A complex examination of 122 patients with bronchial asthma (BA) was done to find out the interrelationship between airway hyperresponsiveness to cold (isocapnic cold air hyperventilation - ICAH) and hyposmolar (ultrasonic nebulized distilled water - UNDW) stimuli, the disturbance of lung function, the character of inflammation in the respiratory tract and immune-metabolic status. All the patients were studied upon the lung function and airway response to cold and osmotic stimuli, the values of oxidative stress, cytokines spectrum (IL-4, IL-5, IL-6, IL-8, IFNγ) in the exhaled breath condensate (EBC) and the blood serum, the level of cortisol and adrenocorticotropic hormone. The functional state of β₂-adrenoreceptive complex of airways was studied by the level of 3ʹ5ʹ-cyclic adenosine monophosphate (cAMP) increase. To find phenotypic differences in the inflammation and immune-metabolic status features, all the patients were divided into 4 groups: the 1^st group (26%) was with airway hyperresponsiveness to both stimuli (cold and osmotic), the 2^nd group (15%) was with airway hyperresponsiveness only to UNDW, the 3^rd group (26%) only to ICAH, the 4^th group (33%) did not have any response to both triggers. Significant differences in the relationship of the respiratory function and main biochemical values were found. In the patients with the response to both stimuli maximal values of the base level of Н₂О₂ and IL-4 in EBC as well as the high level of IL-6 in the blood serum were revealed in comparison with other groups. These patients had a close correlation of TNFα in EBC and the airway response (DFEV₁) to ICAH (r=-0.76; р˂0.05), as well as of bronchi hyperresponsiveness and the contents of cAMP (r=0.70; р˂0.01) in the blood serum, which proved a more severe clinical course of the disease. In the patients of the second group FEV₁ correlated with IL4 contents in EBC (r=-0.48; р˂0.01), and DFEV₁ after UNDW depended on the contents of IL-4 (r=-0.42; р˂0.05) in the blood serum and IL-4/IFNg (r=-0.50; р˂0.05). In the patients of the 3^rd group eosinophilic-neutrophilic type of bronchi inflammation dominated. The initial level of Н₂О₂ production and secondary products oxidation index in EBC was connected with the response of FEV₁ to ICAH (r=-0.49, р˂0.01 and r=0.28, р˂0.05, respectively). The initial FEV₁ correlated with с IL-6 (r=-0.67; р˂0.001) and IL-5 (r=0.84; р˂0.05), and DFEV₁ after ICAH with the level of IFNg (r=-0.65; р˂0.001) in the blood serum. The allergic type of inflammation dominated in the 4^th group, the correlation of FEV₁, secretion of IL-4 in EBC (r=-0.66; р˂0.01) and the quantity of eosinophils in the blood (r=-0.23; р˂0.05) was found. We suggested there are different molecular subtypes of the inflammation reaction in the asthmatics with cold and osmotic airway hyperresponsiveness. They have potential clinical importance and open new possibilities in understanding the mechanisms responsible for the formation of bronchoobstructive syndrome and the prospects of its correction.

drop (r=0.60; p<0.05) to UNDW, as well as by high formation of lipid hydroperoxides in blood serum and further bronchi reaction to hyposmolar solution (r=-0.65; р<0.05). The data presented suggest that intensification of free-radical oxygenation is one of the most important mechanisms of worsening of airway bronchoconstrictor response to osmotic stimulus, which results in the loss of asthma control.

The purpose of the research was to study the influence of single-nucleotide polymorphisms rs1800470 of TGFВ1 gene and rs231775 of CTLA4 gene on the susceptibility to the development of bronchial asthma among the population of Krasnoyarsk. The group of patients with bronchial asthma were 100 people; two control groups, respectively, for each polymorphism - 282 and 338 people. Genome DNA was extracted from 10 ml of venous blood with phenol-chloroform extraction technique. Single nucleotide gene polymorphism was tested with the help of polymerase chain reaction in real time in accordance with the firm producer protocol (probes TaqMan, Applied Biosystems, USA) on the apparatus ABI 7900HT. While studying the polymorphism rs1800470 of gene TGFВ1 for a group of patients with non-allergic asthma the absence of rare homozygous GG was demonstrated. Development of non-allergic asthma significantly associated with genotype AA and AG, in comparison with both the control group (p=0.025) and a group of patients suffering from allergic forms of asthma (p=0.006). If there is evidence of genotypes, non-allergic asthma risk increases compared with the control group (ОR=1.631; 95% CI=1.37-1.94) and with a group of patients with allergic asthma (ОR = 1.128; 95% CI=1.08-3.17). When studying polymorphism rs231775 CTLA4 gene, increased frequency of genotype GG in the group of patients with allergic asthma, including women, was revealed. Taking into consideration the results obtained, it can be concluded that the presence of the genotype GG (ОR=2.036; 95% CI=1.16-3.58) causes an increased risk of allergic asthma in comparison with the control group.

The analysis of the causes of mucociliary clearance decrease in 140 patients with bronchial asthma was done. All the patients had clinical-functional examination, biopsy of bronchi mucosa with the study of morphological structure of mucous and functional activity of respiratory cilia, the study of viscoelastic properties of bronchi secretion and biochemical composition of glycosaminoglycans in the bronchial secretion. It was found out that the more severe the disease was, the more intensive morphofunctional changes, especially in the low parts of the bronchial tree, there were in the patients with bronchial asthma. Against the chronic inflammatory process the growth of the conjunctive tissue increases in bronchi mucosa, which leads to the decrease of the number of tiny blood vessels and to the formation of tissue liquid. In the mucosa epithelium there is the alteration of the epithelium layer: the number of beaker cells secreting the liquid secretion decreases. In bronchi lumen in the patients with severe bronchial asthma the number of chondroitin sulfate grows and the contents of hyaluronic acid and heparin decreases, which increases the viscosity of bronchial secretion. The rest ciliary cells lose cilia and die in 50% of cases. In the bronchial lumen the situation of low activity of secretion escalation into the outside is created.

In order to assess the state of lipid metabolism, blood plasma and erythrocyte membranes were studied in 25 patients with severe asthma during the exacerbation of the disease and after the treatment with zafirlukast. We established a unidirectional change in the ratio of essential fatty acids, phospholipids and the content of TBA-active end product of lipoperoxidation - malondialdehyde in blood plasma and erythrocyte membranes that were particularly pronounced during the exacerbation. A statistically significant decrease was found in the total amount of saturated compounds - pentadecanoic, palmitic, margaric and stearic, polyunsaturated ω-9, oleic and linoleic acids while the level of ω-6 arachidonic acid was increased. Changes in phospholipid spectrum included increase in the content of phosphatidylserine, phosphatidylinositol, and lysophosphatidylcholine and reduction in the amount of phosphatidylcholine and sphingomyelin. There was an intensification of lipid peroxidation in blood cells and tissues of the lung, which appeared as accumulation of TBA-reactive products (malondialdehyde) in the peripheral blood. Zafirlukast treatment did not lead to the effective elimination of lipid metabolism disorders, which was reflected in the development of oxidative stress maintaining chronic inflammation in the lungs.

The aim of this study was to assess the level of inflammatory markers, the state of respiratory function and the quality of life (QOL) for pathogenetic substantiation of hydrokinesitherapy (HKT) at the stage of long-term rehabilitation of children with bronchial asthma. 45 children with asthma of various severity were examined, their mean age was 9.5±3.4 years old. HKT included strengthening exercises and dynamic respiratory gymnastics, track and field and team sports elements, complex swimming, underwater breath-hold exercises. Active airway inflammation was evaluated by measurement of alpha-1-acid glycoprotein and nitric oxide in exhaled breath condensate. Peak expiratory flow rate at the beginning and the end of each lesson was measured. The spirography was done initially and after 12 months of HKT. QOL was assessed by A.West, D.French «Childhood asthma questionnaire». The frequency of attacks and the duration of exacerbations, the number of hospitalizations, drug doses, the incidence of acute respiratory diseases, treatment costs, visits to doctors, the number of ambulance calls were analyzed. The results showed that the effects of the annual program of HKT training reduce bronchial inflammation, improve the respiratory function, reduce the frequency, duration and severity of exacerbations which do not require emergency care, improve QOL, contribute to the prevention of intercurrent acute respiratory diseases, achieving disease control and improvement of children sports achievements. The highest efficiency of the method is observed in the combination with drugs. The results obtained substantiate the HKT pathogenetic significance in addressing medical and social problems of long-term rehabilitation of children with asthma.

Clinical and functional state of bronchopulmonary system in 24 patients with chronic idiopathic myelofibrosis was studied. Bronchoscopy with endobronchial laser Doppler flowmetry, biopsy of bronchi mucosa, complex ultrasound study of the heart and functional state of diaphragm were done to all patients. At idiopathic myelofibrosis the disorder of endobronchial microhemocirculation was diagnosed, important causes of which are anemic syndrome, thrombocytosis, endothelium dysfunction, and hyperleukocytosis for the development of blast crisis. A consequence of the observed changes in the microcirculation in idiopathic myelofibrosis is a disorder of tissue trophism, tissue hypoxia, local metabolic disorder, resulting in developing atrophic changes in bronchial mucosa. The decrease of diaphragm contractility in the patients with idiopathic myelofibrosis is conditioned by its compression by significantly enlarged lien and liver, and in the stage of blast crisis by specific leukemic damage (leukemic infiltration, atrophic changes, hemorrhage, leukostasis in vessels). Under progression of idiopathic myelofibrosis there are disorders of systolic and diastolic function of right and left ventricles. At the late stages of neoplastic progression of idiopathic myelofibrosis hypoxemia and pulmonary hypertension develop.

Ultrasound indicators of fetoplacental system in the III trimester of gestation in 109 mothers with the latent course and reactivation of chronic cytomegalovirus infection (CMVI) at antenatal, intranatal and postnatal death of their children were studied. The group of comparison consisted of 25 women and their echographic parameters of fetoplacental complex at the same stages of pregnancy, whose children died in intra- an postnatal periods of development after birth trauma. The control figures were the data obtained from ultrasound scans of uterine, placenta, umbilical cord and fetus at 30-36^th weeks of gestation in 32 mothers with physiologic course of pregnancy and the birth of health children. It was found out at CMVI reactivation (IgM antibodies to CMVI are 1:200-1:400, IgG antibodies titer to CMV is 1:400-1:800 and avidity index of IgG to CMV is 56-70%) against latent herpes virus infection in comparison with latent course of CMVI (the absence of IgM antibodies to CMV, the antibody titer of IgG to CMV is 1:400-1:800, avidity index of IgG to CMV is 68-75%), the thickening (in 9, р<0.05) and thinning of placenta (in 12, р<0.05), calcificates (у 10, p<0.05), low placentation (in 11, р<0.05), miscarriage (in 10, р<0.05), low optimal conditions of blood flow of provisory organ and increasing its conductance for antigens and antibodies are diagnosed most often. This induces the delay of intrauterine growth of the fetus (in 10, p<0.05), the development of hepatomegalia (in 8, р<0.05) and ventriculomegalia (in 9, p<0.05). Mothers with chronic CMVI reactivation (IgM antibodies to CMV are 1:200-1:400, IgG antibodies to CMV are 1: 400-1:1600 and avidity index of IgG to CMV is 56-70%) in comparison with the same active virus infection in the III trimester of gestation (antibodies of IGM to CMV in the titer are 1:200-1:400, IgG antibodies to CMV are 1: 400-1:800 and avidity index of IgG to CMV is 56-70%) oftener had the thinning of placenta, the enlargement of its venous vessels and umbilical cord hydrops, which leads to antenatal death of the fetus (in 8, р<0.05) caused by penetration of virus infection agents through the damaged hematoplacental barrier.

group had the signs of hyperexcitability and physical disorders much longer and echographic markers of brain immaturity (in 32.0 and 3.7%, р<0.05) were registered oftener at the absence of any changes of the vessel resistance in the middle cerebral artery. At the same time the dead infants of this group morphologically were found to have the parts of the increase of collagenisation of soft brain tunic blood vessels, alternative neuron changes, glial cellular elements and ependymocytes of lateral ventricles of cerebrum, more intensive perivascular edema, full-blown vascular congestion and vascular plexus as well as tiny hemorrhages, which is explained by significant neurotoxic and angiotoxic influence of some viruses and products of their metabolism.

trimester and persists until the end of gestation, and the fact that throughout the pregnancy there is a low activity of antioxidant protection is quite negative.

Prolonged exposure of ultraviolet radiation on the human organism induces the development of critical condition accompanied by exhaustion of energy and other reserves, reduction of tissue metabolism. Stage development of consequences of ultraviolet radiation leads to hypoxia. It is known that in the base of any kind of hypoxia there is insufficiency of the main energy forming system of mitochondrial oxidative phosphorylation conditioned by considerable decrease of oxygen delivery to the tissues or inhibition of oxidative enzymes. At present in the clinical practice compounds of succinic acid having antioxidant and cytoprotective properties are used as pharmacological active substances with a wide range of biological activity. In experimental conditions the possibility to correct free radical lipid oxidation of rats’ organism membranes was studied with the introduction of the succinate containing drugs called Remaxol^® and Cytoflavin^® (Polysan, St. Petersburg). The animals were divided into 4 groups and each of them had 15 rats: intact animals which were held in standard conditions of vivarium; the control group in which rats were exposed to ultraviolet radiation during three minutes daily; the experimental group in which before ultraviolet radiation animals had a daily intake of the Remaxol in a dose of 50 mg/kg; the experimental group in which before ultraviolet radiation animals had a daily intake of the Cytoflavin in a dose of 50 mg/kg. It was found out that in the blood of experimental animals a daily ultraviolet radiation during three minutes contributes to the increase of lipid hydroperoxides level (by 26-48%), of diene conjugate (by 29-53%), and of malonic dialdehyde (by 40-62%) against the decrease of antioxidant system activity in the blood of intact animals. The introduction of the succinate containing drugs to rats in the conditions of ultraviolet radiation contributes to the reliable decrease in the blood of lipid hydroperoxides by 11-19%, of diene conjugates - by 14-20%, malonic dialdehyde - by 17-29% in comparison with the rats of the control group. While analyzing the effect of the succinate containing drugs on the activity of the components of antioxidant system it was shown that the level of ceruloplasmin in the blood of animals was reliably higher by 9-17%, of vitamin E by 11-26%, of catalase by 28-52% in comparison with the same parameters of the rats of the control group. So, the application of the succinate containing drugs called Remaxol and Cytoflavin in the conditions of ultraviolet radiation of the organism of animals under experiment leads to the stabilization of the processes of peroxidation against the increase of antioxidant system activity.

Studies have been conducted about the induction of lipid peroxidation (free-radical) of rats liver microsomes by non-enzymatic (ascorbate-dependent) and enzymatic (NADP·H-dependent) mechanisms with acetylcholine in the incubation medium. The obtained data indicate that the presence of acetylcholine in the incubation medium reduces the ability of microsomal lipid oxidation. After the heat treatment of liver microsomes, the presence of acetylcholine in the incubation medium also reduces the ability of the microsomal lipid oxidation induced by enzymatic (NADP·H-dependent) mechanism. The decrease of protein activity of endoplasmatic reticulum of hepatocytes by the heat treatment of liver microsomes dramatically reduces the ability of lipid oxidation by enzymatic (NADP·H-dependent) mechanisms.

Determination of pharmacokinetics of actively metabolized drugs is a key problem of assessing their bioavailability. Taking trimebutine as an example, possible solutions to this problem are presented in the work. In the experiment in vitro at the original model solution metabolic liver homogenate was determined by the concentration of the active metabolite of trimebutine concentration as the difference in the solution before and after incubation. By using the technology of detecting LS-MS mass-spectrum basic ion trimebutine (388 m/z) and mass-spectrum of the main metabolite of trimebutine ion (370.3 m/z) were identified. The calibration dependence (correlation coefficient 0.988), which was used to determine the main metabolite of trimebutine, was created on its ion mass-spectrum with 370.3 m/z. There was described a new method for the quantitative determination of the major metabolite of trimebutine - N-monodesmethyl trimebutine using liquid chromatography-mass spectrometry, which allowed to assess adequately on rabbits the pharmacokinetics of various forms of the medication in the experiment.

The aim of the study was to evaluate of up-to-date opportunities to diagnose intrauterine and perinatal infections in premature children. Seventy-eight premature low-weight newborns, including those with low and extremely low birth weight, and their mothers were examined. Methods used: molecular diagnostics (PCR) to identify genetic material of perinatally significant bacterial and viral agents, and serological assay (ELISA) to identify serological markers of active stages of Herpes virus (Herpes simplex virus, Cytomegalovirus) and Chlamydial infections. A group of mothers of low-weight children was found to consist mainly of women with compromised obstetric history and signs of placental insufficiency probably due to intrauterine infections. PCR investigation of placental tissue specimens revealed nucleic acids of bacterial and viral agents in 73.5% of women. Morphological examination of infected placentas revealed inflammatory changes (placentites, choriodeciduites, villusites) in 100% of cases, and different abnormalities (improperly attached cord, disorders of implantation and placentation) in 46.1% of cases. Upon examination of clinical specimens of newborns, markers of perinatally significant infections were diagnosed in 41.0% of cases. Most frequently found were Cytomegalovirus (14.1%) and Ureaplasma spp. (17.9%). Upon serological examination, no markers of active stages of the given infections were found. To increase efficiency of diagnostics of intrauterine infections in a newborn, it is important to take the maximum possible number of tests of body fluids by PCR method. Intrauterine infection is diagnosed using the entire set of clinical, laboratory and morphological data with account for the time of examination (optimal time: first days of life).

The aim of the study was to determine qualitative and quantitative composition of genital tract microbiosis in pregnant women with preterm rupture of membranes. Cervical smears of 28 pregnant women admitted to the Perinatal Center at 26-34 weeks of gestation for preterm rupture of membranes were studied. A control group consisted of 11 women with normally progressing pregnancy at 20-25 weeks of gestation. Genital smears were studied using a real-time polymerase chain reaction. «Femoflor-16» reagents and detecting amplifier DT-96 (RNA-Technology, Russia) were employed. Decrease in the level of Lactobacillus spp. and bacterial dysbalance in pregnant women with preterm rupture of membranes was identified in 64.3% of cases. At the same time, the decrease in lactobacillus level in normally progressing pregnancies was only found in 9.1% of cases (p<0.002), the majority of cases presenting with normocytosis. The structure of dysbiosis in pregnant women with preterm rupture of membranes was represented by anaerobes (50.0%) with involvement of Gardnerella vaginalis (17.8%), fungi of Candida spp. (10.7%), Ureaplasma ( urealyticum+parvum - 17.8%), and Atopobium vaginae (7.1%). Aerobic dysbiosis was only identified in two women (7.1%) with involvement of Streptococcus spp. and fungi of Candida spp. , mixed dysbiosis was found in 2 (7.1%) cases. High dysbiosis rate identified in women of the basic group confirms the significance of bacterial vaginosis in the genesis of preterm delivery, indicates the need for detection of dysbiosis during preconception preparation with subsequent recovery of normal microflora and selective decontamination of aerobes and fungi.

The results of the study of the snow cover in a zone of influence of an industrial hub of the city of Angarsk by methods of laser granulometry and mass spectrometry of high definition with inductively connected plasma during the winter season of 2013-2014 are given. The samples were taken in 11 points remote from the city-forming enterprises on the distance to 80 km. The distribution of Al, Cr, Mn, Fe, Ni, Cu, Zn, As, Cd, Ba, Pb and microdimensional particles was revealed. It was shown that in 4 points from 11 investigated, microparticles of the suspensions having small average arithmetic diameter (from 11.54 - 41.79 microns) with a big area of specific surface (to 15783.76 cm²/cm³) and representing potential health hazard for the person were found. It is shown that in 8 of 11 points the increased content of heavy metals (Cr, Mn, Fe, Ni, Cu, Zn, Ba) was revealed.

The role of gold in the history of mankind, some of its properties, the content in the soil, water and living organisms, the possible significance for the organism have been shown. The use of metal and colloidal gold as drugs for the treatment of various diseases, storing of metal in bodies, complications and contraindications to gold prescription were analyzed. The influence of gold nanoparticles on the internal organs (edema, hemodynamic abnormalities, malnutrition, changing of the cells of mesenteric lymph nodes, etc.) of experimental animals was studied, the development of plasmolysis, the destruction of the cell wall, cytoplasm structures contrasting and inlay of conidia in fungi was shown. All these data indicate the toxicity of gold, which does not allow the use of its drugs in clinical practice.

The prevalence, sources of infection, clinical features, treatment and prevention of trichinosis in the Far East are discussed in this work. The results of personal studies of efficiency of some medications for trichinosis treatment are shown, the increase of anty-trichinella activity of benzimidazole carbomate (parbendazol, fenbendazol, mebendazol) and the weakening of their toxic effect on the body of the laboratory animals with protein anabolices (pyrimidine derivatives), namely methyluracil and pentoxyl, were found out first time. The scheme of treatment of the acute stage of trichinosis has been offered. In general the situation with trichinosis in the Far East is quite difficult and to resolve this problem further epidemiologic, clinic and experimental studies should be done.

The lecture presents the general concept and characteristics of local immunity, T- and B- cellular principles of mucosal immunity operation leveled on pharyngeal tonsil and upper airway. It also reviews the structure of secretory immunoglobulin A, highlights the main systems involved in the synthesis of secretory immunoglobulin A, and presents cellular and cytokine immunoregulatory control of mucosal immunity. The lecture represents the mechanisms of antiviral and antimicrobial activities on the surface of mucosal upper airway, which helps to understand the importance of the barrier function of mucous membrane and gives an opportunity to assess local resistance of respiratory system to infectious diseases in order to specify diagnose and treatment.