CATALASE CRS-262T GENE POLYMORPHISM AND CHANGES IN VENTILATION LUNG CAPACITY IN CHILDREN-RESIDENTS OF RADIOACTIVELY CONTAMINATED TERRITORIES. / POLIMORFIZM SRS-262T GENA KATALAZY I ZMINY VENTYLIaTsIINOÏ SPROMOZhNOSTI LEGENIV U DITEI - MEShKANTsIV RADIOAKTYVNO ZABRUDNENYKh TERYTORII.

OBJECTIVE: to determine the association of catalase С-262Т gene polymorphism with the presence of bronchial hyper-reactivity in children living in radioactively contaminated territories. MATERIALS AND METHODS: There were examined school-age children-residents of radioactively contaminated territories (RCT), who did not have clinical signs of respiratory pathology. Catalase (CAT) С-262Т gene deletion polymorphism was studied in the molecular genetic laboratory of the State Institution «Reference Center for Molecular Diagnostic of Public Health Ministry of Ukraine¼. Determination of the polymorphic variant by the catalase С-262Т gene was performed by Polymerase Chain Reaction (PCR) using specific oligonucleotide primers, followed by Restriction Fragment Length Polymorphism (RFLP) analysis. The CAT С-262Т gene polymorphism in children living in RCT was compared with that in the reference group of practically healthy individuals. Ventilation lung capacity was performed by computer spirometry according to the analysis of the loop «the flow-volume¼. A pharmacological inhalation test with a bronchodilator that acts on ß2-adrenergic receptors of the lungs was used to detect early changes in the ventilatory capacity of the lungs - bronchial hyperreactivity. RESULTS: Comparative analysis showed that in the presence of bronchial hyperreactivity in children living in RCT, the CT genotype was more common than in children without bronchial hyperreactivity, and the frequency of the CC genotype was correspondingly reduced. There was a trend towards a decrease in the frequency of the TT genotype. An analysis of the frequency distribution of allelic variants of the CAT С-262Т gene polymorphism in children living in the RCT revealed a tendency to increase in the frequency of the T-allele and according to the decrease in the frequency of C-allele in the presence of bronchial hyperreactivity.Сonclusions. Thus, among children living in RCT, CT-homozygotes of CAT С-262Т gene polymorphism had bronchial hyperreactivity probably more often than CC-heterozygotes. In the presence of bronchial hyperreactivity, there was a trend towards an increase in the frequency of the T-allele and, accordingly, a decrease in the frequency of the C-allele.

ROLE OF GENETIC PREDISPOSITION, GENE POLYMORPHISM OF GLUTATHIONE-S-TRANSFERASE (GSTT1, GSTM1, GSTP1) AND SOME ADVERSE FACTORS IN DEVELOPMENT OF BRONCHIAL ASTHMA IN CHILDREN - RESIDENTS OF RADIOACTIVELY CONTAMINATED AREAS. / ROL' SPADKOVOÏ SKhYL'NOSTI, POLIMORFIZMU GENIV GLUTATION/S/TRANSFERAZ (GSTT1, GSTM1, GSTP1) TA DEIaKYKh NESPRYIaTLYVYKh ChYNNYKIV U ROZVYTKU BRONKhIAL'NOÏ ASTMY U DITEI ­ MEShKANTsIV RADIOAKTYVNO ZABRUDNENYKh TERYTORII.

OBJECTIVE: to determine the influence of hereditary predisposition, polymorphism of GSTT1, GSTM1, GSTP1 genes andenvironmental factors on the development of bronchial asthma in children - residents of radioactively contaminat-ed areas. MATERIALS AND METHODS: School-age children-residents of radioactively contaminated areas with bronchial asthma,and those without clinical signs of respiratory pathology were examined. Genetic, medical, biological and social riskfactors were determined based on the study of anamnestic data and medical records. Ventilation lung capacity wasassessed by the method of computer spirometry. Molecular genetic studies were carried out using polymerase chainreaction (PCR) and restriction fragment length polymorphism (RFLP) for further analysis. RESULTS: Molecular genetic studies of the distribution of genotypes and frequencies of polymorphic variants of thegenes GSTT1, GSTM1, GSTP1 were performed in children living under long-term intake of 137Cs by food chains. It wasfound that in children with BA the tendency to frequency of the deletion variant of the GSTT1 and GSTM1 genes incomparison with children without bronchial and pulmonary pathology was increased. The study of distributing theGSTP1 A313G gene polymorphic variants revealed in children with BA a significant increase in the frequency of AG-genotype, compared with the data of reference group. Adverse factors that increase the risk of developing bron-choobstructive disorders and the probability of their implementation in the form of bronchial asthma in children -residents of RCA have been identified. It is established that among them the leading role is played by hereditarypredisposition to this disease. On the part of the child, such negative factors were unfavorable conditions of fetaldevelopment, the presence of signs of exudative-catarrhal diathesis, manifestations of allergies and frequent respi-ratory diseases from the first months of life. It was found that the risk of developing BA was significantly increasedin children with the GSTT1 and GSTM1 gene deletion genotypes; an increased risk of developing BA in children witha combination of the GSTP1 A313G gene polymorphism with deletion polymorphism of the GSTT1 or GSTM1 gene wasdetermined. Сonclusion. Оne of the leading mechanisms, due to which there is a realization of hereditary predisposition tobronchial asthma in children living under constant intake of radionuclides with a long half-life, is the polymorphismof certain glutathione-S-transferase genes, namely, GSTT1, GSTM1 and A313G gene deletion polymorphism and GSTP1gene polymorphism.

MOLECULAR GENETIC ASPECTS OF BRONCHIAL HYPERREACTIVITY IN CHILDREN - RESIDENTS OF RADIOACTIVELY CONTAMINATED AREAS. / MOLEKULIaRNO-GENETYChNI ASPEKTY BRONKhIAL'NOÏ GIPERREAKTYVNOSTI U DITEI-MEShKANTsIV RADIOAKTYVNO ZABRUDNENYKh TERYTORII.

OBJECTIVE: to determine the relationship between polymorphisms of glutathione S-transferase gene family andbronchial hyperreactivity in children living in radioactively contaminated areas. MATERIALS AND METHODS: School age children-residents of radioactively contaminated areas (RCA), without clinicalsigns of respiratory pathology were examined. Molecular genetic studies were carried out by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) for further analysis. The GSTT1, GSTM1 gene deletion polymorphism was investigated using multiplex PCR. PCR and PCR-RFLP analyses were performed in the studyof the GSTP1 gene A313G polymorphism. The ventilation lung capacity was examined by the pneumotachographicmethod according to the analysis of «the flow-volume¼ loop. The pharmacologic inhalation test with bronchodilator drug, affecting the ß2-adrenergic lung receptors was used to detect the early changes in the ventilation lungcapacity - the bronchial hyperreactivity (latent and nonlatent bronchospasm). RESULTS: Molecular genetic studies showed that the GSTM1 gene deletion genotype and the GSTP1 gene A313G polymorphism were found significantly more often in the subgroup of children with bronchial hyperreactivity living inRCA than in children without bronchial hyperreactivity and children of the control group. The frequency of GSTT1deletion polymorphism did not have a statistically significant difference in all subgroups. CONCLUSIONS: The GSTM1 gene deletion polymorphism and the GSTP1 gene A313G genotype may be a risk factor fordeveloping bronchial hyperreactivity in children living under adverse environmental conditions, including radioactively contaminated areas.

Experience of correcting endothelial dysfunction in children-residents of radioactively contaminated areas by nitric oxide potential donator citrulline. / DOSVID KOREKTsIÏ ENDOTELIAL'NOÏ DYSFUNKTsIÏ U DITEY̆, MEShKANTsIV RADIOAKTYVNO ZABRUDNENYKh TERYTORIY̆, ZA DOPOMOGOIu POTENTsIY̆NOGO DONATORA OKSYDU AZOTU ­ TsYTRULINU.

OBJECTIVE: to determine the effectiveness of citrulline use for correcting endothelial dysfunction in children resi dents of radioactively contaminated areas. MATERIALS AND METHODS: A group of children residents of radioactively contaminated areas with the presence of clinical and paraclinical signs of endothelial dysfunction was selected to assess the effectiveness of correcting endothelial dysfunction by the usage of NO potential donator - citrulline according to the data of selective screen ing. There were determined the biochemical parameters of the content of NO stable metabolites, L arginine, lipid peroxidation, antioxidant enzymes in the blood serum; the indices of cellular and humoral immunity; the instrumen tal indices of vascular endothelium dependent reaction on occlusion test, the lung ventilation capacity, the bioelec tric activity of the myocardium, the autonomic regulation of the cardiovascular system.Examined children were received a course of citrulline malate. RESULTS AND CONCLUSIONS: An increased content of serum L arginine, nitrite, and amounts of NO metabolites was established in children with endothelial dysfunction who were received a course of citrulline malate. Bronchospasm elimination was noted in the significant part of examined patients after the drug use. Decreased recovery period and increased period of hypercompensation for thermographic circulation index in the test with post occlusion reac tive hyperemia were detected by an evaluation of indicators for vascular endothelium dependent vasodilatation using thermographic method indicating an increased endothelial vasomotor capacity. There was tendency to improve the processes of autonomic regulation of the heart rhythm and repolarization of the heart muscle. The antioxidant effect of used citrulline malate course was determined as: decreased content of serum LPO end products that react with thiobarbituric acid under elevated activity of antioxidant - catalase. An increase in the percentage of T lymphocyte, normalization of their subpopulation composition was noted in dynamics of citrulline malate application.

Efficiency of endothelial dysfunctioncorrection in children residents of radioactively contaminated areas using the method of intermittent normobaric hypoxi therapy. / EFEKTYVNIST' KOREKTsIÏ ENDOTELIAL'NOÏ DYSFUNKTsIÏ U DITEY̆ MEShKANTsIV RADIOAKTYVNO ZABRUDNENYKh TERYTORIY̆ ZA DOPOMOGOIu METODU PERERYVChASTOÏ NORMOBARYChNOÏ GIPOKSYTERAPIÏ.

Objective is to evaluate the effectiveness of intermittent normobaric hypoxi therapy as the means that can posi tively influence on the different links in the pathogenesis of endothelial dysfunction in children residents of radioactively contaminated areas. MATERIALS AND METHODS: Disorders of personal and emotional sphere, symptoms of asthenic vegetative and neurot ic character, the signs of the cardiovascular and respiratory systems, abdominal and dyspeptic syndromes are attrib uted to the clinical signs of endothelial dysfunction. There were determined the biochemical parameters of the con tent of stable metabolites of NO, L arginine, lipid peroxidation, antioxidant enzymes in the blood serum; the indices of cellular and humoral immunity; the instrumental indices of vascular endothelium dependent reaction to occlu sion test, ventilating ability of the lungs, the bioelectric activity of the myocardium. Intermittent normobaric hypoxi therapy (INHT) was performed using the individual device of mountain air of the «Borei¼ type produced by State Research Medical Engineering Center «NORT¼ NAS of Ukraine (Kyiv). RESULTS AND CONCLUSIONS: The clinical examination showed that the administration of additional intermittent nor mobaric hypoxi therapy to the basic treatment of 44 children with endothelial dysfunction who live in the radioac tively contaminated areas, promoted to reduce the frequency of complaints and intensity of clinical manifestations in the mentioned symptom complex. An increase of serum L arginine in the absence of significant changes in the content of NO stable metabolites was revealed in the most examined children residents of radioactively contami nated areas by studying NO system after using the course of intermittent normobaric hypoxi therapy. Positive changes in vascular endothelium dependent reaction to occlusion test, indicating the reduction length of the recovery period for thermographic circulation index after occlusive test, were determined. The decrease in the inten sity of lipid peroxidation processes - a reduction of serum LPO end products content that react with thiobarbituric acid - was observed. The bronchospasm elimination was revealed in a large number of children with the study of the lung ventilation capacity. There were trends to reduce the imbalance of different chain of the heart rhythm man agement. The immunomodulatory effect was detected as: the increase in the functional activity of neutrophils, the normalization of humoral immunity link indices. Intermittent normobaric hypoxi therapy is an effective tool that can positively affect the condition of nitric oxide system and endothelium dependent functions of the organs and systems in children residents of radioactively contaminated areas.

Influence of eNOS gene 4a/b VNTR polymorphism on development of endothelial dysfunction and respiratory system disorders in children - residents of radioactively contaminated areas. / VPLYV VNTR (4a/b) POLIMORFIZMU GENA eNOS NA ROZVYTOK ENDOTELIAL'NOI DYSFUNKTsII TA PORUShEN' SYSTEMY DYKhANNIa U DITEY - MEShKANTsIV RADIOAKTYVNO ZABRUDNENYKh TERYTORIY.

UNLABELLED: Objective is to study the role of еNOS gene polymorphism in the development of endothelial dysfunction and func tional disorders of the respiratory system in children - residents of radioactively contaminated areas. MATERIALS AND METHODS: Total of 184 children were examined to determine the possible associative links between еNOS gene intron 4m polymorphism and indices characterizing the functional state of the endothelium and the bronchopulmonary system. Of them the main group of children consisted of 135 children residents of radioactively contaminated areas, the control group - of 49 healthy children who lived in "clean" regions by the radioactive con tamination and were not belonging to victims of the Chernobyl accident contingents. The molecular genetic study determining the еNOS gene intron 4 polymorphism was performed. An examination of lung ventilation capacity was evaluated using the pneumotachography method. The thermographic method was used for registering the endothe lium dependent reaction of the vascular bed to changes in blood supply conditions. The levels of nitrogen com pounds (NO2 and NO3 ) were determined by the standard method using Hriss reagent. The level of body incorporat ed 137Cs was determined using human radiation counter Skrynner 3M (Institute of Human Ecology). RESULTS: Children of the main group did not differ from that of control and literature data by the frequency of geno types 4a/b and еNOS gene allele polymorphism. An increase in the duration of circulation restoration up to the ini tial level after occlusion test was noted in children of the main group with genotype 4a/4b comparing to children with genotype 4b/4b; a decrease in the nitrite content was observed in blood serum. The integral indices of elastic ity and tensility of the lung tissue, respiratory permeability were decreased; the signs of bronchospasm were record ed 1.5 times more often. These adverse effects were associated with the presence of genotype allele 4a, the signs of endothelial dysfunction and the level of the incorporated 137Cs. CONCLUSIONS: More pronounced changes in vascular endothelial reaction to occlusion and the significant decrease of serum nitrite level in allele 4a carriers, especially in children who live in adverse ecological conditions, give the right to include them into the risk group for the development of endothelial dysfunction, and to conside pulmonary dysfunction as one of its manifestations.

Changes in stable metabolites of nitric oxide in children-residents of radioactively contaminated territories. / Zminy stabil''nyh metabolitiv oksydu azotu u ditejmeshkanciv radioaktyvno zabrudnenyh terytorij.

Objective. An evaluation of the changes in nitric oxide system by the level of its stable metabolites in the blood serum and their comparison with content of 137Сs in the body of children-residents of radioactively contaminated territories. Materials and methods. The children of school age, the residents of radioactively contaminated territories were examined. The levels of nitrogen compounds (NO2- and NO3-) were determined by the standard method using Grissreagent. 137Сs content was determined in the children body by whole-radioactive body counter. Results. Studies of nitric oxide metabolite content in the blood serum revealed the decrease in nitrite level under an absence of the significant changes in nitrate content and sum of NO metabolites in the children-residents of radioactively contaminated territories. An increase in 137Cs content in the body was accompanied by a decrease of nitrite level in the blood serum of a significant part of children.

[Evaluation of systemic involving of the connective tissue in children with different localisation of isolated abnormal chords of the left ventricle (ACLV)].

Evaluation of the systemic involving of the connective tissue (SICT) under the new Ghent nosology (2010) showed that in children with isolated ACLV born to parents exposed to the Chernobyl disaster, its expression is associated with their location and quantity. The degree of systemic involvement of connective tissue is confirmed by the results of the analysis of features echostructure of isolated ACLV (the presence of thickening and calcification), echomorphometry, assessment of systolic (hypokinetic organization of the central hemodynamics), and the relaxation functions of the heart (initiation of diastolic dysfunction). High level of SICT (score greater than 5) indicates systemic damage to the body and particularly the heart, which requires dynamic monitoring and preventive measures. Found that the diagnostic and monitoring of children with isolated ACLV may be based on registration of systemic involvement of connective tissue with the calculation of points under the new Ghent nosology of 2010.

[Endothelium dependent vascular reactivity and autonomic homeostasis in children living in radiation-contaminated areas].

In order to study the mechanisms of development of pathological changes in children living in contaminated areas and chronically exposed to radionuclides as a result of exposure through the food chain, studied the vegetative homeostasis and thermographic study endothelium-dependent vascular reactions with occlusive tests. Showed signs of dysregulation of the autonomic nervous system dysfunction, the secretory activity of the endothelium and increased secretion of substances endothelial origin.

[Autonomic homeostasis of children born to parents irradiated in the result of the Chernobyl catastrophe with isolated abnormal chords of the left ventricle].

156 children of the main group (were born to parents irradiated in the result of Chernobyl disaster), in which according to Doppler echocardiography isolated abnormal chords of the left ventricle (AHLV) identified, 44 children of control group and 50 children of referent group were involved in the study Analysis of indicators of operational regulation of heart rate in children of primary group indicate the existence of autonomic dysregulation, which has the maximum expression in children with a threshold number of isolated abnormal chords. Evidence of autonomic dysregulation in children born to parents irradiated in the result of the Chernobyl disaster with isolated AHLV requires primary and secondary prevention to reduce the frequency of unfavourable clinical course.

[Evaluation of immunity parameters and free radical processes in children-residents of radioactive contaminated territories born to parents irradiated in childhood].

The children--residents of contaminated territories, born from mothers irradiated in their childhood had in remote period of the Chernobyl Disaster an increase in the frequency of disorders connected with immune system activation and depressive types, increase in intensity of free radical processes in blood serum and erythrocytes.

[Analysis of structural and functional indices of the children hearts with isolated abnormal chords of the left ventricle and who were born to parents irradiated during the Chernobyl accident].

156 children of the main group, born to parents irradiated in the result of Chernobyl disaster have been involved in the study. These children were identified with isolated abnormal chords of the left ventricle (AHLV) according the results of Doppler echocardiography. 39 practically healthy children and 24 children of the nosology control group have also been observed. Threshold quantity of AHLV were determined in 33 children, main group, (subgroup Ia), sub-threshold--in 123 children (subgroup I(B)). The children of the control group with threshold quantity of AHLV were found with decreased adaptation capacity of the cardio-vascular system through shifts in dynamics and energetics of the heart contraction. Reduction in systolic output, systolic and heart indices justify hypokinetic type of organization of central hemodynamics, which can be considered an early sign of tension of functional capabilities of the heart and blood vessels. This subgroup of children was found to have changes of transmitral blood flow indicating the initiation of the heart's diastolic dysfunction. Almost 1/3 of children with subthreshold number of AHLV were also revealed to have signs of initiation of the heart's diastolic dysfunction.

[Bioelectrical activity of the myocardium in children born to parents irradiated during the Chernobyl disaster with isolated abnormal chords of the left ventricle].

A total 156 children of the main group (children born to parents irradiated during the Chernobyl disaster), who according to echocardiography revealed a different number of isolated abnormal chords of the left ventricle, 20 healthy children, 24 children of nosological control group and 50 children of referent group have been observed. It was found that isolated AHLV in children born to irradiated parents, was associated with changes in standard ECG, reflecting the presence of arrhythmias or predictors of their development. No significant differences in subgroups of children with different number of isolated AHLV have been established. Children with isolated AHLV born to parents irradiated during the Chernobyl accident, as all patients with minor structural anomalies of the heart, should be refered to a risk group in connection with the possibility of the development, in the first place, ventricular extrasystoles, paroxysmal ventricular tachycardia. Early diagnosis of isolated AHLV will allow to assess the outlook for further course of the disease and develop a plan of treatment and preventive measures.