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Background Oxidoreductive imbalance is a major cause of excessive haemolysis in in vitro conditions. Leucocytes and blood platelets present in red blood cell concentrates ( RBCs) are one of the sources of free radicals, which have a significant effect on the status of stored erythrocytes. The study objective was to assess the effect of leucoreduction on the intensity of lipid peroxidation and the activity of antioxidant barrier enzymes in RBC. Study Design and Methods Red blood cell concentrates units obtained from 10 whole-blood units were split into two equal units, one of which was leucoreduced on the day of donation. Both units were stored for 35 days. The following markers of oxidoreductive balance were measured on day 0 (donation day) and on storage days 7, 14, 21 and 35: concentration of malondialdehyde ( MDA) and activities of antioxidant barrier components, that is superoxide dismutase, glutathione peroxidase and glutathione reductase. Results Lipid peroxidation in leucodepleted units ( LRBC) was slower than that in non-leucodepleted ones. The analysis of LRBC revealed statistically significant decrease in concentrations of MDA. The activities of superoxide dismutase, glutathione peroxidase and glutathione reductase were higher throughout the storage period as compared to non-leucoreduced RBC. Statistically significant differences between RBC and LRBC units were noted throughout the storage in the activity of lactate dehydrogenase, and concentrations of K+ ions and free haemoglobin. Conclusions Leucoreduction of RBC before storage helps to preserve the activity of antioxidant barrier enzymes in stored RBCs and significantly improves the quality of stored red blood cell components. [ABSTRACT FROM AUTHOR]

Purpose: The role of MAP kinases in the activation of AP-1 (c-Jun, c-Fos) and NF-κB p65 engaged in the regulation of iNOS expression in human neutrophils (PMNs) exposed to N-nitrosodimethylamine (NDMA) was analyzed in the study. Material and Methods: The study included a group of 20 healthy individuals. Isolated human PMN were incubated in the presence of NDMA. Selective MAP kinases inhibitors were used. The expression of proteins in the cytoplasmic and nuclear fractions was assessed using Western blot method. Results: The results show that NDMA intensifies iNOS, c-Jun, NF-κB p65 and IκB-α expression in the analyzed PMNs. The blocking of the p38 pathway led to lower iNOS expression, and higher expression of c-Jun and c-Fos in the cytoplasmic fraction, and also lower c-Jun expression in the nuclear fraction of PMNs exposed to NDMA. A decrease in iNOS expression in the cytoplasmic fraction, and also c-Jun in both fractions of the examined cells, was observed as a result of JNK pathway inhibition. The blocking of the ERK5 pathway led to higher iNOS, c-Jun and c-Fos expression in the cytoplasmic fraction, and higher c-Jun expression in the nuclear fraction of PMNs exposed to NDMA. The study also demonstrated that blocking of the p38 and JNK pathways resulted in higher expression of NF-κB p65 and IκB-α in the cytoplasmic fraction and their lower expression in the nuclear fraction of these cells. Conclusion: Our data indicate the role of MAP kinases p38 and JNK in the activation of c-Jun and NF-κB p65 transcription factors engaged in the regulation of iNOS expression in human neutrophils exposed to NDMA. However ERK5 kinase is not involved in the regulation of iNOS and NO production by those cells. [ABSTRACT FROM AUTHOR]

Purpose: Short-term and saturated simulated dives followed by decompression with air, cause a decrease in platelet count and increased activation of fibrinolysis. The aim of this study was to determine whether short-term dives with trimix as a breathing mixture induce the activation of platelets, and/or fibrinolysis.Material and Methods: 30 male divers were subjected to short-term hyperbaric exposures to 0.7 MPa. Thirty divers used air and then the same divers used trimix as a breathing mixture. Results: The mean platelet count dropped significantly after decompression only in the group breathing air. The number of CD62P positive platelets and the amount of platelet-derived micro particles were statistically significant higher after decompression in both exposures. The number of CD61 positive platelets increased significantly only in the group breathing air. We observed a significant decrease of factor XII and fibrinogen concentrations after decompression only in the group breathing air. A significant increase in the concentration of plasminantiplasmin complex in both groups was detected.Conclusions: Short-term hyperbaric exposure and decompression performed according to current safety standards activates platelets and the fibrinolytic system. Trimix protects divers from a reduction in the amount of platelets, fibrinogen and factor XII in the course of these exposures. [ABSTRACT FROM AUTHOR]

Blood circulating in extracorporeal circuit of the apheresis sets has a contact with an artificial surface. The data on the influence of plateletpheresis on fibrinolytic activity are very limited and difficult to interpret. The aim of our study was to estimate the effect of plateletpheresis on the activation of fibrinolysis. Plateletpheresis was performed in 17 healthy blood donors using continuous-flow cell separator COM.TEC (Fresenius, Bad Homburg, Germany). Before and after plateletpheresis, blood samples were taken and markers of fibrinolysis (PAP, t-PA, PAI-1) as well as factor XII activity have been measured. We observed statistically significant decrease in t-PA and factor XII activities after plateletpheresis. There were no significant changes in concentrations of t-PA, PAI-1 and PAP as well as PAI-1 activity after plateletpheresis. Plateletpheresis performed by COM.TEC cell separator has very little, if any, effect on the activation of fibrinolysis. The mechanism of the inhibition of t-PA activity needs further investigations. [ABSTRACT FROM AUTHOR]

Design: The studies reported were designed to evaluate the effects of ML3000 on platelet aggregation and platelet-induced thrombin generation in human platelet rich plasma and its antithrombotic effect in a rat thrombosis model. ML3000 is a potent inhibitor of both COX-1/2 and 5-LOX with demonstrated antiinflammatory activity and a low incidence of GI mucosal injury in animal and human studies.¶ Methods and results: The antithrombotic activity of ML3000 (10, 30 and 100 mg/kg) and aspirin (30 and 100 mg/kg) was measured in the mesenteric venules of rats using the laser-induced thrombus model. Both ML3000 and aspirin, at all doses tested, showed significant antithrombotic activity. The mean number of laser injuries necessary to induce a thrombus that blocked the vessel was 1.93 ± 0.28 in the control group, 3.3 ± 0.53, 3.6 ± 0.14 or 4.07 ± 0.37 in the groups treated with ML3000 at 10, 30 or 100 mg/kg p.o. and 3.4 ± 0.55 or 3.9 ± 0.3 in the groups treated with Aspirin at 30 or 100 mg/kg p.o. The antithrombotic activity in this model was significant up to 12 h post-administration of 100 mg/kg ML3000 or Aspirin.¶ The aggregation inhibiting activity of ML3000 (1-100 μg/ml) and indomethacin (1 μg/ml) was studied using the following inducing agents: ADP (1 and 2 μM), epinephrine (25 and 50 μM), collagen (0.5 and 1 μg/ml), and the thromboxane mimetic U46619 (0.8 and 1.6 μM). Aggregation inhibitory activity was observed with ML3000 in all assays except with the higher concentration of U46619 at 1.6 μM. Indomethacin (1 μg/ml) inhibited aggregation in all assays.¶ Conclusions: ML3000 has significant antithrombotic activity and a marked platelet aggregation inhibiting effect. Given its demonstrated antiinflammatory activity, platelet function inhibition, and antithrombotic effects along with a lack of effect on the GI mucosa, ML3000 may offer an alternative to the combination of a COX-2 inhibitor and aspirin in arthritis patients at risk for cardiovascular disease. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the possible interactions of LW 10082 with several other antithrombotic agents. The antithrombotic effects of all agents were studied in a thrombosis model in which rat mesenteric venules (diameter 20–30 μm) were injured by well-defined argon laser lesions. The number of laser injuries which were needed to induce a thrombus that intermittently occluded the vessel was used to quantify the results. LW 10082 was injected s.c. 2 h before testing. The minimal effective dose which significantly inhibited thrombus formation was 5 mg/kg−1. The minimal effective dose of Daltroban (orally 2 h before testing) was 10 mg/kg−1. At 30 min after i.v. injection of 0.1 mg/kg−1 Molsidomin, a significant antithrombotic activity was present. Ticlopidine inhibited thrombus formation if administered orally for 3 days at a dose of 2×10 mg/kg−1. A 5 mg/kg−1 dose of LW 10082 given together with Molsidomin produced a strong additive effect. The combination of LW 10082 and Daltroban also had a significant additive effect. There was a slight but not significant additive effect between LW 10082 and Ticlopidine. In conclusion, LW 10082 and some other antithrombotic agents show additive effects in the prevention of laser-induced thrombus formation in the rat microcirculation. The clinical use of such combinations seems possible in patients at high risk of thrombotic vascular occlusion. [ABSTRACT FROM AUTHOR]

Von Willebrand factor antigen (vWF:Ag) is synthesized and secreted by endothelial cells. In the present study we tried to assess the relationship between plasma level of vWF:Ag and vascular damage in patients with vasculitis. The study was carried out on 59 patients with connective tissue diseases. Vasculitis was diagnosed by biopsies of the skin. The patients with vasculitis had a significantly elevated level of vWF: Ag; however, no significant correlation between the amount of plasma vWF:Ag and the degree of vasculitis was found. The obtained results show that the plasma level of vWF: Ag may reflect the presence of vascular, especially endothelial, damage in patients with connective tissue diseases. [ABSTRACT FROM AUTHOR]