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Biomedical subjects

J Netíková

Publications and source records attributed to J Netíková.

At least 37 records · Page 2Linked to original sources

Enhancement of hematopoietic recovery in gamma-irradiated mice by the joint use of diclofenac, an inhibitor of prostaglandin production, and glucan, a macrophage activator.

The effects of diclofenac (inhibitor of prostaglandin production) and carboxymethylglucan (immunomodulator and an agent stimulating hematopoiesis), when given to mice 1 day before gamma-irradiation, were studied. Both of the agents were administered either alone or in combination. The investigations included the assessment of post-irradiation hematopoietic recovery in terms of bone marrow and spleen cellularity and endogenous spleen colony formation, as well as the determination of the survival of lethally irradiated mice. The results demonstrated at least additive radioprotective effects when mice were given diclofenac and carboxymethylglucan in combination. Experimental evidence provided by the increased 125iodo-deoxyuridine incorporation into the spleen and elevated hydroxyurea kill of endogenous spleen colony-forming units indicated that the beneficial action of the combined treatment could be a consequence of increased cell proliferation in the hematopoietic tissue. It is likely that the inhibition of prostaglandin production (diclofenac action) and the concomitant increased release of growth factors (glucan action) shift the regulatory balance towards the predominance of positive hematopoietic control.

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Radioprotective effect of inosine and its enhancement by magnesium and global hypoxia.

The slight radioprotective action of inosine, when injected intraperitoneally to mice shortly before gamma-irradiation, can be enhanced by the administration of magnesium aspartate. This effect can be explained by the additivity of the vasodilatory actions of both agents. Inosine increases the radioprotective effectiveness of hypobaric hypoxia (10% O2), probably due to the additivity of the hypoxic effects in radiosensitive tissues. Acute hypoxic toxicity, however, is decreased by inosine administration. The cumulation of radioprotective effects of inosine and of its antihypoxic action in vitally important organs can have a favourable influence in hypoxic radiotherapy.

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Possibilities of the combined use of non-steroidal anti-inflammatory drugs and sulfhydryl compounds in radioprotection.

The combined preirradiation administration of indomethacin and cystamine was found to enhance synergistically the recovery of hemopoiesis in sublethally gamma-irradiated mice. This effect can be explained by a common operation of two mechanisms of radioprotection, i.e. of an increased survival of hemopoietic stem cells due to cystamine action and of stimulatory effects of indomethacin on the proliferation of surviving cells, mediated by the inhibition of prostaglandin synthesis. Attempts to prove such enhancement of protective effects on irradiated mice in terms of postirradiation lethality were unsuccessful. The reason seems to be the influence of toxic effects of the indomethacin-cystamine combination on the gastrointestinal tract. When using the less toxic combination, i.e. diclofenac and WR-2721, the additivity of protective effects is manifested even in the survival of lethally irradiated mice. The results suggest that under suitable conditions avoiding the unfavourable toxic effects, non-steroidal anti-inflammatory drugs can be successfully used with the aim to enhance the efficiency of sulfhydryl radioprotectors.

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Combined radioprotection by preirradiation peroral cystamine and postirradiation glucan administration.

The possibilities of combined radioprotection, using preirradiation peroral cystamine and postirradiation intraperitoneal glucan administration in sublethally and lethally whole-body gamma-irradiated mice were investigated. The results demonstrated at least additive radioprotective effects of both agents, manifested in the enhancement of postirradiation haemopoietic recovery and increased survival of irradiated mice. The effects appear to depend on the sequential cell protection mediated by cystamine and enhanced haemopoietic repopulation induced by glucan.

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Enhancement of haemopoietic recovery in sublethally gamma-irradiated mice by the joint use of indomethacin and cystamine.

The effects of indomethacin and cystamine, administered prior to gamma-irradiation of mice, were investigated. Synergistic enhancement of haemopoietic recovery was observed under the conditions of a joint use of both drugs. The reason for this synergistic action is probably a joint operation of two mechanisms, i.e., the lowering of the radiosensitivity of haemopoietic stem cells by cystamine and the increase of the proliferation of surviving haemopoietic cells by indomethacin.

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Effect of indomethacin, diclofenac sodium and sodium salicylate on peripheral blood cell counts in sublethally gamma-irradiated mice.

Treatment with indomethacin and diclofenac sodium was found to increase granulocyte counts in the blood of sublethally gamma-irradiated mice. Treatment with sodium salicylate was ineffective in this respect, administration of sodium salicylate together with indomethacin even decreased the indomethacin-induced effects. The results suggest that the hemopoiesis-stimulating effects of non-steroidal anti-inflammatory drugs cannot be correlated with the anti-inflammatory activity but rather with the side effects of these compounds, including the action on gastro-intestinal prostanoid production. This conclusion doubts on the possibility of the usefulness of non-steroidal anti-inflammatory drugs in conditions of the radiation syndrome.

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Interstrain differences in the responsiveness of mice to glucan with respect to hematological effects and manifestations of late damage.

A study was made of the effect of a single s.c. injection of 4 mg glucan in the mouse strains C57BL/10, C3H and a hybrid population of mice. In mice of the strain C57BL/10 high responsiveness was demonstrated, manifested in a long-term increase in the granulocyte counts in the peripheral blood. These effects were accompanied by a fall in the mean red cell volume and the mean corpuscular hemoglobin, a fall in body weight, and mortality. 10 weeks after administration of glucan histology revealed necrotic foci in the livers of animals of the C57BL/10 strain, and an increased amount of the fibrous connective component in the pulmonary interstitium. The strain C3H exhibited a low responsiveness in respect of the hematological indices, while the hybrids did not show any significant response.

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Effect of indomethacin on the proliferative and differentiation activity in the haemopoietic system of lethally irradiated mice after syngeneic bone marrow transplantation.

The effects of indomethacin treatment on the proliferation and differentiation of haemopoietic stem cells of bone marrow grafts in lethally irradiated mice were investigated. Indomethacin was given subcutaneously, on days 3 to 5 after irradiation, in 6 doses of 0.05 mg per mouse. On day 6 after irradiation, an increased self-renewal of the settled colony-forming cells and an increased amount of differentiated cells were observed in the spleens of the mice treated. Simultaneously, a decreased maturation of the erythroid cells was demonstrated. The effects observed may be explained by the indomethacin-induced inhibition of prostaglandin biosynthesis.

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Comparison of cell proliferation in the regenerating bone marrow and spleen of irradiated mice with the use of 125I-iododeoxyuridine.

The method of 125IUdR labelling of hemopoietic cell populations was used to estimate differences of repopulation kinetics in the femoral bone marrow and spleen of sublethally irradiated mice. In regenerating bone marrow the cellularity and proliferation index, as measured by 6 h 125IUdR incorporation, were found to be inversely related. In the spleen the proliferation index increased parallelly with the increase in cellularity and indicates an ineffectiveness of a change in the set point of local cellularity control. Experiments with measuring the retention of 125IUdR in hemopoietic organs revealed, in the spleen of irradiated animals, phases of increased cell losses as well as immigration of labelled cells into this organ.

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Chloramphenicol toxicity in radiation disease.

The effect of chloramphenicol given in high therapeutic doses, in the course of postirradiation syndrome in irradiated mice of C57Bl/10 strain, is reported. Chloramphenicol treatment increased postirradiation mortality of animals and intensified suppression of the proliferating and differentiating processes in hemopoietic organs of the irradiated animals. The results support the assumption that postirradiation depression of hemopoiesis is a contraindication to the therapeutic employment of this antibiotic.

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Influence of the thyroid hormones on erythropoiesis and radiation resistance in C 57 black mice.

Oral administration of dried thyroid gland to C57Bl adult male mice in a dose of 0.6 g per 100 g diet during 10 days increased the metabolic rate and stimulated the erythropoiesis. Three to six days after thyroid pretreatment the radiation resistance of the mice increased, as revealed by their 30-day survival and a higher recovery of peripheral blood cell counts. The period of increased resistance to radiation was correlated with the receding of hypermetabolic effects and with the increase of repopulating abilities of the bone marrow cells.

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Effect of K and Mg salts of aspartic acid on haemopoiesis and recovery from radiation damage in mice.

Male mice of a non-inbred strain "H" were used to verify the effect of a 10-day peroral administration of K and Mg aspartates on haemopoietic functions. The salts were proved to stimulate the proliferation and differentiation processes in the thymus, bone marrow and spleen tissues. Mice exposed to a single whole-body X-irradiation after pretreatment with K, Mg aspartate exhibited a more conspicuous postirradiation regeneration of haemopoietic organs and an increased postirradiation survival. The results suggest the possibility of using K, Mg aspartate for radioprotective purposes.

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The effect of preirradiation application of aspartic acid salts on hemopoietic recovery in X-irradiated mice.

The possibility of radioprotective action of K and Mg aspartate administered in tap water for ten days prior to X-irradiation was investigated in male mice of the strain C 57 Bl/10. In normal animals, thymus weight was found to be increased by 10-day treatment with K and Mg aspartate. The postirradiation regeneration of spleen weight and incorporation of radioactive iron into the spleen and femoral marrow following sublethal irradiation was favorably modified by the treatment used. Pretreatment of mice with K and Mg aspartate delays the onset of early deaths at irradiation with an absolutely lethal X-ray exposure and raises the percentage of surviving animals after nearly lethal exposures.

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