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Biomedical subjects

V S Oganov

Publications and source records attributed to V S Oganov.

At least 19 recordsLinked to original sources

Modern analysis of bone loss mechanisms in microgravity.

A summary of results of investigations by the author and a brief review of some literature data on human bone tissue deprived of mechanical loading (spaceflight, hypokinesia) is given. The direction and markedness of changes in bone mass--the bone mineral density and the bone mineral content--in different skeletal segments depend on their position relative to the gravity vector. A theoretically expected bone mass reduction was revealed in the trabecular structures of the bones of the lower part of the skeleton (local osteopenia). In the upper part of the skeleton, an increase in the bone mineral content is observed, which is considered as a secondary response and is due to redistribution of body fluids cephalad. The main cause of osteopenia is mechanical unloading. Arguments are presented that osteocyte osteolysis, delayed osteoblast histogenesis, and osteoclast resorption provoked by rearrangement in the hierarchy of the systems of fluid volume and ion regulation, and the endocrine control of calcium homeostasis are the main mechanisms of osteopenia.

Absorptiometry, Photon↗

Interactions of cells in zones of bone resorption under microgravity and hypokinesia.

With the use of the methods of electron microscopy and autoradiography employing 3H-glycine the study was made of some morpho-functional cells-cells interactions (osteoblasts, osteocytes, macrophages, fibroblasts) in zones of adaptive remodeling of bone structures of the metaepiphyseal femoral bones of white rats which were during 28 days under experimental hypokinesia conditions, as well as of rats, flown on SLS-2 during 2 weeks. It is established that in zones of an increase of mineral matrix resorption some osteoblasts and osteocytes undergo destruction; a part of osteoblasts remains intact. The osteoclasts don't take part in destruction of osteoblasts and osteocytes. The utilization of the osteogenic cells detritus is accomplished by macrophages, coming to these zones. The resorption loci are filled not with the differentiating osteoblastic cells, as it is the case in the norm, but with fibroblasts and the bundles of collagen fibrils (fibrotic tissue) which do not undergo mineralization. Such changes are considered as one of the mechanisms of bone tissue response to a reduction of the supporting load.

Adaptation, Physiological↗

Changes of cell-vascular complex in zones of adaptive remodeling of the bone tissue under microgravity conditions.

We examined the peculiarities of the structure of the blood-vascular bed and perivascular cells in zones of osteogenesis in the epiphyses and metaphises of femoral bones of rats, flown aboard the US laboratory SLS-2 for two weeks by electron microscopy and histochemistry. In zones of bone remodeling, there was a tendency for a reduction of sinusoid capillary specific volume. Endotheliocytes preserve the typical structure. In the population of perivascular cells, we discovered differentiating osteogenic cells that contained alkaline phosphomonoesterase as well as cells that don't contain this enzyme and differentiate into fibroblasts. The fibroblasts genesis in zones of adaptive remodeling of spongy bones leads to a further development of fibrous tissue that is not subject to mineralization.

Alkaline Phosphatase↗

[Study of skeleton gravitation physiology and problem of osteoporosis].

Main osteoporosis definitions and some results of bone tissue research in Russian astronauts, patients, and healthy subjects, using modern osteodensitometry, are presented. Bone mineral density (BMD) was regularly decreased at lower segments of skeleton. In the skull bone and some other sites of upper part of skeleton, a tendency was revealed for an increase of the bone mineral content (BMC). The mean value of bone loss was within the normal range and not correlated with duration of space flight; it revealed a high individual variability and in some cases was clinically qualified as local osteopenia. On the ground of analysis of own results and animal and bone cultural experiments data in microgravity conditions, the described changes seem to be reflecting a deceleration of bone formation as an adaptive response of bone tissue to the mechanical unloading. The response is realized mainly on the tissue level. It does not exclude bone resorption activity as a result of changes in hierarchy of water and electrolytes metabolism as reflected by body fluid redistribution in cranial direction. The results obtained broaden our notions on pathogenesis of some types of osteoporosis in clinic.

Absorptiometry, Photon↗

Ultrastructural changes in osteocytes in microgravity conditions.

We examined the histology and morphometry of biosamples (biopsies) of the iliac crest of monkeys, flown 14 days aboard the "Bion-11", using electron microscopy. We found, that some young osteocytes take part in the activation of collagen protein biosynthesis in the adaptive remodeling process of the bone tissue to microgravity conditions. Osteocyte lacunae filled with collagen fibrils; this correlates with fibrotic osteoblast reorganization in such zones. The osteolytic activity in mature osteocytes is intensified. As a result of osteocyte destruction, the quantity of empty osteocytic lacunae in the bone tissue increases.

Acid Phosphatase↗

Mechanisms of gravity-dependent changes in the bone tissue.

The most typical changes for the bone under the space flight conditions and a long-term hypokinesia are the following: the decreasing in bone mass, the demineralization and a reducing of a mechanical strength. It can lead to osteopenia and osteoporosis development. Also it increases the risk of fractures of supporting bones. Osteopenies, caused by the microgravity, are partially connected with the increasing of a reduction of trabecular bones. [Cytological mechanisms of gravity-dependent reactions in a bone tissue remain in many respects not clear. The study purpose was the analysis of some ultrastructural changes in bone tissue cells of the monkeys (Macaca mulatta), staying during 2 weeks onboard the biosatellite "Bion-11".

Journal Article↗

Cytogenetic characteristic of osteogenic cells in vitro as perspective predictors of osteopenia under microgravity.

Mechanical stimulation of bone tissue determined by earth gravity is one of the main factors mediating the nature, rate and direction of functional adaptation of the bone system in the process of onto- and phylogenesis. Theoretically expected losses of bone mass under condition of mechanical load deficit under microgravity (osteopenia, osteoporosis) may become a factor that limits the duration of space flights. As a result of long-term studies some properties and regularities of change in human tissue after prolonged space flights (for 5-7 months) were established.

Animals↗

Morpho-functional adaptations in the bone tissue under the space flight conditions.

Microgravity in space flight--situation of a maximum deficit of supporting loading on the skeleton and good model for finding-out of osteopenia and osteoporosis development laws, which are wide-spreading now and are "civilization diseases". Most typical for bones in conditions of a microgravitation by changes are: a decrease of intensity growth and osteoplastic processes, osteopenia and osteoporosis, decreasing of a mechanical strength and the risk of breaches arising (Oganov V.S., Schneider V. (1996)). Cytological mechanisms of gravity-dependent reactions in a bone tissue remain in many respects not-clear. By the purpose of our work was the analysis of some ultrastructural changes in bone tissue cells of the monkeys (Macaca mulatta), staying during two weeks onboard the biosatellite BION -11.

Adaptation, Physiological↗

Bone ultrastructural changes in Bion 11 rhesus monkeys.

Iliac crest biopsies of Bion 11 monkeys were examined by electron microscopy. The flight samples contained a large number of inactive osteoblasts. Together with ultrastructural changes of the rough endoplasmic reticulum and the Golgi complex, the predominance of inactive osteoblasts pointed to a lower rate of specific syntheses. Some osteoblasts were transformed to fibroblast-like cells. It was found that osteogenesis declined, osteoid mineralization changed, and fibrotic zones developed.

Adaptation, Physiological↗

Change and recovery of bone mass and acoustic properties of rhesus monkeys after Bion 11 spaceflight.

Bone mineral density (BMD) of lumbar spine and tibia, as well as ultrasound propagation speed along the tibia, was measured in Bion 11 flight and control monkeys. The flight monkeys showed a delay in the growth-related (L-1) bone mass increase compared to the preflight period. Similar changes were detected in some control animals. The changes occurred primarily in metabolically active spongy bone, as shown by ultrasound data.

Animals↗

[Clinical and physiological evaluation of bone changes among astronauts after long-term space flights].

Results of the joint Russian/US studies of the effect of microgravity on bone tissues in 18 cosmonauts on return from 4.5- to 14.5-month long missions are presented. Dual-energy x-ray gamma-absorbtiometry (QDR-1000 W, Hologic, USA) was used to measure bone mineral density (BMD, g/cm2) and mineral content (BMC, g) in the whole body, the scalp including cervical vertebra, arms, ribs, sternal and lumbar regions of the spinal column, pelvis and legs. A clearly defined dependence of topography of changes upon the position of a skeletal segment in the gravity vector was established. The greatest BMD losses have been observed in the skeleton of the lower body, i.e. in pelvic bones (-11.99 +/- 1.22%), lumbar vertebra (-5.63 +/- 0.817%), and in proximal femur, particularly in the femoral neck (-8.17 +/- 1.24%). Bones of the upper skeleton were either unchanged (insignificant) or showed a positive trend. Overall changes in bone mass of the whole skeleton of male cosmonauts during the period of about 6 months on mission made up -1.41 +/- 0.406% and suggest the mean balance of calcium over flight equal to -227 +/- 62.8 mg/day. Reasoning is given to qualify these states of cosmonauts' bone tissues as local osteopenia. On the literature and results of authors' clinical evidence, discussed is availability of the densitometric data for predicting risk of trauma. A biological nature of the changes under observation is hypothesized.

Astronauts↗

[Changes in bone tissue of women under condition of 120 days antiorthostatic hypokinesia].

The state of bone tissue has been studied in 8 women subjected to a 120-day HDT. Four test subjects (Group A) performed physical exercises during the experiment. Mineral content (MC) in bone tissue and mineral density of the bones (MD) were determined with the help of dichromatic x-ray bone densitometer HOLOGIC QDR--100/W. The velocity of propagation of ultrasound in the shin bone was also determined. It is found that the hypokinesia-associated losses of bone mass in the lower segments of the skeleton of women were insignificant. In the control group (Group B, non-exercising subjects), there markedly increased MC in the bones of the upper body and there were the slight signs of hypomineralization of the segments of the lower body as well as the significant (in 2 test subjects) decrease of MC in the pelvic bones in the recovery period to the level lower than at the beginning of the experiment. In group A, the increase of MC in the upper skeleton was expressed to a lesser degree. At the recovery period the all changes were practically neutralized and there were no signs of bone mass loss. The velocity of ultrasound by the Day 90 of the experiment had the marked tendency for a decrease in group A persisting up to the end of experiment while in the group B its changes were oppositely directed. Within 2 months after the experiment in the majority of women the tendency for recovery of the initial state both by the absolute values of ultrasound velocity and by the profile of curves of their distribution over the anterior surface of the shinbone was noted. The results are discussed in comparison with findings obtained in the experiments with long-term hypokinesia in men and in the space missions.

Adaptation, Physiological↗

Histology and histochemistry of intervertebral discs of rats participated in spaceflight.

The qualitative and quantitative histological and histochemical changes in the structure and macromolecular composition of lumbar intervertebral discs of rat during a 12.5-day space flight (Cosmos 1887 biosatellite) were determined using light and polarization microscopy. Semiquantitative histochemical, topo-optical reactions were measured and evaluated by retardation values of birefringence. (a) Lateral expansion and accumulation of the notochordal cells in the nucleus pulposus was observed in contrast with the vivarium control, where the chondroid cells dominated. (b) The cartilage and plate showed a swelling, which consisted mainly of hypertrophied cells sometimes with mild extracellular mineralization. (c) In the external zone of annulus fibrosus and cartilage end plate a mild decrease of orientation of collagen fibers was found. (d) A significant increase of orientation of hyase sensible glycosaminoglycans in the internal zone of annulus fibrosus and nucleus pulposus was observed. (e) In the external and internal zones of annulus fibrosus an increase of orientation of glycoproteids was revealed. The alterations of macromolecular components of intervertebral discs, cartilage end plates, and the osteoporotic changes of the lumbar vertebral bodies producing the looser structure of vertebral column after 12.5 day space flight suggest the necessity of the common evaluation of these structures, and may explain the heavy spinal pains of astronauts.

Animals↗

Effect of short- and long-term spaceflight on the contractile properties of rat skeletal muscles with different functions.

In the Cosmos biosputnik 1514, 1667, 1887, 2044 and 1129 the rats 5, 7, 12,5, 15, 18,5 days were in weightlessness state. Due to the adaptation of the skeletal muscles' weightlessness the adaptation was different in various muscles, which depends on the time of participation in antigravitation, the composition of the fibers and from the biometrical characteristics. In different muscles, the changing of the metabolism and the structure of the muscles more than likely in connection with the changing of the myosin subordinate unit compositions. In our experiments we had studied, as to how the muscular atrophy changes, does it increase all the time, or does it balances out after reaching a certain stage.

Adaptation, Physiological↗

Effect of exercise and bisphosphonate on mineral balance and bone density during 360 day antiorthostatic hypokinesia.

As we enter a phase of space exploration that will involve long-duration flights, there is a need to use ground-based models to study the long-term effects of countermeasures to prevent the loss of bone mineral in microgravity. Mineral balances, hormone levels, and bone density were measured for 360 days in nine bed rest subjects treated with an exercise program used by cosmonauts. Four of these subjects received the bisphosphonate, ethane-1-hydroxy-1-disphosphonate, 900 mg daily, a drug known to inhibit bone resorption. Compared to a 120 day control period, the bisphosphonate combined with exercise reduced negative calcium balances by 50% for the first 120 days, 80% for the second 120 days, and 69% during the third 120 days. Exercise alone had no effect until the second 120 day period, when calcium balance improved 52%. Negative phosphorus balances were not affected by either treatment. Magnesium balances were negative during the first 120 days and returned to nearly normal during the last 240 days in both groups. The combined exercise and bisphosphonate treatment prevented increases in serum ionized calcium and decreases in plasma calcitonin during the first 120 days, as well as trends toward decreases in the mineral density of the femoral neck. These results suggest that bisphosphonates can be efficiently used together with exercise to reduce calcium loss and prevent some of the changes in mineral metabolism during long-term simulated microgravity.

Adult↗

Altered distribution of mitochondria in rat soleus muscle fibers after spaceflight.

The influence of spaceflight on the distribution of succinate dehydrogenase (SDH) activity throughout the cross section of fibers in the soleus was studied in five male rats and in five rats maintained under ground-based simulated flight conditions (control). The flight (COSMOS 1887) was 12.5 days in duration, and the animals were killed approximately 2 days after return to 1 G. Fibers were classified as slow-twitch oxidative or fast-twitch oxidative-glycolytic in histochemically prepared tissue sections. The distribution of SDH activity throughout the cross section of 20-30 fibers (each type) was determined using quantitative histochemical and computer-assisted image analysis techniques. In all the fibers, the distribution of SDH activity was significantly higher in the subsarcolemmal than in intermyofibrillar region. After spaceflight the entire regional distribution of SDH activity was significantly altered in the slow-twitch oxidative fibers. The fast-twitch oxidative-glycolytic fibers of the spaceflight muscles exhibited a significantly lower SDH activity only in their subsarcolemmal region. These data suggest that when determining the influence of spaceflight on muscle fiber oxidative metabolism enzymes, it is important to consider the location of the enzyme throughout the cross section of a fiber. Furthermore the functional properties of the soleus that depend on the metabolic support of mitochondria in the subsarcolemmal region may be primarily affected by exposure to microgravity.

Animals↗