Drug Resistance of Mouse Somatic Cells to Rifampicin in Experimental Tuberculosis.

We have demonstrated that long-term exposure of intact mice to rifampicin (6 months) induces resistance to this drug, which manifested in inability of rifampicin to suppress the growth of Mycobacterium tuberculosis in the lungs and spleen during subsequent infection. It the same time, isoniazid is still effective in these mice. In this case, the phenomenon of somatic resistance to rifampicin in mice was observed if the treatment was started in a short period (within 4 days) after infection with M. tuberculosis. If the interval between infection and rifampicin administration was longer (3 weeks), the resistance disappeared.

Changes in Microbiota and Development of Nonspecific Inflammation of Genitals in Female C57Bl/6 Mice after Aerosol Infection with Mycobacterium tuberculosis.

Infectious process even at the initial stage after aerosol infection with Mycobacterium tuberculosis induced rapid changes in vaginal microbiota in mice. Rapid decrease in both the quantity and diversity of microbiota was noted, and then, partial recovery of normal flora was observed. Changes in vaginal microbiota was detected as soon as in 3-7 days after lung infection, while inflammatory changes appeared by day 35. At the early stage of infection, no signs of inflammation were observed, neither M. tuberculosis nor its DNA were detected in mouse genital organs.

Peculiarities of the Inflammatory Process in the Reproductive Organs of C57Bl/6 Female Mice with Experimental Tuberculosis.

Intravenous infection of C57Bl/6 female mice with M. tuberculosis H37Rv led to involvement of the lungs and dissemination of the tuberculous infection to the abdominal and pelvic organs. M. tuberculosis were detected in the lungs and spleen in 14, 35, and 90 days and in the uterine horns in 90 days after infection. Morphological analysis of organs showed successive development of exudative necrotic tuberculosis of the lungs, acute and chronic nonspecific inflammation in the reproductive organs (vagina, uterus, and uterine horns). The inflammatory process in the reproductive organs was associated with the development of anaerobic dysbiosis, that was most pronounced in 35 days after infection. Antituberculous therapy was followed by reduction of M. tuberculosis count in the lungs and spleen in 60 and 90 days after infection, eliminatation of M. tuberculosis in the uterine horns, arrest of nonspecific inflammation in female reproductive organs, recovery of the balance between aerobic and anaerobic microflora, and development of candidiasis of the urogenital mucosa.

[Selective effects of pulmonary surfactant on various subpopulations of alveolar macrophages in the model of experimental tuberculosis].

Pulmonary surfactant is necessary component for maintenance of high level of phagocytic activity of alveolar macrophages. Tuberculosis inflammation reduces the production of surfactant by type II cells and phagocytic activity of alveolar macrophages. The effects of exogenous pulmonary surfactant on the ultrastructural changes of various subpopulations of alveolar macrophages were studied by TEM-method. For investigations the bronchial alveolar lavage fluid from guinea pigs infected of M. tuberculosis and treated by isoniatid or isoniazid + exogenous pulmonary surfactant were used. It was shown that isoniazid + exogenous pulmonary surfactant normalizes the heterogeneous population of alveolar macrophages providing stimulating effects on their maturation and phagocytic activity more effectively than isoniazid therapy.

[Effectiveness of new diagnostic drug Diaskintest in children for tuberculosis diagnostic].

DST was ascertained to have a high sensitivity in virtually all patients with tuberculosis and a positive reaction was first noted in the infected. With stabilization and regression, the response to DST was much less pronounced than that in clinical and primary infection (that to the Mantoux test being more evident). DST showed its use as a marker of active tuberculosis not only in its local forms, but also in latent tuberculous infection. This makes it possible to apply DST when preventive treatment is performed. The agent may be used to monitor the progress of treatment. DST has a high specificity--healthy individuals had a negative response to DST while the Mantoux test was positive in many cases. The high specificity of DST was suggested by the fact that the persons vaccinated with (this caused BCG ostitis) had a negative reaction to DST while the Mantoux test was positive in all cases BCG-vaccinated BCG. The findings warrant the use of DST for the differential diagnosis of tuberculosis and BCG-associated complications and the possibility of differentiating postvaccinal and infection allergy in children and adolescents.

[Effect of use of bone marrow cells in therapy for experimental tuberculosis].

The authors studied the efficiency of use of bone marrow cells in the treatment of experimental tuberculosis. Bone marrow cell transplantation to H37Rv tuberculosis-infected H37Rv mice was shown to prolong the life span in the animals as compared to untreated animals. Examination of humoral immunity indicated that administration of allogenic bone marrow cells resulted in the nonspecific polyisotypic stimulation of antituberculosis antibodies, which is essential in producing the protective humoral background. A more significant generation of IgG2a antibodies than that of IgG1 antibodies was also found in therapy with bone marrow cells, which pointed to the fact that there was a Th1 response that is obviously protective in tuberculosis. The high level of IgG2a antibodies correlated with the high specific cellular immune response estimated by the delayed hypersensitivity reaction.

[Antimycobacterial activity of a dry birch bark extract on a model of experimental pulmonary tuberculosis].

The study deals with the evaluation of antimycobacterial activity of betulinol, a dry birch bark extract (BBE), on a model of infection caused by Mycobacterium tuberculosis (MBT). It has established the inhibitory action of betulinol on the in vitro and in vivo growth of MBT and its positive effect on reparative processes in the lung, liver, and spleen of tuberculosis-infected mice.

[Modulation of the course of experimental tuberculosis in mice by in vivo administration of monoclonal antibodies to interleukin-2, gamma-interferon and interleukin-4]. / Modulatsiia techeniia éksperimental'nogo tuberkuleza u myshei vvedeniem in vivo monoklonal'nykh antitel k interleikinu-2, gamma-interferonu i interleikinu-4.

The impact of the in vivo administration of monoclonal antibodies against cytokines on the development of a pathological process in mice infected with Mycobacterium tuberculosis H37Rv-infected mice. The susceptibility to fatal experimental tuberculosis, the level of DTH to mycobacterial antigens, the production of specific antimycobacterial IgG and IgM, T-cell proliferative responses to M. tuberculosis H37Rv antigens. Anti-gamma-interferon and anti-IL-2 treatment was found to provide virtually no effects on the course of experimental tuberculosis, the intravenous administration of anti-IL-4-monoclonal antibodies on days 2, 4, and 6 after inoculation with a lethal dose of M. tuberculosis significantly increases the median survival time (MST). This increase in MST is accompanied by a more prominent DTH response and lymphocytic proliferative reaction on the one hand, and by lower concentrations of specific IgG on the other. The therapeutical prospects of anti-IL-4 treatment in tuberculosis are discussed.

[Production of immune interferon in experimental tuberculosis and antituberculosis vaccination in mice]. / Produktsiia immunnogo interferona pri éksperimental'nom tuberkuleze i protivotuberkuleznoi vaktsinatsii u myshei.

The serum content of interferon (IF) and its correlation with diverse immunologic parameters were studied in tuberculosis-resistant mice. In primary contamination the IF level was much higher in B10 mice highly sensitive to tuberculosis infection in all periods of the study than that in highly resistant A/Sn mice. In the vaccinated mice which were later infected this tendency remained but IF levels were 1.5--2 times higher than in primary contamination. Comparison of the IF level and the studied resistance parameters in the resistant mice revealed an inverse correlation. If the immunologic parameters in resistant A/Sn mice are higher than those in B10 mice the latter have significantly higher serum IF levels.