Dextran loading protects macrophages from lipid peroxidation and induces a Keap1/Nrf2/ARE-dependent antioxidant response.

Aims: Linear dextrans are often proposed as drug delivery systems with milder adverse effects and lower effective drug concentrations. Linear dextrans are polysaccharides that can potentially be used to load macrophages with drugs to transport them to a site of inflammation. Recently, it was reported that dextrans may exert a protective effect vis-à-vis drug cytotoxicity and during wound healing.

[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.

Association of Helicobacter pylori and iNOS production by macrophages and lymphocytes in the gastric mucosa in chronic gastritis.

Helicobacter pylori is one of the most common causes of chronic gastritis. With the development of the disease cellular inflammatory infiltrates composed of lymphocytes, plasma cells, and macrophages are formed in epithelium and lamina propria of the stomach. These cells are capable of secreting a number of active substances, including inducible nitric oxide synthase (iNOS).

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.

Immunomorphologic manifestations in mice liver infected with influenza A/H5N1, A/goose/Krasnoozerskoye/627/05 strain.

Highly pathogenic avian influenza H5N1 (HPAI H5N1) viruses can infect mammals, including humans, causing severe systemic disease with the inhibition of the immune system and a high mortality rate. In conditions of lymphoid tissue depletion, the liver plays an important role in host defence against viruses. The changes in mice liver infected with HPAI H5N1 virus A/goose/Krasnoozerskoye/627/05 have been studied.

Oxidative stress and free-radical oxidation in bcg granulomatosis development.

Background: Little is known about the role of free-radical and oxidative stress signaling in granuloma maturation and resolution. We aimed to study the activity of free-radical oxidation processes in the dynamics of BCG-induced generalized granulomatosis in mice.

Methods: Chronic granulomatous inflammation was induced in male BALB/c mice by intravenously injecting the BCG vaccine, and the production of oxidative stress (activity of free-radical oxidation processes) and histological changes in the lungs, liver, and peritoneal exudate were measured 3, 30, 60, and 90 days after infection.

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.

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).

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.

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.

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.

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).

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.

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.

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.

Lipid peroxidation in the liver of mice during development of granulomatous inflammation after combined infection with C. albicans and M. tuberculosis.

Activity of LPO in the liver of CBA mice during the development of granulomatous inflammation after combined infection with C. albicans and M. tuberculosis was evaluated by the levels of conjugated dienes, ketodienes, conjugated trienes, and products of interactions between intermediate LPO products and 2-TBA.

Comparative study of the in vitro effect of nanoliposomes with oxidized dextrans on peritoneal cells.

We studied the in vitro effect of hybrid molecular-nanosomal biocompatible compositions on cultured peritoneal cells. The compositions consisted of oxidized dextrans with a mean molecular weight of 35 and 60 kDa, which were obtained by chemical and radiochemical oxidation of dextran. Hybrid nanoliposomal compositions of chemically oxidized dextran (permanganate method) had greater biocompatibility and tropic activity to macrophages compared to nanoliposomes of radiochemically oxidized dextran.

In vitro effect of oxidized dextrans on peritoneal cells.

We studied the dependence of in vitro dextran biocompatibility on the method of oxidation of 35-kDa dextran. The biocompatibility of dextran oxidized with potassium permanganate was higher compared to that obtained by radiochemical oxidation. It was related to the formation of peroxide compounds during radiochemical oxidation.

Structural changes in the liver parenchyma and granulomas of mice with chronic BCG granulomatosis during therapy with composition of isoniazid and dialdehyde dextran.

Male BALB/c mice were intraperitoneally infected with BCG vaccine. The therapy with isoniazid or composition of isoniazid with dialdehyde dextran (intraperitoneally, twice a week for 5 months) was started 1 month after infection. The retention time of the isoniazid-dialdehyde dextran composition in hepatocytes was much longer compared to that of isoniazid.

Effect of dialdehyde dextran on structural changes in the liver and lungs during chronic BCG granulomatosis.

Male BALB/c mice were intraperitoneally infected with BCG vaccine. Cytomorphological changes in BCG granulomas of the liver and lungs were compared during spontaneous tuberculous inflammation and after intraperitoneal injection of dialdehyde dextran for 5 months. Administration of dialdehyde dextran to mice infected with mycobacteria of BCG vaccine was followed by a decrease in the number and size of BCG granulomas in organs, contributed to the increase in the count of fibroblasts in hepatic and pulmonary granulomas, decreased the severity of destructive changes in the liver parenchyma, promoted reparative processes in hepatocytes, and reduced the degree of fibrosis in the liver and lungs due to a decrease in fibroplastic activity of fibroblasts in BCG granulomas.

Functional state of pulmonary macrophages after partial hepatectomy in mice.

Partial hepatectomy leads to qualitative and quantitative changes in the pulmonary compartment of the mononuclear phagocyte system during different periods after surgery. These changes have compensatory and adaptive nature because of loss and subsequent partial recovery of the hepatic compartment of the mononuclear phagocyte system.

Morphological study of the efficiency of isoniazid and dialdehyde dextran composition in the treatment of mice with BCG granulomatosis.

Male BALB/c mice were intraperitoneally injected with BCG vaccine. After 1 month therapy was started: isoniazid or composition of isoniazid with dialdehyde dextran (CID) obtained by chemical and radiochemical methods. The therapeutic efficiency evaluated by the number granulomas in the liver and lungs and granuloma size was higher in mice treated with CID obtained by the radiochemical method in comparison with mice treated with isoniazid and with CID obtained by the chemical method.

Dynamics of myocytes of different types in rat myometrium during pregnancy and early postpartum involution.

Light and electron microscopy and morphometry of rat myometrium revealed 5 morphological types of myometrial smooth muscle cells. Quantitative evaluation of all cytotypes was performed in nonpregnant animals, during normal pregnancy, and during the early postpartum period. Transformation of some cells with nonvacuolated cytoplasm and clear nuclei (type 1) into type 3 cells (with small vacuoles in the cytoplasm), type 4 cells (in a state of balloon degeneration), and type 5 cells (apoptotic bodies) was observed during gestation and early postpartum period.

Structural transformations of myocytes during gestation and early postpartum involution of the uterus.

Myocytes with large homogeneous vacuoles and numerous protrusions of the cytoplasm into extracellular space (manifestations of clasmatosis) were detected in rat myometrium during normal gestation and early postpartum period. The percentage of vacuolated smooth-muscle cells and numerical density of inflammatory cells in the myometrium were evaluated. The data indicate the absence of typical inflammatory reaction in the myometrium during elimination of smooth-muscle cells in the course of postpartum involution.