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Changes in vitamin A status following prolonged immobilization (simulated weightlessness).

A study was conducted to investigate the effects of a simulated weightlessness induced by chronic immobilization on vitamin A status. To simulate the stress condition of weightlessness, rats were suspended for 10 days in a special jacket to which metal chains were attached. Animals received a commercial stock diet. Control rats were pair-fed in reference to the suspended rats. As compared with the control, prolonged immobilization resulted in a decrease in body weight gain and an increase in adrenal weight occurred. In the suspended rats, serum concentrations of retinol and retinol-binding protein (RBP) declined. Hepatic retinyl palmitate content increased, and the hepatic retinol level was decreased. The prolonged immobilization led to significantly reduced retinyl palmitate levels in the testis and lung as well as lowered testicular retinol levels. The results suggest that the stress state induced by prolonged immobilization caused accumulation of hepatic retinyl palmitate, decreasing the serum retinol concentration and retinyl ester content in the extrahepatic tissues.

Adrenal Glands↗

Biomedical study on combined effects of simulated weightlessness and emergent depressurization of spacecraft.

Cabin emergent depressurization (CED) may occur in spacecraft during manned space flight. The purpose of this paper was to study the combined effects of simulated weightlessness (SW) and CED factors on humans and animals. It was found that the amplitude of T wave of human electrocardiograms (ECG) significantly decreased in bed rest and hypoxia compared with the control condition (P<0.05), and that suspension with pure O2 induced severer edema in the lungs of rats than that in only a pure O2 environment. SW and pure O2 caused middle ear congestion and decreased the barofunction during pressure changes. These results indicate that human response to CED factors become more serious under SW because of the blood redistribution.

Aerospace Medicine↗

Effect of gender on bone turnover in adult rats during simulated weightlessness.

Prologned spaceflight results in bone loss in astronauts, but there is considerable individual variation. The goal of this rat study was to determine whether gender influences bone loss during simulated weightlessness. Six-month-old Fisher 344 rats were hindlimb unweighted for 2 wk, after which the proximal tibiae were evaluated by histomorphometry. There were gender differences in tibia length, bone area, cancellous bone architecture, and bone formation. Compared with female rats, male rats had an 11.6% longer tibiae, a 27.8% greater cortical bone area, and a 37.6% greater trabecular separation. Conversely, female rats had greater cortical (316%) and cancellous (145%) bone formation rates, 28.6% more cancellous bone, and 30% greater trabecular number. Hindlimb unweighting resulted in large reductions in periosteal bone formation and mineral apposition rate in both genders. Unweighting also caused cancellous bone loss in both genders; trabecular number was decreased, and trabecular separation was increased. There was, however, no change in trabecular thickness in either gender. These architectural changes in cancellous bone were associated with decreases in bone formation and steady-state mRNA levels for bone matrix proteins and cancellous bone resorption. In conclusion, there are major gender-related differences in bone mass and turnover; however, the bone loss in hindlimb unweighted adult male and female rats appears to be due to similar mechanisms.

Animals↗

[Effects of Qiang Gu Kang Wei prescription on morphology of bone in rats under simulated weightlessness].

OBJECTIVE: To investigate effects of Qiang Gu Kang Wei prescription on bone morphology in tail-suspended rats. METHOD: Rats were tail-suspended (-30 degrees) for 21 d to simulate weightlessness. The effects of this prescription on thickness of periost and cortex at epiphyseal plate of tibial shaft and 3 mm under it were examined. The effects of this prescription on histology and ultrastructure of tibia were also observed. RESULT: Compared with the normal control, cortex at both epiphyseal plate of tibial shaft and 3 mm under it in suspended rats thinned significantly (P<0.01 or P<0.05). Histological observation showed that in bone of suspended rats, uncalcific matrix was more, bone cells' number was lower and their appearance was more infantile, osteoblasts were less and smaller, while osteoclasts were more and larger, haversian system of transection also showed more irregular than in bone of normal control. Ultrastructure observation showed that the function of osteoblasts was inhabited and that of osteoclasts was active. All the three doses groups of the prescription could increase cortex at either epiphyseal plate of tibial shaft or 3 mm under it (P<0.01 or P<0.05) compared with the tail-suspended group. The appearance of bone in the three groups was improved as well under optical or electron microscope. CONCLUSION: This prescription could improve abnormal change in bone morphology resulted from being tail-suspended in rats and make it normal.

Animals↗

[Effects of N omega-nitro-L-arginine methyl ester on pulmonary artery of rats during simulated weightlessness].

OBJECTIVE: To investigate the effects of the N omega-nitro-L-arginine methyl ester (L-NAME) on pulmonary artery of rats during 14 days simulated weightlessness. METHODS: Sixteen male Wistar rats were randomly divided into control group and tail-suspension (TP) group (each n=8). Vascular bathing technique was used to measure the contractile responses of rats pulmonary artery rings to phenylephrine (PE), dilatory responses to acetylcholine (Ach) and contractile response to PE in presence of L-NAME. Nitric oxide (NO) content in pulmonary tissues was determined using nitrate enzyme reduction method. RESULTS: After simulated weightlessness for 14 days,the contractile response of rat pulmonary artery to PE (1x10(-5)-1x10(-7) mol/L) decreased significantly (all P<0.01); the dilatory response to Ach (1x10(-6)-1x10(-8) mol/L) increased significantly (all P<0.05). L-NAME abolished the differential responses to PE in TS and control groups, had no significant differences compared with control group, and NO content was also significantly increased. There were significant differences between the two groups (P<0.05). CONCLUSION: Larger amount of NO is released in vascular endothelium after 14 days TS, which might partly explain the decrease in the contractile responses of pulmonary artery.

Animals↗

Effect of simulated weightlessness on TNF-alpha production and the response of bone marrow cells to GM-CSF in rats.

The purpose of this experiment was to investigate the effect of 15 and 30 d simulated weightlessness (SWL) on tumor necrosis factor-alpha(TNF-alpha) production secreted by macrophage stimulated with lipopolysaccharide(LPS) and the ability of bone marrow cells to respond to granulocyte/monocyte colony-stimulating factor(GM-CSF) in tail-suspension rats. The TNF-alpha production was assessed by radioimmunoassay. The ability of bone marrow cells to respond to GM-CSF was measured by 3H-TdR incorporation method. The results showed that after 15 d SWL, TNF-alpha production showed a tendency to decrease; and that after 30 d SWL, the decrease became significant (P < 0.05). The results also demonstrated that the ability of bone marrow cells to respond to GM-CSF decreased significantly after 15 d SWL (P < 0.01); and there was no significant change after 30 d SWL. It suggested that SWL could depress immune function, and that reduction of TNF-alpha production might be related to bone marrow cell proliferation function.

Animals↗

[Interrelationship between pulse filling of earlobe vessels and cardiac extrasystole during "head--foot" loading following exposure to simulated weightlessness].

The relationship between changes in the pulse blood filling of earlobe vessels and cardiac arrhythmias was studied in 91 manned experiments during which test subjects were exposed to simulated weightlessness and then to acceleration of +3 Gz for 5 min in a 7.25 m arm centrifuge. The studies demonstrated that the vascular type of functional decompensation may transform into the cardiac type in normal men during recovery from an exposure to +3 Gz and simulated weightlessness. This may be of theoretical and practical importance for space programs.

Adult↗

[Effects of "Qiang Gu Kang Wei" compound prescription on biochemical indices of bone and related organs in rats under simulated weightlessness].

OBJECTIVE: To investigate effects of "Qiang Gu Kang Wei" prescription on biochemical indices of bone and related organs in tail-suspended rats. METHOD: Rats were tail-suspended (-30 degrees) for 21 d to simulate weightlessness. The effect of this prescription on biochemical indices such as Ca, P in serum, osteocalcin (BGP) in serum and bone, oxyproline hydroxyproline (Hyp) in bone, alkaliphosphatase (ALP) in serum, small intestine and bone in these rats were examined. RESULT: Comparing with the normal control, serum Ca decreased significantly (P<0.05) while serum P showed only a trend to decrease, at the same time BGP dropped in both serum and bone (P<0.05) and Hyp dropped only in bone (P<0.05). There was significant decrease of ALP activity in serum, small intestine and bone (P<0.01 or P<0.05) in suspended rats. The prescription showed different effects with different doses. In all the three dose groups (30 g/kg, 20 g/kg, 10 g/kg) Ca and P in serum levels increased (P<0.01 or P<0.05), BGP in serum and bone improved (P<0.05) or showed only a trend to increase. ALP activity increased in serum, small intestine and bone (P<0.05). Increase of Hyp in bone was found in the middle and the small dose groups (P<0.05). CONCLUSION: This prescription shows an effect of improving biochemical indices in bone and related organs such as serum and small intestine in tail-suspended rats. But no distinct concentration-dependence was found.

Alkaline Phosphatase↗

Simulated weightlessness and hyper-g results in opposite effects on the regeneration of the cortical microtubule array in protoplasts from Brassica napus hypocotyls.

Enzymatic digestion of the cell wall of Brassica napus hypocotyls gave a heterogeneous suspension of protoplasts with the cortical microtubules (CMTs) randomly organised or CMTs organised in parallel. The effect of variable g-influences has been tested on CMT organisation. In contrast to the 1 g-protoplasts, which reorganised the CMTs into parallel arrays during the 96 h test period, the frequency of randomly-oriented CMTs in the protoplasts exposed to simulated weightlessness (0 g) on a 2-D clinostat increased significantly during the same period. The opposite effect was obtained when the protoplasts were exposed to hyper-g (7 or 10 g), where the reorganisation of the CMTs into parallel arrays was accelerated compared to the 1 and 0 g-protoplasts. These results indicate that a unidirectional gravity force is a necessity for the reorganisation of CMTs in protoplasts to parallel arrays and that CMTs act as responding elements that are able to sense different levels of gravity. Besides the inability of the protoplasts to reorganise the CMTs into parallel arrays, the quantity of CMTs in the individual protoplast decreased during 4 days of simulated weightlessness, both compared to the CMTs quantity in the protoplasts immediately after isolation and compared to the 1 g- and hyper-g-protoplasts after 24 and 48 h of g-exposure. The size of the protoplasts was also affected by the g-exposure. Protoplasts exposed to simulated 0 g increased significantly after 24 and 48 h, whereas the 1 g- and 10 g-protoplasts maintained the same size during the 48 h test period.

Brassica↗

Brain norepinephrine changes with simulated weightlessness and relation to exercise training.

Maintenance of nervous system function during periods of a deconditioning syndrome is important to prevent diminished psychological/behavioral, and physiological function observed during periods of bed rest, physical inactivity, and weightlessness. A main neurotransmitter is norepinephrine (NE), and its regulation yields insight into nervous system function. This research tested the hypotheses that, 1) deconditioning syndrome induced by simulated weightlessness of 9 days via the head-down tilt (HDT) model results in a blunted noradrenergic turnover rate in selected brain tissue and, 2) that exercise training acts as a countermeasure for these changes in noradrenergic activity. Male Sprague-Dawley rats (3 months, n = 60) were divided into either a HDT (HDT, n = 20), cage control (CAGE-CN, n = 20) or an exercise trained HDT (HDT-EX, n = 20) group. Each group was further subdivided into a saline (n = 10) or alpha-methyl-tyrosine (AM, n = 10) (200 mg/kg) injected subgroup. Animals in the HDT groups were tail suspended in a 30 degrees head-down tilt position for 9 days. Norepinephrine turnover was determined 3 h following administration of saline or alpha-methyl-para-tyrosine. The NE turnover rate (ng gm(-1) x h(-1)) for the CN, HDT, and HDT-EX groups, respectively, were as follows: locus coeruleus, 63 +/- 33, *134 +/- 65, 85 +/- 61; hypothalamus, 195 +/- 50, *47 +/- 47; *93 +/- 34; cerebellum, 10 +/- 18, *65 +/- 15, *53 +/- 19; cerebral cortex, 6 +/- 20, *28 +/- 15, *68 +/- 22. (*Denotes significant difference from the control group at the p < or = 0.05 level of significance; +denotes significant difference from the HDT group at the p < or = 0.05 level of significance.) These findings suggest that: 1) norepinephrine turnover rate adapts in a tissue-specific manner following a 9-day tail suspension, 2) increased norepinephrine turnover rates and norepinephrine tissue content in the HDT group are consistent with neural adaptation to a chronic stress response.

Analysis of Variance↗

Effect of a simulated weightlessness model on the production of rat interferon.

A rat model simulating some aspects of weightlessness was used to determine whether simulated weightlessness might alter interferon production. The optimum time for in-vivo induction of alpha/beta interferon (alpha/beta-IFN) by polyriboinosinic-polyribocytidylic acid was determined to be four hours in normal, mature rats. Rats suspended in the model for two weeks were injected with polyriboinosinic-polyribocytidylic acid and bled four hours later. A dramatic decrease (80%) in alpha/beta-IFN production was observed in those animals exposed to simulated weightlessness as compared to control rats. These data suggest that weightlessness may alter certain immunological functions.

Animals↗

Effect of tail suspension (or simulated weightlessness) on the lumbar intervertebral disc: study of proteoglycans and collagen.

STUDY DESIGN: An experiment to measure the proteoglycan and collagen content of the lumbar intervertebral discs of rats that had been tail-suspended for up to 4 weeks. OBJECTIVES: To determine the effect of tensile force (or simulated weightlessness) on the intervertebral disc. SUMMARY OF BACKGROUND DATA: During space flight the intervertebral disc experiences low compressive force (because of so-called "weightlessness"), which, in turn, produces, among other things, low hydrostatic pressure acting on the disc cells. Although disc cells respond (in vitro) to changes in hydrostatic pressure, it is unclear what effect low levels of hydrostatic pressure have in vivo and whether they lead to a degenerative catabolic process. The rat tail-suspension model is appropriate for studying the effects of tensile force on the disc. The disc (especially the anulus) is subjected to tension during various body movements (e.g., bending stretches the posterior anulus, and twisting tensions the whole anulus). METHODS: Thirty-two Sprague-Dawley rats were tail-suspended for either 2 weeks (16 rats) or 4 weeks (16 rats). Sixteen other rats were left unsuspended for 4 weeks; these were used as controls. At the end of 2 or 4 weeks, as appropriate, the rats were killed and their lumbar spines were removed. In each rat the six lumbar discs were bisected and the discs (anulus and nucleus together) were carefully removed. The six lumbar discs from one rat were pooled with the six lumbar discs of a second matching rat (i.e., from the same group) to give one sample. The disc samples were then assessed using enzyme-linked immunosorbent assays. RESULTS: There was a 35% statistically significant decrease in proteoglycan content going from the control group down to the 4-week group, but no significant differences between the control group and the 2-week group or between the 2-week group and the 4-week group. There were no statistically significant differences between the three groups for collagen I or collagen II. CONCLUSIONS: These findings clearly establish a link between decreased proteoglycan content and tension on the disc, as modeled by the tail-suspended rat.

Animals↗

[The progress in research on changes of central venous pressure under simulated weightlessness and microgravity].

One of the most profound circulatory changes that occur in man during exposure to microgravity is a cephalad redistribution of fluid. Central venous pressure (CVP) is not only an important standard for determining the cephalad redistribution of fluid but also the unique valuable means for measuring continuously cardiac filling pressure under simulated weightlessness (SW) and microgravity, and has a relationship with neurohumoral [correction of nerohumoral] regulation. With the development of manned spaceflight, the researches in space suggested that CVP did not increase, which is directly contradictory to the previous results under SW. This paper mainly discusses the changes of CVP and the effects of countermeasures on CVP under SW and microgravity, and the mechanisms of decreased CVP under microgravity. It is postulated that more suitable SW models, more studies about the area of low pressure including especially pulmonary circulation, and comprehensive studies in multiple systems are needed.

Cardiovascular Deconditioning↗

Simulated weightlessness changes the cytoskeleton and extracellular matrix proteins in papillary thyroid carcinoma cells.

Studies of astronauts, experimental animals, and cells have shown that, after spaceflights, the function of the thyroid is altered by low-gravity conditions. The objective of this study was to investigate the cytoskeleton and extracellular matrix (ECM) protein synthesis of papillary thyroid cancer cells grown under zero g. We investigated alterations of ONCO-DG 1 cells exposed to simulated microgravity on a three-dimensional random-positioning machine (clinostat) for 30 min, 24 h, 48 h, 72 h, and 120 h (n=6, each group). ONCO-DG 1 cells grown under microgravity exhibited early alterations of the cytoskeleton and formed multicellular spheroids. The cytoskeleton was disintegrated, and nuclei showed morphological signs of apoptosis after 30 min. At this time, vimentin was increased. Vimentin and cytokeratin were highly disorganized, and microtubules (alpha-tubulin) did not display their typical radial array. After 48 h, the cytoskeletal changes were nearly reversed. The formation of multicellular spheroids continued. In parallel, the accumulation of ECM components, such as collagen types I and III, fibronectin, chondroitin sulfate, osteopontin, and CD44, increased. The levels of both transforming growth factor beta-1 (TGF-beta(1)) and TGF-beta receptor type II proteins were elevated from 24 h until 120 h clinorotation. Gene expression of TGF-beta(1) was clearly enhanced during culture under zero g. The amount of E-cadherin was enhanced time-dependently. We suggest that simulated weightlessness rapidly affects the cytoskeleton of papillary thyroid carcinoma cells and increases the amount of ECM proteins in a time-dependent manner.

Carcinoma, Papillary↗

Daily head-up tilt, standing or centrifugation can prevent vasoreactivity changes in arteries of simulated weightless rats.

Artificial gravity will be considered for long-duration spaceflight missions. Recent studies have shown that continuous exposure to gravity does not appear necessary to prevent the adverse effects of weightlessness, instead intermittent exposure may suffice. Vernikos et al reported that 1 G intermittent exposures with and without walking exercise was effective in preventing physiologic deconditioning with 4-d, -6 degrees bedrest, and standing at 1 G was most effective in preventing orthostatic intolerance. Our previous work has demonstrated differential adaptational changes in structure, function, and innervation state of arterial vasculature in different body regions of rat during simulated weightlessness and further suggested that these changes might be one of the most important mechanisms accounting for postflight orthostatic intolerance. We therefore designed the present study involving a comprehensive evaluation of the effect of intermittent G exposure in preventing the differential functional changes of the arteries at the end of 3-wk head-down tail suspension in rats to answer the following questions: (1) do intermittent G exposure have counteracting effect in preventing differential functional changes in arterial vasculature with tail-suspension? (2) among the treatments used in the present study, i.e., head-up tilt (HUT), standing (STD), and centrifugation (CEN), what kind of exposure is more effective? (3) how much time in daily 1 G exposure is needed to maintain the normal (1 G) vascular responsiveness?

Adaptation, Physiological↗

Logistic risk model for the unique effects of inherent aerobic capacity on +Gz tolerance before and after simulated weightlessness.

Small sample size (n less than 10) and inappropriate analysis of multivariate data have hindered previous attempts to describe which physiologic and demographic variables are most important in determining how long humans can tolerate acceleration. Data from previous centrifuge studies conducted at NASA/Ames Research Center, utilizing a 7-14 d bed rest protocol to simulate weightlessness, were included in the current investigation. After review, data on 25 women and 22 men were available for analysis. Study variables included gender, age, weight, height, percent body fat, resting heart rate, mean arterial pressure, VO2max, and plasma volume. Since the dependent variable was time to greyout (failure), two contemporary biostatistical modeling procedures (proportional hazard and logistic discriminant function) were used to estimate risk, given a particular subject's profile. After adjusting for pre-bed-rest tolerance time, none of the profile variables remained in the risk equation for post-bed-rest tolerance greyout. However, prior to bed rest, risk of greyout could be predicted with 91% accuracy. All of the profile variables except weight, MAP, and those related to inherent aerobic capacity (VO2max, percent body fat, resting heart rate) entered the risk equation for pre-bed-rest greyout. A cross-validation using 24 new subjects indicated a very stable model for risk prediction, accurate within 5% of the original equation. The result for the inherent fitness variables is significant in that a consensus as to whether an increased aerobic capacity is beneficial or detrimental has not been satisfactorily established. We conclude that tolerance to +Gz acceleration before and after simulated weightlessness is independent of inherent aerobic fitness.

Acceleration↗

Osteoblast histogenesis in periodontal ligament and tibial metaphysis during simulated weightlessness.

According to nuclear size, fibroblast-like cells adjacent to bone surfaces in the periodontal ligament (PDL) and tibial primary spongiosa (PS) were classified as less differentiated progenitors and committed osteoprogenitors (A/A'), nonosteogenic cells (B), or preosteoblasts (C/D). The ratio of A/A' to C/D cells reflects osteogenic status of bone lining tissue. When 83-day-old rats were subjected to simulated weightlessness (S-W) for 17 d and examined for changes in osteoblast histogenesis, PDL and PS cell populations increased in A/A' cells (p less than 0.01; less than 0.05) but decreased in C/D cells (p less than 0.01; less than 0.05) compared to controls. These data indicate that the nuclear volume method, originally developed in PDL, can also be used to assess osteoblast histogenesis in PS of long bones, and that simulated weightlessness in the present experimental context interferes with osteoblast histogenesis. Since the surfaces of both weightbearing (PS) and nonweightbearing (PDL) bones were affected, systemic factors appear important in the gravity-related mechanism of osteoblast histogenesis. Although unloading of the tibia and cephalad fluid shifts occur during S-W, the data attained in this experiment could also be explained by stress and/or cessation of growth in the S-W rats.

Animals↗

Changes of brain response induced by simulated weightlessness.

The characteristics change of brain response was studied during 15 degrees head-down tilt (HDT) comparing with 45 degrees head-up tilt (HUT). The brain responses evaluated included the EEG power spectra change at rest and during mental arithmetic, and the event-related potentials (ERPs) of somatosensory, selective attention and mental arithmetic activities. The prominent feature of brain response change during HDT revealed that the brain function was inhibited to some extent. Such inhibition included that the significant increment of "40Hz" activity during HUT arithmetic almost disappeared during HDT arithmetic, and that the positive-potential effect induced by HDT presented in all kinds of ERPs measured, but the slow negative wave reflecting mental arithmetic and memory process was elongated. These data suggest that the brain function be affected profoundly by the simulated weightlessness, therefore, the brain function change during space flight should be studied systematically.

Adolescent↗