ANALYSIS OF THE EFFICIENCY OF A THERAPEUTIC PROGRAM USING 10.2-MEV FAST NEUTRONS. OPTIMIZATION AND PROSPECTS OF THE DEVELOPMENT OF A PROCEDURE FOR COMBINED PHOTON-NEUTRON THERAPY. THE EXPERIENCE OF THE URAL CENTER FOR NEUTRON THERAPY

The Ural Center for Neutron Therapy performs combined photon-neutron therapy for cancer patients, by applying an ELLIT-80 gamma unit and a NG-12I neutron generator. After modernization of the NG-12I generator, there was a need for redetermination of the relative biological efficiency (RBE) to optimize radiotherapy for the patients. An exotest was used to experimentally estimate RBE according to the survival criteria for stem hematopoietic cells in CBA mice after modernization of the equipment generated by the NG-12I unit with respect to the gamma radiation generated by the ELLIT-80 unit. The investigation established that the RBE factor of NG-12I unit-induced radiation determined as the ratio of equally effective doses (our study used D0) was 1.53 for an acute radiation regimen. During fractional radiation, the RBE factor of neutron radiation was 3.05. That is to say, the total neutron radiation dose replacing 20 % gamma radiation (13 Gy) in the used photon-neutron therapy regimen is 4.26 Gy. The experimental findings have led us to conclude that the previously described neuron therapy regimen may be optimized, by increasing the contribution of neutrons to the total course of radiotherapy in a definite category of patients with radioresistant tumors of the head and neck

Субпопуляционный состав моноцитов крови и костного мозга у больных с хронической сердечной недостаточностью

The aim of the investigation was to evaluate the ratio of classical (CD14++CD16-), intermediate (CD14++CD16+), nonclassical (CD14+CD16+) and transient (CD14+CD16–) monocytes in the blood and bone marrow in patients with chronic heart failure (CHF) against ischemic cardiomyopathy (ICMP).Materials and methods. 17 patients with ICMP and 14 practically healthy donors were observed. The material of the study was venous blood (in patients and healthy donors) and red bone marrow (in patients). In the materials the relative content of different monocytes subpopulations was determined by flow cytometry. The obtained results were analyzed by statistical methods.Results. It is shown that in the blood of patients the proportion of monocytes with the phenotype CD14++CD16- is 57.77 [of 46.35; 79.76]%, CD14++CD16+ – 25.06 [4.96; 42.31]%, CD14+CD16+ 5.05 [4.08; 6.58]% and CD14+CD16- – 6.03 [3.58; 10.89]%; in the bone marrow – 43.44 [40.54; 44.68]%, 0.16 [0; 1.07]%, 0,54 [0.35; 1.07]% and 54,32 [52.83; 56.08]%, respectively, which is different from the content of the data cells subpopulations in the blood (p < 0.05). At the same time, the content of non-classical monocytes in the patients’ blood is 2 times lower than in healthy donors, and the number of other cells varies within the norm.Conclusion. The differentiation of monocytes into 4 subpopulations in patients with CHF occurs directly in the bloodstream, since mainly the classical and transitional monocyte fractions with the prevalence of the latter are present in the bone marrow. Deficiency of non-classical monocytes of blood in CHF is probably associated with a disruption of their extramedullary differentiation.Цель работы – оценить соотношение классических (CD14++CD16-), промежуточных (CD14++CD16+), неклассических (CD14+CD16+) и переходных (CD14+CD16-) моноцитов в крови и костном мозге у больных с хронической сердечной недостаточностью (ХСН) на фоне ишемической кардиомиопатии (ИКМП).Материалы и методы. Обследованы 17 больных ИКМП и 14 практически здоровых доноров. Материалом для исследования служили венозная кровь (у больных и здоровых доноров) и красный костный мозг (у больных). В материале определяли относительное содержание различных субпопуляций моноцитов методом проточной цитометрии. Полученные результаты анализировали статистическими методами.Результаты. Показано, что в крови у больных доля моноцитов с фенотипом CD14++CD16- составляет 57,77 [46,35; 79,76]%; CD14++CD16+ – 25,06 [4,96; 42,31]%; CD14+CD16+ – 5,05 [4,08; 6,58]% и CD14+CD16- – 6,03 [3,58; 10,89]%; в костном мозге – 43,44 [40,54; 44,68]%; 0,16 [0; 1,07]%; 0,54 [0,35; 1,07]% и 54,32 [52,83; 56,08]% соответственно, что отличается от содержания клеток данных субпопуляций в крови (р < 0,05). При этом содержание неклассических моноцитов в их крови в два раза ниже, чем у здоровых доноров, а численность остальных клеток варьирует в пределах нормы.Заключение. У больных ХСН распределение моноцитов на четыре субпопуляции происходит непосредственно в кровотоке, так как в костном мозге обнаруживаются в основном классическая и переходная фракции моноцитов с преобладанием клеток CD14+CD16+. Дефицит неклассических моноцитов в крови при ХСН, вероятно, связан с нарушением их экстрамедуллярной дифференцировки

Субпопуляции моноцитов крови у больных с генерализованной гипоксией

The aim of the work is to establish general regularities and features of differentiation of blood monocytes into 4 subpopulations in diseases associated with circulatory and respiratory hypoxia.Materials and methods. 18 patients with ischemic heart disease (IHD), 12 patients with ischemic cardiomyopathy (ICMP), 14 patients with chronic obstructive pulmonary disease (COPD), 15 patients with newly diagnosed infiltrative pulmonary tuberculosis (PTB) and 12 healthy donors were examined. In whole blood, we determined the relative number of different subpopulations of monocytes by flow cytometry. The results were analyzed by statistical methods.Results. It is shown that an increase in the number of classical (80.56 [77.60; 83.55]%) and the deficit of intermediate (10.38 [9.36; 11.26]%), non-classical (6.03 [5.24; 6.77]%) and transitional (2.14 [1.41; 3.92] %) monocytes in the blood is determined in patients with COPD when compared with the group of healthy donors (p < 0.05). In groups of patients with PTB and IHD, an increase in the number of intermediate monocytes (26.24 respectively [22.38; 42.88] % and 25.27 [15.78; 31.39]%) and the lack of transitional cells (1.77 [1.36; 3.74]% and 2.68 [2.63; 4.0]%) at the normal content of classical and non-classical forms of monocytes (p < 0.05) is detected. In patients with ICMP, a decrease in the number of non-classical monocytes (up to 5.05 [4.08; 6.58]%) is combined with the normal cell content of other subpopulations (p < 0.05). The interrelation between the number of classical and intermediate monocytes in patients with COPD (r = –0.63; p < 0.05), PTB (r = –0.72; p < 0.01), IHD (r = –0.59; p < 0.05), ICMP (r = –0.58; p < 0.05) was established.Conclusion. In COPD associated with generalized hypoxia, an increase in the number of classical monocytes is combined with a deficiency of their other subpopulations in the blood. In PTB and IHD, antigenic stimulation of the immune system mediates accelerated differentiation of monocytes from classical to intermediate forms with a decrease in the number of transitional cells regardless of the etiology of the disease (infectious or non-infectious) and the type of hypoxia (respiratory or circulatory).Цель работы – установить общие закономерности и особенности дифференцировки моноцитов крови на четыре субпопуляции (классические (CD14hiCD16-), промежуточные (CD14hiCD16lo), неклассические (CD14loCD16lo) и переходные (CD14loCD16-)) при заболеваниях, ассоциированных с циркуляторной и дыхательной гипоксией.Материалы и методы. Обследованы 18 больных ишемической болезнью сердца (ИБС), 12 больных ишемической кардиомиопатией (ИКМП), 14 больных с хронической обструктивной болезнью легких (ХОБЛ), 15 больных с впервые выявленным инфильтративным туберкулезом легких (ТБЛ) и 12 здоровых доноров. В цельной крови определяли относительное количество различных субпопуляций моноцитов методом проточной цитометрии. Полученные результаты анализировали статистическими методами.Результаты. Показано, что у больных ХОБЛ определяется увеличение доли классических (80,56 [77,60; 83,55]%) и дефицит промежуточных (10,38 [9,36; 11,26]%), неклассических (6,03 [5,24; 6,77]%) и переходных (2,14 [1,41; 3,92]%) моноцитов в крови по сравнению с группой здоровых доноров (р < 0,05). В группах больных с ТБЛ и ИБС обнаруживается повышение количества промежуточных моноцитов (соответственно 26,24 [22,38; 42,88]% и 25,27 [15,78; 31,39]%) на фоне дефицита переходных клеток (1,77 [1,36; 3,74]% и 2,68 [2,63; 4,0]%) при нормальном содержании классических и неклассических форм моноцитов (р < 0,05). У больных ИКМП снижение численности неклассических моноцитов (до 5,05 [4,08; 6,58]%) сочетается с нормальным содержанием клеток остальных субпопуляций (р < 0,05). Установлена взаимосвязь между численностью классических и промежуточных моноцитов у больных ХОБЛ (r = –0,63; p < 0,05), ТБЛ (r = –0,72; p < 0,01), ИБС (r = –0,59; p < 0,05), ИКМП (r = –0,58; p < 0,05).Заключение. При ХОБЛ, ассоциированной с генерализованной гипоксией, увеличение числа классических моноцитов сочетается с дефицитом остальных их субпопуляций в крови. При ТБЛ и ИБС антигенная стимуляция иммунной системы опосредует ускоренную дифференцировку моноцитов из классических в промежуточные формы при снижении числа переходных клеток вне зависимости от этиологии заболевания (инфекционная или неинфекционная) и вида гипоксии (дыхательная или циркуляторная)

Addressing ecological effects of radiation on populations and ecosystems to improve protection of the environment against radiation: Agreed statements from a Consensus Symposium

This paper reports the output of a consensus symposium organized by the International Union of Radioecology in November 2015. The symposium gathered an academically diverse group of 30 scientists to consider the still debated ecological impact of radiation on populations and ecosystems. Stimulated by the Chernobyl and Fukushima disasters' accidental contamination of the environment, there is increasing interest in developing environmental radiation protection frameworks. Scientific research conducted in a variety of laboratory and field settings has improved our knowledge of the effects of ionizing radiation on the environment. However, the results from such studies sometimes appear contradictory and there is disagreement about the implications for risk assessment. The Symposium discussions therefore focused on issues that might lead to different interpretations of the results, such as laboratory versus field approaches, organism versus population and ecosystemic inference strategies, dose estimation approaches and their significance under chronic exposure conditions. The participating scientists, from across the spectrum of disciplines and research areas, extending also beyond the traditional radioecology community, successfully developed a constructive spirit directed at understanding discrepancies. From the discussions, the group has derived seven consensus statements related to environmental protection against radiation, which are supplemented with some recommendations. Each of these statements is contextualized and discussed in view of contributing to the orientation and integration of future research, the results of which should yield better consensus on the ecological impact of radiation and consolidate suitable approaches for efficient radiological protection of the environment.Keywords: Consensus development, Environmental protection, Populations, Radiation effects, Ecosystems, Ecological risk assessmen

Internal in vitro dosimetry for fish using hydroxyapatite-based EPR detectors

A number of aquatic ecosystems were exposed to ionizing radiation as a result of the activities of the Mayak Production Association in the Southern Urals, former Soviet Union, in the 1950s. Currently, fishes inhabiting contaminated lakes are being actively studied. These investigations need dosimetric support. In the present paper the results of a pilot study for elaborating an EPR dosimeter which can be used for internal dosimetry in vitro are described. Biological hydroxyapatite is proposed here to be used as a detecting substance. More specifically, small hydroxyapatite grains are proposed for use as point detectors fixed in a solid matrix. After having been pelletized, the detectors were covered by Mylar and placed in the body of a fish to be stored in the fridge for several months. Application of the detectors for internal fish dosimetry demonstrated that the enamel sensitivity is sufficient for passive detection of ionizing radiation in fishes inhabiting contaminated lakes in the Southern Urals

Fish otoliths as biological dosimeter: internal dose calculation

Otoliths are organs used by fish for hearing and keeping balance. They consist of biogenic crystals of hydroxyapatite and do not contain any living cells. Upon exposure to ionizing radiation, otolith hydroxyapatite accumulates radiation-induced stable CO radicals whose amount is proportional to absorbed dose. In electron paramagnetic resonance (EPR) dosimetry, carbonate ions are registered and, hence, the total accumulated dose in the fish otolith can be quantified. Therefore, otoliths can be used as individual fish dosimeters to support radiobiological and radioecological studies. An important aspect of otolith-based EPR dosimetry on fish from contaminated water bodies is the potential presence of bone-seeking Sr. Consequently, cumulative absorbed doses measured with EPR in otoliths may reflect the superposition of internal exposure to Sr/ Y and external exposure due to radionuclides circulating in soft tissue of the fish as well as due to environmental contamination. The objective of the present study was to develop a method that allows for an assessment of the contribution of Sr to the total dose in otolith. The method has been tested using otoliths from seven fish taken from reservoirs located in the Southern Urals contaminated with radionuclides including Sr. It has been shown that dose to otoliths is largely determined by Sr in the hydroxyapatite. The internal dose component can be calculated using activity concentration-to-dose conversion factors, which vary slightly in the range of 2.0-2.8 × 10  Gy year per Bq g depending on fish species and age. Internal doses to fish from water bodies with different levels of Sr contamination were calculated in the range from 2 mGy to ~ 200 Gy. External dose contribution was derived for two fish only to be about 100 and 40 Gy. It is concluded that EPR dosimetry on fish otoliths is a promising tool when external exposure prevails or is comparable to internal exposure due to Sr

Otoliths as object of EPR dosimetric research

Otoliths are the organs which fish use for hearing and keeping balance. Otoliths are the most calcified tissues in the fish body. In contrast to bones, otoliths are not affected by remodeling and, therefore, they are expected to accumulate any dose from ionizing radiation during lifetime. Therefore, EPR dosimetry with fish otoliths could be an important tool for dose reconstruction in radiobiology and radioecology. It could also provide useful information remediation actions to de-contaminate waterbodies. Consequently, in the present study, otoliths of three contaminated fish species (roach (Rutilus rutilus), pike (Esox lucius) and perch (Perca Fluviatilis)) were examined with Electron Paramagnetic Resonance (EPR) spectroscopy. The fish were caught at storage reservoirs of liquid radioactive waste from Mayak PA and from the upper reach of the Techa River, which have been contaminated with different levels of radionuclide activity concentrations. It is shown that the radiationinduced EPR signal of otolith is stable and characterized by a linear dose response. However, the slope of the calibration curve (corresponding to the radiation sensitivity of the material) is not the same for different species; this may be caused by differences in mineralization. The reconstructed doses were found to be in the range from undetectable (in fish from the upper stream of the Techa River) up to 265 Gy (in roach from the most contaminated waterbody). In parallel, otoliths were measured with beta-counter to detect Sr-90/Y-90. Samples were also tested on the presence of alpha-emitters, but no alpha activity above background could be detected. However, a significant activity concentration of Sr-90 was detected (from 1 x 10(1) to 2 x 10(4) Bq/g). The EPR doses measured correlated with the Sr-90 activity concentration measured in the otolith samples