[STUDYING THE ACUTE TOXICITY OF DEXTRAN POLYALDEHYDE CONJUGATE WITH ISONICOTINIC ACID HYDRAZIDE.]

The acute toxicity of a new antubercular drug, dextran polyaldehyde conjugate with isonicotinic acid hydrazide (dextrazide), has been studied on animals, HepaRG cell line, and FRSN human skin fibroblasts. Average tolerable doses (LD(10), LD(16)), half-lethal doses (LD(50)), and lethal doses (LD(84)) of dextrazide have been determined for intraperitoneal introduction in mice and rats and intravenous injection in rabbits.

Study of fibrotic complications and hydroxyproline content in mouse liver at different stages of generalized BCG-induced granulomatosis.

Generalized BCG-induced granulomatous was simulated in BALB/c male mice. The number of tuberculous granulomas in the liver and their size as well as the number of hepatocytes showing vacuolar degeneration increased from day 3 to 180 postinfection. Necrotic changes in hepatocytes were most pronounced at the acute phase of inflammation (days 3 to 30). Proliferative processes in the liver parenchyma in the experimental group were less marked than in the control. Increased content of collagen fibers in the liver was determined by excessive collagen synthesis in necrotic areas as well as increased amount of granulomas and fibroblasts. Enhanced proliferative and fibroplastic activity of fibroblasts in granulomas and liver parenchyma was evidently determined by activated granuloma macrophages. These shifts determined changes in the liver content of hydroxyproline during the acute and chronic periods of the disease.

Expression of profibrotic growth factors and their receptors by mouse lung macrophages and fibroblasts under conditions of acute viral inflammation in influenza A/H5N1 virus.

Morphological signs of early interstitial fibrosis, developing under conditions of acute viral inflammation (postinfection days 1-14), were observed in C57Bl/6 mice infected with influenza A/H5N1 A/goose/Krasnoozerskoye/627/05 virus. The development of fibrosis was confirmed by an increase in the number of lung cells expressing TNF-α. These changes were recorded in the presence of a many-fold increase in the counts of macrophages and fibroblasts expressing FGF, EGF, and their receptors.

Biological characteristics of influenza A(H1N1)pdm09 virus circulating in West Siberia during pandemic and post-pandemic periods.

We studied biological characteristics of influenza A(H1N1)pdm09 virus circulating in Siberia during the 2009 pandemic and the post-pandemic period of 2011. BALB/c mice were chosen as the experimental model. Virus titers in the lungs were evaluated on days 1, 3, 6 and blood serum titers on day 15 after infection with different strains. Blood sera of convalescents after influenza of 2010-2011 epidemic season were analyzed. Influenza A(H1N1)pdm09 virus strains isolated during the post-pandemic period of 2011 were characterized by low epidemic activity and virulence in comparison with the strains isolated during 2009 pandemic period, which indicates completion of the pandemic cycle.

Role of matrix metalloproteinases and their inhibitor in the development of early pulmonary fibrosis in mice infected with influenza A/H5N1 A/goose/Krasnoozerskoye/627/05 virus.

High levels of macrophages and fibroblasts expressing MMP-2, MMP-9, and MMP-10 against the background of progressing early fibrosis of the lungs (manifesting in an increase in volume density of type I, III, IV, and VI collagens) were found in C57Bl/6 mice infected with influenza A/H5N1 A/goose/Krasnoozerskoye/627/05 virus. Progressing fibrosis of the lungs in infected mice was associated with imbalance of collagen synthesis and degradation processes conjugated with high levels of macrophages and fibroblasts expressing TIMP-2.

[Oxidised dextrans influence on reactive oxygen species generation by murine peritoneal exudate phagocytic cells].

The effects of oxidized dextrans of different molecular weight on reactive oxygen species production and transmembrane mitochondrial potential of macrophages and neutrophils have been studied in vivo and in vitro. Oxidised dextrans demonstrated moderate direct antioxidant ability but induced intracellular oxidative stress through the increase of oxygen radical generation. This effect of the investigated compounds amplifies the cytotoxic and bactericidal potential of phagocytes and can influence isoniazid metabolism, thus increasing its efficiency in therapy of infectious diseases.

[The placental structural organization in pulmonary tuberculosis].

The placentas taken from 83 pregnant women with gestation of 37-40 weeks were morphologically and morphometrically studied. Group 1 comprised 23 pregnant women with pulmonary tuberculosis. Group 2 included 40 pregnant women whose pregnancy was complicated by gestosis. Group 3 (control) consisted of 20 healthy pregnant women. Group 1 was found to have chronic placental insufficiency caused by abnormal placental villous immaturity the basis of which was impaired processes of villous differentiation and terminal villous angiogenesis. In most cases, chronic placental insufficiency was compensatory in all the groups under study; but there were differences in compensatory mechanisms. The leading mechanism was cellular in Groups 1 and 2, the mixed (vascular and cellular) types of compensation was predominant in Group 3 (control).

Effect of oxidized dextrans on NO synthase and arginase activities of mouse macrophages.

We studied the effect of oxidized dextrans with molecular weights of 30-35 kDa and 60-65 kDa on NO synthase and arginase activities of mouse peritoneal macrophages in vivo and in vitro. Oxidized dextrans irrespective of molecular weight shifted the NO synthase/arginase balance towards predominance of NO production under in vivo and in vitro conditions. Administration of the test compounds to intact mice considerably increased NO synthase activity, while culturing of peritoneal macrophages in the presence of modified dextrans reduced arginase activity in these cells. These effects of oxidized dextrans create conditions for predominant stimulation of Th1-mediated immune reactions.

Ultrastructural characteristics of type A epithelioid cells during BCG-granulomatosis and treatment with lysosomotropic isoniazid.

We studied BCG-granulomas, their cellular composition, and ultrastructure of type A epithelioid cells in the liver of male BALB/c mice with spontaneous granulomatous inflammation. The animals received free isoniazid or isoniazid conjugated with lysosomotropic intracellularly prolonged matrix (dialdehyde dextran, molecular weight 65-75 kDa). Lysosomotropic isoniazid was accumulated in the vacuolar apparatus of epithelioid cells and produced a stimulatory effect on plastic processes in these cells.

[Use of essential oil of peppermint (Mentha piperita) in the complex treatment of patients with infiltrative pulmonary tuberculosis].

The paper describes the effects of peppermint (Mentha piperita) essential oil inhaled by patients with infiltrative pulmonary tuberculosis in the penitentiary system. This procedure is shown to be most effective in infiltrative pulmonary tuberculosis in the phase of resorption of infiltrates and/or closure of decay cavities. The efficiency is determined by the rapid positive changes in a tuberculous process, which appear as a rapider regression of tuberculous inflammation, causing small residual changes. This procedure may be used to prevent recurrences and exacerbations of pulmonary tuberculosis.

[Computer morphometry in the differential diagnosis of thyroid neoplasms].

The quantitative studies of follicular thyroid tumors were applied for their morphological differentiation. The computer-aided analysis of the images permits objective and prompt estimation of the quantitative parameters of the structural components of a tumor in the histological sections. The comparison of the values obtained in the tissue samples could identify the most typical differentially diagnostic criteria that could help to define the type of a tumor, by replacing a routine morphological study based on the analysis of qualitative morphological signs. Its effectiveness is largely determined by the skill of a physician and the subjectivity of assessments of observed phenomena.

[The results of quantitative cytological analysis of the structure of follicular thyroid tumors using computer and neural network technologies].

Artificial neural network is a complex system capable of gathering and synthesizing data and capable of learning using particular given parameters. This technology was applied to studying cytological diagnostics of thyroid diseases to differentiate between follicular cancer and follicular adenoma. A complex of quantitative cytological characteristics was used to describe cytological preparations by examples of known cytological diagnosis to train the neural network. Among offered cytological examples, 96% were recognized correctly during testing.

Mononuclear phagocyte system in mice with intrauterine Candida albicans infection and postnatal experimental tuberculosis.

Intrauterine Candida albicans infection in mouse fetuses affected the type of granulomatous inflammation induced by BCG vaccine during the postnatal period. It manifested in increased formation of granulomas and variations in their cellular composition.

[Differential diagnostic capacities of computer-aided analysis of thyroid follicular tumor images].

To establish the objective quantitative cytological parameters of thyroid follicular tumor cells for their further use as criteria for differential cytological diagnosis, the authors made a mathematical analysis of their values obtained by computer-aided karyocytometry of thyroid follicular tumors. It is recommended that the arithmetic mean values of nuclear areas, perimeters, and optic densities should be used as criteria for differential diagnosis when there are qualitative cytological signs indicating that the tumor under study may belong to the follicular type of papillary carcinoma.

[Human fetal liver in hematogenic infection (a morphometric study)].

The results of a morphometric study of 40 human fetus livers at a 26-27 week of gestation are presented. There were fetuses with signs of intrauterine hypoxia, generalized intrauterine infection. It is shown that intrauterine hematogenic fetus infection is accompanied with evident destructive changes in the liver parenchyma as compared with the controls and numerous sites of hemopoiesis. The conditions for development of a generalized infectious process and sclerosis of portal tracts appear due to destructive changes as well as intoxication, secondary hypoxia and decrease of Kupffer's cells number.

Response of mononuclear phagocyte system to experimental tuberculosis in mice of opposite strains.

Genetically determined peculiarities of the reaction of the mononuclear phagocyte system to BCG vaccine manifested in CBA and C57Bl/6 mice by differences in the number and size of granulomas and time course of changes in the cellular composition of granulomas, peripheral blood, and bone marrow.

Functional activity of the adrenal cortex in mice of opposite strains with candidiasis.

Experiments were performed on two opposite strains of mice differing in the basal blood glucocorticoid concentration in the blood. Infection of animals with C. albicans fungi led to the development of hypocorticism. C57Bl/6 and CBA mice with progressive candidiasis showed a persistent and phasic course of hypocorticism, respectively.

Effect of IFN-alpha on CC1 4-induced fibrosis of the liver and immune status in mice of different age.

In young, adult, and old mice fibrosis was induced by administration of CC1(4) and treated with IFN-alpha; liver fibrosis was evaluated by morphometry of argyrophilic fibers, immune status by the splenocyte proliferative response. minimum immunosuppression and maximum antifibrotic effect were observed in young mice, while adult mice exhibited pronounced immunotoxicity and weak response to interferon therapy.

Level of liver fibrosis and immune status of mice of different age after heroin treatment and long abstinence.

Young and middle-aged CBA mice were injected with "street" heroin in increasing doses for 14 days. Volume density of perisinusoid argirophilic fibers increased in both age groups (the increase being more pronounced in middle-aged mice), while the levels of spontaneous, LPS- and ConA-stimulated splenocyte proliferation decreased in young mice. Six months after heroin discontinuation further progress of liver fibrosis was observed in young mice.

[Dynamics of cellular transformations in Candida-induced granulomas in lymph nodes after treatment with a lysosomotropic form of amphotericin B: an experimental study].

In an experiment conducted using male CBA mice, cellular events during granulomatous Candida-induced inflammation were studied both in untreated animals and in animals treated with a new lysosomotropic composition, consisting of amphotericin B in intracellularly prolonged dextran immunomodulating matrix. To induce systemic Candida granulomatous inflammation, mice were given a single 0.2 ml intraperitoneal injection of Candida albicans culture (2.5 x 10(9) microbial bodies) dissolved in 0.9% isotonic saline. The findings obtained indicate greater therapeutic effect of amphotericin B and dextran dialdehyde composition as compared with a free (unconjugated) form of amphotericin B, that was manifested by the disappearance of granulomas and the capacity to prevent the development of spontaneous destructive processes in granulomas. Independent antimycotic effect of dextran dialdehyde was also demonstrated.