Quantification of the radiosensitization effect of high-Znanoparticles on photon irradiated cells: combining Monte Carlo simulations and an analytical approach to the local effect model.

In vitroexperiments show significant reduction in the survival fraction of cells under irradiation treatments assisted with high-Znanoparticles (NPs). In order to predict the radiosensitization effect of NPs, a modification of the local effect model (LEM), in which the energy deposition from NPs is assessed by Monte Carlo (MC) radiation transport codes, has been employed in the past. In this work, a combined framework that splits the consideration of the radiosensitization effect into two steps is proposed. The first step is the evaluation of the radial dose distribution (RDD) around a single NP ionized by a photon beam with given energy spectrum using MC simulation. Thereafter, an analytical approach based of the LEM and the calculated RDD is used for evaluation of the average dose and the average number of lethal lesions in a cell target due to a set of ionized NPs. The explicit expressions were derived for the case of a spherical cell target and the RDD describing by the power law function. RDDs around gold NPs (GNPs) of different radii were simulated using the MC technique and fitted by a power law function. The fitted RDD and the derived expressions were applied for calculation of the survival curves and relative biological effectiveness of a spherical MDA-MB-231 cell loaded with GNPs and irradiated with monoenergetic photons of 10-150 keV. The proposed framework provides a practical alternative to time-consuming MC simulations, enabling the assessment of the response of cell cultures to an irradiation treatment assisted with NPs for a wide variety of cell geometries, NP distributions and irradiation schemes.

[Nutrition of the elderly: sociological aspect.]

The paper belongs to the general field of nutritional sociology. It presents the data of a study of everyday nutrition practices of older people. Based on an empirical study, held in St. Petersburg and the Leningrad Oblast Region (telephone survey of 516 respondents; in-depth interviews), information is given on the following thematic blocks: the purchase of food items by older people; proper nutrition, the consumption of healthy foods; eating out and tastes; alcohol consumption and unhealthy eating habits; diets and dietary restrictions, physical activity; visiting cafes and restaurants; daily menus and gastronomic preferences. As part of the discussion, a gastronomic portrait of an elderly person is presented. A comparative analysis of nutrition practices of the elderly, young people and middle-aged people is held. The main problems in the nutrition of the elderly are identified; ways to solve them are outlined as well.

Nanoscale dose deposition in cell structures under X-ray irradiation treatment assisted with nanoparticles: An analytical approach to the relative biological effectiveness.

In this study, an analytical model for the assessment of the modification of cell culture survival under ionizing radiation assisted with nanoparticles (NPs) is presented. The model starts from the radial dose deposition around a single NP, which is used to describe the dose deposition in a cell structure with embedded NPs and, in turn, to evaluate the number of lesions formed by ionizing radiation. The model is applied to the calculation of relative biological effectiveness values for cells exposed to 0.5mg/g of uniformly dispersed NPs with a radius of 10nm made of Fe, I, Gd, Hf, Pt and Au and irradiated with X-rays of energies 20keV higher than the element K-shell binding energy.

[Influence of indoinetophene on the antiradiation properties of indralin].

Radioprotective properties of indralin were studied at its combined administration with indometophene in the periods optimal for each preparation before acute radiation exposure. Animals were subjected to total radiation on the IGUR installation (137Cs): mice of the strain (CBA x C57B1) F1 at a dose of 9 Gy (LD100/30), purebred dogs--4 Gy (LD100/45). It was established in the experiments on mice that considerable radioprotective effect can be obtained by the use of indralin at a dose that is half the optimal radioprotective dose if it is applied against the background of indometophene administered at its optimal radioprotective dose four days before. The survival of mice increased on the average by 30-35% and provided the same effect of protection as a single indralin at the optimal radioprotective dose (100 mg/kg). The survivability of dogs after the combined application of the two radioprotectors makes up 43% against 14% after application of only indralin at a dose of 5 mg/kg (half the optimal radioprotective dose). Indometophene, along with strengthening the antiradiation activity of indralin at the ineffective (half the optimal) dose, allows the reduction of its undesirable postradiation effects in the hemopoietic tissue. The important role in the mechanism of the antiradiation activity of indometophene and indralin belongs to the increased ribonucleotide reductase activity and induction of the ribonucleotide synthesis that provides effective reparation of the damage to the DNA of the cells in radiosensitive tissues and organs as a result of administration of protective doses of radioprotectors at the optimal doses before radiation exposure.

[Indometofen causes biochemical changes in the blood cells characteristic for a radioresistant state of the body]. / Indometofen vyzyvaet v kletkakh krovi biokhimicheskie izmeneniia, kharakternye dlia radiorezistentnogo sostoianiia organizma.

The DNA and RNA contents, RNA/DNA ratio, and spontaneous and latex-induced oxidant activity indices of the whole blood were studied in the nitroblue tetrazolium test of mono- and polymorphonuclear blood leucocytes of intact dogs after injection of lipopolysaccharide pyrogenal. Significant changes in the above parameters were revealed for radioresistant (survived) and radiosensitive (lost) animals exposed to a subsequent prolonged gamma irradiation with a lethal dose of 7.64 Gy (LD75/45). Peroral introduction of 30 mg/kg indometofen (an indole analog of tamoxifen), which is a potential radioprotector, to dogs increased the survival rates of the irradiated dogs up to 93% and aided in the adaptive biochemical changes in the nuclear cell compartment of blood to induce a radioresistant status of the organism.

[The role of the vasoconstrictor effect in realizing the radioprotective properties of indralin in experiments on dogs]. / Rol' vazokonstriktornogo éffekta v realizatsii protivoluchevykh svoistv indralina v opytakh na sobakakh.

In the experiments on dogs, the role of a pharmacological circulatory hypoxia in the mechanism of radioprotective effect of indraline and mexamine was studied. Angiography revealed 20-40% vasoconstriction of major arteries of legs of animals, of pelvis and abdomen caused by mexamine (10 mg/kg) and the absence of a significant effect of indraline. Disruption of a regional blood circulation in the marrow and spleen (40-50% and 70-80%, respectively) was caused by indraline to the same extent as by mexamine. For indraline, a decrease in pO2 in the marrow was about 50%. With these hemodynamic disturbances, indraline showed 80 to 100% radioprotective effect, while mexamine was inefficient. Acute hypoxic hypoxia (5-7% O2) increased a post-radiation survival rate for dogs by 40%. The radioprotective effect of indraline was blocked by tropaphen and reduced in cases of breathing with pure oxygen. Splenectomy has no effect on radioprotective properties of indraline. Thus, a hypothesis of the mechanism of a radioprotective effect of alpha-adrenomimetics was proposed.

[Width of radiation protective effects of indralin in comparative studies using different animal species]. / Shirota radiozashchitnogo deistviia indralina v sravnitelnykh issledovaniiakh na razlichnykh vidakh zhivotnykh.

In the experiments on mice, rats, hamsters, guinea pigs, dogs and Macaca Rhesus ED50, the width of radioprotective effect of indralin from alpha-adrenomimetics was investigated. It was made an estimate by ED50, LD50 and therapeutic index (TI): ED50/LD50. ED50 of indralin i.m. on mice is 21.9 (16.2-29.4) mg/kg, on guinea pigs --28.8 (17.0-49.0) mg/kg, on hamsters --50.7 (42.9-59.8) mg/kg and on dogs --6.0 (4.3-8.3) mg/kg. TI of indralin i.m. for same animals is correspondingly equal to 23.7 (15.3-36.5), 25.6 (13.7-47.4), 17.8 (14.8-24.1) and 31.1 (20.6-47.3). TI of indralin p.o. for rats and dogs is close to 18.2 and 23.7. Under the equal conditions TI of cystamine for mice, rats (i.p.) and dogs (i.v.) is respectively 3.3 (2.82-3.70), 2.1 (1.57-2.82) and 1.22. T50 of the elimination of indralin on mice (100 mg/kg i.p. and i.m.) for toxicologic properties measured circa 5-10 min. Under the conditions of repeated application in 30-60 min indralin desensitization to toxic doses happened as the rise of LD50 by 15-30%. T50 of the elimination of indralin in optimum doses for the pharmacodynamic of radioprotective effect is 19.3 (13.3-28.0) min on mice, --19.2 (15.3-25.9) on hamsters, --26.9 (20.4-35.5) on rats and --40.2 (30.5-53.1) min on dogs. In the transition from the experiment on mice to dogs twofold rise of T50 of the elimination of indralin doesn't combine with adequate increase the toxicity of the radioprotector. Pathophysiologic foundation of distinctions between aminothiols and radioprotector realizing the effect through cell receptor in the width of radioprotective effect is discussed.

[The molecular mechanisms of the action of the radioprotector indometafen. The biosynthetic and bioenergetic aspects]. / Molekuliarnye mekhanizmy deistviia radioprotektora indometafena. Biosinteticheskie i bioénergeticheskie aspekty.

It was shown that indomethaphen (IM) is capable of stimulation of the synthesis of DNA, RNA, and protein precursors in mice. The IM-induced elevated level of the ribonucleotide reductase activity and, hence, deoxyribonucleotide pool in the spleen at the moment of irradiation and during the early postradiation period provides for complete DNA repair. As a result, the damaging effect of ionizing irradiation is weakened. At later stages (2-20 days) IM activates protein and DNA synthesis leading to the recovery of the ribonucleotide reductase activity in the spleen, on increased content of Fe3(+)-transferrin, cytochrome-c-oxidase, and ferrosulfuric components of the mitochondrial electron transport chain, and increased potential of the detoxication system due to the elevated content of cytochrome P-450. IM stimulates ATP synthesis. Thus, IM enhances compensatory-restorative reactions of the cell systems, more pronounced in the spleen than in the liver.

[Studies of the radiation-protective effects of indralin on the hematopoietic system of different species of animals]. / Issledovanie radiozashchitnogo éffekta indralina na krovetvornoi sisteme u razlichnykh vidov zhivotnykh.

The experiments were made on mice, guinea pigs and dogs. Radioprotector indraline increased radioresistant state of hematopoietic stem cells in vivo and in vitro, decreased the amount of post-radiation chromosome aberrations in marrow, induced more early and intensive post-radiation proliferative repair of marrow and spleen, faster regeneration of the initial amount of leukocytes, thrombocytes and erythrocytes in blood of mice, guinea pigs and dogs. Antiradiation efficiency of indraline in hematopoietic system is equal to 1.5-2 by FMD. Radioprotective mechanism of indraline effect on hematopoietic system is discussed.

[Mechanism of the radiation-protective effect of indralin]. / K mekhanizmu protivoluchevogo deistviia indralina.

Pharmacological test demonstrated that radioprotective activity of indralin occurs by interaction with alpha-adrenoreceptor. Radioprotective effect of indralin decreased by alpha-adrenoblocker, aminazine and theophylline. Normobaric hyperoxia during irradiation reduced radioprotective effect of indralin in doses about ED50. In experiment with mice and rats it was shown that indralin induced acute hypoxia, impaired oxygen consumption and heat production by 30-46%, spleen bloodflow to 26.3% of control level, rectal temperature by 1.5-2 degrees C (mouse). After 30-min indralin raised resistance of mice to hypoxic hypoxia that is believed due to rapid development of biochemical adaptive process in hypoxic cells.

[The effect of the potential antiradiation agent compound HC-1539 on reparative DNA synthesis induced by the damaging action of the chemical mutagen N-nitroso-N-methylurea and radiation]. / Vliianie potentsial'nogo protivoluchevogo sredstva--soedineniia HC-1539--na reparativnyi sintez DNK, indutsiruemyi povrezhdaiushchim deistviem khimicheskogo mutagena N-nitrozo-N-metilmocheviny i izluchenii.

The influence of NS-1539, a potential anti-irradiation agent and indole analogues of tamoxifen on the DNA repair synthesis in the bone marrow and lymphocytes of peripheral blood was studied. It was found that the DNA repair processes from damages caused by chemical mutagen N-nitroso-N-methylurea or physical factor UV-irradiation in the bone marrow cells after the NS-1539 protection of mice as well as in lymphocytes of peripheral blood of human donors were enhanced. The enhancing of DNA repair synthesis was seen not earlier than 18 hours after the NS-1539 injection to mice in vivo or when NS-1539 was added to lymphocyte suspension in vitro and observed up to the third day. This period of time coincides with the time of formation of radioresistance of organism under the influence of this agent as well as with the time of realization effects of steroid hormones on target cells.

[The molecular aspects of the action of the radioprotector indralin]. / Molekuliarnye aspekty deistviia radioprotektora indralina.

The effect of indralin on the metabolic parameters in peripheral blood and organs of irradiated dogs and mice have been studied by EPR, NMR and radioisotope methods. It has been shown that indralin stimulated biosynthesis of DNA precursors as well as of DNA and proteins in the organs and stabilized the rate of ATP and glycogen synthesis. As a result indralin reduced considerably the changes produced by gamma-irradiation on the macromolecular biosynthesis during the early post-irradiation period. Indralin has induced marked favorable changes in the rate of macromolecular synthesis, normalized the ATP and glycogen content, induced ribonucleotide reductase activity and increased the Fe(3+)-transferrin content during development of compensatory-repair response in the irradiated animals. Indralin prevented hyperdevelopment of the repair response and its breakdown due to radiation-induced exhaustion of viability of many important cellular and body systems after irradiation with lethal doses.

[The dose dependence of the development of compensatory-restorative body reactions to irradiation. The EPR method]. / Dozovaia zavisimost' razvitiia kompensatorno-vosstanovitel'nykh reaktsii organizma pri obluchenii. Metod EPR.

The study deals with the mechanism of organism's adaptive responses to the effect of radiation in widely ranging dose. Post-irradiation metabolic changes were evaluated in canine blood as well as in murine blood, spleen, bone marrow and liver using the EPR spectroscopy. It was shown that the dynamics of changes in transferrin and ceruloplasmin pools and ribonucleotide reductase activity were phase-dependent with the maxima at the 2nd, 6th and 10-12th days after irradiation. Such dynamics was observed at various irradiation doses applied. The data allow us to suggest that the nonspecific compensatory--adaptive reactions of organisms develop as the response to irradiation. The dose-response function of the reaction intensity was found to be linear. The shape of the dose-response curve indicates that the minimum response of organism depends on the dose linearly up to 3.2 Gy (for dogs) as well as the maximum one. However, in the case of low-dose irradiation (0.25 or 0.5 Gy) there were deviations of maximum responses from the linearity, i.e. the amplification of the amplitude of compensatory adaptive reactions. These effect were shown to be dependent upon initial individual characteristics of animal blood and to be related to the "depressed" or "activated" state of organism prior to irradiation. The ribonucleotide reductase activity was measured in bone marrow and spleen of animals by the EPR method. The nature of non-repairable DNA damage is discussed in view of the inactivation of ribonucleotide reductase.

[Mathematical modelling of perorally induced immunological tolerance]. / Matematicheskoe modelirovanie peroral'no indutsirovannoi immunologicheskoi tolerantnosti.

A mathematical model of the mechanism of development of orally induced immunologic tolerance has been suggested. The model presents a system of differential non-linear equations, and it is realized as a program in FORTRAN. The model describes primary and secondary immune responses, reflects the main features of the immune system response to antigen intake with food. The immune system model response to varying doses and frequency of the antigen intake with food has been studied. It has been established that repeated administration of small doses of the food antigen leads to a deeper tolerance due to lower stimulation of the immune system. The existence of optimal tolerogenic doses of the food antigen has been proved. Qualitative changes in the immune system response to the food antigen have been recorded in case of increased permeability of the intestinal wall.

[Radioprotective effectiveness and toxicity of 4,5-disubstituted tryptamines]. / Radiozashchitnaia éffektivnost' i toksichnost' 4,5-dizameshchennykh triptaminov.

In experiments on mice a study was made of different substituents in the 4th position of the indole ring of 5-methoxytryptamines (5-MOT) on toxicity and radioprotective efficiency of the compounds of this class. It was shown that the administration of the amino-group to a mexamine molecule increased the preparation toxicity; the nitro-group somewhat diminished the toxic properties, and the acetylamino group did not change 5-MOT toxicity. A 5-MOT derivative with a nitro group possessed the strongest radioprotective action. The radioprotective efficiency of these compounds persisted for 1-2 h.