V. E. Pastorova

Comparison of anticoagulant effects of regulatory proline-containing oligopeptides. Specificity of glyprolines, semax, and selank and potential for their practical application

Experimental and theoretical demonstrations of different effect of certain regulatory peptides (RPs) on blood coagulation are available. The problem of the role of RPs in hemostatic processes becomes particularly significant since, first, the peptides are widespread in nature both in animal and plant tissues, second, there is a relationship between the peptide structure and function and, third, both natural and synthetic peptides are used in practical medicine to correct functions of some factors of the hemostatic system. Many peptide inhibitors of the primary and plasma hemostasis potentiating anticoagulant effects in the body have been described.

Antidiabetic and Anticoagulant Properties of Heparin–Glutamic Acid Complex

Natural heparin complexes proved to activate the anticoagulation system. The obtained experimental data convincingly confirm that glutamic acid alone, and particularly in a complex with heparin, has a considerable preventive potential and efficiently protects experimental animals with induced diabetes mellitus.

Investigation of the Anticoagulant Activity of Several Low-Molecular-Weight Endogenous Ligands of Blood Plasma by Methods of Computer Simulation and Universal Biological Assay

A new method for the computer simulation of chemical equilibria in multicomponent biological liquids has been developed on the basis of a consistent analysis of the databank on equilibria in solutions, combined with the AUTOEQUIL program for the calculation of such equilibria. This method has been applied to the search for new low-molecular-weight endogenous blood anticoagulants with a mechanism of action based on reduction of the equilibrium concentration of biologically active Ca2+ ions by means of complex formation. Using the results of simulation of the metal-ion equilibria in blood plasma with a databank including over 800 units, an adequate model is created, which is capable of describing 64 equilibria in a basis set of 29 components. An analysis of these equilibria revealed four endogenous ligands capable of forming stable complexes with Ca2+, including glutamate (GLU), lactate (LAC), citrate (CIT) and adenosinetriphosphate (ATP). Their anticoagulant properties have been confirmed by universal biological assays in rats in terms of the plasma recalcification time (RCT) and the activated partial thromboplastin time (APTT). It has been found that the anticoagulant activities of components are as follows: LAC, 500%; ATP, 240%; GLU, 176%; CIT, 154%(relative to the substrate plasma activity of 100%).

[Hemostaseological description of the heparin-adenosine triphosphate (ATP) complex].

Biochemical methods confirmed the presence of the heparin-ATP complex. Acidic sulfur and carboxyl groups proved to mediate heparin-ATP complex formation. The technique for preparation of the heparin complex at a 1:20 weight ratio of the components and different pH was developed. Intramuscular administration of the resulting complex increased anticoagulant and fibrinolytic activities of animal (rat) plasma. The obtained data indicate the presence of physiologically active heparin-ATP complex providing for anticoagulant effects in the body.

[Effect of the heparin-lysine complex on the hemostatic and insular systems].

We studied the effect of chronic intraperitoneal administration of heparin–lysine complex on the state of the hemostatic and insular systems in young and senescent animals (rats). This complex exerted a positive effect on physiological function of the coagulant, anticoagulant, and fibrinolytic components of the hemostatic system in the norm and in developing experimental alloxan diabetes. In this case, both the complex and its components, lysine and heparin, had a pronounced antidiabetogenic effect.

[Fibrin-depolymerization activity and the antiplatelet effect of small cyclic and linear proline-containing peptides].

In our study of the effect of proline-containing linear di- and tri-peptides (Pro-Gly, Pro-Gly-Pro) and cyclic peptide cPro-Gly in vitro, we have found that they show depolymerizing activity towards the nonstabilized form of fibrin in the presence and in the absence of Σ-aminocapronic acid, an inhibitor of enzymatic fibrinolysis. The peptides have an inhibitory effect on platelet aggregation in platelet-enriched blood plasma, when the process is induced by ADP, they also diminish the activity of factor XIIIa in blood plasma.

Effect of Chronic Intramuscular Administration of Low Molecular Weight Heparin-Collagen Complex on Hemostatic Indices and Development of Alloxan-Induced Diabetes

Repeated intramuscular administration of low molecular weight heparin-collagen complex proved to increase fibrinolytic activity and to decrease platelet aggregation in the blood of rats (11 months) with depressed anticoagulant system. Administration of diabetogenic alloxan dose induced no diabetes mellitus in such animals.

Antiplatelet effect of adenosine triphosphate administration to animals under different experimental conditions

A significant and considerable decrease in abnormally high platelet aggregation has been demonstrated after intramuscular administration of sodium adenosine triphosphate (ATP) to rats with depressed anticoagulant system (in aging rats at the age of 11–12 months) and to rats with experimental diabetes both preliminarily and at the background of progressing diabetes. The elimination of one of thrombotic risk factors (decreasing elevated platelet aggregation) points to possible antithrombotic activity of ATP under these experimental conditions.

Comparative study of hemostatic properties of the complex and mixture of high molecular weight heparin and adenosine triphosphate

Anticoagulant and nonenzymatic fibrinolytic activities increased in blood plasma of 6–7-month-old rats after repeated intramuscular administration of the heparin-adenosine triphosphate complex (G-ATP). The mixture of heparin and ATP had no fibrin depolymerizing activity in vitro. Repeated intramuscular administration of the mixture had anticoagulant effect although it was 1.5–1.6 times less pronounced compared to the complex. A higher anticoagulant and fibrinolytic efficiency of the G-ATP complex compared to the mixture is concluded.

[Antidiabetic properties of high molecular weight heparin-adenosine triphosphate complex].

Repeated intramuscular administration of the heparin-adenosine triphosphate (ATP) complex or ATP increased plasma anticoagulant and fibrinolytic activities and depressed the anticoagulation system in rats at the age of 10–11 months. Diabetogenic dose of alloxan induced no diabetes mellitus in such animals.