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.     

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.     

The protective effect of the arginine-heparin complex under simulation of insulin-dependent diabetes

Daily intramuscular injections of the arginine-heparin complex for 5 days before injection of diabetogenic metabolite alloxan did not cause insulin-dependent diabetes in animals for 3 weeks. As a result of these injections, the anticoagulant fibrinolytic pattern of the anticoagulant system was activated and the platelet aggregation decreased. This effect held for 7 days after injection.     

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.     

The Status of the Hemostasis System under the Influence of Proline Peptides during the Development of Experimental Metabolic Syndrome

A comparative study of the influence of regulatory proline peptides Pro–Gly–Pro, Pro–Arg–Pro, Pro–Gly–Pro–Leu, and Arg–Pro–Gly–Pro on the state of the hemostasis system was carried out in an experiment on male rats with metabolic syndrome. Under these conditions, repeated (7-fold) intranasal administration of the peptides in a daily dose of 50 μg/kg resulted in an increase in the anticoagulant potential of the blood, namely, in an increase in the anticoagulant, fibrinolytic, and antiplatelet activity 20 h and 7 days after the last peptide injection. The arginine–containing peptide Arg–Pro–Gly–Pro had the most pronounced and stable effect on haemostasis under these experimental conditions.     

Anticoagulant, Fibrinolytic, and Antithrombotic Effects of the Heparin–Insulin Complex

Formation of heparin–insulin complex at the 1 : 10 molar ratio of the components has been demonstrated by spectral methods. The derived complex had anticoagulant, antithrombotic, and fibrinolytic properties of nonenzymatic nature in vitro. Intravenous injection of the complex in the animals (rats) increased anticoagulant and fibrinolytic background and at the same time decreased the plasma coagulation factors fibrinogen and factor XIIIa in the bloodstream. We propose the heparin–insulin complex as a promising antithrombotic drug.     

Anticoagulant and nonenzymatic fibrinolytic activity of plasma in animals after intravenous injection of a heparin-antithrombin III complex

The heparin-antithrombin III complex with a weight ratio 1:3 had a powerful anticoagulant and non-enzymatic fibrinolytic activity in vitro. Seven and 30 min after intravenous injection of the complex the animal blood plasma showed a considerable prolongation of the thrombin time and an increase in non-enzymatic fibrinolytic activity. The effect of heparin injected in a dose equivalent to its content in the complex on the parameters under study was appreciably less and disappeared by the 30th minute of the observation period.     

Anticoagulation system in animals during learning under the effects of mild magnetic field and opioid peptide opilong

Information load in Wistar rats has not affected the functional state of the anticoagulant system after 20 sessions of learning to solve a food-searching task in comparison with intact animals. Learning under the combined effect of mild magnetic field and pretreatment with five intramuscular injections of an opioid peptide opilong has significantly improved the cognitive behavior but induced an increase in coagulation, imbalance in fibrinolytic processes, and inhibition of the anticoagulation system.     

The interaction of histone and protamine with actin. Possible involvement in the formation of the mitotic spindle

At low ionic strength 1–2 μM protamine or 1–2 μM H1 histone induce the nucleation of G-ATP actin. At high ionic strength 1–2 μM protamine or 0.1 to 0.2 μM H1 histone accelerate by 3 to 4 times the rate of polymerisation of G-ATP actin. It is suggested that histone may trigger the formation of actin fibers running from the kinetochore of the chromosome to the pole of the mitotic spindle.     

Fibrinolytic and anticoagulant complexes of low-molecular heparin with tuftsin]

The complex of immunopeptide taftsin with low-molecular heparin has been obtained. The complex has fibrinolytic and anticoagulant activities in vitro and in vivo after the injection to albino rats.     

Comparative studies of anticoagulant and fibrinolytic effects of glyprolines Gly-Pro and Gly-Pro-Arg in conditions of immobilization stress

It has been shown that proline-containing peptides Gly-Pro and Gly-Pro-Arg in vitro had anticoagulant and nonenzymatic fibrinolytic activity. It was established that after intranasal introduction of these peptides to a rat, anticoagulant and fibrinolytic activity of enzymatic and nonenzymatic nature increased in the rat blood. The peptide protective effect against hypercoagulation induced by immobilization stress was found after repeated intranasal introduction of each peptide into the animal.     

Complex Compound of Heparin and Glutamic Acid: Synthesis and Effect on Hemostatic Indices in vitro and in vivo

A complex compound of high-molecular heparin and glutamic acid has been synthesized. This compound has anticoagulant, fibrinolytic, and antithrombotic properties in vitro. Single intravenous or chronic peroral introduction of the complex in normal animals imitates the activation of anticoagulation system. When the anticoagulation system in depressed, the complex restores or even activates the anticoagulant–fibrinolytic background of the serum it. The obtained data are discussed in physiological terms.     

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.Translated from Izvestiya Akademii Nauk, Seriya Biologicheskaya, No. 2, 2005, pp. 221–225.Original Russian Text Copyright © 2005 by Lyapina, Pastorova, Nikolaeva.     

Isolation, purification, and separation of the complex preparation of extracellular proteinases with fibrinolytic and anticoagulant properties from Aspergillus ochraceus 513]

The extracellular proteinase complex of the microscopic fungus Aspergillus ochraceus 513 was isolated, purified, and separated by affinity chromatography on bacillichin-silochrom and subsequent column chromatography on DEAE-Toyopearl 650 M. The extracellular enzyme of the protein C activator type had a molecular mass of 36.5 kDa and activity close to that of the Agkistrodon snake venom protein C activator. The fibrinolytic and anticoagulant activities of the enzyme were investigated.     

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.     

Effects of anticoagulant from Spirodela polyrhiza in rats

A fibrinolytic protease was purified from an Oriental medicinal herb, Spirodela polyrhiza (Choi, H. S., et al., Biosci. Biotechnol. Biochem., 65, 781-786 (2001)). The protease hydrolyzed not only fibrin but also fibrinogen. The enzyme had an anticoagulant activity measured with activated partial thromboplastin time, thrombin time, and prothrombin time in rat plasma. It doubled all three at 69, 29, and 221 nM, respectively. The protein had anticoagulant activity when given intravenously and orally. The maximum delay in the activated partial thromboplastin time was at the dose of 0.52 and 4.2 mg/kg for intravenous and oral administration, respectively. This protein may be useful in clinical applications for anticoagulation.     

Isolation,Purification, and Resolution of the Extracellular Proteinase Complex of Aspergillus ochraceus513 with Fibrinolytic and Anticoagulant Activities

The extracellular proteinase complex of the microscopic fungus Aspergillus ochraceus513 was isolated, purified, and resolved by affinity chromatography on bacillichin-silochrom and subsequent column chromatography on DEAE-Toyopearl 650M. The extracellular enzyme of the protein C activator type had a molecular mass of 36.5 kDa and activity close to that of the Agkistrodonsnake venom protein C activator. The fibrinolytic and anticoagulant activities of the enzyme were investigated.     

Status of fibrinolysis in systemic lupus erythematosus

In patients with systemic lupus erythematosus (SLE) both a haemorrhagic diathesis and a tendency to thrombosis of the venous and arterial vessels can be observed. In the course of the disease, thrombosis of the leg or pelvic veins developed in 20 per cent of 188 patients. The levels of alpha 2-plasmin inhibitor, plasminogen, fibronectin and of factor VIII complex were increased in patients with SLE compared with a control group. Fifty per cent of the patients showed no increase in fibrinolytic activity after venous occlusion measured with the fibrin plate method. This suggests a reduced fibrinolytic capacity in SLE probably caused by alteration of the endothelial cells through immune complex vasculitis. In addition, the lupus anticoagulant and an acquired antithrombin III deficiency in nephrotic syndrome in SLE are to be considered thrombophilic mechanisms. In the individual case there is an overlapping of hyper- and hypocoagulability.     

Peculiarities of hemostasis reactivity under stress load in persons with different degree of physical training

Healthy young persons with different degrees of physical training have been impacted with exposure to a stress (a single physical exercise). It caused unidirectional hypercoagulative shifts and activation of anticoagulant and fibrinolytic blood systems. It was shown that changes of the untrained individuals' haemostatic parameters could be adjusted with adaptogen preliminary administration. The adaptogen administration in trained individuals resulted in disadaptive shifts in the haemostatic system. These contradictory changes indicate different levels of subject's adaptive potential.     

Correction of impairments in functions of anticoagulation and insular systems of an organism by the regulatory peptide Leu-Pro-Gly-Pro

It has been established that fivefold intranasal administration of the peptide Leu-Pro-Gly-Pro (1 mg/kg) to rats with developing refractory hyperglycemia leads to restoration and normalization of the functions of anticoagulation and insular systems. In the blood of experimental animals, there was a decrease in the sugar level and platelet aggregation and an increase in anticoagulant and all kinds of fibrinolytic (total, enzymatic, non-enzymatic, Hageman-dependent) activity.