High level of population alcoholization is the cause of many cases of acute alcohol and alcoholic surrogate intoxication. The number of alcohol intoxication cases in Kazakhstan in 2014 amounted to 13891 (80.3 per 100 000 people), the number of fatal intoxication cases amounted to 882 (5.1 per 100 000 people). The problem of alcoholization in Russia remains urgent as well: according to the statistics of 2014,152 551 cases of acute intoxication of chemical etiology were registered, 33.9 % of cases occurred due to alcohol intoxication. Alcoholic beverages in the course of their biotransformation to acetic acid can form oxygen free radicals in particular superoxide anion as a byproduct of acetic aldehyde oxidation reaction. Studies on oxidative metabolism of ethanol intoxication are currently being conducted. At the same time, the state of oxidative metabolism during alcoholic surrogate intoxication was not practically investigated. Evaluation of oxidative metabolism depending on the severity of alcohol or its surrogate intoxication is of special interest. The aim was to compare oxidative metabolism indicators among patients with acute alcohol and alcoholic surrogate intoxication of different severity. The object of the study was blood of 62 people with diagnosed moderate or severe degrees of acute alcohol and alcoholic surrogate intoxication. Indicators of oxidative metabolism in erythrocytes and blood plasma were estimated. Significant differences were found in product concentration of protein oxidation containing bityrosine crosslinks in blood plasma under increase of alcohol intoxication degree.

The aim of study is to assess lipid peroxidation and antioxidant system in men with diabetes mellitus type 1. The objective of this study was to identify features of the lipid peroxidation-antioxidant defense system in men of reproductive age with diabetes mellitus type 1. 22 men with diabetes mellitus type 1 (the average age of 27.1 ± 7.38years) and30 healthy men of the same age (control group) (the average age of 28.0 ± 4.3 years) were involved in the study. The main and control groups were formed on the principle of "copy - pair". Standard clinical examination methods were used: history taking, physical examination and consultation of specialists to identify complications of diabetes. To determine the indicators of the system of free-radical lipid oxidation and activity of antioxidant protection, the spectrophotometric and fluorometric methods were used. In men with diabetes mellitus 1 type, there is increase in the level of active products reacting with thiobarbituric acid compared to the same indicator in the control group. The level of antioxidant protection in men with diabetes mellitus 1 type unlike the control was characterized by decrease in total antioxidant activity. However, stability of processes of superoxide dismutase activity and the glutathione system in comparison with control is observed against the backdrop of intensity increase of oxidative processes. Activation of lipid peroxidation is observed in men with diabetes mellitus type 1.

The research focuses on peculiarities of lipid peroxidation processes in women with reproductive disorders associated with chronic endometritis. The control group included 50 women of reproductive age with chronic endometritis, whose average age was 29.7 ± 4.7years. The comparison group consisted of 50 women of the same age with reproductive disorders without chronic endometritis, who had signed informed consent. We followed ethical principles and requirements of the Declaration of Helsinki of the World Medical Association. Insufficient activity of peroxidation processes which is characterized by a decrease in the concentration of primary ((DC - 1.11 ± 0.05 for the control group and 1.43 ± 0.08 for the comparison (p < 0.05)) peroxidation products, an increase in concentration of intermediate ((KD) - 0.53 ± 0.03 and 0.36 ± 0.03 respectively (r < 0,001)) peroxidation products and increased content of double bond substrates: 1.82 ± 0.07 and 1.11 ± 0.07 respectively (r < 0,001) compared to the patients with reproductive disorders without chronic inflammation of the endometrium which therefore indicates the presence of oxidative stress in women with reproductive disorders and chronic endometritis. The results of discriminant analysis showed that the diene conjugates are the most informative indicators of the lipid peroxidation system, indicating the differences between the group of patients with chronic endometritis and the group of patients without inflammation.

Background. Oxidative stress is an acknowledged pathogenic mechanism in diabetes mellitus type 1. Incidence, severity, and rate of complications of diabetes mellitus type 1 are associated with many factors including geographic location and ethnicity. Material and methods. The features of POL-AOD processes, the levels of lactate, pyruvate, and their relationships in 30 women of Buryat and Russian ethnic groups with diabetes mellitus type 1. The materials for biochemical studies were blood serum and red cells. Spectrophotometric and fluorometric methods were used. Results. Increase of lipid peroxidation activity at the initial stages and increase of total antioxidant blood activity in Buryat patients were marked. Increase of primary and secondary lipid peroxidation products concentrations and decrease of superoxide dismutase activity in group of Russian patients were marked. It is confirmed to the oxidative stress factor. The reduced concentration of lactate and the ratio lactate/pyruvate levels in patients Buryat ethnic group were observed. More intensive accumulation of lactate and ratio of lactate/pyruvate can contribute to hypoxic events and worsen the prognosis of the disease in Russian patients. Conclusions. It was found that the degree of intensity lipid peroxidation process and lactate and the ratio lactate/pyruvate levels in patients Buryat ethnic group reduced in comparison with Russian patients. This work was supported by grant of the President of Russian Federation (№ 5646.2014.7).

Free radical oxidation plays an important role in the development and exacerbation of the pathological process. Oxidative stress causes a disturbance of the rheological properties of red blood cells and modification of their membrane. Activation of processes of peroxidation of lipids disturbs the integrity of the erythrocyte membrane. In community-acquired pneumonia the study of oxidative metabolism of red blood cells, especially the oxidative modification of their proteins, dedicated to a limited number of studies. Oxidative modification of hemoglobin dissipate a key role in the development of inflammation induced by hypoxia. The aim of the research was to study indicators of oxidative stress, the content of oxidized modified proteins in the red blood cells and the permeability of their membranes to low-molecular-weight hydrophilic substances in patients with community-acquired pneumonia. The object of the study were the erythrocytes of blood of 33 patients with community-acquired pneumonia and 19 practically healthy persons of young and middle age from 27 to 42 years. Evidence of oxidative processes in red blood cells was a significant increase of the oxidized-modified proteins (carbonyl derivatives) in erythrocytes. The increase in the content of membrane-bound hemoglobin may also be due to the high level of lipid peroxidation in erythrocyte membranes. The results of the study showed the presence of intracellular oxidative stress in erythrocytes of patients with community-acquired pneumonia, which leads to damage to their membranes and release of hemoglobin into the blood plasma.

To examine the correlation of changes of ω-6 polyunsaturated fatty acids and free-radical processes in the blood of the umbilical cord of newborns to mothers with cytomegalovirus infection, the content of ω-6 polyunsaturated arachidonic, linoleic fatty acids, the concentration of the products of reacting with thiobarbituric acid and activity of phospholipase A2 in the membrane of red blood cells of the umbilical cord were studied. The material for the study was the umbilical cord blood of 40 newborns from mothers who had cytomegalovirus infection in the HI trimester (titer of IgG antibodies to cytomegalovirus 1: 1600) - the main group. The control group consisted of 40 infants from healthy women It was found that the aggravation of chronic cytomegalovirus infection in mothers (titer of IgG antibodies to cytomegalovirus infection 1: 1600) contributes to the activation of lipid peroxidation (the repression of antioxidant protection) in the cord blood of newborns, increasing the concentration of TBA-active products on the background of the high activity of phospholipase A (more than 2-fold; p < 0.001) and is associated with the generation of large amounts of precursors of pro-inflammatory eicosanoids acids ω-6 family: linoleic (56 %; p < 0.001) and arachidonic (34 %; p < 0.001). Increase in TBA-active products has a close relation to the content of arachidonic acid in umbilical cord blood of newborns from mothers with cytomegalovirus infection, the correlation coefficient r was 0.78 (p < 0.001). The revealed changes in the membrane of red blood cells from the umbilical cord of newborns from mothers with cytomegalovirus infection may become the adverse gestation factor.

The article presents a comparative analysis of the effectiveness of various methods of reflexotherapy in patients with arterial hypertension and metabolic disorders. It is shown that the inclusion of therapeutic complexes of different variants of acupuncture significantly change clinical and metabolic parameters (blood pressure level, body mass index, atherogenic index, resistance index to insulin, etc.); the most significant results were obtained using pharmacopuncture with Ubichinon compositum. It was found that the standard method of treatment provides a reliable improvement in lipid metabolism (reduction of atherogenic ratio by 12.6 % and a decrease in the activity of prooxidant processes in the system of lipid peroxidation by 11.8 %, a reliable drop in fasting insulin overproduction by 8.5 %, a decrease in insulin resistance index (an average by 11.0 %). Inclusion of classical acupuncture in treatment complex improves the results of standard therapy: atherogenic index decreased by 22.3 %, index of insulin resistance - by 21.9 %. Wherein marked and significant drop of malondialdehyde and glucose concentrations in the blood (19.8 %) (6.3 %) was marked. The introduction of physiological solution (placebo for pharmacopuncture) into acupuncture points had an impact on the studied biochemical and hormonal parameters approximately to the same extent as the classic acupuncture. At the same time, pharmacopuncture with Ubichinon compositum preparation has led to the most expressed favorable changes in the system of insulin regulation of metabolism of carbohydrates and lipids: atherogenic index and resistance index to insulin decreased respectively by 28.1 % and34.1 % indicating markedsanogenetic character of pharmacopuncture on the body of patients with arterial hypertension and metabolic disorders.

The research is devoted to studying the features of antioxidant protection system in fertile men of various ethnic groups. Studying the features of antioxidant protection processes in the populations of various ethnic origins, living in identical geographical conditions, is of scientific interest. 126 men of reproductive age (84 men of Russian population and 42 men of Buryat population living in Ulan-Ude) were examined. Blood plasma and hemolysate were used as the material for the biochemical research. Modern spectrophotometric, fluorometric and statistical methods were used. The basic indicators of lipid peroxidation, reflecting different stages of oxidation (рrimary,, intermediate, final products] and total antioxidant activity of blood, which characterizes the total activity of inhibitors of radical oxidation, and determining its buffering capacity were studied. We investigated the basic units of antioxidant protection - enzymatic (superoxide dismutase) and non-enzymatic (low molecular weight soluble vitamins retinol and а-tocopherol, oxidized and reduced glutathione). The peculiarities of Ирid peroxidation and antioxidant protection processes in fertile men have significant differences. They can be attributed to the ethnic origin and characterize various degrees of activity of metabolic processes in the surveyed groups. Studying the condition of antioxidant protection system will significantly expand ideas of organism adaptation opportunities to external conditions and will be able to become a basis for effective monitoring of reproductive health.

The analysis of scientific researches shows that the problem of alcohol consumption (beer, dry wine, champagne), in small doses during pregnancy has been actually disregarded for many years. So the problem has become quite urgent, especially in Russia. In order to determine the effect of alcohol on pregnancy and childbirth, women and babies were divided into three groups. Group 1 (n = 101) (control group) included women who did not use alcohol during pregnancy. Group 2 (n = 75) included drinking women whose alcohol consumption during pregnancy was less than 2 doses or 750 ml. Group 3 (n = 33) included moderately drinking women whose alcohol consumption during pregnancy ranged from 3 to 11 doses (from 750 ml to 3850 ml). The study of the lipid peroxidation-antioxidant protection system as a sensitive marker of integrated health disorders in women, consuming alcoholic beverages in a prenatal period, was conducted. It was indicated that a statistically significant decrease in overall antioxidant activity was found in the context of lipid peroxidation activation in women consuming low-alcohol drinks, which demonstrates a lack of functioning of lipid peroxidation system and oxidative stress regardless of the dose of low-alcohol drinks.

One of the most topical problems in the field of healthcare is to solve the issues of an early diagnosis, timely prevention and effective treatment of cardiovascular diseases, which include arterial hypertension (the AH]. Prevalence of EAH in the pediatric population in Russia amounts to 20 %. Despite the fact that the mechanisms of the disease were studied in detail, metabolic changes that led to its early deve^ment in teenagers were still not entirely clear. In the Clinic of FSBSI Scientific Center for Family Health Problems and Human Reproduction (Irkutsk], clinical and functional examination of 48 male adolescents aged 14-17 years, of which 25 patients with stable arterial hypertension and 23 adolescents without somatic pathology with normal blood pressure, was conducted. Antioxidant status was studied in blood plasma and hemolysate. A comparative analysis of the following indicators was conducted: total antioxidant activity, superoxide dismutase activity, level of retinol and α-tocopherol, glutathione system parameters. Patients with stable arterial hypertension were recorded with level of overall antioxidant activity in blood 29 % higher than the benchmark, decreased superoxide dismutase activity by 11 % and content of а-tocopherol by 44 %. Retinol concentration in teenagers with hypertension was two times higher than the content of this indicator in the control group (р = 0.00]. Decrease in the antioxidant levels was found in adolescents with arterial hypertension that can be the cause of the oxidative stress development.

Viral hepatitis is a traditionally complexglobal problem for humans and is still far from being solved. For the last decade the incidence of chronic viral hepatitis in the Russian Federation has grown by 2.2 times. Many researchers point out aggravating mutual influence of viral hepatitis and рregnancy. The severity and development prognosis of liver diseases are closely interlinked with the functional state of oxidant and antioxidant systems of hepatocytes. Objective is to estimate the intensity rate of liрid peroxidation in рregnant women with chronic viral hepatitis. The material for biochemical studies was blood plasma. The content of the substrates for Ирid peroxidation - compounds with isolated double bonds and the products of lipid peroxidation processes (diene conjugates, ketodienes and conjugated trienes, thiobarbituric acid active products] was determined with spektrofluorofotometre "SHIMADZU-1501" (Japan]. We used modern spectrophotometric and statistical methods. It was found that there is increased activity of Ирid oxidation in patients with chronic viral hepatitis. Blood plasma levels of intermediate and final products of Ирid peroxidation are significantly elevated in patients with chronic viral hepatitis, compared to the control groups. Increase in plasma peroxidation products indicates the рresence of oxidative stress in patients with viral hepatitis. Study of parameters of liрid peroxidation is an informative method for the correction of the disease in рregnant women with chronic viral hepatitis.

In recent years, the number of children with attention deficit hyperactivity disorder (ADHD) increased, which may be due to the increasing information stress and wide introduction of new information technologies. Manifestations of ADHD may be the cause of impaired social and school adaptation, learning difficulties, reduced academic achievements. The syndrome is believed to cause suffering to the frontal lobe of the brain, subcortical structures of the brain, reticular formation and stem structures. The features of the formation of the metabolic processes underlying the adaptive-compensatory mechanisms in children with different interhemispheric relations of brain and ADHD are studied insufficiently. Lipids form the basis of the central nervous system and the lipid matrix of cell membranes. The processes of lipid peroxidation have damaging effect on a cell by altering the structure of cell membranes. The aim of the study was to investigate peculiarities of the carbohydrate and lipid metabolism, peroxidation that determine the normal functioning of metabolic and cellular homeostasis in children with attention deficit hyperactivity disorder, and different hemispheric relations. 54 children of 7-11 years, living in Irkutsk, were examined. Patients were characterized by the normal level of general mental development, the absence of anemia, endocrine diseases, by the absence in the anamnesis of craniocerebral traumas, neuroinfections, epilepsy, mental illness. Changes of metabolic reactions had distinct individual differences of patients, due to specific functional activity of the cerebral hemispheres.

We have found out in our previous studies that results of quantitative spectrometry of electrogenic metals (Ca, K, Na) in epidermal cells (hair) of healthy people and the Chernobyl liquidators (chronic oxidative/nitrosative stress) are conjugated. The nature of this «conjugation», like many intimate mechanisms of the metal-ligand homeostasis in the epidermis, remains unsolved. Transmembrane traffic of electrogenic metals (and especially the Na⁺ ion) is directly related to cell bioenergetics. Therefore, intracellular bioenergetics processes in the membrane and in the mitochondrial respiratory chain, can determine homeostasis of electrogenic metals. It has been shown that in the cell, that is an open dynamic system, there are signs of self-organized criticality (SC). Thus we can classify electrogenic metal homeostasis as SC-phenomenon.

Aging is accompanied by intensification of oxidative degradation of proteins, including lipoproteins, proteolytic system dysfunction and accumulation of oxidized proteins. Similar changes are found in drug addiction. In this regard, we carried out a comparative study of conformational changes of plasma proteins and red blood cells of people of different age groups and people who use drugs. The study was carried out with the use of fluorescence analysis to measure the spectra of fluorescence of amino acid residues in proteins (summary fluorescence and tryptophan). In the analysis of fluorescence spectra it is preferable to use the second derivative of the fluorescence spectra as it is the most informative. The application of this research method was chosen because it has high sensitivity. It provides information on the status of living systems without damaging them; it requires large quantities of biological material; it makes it possible to differentiate between the various stages of the disease. Changes in the general phase and tryptophan fluorescence plasma proteins in older people and drug addicts indicate increase in the availability of tryptophan residues to the aqueous environment as a result of conformational changes of macromolecules and the disruption of the lipid layer due to the intensification of free radical processes.

Increased percentage of incidence of chronic parenteral viral hepatitis in women is an negative sign. The objective of this study was to identify features of the lipid peroxidation-antioxidant defense system in women of reproductive age with the chronic form of parenteral viral hepatitis depending on a degree of infection process activity. The study involved 44 women with chronic parenteral viral hepatitis (including 24 patients with minimum and low degrees of activity and 20 patients with moderate and high degrees of activity) and 28 healthy women of the same age. Spectrophotometric and fluorometric methods were used. Patients with minimum and low degrees of activity of chronic parenteral viral hepatitis had lower levels of diene conjugates - 22.6 % less, an increased TBA-reactive product level - 53.4 % less, reducing superoxide dismutase activity (21.2 %) compared with the control. In the group with moderate and high activities of chronic parenteral viral hepatitis TBA-reactive product level was increased by 2.3 times and superoxide dismutase activity was decreased by 20.7 % in comparison with the control. The chronic form of parenteral viral hepatitis was characterized by the series of metabolic disorders depending on the degree of inflammatory process activity. This requires a more careful approach to therapeutic and diagnostic activities.

According to the current data, most menopausal women have reduced life quality and one of the main criteria is sleep quality. It is well known, that sleep loss may cause oxidative stress. The aim of this study was to assess lipid peroxidation and antioxidant system in postmenopausal women with insomnia. Materials and methods: 41 postmenopausal women (18 patients with insomnia, 23 women without insomnia (control)) were examined. Sleep disorders were assessed by using sleep questionnaire (Stanford Sleep Research Center, USA), Epworth Sleepiness Scale, Insomnia Severity Index. The materials for biochemical studies were blood plasma and red cells. Lipid peroxidation and antioxidant system parameters by spectrophotometric and fluorometric methods were determined. Statistical analysis was performed by non-parametric test. The study results showed increase primary products levels in patients with insomnia compared with the control group. Main and control group antioxidant system parameters have no differences. Oxidative stress coefficient in group with insomnia higher than control. Conclusions: insomnia in postmenopausal women is associated with the development of oxidative stress.

The aim of our investigation was to estimate the mucociliary clearance (MC), the spectrum of bacterial communities discharged from the middle meatus and sinus aspirates in patients with chronic rhinosinusitis (CRS) associated with gastroesophageal reflux disease (GERD), patients with CRS without GERD and healthy volunteers. The study included 30 patients with CRS and GERD, 34 patients without GERD аnd 30 healthy volunteers. Association with CRS and GERD was characterized by statistically significant slowing of MC and quantitative and qualitative changing of characteristics of the nasal mucosa microflora, but not of the paranasal sinuses. In the group of patients with CRS with GERD, MC amounted to 28.5 ± 4.7 min, in the group without GERD - 23.6 ± 2.7 min, in the healthy group - 5.8 ± 1 min. S. аureus (р = 0.009), E. mli (р = 0.029) and Candida albicans (р = 0.013) were detected in the mucosa of the middle meatus of patients with CRS and GERD more than in patients with CRS without GERD. No significant differences in the microflora of the paranasal sinus aspirate were revealed.

We studied the response of trigger systems in healthy volunteers living in areas with different levels of air pollution. We determined that particles with the size of 800 microns and higher of relatively favorable region, particles with the size of less than 50 microns dominated in the air of the unfavorable area, among which there were the most hazardous to health amounts of microparticles - from 200 to 300 nm. Microparticles of unfavorable area causes the development of oxidative modifications of proteins and DNA contributing to the change of leukocyte potential energy. The increase in total antioxidant activity and response of thiol-disulfide system (the increase in thioredoxin, glutathione with a stable reductase level] maintains a balance of oxidation and antioxidant processes contributing to protection of the cellular and subcellular structures against considerable oxidative damage.

Hypochlorous acid (HOCl) is produced with myeloperoxidase (MPO) in activated neutrophils. To assay MPO activity we chose a HOCl-selective dye i.e. celestine blue B (CB) that changes into pink glycol after oxidation. Our aim was to elaborate fluorescent methods of measuring HOCl production with activated neutrophils. Scanning CB fluorescence before and after its reaction with HOCl revealed activation and maximum emission, at 487 and 578 nm respectively, which are specific for oxidized product. Activated with Phorbol 12-myristate 13-acetate (PMA), the neutrophils were incubated with MPO inhibitor, 4-aminobenzoic acid hydrazide, which decreased fluorescence intensity (activation 487 nm, emission 578 nm) as compared with inhibitor-free samples. By confocal microscopy method we obtained images of CB- and DAPI-stained neutrophils. Neutrophil extracellular traps (NET) are clearly visible: DAP1 staining of multiple DNA bands co-localizes with fluorescence of oxidized CB. Flow cytometry showed that intensity of neutrophils activated by 50 nM PMA was 5 times higher (p < 0.05) than in PMA-free cells.

The emergence of drug-resistant TB caused by resistance to antibiotic strains of bacteria, prompted to search for new "organism-oriented" ("host-targeted") adjuvant treatment strategies. Free radical oxidation plays an important role in the development and exacerbation of the pathological process. The main system of cell protection from oxidative stress is the redox-sensitive signaling system of the antioxidant-responsive element of the Keap1/Nrf2/ARE, which includes the transcription factor Nrf2, which is under constant control of a repressor protein Keapl. Nrf2 regulates the expression of genes containing the antioxidant-responsive element ARE in their promoters, Keapl is a kind of molecular "sensor" of modifications in the intracellular homeostasis. The inextricable link between these molecular structures allows combining them into a single redox-sensitive signaling system Keap1/Nrf2/ARE. Nrf2 modulates resistance of the organism to various infections: activation of Nrf2 prevents the penetration and replication of influenza A virus, contributes to resistance to various bacterial agents (Salmonella typhimurium, Pseudomonas aeruginosa). The aim of this work was to study the influence of induction system Keap1/Nrf2/ARE on the formation of mycobacterial granulomas in vitro. In vitro model was used to study effect of induction of the redox-sensitive signaling system Keap1/Nrf2/ARE in time course of granuloma formation. It was found that the activation of Keap1/Nrf2/ARE system led to acceleration of granuloma formation, which was then replaced by the dissociation process. These data allowed us to consider Keapl/Nrß/ARE system as a new therapeutic target in the tuberculosis treatment.

A plant of the Euphrasia L. genus is promising to be introduced into medical practice and being used in traditional medicine for eye, gastrointestinal tract, upper respiratory tract disease treatment. Euphrasia pectinata Ten is widespread and growing abundantly in the Central Siberia. Study of the composition and quantitative content of phenolic compounds of Euphrasia pectinata Ten. growing in Irkutsk Region was studied by HpLC method. Organ-specific distribution and dynamics of accumulation depending on the phase of vegetation of 8 compounds (3-O-caffeoylquinic acid(chlorogenicacid), hyperozide, acteoside, cynaroside, diosmetin-7-O-β-D-glucuronide, dihydroquercetin, luteolin, quercetin) were studied. The maximum of flavonoid glycosides is accumulated in flowers and leaves, and the maximum of flavonoid aglycone is accumulated in stems. The maximum quantity of flavonoids in aboveground organs is observed in the flowering period, and maximum of phenylethanoid acteoside is observed in the fruiting period. Thus, as a medicinal plant, the materials can be recommended for harvesting of the aboveground organs E. pectinata during the flowering period.

By means of calculation of the incidence mean value, the amplitude of oscillation and a dynamic analysis, we investigated data from official statistical collections of the Federal State Statistics Service (Public Health in Russia, Russian Statistical Yearbook). We assessed the incidence rate using medical aid appealability of adolescents (15-І7 years) in the Russian Federation and Novosibirsk region during the period from 2004 to 2013. A comparative dynamic analysis of general incidence of the adolescents of the Russian Federation and Novosibirsk region has shown that the medical referral level is higher in the Russian Federation by 33.8 % with an average increase by 3.4 % per year on average, especially for such types of diseases as digestive diseases, diseases of the endocrine system, diseases of the musculoskeletal system and connective tissue, circulatory system diseases, diseases of the eye and adnexa, diseases of the ear and mastoid process, nervous system diseases (44.1 %; 31.9 %; 26.0 %; 24.9 %; 23.8 %; 22.9 %; 21.3 %; 19.8 % respectively); the medical referral level of Novosibirsk region was higher by 30.2 % with an average increase by 3.0 % per year on average, infectious and parasitic pathology was higher by 43.0 % mainly. The differences in the levels of medical help and the structure of the main types of diseases that determine the nature of adolescent morbidity in the Russian Federation and Novosibirsk region, which predetermines the need to ensure appropriate coordination of medical activities and services.

We have suggested that the molecular mechanism of vascular wall damage in diabetes is not substantially different from that in atherosclerosis. Thus, it can be assumed that aldehyde-modified LDL should be eliminated from the blood stream with much greater speed than non-oxidized LDL. In the available literature there is information about the clearance of native human LDL from the bloodstream, whereas information on the clearance of the aldehyde-modified LDL in animals or humans was not found. Based on this, the present work is devoted to the clearance of aldehyde-modified LDL of rabbits and humans introduced into the bloodstream of rabbits. We investigated the clearance of glyoxal-, methylglyoxal- and MDA-modified LDL from the bloodstream of rabbits. We used biotinylated LDL of rabbit blood plasma and FITC-labeled LDL of human blood plasma. LDL was isolated with preparative ultracentrifugation in NaBr gradient. It was shown that glyoxal- and methylglyoxal-modified LDL of rabbits and humans circulated in the bloodstream for the same time as native LDL while MDA-modified LDL was rapidly eliminated from the bloodstream. The data obtained indicated the possibility of greater atherogenic potential of glyoxal- and methylglyoxal-modified LDL as they circulate in the bloodstream for a rather long time. At the same time, MDA-modified LDL is likely to be exposed to enhanced elimination by macrophages after their "linkage" to blood cells.

In order to reveal the causes of age-related changes in sensitivity of the organism to oxidative stress, the spectrum of aldoketoreductases in blood serum of rats of different ages was investigated. It was discovered that 0.5- and 24-month old rats have the similar spectrum of aldoketoreductase in the blood. There are only four electrophoretic fractions of aldoketoreductases in their spectrum. The share of 3^rd fraction increases the spectrum of 1.5-, 2- and 3- month old rats. The pubertal rats contain additional 5^th fraction in aldoketoreductase spectrum of the blood. This electrophoretic fraction has maximal electrophoretic mobility, but there is inconstancy in spectrum. There are 6 electrophoretic fractions of aldoketoreductases in the blood of 3-month old rats. Two of them with maximal electrophoretic mobility are absent in the spectrum of 0.5- and 24- month old rats. There are the same shares of 3^rd and 4^th fraction in the aldoketoreductase spectrum of the blood 12-month old rats, and 5^th fraction there is inconstancy. The cause of age-related changes in the aldoketoreductase spectrum of blood may be coupled with existence of age-related differences in the gene expression of the encoded enzymes of aldoketoreductase family. Due to the fact that 0.5- (early childhood) and 24-month old (senescence) rats have similar aldoketoreductase spectrum of the blood, we propose that the cause ofthat phenomenon coupled with age-related changes in the production and secretion of sex steroids.

An experimental study was performed on outbred male rats. In the first series of chronic experiments we studied the process of glucose absorption in an isolated loop of a jejunum in 12 rats. In the second series we studied the changes of lipid peroxidation during immobilization with the introduction of MFB and without in 18 rats in each group. Rats were operated in a special way. During all the days of immobilization there is an increased DK in serum of rats, reaching maximum on the seventh day of daily one hour immobilization. Lipid peroxidation products (conjugated dienes, malonicdialdehyde) and antioxidant activity of serum in chronic immobilization stress (1 hour a day during 7 days) and glucose absorption in a jejunum were investigated. Activation of lipid peroxidation (LPO) and its correlation with inhibition of glucose absorption rate were revealed. 2-ethyl-6-methyl- 3-hydroxypyridine succinate (EMHPS) administration of a 10 mg/kg a day dose for 7 days resulted in primary and end lipid peroxidation product decrease and increase in blood serum antioxidant activity. Under EMHPS correction, the glucose absorption rate approached the control group level in chronic immobilization stress. Activation of lipid peroxidation was suggested as one of the possible mechanisms of glucose absorption reduction during stress. Activation of the POL can be one of the decline reasons of the glucose absorption process during stress.

Endotoxin shock in rats led to intravenous bolus of bacterial lipopolysaccharide (LPS) was accompanied by oxidative stress and increase of NO level in livers, lungs, kidneys, hearts of animals. The intravenous administration of bienzyme superoxide dismutase - chondroitin sulphate - catalase conjugate (SOD-CHS-CAT) showed its anti-endotoxemia action in rats at preventive (before initiation of injury) and therapeutic (after start of injury) application during cytokine phase of injury and influence on further stages of the damage. The injection of antioxidant SOD-CHS-CAT conjugate in a therapeutic regime did not demonstrate significant alterations of No level in livers, lungs, kidneys, hearts of rats (as compared to indices of the rat group with LpS action only) and displayed protective action on the kidney function by altered urea and creatinine in blood. The therapeutic effect of SOD-CHS-CAT was demonstrated by increase in organism viability. The effects of intravenous injection of SOD-CHS-CAT in a rat model of endotoxin shock showed a variety in the activity of this conjugate in addition to prevention of NO conversion in peroxynitrite upon interaction with O₂ superoxide radical. The results of accelerated normalization of arterial blood pressure and heart rate, a significant decrease in rat lethality because of using SOD-CHS-CAT conjugate indicate the importance of the determination of action mechanism of the cardiovascular injury models associated with other vasoactive agents besides NO. The further research of vascular damage pathogenesis and evaluation of its role in oxidative stress (time and place) are of paramount importance.

It is well known that much pathology observed immediately after birth or in later periods of postnatal life is associated with adverse prenatal development. The mechanisms of this phenomenon, however, warrant further investigation. Accordingly, the aim of the present study was to compare oxidative damage caused to macromolecules, especially proteins and nucleic acids, and to assess the state of the antioxidant system in rats with chronically elevated blood plasma L-homocysteine (Hcy), as well as in their offsprings exposed to hyperhomocysteinemia (HHcy) throughout pregnancy. It was shown that blood Hcy was elevated in both studied models, but in the rats with past HHcy, it returned back to normal values in two months of postnatal life. Both alimentary and prenatal HHcy increased nitrotyrosine production and changed the activity of superoxide dismutase in the experimental animals and their matured offspring. The high activity of the enzyme in late periods found in animals that underwent prenatal HHcy gave indirect evidence to hypergeneration of superoxide radical. Despite the restored level of Hcy, free radical oxidation activation was observed in the rats, whose mothers had been administered with L-methionine throughout pregnancy, which was confirmed by elevated blood serum nitrotyrosine. The data obtained were concordant with the idea that the elevated blood plasma Hcy found in pregnant rats resulted in oxidative stress developed in their offsprings, which manifested itself months later on their postnatal life.

Oxidative stress is a risk factor for disease development and cardiovascular system, diabetes, neurodegenerative diseases, etc. The resulting product is thus free radical lipid peroxidation - malondialdehyde (MDA) is atherogenic modification of low density lipoproteins (LDL), so that they acquire the ability to be rapidly accumulated in the cells of the vessel walls, causing pre-aterosklerotic lipoid damages. The aim of this study was to investigate the effect of high temperature (one of the environmental factors) for key operating parameters: the content of secondary products of free radical oxidation polyene lipids - mDa in blood plasma and erythrocyte antioxidant activity of key enzymes. Hyperthermia was triggered in practically healthy volunteers (6 males, 22-46years). The analysis was made using a recording spectrophotometer Hitachi-557 (Japan). The statistical analysis was performed using the non-parametric Wilcoxon-test (Attestat program). MDA levels in the blood plasma, the activity of key antioxidant enzymes in erythrocytes were determined through divided intervals in study participants. A significant increase in MDA content (62 %) and reduction of catalase activity (11 %) and glutathione peroxidase (19 %) were revealed after 30 days in the conditions of hyperthermia test.

It is believed that reactive oxygen species (ROS) are involved in the performance of this adaptive hepatoprotective effect phenomenon. However, the role of ROS in the signaling mechanism of the early hypoxic preconditioning (early HP) and the contribution of individual types of oxygen radicals in the infarct-limiting effect of early HP remains uncertain to the end. Objective was to investigate the role of various types of reactive oxygen species in the signaling mechanism of the infarct-limiting effect of early hypoxic preconditioning. We investigated the role of reactive oxygen species in the signaling mechanism of early HP in vivo. Adaptation of animals was conducted with 6 transient hypoxia-reoxygenation sessions before prolonged ischemia (45 min) and reperfusion (120 min). Low molecular weight antioxidants were administered 15 minutes prior to the HP. We found out that pretreatment with the nonselective antioxidant indirect action of N-(2-mercaptopropionyl)-glycine and "trap" of hydroxyl radicals 1,3-dimethylthiourea completely eliminated the infarct-limiting effect of adaptation. Administration of antioxidants tempol and trolox, as well as the use of N-(2-mercaptopropionyl)-glycine after HP had no effect on the protective effect of adaptation. Consequently, reactive oxygen species, including hydroxyl radical, operate as the trigger function in the signaling mechanism of early HP.

We studied capabilities of confocal laser scanning microscopy in the analysis of lipid droplets volume and of quantity of functional mitochondria and reactive oxygen species production in liver cells for early diagnosis of cytochemical disturbances at dyslipoproteinemia (16 days of experiment). The results showed the increase of lipid droplets volume in hepatocytes, decrease of functional mitochondria and increase of reactive oxygen species production. We evaluated the potential of real-time PCR method in the analysis of mitochondrial DNA of blood plasma at early stages of dyslipoproteinemia and in experimental infarction. On the background of registered blood lipid metabolism disorders and structural and functional changes in liver cells, we determined the tendency to three-time increase in concentration of circulating cell-free mtDNA on the 16^th day of dyslipoproteinemia as compared to the control data. We used a model of myocardial infarction to show statistically significant increase in the level of circulating cell-free blood mtDNA from 48 hours after adrenaline injection and we found that this level maintained up to 144 hours after adrenaline injection. Obtained data can serve as a basis for creation of technologies for diagnostic monitoring of atherosclerosis and myocardial infarction severity.

Tumor progression is accompanied by dysregulation of cell proliferation and apoptosis, which plays an essential role in breast cancer pathogenesis and cell resistance to chemotherapy. The role of protein carbonylation in molecular mechanisms of regulating MCF-7 breast cancer cell proliferation under the effect of roscovitine, a selective inhibitor of cyclin-dependent kinases, was evaluated. The cells were grown in adherent cell culture with or without roscovitine. The levels of reduced/oxidized glutathione and the concentration of protein carbonyl derivatives were determined by spectrophotometry. The cell cycle was evaluated by the flow cytometry; the same technique was used to measure the reactive oxygen species (ROS) concentration. Cell culture with roscovitine resulted in a decrease in the redox potential of the glutathione system and a rise in the ROS and protein carbonyl derivative concentrations. Roscovitine contributed to the G₀/G₁ and G₂/М phase arrest due to its interaction with ATP-binding sites of cyclin-dependent kinases. Roscovitine could also promote enzyme carbonylation. The obtained results can be further used for development of personalized approaches to breast cancer therapy.

Climatic and geographical features always influenced on adaptation to the environment as well as the development level of economy and culture. The formation of certain food behavior in population determined fixation of specific gene alleles and mutation. They were responsible for digestion a typical food for the population. At the moment there is information about such genetic features as metabolism of proteins, carbohydrates and fats for many races and nations. But a few studies are about causes of prevalence differences of gene polymorphisms of folate cycle in the world's populations. The main objective was to explore 677C>T mutation MTHFR gene among Russian and Buryat to compare it with ones in other populations. The total of399 children and adolescents (200 Russians and 199 Buryats) were involved in this study. Genotyping of MTHFR 677C>T was performed by PCR-RT We used soft "STATISTICA 8.0" to compare results. As a result, T-allele frequency was 30 % in Russians and 21,1 % in Buryats. We found significant differences of prevalence of polymorphism 677C>T between studied groups (p = 0.011). Also we found significant difference between Russian and British (p = 0.054), French (p = 0.0263), Spanish (p < 0.0001), Italian (p < 0.0001) and Greek samples (p = 0.0454). The Buryat group had significant differences with Chinese (p < 0.0001), Korean (p < 0.0001), Mongolian (p < 0.004), Japanese (p < 0.0001), Kazakh (p = 0.0198) samples and two samples of Hans (p < 0.0001; p = 0.0390).

We determined three isoforms of APOEprotein differing by amino acid residues in 112 and 158 positions: aroE2 (112Cys, 158Cys), apoE3 (112Cys, 158Arg) and aroE4 (112Arg, 158Arg). Protein isoforms differed in the degree of effectiveness of protein interaction with the liver cell receptors during cholesterol transport. We studied the prevalence of genotypes and alleles of polymorphic variant ε2/ε3/ε4 of apolipoprotein E gene in a group of healthy Russian adolescents living on a territory of Eastern Siberia (Irkutsk region). 73 healthy Russian adolescents (13-18 years) were included in the study. A biochemical analysis of blood lipids was carried out for each adolescent. We also genotyped the carriage of genotypes and alleles of polymorphic variant ε2/ε3/ε4 of apolipoprotein E gene. In the study the mostfrequently met genotypes were: ε3/ε3 in 57.5 % of cases, the genotype ε2/ε3 -16.4 %, ε3/ε4 -19.2 %, ε2/ε4 - 82.7 %, ε4/ε4 - 4.1 %. APOE gene genotype distribution was consistent with Hardy - Weinberg equilibrium in the studied sample (p = 0.498). The analysis of the allele and genotype distribution of polymorphic variants ε2/ε3/ε4 of APOE gene, and comparison with the previous population-based data showed that the frequency of alleles and genotypes ε2/ε3 ε4 APOE gene in the studied sample of adolescents corresponds to frequencies in the previously studied samples of the Caucasians. Comparison of lipid carriers between genotypes in the studied sample of adolescents showed no connection of genotypes with the level of blood lipid profile.

The processes of lipid peroxidation are universal phenomena which to a greater or lesser degree always develops in membranous and lipoprotein complexes of living organisms. Arising alongside lipid peroxidation intensification, the oxidative stress is an important pathogenetic factor of wide range of pathoses and pathological disease development, such as widely spread cardiovascular, phlogistic, oncological and endocrine diseases. Natural and synthetic phenolic antioxidants effectively inhibit lipid peroxidation in vitro and in vivo and attract attention of specialists as means of disease and pathosis prevention and treatment connected to oxidative stress development. The majority of biologically active antioxidants have lipophilic properties while their hydrophilic analogues differ favorably by higher velocity of transportation, convenient dosing and injecting which make them irreplaceable for pathosis treatment. The promising character of creation of water-soluble antioxidants, simultaneously possessing antiradical and antiperoxide activities are justified in the review. It is demonstrated that specimens of hydrophilic sulphurous phenolic antioxidants have marked biological activity. Such compounds as S-[3-(hydroxyaryl]propyl]thiosulfates have bioantioxidant, cardioprotective, anti-inflammatory and anti-tumor properties and can be used for correction of pathological conditions associated with the development of oxidative stress. Prospectivity of the further research is determined by the necessity to develop acting medicine components for free-radical pathology therapy.

The article analyzes various mechanisms of ROS participation in the processes that determine the response of automatism and cardiac contractile function under natural short- or long-term physiological stress, and acute disturbance of energy production in cardiomyocytes. Superoxide and hydrogen peroxide are believed to have a similar effect, while the effect of nitroxide noticeably different. It was noted that increased CA++ in bioplasma not only enhances the contraction of myofibrils, but at the same time accelerates the rate of ATP synthesis. Regulation of volume load on the cellular level is realized by stretching of the sarcomeres, which increases the degree of actomyosin interaction. This corresponds to increase in the number of CA++ activators. Perhaps the formation of ROS in cardiomyocytes in response to stretching is a permanent and mandatory component of physiological responses that can synchronize the release of CA++ from SR and modulate its magnitude. However, in pathological conditions, overproduction of ROS can trigger arrhythmogenic CA++ waves. Some changes of DNA molecules under the influence of ROS may also be helpful to consolidate as a result of natural selection. Reactive oxygen species (ROS) are often considered as selected in the course of evolution as means of combating a variety of infections, but in the course of phylogeny they also were selected as a means of intracellular and extracellular exchange of information.

The review presents the results of the authors' work of many years and the data of foreign studies, indicating the importance of free radical processes in etiology and pathogenesis of atherosclerosis. The justification of the idea that oxidative stress in atherosclerosis develops more often during disorders of carbohydrate metabolism, contributing to emergence of carbonyl stress in diabetes. It is hypothesized that there is a single molecular mechanism of primary pro-atherogenic injuries of vessel walls in atherosclerosis and diabetes, which enhances the formation of carbonyl-modified low-density lipoproteins, accumulating in the foam cells. The results of recent studies indicate that oxidatively modified LDL involved not only the primary injury to the vessel walls, but also provoked the development of endothelial dysfunction, so that once again raises the issue of the need for the use of antioxidants to prevent injuries in vascular walls. It can be assumed that the result of years of intensive research of free radical process mechanisms in atherosclerosis and diabetes will be the development of new drugs for the combined therapy of these diseases that can be disposed not only reactive oxygen species and organic free radicals and reactive carbonyls, which are clearly playing an important role in the development of pro-atherogenic injuries.

Based on own results, conception of mobile synbiotope microcenosis against pathogens as well as new antimicrobial strategies connected to conception are proposed. Synbiotope mobility is determined by the presence (in varying combinations] of cofunctioning antimicrobial ways which can be realized with participation of highly molecular mass metabolites of probiotic bacterial cultures. Thus, probiotic enzymatic systems (proteinases, EPS-depolymerases and/ or oxidoreductases] reveal cofunctioning with probiotic lectins. New antipathogen strategies use technological advantages of choice and selection of symbiotic strains and consortia producing synergistical enzyme-lectin-glycoconjugate systems against microfungal and Gram-positive pathogens. Additional strategies involve construction of synbiotic systems supporting probiotic compartment of biotope.

The concept of oxidative stress remains attractive to researchers combining the chemical nature of activated oxygen metabolites (AOM] and antioxidants, physical and biochemical mechanisms of action, including conditional simplicity of their versatility as redox regulators, with the original meaning of the word "stress" as Selye's general adaptation syndrome. Attempts to classify the oxidative stress on the basis of its intensity and dynamics were made. The main components and driving forces of oxidative stress are pro-oxidants and antioxidants in determining that there is also a mass of inconsistencies. The main components and driving forces of oxidative stress are pro-oxidants and antioxidants in determining that there is also a mass of inconsistencies. The article discusses the basic concepts of direct relevance to the concept of oxidative stress. Existing approaches in its analysis are analyzed and it is noted that oxidative stress per se cannot be "measured". Instead, using a variety of methods, one can assess: 1] the severity and/or the stationary concentration of various types of reactive oxygen species; 2] oxidative damage of biomolecules; 3] antioxidant content/ activity, - and to apply a particular combination of parameters in order to characterize the oxidative stress intensity. The main methods, recently used for the registration of oxidative stress components, are outlined.