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[Repeated hypergravity: morphologic investigations of pituitary, thyroid, blood and bone marrow in rats].

To elicit the mechanism of facilitating the mammals' adaptation to repeated changed gravity influence, the pituitary, thyroid, blood and bone marrow were investigated morphologically in rats exposed to single and repeated hypergravity (2 g) and Coriolis accelerations for 5 days during rotation on centrifuge. No distinct difference in blood and bone marrow cytology was determined after single and repeated exposure to 2 g and the Coriolis accelerations. Compared to single and in contrast to single and repeated exposures to the Coriolis accelerations, a repeated 2 g influence produced some structural changes in somatotropic cells of the pituitary and thyroid parenchyma of the thyroid. These changes were indicative of a significant intensification of synthesis and secretion of somatotropic and thyroid hormones. Elevated functional activity of the somatotropic cells and thyroid parenchyma during repeated exposure to 2 g appears to be a part of mechanism that makes adaptation to repeated hypergravity easier and points to the ability of mammals "to remember" changed gravity. It also advocates for the potentiality of intermittent centrifugation as a means of generating artificial gravity forces in space flight.

Adaptation, Physiological↗

The effect of hypogravity and hypergravity on cells of the immune system.

This article reviews the gravity effects discovered in T lymphocytes and other cells of the immune system. The strong depression of mitogenic activation first observed in an experiment conducted in Spacelab 1 in 1983 triggered several other investigations in space and on the ground in the clinostat and in the centrifuge in the past 10 years. During this period, great progress was made in our knowledge of the complex mechanism of T cell activation as well as the technology to analyze the lymphokines produced during stimulation. Nevertheless, several aspects of the steps leading to activation are not yet clear. Studies in hypogravity and hypergravity may contribute to answering some of the questions. A recent investigation in the U.S. Spacelab SLS-1, based on a new technology in which leukocytes are attached to microcarrier beads, showed that the strong inhibition of activation in microgravity is due to a malfunction of monocytes acting as accessory cells. In fact, interleukin-1 production is nearly nil in resuspended monocytes, whereas T cell activation is doubled in attached cells. In hypergravity, but not at 1g, concanavalin A bound to erythrocytes activates B lymphocytes in addition to T cells. The activation of Jurkat cells is also severely impaired in space. These recent results have raised new questions that have to be answered in experiments to be conducted in space and on Earth in this decade. The experimental system, based on the mitogenic activation of T lymphocytes and accessory cells attached to microcarriers, offers an optimum model for studying basic biological mechanisms of the cell to assess the immunological fitness of humans in space and to test the feasibility of bioprocesses in space as well as on Earth.

Gravitation↗

Intrauterine fetal response to hypergravity by reduction of plasma prolactin levels in the rat.

Rats were conceived after adaptation to 3.14 g. Maternal and fetal plasma prolactin levels were reduced on day 22 of gestation in the rats exposed to hypergravity. The fact that fetuses in utero respond in the same way as their mothers indicates that they too are sensitive to hypergravity and that the bouyant condition of the fetus does not interfere with such external stimulus.

Animals↗

Saccule contribution to immediate early gene induction in the gerbil brainstem with posterior canal galvanic or hypergravity stimulation.

Immunolabeling patterns of the immediate early gene-related protein Fos in the gerbil brainstem were studied following stimulation of the sacculus by both hypergravity and galvanic stimulation. Head-restrained, alert animals were exposed to a prolonged (1 h) inertial vector of 2 G (19.6 m/s2) head acceleration directed in a dorso-ventral head axis to maximally stimulate the sacculus. Fos-defined immunoreactivity was quantified, and the results compared to a control group. The hypergravity stimulus produced Fos immunolabeling in the dorsomedial cell column (dmcc) of the inferior olive independently of other subnuclei. Similar dmcc labeling was induced by a 30 min galvanic stimulus of up to -100 microA applied through a stimulating electrode placed unilaterally on the bony labyrinth overlying the posterior canal (PC). The pattern of vestibular afferent firing activity induced by this galvanic stimulus was quantified in anesthetized gerbils by simultaneously recording from Scarpa's ganglion. Only saccular and PC afferent neurons exhibited increases in average firing rates of 200-300%, suggesting a pattern of current spread involving only PC and saccular afferent neurons at this level of stimulation. These results suggest that alteration in saccular afferent firing rates are sufficient to induce Fos-defined genomic activation of the dmcc, and lend further evidence to the existence of a functional vestibulo-olivary-cerebellar pathway of adaptation to novel gravito-inertial environments.

Animals↗

A genetic effect of altered gravity: mutations induced by simulated hypogravity and hypergravity in microsatellite sequences of human tumor cells.

To determine the possible genetic effects of gravity alterations, we analyzed mutation induction in microsatellite sequences of human tumor cells treated with simulated hypogravity provided by a clinostat or hypergravity by a centrifuge. Microsatellite mutations were detected as changes in the size of polymerase chain reaction (PCR)-amplified allelic markers. The frequencies of mutant clones in cultures treated with simulated hypogravity for 24 or 48 h were almost the same as those of controls, but after 72 h of treatment, the mutant frequencies had increased significantly in all three microsatellite loci examined. Significantly higher mutant frequencies were similarly detected in cultures treated for 72 h with a hypergravity condition as low as 18xg, but not detected in 24 or 48 h treated cultures. These findings clearly show that gravity alterations that last for 3 days can induce microsatellite mutations in human cells. A genetic effect of gravity change, therefore, is established for the first time. Moreover, high frequencies of microsatellite mutations were induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) which activates protein kinase C-mediated signal transduction pathways and causes genetic instability. These findings suggest that gravity change induces microsatellite mutations by modulating the pattern of gene expression involved in signal transduction pathways.

DNA Primers↗

Optospectroscopic detection of primary reactions associated with the graviperception of Phycomyces. Effects of micro- and hypergravity.

The graviperception of sporangiophores of the fungus Phycomyces blakesleeanus involves gravity-induced absorbance changes (GIACs) that represent primary responses of gravitropism (Schmidt and Galland, 2000). GIACs (DeltaA(460-665)) of sporangiophores were measured in vivo with a micro-dual wavelength spectrometer at 460 and 665 nm. Sporangiophores that were placed horizontally displayed an instant increase of the GIACs while the return to the vertical position elicited an instant decrease. The GIACs are specific for graviperception, because they were absent in a gravitropism mutant with a defective madJ gene. During parabola flights hypergravity (1.8 g) elicited a decrease of the GIACs, while microgravity (0 +/- 3 x 10 (-2) g) elicited an instant increase. Hypergravity that was generated in a centrifuge (1.5-6.5 g) elicited also a decrease of the GIACs that saturated at about 5 g. The GIACs have a latency of about 20 ms or shorter and are thus the fastest graviresponses ever measured for fungi, protists, and plants. The threshold for eliciting the GIACs is near 3 x 10 (-2) g, which coincides numerically with the threshold for gravitropic bending. In contrast to gravitropic bending, which requires long-term stimulation, GIACs can be elicited by stimuli as short as 20 to 100 ms, leading to an extremely low threshold dose (acceleration x time) of about 3 x 10 (-3) g s, a value, which is four orders of magnitude below the ones described for other organisms and which makes the GIACs of Phycomyces blakesleeanus the most sensitive gravi-response in literature.

Gravitation↗

Adaptive response of human skeletal muscle to simulated hypergravity condition.

The mechanical behaviour of leg extensor muscles of five international-level athletes was evaluated during 13 months training period. Drop jumps, average mechanical power during 15 S continuous jump, and vertical jumps performed with and without extra weights were used to measure explosive power characteristics. The data recorded in vertical jumps was utilized for construction of force-velocity relationship (F-V curve). The athletes did not show improvement in any of the variables studied after 12 months of intensive systematic training programme. It was assumed that the subjects already had reached their upper limit of performance. However, after that the athletes underwent a simulated 3 weeks high-gravity period. The hypergravitational condition was created by wearing a special vest filled with extra loads (11% of BW). The vest was used from morning to evening. No changes in the ordinary training programme were allowed. After the simulated high-gravity conditioning period significant improvement in almost all the variables studied was observed (P less than 0.05-0.001). Vertical jump performance was enhanced from 44.3 to 54.9 cm. The F-V curve remained stable all year but after hypergravity period shifted markedly to the right. The drastic improvement was attributed to be caused by a fast adaptation to the new functional requirements (I.I g). Therefore, once the biological adaptation occurred the mechanical behaviour of the athlete's leg extensor muscle was similar to that which could be experienced in a field at low gravity condition (0.9 g). Adaptive response to the hypergravity conditioning was speculated to occur mainly at neurogenic level and less in myogenic component.

Adaptation, Physiological↗

Thermoregulation in hypergravity-acclimated rats.

To determine the effect of hypergravity acclimation on thermoregulation, core temperature (Tc), tail temperature (Tt), and O2 consumption (VO2) were measured in control rats (raised at 1 G) and in rats acclimated to 2.1 G. When the animals were exposed to a low ambient temperature of 9 degrees C, concurrently with a hypergravic field of 2.1 G, Tc of rats raised at 1 G fell markedly by approximately 6 degrees C (to 30.8 +/- 0.6 degrees C) while that of the rats raised at 2.1 G remained relatively constant (falling only approximately 1 degree C to 36.4 +/- 0.3 degrees C). Thus prior acclimation to a 2.1-G field enabled rats to maintain Tc when cold exposed in a 2.1-G field. To maintain Tc, thermogenic mechanisms were successfully activated in the 2.1-G-acclimated rats as shown by measurements of VO2. In contrast, VO2 measurements showed that rats reared at 1 G and then cold exposed at 2.1 G did not activate thermogenic mechanisms sufficiently to prevent a fall in Tc. In other experiments, rats acclimated to either 1 or 2.1 G were found to lack the ability to maintain their Tc when exposed to a 5.8-G field or when exposed to prolonged cold exposure at 1 G. Results are interpreted as showing that when placed in a 2.1-G field, rats acclimated to 2.1 G can more closely maintain their Tc near 37 degrees C when cold exposed than can rats acclimated to 1 G. However, this enhanced regulatory ability of 2.1-G-acclimated rats over 1.0-G-acclimated rats is restricted to 2.1-G fields and is not observed in 1.0- and 5.8-G fields.

Adaptation, Physiological↗

Effects of hypergravity environment on the parathyroid gland of the isoproterenol-treated hamster.

The ultrastructure of the parathyroid glands of hamsters subjected to 5 g environment after an intraperitoneal injection of isoproterenol was studied. In the isoproterenol-treated hamsters exposed to hypergravity environment, the Golgi complexes, cisternae of the granular endoplasmic reticulum and lipid droplets were significantly increased and secretory granules were significantly decreased compared with those of the control group. In addition, many chief cells contained numerous prosecretory granules in the Golgi areas and several secretory granules were situated close to the plasma membrane of the chief cells. These results suggest that the synthesis and release of parathyroid hormone may be markedly stimulated in the parathyroid glands of the isoproterenol-treated hamsters exposed to hypergravity environment.

Animals↗

Hypergravity and aging in Drosophila melanogaster. 5. Patterns of movement.

The paths of young, middle-aged and old Drosophila melanogaster flies, kept at various gravity levels (1-5 g) throughout life, have been recorded in a cross-sectional study. Aging flies exhibit more sinuous paths and do not move as far away from their release point as younger ones. These age-related changes in the patterns of movement are expressed at younger ages in flies submitted to hypergravity. As for the climbing activity experiment, the patterns of movement do not clearly vary with the gravity level at young age. Results are discussed in relation to the hypothesis of increased aging rate in hypergravity.

Aging↗

GRAVIRESPONSES IN PARAMECIUM CAUDATUM AND DIDINIUM NASUTUM EXAMINED UNDER VARIED HYPERGRAVITY CONDITIONS

The swimming behaviours of two species of ciliates characterized by different mechanosensory and ciliary motor properties were investigated under hypergravity up to 5.4 g. The experiments were designed to examine large numbers of cells using video recording, digital data processing and statistics for the documentation of the rates and orientations of swimming. The gravikinetic responses (change in active swimming rates) were calculated from (1) the velocities of vertical swimming in the gravity field, (2) sedimentation of Ni2+-immobilized cells and (3) the intrinsic rate of propulsion, independent of gravity. Propulsion was determined from the intersection of regression lines of the gravity-dependent upward and downward swimming velocities. The rates of swimming and sedimentation, and consequently the gravikineses, were linear functions of gravitational acceleration. Comparisons of cell populations from different cultures suggest that there is an age-dependent change in gravikinesis. In starved Paramecium caudatum (7-day cultures), the kinetic responses antagonizing sedimentation (negative gravikinesis) increased with acceleration. In Didinium nasutum, negative gravikinesis was documented at 1 g in downward-swimming specimens only, which agrees with the mechanosensory organization of this cell. Hypergravity induced the gravikinesis of Didinium to change sign. In both species, and at all accelerations tested, a neutral gravitaxis was documented. Such behaviour incorporates distinct acceleration-dependent orientational and velocity responses, keeping populations of cells stationary in the gravity field (taxis coefficients close to zero).

Journal Article↗

Effects of hypergravity on morphology and osteopontin expression in the rat otolith organs.

Recovery from balance disorders after spaceflight is supposed to reflect the process of readaptation to normal gravitational environment (1G) from microgravity. Linear acceleration including gravity is perceived by otolith pathways, therefore, it could be assumed that possible plastic changes in any part of otolithic pathways from the level of the vestibular periphery to the central vestibular system might be responsible for adaptive mechanisms to an altered gravitational environment. In the present study, to elucidate a role of otoconia in adaptation to altered gravity, we examined the effects of hypergravity (2G) on morphology and synthesis of saccular and utricular otoconia in young adult rats. Morphology of otoconia was examined by scanning electron microscopy. Otoconial synthesis was assessed by mRNA expression of osteopontin, a matrix protein of otoconia, in otolithic maculae as a marker of otoconial genesis determined by a real-time quantitative PCR method. The present results showed that neither otoconial morphology nor otoconial synthesis was affected by up to one week exposure to hypergravity. These findings suggest that changes in neurotransmission at the synapses of the peripheral and/or central vestibular system rather than the changes in otoconial morphology and synthesis may be involved in adaptive mechanisms to an altered gravitational environment.

Animals↗

Effects of long duration +2G hypergravity on MHC distribution and maximal tension of rat m.soleus fibers.

Effects of long duration hypergravity on skeletal muscles are much less studied than effects of microgravity. For instance, it was revealed that hypergravity of 2 week duration induces decrease in cross sectional area (CSA) of slow fibers (SF), while their size remains constant, or increases. Exposure to +2G of 14 day duration results in decreased number of type I fibers, and in changed myosin heavy chain (MHC) profiles of rat hindlimb extensor muscle. It is interesting that gravitational unloading also decreases number of type I fibers. However, while effects of microgravity on relationship between the structural and functional characteristics of skeletal muscles are studied in detail, similar characteristics of skeletal muscles under conditions of gravitational overloading are very much understudied. The aim of our work was to follow dynamics of MHC in rat m.soleus after exposure to 19 and to 33 days of +2G acceleration, and to compare content of contractile proteins in muscle fibers, and their contractile properties.

Journal Article↗

The effect of hypergravity on carcinogenesis in mice.

In recent years, investigators began studying the effect of hypergravity on pathological developments in the animal and human body. It was shown that a regular exposure of tail suspended rats to normal gravity diminished osteopenia and muscle atrophy. Moderate gravitational loading produced by a G-suit dramatically increased the therapeutic success rate in children with cerebral palsy. Rotation of patients with obliterating endarteritis and limb bone fractures in a short-radius centrifuge in hospitals of the city of Samara (Russia) yielded promising results. The purpose of our investigations was to investigate the effects of hypergravity on chemically induced carcinogenesis in mice. We hypothesized that gravitational loading may produce a generalized effect on the animal body and thus to enhance its nonspecific anti-tumor resistance.

Journal Article↗

Pilot performance is increased after alternating hypo- and hypergravity states.

An increase of performance of six experienced pilots in a complex in-flight aerobatics test repeated after a period of alternating zero-hypergravity conditions, lasting for 30 minutes, was observed, if compared with the same test before such exposition. There was no difference in the increase of the pilot performance, if the in-flight test was repeated after a period of rest of the same duration. We conclude that in experienced pilots adaptation to a complex in-flight test remains uninfluenced by alternating zero-hypergravity conditions, realized in a light transport plane. Perhaps adaptation to alternating gravity conditions is implemented better than to full weightlessness in experienced subjects. This is to be proved in real space flights.

Adaptation, Physiological↗

The immune system: effects of hypergravity and hypogravity.

The force of gravity has been inescapable until only the last few decades. Space programs conducted by several nations now make possible the study of hypergravity and hypogravity in a variety of scientific areas. Although much work has focused on the physiological aspects of gravity, its effects on the immune system are only beginning to be appreciated. An understanding of these effects is not only of theoretical interest, but important in predicting the health of astronauts exposed to hypergravity and hypogravity. These studies may also help to answer the larger question of how stress affects the immune response.

Animals↗

Studies on the erythron and the ferrokinetic responses in beagles adapted to hypergravity.

Red cell survival, ferrokinetics, and hematologic parameters were investigated in Beagle dogs exposed to chronic hypergravity (2.6 Gx). Ineffective erythropoiesis, red cell mass, plasma volume, and 51 Cr elution were significantly increased; maximum 59Fe incorporation was decreased; and there was no change in the mean erythrocyte life span following autologous injection of 51Cr-labeled red cells and 59Fe-labeled transferrin. Red cell count, Fcells, total body hemoglobin (Hb), susceptability to osmotic lysis, and differential reticulocyte count were increased. White blood cell count, venous blood %Hb, mean cell volume, mean cell Hb, mean cell Hb concentration, and serum iron were decreased. No changes were observed for body mass, mg Fe per g Hb, iron binding capacity, percent saturation of iron carrying capacity, or the electrophoretic mobility of purified Hb. This study indicated that chronic exposure to hypergravity induced changes in red cell size, volume, total mass, and membrane permeability.

Adaptation, Physiological↗

[Effects of hypergravity on Paramecium tetraurelia].

Previous space experiments carried out in Paramecium tetraurelia have shown that exposure to microgravity results in an enhancement of cell multiplication. An opposite effect occurs when paramecia are exposed to hypergravity. Changes in cell growth rate observed in hypergravity cannot be ascribed to the bacteria present in the culture medium, the same effect being observed when paramecia grow in sterile medium.

Animals↗