Résumé
The glycosylation heterogeneity of recombinant human pro-urokinase (pro-UK) was assessed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Firstly, the source of heterogeneity was determined by measuring the Mr of intact protein before and after N-deglycosylation. Glycosylation sites and the proportion of O-glycopeptides then were determined at the peptide level. Finally, the N-glycans were confirmed and quantified using the N-glycan profile. Results show that the structural heterogeneity of pro-UK is mainly caused by glycosylation. All T18 were fucosylated, and 6.4% of S138/139 was O-glycosylated with two kinds of oligosaccharides with a ratio of 6.0% and 0.4% respectively. All N302 positions were N-glycosylated by more than ten types of glycans, among which A2F and A3F accounted for 80% of the total. The assessment of glycosylation heterogeneity of pro-UK will provide a reference for quality standardization.
Résumé
Objective To investigate the efficacy and safety of recombinant human Pro urokinase ( rhPro-uk) in treatment of patients with acute ST segment elevation myocardial infarction.Methods 90 cases from 2014 to 2015 selected in three hospital diagnosed with STEMI were randomly assigned into experimental group and control group, 45 cases in each test group.Experimental group received rhPro-uk thrombolytic therapy, control group received urokinase thrombolytic therapy, thrombolytic efficacy and incidence of adverse events were observed and compared between two goups.Results After thrombolysis 2 h, ST segment decline ≥50% of patients in experimental group was 80.00%, ST segment completely fall rate was 55.56%, coronary recanalization rate was 77.78%, all significantly higher than that in control group(60.00%, 33.33%, 55.56 %,separately.P<0.05).After thrombolysis 2h, the difference of TIMI grade between two group was significant (Z=-3.198, P<0.05).After thrombolytic therapy, CTn-I, CK-MB peak levels between two groups were not significantly different.The peak time and average time of experimental group were significantly lower than that in control group (P<0.05).The incidence of adverse events of experimental group 13.33%, significantly lower than 33.33% in control group(P <0.05).Conclusion Therapeutic effect of rhPro-uk on acute ST-segment elevation myocardial infarction is better than urokinase, and has higher safety.
Résumé
Objective In this angiographic trial,we compared the efficacy and safety of Pro-UK with urokinase in Chinese patients with acute myocardial infarction.Methods We recruited patients with acute ST-elevation myocardial infarction presented within 6 hours in Beijing Tongren Hospital offiliated to Capital Vnirersity of Medical Sciences from Feb.2003 to Mar.2004.After giving informed consent,patients were assigned a bolus and infusion of Pro-UK or a infusion of urokinase.The primary efficacy end points and safety end points were observed.Results Overall 26 patients were enrolled in the trial,of whom 16 patients were assigned to receive Pro-UK(6 patients to 40mg,6 patients to 50 mg,4 patients to 60 mg),and 10 patients to urokinase.The rates of TIMI grade 3 flow were 56.25%(9/16)with Pro-UK and 70%(7/10) with urokinase(P=0.683),of whom 66.7%(4/6) with 50 mg Pro-UK,75%(3/4)with 60 mg Pro-UK. The rates of TIMI grade 2 or 3 were similar for patients treated with Pro-UK versus urokinase(56.25% and 80%,respectively,P=0.399). All safety end points were similar between the two groups. The level of fibrinogen in blood plasma was significantly higher in Pro-UK group than that in urokinase group,indicating that Pro-UK had higher fibrin-specificity.Conclusion The bolus and 30 minutes infusion of Pro-UK 50 mg and 60 mg was clinically safe and effective thrombolytic regimen,but need further study.