NMR spectroscopy based metabolic profiling of urine and serum for investigation of physiological perturbations during radiation sickness

Radiation accidents are rare events that induce radiation syndrome, a complex pathology which is difficult to treat. In medical management of radiation victims, life threatening damage to different physiological systems should be taken into consideration. The present study was proposed to identify metabolic and physiological perturbations in biofluids of mice during different phases of radiation sickness using ¹H nuclear magnetic resonance (¹H NMR) spectroscopy and pattern recognition (PR) technique. The ¹H NMR spectra of the biofluids collected from mice irradiated with 5 Gray (Gy) at different time points during radiation sickness were analysed visually and by principal components analysis. Urine and serum spectral profile clearly showed altered metabolic profiles during different phases of radiation sickness. Increased concentration of urine metabolites viz. citrate, α ketoglutarate, succinate, hippurate, and trimethylamine during prodromal and clinical manifestation phase of radiation sickness shows altered gut microflora and energy metabolism. On the other hand, serum nuclear magnetic resonance (NMR) spectra reflected changes associated with lipid, energy and membrane metabolism during radiation sickness. The metabonomic time trajectory based on PR analysis of ¹H NMR spectra of urine illustrates clear separation of irradiated mice group at different time points from pre dose. The difference in NMR spectral profiles depicts the pathophysiological changes and metabolic disturbances observed during different phases of radiation sickness, that in turn, demonstrate involvement of multiple organ dysfunction. This could further be useful in development of multiparametric approach for better evaluation of radiation damage as well as for medical management during radiation sickness.     

Comparative investigation of structural and gene somatic mutations in workers of nuclear chemical plants. I. A study of stable and unstable chromosome aberrations

A study of frequency of unstable chromosome aberrations in 50 workers of nuclear chemical plants in remote period after beginning or finishing professional contact with ionizing radiation was carried out. 14 persons from this cohort were mainly whole-body exposed to external gamma-rays and 36 were exposed to combined external and internal radiation from incorporated Pu nuclides. In results of this irradiating practically every subject had a chronical radiation sickness. In the 1-st group the frequency of unstable aberrations varied from 0.2 to 3.6 per 100 cells and exceeded reliably control level in 5 persons. In the 2-nd group the frequency of unstable aberrations varied from 0 to 11.6 per 100 cells and exceeded reliably control level in 20 examined workers. The FISH study of frequency of stable aberrations was performed in 13 subjects who were exposed to combined external and internal radiation. Total frequency of complete and incomplete translocations varied from 0.6 to 18.5 aberrations per genome per 100 cells and reliable exceeded control level in 9 subjects. Non-random participation in exchange rearrangements (translocations) was revealed for used set of chromosomes (2, 3 and 8).     

The distribution of radiation-induced breaks in the chromosomes of irradiated subjects

Distribution of radiation-induced breakpoints in chromosomes and its bands in persons recovered from acute radiation sickness and personnel from Chernobyl NPP were investigated using G-banding staining. The frequency of damaged bands and breakpoints in groups exposed to radiation was significantly higher as compared with the control group. It was shown that in exposed to radiation persons damage depends on its length. Most frequently damaged bands in the observed groups were determined. The G-negative bands and telomeres of chromosomes were more sensitive to radiation.     

Erythrocyte elastic and mechanical properties and mechanism of their change during irradiation

A decrease in erythrocyte deformation, which was maximum at the height of radiation sickness, was registered as early as 1-3 days following 6 Gy irradiation of rats. The aggregation of erythrocytes increased during the latent period of radiation sickness then sharply decreased. The role of the observed changes in radiation sickness then pathogenesis is discussed. It is established that they are associated with the altered fatty acid composition of the lipid phase of erythrocytic membranes, on the one hand, and with the disturbances in its ionic permeability, on the other.     

Effect of ionizing radiation on the functional state of the vascular-thrombocytic component of the hemostasis system

The influence of ionizing radiation (gamma-rays 60Co) on aggregation activity of the vascular wall and functional (aggregation) platelet activity was studied in the course of the development of acute radiation sickness. The decrease in the aggregation properties of the vascular wall and high functional activity of platelets were inversely proportional, correlating with the periods of acute radiation sickness development and depending on the radiation dose. It is suggested that the changes detected may play a role in the pathogenesis of the development of the postirradiation thrombohemorrhagic syndrome.     

核辐射对大深度快速上浮脱险致减压病大鼠相关指标的影响*

目的: 探讨不同剂量核暴露后不同时间对大深度快速上浮脱险致减压病大鼠模型的发病率、死亡率及损伤指标的影响。方法: 80只SD雄性大鼠,随机分成空白对照组、脱险对照组和6个干预组(4 Gy辐射后4 h脱险、6 Gy辐射后4 h脱险、12 Gy辐射后4 h脱险、4 Gy辐射后8 h脱险、6 Gy辐射后8 h脱险、12 Gy辐射8 h后脱险),每组10只。干预组动物先采用不同剂量γ射线外照射(4、6、12 Gy),再进行大深度快速上浮脱险实验(最大加压深度150 m),分析大鼠肺W/D、脾指数及血浆IL-1β的变化。结果: 与脱险对照组比较,核辐射后脱险大鼠的减压病发病率及死亡率明显上升。4 Gy、6 Gy照射4 h后上浮脱险的大鼠发病率和死亡率较照射8 h后高。12 Gy辐射后4 h及8 h脱险大鼠的减压病的发病率及死亡率均比低剂量照射组明显增高,死亡率尤其明显。和发病率及死亡率的变化相一致,肺组织湿/干比、肺组织病理损伤程度、脾指数下降也表现同样的变化趋势:较低剂量(4 Gy、6 Gy)辐射后4 h改变明显,8 h改变不明显,而高剂量(12 Gy)辐射后4、8 h均变化明显。和空白对照组及脱险对照组相比较,各辐射后脱险组的血浆IL-1β浓度均显著上升。结论: 核辐射引起放射性肺损伤、免疫功能下降及血浆炎症因子浓度升高,会增加大鼠快速上浮脱险致减压病的风险。     

Combined effect of normobaric hyperoxia and vibration on the radiosensitivity of animals

In experiments with hybrid mice (CBA X C57B1)F1 and F2(CBWA), a study was made of the combined effect of normobaric hyperoxia and vibration on sensitivity of the organism to gamma-radiation. A single and protracted (for 5 days, daily) vibration before irradiation aggravated acute radiation sickness. A modifying effect of hyperoxia on the development of the intestinal form of radiation sickness was the same as that observed under the effect of vibration. In the experiments with tetrahybrids, the combined effect of the two factors aggravated drastically the intestinal syndrome of acute radiation sickness (DMF = 1.24).     

Low survival of mice following lethal gamma-irradiation after administration of inhibitors of prostaglandin synthesis.

An impairment of the survival of mice subjected to whole-body gamma-irradiation with a lethal dose of 10 Gy and treated with a repeated postirradiation administration of prostaglandin synthesis inhibitors (PGSIs), indomethacin or diclofenac, was observed. Morphological examination of the gastrointestinal tract and the estimation of blood loss into its lumen in animals treated with diclofenac did not show serious damage such as haemorrhages or perforation, but revealed structural injury to the intestinal mucosa indicating inflammatory processes. The lesions found are supposed to be connected with increased intestinal permeability which leads to endotoxin escape from the gut and a subsequent increased mortality rate of irradiated animals. It may be concluded that PGSIs are not suitable for the management of radiation sickness after an exposure to lethal doses of ionizing radiation.     

内耳减压病豚鼠听力和耳蜗组织的病理变化

研究探讨了内耳减压病豚鼠皮层听觉诱发电位阈值、耳蜗火棉胶切片、酶组织化学和透射电镜观察的变化。结果表明,豚鼠内耳减压病导致听力损失,耳蜗广泛的病理损害.毛细胞琥珀酸脱氢酶活性降低。提出了加压治疗内耳减压病时配合改善微循环、增加能量供应等见解。     

Dosimetric criterion for the intestinal form of acute radiation lesions in man. The loss of the barrier properties of the small intestine--an index of the severity of the lesion

Dynamics of cell regeneration in the small intestine epithelium of man has been investigated in normal conditions and after acute exposure to ionizing radiation. It is suggested that the severity and outcome of the intestinal form of acute radiation sickness are determined by the time interval within which the number of functional cells of the epithelium villi remains below some threshold level that provides the retention of barrier properties of the small intestine.     

Delayed effects of acute radiation injuries by radioactive carbon (14C-glycine)

A study was made of late biological effects of radioactive carbon (14C-glycine) applied in acute doses. The course of radiation sickness, at its acute stage, is similar to that of acute radiation sickness caused by external gamma-irradiation. The recovery is slow, and the disease becomes chronic exhibiting metabolism disturbances and early death of animals. Radioactive carbon has a pronounced blastomogenic action.     

Morphological types of radiation-induced hematopoietic tissue cell death,its biological essence and significance at various stages of developing acute radiation injury

The results of morphologic investigation of radiation-induced cell death types in human and animal (dogs) hematopoietic tissue within an acute radiation injury are presented. It has been shown that early and late necrobiosis of myelokaryocytes occurs via apoptosis. An attempt to designate the pathogenic role of apoptosis in hematologic syndrome of acute radiation sickness was performed.     

Prostaglandins and interphase death of irradiated cells

The contribution of the post-irradiation changes in prostaglandin transformation to the biochemical mechanism of interphase death of irradiated cells is estimated. It is supposed that prostaglandins are secondary trigger-effectors which initiate the development of primary biochemical reactions giving rise to radiation sickness. It is suggested that the biochemical mechanism of interphase death is complex and involves several concurrent trigger mechanisms including prostaglandin regulation system.     

Severe euthyroid cardiac disease; technique for treatment with radioiodine

It is possible to safely lower the basal metabolism of patients suffering from severe cardiac disease by administering multiple small doses of radioiodine in order to achieve symptomatic relief. From the present study, multiple small doses of I(131) appeared to be as effective as single or multiple large doses of this material and complications such as thyroiditis, temporary thyrotoxicosis and bone marrow depression were almost always avoided. No damage to the parathyroid glands or the recurrent laryngeal nerve was observed. No radiation sickness developed after therapy.A scintigram of the thyroid gland was useful in determining the size, shape and function of the thyroid gland before and during radioiodine treatment and helped to determine the need for additional treatment. In order to prevent the distressing symptoms of the myxedema state, desiccated thyroid was administered when necessary. In the series of 278 euthyroid patients with severe cardiac disease who were treated with radioactive iodine, results were excellent in 35 per cent of cases and good in 44 per cent. In 21 per cent there was no improvement.     

Biochemical reception and ionizing irradiation of the body

The authors present the idea of the importance of studying the mechanism of biochemical reception of biologically active compounds (BAC) particularly the reception of prostaglandins after the effect of ionizing radiation on eucaryotes as a factor playing a significant role in understanding the radiation sickness pathogenesis. The perspectives of studying BAC reception are prognosticated for searching new radiomodifying agents (radioprotectors and means for treating radiation sickness).     

15 years after the accident at the Chernobyl Nuclear Power Plant

Health effects as a result of the accident at the Chernobyl nuclear power plant occurred in 1986 are considered in the paper. Wrong prognosis of the health effects with respect to mortality and morbidity among the population exposed to low radiation doses is shown. Proven increase in thyroid cancer cases among people who were children aged from 0 to 18 at the time of the accident is shown. Linear relationship between thyroid cancer cases and dose to thyroid ranged from 0.2 to 4.0 Gy is considered. An additional absolute risk of thyroid cancer in children varies in the range 1.9-2.6 cases per 10(4) person-year Gy. During the fifteen years following the accident no cases of acute and chronic radiation sickness have been revealed because the population living in contaminated areas received low radiation doses. Also, exposures to low radiation doses did not result in excess of malignant tumors among population. In some cases the outcomes of acute radiation sickness were as follows: radiation damages to the skin, cancer cataracts, development of oncopathology.     

Changes in the dog endocrine system in the hematopoietic form of radiation sickness

The endocrine status of the organism estimated by the cortisol, insulin and triiodothyronine content of blood considerably changes during radiation sickness. The most pronounced changes in the endocrine status occur during the primary response and at the height of radiation sickness. The endocrine status test may be used in the individual radiosensitivity prognosis.     

A possible approach to large-scale laboratory testing for acute radiation sickness after a nuclear detonation

After the detonation of an improvised nuclear device, several key actions will be necessary to save the greatest number of lives possible. Among these tasks, the identification of patients with impending acute radiation sickness is a critical problem that so far has lacked a clear solution in national planning. We present one possible solution: the formation of a public-private partnership to augment the capacity to identify those at risk for acute radiation sickness.     

Proteinase inhibitors of the blood plasma in the early period of the development of acute radiation sickness in monkeys

A study was made of the postirradiation kinetics of blood antiproteinase activity in monkeys (Macaca nemestrina). Whole-body uniform gamma-irradiation (LD100/45) was shown to induce a significant decrease in the activity of alpha 2-macroglobulin during the first 24 h following irradiation: the decreased activity level was retained throughout the entire latent period of radiation sickness. At the height of radiation sickness (the 7th-10th day) up to the animals' death, a sharp increase was registered in the activity of alpha 1-inhibitor of blood plasma proteinases. The authors discuss a pathogenetic role of the diminution of the inhibitory potential of blood in the course of radiation sickness.     

Nod Factor Receptors Form Heteromeric Complexes and Are Essential for Intracellular Infection in Medicago Nodules

Rhizobial Nod factors are the key signaling molecules in the legume-rhizobium nodule symbiosis. In this study, the role of the Nod factor receptors NOD FACTOR PERCEPTION (NFP) and LYSIN MOTIF RECEPTOR-LIKE KINASE3 (LYK3) in establishing the symbiotic interface in root nodules was investigated. It was found that inside Medicago truncatula nodules, NFP and LYK3 localize at the cell periphery in a narrow zone of about two cell layers at the nodule apex. This restricted accumulation is narrower than the region of promoter activity/mRNA accumulation and might serve to prevent the induction of defense-like responses and/or to restrict the rhizobium release to precise cell layers. The distal cell layer where the receptors accumulate at the cell periphery is part of the meristem, and the proximal layer is part of the infection zone. In these layers, the receptors can most likely perceive the bacterial Nod factors to regulate the formation of symbiotic interface. Furthermore, our Förster resonance energy transfer-fluorescence lifetime imaging microscopy analysis indicates that NFP and LYK3 form heteromeric complexes at the cell periphery in M. truncatula nodules.