The study aimed to investigate the impact of intraclot recombinant tissue-type plasminogen activator(rt-PA) on perihematomal edema(PHE) development in patients with intracerebral hemorrhage(ICH) treated with minimally...The study aimed to investigate the impact of intraclot recombinant tissue-type plasminogen activator(rt-PA) on perihematomal edema(PHE) development in patients with intracerebral hemorrhage(ICH) treated with minimally invasive surgery(MIS) and the effects of intraclot rt-PA on the 30-day survival. We reviewed the medical records of ICH patients undergoing MIS between October 2011 and July 2013. A volumetric analysis was done to assess the change in PHE and ICH volumes at pre-MIS(T1), post-MIS(T2) and day 10–16(T3) following diagnostic computed tomographic scans(T0). Forty-three patients aged 52.8±11.1 years with(n=30) or without rt-PA(n=13) were enrolled from our institutional ICH database. The median rt-PA dose was 1.5(1) mg, with a maximum dose of 4.0 mg. The ratio of clot evacuation was significantly increased by intraclot rt-PA as compared with controls(77.9%±20.4% vs. 64%±15%; P=0.046). From T1 to T2, reduction in PHE volume was strongly associated with the percentage of clot evacuation(ρ=0.34; P=0.027). In addition, PHE volume was positively correlated with residual ICH volume at the same day(ρ ranging from 0.39–0.56, P<0.01). There was no correlation between the cumulative dose of rt-PA and early(T2) PHE volume(ρ=0.24; P=0.12) or delayed(T3) PHE volume(ρ=0.19; P=0.16). The 30-day mortality was zero in this cohort. In the selected cohort of ICH patients treated with MIS, intraclot rt-PA accelerated clot removal and had no effects on PHE formation. MIS aspiration and low dose of rt-PA seemed to be feasible to reduce the 30-day mortality in patients with severe ICH. A large, randomized study addressing dose titration and long-term outcome is needed.展开更多
BACKGROUND:The study aimed to compare the therapeutic effect of recombinant tissue plasminogen activator(rt-PA) on the onset of acute cerebral infarction(ACI) at different time points of the first 6 hours.METHODS:A re...BACKGROUND:The study aimed to compare the therapeutic effect of recombinant tissue plasminogen activator(rt-PA) on the onset of acute cerebral infarction(ACI) at different time points of the first 6 hours.METHODS:A retrospective analysis was conducted in 74 patients who received rt-PA thrombolysis treatment within 4.5 hours after ACI and another 15 patients who received rt-PA thrombolysis treatment between 4.5-6 hours after ACI.RESULTS:National Institute of Health Stroke Scale(NIHSS) scores were statistically decreased in both groups(P>0.05) at 24 hours and 7 days after ACI.There was no significant difference in modified ranking scores and mortality at 90 days after the treatment between the two groups(P>0.05).CONCLUSIONS:The therapeutic effect and mortality of rt-PA treatment in patients with ACI between 4.5-6 hours after the onset of the disease were similar to those in patients who received rtPA within 4.5 hours after the onset of this disease.Therefore,intravenous thrombolytic therapy for ACI within 4.5-6 hours after ACI was effective and safe.展开更多
Objective In order to investigate the pharmacological properties of Ginkgo biloba extract (GBE) on improving blood circulation, the regulating action of GBE and quercetin (a main flavonoid ingredient in GBE) on thromb...Objective In order to investigate the pharmacological properties of Ginkgo biloba extract (GBE) on improving blood circulation, the regulating action of GBE and quercetin (a main flavonoid ingredient in GBE) on thrombomodulin (TM) expression and tissue-type plasminogen activator (t-PA) secretion was studied. Methods Using flow cytometer and gel image system respectively, we evaluated the TM expression and the t-PA secretion by human umbilical vein endothelial cells (HUVECs) in vitro. Results The increase of TM expression on HUVECs surface was induced by GBE rather than quercetin in a dose- and time-dependent manner. Both GBE and quercetin increased the t-PA release significantly. Conclusion The effect of GBE on improving blood circulation may be partly attributed to its promoting TM expression and t-PA secretion by endothelial cells, and quercetin participated in the effect of GBE on t-PA secretion. However, the action of GBE on increasing TM expression needs further study.展开更多
The effects of in vivo local expression of recombined human tissue-type plasminogen activator (t-PA) gene on the thrombosis and neointima formation of vein grafts were explored. Jugular vein-to-artery bypass grafting ...The effects of in vivo local expression of recombined human tissue-type plasminogen activator (t-PA) gene on the thrombosis and neointima formation of vein grafts were explored. Jugular vein-to-artery bypass grafting was performed on 72 New Zealand white rabbits. The rabbits were divided into 3 groups according to the different processing methods: transfected t-PA gene group (n=24), vector group (n=24) and blank control group (n=24). Samples of vein grafts were harvested at different time points after surgery. The expression of t-PA gene in vein graft was detected by RT-PCR and the synthesis of t-PA protein by Western-Blot assay. The t-PA activity was measured by chromogenic substrate assay. The Cr51 labeled platelets accumulation in vein grafts was counted. The histopathological changes were compared in intima hyperplasia index among the three groups after operation. The results showed that at the 2 nd, 5 th, 14 th and 28 th day after operation, RT-PCR and Western-blot confirmed the expression of t-PA mRNA and protein at the site of gene transfer. The t-PA activity detected on the 2 nd, 5 th, 14 th and 28 th day in experimental group was 370.63±59.44, 344.13±48.47, 252.87±51.80 and 161.75±68.94 U/g respectively, and disappeared on the 60 th day and undetected in the control groups. The number of platelets accumulated in the vein grafts in gene group, vector group and blank control group was (85.04±21.58) 10 6, (225.87±85.13) 10 6 and (211.57±78.02) 10 6 respectively. The number of platelets accumulated in gene group was significantly fewer than that in the control groups. Morphometric analysis revealed that intimal hyperplasia was markedly reduced in the t-PA gene group as compared with that in the control groups. It was suggested that the local expression of t-PA gene in vein graft significantly inhibited the accumulation of platelets, thrombosis and concomitant intimal hyperplasia, by which stenosis of bypass graft could be prevented effectively.展开更多
Objective To detect the presence of endothelial injury in patients with severe acute respiratory syndrome (SARS) via enhanced levels of tissue-type plasminogen activator (t-PA) and soluble thrombomodulin (sTM). Method...Objective To detect the presence of endothelial injury in patients with severe acute respiratory syndrome (SARS) via enhanced levels of tissue-type plasminogen activator (t-PA) and soluble thrombomodulin (sTM). Methods Case patients were from Xuanwu Hospital (Capital University of Medical Sciences, Beijing, China), and all of them met clinical criteria for SARS. Healthy controls were some of the hospital employees. Endothelial injury bio-markers tPA and sTM were detected by commercial ELISA-methods. Results Classic plasma markers of endothelial injury, tPA and sTM significantly elevated in SARS patients in comparison to controls [t-PA: 1.48±0.16 nmol/L versus 0.25±0.03 nmol/L (P<0.0001), and sTM: 0.26±0.06 nmol/L versus 0.14±0.02 nmol/L (P<0.05)]. The only patient who died had extremely high levels of these endothelial injury markers (t-PA: 2.77 nmol/L and sTM: 1.01 nmol/L). The likelihood ratio analysis indicated the excellent discriminating power for SARS at the optimal cut-point of 0.49 nmol/L for tPA and 0.20 nmol/L for sTM, respectively. Significant numerical correlations were found among these endothelial injury markers in SARS patients. The numerical coefficient of correlation Pearson r between t-PA and sTM was 0.5867 (P<0.05). Conclusion Increased plasma concentrations of tPA and sTM in patients with SARS suggest the possibility of endothelial injury. SARS patients might need anticoagulant therapy or fibrinolytic therapy in order to reverse intraalveolar coagulation, microthrombi formation, alveolar and interstitial fibrin deposition. It may not only provide a useful treatment and prognostic index but also allow a further understanding of the pathological condition of the disease.展开更多
It is here reported for the first time that luteal cells are capable of secreting plasminogen activators(PA),(both tissue-type,tPA,and urokinase-type,uPA),and plasminogen activator inhibitor type-1(PAl-1).Using organ ...It is here reported for the first time that luteal cells are capable of secreting plasminogen activators(PA),(both tissue-type,tPA,and urokinase-type,uPA),and plasminogen activator inhibitor type-1(PAl-1).Using organ culture model,we have demonstrated that tPA,but not uPA,showed markedchange during luteolytic period in rat corpus luteum.A great amount oftPA was secreted in corpusluteum on D 14 and D 17 while very low level of tPA activity was detected before D 12.Correspondingly,the progesterone production in the corpus luteum increased gradually in a time-dependent manner from D 1 to D 12 but dropped abruptly to a very low level on D 14.Additionof exogenous tPA to the CL culture caused considerable decrease in progesterone secretion whileinclusion of purified monoclone tPA antibodies in the culture augmented progesterone productionof CL.It is therefore suggested that tPA may play an important role in luteolytic process.展开更多
Objective To observe the changes of the activity of tissue -type plasminogen activa tor(TPA)after asphyxia.Methods As-phyxia was induced in mouse pups by performing a ‘delayed cesarean section’.The experiment was de...Objective To observe the changes of the activity of tissue -type plasminogen activa tor(TPA)after asphyxia.Methods As-phyxia was induced in mouse pups by performing a ‘delayed cesarean section’.The experiment was designed for a co ntrol group and 4asphyctic groups to detect the activity of TPA.Results TPAactivity of brain increased afte r asphyxia(P <0.01).Conclusion TPAincreased after asphyxia might be able to attack the b asement membrane of microvessels,t hen opened the blood -brain barrier a nd induced neuronal damage.展开更多
Membrane depolarization induces the release of the serine proteinase tissue-type plasminogen activator(t PA) from the presynaptic terminal of cerebral cortical neurons.Once in the synaptic cleft this t PA promotes the...Membrane depolarization induces the release of the serine proteinase tissue-type plasminogen activator(t PA) from the presynaptic terminal of cerebral cortical neurons.Once in the synaptic cleft this t PA promotes the exocytosis and subsequent endocytic retrieval of glutamate-containing synaptic vesicles,and regulates the postsynaptic response to the presynaptic release of glutamate.Indeed,t PA has a bidirectional effect on the composition of the postsynaptic density(PSD) that does not require plasmin generation or the presynaptic release of glutamate,but varies according to the baseline level of neuronal activity.Hence,in inactive neurons t PA induces phosphorylation and accumulation in the PSD of the Ca^(2+)/calmodulin-dependent protein kinase IIα(pCa MKIIα),followed by pCa MKIIα-induced phosphorylation and synaptic recruitment of Glu R1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid(AMPA) receptors.In contrast,in active neurons with increased levels of pCa MKIIα in the PSD t PA induces pCa MKIIα and p Glu R1 dephosphorylation and their subsequent removal from the PSD.These effects require active synaptic N-methyl-D-aspartate(NMDA) receptors and cyclin-dependent kinase 5(Cdk5)-induced phosphorylation of the protein phosphatase 1(PP1) at T320.These data indicate that t PA is a homeostatic regulator of the postsynaptic response of cerebral cortical neurons to the presynaptic release of glutamate via bidirectional regulation of the pCa MKIIα/PP1 switch in the PSD.展开更多
A number of studies have confirmed the existence of tissue-type plasminogen activator-independent roles of neuroserpin, a member of the serine protease inhibitor superfamily. In this review article, we aim to clarify ...A number of studies have confirmed the existence of tissue-type plasminogen activator-independent roles of neuroserpin, a member of the serine protease inhibitor superfamily. In this review article, we aim to clarify this role. These unique roles of neuroserpin are involved in its neuroprotective effect during is chemic brain injury, its regulation of tumorigenesis, and the mediation of emotion and cognition through the inhibition of urokinase-type plasminogen activator and fibrinolysin, modification of Th cells, reducing plaque formation, promoting process growth and intracellular adhesion, and altering the expression of cadherin and nuclear factor kappa B.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81171089 and No.30770751)Key Clinical Program of the Ministry of Health of China(2010)the Future Program of New Technology and New Business in Tongji Hospital,China(2012)
文摘The study aimed to investigate the impact of intraclot recombinant tissue-type plasminogen activator(rt-PA) on perihematomal edema(PHE) development in patients with intracerebral hemorrhage(ICH) treated with minimally invasive surgery(MIS) and the effects of intraclot rt-PA on the 30-day survival. We reviewed the medical records of ICH patients undergoing MIS between October 2011 and July 2013. A volumetric analysis was done to assess the change in PHE and ICH volumes at pre-MIS(T1), post-MIS(T2) and day 10–16(T3) following diagnostic computed tomographic scans(T0). Forty-three patients aged 52.8±11.1 years with(n=30) or without rt-PA(n=13) were enrolled from our institutional ICH database. The median rt-PA dose was 1.5(1) mg, with a maximum dose of 4.0 mg. The ratio of clot evacuation was significantly increased by intraclot rt-PA as compared with controls(77.9%±20.4% vs. 64%±15%; P=0.046). From T1 to T2, reduction in PHE volume was strongly associated with the percentage of clot evacuation(ρ=0.34; P=0.027). In addition, PHE volume was positively correlated with residual ICH volume at the same day(ρ ranging from 0.39–0.56, P<0.01). There was no correlation between the cumulative dose of rt-PA and early(T2) PHE volume(ρ=0.24; P=0.12) or delayed(T3) PHE volume(ρ=0.19; P=0.16). The 30-day mortality was zero in this cohort. In the selected cohort of ICH patients treated with MIS, intraclot rt-PA accelerated clot removal and had no effects on PHE formation. MIS aspiration and low dose of rt-PA seemed to be feasible to reduce the 30-day mortality in patients with severe ICH. A large, randomized study addressing dose titration and long-term outcome is needed.
基金supported by a grant from Shanghai Municipal Health Bureau(GWDTR201219)
文摘BACKGROUND:The study aimed to compare the therapeutic effect of recombinant tissue plasminogen activator(rt-PA) on the onset of acute cerebral infarction(ACI) at different time points of the first 6 hours.METHODS:A retrospective analysis was conducted in 74 patients who received rt-PA thrombolysis treatment within 4.5 hours after ACI and another 15 patients who received rt-PA thrombolysis treatment between 4.5-6 hours after ACI.RESULTS:National Institute of Health Stroke Scale(NIHSS) scores were statistically decreased in both groups(P>0.05) at 24 hours and 7 days after ACI.There was no significant difference in modified ranking scores and mortality at 90 days after the treatment between the two groups(P>0.05).CONCLUSIONS:The therapeutic effect and mortality of rt-PA treatment in patients with ACI between 4.5-6 hours after the onset of the disease were similar to those in patients who received rtPA within 4.5 hours after the onset of this disease.Therefore,intravenous thrombolytic therapy for ACI within 4.5-6 hours after ACI was effective and safe.
基金This work was supported by the National Basic Scientific Research Program of China （973 Program, No. 2007CB935803）, the National Natural Science Foundation of China （No. 30825018） and the Key Clinical Program of the Ministry of Health of China （No. 2010439）.
文摘Objective In order to investigate the pharmacological properties of Ginkgo biloba extract (GBE) on improving blood circulation, the regulating action of GBE and quercetin (a main flavonoid ingredient in GBE) on thrombomodulin (TM) expression and tissue-type plasminogen activator (t-PA) secretion was studied. Methods Using flow cytometer and gel image system respectively, we evaluated the TM expression and the t-PA secretion by human umbilical vein endothelial cells (HUVECs) in vitro. Results The increase of TM expression on HUVECs surface was induced by GBE rather than quercetin in a dose- and time-dependent manner. Both GBE and quercetin increased the t-PA release significantly. Conclusion The effect of GBE on improving blood circulation may be partly attributed to its promoting TM expression and t-PA secretion by endothelial cells, and quercetin participated in the effect of GBE on t-PA secretion. However, the action of GBE on increasing TM expression needs further study.
文摘The effects of in vivo local expression of recombined human tissue-type plasminogen activator (t-PA) gene on the thrombosis and neointima formation of vein grafts were explored. Jugular vein-to-artery bypass grafting was performed on 72 New Zealand white rabbits. The rabbits were divided into 3 groups according to the different processing methods: transfected t-PA gene group (n=24), vector group (n=24) and blank control group (n=24). Samples of vein grafts were harvested at different time points after surgery. The expression of t-PA gene in vein graft was detected by RT-PCR and the synthesis of t-PA protein by Western-Blot assay. The t-PA activity was measured by chromogenic substrate assay. The Cr51 labeled platelets accumulation in vein grafts was counted. The histopathological changes were compared in intima hyperplasia index among the three groups after operation. The results showed that at the 2 nd, 5 th, 14 th and 28 th day after operation, RT-PCR and Western-blot confirmed the expression of t-PA mRNA and protein at the site of gene transfer. The t-PA activity detected on the 2 nd, 5 th, 14 th and 28 th day in experimental group was 370.63±59.44, 344.13±48.47, 252.87±51.80 and 161.75±68.94 U/g respectively, and disappeared on the 60 th day and undetected in the control groups. The number of platelets accumulated in the vein grafts in gene group, vector group and blank control group was (85.04±21.58) 10 6, (225.87±85.13) 10 6 and (211.57±78.02) 10 6 respectively. The number of platelets accumulated in gene group was significantly fewer than that in the control groups. Morphometric analysis revealed that intimal hyperplasia was markedly reduced in the t-PA gene group as compared with that in the control groups. It was suggested that the local expression of t-PA gene in vein graft significantly inhibited the accumulation of platelets, thrombosis and concomitant intimal hyperplasia, by which stenosis of bypass graft could be prevented effectively.
文摘Objective To detect the presence of endothelial injury in patients with severe acute respiratory syndrome (SARS) via enhanced levels of tissue-type plasminogen activator (t-PA) and soluble thrombomodulin (sTM). Methods Case patients were from Xuanwu Hospital (Capital University of Medical Sciences, Beijing, China), and all of them met clinical criteria for SARS. Healthy controls were some of the hospital employees. Endothelial injury bio-markers tPA and sTM were detected by commercial ELISA-methods. Results Classic plasma markers of endothelial injury, tPA and sTM significantly elevated in SARS patients in comparison to controls [t-PA: 1.48±0.16 nmol/L versus 0.25±0.03 nmol/L (P<0.0001), and sTM: 0.26±0.06 nmol/L versus 0.14±0.02 nmol/L (P<0.05)]. The only patient who died had extremely high levels of these endothelial injury markers (t-PA: 2.77 nmol/L and sTM: 1.01 nmol/L). The likelihood ratio analysis indicated the excellent discriminating power for SARS at the optimal cut-point of 0.49 nmol/L for tPA and 0.20 nmol/L for sTM, respectively. Significant numerical correlations were found among these endothelial injury markers in SARS patients. The numerical coefficient of correlation Pearson r between t-PA and sTM was 0.5867 (P<0.05). Conclusion Increased plasma concentrations of tPA and sTM in patients with SARS suggest the possibility of endothelial injury. SARS patients might need anticoagulant therapy or fibrinolytic therapy in order to reverse intraalveolar coagulation, microthrombi formation, alveolar and interstitial fibrin deposition. It may not only provide a useful treatment and prognostic index but also allow a further understanding of the pathological condition of the disease.
基金Project supported by HRP,WHO,The State Family Planning commission State Key Laboratory of Reproductive Biology.
文摘It is here reported for the first time that luteal cells are capable of secreting plasminogen activators(PA),(both tissue-type,tPA,and urokinase-type,uPA),and plasminogen activator inhibitor type-1(PAl-1).Using organ culture model,we have demonstrated that tPA,but not uPA,showed markedchange during luteolytic period in rat corpus luteum.A great amount oftPA was secreted in corpusluteum on D 14 and D 17 while very low level of tPA activity was detected before D 12.Correspondingly,the progesterone production in the corpus luteum increased gradually in a time-dependent manner from D 1 to D 12 but dropped abruptly to a very low level on D 14.Additionof exogenous tPA to the CL culture caused considerable decrease in progesterone secretion whileinclusion of purified monoclone tPA antibodies in the culture augmented progesterone productionof CL.It is therefore suggested that tPA may play an important role in luteolytic process.
文摘Objective To observe the changes of the activity of tissue -type plasminogen activa tor(TPA)after asphyxia.Methods As-phyxia was induced in mouse pups by performing a ‘delayed cesarean section’.The experiment was designed for a co ntrol group and 4asphyctic groups to detect the activity of TPA.Results TPAactivity of brain increased afte r asphyxia(P <0.01).Conclusion TPAincreased after asphyxia might be able to attack the b asement membrane of microvessels,t hen opened the blood -brain barrier a nd induced neuronal damage.
基金supported in part by National Institutes of Health Grants NS-079331(to MY)and NS-091201(to MY)
文摘Membrane depolarization induces the release of the serine proteinase tissue-type plasminogen activator(t PA) from the presynaptic terminal of cerebral cortical neurons.Once in the synaptic cleft this t PA promotes the exocytosis and subsequent endocytic retrieval of glutamate-containing synaptic vesicles,and regulates the postsynaptic response to the presynaptic release of glutamate.Indeed,t PA has a bidirectional effect on the composition of the postsynaptic density(PSD) that does not require plasmin generation or the presynaptic release of glutamate,but varies according to the baseline level of neuronal activity.Hence,in inactive neurons t PA induces phosphorylation and accumulation in the PSD of the Ca^(2+)/calmodulin-dependent protein kinase IIα(pCa MKIIα),followed by pCa MKIIα-induced phosphorylation and synaptic recruitment of Glu R1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid(AMPA) receptors.In contrast,in active neurons with increased levels of pCa MKIIα in the PSD t PA induces pCa MKIIα and p Glu R1 dephosphorylation and their subsequent removal from the PSD.These effects require active synaptic N-methyl-D-aspartate(NMDA) receptors and cyclin-dependent kinase 5(Cdk5)-induced phosphorylation of the protein phosphatase 1(PP1) at T320.These data indicate that t PA is a homeostatic regulator of the postsynaptic response of cerebral cortical neurons to the presynaptic release of glutamate via bidirectional regulation of the pCa MKIIα/PP1 switch in the PSD.
基金supported by the National Natural Science Foundation of China, No. 30700908, 30772343 and 30973215
文摘A number of studies have confirmed the existence of tissue-type plasminogen activator-independent roles of neuroserpin, a member of the serine protease inhibitor superfamily. In this review article, we aim to clarify this role. These unique roles of neuroserpin are involved in its neuroprotective effect during is chemic brain injury, its regulation of tumorigenesis, and the mediation of emotion and cognition through the inhibition of urokinase-type plasminogen activator and fibrinolysin, modification of Th cells, reducing plaque formation, promoting process growth and intracellular adhesion, and altering the expression of cadherin and nuclear factor kappa B.
