[Hypocoagulant effect of the novel dipeptide NGF mimetic GK-2].

The effect of an original dimeric dipeptide NGF mimetic, GK-2 (hexamethylenediamide bis-N-monosuccinyl-L-glutamyl-L-lysine, designed on the basis of the beta-turn of the 4th NGF loop) on the hemostasis and fibrinolysis was studied in intact and diabetic Wistar rats in various periods of disorder development. Model diabetes was induced by single streptozotocin (40 mg/kg i.p.) administration. Blood glucose level, main parameters of thromboelastograms, and euglobulin clot lysis time were measured. The effect of GK-2 was studied under ex vivo conditions, by adding freshly prepared peptide solution to the blood plasma. The maximum increase in the thrombosis probability was observed in ten days after streptozotocin injection, as manifested by an increase in coagulation indices CI and I together with a decrease in the euglobulin clot lysis time. Adding GK-2 (10(-5) M) to the blood plasma was found to normalize these parameters. The tendency to hypocoagulant effect was also observed in experiments with GK-2 adding to the blood plasma of intact animals. The hypocoagulant effect of GK-2 in combination with its antihyperglycemic effect (revealed previously) is of great importance, since diabetes is known to be accompanied by violated microcirculation and increased risk of thrombosis.

[Anticoagulative and anticomplementary activity of endogenous inhibitor preparation from hepatopancreas of red king crab (Paralithosed camtschaticus) towards human blood].

Serpins (SERine Protease INhibitors)--is large and diverse group of proteins with similar structures, which can inhibit both serine and cysteine proteases by an irreversible suicide mechanism. A novel serpin from hepatopancreas of Red King Crab (Paralithosed camtschaticus) was obtained and was studied its effect on the process of human blood plasma clotting. The investigated serpin shows a noticeable anticoagulative activity, which increases dramatically in the combined action with heparine. Though the inhibitor has almost no effect on thrombin, it inhibits C1s (C1-esterase). We studied the action of the serpin from P. camtschaticus on C1s via its competitive inhibition by C1 inhibitor and the novel enzyme. The calculated inhibition constant of the serpin from P. camtschaticus towards C1s is 2.02 +/- 0.71 M. Unlike C1 inhibitor, the novel serpin from P. camtschaticus doesn't suppress fibrinolysis and at the same time prevents blood clotting. These features may be of interest for medical purposes.

[Use of biologically active supplement containing omega-3 polyunsaturated fatty acids in patients with type 2 diabetes mellitus]. / Primenenie biologicheski aktivnoi dobavki, soderzhashchei polinenasyshchennye zhirnye kisloty semeistva omega-3, u bol'nykh sakharnym diabetom 2 tipa.

35 patients with diabetes mellitus type 2 complicated with hyperlipidemia, coronary heart disease were treated during 8 months with poseidonol--polyunsaturated fatty acid family omega 3 (PUFA--omega 3). It was shown that hypercoagulation and hypofibrinolysis in these patients occurred. Treatment with poceidonol increased plasminogen activator activity and decreased coagulation and reduced atherogenic index.

[Effect of diet therapy on status of hemocoagulation and fibrinolysis in type 2 diabetes patients]. / Vliianie dietoterapii na sostoianie gemokoaguliatsii i fibrinoliz u bol'nykh sakharnym diabetom 2 tipa.

The changes in parameters of blood coagulation and the fibrinolytic system in 60 patients with type 2 diabetes mellitus was studied. We conclude what the non insulin depended diabetes mellitus is associated with disturbances in hemostatic and fibrinolytic systems that could contribute to the development of diabetic vascular disease. Besides favorable influence to a clinical picture of disease universal normalizing influence of traditional diet therapy on parameters of coagulation and the fibrinolytic system. Our results show that diet therapy improve metabolic control in type 2 diabetic patients could reflect a reduces thrombotic potential and decreased cardiovascular risk.

[Effects of tycveinol on the lipid transport system and hemostasis and fibrinolysis systems in patients with ischemic heart disease]. / Vliianie tykvéinola na lipidtransportnuiu sistemu i sistemy gemostaza, fibrinoliza bol'nykh ishemicheskoi bolezn'iu serdtsa.

33 patients with ischemic heart diseases, hyperlipidemia and blood hypercoagulation took tycveinol which consists of polyunsaturated fatty acids in a dose of 2.0 g twice a day for 2 months. A positive result manifested by a 14% drop in cholesterol, 29.7% in triglycerides, 21% in beta-lipoproteins. Alpha-lipoproteins rose by 26%, atherogenic index reduced from 3.24 to 1.89. Hypercoagulatory tension relieved due to normalization of euglobulin lysis, higher activity of plasminogen tissue activator, slow blood clotting. Side effects on hepatic or renal function, mineral metabolism were not observed.

[Influence polyunsaturated fatty acids omega-3 on coagulation and fibrinolysis systems in patients with NIDDM]. / Vliianie polinenasyshchennykh zhirnykh kislot omega-3-klassa na sistemy svertyvaniia krovi i fibrinoliza bol'nykh sakharnym diabetom tipa 2]

35 patients with diabetes mellitus type 2 complicated with hyperlipidemia, coronary heart disease, were treated for 8 months with poseidonol which incorporates essential polyunsaturated fatty acids and fat-soluble vitamins. Poseidonol reduced atherogenic index from 4.2 to 3.15. The study of blood coagulation and fibrinolysis points to signs of hypocoagulation and normalization of fibrinolytic activity against previous hypercoagulation and fibrinolysis depression.

[Effect of the proteolytic substance morikrase on the status of scar tissue under in vitro conditions]. / Deistvie proteoliticheskogo preparata morikrazy na sostoianie rubtsovoi tkani v usloviiakh in vitro.

Proteolytical preparation moricrasa was isolated from hepatopancreas of Paralithodes camtshatic. Moricrasa and its fractions were used for lysis of cicatricial tissue under in vitro conditions. It was found that moricrasa in concentrations 0.5 mg/ml and 2 mg/ml lysed the cicatrix during 72 and 14-16 hours, respectively. The fraction consisted of collagenolytic proteinase PC and trypsin revealed maximal activity of fraction of moricrasa was absent.

[Role of local fibrinolytic activity of the uterine horns in rats in the pathogenesis of formation of postoperative adhesions]. / Rol' lokal'noi fibrinoliticheskoi aktivnosti matochnykh rogov u krys v patogeneze formirovaniia posleoperatsionnykh spaek.

Experimental models were used to examine the impact of corrections of the uterine horns on the activity of tissue plasminogen activator (tPA). The application of sutures was shown to suppress the activity of tPA in the uterine horns to a greater extent than other surgical techniques. With this, the use of catgut caused the highest suppression of tPA activity and increases in the frequency and density of formation of postoperative adhesions. Depleted tPA reserves and its higher inhibitor levels were found to lead to depressed fibrinolysis, which is a pathogenetic factor for developing an adhesive process.

[Effect of docanol on the status of hemostasis and fibrinolysis systems, as well as lipid spectrum in patients with ischemic heart disease depending on the initial level of fibrinolytic activity]. / Vliianie dokanola na sostoianie sistem gemostaza, fibrinoliza i lipidnyi spektr u bol'nykh ishemicheskoi bolezn'iu serdtsa v zavisimosti ot iskhodnogo urovnia fibrinoliticheskoi aktivnosti.

Forty patients with coronary heart disease (CHD) concurrent with hyperlipidemia were divided into 2 groups according to the baseline fibrinolytic activity. The group with the depressed fibrinolytic system displayed the highest atherogenicity index and levels of cholesterol, low and very low density lipoprotein cholesterol and half levels of high density lipoproteins. After 45-day ingestion of docanol, a new Russian food additive containing docosahexanoic and eicosapentaenoic acids there were positive changes in the lipid spectrum in the both groups. The fibrinolytic changes were heterodirectional: activator and plasma activities increased in the group of fibrinolytic depression while in the group of baseline normal fibrinolysis the activity of plasminogen activator fell.

[Fibrinolytic and thrombolytic properties of the drug morikrase]. / Fibrinoliticheskie i tromboliticheskie svoistva preparata morikrazy.

Fibrinolytic and thrombolytic properties of morikrase, a complex of proteinases obtained from hepatopancreatic tissues of king crab (Paralithodes camtschatica), were studied in vivo and in vitro. High fibrinolytic activity and dose-dependent activating properties were detected on standard and heated fibrin plates. The preparation maintained its properties during long-term storage at 4 degrees and 22 degrees C. The thrombolytic activity of the drug, affecting the preformed thrombus, was observed both in vitro and in vivo, in rats with experimental thrombosis. Two-phase alteration of the fibrinolytic system and moderate hypocoagulation were found after intravenous administration of morikrase.

[The wound healing effect of ointment with morikrase]. / Ranozazhivliaiushchee deistvi mazi s morikrazoi.

An ointment containing, 1% morikrase (a complex of proteinases isolated from hepatopancreatic tissues of king crab Paralithodes camtschatica) exhibited the wound healing properties and did not irritate the skin tissues during long-term treatments of rats. Only slight hypocoagulation was observed in intact animals after external application of the ointment. At the same time, the drug caused an increase in fibrinolytic activity in blood of rats with purulent wounds due to activation of the plasminogen activator.

[Newly developed stenocardia: effect of intensive physical training on the indicators of the blood coagulation system and fibrinolysis]. / Vpervye voznikshaia stenokardiia: vliianie intensivnykh fizicheskikh trenirovok na pokazateli svertyvaiushchei sistemy krovi i fibrinoliza.

The impact of 6-week strenuous exercise training (SET) on blood coagulative and fibrinolytic parameters (levels of fibrinogen, soluble fibrin, fibrinogen-fibrin degradation products, activities of plasminogen and plasmin) was studied in 28 patients with first angina pectoris, in 16 of whom in the first 3 months of onset of the disease, but angina pectoris lasting 3-4 prior to SET. The 6-week strenuous exercises in patients with first angina were found to cause a decrease in fibrinogen levels, exert no action on thrombin and fibrin formation. They did not diminish plasminogen activator release during exercise in patients with pre-exercise unstable angina.

[Study of the thrombolytic and fibrinolytic properties of thiol- dependent serine proteinase (TSP) from Thermoactinomyces vulgaris in vivo]. / Izuchenie tromboliticheskikh i fibrinoliticheskikh svoistv preparata tiolzavisimoi serinovoi proteinazy (TSP) iz Termoactinomyces vulgaris v usloviiakh in vivo.

Experiments on male albino rats showed that the thyol-dependent serine proteinase (TSP) dissolved the thrombus in the jugular vein for 2-5 hr. Intravenous injection of TSP activated the fibrinolytic system of intact animals by increasing the levels of the plasminogen activator and plasmin in the euglobulin fraction. The response of the fibrinolytic system on the intravenous injection of TSP (2mg/200 g) was different: in some rats, fibrinolysis was activated, while on others, it was inhibited. TSP in high doses caused the death of 60% of experimental animals.

[Fibrinolytic properties of protease complex isolated from the culture fluid of Nocardia minima]. / Fibrinoliticheskie svoistva kompleksa proteaz, vydelennogo iz kul'tural'noi zhidkosti Nocardia minima.

The protease complex isolated form the Nocardia minima culture liquid was studied in vitro. The preparation had two different activities (fibrinolytic and activating), i.e. it was able to convert plasminogen into plasmin. At a concentration of 250 micrograms/ml and above the preparation lysed experimental thrombi. The fibrinolytic activity of the preparation was completely inhibited with normal human plasma.

[Interleukin-1 and fibrinolysis. In vivo studies]. / Interleikin-1 i fibrinoliz. Issledovaniia v usloviiakh in vivo.

Distinct decrease in fibrinolytic activity of both whole blood plasma and its euglobulin fraction, occurring due to liberation of an inhibitor of plasminogen activator into circulation, was observed within 2-4 hrs after a single intravenous administration of rabbit interleukin-I into rats at a dose of 50 micrograms/kg, while the activator activity was increased in kidney heart, spleen and lung tissues. The similar data were obtained if the dose was either increased up to 150 micrograms/kg or decreased down to 5 micrograms/kg and 0.5 micrograms/kg, but the effect observed proved to be dose-dependent. Three injections of interleukin-I caused more pronounced increase in concentration of fibrinogen and antiplasmins as compared with controls.

[Newly developed stenocardia: fibrinolysis and hemostasis at rest and during physical exercise after myocardial infarction]. / Vpervye voznikshaia stenokardiia: fibrinoliz i gemostaz v pokoe i pri fizicheskoi nagruzke u bo'lnykh, perenesshikh v étot period infarkt miokarda.

Postmyocardial infarction patients with angina of new onset showed increased blood levels of fibrinogens, soluble fibrin and fibrinogen-fibrin degradation products one month after the acute onset of MI, while their baseline fibrinolysis had been normal. A variety of fibrinolytic disorders were revealed in response to physical stress.