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1.
Thromb Res ; 74(4): 321-34, 1994 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-8085234

RESUMO

Subendothelial collagen is one of the main triggers of platelet-dependent thrombus formation in arteries. The antithrombotic effects of rabbit polyclonal inhibitory antibodies to rat collagen type I-III and of murine non-inhibitory monoclonals to human recombinant single-/two-chain urokinase-type plasminogen activator (rscu-/rtcu-PA), cross-reacting with rat scu-/tcu-PA and their chemically synthesized conjugate, were studied both in vitro and in vivo. Anticollagen antibodies and bispecific conjugate inhibited human platelet adhesion, aggregation and formation of thrombus-like structures induced by rat collagen immobilized on the polystyrene surface in a condition mimicing a high shear rates in the large elastic arteries. Monoclonals to human rscu-/rtcu-PA did not block the collagen-induced platelet activation in vitro. The short-term treatment of the collagen-soaked silk thread by the collagen antibodies suppressed the platelet-dependent thrombus formation in the arterio-venous shunt in rats by 56 +/- 4% (P < 0.05). Bispecific conjugate, directed to collagen and endogenous rat scu/tcu-PA inhibited thrombus formation by the same factor as anticollagen antibodies. The treatment of collagen-adsorbed conjugate by human rtcu-PA did not increase the antithrombotic effect. The present results suggest, that the local administration of the anticollagen antibodies to the site of vascular injury can be an efficient tool for prophylaxis of platelet-dependent thrombus formation in arteries at thrombolysis or percutaneous transluminal coronary angioplasty.


Assuntos
Anticorpos/sangue , Plaquetas/imunologia , Colágeno/imunologia , Trombose/imunologia , Ativador de Plasminogênio Tipo Uroquinase/imunologia , Animais , Anticorpos Monoclonais , Derivação Arteriovenosa Cirúrgica , Modelos Animais de Doenças , Humanos , Masculino , Ratos , Ratos Wistar , Proteínas Recombinantes/imunologia , Trombose/sangue
2.
Thromb Res ; 70(5): 385-93, 1993 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-8378894

RESUMO

Protein C (PC) is an anticoagulant protein which, being activated by thrombin, degrades factors V/Va and VIII/VIIIa and releases a tissue-type plasminogen activator. Some Agkistrodon snake venoms contain PC activators which, in experiments, exert an anticoagulant action. An antithrombotic effect of the PC activator from the venom of A. blomhoffi ussuriensis on the model of thrombus formation in the arterio-venous shunt in rats was under investigation. Administration of the PC activator resulted in a dose-dependent prolongation of the thrombus formation time and a decrease in plasma PC activity, which were accompanied by a decrease in factor V activity and APTT prolongation. No reliable changes in the t-PA level, ADP- and epinephrine-induced platelet aggregation were observed. Platelet adhesion to glass beads diminished. We assume that the antithrombotic effect of the PC activator from the A. blomhoffi venom in the platelet-dependent thrombosis model is caused by PC activation and subsequent factor V inactivation as well as by platelet adhesiveness reduction.


Assuntos
Derivação Arteriovenosa Cirúrgica , Coagulação Sanguínea/efeitos dos fármacos , Venenos de Crotalídeos/química , Fibrinolíticos/farmacologia , Peptídeos/farmacologia , Proteína C/metabolismo , Trombose/prevenção & controle , Sequência de Aminoácidos , Animais , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Fator V/metabolismo , Fibrinolíticos/uso terapêutico , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Dados de Sequência Molecular , Tempo de Tromboplastina Parcial , Peptídeos/isolamento & purificação , Peptídeos/uso terapêutico , Adesividade Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Ratos , Ratos Wistar , Especificidade da Espécie
3.
Blood Coagul Fibrinolysis ; 4(6): 993-8, 1993 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-7908542

RESUMO

The changes in conductivity of skeletal muscle vessels of the hind leg and tissue-type plasminogen activator (t-PA) activity in outflowing blood after electrostimulation (5 V, 0.5 ms, 20 Hz, 30 s) at the L4-L5 level of the peripheral end of the transected isolated sympathetic chain were studied in experiments on anaesthetized cats. Stimulation of the sympathetic chain induced vasoconstriction and release of t-PA from the vascular wall into the blood. Pretreatment with the beta-adrenoblocker propranolol neither changed the character of vascular reactions nor blocked t-PA secretion. Efferent stimulation of the sympathetic chain against a background of alpha-adrenoceptor blockade by dihydroergotoxin increased blood flow and was accompanied by a rise in t-PA activity. The M-cholinergic blocker atropine suppressed both vascular relaxation and release of t-PA into the blood. Vasodilatation accompanied by t-PA secretion could be induced by intraarterial infusion of acetylcholine and blocked by atropine. The existence of a neurogenic mechanism controlling t-PA release from the vascular wall involving a sympathetic cholinergic pathway and connected with excitation of vascular M-cholinoceptors by acetylcholine is suggested.


Assuntos
Acetilcolina/fisiologia , Sistema Nervoso Simpático/fisiologia , Ativador de Plasminogênio Tecidual/sangue , Antagonistas Adrenérgicos alfa/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Velocidade do Fluxo Sanguíneo , Gatos , Fibrinólise/fisiologia
4.
Eksp Onkol ; 10(4): 59-62, 1988.
Artigo em Russo | MEDLINE | ID: mdl-3181077

RESUMO

The electrophoretic and spectral analyses have been used to show the possibility to form a complex consisting of doxorubicin and adriamycin with heparin, the molar ratio being 6:1 and pH 4.8-7.4. Doxorubicin and adriamycin had procoagulant properties but the doxorubicin-heparin complex showed an anticoagulant activity. In experiments on rats with the Pliss lymphosarcoma and sarcoma 45 the doxorubicin-heparin complex depressed more efficiently the tumour growth and metastasis spreading. The combination of doxorubicin and the doxorubicin heparin complex with the trypsin-heparin complex which imitate the hyperfunction of anticoagulative system markedly increased the antitumour effects.


Assuntos
Doxorrubicina/uso terapêutico , Hemostasia/efeitos dos fármacos , Heparina/uso terapêutico , Neoplasias Experimentais/tratamento farmacológico , Animais , Combinação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/secundário , Transplante de Neoplasias , Neoplasias Experimentais/sangue , Neoplasias Experimentais/secundário , Ratos , Sarcoma Experimental/sangue , Sarcoma Experimental/tratamento farmacológico , Sarcoma Experimental/secundário , Fatores de Tempo
5.
Ukr Biokhim Zh (1978) ; 63(2): 31-9, 1991.
Artigo em Russo | MEDLINE | ID: mdl-1882461

RESUMO

Kinetics of lysis of fibrin clots from the human, guinea pig, rat and rabbit blood plasma by two active-site-acylated derivatives of the activator plasmin-streptokinase complex with different reaction rate constants has been studied in vitro. It is found that lysis of blood plasma clots in guinea pig is most similar to that of man. Acyl activator dose being increased, the lysis of a plasma clot in guinea pig is accelerated. Two acyl activators exhibit higher fibrinolytic-efficiency as compared to a free activator. Experiments carried out in vivo on guinea pigs with thrombosis show that acyl activators, in contrast to nonmodified plasmin-streptokinase complex induce the less system activation of fibrinolysis and the less fibrinogenolysis.


Assuntos
Anistreplase/metabolismo , Fibrinólise/efeitos dos fármacos , Fibrinolíticos/farmacologia , Acilação , Animais , Sítios de Ligação , Cobaias , Humanos , Cinética , Coelhos , Ratos
6.
Eksp Klin Farmakol ; 57(2): 42-5, 1994.
Artigo em Russo | MEDLINE | ID: mdl-8205048

RESUMO

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.


Assuntos
Agkistrodon , Derivação Arteriovenosa Cirúrgica , Venenos de Crotalídeos/uso terapêutico , Fibrinolíticos/uso terapêutico , Proteína C/efeitos dos fármacos , Trombose/tratamento farmacológico , Animais , Artérias Carótidas/cirurgia , Gatos , Bovinos , Venenos de Crotalídeos/isolamento & purificação , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Fator V/análise , Fator V/efeitos dos fármacos , Fibrinolíticos/isolamento & purificação , Veias Jugulares/cirurgia , Masculino , Agregação Plaquetária/efeitos dos fármacos , Proteína C/análise , Proteína C/isolamento & purificação , Ratos , Ratos Wistar , Trombose/sangue , Trombose/etiologia
7.
Eksp Klin Farmakol ; 59(1): 30-3, 1996.
Artigo em Russo | MEDLINE | ID: mdl-8704629

RESUMO

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.


Assuntos
Anticoagulantes/farmacologia , Quitina/análogos & derivados , Hemostasia/efeitos dos fármacos , Hemostáticos/farmacologia , Heparina/farmacologia , Animais , Quitina/farmacologia , Quitosana , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Feminino , Hemorragia/sangue , Hemorragia/induzido quimicamente , Masculino , Coelhos , Ratos , Trombose/sangue , Trombose/tratamento farmacológico , Fatores de Tempo
8.
Vopr Med Khim ; 38(5): 12-4, 1992.
Artigo em Russo | MEDLINE | ID: mdl-1492385

RESUMO

Anticoagulation effect of chitosan sulfate ester and some mechanisms of its influence on hemostasis were studied in vitro. The chitosan sulfate ester catalyzed more effectively inactivation of the enzymes involved in the inner pathway of blood coagulation affecting only slightly the activity of outer pathway factors. The ester, similarly to heparin, inhibited blood coagulation mainly via accelerated thrombin inactivation by means of blood plasma antithrombin III. Inhibition of the enzyme coagulation activity using heparin cofactor II occurred only at high concentrations of chitosan sulfate ester in blood plasma. Besides, the ester decreased the thrombin catalytic activity in reactions with natural and synthetic peptide substrates. Thus, anticoagulation effect of chitosan sulfate ester is similar to that of heparin.


Assuntos
Anticoagulantes/farmacologia , Quitina/análogos & derivados , Antitrombina III/metabolismo , Catálise , Quitina/farmacologia , Hemostasia , Humanos , Tempo de Protrombina , Trombina/antagonistas & inibidores
9.
Fiziol Zh (1978) ; 36(4): 3-8, 1990.
Artigo em Russo | MEDLINE | ID: mdl-2146171

RESUMO

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.


Assuntos
Fibrinólise/fisiologia , Receptores Colinérgicos/fisiologia , Vasodilatação/fisiologia , Animais , Gatos , Estimulação Elétrica , Fibrinolisina/sangue , Fibrinólise/efeitos dos fármacos , Ativadores de Plasminogênio/sangue , Inativadores de Plasminogênio/sangue , Receptores Colinérgicos/efeitos dos fármacos , Soroglobulinas/análise , Fatores de Tempo , Vasodilatação/efeitos dos fármacos
18.
Biull Eksp Biol Med ; 110(8): 133-6, 1990 Aug.
Artigo em Russo | MEDLINE | ID: mdl-2291954

RESUMO

In the experiments on white rats was conducted a comparative study of 125I-alpha-thrombin clearance and its inactivation by antithrombin III in animals of the control group and rats with the experimental nephrotic syndrome (Heymann nephritis). It was determined that alterations of thrombin binding to the vascular wall in the nephrotic syndrome induced the prolongation of the labelled enzyme half-life in the blood stream. The formation of 125I-alpha-thrombin complexes with antithrombin III was delayed in the nephrotic syndrome, that suggests the violation of mechanisms of thrombin inactivation by antithrombin III. The distortions of endothelium-mediated thrombin elimination and inactivation in the nephrotic syndrome resulted in the enzyme interaction with fibrinogen, which threatened organism by thrombosis.


Assuntos
Antitrombina III/farmacologia , Vasos Sanguíneos/metabolismo , Glomerulonefrite/sangue , Síndrome Nefrótica/sangue , Trombina/metabolismo , Animais , Eletroforese , Fibrinogênio/metabolismo , Meia-Vida , Radioisótopos do Iodo , Ratos , Trombina/análise , Trombose/etiologia
19.
Biull Eksp Biol Med ; 104(9): 278-81, 1987 Sep.
Artigo em Russo | MEDLINE | ID: mdl-3663906

RESUMO

The influence of antithrombin III on hemostasis and renal function was studied in experiments on rats with nephrotic syndrome. The development of nephrotic syndrome was accompanied by the activation of blood coagulation and appearance of acquired antithrombin III deficiency due to its loss with the urine. The replacement therapy by bovine antithrombin III at a dose of 25 U/kg a day for 10 days decreased the signs of excessive thrombinogenesis in experimental animals and increased the amount of thrombin-antithrombin III complexes in the blood flow. The activation of coagulation in rats with nephrotic syndrome predominantly induced the disturbances of the excretory renal function which could be efficiently corrected by antithrombin III.


Assuntos
Deficiência de Antitrombina III , Síndrome Nefrótica/sangue , Animais , Antitrombina III/administração & dosagem , Hemostasia , Rim/fisiopatologia , Masculino , Síndrome Nefrótica/fisiopatologia , Síndrome Nefrótica/terapia , Ratos
20.
Fiziol Zh Im I M Sechenova ; 82(10-11): 52-7, 1996.
Artigo em Russo | MEDLINE | ID: mdl-9162395

RESUMO

Human plasmin (Pm) caused a rapid dose-dependent relaxation of norepinephrine-preconstricted isolated aortic ring and vascular net in the Wistar rat hindlimbs. Neither atropine, nor obsidan or indomethacin suppressed the Pm-induced vasodilatation of the aortic ring. Mechanical removal of endothelium and NO-blocker N-Nitro-L-Arg almost completely abolished the Pm-induced relaxation. DIP-Pm, AN-Pm and Glu-plasminogen did not change the vascular tone of the preconstricted rings. Both aprotinin and E-aminocapronic acid inhibited the relaxing effect of the Pm. Besides the circulating Pm, the enzyme forming on the endothelial surface from plasminogen under the action of urokinase, produced the vascular dilatation as well.


Assuntos
Fibrinolisina/farmacologia , Fibrinólise/efeitos dos fármacos , Fibrinolíticos/farmacologia , Ativadores de Plasminogênio/farmacologia , Ativador de Plasminogênio Tecidual/farmacologia , Ativador de Plasminogênio Tipo Uroquinase/farmacologia , Sistema Vasomotor/efeitos dos fármacos , Animais , Aorta/efeitos dos fármacos , Aorta/fisiologia , Interações Medicamentosas , Fibrinólise/fisiologia , Membro Posterior/irrigação sanguínea , Técnicas In Vitro , Masculino , Ratos , Ratos Wistar , Resistência Vascular/efeitos dos fármacos , Resistência Vascular/fisiologia , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia , Sistema Vasomotor/fisiologia
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