BRAIN AND EYE AS POTENTIAL TARGETS FOR IONIZING RADIATION IMPACT: PART II - RADIATION CEREBRO/OPHTALMIC EFFECTS IN CHILDREN, PERSONS EXPOSED IN UTERO, ASTRONAUTS AND INTERVENTIONAL RADIOLOGISTS. / GOLOVNYI MOZOK TA ORGAN ZORU IaK POTENTsIINI MIShENI DLIa VPLYVU IONIZUIuChOGO VYPROMINIuVANNIa: ChASTYNA II ­ RADIATsIINI TsEREBROOFTAL'MOLOGIChNI EFEKTY U DITEI, OSIB, EKSPONOVANYKh VNUTRIShN'O/UTROBNO, ASTRONAVTIV TA INTERVENTsIINYKh RADIOLOGIV.

BACKGROUND: Ionizing radiation (IR) can affect the brain and the visual organ even at low doses, while provoking cognitive, emotional, behavioral, and visual disorders. We proposed to consider the brain and the visual organ as potential targets for the influence of IR with the definition of cerebro-ophthalmic relationships as the «eye-brain axis¼. OBJECTIVE: The present work is a narrative review of current experimental, epidemiological and clinical data on radiation cerebro-ophthalmic effects in children, individuals exposed in utero, astronauts and interventional radiologists. MATERIALS AND METHODS: The review was performed according to PRISMA guidelines by searching the abstract and scientometric databases PubMed/MEDLINE, Scopus, Web of Science, Embase, PsycINFO, Google Scholar, published from 1998 to 2021, as well as the results of manual search of peer-reviewed publications. RESULTS: Epidemiological data on the effects of low doses of IR on neurodevelopment are quite contradictory, while data on clinical, neuropsychological and neurophysiological on cognitive and cerebral disorders, especially in the left, dominant hemisphere of the brain, are nore consistent. Cataracts (congenital - after in utero irradiation) and retinal angiopathy are more common in prenatally-exposed people and children. Astronauts, who carry out longterm space missions outside the protection of the Earth's magnetosphere, will be exposed to galactic cosmic radiation (heavy ions, protons), which leads to cerebro-ophthalmic disorders, primarily cognitive and behavioral disorders and cataracts. Interventional radiologists are a special risk group for cerebro-ophthalmic pathology - cognitivedeficits, mainly due to dysfunction of the dominant and more radiosensitive left hemisphere of the brain, andcataracts, as well as early atherosclerosis and accelerated aging. CONCLUSIONS: Results of current studies indicate the high radiosensitivity of the brain and eye in different contingents of irradiated persons. Further research is needed to clarify the nature of cerebro-ophthalmic disorders in different exposure scenarios, to determine the molecular biological mechanisms of these disorders, reliable dosimetric support and taking into account the influence of non-radiation risk factors.

BRAIN AND EYE AS POTENTIAL TARGETS FOR IONIZING RADIATION IMPACT. Part І. THE CONSEQUENCES OF IRRADIATION OF THE PARTICIPANTS OF THE LIQUIDATION OF THE CHORNOBYL ACCIDENT. / GOLOVNYI MOZOK TA ORGAN ZORU IaK POTENTsIINI MIShENI DLIa VPLYVU IONIZUIuChOGO VYPROMINIuVANNIa. Chastyna I. TsEREBROOFTAL'MOLOGIChNI EFEKTY OPROMINENNIa V UChASNYKIV LIKVIDATsIÏ NASLIDKIV AVARIÏ NA ChAES.

BACKGROUND: Exposure to ionizing radiation could affect the brain and eyes leading to cognitive and vision impairment, behavior disorders and performance decrement during professional irradiation at medical radiology, includinginterventional radiological procedures, long-term space flights, and radiation accidents. OBJECTIVE: The objective was to analyze the current experimental, epidemiological, and clinical data on the radiation cerebro-ophthalmic effects. MATERIALS AND METHODS: In our analytical review peer-reviewed publications via the bibliographic and scientometric bases PubMed / MEDLINE, Scopus, Web of Science, and selected papers from the library catalog of NRCRM - theleading institution in the field of studying the medical effects of ionizing radiation - were used. RESULTS: The probable radiation-induced cerebro-ophthalmic effects in human adults comprise radiation cataracts,radiation glaucoma, radiation-induced optic neuropathy, retinopathies, angiopathies as well as specific neurocognitive deficit in the various neuropsychiatric pathology including cerebrovascular pathology and neurodegenerativediseases. Specific attention is paid to the likely stochastic nature of many of those effects. Those prenatally and inchildhood exposed are a particular target group with a higher risk for possible radiation effects and neurodegenerative diseases. CONCLUSIONS: The experimental, clinical, epidemiological, anatomical and pathophysiological rationale for visualsystem and central nervous system (CNS) radiosensitivity is given. The necessity for further international studieswith adequate dosimetric support and the follow-up medical and biophysical monitoring of high radiation riskcohorts is justified. The first part of the study currently being published presents the results of the study of theeffects of irradiation in the participants of emergency works at the Chornobyl Nuclear Power Plant (ChNPP).

Myastenia and small doses of ionizing radiation: experience of successful use of rituximab for treatment of an irradiated with myasthenia gravis. / MIASTENIIa I MALI DOZY IONIZUIuChOÏ RADIATsIÏ: DOSVID USPIShNOGO ZASTOSUVANNIa RYTUKSYMABU DLIa LIKUVANNIa OPROMINENOGO Z MYASTHENIA GRAVIS.

A clinical case of the rituximab («Rituksim¼, «Mabthera¼) use to treat a man affected by the Chornobyl NPP acci dent with malignant resistant form of myasthenia gravis in conjunction with chronic mixed infection by Toxoplasma, Epstein Barr virus, Cytomegalovirus and Herpes simplex virus is described. In the dynamics of two year's observa tion the clinical efficacy of monoclonal antibodies was shown as the main symptoms stabilization and reducing doses of glucocorticoid and anticholinergic therapy. The positive effect was marked in the nearest and remote peri ods. Taking to account the efficacy, safety and good tolerability of rituximab, it is advisable to recommend treat ment for people exposed to ionizing radiation and developing myasthenia associated with chronic mixed infection by Toxoplasma, Epstein Barr, Cytomegalovirus and Herpes simplex virus.

[SELENIUM EFFICIENCY IN PROPHYLAXIS AND COMPLEX TREATMENT OF DIFFUSE GOITER].

Efficiency of the combined prophylaxis and treatment of a diffuse goiter by preparations of sele- nium and iodine at 54 patients--men at the age of 41-50 years with the diagnosis of a diffuse goiter of 1st and 2nd degree was investigated. The diagnosis of a diffuse goiter was based on palpatory and ultrasonic research of the thyroid gland, which volume was compared with a body surface area. All surveyed have been divided into three groups. Patients of the first group accepted preparations of selenium and the iodine throughout three months, the second group--iodine preparations, in control group only dynamic supervision was spent. Thyroid gland volume at men who constantly used iodated salt and had no palpatory signs of a goiter was also measured for control. In the group which members accepted selenium and iodine preparations, at 11,8 % of patients was noted reduction of thyroid volume to normal and was revealed more expressed reduction of thyroid volume (for 2.15 sm3/M2 ± 0.07 sm3/M2), than at monotherapy by iodine preparations (for 0.92 sm3/M2 ± 0.17 sm3/M2). The conclusion was made that it is possible to recommend selenium preparations in a dose of 100 mkg a day together with preparations of iodine for prophylaxis and treatment of a diffuse goiter in conditions of the combined insufficiency in consumption of selenium and light deficiency of iodine.

[Monitoring of iodine supply of the population of Kiev and Kiev region (according to the observation of representative groups)].

720 women and children living in Kiev and Kiev region have been observed to detect iodine supply of people. The authors revealed iodine deficit of mild degree in both groups. The women had median of urine iodine excretion equal to 85.9 microg/l and children--96.8 microg/l. The great frequency of cases of diffuse enlargement of the thyroid gland shows also the presence of iodine endemic disease: 61.2% of Kiev schoolboys and schoolgirls and 40.8% of children of Kiev region had exceeding volume of the thyroid comparing age norms. The autors showed the necessity of introduction of the programm of global rodine prophylaxy by iodating salt.

Seasonality of birth in children and young adults (0-29 years) with type 1 diabetes in Ukraine.

AIMS/HYPOTHESIS: Numerous epidemiological studies have shown differences in seasonality of birth patterns between the general population and the group who develop type 1 diabetes mellitus. This finding indicates that environmental factors operating during pre- and/or postnatal development could be aetiologically important. We examined whether the pattern of month of birth for type 1 diabetes patients in Ukraine differs from that for total live births. METHODS: Data consist of prevalent cases of type 1 diabetes in Ukraine by the end of 2003. Cases are restricted to persons born after 1 January 1960, diagnosed with type 1 diabetes before the age of 30 years (n = 20,117). People born during the same time in the general population (n = 29,105,560) were the reference standard. Seasonal patterns were estimated using logistic regression with harmonic terms. RESULTS: We found a strongly significant seasonal pattern of type 1 diabetes incidence rates (p < 0.001), with the lowest rates in December and the highest in April. The rate ratio between the extremes was 1.32 (95% CI 1.27-1.39). Tests for seasonal patterns in subgroups defined by sex and age or by sex and date of birth were all significant with p values less than 0.02. We found no interactions with sex (p = 0.142) or age at diagnosis (p = 0.207), but found a strong interaction with period of birth (p < 0.0001). CONCLUSIONS/INTERPRETATION: The results obtained indicate that early-life factors linked to seasons may influence type 1 diabetes risk later in life.

[Role of seasonal factors in pre- and postnatal ontogenesis for etiology of type 1 diabetes mellitus].

Type 1 diabetes mellitus is a chronic disease characterized by autoimmune degradation of insulin-producing beta-cells. It was shown in a number of epidemiological studies of seasonality of birth in children with type 1 diabetes that the autoimmune process began during fetal and postnatal development. No such studies were carried out in the former Soviet Union countries. The aim of the present study is to compare the seasonal birth month pattern in patients with type 1 diabetes (10780 men and 9337 women) born in 1960-2002 to that in the total population of Ukraine (14 785601 men and 13 911370 women) born during the same period. Significant differences were found between these two populations: chi-squared = 103.97, p < 0.0001 and 135.17, p < 0.0001 in men and women, respectively. The results of cosinor analysis showed similar sinusoidal birth patterns of patients with type 1 diabetes in all sub-groups, irrespective of the age of clinical disease expression: 0-9, 10-19, or 20-29 years. In all cases, the highest and lowest predispositions to type 1 diabetes were inherent in the people born in spring and autumn, respectively. We propose that seasonal differences in the birth pattern in the two above populations could be due to long-term programming of glucose-insulin metabolism determined by the effect of certain seasonal factors during early ontogenesis.

[Gender-related risk of non-fatal stroke, myocardial infarction and blindness in the type 2 diabetic patients depend on the type of treatment].

The aim of present observational cross-sectional study was the estimation of the gender-related risk of non-fatal stroke, myocardial infarction and blindness in type 2 diabetics (T2D) depending on treatment in Ukraine. In Dec 2005 the data from 11 Ukrainian regions for all living T2D already included into the nationwide population-based diabetes register (start of creation Jan 2001) was extracted. Male/female relative risks (RRs) for non-fatal stroke, myocardial infarction and blindness were calculated in treatment groups: Diet only (DO) 7273/15901; oral antidiabetic drugs (OAD) 15109/ 33913; insulin (I) 5529/12462 male/female respectively. 95% confidence intervals were estimated using logarithmic transformation, chi-square test was used to compare the differences between groups. The higher prevalence of stroke among men was in those patients treated with OAD or DO:RRs = 1.38 (1.26-1.51) and 1.48 (1.25-1.76), respectively. The gender differences were absent among those treated with I:RR = 0.98 (0.87-1.10). An excess male risk of myocardial infarction was in persons treated with I:RR = 1.37 (1.21-1.55), though smaller than in those treated without I - male/female RRs: 2.18 (1.97-2.41) and 2.37 (1.99-2.86), respectively for OAD and DO (P<0.001 in both cases). The significantly increased female prevalence of blindness was in patients treated with I:RR = 0.80 (0.70-0.92). The latest is in accordance with our earlier results, which have demonstrated the raised prevalence of both low sight and proliferative retinopathy among the insulin-treated diabetic women. No sex-related differences in blindness prevalence were revealed in patients treated with OAD or DO. The gender risks of not-fatal stroke, myocardial infarction and blindness in T2D are significantly different depending on the fact of insulin treatment. Further research could clarify if it depends upon insulin-related hyperandrogenisation in T2D women.

First experience of the use bone marrow mesenchymal stem cells for the treatment of a patient with deep skin burns.

Female patient with extensive skin burn (I-II-IIIAB skin burn, total area 40%, area of IIIB degree 30%) was treated using transplantation of allogenic fibroblast-like bone marrow mesenchymal stem cells onto the surface of deep thermal burn. The study of wound healing dynamics after transplantation of allogenic fibroblast-like mesenchymal stem cells confirmed high tempo of wound regeneration in the presence of active neoangiogenesis. Due to this, autodermoplasty of burn wounds could be carried out with good results as early as on day 4 after transplantation of fibroblast-like mesenchymal stem cells; this led to more rapid healing of donor zones and accelerated rehabilitation of the patient.

[Incidence of proliferative retinopathy and sex-related differences in death rate among patients with diabetes mellitus and sight impairment treated with insulin (according to the data from national diabetic registry)]. / Rasprostranennost' proliferativnoi retinopatii i gendernye razlichiia v urovne smertnosti sredi poluchaiushchikh insulin bol'nykh sakharnym diabetom s narusheniem zreniia (po dannym natsional'nogo diabetologicheskogo registra).

The article presents the analysis of the occurrence of diabetes mellitus-linked sight impairment and proliferative retinopathy after data of National Diabetes Population Register among patients receiving insulin therapy. The number of women with above mentioned impairments has been found to prevail significantly over that of men. This tendency is also observed among the patients aged to 50 y. o., although in this age group the number of men with diabetes mellitus prevails over that of women. This discrepancy can be explained through higher death rate linked with diabetes mellitus among men as compared with women. Death rate statistics concerning patients with diabetes mellitus complicated with sight impairment for 2003 y. confirms this supposition.

[The study of iodine sufficiency in children of Kiev]. / Vyvchennia iodnoï zabezpechenosti ditei m. Kyieva.

A total of 576 pupils in different age groups of a school in Kiev were examined. Determined in the above pupils by palpation and echography were sizes of the thyroid gland, urine excretion of iodine. Thyroid enlargement was identified in nearly 30 percent of the examined children, nodal pathology of the gland was in 0.52 percent. It was only in 34 percent of the examinees that the level of iodine excretion was more than 100 mcgrm/l, i.e. did not deviate from the norm; 5.3% of children had ioduria indices < 20 mcgrm/l, which observation suggested a severe iodine deficiency. In the major proportion of children the level of ioduria ranged from 50 up to 100 mcgrm/l, the median value for the group of children as a whole came up to 62.9 mcgrm/l. According to results of the studies made on goiter rates among children and on the level of urine excretion of iodine, the population are in want of bodily iodine, and Kiev falls in to a zone of mild iodine deficiency.

[Clinical significance of urinary albumin excretion in patients with essential hypertension]. / Klinicheskoe znachenie ékskretsii al'bumina s mochoi u bol'nykh gipertonicheskoi bolezn'iu.

In the studies made, the role of microalbuminuria as a diagnostic marker of greater load of essential hypertension in the examined patients has been ascertained.

Iodine nutrition and the risk from radioactive iodine: a workshop report in the chernobyl long-term follow-up study.

The major fallout of radionuclides from the nuclear power station accident at Chernobyl on 26 April, 1986, occurred in regions of Ukraine and Belarus that are believed to be moderately deficient in dietary iodine. On 17 November, 2000, in conjunction with the Ukraine-Belarus-USA study of developing thyroid disease in a cohort of individuals exposed as children, a workshop was held to review what is known about iodine nutrition in the region, how this might influence the risk of thyroid tumor formation from radioiodine, and whether and how iodine nutrition should be monitored in this long-term project. This report is a summary of the workshop proceedings. Although no precise information about iodine intake in 1986 was found, the prevalence of mild goiter in the region's children suggested iodine deficiency and urinary iodine measurements begun in 1990 indicated that mild to moderate deficiency existed. Increased thyroid iodine uptake and increased thyroid size in 1986 resulting from iodine deficiency would have had counteracting influence on the thyroid radiation dose and knowledge of these parameters is required for dose reconstruction. More problematic is the possible role of iodine deficiency in the years following the accident. Theoretically, the resulting increase in thyroid cellular activity might increase the risk of tumorigenesis but experimental or clinical evidence supporting this hypothesis is meager or absent. Despite this limitation it was considered important to monitor iodine nutrition in the cohort subjects in relation to their place of residence and over time. Methods to accomplish this were discussed.

Prevalence of diabetes mellitus and its complications in the Ukraine.

Analysis of the prevalence of insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) in various climato-geographic and administrative regions of the Ukraine was performed. The prevalence of diabetes mellitus (DM) complication in the west and north zones of the Ukraine was studied. The role of prophylactic measures in decreasing the number of complications was elucidated. The statistical reports from the specialized endocrinologic institutions of the Ukraine were analysed in the Laboratory of Epidemiology of Endocrine disease of Institute and results from 3450 and 673 diabetic patients in the west and north zone of the Ukraine were used, respectively. In various administrative regions of the Ukraine the prevalence of IDDM significantly varied from 1740 to 3813 patients per 1 million population. Significant differences in the prevalence of NIDDM were found. Generally in the west zone of the Ukraine the prevalence of DM was less than that of average in the Ukraine. Angiopathy of the lower extremities, neuropathy and retinopathy were registered in 92, 24, and 21% of diabetes cases in the west zone, respectively. Prophylactic measures directed at a decrease in patient weight, the normalization of metabolism, arterial pressure and the elimination of pernicious habits promoted a decrease in the number of complications.

Virulent non-capsulate Yersinia pestis variants constructed by insertion mutagenesis.

Insertion mutagenesis with the help of the plasmid pFS23 was used to generate Yersinia pestis fra mutants. The results of pFra- strain production under non-selective conditions suggested that such Y. pestis variants may be generated in natural plague foci at high frequency and may participate in supporting the epizootic process. Present data suggest that the reduction of virulence in Fra- strains reported by the majority of investigators was connected with the use of Y. pestis variants carrying additional unidentified mutations. It was shown that the loss of the ability to produce capsular antigen (FI) alone or in combination with absence of murine toxin production did not lead to an increase in LD50 absolute values. Simultaneous loss of these two virulence determinants did not influence the duration of survival of the infected animals. However, absence of only FI antigen production in the infecting strain resulted in prolonged survival of the infected animals. Conversion of plague infection from acute to chronic form is probably dependent on the animal host species and the Y. pestis parent strain subjected to mutagenesis.

[The importance of the pyruvate test for the early detection of diabetes mellitus in a mass examination of the population]. / Znachenie piruvatnogo testa dlia rannego vyiavleniia sakharnogo diabeta pri massovom obsledovanii naseleniia.

The levels of carbohydrate metabolism were examined in 329 inhabitants of Lvov (age: from 6 to 68 years). Determination of the pyruvate level, pyruvate dehydrogenase activity of the blood on the 120 minute after carbohydrate meal allowed to establish in healthy persons four-modal levels of distribution of the content of pyruvate in the capillary blood. These levels correspond to normal tolerance to glucose, increased glucose tolerance (hyperinsulinism), potential glucose tolerance disorders (diabetic type). The authors propose a chart of prophylactic evaluation of glucose tolerance.