The effects of hyperglycaemia on thrombin-activatable fibrinolysis inhibitor.
ABSTRACT Epidemiological studies have shown a strong association between type 2 diabetes mellitus and cardiovascular diseases, and hypofibrinolysis may contribute to this phenomenon. The aim of this study was to determine the effect of hyperglycaemia on thrombin-activatable fibrinolysis inhibitor (TAFI). Hyperglycaemia was mimicked in vitro by incubation of TAFI with glyceraldehyde and in vivo by hyperglycaemic clamping of healthy volunteers. The effects of long-term hyperglycaemia in vivo on TAFI were investigated by comparing TAFI from poorly regulated and tightly regulated patients with type 2 diabetes. In vitro glycated TAFI showed an altered migration pattern on SDS-PAGE due to aggregation. Glycated TAFI showed decreased activity after activation by thrombin-thrombomodulin in a glyceraldehyde-dose-dependent manner and a reduced anti-fibrinolytic potential. In vivo, no differences in TAFI parameters were found after hyperglycaemic clamping of healthy volunteers and between tightly and poorly regulated patients with type 2 diabetes. Moreover, TAFI purified from poorly regulated and tightly regulated patients with type 2 diabetes migrated similarly on SDS-PAGE, indicating little or no glycation of the protein. Despite the deleterious effects of glycation of TAFI in vitro on its function, TAFI was neither affected by hyperglycaemic clamping, nor by long-term hyperglycaemia in patients with type 2 diabetes. This is in contrast to fibrinolytic factors as plasminogen-activator inhibitor I and tissue-type plasminogen activator, which are affected. We therefore hypothesise that a normally functioning TAFI under hyperglycaemic conditions may tip the haemostatic balance towards hypofibrinolysis, which may contribute to the development of cardiovascular diseases in type 2 diabetic patients.
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ABSTRACT: The main limitation to the accuracy of the detection of a bridge deflection using laser-based optical solutions is atmospheric turbulence because of the laser beam propagation in ground proximity. The multi-beam method is presented to increase the stability of bridge deflection measurement. It is based on the use of a four-beam optical system and a subpixel resolution algorithm for the measurement of the deflection of a laser beam that propagates through the system. To obtain accurate results, different algorithms for measuring the position of the deflected beam in different optical systems are tested and compared. Based on this comparison, the four-beam method based on the macropixels iteration centroid and four-beam optical system is selected, and an accuracy of 0.16 pixels is obtained by the determination of the beam position in our setup. The proposed method is adopted to detect the bridge deflection and an accuracy of 0.01mm is gained when the scintillation index Cn2 is 3×10−4m−2/3.Optics & Laser Technology 01/2011; 43(7):1198-1202. · 1.37 Impact Factor
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ABSTRACT: We aimed to determine plasma thrombin-activatable fibrinolysis inhibitor (TAFI) antigen levels in women with previous gestational diabetes mellitus (GDM) and to evaluate the possible association of plasma TAFI with glucose intolerance and markers of subclinical atherosclerosis. This cross-sectional study was performed in 111 women with previous GDM and 60 controls. Glucose intolerance was evaluated. Homeostasis model assessment score was calculated. Circulating lipids, interleukin-6, matrix metalloproteinase-1, fibrinogen, plasminogen activator inhibitor-1, and TAFI antigen levels were assayed. Carotid intima media thickness (IMT) was measured. Women with previous GDM had increased levels of atherosclerosis markers and carotid IMT. On the other hand, plasma TAFI antigen levels were similar (P = .395). Thrombin-activatable fibrinolysis inhibitor was not associated with the indices of insulin resistance, glucose intolerance, markers of atherosclerosis, and carotid IMT. Our data demonstrated that plasma TAFI was not altered in women with previous GDM. TAFI was not associated with glucose intolerance and subclinical atherosclerosis.Clinical and Applied Thrombosis/Hemostasis 03/2011; 17(6):E224-30. · 1.02 Impact Factor