Dynamics of Changes in the cAMP/cGMP Concentration Ratio in the Thymus and Spleen of Laboratory Mice during Vaccination against Plague and Tularemia against the Background of Immunomodulation.

Vaccine strains Yersinia pestis EV NIIEG at a dose of 103 CFU and Francisella tularensis 15 NIIEG at a dose of 102 CFU induced changes in the concentration of cyclic nucleotides in the thymus and spleen of white mice. Antigen-induced changes in the cAMP/cGMP ratio in immunocompetent organs had a phase or oscillatory character, which seems to be related to the regulation of postvaccination immunoreactivity in the body. Synthetic organoselenium compound 974zh stimulated an increase in the amplitude of cAMP/cGMP oscillations, indicating its stimulating effect on the immunogenic properties of vaccine strains at doses an order of magnitude below the standard doses.

The Influence of the Synthetic Organoselenium Preparation 974zh on the Immunogenic Activity of Yersinia pestis EV Vaccine Strain NIIEG.

In the present study, a stimulating effect of a new synthetic organoselenium compound 2,6-dipyridinium-9-selenabicyclo[3.3.1]nonandibromide (974zh) on the immunogenic activity of the vaccine strain Yersinia pestis EV NIIEG was revealed. After infection with the virulent plague strain, the survival rate of laboratory mice immunized with the vaccine strain grown on Hottinger's agar in the presence of 974zh (300 µg/ml) increased in comparison with control animals immunized with the Y. pestis EV NIIEG culture grown on agar without the studied compound. Plasmid screening of cultures grown on medium with and without 974zh showed that plasmid DNA of Y. pestis EV culture grown in the presence of 974zh had broader bands in the control grown without 974zh. This phenomenon can indicate activation of replication of plasmid DNA of Y. pestis EV under the influence of the experimental compound.

Effect of a Synthetic Organoselenium Compound on Post-Vaccination Immunopoiesis in the Red Bone Marrow and Cell Composition of Peripheral Blood of White Mice Vaccinated with Yersinia pestis EV.

We studied the effect of an experimental synthetic organoselenium compound 2,6-dipyridinium- 9-selenabicyclo[3.3.1]nonane dibromide (974zh) on the cell composition of the red bone marrow and peripheral blood in white mice. The study drug co-administered with Yersinia pestis EV vaccine strain (103 CFU) potentiated maturation and migration of mature neutrophils from the bone marrow into the circulation. Reducing the dose of the live vaccine and the anti-inflammatory properties of the study drug made it possible to reduce the allergic reaction during the vaccination process.

Immunotropic Properties of an Experimental Synthetic Selenium-Organic Compound.

We studied immunotropic properties of synthetic selenium-organic preparation 2,6-dipyridinium-9-selenabicyclo[3.3.1]nonyl dibromide (974zh). The experimental preparation reduced the cAMP/cGMP ratio, which indicated an increase in proliferative activity of cells of immunocompetent organs (thymus and spleen) in experimental animals. It was shown that 974zh intensified the immune response to Yersinia pestis EV thereby increasing the resistance to the plague agent.

Effect of Synthetic Organoselenium Drug on the Degree of Pathological Changes in the Organs of White Mice Immunized with Tularemia and Brucellosis Vaccines.

We studied the effect of the organoselenium compound 2,6-dipyridinium-9-selenium-bicyclo[ 3,3,1]nonan dibromide (974zh) on the severity of pathological changes in the organs of experimental animals immunized with live tularemia and brucellosis vaccines. It was found that 974zh reduced reactogenicity of vaccines for experimental animals. Our findings indicate the prospects for further studies of the effects of 974zh on the functional state of experimental animals.

Effects of Thermoextracts of Brucella S and L Forms on Lipid Peroxidation and Antioxidant Defense in Organs of Laboratory Animals.

The dynamics of LPO marker malondialdehyde formation and peroxidase-destroying activity was studied in homogenized organs of guinea pigs, immunized with thermoextracts from S and L forms Brucella abortus I-206. The L form brucella thermoextract exhibited a lower reactogenicity and adequately activated the antioxidant system, due to which the destructive effects of ROS could be partially neutralized during the vaccinal process.

Effect of Metal-Containing Nanocomposites on Functional Status of the Thymus in Experimental Animals.

The effects of nanostructurized composites argentogalactomannan and argento-poly-1-vinyl-1,2,4-triasole on the kinetics of T cell maturation in the thymus of albino mice were studied. These nanocomposites stimulated the formation of CD3+CD4+CD8- and CD3+CD4-CD8+ cells from CD3-CD4-CD8- cells, the effect of argentogalactomannan was more potent. The efficiency of these compounds as agents improving the defense potential deserves special studies.

Immunogenesis in White Mice Infected with Yersinia pestis with Different Plasmid Composition.

Morphological changes in the immunocompetent organs of white mice with experimental plague infection manifested in activation of the immune response of different degree and pathological process of different severity that depended on the plasmid composition of Y. pestis. Widening of the T-dependent zones in the immune organs of white mice infected with isogenic strains of Y. pestis with different plasmid composition attests to activation of cellular immunity. Our findings allow considering Y. pestis subsp. altaica I-2948/3, Y. pestis subsp. pestis I-3479 and Y. pestis subsp. pestis I-3480 as promising candidates for vaccine strains.

[Experimental anthrax infection in laboratory animals with differing species susceptibility to the causative agent]. / Eksperimental'naia sibireiazvennaia infektsiia u laboratornykh zhivotnykh s raznoi vidovoi vospriimchivost'iu k vozbuditeliu.

In guinea pigs and noninbred white mice, infected subcutaneously with anthrax which resulted in their death, characteristic generalized infection with the hematogenic contamination of their organs and the signs of intoxication and shock could be observed. In inbred white rats (Fisher 344) the invasion and dissemination of B. anthracis are relatively slightly pronounced, the phenomena of intoxication and shock being clearly prevalent.

[Experimental characteristics of anthrax intoxication]. / Eksperimental'naia kharakteristika sibireiazvennoi intoksikatsii.

In experimental anthrax intoxication, a highly important stage of its pathogenesis consists in microcirculatory disturbances with the phenomena of blood sludge, accompanied by the increased permeability of blood vessels not only for plasma, but also for red blood cells. These disturbances result in perivascular hemorrhages, hemorrhagic infiltrations, edema and cavitary transudates. Pulmonary edema and, as a consequence, the accumulation of fluid in pulmonary alveoli and the respiratory tract are of particular importance and, probably, can be considered the basic cause of the ensuing acute and fatal asphyxia. Such vascular and pulmonary insufficiency is accompanied by a decrease in the content of macroergic compounds (and in particular ATP), the characteristic deformation of red blood cells and disturbances in their oxygen transport function, which is linked with the decreased content of 2,3-diphosphoglycerate.

[Evaluation of vaccinal immunogenesis by the peroxidase method]. / Otsenka vaktsinal'nogo immunomorfogeneza peroksidaznym metodom.

The possibility of evaluating functional immunomorphogenesis in the course of the vaccinal process after the injection of conjugated and live brucellosis vaccines, as well as conjugated plague antigen and Yersinia pestis strain EV, to guinea pigs has been shown by means of the direct and two-layer variants of the immunoperoxidase assay. The dynamics of the accumulation of globulin-producing cells in the immunocompetent organs and the time course of immunoglobulin titers in the peripheral blood after the injection of live and conjugated vaccines have been followed up. These data may be used for the morphological evaluation of approved preparations.