[On the occasion of the 80th anniversary of the Department of Pathologic Anatomy, Novosibirsk State Medical University].

The paper gives a brief overview of the history of the Department of Pathologic Anatomy, Novosibirsk State Medical University, which is 80 years old in 2015.

Fibrogenesis in granulomas and lung interstitium in tuberculous inflammation in mice.

The study in mouse model of BCG-induced granulomatous inflammation showed that early pulmonary fibrosis (day 3-30 postinfection) in tuberculous inflammation was primarily determined by increased number of fibroblasts in the lung interstitium and granulomas and enhanced fibroplastic activity. Fibroplastic processes are initiated via an increase in secretory activity of activated granuloma macrophages caused by the persistence of the pathogen in the cells of the mononuclear phagocytic system. The dynamics of hydroxyproline concentration under these conditions is determined by changes in the number and differentiation degree of fibroblasts in granulomas and lung interstitium at various stages of tuberculous inflammation.

Hydroxyproline content and fibrogenesis in mouse liver and lungs during the early stages of BCG granulomatosis.

In generalized BCG granulomatosis, fibrosis starts early (on day 3) and not only around the granulomas, but also in the organs. The severity of organ fibrosis is apparently determined by the concentration of granulomas, in particular their macrophages inducing proliferation of fibroblasts in organs and granulomas as well as activation of fibrogenesis. On day 30 after infection, the degree of fibrosis in the lungs was by 6 times higher than in the liver. The increase in hydroxyproline concentration in organs in early period of infection was determined by acute stress, while on day 30 it resulted from its enhanced synthesis by granuloma fibroblasts and resident fibroblasts in organs.

Effect of oxidized dextran on reparative regeneration of the skin after burn injury.

In adult Wistar rats, a 3B degree skin burn was modeled and treated by daily application of 5% aqueous solution of oxidized dextran (molecular weight of 60 kDa) on the wound surface. In animals treated with oxidized dextran, neutrophil count in the connective tissue adjacent to the wound increased by day 5 and then decreased by day 21 after burn infliction; proliferation of fibroblasts was observed later than in untreated animals, in whom inflammation run a subacute course. Oxidized dextran increased the content of macrophages in the wound and surrounding connective tissue from days 14 to 21 after burn infliction and promoted effective and complete healing of the skin defect. Regeneration was realized mainly due to proliferation of keratinocytes at the wound edges and was completed by 7 days earlier than in untreated animals, in whom the area of injury by day 21 decreased by only 2 times (vs. 10 times in treated rats).

Changes in activity of free radical oxidation processes in the early stages of BCG granulomatosis.

We studied the intensity of free radical oxidation in the liver and activity of oxidative metabolism in mouse peritoneal exudate phagocytes at the early stages of chronic generalized BCG-induced granulomatosis (days 3 and 30 after a single intraperitoneal or intravenous administration of 0.5 mg of BCG vaccine). It was found that both methods of injection did not change the intensity of free radical lipid peroxidation in the liver in comparison with the control, but activity of free radical oxidation mediated by production of hydrogen peroxide was increased in the liver and peritoneal exudate at the stages of mature granuloma formation (day 30). At the same time, intraperitoneal injection contributed to more pronounced activation of lipid peroxidation and synthesis of hydrogen peroxide in the liver.

Morphological study of the main mechanisms of myometrium involution after repeated pregnancies in mice.

Elimination of "excessive" myocytes and their structures during involution of the myometrium after the first and third pregnancies was realized by clasmocytosis (eliminating the greatest volume of myocyte cytoplasm fragments), apoptosis, and necrosis (equal percentage by volume). In contrast to the first pregnancy, involution after the third one was not over by day 10 because of inhibited elimination of functionally lost myocytes by necrosis and apoptosis mechanisms. Presumably, this was caused by slower hydrolysis of apoptotic bodies by macrophages. The concentration of macrophages in the myometrium on day 10 of the involution period in females after the third delivery was 4-fold higher than in intact mice and in females after the first delivery during the same period.

Morphological changes in the brain of mice with systemic candidiasis treated with composition of amphotericin B and oxidized dextran.

We observed morphological manifestation of encephalitis 3, 7, 10 and 28 days after intravenous infection of adult male CBA mice with Candida albicans. Compounds were administered intraperitoneally every other day starting from the next day postinfection. Untreated animals (100%) died over the period between days 18 and 20 postinfection; 60% animals receiving oxidized dextran alone survived by day 28 of observation. All animals treated with amphotericin B and composition of amphotericin B and oxidized dextran survived. On day 3 postinfection, the count of macrophage infiltrates and granulomas in the cerebral interstitium of mice treated with amphotericin B was equal to that in untreated mice, but was sufficiently lower in animals treated with the composition or oxidized dextran alone. On day 10, this index was similar in all groups and was approximately 5 times lower than in untreated animals on day 3. On day 28, macrophage infiltrates and granulomas were absent in the brain of all treated mice. These data suggest that oxidized dextran produced a therapeutic effect, which manifested earlier than the effect of amphotericin B and potentiated its effect, probably due to its competition with Candida albicans for mannose receptors on the brain-blood barrier endothelium.

Structural and functional peculiarities of mast cells in undifferentiated connective tissue dysplasia.

We performed an immunomorphological study of mast cells from undamaged skin in women with phenotypical evidence of undifferentiated connective tissue dysplasia syndrome, patients of cosmetological clinics. It was found that the numerical density of mast cells containing chymase granules in this condition 1.7-fold surpassed the corresponding parameter in patients without signs of connective tissue dysplasia syndrome, which probably was a result of compensatory and adaptive reaction aimed at activation of the synthesis of the connective tissue extracellular matrix components. It was hypothesized that increased content of chymase-positive mast cells in the skin of patients with connective tissue dysplasia syndrome contributed to the formation of associated arterial hypertension.

Preventive efficacy of oxidized dextran and pathomorphological processes in mouse lungs in avian influenza A/H5N1.

Oxidized dextran (60 kDa) exerted a pronounced preventive effect in laboratory mice infected with avian influenza subtype H5N1 A/Goose/Krasnoozerskoye/627/05 virus, which manifested in a significant increase in mouse lifetime (by 24.4%) and a decrease in mortality rate (3.3-fold). This was probably related to significant alleviation of pathological changes in the lungs and severity of hemodynamic and inflammatory complications and early fibrosis [corrected].

Morphofunctional characteristics of the immune system in CBA and C57Bl/6g mice.

We studied peculiarities of morphofunctional organization of the immune system in C57Bl/6g and CBA mice differing by their susceptibility to various types of infectious agents. The revealed differences in the structure of lymphoid organs, T lymphocyte subpopulation ratio and their differentiation into Th1/Th2 cells after mitogen stimulation drove us to a conclusion on genetically determined regularities in the development of the immune response in these animal strains.

Adrenocortical system response to induction of inflammation with silicon dioxide in rats with alloxan-induced diabetes mellitus.

Alloxan-induced diabetes mellitus in rats was characterized by persistent increase in blood levels of corticosterone, while chronic granulomatous inflammation induced by silicon dioxide and its combination with alloxan-induced diabetes mellitus were associated with transient increase in blood corticosterone level followed by gradual development of hypoadrenocorticism. The content of corticosterone in the adrenal glands of rats with alloxan-induced diabetes mellitus remained unchanged in the dynamics of the disease, but the level of progesterone decreased at the early terms of diabetes and then returned to the initial values. After administration of silicon dioxide to intact rats and to rats with diabetes mellitus, changes in hormone content in the adrenal glands were observed only at the initial stages of inflammation and consisted in elevation of corticosterone concentration against the background of reduced progesterone content.

[EFFECT OF THE POLYENZYME DRUG WOBENZYM ON THE ACTIVITY OF A DESTRUCTIVE INFLAMMATORY PROCESS IN THE COMPLEX THERAPY OF PULMONARY TUBERCULOSIS].

Ninety patients with new-onset pulmonary tuberculosis were examined prior to therapy The patients were randomized into 2 groups: 1) 20 patients receiving the standard antibiotic therapy regimen; 2) 70 patients taking the standard antibiotic therapy and the polyenzyme drug Wobenzym. The use of the latter in the complex therapy of patients with pulmonary tuberculosis was shown to cause an increase in the activity of the destructive inflammatory process and to regulate the function of the immune system as compared with those during the standard therapy.

Involvement of interstitial structures of the kidney into hydrosmotic effect of vasopressin (morphofunctional study).

Administration of desmopressin for 4 days to homozygous Brattleboro rats lacking endogenous vasopressin induced an increase in osmotic concentration and was accompanied by typical changes in the morphofunctional state of interstitial cells of the renal papilla. These changes increase the permeability of extracellular matrix, which attested to the involvement of interstitial cells into hydrosmotic reaction to vasopressin.

Effect of lysosomotropic form of amphotericin B on functional state of phagocytes in experimental candidiasis.

Effect of antifungal preparation amphotericin B and its lysosomotropic composition with dialdehyde-dextran on functional state of phagocytizing cells in the dynamics of granulomatous inflammation induced by C. albicans was studied on CBA mice. A stimulating effect of amphotericin B on the production of reactive oxygen species by peritoneal and bone marrow phagocytes was observed, while lysosomotropic form of the antibiotic did not stimulate generation of oxygen radicals.

Structural changes in the liver and content of steroid hormones in the blood and adrenal glands of mice with systemic candidiasis treated with a composition of amphotericin B and dialdehyde dextran.

In CBA mice infected with C. albicans, phasic pattern of granulomatosis development was observed. In all groups, the number of granulomas in the liver was minimum on day 56 after infection. Treatment with free amphotericin B and its composition with dialdehyde dextran (CA) reduced the number of infiltrations and granulomas in the liver, the changes were more pronounced in animals receiving CA. A different pattern of cyclic fluctuations of cortisol content in the blood and adrenal glands and progesterone content in the adrenal gland was observed. By the end of observation (day 84), cortisol content in the blood and adrenals of mice treated with CA was considerably lower than in untreated mice and animals receiving amphotericin B.

Content of steroid hormones in the blood and adrenal glands of mice in the dynamics of BCG- and SiO2-induced granulomatous inflammation.

Individual or combined administration of BCG vaccine and silicon dioxide to male mice induced a nonspecific stress response of the adrenal glands and gonads judging from changes in the concentration of blood cortisol and testosterone. The dynamics of cortisol concentration in the adrenal glands was similar, while changes in progesterone concentration were in antiphase to those in the blood. After combined administration of both inductors of granulomatous inflammation, changes in the concentrations of the studied hormones to a greater extent corresponded to their dynamics after injection of BCG.

Effect of oxidixed dextrans on oxidative and metabolic function of mouse peritoneal macrophages in vitro and in vivo.

We compared the effects of dextrans with a molecular weight of 35 kDa oxidized by chemical (OD(ch)) and radiochemical (OD(r)) methods on oxidative and metabolic functions of peritoneal macrophages from BALB/c mice in vitro and in vivo. It was found that none type of dextrans exhibits chemiluminescent properties. In vitro study showed that OD(ch) had a priming effect on mouse peritoneal macrophages, while OD(r) did not potentiate the oxidative and metabolic response of cells to zymosan. Being injected intraperitoneally, OD(r) more markedly enhanced chemiluminescent response of mouse peritoneal macrophages and reduced their viability than OD(ch). Thus, both dextrans are biocompatible, but in OD(ch) this parameter is higher.

Pathogenesis of infectious disease of mice caused by H5N1 avian influenza virus.

The pathogenesis of a disease caused by Qinghai-like H5N1 influenza virus in BALB/c mice was studied. Clinical, morphological, and immunological characteristics of the experimental infection caused by highly pathogenic A/duck/Tuva/01/06/ (H5N1) virus are described.

Morphological changes in bird viscera in experimental infection by highly pathogenic H5N1 avian influenza virus.

Intravenous infection of chicken with H5N1 avian influenza virus (strain A/Gs/Krasnoozerskoye/627/05) causes rapid lethal outcome. Pathomorphological study of bird viscera showed manifestations of disseminated intravascular coagulation syndrome, generalized inflammatory reaction, and wide-scale necrobiotic changes in tissues.

Potentialities of differential immunohistochemical diagnosis of some follicular tumors of the thyroid gland.

Differential diagnosis of thyroid follicular adenomas, follicular cancer, and papillary cancer with follicular structure was carried out. Proliferation coefficients, probability of atypia, and tumor growth activity were evaluated on the basis of quantitative proportions of proliferation and apoptosis genes expression, derived from indexes of labeled nuclei expressing Ki-67, bcl2, p53 and cytoplasm with expression of bcl2, p53 in cells of these tumors. Significant differences between all the studied tumors of the thyroid grand with follicular structure were detected. The proposed criteria supplement the postoperative morphological differential diagnosis of thyroid tumors.