[Radiation lesion formation and character of repair processes in the hematopoietic system of primates exposed to continuous and fractionated gamma-irradiation by equally effective doses].

The article is dedicated to comparison of the biological effectiveness of continuous and fractionated gamma-irradiation of rhesus macaques by equally effective doses. These radiation conditions are broadly used in radiobiological experiments. Specifically, they are applied in modeling radiation effects on cosmonauts during extended exploration mission. A model of radiation damage and repair on the cell, tissue and organism levels, i.e., a model of effective residual dose responsible for change in mammals' resistance to irradiation of varying duration was used to calculate equally effective doses in the experiment with primates subject to continuous and fractionated exposure. The authors publish data related to formation of radiation lesion and rate of ensuing hemopoiesis reparation. Two groups of animals were compared in resistance modification followed after testing by acute irradiation. The test was to reproduce a radiation situation for cosmonauts in the event of a cannonade of powerful solar proton events resulting in an effective residual dose of 1 Sv total The experiment evidenced close resemblance of the hemopoietic effects in primates exposed to the compared radiation conditions.

[Blood plasma volume dynamics in monkeys during immersion]. / Dinamika ob"ema plazmy u obez'ian v usloviiakh immersii.

Dynamics of blood plasma volume (PV) was studied with indirect methods (hematocrit count, hemoglobin, total protein and high-molecular protein) during 9-d immersion of monkeys Macaca mulatta. The animals were donned in waterproof suits, motor restrained in space seat liners and immersed down to the xiphisternum. Two monkeys were immersed in the bath at one time. The suits were changed every day under ketamine (10 mg/kg of body mass). There were two groups with 12 animals in each. The first group was kept in the bath 3 days and the second--9 days. Prior to the experiment, the animals had been trained to stay in the seat liner put down into the dry bath. It was shown that already two days of exposure to the hydrostatic forces (approximately 15 mm Hg) and absence of negative pressure breathing reduced PV by 18-20% on the average in all animals. Subsequent PV dynamics was individual by character; however, PV deficit persisted during 4 days of immersion in the whole group. In this period, albumin filtration was increased significantly, whereas high-molecular protein filtration was increased to a less degree. During the remaining days in immersion PV regained normal values. Ten days of readaptation (reclined positioning of monkeys brought back into cage) raised VP beyond baseline values. This phenomenon can be attributed to the necessity to provide appropriate venous return and sufficient blood supply of organs and tissues following extension of blood vessels capacity.

[The effect of microgravity and head down immobilization on hemopoiesis in primates]. / Vozdeistvie nevesomosti i antiortostaticheskoi gipokinezii na krovetvorenie u obez'ian.

Objects of the investigation were peripheral blood and bone marrow cytology in 6 primates during readaptation following the 2-wk. space flights (SF) aboard biosatellites BION-9, 10 and 11, and ground-based simulations of 17-d sitting in the chairs of the Bios-primat capsule (4 primates) and 4-wk. head-down immobilization (-5 degrees, 12 primates). On completion of each of the three experiments, the hemopoietic system was characterized by a distinct nonspecific stress-reaction, i.e. neutrophilous leukocytosis against reductions of the lymphocyte and eosinophil counts. After SF and HD immobilization, the blood profile carried signs of a specific reaction which consisted of a hemoconcentration (hematocrit and hemoglobin) reduction during early readaptation and recovery as a result of erythropoiesis activation due to, primarily, blood redistribution and a decreased weight-bearing load. The specific reactions to HD immobilization were less significant and did not reveal themselves at all in the chaired primates.

[Repeated hypergravity: morphologic investigations of pituitary, thyroid, blood and bone marrow in rats]. / Povtornoe vozdeistvie gipergravitatsii: morfologicheskoe issledovanie gipofiza, shchitovidnoi zhelezy, krovi i kostnogo mozga krys.

To elicit the mechanism of facilitating the mammals' adaptation to repeated changed gravity influence, the pituitary, thyroid, blood and bone marrow were investigated morphologically in rats exposed to single and repeated hypergravity (2 g) and Coriolis accelerations for 5 days during rotation on centrifuge. No distinct difference in blood and bone marrow cytology was determined after single and repeated exposure to 2 g and the Coriolis accelerations. Compared to single and in contrast to single and repeated exposures to the Coriolis accelerations, a repeated 2 g influence produced some structural changes in somatotropic cells of the pituitary and thyroid parenchyma of the thyroid. These changes were indicative of a significant intensification of synthesis and secretion of somatotropic and thyroid hormones. Elevated functional activity of the somatotropic cells and thyroid parenchyma during repeated exposure to 2 g appears to be a part of mechanism that makes adaptation to repeated hypergravity easier and points to the ability of mammals "to remember" changed gravity. It also advocates for the potentiality of intermittent centrifugation as a means of generating artificial gravity forces in space flight.

[The characteristics of the reparative process in the muscles when deprived of their functional loads]. / Osobennosti reparatsionnogo protsessa v myshtsakh pri lishenii ikh funktsional'nykh nagruzok.

The time course of repair process in the tonic soleus and phasic gastrocnemius muscles of the head-down tail-suspended rats being traumatized directly prior to suspension or immediately after it. During first, suspension, the animals have been studied on the 17th suspension day and in the second 14-day suspension they were tested on the 14th and 17th post-traumatic days. It was indicated that the suspension results in muscle atrophy with a severely affected m. gastrocnemius loosing more than 40% of its mass. Under the effect of atrophy-induced factors in both muscles there equally occurred an inhibition of both the formation of connective stroma of repair field and the isolation of myoblasts from dedifferentiated muscular fibers due to which an extremely small-size repair field with the irregularly oriented muscular fibers and myoblasts has been originated.

[The healing of bone fractures in rats during the readaptation after a 14-day head-down suspension]. / Zazhivlenie perelomov kostei u krys v periode readaptatsii posle 14-sutochnogo vyveshivaniia.

Histological, histochemical and histomorphometric methods have been used to study an effect of a 14-day head-down suspension on healing the fractured fibular diaphysis in the rats traumatized immediately after suspension. The study of the fibulae on Days 11 and 17 following an operative fracture indicated that both in control and experimental rats the ends of fractured bones were tightly interconnected by the calluses. A comparative study of the calluses and their structural components as well as detailed investigation of histological structure of calluses on the 11th and 17th post-traumatic days did not reveal significant differences between control and experimental animals. Furthermore, the rate of cartilage replacement by spongy bone tissue in calluses of experimental animals was even somewhat higher than that in control rats. Thus the data obtained give ground to believe that in a readaptation period after 14-day suspension resulting in the osteoporotic changes of weight-bearing bones a repair process in the bones is rapidly normalized and in some parameters exceeds it in control animals.

[The hematological status of rats born and raised under increased gravitational force]. / Gematologicheskii status krys, rodivshikhsia i vyrosshikh v usloviiakh povyshennoi sily tiazhesti.

Blood and bone marrow morphology of the rats the pre- and postnatal development of which up to the ages of 60 and 75 days took place under 2g environments induced by a continuous centrifuge rotation. The response to a reduced gravity was studied in 60-day-old rats on post-rotation days 2 and 15. Immediately post-rotation, these animals exhibited: an intensified erythropoiesis resulting in an elevated erythroid cell counts, an activated eosinophilopoiesis and decreased level of neutrophilopoiesis. Return of the animals to a terrestrial environment during a 2-week period has caused a greater increase of erythroid production and the tendency toward normalizing granulocytopoiesis. In the 75-day-old rats developed under 2g, erythro- and granulocytopoiesis have tended to be recovered and bone marrow population of lymphoid and plasma cells was significantly decreased. The results point to the fact that hemopoiesis adaptation to an increased gravity during the studied period of time is not accomplished and this hematologic status depends on a changed status, of the controlling systems.

[Effect of weightlessness on the course of the reparative process in the muscles of the biosatellite Kosmos-2044 rats]. / Vliianie nevesomosti na techenie reparativnogo protsessa v myshtsakh krys, éksponirovannykh na biosputnike "Kosmos-2044".

The repair process in the soleus and gastrocnemius muscles of SPF Wistar rats flown for 14 days on the biosatellite Cosmos-2044 was investigated. The muscles were injured 2 days before launch by means of clamp forceps. The exposure inhibited the process but did not impair its phasic development. As a result, the reparative field diminished and took the size of an atrophic muscle; thinner myofibers appeared that originated from the ends of injured atrophic fibers and fibers that underwent splitting. It is postulated that repair inhibition is caused by the same mechanisms that produce muscle atrophy in microgravity. It is suggested that both repair inhibition and muscle atrophy are induced by disorders in the neurotrophic regulation of metabolism due to partial disuse.

[The effect of weightlessness on fracture healing of rats flown on the biosatellite Cosmos-2044]. / Vliianie nevesomosti na zazhivlenie perelomov kostei u krys, éksponirovannykh na biosputnike "Kosmos-2044".

Two days before launch of the biosatellite Cosmos-2044 five rats were exposed to surgical intervention: their fibulas were cut bilaterally. The purpose was to study the effect of microgravity on bone fracture healing. Histologically and histomorphometrically it was demonstrated that healing was inhibited; as a result, bone callus was poorly developed and bone fragment consolidation was inadequate. An increase in the relative volume of osteoid and a simultaneous decrease in the number and activity of osteoblasts point to mineral disorders of newly formed bone in microgravity. Study of untreated tibia showed that exposure to microgravity led to osteoporosis of proximal metaphyses. This osteoporosis was produced by inhibited neoformation and enhanced resorption of bone. Comparative analysis of injured fibula and untreated tibia of rats exposed to real microgravity for 14 days or tail suspended demonstrated similarity of changes. This indicates that tail suspension can be viewed as an adequate simulation of microgravity with respect to changes in hindlimb bones.

[Trace element composition of bone tissue of mice in the normal state and in hypokinesia]. / Elementnyi sostav kostnoi tkani myshei v norme i pri gipokinezii.

Using neutron activation analysis, the concentration of 13 elements was measured in functionally different bones of mice: weight-bearing and dynamic femurs, essentially stationary temporal bones, and newly formed ectopis bones under the renal capsule developed at the site of implantation of syngenic bone marrow. It was found that the elementary composition of the above bones was different in the norm and that it varied in the course of 3-week hypokinesia produced by small-size cages. It was shown that during hypokinesia the elementary composition changed according to four different patterns. Progressive demineralization due to Ca, P, Mg and Fe losses was accompanied by compensatory incorporation of Sr. In the course of the hypokinetic stress the content of trace elements (Zn, Cr, Ru, Rb, Br, Co, Sb) varied significantly. The mechanisms of action of these elements was related to the mobilization of activating elements at different stages of the general adaptation syndrome.

[Effect of hypokinesia on the osteogenetic and hematopoietic functions of the bone marrow in mice. The ectopic bone model]. / Vliianie gipokinezii na kosteobrazovatel'nuiu i krovetvornuiu funktsiiu kostnogo mozga u myshei na modeli ektopicheskoi kosti.

Using heterotrophic transplantation of syngenic bone marrow under the renal capsule, the effect of hypokinesia on osteogenic and hemopoietic cells-precursors as well as on de novo formed bone marrow was investigated. Altogether 16 experiments were performed, employing 260 recipients and 200 donors in two modifications: 1) bone marrow from animals exposed to hypokinesia for 3 days or 3 weeks (stage I or II of the general adaptation syndrome) was implanted to intact mice; 2) recipients who 5 to 7 day before exposure were implanted with bone marrow from intact donors were hypokinetic for 3 weeks. It was found that determined bone marrow precursors of osteogenic tissue as well as cells transferring hemopoietic microenvironment remained insensitive to hypokinesia. Three-week hypokinesia produced noticeable inhibition of osteogenesis and hemopoiesis. It is concluded that the stress-reaction plays the leading role in the changes that develop in hypokinetic mice.

[Effect of hydrocortisone on the osteogenetic function of the bone marrow of the mouse]. / Vliianie gidrokortizona na kosteobrazovatel'nuiu funktsiiu kostnogo mozga myshei.

Bone marrow cells were implanted into the capsule of the kidney of mice which were then given intraperitoneal injections of hydrocortisone in the dose of 5 mg per animal. The drug influenced different stages of bone histogenesis in a different manner. The stage of the onset of bone formation proved to be most sensitive, whereas the earlier and later stages were less sensitive to hydrocortisone. It is concluded that the target cells for hydrocortisone are osteoblasts at the stage of active synthesis of bone proteins rather than cells-precursors of osteogenesis.

[Effect of 24,25-dihydroxyvitamin D3 on precursor cells of osteogenesis in immobilized rats]. / Vliianie 24,25-dioksivitamina D3 na kletki-predshestvenniki osteogeneza krys v usloviiakh immobilizatsii.

The experiments were carried out on Wistar SPF rats that were immobilized for 35 days. By heterotopic marrow cell transplantation under the kidney capsule to the normal rats and by cloning these cells in vitro it was found that osteogenetic potentials were significantly inhibited and the amount of osteogenetic precursor cells was reduced. The addition of 24,25(OH)2D3 vitamin (at a dose of 1.25 micrograms per day) to the animal diet led to the normalization of the above parameters. It is assumed that immobilization-associated osteoporosis develops via, among other mechanisms, inhibition of histogenesis of stromal precursor cells. The beneficial role of vitamin D3 is actually the activation of histogenesis of these cells which results in the recovery of bone remodelling during immobilization.

[Cytokinetic evaluation of erythropoiesis on prolonged orbital flights]. / Tsitokineticheskaia otsenka éritropoeza pri dlitel'nykh orbital'nykh poletakh.

The purpose of the investigation was to understand better the mechanisms of erythropoietic changes at the cellular level during a prolonged exposure to weightlessness. Following 96-, 140- and 175-day space flights cytokinetic and morphological changes in erythropoiesis were observed. The count of circulating erythrocytes decreased inflight and their life time reduced postflight. The shortening of the life time of erythrocytes postflight was paralleled by increased proliferative activity of erythroid cells. The erythrocytic balance was not reached as late as R + 36. It is recommended that the number of research methods be enlarged.

[Erythrocyte balance during 182 days of hypokinesia]. / Eritrostsitarnyi balans pri 182-sutochnoi gipokinezii.

A prolonged head-down tilt resulted by the end of the second month in a significant decrease in the circulating blood volume at the expense of plasma and erythrocyte volumes. One of the factors that caused a reduction in the erythrocyte volume was their survival time shortening. The fact that during the rest four hypokinetic months there was no further decline in the erythrocyte count was attributed to adaptive developments: increase of bone marrow production and rate of differentiation of erythroid elements. Exercises used as a countermeasure could slightly counteract the adverse effects of head-down tilt.

[State of hematopoiesis during irradiation simulating radiation exposure in prolonged space flight]. / Sostoianie krovetvoreniia pri obluchenii, imitiruiushchem radiatsionnoe vozdeistvie v usloviiakh dlitel'nogo kosmicheskogo poleta

The paper presents the results of studies of the peripheral blood and bone marrow of 36 male dogs exposed to a chronic 3 year gamma-irradiation (from the Co60 source) at a dose rate of 0.17 rad per day which was combined with acute irradiations. The animals received two doses -360 and 564 rad in total. The leukoblastic system showed inhibition and decreased reactivity in case of irradiation with a higher dose. The red blood cell balance remained stable for a long period of time due to activated erythropoiesis.

[Seasonal changeability in the leukocytic composition of blood in dogs]. / Sezonnaia izmenchivost' leikotsitarnogo sostava krovi u sobak.

The leukocyte blood composition was studied for seven years in dogs kept outdoors. The lymphocyte count proved to be higher from May to September than from November to March. Variations in the neutrophil and monocyte count were subject to reverse regularity. Changes in the total leukocyte count failed to coincide with the seasonal periodicity.