Search

The level of lipoperoxidation products in radioresistant tumour is 3 times lower and superoxide dismutase activity--3.5 times higher than in the intact tumour. That is an evidence of high stability. The level of lipoperoxidation products in the brain and liver of rats with radioresistant variant of Guerin carcinoma is essentially less and catalase activity--considerably higher, than in the rats with intact tumour. This evidences for the corresponding increase of antioxidant protection of the organisms in the process of acquiring the tumour radioresistance.

This study examines the influence of low dose X-ray irradiation on purine nucleotide metabolites such as adenosine, inosine, hypoxanthine, xanthine and uric acid, and hence generation of ATP-mediated energy in mouse splenocytes. It was found that, unlike high dose irradiation which promotes membrane damage, low dose irradiation enhances the ability to regulate the energy metabolisms as reflected by the increase in Na+, K(+)-ATPase activity and the adequate activation of the above salvage pathway. Namely, the levels of adenosine, inosine and uric acid significantly increased, while the levels of xanthine and hypoxanthine decreased significantly. Moreover, the cysteine level and superoxide dismutase activity significantly increased at a dosage of 20 cGy.

Antarctica is a unique and challenging environment where members of expeditions face a range of conditions not normally experienced. Ultraviolet (uv) radiation levels show marked variation during the year. The 25-hydroxy metabolite of vitamin D [25(OH)D] is largely produced by sunlight and shows a yearly variation in concentration that corresponds to uv radiation levels. The active metabolite 1,25-dihydroxyvitamin D [1,25(OH)2D] does not generally show any such variation provided 25(OH)D concentrations are sufficient. Previous studies have shown a seasonal variation in 25(OH)D with a significant winter drop. No other study of 1,25(OH)2D has been reported on members of Antarctic expeditions. A group of 19 men wintering at Davis Station (68 degrees 34' S) had four blood samples taken at 3-monthly intervals beginning in the Antarctic summer. Analysis for 25(OH)D showed a drop in concentration for each of the latter three sampling periods (P < 0.005). This correlated with uv radiation levels and would suggest that endogenous production of 25(OH)D ceases for at least the duration of the Antarctic winter. There were no significant alterations in 1,25(OH)2D or calcium concentrations over the same period. Providing that individuals with pre-existing vitamin D deficiencies are detected before departure for Antarctica and missions are limited in duration, clinical deficiency is unlikely to occur.

The trial covered 58 patients with prostatic cancer aged 50-79. Before treatment these patients exhibited weak proliferative response of T-cells to PHA, increased number of T-suppressors/killers, enhanced suppressive influence of regulatory cells. Hormone chemotherapy produced immunodepressive and immunomodulating effects (normalization of the count of T-suppressors/killers and their function). Subsequent radiotherapy on the prostatic region (total dose 60 Gy) worsened immunodepression. Efficacy of placental suspension and levamisol depends on the treatment stage at which the latter were used: during hormone chemotherapy the addition of the suspension and levamisol corrects its immunodepressive effects, in subsequent radiotherapy immunodeficiency greatly increased.

Immunoendocrinological studies were carried out in mice during a year after local X-ray irradiation of thymus, hypothalamus-hypophysis, gonads, spleen and thigh muscles. Irradiation of the organs caused the stress regardless of the dose and localisation. No stable immunoendocrinological changes was observed in exposed spleen and thigh muscles. Post-irradiation disfunction of the central and peripheral endocrine gland (hypothalamus-hypophysis, gonads, thymus) induced alterations in function of other endocrine glands and depressive state of the endocrine system. Functional deviations in immune and endocrine systems has a phase character with some dose dependence. The effect of combined irradiation of thymus and hypothalamus-hypophysis is similar to those under separate irradiation.

The satisfied differential distinctions between diseases (7 nosological groups) observed in population of so-called Ural radiation trace are established using laser correlation spectroscopy (LCS). Unsatisfied differentiation (less then 65%) was observed between cancer and pre-cancer diseases relative to gastric, bronchial and exchange pathologies. The most significant distinctions are established for autoimmune pathologies and osteochondroses and for cancer and pre-cancer differentiation. Marked differentiation degree is less than that earlier registered between the same pathologies in regions, where radiation level was normal. On the base of the measurements is planned to study the dose effect of pathology radiomodification.

Concentrations of hormones of the hypophysis, thyroid gland and adrenal cortex were measured in blood plasma of those patients presenting with neurodermatitis. A statistically significant reduction in the blood content of thyroid-stimulating hormone (TSH) and hydrocortisone and rise in aldosterone, adrenocorticotrophic hormone (ACTH), triiodothyronine and thyroxin were revealed in this patient population. Combined non-drug therapy treatments involving endovascular helium-neon laser therapy and EHF electromagnetic radiation resulted in improvement in more than half of the measurements done: blood levels of TSH and hydrocortisone got increased while those of ACTH, thyroxin and aldosterone decreased, which fact correlated with the positive clinical picture of the condition in question.

Breast cancer patients residing in those territories controllable because of Chernobyl APP accident demonstrated significant disturbances in functional state of hypophyseal-thyroid and pituitary-adrenal axes, with central regulatory mechanisms being affected to the greatest extent. The above disturbances may arouse augmentation of prolactin secretion, which fact tends to aggravate the morbus course worsening the prognosis as well as leading to a variety of disorder in the reproductive system.

The critical period in a chicken embryonic development (the 10-13-th days of incubation) is revealed under total electromagnetic radiation. This external factor is a physiologically active irritant which can influence functional state of the brain. The increased absorption of electromagnetic energy takes place in this incubation period. Its dynamics within 20 days of embryonic development has phasic, up and down character. Electromagnetic exposure (4 hours a day daily) in the above mentioned period evokes a delay in embryo adaptive motor behavior (biofeedback learning). Morphological investigation shows significant pathological changes--destruction of share brain synapses. The delay in embryo hatching for a day is also detected. Radiation exposure within other periods of incubation (3-6-th or 12-15-th days) was not effective with respect to formation of normal motor pattern in biofeedback experiment.

Free cytosolic [Ca2+] ([Ca2+]f) was measured at the single cell level using digitized video-intensified fluorescence microscopy and the fluorescent Ca2+ indicator, fura-2. Cells were irradiated at 1-4 Gy (dose rate of 6 Gy/min) with a 90Sr eye applicator mounted on the microscope. HeLa cells responding to ionizing radiation exhibited a maximal 3-4-fold transient rise in cytosolic and nuclear [Ca2+]f immediately upon irradiation, which persisted for at least 5 min before returning to baseline in most but not all cells. The radiation-induced rise in [Ca2+]f was blocked by 1 mM La3+, 100 nM nifedipine, or membrane potential depolarization, suggesting that HeLa cells possess a voltage-dependent Ca2+ channel that mediates the response to radiation. Experiments with Mn2+, a paramagnetic probe for extracellular Ca2+, showed that radiation stimulated an increase in Mn2+ influx, as witnessed by loss of fura-2 fluorescence. Thapsigargin and ryanodine, inhibitors of intracellular Ca2+ mobilization, also completely blocked the radiation effect, implying a linkage between the radiation-induced influx and mobilization of internal Ca2+ stores. Not all cells in an asynchronous culture responded identically to radiation. Upon synchronization with thymidine/aphidicolin, cells in the S- and G2/M-phase exhibited radiation-induced changes in [Ca2+]f, whereas G1-phase cells did not. In addition, the increased [Ca2+]f of irradiated G2/M phase cells did not fully return to pretreatment levels. Further studies utilizing MDA-MB-231 and MCF-7 human breast and HT-29 human colon cancer cell lines indicate that radiation can alter Ca2+ homeostasis in other epithelial cell types. In the case of MDA-MB-231 and HT-29 cells, oscillations in cytosolic [Ca2+]f levels were observed that persisted for up to 50 min. The kinetics and inhibitor sensitivities differed from HeLa cells, indicating a different type of mechanism for the radiation effects on cell [Ca2+]f. Survival studies with HeLa and MDA-MB-231 cells did not reveal a connection between the radiation effects on cellular Ca2+ homeostasis and cell survival.

Following radiation damage from LD50-LD97, changes in blood, immune and endocrine parameters were revealed and followed up in dogs at the time of late effects development, 3-18 months after exposure. The changes result from post-radiation immunodeficiency and resemble those observed in residents of radioactive contaminated areas or in men participated in Chernobyl accident amelioration.

Peculiarities of the processes of lipids peroxidation under effect of ionizing radiation in small doses and its low intensity have been considered. Data from literature concerning the threshold doses of lipids peroxidation activation have been generalized.

The state of pro-oxidant-antioxidant homeostasis in guinea pigs exposed to whole-body fractionated X irradiation (5 fractions of 0.2 Gy at a 24 hr interval, up to total dose of 1.0 Gy, at a dose rate of 0.425 R/min) and a possibility of its disturbance correction with the complex of vitamins C, E and P was studied. Accumulation of primary and secondary lipid peroxidation products, decrease of the ascorbic acid content, increase of the content of its oxidized forms (dehydroascorbic acid and diketogulonic acid) in radiosensitive (spleen and small intestine) and radioresistant organs were found. Antioxidant complex administration reduced the disturbances of pro-oxidant-antioxidant homeostasis, but did not provide complete normalization.

On the basis multiannual personal experience in millimeter resonance therapy in the treatment of several diseases (diabetes mellitus, ulcers, etc. [correction of and oth]) data are reported on substantiating the theory of sanogenesis of this method. Various biochemical, immunological, hormonal studies in the experiment and clinic indicate that the basis of the treatment effect of electromagnetic radiation is restoration of homeostasis by activation of compensatory systems. The levels and systems influenced by electromagnetic radiation are indicated. The stage-like character of these influences is stressed.

Activity-related transient changes in extracellular K+ concentration ([K+]e) and pH (pHe) were studied by means of ion-selective microelectrodes in neonatal rat spinal cords isolated from pups 2-14 days of age. Pups 1 to 2 days old were X-irradiated to impair gliogenesis and spinal cords were isolated 2-13 days postirradiation (PI). In 2- to 14-day-old pups PI stimulation produced ionic changes that were the same as those in 3- to 6-day-old control (non-irradiated) pups; e.g. the [K+]e increased by 4.03 +/- 0.24 mM (mean +/- S.E.M., n = 30) at a stimulation frequency of 10 Hz and this was accompanied by an alkaline shift of 0.048 +/- 0.004 pH units (mean +/- S.E.M., n = 32) pH units. By contrast, stimulation in non-irradiated 10- to 14-day-old pups produced smaller [K+]e changes, of 1.95 +/- 0.12 mM (mean +/- S.E.M., n = 30), and an acid shift of 0.035 +/- 0.003 pH units which was usually preceded by a scarcely discernible initial alkaline shift, as is also the case in adult rats. Our results show that the decrease in [K+]e ceiling level and the development of the acid shift in pHe are blocked by X-irradiation. Concomitantly, typical continuous development of GFAP-positive reaction was disrupted and densely stained astrocytes in gray matter of 10- to 14-day-old pups PI revealed astrogliosis. In control 3- to 6-day-old pups and in pups PI the stimulation-evoked alkaline, but not the acid, shift was blocked by Mg2+ and picrotoxin (10(-6) M). The acid shift was blocked, and the alkaline shift enhanced, by acetazolamide, Ba2+, amiloride and SITS. Application of GABA evoked an alkaline shift in the pHe baseline which was blocked by picrotoxin and in HEPES-buffered solution. By contrast, the stimulus-evoked alkaline shifts were enhanced in HEPES-buffered solutions. The results suggest a dual mechanism of the stimulus-evoked alkaline shifts. Firstly, the activation of GABA-gated anion (Cl-) channels induces a passive net efflux of bicarbonate, which may lead to a fall in neuronal intracellular pH and to a rise in the pHe. Secondly, bicarbonate independent alkaline shifts may arise from synaptic activity resulting in a flux of acid equivalents.

The rats were irradiated in the doses 1, 5, 4, 7 and 10 Gr and on the 1, 8, 15, 22 and 30 day after the irradiation activity of Ca(2+)-ATPase and Mg(2+)-ATPase and peroxidation lipids in the thymocytes was determined. It was found that postradiation changes in activity of Mg(2+)-ATPase were characterized by a higher sensitivity to the processes of lipids peroxidation as compared to Ca(2+)-ATPase.

The complex investigation has been provided to control the genetically influenced processes after Chernobyl accident in some Ukrainian regions. Some dangerous trends in genetic populational status were revealed in the Ukrainian regions surrounding Chernobyl power plant allowing for the increasing number of congenital anomalies among the newborns and the spontaneous abortions as well as higher proportion in aberrations of chromosome type in human somatic and embryos cells, higher incidence of structural defects in embryonal bone system and higher, compared with control, proportion of children with intensive catabolism (R-protein homeostasis).

A study was made of the distribution of plutonium-239 injected intratracheally within different bones of the skeleton, the iron status in the blood being changed. The iron preparation caused a 2.5-3-fold decrease in the plutonium loading onto cancellous bone tissue that displayed, in ordinary conditions, a higher tropism to the radionuclide than a cortical highly mineralized bone did.

Simple and complex forms of behaviour, gas composition and acid-alkaline blood status in rats following exposure to the electro-static field (ESF) and iraionization, as well as in their offspring were studied. It has been found out, that ESF combined with the negative polarity air ionization damage motor and sex activity, conditioned-reflectory activity, changes blood indices. The observed disturbances in the organism of parent animals influenced fetus development.

The inability of normal cells to maintain themselves for ever is a reflection of homoeostatic imbalance and a progressive failure of maintenance. Ageing cells respond less to growth stimulants whereas they show increased sensitivity to toxic agents including antibiotics, phorbol esters, radiation and other physical stresses. No major quantitative and qualitative defects in the receptor systems have been detected that could explain the reasons for altered responsiveness during ageing. Random metabolic defects in the processes involved in maintaining homoeostasis may be critical for causing homoeostatic imbalance, cellular ageing and death.

Immunologic parameters in head and neck cancer patients measured prior to treatment, in remission, at relapse and in cases of lymph node metastases developing 1-3 years following radiation treatment proved different. Evaluation of immune status, alongside with other diagnostic methods, can be used to confirm remission and diagnose relapse.

The beneficial effect of low-energy laser radiation on the natural course of disease, morphologic characteristics of gastric mucosa and key elements of systemic hemostasis was observed in 98 patients with precancer of the stomach (gastric ulcer and chronic atrophic-hyperplastic gastritis with epithelial dysplasia). A correlation between clinical response and normalization of morphologic appearance and homeostasis makes the above-mentioned treatment modality promising and worth further development.

Six to nine months (7.2 months, on the average) after injection of 198Au into large joints of patients with rheumatoid arthritis there was a decrease of blood thrombophilia characteristics of these patients and refractory to correction with conventional remedies. Functional activity of platelets and fibrinolysis studies were the most sensitive laboratory tests enabling one to reveal the lowering of the patients' blood thrombogenic potential after radionuclide therapy. Comparison of the time-course of changes in these parameters with those of the immunological blood status of the treated patients forms the basis for suggestions that the coagulologic laboratory tests may be used for estimating the efficacy of the treatment carried out.

Data are reported on the possible mechanism of biological effects of small doses of ionizing radiation on the human body. The lesioning effect of this radiation resulted in some of the persons in the development of disorders of the function of information and vegetative-regulatory systems determined as a disintegration syndrome. This syndrome is manifested in unspecific neuro-vegetative disorders of the function of most important physiological and homeostatic system of the body leading to weakening of the processes of compensation and adaptation. This condition is characterized by an unspecific radiation syndrome as distinct from acute or chronic radiation disease which is a specific radiation syndrome.

In human infants and newborn rats, white light at the intensity used to treat hyperbilirubinemia lowers serum calcium concentration. Occipital shielding or (in newborn rats) exogenous melatonin prevents this effect. Propranolol, by inhibiting melatonin synthesis, also causes hypocalcemia, which is preventable by melatonin. Metyrapone or adrenalectomy prevents hypocalcemia after light exposure or propranolol. Exogenous corticosterone lowers serum calcium; this is prevented by supplementary melatonin. In adult rats, the change in calcium after light, propranolol, or corticosterone is minimal. After parathyroidectomy or a diet with a high calcium/low phosphorus ratio, the hypocalcemic effect of these three agents is restored. Bone samples removed after light exposure or corticosterone administration show increased calcium uptake; this is blocked by supplementary melatonin in vivo or by addition of melatonin to the incubation medium. We postulated that the hypocalcemic effect of light or propranolol was due to an acute increase in corticosterone-mediated bone calcium uptake when circulating melatonin was decreased by reduction of the rate of melatonin synthesis. In our study, pinealectomized rats showed no change in serum calcium after light or propranolol; their hypocalcemic response to corticosterone was greater than that of sham-operated controls. Exogenous parathyroid hormone prevented light-induced hypocalcemia in newborn rats.

A hypothesis is reported postulating that the range within which the intracellular oxygen content varies with changes in the external oxygenation conditions is responsible for the oxygen-dependent radiosensitivity modification that may be controlled by the diffusion resistance of a cytoplasmic membrane. The adaptation mechanism of intracellular Po2 autoregulation is involved when drastic changes in the oxygen content of the environment occur. As the oxygen content decreases this mechanism provides maximal values of the intracellular Po2 required for optimizing cell viability; the increased oxygen content prevents cells from oxygen intoxication.

(CBA X C57B1/6)F1 mice were injected with 125I and 131I-sodium iodide at a dose of 5.74 X 10(4) Bq/g. For a long time after such treatment the animals manifested an increased level of spleen cells humoral immune response to a foreign antigen (sheep erythrocytes), the autoreactivity of spleen and lymph node lymphocytes to autologous erythrocytes was also elevated. At the same time the selective migration of 51Cr-labeled spleen lymphocytes to the peripheral lymphoid organs was suppressed. The use of a model system of adoptive cell transfer revealed an increase in the functional activity of cells suppressing a humoral response in mice treated with radiopharmaceuticals. The most pronounced disturbances of immunological reactivity in mice took place 6 mos. after the beginning of the experiment. The results obtained indicated that mechanisms of immune response regulation played a certain role in disturbances of immunological homeostasis induced by radioactive iodine agents.

Low sensitizing doses given to patients with cervical carcinoma in the course of complex radiation treatment were responsible for a greater decrease in the frequency of radiation injuries to the intestine as compared with standard complex radiation procedure. This was matched by an increase in the incidence of exacerbation of chronic adnexitis. Radiation appeared to inhibit thyroid function. Low sensitizing dose treatment given in the course of complex radiotherapy did not affect the gland's function. However, cases of stage III cancer exhibited a more pronounced decrease in thyrotrophin levels accompanied by higher somatotropin levels.

Immunologic recovery from radiation injury was used to assess age-related loss of immunologic homeostasis. Mice were exposed to 500 rad to determine whether macrophages, T helper cells and/or T responder cells were responsible for the age-related delay in recovery of PHA-induced mitogenesis. Recovery of macrophages was determined by facilitation of macrophage-deficient cultures, recovery of T helper cells by interleukin 2 production, and recovery of T responder cells by incorporation of tritiated thymidine. The results showed that in old mice macrophages are resistant to radiation and aging, T helper cells recover completely from radiation, and recovery is incomplete for T responder cells.

The influence of hydrocortisone and radiation on potassium homeostasis in isolated hepatocytes (in vivo experiments) and perfusing liver of mongrel rats has been investigated. The effects of hydrocortisone and radiation (7 Gy) on redistribution of intracellular potassium are shown to be similar with respect to their depth and direction. However with the hormone and ionizing radiation delivered simultaneously no additivity of the effects is registered.

After intravenous blood exposure to low-intensity radiation of Helium-Neon laser patients with haemorrhagic pancreatitis exhibited inhibition of the blood proteolytic activity; enhancement of free-radical oxidation, kallikrein-kinin system activity, blood oxygen transport, correction of endotoxic pancreatogenic syndrome. In addition, the positive shifts were also observed in the immunological status, morphofunctional characteristics of the red blood cells and hemoglobin, hepatic and renal functions. In severe pancreatogenic endotoxicosis the highest response was achieved with combined use of hemosorption and intravenous laser irradiation.

Reliability of biosystems in processes of adaptation and homeostasis after whole-body irradiation of rats with different doses was determined in terms of the stochastic process theory developed for the autoregulatory systems with random parameters. Fluctuations in the rate of spontaneous chemiluminescence of blood serum and accumulation of lipid peroxidation products by erythrocyte membranes of rat blood were taken as the initial material. The analysis of fluctuations of peculiar parameters permitted to predict the adaptability of the system and to make timely corrections.