Aptamer RA36 inhibits of human, rabbit, and rat plasma coagulation activated with thrombin or snake venom coagulases.

RA36 DNA aptamer is a direct anticoagulant prolonging clotting time of human, rabbit, and rat plasma in the thrombin time test. Anticoagulant activity of RA36 is lower than that of recombinant hirudin. During inhibition of human plasma clotting activated with echitox (coagulase from Echis multisquamatus venom), the aptamer presumably binds to meisothrombin exosite I. The sensitivity of human plasma to the aptamer 5-fold surpasses that of rat plasma. Analysis of RA36 binding to coagulase of Agkistrodon halys venom (ancistron) is required for proving the effect of aptamer on polymerization of human fibrinogen.

[Dependence of the anticoagulant activity of starch and inulin on their degree of sulfonation].

We have studied a relationship between the degree of sulfonation and anticoagulant activity of starch from Solanum tuberosum (molecular weight, 25000-30000 Da; sulfonation degree, 0.4-2.5) and inulin from Helianthus tuberosus (molecular weight, 7000-8000 Da; sulfonation degree, 0.6-1.6). Starch and inulin sulfates (i) increased the time of appearance of fibrin clots in plasma in coagulometric tests and (ii) reduced (via antithrombin) the rate of thrombin-induced hydrolysis of a chromogen substrate. The antithrombin (aIIa) activity of starch sulfates reached 16.8-70.0 IU/mg and the activity against factor Xa (aXa activity) was 2.3-16.6 IU/mg. The antithrombin activity of inulin sulfates was within 5.5-11.4 IU/mg and the activity against factor Xa (aXa activity) was within 0-1.4 IU/mg. An increase in the degree of sulfonation led to a growth in the anticoagulant activity of starch sulfates. The anticoagulant activity of starch sulfates and inulin sulfate with sulfonation degree 1.0 is mediated by antithrombin, which is the plasma inhibitor of serine proteases.

[Influence of new 1,3,4-thiadiazines on platelet aggregation in vitro and ex vivo].

The influence of new original 1,3,4-thiadiazines on the human platelet aggregation in vitro was studied. All substances inhibited the platelet aggregation induced by both ADP and arachidonic acid. 1,3,4-Thiadiazines L-19, H-30 and L-37 were the most effective inhibitors. Effect of the intravenous injection of L-19 in various doses on platelet aggregation and some parameters of plasmatic hemostasis were studied ex vivo.

[Anticoagulant activity of extracts from cedar bark, anthocyanidins of spruce and birch bark, and cellulose of aspen, fir, and wheat straw].

We have investigated in vitro the anticoagulant (AC) activity of proanthocyanidins from the bark of birch, cedar, spruce, pine, and larch; sulfated arabinogalantan and dihydroquercetin from larch wood; extracts from birch, cedar, and spruce; microcrystalline cellulose (MCC) from aspen and fir wood and wheat straw; and methylcellulose (MC) from aspen wood. The AC properties of the investigated substances are related mostly to their antithrombin activity. The AC activity increases with the content of sulfur in MCC of wheat straw, MC of aspen wood, and arabinogalañtan of larch wood. The maximum AC activity was observed in samples of sulfated MCC from fir wood and wheat straw. Their antithrombin activity (134 +/- 8 and 96 +/- 6, respectively) is worth of carrying out model tests in vivo.

Synthesis of sulfated pectins and their anticoagulant activity.

The following pectins were sulfated: bergenan BC (the pectin of Bergenia crassifolia L), lemnan LM (the pectin of Lemna minor L), and galacturonan as a backbone of pectins. Pyridine monomethyl sulfate, pyridine sulfotrioxide, and chlorosulfonic acid were used as reagents for sulfation. Chlorosulfonic acid proved to be the optimal reagent for sulfation of galacturonan and other pectins. Galacturonan and pectin derivatives with different degrees of sulfation were synthesized and their anticoagulant activities were shown to depend on the quantity of sulfate groups in the pectin macromolecules.

Antileprosy activity and preliminary toxicological characteristics of some dialkyldithiocarbamate derivatives.

Antileprosy activity of dialkyldithiocarbamate derivatives was studied in experiments on mice infected with M. leprae into paw pads. We found that 2-diethyldithiocarbamoyl-3-cyano-5-nitropyridine is the most promising antileprosy agent; it effectively suppresses multiplication of M. leprae and is well tolerated under conditions of chronic animal experiment.

[Anticoagulant activity of arabinogalactane sulfate and cedar bark extract studied in vitro].

We have studied in vitro the ability of the Siberian cedar crust (SCC) extract (Pinus sibirica Du Tour) and arabinogalactan sulphate (AGS) extracted from wood of Siberiam pine-tree (Larix sibirica Ledeb.) to increase the human blood plasma coagulation time and also to inhibit the amydolytic activity of thrombin (aIIa) and the coagulation factor Xa (aXa). A method has been developed by means of which SCC increases the aXa activity by a factor of 3.7 and the aIIà activity by a factor of 2.5. The AGS preparation increased the blood plasma coagulation time in the test for activated partial thromboplastin time. An effective concentration, at which the time of plasma coagulation was increased by a factor of 2 (in comparison to the control) was 2.94 +/- 0.33 mg/ml. AGS did not exhibit the ability to inhibit the Xa activity.

Study of antileprosy activities of some dialkyldithiocarbamate derivatives.

Effects of some dialkyldithiocarbamate derivatives on multiplication of M. leprae were studied in infected mice. Compounds significantly suppressing M. leprae proliferation were selected. By antibacterial activity one of these compounds was superior to dapsone, the main antileprosy drug.

[The antithrombotic activity of para-aminobenzoic acid in experimental thrombosis]. / Antitromboticheskaia aktivnost' paraaminobenzoinoi kisloty pri éksperimental'nom tromboze.

It was shown for the first time that p-aminobenzoic acid (PABA), in addition to the previously described fibrinolytic activity, exerts the properties of a direct anticoagulant both in vitro and in vivo. PABA not only displays antithrombin activity, but also inhibits activated factor X and, upon intravenous injection to rats and rabbits, shows the antithrombotic effect. The most pronounced antithrombotic affect was observed at a dose of 1.5 mg/kg. PABA at 0.5 mg/kg has insignificant efficacy and at 3 mg/kg, a high efficacy, but induces hemolysis of erythrocytes in about a half of cases. Equally efficient antithrombotic activity of blood plasma of rats was noted after intravenous injection of low molecular weight heparin "Fraxiparin" at 40 anti-Xa U/kg and PABA at 25 anti-Xa U/kg (1.5 mg/kg). Unlike "Fraxiparin", which exerts an immediate effect, the effect of PABA was expressed within 1.5 to 5 h after injection with a peak of antithrombotic activity at 3 h (which correlates with anti-IIa and anti-Xa activities of plasma) and terminated by 5 h after injection. For PABA, the ratio of anti-Xa to anti-IIa activities (an important parameter, which determines the antithrombotic potential of drugs) equals 2.4. PABA at 0.5 or 1.5 mg/kg did not affect the number of thrombocytes, while at 3 mg/kg, it decreased the number of thrombocytes by 20%. Thus PABA at 1.5 mg/kg, which has a high anticoagulant activity and does not cause side effects, is most interesting for further studies.

[The effect of the combined use of mineral water and rutin on the function of the adrenal cortex and pancreatic islet apparatus (an experimental study)]. / Vliianie sochetannogo primeneniia mineral'noi vody i rutina na funktsional'noe sostoianie kory nadpochechnikov i insuliarnyi apparat podzheludochnoi zhelezy (éksperimental'noe issledovanie).

Before modelling of experimental ulcer according to I. S. Zavodskaia the animals (157 male Wistar rats) were given for 24 days mineral water Essentuki N 17 and rutin in a dose 20 or 40 mg. Those given 20 mg of rutin in combination with mineral water demonstrated a higher rise in blood concentrations of hydrocortisone, insulin and thyroxine. Gastric mucosa and levels of serum alpha-1, alpha-2, beta-globulins and albumins were less damaged.

[The effect of n-3 polyunsaturated fatty acids on the blood coagulation system]. / Vliianie n-3 polinenasyshchennykh zhirnykh kislot na svertyvaiushchuiu sistemu krovi.

The article presents the epidemiologic data on the antithrombotic and antiatherosclerotic effect of n-3 polyunsaturated fatty acids, and the current information on the mechanism of the effect of these compounds on the system of blood coagulation.

[The effect of the joint administration of heparin and chitosan sulfate ether on hemostatic function]. / Vliianie sovmestnogo vvedeniia geparina i sernokislogo éfira khitozana na funktsiiu gemostaza.

We studied anticoagulant effects of combined administration of heparin (H) and chitosan sulfate ether (CS) (specific activity 20 UE/mg) in the ratio 1 : 1. CS enhanced anticoagulant activity of heparin in rabbits by a factor of 1.95 +/- 0.15. The intravenous injection of the mixture in a dose of 0.5 mg(H)/kg + 0.5 mg(CS)/kg and heparin injection in a dose of 1mg/kg induced the same effect. Haemorrhagic effect of this mixture was less pronounced compared to heparin, anticoagulant and antithrombotic activities remained the same. The mixture was found to decrease a number of platelets, however, this was also less pronounced compared to heparin. Thus, the use of the mixture CS + H (1 : 1) instead of double heparin dose resulted in the same effect.

[The antithrombotic action of a protein C activator from the venom of Agkistrodon blomhoffi ussuriensis in thrombus formation in an extracorporeal shunt in rats]. / Antitromboticheskoe deistvie aktivatora proteina C iz iada Agkistrodon blomhoffi ussuriensis pri tromboobrazovanii v ékstrakorporal'nom shunte u krys.

An antithrombotic action of the protein C (PC) activator from the venom of Agkistrodon blomhoffi ussuriensis on the model of platelet-dependent thrombosis in the arteriovenous shunt in rats was under investigation. Administration of the PC activator to rats resulted in a dose-dependent prolongation of the thrombus formation time, in a decrease in PC and factor V levels in blood and in APTT prolongation. There were no changes in the tissue-type plasminogen activator level and in the ADP- or epinephrine-induced platelet aggregation, but platelet adhesion to glass decreased. The possible mechanism of the antithrombotic action of the PC activator appeared to be the factor V inactivation mediated by protein C activation and the decrease in platelet adhesion.

[The effect of a new drug form for the intravenous administration of vitamin K1 on the blood coagulation system]. / Vliianie novoi lekarstvennoi formy dlia vnutrivennogo vvedeniia vitamina K1 na svertyvaiushchuiu sistemu krovi.

In rabbits with experimental hypocoagulation induced by phenylin, the use of a new dosage form of vitamin K1 for intravenous injections in does of 1 and 5 mg/kg led, in contrast to vicasol in a dose of 0.4 mg/kg, to an increase of the prothrombin index after 2 hours and to its complete normalization after 4 hours. Intravenous injection of vitamin K1 into intact animals did not entail any changes in the activated partial thromboplastin time, thrombin and prothrombin time, in the content of fibrinogen and products of its biotransformation, antithrombin III activity, and fibrinolytic activity or in the count of platelets and their aggregation capacity.

[The thrombolytic activity of acylated activator complexes of plasmin-streptokinase with different rates of reactivation]. / Tromboliticheskaia aktivnost' atsilirovannykh aktivatornykh kompleksov plazmin--streptokinaza s razlichnymi skorostiami reaktivatsii.

In the experiments on guinea-pigs with venous thrombosis there were studied the fibrin- and thrombolytic effects of streptokinase, the plasmin-streptokinase complex and the acylated derivatives of the complex with various rates of reactivation. It was established that the acylated derivatives of the plasmin-streptokinase complex possess greater stability in the blood flow and lead to more prolonged stimulation of fibrinolysis at less magnitude of its systemic activation. Due to this the acylated derivatives of the plasmin-streptokinase complex produce less pronounced fibrinogenolysis. In connection with a high affinity to fibrin their thrombolytic action does not depend on the systemic activation of fibrinolysis.

[The stimulation of fibrinolysis during cholinergic vasodilating reactions]. / Stimuliatsiia fibrinoliza pri kholinergicheskikh sosudorasshiriaiushchikh reaktsiiakh.

Changes in the fibrinolytic activity of blood flowing from the skeletal muscles during electrostimulation of the peripheral end of the cut-off sympathetic chain at the blockade of alpha-adrenoceptors have been studied in the acute experiments on cats. It is stated, that this action induces not only an increase of vascular conductivity but also fibrinolysis stimulation relating to the secretion of plasminogen activators to the blood. The effect of fibrinolysis stimulation was reproduced during intraarterial infusion of acetylcholine and was blocked by atropine. The vasodilating reactions on sodium nitroprusside and papaverine similar by intensity to the cholinergic reactions induce no plasminogen activator release. The existence of the specific regulation mechanism of plasminogen activator secretion, mediated by M-cholinoceptors is suggested.

[An evaluation of the vascular factors of the hemostatic system during the rehabilitation of patients after cerebral circulatory disorders]. / Otsenka sosudistykh faktorov sistemy gemostaza v protsesse reabilitatsii bol'nykh posle narushenii mozgovogo krovoobrashcheniia.

Functional diagnosis of the system "blood-vascular wall" early upon acute failure of cerebral circulation was found valuable both in the detection of various hemostatic functional alterations and development of differential treatment with preformed balneological factors. Compensatory potential present in the system of hemostasis promotes wider introduction of oxygen and carbon dioxide baths in early rehabilitation. The use of balneotherapy leads to modulation of antithrombotic properties of the vascular wall.

[Research in the field of clinical pharmacology in the USSR]. / Razvitie issledovanii v oblasti klinicheskoi farmakologii v SSSR.

The authors analyze the results of research on clinical pharmacology carried out at various institutions in this country. The overwhelming majority of works are concerned with clinical studies on the pharmacodynamics and pharmacokinetics of the drugs, their interaction, and detection of drug side effects. Special attention is paid to the improvement of the methods for determination of the pharmacological agents in biological fluids, and to the design of the maximally adequate parameters of assessing the pharmacodynamics of the main groups of the drugs. Considerable part of investigations is devoted to clinical pharmacogenetics, chronopharmacology, age pharmacology, prediction of the drug effects, approaches to the extrapolation of experimental data to the clinical trials of the drugs. The authors also provide evidence on the system of clinical trials of new drugs and detection of untoward effects of the medicines used.