[Comparison of different G-CSF treatment effectiveness in experiments on irradiated mice].

In the experiments on F1 (CBA x C57BL) and BALB mice irradiated by 137Cs gamma-rays, preparations of unglycosilated G-SCF such as Neupogen and their domestic analogs Leucostim and Neupomax were investigated. The tests such as 9-day bone marrow cellularity (BMC) and endogenous CFUs, the neutrophile number restoration, the 30-day survival index have shown that all three preparations have an approximately equal effectiveness relating to acute radiation disease treatment and granulopoiesis stimulation after a 5-10 day consecutive administration following irradiation of mice at lethal and sublethal doses. We have come to the conclusion that Leucostim and Neupomax can be regarded as adequate substitutes for Neupogen.

[Mesenchymal stem cells transplantation in the treatment of radiation skin lesions].

Transplantation of mesenchymal stem cells, both at early and later stage after local exposure of rats source beta radiation dose, 90Sr/90Y 140 GR, stimulates recovery of damaged skin. Diminution area local radiation injuries and accelerate healing radiation ulcers. Clinically shows the high efficiency of the transplantations autologous mesenchymal stem cells in treatment of deep beam ulcers, intractable standard conservative treatment. Found promising application of mesenchymal stem cells for treatment of severe local radiation injuries and the need to develop the best possible conditions for their use.

[Antiradiation effects of vaccine Grippol].

The propose of these examination was the study of antiradiation effects of vaccine Grippol (VG). It was determined, that subcutaneous injection VG mice (0.2 ml), hamsters (0.2 ml), dogs (0.5 ml) before 1-14 days of total gamma-irradiation (2.5-8.5 Gy) had positive effect of acute radiation disease. This effect was expressed in increase of survival the mice and hamsters on 30-60%, increase number cells in bone marrow and neutrophiles, erythrocytes, lymphocytes and hemoglobin in blood by comparison with control mice. VG stimulated increase of contents of leucocytes in blood of irradiated (2.5 Gy) dogs.

[Antiradiation effects of lactoferrin].

The propose of these examination was studied antiradiation effect of lactoferrin (LF). It was determined, that subcutaneous injection LF (65 or 300 mkg/kg) guinea-pigs irradiated after 1-14 days after of total gamma-irradiation (2.5 Gr) had therapeutically effect attached to the bone marrow form of acute radiation disease (ARD). This effect was explained in increase of survive the animals with 53.8% to 92.8% and stimulation erythropoiesis, judge by number of reticulocytes and increase neutrophiles (12 days ARD) and lymphocytes (12 and 16 days ARD) by comparison with control animals. LF had no effect attached to intestinal form of acute radiation disease by mice. The injection of LF before total irradiation rats of electrons (energy 25 MeV) in doses 255 Gr decreased expression of some symptom of cerebral form of acute radiation disease: prolong time of beginning convulsive period with 5.7 hours to 14.1 hours and duration of life with 7.7 hours to 15.3 hours. LF had antioxidative activity.

[The influence of mexidol on post-radiation recovery of hemopoietic system].

The purpose of this work was the study in experiments on mice of influence of mexidol on current and outcome of an acute radiation sickness. At an irradiation in a dose 6.0 Gy was studied a condition of hemopoietic system, and at an irradiation in a dose 7.7 Gy a survival rate of animals. In all experiments mexidol applied in two circuits of introduction. The first circuit - once per day with 1 for 8 day after the irradiation. The second circuit of introduction: with 1 for 5 day--two times per day and on 6-8 day once per day. The introduction of mexidol after influence of ionizing radiation reduces a degree of radiative defeat of bone marrow and promotes the activization post-radiation recovery of an erythropoiesis, neutrophilopoiesis in an bone marrow and lymphopoiesis in a thymus gland. This effect is more expressed at introduction mexidol two times per day. At influence of ionizing radiation in a dose 7.7 Gy has survived 56% of mice. The introduction of mexidol two times per day was enlarged by survival rate animal up to 94%. The application of mexidol once per day essentially did not influence on the survival rate of the irradiated mice. The received data show, that the introduction of mexidol with 1 for 8 day after an irradiation, frameing a favorable metabolic background, stimulates recovery processes in hemopoietic system, reduces gravity of a acute radiation sickness and by that enlarges the survival rate of the irradiated animals.

[The influence of multipotent mesenchymal stromal cells of bone marrow on process of local radiation injury in rats after local beta-irradiation].

The influence of multipotent mesenchymal stromal cells (MMSC), got from allogenic bone marrow, on local radiation injury in rats after beta-irradiation by a source 90Sr/90Y in a dose 140 Gy under various conditions and ways transplantation was studied. It was established, that transplantation MMSC, allocated on biodegradative membranes, which have been carried out for 21 day after an irradiation in conditions minor surgical of ulcers, resulted in reduction of the area of local beam defeats and acceleration of healing of skin, in comparison with the control of an irradiation. The introduction of suspension MMSC subcutaneous around of the center of a defeat at 8 day after an irradiation caused earlier healing of ulcers. It was concluded, that application of MMSC is perspective for treatment of local radiation injury and necessity of development of optimum conditions of their use at cell therapy of radiation injury of skin.

[Recombinant human interleukine-1beta (betaleukine) usage for acute radiation sickness of severe degree treatment at canines].

Recombinant human interleukine-1beta (betaleukune) of Institute of especially pure biopreparation production had been examined as a treatment means at acute radiation disease of severe degree at dogs. Dogs were irradiated totally in doses above the LD95/45. Betaleukine had been administered s/c twice in day in 15 min - 2 h after irradiation. All the dogs, including control ones, received in acute period 8-24/26 days after irradiation antibiotics ampicillin and gentamycin i/m. Betaleukine increased 45 day-survival by 37% at 4 Gy and by 25% at 4.4 Gy. The effect correlated with more high level of nadir and more early beginning the leucocyte number restoration. We observed the regularity at all the dogs that received betaleukine as survived as died, but in the latter case in a lesser degree certainly. Besides the noticed character of leucocytes kinetics had been repeated at all the blood cell types but in the different degree. It had been concluded on the base of these observations that betaleukine acts on hemopoietic stem cells preferentially. The effect is in preventing death of a stem cells part, or in stimulating survived stem cells proliferation, or in both together. Betaleukin can be regarded as a suitable means of urgent pathogenic therapy at radiation accidents.

[Acute radiation sickness in experiment. Efficacy of mexidol].

Experiments on mice were made to examine mexidol effects on the course and outcome of acute radiation sickness (ARS). Regenerative processes in hemopoietic system were studied after 6.0 Gy radiation, survival of the animals was studied in 7.7 Gy radiation. Mexidol was used in two schemes. Scheme one--once a day on days 1-8 after radiation. Scheme 2--twice a day on days 1-5, and once a day on days 6-8 after radiation. Administration of mexidol after exposure to ionizing radiation promotes activation of postradiation recovery of erythropoiesis, neutrophilopoiesis in bone marrow and lymphopoiesis in the thymus. This effect was stronger in mexidol administration twice a day. After ionizing radiation in a dose 7.7 Gy only 56% mice survived. Twice a day mexidol increased the survival to 94%. Once a day mexidol had insignificant effect on survival of mice. Thus, administration of mexidol on days 1-8 after radiation had a good effect on metabolism, stimulates regenerative processes in hemopoietic system, attenuates severity of ARS and increases survival of irradiated animals.

[Effect of mexidol on hemopoietic system in conditions of an emotional stress after exposure to ionizing radiation].

The emotional stress after an irradiation can complicate the current of radiative defeats. At an emotional stress developing in early terms after an irradiation in low doses, are reduced adaptive and compensator capabilities of hemopoietic system. The emotional stress after a lethal dose irradiation inhibits the post-radiation recovery of haemopoiesis, aggravates the course of acute radiation disease and decreases the efficiency of the radioprotector--indralin. These disorders are especially pronounced under a prolonged and intensive stress. The use of the mexidol, having anxiolytic and antistress by activity, made it possible to arrest completely disturbances in the development of adaptive reactions to stress in the blood system and to normalize its compensatory potentialities in animals under conditions of combined influence of intensive long-term emotional stress and of low-dose irradiation. In the case of lethally irraiated animals, the treatment of stressed animals with mexidol favorably influenced the course of acute radiation disease, enhanced recovery processes in the blood system. Under these conditions, the use of mexidol completely removes the negative effect of emotional stress in indralin-protected animals. The pharmacological correction by mexidol from displays of an intensive emotional stress, developing after an irradiation in various doses, can be a part in system of medical measures.

[Using aphobazol for treatment of the emotional stress after exposure to ionizing radiation].

Emotional stress after radiation may aggravate the course of radiation-induced diseases. The use of the selective anxiolytic aphobazol (a drug from a mercaptobenzamidasol group) corrects development of adaptive reactions to stress in the blood system and normalizes its compensatory potentialities in animals under conditions of combined influence of intensive long-term emotional stress and low-dose irradiation. In lethally irradiated animals the treatment of stressed animals with aphobazol favourably influenced the course of acute radiation disease, enhanced recovery processes in the blood system, increased the animals' survival. The use of aphobazol completely removed a negative effect of emotional stress in indralin-protected animals. Thus, pharmacological correction of the emotional stress caused by different doses of radiation is not only a symptomatic but also a pathogenetically justified form of treatment.

[The adaptive reactions in hemopoietic system of the irradiated mice of two lines, differing in the level of emotionally-stress reactions on the emotional stress].

On lines of the mice genetically differing on the sensitivity on emotional stress (steady--of the mouse of the line C57BL/6 or sensitive--of the mouse of the line BALB/c), the research of the development of the adaptive reactions in the system of the blood on the emotional stress influencing animals on the background of the preliminary irradiation in a low dose (0.9 Gy) is carried out. The unirradiated mice of the line C57BL/6 adequately reacted on the stress, that was shown in a moderate behavioural reaction during the period of stress, and the development of high-grade adaptive reactions in the hemopoietic system. Among the mice of the line C57BL/6 in conditions of the combined influence of ionizing radiation and of the emotional stress was not revealed of the infringements of the adaptive reactions of the hemogenesis. As opposed to these data, among unirradiated mice of the line BALB/c the sharply expressed behavioural reactions during the stress were marked, that was accompanied by incomplete development of the adaptive reactions in the system of a blood on the stress. Under the influence of stress on the previously irradiated animal line BALB/c was observed the inhibition of the medullar hemopoiesis.

[The effect of prodigiozan on the postradiational recovery of hemopoiesis in long-term bone morrow cultures of mice of different genotypes].

The influence of prodigiozan on the processes of postirradiation recovery of hemopoiesis in long-term bone morrow cultures of two strain mice, having genetic distinctions in the condition of systems of the reparation DNA was investigated. It was showh, that the irradiation of long-term bone morrow cultures of mice reparation-defective strain 101/H resulted in the greater degree damage of early haemopoietic precursors (GM-CFC), reduction of the amount of the immature and of the mature granulocytes and of the decrease of the number of stromall cells in the comparison with the bone morrow of reparation-capable mice (CBA x C57B1)F1. Under the introduction in cultures of prodigiozan for 24 hours prior to an radiation the distinctions of the speed of postirradiation recovery of hemopoiesis substantially smoothed out, and the protective effect of the drag in bone morrow cultures of mice 101/H was comparable to those, marked in bone morrow cultures of reparation-capable strain mice (CBA x C57B1)F1. It is supposed, that this effect can be caused by the activation of the hematopoietic microenvironment cellular elements and inclusion of the mechanisms of intercellular of interactions, which provide stimulation of the regenerative processes at action radioprotective drags and can in the certain degree to compensate the defect of the systems of the reparation DNA.

[Antiradiation effects of leucynferon on dogs and guinea pigs]. / Protivoluchevaia éffektivnost' leikinferona u sobak i morskikh svinok.

In experiments with two species of animals (dogs, guinea pigs) irradiated with sublethal and lethal doses of gamma-rays, it was observed, that leucynferon had antiradiation effect. Course of injections: dogs--8 injections subcutaneus: 2.0 ml (1, 3, 5, 8, 12, 14, 21, 34 days after irradiation); guinea pigs--14 injections subcutaneus, 0.2 ml (1-14 days after irradiation). Therapeutical effect was explained by capacity of the preparation to defend the hemopoietic organs from the radiation and to stimulate hemopoiesis. Leucynferon hindered the development of acute radiation sickness symptoms. Immunoreactivity of dogs and guinea pigs in experimental group was more complete and restored faster. The growth of the automicroflora on the skin was restrained. Production of interferon-gamma (which is a function of T-lymphocytes) was restored faster.

[The role of hematopoietic microenvironment in prodigiozan' mechanism of action on postradiation recovery of hemopoiesis in long-term bone marrow cultures]. / Rol' gemopoézindutsiruiushchego mikrookruzheniia v mekhanizme deistviia prodigiozana na protsessy postradiatsionnogo vosstanovleniia krovetvoreniia v dlitel'nykh kul'turakh kostnogo mozga.

Influence of prodigiozan in different concentrations on the process of postirradiation recovery of haemopoietic precursors (GM-CFC) and morphologically recognizable elements of the bone marrow were studied in long-term bone marrow cultures during 28 days after 2 Gy gamma-irradiation. Also, prodigiozan was studied for action on the contents of GM-CFC and induction of GM-CSF three, 24 and 48 hours after injection in cultures unexposed to radiation. It is shown that injection of prodigiozan in concentration 0.1-1.0 microg/ml 24 hours prior to irradiation stimulates postradiation recovery of GM-CFC number and a total number of myelocaryocytes in irradiation of long-term bone marrow cultures. In saved cultures there was an increase in the number of stromal cells 1 and 2 days after radiation. In non-exposed to radiation long-term bone marrow cultures injection of prodigiozan increased induction of GM-CSF and raised contents of GM-CFC. The maximal increase occurred 24 hours after introduction of radioprotector. It is suggested that one of the mechanisms of a radioprotective action of prodigiozan may be stimulation of hematopoietic microenvironment cellular elements leading to a marked release of GM-CSF or/and other cytokines and stimulation of recovery of hemopoietic precursors.

[Role of hematopoietic microenvironment in the mechanism of radioprotective action of interleukin-1 beta in long-term bone marrow cultures]. / Izuchenie roli gemopoézindutsiruiushchego mikrookruzheniia v mekhanizme radiozashchitnogo deistviia interleikina-1 beta na modeli dlitel'nykh kul'tur kostnogo mozga.

The influence of human interleukin-1 beta in different concentration on processes of postirradiation recovery of haemopoietic precursors (GM-CFC) and morphology of recognized elements of bone marrow were studied in long-term bone marrow cultures during 28 days after gamma-irradiation with a dose of 2 Gy. It was studied also the action of interleukin-1 beta on proliferation, the contents of GM-CFC and the induction of GM-CSF in non-irradiated cultures. It was shown that the injection of interleukin-1 beta increased proliferation and the content of GM-CFC and also raised an induction of GM-CSF in the non-irradiation cultures. The maximum increase of a level of GM-CSF, amount of GM-CFC and proliferation of GM-CFC was marked in 20 hours after the injection of cytokine. Under irradiation of long-term bone marrow cultures the maximum stimulation effect to recovery of GM-CFC, total number of myelocaryocytes and the content of immature and mature granulocytes were observed after the injection of interleukin-1 beta in concentration of 0.005 microgram/ml 20 hours prior to radiation exposure. The data of this report suggest that one of the mechanisms of radioprotective action of interleukin-1 beta apparently is connected with stimulation action on hematopoietic microenvironment cellular elements that causes the release of GM-CSF or/and other cytokines, and stimulation recovery of haemopoietic precursors.

[Bone marrow hemopoiesis at emotional stress reactions of various intensity upon a background of exposure to low dose ionizing radiation]. / Kostnomozgovoe krovetvorenie pri émotsional'no-stressornykh reaktsiiakh razlichnoi intensivnosti na fone deistviia ioniziruiushchei radiatsii v nizkoi doze.

Rats preliminary exposed to 0.9 Gy of ionizing radiation showed disturbances in the development of adaptive reactions of blood system to emotional stress, compensatory capacity of the blood system being decreased. A degree of the disturbances directly depended on the duration and intensity of the emotional stress: at the prolonged intensive emotional stress a sharp decrease in the adaptive and compensatory capacity of blood system was found; at short intensive or moderate stress the changes in the adaptive and compensatory capacity of hemopoiesis were less pronounced. A combined action of low-dose ionizing radiation and short weak emotional stress did non affect the adaptive and compensatory capacity of hemopoietic system.

[Pharmacological correction of emotional stress after exposure to ionizing radiation and treatment with a radioprotector indralin]. / Farmakologicheskaia korrektsiia émotsional'nogo stressa v usloviiakh vozdeistviia na organizm ioniziruiushchego izlucheniia i primeneniia radioprotektora - indralina.

A possibility to use tranquilizers (aphobazole, phenazepamum) for reducing symptoms of prolonged emotional stress influencing rats after irradiation under treatment with a radioprotector indralin was investigated. It was found that indralin showed the protective effect and activated regenerative processes in the hemopoietic system of animals exposed to doses of 6.0 and 7.0 Gy. The prolonged emotional stress developing in the early periods after the exposure, essentially reduced the favourable action of the radioprotector on restoration of hemopoiesis. The application of tranquilizers stopped the inhibiting action of the emotional stress on the hemopoietic system of the irradiated animals in conditions of radioprotective administering.

[Emotional stress and problems of radiation medicine]. / Emotsional'nyi stress i problemy radiatsionnoi meditsiny.

The influence of emotional stress on behaviour and industrial activity of man as well as on the development of posttraumatic stressful frustration and other disorders is considered in connection with real or possible action of ionizing radiation, and on the course of radiation injuries. It is shown that a problem of emotional stress and radiation safety are closely connected. The study is important for solving problems facing emergency medicine.

[Study of mechanisms of anti-irradiation effects of interleukin-1beta in long-term bone marrow cultures]. / Issledovanie mekhanizmov protivoluchevogo deistviia interleikina-1beta na modeli dlitel'nykh kul'tur kostnogo mozga.

The influence of betaleukin (human recombinant interleukin-1 beta) on the processes of postirradiation recovery of haemopoietic precursors (GM-CFC) and the level of granulocyte-macrophag colony-stimulating factor (GM-CSF) were studied in long-term bone marrow cultures after gamma-irradiation with a dose 2 Gy. Then the betaleukin action on the contents of GM-CFC and induction of GM-CSF in the non irradiated cultures was studied. It was shown that betaleukin increased the induction of GM-CSF and raised the contents of GM-CFC in long-term bone marrow cultures, and the maximal increase of a GM-CSF level and GM-CFC amount was marked in 20 hours after introduction. At an irradiation of long-term bone marrow cultures in conditions of betaleukin introduction 20 hours prior to influence of radiation the smaller degree of damage and faster recovery of GM-CFC was observed. The data in this report suggest that one of the mechanisms of antiirradiation action of betaleukin apparently is connected to the action of the preparation on hematopoietic microenvironment cellular elements, that causes the release of a colony-stimulating factor and stimulation of recovery of haemopoietic precursors.

[Dependence of the therapeutic effectiveness of interleukin-1beta on the time of the drug administration after irradiation of mice]. / Zavisimost' lechebnoi éffektivnosti interleikina-1beta ot sroka vvedeniia preparata posle oblucheniia myshei.

In experiments on mice F1(CBA x C57BL/6) the dependence of 30th days survival on the time of betaleukin (medicine form of interleukin-1 beta) administering after exposure to 7.5 Gy whole body gamma-irradiation from 137Cs (approximately DL80/30) was studied. Betaleukin was injected subcutaneously in dose 25 mcg/kg 0.2, 1, 3, 6 and 24 h after the exposure. The highest therapeutic effect took place in case of 0.2 h interval, then it dropped but was slightly expressed at 1 h. The hemopoiesis condition was studied in 7 or 9 days after the mice exposure to 6 Gy and betaleukin administering 1 h later in dose 25 or 50 mcg/kg. The positive effect on granulopoiesis beginning from the level of CFU-GM was observed. There were analyzed the reasons of weaker betaleukin effect and shorter period of its effectiveness after exposure in comparison with literature data regarding IL-1.