Objective:Discussion and analysis of the effect of the early application of Tirofiban on acute ischemic stroke(AIS)after intravenous thrombolysis with urokinase.Method:The subjects of this study are 40 patients with A...Objective:Discussion and analysis of the effect of the early application of Tirofiban on acute ischemic stroke(AIS)after intravenous thrombolysis with urokinase.Method:The subjects of this study are 40 patients with AIS admitted at the Yibin Fourth People’s Hospital,of which were computer-randomized into a control group(20 cases,with regular urokinase intravenous thrombolysis therapy)and a research group(20 cases,combined with early Tirofiban treatment)from January 2018 to December 2022.The intervention outcomes between these two groups were compared and analyzed.Result:The blood platelet-related parameters before treatment had no statistical difference between the two groups(P>0.05),but the research group was higher than that of the control group after treatment(P<0.05).The Barthel index before treatment in both groups had no statistical difference(P>0.05),but the research group was higher than that of the control group after treatment(P<0.05).Conclusion:Early Tirofiban treatment for patients with AIS after intravenous thrombolysis with urokinase could effectively regulate the blood platelet-related parameters,hence improving treatment benefits and living capacity for patients,with definite clinical benefits.展开更多
AIM: To evaluate the therapeutic effects of bone marrow-derived mesenchymal stem cells(BMSCs) with human urokinase-type plasminogen activator(u PA) on liver fibrosis, and to investigate the mechanism of gene therapy.M...AIM: To evaluate the therapeutic effects of bone marrow-derived mesenchymal stem cells(BMSCs) with human urokinase-type plasminogen activator(u PA) on liver fibrosis, and to investigate the mechanism of gene therapy.METHODS: BMSCs transfected with adenovirusmediated human urokinase plasminogen activator(Adu PA) were transplanted into rats with CCl4-induced liver fibrosis. All rats were sacrificed after 8 wk, and their serum and liver tissue were collected for biochemical, histopathologic, and molecular analyzes. The degree of liver fibrosis was assessed by hematoxylin and eosin or Masson's staining. Western blot and quantitative reverse transcription-polymerase chain reaction were used to determine protein and m RNA expression levels.RESULTS: Serum levels of alanine aminotransferase, aminotransferase, total bilirubin, hyaluronic acid, laminin, and procollagen type Ⅲ were markedly decreased, whereas the levels of serum albumin were increased by u PA gene modified BMSCs treatment. Histopathology revealed that chronic CCl4-treatment resulted in significant fibrosis while u PA gene modified BMSCs treatment significantly reversed fibrosis. By quantitatively analysing the fibrosis area of liver tissue using Masson staining in different groups of animals, we found that model animals with CCl4-induced liver fibrosis had the largest fibrotic area(16.69% ± 1.30%), while fibrotic area was significantly decreased by BMSCs treatment(12.38% ± 2.27%) and was further reduced by u PA-BMSCs treatment(8.31% ± 1.21%). Both protein and m RNA expression of β-catenin, Wnt4 and Wnt5 a was down-regulated in liver tissues following u PA gene modified BMSCs treatment when compared with the model animals.CONCLUSION: Transplantation of u PA gene modified BMSCs suppressed liver fibrosis and ameliorated liver function and may be a new approach to treating liver fibrosis. Furthermore, treatment with u PA gene modified BMSCs also resulted in a decrease in expression of molecules of the Wnt signaling pathway.展开更多
AIM 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.METHODS From J...AIM 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.METHODS 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 therapyand TIPS, respectively. The total follow-up time was24 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.RESULTS 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 < 0.001), and there was no significant difference between them(P= 0.304). In the SMA group, superior 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).CONCLUSION Transcatheter selective SMA urokinase infusion and TIPS are safe and effective for acute symptomatic PVT in cirrhosis.展开更多
The last two decades have witnessed a rapid decrease in mortality due to acute cerebral ischemia that paradoxically has led to a rapid increase in the number of patients that survive an acute ischemic stroke with vari...The last two decades have witnessed a rapid decrease in mortality due to acute cerebral ischemia that paradoxically has led to a rapid increase in the number of patients that survive an acute ischemic stroke with various degrees of disability.Unfortunately,the lack of an effective therapeutic strategy to promote neurological recovery among stroke survivors has led to a rapidly growing population of disabled patients.Thus,understanding the mechanisms of neurorepair in the ischemic brain is a priority with wide scientific,social and economic implications.Cerebral ischemia has a harmful effect on synaptic structure associated with the development of functional impairment.In agreement with these observations,experimental evidence indicates that synaptic repair underlies the recovery of neurological function following an ischemic stroke.Furthermore,it has become evident that synaptic plasticity is crucial not only during development and learning,but also for synaptic repair after an ischemic insult.The plasminogen activating system is assembled by a cascade of enzymes and their inhibitors initially thought to be solely involved in the generation of plasmin.However,recent work has shown that in the brain this system has an important function regulating the development of synaptic plasticity via mechanisms that not always require plasmin generation.Urokinase-type plasminogen activator(uPA)is a serine proteinase and one of the plasminogen activators,that upon binding to its receptor(uPAR)not only catalyzes the conversion of plasminogen into plasmin on the cell surface,but also activates cell signaling pathways that promote cell migration,proliferation and survival.The role of uPA is the brain is not fully understood.However,it has been reported while uPA and uPAR are abundantly found in the developing central nervous system,in the mature brain their expression is restricted to a limited group of cells.Remarkably,following an ischemic injury to the mature brain the expression of uPA and uPAR increases to levels comparable to those observed during development.More specifically,neurons release uPA during the recovery phase from an ischemic injury,and astrocytes,axonal boutons and dendritic spines recruit uPAR to their plasma membrane.Here we will review recent evidence indicating that binding of uPA to uPAR promotes the repair of synapses damaged by an ischemic injury,with the resultant recovery of neurological function.Furthermore,we will discuss data indicating that treatment with recombinant uPA is a potential therapeutic strategy to promote neurological recovery among ischemic stroke survivors.展开更多
Partition coefficients of Urokinase(UK)were measured in aqueous two-phase systems con-taining polyethylene glycol and potassium phosphate at 273.2K.Based on the Diamond-Hsu model,a modified expression was obtained for...Partition coefficients of Urokinase(UK)were measured in aqueous two-phase systems con-taining polyethylene glycol and potassium phosphate at 273.2K.Based on the Diamond-Hsu model,a modified expression was obtained for the correlation of enzyme partitioning in theabove-mentioned systems.Utilizing a modified form,the partitioning data of UK and heteroproteinwere correlated.The results show that the modified model is simple gives good precision.and will fa-cilitate engineering scale-up of aqueous two-phase systems for certain proteins purification.展开更多
To clarify the role of urokinase plasminogen activator(uPA) in the mechanisms of regulating sperm motility and the ability of fertilizing, we investigated the quantities and activities of uPA in human seminal Plasma a...To clarify the role of urokinase plasminogen activator(uPA) in the mechanisms of regulating sperm motility and the ability of fertilizing, we investigated the quantities and activities of uPA in human seminal Plasma and on the membrane of spermatozoa.Semens were harvested from 22 infertile patients with asthenospermia and 20 healthy fertile men according to WHO standards. To quantify the membrane-bound uPA in the samples, polyclonal antibodies against human urokinase were employed by means of a sandwich ELISA. The uPA activities in seminal plasma and on the surface of spermatozoa were determined using Agarose-Fibrine-Plate method and the experiment of immunological identification with polyclonal antibodies against urokinase. In lysates of spermatozoa, significantly lower levels of uPA(23. 1±7.35 mu/106 cells ) and uPA activity (5.13±3.85 mu/106 cells) were found in patient group as compared to healthy fertile men exhibiting normospermia (29. 89±9. 40 mu/105 cells and 10. 17±6. 18 mu/106 cells). In seminal plasma, uPA activity in patient group (2134±1581. 3 IU/L)was also found significantly lower than that of normal group (3365±1859. 5 IU/L). Positive correlations were observed between sperm motility and uPA quantities (r=0. 48, P＜0. 005), as well as with uPA activities (r= 0. 45,P＜0. 005).Thus, it is inferred that membrane associated uPA on human spermatozoa may be related directly to sperm motility and fertility.展开更多
1 INTRODUCTIONIn literature,most matrices of affinity chromatography for urokinase(EC 3.4.99.26)purification were prepared by cyanogen bromide activation.However,theseadsorbents usually suffered from the drawback of l...1 INTRODUCTIONIn literature,most matrices of affinity chromatography for urokinase(EC 3.4.99.26)purification were prepared by cyanogen bromide activation.However,theseadsorbents usually suffered from the drawback of leakage of the ligand,particularly inalkaline medium,because of the instability of the isourea linkage between the ligandand the spacer or agarose.Moreover,the positively charged imido group of theN-substituted isourea derivative and the hydrophobicity of the spacers might promotenonspecific adsorption.On the contrary,the adsorbents prepared by the method展开更多
BACKGROUND Suprachoroidal hemorrhage(SCH) is a rare but potentially catastrophic ocular event. Surgery for SCH is often challenging because of the difficulty in resolving the retinal and choroidal detachment. Here, we...BACKGROUND Suprachoroidal hemorrhage(SCH) is a rare but potentially catastrophic ocular event. Surgery for SCH is often challenging because of the difficulty in resolving the retinal and choroidal detachment. Here, we describe a novel surgical technique in which urokinase is administered by sub-Tenon's injection to target an organized clot in SCH prior to drainage.CASE SUMMARY A consecutive case series of four eyes with serous and hemorrhagic choroidal detachments secondary to cataract surgery or trauma was documented to evaluate the feasibility of using a sub-Tenon's urokinase injection-assisted 23-gauge and 20-gauge incision to drain choroidal detachments. Urokinase(2000 IU) was given by sub-Tenon's injection one day before surgery for clot liquefaction. A 23-gauge infusion line was placed in the anterior chamber. A 20-gauge incision was created in the suprachoroidal space 3.5 mm from the limbus. After drainage, pars plana vitrectomy was performed because of concomitant pathology that demanded this additional procedure. Visual acuity, ocular findings, the timing of surgical interventions, surgical procedures, and outcomes were retrospectively reviewed in four patients. Postoperative follow-up of the patients ranged from 6 to 24 mo(mean, 13 mo). After the treatment, all patients achieved excellent anatomical recovery. CONCLUSION Sub-Tenon's urokinase injection-assisted vitrectomy makes clot liquefaction happen in the early treatment stage, resulting in marked stability during the procedure.展开更多
Purpose:To evaluate the clinical efficacyof thrombolysis injecting urokinase inperipheral artery for treatment of arterialocclusion.Materials and methods:12 patientswere treated with injecting urokinase inartery.Resul...Purpose:To evaluate the clinical efficacyof thrombolysis injecting urokinase inperipheral artery for treatment of arterialocclusion.Materials and methods:12 patientswere treated with injecting urokinase inartery.Results:The mean dose of urokinase was500000U,the mean time of thrombolysis was200 minutes.The rate of clinic efficacy was83%.Conclusion:The indication of urokinasethrombolysis in artery is for those patientswith arterial occlusion in whom catheteriza-tion is feasible and clinical course is inone month.This operation is simple and conv-enient,it does not require special equipment.The method can be used safely and effectivelyin patients with arterial occlusion.展开更多
To study the influence of irbesartan combined with low dose urokinase on treatment effect and serologic indexes in elderly isolated systolic hypertension patients. Methods: One hundred and ten cases of elderly isolate...To study the influence of irbesartan combined with low dose urokinase on treatment effect and serologic indexes in elderly isolated systolic hypertension patients. Methods: One hundred and ten cases of elderly isolated systolic hypertension patients in our hospital during January 2013–January 2016 were randomly divided into observation group with 55 cases and control group with 55 cases. Patients in observation group received irbesartan combined with low dose hydrochlorothiazide treatment and those in control group received amlodipine combined with low dose hydrochlorothiazide treatment, each lasted for 4 weeks. After 4 weeks treatment, non-invasive blood pressure and blood pressure variability indexes were measured, serum endothelial function, inflammatory factors and oxidative stress indexes were measured. Results: After 4 weeks treatment, patients systolic blood pressure (SBP), 24 h mean systolic blood pressure (24 h SBP), 24 h systolic blood pressure standard deviation (24 h SSD) were significantly lower in observation group than in control group (P<0.05);serum endothelial function index EF-1 was lower in observation group than in control group, while NO and endothelial nitric oxide synthase (eNOS) were higher in observation group than in control group (P<0.05);serum high sensitivity C-reactive protein (hs-CRP), interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α (TNF-α) contents were lower in observation group than in control group (P<0.05);serum oxidation index such as malondialdehyde (MDA) was lower in observation group than in control group, while antioxidant indexes such as total anti-oxidative capacity (TAC), superoxide dismutase (SOD), GSH were higher in observation group than in control group (P<0.05). Conclusions: Irbesartan combined with low dose hydrochlorothiazide can effectively reduce systolic hypertension and blood pressure variability in elderly isolated systolic hypertension patients, while optimizing the systemic inflammation and oxidative stress status.展开更多
Objective:To observe the clinical efficacy of urokinase in combined with minimally invasive hematoma puncture with YL-1 type needle in the treatment of hypertensive cerebral hemorrhage and the effect on blood sugar an...Objective:To observe the clinical efficacy of urokinase in combined with minimally invasive hematoma puncture with YL-1 type needle in the treatment of hypertensive cerebral hemorrhage and the effect on blood sugar and serum CRP.Methods:A total of 84 patients with hypertensive cerebral hemorrhage who were admitted in our hospital were included in the study and divided into the minimally invasive group (n=53) and the conservative group (n=31) according to different treatment protocols. The patients in the two groups were given routine drug treatments. The patients in the observation group were given urokinase in combined with minimally invasive hematoma puncture with YL-1 type needle. The blood sugar and serum CRP levels before and after treatment in the two groups were compared. CT was performed to reexamine the cerebral hematoma and edema volume.Results: The serum CRP and blood sugar levels 3, 7 and 14 d after treatment in the minimally invasive group were significantly lower than those in the conservative group (P<0.05). The cerebral hematoma and edema volume 1, 3, 7, and 14 d after treatment in the minimally invasive group was significantly lower than that in the conservative group (P<0.05).Conclusions: Urokinase in combined with minimally invasive hematoma puncture with YL-1 type needle in the treatment of hypertensive cerebral hemorrhage can significantly alleviate the brain tissue injury, reduce the systemic inflammatory reaction and blood sugar level, and contribute to the rehabilitation.展开更多
Objective To analyse the efficacy and safety of elderly patients with acute ischemic stroke who underwent intravenous thrombolysis with alteplase(recombinant tissue plasminogen activator,r-tPA)and urokinase(UK)within ...Objective To analyse the efficacy and safety of elderly patients with acute ischemic stroke who underwent intravenous thrombolysis with alteplase(recombinant tissue plasminogen activator,r-tPA)and urokinase(UK)within 4.5 h of onset.Methods Based on the intravenous thrombolysis registry for Chinese ischemic stroke within 4.5 h of onset(INTRECIS)cohort.展开更多
In view of the similarity of the charge distribution between fibrin A_α148--161 and Achain 149--157 of urokinase,the latter might compete with fibrin A_α148--161 when singlechain pro-urokinase is converted to double...In view of the similarity of the charge distribution between fibrin A_α148--161 and Achain 149--157 of urokinase,the latter might compete with fibrin A_α148--161 when singlechain pro-urokinase is converted to double chain urokinase.To test this, the stretch of uro-kinase A chain 135--157 was separated from the low molecular weight urokinase, a competi-tive binding between this stretch and fibrin to tPA kringle-2 was shown by radio-bindingassay. The inhibition of the stretch on the fibrin stimulated activation of plasminogen wasdemonstrated in the caseinolytic system. The synthesized novapeptide urokinase A chain 149--157 (R-peptide) showed a significant inhibition on the activation of plasminogen in the pres-ence of fibrin. By contrasting finely with R-peptide, a synthesized novapeptide in which Arg154and Arg156 were replaced by Asp (D-peptide) did not show any inhibition effect on the fi-brin stimulated activation of plasminogen by tPA. These results suggest that the positivelycharged residues in展开更多
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 dia...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.展开更多
The Kringle-1 structure of plasminogen (PGK-1), the Kringle-2 structure of tissue plasminogen activator (PAK-2) and the Kringle structure of prourokinase (UKK) has been modeled on the basis of the three-dimensional st...The Kringle-1 structure of plasminogen (PGK-1), the Kringle-2 structure of tissue plasminogen activator (PAK-2) and the Kringle structure of prourokinase (UKK) has been modeled on the basis of the three-dimensional structure of Kringle-1 of prothrombin (PTK-1) at 2.8 resolution. The predicted three-dimensional structure of these Kringles shows that the binding site of PGK-1 is characterized by an apparent dipolar site, the polar parts of which are separated by a hydrophobic region. PAK-2 possesses the anionic center but has not a cationic binding center which might be provided by a guanidinium group from Arg-69 located adjacent to the Arg-71 position. UKK possesses neither the anionic binding center nor the cationic center which are probably the main reason for the poor fibrin specificity of urokinase.展开更多
Pro-urokinase is a kind of protease existing in human body. It has the character of fibrinolysis, so it has been clinically applied to the treatment of thrombolytic diseases. In order to produce a large amount of pro-...Pro-urokinase is a kind of protease existing in human body. It has the character of fibrinolysis, so it has been clinically applied to the treatment of thrombolytic diseases. In order to produce a large amount of pro-urokinase by genetic engineering method and reform it with protein engineering, we have chemically synthesized the pro-urokinase gene, which展开更多
The B-chain of urokinase (UK) was covalently linked by disulfide bond to the Fab fragment of an anti-human activated platelet monoclonal antibody(SZ-51). The UKSZ-51 conjugate retained the original binding specificity...The B-chain of urokinase (UK) was covalently linked by disulfide bond to the Fab fragment of an anti-human activated platelet monoclonal antibody(SZ-51). The UKSZ-51 conjugate retained the original binding specificity of its parent antibody, and produced about a 5-fold enhancement in clot lysis in plasma over that of the urokinase in vitro. Whereas UK significantly decreased the concentration of fibrinogen in plasma clot assay supernatants, UK-SZ-51 did not.展开更多
文摘Objective:Discussion and analysis of the effect of the early application of Tirofiban on acute ischemic stroke(AIS)after intravenous thrombolysis with urokinase.Method:The subjects of this study are 40 patients with AIS admitted at the Yibin Fourth People’s Hospital,of which were computer-randomized into a control group(20 cases,with regular urokinase intravenous thrombolysis therapy)and a research group(20 cases,combined with early Tirofiban treatment)from January 2018 to December 2022.The intervention outcomes between these two groups were compared and analyzed.Result:The blood platelet-related parameters before treatment had no statistical difference between the two groups(P>0.05),but the research group was higher than that of the control group after treatment(P<0.05).The Barthel index before treatment in both groups had no statistical difference(P>0.05),but the research group was higher than that of the control group after treatment(P<0.05).Conclusion:Early Tirofiban treatment for patients with AIS after intravenous thrombolysis with urokinase could effectively regulate the blood platelet-related parameters,hence improving treatment benefits and living capacity for patients,with definite clinical benefits.
基金Supported by National Natural Science Foundation of ChinaNo.81460114+5 种基金Natural Science Foundation of Guangxi Zhuang Autonomous RegionNo.1355005-3-2 and No.2012GXNSFAA053143Chinese Traditional Medicine Science Foundation of Guangxi Zhuang Autonomous RegionNo.GZPT1238Science Foundation of Guangxi Department of EducationNo.201203YB036 and No.2013LX031
文摘AIM: To evaluate the therapeutic effects of bone marrow-derived mesenchymal stem cells(BMSCs) with human urokinase-type plasminogen activator(u PA) on liver fibrosis, and to investigate the mechanism of gene therapy.METHODS: BMSCs transfected with adenovirusmediated human urokinase plasminogen activator(Adu PA) were transplanted into rats with CCl4-induced liver fibrosis. All rats were sacrificed after 8 wk, and their serum and liver tissue were collected for biochemical, histopathologic, and molecular analyzes. The degree of liver fibrosis was assessed by hematoxylin and eosin or Masson's staining. Western blot and quantitative reverse transcription-polymerase chain reaction were used to determine protein and m RNA expression levels.RESULTS: Serum levels of alanine aminotransferase, aminotransferase, total bilirubin, hyaluronic acid, laminin, and procollagen type Ⅲ were markedly decreased, whereas the levels of serum albumin were increased by u PA gene modified BMSCs treatment. Histopathology revealed that chronic CCl4-treatment resulted in significant fibrosis while u PA gene modified BMSCs treatment significantly reversed fibrosis. By quantitatively analysing the fibrosis area of liver tissue using Masson staining in different groups of animals, we found that model animals with CCl4-induced liver fibrosis had the largest fibrotic area(16.69% ± 1.30%), while fibrotic area was significantly decreased by BMSCs treatment(12.38% ± 2.27%) and was further reduced by u PA-BMSCs treatment(8.31% ± 1.21%). Both protein and m RNA expression of β-catenin, Wnt4 and Wnt5 a was down-regulated in liver tissues following u PA gene modified BMSCs treatment when compared with the model animals.CONCLUSION: Transplantation of u PA gene modified BMSCs suppressed liver fibrosis and ameliorated liver function and may be a new approach to treating liver fibrosis. Furthermore, treatment with u PA gene modified BMSCs also resulted in a decrease in expression of molecules of the Wnt signaling pathway.
基金Supported by the National Natural Science Foundation of China,No.81572888
文摘AIM 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.METHODS 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 therapyand TIPS, respectively. The total follow-up time was24 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.RESULTS 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 < 0.001), and there was no significant difference between them(P= 0.304). In the SMA group, superior 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).CONCLUSION Transcatheter selective SMA urokinase infusion and TIPS are safe and effective for acute symptomatic PVT in cirrhosis.
基金supported in part by National Institutes of Health Grant NS-091201(to MY)VA MERIT Award IO1BX003441(to MY)
文摘The last two decades have witnessed a rapid decrease in mortality due to acute cerebral ischemia that paradoxically has led to a rapid increase in the number of patients that survive an acute ischemic stroke with various degrees of disability.Unfortunately,the lack of an effective therapeutic strategy to promote neurological recovery among stroke survivors has led to a rapidly growing population of disabled patients.Thus,understanding the mechanisms of neurorepair in the ischemic brain is a priority with wide scientific,social and economic implications.Cerebral ischemia has a harmful effect on synaptic structure associated with the development of functional impairment.In agreement with these observations,experimental evidence indicates that synaptic repair underlies the recovery of neurological function following an ischemic stroke.Furthermore,it has become evident that synaptic plasticity is crucial not only during development and learning,but also for synaptic repair after an ischemic insult.The plasminogen activating system is assembled by a cascade of enzymes and their inhibitors initially thought to be solely involved in the generation of plasmin.However,recent work has shown that in the brain this system has an important function regulating the development of synaptic plasticity via mechanisms that not always require plasmin generation.Urokinase-type plasminogen activator(uPA)is a serine proteinase and one of the plasminogen activators,that upon binding to its receptor(uPAR)not only catalyzes the conversion of plasminogen into plasmin on the cell surface,but also activates cell signaling pathways that promote cell migration,proliferation and survival.The role of uPA is the brain is not fully understood.However,it has been reported while uPA and uPAR are abundantly found in the developing central nervous system,in the mature brain their expression is restricted to a limited group of cells.Remarkably,following an ischemic injury to the mature brain the expression of uPA and uPAR increases to levels comparable to those observed during development.More specifically,neurons release uPA during the recovery phase from an ischemic injury,and astrocytes,axonal boutons and dendritic spines recruit uPAR to their plasma membrane.Here we will review recent evidence indicating that binding of uPA to uPAR promotes the repair of synapses damaged by an ischemic injury,with the resultant recovery of neurological function.Furthermore,we will discuss data indicating that treatment with recombinant uPA is a potential therapeutic strategy to promote neurological recovery among ischemic stroke survivors.
基金Supported by National Natural Science Foundation of China
文摘Partition coefficients of Urokinase(UK)were measured in aqueous two-phase systems con-taining polyethylene glycol and potassium phosphate at 273.2K.Based on the Diamond-Hsu model,a modified expression was obtained for the correlation of enzyme partitioning in theabove-mentioned systems.Utilizing a modified form,the partitioning data of UK and heteroproteinwere correlated.The results show that the modified model is simple gives good precision.and will fa-cilitate engineering scale-up of aqueous two-phase systems for certain proteins purification.
文摘To clarify the role of urokinase plasminogen activator(uPA) in the mechanisms of regulating sperm motility and the ability of fertilizing, we investigated the quantities and activities of uPA in human seminal Plasma and on the membrane of spermatozoa.Semens were harvested from 22 infertile patients with asthenospermia and 20 healthy fertile men according to WHO standards. To quantify the membrane-bound uPA in the samples, polyclonal antibodies against human urokinase were employed by means of a sandwich ELISA. The uPA activities in seminal plasma and on the surface of spermatozoa were determined using Agarose-Fibrine-Plate method and the experiment of immunological identification with polyclonal antibodies against urokinase. In lysates of spermatozoa, significantly lower levels of uPA(23. 1±7.35 mu/106 cells ) and uPA activity (5.13±3.85 mu/106 cells) were found in patient group as compared to healthy fertile men exhibiting normospermia (29. 89±9. 40 mu/105 cells and 10. 17±6. 18 mu/106 cells). In seminal plasma, uPA activity in patient group (2134±1581. 3 IU/L)was also found significantly lower than that of normal group (3365±1859. 5 IU/L). Positive correlations were observed between sperm motility and uPA quantities (r=0. 48, P＜0. 005), as well as with uPA activities (r= 0. 45,P＜0. 005).Thus, it is inferred that membrane associated uPA on human spermatozoa may be related directly to sperm motility and fertility.
基金Supported by the National Natural Science Foundation of China.
文摘1 INTRODUCTIONIn literature,most matrices of affinity chromatography for urokinase(EC 3.4.99.26)purification were prepared by cyanogen bromide activation.However,theseadsorbents usually suffered from the drawback of leakage of the ligand,particularly inalkaline medium,because of the instability of the isourea linkage between the ligandand the spacer or agarose.Moreover,the positively charged imido group of theN-substituted isourea derivative and the hydrophobicity of the spacers might promotenonspecific adsorption.On the contrary,the adsorbents prepared by the method
基金Supported by the Project of Science and Technology of Social Development Fund of Shaanxi Province,No.2016SF-100 and No.2016SF-133Xi’an No.4 Hospital Research Incubation Fund,No.2018LH-2
文摘BACKGROUND Suprachoroidal hemorrhage(SCH) is a rare but potentially catastrophic ocular event. Surgery for SCH is often challenging because of the difficulty in resolving the retinal and choroidal detachment. Here, we describe a novel surgical technique in which urokinase is administered by sub-Tenon's injection to target an organized clot in SCH prior to drainage.CASE SUMMARY A consecutive case series of four eyes with serous and hemorrhagic choroidal detachments secondary to cataract surgery or trauma was documented to evaluate the feasibility of using a sub-Tenon's urokinase injection-assisted 23-gauge and 20-gauge incision to drain choroidal detachments. Urokinase(2000 IU) was given by sub-Tenon's injection one day before surgery for clot liquefaction. A 23-gauge infusion line was placed in the anterior chamber. A 20-gauge incision was created in the suprachoroidal space 3.5 mm from the limbus. After drainage, pars plana vitrectomy was performed because of concomitant pathology that demanded this additional procedure. Visual acuity, ocular findings, the timing of surgical interventions, surgical procedures, and outcomes were retrospectively reviewed in four patients. Postoperative follow-up of the patients ranged from 6 to 24 mo(mean, 13 mo). After the treatment, all patients achieved excellent anatomical recovery. CONCLUSION Sub-Tenon's urokinase injection-assisted vitrectomy makes clot liquefaction happen in the early treatment stage, resulting in marked stability during the procedure.
文摘Purpose:To evaluate the clinical efficacyof thrombolysis injecting urokinase inperipheral artery for treatment of arterialocclusion.Materials and methods:12 patientswere treated with injecting urokinase inartery.Results:The mean dose of urokinase was500000U,the mean time of thrombolysis was200 minutes.The rate of clinic efficacy was83%.Conclusion:The indication of urokinasethrombolysis in artery is for those patientswith arterial occlusion in whom catheteriza-tion is feasible and clinical course is inone month.This operation is simple and conv-enient,it does not require special equipment.The method can be used safely and effectivelyin patients with arterial occlusion.
基金National Natural Science Foundation of China(2016D01C245).
文摘To study the influence of irbesartan combined with low dose urokinase on treatment effect and serologic indexes in elderly isolated systolic hypertension patients. Methods: One hundred and ten cases of elderly isolated systolic hypertension patients in our hospital during January 2013–January 2016 were randomly divided into observation group with 55 cases and control group with 55 cases. Patients in observation group received irbesartan combined with low dose hydrochlorothiazide treatment and those in control group received amlodipine combined with low dose hydrochlorothiazide treatment, each lasted for 4 weeks. After 4 weeks treatment, non-invasive blood pressure and blood pressure variability indexes were measured, serum endothelial function, inflammatory factors and oxidative stress indexes were measured. Results: After 4 weeks treatment, patients systolic blood pressure (SBP), 24 h mean systolic blood pressure (24 h SBP), 24 h systolic blood pressure standard deviation (24 h SSD) were significantly lower in observation group than in control group (P<0.05);serum endothelial function index EF-1 was lower in observation group than in control group, while NO and endothelial nitric oxide synthase (eNOS) were higher in observation group than in control group (P<0.05);serum high sensitivity C-reactive protein (hs-CRP), interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α (TNF-α) contents were lower in observation group than in control group (P<0.05);serum oxidation index such as malondialdehyde (MDA) was lower in observation group than in control group, while antioxidant indexes such as total anti-oxidative capacity (TAC), superoxide dismutase (SOD), GSH were higher in observation group than in control group (P<0.05). Conclusions: Irbesartan combined with low dose hydrochlorothiazide can effectively reduce systolic hypertension and blood pressure variability in elderly isolated systolic hypertension patients, while optimizing the systemic inflammation and oxidative stress status.
文摘Objective:To observe the clinical efficacy of urokinase in combined with minimally invasive hematoma puncture with YL-1 type needle in the treatment of hypertensive cerebral hemorrhage and the effect on blood sugar and serum CRP.Methods:A total of 84 patients with hypertensive cerebral hemorrhage who were admitted in our hospital were included in the study and divided into the minimally invasive group (n=53) and the conservative group (n=31) according to different treatment protocols. The patients in the two groups were given routine drug treatments. The patients in the observation group were given urokinase in combined with minimally invasive hematoma puncture with YL-1 type needle. The blood sugar and serum CRP levels before and after treatment in the two groups were compared. CT was performed to reexamine the cerebral hematoma and edema volume.Results: The serum CRP and blood sugar levels 3, 7 and 14 d after treatment in the minimally invasive group were significantly lower than those in the conservative group (P<0.05). The cerebral hematoma and edema volume 1, 3, 7, and 14 d after treatment in the minimally invasive group was significantly lower than that in the conservative group (P<0.05).Conclusions: Urokinase in combined with minimally invasive hematoma puncture with YL-1 type needle in the treatment of hypertensive cerebral hemorrhage can significantly alleviate the brain tissue injury, reduce the systemic inflammatory reaction and blood sugar level, and contribute to the rehabilitation.
文摘Objective To analyse the efficacy and safety of elderly patients with acute ischemic stroke who underwent intravenous thrombolysis with alteplase(recombinant tissue plasminogen activator,r-tPA)and urokinase(UK)within 4.5 h of onset.Methods Based on the intravenous thrombolysis registry for Chinese ischemic stroke within 4.5 h of onset(INTRECIS)cohort.
基金Project supported by the National High-Technology Development Plant of China (Grant 863-103-19).
文摘In view of the similarity of the charge distribution between fibrin A_α148--161 and Achain 149--157 of urokinase,the latter might compete with fibrin A_α148--161 when singlechain pro-urokinase is converted to double chain urokinase.To test this, the stretch of uro-kinase A chain 135--157 was separated from the low molecular weight urokinase, a competi-tive binding between this stretch and fibrin to tPA kringle-2 was shown by radio-bindingassay. The inhibition of the stretch on the fibrin stimulated activation of plasminogen wasdemonstrated in the caseinolytic system. The synthesized novapeptide urokinase A chain 149--157 (R-peptide) showed a significant inhibition on the activation of plasminogen in the pres-ence of fibrin. By contrasting finely with R-peptide, a synthesized novapeptide in which Arg154and Arg156 were replaced by Asp (D-peptide) did not show any inhibition effect on the fi-brin stimulated activation of plasminogen by tPA. These results suggest that the positivelycharged residues in
基金This work is financially supported by the National Natural Science Foundation of China(81400941,51473169).
文摘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.
基金This work is supported by the Chinese National High Technology Development Program 863-103-19
文摘The Kringle-1 structure of plasminogen (PGK-1), the Kringle-2 structure of tissue plasminogen activator (PAK-2) and the Kringle structure of prourokinase (UKK) has been modeled on the basis of the three-dimensional structure of Kringle-1 of prothrombin (PTK-1) at 2.8 resolution. The predicted three-dimensional structure of these Kringles shows that the binding site of PGK-1 is characterized by an apparent dipolar site, the polar parts of which are separated by a hydrophobic region. PAK-2 possesses the anionic center but has not a cationic binding center which might be provided by a guanidinium group from Arg-69 located adjacent to the Arg-71 position. UKK possesses neither the anionic binding center nor the cationic center which are probably the main reason for the poor fibrin specificity of urokinase.
文摘Pro-urokinase is a kind of protease existing in human body. It has the character of fibrinolysis, so it has been clinically applied to the treatment of thrombolytic diseases. In order to produce a large amount of pro-urokinase by genetic engineering method and reform it with protein engineering, we have chemically synthesized the pro-urokinase gene, which
基金Project supported by the Chinese National High Technology Development Program(863-103-19).
文摘The B-chain of urokinase (UK) was covalently linked by disulfide bond to the Fab fragment of an anti-human activated platelet monoclonal antibody(SZ-51). The UKSZ-51 conjugate retained the original binding specificity of its parent antibody, and produced about a 5-fold enhancement in clot lysis in plasma over that of the urokinase in vitro. Whereas UK significantly decreased the concentration of fibrinogen in plasma clot assay supernatants, UK-SZ-51 did not.
