Hyperammoniemia in rats with barbiturate coma.

Sodium thiopental in the comatogenic (but not soporogenic) dose caused hyperammoniemia in rats. Blood ammonium level increased 3-fold within 3 h and 5-fold within 18 h. Blood urea level increased by one-third within 18 h against the background of unchanged creatinine level and hematocrit. Urinary excretion of ammonium did not decrease, while its release with exhaled air increased, indicating intensification of ammonium formation in the body. Barbiturate coma did not change the slope of curves of dose-dependent increase of ammonium or urea levels in the blood of rats injected with ammonium acetate, which attested to the absence of appreciable disorders in the ammonium detoxifying function of the liver. Ammonium hyperproduction could be caused by gastrointestinal stasis verified by X-ray examination and confirmed by correlation between blood urea level and stool retention in narcotized rats.

Metabolic correction of gas exchange disturbances in rats with barbiturate coma.

Krebs cycle intermediates normalized gas exchange and decreased the mortality rate in rats with barbiturate coma. Treatment with other substrates including glucose and products of glycolysis was ineffective. Oxygen inhalation had no effect on oxygen consumption and indexes of external respiration. Our results suggest that deficiency of endogenous intermediates of the Krebs cycle, but not disturbances in oxygen mass transfer, serves as a limiting factor for oxygen consumption in rats with barbiturate coma.

Effect of sodium succinate on gas exchange in rats with barbiturate-induced coma.

Injection of sodium succinate in doses of 5 or 10 mmol/kg (but not 1 mmol/kg) intensified oxygen consumption in rats with sodium thiopental-induced coma. Injection of SDH inhibitor (sodium malonate) inhibited gas exchange and abolished the effect of sodium succinate. The effect of succinate on rat survival was positive, while that of malonate was negative, but manifested only as a trend. The critical role of succinate oxidation in preventing lethal complications of barbiturate-induced coma is proved.

[Gas exchange intensity: relation to the body radiation resistance]. / Intensivnost' gazoobmena: sviaz' s radioresistentnost'iu organizma.

In the absence of immobilization stress gas exchange in rats does not increase in response to exposure to 6 to 13 Gy. Oxygen uptake intensity by intact animals at room and low ambient temperature is a stable individual characteristic positively correlating with life span following acute bone marrow irradiation. It is hypothesized that high gas exchange in radioresistant animals is linked with high inherent DNA synthesis and reparation. In animals experiencing immobilization stress the correlation between gas exchange reactivity and body radioresistance is supposed to be a result of more intensive uptake of oxygen diffusing in cells and consequent reduction in nucleus oxygenation and mitigation of DNA radiation-induced damage.

[Mechanisms of cerebral radiation syndrome]. / Mekhanizmy tserebral'nogo luchevogo sindroma.

Postradiation DNA breaks activate the repair enzyme, Adenosine diphosphoribosil transferase, which consumes NAD as a substrate and causes neuronal NAD and then ATP pool depletion; here this is considered to be the crucial links of the cerebral radiation syndrome (CRS) mechanism. Two ways of its metabolic correction were examined: (a) prevention of postradiation NAD depletion by administration of the enzyme inhibitor and (b) shunting NAD-dependent oxidative phosphorilation path of ATP resynthesis by administration of substrate of NAD-independent oxidation.

[Gas exchange as a factor of the body radiation resistance]. / Reaktivnost' gazoobmena kak faktor radiorezistentnosti organizma.

Cold-provoked intensification of oxygen consumption was correlated with individual radioresistance of mice. There was a positive correlation between the parameters in normoxia and hyperoxia, and a distinct negative correlation in hypoxia. Radiosensitizer of hypoxic cells, metronidasol, severed the correlation no matter what level of oxygenation in the course of irradiation. The hypothesis for intracellular pO2 as a mediator of the dependence of individual radioresistance on the gas exchange reactivity has been put forward.

[Rationale for social and hygienic methods of rehabilitation of the population of the areas exposed to radioactive contamination resulting from the Chernobyl accident]. / Obosnovanie sotsialno-gigienicheskikh meropriiatii po reabilitatsii naseleniia territorii, podvergshikhsia radiatsionnomu zagriazneniiu v rezultate Chernobylskoi avarii.

The factors preventing the stabilization of life in the contaminated areas include sociopsychic epidemic of "victim's syndrome" among the population; unfavourable information environment; secondary negative action of contrameasures (obligatory behavioral limitations, privileges, compensations, etc.). The rehabilitation of the population's life is based on the activization of a personal position and initiative of individuals, stimulation of economic activity in the areas.

[ Multigeneration carcinogenesis in the evaluation and prognosis of delayed radiation effects]. / Znachenie multigeneratsionnogo kantserogeneza v otsenke i prognoze otdalënnykh radiatsionnykh éffectov.

Radiation multigeneration carcinogenesis' mechanisms are associated with inheritance of non-specific genome lesions. Evidence indicates that the effect is significantly enhanced by some chemical carcinogens action on the offspring of irradiated parents. Hereditary character of the phenomenon is a prerequisite to accumulation of these genetic determinants in the population. The risk of radiation multigeneration carcinogenesis for man could be as much as 0.4 x 10(-2) Sv-1 over one generation.

[Acute radiation cerebral disorders as an effect of neuronal DNA damage]. / Ostrye luchevye tserebral'nye narusheniia kak éffekt povrezhdeniia DNK neironov.

Early transient incapacity and cerebral radiation syndrome were shown to result from the de-energizing of the brain due to NAD and ATP neuron pools depletion since DNA breaks stimulate the repair enzyme, ADP-ribosyltransferase, that consumes NAD as a substrate. The phenomenology of syndromes, peculiarities of the CNS repair and neutron RBE might be attributed to this mechanism. DNA is thus a common target for stochastic, deterministic and physiological effects of radiation.

[The radiation hygiene problems of multigenerational carcinogenesis]. / Radiatsionno-gigienicheskie problemy mul'tigeneratsionnogo kantserogeneza.

This review deals with a phenomenon of multigeneration carcinogenesis; the carcinogenic risk for offsprings of irradiated persons can be estimated as 4.10(-3) Sv-1. Though some epidemiological findings in this area are contradictory, multigeneration carcinogenesis may present a part of a population risk (genetic load). There is a need for recording the phenomenon in the normal ranges of radiation safety, i.e. to limit the planned irradiation of males aged 30-40 years, as well as females of the same age.

[An experimental assessment of the genetic effects of low doses of internal irradiation]. / Eksperimental'naia otsenka geneticheskikh éffektov malykh doz vnutrennego oblucheniia.

Genetic study of rats showed the possibility of registration of the minor doses of the inside and outside irradiation. The postmiosis mutations, number of reciprocal translocations in spermatogonia may be used for indexation of the effects.

[A comparative evaluation of the genetic effects of uniform internal (137Cs) and local x-ray (testes) irradiation of rats]. / Sravnitel'naia otsenka geneticheskikh éffektov ravnomernogo vnutrennego (137Cs) i lokal'nogo rentgenovskogo (semenniki) oblucheniia krys.

In experiments with rats it was shown that with equal absorbed doses after single injection of 137Cs and local X-irradiation of testes the mutation yield in gametes was different when tested by the frequency of dominant lethals and half-lethals, reciprocal translocations, univalents, and chromosome fragments. A higher efficiency of whole-body irradiation as compared to local exposure of testes, with respect to genetic damages induction, and the statistically significant increase in the number of the damages during a long period of time after cessation of the absorbed dose formation indicated that indirect effects of whole-body irradiation contributed to the injury to hereditary structures and permitted to estimate approximately their contribution (up to 50%).

[Patterns in the formation of cerebral damage and recovery from supralethal irradiation]. / Zakonomernosti formirovaniia tserebral'nogo porazheniia i vosstanovleniia pri sverkhsmertel'nykh oblucheniiakh.

In experiments with rats it has been shown that dose-rate and radiation fractionation influence the dose dependence of early transient incapacity (ETI) and the development of tolerance to ETI. The authors discuss the possibility of interpreting the tolerance to ETI as a form of the cerebral damage displayed by the impairment of the brain response to radiation. A correlation has been revealed between the cerebral damage and recovery and repair of radiogenic damages to DNA.

[Regulatory disorders of locomotor functions in dogs during prolonged irradiation in a wide range of dose rates]. / Reguliatornye narusheniia lokomotornykh funktsii u sobak v khode prolongirovannogo oblucheniia v shirokom diapazone moshchnostei dozy.

A biphase pattern of the development of locomotor disturbances, connected with the primary response and cerebral radiation syndrome, was demonstrated in experiments with dogs subjected to prolonged irradiation, just as it was observed after acute exposure. Dose thresholds for the development of these states were somewhat higher with the prolonged irradiation. The time of the appearance of disturbances increased due to the delay of achievement the dose threshold increase with dose-rate decrease, the time interval needed for the development of the corresponding pathological process being unchanged. Due to the repair process the above syndromes were not manifested until the appropriate dose-rate thresholds were reached.

[The physical work capacity parameters of rodents studied by repeated high-speed swimming following uniform and nonuniform irradiation at high doses]. / Issledovanie parametrov fizicheskoi rabotosposobnosti gryzunov metodom mnogokratnogo skorostnogo plavaniia posle ravnomernogo i neravnomernogo oblucheniia v vysokikh dozakh.

Physical fitness of irradiated (20-200 Gy) mice and rats was estimated by the method of repeated swimming at a fixed distance. Revealed was the reduction adequacy of the two indices, that is the starting time and the fatigue coefficient, the latter being changed more considerably. The dose of 80-100 Gy determined the threshold of the cerebral damage and caused an irreversible decrease in the physical fitness of rodents. The role of exposure of the head in the impairment of the physical fitness of rats has been confirmed by the experiments with some body parts being shielded.

[Physiological characteristics of posture maintenance by dogs during immediate reaction to irradiation]. / Fiziologicheskie osobennosti podderzhaniia pozy sobak v period pervichnoi reaktsii na obluchenie.

The ability of dogs to maintain a vertical posture during the first hours after irradiation at a dose of 10 or 80 Gy was investigated. Two experiments were performed. In the first experiment, during 5 hours after irradiation the vector stabilogram area, peak muscle efforts and sensorimotor coordination were measured 10 times every 30 min. In the second experiment, postural responses to perturbations were measured before and after irradiation at a dose of 10 Gy. During exposure to 10 Gy maximum values of the vector stabilogram area reflected initial excitation and motor unrest, that preceded vomiting, while minimum values of the parameter were related to hypodynamia during 3-5 hours after exposure. During exposure to 80 Gy minimum values of the vector stabilogram area reflected the hypodynamic phase while maximum values were related to the phase of distinct cerebral lesions. A reliable indicator of the quality of vertical posture maintenance, that correlates with the post-irradiation quality of purposeful actions, including intermittent physical acts, or actions, requiring highly precise coordination, is the rate of posture recovery after instantaneous platform displacement. This parameter declined after irradiation, the maximum decrease being during the 4-5th hour.

[The mechanism of the neuromotor disorders in the period of the primary reaction to irradiation]. / K mekhanizmu neiromotornykh narushenii perioda pervichnoi reaktsii na obluchenie.

In experiments with dogs it was shown that the impairment of the capacity of fulfilling some actions (e. g. high jumping, equilibration, racing) was maximum 4h after gamma-irradiation with doses of 10 and 40 Gy and did not coincide with vomiting. By shielding body segments it was found that irradiation of abdomen was responsible for the disturbances observed. Novocaine blockade of innervation of abdomen prevented the impairment of the physical capacity, but not vomiting, during the first hours which was indicative of a major role of the reflex mechanism in motor disturbances genesis.

[Postradiation motor disorders in rodents as the equivalent of the clinical manifestations of a primary radiation reaction]. / Postluchevye motornye narusheniia u gryzunov kak ékvivalent klinicheskikh proiavlenii pervichnoi luchevoi reaktsii.

In experiments with albino mice it was found that during the first hours following gamma irradiation with doses of 10-80 Gy stability of implementation of loading and coordination tests was impaired and hard work endurance decreased. With doses exceeding 100 Gy, cerebral damages were stably manifested. There was a similarity between the postirradiation motor disturbances in animals of various species.

[The dosage thresholds for disordered physical work capacity in mice and rats following irradiation]. / Dozovye porogi narusheniia fizicheskoi rabotosposobnosti myshei i krys posle oblucheniia.

Physical efficiency of mice and rats at early times following irradiation with doses of 35 to 200 Gy was estimated by the muscle endurance and motor coordination indices. A threshold nature of the effects was exhibited at high doses. For instance, as large as 40 Gy was the dose threshold at which stability in the accomplishment of the known operations was impaired; at 70-100 Gy, the accomplishment decreased down to 50% of the initial level, by the 2nd hour after irradiation, with the subsequent partial restoration; 200 Gy was the threshold dose at which the disturbances were irreversible. These values were also similar to those of the threshold doses at which clinical picture of the affection was changed.

[The phasic structure of early disorders of functional capacity following irradiation in rats]. / Fazovaia struktura rannikh narushenii deesposobnosti posle oblucheniia krys.

In experiments with rats it was shown that an early decrease in physical efficiency after irradiation involves some partially mutually superimposed phases. Phases of excitation, hypokinesia and neurological disorders are identified in early transient inefficiency followed by phases of an early transient diminution of efficiency and a reversible disturbance of the accomplishment of the known operations. Simultaneously, there is a phase of an irreversible decrease of the informational capacity of CNS as well as the tolerance to early transient in efficiency upon repeated exposure.