[Nuclear activation analytical methods and X-ray fluorescence analysis in application to determination of pollutants and trace elements in food and for studying biokinetics of nanoparticles].

For assurance of food quality and safety, it is necessary to control routes of food pollutants, including toxic trace elements in all stages of handling, ranging from the production of agricultural products, including the processing, storage, transportation, and ending with cooking and consumption. For this control the nuclear activation analytical methods (NAAMs) and X-ray fluorescence analysis (XRFA) are studied and developed for the detection of chemical elements in different environments. NAAMs involve two stages: the activation of nuclear isotopes with thermal neutrons or fast charged particles and gamma spectrometry. XRFA technique is based on detecting characteristic fluorescent X-rays of elements. Interest in these methods is due to the relative simplicity of the analysis, the ability to provide the required sensitivity and accuracy of detection of chemical elements. The main objective of the research work is to demonstrate the potential of these techniques for controlling the quality and safety of food products and for research of trace elements' biokinetics with achieving the required accuracy (no worse than 15%) and sensitivity (below the permissible concentrations of harmful substances) and to prepare them for the practical application. Both methods complement each other in terms of expanding the list of detected chemical elements and choosing the best option in the analysis depending on the type of the test sample and readiness of technical means. In addition to the analysis of NAAMs and XRFA capabilities two different but partly connected research options were performed using NAAMs: 1) control of food quality and safety; 2) research of biokinetics of nanoparticles (NPs), incoming with food and water into laboratory animals with special attention to overcoming biological barriers. One of the important result is the demonstration of overcoming the blood/brain barrier by silver NPs when they are ingested into the animals with food or water, and possibility of their accumulation in brains with extremely low excretion (≈6% per month).

[Bioaccumulation of silver and gold nanoparticles in organs and tissues of rats by neutron activation analysis].

Bioaccumulation of silver (Ag) and gold (Au) nanoparticles (NPs) with mean sizes of 6 nm and 35 nm, respectively, has been studied after their intragastric administration to rats at a dose of 100 µg/kg of body weight for 28 or 14 days. The organs and tissues (liver, kidney, spleen, heart, gonads brain, and blood) were subjected to thermal neutron activation, and, then, the activity of the 110mAg and 198Au isotopes generated was measured. The NPs of both metals were detected in all biological samples studied, the highest specific weight and content of Ag NP being found in the liver, and those of Au being found in kidneys of animals. The content of Ag NPs detected in the brain was 66.4 ± 5.6 ng (36 ng/g tissue), no more than 7% ofthese NPs being localized in the lumen of brain blood vessels. The content of Ag and Au NPs found in organs and tissues of rats could be regarded as nonhazardous (nontoxic) in accordance with the known literature data.

[The methods of assessment of health risk from exposure to radon and radon daughters].

The critical analysis of existing models of the relationship dose-effect (RDE) for radon exposure on human health has been performed. Conclusion about the necessity and possibility of improving these models has been made. A new improved version ofthe RDE has been developed. A technique for assessing the human health risk of exposure to radon, including the method for estimating of exposure doses of radon, an improved model of RDE, proper methodology risk assessment has been described. Methodology is proposed for the use in the territory of Russia.

Transfer of Silver Nanoparticles through the Placenta and Breast Milk during in vivo Experiments on Rats.

Silver nanoparticles (NPs), widely used in the manufacture of various types of consumer products and for medical applications, belong to novel types of materials that pose potential risks to human health. The potential negative effects of the influence of these NPs on reproduction are insufficiently researched. A quantitative assessment of the transfer of metallic silver nanoparticles through the placenta and breast milk was carried out during an in vivo experiment. We used 34.9 ± 14.8 nm in size silver NPs that were stabilized by low-molecularweight polyvinylpyrrolidone and labeled with the (110m)Ag radioactive isotope using thermal neutron irradiation in a nuclear reactor. [(110m)Ag]-labeled NPs preparations were administered intragastrically via a gavage needle to pregnant (20(th) day of gestation) or lactating (14-16th day of lactation) female rats at a dose of 1.69-2.21 mg/kg of body weight upon conversion into silver. The accumulation of NPs in rat fetuses and infant rats consuming their mother's breast milk was evaluated using a low-background semiconductor gamma-ray spectrometer 24 and 48 hours following labeling, respectively. In all cases, we observed a penetration of the [(110m)Ag]-labeled NPs through the placenta and ther entry into the mother's milk in amounts exceeding by 100-1,000 times the sensitivity of the utilized analytical method. The average level of accumulation of NPs in fetuses was 0.085-0.147% of the administered dose, which was comparable to the accumulation of the label in the liver, blood, and muscle carcass of adult animals and exceeded the penetration of NPs across the hematoencephalic barrier into the brain of females by a factor of 10-100. In lactating females, the total accumulation of [(110m)Ag]-labeled NPs into the milk exceeded 1.94 ± 0.29% of the administered dose over a 48 h period of lactation; not less than 25% of this amount was absorbed into the gastrointestinal tract of infant rats. Thus, this was the first time experimental evidence of the transfer of NPs from mother to offspring through the placenta and breast milk was obtained.

[The Russian and international standards of age-related allocation of population for medical statistics, medical demographic analysis and risk assessment].

The actual European standard of age-related allocation of population in action is largely implemented in medical demographic studies of international (WHO etc.) and national organizations. The Rosstat also implements this standard in its demographic yearbooks and other publications. The standard is applied in computing the standardized indicator of population mortality in different countries and territories and also in assessing risk factors. The standard is based on the idea of evaluating mortality with an integrated standard in order to compare between different countries mortality of population, genders and calendar years. The analysis of results of testing calculations of values of standardized indicator of mortality of population of Russia and EU countries applying European standard in action revealed serious shortcomings. For example. unfounded overstating of values of standardized indicator, of mortality for males and its understating for females artificially increases already wide difference in mortality of males and females in the Russian Federation. The calculation on this background of standardized indicator of mortality for particular causes of death results in erroneous values due to neglected concurrence of risks. Because of necessity of improvement of standard a new concept of development of national and international standards is proposed. This concept is based on application of notion of balanced age-related allocation of population and its number values.

[Development of national and international standards of population age distribution for medical statistics, health-demographic analysis and risk assessment].

The current European standard (CES) and the World population age distribution standard is widely used in medical and demographic studies, performed by international (WHO, etc.) and national organizations. The Russian Federal Service of States Statistics (RosStat) uses CES in demographic yearbooks and other publications. The standard is applied in calculation of the standardized mortality rate (SMR) of the population in different countries and territories. Risk assessment is also used CES. In the basis of the standards there has been laid the idea to assess mortality according to uniform standard, so to get possibility to compare the mortality rate of the population in different countries and regions, different genders and different calendar years. Analysis of the results of test calculations of the values of the SMR for the population of Russia and other countries with the use of current standards has revealed serious shortcomings of the latters and set up the task of improving them. A new concept of the development of standards based on the use of the concept of stable equilibrium of the age distribution of the population and survivorship function is proposed.

[Health risk from ionizing radiation and other harmful sources: assessment methods and practical application].

The modern health risk assessment (HRA) methodology allows the development of the general HRA method applicable to any harmful source (ionizing radiation, harmful chemicals, nanomaterials and others). Specific methods and their simplified versions are developed on the basis of the general method. The main items of this approach to developing HRA methodology (risk indices and calculation formulas, exposure-response dependences, single and extended exposure to a harmful source, risk competition, etc.) are shortly described. The most suitable risk index for elaborating health safety standards (HSSs) and risk comparison on the unique methodological basis in different areas of the human activity are proposed. The approach to the risk standardization (establishment of HSSs and other safety levels) is described. HSSs and other safety levels are sequentially established in this approach according to the scheme: united main universal HSSs --> main branch HSSs --> derivative (secondary) HSSs with practically suitable indices. This approach allows resolution of the actual problem of harmonizing HSSs in different areas of human activity as well as in different countries. The principal role of HRA results in the development and justification of HSSs is shown on the example of developing radiological HSSs.

[The bioavailability of zinc oxide nanoparticles. Study using methods of radionuclide indicators].

Zinc oxide nanoparticles labeled with 65Zn were administered once intragastrically to male Wistar rats. The distribution of radionuclide-marker (65Zn) was measured by gamma-spectrometer in tissue samples of animals the organs through 4 hours, 1, 3 and 5 days after administration, and in the wastes of animals through 1 since 5 days. The data obtained demonstrate for the first time the bioavailability of zinc trace element in the form of its oxide nanoparticles.

[General approach to evaluation, comparison and norm-setting of health risks associated with various environmental factors].

The authors analyze modern approaches to health risk evaluation and establishing safety standards concerning ionizing radiation, chemicals, and other health hazard sources. Some recommendations on general approaches are given. A special individual risk index is offered to make decisions concerning human safety: establishing safety standards and other levels of protection, comparing different health hazard sources, etc. General approach to establishing public and occupational safety standards in terms of this index has been developed.

[Processes of absorption and utilization of glucose in newborn infants with intrauterine hypotrophy]. / Protsessy vsasyvaniia i utilizatsii gliukozy u novorozhdennykh s vnutriutrobnoi gipotrofiei.

Overall 75 neonates with intrauterine hypotrophy (IH) and 19 healthy children were examined for glucose absorption and utilization according to the glucose tolerance test data. IH neonates were revealed to have and increase of glucose absorption and retardation of its utilization. The high blood glucose concentrations seen 2 hours after the test support functional insufficiency of the pancreas in IH.

[Study of the formation of intestinal microflora in newborn infants staying with or separated from their mothers]. / Izuchenie formirovaniia mikroflory kishechnika u novorozhdennykh detei pri sovmestnom i razdel'nom prebyvanii s mater'iu.

In children of the first month of life, the formation of normal intestinal microflora was studied depending on whether they stayed with mothers or alone in the maternity home. Thirty healthy neonates born to young healthy mothers with a history of a favourable course of pregnancy which progressed to the delivery via the natural maternal passages were examined. Intestinal microbiocenosis in the newborn turned out more physiological provided they were placed at the "mother-child" department as compared to that when the newborn stayed alone. Organization of the joint staying of mothers and children in the wards of the maternity home increases the colonization resistance of the newborn, favours normal adaptation and may be one of the factors bringing about the diminution of the rate of pyoseptic diseases in the newborn.

[Effect of chronic intrauterine hypoxia on purine compound metabolism in the erythrocytes of newborn infants in the early neonatal period]. / Vliianie khronicheskoi vnutriutrobnoi gipoksii na obmen purinovykh soedinenii v éritrotsitakh krovi novorozhdennykh v rannem neonatal'nom periode.

The content of purine compounds in red blood cells was measured and compared in 21 neonates with a history of chronic intrauterine hypoxia, depending on the condition at birth and the early period of adaptation. The content of purine compounds in whole blood was measured at the moment of birth and on days 1, 3 and 5 of life. It has been disclosed that the pattern of purine metabolism abnormality in funic red blood cells makes it possible to predict the course of the early period of adaptation. Changes in the content of hypoxanthine and inosine monophosphate appeared to be most remarkable.

[Contents of bioelements in blood of newborn infants with a history of chronic intrauterine hypoxia]. / Soderzhanie bioélementov v krovi novorozhdennykh, perenesshikh khronicheskuiu vnutriutrobnuiu gipoksiiu.

Emission analysis with the use of induced plasma was employed to measure the content of 9 bioelements (potassium, sodium, calcium, magnesium, phosphorus, iron, copper, zinc and selenium) in the blood serum of 82 neonates with a history of chronic intrauterine hypoxia and in 19 normal children at birth and in the course of early adaptation. It has been shown that the content of bioelements in the blood of normal neonates was marked by a number of characteristic features reflecting to a considerable degree the processes of metabolic adaptation of the children to the intrauterine life. The neonates with a history of hypoxia demonstrated the unbalance of bioelements most pronounced by day 3 of life. The treatment instituted did not make the content of bioelements in the neonates' blood return to normal.

Influence of perinatal hypoxia on purine contents in erythrocytes of newborn infants.

Alterations in the levels of hypoxanthine and some other purine derivatives occurring in the erythrocytes from umbilical cord blood of newborn infants with perinatal hypoxia were examined. Newborn babies were divided into two groups which included infants with favourable (Group 1) and complicated (Group 2) periods of early adaptation. Purine metabolites of erythrocytes were analyzed by isocratic reversed-phase HPLC. It was shown a reciprocal relation between concentrations of hypoxanthine and IMP in erythrocytes of infants from two groups that was expressed in elevation (Group 1) and a fall (Group 2) of hypoxanthine level while in Group 1 the IMP content had a tendency to decrease and Group 2 was characterized by an elevated level of this compound. The alterations in the concentrations of these interrelated metabolites may be due to the effects of hypoxia upon purine metabolism in erythrocytes.