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Over-activation of the fibrinolytic system may result in proteolytic destruction of fibrinogen. However, the effect of the degradation products formed during fibrinogenolysis on fibrinolytic process and plasminogen/plasmin properties remains unclear. To investigate this effect and its mechanism, the ability of fibrinogen fragments E and D to act on plasminogen and tPA binding, proenzyme activation, fibrin clot lysis and plasmin inhibition by plasma α2-antiplasmin, were studied. It was found that early product fragment EE binds to plasminogen and tissue-type plasminogen activator and enhances plasminogen conversion into plasmin. C-terminal lysine residues of all 3 chains pair and 16 or 23 amino acid residues of Aα- chain are essential for this process. C-terminal lysines of fragment E Aα- and γ-chains and lysine-binding site of tPA kringle 2 are responsible for the interaction between these proteins. Binding of fragment E to plasminogen is provided by N-terminal Aα1–19 and C-terminal Bβ120–122 regions. Late plasmic fibrinogen degradation product fragment EL loses the ability to potentiate plasmin generation but can bind proenzyme and its activator. Fragment D has no binding properties towards plasminogen and tPA. None of fibrinogen fragments protects plasmin from α2-antiplasmin inhibition. It is concluded that at over-activation of the fibrinolytic system and subsequent fibrinogenolysis, the products of fibrinogen degradation, can bind plasminogen and tPA and potentiate generation of plasmin, which will be neutralized under the normal level of the plasmin inhibitor.
Uric acid is the end product of dietary and endogenous purine metabolism in humans and higher primates. In all lower mammalian species it is converted to allantoin by liver uricase. The aim of this study was to investigate the uric acid turnover in pig model after nephrectomy surgery, fructose-enriched diet and potassium oxonate application. The first experiment was performed using 4 intact control pigs and 8 nephrectomized (5/6 nephrectomy) pigs. Both groups were fed high-fat diet enriched with 20% of fructose for 3 weeks. During the second experiment, as another approach to induce hyperuricemia, potassium oxonate solution (POx) was administered intravenously to 4 healthy pigs, once or twice per day. In the third preliminary experiment one healthy and two nephrectomized (9/10 nephrectomy) pigs were infused with POx to induce hyperuricemia. Results showed that 5/6 nephrecotomy did not affect plasma uric acid concentration for 25 days following surgery. The consumption of the highfat diet enriched with 20% of fructose did not result in the rise of plasma uric acid, either in healthy or nephrectomized pigs. Administration of POx solution to healthy and 9/10 nephrectomized pigs resulted in significantly increased plasma uric acid concentrations for 18 h and 24 h, respectively, following a single POx infusion. The present study expands today available data on uric acid metabolism in pigs as a model for exploring uricemia in human with kidney dysfunction
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