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Microsatellite instability (MSI) is involved in the pathogenesis of about 30% of endometrial cancer cases. In accumulating data from the past few years MSI is shown to have both clinical and prognostic value. In the present work we are discussing the components and molecular mechanisms of functioning of the mismatch repair system (MMR). MSI is a hallmark of endometrial tumors with DNA MMR deficiency. We summarized the main pathways for accumulating mutations in coding and non-coding DNA sequences, which is a result of errors during replication of microsatellite tandem repeats. A few studies rising valuable conclusions about the correlation between MSI and endometrial cancer are revised.

In experiment on adult rats male the anxiolitic action of new plant origin drug Iridol, enriched with compounds iridoids, is shown. This effect of Iridol was approximately the same as by diazepam. In patients with arterial hypertension I - II degree, accompanied by psychoemotional disturbances, the use of Iridol in complex treatment increases efficacy of therapy.

The role of hypoxia as one of the main factors in the development of various pathologic processes is discussed. The anthihypoxic efficacy and mechanisms action of synthetic drugs (oliphen, amtizole, mexidol) and some polyphenolic agents of plant origin are considered. Among the mechanisms of antihypoxant action of these drugs, an especially important role belongs to the stimulation of expression of heat shock proteins and hypoxia-induced factors, which increase the stability of organism under the conditions of oxygen insufficiency.

The elixir Bronchofit is an aqueous-alcoholic extract from 7 kinds of plants. It is a balanced compound, rich in biologically active substances including essential oils and flavonoids, possessing a wide spectrum of pharmacological activity. On the model of frog's palate the elixir enhanced the transport function of the ciliated epithelium. On the model "karragenin edema" bronchofit showed a marked anti-inflammatory activity. A noticeable therapeutic effect was registered in rats with induced bronchopulmonary inflammation. Bronchial secretion contained reduced content of glycosaminoglycans while bronchial lavage did of histamine. Also, bronchofit demonstrated a prominent antioxidative activity, an antibacterial action in relation to Str. pyogenes and Bac. cereus. By a total complex of the activities bronchofit is a promising medicine against bronchopulmonary inflammation.

Studies dealing with the design of new antituberculous agents based on goal-oriented synthesis have provided the agent Perchlosone which is similar to isoniazid and rifampicin, produces in tuberculostatic activity against sensitive laboratory cultured mycobacteria, produces an inhibitory action on polyresistant clinical strains. Experiments on animals (mice, rabbits) with experimental tuberculosis have established that Perchlosone and isoniazid have equal therapeutical properties, and the former shows a synergist interaction with rifampicin, has neither mutagenic activity nor negative effects on immunity and the surfactant system of the lung.

The authors investigated spontaneous and induced secretion of cytokins at different stages of generalized tuberculosis. In the development of infection there were inhibited IL-2 synthesis in response to ConA, emerging activity of PNO-alpha in response to the inductors in blood serum and culture of peritoneal macrophages, enhanced secretion of IL-6. Complete immunodeficiency was associated with cessation of IL-2 synthesis by splenocytes, elevated production of IL-6 by peritoneal macrophages, low concentrations of PNO-alpha in the serum and peritoneal macrophage cultures. In the treatment of M. bovis-infected mice with antibacterial drugs alone IL-6 secretion by peritoneal macrophages and PNO-alpha activity in the serum were increased. Immunocorrection resulted in marked activation of IL-2 production by splenocytes in response to ConA as well as enhanced synthesis of IL-6 in unstimulated cultures of peritoneal macrophages.

Mice with experimental tuberculosis were given isoniazid, rifampicin, erythromycin, cefotaxime, ofloxacin. Erythromycin, cefotaxime and ofloxacin enhanced macrophage activity if their course did not exceed 2-4 weeks. Isoniazid and rifampicin for a short time inhibited macrophage activity then stimulated it. These findings led the authors to the conclusion that erythromycin, cefotaxime and ofloxacin must be used only in short courses.

An experimental model of tuberculosis-opisthorchiasis pathology was developed. The results of two experimental series with the use of this model showed that in cases with mixed pathology the specific process is aggravated irrespective of whether the infectious process develops in opisthorchiasis or the latter occurs in attendance to tuberculosis. Delayed hypersensitivity in such cases is suppressed markedly in the absence of its initial activation.

Cephalosporin antibiotics cefamezin (I generation drug sensitive to beta-lactamase) and cefotaxime (III generation drug resistant to beta-lactamase) have been tested for antituberculous activity. The latter was found dependent on resistance to mycobacterial beta-lactamase. A minimal inhibiting concentration of cefotaxime was similar to that of etambutol and tisamid. Cefotaxime also enhanced tuberculostatic and bactericidal effect of isoniazid and rifampicin. Combination cefotaxime+isoniazid+rifampicin proved more effective than cefotaxime+etambutol+tisamid. The effectiveness against tuberculosis of the beta-lactamase resistant cephalosporin points to the validity of further research for active phthisiatric drugs among III generation cephalosporins.

A method for quantitative evaluation of lung affection degree in experimental tuberculosis mice has been elaborated according to the findings of macroscopic study. Consideration is given not only to the productive changes in the lungs, but also to the manifestation degree of exudative reactions. The proposed criteria are presented in a formalized pattern that is suitable for any mathematical treatment.

The influence of a tumor necrosis factor, administered 16 h before irradiation of rats, on the radiation response of thymus and bone marrow cells has been investigated. Three and 6 h after irradiation the following indices were analyzed: the number of apoptotic cells in the thymus; the accumulation of polydeoxyribonucleotides and the appearance of single-strand breaks in DNA of bone marrow and thymus cells; and the electrophoretic properties of thymocyte DNA. The injection of a tumor necrosis factor reduced the number of polydeoxyribonucleotides, inhibited internucleosome DNA fragmentation, and did not influence the formation of single-strand breaks in DNA.

A plasmapheresis (PA) model was developed to be used in chronic rabbit experiments. Test results obtained in 96 generalized tuberculosis animals demonstrated a more benign tuberculosis process in animals subjected to plasmapheresis, which was confirmed by parameters of the coefficients of mass and indices of animals' organ affecting, findings of the cation-lysosomal test and peptide molecules content in the peripheral blood. Rabbit studies involving registration of bromsulphalein half-life, hepatic blood flow and relative parenchymatous clearing showed that the isoniazide and rifampicin action significantly decreased under the PA influence. Studies in a hospital accommodating 90 patients with different renal tuberculosis forms and poor tuberculostatic tolerance showed that PA promoted restoration of tolerance to specific preparations and renal function improvement. PA was found to be practicable and safe method which relieves side effects of antituberculous preparations and contributes to tuberculosis treatment efficiency.

The results of a study of a new synthetic drug dimephosphon used as a pathogenetic means in the treatment of experimental tuberculosis are presented. Dimephosphon was found to be responsible for both the in vivo and in vitro decrease of the degree of MBT resistance to rifampicin. The findings of macroscopic, histologic and bacteriologic examinations demonstrated a significant increase in the effectiveness of antituberculous therapy. Dimephosphon monotherapy in mice elicited manifested stimulation of peritoneal macrophages: increase in O2- production, and decline in extracellular 5-nucleotidase activity. Nemolysine-synthetic cellular splenic activity in mice rose essentially. No direct stimulating influence of dimephosphon on functional macrophage activity in vitro was found.

The method of electron microscopy was used to study the phenomenon of "paradoxical resistance" of thymocytes to very high radiation doses (40 and 200 Gy). The formation of "pseudonormal" thymocytes, which represented a peculiar form of radiation death of these cells, was shown to be a function of radiation dose and time after irradiation.

Using immunohistochemical and electron microscopic methods the presence of serotonin and prostaglandin F2 containing granules in some epithelial cells of rat thymus has been shown. The modulatory role of these hormones in the thymic immunocompetent cells production is discussed.

The level of chromatin degradation was studied and the method of electron-microscopy was used to estimate the changes in the ultrastructure of irradiated and nonirradiated thymocytes of rats treated with cycloheximide. The latter was found to decrease the degree of derangement of nuclear ultrastructure and the level of chromatin degradation in exposed animals and to increase the yield of these damages in thymocytes of nonirradiated animals. The electronmicroscopic determinations showed that the percentage of thymocytes with the impaired nucleus structure is twice as high as that of degraded chromatin. The causes of the quantitative disagreement between the morphological and biochemical indices of the interphase thymocyte death are discussed.

Pathomorphological and biochemical investigations on liver and blood serum laying hens affected by the liver obesity syndrome were carried out. It was established that the mortality due to the liver obesity syndrome varies within the range of 3.1 and 3.7% for the entire period of exploitation. A rise in mortality is observed in case fodder mixtures with higher peroxide and aldehyde number are prepared. Besides the typical changes in the liver, the pathologo-anatomical investigation established varying in its expression duodenitis of rupture of the liver and hemorrhage. In hens suffering from advanced liver obesity an increased content of total protein in the blood serum was observed. The relative and absolute content of prealbumens and albumens was also higher, while the content of globulins was relatively lower. The content of beta-lipoproteins was raised and total lipids in the blood serum were considerably increased. The investigation on total lipids and lipid fractions in the liver established a correlation between the extent of obesity and the content of total lipids. A trend toward increasing the total and particularly the esterificated holesterin was evident in affected birds. The chemical investigation of various lots of fodder mixtures established often cases of rancid fats, which was manifested by high values of the peroxide and aldehyde number. The aminoacid composition of fodder also varied too much. It is assumed that besides the genetic control of liver obesity rancid fats and insufficient content of essential amino acids in the fodder mixtures also lead to an increased mortality percentage in the affected birds.

Female rats have been maintained at simulated altitudes 8,000-9,000 for 15-60 min. Under the hypoxic conditions there was noted an increase in the respiratory activity of fresh nonwashed liver mitochondria, using endogenous substrates in the uncoupled state, as well as coupling of the endogenous respiration with phosphorylation. After 40 min storage of the mitochondrial preparations from hypoxic animals in an ice-bath, an increase in the endogenous respiration and decrease in its coupling with phosphorylation occurred but the values did not reach the control level. Many parameters of respiration were increased in mitochondria hypoxic rats in presence of succinate: respiratory activity in the active metabolic state/V3/ and in the state V4, the respiratory control ratio, the rate of ADP phosphorylation, the coupling of respiration with phosphorylation in the state V4. All the changes found were considered as adaptive.

Use was made of Wistar albino rats in which an inflammation was induced via the simultaneous injection of caraginan and prostaglandin E1 in order to evaluate the antiinflammatory activity of 6 freeze dried plant extracts. It was found that with such model of inflammation the inflammatory effect of caraginan was strongly enhanced, which was accompanied by the rapid and prolific white blood cell extravasates. The freeze-dried extracts of St. John's-wort (Hypericum perforatum L.), potmarigold calendula (Calendula officinalis L.), camomile (Matricaria chamomilla L.) and plantain (Plantago lanceolata L. et Pl. major L.) were found to suppress both the inflammatory effect and the leukocyte infiltration. The extracts of symphytum (Symphytum officinale L.) and those of flax seed (Linum usitatissimum L.) did not inhibit the inflammation, however, they suppressed the leukocyte infiltration at the 3rd and 4th hour of the induced inflammation.

Studied was the morphologic picture in a total of 13 calves spontaneously intoxicated with furazolidon following its overrating and use once and severalfold as a therapeutic means against infectious enteritis. There were hemorrhages in the subcutaneous tissue and the muscles, kidneys, abomasum, spleen, and heart as well as liver dystrophia and hyperemia and edema of the leptomeninges and the brain cortex. Histologically, there were hyperemia, strong and diffuse pericellular and perivascular edema of the cerebrum and the cerebellum with degenerative changes in the Purkinje layer, fatty degeneration and biliary thrombi in the liver, hemorrhages and activation of the endothelial cells and glomeruli of the kidneys, hyperemia and fatty infiltration of the myocardium, and hemorrhages in the spleen.

A long-term (for 3 hours) hypoxic hypoxia was accompanied in rats by wave changes of the brain tissue Na++K+-ATPase activity. This activity decreased after a 15-minute exposure; it increased after 2 hours and fell again after a 3-hour hypoxia (decompensation period). The membrane transport enzymes of erythrocytes proved to be more resistant to hypoxia than the brain cell enzymes.

The effects were studied of the degree of immunodeficiency produced by thymectomy of one-month-old rats on the course of experimental tuberculosis induced 3, 6 and 9 months after thymectomy. Subject to study was also the effect of immunodeficiency correction with thymalin on the tuberculous process. It was established that the lungs of thymectomized rats infected 9 months after the thymectomy were damaged more severely as compared with control or thymalin-treated animals. In thymectomized rats treated with thymalin, the absolute content of medium-sized and big lymphocytes in peripheral blood was found to be lower, the content of small lymphocytes being unchanged throughout all observation periods. The time course of migration activity (spontaneous and in response to PPD) in rats treated with thymalin corresponded with the time course in controls in contrast to thymectomized rats which did not receive the treatment. The results indicate that tuberculosis severity depends on the degree of immunodeficiency and that the functional properties of immunocompetent cells may be corrected with thymalin.

The protective action in hypoxic hypoxia of 29 synthetized alpha-dicarbonyl compounds were studied. In this series of substances the natihypoxic activity was found to be most marked in drugs whose redox potential amounted to 0.15--0.3 V and which displayed a high dehydrating activity. Such compounds include isatin, its 3-anyl, 3-thiosemicarbation of ethyl either, isatin-1 of acetic acid and acenaphthequinone. Substitution is position 1 and 3 of isatin can lead to the formation of active substances, whereas substitution in position 2 usually reduces the antihypoxic activity.