma. t-PA expression...

  11. Cloning and expression of the receptor for human urokinase plasminogen activator, a central molecule in cell surface, plasmin dependent proteolysis

    DEFF Research Database (Denmark)

    Roldan, A.L.; Cubellis, M.V.; Masucci, M.T.

    1990-01-01

    , and therefore the capacity of cells to migrate and invade neighboring tissues. We have isolated a 1.4 kb cDNA clone coding for the entire human uPAR. An oligonucleotide synthesized on the basis of the N-terminal sequence of the purified protein was used to screen a cDNA library made from SV40 transformed human......, a size very close to that of the cloned cDNA. Expression of the uPAR cDNA in mouse cells confirms that the clone is complete and expresses a functional uPA binding protein, located on the cell surface and with properties similar to the human uPAR. Caseinolytic plaque assay, immunofluorescence analysis...... fibroblasts [Okayama and Berg (1983) Mol. Cell Biol., 3, 280-289]. The cDNA encodes a protein of 313 amino acids, preceded by a 21 residue signal peptide. A hydrophobicity plot suggests the presence of a membrane spanning domain close to the C-terminus. The cDNA hybridizes to a 1.4 kb mRNA from human cells...

  12. Structure-function relationships in the interaction between the urokinase-type plasminogen activator and its receptor

    DEFF Research Database (Denmark)

    Ploug, Michael

    2003-01-01

    activation potential in proximity of the cell surface. This review will focus on molecular properties of uPAR including its membrane attachment by glycosyl-phosphatidylinositol, its multidomain structure and its relationship to the Ly-6/uPAR/alpha-neurotoxin protein domain family. Furthermore a mapping...

  13. The plasma level of soluble urokinase receptor is elevated in patients with Streptococcus pneumoniae bacteraemia and predicts mortality

    DEFF Research Database (Denmark)

    Wittenhagen, p; Kronborg, Gitte; Weis, Nina Margrethe

    2004-01-01

    increased significantly (median 5.5; range 2.4-21.0 ng/mL) in 141 patients with pneumococcal bacteraemia, compared to 31 healthy controls (median 2.6, range 1.5-4.0 ng/mL, p 0.001). Furthermore, suPAR levels were elevated significantly in patients who died from the infection (n = 24) compared to survivors...... (n = 117; p hypotension, renal failure, cerebral symptoms and high serum concentrations of protein YKL-40 and suPAR were associated significantly with mortality (p

  14. Expression of urokinase plasminogen activator, its receptor and type-1 inhibitor in malignant and benign prostate tissue

    DEFF Research Database (Denmark)

    Usher, Pernille Autzen; Thomsen, Ole Frøkjær; Iversen, Peter

    2005-01-01

    RNAs was predominantly seen in cells identified as macrophages, which in most of the carcinomas (approximately 90%) were located in the interstitial tissue between the tumor cell islands, while in most of the benign hyperplasias they were located in the lumen of the glands and were in only a few cases (approximately 30......%) found in the interstitial tissue. uPAR immunoreactivity correlated with the mRNA expression and was, in addition, found in neutrophils. PAI-1 mRNA was detected in 13 of the 16 carcinomas and in 8 of the 9 benign hyperplasias, located in scattered fibroblast-like cells in both groups, in some vascular...... structures and in a few macrophages located in the interstitial tissue of both malignant and benign lesions. A similar expression pattern was found for PAI-1 immunoreactivity. In 8 of the 16 carcinomas, all 3 components were present, and in several areas colocalization was observed in stromal cells in close...

  15. Rational targeting of the urokinase receptor (uPAR): development of antagonists and non-invasive imaging probes

    DEFF Research Database (Denmark)

    Kriegbaum, M C; Persson, M; Haldager, L

    2011-01-01

    -ray crystallography and surface plasmon resonance studies. Importantly, these structural studies also define possible druggable target sites in uPAR for small molecules and provide guidelines for the development of reporter groups applicable for non-invasive molecular imaging of uPAR expression in vivo by positron...... emission tomography. In this review, we will discuss recent advances in our perception of the structure-function relationships of uPAR ligation and how these may assist translational research in preclinical intervention studies of uPAR function....

  16. A flexible multidomain structure drives the function of the urokinase-type plasminogen activator receptor (uPAR)

    DEFF Research Database (Denmark)

    Mertens, Haydyn D.T.; Kjærgaard, Magnus; Mysling, Simon

    2012-01-01

    -deuterium exchange, and surface plasmon resonance to develop a structural model describing the allosteric regulation of uPAR. We show that the flexibility of its N-terminal domain provides the key for understanding this allosteric mechanism. Importantly, our model has direct implications for understanding uPAR-assisted...... cell adhesion and migration as well as for translational research including targeted intervention therapy and non-invasive tumor imaging in vivo....

  17. Tumor cells secrete an angiogenic factor that stimulates basic fibroblast growth factor and urokinase expression in vascular endothelial cells

    NARCIS (Netherlands)

    Peverali, F.A.; Mandriota, S.J.; Ciana, P.; Marelli, R.; Quax, P.; Rifkin, D.B.; Della Valle, G.; Mignatti, P.

    1994-01-01

    Culture medium conditioned by human SK-Hep1 hepatoma cells or mouse S180 sarcoma cells rapidly up-regulates endothelial cell expression of basic fibroblast growth factor (bFGF) and induces formation of capillary-like structures by vascular endothelial cells grown on three-dimensional fibrin gels (in

  18. A conserved TATA-less proximal promoter drives basal transcription from the urokinase-type plasminogen activator receptor gene

    DEFF Research Database (Denmark)

    Soravia, E; Grebe, A; De Luca, P

    1995-01-01

    have cloned an uPAR DNA segment containing upstream regulatory sequences from both the human and murine genomes. We report that a proximal promoter, contained within 180 bp from the major transcription start sites of the human uPAR gene, drives basal transcription. This region lacks TATA and CAAT boxes...

  19. Intact and cleaved plasma soluble urokinase receptor in patients with metastatic colorectal cancer treated with oxaliplatin with or without cetuximab

    DEFF Research Database (Denmark)

    Tarpgaard, Line Schmidt; Christensen, Ib Jarle; Høyer-Hansen, Gunilla

    2015-01-01

    ) in a ligand-independent manner. The purpose of the study was to evaluate whether plasma soluble intact and cleaved uPAR(I-III)+(II-III) levels could identify a subpopulation of patients with metastatic colorectal cancer (mCRC) where treatment with cetuximab would have a beneficial effect. Plasma samples were...... with FLOX + cetuximab as compared to patients with KRAS wild-type and high levels of suPAR. These results thus support the preclinical findings and should be further tested in an independent clinical data set....

  20. Binding of the urokinase-type plasminogen activator to its cell surface receptor is inhibited by low doses of suramin

    DEFF Research Database (Denmark)

    Behrendt, N; Rønne, E; Danø, K

    1993-01-01

    micrograms/ml when using U937 cells and a ligand concentration of 0.3 nM. This concentration of the drug is well below the serum levels found in suramin-treated patients. Inhibition of binding was also demonstrated at the molecular level, using chemical cross-linking or an enzyme-linked immunosorbent assay...... to the anti-invasive properties of suramin by destroying the cellular potential for localized plasminogen activation and proteolytic matrix degradation....

  1. Antibody-mediated Targeting of the Urokinase-type Plasminogen Activator Proteolytic Function Neutralizes Fibrinolysis in Vivo

    DEFF Research Database (Denmark)

    Lund, Ida K.; Jögi, Annika; Rono, Birgitte

    2008-01-01

    models, we have now developed murine monoclonal antibodies (mAbs) directed against murine uPA by immunization of uPA-deficient mice with the recombinant protein. Guided by enzyme-linked immunosorbent assay, Western blotting, surface plasmon resonance, and enzyme kinetic analyses, we have selected two...... highly potent and inhibitory anti-uPA mAbs (mU1 and mU3). Both mAbs recognize epitopes located on the B-chain of uPA that encompasses the catalytic site. In enzyme activity assays in vitro, mU1 blocked uPA-catalyzed plasminogen activation as well as plasmin-mediated pro-uPA activation, whereas mU3 only...... fibrinolysis in tissue-type plasminogen activator (tPA)-deficient mice, resulting in a phenotype mimicking that of uPA;tPA double deficient mice. Importantly, this is the first report demonstrating specific antagonist-directed targeting of mouse uPA at the enzyme activity level in a normal physiological...

  2. Plasminogen activation by receptor-bound urokinase. A kinetic study with both cell-associated and isolated receptor

    DEFF Research Database (Denmark)

    Ellis, V; Behrendt, N; Danø, K

    1991-01-01

    .67 microM, below the physiological Plg concentration of 2 microM. A concomitant 6-fold reduction in kcat resulted in an increase in the overall catalytic efficiency, kcat/Km, of 5.7-fold. This high affinity Plg activation was abolished in the presence of a Plg-binding antagonist. In contrast to intact...

  3. Urokinase plasminogen activator receptor is expressed in invasive cells in gastric carcinomas from high- and low-risk countries

    DEFF Research Database (Denmark)

    Alpizar Alpizar, Warner Enrique; Nielsen, Boye Schnack; Sierra, Rafaela

    2010-01-01

    , and its presence on gastric cancer cells is linked to micro-metastasis and poor prognosis. Immunohistochemical analyses of a set of 44 gastric cancer lesions from Costa Rica showed expression of uPAR in cancer cells in both intestinal subtype (14 of 27) and diffuse subtype (10 of 17). We compared...... the expression pattern of uPAR in gastric cancers from a high-risk country (Costa Rica) with a low-risk country (Norway). We found uPAR on gastric cancer cells in 24 of 44 cases (54%) from Costa Rica and in 13 of 23 cases (56%) from Norway. uPAR was seen in macrophages and neutrophils in all cases. We also......PAR in cancer cells in more than half of the gastric cancer cases suggests that their uPAR-positivity do not contribute to explain the different mortality rates between the 2 countries, however, the actual prevalence of uPAR-positive cancer cells in the gastric cancers may still provide prognostic information....

  4. Efficacy and safety of rotating pigtail catheter: lower extremity deep vein thrombosis of may-thurner syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoon Kyung; Kang, Byung Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of); Gang, Sung Gown [College of Medicine, Ewha Womans Univ., Seoul (Korea, Republic of)

    2004-07-01

    The purpose of this study was to evaluate the efficacy and safety of mechanical fragmentation of iliofemoral deep vein thromboses (DVTs) with a rotating pigtail catheter followed by aspiration thrombectomy. Ten patients (eight females, two males, 56.8 +/- 21.37 years) with iliofemoral DVT underwent treatment for a total of ten affected limbs. Approximately 5-10 min after infusing 400,000-700,000 IU urokinase (UK) into the thrombosed deep veins, the thromboses were fragmented by the mechanical action of the rotating pigtail catheter tip. Following their fragmentation, the fragmented thromboses were aspirated. After completion of the above procedure, a stent was inserted if iliac vein stenosis was demonstrated. We evaluated the total procedure time, volume of thrombolytic agent (urokinase), valvular injury, symptom-free time interval and success rate (primary patency rate). In all 10 patients, the iliofemoral deep vein thrombosis was successfully fragmented and aspirated using the combination method of a rotating pigtail catheter and aspiration thrombectomy (clinical and technical success rate, 100%). The thromboses were declotted by means of a rotating pigtail catheter with an average treatment time of 5.7 minutes. The average duration of the total intervention was 108 min. The mean primary patency was approximately 4 months with no recurrence. The total UK dose was 890,000 IU on average. There were no major complications, such as pulmonary embolism or cerebral hemorrhage, while performing the thrombus-fragmentation procedure using the rotating pigtail catheter. The combination method of a rotating pigtail catheter and aspiration thrombectomy for the treatment of iliofemoral deep vein thrombosis was found to be rapid, safe and effective for accomplishing recanalization in all cases without complication. Therefore, this procedure constitutes a potential treatment option in patients presenting with iliofemoral vein thrombosis.

  5. Endovascular recanalization of a thrombosed native arteriovenous fistula complicated with an aneurysm: Technical aspects and outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Su Yeon [Dept. of Radiology, Seoul National University Hospital, College of Medicine, Seoul National University, Seoul (Korea, Republic of); So, Young Ho; Choi, Young Ho; Jung, In Mok; Chung, Jung Kee [Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul (Korea, Republic of)

    2015-04-15

    To evaluate the technical aspects and outcomes of endovascular recanalization of a thrombosed native arteriovenous fistula (AVF) complicated with an aneurysm. Sixteen patients who had a thrombosed AVF complicated with an aneurysm (two radiocephalic and 14 brachiocephalic) were included in this study. Recanalization procedures were performed by mechanical thrombectomy using the Arrow-Trerotola percutaneous thrombectomy device and adjunctive treatments. We evaluated dose of thrombolytic agent, underlying stenosis, procedure time, technical and clinical success, and complications. The primary and secondary patency rates were calculated using the Kaplan-Meier analysis. The thrombolytic agents used were 100000 U urokinase mixed with 500 IU heparin (n = 10) or a double dose of the mixture (n = 6). The thrombi in aneurysms were removed in all but two patients with non-flow limiting residual thrombi. One recanalization failure occurred due to a device failure. Aspiration thrombectomy was performed in 87.5% of cases (n = 14). Underlying stenoses were found in the outflow draining vein (n = 16), arteriovenous anastomosis or juxtaanastomosis area (n = 5), and the central vein (n = 3). Balloon angioplasty was performed for all stenoses in 15 patients. Two patients with a symptomatic central vein stenosis underwent insertion of a stent after balloon angioplasty. Mean procedure time was 116.3 minutes. Minor extravasation (n = 1) was resolved by manual compression. Both technical and clinical success rates were 93.8% (n = 15). The primary patency rates at 3, 6, and 12 months were 70.5%, 54.8%, and 31.3%, respectively. The secondary patency rates at 3, 6, and 12 months were 70.5%, 70.5%, and 47.0%, respectively. Thrombosed AVF complicated with an aneurysm can be successfully recanalized, and secondary patency can be prolonged with endovascular treatment.

  6. Sex-based differences in the effect of intra-arterial treatment of stroke: analysis of the PROACT-2 study.

    Science.gov (United States)

    Hill, Michael D; Kent, David M; Hinchey, Judith; Rowley, Howard; Buchan, Alastair M; Wechsler, Lawrence R; Higashida, Randall T; Fischbein, Nancy J; Dillon, William P; Gent, Michael; Firszt, Carolyn M; Schulz, Gregory A; Furlan, Anthony J

    2006-09-01

    Sex influences outcome after intravenous thrombolysis. In a combined analysis of the tissue plasminogen activator clinical trials, a sex-by-treatment interaction was observed. We sought to confirm that observation in an independent data set. Data were from the Pro-Urokinase for Acute Cerebral Thromboembolism-2 (PROACT-2) trial. Baseline factors were compared by sex. The primary outcome was an assessment of a sex-by-treatment interaction term within a logistic regression model, using a modified Rankin Scale score thrombolytic treatment nullifies the worse outcome for untreated women compared with men. The reasons for effect modification do not include improved recanalization at 2 hours among women. Women with middle cerebral artery ischemic stroke benefit more from intra-arterial therapy. Further study of how sex affects stroke outcome is needed.

  7. Intraarterial therapy for acute ischemic stroke. Investigation of prognostic factors

    International Nuclear Information System (INIS)

    Noguchi, Tomoyuki; Yoshiura, Takashi; Oguri, Shuichi

    2007-01-01

    Intraarterial therapy (IAT) for acute cerebral infarction has been proven to be profitable. However, the criteria for the indications, the choice of the thrombolytic agents, and the use of adjunctive agents are controversial. We retrospectively analyzed the prognostic factors of IAT. From 1994 to 2003, 28 patients underwent IAT due to middle cerebral artery occlusion (17 women and 11 men; median age, 69 years old). We evaluated the following prognostic parameters: institution of treatment, degree of paralysis at visit, size of high-intensity area on diffusion-weighted images, dose of intraarterial urokinase administration, elapsed time from symptom onset to completion of IAT, presence of penetration of embolus by microcatheter and microguidewire, recanalization after IAT, intracranial hemorrhage (ICH) within 24 hours after IAT, and intravenous heparin administration after IAT. The outcome was evaluated at discharge and was classified into the following categories according to the modified Rankin Scale: independence (0 to 2), dependence (3 to 5), and death (6). Seven patients were judged to be independent, 16 patients were judged to be dependent, and five patients died. Patients with recanalization after IAT had a better outcome than those without (p<0.05); patients with intracranial hemorrhage had a worse outcome than those without (p<0.05); and patients with intravenous heparin administration after IAT had a better outcome in activities of daily living than those without (p<0.05). In addition to ICH and recanalization, our results suggested that intravenous heparin administration after IAT had a favorable effect on patient outcome. (author)

  8. Clinical application of interventional therapy for avascular necrosis of the femoral head

    International Nuclear Information System (INIS)

    Han Xu; Jin Kesi; Liu Wei; Ma Jun; Shen Jianming; Aziken

    2004-01-01

    Objective: To evaluate the possibility of interventional therapy for avascular necrosis of the femoral head, with different curing methods, way of introduction and cultural heritages. Methods: Vasodilator, thrombolytics and promoting microcirculatory drug were directly injected into the feeding arteries of the avascular necrotic femoral heads, under the condition of applying the blood stoppage belt at the root of thigh with pressure before the drug injection into the femoral pronator and extension arteries. The treatment was repeated 45 d later. Urokinase 10 5 unite/d x 10 were administrated with venous infusion ipsilaterally on the 15th day after the beginning of the therapy. Imaging features and clinical symptoms were recorded and correlatively studied before and after the treament. Results: Symptoms relief especially the pain reached 100% after the treatment with various degrees of bony repair and new bone formation. Furthermore, increase caliber of feeding small arteries for femoral head and multiplicity of microvasculature, shortening of opacification time were revealed by DSA. IV stage bony change showed mild or inconspicuous. Conclusions: Interventional catheterization treatment for avascular femoral head necrosis, especially the patients of fore III stage, is safe and effective. (authors)

  9. Nano-zymography Using Laser-Scanning Confocal Microscopy Unmasks Proteolytic Activity of Cell-Derived Microparticles.

    Science.gov (United States)

    Briens, Aurélien; Gauberti, Maxime; Parcq, Jérôme; Montaner, Joan; Vivien, Denis; Martinez de Lizarrondo, Sara

    2016-01-01

    Cell-derived microparticles (MPs) are nano-sized vesicles released by activated cells in the extracellular milieu. They act as vectors of biological activity by carrying membrane-anchored and cytoplasmic constituents of the parental cells. Although detection and characterization of cell-derived MPs may be of high diagnostic and prognostic values in a number of human diseases, reliable measurement of their size, number and biological activity still remains challenging using currently available methods. In the present study, we developed a protocol to directly image and functionally characterize MPs using high-resolution laser-scanning confocal microscopy. Once trapped on annexin-V coated micro-wells, we developed several assays using fluorescent reporters to measure their size, detect membrane antigens and evaluate proteolytic activity (nano-zymography). In particular, we demonstrated the applicability and specificity of this method to detect antigens and proteolytic activities of tissue-type plasminogen activator (tPA), urokinase and plasmin at the surface of engineered MPs from transfected cell-lines. Furthermore, we were able to identify a subset of tPA-bearing fibrinolytic MPs using plasma samples from a cohort of ischemic stroke patients who received thrombolytic therapy and in an experimental model of thrombin-induced ischemic stroke in mice. Overall, this method is promising for functional characterization of cell-derived MPs.

  10. Risk factors of mesenteric venous thrombosis and current situation of diagnosis and treatment in China

    International Nuclear Information System (INIS)

    Zhuang Zhiwei; Zhu Huanxing; Xu Changsheng

    2010-01-01

    Objective: To investigate risk factors of mesenteric venous thrombosis and current situation of diagnosis and treatment in China. Methods: One hundred and seven case of mesenteric venous thrombosis reported in literature were analyzed. The literature from 2003 to 2007 were retrieved from Chinese Scientific and Technical Periodical Database and Wanfangdata. Results: One hundred and seven papers included 978 MVT patients, male: female = 1. 9:1, the average age was 47. 9. The most common risk factors were portal hypertension (28. 9% ), splenectomy (18. 8%) and thrombophlebitis (11. 5%) in 833 cases with integrated medical history. Final diagnosis was established by medical imageology (40. 0%) and exploratory laparotomy (60. 0%). The achievement ratio of thrombolysis therapy was 83. 9% (73 /87) by peripheral vein and 90. 0% (63 /70) by superior mesenteric artery. 34. 7% patients took warfarin orally after discharge. Conclusions: Portal hypertension, splenectomy and thrombophlebitis may be the most common risk factor for MVT; through peripheral vein or superior mesenteric artery urokinase thrombolytic therapy is an effective means of treatment of early MVT; MVT diagnostic awareness and anticoagulant therapy after surgery awareness of the importance is to be strengthened. (authors)

  11. Benefit of Thrombolytic Therapy is Sustained Throughout Five Years and Is Related to TIMI Perfusion Grade 3 But Not Grade 2 Flow at Discharge

    NARCIS (Netherlands)

    T. Lenderink (Timo); M.L. Simoons (Maarten); G.A. van Es (Gerrit Anne); M. Verstraete (Marc); A.E.R. Arnold (Alfred); F.J.J. van de Werf (Frans)

    1995-01-01

    textabstractBACKGROUND: Long-term follow-up in patients treated with thrombolysis for acute myocardial infarction thus far has been reported in a few studies only, and no long-term follow-up is available for patients who underwent additional percutaneous transluminal coronary angioplasty (PTCA).

  12. Understanding clinicians' decisions to offer intravenous thrombolytic treatment to patients with acute ischaemic stroke: a protocol for a discrete choice experiment.

    Science.gov (United States)

    De Brún, Aoife; Flynn, Darren; Joyce, Kerry; Ternent, Laura; Price, Christopher; Rodgers, Helen; Ford, Gary A; Lancsar, Emily; Rudd, Matthew; Thomson, Richard G

    2014-07-09

    Intravenous thrombolysis is an effective emergency treatment for acute ischaemic stroke for patients meeting specific criteria. Approximately 12% of eligible patients in England, Wales and Northern Ireland received thrombolysis in the first quarter of 2013, yet as many as 15% are eligible to receive treatment. Suboptimal use of thrombolysis may have been largely attributable to structural factors; however, with the widespread implementation of 24/7 hyper acute stroke services, continuing variation is likely to reflect differences in clinical decision-making, in particular the influence of ambiguous areas within the guidelines, licensing criteria and research evidence. Clinicians' perceptions about thrombolysis may now exert a greater influence on treatment rates than structural/service factors. This research seeks to elucidate factors influencing thrombolysis decision-making by using patient vignettes to identify (1) patient-related and clinician-related factors that may help to explain variation in treatment and (2) associated trade-offs in decision-making based on the interplay of critical factors. A discrete choice experiment (DCE) will be conducted to better understand how clinicians make decisions about whether or not to offer thrombolysis to patients with acute ischaemic stroke. To inform the design, exploratory work will be undertaken to ensure that (1) all potentially influential factors are considered for inclusion; and (2) to gain insights into the 'grey areas' of patient factors. A fractional factorial design will be used to combine levels of patient factors in vignettes, which will be presented to clinicians to allow estimation of the variable effects on decisions to offer thrombolysis. Ethical approval for this study was obtained from the Newcastle University Research Ethics Committee. The results will be disseminated in peer review publications and at national conferences. Findings will be translated into continuing professional development activities and will support implementation of a computerised decision aid for thrombolysis (COMPASS) in acute stroke care. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  13. A review of decision support, risk communication and patient information tools for thrombolytic treatment in acute stroke: lessons for tool developers.

    Science.gov (United States)

    Flynn, Darren; Ford, Gary A; Stobbart, Lynne; Rodgers, Helen; Murtagh, Madeleine J; Thomson, Richard G

    2013-06-18

    Tools to support clinical or patient decision-making in the treatment/management of a health condition are used in a range of clinical settings for numerous preference-sensitive healthcare decisions. Their impact in clinical practice is largely dependent on their quality across a range of domains. We critically analysed currently available tools to support decision making or patient understanding in the treatment of acute ischaemic stroke with intravenous thrombolysis, as an exemplar to provide clinicians/researchers with practical guidance on development, evaluation and implementation of such tools for other preference-sensitive treatment options/decisions in different clinical contexts. Tools were identified from bibliographic databases, Internet searches and a survey of UK and North American stroke networks. Two reviewers critically analysed tools to establish: information on benefits/risks of thrombolysis included in tools, and the methods used to convey probabilistic information (verbal descriptors, numerical and graphical); adherence to guidance on presenting outcome probabilities (IPDASi probabilities items) and information content (Picker Institute Checklist); readability (Fog Index); and the extent that tools had comprehensive development processes. Nine tools of 26 identified included information on a full range of benefits/risks of thrombolysis. Verbal descriptors, frequencies and percentages were used to convey probabilistic information in 20, 19 and 18 tools respectively, whilst nine used graphical methods. Shortcomings in presentation of outcome probabilities (e.g. omitting outcomes without treatment) were identified. Patient information tools had an aggregate median Fog index score of 10. None of the tools had comprehensive development processes. Tools to support decision making or patient understanding in the treatment of acute stroke with thrombolysis have been sub-optimally developed. Development of tools should utilise mixed methods and strategies to meaningfully involve clinicians, patients and their relatives in an iterative design process; include evidence-based methods to augment interpretability of textual and probabilistic information (e.g. graphical displays showing natural frequencies) on the full range of outcome states associated with available options; and address patients with different levels of health literacy. Implementation of tools will be enhanced when mechanisms are in place to periodically assess the relevance of tools and where necessary, update the mode of delivery, form and information content.

  14. Primary coronary angioplasty compared with intravenous thrombolytic therapy for acute myocardial infarction : Six-month follow up and analysis of individual patient data from randomized trials

    NARCIS (Netherlands)

    Grines, C; Patel, A; Zijlstra, F; Weaver, WD; Granger, C; Simes, RJ; Ellis, S; Betriu, A; Grines, C; Garcia, E; Grinfeld, L; Gibbons, R; Ribeiro, E; Ribichini, F; Akhras, F; Jones, M; Topol, E; Califf, R; Van der Werf, F; Ardissino, D; Armstrong, PW; Aylward, P; Bates, E; Beatt, K; Cheseboro, J; Col, J; Emanuelsson, H; Fuster, [No Value; Gibler, WB; Gore, J; Guerci, A; Hochman, J; Holmes, D; Kleiman, N; Morris, D; Neuhaus, K; Ohman, M; Pfisterer, M; Phillips, H; Rutsch, W; Vahanian, A; White, H; Stone, G; Browne, K; Marco, J; Rothbaum, D; O'Keefe, DRJ; Overlie, P; Donohue, B; O'Neill, W; de Boer, MJ; van 'T Hof, AWJ; Hoorntje, JCA; Ottervanger, JP; Suryapranata, H; Moreno, R; Abeytua, M; de Sa, EL; Lopez-Sendon, JL; Delcan, JL; Berrocal, D; Bellardi, J; Steffenino, G; Dellavalle, A; Holmes, DR; Gersh, BJ; Hopfenspirger, MR; Silva, LA; Carneiro, R; Akhras, F; Abu Ousa, A

    Background Overviews of trials suggest that percutaneous transluminal coronary angioplasty (PTCA) may be more effective than thrombolysis. However, whether these effects are sustained beyond hospital discharge, and the extent to which the results are applicable to a broad cross section of patients

  15. Prognostic significance of precordial ST segment depression during inferior myocardial infarction in the thrombolytic era: Results in 16,521 patients

    NARCIS (Netherlands)

    E.D. Peterson; W.R. Hathaway; K.M. Zabel; K.S. Pieper (Karen); C.B. Granger (Christopher); G.S. Wagner (Galen); E.J. Topol (Eric); E.R. Bates (Eric); M.L. Simoons (Maarten); R.M. Califf (Robert)

    1996-01-01

    textabstractObjectives. We examined the prognostic significance of precordial ST segment depression among patients with an acute inferior myocardial infarction. Background. Although precordial ST segment depression has been associated with a poor prognosis, this correlation has not been adequately

  16. Focal cerebral ischemia measured by the intra-arterial 133xenon method. Limitations of 2-dimensional blood flow measurements

    DEFF Research Database (Denmark)

    Skyhøj Olsen, T; Larsen, B; Bech Skriver, E

    1981-01-01

    The limitations of 2-dimensional isotope techniques in the study of focal cerebral ischemia were investigated using the intra-carotid 133 xenon injection method and a 254 multidetector scintillation camera. To make sure that the detectors "look" directly on infarcted areas, only patients with inf...

  17. Urokinase-type plasminogen activator-like proteases in teleosts lack genuine receptor-binding epidermal growth factor-like domains

    DEFF Research Database (Denmark)

    Bager, René; Kristensen, Thomas K.; Jensen, Jan

    2012-01-01

    PA by lacking the exon encoding the uPAR-binding epidermal growth factor-like domain; zfuPA-b differs from mammalian uPA by lacking two cysteines of the epidermal growth factor-like domain and a uPAR-binding sequence comparable with that found in mammalian uPA. Accordingly, no zfuPA-b binding activity could...

  18. Soluble urokinase plasminogen activator receptor is in contrast to high-sensitive C-reactive-protein associated with coronary artery calcifications in healthy middle-aged subjects

    DEFF Research Database (Denmark)

    Sørensen, Mette Hjortdal; Gerke, Oke; Eugen-Olsen, Jesper

    2014-01-01

    samples were analysed for suPAR and hs-CRP. The association of suPAR and hs-CRP to CAC was evaluated by logistic regression analyses adjusting for categorised SCORE. The additive effect of suPAR to SCORE was evaluated by comparing area under curve (AUC) and net reclassification improvement (NRI). RESULTS...... with CAC category (OR 1.00, p = 0.90). When adding suPAR to categorised SCORE, AUC increased from 0.66 to 0.70 (p = 0.04) in women and from 0.65 to 0.68 (p = 0.03) in men. NRI was significant in men (NRI 19.3%, 95% CI 6.1-32.6, p = 0.004) as well as in women (NRI 20.8%, 95%CI 1.0-40.7, p = 0.04), without...

  19. Aspirin Inhibits IKK-β-mediated Prostate Cancer Cell Invasion by Targeting Matrix Metalloproteinase-9 and Urokinase-Type Plasminogen Activator

    OpenAIRE

    Chongjun Shi; Nini Zhang; Yang Feng; Jiewei Cao; Xuyi Chen; Bin Liu

    2017-01-01

    Background/Aims: Aspirin has been demonstrated to possess potent chemopreventive and anticancer effects on prostate cancer. However, the more detailed molecular mechanisms of aspirin to suppress prostate cancer cell invasion have not been clearly elucidated. Methods: Transwell assays were performed to evaluate the effects of aspirin on cell invasion. Matrix metalloproteinases (MMPs) and serine proteinases activities in cell media were examined by gelatin zymography and ELISA. In addition, inh...

  20. Reduced release of intact and cleaved urokinase receptor in stimulated whole-blood cultures from human immunodeficiency virus-1-infected patients

    DEFF Research Database (Denmark)

    Ostrowski, S R; Piironen, Timo; Høyer-Hansen, G

    2005-01-01

    . The release of different uPAR forms in whole-blood cultures incubated 24 h with or without phytohemagglutinin and lipopolysaccharide was analysed in 47 HIV patients and 19 controls. suPAR was measured by enzyme-linked immunosorbent assay (ELISA) (bulk-suPAR) and three different time-resolved fluorescence...

  1. Expression and crystallographic studies of the D1D2 domains of C4.4A, a homologous protein to the urokinase receptor

    DEFF Research Database (Denmark)

    Chen, Shanli; Lin, Lin; Yuan, Cai

    2017-01-01

    various pathological conditions and it is a robust biomarker for poor prognosis in various malignant conditions such as pulmonary adenocarcinoma. To facilitate crystallization, the two LU domains were excised from intact C4.4A by limited proteolysis, purified and crystallized by the sitting-drop vapour...... of C4.4A were excised by limited proteolysis and were crystallized using the sitting-drop vapour-diffusion method. The crystals diffracted to 2.7 Å resolution, giving good-quality data....

  2. Plasma concentrations of soluble urokinase-type plasminogen activator receptor are increased in patients with malaria and are associated with a poor clinical or a fatal outcome

    DEFF Research Database (Denmark)

    Ostrowski, Sisse R; Ullum, Henrik; Goka, Bamenla Q

    2005-01-01

    in healthy children (3.94 ng/mL [IQR, 3.46-4.82 ng/mL]; P logistic regression analysis, a 1 ng/mL increase in plasma concentration of suPAR was associated...... with increased risk of mortality (odds ratio, 1.42 [95% confidence interval, 1.09-1.86]; P = .009). In multivariate linear regression analysis, lower platelet count, lower hemoglobin level, and higher neutrophil count were independently associated with a higher plasma concentration of suPAR. CONCLUSIONS...

  3. Urokinase-type plasminogen activator receptor (uPAR) expression is associated with T-stage and survival in urothelial carcinoma of the bladder

    DEFF Research Database (Denmark)

    Dohn, Line Hammer; Illemann, Martin; Høyer-Hansen, Gunilla

    2015-01-01

    during cancer invasion and metastasis and is an established prognostic marker in cancer. The expression and localization of uPAR and its prognostic significance is only limitedly investigated in urothelial bladder neoplasia. MATERIALS AND METHODS: The expression-and localization pattern of u......PAR was investigated in formalin-fixed paraffin-embedded tumor tissue from 149 patients treated with radical cystectomy between 1988 and 2005. uPAR expression was determined by immunohistochemistry and scored as either negative or positive. Separate values were obtained for cancer cells, macrophages...... comparisons). In univariate analysis, the uPAR positive group had a shorter survival than the uPAR negative group (hazard ratio = 2.39; 95% CI: 1.15-5.01; P = 0.020). CONCLUSIONS: The expression of uPAR is a possible prognostic marker that could be useful in identification of patients with aggressive, highly...

  4. Altered expression of the urokinase receptor homologue, C4.4A, in invasive areas of human esophageal squamous cell carcinoma

    DEFF Research Database (Denmark)

    Hansen, L.V.; Laerum, O.D.; Illemann, M.

    2008-01-01

    . In the present study, we have therefore analyzed the expression of C4.4A in 14 esophageal squamous cell carcinomas (ESCC). Normal squamous esophageal epithelium shows a strong cell surface associated C4.4A expression in the suprabasal layers, whereas basal cells are negative. Upon transition to dysplasia...... and carcinoma in situ the expression of C4.4A is abruptly and coordinately weakened. Double immunofluorescence staining of normal and dysplastic tissue showed that C4.4A colocalizes with the epithelial cell surface marker E-cadherin in the suprabasal cells and has a complementary expression pattern compared...... to the proliferation marker Ki-67. A prominent, but frequently intracellular, C4.4A expression reappeared in tumor cells located at the invasive front and local lymph node metastases. Because C4.4A was reported previously to be a putative laminin-5 (LN5) ligand, and both proteins are expressed by invasive tumor cells...

  5. Cell-induced potentiation of the plasminogen activation system is abolished by a monoclonal antibody that recognizes the NH2-terminal domain of the urokinase receptor

    DEFF Research Database (Denmark)

    Rønne, E; Behrendt, N; Ellis, V

    1991-01-01

    -u-PA and plasminogen with U937 cells. This antibody, which is also the only one to completely inhibit the binding of DFP-inactivated [125I]-u-PA to U937 cells, is directed against the u-PA binding NH2-terminal domain of u-PAR, a well-defined fragment formed by limited chymotrypsin digestion of purified u......-PAR, demonstrating the functional independence of the u-PA binding domain as well as the critical role of u-PAR in the assembly of the cell-surface plasminogen activation system....

  6. Mimicry of the regulatory role of urokinase in lamellipodia formation by introduction of a non-native interdomain disulfide bond in its receptor

    DEFF Research Database (Denmark)

    Gårdsvoll, Henrik; Kjærgaard, Magnus; Jacobsen, Benedikte

    2011-01-01

    -natural interdomain disulfide bond (uPAR(H47C-N259C)). The corresponding soluble receptor has 1) a smaller hydrodynamic volume, 2) a higher content of secondary structure, and 3) unaltered binding kinetics towards uPA. Most importantly, the purified uPAR(H47C-N259C) also displays a gain in affinity...

  7. Improved positron emission tomography imaging of glioblastoma cancer using novel 68Ga-labeled peptides targeting the urokinase-type plasminogen activator receptor (uPAR)

    DEFF Research Database (Denmark)

    Loft, Mathias Dyrberg; Sun, Yao; Liu, Changhao

    2017-01-01

    to the non-spacer version, NODAGA-AE105-NH2. Following radiolabeling with68Ga, we evaluated the in vitro and in vivo performance in mice bearing subcutaneous tumors derived from the uPAR-expressing human GBM cell line U87MG. In vivo PET/CT imaging showed that introduction of PEG spacers more than doubled...

  8. Urokinase-type plasminogen activator receptor (uPAR) on tumor-associated macrophages is a marker of poor prognosis in colorectal cancer

    DEFF Research Database (Denmark)

    Illemann, Martin; Laerum, Ole Didrik; Hasselby, Jane Preuss

    2014-01-01

    Patients were identified from a population-based prospective study of 4990 individuals with symptoms associated with colorectal cancer (CRC). A total of 244 CRC tissue samples were available for immunohistochemical staining of uPAR, semiquantitatively scored at the invasive front, and in the tumor...... core on cancer cells, macrophages, and myofibroblasts. In addition, the levels of the intact and cleaved uPAR-forms in blood from the same patients are evaluated in this study. In a univariate analysis, the number of uPAR-positive versus uPAR-negative macrophages (HR = 2.26, [95% CI: 1.39-3.66, P = 0.......0009]) and cancer cells (HR=1.49, [95% CI: 1.01-2.20, P = 0.047]) located in the tumor core were significantly associated to overall survival. In a multivariate analysis, uPAR-positive versus uPAR-negative macrophages located in the tumor core showed the best separation of patients with positive score associated...

  9. Structure, function and expression on blood and bone marrow cells of the urokinase-type plasminogen activator receptor, uPAR

    DEFF Research Database (Denmark)

    Plesner, T; Behrendt, N; Ploug, M

    1997-01-01

    patients with the rare blood disease paroxysmal nocturnal hemoglobinuria (PNH) that fail to express glycosyl-phosphatidylinositol-anchored proteins including uPAR, show a very significantly reduced transmigration over an endothelial barrier. Cell-associated plasminogen activation by PNH......), most importantly PAI-1 and PAI-2, providing means of temporally restricting the process of plasminogen activation. In addition to its role in plasminogen activation, compelling evidence has demonstrated a role for uPAR in cell-cell and cell-extracellular matrix adhesion, both directly and indirectly. u......PAR is directly involved in binding to the extracellular matrix molecule, vitronectin, and the affinity of this binding is increased when uPAR is occupied by (pro-)uPA. A more indirect but presumably very important role of uPAR in cell adhesion seems to be mediated through interactions between uPAR and beta 1...

  10. Soluble urokinase plasminogen activator receptor, C-reactive protein and triglyceride are associated with heart rate variability in non-diabetic Danes

    DEFF Research Database (Denmark)

    Intzilakis, Theodoros; Hartmann, Gro; Mouridsen, Mette R

    2013-01-01

    and is a predictor of poor outcome. As HRV and its determinants in non-diabetic individuals have not been studied properly, the aim of this observational study was to evaluate possible associations between HRV vs. impaired fasting glucose, insulin resistance, lipidaemia and markers of inflammation and immune......Heart rate variability (HRV) is associated with an increased risk of cardiovascular morbidity and mortality. HRV is in part a function of the activity of the autonomic nervous system and has been associated with low-grade inflammation. In patients with type 2 diabetes, HRV is decreased...

  11. Protection of single-chain urokinase-type plasminogen activator (scu-PA) in aprotinin treated cardiac surgical patients undergoing cardiopulmonary bypass

    NARCIS (Netherlands)

    Spannagl, M.; Dooijewaard, G.; Dietrich, W.; Kluft, C.

    1995-01-01

    Intraoperative high-dose aprotinin administration has been shown to reduce the intra-and postoperative blood loss in cardiac surgery. The haemostatic effect has been attributed to platelet preserving properties and to inhibition of contact activation reducing thrombotic and fibrinolytic activity

  12. Intact and cleaved forms of the urokinase receptor enhance discrimination of cancer from non-malignant conditions in patients presenting with symptoms related to colorectal cancer

    DEFF Research Database (Denmark)

    Lomholt, A F; Høyer-Hansen, G; Nielsen, H J

    2009-01-01

    plasminogen activator receptor (suPAR) was proposed as a marker in CRC patients. This study was undertaken to evaluate the individual molecular forms of suPAR as discriminators in a group of patients undergoing endoscopical examination following symptoms related to colorectal cancer. METHODS: In a case......-control study comprising 308 patients undergoing endoscopical examination following CRC-related symptoms, 77 CRC patients with adenocarcinoma were age and gender matched to: 77 patients with adenomas; 77 with other non-malignant findings, and 77 with no findings. The different uPAR forms were measured...

  13. Extracellular Matrix Biomarker, Fibulin-1, Is Closely Related to NT-proBNP and Soluble Urokinase Plasminogen Activator Receptor in Patients with Aortic Valve Stenosis (The SEAS Study)

    DEFF Research Database (Denmark)

    Kruger, Ruan; Rasmussen, Lars M; Argraves, William S

    2014-01-01

    associated with subclinical atherosclerosis. Therefore, we aimed to explore the interplay between these biomarkers and mild to moderate aortic valve stenosis (AS). METHODS: In 374 patients with mild to moderate AS, we investigated the relationship of fibulin-1 with NT-proBNP, levels of suPAR and the degree.......01), and suPAR (βyear0 = 0.09, p = 0.26, βyear1 = 0.23, βyear4 = 0.21, both plevels of fibulin-1 were independently associated with higher levels of suPAR and NT-proBNP especially in patients with lower AVAI, suggesting...

  14. A 55,000-60,000 Mr receptor protein for urokinase-type plasminogen activator. Identification in human tumor cell lines and partial purification

    DEFF Research Database (Denmark)

    Nielsen, L S; Kellerman, G M; Behrendt, N

    1988-01-01

    -PA-R consists of one polypeptide chain. Two forms of u-PA-R, which differed with respect to affinity to concanavalin A, were identified. u-PA-R retained its ability to bind to ATF after cell lysis, and it was purified approximately 2,200-fold from biosynthetically labeled U937 cells by affinity chromatography...... protein (u-PA-R). In the human monocyte cell line U937 cultivated in the presence of phorbol ester, the amount of complex was strongly increased, and a fraction of the complex had a slower electrophoretic mobility. Comparison between autoradiograms of reduced and unreduced samples suggests that u...... with proenzyme u-PA coupled to Sepharose. The purified Mr 55,000-60,000 protein was specifically bound and cross-linked to u-PA, proenzyme u-PA, and ATF, but not to tissue-type plasminogen activator or other unrelated proteins....

  15. Altered expression of the urokinase receptor homologue, C4.4A, in invasive areas of human esophageal squamous cell carcinoma

    DEFF Research Database (Denmark)

    Hansen, Line V.; Laerum, Ole D; Illemann, Martin

    2008-01-01

    . In the present study, we have therefore analyzed the expression of C4.4A in 14 esophageal squamous cell carcinomas (ESCC). Normal squamous esophageal epithelium shows a strong cell surface associated C4.4A expression in the suprabasal layers, whereas basal cells are negative. Upon transition to dysplasia...... to the proliferation marker Ki-67. A prominent, but frequently intracellular, C4.4A expression reappeared in tumor cells located at the invasive front and local lymph node metastases. Because C4.4A was reported previously to be a putative laminin-5 (LN5) ligand, and both proteins are expressed by invasive tumor cells...

  16. Imaging of urokinase-type plasminogen activator receptor expression using a 64Cu-labeled linear peptide antagonist by microPET

    DEFF Research Database (Denmark)

    Li, Zi-Bo; Niu, Gang; Wang, Hui

    2008-01-01

    for positron emission tomography (PET) imaging. A linear, high-affinity uPAR-binding peptide antagonist AE105 was conjugated with 1,4,7,10-tetraazadodecane-N,N',N'',N'''-tetraacetic acid (DOTA) and labeled with (64)Cu for microPET imaging of mice bearing U87MG human glioblastoma (uPAR positive) and MDA-MB-435...... human breast cancer (uPAR negative). RESULTS: Surface plasmon resonance measurements show that AE105 with DOTA conjugated at the alpha-amino group (DOTA-AE105) has high affinity toward uPAR. microPET imaging reveals a rapid and high accumulation of (64)Cu-DOTA-AE105 in uPAR-positive U87MG tumors (10.......8 +/- 1.5%ID/g at 4.5 hours, n = 3) but not in uPAR-negative MDA-MB-435 tumors (1.2 +/- 0.6%ID/g at 4.5 hours, n = 3). Specificity of this peptide-based imaging of uPAR was validated by further control experiments. First, a nonbinding variant of AE105 carrying a single amino acid replacement (Trp...

  17. Tumour cell expression of C4.4A, a structural homologue of the urokinase receptor, correlates with poor prognosis in non-small cell lung cancer

    DEFF Research Database (Denmark)

    Hansen, Line V.; Skov, Birgit G; Ploug, Michael

    2007-01-01

    expression. In the present study, we therefore explored the possible association between C4.4A expression and prognosis in patients with non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Tissue sections from 108 NSCLC patients were subjected to immunohistochemical staining using a polyclonal antibody...

  18. A 55,000-60,000 Mr receptor protein for urokinase-type plasminogen activator. Identification in human tumor cell lines and partial purification

    DEFF Research Database (Denmark)

    Nielsen, L S; Kellerman, G M; Behrendt, N

    1988-01-01

    a bifunctional amino-reactive reagent followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography revealed with the four cell lines studied the occurrence of a single band migrating with an Mr of 70,000-75,000, indicating complex formation with an Mr of 55,000-60,000 u-PA receptor...

  19. Cleaved forms of the urokinase plasminogen activator receptor in plasma have diagnostic potential and predict postoperative survival in patients with ovarian cancer

    DEFF Research Database (Denmark)

    Henic, E.; Borgfeldt, C.; Christensen, I.J.

    2008-01-01

    -FIA 3 measuring the liberated uPAR(I). Tumors were classified as benign (n = 211), borderline (possibly malignant; n = 30), and well (n = 19), moderately (n = 15), and poorly (n = 60) differentiated malignant. RESULTS: All uPAR forms as well as CA125 were statistically significant in univariate analysis...... discriminating between benign, borderline, and invasive tumors. Restricting the analysis of invasive tumors to early stage (I and II) showed similar results. A combination of CA125 and suPAR(I-III) + suPAR(II-III) discriminated between malignant (all stages) and benign tumors [AUC, 0.94; 95% confidence interval.......011) in multivariate analyses including age and CA125. CONCLUSIONS: High concentration of plasma uPAR(I) is an independent preoperative marker of poor prognosis in patients with ovarian cancer. The combination of plasma suPAR(I-III) + suPAR(II-III) and CA125 discriminates between malignant and benign tumors...

  20. Low-pressure balloon angioplasty with adjuvant pharmacological therapy in patients with acute ischemic stroke caused by intracranial arterial occlusions

    International Nuclear Information System (INIS)

    Nogueira, Raul G.; Schwamm, Lee H.; Buonanno, Ferdinando S.; Koroshetz, Walter J.; Yoo, Albert J.; Rabinov, James D.; Pryor, Johnny C.; Hirsch, Joshua A.

    2008-01-01

    The use of coronary balloons in the cerebral vasculature is limited due to their poor trackability and increased risk of vessel injury. We report our experience using more compliant elastomer balloons for thrombus resistant to intraarterial (IA) pharmacological and mechanical thrombolysis in acute stroke. We retrospectively analyzed 12 consecutive patients with an occluded intracranial artery treated with angioplasty using a low-pressure elastomer balloon. Angiograms were graded according to the Thrombolysis in Cerebral Infarction (TICI) and Qureshi grading systems. Outcomes were categorized as independent (modified Rankin scale, mRS, score ≤2), dependent (mRS score 3-5), or dead (mRS score 6). Included in the study were 12 patients (mean age 66±17 years, range 31-88 years; mean baseline National Institutes of Health stroke scale score 17±3, range 12-23). The occlusion sites were: internal carotid artery (ICA) terminus (five patients, including two concomitant cervical ICA occlusions), M1 segment (two patients), and basilar artery (two patients). Pharmacological treatment included intravenous (IV) t-PA only (two patients), IA urokinase only (nine patients), both IV t-PA and IA urokinase (one patient), and IV and/or IA eptifibatide (eight patients). Mean time to treatment was 5.9±3.9 h (anterior circulation) and 11.0±7.2 h (posterior circulation). Overall recanalization rate (TICI grade 2/3) was 91.6%. Procedure-related morbidity occurred in one patient (distal posterior inferior cerebellar artery embolus). There were no symptomatic hemorrhages. Outcomes at 90 days were independent (five patients), dependent (three patients) and dead (four patients, all due to progression of stroke with withdrawal of care). Angioplasty of acutely occluded intracranial arteries with low-pressure elastomer balloons results in high recanalization rates with an acceptable degree of safety. Prior use of thrombolytics may increase the chances of recanalization, and glycoprotein IIb

  1. Expression of Oestrogen and progesterone receptors, Ki-67,p53 and ...

    African Journals Online (AJOL)

    Expression of Oestrogen and progesterone receptors, Ki-67,p53 and bcl-2 proteins, cathepsin D, urokinase plasminogen activator and urokinase plasminogen activator-receptors in carcinomas of the female breast in an African population.

  2. Percutaneous transluminal angioplasty of chronic arterial occlusive disease below the knee joint

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Woong; Kim, Jae Kyu; Park, Soo Min; Kim, Yun Hyeon; Kang, Heoung Keun [Chonnam Univ. Medical School, Kwangju (Korea, Republic of)

    1996-01-01

    The purpose of this study was to determine the safety and efficacy of the percutaneous transluminal angioplasty(PTA) in patients with chronic arterial occlusive disease below the knee joint. We retrospectively analyzed the results of 36 procedures in 16 patients. There were 15 men and one woman, aged 57-75 years(mean, 62 years). Indications were disabling claudication (SVS/ISCVS grade 1, category 3) in five cases, rest pain(grade 2, category 4) in three cases, and non-healing ulceration or gangrene(grade3, category 5) in eight cases. PTA was performed by using small vessel balloon catheter of 2-4 mm and 3 mm monorail balloon catheter in tibioperoneal vessels and 5-6 mm balloon catheter in distal popliteal artery and tibioperoneal trunk. Combined thrombolytic therapy with Urokinase was performed in 14 patients. Involved infrapopliteal vessels were four distal popliteal arteries, 15 tibioperoneal trunks, six anterior tibial arteries, five posterior tibial arteries, and seven peroneal arteries. Technical success was determined when post-PTA angiogram showed less than 30% of residual stenosis. Clinical success was defined as improvement of clinical symptoms, such as disappearance of claudication or rest pain, and healing of ulcereation. Technical success was achieved in 30 of 36 arteries(83%). Clinical success was achieved in 12 of 16 patients(75%) at an average follow-up of 13.3 months(range, 2-46 months). Clinical success rate was 100% in grade 1 category 3 patients, 67% in grade 2 category 4 patients, and 63% in grade 3 category 5 patients. Complication included two distal emboli, one vessel rupture, one vessel thrombosis, and one occluding intimal flap. PTA was an effective method for treatment of chronic arterial occlusive disease below the knee joint and considered as the procedure of first choice. Severe claudicant(grade1) should be included in the indication of the tibioperoneal PTA.

  3. Intra-arterial thrombolysis in acute embolic stroke

    International Nuclear Information System (INIS)

    Shi Mingchao; Fang Shaokuan; Li Dong; Zhu Hui; Pang Meng; Wu Jiang; Wang Shouchun

    2008-01-01

    Objective: To evaluate the efficacy and safety of intra-arterial thrombolysis in acute embolic stroke (AES). Methods: 21 patients with AES were undertaken urokinase or recombinated tissue plasminogen activator through percutaneous femoral intraarterial thrombolysis (IAT) as the treated group, and another 42 patients without thrombolytic treatment were assigned as the control group, which were matched to the baseline National Institutes of Health Stroke Scale (NIHSS) scores with selected gender and age. 24 h NIHSS scores, 90 d modified Rankin Scale (mRS) scores, incidences of hemorrhagic transformation (HT) and mortalities of the two groups were compared after the treatment. Results: (1) The results of cerebral angiography showed that the total re-perfusion rate was 61.90%. The middle cerebral artery (MCA), the internal carotid artery (ICA) and the basilar artery (BA) re-perfusion rates were 83.33%, 28.57% and 50.00%, respectively. (2) The NIHSS scores after 24 h were lower in the treated (IAT) group than those in the control group (12.05±5.61 vs, 14.83±4.05, P<0.05). A favorable outcome (mRS of 0-2) was more frequently observed in the 1AT group (66.67%) than that in the control group (35.71%, P<0.05). (3) There was no significant difference between the rates of HT (28.57% vs. 16.77%) and also the similar mortality rates (19.05% vs. 16.67%) not significant between the two groups. No patient died of HT in both two groups. Conclusion: IAT may be an effective treatment for AES with comparative safety. (authors)

  4. 76 FR 31616 - Government-Owned Inventions; Availability for Licensing

    Science.gov (United States)

    2011-06-01

    ... thrombolytic agent is encapsulated within temperature- sensitive liposomes. This composition is administered... endogenous heat that facilitates local thrombolytic drug release. The thermosensitive liposome can also be... be varied, depending on the specific composition of the liposome. Applications: Thrombolysis of blood...

  5. Comparative analysis of intramyocardial autotransplantation of postnatal stem cells from peripheral blood and adipose tissue in patients with acute phase of myocardial infarction, ST segment elevation, after effective thrombolytic reperfusion and coronary artery stenting

    NARCIS (Netherlands)

    Kharlamov, A. N.; Smolenskaya, O. G.; Gabinsky, Ya. L.; Bos, E. K.

    2007-01-01

    Aim. To compare various techniques of peripheral blood and adipose tissue stem cell (SC) transplantation and identify its optimal method for acute phase of myocardial infarction (MI). Material and methods. The study included 90 patients with acute MI. The participants were randomized into three

  6. Urokinase receptor-associated protein (uPARAP) is expressed in connection with malignant as well as benign lesions of the human breast and occurs in specific populations of stromal cells

    DEFF Research Database (Denmark)

    Schnack Nielsen, Boye; Rank, Fritz; Engelholm, Lars H

    2002-01-01

    PAR-associated protein (uPARAP), an internalization receptor that interacts with the pro-uPA:uPAR complex. In our study, we generated a specific polyclonal peptide antibody against human uPARAP and used it for the localization of uPARAP in different breast lesions. The affinity-purified antibodies specifically...... conclude that expression of uPARAP is associated with the abnormal breast and that expression appears in myofibroblasts, macrophages and myoepithelium. We suggest that uPARAP is involved in the clearance of the uPA:uPAR complex as well as other possible ligands during benign and malignant tissue remodeling....

  7. Urokinase receptor-associated protein (uPARAP) is expressed in connection with malignant as well as benign lesions of the human breast and occurs in specific populations of stromal cells

    DEFF Research Database (Denmark)

    Schnack Nielsen, Boye; Rank, Fritz; Engelholm, Lars H

    2002-01-01

    -associated mesenchymal cells. Double immunofluorescence analysis of invasive ductal carcinoma using antibodies against specific cell markers showed that uPARAP was localized in myofibroblasts and macrophages. No malignant cells, no endothelial cells and no vascular smooth muscle cells showed uPARAP immunoreactivity. We......PAR-associated protein (uPARAP), an internalization receptor that interacts with the pro-uPA:uPAR complex. In our study, we generated a specific polyclonal peptide antibody against human uPARAP and used it for the localization of uPARAP in different breast lesions. The affinity-purified antibodies specifically...... lesions. Whereas the normal breast tissue was uPARAP-negative, all benign lesions and ductal carcinoma in situ lesions showed immunoreactivity in fibroblast-like cells and myoepithelial cells associated with the lesion. In invasive carcinoma, uPARAP immunoreactivity was limited to tumor...

  8. The diagnostic value of soluble urokinase plasminogen activator receptor (suPAR) compared to C-reactive protein (CRP) and procalcitonin (PCT) in children with systemic inflammatory response syndrome (SIRS).

    Science.gov (United States)

    Şirinoğlu, Melis; Soysal, Ahmet; Karaaslan, Ayşe; Kepenekli Kadayifci, Eda; Yalındağ-Öztürk, Nilüfer; Cinel, İsmail; Yaman, Ali; Haklar, Goncagül; Şirikci, Önder; Turan, Serap; Altınkanat Gelmez, Gülşen; Söyletir, Güner; Bakır, Mustafa

    2017-01-01

    The aim of the present study was to determine the diagnostic and prognostic values of suPAR and to compare them to CRP and PCT in pediatric patients with systemic inflammatory response syndrome (SIRS). A prospective case-control study was performed.The study was performed in a tertiary university hospital which has a 649-bed capacity. Patients included 27 children with SIRS and 27 control subjects without any infection or immunosuppressive condition. Blood samples were obtained on the day of admission and on the 4-7th days of the hospital stay. The median (min-max) serum levels of suPAR obtained on the first day of the admission were 10.06 (2.7-57.46) and 2.22 (1.08-5.13) ng/Ml for the SIRS group and control group, respectively. The median serum levels of suPAR in the SIRS group was significantly higher than that in the control group (p SIRS group (p SIRS group, the area under the receiver operating characteristics curve (AUC ROC ) for suPAR revealed an optimum cut-off value, sensitivity, specificity, NPV and PPV of 0.978, 3.8 ng/mL, 96%, 96%, 96%, and 96%, respectively. We conclude that suPAR does have diagnostic value in children with SIRS. Additionally, persistent high serum suPAR level predicts mortality in SIRS in children. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  9. Use of plasma C-reactive protein, procalcitonin, neutrophils,macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Andersen, Ove; Kronborg, Gitte

    2007-01-01

    Introduction: Accurate and timely diagnosis of community acquired bacterial infections in patients with systemic inflammation remains challenging both for clinician and laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis and thereby survival. We therefore compared...... with standard measurements of C-reactive protein (CRP), procalcitonin (PCT), and neutrophils. Two composite markers were constructed – one including a linear combination of the three best performing markers and another including all six – and the area under the receiver operating characteristic curve (AUC...

  10. Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Andersen, Ove; Kronborg, Gitte

    2007-01-01

    Accurate and timely diagnosis of community-acquired bacterial infections in patients with systemic inflammation remains challenging both for clinician and laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis and thereby survival. We therefore compared the diagnostic...

  11. Mutant prourokinase with adjunctive C1-inhibitor is an effective and safer alternative to tPA in rat stroke.

    Directory of Open Access Journals (Sweden)

    Simone Tomasi

    Full Text Available A single-site mutant (M5 of native urokinase plasminogen activator (prouPA induces effective thrombolysis in dogs with venous or arterial thrombosis with a reduction in bleeding complications compared to tPA. This effect, related to inhibition of two-chain M5 (tcM5 by plasma C1-inhibitor (C1I, thereby preventing non-specific plasmin generation, was augmented by the addition of exogenous C1I to plasma in vitro. In the present study, tPA, M5 or placebo +/- C1I were administered in two rat stroke models. In Part-I, permanent MCA occlusion was used to evaluate intracranial hemorrhage (ICH by the thrombolytic regimens. In Part II, thromboembolic occlusion was used with thrombolysis administered 2 h later. Infarct and edema volumes, and ICH were determined at 24 h, and neuroscore pre (2 h and post (24 h treatment. In Part I, fatal ICH occurred in 57% of tPA and 75% of M5 rats. Adjunctive C1I reduced this to 25% and 17% respectively. Similarly, semiquantitation of ICH by neuropathological examination showed significantly less ICH in rats given adjunctive C1I compared with tPA or M5 alone. In Part-II, tPA, M5, and M5+C1I induced comparable ischemic volume reductions (>55% compared with the saline or C1I controls, indicating the three treatments had a similar fibrinolytic effect. ICH was seen in 40% of tPA and 50% of M5 rats, with 1 death in the latter. Only 17% of the M5+C1I rats showed ICH, and the bleeding score in this group was significantly less than that in either the tPA or M5 group. The M5+C1I group had the best Benefit Index, calculated by dividing percent brain salvaged by the ICH visual score in each group. In conclusion, adjunctive C1I inhibited bleeding by M5, induced significant neuroscore improvement and had the best Benefit Index. The C1I did not compromise fibrinolysis by M5 in contrast with tPA, consistent with previous in vitro findings.

  12. Cerebral blood flow changes in cluster headache

    International Nuclear Information System (INIS)

    Norris, J.W.; Hachinski, V.C.; Cooper, P.W.

    1976-01-01

    Serial cerebral blood flod studies performed by the intra-carotid 133 Xenon method were fortuitously determined during the course of a cluster headache in a 32 year old man. The initial study was performed about 10 min after the headache began and showed values at the upper limit of normal. Twenty min after the headache started a second procedure showed that the autoregulatory response on hyperventilation was normal. Ergotamine tartrate was given intra-muscularly 23 min after the headache began and there was partial relief. A third cerebral blood flow estimation showed abnormally high values. The probable reasons for this are discussed. (author)

  13. Trombolysebehandling af akut cerebralt infarkt

    DEFF Research Database (Denmark)

    Boysen, G; Vorstrup, S; Meden, Per

    2001-01-01

    Thrombolytic therapy of acute ischaemic stroke within three hours of the onset of symptoms is approved by health authorities in the USA and Canada, but not in Europe.......Thrombolytic therapy of acute ischaemic stroke within three hours of the onset of symptoms is approved by health authorities in the USA and Canada, but not in Europe....

  14. Reduction of infarct volume by thrombolysis with rt-PA in an embolic rat stroke model

    DEFF Research Database (Denmark)

    Overgaard, K.; Sereghy, T.; Boysen, G.

    1993-01-01

    Rat, thrombolytic therapy, recombinant tissue plasminogen activator, acute ischaemic stroke, cerebral infarction and embolism, experimental thromboembolism, in vitro thrombotic clotting, cerebral ......Rat, thrombolytic therapy, recombinant tissue plasminogen activator, acute ischaemic stroke, cerebral infarction and embolism, experimental thromboembolism, in vitro thrombotic clotting, cerebral ...

  15. Peculiaridades da terapia trombolítica na síndrome nefrótica pediátrica: monitorização do fator anti-Xa Particularities of thrombolytic therapy in pediatric nephrotic syndrome: anti-factor Xa monitoring

    Directory of Open Access Journals (Sweden)

    Patrícia Zambi Meirelles

    2008-06-01

    Full Text Available OBJETIVO: Descrever a importância do tromboembolismo pulmonar (TEP na síndrome nefrótica pediátrica e o uso da heparina de baixo peso molecular como opção terapêutica segura e eficaz. DESCRIÇÃO DO CASO: Menino de 5,7 anos com síndrome nefrótica córtico-resistente e glomérulo-esclerose segmentar e focal foi internado devido à diarréia, distúrbios eletrolíticos e anasarca. No 11º dia de internação, evoluiu com desconforto respiratório súbito, cuja investigação mostrou área de alta probabilidade de TEP na cintilografia pulmonar ventilação/perfusão e obstrução em veia jugular interna esquerda ao ultra-som doppler. Iniciado suporte ventilatório com nebulização de oxigênio e anticoagulação com enoxaparina (2mg/kg/dia. Após seis dias, evoluiu com sintomas neurológicos compatíveis com episódio isquêmico transitório, sem alteração na tomografia computadorizada de crânio. A monitorização do fator anti-Xa no soro demonstrou nível subterapêutico e a dose de enoxaparina foi ajustada para 3mg/kg/dia. O edema e os sintomas pulmonares melhoraram e o paciente recebeu alta hospitalar após 33 dias. COMENTÁRIOS: Embora o TEP seja raro em crianças, a síndrome nefrótica é uma condição pró-trombótica que favorece a complicação. A heparina de baixo peso molecular pode ser considerada no tratamento e na profilaxia secundária do TEP, sendo importante monitorizar o nível sérico do fator anti-Xa para ajustar sua dose e promover tratamento seguro e eficaz.OBJECTIVE: Report the importance of pulmonary thromboembolism (PTE in pediatric nephrotic syndrome and the use of low molecular weight heparin (LMWH as an effective and secure therapeutic option. CASE DESCRIPTION: A 5.7 year-old boy with steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis was admitted to the pediatric unit with diarrhea, electrolyte disturbances and anasarca. On the 11th day of hospital stay, he developed a sudden respiratory discomfort. Pulmonary ventilation/perfusion cintilography scan demonstrated high probability of PTE and the doppler ultrasonography showed obstruction of the left internal jugular vein. Oxygen support as well as enoxaparin, at a dose of 2mg/kg/day, were prescribed. Six days later, the patient developed transitory cerebrovascular symptoms without alterations in the cranial CT. The serum anti-Xa factor level was lower than the therapeutic range and enoxaparin was increased to 3mg/kg/day. The edema and the pulmonary symptoms improved and the boy was discharged at the 33rd day of stay. COMMENTS: Although PTE is rare in children, nephrotic syndrome is a prothrombotic condition amenable to this complication. LMWH can be considered for treatment and for secondary prophylaxis of PTE. Anti-factor Xa serum level monitoring is necessary to adjust LMWH dosage and to promote an effective and safe treatment.

  16. Neutralisation of uPA with a monoclonal antibody reduces plasmin formation and delays skin wound healing in tPA-deficient mice

    DEFF Research Database (Denmark)

    Jögi, Annika; Rønø, Birgitte; Lund, Ida K

    2010-01-01

    Proteolytic degradation by plasmin and metalloproteinases is essential for epidermal regeneration in skin wound healing. Plasminogen deficient mice have severely delayed wound closure as have mice simultaneously lacking the two plasminogen activators, urokinase-type plasminogen activator (u...

  17. Use of sodium hydroxide solution to clear partially occluded vascular access ports

    NARCIS (Netherlands)

    ter Borg, F.; Timmer, J.; de Kam, S. S.; Sauerwein, H. P.

    1993-01-01

    Gradual vascular access port or tunneled central venous catheter occlusion during total parenteral nutrition is a common complication of unknown etiology, usually unresponsive to treatment with urokinase, ethanol, or hydrochloric acid. After establishing safety with regard to catheter materials and

  18. CT-Detected Growth of Coronary Artery Calcification in Asymptomatic Middle-Aged Subjects and Association With 15 Biomarkers

    DEFF Research Database (Denmark)

    Diederichsen, Søren Zöga; Grønhøj, Mette Hjortdal; Mickley, Hans

    2017-01-01

    , vitamin D3, parathyroid hormone, osteoprotegerin), lipid metabolism (triglyceride, high- and low-density lipoprotein, total cholesterol), inflammation (C-reactive protein, soluble urokinase-type plasminogen activator receptor), kidney function (creatinine, cystatin C, urate), and myocardial necrosis...

  19. Inflammation in HIV-Infected Patients

    DEFF Research Database (Denmark)

    Langkilde, Anne; Petersen, Janne; Klausen, Henrik Hedegaard

    2012-01-01

    To examine mechanisms underlying the increased inflammatory state of HIV-infected patients, by investigating the association of HIV-related factors, demography, lifestyle, and body composition with the inflammatory marker soluble urokinase plasminogen activator receptor (suPAR)....

  20. Which criteria demand additive stenting during catheter-directed thrombolysis?

    DEFF Research Database (Denmark)

    Bækgaard, N; Just, S; Foegh, P

    2014-01-01

    Many factors are necessary for obtaining satisfactory results after catheter-directed thrombolysis (CDT) for iliofemoral deep venous thrombosis (DVT). Selections of patients, composition of the thrombolytic fluid, anticoagulation per- and post-procedural, recognition and treatment of persistent...

  1. Blood Clots

    Science.gov (United States)

    ... a doctor immediately. There have been many research advances that have improved the prevention and treatment of blood clots. Some current treatments include: Anticoagulants - medicine that prevents clots from forming Thrombolytics - medicine that ...

  2. Dabigatran for left ventricular thrombus

    Directory of Open Access Journals (Sweden)

    Satishkumar Kolekar

    2015-09-01

    Dabigatran is a reversible direct thrombin inhibitor and currently approved for the prevention of thromboembolic episodes in non-valvar atrial fibrillation. This case demonstrates possible thrombolytic properties of dabigatran in resolution of left ventricular thrombus.

  3. Synergism of Selective Tumor Vascular Thrombosis and Protease Activated Prodrug

    National Research Council Canada - National Science Library

    Liu, Cheng

    2008-01-01

    ... by administration of protease-activated prodrug. The activation of coagulation cascade and tumor vascular thrombosis as well as the following activation of the thrombolytic pathways led to explosive amplification of serine protease cascades...

  4. Pre-stroke use of statins on stroke outcome : a meta-analysis of observational studies

    NARCIS (Netherlands)

    Cordenier, Ann; De Smedt, Ann; Brouns, Raf; Uyttenboogaart, Maarten; De Raedt, Sylvie; Luijckx, Gert-Jan; De Keyser, Jacques

    2011-01-01

    Background: Animal pre-clinical studies suggest that statins may have neuroprotective effects in acute ischaemic stroke. Statins might also increase the risk of developing haemorrhagic transformation after thrombolytic treatment. Methods: We performed a systematic review and included studies that

  5. Intra-arterial thrombolysis of digital artery occlusions in a patient with polycythemia vera.

    Science.gov (United States)

    Jud, Philipp; Hafner, Franz; Gary, Thomas; Ghanim, Leyla; Lipp, Rainer; Brodmann, Marianne

    2017-01-01

    There are limited therapeutic options for the resolution of digital artery occlusions. Intra-arterial thrombolysis with anticoagulative and thrombolytic drugs successfully restored the blood flow in the affected digital arteries.

  6. Bilateral catheter-directed thrombolysis in a patient with deep venous thrombosis caused by a hypoplastic inferior vena cava

    NARCIS (Netherlands)

    Sloot, S.; Van Nierop, J.; Kootstra, J. J.; Wittens, C.; Fritschy, W. M.

    Introduction Deep venous thrombosis treatment using catheter-directed thrombolysis is advocated over systemic thrombolysis because it reduces bleeding complications. With the development of a catheter that combines ultrasound vibrations and the local delivering of thrombolytics, new and safer

  7. Popliteal artery thrombosis in a patient with Cogan syndrome: Treatment with thrombolysis and percutaneous transluminal angioplasty

    International Nuclear Information System (INIS)

    Bastug, Demir E.; Dominic, Anthony; Ortiz, Orlando; DiBartolomeo, Anthony G.; Kotzan, Jeffrey M.; Abraham, F. Matthew

    1997-01-01

    A 31-year-old woman with Cogan syndrome (a rare form of systemic vasculitis) was evaluated for a cold, painful left foot with diminished pulses. Arteriography demonstrated thrombosis of the left popliteal artery with evidence of vasculitis. Thrombolytic therapy was begun with initial success but eventual rethrombosis. After reinitiating thrombolytic therapy combined with intraarterial vasodilator therapy, successful angioplasty was performed with sustained results, at 6-month follow-up

  8. Soluble urokinase-type plasminogen activator receptor (suPAR – a possible biomarker for bacteremia in sepsis / Forma solubilă a receptorului pentru activatorul de plasminogen de tip urokinază (suPAR – un biomarker posibil pentru bacteriemie în sepsis

    Directory of Open Access Journals (Sweden)

    Georgescu Anca-Meda

    2015-03-01

    Full Text Available Introducere. Validarea unor noi biomarkeri în sepsis poate contribui la diagnosticul mai precoce al acestuia şi la iniţierea mai rapidă a terapiei. Scopul acestui studiu este acela de a evalua capacitatea formei solubile a rolului său în evaluarea prognosticului. Material şi metodă. Am realizat un studiu pilot, prospectiv pe 49 de pacienţi cu sindrom de răspuns inflamator sistemic (SIRS internaţi în Clinica de Terapie Intensivă, care au fost împărţiţi, în funcţie de existenţa bacteriemiei, în lotul A (SIRS cu bacteriemie, n=14 şi lotul B (SIRS fără bacteriemie, n=35. S-au recoltat în prima zi probe sanguine pentru determinarea suPAR, proteina C reactivă (CRP, procalcitonina (PCT şi hemocultura. Am urmărit identificarea unor valori de cut-off cu semnificaţie statistică în estimarea bacteriemiei şi a mortalităţii la pacienţii septici. Rezultate. În lotul A valorile suPAR au fost de 14,3 ng/mL (interval 10-45,5 ng/mL iar în lotul B, de 9,85 ng/mL (interval 3,4-48 ng/mL, p=0,008. Aria de sub curbă (AUC pentru suPAR a fost de 0,745 (95% CI: 0,600-0,859; pentru CRP, AUC a fost de 0,613 (95% CI: 0,522-0,799; pentru PCT, AUC a fost de 0,718 (95% CI: 0,477-0,769. Valoarea de cut-off a suPAR în predicţia bacteriemiei a fost de 9,885 ng/mL, cu sensibilitate de 100% şi specificitate de 51,43%. Mortalitatea în lotul A a fost de 85,7% (12/14, iar în lotul B de 74,3% (26/39, p>0,05. AUC pentru suPAR a fost de 0,750 (95% CI: 0,455-0,936; pentru CRP, AUC a fost de 0,613 (95% CI: 0,413-0,913; pentru PCT, AUC a fost de 0,618 (95% CI: 0,373-0,888. Valoarea de cut-off a suPAR în predicţia mortalităţii a fost de 11,5 ng/mL, cu sensibilitate de 66,67% şi specificitate de 100%.

  9. Regional cerebral blood flow in various types of brain tumor. Effect of the space-occupying lesion on blood flow in brain tissue close to and remote from tumor site

    DEFF Research Database (Denmark)

    Kuroda, K; Skyhøj Olsen, T; Lassen, N A

    1982-01-01

    Regional cerebral blood flow (rCBF) was measured in 23 patients with brain tumors using the 133Xe intra-carotid injection method and a 254 channel gamma camera. The glioblastomas (4) and astrocytomas (4) all showed hyperemia in the tumor and tumor-near region. This was also seen in several...... meningiomas (4 of 7 cases) in which most of the tumor itself did not receive any isotope. Brain metastases (6) usually had a low flow in the tumor and tumor-near region. The glioblastomas tended to show markedly bending 133Xe wash-out curves pointing to pronounced heterogeneity of blood flow. Most of the flow...... maps, regardless of the tumor types, showed widespread abnormalities of rCBF not only in the tumor region but also in the region remote from the tumor. It is concluded that measurement of rCBF cannot yield accurate differential diagnostic information, but that the widespread derangement of the brain...

  10. Blood flow and vascular reactivity in collaterally perfused brain tissue. Evidence of an ischemic penumbra in patients with acute stroke

    DEFF Research Database (Denmark)

    Olsen, T S; Larsen, B; Herning, M

    1983-01-01

    In a group of 48 patients with completed stroke, 8 patients had viable collaterally perfused brain tissue which was accessible for rCBF recordings with a two dimensional technique. All 8 had deep subcortical infarcts on CT-scan, and angiographic occlusion of the arteries normally supplying...... the infarcted territory. The brain tissue overlying the deep infarcts appeared normal on CT-scan and was supplied by collateral circulation. rCBF was measured in all within 72 hours after the stroke. The intra-carotid Xe-133 injection method and a 254 multidetector camera were used to study rCBF. Relatively...... ischemic low flow areas were a constant finding in the collaterally perfused tissue. In 6 of the patients, the collaterally perfused part of the brain had low flow values comparable to those of an "ischemic penumbra" (viable, but functionally depressed brain tissue due to inadequate perfusion...

  11. Medical Management of Pump-Related Thrombosis in Patients with Continuous-Flow Left Ventricular Assist Devices: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Dang, Geetanjali; Epperla, Narendranath; Muppidi, Vijayadershan; Sahr, Natasha; Pan, Amy; Simpson, Pippa; Baumann Kreuziger, Lisa

    Pump thrombosis is a dreaded complication of left ventricular assist devices (LVADs). We completed a systematic review to evaluate the efficacy and complications associated with medical management of LVAD thrombosis. Databases were searched using the terms "vad*" or "ventricular assist device" or "heart assist device" and "thrombus" or "thrombosis" or "thromboembolism." Of 2,383 manuscripts, 49 articles met the inclusion criteria. The risk of partial or no resolution of LVAD thrombosis did not significantly differ between thrombolytic and nonthrombolytic regimens (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.20-1.16). When response to therapy was evaluated based on pump type, there were no significant differences in how patients with a HeartMate II or HeartWare ventricular assist device responded to thrombolytic or nonthrombolytic treatment. Pooled risk of major bleeding in the thrombolytic group was 29% (95% CI, 0.17-0.44) and 12% (95% CI, 0.01-0.57) in the nonthrombolytic group. Odds of death did not differ between thrombolytic and nonthrombolytic regimens (OR, 1.28; 95% CI, 0.42-3.89). Although thrombolytic and nonthrombolytic treatment similarly resolved LVAD thrombosis, major hemorrhage may be increased with the use of thrombolysis. Randomized clinical trials comparing thrombolytic and nonthrombolytic treatment of LVAD thrombosis are needed to establish the most effective and safe option for patients who are not surgical candidates.

  12. Platelet microparticle-inspired clot-responsive nanomedicine for targeted fibrinolysis.

    Science.gov (United States)

    Pawlowski, Christa L; Li, Wei; Sun, Michael; Ravichandran, Kavya; Hickman, DaShawn; Kos, Clarissa; Kaur, Gurbani; Sen Gupta, Anirban

    2017-06-01

    Intravascular administration of plasminogen activators is a clinically important thrombolytic strategy to treat occlusive vascular conditions. A major issue with this strategy is the systemic off-target drug action, which affects hemostatic capabilities and causes substantial hemorrhagic risks. This issue can be potentially resolved by designing technologies that allow thrombus-targeted delivery and site-specific action of thrombolytic drugs. To this end, leveraging a liposomal platform, we have developed platelet microparticle (PMP)-inspired nanovesicles (PMINs), that can protect encapsulated thrombolytic drugs in circulation to prevent off-target uptake and action, anchor actively onto thrombus via PMP-relevant molecular mechanisms and allow drug release via thrombus-relevant enzymatic trigger. Specifically, the PMINs can anchor onto thrombus via heteromultivalent ligand-mediated binding to active platelet integrin GPIIb-IIIa and P-selectin, and release the thrombolytic payload due to vesicle destabilization triggered by clot-relevant enzyme phospholipase-A 2 . Here we report on the evaluation of clot-targeting efficacy, lipase-triggered drug release and resultant thrombolytic capability of the PMINs in vitro, and subsequently demonstrate that intravenous delivery of thrombolytic-loaded PMINs can render targeted fibrinolysis without affecting systemic hemostasis, in vivo, in a carotid artery thrombosis model in mice. Our studies establish significant promise of the PMIN technology for safe and site-targeted nanomedicine therapies in the vascular compartment. Copyright © 2017. Published by Elsevier Ltd.

  13. Local Intraarterial Thrombolysis: In Vitro Comparison Between Automatic and Manual Pulse-Spray Infusion

    International Nuclear Information System (INIS)

    Froelich, Jens J.; Freymann, Christina; Hoppe, Martin; Thiel, Thomas; Wagner, H. Joachim; Barth, Klemens H.; Klose, Klaus J.

    1996-01-01

    Purpose: Manual and automatic pulse-spray infusion techniques are compared in vitro to evaluate the efficacy of thrombolysis and the distribution of urokinase and saline solution within thrombus using a pulse-spray catheter. Methods: A pulse-spray catheter was introduced into a human thrombus within a stenotic flow model. Automatic and manual pulsed infusion of urokinase and automatic pulsed infusion of saline solution were compared. To quantify the efficacy of thrombolysis, pressure gradients were recorded proximal and distal to the thrombus and during the course of infusion. Distribution of infused urokinase was assessed radiographically. Results: The fastest and most homogeneous dissolution of the thrombus was achieved with automatic pulsed infusion of urokinase, shown by decreasing transthrombotic pressure gradients (p < 0.001, Wilcoxon, matched pairs). Manual pulsed infusion of urokinase or saline solution resulted in inhomogeneous thrombus dissolution and delayed thrombolysis. Conclusion: Application of automatic pulse-spray injectors seems beneficial for more effective and homogeneous intraarterial pulse-spray thrombolysis when compared with conventional manual pulsed technique

  14. Nursing care of indwelling catheter thrombolysis for acute thrombosis in the arteriovenous fistula in hemodialysis patients

    International Nuclear Information System (INIS)

    Gao Peizhu; Ding Wenbin; Ming Zhibing; Sun Juyun

    2010-01-01

    Objective: To summarize the experience of the nursing care of indwelling catheter thrombolysis for acute thrombosis in the arteriovenous fistula in eight hemodialysis patients. Methods: After breaking thrombus through indwelling catheter, both bolus injection and micro-pump continuous infusion of urokinase was employed in eight hemodialysis patients with acute thrombosis in the arteriovenous fistula. The necessary nursing measures were carried out to assist the whole therapeutic procedure. Results: All the patients could well cooperate with the procedure of indwelling catheter thrombolysis and urokinase infusion. The reopening rate of the obstructed fistula was 100%. Conclusion: Indwelling catheter thrombolysis with urokinase infusion is a simple, effective and safe treatment for acute thrombosis in the arteriovenous fistula in hemodialysis patients. In order to obtain optimal results, necessary nursing measures must be carried out. (authors)

  15. Local intra-arterial thrombolysis in acute ischemic stroke of the anterior circulation

    International Nuclear Information System (INIS)

    Zhang Yongwei; Liu Jianmin; Hong Bo; Deng Benqiang; Xu Yi; Ding Suju

    2003-01-01

    Objective: To evaluate the safety and efficacy of local intra-arterial thrombolysis (LIT) using urokinase in patients with acute ischemic stroke of the anterior circulation. Methods: Fifty-four patients were treated with LIT using urokinase. The locations of occlusion included 3 of internal carotid artery (ICA), 46 of middle cerebral artery (MCA) and 5 of anterior cerebral artery. Results: Outcome was good in 41 patients (75.9%). Recanalization >50% was obtained in 72.2% of patients and <50% recanalization in 27.8% of patients. Cerebral hemorrhage occurred in 11 patients (20.4%). Four patients died (7.4%). Conclusion: LIT using urokinase can improve the recanalization rate and achieve better functional recovery in patients of acute ischemic stroke

  16. Usefulness of radionuclide scintiphotography to evaluate preserved kidney viability

    International Nuclear Information System (INIS)

    Sato, Koshi; Yokota, Kazuhiko; Uchida, Hisanori

    1987-01-01

    GAMMA imaging of the renal cortical microcirculation is a safe and non-invasive method for assessment of kidney viability before transplantation. We used trifluoperazine (TFP), urokinase and verapamil from 24 to 120 hour kidney preservation in dogs. For these preserved kidneys, we used radionuuclide scintiphotography to evaluate kidney viability. After preservation, these kidneys were perfused with technitium -99m labeled microspheres, and imaging of the renal vasculature was obtained by scintigraphy. The distribution of the microspheres was assessed visually and by computer analysis. Modified Collins' solution perfused kidneys show very poor cortical uptake with marked increase in uptake in the hilar region after preservation. In contrast, cortical flow remained relatively well preserved in kidneys perfused and preserved by use of modified Collins' solotion with TFP, urokinase and urokinase + verapamil. There was a direct correlation between these results and the capacity of kidneys treated in the same fashion to sustain life after retransplantation into the original host. (author)

  17. Curative effect of minimally invasive puncture and drainage assisted with alteplase on treatment of acute intracerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    Jun-Lin Hu

    2017-01-01

    Full Text Available Objective: To investigate the different effects on evacuation of hematoma, the severity of nerve injury, inflammatory reaction and oxidative stress response in the treatment of acute intracerebral hemorrhage by using minimally invasive puncture and drainage assisted with alteplase or urokinase. Methods: A total of 114 patients with acute intracerebral hemorrhage treated with minimally invasive puncture and drainage in our hospital from May 2012 to October 2015 were retrospectively analyzed and divided into alteplase group and urokinase group, which received adjuvant therapy with alteplase and urokinase, respectively. Before and after treatment, CT was used for scanning, and the volume of hematoma and edema and the distance of midline shift were examined. After treatment, serum was collected for detecting the contents of molecular markers of nerve injury, inflammatory reaction and oxidative stress response. Results: On the 3rd day after treatment, the volume of hematoma and edema and the distance of midline shift in minimally invasive group were significantly lower than those of craniotomy group, and incidence of intracranial infection was lower than that of craniotomy group. There was no significant difference of rebleeding incidence compared to craniotomy group. The serum contents of osteopontin, S100β, glial fibrillary acidic protein, neuron-specific enolase, myelin basic protein, neuropeptide Y, ischemia modified albumin, tumor necrosis factor alpha, interleukin-1β, interleukin-6, interleukin-8, soluble intercellular adhesion molecule-1, highmobility group protein 1, malonaldehyde, advanced oxidation protein products and 8-hydroxy- 2'-deoxyguanosine urine of patients from alteplase group were significantly lower than those of urokinase group. The content of total antioxidant capacity was obviously higher than that of urokinase group. Conclusions: As for the effect on evacuation of hematoma and also the ameliorative effect on nerve injury

  18. Experimental thrombolysis of middle cerebral artery thromboemboli

    International Nuclear Information System (INIS)

    Hirschberg, M.; Wiesmann, W.; Korves, M.; Koc, I.; Hofferberth, B.; Muenster Univ.

    1988-01-01

    Since the majority of ischaemic cerebral infarcts is caused by thromboemboli, we determined the benefit of firbrinolytic therapy in acute stroke. Thromboemboli were induced in the middle cerebral artery of 21 dogs. Urokinase was started at different time intervals after infarction (1, 3 and 5 hours) at a rate of 1000 IU/kg/min. Angiographically controlled thrombolysis was achieved in all 15 treated cases, whereas in the control group (n=6) no case of recanalisation was observed. Systemic fibrinolysis occurred in all cases. Postmortem examinations of the brains showed no intracerebral haemorrhages. Our findings indicate the urokinase treatment may be of value in acute ischaemic stroke. (orig.) [de

  19. Crystal structures of the ligand-binding region of uPARAP

    DEFF Research Database (Denmark)

    Yuan, Cai; Jürgensen, Henrik J; Engelholm, Lars H

    2016-01-01

    The proteins of the mannose receptor (MR) family share a common domain organization and have a broad range of biological functions. Urokinase plasminogen activator receptor-associated protein (uPARAP) (or Endo180) is a member of this family and plays an important role in extracellular matrix...... remodelling through interaction with its ligands, including collagens and urokinase plasminogen activator receptor (uPAR). We report the crystal structures of the first four domains of uPARAP (also named the ligand-binding region, LBR) at pH 7.4 in Ca(2+)-bound and Ca(2+)-free forms. The first domain...

  20. Amiloride lowers blood pressure and attenuates urine plasminogen activation in patients with treatment-resistant hypertension

    DEFF Research Database (Denmark)

    Stolzenburg Oxlund, Christina; Buhl, Kristian Bergholt; Jacobsen, Ib A

    2014-01-01

    In conditions with albuminuria, plasminogen is aberrantly filtered across the glomerular barrier and activated along the tubular system to plasmin. In the collecting duct, plasmin activates epithelial sodium channels (ENaC) proteolytically. Hyperactivity of ENaC could link microalbuminuria....../proteinuria to resistant hypertension. Amiloride, an ENaC inhibitor, inhibits urokinase-type plasminogen activator. We hypothesized that amiloride (1) reduces blood pressure (BP); (2) attenuates plasminogen-to-plasmin activation; and (3) inhibits urine urokinase-type plasminogen activator in patients with resistant...

  1. PHARMACOEPIDEMIOLOGIC ANALYSIS OF ST-ELEVATION MYOCARDIAL INFARCTION REPERFUSION THERAPY AT SARATOV REGION HOSPITALS OF DIFFERENT TYPES

    Directory of Open Access Journals (Sweden)

    O. V. Reshetko

    2016-01-01

    Full Text Available Aim. To evaluate the real practice of thrombolytic therapy of patients with ST-elevation myocardial infarction (STEMI at cardiological departments of Saratov and Saratov region hospitals.Material and methods. Retrospective pharmacoepidemiologic study was carried out. Case histories of STEMI patients discharged from cardiologic departments of several central district hospitals (CDH of Saratov region, cardiologic department of one of Saratov general municipal hospitals (MH and urgent cardiology department of Saratov clinical hospital (CH in 2006 were analyzed.Results. In CH all patients received thrombolytic therapy given they did not have contraindications and were admitted to the hospital timely. Few patients received thrombolytic therapy in MH and CDH in 2006.Conclusion. Correlation between hospital type and quality of STEMI management has been revealed.

  2. Rescuing the ischemic penumbra: Our experience

    Directory of Open Access Journals (Sweden)

    Milosavljević Tamara

    2013-12-01

    Full Text Available Objectives: Over one million strokes per year are occurring in Europe. Brain stroke is one of the most important death and disability causes in Europe and USA. The main role of perfusion is to determine the border of insult core and ischemic penumbra. Penumbra can be saved with thrombolytic therapy but core have irreversible injuries and represent death of brain cells. Aim: to determine the role of CT brain perfusion in cases of acute brain stroke and following thrombolytic therapy. Methods: We examined 64 patients with acute brain stroke who received thrombolytic therapy after that. All patients were examining on 16 MDCT with 50 ml of iodine contrast agent following the standard procedure for CT perfusion. Patients were 34 male and 30 female with middle age of 64 years. MRI was made after thrombolytic therapy and compare with perfusion results before therapy. Results: Using an artery and a vein as reference three parameters were measured - blood flow (CBF, blood volume (CBV and mean transit time (MTT, for each patient. Hemorrhagic was find in 9 (14.01% patients after thrombolytic therapy. 4 (6.25% other patients develop new stroke of same but mostly other side of brain. 8 (12.50% more patients finished lethally. From other 42 patients with thrombolytic therapy we can positively say that in 31 (48.44% patients penumbra was rescued. For other 11 (17.19% stroke was same size like firstly involved core and penumbra but not bigger. Conclusion: CT perfusion plays major role by showing a curable parts of tissue in brain strokes.

  3. Salvage of critical limb ischemia with the "trellis reserve'' of subintimal superficial femoral-popliteal artery occlusion: a new modality in managing critical limb ischemia--a case report.

    LENUS (Irish Health Repository)

    Sultan, Sherif

    2005-01-01

    Subintimal angioplasty is a safe, effective, but nondurable procedure in treating long superficial femoral artery occlusions in patients with severe lower limb ischemia. The authors report a case of acute thrombosis that presented 16 weeks after subintimal angioplasty. The ;;Trellis\\'\\' percutaneous thrombolytic infusion system permitted a controlled site-specific infusion of recombinant tissue-type plasminogen activator (rtPA). The unique design of the ;;Trellis\\'\\' allowed complete aspiration of thrombus and avoiding regional and systemic thrombolytic side effects. The ;;Trellis\\'\\' system is effective in percutaneous management of thrombotic lesions; however, intimal dissection may need to be addressed.

  4. The contact-system dependent plasminogen activator from human plasma: Identification and characterization

    NARCIS (Netherlands)

    Binnema, D.J.; Dooijewaard, G.; Iersel, J.J.L. van; Turion, P.N.C.; Kluft, C.

    1990-01-01

    Apart from tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), a third PA appears to occur in human plasma. Its activity is initiated when appropriate triggers of the contact system are added, and the activation depends on the presence of factor XII and

  5. A phase 2, randomized, double-blind, placebo-controlled trial of clinical activity and safety of subcutaneous Å6 in women with asymptomatic CA125 progression after first-line chemotherapy of epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Ghamande, Sharad A.; Silverman, Michael H.; Huh, Warner

    2008-01-01

    OBJECTIVES: A6 is a novel peptide that interferes with single-chain urokinase plasminogen activator activity and has shown anti-angiogenic, anti-migratory, and anti-invasive properties. We evaluated clinical efficacy and safety of subcutaneously administered A6 in women with epithelial ovarian ca...

  6. Cancer therapy trials employing level-of-evidence-1 disease forecast cancer biomarkers uPA and its inhibitor PAI-1

    DEFF Research Database (Denmark)

    Schmitt, Manfred; Harbeck, Nadia; Brünner, Nils

    2011-01-01

    Clinical research on cancer biomarkers is essential in understanding recent discoveries in cancer biology and heterogeneity of the cancer disease. However, there are only a few examples of clinically useful studies that have identified cancer biomarkers with clinical benefit. Urokinase-type plasm...

  7. Tuberculosis case finding and mortality prediction

    DEFF Research Database (Denmark)

    Rudolf, F; Wagner, A-J; Back, F M

    2017-01-01

    SETTING: A suburban area of Bissau, the capital of Guinea-Bissau; the study was conducted among presumptive pulmonary tuberculosis (prePTB) patients seeking medical care for signs and symptoms suggestive of PTB. OBJECTIVE: To determine if a clinical TB score and a biomarker suPAR (soluble urokinase...

  8. First (18)F-labeled ligand for PET imaging of uPAR

    DEFF Research Database (Denmark)

    Persson, Morten; Liu, Hongguang; Madsen, Jacob

    2013-01-01

    Urokinase-type plasminogen activator receptor (uPAR) is overexpressed in human prostate cancer and uPAR has been found to be associated with metastatic disease and poor prognosis. AE105 is a small linear peptide with high binding affinity to uPAR. We synthesized an N-terminal NOTA-conjugated vers...

  9. suPAR associates to glucose metabolic aberration during glucose stimulation in HIV-infected patients on HAART

    DEFF Research Database (Denmark)

    Andersen, Ove; Eugen-Olsen, Jesper; Kofoed, Kristian

    2008-01-01

    OBJECTIVE: We have recently shown that the level of soluble urokinase plasminogen activator receptor (suPAR), which is associated with the immune status of HIV-infected patients undergoing highly active antiretroviral therapy (HAART), correlates with the insulin action of such patients. Here we e...

  10. Curative effect of minimally invasive puncture and drainage assisted with alteplase on treatment of acute intracerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    Jun-Lin Hu

    2017-01-01

    >Conclusions: As for the effect on evacuation of hematoma and also the ameliorative effect on nerve injury, inflammatory reaction and oxidative stress response in treatment of acute intracerebral hemorrhage, minimally invasive puncture and drainage assisted with alteplase was superior to adjuvant therapy with urokinase.

  11. suPAR

    DEFF Research Database (Denmark)

    Hodges, Gethin W; Bang, Casper N; Wachtell, Kristian

    2015-01-01

    The fundamental role of inflammation in cardiovascular disease (CVD) has prompted interest in numerous biomarkers that detect subclinical levels of inflammation. Soluble urokinase plasminogen activator receptor (suPAR) is a novel biomarker that correlates significantly with cardiovascular events...... comprehensive review of suPAR in CVD and explore its function and usefulness in predicting cardiovascular events....

  12. suPAR: the molecular crystal ball

    DEFF Research Database (Denmark)

    Thunø, Maria; Macho, Betina; Eugen-Olsen, Jesper

    2009-01-01

    soluble urokinase Plasminogen Activator Receptor (suPAR) levels reflect inflammation and elevated suPAR levels are found in several infectious diseases and cancer. suPAR exists in three forms; suPAR(I-III), suPAR(II-III) and suPAR(I) which show different properties due to structural differences. ...

  13. Effect of changes in liver blood flow on the pharmacokinetics of saruplase in patients with acute myocardial infarction

    NARCIS (Netherlands)

    van Griensven, J. M.; Koster, R. W.; Hopkins, G. R.; Beier, H.; Günzler, W. A.; Kroon, R.; Schoemaker, R. C.; Cohen, A. F.

    1997-01-01

    BACKGROUND: The recombinant unglycosylated single chain urokinase-type plasminogen activator saruplase is cleared for a large part by the liver. A large interindividual variation in saruplase concentration is found in acute myocardial infarction (AMI) patients. The variable cardiac performance after

  14. Bone matrix degradation by the plasminogen activation system; possible mechanism of bone destruction in arthritis

    NARCIS (Netherlands)

    Ronday, H.K.

    1997-01-01

    The observed increase in urokinase-type plasminogen activator (u-PA) and its receptor (u-PAR) in synovial tissue of patients with rheumatoid arthritis (RA) suggests pathophysiological involvement of the plasminogen activation PA system in inflammatory joint disease. In the present study we

  15. Serum suPAR in patients with FSGS: trash or treasure?

    NARCIS (Netherlands)

    Maas, R.J.H.; Deegens, J.K.J.; Wetzels, J.F.M.

    2013-01-01

    The urokinase-type plasminogen activator receptor (uPAR) has important functions in cell migration. uPAR can be shed from the cell membrane resulting in soluble uPAR (suPAR). Further cleavage gives rise to shorter fragments with largely unknown functions. Recent studies have demonstrated that both

  16. Author Details - African Journals Online

    African Journals Online (AJOL)

    Agrawala, D. Vol 10, No 8 (2011) - Articles Isolation, production, purification, assay and characterization of fibrinolytic enzymes (Nattokinase, Streptokinase and Urokinase) from bacterial sources. Abstract PDF. ISSN: 1684-5315. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians ...

  17. Serine protease inhibitor Serp-1 strongly impairs atherosclerotic lesion formation and induces a stable plaque phenotype in ApoE-/-mice

    NARCIS (Netherlands)

    Bot, Ilze; von der Thüsen, Jan H.; Donners, Marjo M. P. C.; Lucas, Alexandra; Fekkes, Madelon L.; de Jager, Saskia C. A.; Kuiper, Johan; Daemen, Mat J. A. P.; van Berkel, Theo J. C.; Heeneman, Sylvia; Biessen, Erik A. L.

    2003-01-01

    The myxoma virus protein Serp-1 is a member of the serine protease inhibitor superfamily. Serp-1 potently inhibits human serum proteases including plasmin, urokinase-type plasminogen activator (uPA), and tissue-type plasminogen activator (tPA). Serp-1 also displays a high antiinflammatory activity,

  18. Structure-driven design of radionuclide tracers for non-invasive imaging of uPAR and targeted radiotherapy. The tale of a synthetic peptide antagonist

    DEFF Research Database (Denmark)

    Ploug, Michael

    2013-01-01

    Research performed during the last two decades has provided a wealth of information to highlight the role of the urokinase-type plasminogen activator receptor (uPAR) in the progression and dissemination of invasive and metastatic cancer. In parallel, our perception of the structure-function relat...

  19. Local intra-arterial thrombolysis in a 4-year-old male with vertebrobasilar artery thrombosis

    NARCIS (Netherlands)

    Janmaat, Mirjam; Gravendeel, Joost P; Uyttenboogaart, Maarten; Vroomen, Patrick C; Brouwer, Oebele F; Luijckx, Gert-Jan

    We report the case of a 4-year-old male with vertebrobasilar artery thrombosis for which he was treated with local intra-arterial urokinase 60 hours after onset of symptoms. Initially the patient had dysarthria and dysphagia. Brain magnetic resonance imaging (MRI) in a community hospital showed

  20. Low plasminogen activator inhibitor-1 levels in thyroid carcinoma: uPA/PAI-1 paradox in cancer proggression

    Directory of Open Access Journals (Sweden)

    Bekir Ucan

    2017-06-01

    Conclusions: Serum PAI-1 levels were lower in patients with papillary thyroid carcinoma. Our results might support the thesis of PAI-1 is expected to suppress cancer progression due to its ability to inhibit urokinase plasminogen activator activity. [J Contemp Med 2017; 7(2.000: 121-125