Analysis of circulating tumor cells in patients with triple negative breast cancer during preoperative chemotherapy.

The presence of circulating tumor cells in the blood of patients with triple negative breast cancer (early and locally advanced cancer) before and after preoperative chemotherapy was assessed using expression markers. Before therapy, circulating tumor cells were detected in 5 of 13 (38%) patients with early cancer and in 7 of 17 (41.2%) patients with locally advanced cancer. After therapy, the circulating immune cells were detected in one patient with locally advanced cancer, who had no circulating cells before therapy. The tumor was resistant to chemotherapy and the disease progressed. The detected circulating tumor cells were HER-2-positive, while the primary tumor was HER-2-negative. It was concluded that the circulating immune cells can be a potential marker of the efficiency of therapy and predictors of the disease course, while their phenotype can differ from the phenotype of the primary tumor.

[Functional activity of alveolar macrophages in patients with bronchial asthma and gastroesophageal reflux disease].

Combination of bronchial asthma (BA) and gastroesophageal reflux disease (GERD) is a widespread clinical situation. The two pathologies are known to influence each other leading to disturbances in immune responsiveness. We studied phenotypes and phenotypic plasticity of immune cells (alveolar macrophages) in patients with BA and GERD. It was shown that BA and GERD are largely associated with AM of proinflammatory M2 and anti-inflammatory M1 phenotypes respectively. Population of AM with MI phenotype increases in patients having both BA and GERD compared with that in BA alone. In vitro experiments showed that acidic milieu promotes shifting the phenotype toward the predominance of M1, i.e. simulates the situation characteristic of GERD. Combination of BA and GERD narrows the interval within which AM can change MI phenotype (i.e. makes them more "rigid") but broadens the range in which they can change M2 phenotype. Also, GERD promotes the development of morphological rigidity of AM. Patients with BA given steroid therapy undergo inversion of phenotypic plasticity of AM. These data characterize the immunological component of BA and/or GERD pathogenesis. They help to better understand mechanisms of development of broncho-pulmonary pathology in GERD patients and can be used to work out new methods for the treatment of these diseases.

[Resistance to acute hypoxia and changes in the phenotype and phenotypic plasticity of macrophages in mice of different genetic strains].

The aim of study was to investigate the effect of hypoxia on the macrophage phenotype and phenotypic plasticity and to determine the resistance to acute hypoxia in C57/BL mice, which have the pro-inflammatory M1 macrophage phenotype, and in BALB/c mice, which have the anti-inflammatory M2 macrophage phenotype. The following results were obtained. 1) The response of macrophages to acute hypoxia has two successive phases, the immediate, anti-inflammatory phase, and the delayed, pro-inflammatory phase. This response was more distinctly inverted in C57/BL6 M1 macrophages than in BALB/c M2 macrophages; 2) the effect of acute hypoxia on macrophage phenotypic plasticity depends on the genetically predetermined, original macrophage phenotype. In this process, a clear regularity was observed: hypoxia increased the capability of macrophages for changing into the pro-inflammatory M1 phenotype, while their capability for changing into the anti-inflammatory M2 phenotype remained virtually unaffected. 3) BALB/c mice were more resistant to acute hypoxia than C57/BL6 mice. Taken together, these data expand our understanding of mechanisms for pathogenetic effects of hypoxia.

[Evaluation of functional adaptation level in air specialists according to biochemical indexes of saliva secretion].

It was examined a capability of evaluation of functional condition of air staff by indexes of natrium, kalium, cortisol and glucose in saliva. There were realized 5 series of examinations with participations of 71 airplane pilot of the same level in conditions of realizing flies of different difficultness. Saliva sampling was effectuated before and after the flies not later then 10-15 minutes after landing. On pre-flight medical examination and after performance of task of air relay there was registration of systolic, diasystolic blood pressure and cardiac rate. It was posed the correlation of physiological indexes with percentage of examined ingredients in saliva in different flight loads. The results of examinations speak for capability of using of indexes of percentage of natrium, kalium, cortisol and glucose in saliva for evaluation of functional condition of airplane pilots during effectuating the flies and rating of value of flight load with account of individual peculiarities.

[Complex evaluation of parachutists' stress-endurance by biochemical characteristics of saliva].

Variations in saliva biochemical characteristics of parachuting sportsmen were analyzed after flight duty. The investigation revealed three types of saliva biochemical reactions to the stresses of parachuting. Our data point to the possibility to judge about the level of tension in organism of people engaged in difficult and extreme activities by saliva concentrations of Na+, K+, cortisol and glucose along with the physiological and psychological investigations traditionally employed by aviation and sport medicine.

Intracellular and extracellular NO differentially modulates the stress response and apoptosis in macrophages exposed to the influence of biological or physical factors.

We studied the role of extracellular and intracellular NO in the regulation of the stress response and apoptosis in macrophages of proinflammatory and antiinflammatory phenotypes under the influence of S. aureus and heat shock. Blockade of extracellular nitric oxide synthesis in cells with antiinflammatory phenotype inhibited the stress response induced by S. aureus and heat shock. The decrease in extracellular nitric oxide concentration around antiinflammatory macrophages potentiated the stress response induced by S. aureus, but had no effect on the stress response induced by heat shock. Hence, intracellular NO mediates the stress response induced by S. aureus and heat shock, while extracellular NO inhibits the stress response induced by S. aureus, but has no effect on the stress response induced by heat shock. In cells with antiinflammatory phenotype, intracellular NO plays an antiapoptotic role. S. aureus and heat shock did not cause apoptosis in macrophages with proinflammatory phenotype, while intracellular NO did not play a role in antiapoptotic activity of the proinflammatory phenotype. Extracellular NO synthesized by macrophages protects these cells from apoptosis induced by S. aureus and heat shock.

Inversion of stress response reprogramming phenomenon in lipopolysaccharide-stimulated alveolar macrophages.

The stress response and NO production in reprogrammed proinflammatory or antiinflammatory alveolar macrophages were studied after lipopolysaccharide treatment. Experiments with macrophages not containing HSP70 showed that lipopolysaccharide in a dose of 500 ng/ml induced stress response in cells with the proinflammatory phenotype (as distinct from an antiinflammatory phenotype). The stress response was not observed in HSP70-containing lipopolysaccharide-stimulated proinflammatory macrophages, but occurred in cells with antiinflammatory phenotype. Hence, the presence of HSP70 in alveolar macrophages results in the inversion of the phenomenon of reprogramming of the stress response. Independently on the phenotype, stimulation with lipopolysaccharide was accompanied by a 60-70% increase in NO production by macrophages not containing HSP70. However, NO production by HSP70-containing macrophages did not increase in response to lipopolysaccharide treatment. Our results indicate that reprogramming of the cell response in macrophages does not concern the system for NO synthesis. HSP70 prevents the lipopolysaccharide-induced activation of NO synthesis in alveolar macrophages.

Role of extracellular and intracellular nitric oxide in the regulation of macrophage responses.

We studied the role of nitric oxide in the stress response and apoptosis. Intracellular nitric oxide potentiated the stress response. However, intracellular nitric oxide suppressed the stress response in macrophages of proinflammatory and antiinflammatory phenotypes. Intracellular nitric oxide promoted apoptosis in macrophages of the proinflammatory phenotype, but inhibited this process in cells of the antiinflammatory phenotype. Exogenous nitric oxide synthesized by macrophages protected them from lipopolysaccharide-induced apoptosis. Our results indicate that nitric oxide produces various effects on the stress response and apoptosis in macrophages, which depends on modus operandi.

Caspase inhibitor Z-VAD-FMK potentiates heat shock-induced apoptosis and HSP70 synthesis in macrophages.

Caspase inhibitor Z-VAD-FMK potentiated heat shock-induced apoptosis in macrophages. Z-VAD-FMK did not activate HSP70 synthesis, but significantly increased the intensity of this process during heat shock. It cannot be excluded that caspases abolish HSP70 accumulation under these conditions. The HSP70 synthesis inhibitor quercetin potentiated DNA fragmentation in macrophages cocultured with Z-VAD-FMK after heat shock. HSP70 play an important role in the protection of macrophages from caspase-independent apoptosis.

Stress response and apoptosis in pro- and antiinflammatory macrophages.

We showed that stress response and apoptosis in macrophages depend on the phenotype of their secretory activity and specific biological and physical characteristics of the factor inducing stress-response or apoptosis.

[Endothelial hyperactivation in heat shock in rats of different genetic strains]. / Giperaktivatsiia éndoteliia pri teplovom shoke u krys raznykh geneticheskikh linii.

Heat shock was found to induce a drop in the AP due to the endothelium-dependent relaxation of the vessels and potentiation of the endothelium suppression of the vasoconstrictor responses. The responses were more obvious in the August rats as compared with the Wistar line. No lines or rats revealed any changes in the sensitivity of adrenoceptors to the agonist which suggests a leading role of the nitrogen oxide hyperproduction in these effects of the heat shock. The data obtained show that inherent endothelial-dependent vascular responses to heat shock may play a role in resistance against the shock in rats of different genetic lines.

Is HSP70 involved in nitric oxide-induced protection of the heart?

It is known that HSP70 plays an important role in the antiischaemic effect of adaptation to stress. The aim of our study was to verify the hypothesis that nitric oxide (NO) may contribute to the activation of HSP70 synthesis and to enhance thereby the resistance of organism to the ischaemic and reperfusion damages. We observed that heat shock potentiated NO production in the heart. NO formation was completely blocked by the NO synthase inhibitor N omega-nitro-L-arginine (L-NNA). L-NNA also significantly attenuated the heat shock-induced accumulation of HSP70 (by 45% in heart). Both heat shock and NO donor induced time- and concentration-dependent HSP70 synthesis in the culture of human hepatoblastoma cells Hep G2. Prior injection of NO donor (30-100 mg per rat) exerted a dose-dependent protective effect on the isolated heart in ischaemia and reperfusion within 24 hours. We suggest that NO is involved in the activation of HSP70 synthesis which can play an important role in the delayed protective effect of NO donors.

[Urogenital mycoplasmosis and Mycoplasma carriage during pregnancy and in inflammatory processes of the genitalia in workers in the electronics industry]. / Urogenital'nyi mikoplazmoz i mikoplazmonositel'stvo pri beremennosti i vospalitel'nykh protsessakh genitalii u rabotnits élektronnoi promyshlennosti.

To find out the spread of urogenital Mycoplasma carriership urogenital mycoplasmosis (UGM) among women living and working under similar conditions and making up risk groups with respect to these infections, pregnant women, gynecological patients and clinically healthy women were specially surveyed. As revealed in this survey, UGM and Mycoplasma carriership were found in clinically healthy female workers significantly more often than in other similar groups of the same region. In the group of pregnant women the occurrence of Mycoplasma carriership and UGM reached 90%. In cases of sterility the facts of asymptomatic Mycoplasma carriership and UGM were registered.