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 Ca...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
Tissue plasminogen activator （tPA） use in the treatment of isch- emic stroke： tPA is a serine protease that catalyzes the breakdown of blood dots. Because of its thrombolytic properties, tPA is used to treat specif...Tissue plasminogen activator （tPA） use in the treatment of isch- emic stroke： tPA is a serine protease that catalyzes the breakdown of blood dots. Because of its thrombolytic properties, tPA is used to treat specific types of stroke, including ischemia, but is contra- indicated for treatment of hemorrhagic stroke or head trauma. Although a life saving and powerful ＇dot buster＇, tPA has a short therapeutic window. When administered outside of this prescribed timeframe, research suggests that tPA can produce neurotoxic ef- fects in the brain, due in part to activation of several signalling pro- cesses associated with cell apoptosis, degradation of the extracel- lular matrix, and increase in the permeability of the neurovascular unit （Yepes et al., 2009）. Concerted research has been dedicated to- ward understanding the mechanisms mediating the impact of tPA on the brain, using both in vivo and in vitro animal models.展开更多
文摘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.
文摘Tissue plasminogen activator （tPA） use in the treatment of isch- emic stroke： tPA is a serine protease that catalyzes the breakdown of blood dots. Because of its thrombolytic properties, tPA is used to treat specific types of stroke, including ischemia, but is contra- indicated for treatment of hemorrhagic stroke or head trauma. Although a life saving and powerful ＇dot buster＇, tPA has a short therapeutic window. When administered outside of this prescribed timeframe, research suggests that tPA can produce neurotoxic ef- fects in the brain, due in part to activation of several signalling pro- cesses associated with cell apoptosis, degradation of the extracel- lular matrix, and increase in the permeability of the neurovascular unit （Yepes et al., 2009）. Concerted research has been dedicated to- ward understanding the mechanisms mediating the impact of tPA on the brain, using both in vivo and in vitro animal models.
