Recombinant staphylokinase variant(Katholieke Universiteit Leuven)

The fibrin-specificity and procoagulant effects of recombinant staphylokinase (Sak42D) were compared with those of recombinant tissue-type plasminogen activator (rt-PA) in patients with acute myocardial infarction. Plasma samples were obtained at baseline and at 25 and 90 min, from 24 patients who were randomly assigned to a double bolus (15 mg each, 30 min apart) administration of Sak42D or to accelerated weight-adjusted rt-PA (maximum of 100 mg over 90 min). Baseline levels of fibrinopeptide A (FPA), prothrombin fragment 1+2 and thrombin-antithrombin III complex (TAT) were comparable in the Sak42D and rt-PA groups (p ≥ 0.6). In patients treated with Sak42D, plasma levels of FPA, prothrombin fragment 1+2 and TAT did not markedly increase during treatment (p = 0.06, p = 0.4 and p = 0.03, respectively). In contrast, during administration of rt-PA the levels of FPA, prothrombin fragment 1+2 and TAT increased significantly over baseline (p = 0.003, p < 0.0001 and p = 0.001, respectively). As a result, the levels of all three procoagulant parameters were significantly lower during treatment with Sak42D as compared to rt-PA. Thus, FPA levels in the Sak42D group (median values) were 40 ng/ml at 25 min and 11 ng/ml at 90 min, as compared to 88 ng/ml and 50 ng/ml in the rt-PA group (p = 0.0007 and p = 0.009, respectively). Prothrombin fragment 1+2 levels in the Sak42D group were 1.3 nM at 25 min and 1.2 nM at 20 min, as compared to 11 nM and 5.3 nM in the rt-PA group (both p < 0.0001). TAT levels were 4.7 ng/ml at 25 min and 6.2 ng/ml at 90 min in the Sak42D group, with corresponding values of 16 ng/ml and 9.6 ng/ml in the rt-PA group (p = 0.02 and p = 0.03, respectively).In the patients treated with Sak42D, no significant systemic fibrinolytic activation was observed, as revealed by unaltered levels of clotta-ble fibrinogen, plasminogen and a2-antiplasmin up to 90 min after the start of therapy. In contrast, the corresponding residual levels at 90 min in patients treated with rt-PA decreased to (mean ± SEM; n = 12) 62 ± 6%, 45 ± 5% and 52 ± 10%, respectively (all p < 0.01 versus the Sak42D group)These data confirm the high degree of fibrin-specificity of Sak42D and demonstrate that this is associated with significantly less generation of procoagulant activity in plasma after intravenous administration in patients with acute myocardial infarction

This study aimed to determine the effects of different dietary threonine levels on the antioxidant and immune capacity and the immunity of broilers. A total of 432 one-day-old Arbor Acres (AA) broilers were randomly assigned to 4 groups, each with 6 replicates of 18 broilers. The amount of dietary threonine in the four treatments reached 85%, 100%, 125%, and 150% of the NRC (Nutrient Requirements of Poultry, 1994) recommendation for broilers (marked as THR85, THR100, THR125, and THR150). After 42 days of feeding, the cecum contents and jejunum mucosa were collected for metabolic analysis and transcriptional sequencing. The results indicated that under the condition of regular and non-disease growth of broilers, compared with that of the THR85 and THR150 groups, the metabolic profile of the THR125 group was significantly higher than that of the standard requirement group. Compared with the THR100 group, the THR125 group improved antioxidant ability and immunity of broilers and enhanced the ability of resisting viruses. The antioxidant gene CAT was upregulated. PLCD1, which is involved in immune signal transduction and plays a role in cancer suppression, was also upregulated. Carcinogenic or indirect genes PKM2, ACY1, HK2, and TBXA2 were down-regulated. The genes GPT2, glude2, and G6PC, which played an important role in maintaining homeostasis, were up-regulated. Therefore, the present study suggests that 125% of the NRC recommendations for Thr level had better effects on antioxidant and immune capacity, as well as maintaining the homeostasis of the body.