EFFECT OF IRON ON BONE TISSUE METABOLISM AND THYROID FUNCTION IN CHILDREN LIVING ON RADIOLOGICALLY CONTAMINATED TERRITORIES SINCE THE ChNPP ACCIDENT. / ВПЛИВ ЗАЛІЗА НА ПРОЦЕСИ МЕТАБОЛІЗМУ В КІСТКОВІЙ ТКАНИНІ ТА ФУНКЦІЮ ЩИТОПОДІБНОЇ ЗАЛОЗИ УДІТЕЙ, ЯКІ ЖИВУТЬ НА РАДІОАКТИВНО ЗАБРУДНЕНИХ ТЕРИТОРІЯХ ПІСЛЯ АВАРІЇ НА ЧАЕС.

OBJECTIVE: identification of clinical and metabolic characteristics of osteogenesis and factors affecting bone mineral density (BMD) in children living in radioactively contaminated territories (RCT) after the ChNPP accident for the use of therapeutic and preventive measures aiming to reduce the incidence of disorders. MATERIALS AND METHODS: Children aged 4 to 18 years old (n = 539) were involved in the study within 4 age groups, namely under 7 years old, 7-10 years old, 10-14 years old, older than 14 years old. Studied parameters in children with a reduced BMD (85-65 relative units and under 65 relative units) were estimated vs. the normative BMD (100-85 relative units) cases. Diagnosis of osteopenia and osteoporosis in children was established according to the BMD T-index. Family history of the relatives of children was studied. Body weight at birth, fractures of the long bones, complaints of osalgia, jaw anomalies, dental caries, presence of obesity, and hypermobility syndrome (HMS) were assessed. Peripheral blood biochemical tests were performed featuring the serum total protein, alkaline phosphatase (APh), calcium, vitamin D, creatinine, serum iron (SI), ferritin, cortisol, pituitary thyroid-stimulating hormone (TSH), and free thyroxine (FT4) assay. BMD was measured and radiation doses in children were reconstructed. RESULTS: BMD depended on the age of children. A direct correlation was established between the cholelithiasis and urolithiasis incidence (р < 0.01), cancer and endocrine diseases (р < 0.05) in the relatives of children that had BMD under 65 relative units. Dental caries developed more often (р < 0.05), while obesity was less frequent (р < 0.05) in the subjects with BMD < 65 relative units. A direct correlation was established between the level of serum creatinine and BMD (р < 0.01), and there was an inverse correlation between the serum APh level and BMD (р < 0.001).Every third child had a vitamin D deficiency. Fractures of long bones and increased content of SI and TSH were characteristic for the children having got osteopenia (BMD within 85-65 relative units), while besides a predisposition to bone fractures the higher levels of SI, APh, cortisol both with calcium deficiency were found in children with osteoporosis (BMD < 65 relative units) compared to the general group with a similar BMD. An increased incidence of HMS was characteristic too. Radiation doses in children with osteopenia were higher than in those with osteoporosis: (1.17 ± 0.09) mSv and (0.92 ± 0.06) mSv respectively (р < 0.05). No correlation was found between the radiation doses and clinical signs, blood biochemistry or BMD. CONCLUSIONS: Study of the functional mechanisms of bone structures in children, depending on their metabolism, had made it possible to reveal the factors that affect bone formation in children living in RCT after the ChNPP accident, and to form the population groups for the timely application of therapeutic and preventive measures aiming to reduce the incidence of disorders of musculoskeletal system.

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.

THE ROLE OF HEREDITARY PREDISPOSITION (POLYMORPHIC MARKERS OF GLUTATHIONE-S-TRANSFERASE, CATALASE, ENDOTHELIAL NITROGEN OXIDE SYNTHASE GENES) AND SOME ADVERSE ENVIRONMENTAL FACTORS IN THE DEVELOPMENT OF BRONCHO-OBSTRUCTIVE PATHOLOGY IN CHILDREN LIVING IN RADIOACTIVELY CONTAMINATED AREAS. / РОЛЬ СПАДКОВОЇ СХИЛЬНОСТІ (ПОЛІМОРФНИХ МАРКЕРІВ ГЕНІВ ГЛУТАТІОН-S-ТРАНСФЕРАЗ, КАТАЛАЗИ, ЕНДОТЕЛІАЛЬНОЇ СИНТАЗИ ОКСИДУ АЗОТУ) ТА ДЕЯКИХ НЕСПРИЯТЛИВИХ ЧИННИКІВ ДОВКІЛЛЯ У ВИНИКНЕННІ БРОНХООБСТРУКТИВНОЇ ПАТОЛОГІЇ У ДІТЕЙ, МЕШКАНЦІВ РАДІОАКТИВНО ЗАБРУДНЕНИХ ТЕРИТОРІЙ.

OBJECTIVE: summarizing the results of many years of research by the authors on the influence of gene polymorphisms encoding xenobiotic biotransformation enzymes (GSTТ1, GSTM1, GSTР1), antioxidant protection (С^262Т of the catalase gene), endothelial nitric oxide synthase (4a/4b VNTR polymorphism of the eNOS gene), and some environmental factors on the occurrence of broncho-obstructive disorders and the development of bronchial asthma in children, residents of radioactively contaminated areas. MATERIALS AND METHODS: The examined school-aged children were residents of radioactively RCA who had no clinical signs of respiratory pathology. Deletion polymorphism of catalase gene (CAT C^262T), polymorphism of glutathione-S-transferase gene (GSTТ1, GSTM1, GSTР1) and the polymorphism in the 4th intron (4a/4b) of the eNOS gene were studied in the molecular genetics laboratory of the State Institution «Reference Center for Molecular Diagnostics of Public Health Ministry of Ukraine¼. Molecular genetic studies were performed by polymerase chain reaction. The study of the ventilation lung capacity was carried out by the method of computer spirometry based on the data of the «flow-volume¼ loop analysis. A pharmacological inhalation test with a bronchodilator drug which affects the ß2-adrenergic receptors of the lungs was used to detect early changes in the ventilatory lung capacity - bronchial hyperreactivity. RESULTS AND CONCLUSIONS: One of the leading mechanisms, due to which the implementation of hereditary predisposition to bronchial asthma in children living in radioactively contaminated areas is the polymorphism of certain genes of glutathione-S-transferase, catalase, endothelial nitric oxide synthase. With such polymorphic variants of the GST genes, isoforms of enzymes with reduced activity are produced, which limits their ability to effectively neutralize free radicals, which are formed in excess when free radical oxidation processes are activated due to the constant intake of radionuclides with a long half-life into the body of children. Unfavorable factors that increase the risk of developing broncho-obstructive disorders and the likelihood of their implementation in the form of bronchial asthma in children, residents of radioactively contaminated areas, have been identified. It has been established that among them the leading role is played by hereditary predisposition to this disease. On the part of the child, such negative factors were unfavorable conditions of intrauterine development, the presence of signs of exudative-catarrhal diathesis, manifestations of allergies and frequent respiratory diseases from the first months of life.

FACTORS AFFECTING MECHANISMS OF INCREASED BONE DENSITY FORMATION IN CHILDREN LIVING ON RADIOLOGICALLY CONTAMINATED TERRITORIES AFTER THE ChNPP ACCIDENT. / ChYNNYKY, IaKI VPLYVAIuT' NA MEKhANIZMY FORMUVANNIa PIDVYShchENOÏ ShchIL'NOSTI KISTKOVOÏ TKANYNY U DITEI, ZhYTELIV RADIOAKTYVNO ZABRUDNENYKh TERYTORII, PISLIa AVARIÏ NA ChAES.

OBJECTIVE: to determine the causes of increased bone mineral density (BMD) based on case history, clinical and laboratory data, including the assay of hormones involved in ossification processes in children, living on radiologically contaminated territories (RCT) after the accident at the ChNPP, compared to the normative BMD patterns. MATERIALS AND METHODS: There were 289 children involved in the study. The 1st group included persons with a BMD above 100 IU, 2nd group - with normative BMD (100-85 IU). Family history of diseases was assessed featuring cancer and endocrine diseases, cholelithiasis, and urolithiasis. Weight of the child at birth, frequency of bone fractures, complaints about osalgia, jaw abnormalities, dental caries, presence or absence of obesity, peripheral blood count, blood biochemical parameters (total protein, creatinine, iron, alkaline phosphatase, calcium), serum pituitary thyroid-stimulating hormone and cortisol were accounted. Children's radiation doses were calculated according to the materials of the «General dosimetric certification of settlements of Ukraine that were exposed to radioactive contamination after the Chornobyl accident¼. RESULTS: Higher than normative BMD values were found in children after puberty, while normative ones - in puberty (р < 0.001), regardless of gender. A direct correlation between the bone fractures frequency was established in children with increased BMD (р < 0.01). Jaw anomalies and dental caries occurred at that significantly less often than in normative BMD (р > 0.05). A direct correlation was established between the obesity and BMD (р < 0.001).Increased alkaline phosphatase activity was inversely correlated with BMD (rs = -0.21; р < 0.05). In children with elevated BMD a direct correlation was established between the level of iron and endocrine disorders in the family history (р > 0.001). Serum level of cortisol was directly correlated with dental caries (р < 0.05). In children, regardless of BMD value, a direct correlation was established between the radiation dose, age and obesity (р < 0.001). CONCLUSIONS: Higher than normative BMD is accompanied by an increased frequency of bone fractures, jaw abnormalities, metabolic changes in bone tissue and bone tissue hormonal regulation in children, which requires application of pathogenetic therapy for the osteogenesis.

[LIFE QUALITY OF CHILDREN WITH SMALL ANOMALIES OF HEART DEVELOPMENT, BORN TO PARENTS IRRADIATED IN CHILDHOOD IN THE CHERNOBYL ACCIDENT].

The study involved 162 children with small anomalies of heart development (SAHD) in core group (children born to parents evacuated from the 30-km zone in childhood) and 39 children in the control group. Quality of life of adolescents was assessed by questionnaire MOS-SF-36 in the Russified version (changed by International reseach centre of life quality, Russia, St. Petersburg, 1998). In children of main group with SAHD, was established systemic pathological process involving not only the cardiovascular system, but also an autonomic nervous systems, hemostasis, upper gastro-intestinal tract, hepatobiliary, urinary system, musculoskeletal system and others, which causes polymorphic clinical picture. Quality of life in children with SAHD, born from parents evacuated from the 30-km Chernobyl zone in childhood was reduced in comparison with practically healthy children. The quality life reduction relate, primarily, physical functioning. Clinical polymorphism and reduced quality of life require the development of approaches to improve diagnosis, treatment and rehabilitation of these patients.

[HEMODYNAMIC CHILDREN WITH ISOLATED ANOMALOUS CHORDS OF THE LEFT VENTRICLE DEPENDING ON LOCATION AND QUANTITY].

A total of 156 children group (children born to parents exposed to the Chernobyl disaster), in which, according to Doppler echocardiography, revealed isolated abnormal chords of the left ventricle (AHLV). Analysis of morphometric parameters and central hemodynamics conducted according to the localization AHLV. Found that concomitant localization AHLV at the threshold of the number of the most influencing change morphoinetric indicators and central hemodynamics. Condition of systemic circulation indicates a decline in their adaptive capacity of the cardiovascular system due to changes in the dynamics and power of the heartbeat. The decrease in stroke volume, stroke and cardiac index suggests hypokinetic type of organization of central hemodynamics, which can be considered an early sign of stress features of the heart and blood vessels. In this subgroup of children revealed significant changes in transmitral flow, indicating the initiation they have diastolic dysfunc tion. When the number of prethreshold AHLV most pronounced changes were found in the middle of their localization. Almost a third of children in this subgroup with individual assessment also revealed signs of initiation of diastolic dysfunction.

Gut microbiota among children living in areas contaminated by radiation and having the cardiac connective tissue dysplasia syndrome. / Mikrobiocenoz kyshechnyka u ditej-meshkanciv radioaktyvno zabrudnenyh terytorij iz syndromom dyplazii' spoluchnoi' tkanyny sercja.

Objective. The study examined the gut (colonic) microbiota in children being domiciled in contaminated zones and suffering the cardiac connective tissue dysplasia syndrome (CCTDS). Materials and methods. The study included 99 children living in contaminated zones. Study subjects were divided into subgroup IA (a comparison subgroup) of 44 children with no signs of CCTDS and subgroup IB of 55 children having the CCTDS. The control group included 24 children aged from 7 to 17 years old. Study groups were of the same gender and age. Results. In the absence of any specific complaints the abnormal gut microbiota was revealed in children living in contaminated areas with a high incidence of 96.36 % featuring both quantitative and qualitative abnormalities that can be considered a dysadaptation phenomenon of both digestive system and body as a whole. Under the concomitant CCTDS these disorders are more expressive, being characterized by a significant decrease in the number of obligate gut flora and failure of its protective capabilities. Incidence of dysbacteriosis grade III in children having the CCTDS is significantly higher vs. children of the control group and comparison subgroup. Under CCTDS the gut microbiota abnormalities were represented with a severe bowel contamination by E. coli with altered enzymatic properties, various types of opportunistic microorganisms, and a high identification incidence of genus Candida fungi at the background of a significant depression of normal colonic flora. Presence of 3-5-component associations of opportunistic pathogens in the colon was found with high incidence. Conclusion. According to received results the examination of intestinal bacterial flora is expedient in children living in areas contaminated by radiation. Application of health care arrangements aimed at normalization of gut microbiota is obligate.

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.

Peculiarities of gastrointestinal disease concomitant to heart connective tissue dysplasia in children born from persons exposed to ionizing radiation in childhood after the ChNPP accident. / Osoblyvosti patologii' shlunkovo-kyshkovogo traktu u ditej iz syndromom dysplazii' spoluchnoi' tkanyny sercja, jaki narodylysja vid bat''kiv, oprominenyh v dytjachomu vici v rezul''tati avarii' na ChAES.

Study objective. The study examined the peculiarities of upper gastrointestinal tract diseases in children suffering from a syndrome of heart connective tissue dysplasia (HCTDS) born from persons exposed to ionizing radiation in a childhood after the ChNPP accident. Materials and methods. The study included 120 children suffering from HCTDS (group I) and 75 persons having no signs of the syndrome (Group II). Diagnosis of HCTDS was obtained from echocardiography in Band M-modes and Doppler echocardiography. Esophagogastroduodenoscopy was performed using a flexible endoscope "OLYMPUS" model GIF-P3. Abdominal diagnostic ultrasound was used to assay the structure of abdominal parenchymal viscera. Results. Upper gastrointestinal tract diseases (UGITD) manifest earlier in children suffering the HCTDS (beginning from a preschool age). Along with age the systemic pattern of organ and system injury becomes evident i.e. there were 6.8 clinical/nosological entities per one child in Group I and 4.9 in Group II. Clinical presentation of chronic UGITD diseases in children suffering concomitant HCTDS were characterized by more frequent exacerbation after the psychoemotional and physical strain, more frequent intestinal motor dysfunction, nervous system disorders (80 %), and chronic infections (62.2 %). Endoscopic pattern of chronic UGITD with concomitant HCTDS featured a combination of mucosal inflammation (a range of various forms of esophagitis, erythematous and hypertrophic gastroduodenopathy) with abnormal gastrointestinal motor function i.e. gastroesophageal and duodenogastric reflux (73.34 %). Destructive lesions at most of duodenal zone were found in 20 %. Conclusions. UGITD namely chronic gastroduodenitis with typically concomitant involvement of several parts of digestive tract are most prevalent within all digestive system diseases in remote period upon the Chornobyl disaster in children born from persons exposed to ionizing radiation in a childhood. Presentation of UGITD occurs earlier in children suffering HCTDS with evident systemic pattern of organ and system injury along with an age. Refluxes of various nature and localization are the leading factors for UGITD onset in children suffering HCTDS. Thus a range of multidirectional tools of reflux disease prophylaxis is required for inclusion to the disease management.

[Abnormal chords of the left ventricle].

The analysis of literature data has showed that evaluation of prognostic significance of abnormal chords of the left ventricle (ACLV) is ambiguous. It remains an open question on the participation of ACLV in the pathogenesis of cardiovascular disease. Obviously, the prognosis of ACLV is determined not so much by the fact of its existence, as degree of connective tissue dysplasia, the number and topic of anomalous chords, the presence of hemodynamic and/or arrhythmic complications. Identification and verification of the anomalous intracavitary structures are important, because they often serve as potential sources of echodiagnostic mistakes, for they can mask more important pathological findings.

[The hematological effects of the Chernobyl accident in children]. / Gematologicheskie éffekty Chernobyl'skoi avarii u detei.

A total of 878 children from the regions with unfavourable radiation situation were investigated in varying periods after the catastrophe. The data obtained were compared with the results of the study of 317 children from "pure" regions. Morphological, metabolic and ultrastructural changes were detected in blood cells of the children from radioactively contaminated regions after the Chernobyl catastrophe. A tendency to normalization of these parameters was noted in the time course of the post-catastrophe period. No clear relationship was established between the dose and effect. However, significant correlations between the severity of disorders in blood cells and the intensity of free-radical processes in the body were recorded.

[Effects of the consequences of the Chernobyl accident on the child's body]. / Effekty vozdeistviia posledstvii Chernobyl'skoi avarii na detskii organizm.

Overall 1580 children from the regions with unsafe radiation situation were examined comprehensively at different times after the accident. The data obtained were correlated to the results of examining 610 children of the control group. The basic group children manifested a higher incidence of diverse alterations on the part of many organs and systems, which was accompanied by an increase of free radical processes signs of destabilization of cellular membranes, activation of blood cell metabolism, suppression of the T cell component of immunity in the presence of vegetovascular dysfunction. A tendency was noted toward normalization of these alterations seen over time after the accident. No clear-cut dose-effect dependence was found.