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Varna, Bulgaria

Kovacs A.,Semmelweis University | Szabo L.,Hungarian Academy of Sciences | Longstaff C.,UK National Institute for Biological Standards and Control | Tenekedjiev K.,Ny Vaptsarov Naval Academy | And 2 more authors.
Thrombosis Research | Year: 2014

Background Removal of C-terminal lysine residues that are continuously exposed in lysing fibrin is an established anti-fibrinolytic mechanism dependent on the plasma carboxypeptidase TAFIa, which also removes arginines that are exposed at the time of fibrinogen clotting by thrombin. Objective To evaluate the impact of alterations in fibrin structure mediated by constitutive carboxypeptidase activity on the function of fibrin as a template for tissue plasminogen activator-(tPA) induced plasminogen activation and its susceptibility to digestion by plasmin. Methods and results We used the stable carboxypeptidase B (CPB), which shows the same substrate specificity as TAFIa. If 1.5 - 6 μM fibrinogen was clotted in the presence of 8 U/mL CPB, a denser fibrin network was formed with thinner fibers (the median fiber diameter decreased from 138 - 144 nm to 89 - 109 nm as established with scanning electron microscopy). If clotting was initiated in the presence of 5 - 10 μM arginine, a similar decrease in fiber diameter (82 -95 nm) was measured. The fine structure of arginine-treated fibrin enhanced plasminogen activation by tPA, but slowed down lysis monitored using fluorescent tPA and confocal laser microscopy. However, if lysis was initiated with plasmin in CPB-treated fibrin, the rate of dissolution increased to a degree corresponding to doubling of the plasmin concentration. Conclusion The present data evidence that CPB activity generates fine-mesh fibrin which is more difficult to lyse by tPA, but conversely, CPB and plasmin together can stimulate fibrinolysis, possibly by enhancing plasmin diffusion. © 2013 The Authors. Published by Elsevier Ltd. All rights reserved. Source


Varju I.,Semmelweis University | Sotonyi P.,Semmelweis University | Machovich R.,Semmelweis University | Szabo L.,Hungarian Academy of Sciences | And 4 more authors.
Journal of Thrombosis and Haemostasis | Year: 2011

Background: Recent data indicate that stretching forces cause a dramatic decrease in clot volume accompanied by gross conformational changes of fibrin structure. Objective: The present study attempts to characterize the lytic susceptibility of fibrin exposed to mechanical stress as a model for fibrin structures observed in vivo. Methods and results: The relevance of stretched fibrin models was substantiated by scanning electron microscopic (SEM) evaluation of human thrombi removed during surgery, where surface fibrin fibers were observed to be oriented in the direction of shear forces, whereas interior fibers formed a random spatial meshwork. These structural variations were modeled in vitro with fibrin exposed to adjustable mechanical stress. After two- and three-fold longitudinal stretching (2×S, 3×S) the median fiber diameter and pore area in SEM images of fibrin decreased two- to three-fold. Application of tissue plasminogen activator (tPA) to the surface of model clots, which contained plasminogen, resulted in plasmin generation which was measured in the fluid phase. After 30-min activation 12.6±0.46pmolmm-2 plasmin was released from the non-stretched clot (NS), 5.5± 1.11pmolmm-2 from 2×S and 2.3±0.36pmolmm-2 from 3×S clot and this hampered plasmin generation was accompanied by decreased release of fibrin degradation products from stretched fibrins. Confocal microscopic images showed that a green fluorescent protein-fusion variant of tPA accumulated in the superficial layer of NS, but not in stretched fibrin. Conclusion: Mechanical stress confers proteolytic resistance to fibrin, which is a result of impaired plasminogen activation coupled to lower plasmin sensitivity of the denser fibrin network. © 2011 International Society on Thrombosis and Haemostasis. Source


Hristova A.,Ny Vaptsarov Naval Academy | Dimov T.,University of Shumen | Iliev I.,University of Shumen
Bulgarian Chemical Communications | Year: 2015

There have been studied the features of absorption of uniaxial gyrotropic crystals Magnesium sulfite hexahydrate, doped with impure Co-ions (MgSO3.6H2O:Co). The experiment have been conducted using linear polarized light E→||c and E→⊥c (c is the optical axis of the crystal) in the visible spectra range from 400 nm to 650 nm, where is the Co-ion's absorption band. Impurities cause the appearance of additional structures in the spectra of the crystal, which have been described and analyzed on qualitative level. The linear dichroism in the absorption of impurity ions inside the crystal lattice has been analyzed. © 2015 Bulgarian Academy of Sciences, Union of Chemists in Bulgaria. Source

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