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PubMed1990

Effects of hypergravity on lung carcinoma cells maintained in continuous organotypic culture.

The effects of hypergravity levels ranging from 1 to 15 g were studied on A549 lung adenocarcinoma cell line, cultivated as nodules. This organotypic culture model preserves as closely as possible the cellular structures and differentiation functions of the in vivo situation. Nodules submitted to hypergravity conditions for 27 d did not show any change of cell growth, protein and DNA contents, compared with controls. Also, cellular differentiation, as regards intracellular phospholipid composition and more particularly phosphatidylcholine content, appeared undisturbed. The only obvious effect of hypergravity was a modification of the structural organization, with a disappearance of the large alveoli present at the surrounding of control nodules and the development of a dense cellular mass instead.

Adenocarcinoma↗
PubMed1984

The unresponsiveness of the immune system of the rat to hypergravity.

The immune response in rats exposed to simulated hypergravity (2.1 G and 3.1 G) by chronic centrifugation was assessed. Rats were immunized with sheep red blood cells (SRBC), either on the day of initial exposure to hypergravity (hyper-G), or after being centrifuged for 28 d and remaining on the centrifuge thereafter. Pair-fed and ad libitum fed noncentrifuged controls were used. Although there were some alterations in leukocyte counts, hyper-G did not systematically affect the primary or secondary anti-SRBC response, hematocrits, or the sizes of the liver, spleen, kidneys, thymus, or adrenal glands. The immune system is thus remarkably homeostatic under hypergravity conditions which do affect other physiologic parameters.

Adaptation, Physiological↗
PubMed1976

Hypergravity effects on normal and avulsed developing avian radii.

Rhode Island Red female chicks were subjected to complete closed fracture of the right radius at 2 weeks post-hatching. The animals were allowed to heal for 1 week at either earth gravity or 2 G hypergravity state with control and estrogen-injected groups. Intact and fractured radial length, weight, average epiphysial-diaphysial diameters, and length, width, and weight of healing fracture callus were measured. Daily 2000 IU estrogen administration for 7 d increased intact radial length. Estrogen augments the effects of the 2-G state by inhibiting growth and depleting the mass of both intact and fractured radii and by decreasing the average distal epiphysial diameter of fractured bones. Animals exposed to the hypergravity state without hormonal treatment showed decreased fractured radial length, weight, and smaller proximal epiphysial diameters. The measurable parameters of the fracture callus (width, length, and weight) were depressed by the hypergravity state regardless of whether the animal was untreated or supplemented with estrogen.

Animals↗
PubMed1976

Accumulative effects of 2 weeks' exposure to a 2-G hypergravity state and estrogen treatment upon intact and fractured radii of young female birds.

Female birds were subjected to closed fractured of the right radius at 2 weeks post-hatching and allowed to heal for 14 d. The animals were maintained at either earth gravity or a 2-G hypergravity state with control and 2000 and 4000 IU Estrone-(estrogen) injected groups. Intact and fractured radii were measured for length, weight, average epiphysial-diaphysial diameters, and length, width and weight of fracture callus. Animals receiving 2000 IU estrogen treatment showed decreased intact and fractured bone weight, as well as smaller diaphysial diameters. Fractured, but not intact, bone length was decreased by the two estrogen levels without affecting the callus parameters. Bone weight and average epiphysial diameters of both intact and fractured radii were decreased by the hypergravity state. Intact bone diaphysis and fractured bone length were similarly affected. Large, 4000 IU, estrogen levels potentiated the hypergravity state and reduced distal epiphysial diameter of intact radii.

Animals↗
PubMed1998

Effects of hypergravity on optokinetic after-nystagmus and perceived direction of optokinetic stimulation.

BACKGROUND: Previous observations made in parabolic flight and centrifuge studies have shown the presence of a vertical nystagmus (Lz-nystagmus) induced by changes in gravitoinertial forces, and its interaction with oculomotor reflexes. HYPOTHESIS: This Lz-nystagmus is also responsible for the changes in optokinetic after-nystagmus (OKAN) and the subjective perception of optokinetic stimulation direction during hypergravity. METHODS: OKAN was recorded during the 1.8-g phase of parabolic flight after exposure to horizontal or vertical optokinetic stimulation during the preceding 1.0-g or 0-g phases. Changes in the apparent direction of image motion in subjects presented with an optokinetic stimulus were investigated in another experiment where longer exposure to hypergravity was generated by flying an airplane along a spiral path. RESULTS: In upright subjects, the time constant of OKAN with slow phase up decreased during 1.8 g, whereas the horizontal OKAN showed no change in 1.8 g compared with OKAN recorded in 1.0 g. When the subjects were lying on their left side, the OKAN with slow phase right (slow phase up with respect to gravity) decreased in 1.8 g. The subjects tested showed larger error in setting the optokinetic stimulus in a pure horizontal plane in 1.8 g than in 1.0 g. The error was also larger for oblique stimulus in 1.8 g than in 1.0 g, but no differences were seen for the vertical stimulation. CONCLUSION: The changes in OKAN can be explained by an interaction between slow phase eye movements generated by OKAN and the Lz-nystagmus generated by change in the gravitational force level. The error of the perceived direction of the optokinetic stimulus measured during horizontal and oblique stimulation is also presumably due to the interaction between the visual system and the Lz-nystagmus generated by hypergravity.

Aerospace Medicine↗
PubMed1996

Cerebral blood flow velocity response induced by a 70-hPa Valsalva manoeuvre associated with normo- and hypergravity in humans.

Anti-G straining manoeuvres, derived from the Valsalva manoeuvre (VM), are physiological methods for protecting fighter pilots against positive accelerations (+Gz). The aim of this study was to investigate the effects of a standard VM on cerebral haemodynamics, in normo- and hypergravity. In six healthy male volunteers, we investigated the cerebral blood flow velocity response induced by a 10-s, 70-hPa (52.5 mmHg) VM, under normogravity, +2, +3 and +4 Gz acceleration plateaus. Mean blood flow velocity [formula: see text] in middle cerebral artery was monitored by transcranial Doppler velocimetry. In normogravity, no significant variation in [formula: see text] was observed at the onset of VM. After a maximal period of 1.2 s, while VM was sustained, [formula: see text] decreased significantly (P < 0.05). Following the end of the manoeuvre [formula: see text] did not change significantly. When the expiratory pressure had returned to the control value, [formula: see text] was transiently increased (P < 0.05) before returning to control values. During hypergravity, [formula: see text] was significantly decreased at +3 and +4 Gz (P < 0.05) before the onset of VM. While performing VM under +Gz, the main difference compared to the normogravity condition was a significant increase of [formula: see text] (P < 0.05) at the onset of the manoeuvre. Our findings would suggest that when performed under +Gz stress, a 70-hPa VM can transiently improve cerebral haemodynamics. However, when VM is sustained for more than 1.2 s it results in a lasting decrease of cerebral perfusion which may lower +Gz tolerance.

Adult↗
PubMed1995

Microgravity and hypergravity effects on collagen biosynthesis of human dermal fibroblasts.

Astronauts experiencing long periods of space flight suffer from severe loss of bone tissue, particularly in those bones that carry the body weight under normal gravity. It is assumed that the lack of mechanical load decreases connective tissue biosynthesis in bone-forming cells. To test this assumption, quantitative and qualitative aspects of collagen synthesis under microgravity, normal gravity, and hypergravity conditions were investigated by incubating human fibroblast cultures with [3H]-proline for 4, 7, 10, and 20 h during the Spacelab D2-mission in 1993. Quantitative analysis revealed an increase of collagen synthesis under microgravity conditions, being up to 143% higher than in 1 g controls. In contrast, hypergravity samples showed a decrease in collagen synthesis with increasing g, being at the 13% level at 10 g. The relative proportion of collagen in total synthesized protein showed a slight decrease with increasing g. The secretion of collagen by the cells, proline hydroxylation of individual collagen alpha-chains, and the relative proportions of synthesized collagens I, III, and V were not affected under any of the applied conditions.

Adult↗
PubMed1997

Effects of long-term hypergravity on muscle, heart and lung structure of mice.

Quantitative changes in lung, heart and muscle structure were assessed in mice exposed for 14 weeks to a gravitational field of 3 G since the age of 4 weeks; matched controls were kept at normal gravity (1 G). The body mass of 3-G-exposed mice was significantly reduced by 9%, while total skeletal muscle mass remained the same fraction of body mass. The mass of the soleus muscle was found to be significantly larger in 3-G-exposed mice both in absolute (+27%) and body mass specific terms (+42%). Capillary density was significantly reduced by 22% because of a relatively larger increase of fiber cross-sectional area (+47%) than of capillary to fiber ratio (+16%). Other morphometric variables remained unchanged with hypergravity. Heart mass and mitochondrial volume were both larger in 3-G-exposed mice (+15% and +27%, respectively). This difference reached statistical significance when normalized to body mass. The only significant difference in lung structure detectable by morphometric methods were a smaller volume (-9%), that paralleled lower body mass, and thinner alveolar septa (-12%). From these results it is concluded that the lung's support structures in mice are sufficiently strong to withstand the stress of long-term hypergravity; however, 3-G exposure leads to a selective hypertrophy of soleus muscle fibers while absolute capillary length in this muscle remains unaltered.

Adaptation, Physiological↗
PubMed1998

Cerebral cortical blood flow in rabbits during parabolic flights (hypergravity and microgravity).

We studied the effect of gravity on cerebral cortical blood flow (CBF), mean arterial blood pressure (BPa) and heart rate in six rabbits exposed to parabolic flights. The CBF was obtained using a laser-Doppler probe fixed on to a cranial window. Before weightlessness, the animals were exposed to chest-to-back directed acceleration (1.8-2.0 g). The CBF values were expressed as a percentage of CBFo (mean CBF during 60 s before the 1st parabola). Propranolol (1 mg x kg[-1] i.v.) was given after the 11th parabola and pentobarbital (12-15 mg x kg[-1] i.v.) after the 16th parabola. Before the administration of the drugs, CBF increased (P < 0.01) during hypergravity [i.e. maximal CBF 151 (SD 64)% CBFo. Simultaneously BPa increased [maximal BPa, 119 (SD 11) mmHg (P < 0.01)]. At the onset of weightlessness, CBF and BPa reached maximal values [194 (SD 96)% CBFo (P < 0.01) and 127 (SD 19) mmHg, (P < 0.01) respectively]. The microgravity-induced increase in CBF was transient since CBF returned to its baseline value after 8 (SD 2) s of microgravity. After propranolol administration, CBF was not statistically different during hypergravity but an elevation of CBF was still observed in weightlessness. The increases in CBF and BPa also persisted during weightlessness after pentobarbital administration. These data would indicate that CBF of nonanesthetized rabbits increases during the first seconds of weightlessness and demonstrate the involvement of rapid active regulatory mechanisms since CBF returned to control values within 8 (SD 2) s. We concluded that this elevation in blood flow was not related to stress because it persisted after the administration of propranolol and pentobarbital.

Adrenergic beta-Antagonists↗
PubMed1995

Modulation by hypergravity of extracellular matrix macromolecules in in vitro human dermal fibroblasts.

In vitro human dermal fibroblasts were submitted to normal gravity (1 g) or to chronic hypergravity (20 g) over a period of 8 days. Changes in organization of extracellular matrix molecules were seen by indirect immunofluorescence. In the fibronectin layer, bundles of fibrils were gathered together leading to a disorganisation of the normal parallel pattern of fibers seen in control cultures. Type I collagen fibrils appeared with wooly outlines in controls whereas thick fibers were closely packed in 20-g cultures. A moderate increase of type III collagen fibril density was observed. No elastic fibers were seen in control or in 20-g cultures. In the culture medium, the release of soluble elastin (ELISA) and type I and III collagens (RIA) was undisturbed. Assays of enzymes involved in the remodeling of extracellular matrix showed an increase of cellular elastase activity (10%) and a decrease of the spontaneously active collagenase. Nevertheless, the total collagenase activity, (activated by trypsin), was increased by up to 30%. These data show a significant rise of the latent collagenase activity and suggest that release of the tissue inhibitor of metalloproteinase (TIMP1) was enhanced by hypergravity.

Adolescent↗
PubMed2002

Microtubule associated protein (MAP1A) mRNA was up-regulated by hypergravity in the rat inner ear.

Differential display analysis of differential mRNA expression in the rat inner ear under hypergravity identified two down- and four up-regulated genes. The up-regulation of microtubule associated protein 1A (MAP1A) in one of these was confirmed by real-time polymerase chain reaction. Since MAP1A is believed to work as a cell stabilizer connecting the actin with microtubule, this is possibly a response to strengthen this stabilizer under hypergravity. The MAP1A gene is the first found to be affected by gravity change in the inner ear.

Animals↗
PubMed2000

Inhibitory effect of hypergravity on photosynthetic carbon dioxide fixation in Euglena gracilis.

Photosynthesis, the conversion of light energy into chemical energy, is a critical biological process, whereby plants synthesize carbohydrates from light, carbon dioxide (CO2) and water. The influence of gravity on this biological process, however, is not well understood. Thus, centrifugation was used to alter the gravity environment of Euglena gracilis grown on nutritive agar plates illuminated with red and blue light emitting diodes. The results showed that hypergravity (up to 10xg) had an inhibitory effect on photosynthetic CO2 fixation. Chlorophyll accumulation per cell was essentially unaffected by treatment; however, Chl a/Chl b ratios decreased in hypergravity when compared to 1xg controls. Photosynthesis in Euglena appears to have limited tolerance for even moderate changes in gravitational acceleration.

Animals↗
PubMed2002

Crickets in space: morphological, physiological and behavioral alterations induced by space flight and hypergravity.

"Crickets in Space" was a Neurolab experiment by which the balance between genetic programs and the gravitational environment for the development of a gravity sensitive neuronal system was studied. The model character of crickets was justified by their external gravity receptors, identified position-sensitive interneurons (PSI) and gravity-related compensatory head response, and by the specific relation of this behavior to neuronal arousal systems activated by locomotion. These advantages allowed to study the impact of modified gravity on cellular processes in a complex organism. Eggs, 1st, 4th and 6th stage larvae of Acheta domesticus were used. Post-flight experiments revealed a low susceptibility of the behavior to micro- and hypergravity while the physiology of the PSI was significantly affected. Immunocytological investigations revealed a stage-dependent sensitivity of thoracic GABAergic motoneurons to 3 g-conditions concerning their soma sizes but not their topographical arrangement. The morphology of neuromuscular junctions was not affected by 3 g-hypergravity. Peptidergic neurons from cerebral sensorimotor centers revealed no significant modifications by microgravity (micro g). The contrary physiological and behavioral results indicate a facilitation of 1 g-readaptation originating from accessory gravity, proprioceptive and visual sense organs. Absence of anatomical modifications point to an effective time window of micro g or 3 g-expo-sure related to the period of neuronal proliferation. The analysis of basic mechanisms of how animals and man adapt to altered gravitational conditions will profit from a continuation of the project "Crickets in Space".

Adaptation, Physiological↗
PubMed1997

Increased longevity and resistance to heat shock in Drosophila melanogaster flies exposed to hypergravity.

In recent years, attempts have been made to increase longevity in animal models (caloric restriction in rodents or overexpression of catalase and superoxide dismutase in transgenic flies, for instance). We report here that flies submitted to hypergravity (3 or 5 g), for 1 or 4 weeks starting from the second day of imaginal life and transferred after that time to 1 g, have a higher resistance to heat shock than flies living continuously at 1 g. Furthermore, male flies that had lived for 2 weeks from the second day of life at 3 or 5 g, lived longer than those living all the time at 1 g; no longevity increase was observed in females. As far as we know, this is the first example in flies showing that a mild stress at a young age not only increases resistance to an acute stress but also increases longevity. A hypothesis to explain these results could be that heat-shock proteins, which are induced by various stress factors, are synthesized in conditions of hypergravity.

Animals↗
PubMed2001

Effect of hypergravity on the Ca/Sr composition of developing otoliths of larval cichlid fish (Oreochromis mossambicus).

The amounts of calcium and strontium were measured by inductively coupled plasma mass spectrometry (ICP-MS) in saccular and utricular inner ear otoliths (sagittae and lapilli, respectively) of developing cichlid fish. These fish had been maintained for 22 days at 3-g hypergravity conditions within a centrifuge. During this time-span, the animals completed their ontogenetic development from hatch to the free-swimming stage. Neither the morphogenetic development nor the timely onset and gain of performance of the swimming behaviour was impaired by the experimental conditions. Experimental and control animals also did not differ concerning their size (total length). ICP-MS revealed that the otoliths contained significantly less calcium (in microg/otolith) after hyper-g exposure compared to parallelly raised 1-g control specimens (lapilli: 0.74+/-0.21 vs. 1.16+/-0.41; sagittae: 2.09+/-0.49 vs. 2.76+/-0.47). The content of strontium (in microg/otolith: lapilli: 0.0044+/-0.0023 vs. 0.0022+/-0.0013; sagittae: 0.0094+/-0.0026 vs. 0.0081+/-0.0016) and, consequently, the Sr/Ca ratio (Sr/Cax100) was increased (lapilli: 0.607+/-0.267 vs. 0.201+/-0.12; sagittae: 0.439+/-0.093 vs. 0.301+/-0.086). Since the calcium content can be taken as a proxy for otolith weight, and because parallelly undertaken morphometric investigations revealed smaller otoliths (maximum radius and surface area) due to hyper-g exposure, the results suggest that the growth of otoliths at hyper-g is slowed down. Since the concentration of trace elements incorporated into otoliths is likely based on the composition of the respective protein matrix, our findings suggest that the protein metabolism is affected by hypergravity.

Animals↗
PubMed2001

Maternal reproductive experience enhances early postnatal outcome following gestation and birth of rats in hypergravity.

A major goal of space life sciences research is to broaden scientific knowledge of the influence of gravity on living systems. Recent spaceflight and centrifugation studies demonstrate that reproduction and ontogenesis in mammals are amenable to study under gravitational conditions that deviate considerably from those typically experienced on Earth (1 x g). In the present study, we tested the hypothesis that maternal reproductive experience determines neonatal outcome following gestation and birth under increased (hyper) gravity. Primigravid and bigravid female rats and their offspring were exposed to 1.5 x g centrifugation from Gestational Day 11 either through birth or through the first postnatal week. On the day of birth, litter sizes were identical across gravity and parity conditions, although significantly fewer live neonates were observed among hypergravity-reared litters born to primigravid dams than among those born to bigravid dams (82% and 94%, respectively; 1.0 x g controls, 99%). Within the hypergravity groups, neonatal mortality was comparable across parity conditions from Postnatal Day 1 through Day 7, at which time litter sizes stabilized. Maternal reproductive experience ameliorated neonatal losses during the first 24 h after birth but not on subsequent days, and neonatal mortality was associated with changes in maternal care patterns. These results indicate that repeated maternal reproductive experience affords protection against neonatal losses during exposure to increased gravity. Differential mortality of neonates born to primigravid versus bigravid dams denotes gravitational load as one environmental mechanism enabling the expression of parity-related variations in birth outcome.

Animals↗
PubMed2000

Neurobehavioural effects of hypergravity conditions in the adult mouse.

To evaluate the behavioural response to a hypergravity condition in CD-1 mice, young adult subjects of both sexes were exposed to 2 g for a single 60 min rotational session. Motion sickness (MS) and ethological-type scoring of different activities were used to evaluate the behavioural response. Nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) levels were also assessed. Behavioural scores indicated a transient mild sickness associated with hypergravity, with reduction in spontaneous activity. In males kaolin consumption (a MS index) increased following rotation while females consumed more kaolin irrespective of whether they have been rotated or simply exposed to the noise and vibration of the rotational apparatus. In males, hypothalamic NGF levels were markedly increased after rotation while no major changes were observed in central BDNF expression. These results indicate mice may represent a suitable MS model.

Animals↗
PubMed2002

Inter- and intraregional ventilation inhomogeneity in hypergravity and after pressurization of an anti-G suit.

This study assessed the effects of increased gravity in the head-to-foot direction (+G(z)) and anti-G suit (AGS) pressurization on functional residual capacity (FRC), the volume of trapped gas (V(TG)), and ventilation distribution by using inert- gas washout. Normalized phase III slope (Sn(III)) analysis was used to determine the effects on inter- and intraregional ventilation inhomogeneity. Twelve men performed multiple-breath washouts of SF(6) and He in a human centrifuge at +1 to +3 G(z) wearing an AGS pressurized to 0, 6, or 12 kPa. Hypergravity produced moderately increased FRC, V(TG), and overall and inter- and intraregional inhomogeneities. In normogravity, AGS pressurization resulted in reduced FRC and increased V(TG), overall, and inter- and intraregional inhomogeneities. Inflation of the AGS to 12 kPa at +3 G(z) reduced FRC markedly and caused marked gas trapping and intraregional inhomogeneity, whereas interregional inhomogeneity decreased. In conclusion, increased +G(z) impairs ventilation distribution not only between widely separated lung regions, but also within small lung units. Pressurizing an AGS in hypergravity causes extensive gas trapping accompanied by reduced interregional inhomogeneity and, apparently, results in greater intraregional inhomogeneity.

Adult↗