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.

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.

ASSESSMENT OF QUALITATIVE CHANGES IN PERIPHERAL BLOOD CELLS IN CHILDREN - RESIDENTS OF RADIOLOGICALLY CONTAMINATED TERRITORIES IN THE LATE PERIOD AFTER THE ChNPP ACCIDENT. / OTsINKA IaKISNYKh ZMIN V ELEMENTAKh PERYFERYChNOÏ KROVI U DITEI ­ MEShKANTsIV RADIOAKTYVNO ZABRUDNENYKh TERYTORII U VIDDALENYI PERIOD PISLIa AVARIÏ NA ChAES.

OBJECTIVE: to establish the relationship between quantitative and qualitative parameters of peripheral blood cells(lymphocytes, neutrophilic granulocytes, monocytes, platelets) depending on the type of somatic diseases andannual internal radiation doses from 137Cs in children - residents of radiologically contaminated territories in thelate period after the Chornobyl Nuclear Power Plant (ChNPP) accident. MATERIALS AND METHODS: There were 175 children included in the study comprising residents of radiologically con-taminated territories (n = 79) aged from 4 to 18 years. Annual internal radiation doses in children from 137Cs rangedfrom 0.004 to 0.067 mSv. Certain blood parameters were assessed in a comparative mode in children having got theradiation doses up to 0.01 mSv and higher. The comparison group (n = 96) included children living in settlementsnot attributed to the radiologically contaminated ones. Incidence and type of somatic diseases and its impact onquantitative and qualitative changes in blood parameters (i.e. lymphocyte, neutrophilic granulocyte, monocyte, andplatelet count) were studied. The cell size, state of nucleus, membranes and cytoplasm, signs of proliferative anddegenerative processes were taken into account. RESULTS: Incidence and type of somatic diseases in children did not depend on the annual internal radiation dose.Number of cases of monocytosis was significantly higher among the children exposed to ionizing radiation than inthe comparison group (16.6 % vs. 7.3 %). There were, however, no correlation between these changes and radiationdoses. Number of activated blood monocytes with cytoplasmic basophilia and residues of nucleoli in nuclei washigher in individuals with internal radiation doses > 0.01 mSv. A direct correlation between the qualitative param-eters of monocytes and internal radiation doses was established (rs = 0.60; р < 0.001), as well as a direct correlationof different strength between qualitative parameters of blood cells, indicating their unidirectional pattern depend-ing on the somatic morbid conditions. Regardless of annual internal radiation dose, there was an increase in thenumber of degenerative and aberrant cells vs. the comparison group (р < 0.05), which could be due to the role ofnon-radiation factors. CONCLUSIONS: Results of the assessment of quantitative and qualitative parameters of peripheral blood cells reflect-ed the state of morbid conditions in children and are of a diagnostic value. The identified dose-dependent changesin monocyte lineage of hematopoiesis may be the markers of impact of long-term radionuclide incorporation withfood in children living in environmentally unfavorable conditions after the ChNPP accident.

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.

[The results of an examination of those who took part in extinguishing the fire at the Chernobyl Atomic Electric Power Station on 11-12 October 1991]. / Rezul'taty obsledovaniia lits, prinimavshikh uchastie v tushenii pozhara na Chernobyl'skoi AES 11--12 oktiabria 1991 goda.

Out of 106 firemen who had been engaged in extinguishing fire at Chernobyl NPP in October 11-12, 1991, 39 were examined immediately on the spot and 67--in out-patient department of the Ukrainian Scientific Research Centre of Radiation Medicine. Examination included anamnestic inquest, peripheral blood study and determination of incorporated irradiation. Besides this, about 50 measurements of exposure dose were carried out in the town of Chernobyl, in the NPP territory and in immediate proximity to the site of the accident. Analysis of the data showed that there were no signs of primary reaction of acute atomic disease in all subjects. Measurement of exposure and incorporated doses proved their insignificance with respect to those examined. Complaints and health disorders in firemen are likely to be related to somatic diseases and prolonged emotional exertion during combating fire.

[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.