[Effects of complexes of alpha-fetoprotein and amphiphilic docosaenoic acid derivatives on the humoral immune response in C57BL/6 mice].

The immunotropic activity of three derivatives of docosahexaenic acid (N-docosahexaenoyl-L-serine phosphate, N-docosahexaenoyl-L-threonine phosphate, and N-docosahexaenoyl-L-tyrosine phosphate) in complexes with high-purity human alpha-fetoprotein was evaluated. The polyene compounds stimulate the humoral immunity in mice immunized with T-dependent antigen (ram red blood cells). The immunotropic activity of the alpha-fetoprotein-ligand complexes studied depends on the structure and the content of polyene ligands.

Modification of humoral immune response in C57Bl/6 mice with a complex of alpha-fetoprotein and retinoid acid derivatives.

Amides of all trans-retinoic acid and O-phospho-L-threonine, O-phospho-L-tyrosine, and O-phosphoethanolamine injected intravenously in a dose of 6.8 microg/kg 1.5-3.

[Immunopharmacologic properties of 12-iminosubstituted 8-aza-D-homogonan and trimezon].

The immunopharmacological properties of two new compounds with an 8-azasteroidal structure, representing the salts (hydrochloride and acetate) of 12-imino-substituted 8-aza-D-homogonan, were studied in comparison with the properties of the immunostimulant trimeson. Similar to trimeson, both new compounds produce a dose-dependent activation of the humoral chain of immunogenesis in the model of primary immune response to goat erythrocytes in CBA, C57BL/6, and C57W mice. The immunostimulant activity of the 8-aza-D-homogonan derivatives is inversely proportional to the antigen load (2 x 10(7)-2 x 10(9) goat erythrocytes per mice) and depends to a considerable extent of the genotype of experimental animals.

[Radiosensitization of human tumor HeLa cells induced by methyl ester of 6-oxo-6-[2,2-ethylenedioxy-5-(dimethoxycarbonylmethyl)-cyclope nt- 1-yL]-hexanoic acid].

Methyl ester of 6-oxo-6-[2,2-ethylenedioxy-5-(dimethoxycarbonylmethyl)- cyclopent-1-yl]-hexanoic acid (7-keto-9,9-ethylenedioxiprostanoid, that is analogue of 11-deoxy-PGE1 with modified chains) at concentration 10(-6) mol/l displayed maximal (25%) sensitizing effect when was tested in a range of concentrations 10(-7)-10(-5) mol/l and HeLa cells were gamma-irradiated at dose of 2 Gy, that was compared with metronidazol action. Optimal time of prostanoid contact with cells was between 30 and 60 min, and metronidazol--60 min. Prostanoid effect was exhibited at irradiation doses from 2 to 4 Gy and reached maximum of 46% at 4 Gy, its DMF was 1.

[The effect of the immunostimulating agent trimezon on the cells of the mononuclear phagocytosing system].

The effect of the immunostimulator trimeson of the 8-aza-gomogonan series on the cells of the mononuclear monocyte system was studied in C3H and ICR mice in vitro. Intraperitoneal injection of trimeson (50 mg/kg 1 x 10(-7)-1 x 10(6) M) inhibits, as a rule, the initial stages of the phagocytizing process but stimulates the bactericidal properties of the peritoneal phagocytes and their mechanisms of processing and destruction of the antigen material. In the system of adaptive transfer of donor splenocytes and peritoneal macrophages to recipients exposed to lethal radiation, trimeson (20 mg/kg intravenously, 50 mg/kg per os) increases the immunogenic function of the mononuclear phagocytes in formation of the primary immune response to sheep erythrocytes.

[The immunobiological properties of trimezon and levamisole on models of humoral and cell-mediated immunogenesis].

It was shown in mice experiments that intragastric administration of the low-molecular synthetic immunomodulator of the 8-azasteroid series trimesone increases the immune response of humoral and cell-mediated types to the thymus-dependent antigen, the sheep erythrocytes. The stimulating effect of the drug in vivo is determined by the dose, the antigen load, and the animals' genotype and does not yield to the effect of levamisole or exceeds it in identical experimental conditions.

[The modification of a radiation lesion with 9a-homo-13-thiaprostanoids].

The radioprotective properties of 12 compounds of 9a-homo-13-thiaprostanoid series were investigated under gamma irradiation using the molecular model of beta-carotene radio-oxidation in oleic acid in vitro, erythrocyte radiomimetic model in ex vivo-in vitro system as well as in vivo radiation damage in mice. Most of these compounds stimulated the radio-oxidation of beta-carotene, however in this model two prostanoids with natural alpha-chain displayed radioprotective properties. Expressed membrane stabilizing effect of two 9a-homo-13-thiaprostanoid nor-analogues was revealed in radiomimetic model experiments.

[The mechanism of the immunostimulating action of trimezon].

The influence of various concentrations (10(-9) - 10(-6) M) of the new immunostimulator trimezon of 8-aza-D-homogonan range upon in vitro proliferation of human lymphocytes, stimulated by PHA 0.5-10.0 micrograms/ml), was investigated by 3H-thymidine incorporation analysis.

[The gastroprotective and antiaggregant activities of 13-azaprostanoids].

Some 13-azaprostanoic acid derivatives were shown to have a high cytoprotective activity against the damaging effect of ethanol on the gastric mucosa in non-strain rats and affect ATP- and arachidonate-induced platelet aggregation in the whole blood of rabbits and rats in a different way. The gastroprotective activity that is common to natural and synthetic prostanoids is not closely related to the chemical structure of the compounds. On the contrary, the trends of these compounds to affect the induced platelet aggregation depend on the modification of both the cyclic moiety and both chains of a prostanoid molecule.

[The antithromboxane activity of alpha- and omega-modified carbocyclic analogs of PGH1].

In in vitro experiments on a model of arachidonate- and thrombin-induced platelet aggregation, analogues of PG endoperoxides displayed an antiaggregatory effect or stimulated spontaneous platelet aggregation in the whole blood of man and rabbits, but a slight antiaggregatory effect in the rabbit intact organism. The presence of the hydroxyl group instead of the routine alkyl omega-chain produced an antiaggregatory effect due to TxA2 receptor blockade.

[New possibilities in searching for immunomodulators among compounds with a steroid structure].

It was shown that a phytosteroid ecdisterone which is the principle of a new tonic drug ecdisten in doses of 5-20 mg/kg is able to stimulate the primary immune reaction slightly effecting the indices of T-cell immunity activity and phagocyte functions. On increasing ecdisterone dose to 50 mg/kg inhibition of the number of antibody cells in the mouse spleen was marked.

[Immunomodulators with an 8-azasteroid structure as inducers of liver cytochrome P-450].

Two structural analogues of D-homo-8-azasteroids, both an immunostimulant and an immunodepressant, are inductors of the liver cytochrome P-450 in animals. This capability was shown by means of both a decrease of the hexenal sleep duration in the pharmacological test and an increase of the quantity of cytochrome P-450 and the rate of N-demethylation of aminopyrine in the biochemical assays.

[Effect of 7-aza- and 13-aza-prostanoids on platelet aggregation].

The effects of 11 new analogues of 7-aza- and 13-azaprostanoic acid on platelet aggregation of the rat were studied in vitro and ex vivo. The analogues of 13-azaprostanoic acid in vitro (10(-7)-10(-8) mol/l) were found to exhibit the antiaggregation activity in the blood. The compounds containing five-member cycle are more active antiaggregants.

[The pharmacokinetics of an immunomodulator of the D-homo-8-azasteroid series].

The pharmacokinetic investigation and the study of metabolism of an immunostimulator of 8-azasteroid series were performed on a single-compartment model. The main pharmacokinetic parameters of the immunomodulator in mice were established using different routes of administration. The maximal accumulation of tritium-labeled 8-azasteroid was recorded in the kidneys, liver and lung.