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[Ozone hemotherapy and disorders of the functional energy competence of the cell membranes in gestoses].

A study made on biochemical mechanisms of metabolic abnormalities in grave forms of gestosis should allow some judgement about gravity of pathophysiological alterations developing in the patients' organism, efficiency of intensive therapy, and also attest to the need for instituting some additional corrective measures. Measured in the study were the principle indices for bodily metabolic homeostasis (LPO intensity, AOD, thiol metabolism) in physiological pregnancy and labor as well as in grave forms of gestoses (preeclampsia, gestational hypertension, eclampsia). The obtained results indicated that it is necessary that a specific correction of intracellular metabolism should be carried out in order that possible complications might be prevented. Ozonohemotherapy makes for reduction of oxidated forms of glutathione in red cells and also affects in patients bodily content of thiols and AOD.

Blood↗

Destabilization of human balance control by static and dynamic head tilts.

To better understand the effects of varying head movement frequencies on human balance control, 12 healthy adult humans were studied during static and dynamic (0.14, 0.33, 0.6 Hz) head tilts of +/- 30 degrees in the pitch and roll planes. Postural sway was measured during upright stance with eyes closed and altered somatosensory inputs provided by a computerized dynamic posturography (CDP) system. Subjects were able to maintain upright stance with static head tilts, although postural sway was increased during neck extension. Postural stability was decreased during dynamic head tilts, and the degree of destabilization varied directly with increasing frequency of head tilt. In the absence of vision and accurate foot support surface inputs, postural stability may be compromised during dynamic head tilts due to a decreased ability of the vestibular system to discern the orientation of gravity. This instability may compound the risk of falling following recovery from balance disorders or adaptation to altered gravity conditions such as space flight. Thus, dynamic head tilts may improve the diagnostic sensitivity of computerized dynamic posturography, particularly for healthy subjects recovering from temporary balance control deficits.

Adaptation, Physiological↗

Evidence for altered polar and lateral auxin transport in the gravity persistent signal (gps) mutants of Arabidopsis.

Plant shoots do not respond when they are reoriented relative to gravity at 4 degrees C. However, when returned to vertical at room temperature, these organs bend in response to the previous cold gravistimulation. The inflorescence stem of the Arabidopsis thaliana gravity persistent signal (gps) mutants respond abnormally after the cold gravistimulation: gps1 does not bend when returned to room temperature, gps2 bends the wrong way and gps3 over-responds, curving past the predicted angle. In wild type and the mutants, basipetal auxin transport in the inflorescence stem was abolished at 4 degrees C but restored when plants were returned to room temperature. In gps1, auxin transport was increased; in both gps2 and gps3, no significant difference was found when compared to wild type. Expression of the auxin-inducible P(IAA2)::GUS reporter gene, indicated that auxin-induced gene expression was redistributed to the lower side of the inflorescence stem in wild type after gravistimulation at 4 degrees C. In gps1, no asymmetries in P(IAA2)::GUS expression were seen. In gps2, P(IAA2)::GUS expression was localized to the upper side of the stem and in gps3, asymmetric P(IAA2):GUS expression was extended throughout the elongation zone of the inflorescence stem. These results are consistent with altered lateral Indole-3-acetic-acid (IAA) gradients being responsible for the phenotype of each mutant.

Arabidopsis↗

Optomotor behaviour in Xenopus laevis tadpoles as a measure of the effect of gravity on visual and vestibular neural integration.

The ability of aquatic vertebrates to maintain their position requires integration of visual and vestibular sensory information. To understand better how aquatic animals integrate such information, we measured the optomotor behaviour of Xenopus laevis tadpoles raised in growth chambers in microgravity (< 10(-3)g), normal gravity (1 g), hypergravity (3 g) and on a slowly rotating clinostat (simulated microgravity). The goal of this research was to determine how development in an altered gravitational force field affects the visual- and vestibular-dependent behaviour of tadpoles. This research represents the first time that the optomotor behaviour of an organism raised from fertilization in microgravity has been tested. Significant differences were observed in the optomotor behaviour among the four gravity treatments. When first exposed to normal gravity, the microgravity-raised tadpoles exhibited the strongest (or most positive) optomotor behaviour, while the 3 g centrifuge tadpoles showed no optomotor response. Some abnormal behaviours (such as erratic swimming, lying motionless and abnormal swimming posture) were observed in the tadpoles raised in altered gravity on the initial day of testing. One day later, the tadpoles raised in hypergravity did not differ significantly in their optomotor behaviour from control tadpoles raised in normal gravity. However, tadpoles raised in microgravity still displayed an exaggerated optomotor response. One week after the tadpoles had been introduced to normal gravity, there was no longer a significant difference in optomotor behaviour among the different gravity treatments. This convergence of optomotor behaviour by tadpoles from the different treatment reflects the acclimation of their vestibular systems to normal gravity.

Animals↗

Increased and decreased expression of CD69 and CD23, respectively, in gravity-stressed lymphocytes.

BACKGROUND: Recent studies have shown that gravity-changing stress modulates expression levels of cell surface molecules on human lymphocytes. However, previous in vitro microgravity studies have been performed with lymphocytes treated with mitogenic agents. HYPOTHESIS: The aim of the study was to test if exposure of cells to gravity-changing stress alone alters the expression levels of cell surface molecules. Specifically, we examined whether the expression of activation markers is altered after exposure of lymphocytes to combinations of microgravity and hypergravity. METHODS: We used free-fall in parabolic flight for human subjects and a drop-shaft to expose peripheral blood mononuclear cells (PBMC) to gravity-changing stress. After such exposure, PBMC were isolated, and expression levels of CD69, CD23 and CD38 were estimated using three-color flow cytometry. RESULTS: Increased percentages of CD69-positive cells were observed with PBMC from 3 of 4 volunteers who undertook 10 parabolic flights. Exposure of blood to gravity-changing stress in the drop-shaft increased both ratios of CD69-positive cells and levels of CD69 expression on T and B cells. In contrast, the percentages of CD23-positive B cells was decreased. However, gravity-changing stress was not always followed by significant alteration in CD38 expression. CONCLUSIONS: Our findings suggest that CD69 and CD23 might be useful markers that are up- and down-regulated, respectively, after exposure of lymphocytes to gravity-changing stress.

ADP-ribosyl Cyclase↗

Mass-discrimination in weightlessness and readaptation to earth's gravity.

Five members of the first Spacelab mission (STS-9) were tested on several occasions for weight-discrimination before and after the flight, and for mass-discrimination under microgravity in flight. Thresholds for mass-discrimination were higher than for preflight weight-discrimination by a factor of about 1.8, and there was no clear evidence of improvement throughout the ten day mission. Too few tests were conducted to monitor the improvement during the first two days of flight, when adaptation to weightlessness may have occurred. Subjects reported perceptual aftereffects of body heaviness for two or three days after the flight. Their weight-discrimination thresholds were raised during this period, when they were re-adapting to normal gravity. Incomplete adaptation to altered arm weight can only partly explain the raised threshold for mass-discrimination in microgravity. Differences in the sensory information available with and without gravity are discussed.

Adaptation, Physiological↗

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↗

The primary effects of clinorotation on cultured human mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are specific cells capable of long-term proliferation and differentiation into various stromal tissue cell types. The state of MSCs depends on the cellular microenvironment and several soluble factors. We proposed that gravity could, in addition, influence MSCs features. To prove this hypothesis, we studied the effects of prolonged clinorotation on cultured human MSC morphology, proliferation rate and expression of specific cellular markers. Human bone marrow-derived MSCs were isolated by Histopaque-1.077 density centrifugation and cultured in DMEM-LG with 10% FBS. MSC cultures were composed of fibroblastoid cells negative for hemopoietic cell markers and positive for ASMA, collagen-1, fibronectin, CD54, CD105 and CD106. Cells were exposed to clinorotation from 1 hour to 10 days. It was shown that the proliferative rate was decreased in experimental cultures as compared to cells growing in normal conditions. Clinorotated MSCs appeared more flattened and reached confluence at a lower cell density. The obtained results suggest that cultured human mesenchymal stem cells sense the changes in gravity vector and may respond to microgravity by altered functional activity.

Actins↗

Gravitational studies in cellular and developmental biology.

The paucity of data on the role of gravity in cellular and developmental biology has been examined, and a hypothesis has been generated that unifies potential gravity sensitivity in both plant and animal systems. This hypothesis considers the macromolecular order and functional importance of the extracellular matrix compartment, the intracellular cytoskeleton compartment, and the connecting plasma membrane-signal transduction compartment of plant and animal systems as potentially sensitive to alterations in the unit gravity environment in which they evolved.

Animals↗

Effects of gravity on gastric emptying, intestinal transit, and drug absorption.

The effects of microgravity on the physiologic response of the human body, the physical properties of gastrointestinal contents, and the influence these responses have on drug absorption are becoming more and more critical as the duration of humans in the hostile space environment dramatically increases. In this environment, some conventional oral dosage forms may be severely limited as an effective drug regimen. To understand the effects of microgravity, one must first understand the basic forces acting on a particle moving through a walled-tube such as the small intestine: gravity (FG), buoyancy (FB), and drag (FD). These forces can be combined and rearranged into a dimensionless ratio of gravitational forces to viscous forces. This is the most important dimensionless group influencing the motion of a particle relative to the fluid. Gastric emptying is highly influenced by several factors: volume, calories, exercise, size, density, temperature, viscosity, osmolality as well as those factors associated with physiologic responses: splanchnic blood flow, body position, and electrolyte balance. This array of factors can lead to variability in drug plasma levels. In the absence of gravity, the factors of size and density would appear to be most directly altered due to their dependence on the force of gravity. Intestinal transit rate in a gravity environment is highly dependent on the motility state of the GI tract either fasted or fed partly due to the higher viscosities of chyme in the fed state. In space, the absence of gravity may tend to increase the transit rate along the small intestine by decreasing the dimensionless ratio of gravitational forces to viscous forces. In zero gravity, therefore, these alterations in GI emptying and intestinal transit rate could lead to erratic plasma levels and inefficient absorption.

Gastric Emptying↗

Use of an otolith-deficient mutant in studies of fish behavior in microgravity.

The mutant strain (ha) of medaka (Oryzias latipes) lack utricular otoliths as fry, and some never form otoliths for life. The cross (F1 generation) between the strain having good eyesight and another strain having ordinary eyesight augmented visual acuity of the F1 generation. Crossing the good eyesight strain and ha mutant produced fish having good eyesight and less sensitivity to gravity in the F2 population. Their tolerance to microgravity was tested by parabolic flight using an airplane. The fish exhibited less looping and no differences in degree of looping between light and dark conditions, suggesting that loss of eyesight (in darkness) is not a direct cause for looping behavior in microgravity. The ha embryos could not form utricular otoliths. They did form saccular otoliths, but with a delay. Fry of the mutant fish lacking the utricular otoliths are highly dependent on light upon hatching and exhibit a perfect dorsal-light response (DLR). As they grow, they eventually shift from being light-dependent to being gravity-dependent. Continuous treatment of the fry with altered light direction suppressed this shift to gravity dependence. Being less dependent on gravity, these fish can serve as models in studying the differences expected for the vestibular system of fish reared in microgravity. When these fish were exposed to microgravity (parabolic flights) of an airplane, they spent far less time looping than fish reared in an ordinary light regimen.

Animals↗

Life-cycle experiments of medaka fish aboard the international space station.

Fish are the most likely candidates to be the first vertebrate to live their life cycle aboard the International Space Station (ISS). In the space-shuttle experiment using medaka, the fry born in space had the same number of germ cells as the ground control fish, and these germ cells later developed to produce the offspring on the ground. Fry hatched in space did not exhibit any looping behavior regardless of their strain, visual acuity, etc. The aquatic habitat (AQH) is a space habitat designed for long-term breeding of medaka, zebrafish and Xenopus, and recent advancements in this hardware also support fish life-cycle experiments. From the crosses between two strains, fish having good eyesight and less sensitivity to gravity were obtained, and their tolerance to microgravity was tested by parabolic flight using an airplane. The fish exhibited less looping and no differences in degree of looping between light and dark conditions. These are possible candidates for the first adult medaka (parent fish) to start a life cycle aboard ISS. Embryos were treated with a three-dimensional clinostat. Such simulated microgravity caused no differences in tissue architecture or in gene expression within the retina, nor in formation of cartilage (head skeleton). Otolith formation in embryos and fry was investigated for wild-type and mutant (ha) medaka. The ha embryos could not form utricular otoliths. They formed saccular otoliths but with a delay. Fry of the mutant fish lacking the utricular otoliths are highly light-dependent at the time of hatching, showing a perfect dorsal-light response (DLR). As they grow, they eventually shift from being light dependent to gravity dependent. Continuous treatment of the fry with altered light direction suppressed this shift to gravity dependence. Being less dependent on gravity, these fish can serve as model fish in studying the differences expected for the fish that have experienced a life cycle in microgravity.

Animals↗

[Diagnostic possibilities of echography of the pancreas in children with chronic diseases of the gastroduodenal and biliary systems].

Echography of the pancreas in children suffering from chronic pathology of the gastroduodenal and biliary systems may reveal a considerable incidence and the gravity of pancreatic injuries. The relationship may be found between alterations in the pancreas and the gravity of the pathology in question as well as duration, process spreading, gastric secretion reduction, and the disease entity. The results derived well agree with the reported data on pathomorphology and laboratory diagnosis of pancreatic injuries in the above-indicated pathology and provide evidence in favour of the high information content of echography. A considerable incidence and the intensity of the echographic signs of pancreatic lesions in children suffering from chronic pathology of the gastroduodenal and biliary systems support the appropriateness of echographic studies of the pancreas in the given patients' group.

Adolescent↗

Phytochrome-mediated agravitropism in Arabidopsis hypocotyls requires GIL1 and confers a fitness advantage.

Plants use specialized photoreceptors to detect the amount, quality, periodicity and direction of light and to modulate their growth and development accordingly. These regulatory light signals often interact with other environmental cues. Exposure of etiolated Arabidopsis seedlings to red (R) or far-red (FR) light causes hypocotyls to grow in random orientations with respect to the gravitational vector, thus overcoming the signal from gravity to grow upwards. This light response, mediated by either phytochrome A or phytochrome B, represents a prime example of cross-talk between environmental signalling systems. Here, we report the isolation the mutant gil1 (for gravitropic in the light) in which hypocotyls continue to grow upwards after exposure of seedlings to R or FR light. The gil1 mutant displays no other phenotypic alterations in response to gravity or light. Cloning of GIL1 has identified a novel gene that is necessary for light-dependent randomization of hypocotyl growth orientation. Using gil1, we have demonstrated that phytochrome-mediated randomization of Arabidopsis hypocotyl orientation provides a fitness advantage to seedlings developing in patchy, low-light environments.

Amino Acid Sequence↗

Review of primary spaceflight-induced and secondary reloading-induced changes in slow antigravity muscles of rats.

We have examined the light and electron microscopic properties of hindlimb muscles of rats flown in space for 1-2 weeks on Cosmos biosatellite flights 1887 and 2044 and Space Shuttle missions Spacelab-3, Spacelab Life Sciences-1 and Spacelab Life Sciences-2. Tissues were obtained both inflight and postflight permitting definition of primary microgravity-induced changes and secondary reentry and gravity reloading-induced alterations. Spaceflight causes atrophy and expression of fast fiber characteristics in slow antigravity muscles. The stresses of reentry and reloading reveal that atrophic muscles show increased susceptibility to interstitial edema and ischemic-anoxic necrosis as well as muscle fiber tearing with disruption of contractile proteins. These results demonstrate that the effects of spaceflight on skeletal muscle are multifaceted, and major changes occur both inflight and following return to Earth's gravity.

Adaptation, Physiological↗

Regulation of body fluid volume and electrolyte concentrations in spaceflight.

Despite a number of difficulties in performing experiments during weightlessness, a great deal of information has been obtained concerning the effects of spaceflight on the regulation of body fluid and electrolytes. Many paradoxes and questions remain, however. Although body mass, extracellular fluid volume, and plasma volume are reduced during spaceflight and remain so at landing, the changes in total body water are comparatively small. Serum or plasma sodium and osmolality have generally been unchanged or reduced during the spaceflight, and fluid intake is substantially reduced, especially during the first of flight. The diuresis that was predicted to be caused by weightlessness, has only rarely been observed as an increased urine volume. What has been well established by now, is the occurrence of a relative diuresis, where fluid intake decreases more than urine volume does. Urinary excretion of electrolytes has been variable during spaceflight, but retention of fluid and electrolytes at landing has been consistently observed. The glomerular filtration rate was significantly elevated during the SLS missions, and water and electrolyte loading tests have indicated that renal function is altered during readaptation to Earth's gravity. Endocrine control of fluid volumes and electrolyte concentrations may be altered during weightlessness, but levels of hormones in body fluids do not conform to predictions based on early hypotheses. Antidiuretic hormone is not suppressed, though its level is highly variable and its secretion may be affected by space motion sickness and environmental factors. Plasma renin activity and aldosterone are generally elevated at landing, consistent with sodium retention, but inflight levels have been variable. Salt intake may be an important factor influencing the levels of these hormones. The circadian rhythm of cortisol has undoubtedly contributed to its variability, and little is known yet about the influence of spaceflight on circadian rhythms. Atrial natriuretic peptide does not seem to play an important role in the control of natriuresis during spaceflight. Inflight activity of the sympathetic nervous system, assessed by measuring catecholamines and their metabolites and precursors in body fluids, generally seems to be no greater than on Earth, but this system is usually activated at landing. Collaborative experiments on the Mir and the International Space Station should provide more of the data needed from long-term flights, and perhaps help to resolve some of the discrepancies between U.S. and Russian data. The use of alternative methods that are easier to execute during spaceflight, such as collection of saliva instead of blood and urine, should permit more thorough study of circadian rhythms and rapid hormone changes in weightlessness. More investigations of dietary intake of fluid and electrolytes must be performed to understand regulatory processes. Additional hormones that may participate in these processes, such as other natriuretic hormones, should be determined during and after spaceflight. Alterations in body fluid volume and blood electrolyte concentrations during spaceflight have important consequences for readaptation to the 1-G environment. The current assessment of fluid and electrolyte status during weightlessness and at landing and our still incomplete understanding of the processes of adaptation to weightlessness and readaptation to Earth's gravity have resulted in the development of countermeasures that are only partly successful in reducing the postflight orthostatic intolerance experienced by astronauts and cosmonauts. More complete knowledge of these processes can be expected to produce countermeasures that are even more successful, as well as expand our comprehension of the range of adaptability of human physiologic processes.

Body Fluids↗

Influence of changes in gravity on the response of lung and vascular cells to ischemia/reperfusion in vitro.

Gravity and other physical forces (e.g., shear stress or mechanical stretch) will affect organ and cellular function, e.g., blood flow distribution, gas exchange, alveolar size and mechanical stresses within the lung. Microgravity produced marked alterations in lung blood flow and ventilation distribution while hypergravity exaggerated the regional differences in lung structure and function. Microgravity was found to decrease the metabolic activity in cardiac cells, WI-38 embryonic lung cells, and human lymphocytes. These studies show that changes in gravity will affect several aspects of organ and cellular function and produce major changes in blood flow and tissue/organ perfusion. However, these past studies have not addressed whether ischemia-reperfusion injury will be exacerbated or, ameliorated by changes in the gravity environment, e.g., space flight. Currently, nothing is known about how gravity will affect the susceptibility of different lung and vascular cells to this type of injury. Ischemia injury is the underlying cause of many clinical disorders with high morbidity and mortality. The subsequent reperfusion (reoxygenation) further compounds the initial ischemic stress. Understanding the possible exacerbation of transient ischemia under the stress of space flight or an increase in gravity is critical. We conducted studies that examined whether alterations in gravity affect the susceptibility of cells to ischemia-reperfusion injury, using an in vitro anoxia-reoxygenation model.

Animals↗

Is postischaemic water accumulation related to delayed postischaemic hypoperfusion in rat brain?

The effect of reversible cerebral ischaemia on brain oedema development was studied with a gravimetric method. Cerebral blood flow changes after ischaemia were correlated with alterations in brain specific gravity. Forebrain ischaemia (15 min) was induced in rats by reversible bilateral ligation of both carotid arteries plus induction of controlled hypotension to 50 mm Hg. The specific gravity of different brain structures was determined in a Percoll column up to 24 h after ischaemia. In addition, regional cerebral blood flow was measured by 14C-iodoantipyrine autoradiography. Cerebral ischaemia resulted in reduction of cerebral blood flow to less than 1% of normal in cortical structures and the caudatoputamen. One hour after the end of ischaemia blood flows were still reduced to 30-50% of the control level indicative of delayed postischaemic hypoperfusion. Specific gravity in cortex and hypothalamus reached a maximal decrease 10 min after the end of the ischaemia, and was still significantly reduced at 1 h, while it was normal again 6 hrs later. Regression analysis between regional cerebral blood flows and the corresponding specific gravities were made at various time points, but no significant correlations could be established. Other mechanisms, like vasoconstriction, rheologic or metabolic factors may be causative for the delayed postischaemic hypoperfusion.

Animals↗