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Biomedical subjects

B Kaiser

Publications and source records attributed to B Kaiser.

At least 73 records · Page 4Linked to original sources
PubMed1989

Studies on antithrombotic effects of recombinant hirudin.

Recombinant desulfato hirudin (rH) was studied with regard to its effects on various models of thrombosis, its pharmacokinetic behaviour as well as its influence on primary haemostasis in rats. The pharmacological behaviour of rH proved to be similar to that of native hirudin. Depending on the different models of experimental thrombosis different dosages of rH were required to prevent thrombus formation. This corresponds to rH plasma concentrations of 0.5-1.5 micrograms/ml. Primary haemostasis is influenced only after excess dosages and plasma concentrations of 4 micrograms/ml and above.

Animals↗
PubMed1989

[The pharmacology of recombinant hirudin].

A review about comprehensive studies on pharmacological properties of hirudin produced by genetic engineering is given. Anticoagulant effects, influence on platelet functions, studies on toxicity and side effects as well as the pharmacokinetic behaviour and antithrombotic actions of this highly effective thrombin inhibitor are described.

Animals↗
PubMed1989

Pharmacological characterization of a new structural variant of 4-amidinophenylalanine amide-type synthetic thrombin inhibitor.

The synthetic thrombin inhibitor N alpha-(2-naphthylsulfonylglycyl)-4-amidinophenylalanyl-proline (1) was synthesized in order to evaluate the importance of the carboxyl group in its amine portion for fundamental pharmacodynamic and pharmacokinetic properties of these benzamidine derivatives. The compound is better tolerated in mice and rats than are similar compounds lacking this carboxyl group. It has a significantly longer plasma half-life in rabbits compared to the corresponding compound bearing piperidine instead of proline in the amide moiety. The main excretory route of 1 is via the bile. Hepatic uptake and/or biliary excretion show, however, another time course than that seen for the piperidide. Lower toxicity and more suitable pharmacokinetics may compensate for the loss of thrombin inhibitory potency of this new synthetic thrombin inhibitor.

Animals↗
PubMed1988

Experimental studies on the antithrombotic and haemorrhagic effects of heparin and a low molecular weight heparin derivative.

Antithrombotic, haemorrhagic and anticoagulant effects of unfractionated heparin (UH) and the low molecular weight heparin fragment KABI 2165 were studied in rats. In stasis-induced venous thrombosis of the jugular vein intravenous injection of both, UH and KABI 2165, either reduced significantly the size of thrombi or completely prevented thrombus formation in a dose-dependent manner. The dose of KABI 2165 required for prevention of thrombus formation showed a marked anticoagulant activity measured by APTT which was in the same range as that of the equieffective dose of UH. After administration of antithrombotically effective doses only UH caused a significant prolongation of bleeding time after standardized incision of the tail. KABI 2165 produced haemorrhagic effects at about 4-fold higher doses only than those required for the antithrombotic action.

Animals↗
PubMed1988

Antithrombotic and haemorrhagic effects of the naturally occurring thrombin inhibitor hirudin.

Haemorrhagic effects of the naturally occurring thrombin inhibitor hirudin measured by the determination of bleeding time were compared with its antithrombotic actions in different models of experimental thrombosis. In mice and rats intravenous administration of hirudin caused a plasma concentration-dependent prolongation of bleeding time after transection of the tail tip and standardized incision of the tail, respectively. In rats intravenous infusion of hirudin prevented the formation of stasis-induced venous thrombosis of the jugular vein and the occurrence of thrombotic occlusion of the carotid artery after electrically induced damage of the vessel wall. Comparison of the haemorrhagic action of hirudin with its antithrombotic effectiveness showed that it caused haemorrhagic side effects only at plasma concentrations which are not required for the antithrombotic effects.

Animals↗
PubMed1988

Pharmacological survey of recombinant hirudin.

The pharmacological properties of a genetically engineered recombinant hirudin (r-hirudin) were studied in animal experiments. r-Hirudin proved to be a well tolerated substance. I.v. injection of up to 200 mg/kg did not lead to perceptible functional or morphological changes. There were no treatment-related effects on the cardiovascular system of dogs and rats after administration of up to 10 mg/kg. After long-term treatment (4 weeks, 1.0 mg/kg daily), no r-hirudin-related histopathological, haematological or biochemical changes could be found. Formation of antibodies was not detectable. Absorption, distribution, and elimination of r-hirudin were studied in dogs and rats. Pharmacokinetics could be best described by an open two-compartment model with first-order kinetics. After i.v. injection in dogs, r-hirudin is distributed into the extracellular space and eliminated through the kidneys in active form by glomerular filtration. After i.v. administration, a half-life of about 1 h was estimated; s.c. administration prolonged the apparent half-life. Pulmonary absorption was shown. Enteral absorption, placental transfer as well as transfer through the fetal integument were very low. r-Hirudin did not pass the blood-brain barrier. The efficacy of r-hirudin in preventing both venous and arterial thrombosis, vascular shunt occlusion or disseminated intravascular coagulation was demonstrated in rats. Depending on the dose, r-hirudin was able to prevent or reduce stasis-induced venous thrombosis, prolong the patency of an extracorporeal arteriovenous shunt, reduce the incidence of arterial thrombosis caused by vascular wall lesions as well as of microthrombosis induced by thrombin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

[The pharmacodynamics of synthetic thrombin inhibitors of the basic type substituted n-alpha arylsulfonylated phenylalanine amide].

Nonspecific pharmacodynamic effects of synthetic thrombin inhibitors, basically substituted N alpha-arylsulfonylated phenylalanine amides, were studied in animal experiments. Upon intravenous bolus injection they exert a rapid fall in blood pressure, which limitates the tolerance. In contrast to the antithrombin activity, toxicity and side effects of the amidino compounds are not dependent on the position of the amidino group within the molecule. On the other hand, compounds with other basic groups, i.e. the amino, aminomethyl, and guanidinomethyl analogues are less toxic and less hypotensively active. The nonspecific pharmacodynamic effects of synthetic thrombin inhibitors of the benzamidine type must be caused by the highly basic amidino group (the benzamidine moiety) of the compounds.

Amidines↗
PubMed1987

Biliary excretion of synthetic benzamidine-type thrombin inhibitors in rabbits and rats.

In rabbits and rats the excretion via the bile of the highly effective and selective synthetic thrombin inhibitor N alpha-(2-naphthylsulfonylglycyl)-4-amidinophenylalanine piperidide was studied after various routes of administration and varying doses. The concentration in the bile was determined using a biological method, the reliability of which was checked by HPLC-determinations. The compound was excreted in the bile in biologically active unchanged form. Cumulative biliary excretion of the synthetic thrombin inhibitor in rabbits amounted to a high percentage of the administered dose after low doses given either systemically or intraportally. In rats the excretion rates during and after intravenous infusion reached a maximum indicating saturation kinetics. Hepatic uptake and biliary excretion of the highly basic benzamidine derivative essentially contribute to its short plasma half-life.

Amidines↗
PubMed1986

Antithrombotic and haemorrhagic effects of synthetic and naturally occurring thrombin inhibitors.

The effects of the synthetic thrombin inhibitor N alpha-(2-naphthylsulfonylglycyl)-4-amidinophenylalanine piperidide (beta Nas-Gly-(pAm)Phe-Pip) and the naturally occurring inhibitors hirudin and heparin on the bleeding time were studied in mice and rats by the method of transection of the tail tip and of standardized incision of the tail. With both methods the thrombin inhibitors prolonged the bleeding time in dependence on the dose and the plasma concentration obtained. The transection bleeding time was influenced by the inhibitors in a similar manner, whereas in the case of incision of the tail heparin caused a more pronounced effect than hirudin and beta Nas-Gly-(pAm)Phe-Pip. Comparison of the antithrombotic actions of the inhibitors with their effects on the bleeding time showed that, in contrast to the selective thrombin inhibitors hirudin and beta Nas-Gly-(pAm) Phe-Pip, antithrombotically effective doses of heparin induced a clear prolongation of bleeding time.

Animals↗
PubMed1986

Experimental studies on the antithrombotic action of a highly effective synthetic thrombin inhibitor.

The antithrombotic action of the highly effective synthetic thrombin inhibitor N alpha-(2-naphthylsulfonylglycyl)-4-amidinophenylalanine piperidide was studied in various models of experimental thrombosis in rats. Intravenous infusion of the thrombin inhibitor caused a dose-dependent inhibition or prevention of stasis-induced venous thrombosis, of arterial thrombosis after electrically-induced damage of the vessel wall and of thrombotic occlusion of an extracorporeal arterio-venous shunt.

Animals↗
PubMed1985

Pharmacological characterization of a new highly effective synthetic thrombin inhibitor.

The most potent synthetic reversible thrombin inhibitor described so far, N alpha-(2-naphthylsulfonylglycyl)-4-amidinophenylalanine piperidide (Ki = 6 nmol/l), was studied with respect to its pharmacodynamics and pharmacokinetics in mice, rats and rabbits. In mice the LD50 was 54 mg/kg i.v. and greater than 800 mg/kg p.o. Prolongation of bleeding time in mice and reduction of mean arterial blood pressure in rats were seen only at doses above the antithrombotically effective doses. After i.v. injection in rabbits the plasma half-life was estimated to be about 9 min. Subcutaneous injection resulted in measurable inhibitor plasma levels for 4 h. Administration of high does into the duodenum did not give antithrombotically effective plasma levels. The ligature of the functional and nutritive hepatic vessels prolonged the half-life of the thrombin inhibitor, whereas renal excretion seems to be of minor importance. A dose-dependent antithrombotic effect was shown in venous stasis-induced thrombosis in rabbits.

Animals↗
PubMed1984

[3H]dihydroergocryptine binding to alpha-adrenoceptors in human femoral veins and arteries.

In order to characterise subtypes of alpha-adrenoceptors in human vascular tissue, radioligand binding studies with [3H]dihydroergocryptine were carried out in human femoral veins and arteries. Binding of [3H]dihydroergocryptine to venous and arterial membranes was rapid and reversible reaching steady state within 4-6 min at 25 degrees C. [3H]Dihydroergocryptine was displaced from its receptor site on vascular membranes by unlabelled alpha-adrenoceptor agonists and antagonists in a concentration-dependent manner. Yohimbine and guanfacine which possess high affinity for alpha 2-adrenoceptors were more effective in competing for [3H]dihydroergocryptine binding sites in veins than in arteries. Prazosin and phenylephrine with high affinity for alpha 1-adrenoceptors were more effective displacers in arteries than in veins. The results suggest that the alpha-adrenoceptor population differs between human femoral veins and arteries. In veins, predominantly alpha 2-adrenoceptors are present, whereas in arteries the adrenoceptor of the alpha 1 type prevails. The results show that the uneven distribution of alpha 1- and alpha 2-adrenoceptors as has been found in animal experiments and pharmacological investigations with human vessels could also be demonstrated by binding studies with [3H]dihydroergocryptine in human femoral arteries and veins.

Adrenergic alpha-Agonists↗
PubMed1982

[Prenatal AB0(H) blood group determination of amniotic fluid cells by mixed cell agglutination].

A modification of the mixed-cell agglutination reaction (MCAR) was used in prenatal AB0(H) blood typing of cells obtained from 41 samples of amniotic fluid. The findings are compared with results obtained from the use of the agglutination inhibition test in testing water-soluble AB0(H) substances of amniotic fluid based on the same samples. For prenatal AB0(H) typing, MCAR exhibited advantages over the agglutination inhibition test. Completion of data in this field will provide a good foundation for prenatal detection and identification of hereditary factors which can be linked with gene loci of the AB0 system.

ABO Blood-Group System↗