Morphofunctional Changes in Colon after Cold Stress in Male C57BL/6 Mice Susceptible and Tolerant to Hypoxia.

There are individual differences in the tolerance to hypoxia and stress. Stress can contribute to the development of various diseases, including inflammatory bowel disease. It was found that inflammatory bowel diseases in animals susceptible to hypoxia runs more severe course than in tolerant animals. We studied morphofunctional changes in the colon under conditions of modeled cold stress in male C57BL/6 mice susceptible and tolerant to hypoxia. The animals were daily subjected to cold stress (20 min at -20°C) for 2 weeks. Cold stress was followed by an increase in the volume fraction of goblet cells in the colon and production of mucins by these cells in mice tolerant to hypoxia and an increase in cell content in the lamina propria of the colon mucous membrane in animals susceptible to hypoxia. The number of serotoninproducing endocrine cells increased in both groups, but these changes were more pronounced in mice susceptible to hypoxia.

Morphological and Functional Peculiarities of the Immune System of Male and Female Rats with Different Hypoxic Resistance.

The morphological and functional peculiarities of the immune system are studied in adult male and female Wistar rats with high and low hypoxic resistance. Sex-specific differences in the subpopulation composition of the peripheral blood lymphocytes, not depending on the hypoxic resistance of animals, are detected: the males have lower absolute counts of T helpers and higher percentage of regulatory T cells than the females in the diestrus phase. Comparison of the morphofunctional status of the immune system in male and female (diestrus) rats with high resistance to hypoxia has shown a better developed subcapsular zone of the thymus, higher levels of anti-inflammatory cytokine TGF-ß, and lower absolute counts of cytotoxic T lymphocytes in the peripheral blood in the males. Males with low hypoxic resistance have higher counts of phase II thymic bodies in comparison with low-resistant females. Hence, morphofunctional differences in the immune system of male and female rats with different hypoxic resistance are detected, which can determine the course of inflammatory diseases.

Structural Changes in the Nervous Fibers of the Colon Mucosa in Experimental Acute Colitis.

Morphological, morphometric, and ultrastructural analysis of the nerve fibers in the colon mucosa was performed in C57BL/6 mice at various terms of development of acute colitis induced by dextran sodium sulphate. The nerve fibers were labeled with antibodies to pan-neuronal marker ßIII-tubulin. The progression of inflammatory and ulcerative processes in the mucosa on days 3-5 was associated with hyperplasia and hypertrophy of nerve fibers that peaked on day 7 after colitis induction. Ultrastructural analysis at all terms of colitis development showed moderate degeneration of axons. Thus, hypertrophy and hyperplasia of the nervous fibers in colon mucosa in experimental acute colitis correlated with aggravation of the ulcerative process in the mucosa. These changes are determined by alteration of histoarchitectonics and regenerative processes in the mucosa.

Ultradian Rhythms of Body Temperatures in Male Wistar Rats Maintained under Conditions of Constant Illumination.

We studied the dynamics of the body temperature in mature male Wistar rats maintained under condition of constant illumination. It was shown that body temperature under these conditions varied with a 3-5-h period. The daily dynamics of body temperature summed up over 20-23-day intervals showed a 4-h ultradian rhythm with maxima at 3.35-4.30, 7.35-8.30, 11.35-12.30, 15.35-16.30, 19.35-20.30, and 23.35-00.30 h. During these hours, pronounced (>0.9°C) increase in body temperature was observed by 1.6 times more often than in other eriods. Thus, there are periods during the day when the increase in body temperature in rats in the absence of light cues occurs more often than in other periods of the day. Hence, about 4-h ultradian rhythm of body temperature has an external synchronizer that differs from lighting conditions.

Expression of Mucins and Claudins in the Colon during Acute and Chronic Experimental Colitis.

We studied changes in the expression of mRNA for mucins and claudins in the medial part of the colon in male C57Bl/6 mice on the model of acute and chronic colitis induced by substitution of drinking water with 1% solution of dextran sodium sulphate for 5 days. In acute colitis, the expression of the main structural component of glycocalyx, mucin Muc3, decreased and expression of pore-forming claudin Cldn2 increased, which reflected enhanced permeability of tight junctions. In the chronic colitis group, in comparison with the normal group, we observed an increase in expression of mRNA of main structural mucus component Muc2, enhanced of expression of Muc1 associated with carcinogenesis, and reduced expression of Muc13, which led to a more severe course of colitis; the expression of pore-forming claudin Cldn2 was elevated. These findings indicate that the imbalance in the expression of mucins and claudins plays an important role in the mechanisms of development of acute and chronic colitis.

Sex-Related Differences in the Morphology and Subpopulation Composition of Colon Lymphocytes in Experimental Acute Colitis.

Morphological manifestations of acute colitis and subpopulation composition of colon lymphocytes were studied in male and female C57Bl/6 mice with acute dextran-induced colitis. We evaluated the severity of colitis symptoms, morphological changes in the colon, and prevalence of epithelialized and non-epithelialized ulcers. The subpopulation composition of lymphocytes (CD3-CD19+ B cells, CD3+CD4+ T helpers, CD3+CD8+ cytotoxic T cells, and CD4+CD25+FOXP3+ regulatory T cells) was assessed by flow cytofluorometry in suspension of colon cells prepared by enzymatic disintegration. In males, clinical manifestations of acute colitis and morphological changes were more severe and the prevalence of non-epithelialized ulcers was higher than in females. In females, the content of T, B, and regulatory T cells in the colon wall was higher, while the content of cytotoxic T cells was lower than in males. In females with acute colitis, the absolute lymphocyte count and the content of B cells and regulatory T cells decreased, while the percentage of cytotoxic T cells increased in comparison with intact animals. In males with acute colitis, the levels of regulatory T and B cells increased in comparison with the corresponding parameter in intact animals. Morphological changes and changes in the lymphocyte subpopulations, detected in males and females with acute colitis, were determined by different levels of sex steroid hormones.

[On the histogenesis of cardiac myxoma]. / K voprosu o gistogeneze miksomy serdtsa.

OBJECTIVE: to investigate the morphological and phenotypic features of cardiac myxoma (CM), to discuss argumentative issues on the sources of its growth. SUBJECTS AND METHODS: The investigation included 176 sporadic and familial myxomas originating from different cardiac chambers (96% from the atria). The histological, ultrastructural, and immunohistochemical features of the cells and vessels of this tumor were studied. RESULTS: The morphological and phenotypic features of the embryonic endothelium resembling the cells of the primary cardiovascular network were found in the cells and vessels of CM. No signs of other mesenchymal derivatives were detected. DISCUSSION: The authors anticipate that there is focal cessation of maturation of the embryonic endocardial endothelium and its persistence - hamartia. Postnatal proliferation of embryonic hamartia forms the tumor hamartoma. Differentiated cells may retain the phenotypic (but not morphological) features of closely related cells that have a common precursor. CONCLUSION: The results of the study have allowed the authors to consider CM to be hamartoma, a monohistioid benign embryonic endocardial endothelioma. Our findings do not exclude the possibility of developing CM from pluripotent mesenchymal cells.

Dynamics of Expression of Cytokine Genes and Macrophage Content in the Lungs and Kidneys after Subtotal Hepatectomy in Rats.

The role of the lungs and kidneys in liver regeneration after subtotal hepatectomy was studied on a rat model. It was found that production of hepatocyte growth factor (HGF) in the lungs and kidneys and expression of cytokine genes Il1b, Il6, Il10, and tnfa significantly increased. Analysis of the dynamics of lung macrophage population showed that accumulation of HGF and the increase in the expression of cytokine genes in the lungs were accompanied by simultaneous increase in the number of CD68+ cells, which attested to the leading role of macrophages in activation of HGF synthesis in the lungs. Macrophage content in the kidneys after subtotal hepatectomy did not increase.

[Individual differences in the response of target organs and the immune system in experimental endotoxicosis].

Individual morphofunctional differences were studied in the reaction of target organs and the immune system of Wistar rats given large-dose lipopolysaccharides (LPS). A cluster analysis of the indices characterizing the reaction of target organs and the immune system to PLS administration was used to divide the Wistar rats into 2 groups: 1) those with high production of Th1 cytokines (interleukin-2 and interferon-gamma) and 2) those with their low production. In the high production group, hepatic dystrophic changes and a pulmonary inflammatory reaction were more pronounced, which were associated with the alterative changes in the immune organs. On day 7, the morphofunctional differences in the reaction of target organs and the immune system were less marked and mainly seen at the functional level.

[Immunomorphology of granulomatous inflammation with Th-1 and Th-2 types of an immune response].

Experimental granulomatosis inflammation induced by BCG-M shown in mice with different type of an immune response has established that with the Tx1 immune type, the granulomatous inflammatory process is more pronounced and disseminated with the high production of tumor necrosis factor-a and interferon-gamma being found. With Th-2 immune response, this process is less pronounced, the cytokine profile being unchanged. The Th-l (cellular) immune response seems to be prevalent in patients with sarcoidosis, high IL-2 level, a preponderance of a granulomatous component, and evident clinical manifestations of the disease. The Th-2 (humoral) immune response appears to be predominant in persons with elevated IL-4 levels, a predominance of fibrosis, and minor clinical manifestations of the disease, Identification of the variants of the course of sarcoidosis on the basis of clinicomorphological and immunological studies is of great importance since this makes it possible to predict the course of the disease and to perform more adequate therapy.

[The cytokine profile in granulomatous lung diseases].

Twenty-five patients with new-onset pulmonary tuberculosis, 52 patients with active sarcoidosis, and 5 healthy donors were examined. Cytokines (IL-2, IL-4, IL-6, TNF-alpha, and gamma-1FN were determined by enzyme immunoassay in the serum and cultured mononuclear supernatant from peripheral blood. IL-2, TNF-alpha, and gamma-IFN) were found in the sera of all the examinees. There were significant differences in the presence of IL-4 that was more commonly detected in sarcoidosis than in tuberculosis (96.2% versus 68%; p = 0.001) and in healthy individuals (40%; p = 0.0001) and in the presence of IL-6 (84.6% in patients with sarcoidosis; 20% in healthy individuals; p = 0.0015; 12% in patients with tuberculosis; p < 0.0001). Supernatant studies showed that IL-4 was absent in 25% of patients with sarcoidosis, nor gamma-IFN in 21.7% of patients with tuberculosis and in 12.5% of patients with sarcoidosis. In tuberculosis, the mean levels of IL-2, IL-4, IL-6, TNF-alpha, and gamma-IFN were greater than those in the control group; but these differences were not statistically significant primarily due to the fact that there was a great scatter of readings. In sarcoidosis, the serum levels of IL-4 (40.9 +/- 38.5 pg/ml) and IL-6 (19.0 +/- 2.7 pg/ml) were significantly higher than those in healthy individuals (p = 0.01 and p = 0.026, respectively) and in patients with tuberculosis (p = 0.0005 and p < 0.0001). The supernatant from patients with tuberculosis showed no significant differences in the content of cytokines than that from donors. In patients with sarcoidosis, the increase in the level of TNF-alpha (757.8 +/- 142.8 pg/ml) was statistically significant, as compared with the controls (p = 0.036) and patients with tuberculosis (p = 0.018), so as that of gamma-IFN (272.9 +/- 58.0 pg/ml), as compared with patients with tuberculosis (p = 0.046). Thus, the serum levels of IL-6 and IL-4 and the capacity of monocytes and macrophages for synthesizing TNF-alpha and gamma-IFN may be used as an auxiliary criterion for the nosological diagnosis of sarcoidosis and tuberculosis.

[Comparative efficiency of treatment with moxyfloxacin and lomefloxacin for generalized murine tuberculosis caused by drug-resistant Mycobacterium strains].

The antituberculous efficacy of the new fluoroquinolone agent moxyfloxacin was studied on a model of generalized murine tuberculosis caused by a multidrug-resistant Mycobacterium strain. There was evidence for the high therapeutic effect of moxyfloxacin and its advantages over the antituberculous agent lomefloxacin.

[The effect of a potential drug ingamine on a model of noninfectious pneumonia]. / Issledivanie éffektivnosti potentsial'nogo lekarstvennogo sredstva - ingamina TM na modeli neinfektsionnogo vospaleniia legkikh.

The potential drug ingamine (glutarylhistamine) showed pronounced anti-inflammatory activity on a model of acute noninfectious pneumonia and in the stage of chronic inflammation induced by singe instillation of Sephadex (5 mg/kg) in Wistar rats. A 6-day treatment with ingamine (50-500 microg/kg) by inhalation, intragastric, and intraperitoneal administration produced an anti-inflammatory effect (expressed to various degrees), which was manifested by a decrease in alveolitis, bronchitis, obstructive emphysema, lymphocyte-neutrophile infiltration of interalveolar septa, cytosis, and neutrophile component of bronchoalveolar lavage and by normalization of the cytogram. The most pronounced effect was observed upon inhalation in a dose of 500 microg/kg. In the stage of chronic inflammation, the inhalation of ingamine in a dose of 500 microg/kg produced a significant antiinflammatory action for both 10- and 20-day treatment. The effect was comparable with that of the inhaled glucocorticoid budesonide.

Study of pharmacological properties of new drugs for external use by the method of cell monolayer bioindication.

The effects of new plant extracts on phagocytosis-stimulating, antioxidant, antiinflammatory, and mitotic activities were studied by the method of bioindication on cultures of normal human leukocytes, RH cells, and blood neutrophils. The preparations showed dose-dependent antiinflammatory activity and produced wound-healing, antioxidant, and moderate phagocytosis-stimulating effects.

Method of bioindication for evaluation of the effects of plant extracts on cell monolayer in acute and chronic experiments.

Acute and chronic toxicities of plant extracts for external use were studied on a model of cell monolayer. This method detects the toxic dose of the agent during the first stage of the study; the activity of this dose and severity of damaging effect can be further studied on experimental animals. An advantage of the method is high informative value of preliminary investigation in the development of new low-toxic agents.

Antiinflammatory effect of russian-made budesonide in experimental noninfectious pulmonary granulomatosis.

We studied the antiinflammatory effect of a Russian-made glucocorticoid budesonide administered by inhalation and intraperitoneal injection to rats with experimental noninfectious pulmonary granulomatosis. The antiinflammatory effects of budesonide at both administration routes were similar. Intraperitoneal injection, in contrast to inhalation, produced a systemic effect manifested in suppression of hyperplasia of non-encapsulated lymphoid formations in the mucosa.

[Comparative characteristics of granulomatous inflammation in sarcoidosis and tuberculosis]. / Sravnitel'naia kharakteristika granulematoznogo vospaleniia pri sarkoidoze i tuberkuleze.

Comparisons are given of clinical manifestations and pathomorphological changes in lymph nodes and lungs of 76 patients with sarcoidosis and 48 patients with tuberculosis. Two types of tissue reactions were shown: with minimal and marked fibrosis. The former type is characterized by high density of granulomatosis and low density of fibrosis, large granulomas which contained many giant cells. The latter type is characterized by advanced fibrosis, small granulomas with rare giant cells. For clinically marked sarcoidosis, tissue reaction with predominant granulomatosis is typical, for patients with scare symptoms--tissue reaction with evident fibrosis. In the absence of caseous necrosis, differential diagnosis between tuberculosis and sarcoidosis with prevalent granulomatosis is impossible by morphological picture and morphometric evidence.

[Antitubercular activity of lomefloxacin in an experiment]. / Protivotuberkuleznaia aktivnost' lomefloksatsina v éksperimente.

The effect of lomefloxacin was studied on mice with experimental infection due to Mycobacterium tuberculosis. The antibiotic was administered in doses of 100 and 200 mg/kg. It was shown that the use of lomefloxacin for a month provided a lower death rate of the animals with progressing acute generalized tuberculosis, a lower level of the lesions in the internal organs and a lower number of the Mycobacterium isolates from them. The efficacy of the treatment depended on the drug dose. When lomefloxacin was used in a dose of 200 mg/kg, the survival rate was much higher and the number of the epithelial unicellular granulomas in the tissue of the lung and spleen was markedly decreased while with the lower dose the indices did not differ from those in the control.

[Morphofunctional changes of Wistar rat lungs in acute normobaric hypoxia]. / Morfofunktsional'nye osobennosti legkikh krys Vistar pri ostroi normobaricheskoi gipoksii.

Rats were exposed to a single (30 min) or repeated (30 min x 10, daily) normobaric hypoxia by a gas mixture with 10% of O2. In both cases urgent adaptive reactions develop in the lungs in the form of epithelium desquamation, increasing migration of neutrophils into the lung tissue, enhancement of labrocyte degranulation. Long-term adaptive reactions develop after the repeated exposures: proliferation of connective tissue labrocytes, hyperplasia of the lymphoid tissue associated with bronchi.

[Changes in the lesser circulation vessels in chronic nonspecific lung diseases]. / Izmeneniia sosudov malogo kruga krovoobrashcheniia pri khronicheskikh nespetsificheskikh zabolevaniiakh legkikh.

Clinicomorphological study of the pulmonary circulation vessels was performed in 20 patients with bronchiectatic disease without right ventricle hypertrophy and in 14 patients with chronic bronchitis complicated with pulmonary heart. Pathology data of persons dying from diseases other than vitium cordis and lung diseases were used as control. Morphological signs of pulmonary hypertension are found in all cases of chronic nonspecific lung diseases. The most pronounced changes develop in the vascular segment starting from arterioles and up to the arteries of muscle type with the diameter of 400 microns. The dependence of the pulmonary arteries changes on the type of lung disease is established. Pathological changes in the walls of the pulmonary circulation vessels, in parallel with pronounced compensatory alterations, are found in cases complicated with pulmonary heart.