The effect of the synthetic polycation VMII-DEMA (a potential antiheparin agent) on the ion transport through erythrocyte membranes was studied using ion-selective electrodes. We found that the passive ionic permeability of erythrocyte membranes in the presence of VMII-DEMA noticeably increased after the pretreatment of erythrocytes with long-chain fatty acids. When used separately, neither polycation nor fatty acids changed the membrane permeability at the same concentrations. The efficiency of the combined action of the polycation and fatty acids correlated with the length of the fatty acid (C9-C18) and the number of double bonds in it. The fatty acids C12:0, C13:0 and C18:2 were the most efficient. We suggest that in pathologies accompanied with deteriorations in lipid metabolism, polycations used for the correction of blood coagulation may damage the erythrocyte membrane.

It is shown that synthetic polycation quarternary ammonium salt polymetacryloil lupinine (poly-MACL) effects on passive ion permeability of erythrocytes membranes. The amplitude of Cl-/OH- exchange decreased in the buffer with SDS-polycation complex and simultaneously with pH elevation K+ exflux increased. On the contrary, in presence of heparin coeffect of poly-MACL and SDS vanished. Thus, synthetic polycation in the complex with longchain anion (SDS) injure the membranes and effect depends on lipophilic-hydrophilic balance of polycation-SDS complex.

The search for the compounds inducing release of lipoprotein lipase in the blood flow was made in the series of sulfated polysaccharides of brown sea algae of the Japanese Sea--fucoidanes. The effects of the substances on the blood coagulability were studied. Single intravenous injections of the substances were followed by the combined but independent anticoagulant and lipolysis-stimulating effects. Fucoidane isolated from Pelvetia wrightii possessed the greatest lipolysis-stimulating activity along with a weak anticoagulant effect. The degree of the pharmacological effects of the studied compounds did not depend on the degree of sulfation of macromolecules of the polysaccharides. In contrast to heparin fucoidanes exhibited the maximum effect on lipolysis later, 120-180 minutes after the intravenous injection.

The effect of the quaternary ammonium salt of an polyconidine 25-mer (QAS-O-25) on replication and transcription in hepatocytes of whole animals has been compared with features of the structural organization of the DNA of a DNA-QAS-O-25 complex. It was found that polyconidine binds to DNA and forms cross-links, resulting in the formation of an optically inactive liquid crystal dispersion made up of densely packed DNA-QAS-O-25 complexes. Addition of heparin to the polymer solutions disrupted these complexes, the DNA returning to its original native state and forming a cholesteric liquid crystal phase. Transcriptions was increased and DNA synthesis partially synchronized in hepatocytes after a single exposure of rats to QAS-O-25 conidine. These probably arise through changes in the tertiary structure of chromatin caused by formation of the DNA-QAS-O-25 conidine complex.

The authors studied the effect of mast cell population of a new group of synthetic heparin antagonists--quaternary ammonium salts of monodispersed conidine oligomers of different molecular masses and the effect of conidine monomer under the conditions of heparin neutralization and without preliminary administration of the anticoagulant. The conidine monomer was discovered to be a solitary compound that produced a significant shift of the mast cell population toward light forms. Administration of both conidine monomer and oligomers after the neutralization doses of heparin did not disturb the equilibrium of the mast cell population. At the same time no relationship was established between the changes in the status of labrocytes and molecular mass of conidine derivatives. Degranulation of mast cells remained significantly unchanged in all the series of experiments.

A comparative study of the anticoagulant activity of fucoidan, sulfated polysaccharides of brown sea algae, was carried out during in vitro and in vivo experiments. Among the compounds of this class of nonlinear polyanions of sea algae there were detected the substances possessing a low toxicity and anticoagulant activity comparable with that of heparin. However the mechanism of action of the studied compounds differs from that of heparin.

The paper concerns the effect of heparin and its antagonists, protamine and 2,5-ionen, on mast cell population from the standpoint of its potential action on blood coagulation. It has been established that intravenous administration of heparin is accompanied by its deposition in mast cells, that gives rise to rapid excretion of the anticoagulant from the blood flow. It has been also shown that protamine sulfate and 2,5-ionen produce degranulation of mast cells, but the synthetic polycation is superior over protamine sulfate in binding heparin of extracellular granules. Retaining of the increased saturation of mast cells with heparin on neutralization of the anticoagulant effect with protamine forms a structural basis for the origination of recurrent heparinemia. Study of blood coagulation has shown that 2,5-ionen is a more efficacious heparin antagonist than protamine sulfate.

A composite morphometric approach to the analysis of mast cell population is proposed including 4 criteria: the cytogram, the index of heparin saturation, degranulation index, a relative rate of degranulation form. The sensitivity and informative capacity of the composite morphometric analysis were tested in two experimental models: inoculation of heparin and inoculation of its antagonists. Subtle differences in the effect of mast cell degranulaton were found after inoculation of protamine sulphate and a synthetic polycation, 2.5-ionen. Important information on the consumption of exogenous heparin by mast cells was obtained. The simplicity of the analysis as well as the possibility of using its simplified version make the method available for both clinical and experimental pathology.

Antiheparin activity and acute toxicity of a monomer and polymer quaternary ammonium salts obtained on the basis of the alkaloid lupinine were investigated. The monomer was shown to have no antiheparin activity even when administered in high doses. Lupinine polymetakryloyl iodoethylate is a selective heparin antagonist. This activity of polymers is relative to the extent of polymerization. A compound with a molecular weight of 20 000 turned out the most effective in the tested series of ready-made polymers. Acute toxicity of polycations is considerably less than that elicited by the monomer. The effect of heparin complete neutralization is accompanied by transitory thrombocytopenia.