A possibility to predict the severity of individual damage following the exposure to supralethal radiation dosage. Prediction by early radiation response

The experiments on dogs and monkeys have shown that the severity of radiation sickness following the exposure to supralethal radiation doses can be predicted by early response of an individual. For such prediction, the most informative criteria include general severity of clinical manifestations during primary radiation response and evaluated within a few post-damage hours, the degree of tension in cardiac rhythm control, the cortisol level, the endocrine status index.     

A possibility to predict the severity of individual damage following the exposure to supralethal radiation dosage. Prediction of the clinical manifestation of radiation injury in laboratory animals by response to pre-exposure hypobaric hypoxia

The experiments on rats, dogs and monkeys exposed to radiation doses which cause intestinal and cerebral forms of radiation sickness have shown that the severity of a clinical state can be predicted by cardiovascular and endocrine changes when a pre-exposure test with moderate hypobaric hypoxia is performed. The goodness of fit of experimental data to the exposed result is up to 60-80%, still rising if a set of indices of the neuroendocrine status is used.     

Mechanism of circulatory disorders in animals irradiated at high doses

Some data are reported on pathoanatomical changes, a status of the microcirculatory channel and the coagulogram of animals affected by high doses of ionizing radiation. The signs of disseminated intravascular blood coagulation have been revealed. The authors discuss the relationship between clinical manifestations with coagulopathy development and circulatory disturbances during intestinal and cerebral forms of acute radiation sickness.     

Morphofunctional characteristics of the cells of the APUD system of the adrenal glands and the duodenum in the cerebral form of acute radiation sickness

Changes of a phase nature develop in the APVD system cells of rats, dogs, and monkeys exposed to electron radiation of doses inducing a cerebral form of radiation sickness. These changes in the morphofunctional status of APVD system cells may be considered as a syndrome displaying acute radiation apudopathies.     

A possibility to predict the severity of individual damage following the exposure to supralethal radiation dosage. Prediction of working capacity of irradiated rats and dogs by response to pre-exposure physical load

The experiments on rats and dogs exposed to radiation doses which cause intestinal and cerebral forms of radiation sickness have shown that, within the first 24 hours post-exposure, efficiency impairment can be predicted by changes in some indices of the cardiovascular and endocrine systems after physical load used as a non-radiation testing agent. The goodness of fit of experimental data to the expected result is up to 50-70%, still rising if a number of indices for different sections of the neuroendocrine system are used at a time.     

The status of the endocrine function of the thymus in acute radiation sickness resulting from the accident at the Chernobyl Nuclear Power Station

Data are presented on the role of inhibition of endocrine function of the thymus in the pathogenesis of acute radiation sickness resulted from the direct and indirect (via the increased glucocorticoid production) effects of ionizing radiation. The complex treatment, including nonspecific active immunotherapy, permitted to normalize the thymic hormone level and certain parameters of the immune system.     

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.     

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.     

Multivariate statistical analysis of tissue basophils in acute radiation sickness

By means of mark scale estimation method, discriminant and factor analyses, changes in integral indices on the state of mast cells in the rat mesentery have been investigated in dynamics of medullary, intestinal and cerebral forms of an acute radiation sickness. The integral indices are calculated basing on the morphometric parameters of the cells, that are obtained after the histological preparations are treated in a special automatic system for analysing images. At the medullary form of the acute radiation sickness, the greatest structural rearrangements of the mast cells take place during the first hours after the radiation, as well as during the climax of the disease, at the intestinal form, the analogous changes are revealed 1-3 days after the effect, and at the cerebral form--3 h after the radiation. The integral indices, calculated by means of the three methods, are well correlated with each other.     

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.     

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.     

Changes in labrocytes during acute radiation sickness (morphometric study)

Changes in the morphometric parameters of rat mast cells during acute radiation sickness have been studied. The most significant deviation of the quantitative indices of mast cells from the control values were noted at the height of the bone-marrow, at the terminal stage of the intestinal, and during the first few hours of the cerebral forms of acute radiation sickness.     

The effect of ionizing radiation on the vascular bed of the skin in ontogeny. The function of the microcirculatory bed of the skin in the fetuses of white rats sublethally irradiated]

Albino female rats were exposed to X radiation (5 Gy, 180 kV, 10 mA, filter 0.5 mm Cu) on days 10-15 of pregnancy. After 3 and 7 days they were sacrificed (under ether anesthesia) and fetuses were extracted. The status of the lympho- and hemomicrocirculatory beds (LMCB and HMCB) of the fetus back skin was studied by the macro- and microscopic methods. As early as day 3 of radiation sickness the diameter of LMCB vessels increased by 1.4-1.9 times, whereas changes in GMCB were less pronounced. On day 7, there was a progressive increase in dilatation of LMCB vessels, alongside with the narrowing of large units (arteries and veins). The development of the connective framework of the fetus skin was retarded.     

A possibility to predict the severity of individual damage following the exposure to supralethal radiation dosage. Prediction of working capacity of irradiated rats and dogs by response to pre-exposure hypobaric load

In experiments on rats and dogs exposed to radiation doses which cause intestinal and cerebral forms of radiation sickness, hypobaric hypoxia used as an unconventional test of animals' reactivity has enabled the relationship between reactivity and radiosensitivity to be established. Higher post-radiation efficiency is observed in animals with less pronounced changes during a barotest. The goodness of fit of experimental data to the expected result is up to 70%, rising if a set parameters for one index or the sum total of indices are used.     

EPR study of the blood of animals during an acute radiation lesion

The intensity of the ESR signal of methemoglobin, Fe3+-transferrin, and Cu2+-ceruloplasmin in blood and spleen of mice exposed to 6 Gy radiation was shown to undergo considerable changes at early times of acute radiation sickness.     

The RBE of 0.85-MeV neutrons in the intestinal form of radiation sickness in guinea pigs

Relative biological effectiveness (RBE) coefficient of 0.85 MeV neutrons was 1.87 in comparison with 0.66 MeV gamma radiation (137Cs) when estimated by the death rate of guinea pigs with intestinal form of radiation sickness. LD50/5 was 5.9 and 11.06 respectively. Features of the mortality rate dynamics, clinical picture and pathoanatomical changes are discussed.     

Changes in the concentration of serum fibronectin in irradiated animals

A study of the level of fibronectin in blood serum of Wistar rats at different times after gamma-irradiation (7.5 Gy) has demonstrated a considerable increase in its concentration after 3 days. This increase is a function of radiation dose absorbed (within the range from 1 to 10 Gy). The most pronounced changes are observed with serious and extremely serious forms of acute radiation sickness. The administration of cycloheximide 48 h after irradiation removes completely the increase in the level of blood serum fibronectin.     

Early social isolation alters behavioral and physiological responses to an endotoxin challenge in piglets

Psychosocial stress in the form of maternal deprivation and social isolation during early postnatal life induces persistent alterations in behavioral and physiological mechanisms of adaptation. One consequence may be an increased susceptibility to diseases in later life. Therefore, the aim of the present study was to investigate in domestic piglets the effects of a repeated social isolation (2 h daily from day 3 to day 11 of age) on behavioral, endocrine and immune responses to an endotoxin challenge with lipopolysaccharide (LPS) 1 day or 45 days after the isolation period. Peripheral LPS administration caused serious sickness behavior (somnolence, shivering, vomiting) and provoked profound increases in circulating tumor necrosis factor-alpha (TNF-alpha), ACTH and cortisol concentrations. The prior social isolation treatment enhanced signs of sickness and impaired suckling behavior. Early isolated piglets responded to LPS by an increase of shivering on day 12 and by increased vomiting on day 56 compared to controls. Further, there were considerable delays and reductions of time isolated piglets spent suckling on day 12. The repeated isolation stressor diminished TNF-alpha increases after LPS, whereas stress hormone levels were not significantly affected by isolation treatment. Finally, stronger relationships between signs of sickness and physiological measures were revealed in early isolated piglets. The duration of somnolence in isolated piglets was related to changes of cortisol and TNF-alpha concentrations, and the highest impact on duration of shivering was found for changes in cortisol and corticosteroid binding globulin levels. The present results suggest a sustained adaptive sensitization of coping with infection by social stress experience during early development in piglets.     

Early social isolation alters behavioral and physiological responses to an endotoxin challenge in piglets

Psychosocial stress in the form of maternal deprivation and social isolation during early postnatal life induces persistent alterations in behavioral and physiological mechanisms of adaptation. One consequence may be an increased susceptibility to diseases in later life. Therefore, the aim of the present study was to investigate in domestic piglets the effects of a repeated social isolation (2 h daily from day 3 to day 11 of age) on behavioral, endocrine and immune responses to an endotoxin challenge with lipopolysaccharide (LPS) 1 day or 45 days after the isolation period. Peripheral LPS administration caused serious sickness behavior (somnolence, shivering, vomiting) and provoked profound increases in circulating tumor necrosis factor-α (TNF-α), ACTH and cortisol concentrations. The prior social isolation treatment enhanced signs of sickness and impaired suckling behavior. Early isolated piglets responded to LPS by an increase of shivering on day 12 and by increased vomiting on day 56 compared to controls. Further, there were considerable delays and reductions of time isolated piglets spent suckling on day 12. The repeated isolation stressor diminished TNF-α increases after LPS, whereas stress hormone levels were not significantly affected by isolation treatment. Finally, stronger relationships between signs of sickness and physiological measures were revealed in early isolated piglets. The duration of somnolence in isolated piglets was related to changes of cortisol and TNF-α concentrations, and the highest impact on duration of shivering was found for changes in cortisol and corticosteroid binding globulin levels. The present results suggest a sustained adaptive sensitization of coping with infection by social stress experience during early development in piglets.