[The use of EPR spectroscopy to control the changes of organism radiosensitivity/radioresistance. Experimental and clinical results].

The responses of deoxyribonucleotide (dNTP), DNA and protein synthesis systems in blood-forming organs of animals (dogs, mice) as well as changes in Fe(3+)-transferrin (Fe(3+)-TF) and Cu(2+)-ceruloplasmin (Cu(2+)-CP) pools in blood to gamma-irradiation and the administration of radioprotectors have been studied. It has been shown that changes in Fe(3+)-TF and Cu(2+)-CP pools in blood are indices of changes in the body radioresistance and are reliably controlled by the EPR technique. An increase in the Fe(3+)-TF pool promotes the activated synthesis of dNTP, DNA and Fe(3+)-containing proteins which are essential for the repair efficiency during the early post-irradiation time as well as for the development of compensatory and restorative reactions of cellular systems; i.e., they are responsible for the body resistance to DNA-damaging factors. It is important that the intensity of responses depends on the initial state of the organism. It has been shown, that changes in Fe(3+)-transferrin and Cu(2+)-ceruloplasmin pools, which are trust-worthy controlled by the EPR technique in whole blood, blood plasma, and serum, as well as the changes in the extracellular DNA content in blood plasma are the markers of the changes in the organism radioresistance. This has been proved during the medical examination of the Chernobyl accident recovery workers and civil population, including children, exposed to low-intensity radiation.

[Clinical immunological disorders in children from various observation cohorts exposed to radiation factor during various stages of oncogenesis].

The immune status disorders and features depending on the radiation impact type in various cohorts of radiation observations long after the Chernobyl (CNPP) disaster and the possible role of these disorders in development of chronic somatic pathology in children are shown. Lymphocyte depletion, T-cell immunity component disorders in the form of cell contraction with CD3, CD4, CD8 markers and the B-cell immunity component disorders in the form of reducing the quantity of CD10, CD23 marker cells were observed in children subject to combined chronic irradiation by 131I, 137Cs, 90Sr radionuclides. The descendants of irradiated parents (the 1st generation; children of the Chernobyl accident consequences liquidators, children of the citizens of radiation contaminated territories with various 137Cs levels) had immunity disorders of different type. A change in the total amount of NK-cells (CD16(+)-lymphocytes) is the general sign for all radiation risk groups; however, people subject to direct radiation impact demonstrated reduction of the antitumor protection potency, whereas descendants of irradiated ones demonstrated its activation with typically increasing number of CD16(+)-lymphocytes. In all radiation risk groups, a tendency to reduction of a number of cells involved in the leukocytal activation with the "pluripotential activation" marker (CD38 marker cells), proliferating cells (CD71 marker cells) and the increase of relative amount of cells with apoptosis marker (CD95(+)-lymphocytes). Immune disorder markers under the radiation impact in various cohorts of children's observation are suggested: antigens: CD4, CD8, CD10, CD23, CD16, CD38, CB71, CD95.

[The use of EPR spectroscopy to control the changes in organism radioresistance. Clinical results].

It has been shown that changes in Fe(3+)-transferrin and Cu(2+)-ceruloplasmin pools, which are trust-worthy controlled by the EPR technique in whole blood, blood plasma, and serum, as well as changes in the extracellular DNA content in blood plasma are markers of changes in organism radioresistance. This has been proved during the medical examination of the Chernobyl accident recovery workers and civil population, including children, exposed to low-intensity radiation, as well as during clinical investigation of new radioprotectors.

[The problem of the transgeneration phenomenon of genome instability in sick children of different age groups after the accident at the Chernobyl Nuclear Power Plant].

A complex genetic examination of children which belong to two cohorts and their parents were carried out. The first cohort included children and constantly living on territories contaminated with radionuclides (Novozybkov district, Bryansk region). They were subdivided in groups according to the ontogenetic age periods of development of their parents at the time of the Chernobyl accident. In the children born in 1986-1995 the level of aberrant genomes is significantly higher as compared to the control (p < 0.001). In children born in 1998-2002 the differences are insignificant (p > 0.05). The frequency of aberrant genomes had a tendency to decrease with the period of time between the birth date of a child and the moment of the accident. Analysis of the results of cytogenetic investigation for the same living on territories with different densities of radioactive contamination (zone I-- 627-688 kBq/m2, 137Cs and zone II-- 135-402 kBq/m2, 137Cs) revealed insignificant differences in the spectrum and average frequencies of chromosome aberrations. The second cohort included children born in 1987-1991 and 1993-2002 from irradiated fathers (Chernobyl clean-up workers) and unirradiated mothers living on territories without radionuclide contamination. These children also displayed increased frequencies of aberrant genomes as compared to the control (p < 0.001). The analysis of the dynamics years of birth of cytogenetic disturbances in the same cohorts of children showed the average frequencies of aberrant genomes remain higher than the control level. In most of the children of both cohorts the repair synthesis of genome DNA by gamma- and UV-radiation is reduced as compared to one in the children from the control group.

[The organization of medical aid to children of various cohorts of supervision, undergone to the influence of small dozes of radiation].

In clause the stages of organization of medical aid to children who undergone to the influence of the ecopathologic factors, including small dozes of ionizing radiation are submitted. The features of various stages of medical aid in nearest time after influence of the radiating agent are shown. The methodological complexities of diagnostic measures in the late times after the ecopathologic influence of small dozes of ionizing radiation are submitted, the role of the radiosensitivity in formation of pathological somatic diseases of condition at children is considered. The opportunity of the differential treating and preventive help rendering to the children various cohorts of supervision is shown.

[The problem of induced genome instability as the basis of the increased morbidity in children exposed to low-intensity radiation at low doses].

The main results of the complex examination of the genome instability are presented in children constantly living on territories contaminated with radionuclides as a result of the accident at the CNPP (Novozybkov district, Bryansk region, 16-18 Ci/km2, 137Cs) and in children exposed to low-intensity radiation at different stages of ontogenetic development: children exposed to postnatal irradiation in 1986 (born before the accident), children exposed to intrauterine irradiation during the accident in 1986, children of irradiated parents born after the accident in 1987-1992 and in 1994-2000. In all examined groups of irradiated children increased frequencies of certain radiation-induced chromosome aberrations were observed as well as a reduced activity of unscheduled synthesis of genomic DNA in lymphocytes and peculiarities in individual heterozygosity of genes encoding structural and enzymatic proteins of blood. An increased radiosensitivity of lymphocyte genomes to testing in vitro irradiation and peculiarities in the dynamics of the frequencies of chromosome aberrations and sister chromatid exchanges in 3 cell generations were revealed in children from the contaminated areas. The data obtained suggest a systemic character of dysgenomic effects, the reality of induction of genome instability in the growing organism of children exposed to low-intensity radiation at low doses the expression of which is determined by individual genotypic features of the organism. Biological significance of the phenomenon of the post-radiation genome instability, its relation to the state of health and the pathogenetic role in the development of somatic pathology are postulated.

[Characteristics of infection in children during prolonged oxidative stress after radiation exposure]. / Osobennosti infektsionnogo protsessa u detei v usloviiakh dlitel'nogo okislitel'nogo stressa vsledstvie radiatsionnogo vozdeistviia.

In the article on discusses the problems of origin and duration of chlamydia and herpes-virus infection in children with chronic somatic pathology and different degrees of radiation stress in contaminated territories of Brianskaya region (the level of contamination according to 137Cs = 9.37-19.73 Ci/km2).

[Markers of the metabolic changes arising as a result of ionizing radiation exposure]. / Markery metabolicheskikh izmenenii, voznikaiushchikh vsledstvie vozdeistviia ioniziruiushchei radiatsii.

Time-related changes have been studied in the content of extracellular DNA, Fe(3+)-transferrin (TF), and Cu(2+)-ceruloplasmin (CP) in the blood plasma and the activity of ribonucleotide reductase (RR) in the tumor cells and spleen of mice during the development of acute lympholeukosis P-388 and after ionizing irradiation. At the initial stages of leucosis P-388, the content of extracellular DNA increases, the TF and CP pools in the blood plasma enlarge, and the RR activity in the tumor cells and spleen of tumoral mice markedly increases. A dose-dependent increase in RR activity was also recorded in the spleen of 5-day-old rats within 15-30 min after irradiation. The causes of these changes and the possibility for these indices to be used in estimating leucosis risk are discussed. Radiation-induced increases in RR activity are discussed in relation to the SOS-response to DNA damage; an increased pool of deoxyribonucleotides is necessary for repair of DNA. The mean contents of extracellular DNA, TF and CP in the blood plasma were obtained from children of different ages degrees of radioactive contamination suffering the consequences of the accident at the Chernobyl' Nuclear Power Station (n = 155). Groups of children have been isolated with increased, sharply decreased, and close to normal levels of extracellular DNA, TF, and CP. The lowered TF pool was observed in children with thyroid glands damaged by incorporated radioactive iodine with the degree of suppression determined by the dose. For most children subject to general irradiation, the TF and CP pools in the blood were higher than in the control, suggesting an adaptive response to irradiation.

[The psychological characteristics of adolescents with ischemic heart disease in their anamnesis and their linkage to the lipoprotein spectrum indices]. / Psikhologicheskie osobennosti podrostkov s ishemicheskoi bolezn'iu serdtsa v anamneze i ikh sopriazhennost' s pokazateliami spektra lipoproteidov.

A psychological survey (MMPI, Wolff, Rosenzweig, Spielberger, Eysenck tests) of 70 adolescents with family history of coronary heart disease established the following personality traits in them: activity, leadership inclinations, extroversion, impulsiveness, heteroaggressiveness coupled with inner strain, anxiety. The anxiety, heteroaggression, extroversion correlated with atherogenic changes in lipoprotein spectrum.

[Characteristics of the cardiovascular system in children with primary arterial hypotension]. / Kharakteristika serdechno-sosudistoi sistemy u detei s pervichnoi arterial'noi gipotoniei.

Overall 120 children aged 12 to 15 years with primary arterial hypotension and different variants of the disease course (grave, of medium gravity or mild) were examined. The control group was made up to 50 normal children. The program of the examination included electrocardiography, echocardiography, tetrapolar chest rheography and bicycle ergometry. It has been established that in children with arterial hypotension, the intracardiac hemodynamics undergoes compensatory adaptive reconstruction characterized by the enhancement of contractile and pump functions of the myocardium combined with the increased relaxation capacity. The central hemodynamics is characterized by the lowering of the general peripheral vascular resistance. The functional potentialities of the cardiovascular system decline, manifesting in the form of a decrease of exercise tolerance in association with energy losses necessary for its performance. The use of bicycle ergometry made it possible to delineate dysadaptation reactions of arterial pressure to exercise, modified by hereditary factors.

[Changes in central hemodynamics as a risk factor of the development of ischemic heart disease in adolescents with aggravated heredity of atherosclerosis]. / Izmenenie tsentral'noi gemodinamiki kak faktor riska razvitiia ishemicheskoi bolezni serdtsa u podrostkov s otiagoshechennoi nasledstvennost'iu po aterosklerozu.

The authors provide the data on the central hemodynamics, blood plasma lipoproteins and apoproteins in 101 adolescents with aggravated heredity as regards coronary heart disease and in healthy adolescents of the same age serving as control. The hypokinetic variant of circulation is demonstrated to be coupled with the atherogenic nature of the lipoprotein and apoprotein spectra and heredity to contribute greatly to the traits under study. Criteria for the adolescents' inclusion into the group at the highest risk for early development of atherosclerosis are described.

[Atherogenic dyslipidemia in adolescents: its relation to ischemic heart disease in their fathers and the possibility of its prognosis]. / Aterogennye dislipidemii u podrostkov: svia'z s nalichiem ishemi- cheskoi bolezni serdtsa u ottsov, vozmozhnos't prognozirovaniia.

Comparison of a group of adolescents aged 11-16 years whose fathers had angiographically documented coronary atherosclerosis in youth with those matched by sex and age whose parents were clinically healthy yielded the following discriminant function (DF) involving lipid and apoprotein indices of the plasma lipid system: DF = [apo B] X 0.03-[HDL cholesterol] X 0.04-0.81. DF greater than or equal to 0 discriminates from the controls 32% of the offsprings from the fathers with a history, DF less than 0 correctly classifies 98% of adolescents from the controls. The adolescents who have DF greater than or equal to 0 amounted to about 19% in representative samples of Moscow adolescents. Moreover, DF with 80% probability makes it possible to predict the time course of serum lipid levels in adolescents within 2 years.

[Changes in phospholipid composition of high density lipoproteins in children as a possible precursor of the development of ischemic heart disease]. / Izmenenie fosfolipidnogo sostava lipoproteidov vysokoi plotnosti u detei kak vozmozhnyi predvestnik razvitiia ishemicheskoi bolezni serdtsa.

The proportion of apoprotein-AI (apo-AI) phospholipids (PL) and HDLP phospholipid spectrum were determined in addition to principal coronary risk factors; cholesterol (CS), triglycerides (TG) and high-density lipoprotein (HDLP) CS, in high-risk children, whose parents had survived myocardial infarction at a young age, and also in children with vegetovascular dystonia and a control group. It is demonstrated that children with relatively low percentage of lecithin in HDLP, in the absence of changes in CS, TG, apo-B and apo-AI, and HDLP CS, could be found in all the examined groups, and were particularly numerous in the high-risk group. Correlations coefficients for the HDLP PL percentage in the father-child, mother-child and father-mother pairs were estimated, revealing a positive correlation with respect to lecithin in these pairs, an evidence of the contribution of the general familial environment to the variability of the parameter in question in the examined groups. Different correlations were demonstrated between lecithin/sphingomyelin and lecithin/kephalin ratios in boys and girls from the control and high-risk groups.

[Functional status of the cardiovascular system of adolescents with a hereditary predisposition to atherosclerosis]. / Funktsional'noe sostoianie serdechno-sosudistoi sistemy u podrostkov s otiagoshchennoi nasledstvennost'iu po aterosklerozu.

A study of 70 teenagers between 11 and 15, whose parents had suffered, before they were 45, myocardial infarction in the presence of verified coronary arterial atherosclerosis, revealed no organic cardiac changes, while some signs of neurocirculatory dystonia were combined with increased incidence of coronary risk factors and dyslipoproteinemia.

[Status of cerebral structure and hemodynamics in healthy children and those with autonomic-vascular dystonia]. / Sostoianie tserebral'nykh struktur i mozgovoi gemodinamiki u zdorovykh detei i detei s vegetososudistoi distoniei.

From the standpoint of traditional neurology an attempt has been made to evaluate the function of the cerebral structures in 50 children with vegetovascular dystonia and 30 normal ones. On the basis of the data obtained a working hypothesis is advanced about a special role of the defect in the right cerebral hemisphere in the pathogenetic mechanisms of hypertension in the presence of vegetovascular dystonia.