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.

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.

THYROID DISEASE IN THE LATE OBSERVATION PERIOD UPON CHEMO AND RADIOTHERAPY IN CHILDREN/SURVIVORS OF ACUTE LYMPHOBLASTIC LEUKEMIA. / KhVOROBY ShchYTOPODIBNOÏ ZALOZY PISLIa KhIMIO TA PROMENEVOÏ TERAPIÏ U DITEI, IaKI PERENESLY GOSTRU LIMFOBLASTNU LEIKEMIIu, U VIDDALENOMU PERIODI SPOSTEREZhENNIa.

OBJECTIVE: to assess the thyroid disease in the late observation period in children who had received chemo- andradiotherapy for the acute lymphoblastic leukemia (ALL) taking into account gender, age period and disease sub-type. MATERIALS AND METHODS: The incidence and nature of thyroid disease (hypothyroidism, thyroiditis, and thyroid can-cer) were studied in children-survivors of acute lymphoblastic leukemia (ALL) being in remission from 6 to 25 years.The distribution of patients by leukemia subtypes was as follows: «common¼ - 67.4 %, pre-B - 23.9 %, pro-B andT-cell - 4.3 %. Children had been receiving chemo- and radiotherapy according to the protocol. Regarding the ageof patients at the time of ALL diagnosis the prepubertal, pubertal and postpubertal periods were taken into account.The endocrine diseases in family history, body weight at birth, serum content of free thyroxine, pituitary thyroid-stimulating hormone, cortisol, iron, ferritin and thyroperoxidase antibodies were evaluated and assayed. RESULTS: Thyroid disease in children was emerging in the first 2-3 years after the ALL treatment with an incidenceof 22.8 % (hypothyroidism - 14.1 %, autoimmune thyroiditis - 7.6 %, papillary cancer - 1.1 %). Seven children inthis group had received radiotherapy (12-18 Gy doses) on the central nervous system (CNS). No correlation wasfound between the radiation exposure event itself, radiation dose to the CNS and thyroid disease in the long-termfollow-up period. Thyroid cancer had developed in a child 11 years upon chemo- and radiotherapy. Hypothyroidismwas more often diagnosed in the patients of prepubertal age (rs = 0.49). There were endocrine diseases in thefamily history in about a half of children, being significantly higher than in the general sample (р < 0.05). The bodyweight at birth of a child who had later developed hypothyroidism was less than in children having got thyroiditis(rs = 0.57). CONCLUSIONS: Disorders in endocrine regulation and of thyroid in particular can affect the prognosis of blood can-cer course in the long-term follow-up in children, especially in prepubertal age, which requires systematic supervi-sion by hematologist and endocrinologist.

PROGNOSIS OF ACUTE LEUKEMIA DEPENDING ON THE IRON METABOLISM PARAMETERS IN CHILDREN AFTER CHORNOBYL NUCLEAR POWER PLANT ACCIDENT. / PROGNOZ PEREBIGU GOSTRYKh LEIKEMII U DITEI PISLIa AVARIÏ NA ChAES ZALEZhNO VID OBMINU ZALIZA.

OBJECTIVE: To determine the influence of iron metabolism on the prognosis of acute lymphoblastic (ALL) and (AML)myeloblastic leukemia at the different phases of chemotherapy in children after Chоrnobyl accident. MATERIALS AND METHODS: 333 children (295 - ALL, 38 - AML) were examined at the stages of chemotherapy. Thecomparison group included 93 children without leukemia. Acute leukemia variants, patients survival, relapses, thenature of disease (live child or died), iron methabolism (morphometric parameters of erythrocytes, SI, SF, STf, TS),manifestations of dyserythropoiesis, bone marrow sideroblast and patients radiation dose were taken into account. RESULTS: In 295 patients with ALL the following variants of leukemia were established: pro-B-ALL in 23, «common¼type of ALL in 224, pre-B-ALL in 29, T-ALL in 19. Thirty eight patients were diagnosed with AML (11 - M1, 19 - M2,8 - M4). Doses of radiation in patients with AL were (2.78 ± 0.10) mSv and they did not correlate with clinical andhematological parameters, disease variant. Relapse rates and shorter survival were in patients with T-ALL, pro-B-ALLand AML with SF levels > 500 ng/ml (p < 0.05). The amount of children with normochromic-normocytic anemias andmanifestations of dysplasia of erythroid lineage elements was greater in the AML than in ALL. SF content in patientswas elevated during chemotherapy and was lower than the initial one only in the remission period. Transferrin wasreliably overloaded with iron: TS (70.2 ± 2.3) % compared with the control group (32.7 ± 2.1) %. Correlationbetween TS and survival of patients was detected (rs = -0.45). Direct correlation between the number of iron granules in erythrocariocytes and SF level (rs = 0.43) was established, indicating the phenomena of ineffective erythropoiesis. CONCLUSIONS: The negative influence of iron excess in the patients body on the hemopoiesis function, manifestations of ineffective erythropoiesis and the course of acute leukemia in children have been established. Changes inferrokinetic processes in children can be the basis of leukemоgenesis development.

Effect of radiation and non radiation environmental factors on children hematopoietic system. / VPLYV RADIATsIY̆NYKh TA NERADIATsIY̆NYKh FAKTORIV DOVKILLIa NA STAN SYSTEMY KROVOTVORENNIa DITEY̆.

OBJECTIVE: Identification of impact of radiation and non radiation environmental factors on development of hematopoi etic abnormalities in children and justification of criteria for the increased risk groups of hematologic diseases. MATERIALS AND METHODS: The results of clinical and hematological survey of 1465 children living in Kyiv, Zhytomyr and Chernihiv regions for the period from 2008 to 2014 were presented. There were 777 children with anemia, 466 with changes in hemogram, 191 with acute leukemia. The irradiation doses, correlation of integrated pollution degree of territories with hematopoietic parameters and course hematologic diseases were estimated. Metal con tent in hair, nails, and blood was determined in 121 children. RESULTS: We have found the most common cause of anemia in children and peculiarities of acute leukemia depend ing on the area integrated contamination. Number of children living in contaminated areas with pro B ALL and T ALL having an initial leukocytosis and unfavorable course of the disease was higher compared to the number of patients from moderately polluted regions (r = 0.47). There is a direct correlation between percentage of children with monocytosis and degree of territory contamination: the 20.2 % of such children lived in the intensively polluted areas and 10,3 % in moderately contaminated ones (p < 0.05). Content of Pb, Cu, Cr, Mn, Zn in biological tissues did not exceed the permissible MAC. Level of Zn in all children was at the lower normal threshold. Individual levels of metals in hair, nails and blood did not depend on gender of patients and their radiation doses. Criteria of increased risk of hematologic diseases in children living in ecologically unfavorable regions were grounded. CONCLUSIONS: Radiation and non radiation environmental factors influencing the development of changes in hematopoiesis and characteristics of the blood system diseases in children play a role in leukeima development processes. These findings are the basis for a further research in the field of radiobiology and ecology.

[Clinico-immunocytological characteristics of leukemia in persons exposed to ionizing radiation effects due to the Chernobyl AES accident]. / Kliniko-immunotsitologicheskaia kharakteristika leikozov u lits, podvergshikhsia vozdeistviiu ioniziruiushchikh izluchenii v rezul'tate avarii na Chernobyl'skoi AES.

A total of 18 patients with acute leukemia from those exposed to radiation when they had liquidated the consequences of the accident at the Chernobyl Atomic Power Station were examined. Sixteen of them had acute myeloblast cell leukemia, one had acute lymphatic leukemia, and another one had acute promyelocytic leukemia. A complex of hematological, immunocytological, and cytochemical findings, as well as leukocytic and erythrocytic genetically determined antigen typing were used for diagnosis. Signs of severe vegetovascular dystonia was found to be followed by acute leukemia in all the patients. A relationship was established between the therapy resistance and the HLA antigen homozygosity in combination with genetically-determined low reactivity. There were no significant differences between the parameters in question and those in patients with acute leukemia who had been studied in the preaccident period.