DRIVERS OF HYPERFERREMIA IN CHILDREN LIVING ON RADIOLOGICALLY CONTAMINATED TERRITORIES AFTER THE CHNPP ACCIDENT IN UKRAINE. / ЧИННИКИ, ЯКІ ВПЛИВАЮТЬ НА МЕХАНІЗМИ ФОРМУВАННЯ ПІДВИЩЕНОЇ ЩІЛЬНОСТІ КІСТКОВОЇ ТКАНИНИ У ДІТЕЙ, ЖИТЕЛІВ РАДІОАКТИВНО ЗАБРУДНЕНИХ ТЕРИТОРІЙ, ПІСЛЯ АВАРІЇ НА ЧАЕС.

OBJECTIVE: assessment of clinical-hematological and metabolic-biochemical parameters of the of bone tissue and hormonal regulation depending on the serum iron content and radiation dose values in children living on radiologically contaminated territories after the ChNPP accident in Ukraine. MATERIALS AND METHODS: Children (n = 271) living on radiologically contaminated territories (RCT) of Ukraine were involved in the study. Three study groups were formed according to the serum iron level (SIL), namely group I with SIL 10.0-22.0 µmol/l (n = 92), group II with SIL 23.0-34.0 µmol/l (n = 144), and group III with SIL above 35.0 µmol/l (n = 35). Diseases in the family tree, bodyweight at birth, complaints on osalgia, bone fractures, jaw anomalies, dental caries, and obesity were accounted. Morphometric parameters of erythrocytes and hemogram elements were analyzed. Creatinine, alkaline phosphatase, calcium, total protein, iron, cholesterol, bilirubin, and transaminases were assayed in blood serum. The urine content of the 19 free amino acids, serum content of the free thyroxine (FT4), pituitary thyroid-stimulating hormone (TSH), and cortisol were assayed both with bone tissue density. Individual radiation doses were calculated. RESULTS: In 12.9 % of cases the SIL was > 35.0 µmol/l. Relatives with endocrine diseases were often present in the family tree of children with SIL > 23.0 µmol/l. There were increased urine content of the free amino acids (p < 0.05) and signs of protein degradation under high SIL. Contents of amino acids involved in collagen synthesis and antioxidant status (alanine, serine, glutamine, aspartic acid) and iron metabolism (arginine, leucine) were assayed at the highest levels (p < 0.05). Urinary levels of valine, lysine, and methionine, which are associated with iron metabolism, were decreased (p < 0.05). An inverse correlation (rs = -0.58; p < 0.01) was established between the serum TSH and cortisol levels regardless of the SIL. Serum TSH level directly correlated with urine content of amino acids involved in collagen synthesis. An inverse correlation (rs = -0.55; p < 0.001) was established between the serum TSH level and urine content of tyrosine that is essential for the thyroid hormone (triiodothyronine and thyroxine) synthesis.Cortisol was found having a negative effect on protein synthesis. Inverse correlation was established between the serum cortisol level and urine content of the free amino acids essential for collagen synthesis. There was no dependence of the average radiation dose values on the SIL. An inverse correlation was determined between the patient's radiation dose and SIL > 35.0 µmol/l (rs = -0.29; p < 0.05). CONCLUSIONS: The increased SIL in children living on RCT may occur due to both a genetic predisposition and the acquired factors driving protein and mineral metabolism of bone and their hormonal regulation.

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.

Balance of autonomic nervous system in children having signs of endothelial dysfunction, that were born and are domiciled in contaminated territories. / Vegetatyvnyj gomeostaz u ditej z oznakamy endotelial''noi' dysfunkcii', jaki narodylysja ta postijno prozhyvajut'' na radioaktyvno zabrudnenyh terytorijah.

UNLABELLED: Objective. The study examined the features of functional state of the autonomic nervous system in children having endothelial dysfunction and permanently residing in contaminated areas. Materials and methods. Clinical and instrumental examination of 101 children aged 7-18 years that were born and are domiciled in contaminated territories, including 37 persons with signs of endothelial dysfunction (subgroup IA) and 64 ones with no signs of endothelial dysfunction (IB subgroup) was conducted. The control group being comparable to the subgroups IA and IB by age, gender and clinical examination results included 37 children neither been domiciled in contaminated areas nor were belonging to the contingent of Chornobyl accident survivors. There were 20 apparently healthy children also examined. Results. Due to peculiarities of physiological pathways providing adaptive responses the children having signs of endothelial dysfunction are characterized by a more pronounced dysregulation of autonomous nervous system both in a resting state and under a functional load simulation, and also by a high strain of adaptation pathways. The lack of autonomous support of cardiovascular system is caused by inadequate adaptive responses of both central regulatory bodies (hypothalamus, vasomotor center) and peripheral receptors. Mainly the failure of segmental autonomous (parasympathetic) structures was revealed. The mode of their response to stress in this case corresponds to that in healthy individuals but at a lower functional level. There is a reduced aerobic capacity of the organism by the Robinson index, contributing to low adaptive range to non-specific stress in children being domiciled on contaminated territories including children having the endothelial dysfunction. Conclusions. Endothelial dysfunction was associated with more pronounced manifestations of autonomic dysregulation and reduced aerobic capacity of the organism being the risk factors of development of a range of somatic diseases requiring the development of prevention measures in children permanently residing in contaminated areas. KEYWORDS: autonomous nervous system balance, endothelial dysfunction, children, Chornobyl accident.

[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.

[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.