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Biomedical subjects

B V Morukov

Publications and source records attributed to B V Morukov.

At least 19 recordsLinked to original sources

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

Effects of a bisphosphonate (1-hydroxy ethylidene-1,1 bisphosphonic acid) on osteoclast number during prolonged bed rest in healthy humans.

Acute osteoporosis is known to occur after immobilization in spinal cord injured patients and is related to an early increase in osteoclastic bone resorption. Whether osteoporosis develops in healthy immobilized human patients is still a matter of controversy. Furthermore, acute osteoporosis was thought to be a good model to study the effects of weightlessness on the human skeleton and to adapt preventive procedures. A bed rest experiment was developed in the USSR on 15 healthy human volunteers to determine the precise effects on bone structure and cell activities. A preventive protocol, including an anti-osteoclastic drug (1-hydroxyethylidene-1,1 bisphosphonic acid; K salt) was investigated. Two transiliac bone biopsies were performed on the 15 individuals before and at the end of the 120-day bed rest period. Undecalcified bone biopsies were studied with automatic and semi-automatic image analyzers specially devoted to bone histomorphometry. Trabecular bone volume, osteoid amount, and eroded surfaces were measured. Osteoclast number was measured after histochemical identification of tartrate-resistant acid phosphatase. After the bed rest period, an insignificant bone loss was observed in healthy humans while osteoclast number was highly increased. In bisphosphonate-treated subjects, osteoclast number was markedly reduced and so was osteoid amount. Bisphosphonates were shown to present a highly cytotoxic activity on osteoclasts, a finding that has never been demonstrated in normal subjects.

Adult

Calcium homeostasis in prolonged hypokinesia.

Calcium metabolism, its hormonal regulation and renal calciuretic function were investigated in 20 healthy volunteers during 120- and 182-day head-down tilt studies. The content of total and ionized calcium and parathyroid hormone was found to increase during the study. The concentration of calcitonin increased at an early stage of exposure and decreased thereafter. This resulted in negative calcium balance which was on the average 5, 6g per month. Measurements of iliac bone biopsies showed calcium decrease and phosphorus increase.

Adult

Microgravity-induced changes in human bone strength.

A decrease of spongy tissue strength of iliac bone has been identified in healthy men under conditions of simulated weightlessness (bed rest). Countermeasures have significantly prevented this decrease. Additional investigations have indicated probability of degenerative-destructive bone change development under conditions of usual human activity as a consequence of bone strength decrease.

Animals

[Quantitative histological study of the bone mass and cellular activity after 120-days decubitus. Trial of preventive protocols].

Bone biopsies of iliac crests, performed at the beginning and the end of a decubitus period of 120 days, were studied in 20 healthy volunteers men. The purpose of this experiment is to simulate the bony alterations of astronauts. The bony mass of all bed-ridden patients remained constant. In strictly immobilized patients, the rate of bony mineralization is decreased and the osteoclastic resorption activity is stimulated. In bed-ridden patients subjected to preventive physical exercises, the bony formation and resorption are increased. When prevention is administered with the use of a diphosphonate, the osteoid and osteoclastic parameters are decreased. When both types of prevention are administered, the osteoid parameters and the resorption activity are decreased but less markedly than in patients treated with diphosphonate alone.

Adult

[Effect of simulated weightlessness on calcium metabolism and the condition of bone tissue in experimental animals].

Male rats of the Wistar strain were for 40 days exposed to hypokinesia and hypodynamia. After exposure bone biochemical, physical, chemical, morphological and strength parameters were investigated. Both simulation studies led to changes in calcium and phosphorus metabolism but the nature of bone changes was different. It is concluded that the efficacy of drugs used as countermeasures in animal simulation experiments should be assessed by both exposures, viz. small size cages and suspension, because they reproduce different mechanisms of potential bone lesions in microgravity. It is also inferred that various countermeasures should be used in combination to yield the best results.

Animals

[Blood levels of hormones regulating calcium-phosphorus metabolism in men exposed to a 120-day period of hypokinesia].

Nine healthy male volunteers were exposed to head-down tilt (-4.5 degrees) for 120 days. The concentrations of parathormone, calcitonin, gastrin, growth hormone, total and ionized calcium were measured in plasma. Prolonged exposure to antiorthostatic hypokinesia led to significant changes in the hormonal regulation of calcium-phosphorus metabolism, the most important of which was an enhanced secretion of the parathyroid hormone. The increased concentration of calcitonin and gastrin was a secondary response to the higher content of ionized calcium. The phase-like changes in the somatotrophic hormone secretion were induced by variations in the parathormone concentration in blood, on the one hand, and by a reduction of plastic processes, on the other.

Adult

[Lipid peroxidation in the human blood during a 120-day period of anti-orthostatic hypokinesia].

Time-course variations in the accumulation of endogenous products of lipid peroxidation and the state of antioxidative enzymes--superoxide dismutase and catalase--in blood of men exposed to antiorthostatic hypokinesia (-4.5 degrees) for 120 days were investigated. It was found that bed rest led to stimulation of lipid peroxidation which was measured as increased concentrations of lipid hydroperoxides and final products of lipid peroxidation in blood. Vitamin E and drugs with a specific metabolic action produced a normalizing effect on the content of products of lipid oxidative destruction. Special exercise regimens had a similar but less significant effect.

Adult

[Role of active vitamin D3 metabolites in regulating calcium metabolism in rats during hypokinesia].

The rats exposed to prolonged hypokinesia showed hypocalciemia, lower PTH and higher calcitonin concentrations in the serum, decreased calcium absorption in the small intestine, and a trend toward nephro- and arteriocalcinosis. Prophylactic administration of 24,25-hydroxy D3. 1,25-hydroxy D3 and their combinations enhanced calcium absorption and alleviated hypocalciemia. The changes in the hormonal regulation of calcium homeostasis can be viewed as a factor responsible for calcium metabolic disorders associated with hypokinesia.

24,25-Dihydroxyvitamin D 3

[Effect of diphosphonates on bone tissue of the rat during hypokinesia].

The diphosphonate effect on bones was studied in Wistar male rats weighing about 200 g. The rats were kept for 60 days in small-size cages where their motor activity was diminished. Every day the rats were given per os 0.3% solution of 1-hydroxy-ethylene-1,1-diphosphonate (HEDP) containing 9 mg/kg phosphorus. In the course of hypokinetic exposure the rats developed generalized osteoporosis. Histomorphometric measurements demonstrated that the drug did not prevent mineral losses from the tubular bones (humerus, femur). However, the drug led to a complete bone mass recovery in the pelvic and a partial recovery in the sternum. The drug also produced a preventive effect on the population of cells-precursors of osteogenesis the number of which decreases significantly during hypokinesia.

Animals

[Bone examination by noninvasive methods during prolonged hypokinesia].

The effect of 120-day bed rest on skeletal bones of 15 volunteers was investigated by noninvasive methods, viz. gamma-photon absorption, ultrasonic and neutron-activation analysis. The test subjects were divided into 4 groups one of which served as control and three others used different countermeasures (drugs, exercise or drugs in combination with exercise). Calcium loss in skeletal bones was not more than 0.5% per month; calcium loss in leg tubular bones was 1 to 2% per month in 6 test subjects; calcium loss in heel bones was on the average 3-4% per month in the control, exercise and combination groups. No strict correlation between the negative balance of calcium and mineral content in leg compact bones and foot spongy bones was found. There was a correlation between changes in the mineral content of leg bones and ultrasound propagation along certain compartments of the tibial median surface. In terms of negative and positive trends leg and foot bones were in better condition in the drug group. The techniques used were assessed with respect to their diagnostic and prognostic value.

Bone and Bones

[Metabolic characteristics during 120-day head-down tilt hypokinesia].

Nine healthy test subjects, aged 25 to 44 years, were exposed to bed rest (at -5 degrees) for 120 days. Venous blood and 24-hour urine samples were used to measure Na, K, total and ionized Ca, Mg, total protein, protein fractions, creatinine, urea, uric acid, malate, isocitric and lactate dehydrogenases, aspartate and alanine aminotransferases, and creatine phosphokinase and its isoforms, acid and alkaline phosphatase and its isoenzymes. Prolonged exposure to head-down tilting resulted in a negative balance of fluid and electrolytes, lowered concentration of total protein and albumins, and an increased concentration of urea and creatinine, basic products of protein metabolism. In blood, the activity of dehydrogenases of the tricarboxylic acid cycle and creatine kinase decreased at the expense of its muscle isoenzyme and the activity of acid phosphatase, total alkaline phosphatase and bone isoenzyme of alkaline phosphatase increased.

Adult

[Effect of diphosphonates on the development of osteoporosis in the hypokinetic rat].

Using histomorphometric methods, the effect of diphosphonates (hydroxydimethylaminopropylene diphosphonic acid and hydroxyethylene diphosphonic acid) on the development of osteoporosis in spongy matter of tibia and vertebrae of the rats exposed to hypokinesia for 60 days was investigated. It was found that aminopropylene diphosphonic acid in the dose 6 mg phosphorus/kg/day prevented osteoporosis and caused an increase in the volume density and abnormal (cartilage rich and poorly ossified) spongy bone. By contrast, ethylene diphosphonic acid in the dose 9 mg phosphorus/kg/day did not prevent osteoporosis but reduced its severity.

Animals

[Bioelectrical activity of the heart and blood electrolytes in virtually healthy subjects during 120-day head-down tilt hypokinesia].

Electrocardiographic parameters and serum concentrations of potassium, sodium, calcium (total and ionized) and magnesium in 6 essentially healthy men, aged 30-45 years, were measured before, during and after 120-day head-down tilt at -4.5 degrees. A close correlation was demonstrated between T-wave depression and serum concentrations of potassium (direct correlation) and calcium and magnesium (inverse correlation). No consistent changes in the sodium content during the 120-day test were seen. In spite of electrolyte changes in blood induced by head-down tilt, ECG variations showed minor hypokalemia that was not followed by any clinical symptoms. These data can be used to evaluate the status of healthy people exposed to prolonged hypokinesia and to develop adequate prophylactic measures.

Adult

[Water-electrolyte balance and functional state of the kidneys in cosmonauts after a 185-day space flight].

Fluid-electrolyte metabolism and renal function of the crewmembers of the 185-day space flight were examined. Various changes in fluid-electrolyte metabolism and its regulation were seen in the Commander and Flight-Engineer. As most other crewmembers who performed similar flights, Cr showed fluid and sodium retention, whereas FE displayed higher than preflight sodium excretion in the urine. These differences were associated with individual variations of regional hemodynamics which modified the renin-angiotensin-aldosterone system in a different manner. Postflight both crewmembers showed a higher excretion of bivalent ions. The higher excretion of calcium was accompanied by a lower concentration of total and ionized calcium in the serum as well as by a lower concentration of PTH and calcitonin. The loading KC1 test made it possible to assess variations in potassium metabolism that occurred during flight. They included the inability of tissues to retain potassium due to atrophic processes which developed in the weightless state and due to the unloading of the musculoskeletal system.

Adaptation, Physiological