Biomedical subjects
Publications and source records attributed to F Markwardt.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
To establish quantitative structure-activity relationships for the inhibition of trypsin, plasmin and thrombin by 4-amidinophenyl compounds with a keto group, attempts have been made to detect correlations between data on inhibition and substituent constants. The inhibitor activity of the derivatives is described by lipophilic or steric substituent constants using linear free energy relationships. To describe the action of beta-ketones, an additional sigma I term is necessary. The lipophilic or steric term stands for binding of the inhibitor side chain to a second hydrophobic binding site of the enzyme. The electronic term describing inductive influences on the keto group suggests the contribution of the beta-keto group to the enzyme inhibitor binding via a tetrahedral conformation of the carbonyl carbon.
Explore the source record for details and available documents.
The effect of the aromatic diamidine derivative 2,6-bis (4-amidinobenzyl)-cyclohexanon-(1) on blood coagulation and fibrinolysis in vitro and in vivo was compared with that of the benzamidine derivative 4-amidinophenyl pyruvic acid and the aromatic diamidine derivative 4,4'-diamidinophenoxypentane. 2,6-Bis(4-amidinobenzyl)-cyclohexanon-(1) was found to be a strong inhibitor of the clotting enzyme thrombin. Because of the toxic side effects and pharmacokinetic properties of both diamidine derivatives their in vivo use as anticoagulants is limited.
The thrombolytic action of the streptokinase preparation Awelysin was investigated in animal experiments. After evaluation of the optimum fibrinolytically effective streptokinase dose and the changes in the clotting system induced by intravenous application of streptokinase experimentally produced deposition thrombi and clotting thrombi were lysed intravascularly in dogs, rabbits and rats. The success of the therapy was confirmed angiographically or rheographically.
Changes in the clotting system, as well as morphological and functional alterations corresponding to that of the pathologic phenomenon of disseminated intravascular coagulation (DIC) or consumption coagulopathy, were produced by thrombin infusion (550 NIH U X kg-1 X h-1) in rats and simultaneous inhibition of fibrinolysis by PAMBA (100 mg/kg). Changes in the fibrinogen level and platelet count as well as the appearances of fibrin monomers and the formation of microthrombi in several organs were evaluated. Simultaneously, the function of the respiratory system was investigated by continuous measurement of oxygen consumption as well as elasticity and water content of the lung. From the time course of the alterations in the several parameters, conclusions can be drawn for the pathogenesis and the possible therapeutic influence on DIC.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
By the use of native and radioactively labelled streptokinase its distribution and elimination were determined in rabbits and compared to the course of the fibrinolytic action. Particularities of the pharmacokinetics of the activator of fibrinolysis were studied and related to the therapeutic effect.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.