ß-Like DNA polymerases and prospects for their use as targets in chemotherapy of tumors.

DNA polymerases ß are enzymes that perform repair of damaged DNA. In the cells of malignant tumors, there is a change in the production and properties of these enzymes, which is accompanied by altered viability of tumor cells. Analysis of the publications available in Russian and international databases (Pubmed, Elsevier) on the structure and properties of DNA polymerases ß and their role in cell growth and proliferation, published over the past 20 years, has shown overexpression of genes encoding ß-like DNA polymerases in many types of malignant tumors cells. This explains the maintenance of their viability and proliferative activity. Targeted inhibition of ß-like DNA polymerases is accompanied by antiproliferative and antitumor effects. Stable paramagnetic isotopes of magnesium (25Mg2+) or other divalent metals (43Ca2+ and 67Zn2+) with uncompensated nuclear spin isotopes, as well as short single-stranded polydeoxyribonucleotides, can be used as promising antitumor pharmacophores.

[The organization of pre-clinical studies of bactericidal and wound healing effects of the impulse photoherapy device "Zarya"].

The purpose of the study is to determine therapeutic effectiveness of the pulsed high intensity optical irradiation device "Zarya" exemplified by treatment of model wounds in laboratory animals and to compare with traditional methods of wound treatment. The prototype of "Zarya" device was used whose operating principle was based on pulsed irradiation of affected areas with high intensity optical radiation in continuous spectrum generated by pulsed xenon lamp. The therapeutic effect of the "Zarya" device was compared with effectiveness of the certified medical ultraviolet irradiator based on low-pressure mercury lamp and also with known wound-healing and antibacterial medication Levomekol ointment. The mature male rats of Wistar line were used in the study. The animals were distributed to 4 groups: group 1 was irradiated by "Zarya" device, group 2 was irradiated by low-pressure mercury lamp, group 3 was treated with Levomekol ointment and group 4 was exposed to no exposure. The linear wound was modeled according to the standard method under ether anesthesia. The therapeutic procedures were applied daily during 7 days. The bactericidal effect was studied on the basis of smears from wound onto flora on the 2nd, 5th and 7th day. On the 8th day the animals were subjected to euthanasia. It was established that "Zarya" device application permits to reduce considerably both duration of therapeutic procedures and therapy course in general and also to achieve more pronounced bactericidal effect. The obtained data is supposed to be used for development of program of clinical trials.

In Vitro Effects of Sodium Nitroprusside and L-Nω-Nitroarginine Methyl Ester (L-NAME) on Activity of Lysosomal Cysteine Proteinases and Lysosomal Membrane Permeability.

The direct effect of 5 mM L-NAME and 0.1 mM sodium nitroprusside on activity of lysosomal cysteine proteinases and permeability of lysosomal membrane was studied in vitro after 1, 2, and 4 h of incubation. Isolated from the liver of intact female rats lysosome suspensions were used. Both substances reduced total activity of cathepsin H and did not affect cathepsin B at all time intervals. L-NAME increased cathepsin L activity at all incubation times, while sodium nitroprusside increased activity of this enzyme after 2-h incubation and reduced it incubation after 4-h incubation. L-NAME demonstrated a membrane-destabilizing effect in in vitro experiments, while sodium nitroprusside on the contrary stabilized lysosomal membranes.

Age-Specific Peculiarities of Modulation of Blood Aldo-Keto Reductase Isoenzyme Spectrum.

The aldo-keto reductase spectrum of the blood was studied at different stages of ontogeny to elucidate the role of reduction pathway in utilization of the carbonyl products of free radical oxidation in modulation of organism sensitivity to the damaging effect of stress during ontogeny. The studies revealed the age-specific changes in aldo-keto reductase spectrum in the blood. An analogy of the aldo-keto reductase spectrum structure in animals of early maturity and in old rats was found. The appearance of age specificity of the aldo-keto reductase spectrum in the blood creates metabolic prerequisites for changes in the efficiency of utilization of carbonyl products of free radical oxidation via their reductive transformation.

[EXPERIMENTAL TESTING OF THE OPERATOR'S PERCEPTION OF SYMBOLIC INFORMATION ON THE HELMET-MOUNTED DISPLAY DEPENDING ON THE STRUCTURAL COMPLEXITY OF VISUAL ENVIRONMENT].

The experiments showed that pilot's perception of symbolic information on the helmet-mounted display (HMD) depends on type of HMD (mono- or binocular), and structural complexity of the background image. Complex background extends time and increases errors in perception, particularly when monocular HMD is used. In extremely complicated visual situations (symbolic information on a background intricately structured by supposition of a TV image on real visual environment) significantly increases time and lowers precision of symbols perception no matter what the HMD type.

The expression of CCN2, IQSEC, RSPO1, DNAJC15, RIPK2, IL13RA2, IRS1, and IRS2 genes in blood of obese boys with insulin resistance.

The development of obesity and its metabolic complications is associated with dysregulation of various intrinsic mechanisms, which control basic metabolic processes via changes in the expression of numerous regulatory genes. We studied the expression of the subset of genes, which responsible for control of cell growth and glucose metabolism, in blood cells of obese boys with normal and impaired insulin sensitivity as well as in normal (control) individuals. It was shown that obesity with normal insulin sensitivity enhances the expression of IRS1, RIPK2, IL13RA2, RSPO1, IQSEC, and CCN2 genes but decreases the expression level IRS2 and DNAJC15 genes in the blood cells as compared to control group. Insulin resistance in obese boys leads to up-regulation of IRS2, RSPO1, and DNAJC15 gene expressions as wells to down-regulation of IRS1 and RIPK2 genes in the blood cells versus obese patients with normal insulin sensitivity. Results of this study provide evidence that obesity affects the expression of the subset of genes related to cell growth and glucose metabolism in blood cells and that insulin resistance in obesity is associated with changes in the expression level of IRS1, IRS2, RIPK2, RSPO1, and DNA JC15 genes, which contribute to the development of insulin resistance and glucose intolerance and possibly reflect some changes in fat tissue.

[EXPRESSION OF GENES, WHICH CONTROL GLUCOSE METABOLISM, IN BLOOD CELLS OF THE OBESE BOYS WITH INSULIN RESISTANCE].

We studied the expression of genes, which responsible for glucose metabolism, in the blood of obese boys with and without of insulin resistance as well as in normal (control) individuals. It was shown that the expression level of PFKFB3 gene is increased, PFKFB1 and INSIG2--is decreased, but HK2 gene--significantly does not change in the blood cells of obese boys with normal insulin sensitivity as compared to control group. Insulin resistance in obese boys leads to up-regulation of INSIG2 gene expression as well as to down-regulation of PFKFB1, PFKFB3, and HK2 genes in the blood.cells as compared to obese patients with normal insulin sensitivity. Results of this study provide evidence that obesity affects the expression of the subset of glucose metabolism-related genes in the blood cells and that insulin resistance in obesity is associated with changes in the expression level of PFKFB1, PFKFB3, HK2, and INSIG2 genes, which contribute to the development of insulin resistance as well as glucose intolerance.

[Experimental studies of reliability of symbolic information perception from the aviation LCD panel].

Results of tachistiscopic experiments on reliability of symbol recognition on LCD panel as a function of screen definition (640 x 480, 800 x 600 and 1024 x 768 pixels), angular size of a picture element (10, 15, 20 and 30 angular min) and luminance contrast (LC) with the background (0.2 to 1.4 standard units) are presented. The obtained quantitative relations indicate significance of the above parameters for recognition reliability. Symbols with the size of 30 angular min and LC of 0.5 were recognizable irrespective of screen definition in the study. Recognition of symbols 20 and 15 angular min of size was much dependent on screen definition and LC of symbols. For symbols of size 10 angular min and LC ≥ 1.0 the recognition probability did not exceed 0.59-0.7.

[Evaluation of condition and factors affecting activity effectiveness and visual performance of pilots who use night vision goggles during the helicopter flights].

According to analysis of questionnaire authors revealed factors, which affect activity effectiveness, and visual performance of pilots who use night vision goggles during the helicopter flights. These are: difficulty of flight tasks, flying conditions, illusion of attitude. Authors gave possible ways to reduce an impact of these factors.

[Some peculiarities in the manifestation of oxidative stress and current status of antioxidant system in adolescents of different age groups with obesity, complicated by insulin resistance and without it].

The study has shown that neuroendocrine obesity in adolescents is associated with the formation of oxidative stress which is more pronounced in early than in late puberty. Obesity with concomitant insulin resistance increases manifestations of oxidative stress accompanied by a compensatory increase in the activity of catabolic enzymes and reduced capacity of the defense antioxidant system in late puberty. These alterations may be caused by age-related changes in hormonal secretion under conditions of insulin resistance in late puberty.

[Activity of the enzymes which take part in aldehyde catabolism in the mitochondria of skeletal muscle in rats of different ages and its modulation during stress].

The purpose of this study was a comparative investigation of activity of enzymes, which take part in utilization of endogenous aldehydes in mitochondrial fraction of femoral muscle in intact and immobilized rats of different age. It has been shown that 12-months-old (adult) rats have high basal levels of NAD-aldehyde dehydrogenase, NADH-aldehyde reductase and glutathione transferase activity in mitochondrial fraction of femoral muscle. An increased of NAD-aldehyde dehydrogenase activity emerges during immobilization stress in adult rats. These changes contribute to enhancing the effectiveness of utilization of carbonyl products of free radical oxidation in mitochondria of skeletal muscle of 12-months-old rats during stress. Immobilization of old and pubertal rats, is accompanied by a certain arise in metabolic preconditions, leading to accumulation of endogenous aldehydes in mitochondria, and, as a result, to the injury of muscular fibers and an increase in manifestation of sarcopenia.

Oxidative stress and the enzyme system of aldehyde catabolism in the muscle mitochondria of immobilized pubertal rats.

The aim of the work is to find out peculiarities in manifestation of oxidative stress and to determine activity of enzymes, responsible for utilization of endogenous aldehydes in the mitochondrial fraction of the skeletal (femoral) muscle in pubertal rats during immobilization stress. Our study has shown that differently directed changes in the activity of mitochondrial aldehyde dehydrogenases and aldehyde reductases occur in the pubertal immobilized rats, that limits the catabolism effectiveness as regards carbonyl products offree radical oxidation in the muscle cells. Corroboration of the effect under consideration is an increased level of protein free radical oxidation products in the mitochondria of the skeletal muscle. On the basis of the obtained data the authors draw a conclusion about an increased sensitivity of the skeletal muscle to the oxidative stress impact due to modulation in the state of enzyme system, responsible for utilization of endogenous aldehydes in the mitochondria.

[Peculiarities of pilot's perception of flight information presented on on-board liquid crystal displays].

The article deals with results of experimental studies conducted on flight testing desk and covering peculiarities of pilot's perception of flight information presented on on-board liquid crystal display in dependence on changes speed and update rate of the screen. The authors determine frequency characteristics of information update rate, that achieve acceptable quality of the flight parameters perception in accordance with the changes speed. Vigorous maneuvering with high angular velocities of changed parameters of roll and pitch causes visual distortions that are connected with poor frequency of information update rate, deteriorate piloting quality and can cause flight unsafety.

[Spatial orientation of pilot using a cockpit exterior surveillance system].

Spatial orientation of pilots using a cockpit exterior surveillance system was tested in real nighttime helicopter flights. Major factors complicating adequate spatial orientation and provoking visual illusions in pilots are lack of information for spatial depth (relation) perception in two-dimensional TV images altering their position along the horizontal and vertical lines of trajectory and simultaneous piloting and target search-identification operations. Reliability of pilot's spatial orientation could be improved by displaying on the exterior imaging screen also relevant flight navigation parameters.

[The activity of the first line enzymes of the antioxidant defence in the liver of pubertal rats during stress].

The purpose of the work was to study the activity of the first line antioxidant defence enzymes in postmitochondrial fraction of liver of pubertal rats during immobilization stress. During short-term immobilization the activity of catalase and glutathione peroxidase (GPx) decreased. Long-term immobilization was accompanied by activation of GPx and superoxide dismutase in the liver postmitochondrial fraction of late pubertal and adult animals, but not early pubertal rats.

[Aldehyde reductase activity and blood aldo-keto reductase spectrum in adolescents with neuroendocrine obesity].

Investigation of aldehyde-reductase activity and blood aldo-keto reductase spectrum has been performed in 13-15 and 16-18-years old adolescents with obesity to clear up the mechanisms of neuroendocrine obesity at the age of puberty. It has been established that basal aldehyde reductase activity and blood aldo-keto reductase spectrum of healthy adolescents in early puberty do not differ from those of healthy adolescents in late puberty. A decreased aldehyde reductase activity and some alterations in blood aldo-keto reductase spectrum have been observed in late puberty in adolescents with neuroendocrine obesity. In adolescents with obesity there have been registered some changes in blood aldo-keto reductase spectrum which are not accompanied by any alterations in its aldehyde reductase activity. The results obtained suggest that certain prerequisites are formed in late puberty to complicate the course of neuroendocrine obesity.

[Activity of endogenous aldehydes catabolism enzymes in subcellular fractions of liver, heart and brain of rats at pubertal age under stress].

Activities of enzymes involved in redox transformation of endogenous aldehydes have been investigated in subcellular fractions of liver, heart, and brain of pubertal rats exposed to prolonged immobilization stress. In the liver aldo-keto reductase (AKR) activity in the postmitochondrial fraction and aldehyde dehydrogenase (ALDH) acivity of the mitochondrial fraction demonstrated a more pronounced decrease in 2-month-old rats. Rat heart postmitochondrial AKR and ALDH demonstrated opposite changes in their enzymatic activities, while activity of mitochondrial ALDH remained unchanged. Brain cells create conditions that favor effective utilization of endogenous aldehydes in metabolic redox pathways.

[Optimizing visual work of pilot wearing night vision glasses].

The article deals with results of experimental studies on optimizing visual work conditions of pilot in night vision glasses. Prevention of visual fatigue during work in night vision glasses was proved to be contributed mostly by the image brightness (in range of 0.7-1.8 candle/m2) adjustable by the pilot, precise individual settings of optic system in night vision glasses (by viewer's eye base) and regulation of the work duration.

[Activity of aldehyde scavenger enzymes in the heart of rats of different age during immobilized stress].

This study was made to determine the activity of aldehyde scavenger enzymes in the heart's postmitochondrial fraction of rats of different age during immobilization stress. Our study demonstrated, that immobilization of 1.5-, 2- and 12-month rats was accompanied by inhibiting activity of aldehyde dehydrogenase and aldehyde reductase. At the same time we observed an increase in glutathione transferase activity in immobilized 1.5-month-old rats and that in reductase activity in 24-month-old rats. The revealed changes can lead to a decrease in the rate of endogenous aldehyde utilization in the heart during stress at puberty.

[Effect of stress on the content of free radical oxidation products in subcellular brain fractions in rats of pubertal age].

The purpose of the present work is to study the influence of immobilization stress of different intensity on the content of protein and lipid oxidation products in subcellular brain fractions in rats of different age. It has been shown that 30-minute immobilization of 1.5-month, 2-month- and 12-month-old rats was not accompanied by accumulation of protein and lipid oxidation products in subcellular brain fractions. A prolonged immobilization of 1.5-month-old rats was accompanied by manifestations of oxidative stress in subcellular brain fractions; such manifestations were not characteristic of the rats of older age groups.