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Ten healthy men took part in a 360-day antiorthostatic hypokinesia study. They were subdivided into two equal groups that differed in terms of time when they started using counter-measures: Group A began exercising on the first day of exposure and Group B on bed rest day 120. As compared to the baseline, the test subjects showed a decrease of serotonin (Ser) and histamine (HA). The only exception was HA increase on bed rest day 50 in the Group A subjects. The difference in Ser and HA concentrations in Group A and B subjects was insignificant on bed rest days 110 through 350. On the 60th day after the study Ser and HA concentrations did not yet return to norm. These observations indicate that changes in the serotonin- and histaminergic systems cannot be compensated within the above period of time.

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Sympathico-adrenal activity of cosmonauts was studied before, during and after 211- and 237-day flights on the Salyut-7 station. During flight blood and urine samples were drawn, collected and stored using a Plasma-01 unit. Blood was withdrawn from two crewmembers on flight days 217-219 by the physician-cosmonaut and brought to the Earth in a frozen state. After the 211-day flight the sympathico-adrenal system showed stimulation of the hormonal component and inhibition of the transmitter component on the recovery day as well as activation of the transmitter component and metabolic changes during the subsequent recovery period. On days 217-219 of the 237-day flight blood catecholamines slightly increased while their renal excretion remained unchanged and their metabolite excretion decreased. All the parameters under study increased significantly during the recovery period. These observations give evidence that the sympathico-adrenal system was not activated on flight days 217-219 and was significantly stimulated during the recovery period after 211- and 237-day flights.

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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.

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The sympatho-adrenal system, i.e. its hormonal and mediator components, were examined in test subjects who made a 23-day expedition across a desert. The activity of the system was modified using food supplements: whey protein concentrate (50 g) and polyvitamins (Komplivit). It was found that in the arid area the hormonal and mediator components of the sympatho-adrenal system were stimulated. The stimulation degree was reduced by the food supplements which can be used to help the human body get adapted to an arid environment.

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Lipid peroxidation in tissues of rats exposed to antiorthostatic hypokinesia (-15 degrees) for 60 days, heavy-load exercise (swimming) and 2-hour immobilization was investigated polarographically. Antiorthostatic hypokinesia produced activation of free-radical lipid peroxidation in skeletal muscles, myocardium and plasma which reached a peak on hypokinesia day 3 and remained elevated by day 60. Exercise and immobilization applied during hypokinesia led to an accumulation of endogenous lipid peroxidation products in skeletal muscles and in the heart, although in a lesser degree. It is postulated that during hypokinesia lipid peroxidation is most probably activated due to the following factors: increased activity of the hormonal component of the sympathicoadrenal system, accumulation of excessive quantities of free fatty acids, and reduced activity of anti-oxidant enzymes.

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In order to clarify biochemical adaptation of the human body to short-term microgravity, metabolic and hormonal parameters were investigated in 20 cosmonauts who performed orbital flights of 4 to 14 d in duration. The specific feature of adaptation to this exposure is the transition to a new level of hormonal regulation with a significant increase of the content (production) of glucocorticoids, catecholamines, components of the renin-angiotensin-aldosterone system, which determines a modified activity of tissue hormones, and fluid-electrolyte homeostasis, as well as simultaneous increase of insulin secretion that diminishes the metabolic effects of glucocorticoids and catecholamines.

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The method of averted and non-averted segments was used to assess calcium absorption in the small intestine of adult and young rats with hypokinesia. A certain decrease in the active (by 13.8%) and more manifest diminution of the total (by 26.3%) calcium transport was established in adult rats after 4 weeks of hypokinesia. In young rats a significant lowering of the active calcium transport was already noted after 1 week of hypokinesia, however, age-dependent shifts in the process were more significant than those induced by hypokinesia. Changes in the calcium-regulating hormones are considered as a possible cause of decreased calcium absorption in the intestine in relation to hypokinesia and age.

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The plasma alanine concentration was measured in 28 healthy male test subjects exposed to head-down tilt of various duration (2-hour exposure at-12 degrees, 7-day exposure at-6 degrees, 49-day exposure at-4 degrees, and 120-day exposure at-4 degrees). Head-down tilt led to alanine changes that correlated with exposure time. These results suggest that alanine concentrations in blood reflect to a certain extent the rate of hepatic gluconeogenesis and depend significantly on the hypokinetic time. The findings can be clinically used as a measure of hepatic gluconeogenesis in bed-ridden patients that may require preventive or therapeutic treatment.

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Before and after the 150-day Salyut-7 flight the crewmembers were examined for their red blood metabolism, viz: major metabolic pathways (glycolytic and pentosophosphate), erythrocyte resistance, membrane permeability and lipid peroxidation rate. The resulting data indicate that the metabolic and membrane changes were not pathological and can be classified as adaptive.

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The functional activity of serotonin- and histaminergic systems was investigated during 120-day head-down tilt. Serotonin excretion was increased until test day 70 and histamine excretion throughout the entire study. At the final stage of exposure (test days 100-120) the serotonin content decreased. Return to the normal motor activity stimulated the function of serotonin- and histaminergic systems.

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The free amino acid pool of blood of man exposed to 120-day head-down tilt (at -4 degrees) was examined. Beginning with bed rest day 28 and till the end of the study, the amino acid pool increased. The increase involved most free amino acids which was produced by a decline of anabolic and stimulation of catabolic processes during hypokinesia.

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Changes in the amino acid pool in the plasma of test subjects exposed to short-term head-down tilt combined with ultraviolet irradiation were investigated. Exposure to head-down tilt alone (Group 1 of 3 test subjects) and combined with ultraviolet irradiation (10 sessions) (Groups 2 and 3 of 3 test subjects each) acted as a stress-agent that diminished the amino acid pool. Exposure to 2-hour head-down tilt in combination with 20 UV-irradiations (Groups 2 and 3) increased the amino acid pool as a result of inhibition of anabolic and stimulation of catabolic processes. The amino acid pool did not return to normal within the recovery period allowed.

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Taking into consideration metabolic specificities of cosmonauts, the data on their amino acid composition during preflight training were summarized. Seasonal variations produced no effect on the content of free amino acids of plasma. The analysis yielded a physiological norm for this population which can be used to identify more reliably changes in the amino acid composition of plasma after space flight.

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Male Wistar rats that were experimentally hypokinetic were fed 24,25(OH)2D3 or 1,25(OH)2D3 separately or in combination to determine the effect on bone growth and on bone formation and resorption. It was shown that these parameters of bone metabolism are influenced by these metabolites of vitamin D3 by their effect on bone sensitivity to their activity and perhaps in the regulation of bone histogenesis.

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The data obtained show that adaptation to a high altitude environment is accompanied by various metabolic changes. It is recommended to use essential nutrients--vitamins to optimize adaptation to this environment and to maintain adequate work capacity and good health.

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The influence of short-(7 days) and long-term (28 days) hypokinesia on 25-hydroxyvitamin D3 metabolism was investigated in rats fed on a normal calcium (0.6%), normal phosphorus (0.6%), vitamin D-supplemented diet. The animals were given a single intraperitoneal dose of tritiated [26,27-3H]25(OH)D3 (200 pmol) eighteen hours before sacrifice. [3H]Labelled vitamin D3 metabolites were separated by high performance liquid chromatographic procedure, and their radioactivity levels in serum, kidney, intestinal mucosa and femoral bone were measured. Long-term hypokinesia resulted in decreased levels of [3H]1.25(OH)2D3 and increased levels of [3H]24.25(OH)2D3 in serum and kidney (3.15 +/- 0.62 vs. 4.33 +/- 0.41% and 5.34 +/- 0.69 vs. 3.76 +/- 0.29% for [3H]1.25(OH)2D3 and [3H]24.25(OH)2D3 in serum; 7.52 +/- 0.69 vs. 11.6 +/- 0.79% and 9.33 +/- 0.55 vs. 5.94 +/- 0.24% for those in kidney). The levels of [3H]1.25(OH)2D3 as well as of [3H] 24.25(OH)2D3 were decreased in intestinal mucosa and bone (21.5 +/- 1.46 vs. 30.1 +/- 3.04% and 7.30 +/- 0.58 vs. 9.18 +/- 0.78% for [3H]1.25(OH)2D3 and [3H]24.25(OH)2D3 in intestinal mucosa; 6.39 +/- 06.5 vs. 11.5 +/- 1.64% and 7.78 +/- 0.71 vs. 13.9 +/- 1.28% for those in bone). The data obtained suggest a suppressed synthesis of 1.25(OH)2D3 and enhanced production of 24.25(OH)2D3 in kidney as well as a diminished binding of 24.25(OH)2D3 in intestinal mucosa and bone in hypothetic rats. Possible causes of variations in biosynthesis of vitamin D3 active metabolites, and role of these variations in the disorders of calcium metabolism and bone state during hypokinesia are discussed.

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Severe hypokinesia of rats given the diet with a ratio of Ca:P = 1:0.5-1:3 was accompanied by hypocalcemia, development of osteoporosis, and some intensification of renal calcinosis. The decrease of phosphorus consumption (Ca:P = 1:0.5-1:1) prevented a development of these changes in intact animals and increased bone mineralization in hypokinetic ones. Excessive phosphorus consumption (Ca:P = 1:3) produced hypocalcemia, hyperphosphatemia, and some osteoporotic changes in the bones of intact animals and intensified these changes with hypokinesia. Administration of 24,25-dihydroxycholecalciferol, an active metabolite of vitamin D3, at a dose of 1.25 micrograms/d prevented a development of bone disorders, thus effectively stimulating diaphyses and epiphyses mineralization and correcting hypocalcemia in hypokinetic rats. 24,25(OH)2D3 at the same dose did not intensify nephocalcinosis and produced no toxic symptoms with hypokinetic animals.

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Changes in blood parameters (red and white blood cell counts) were examined in 6 healthy male volunteers during an acute stage of adaptation to the exposure simulating physiological effects of weightlessness. The parameters varied, remaining, however, within the physiological limits.

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