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Biomedical aspects of artificial gravity.

Artificial gravity (AG) is the basic challenge for space biology and medicine. The importance of this problem is associated with the fact that duration of the space missions will become progressively longer, but the presently available countermeasures do not provide reason enough to predict the human health safety during space missions of any duration. The creation of AG could be an efficient method for removing the negative effects of microgravity. Two principle methods of generating AG, rotation of space system (SS) and building of short arm centrifuge (SAC), have been proposed. The purpose of the present work is to review the biomedical aspects of AG in the context of its use in long-term space missions.

Aerospace Medicine↗

Cytoplasmic streaming affects gravity-induced amyloplast sedimentation in maize coleoptiles.

Living maize (Zea mays L.) coleoptile cells were observed using a horizontal microscope to determine the interaction between cytoplasmic streaming and gravity-induced amyloplast sedimentation. Sedimentation is heavily influenced by streaming which may (1) hasten or slow the velocity of amyloplast movement and (2) displace the plastid laterally or even upwards before or after sedimentation. Amyloplasts may move through transvacuolar strands or through the peripheral cytoplasm which may be divided into fine cytoplasmic strands of much smaller diameter than the plastids. The results indicate that streaming may contribute to the dynamics of graviperception by influencing amyloplast movement.

Cotyledon↗

Altered gravity modulates 5-lipoxygenase in human erythroleukemia K562 cells.

Mammalian lipoxygenases catalyse the first committed step in the so-called "arachidonate cascade", leading to the production of potent bioactive molecules, such as leukotrienes, lipoxins and hepoxilins. Leukotrienes interact with G protein-couple receptors involved in neuronal plasticity and T lymphocyte activation, lipoxins activate leukocytes, hepoxilines control the insulin release and stimulate the phospholipase C. Lipoxygenase (linoleate:oxygen oxidoreductase; E.C. 1.13.11.34; 5-LOX) are responsible for lymphocyte maturation and programmed death (apoptosis) of neuronal cells. Therefore, 5-LOX might be Space relevant, because among the most striking effects of Space enviroment are indeed those on T lymphocyte activation, neuronal cell growth and suspectedly apoptosis. In this study, the possible effects of the force of gravity on the activity and expression of 5-LOX have been investigated by subjecting human erythroleukemia K562 cells to simulated hypogravity or hypergravity.

Arachidonate 5-Lipoxygenase↗

Lipid peroxidation and polyamine metabolism in K562 cells subjected to altered gravity.

The mechanisms underlying cell sensitivity to the gravistimulus are still largely unknown. Recently, the oxidation of membrane lipids and the alteration of polyamine content have been shown to be involved in several cellular processes, from cell growth and differentiation, to aging and resistance to (a)biotic stress. Such an involvement was mediated by the modification of the activity and expression of lipoxygenase (LOX; E.C. 1.13.11.12) and diamine oxidase (DAO; E.C. 1.4.3.6), the enzymes which control membrane properties (LOX) and the catabolism of polyamines (DAO), respectively. In this study, the possible effects of altered gravity on membrane lipid peroxidation and polyamine metabolism were investigated, by subjecting human erythroleukemia K562 cell cultures to simulated hypogravity (by clinorotation) or hypergravity (by centrifugation).

Amine Oxidase (Copper-Containing)↗

Human sensitivity to gravity (on the problem of gravipreferendum).

Experiments were carried out in a centrifuge with an arm of 7.25 m, the cabin being equipped with a self-contained system of control. During an exposure to head-to-feet accelerations (+gz) of 2 g and an onset rate of 0.1 g s-1 the test subject controlled the centrifugation himself and selected the acceleration values he was instructed to attain. The subjects were shown to be capable of assessing integrally the value of accelerations and estimating it with an error of 0.1-0.12 g. During an exposure to chest-to-back accelerations (+gx) limited to a value of 12 g and a gradient of 0.3 g s-1 the ability to select actively the rate of an acceleration increase was studied. Repeated centrifugations resulted in the formation and strengthening of the skill of maintaining a physiologically optimal rate of an acceleration increase. Onset rates were determined for every level of acceleration. When calculated as a mean, physiologically optimal values of the onset rate for 12 g were 0.16-0.18 g s-1. The findings give insight into important properties of the physiological structure of "gravipreferendum", which is the capability of man to differentiate between gravity levels and to select actively optimal rates of an increase in acceleration.

Acceleration↗

Modern view on the short-arm centrifuge as a potential generator of artificial gravity in piloted missions.

The problem of artificial gravity (AG) in long-term missions is one of the hottest, as the existing countermeasures do not fully cope with the negative consequences of weightlessness. From two variants of AG creation--rotation of space systems around of their mass center or short radius centrifuge (SAC)--the preference is given to SAC, as technically easier variant for realization. However, the rotation of a person on SAC can cause not only positive, but also negative effects. The purpose of the present study was to perform the analysis of data of researches on a problem of AG generated by a of SAC, executed in Russia during last 20 years, and to state modern views on application of SAC as a mean of AG creation in long piloted missions.

Adaptation, Physiological↗

[Effects of centrifugation-related artificial gravity on the human organism. Positive and negative effects].

Data of investigations of the artificial gravity issues in centrifuge experiments in Russian, USA and Japan over the past 40 years were analyzed. Periodic +Gz centrifugation was used to prevent or eliminate body deconditioning after 3- to 56-d simulated microgravity, and to increase the body functional reserve (orthostatic stability) in ordinary life. Positive effects included prevention of a decline of gravitational stability and reduction or averting the negative effects of simulated microgravity on various physiological systems. Better results can be achieved by combining artificial g-loads with the well-proven methods of combating deconditioning, i.e. physical training on bicycle ergometer and induced hydration. Human tolerance of g-loads on a short-arm centrifuge with a high (100%) gravitational gradient was found no worse than on a mid-arm centrifuge with a lower (20%) gravitational gradient. Negative effects of +Gz on a short-arm centrifuge were revealed and counteracting measures were determined.

Centrifugation↗

Plasma concentration of furosemide versus specific gravity of urine in predicting dose of administration in race horses.

This study was undertaken to determine the applicability of plasma concentration of furosemide and specific gravity (SG) of urine in regulating the use of furosemide administered 4 hours prior to race time in Exercise-Induced Pulmonary Hemorrhage (EIPH) race horses. Nonbleeders (CTL) and certified bleeders (FUR) actively racing in Illinois (IL) and Pennsylvania (PA) were used in the study. Various doses (less than 250, 250, 300, 350, 400 and 500 mg) were administered either as a single intravenous (IV) dose or as a combination (IV-IM) of IV and intramuscular (IM) administrations 4 hours before race time. Plasma and urine samples were obtained post race for determination of furosemide concentration in plasma and measurement of SG of the urine in both CTL and FUR groups. Plasma samples were analyzed for furosemide using High Performance Liquid Chromatography with Fluorescence Detection. SG was measured using a digital refractometer. The results indicate a significant difference (p less than 0.0001) in the SG of the urine samples between the CTL and FUR groups irrespective of the route of administration (IV versus IV-IM). However, SG values of the urine in some CTL samples were lower than those in some FUR samples and vice versa. Thus, the use of SG alone is not reliable for predicting either the dose or the administration of furosemide to race horses. The plasma concentrations of furosemide following the administration (IV) of 250 mg or 500 mg 4 hours prior to race time were indistinguishable (25.91 +/- 4.45 versus 28.12 +/- 6.99 ng/ml, respectively); the majority of the horses in the groups had a plasma concentration of less than 40 ng/ml. When taken in total, plasma concentration of furosemide can only be used as a guide in regulating the administration of furosemide to race horses.

Animals↗

Sensorimotor aspects of high-speed artificial gravity: III. Sensorimotor adaptation.

As a countermeasure to the debilitating physiological effects of weightlessness, astronauts could live continuously in an artificial gravity environment created by slow rotation of an entire spacecraft or be exposed to brief daily "doses" in a short radius centrifuge housed within a non-rotating spacecraft. A potential drawback to both approaches is that head movements made during rotation may be disorienting and nauseogenic. These side effects are more severe at higher rotation rates, especially upon first exposure. Head movements during rotation generate aberrant vestibular stimulation and Coriolis force perturbations of the head-neck motor system. This article reviews our progress toward distinguishing vestibular and motor factors in side effects of rotation, and presents new data concerning the rates of rotation up to which adaptation is possible. We have studied subjects pointing to targets during constant velocity rotation, because these movements generate Coriolis motor perturbations of the arm but do not involve unusual vestibular stimulation. Initially, reaching paths and endpoints are deviated in the direction of the transient lateral Coriolis forces generated. With practice, subjects soon move in straighter paths and land on target once more. If sight of the arm is permitted, adaptation is more rapid than in darkness. Initial arm movement trajectory and endpoint deviations are proportional to Coriolis force magnitude over a range of rotation speeds from 5 to 20 rpm, and there is rapid, complete motor adaptation at all speeds. These new results indicate that motor adaptation to high rotation rates is possible. Coriolis force perturbations of head movements also occur in a rotating environment but adaptation gradually develops over the course of many head movements.

Adaptation, Physiological↗

Evaluation of cell culture flasks designed for experiment under altered gravity-vector conditions.

Cell culture flasks applicable for altered gravity conditions, such as centrifugation, clino-rotation or microgravity in space, were manufactured for trial. The flask has flat polystyrene surface for monolayer culture and gas-permeable film window on the opposite face. The space in-between consists the culture chamber to be filled with liquid medium. To reduce the water loss and bubble formation in the culture fluid, another gas permeable window was placed on top to form a space where distilled water may be filled. The double-decker culture flask can be used for both space and ground-based experiments in common.

Cell Culture Techniques↗

[The problem of creation of artificial gravity with the use of a short-radius centrifuge for medical support of interplanetary piloted missions].

On the evidence of orbital flights, the system of countermeasures against the effects of microgravity does not fully make for deconditioning of a number of human organs and systems and recovery of preflight physical status and working ability of members of long-term missions takes 1.5 to 2 mos. of the post-flight rehabilitation. In order to maintain the physical form, health and performance of crews in future interplanetary missions, we should be ready to offer them a novel countermeasure, i.e. regular sessions of artificial gravity generated by a short-radius centrifuge (SRC) on board vehicles. The articles presents the substantiation and concept of ground-based simulation studies of health benefits from SRC in interplanetary missions. Of primary concern is development of SRC regimens that will put up a strong opposition to microgravity, assure crew safety, and reduce to the minimum time to fulfill the in-flight countermeasure program. Answers to arising questions can be found by consolidation of the expertise and resources of the countries willing to meet this challenge.

Adaptation, Physiological↗

Vestibulo-ocular reflex and gravity in fish.

An otolith organ on ground behave as a detector of both gravity and linear acceleration, and play an important role in controlling posture and eye movement for tilt of the head or translational motion. On the other hand, a gravitational acceleration ingredient to an otolith organ disappears in microgravity environment. However, linear acceleration can be received by otolith organ and produce a sensation that is different from that on Earth. It is suggested that in microgravity signal from the otolith organ may cause abnormality of posture control and eye movement. We examined function of otolith organ in goldfish revealed from analysis of eye movement induced by linear acceleration. We analyzed vertical eye movements from video images frame by frame. In normal fish, leftward lateral acceleration induced downward eye rotation in the left eye and upward eye rotation in the right eye. Acceleration from caudal to rostra1 evoked downward eye rotation in both eyes. When the direction of acceleration was shifted 15 degrees left, the responses in the left eye disappeared. These results suggested that otolith organs in each side transmitted different signals.

Acceleration↗

A rodent model for artificial gravity: VOR adaptation and Fos expression.

Vestibulo-ocular reflex (VOR) adaptation and brainstem Fos expression as a result of short radius cross-coupling stimuli were investigated to find neural correlates of the inherent Coriolis force asymmetry from an artificial gravity (AG) environment. Head-fixed gerbils (Meriones unguiculatus, N=79) were exposed, in the dark, to 60--90 minutes of cross-coupled rotations, combinations of pitch (or roll) and yaw rotation, while binocular horizontal, vertical, and torsional eye position were determined using infrared video-oculography. Centripetal acceleration in combination with angular cross-coupling was also studied. Simultaneous sinusoidal rotations in two planes (yaw with roll or pitch) provided a net symmetrical stimulus for the right and left labyrinths. In contrast, a constant velocity yaw rotation during sinusoidal roll or pitch provided the asymmetric stimulus model for AG. We found orthogonally oriented half-cycle VOR gain changes. The results depended on the direction of horizontal rotation during asymmetrical cross-coupling, and other aspects of the stimulus, including the phase relationship between the two rotational inputs, the symmetry of the stimulus, and training. Fos expression also revealed laterality differences in the prepositus and inferior olivary C subnucleus. In contrast the inferior olivary beta and ventrolateral outgrowth were labeled bilaterally. Additional cross-coupling dependent labeling was found in the flocculus, hippocampus, and several cortical regions, including the perirhinal and temporal association cortices. Analyses showed significant differences across the brain regions for several factors (symmetry, rotation velocity and direction, the presence of centripetal acceleration or a visual surround, and training). Finally, animals compensating from a unilateral surgical labyrinthectomy who received multiple cross-coupling training sessions had improved half-cycle VOR gain in the ipsilateral eye with head rotation toward the intact side. We hypothesize that cross-coupling vestibular training can benefit aspects of motor recovery or performance.

Adaptation, Physiological↗

Effect of centrifuge-induced artificial gravity and ergometric exercise on cardiovascular deconditioning, myatrophy, and osteoporosis induced by a -6 degrees head-down bedrest.

We have reported that centrifuge-induced artificial gravity with ergometric exercise could reduce developing cardiovascular deconditioning in humans. In the present study, we examined this load could prevent the myatrophy and osteoporosis induced by head-down bedrest for 20 days. Subjects were ten healthy male volunteers with informed consent. They were requested to lie down at -6 degrees for 20 days, and evaluation for cardiovascular deconditioning, myatrophy, and osteoporosis. As the result, high G-load with low intensity exercise suppressed the orthostatic intolerance and increase in serum osteoporotic marker, whereas low G-load with high intensity ergometric exercise maintained the maximal oxygen intake, heart dimension, and prevented myatrophy. The combination of high/low G-load with low/high intensity exercise will determine the optimal protocol for prevention of cardiovascular deconditioning, myatrophy, and osteoporosis.

Adult↗

Low specific gravity urine with crystalluria as discriminant index for nephrolithiasis.

A community-based study for crystalluria in morning urine (MU) specimens was carried out under light microscopy. The MU specimens were collected from 29 males with renal stones (GI), 36 age-and sex-matched normal controls (GII) and 27 household members of GI who did not have stones (GIII). The findings can be summarized as follows. 1. In the groups as a whole, almost all crystal and crystal aggregate found was oxalate type and with highest prevalence in GI. 2. In urine with low specific gravity (SG) i.e. less than or equal to 0.010, prevalence of oxalate crystals in GI (57.7%) was significantly higher (p less than 0.05) than in both GII (5.9%) and GIII (13%). Furthermore, at this range of SG, 15 per cent of the MU specimens in GI showed aggregation of oxalate crystals, whereas, the condition was neither found in GII nor GIII. 3. Our data suggest urine supersaturation with respect to calcium oxalate was found in both renal stone patients and normal subjects but more frequently in the former and also suggests more deficiency or lack of inhibitors for oxalate crystal nucleation and aggregation in urine of renal stone patients. The occurrence of oxalate crystals and crystal aggregates in urine of low SG may be useful as an index to discriminate stone patients from normal subjects or as an index to indicate the high risk group in the community.

Adult↗

Experimental evaluation of perfluorophenanthrene as a high specific gravity vitreous substitute: a preliminary report.

Perfluorophenanthrene, a liquid fluorocarbon with a specific gravity approximately twice that of water, potentially offers certain advantages as a vitreous substitute in vitreoretinal surgery. To determine its efficacy and safety we first purified it by chemical methods used in the preparation of experimental blood substitutes to a level at which it was not at all or only minimally toxic to culture-grown retinoblastoma cells. Nineteen of 22 vitrectomized eyes of white New Zealand rabbits injected with this purified perfluorophenanthrene showed satisfactory clinical tolerance. Light and electron microscopy showed minimal or no toxic effects in the 19 eyes, although uptake of perfluorophenanthrene by some preretinal cells was observed 28 days after implantation. Postoperative light-adapted electroretinography recordings of eight of the injected eyes showed no significant change. Perfluorophenanthrene injected into the anterior chamber of the rabbit eyes had toxic effects on the cornea. If further experimentations confirm our findings, perfluorophenanthrene may be a suitable transparent high-density liquid for temporary use in surgery to repair retinal detachments.

Animals↗

Passage and rumination of inert particles varying in size and specific gravity as determined from analysis of faecal appearance using multicompartment models.

Plastic particles of defined length (2, 5 mm) and specific gravity (sp.gr. 1.10, 1.34, 1.77) were administered just before feeding into the reticulo-rumen of four cattle and four swamp buffaloes given a diet predominantly of rice straw ad lib. Simultaneously, doses of ground rice straw marked with Cr and Yb were likewise given. Plastic particles were recovered from faeces for 12 d after dosing, and divided into non-ruminated (NR) and ruminated (R) particles. Excretion data of plastic particles were interpreted using a four-pool model incorporating passage of NR (kp) and R from the reticulo-rumen, post-ruminal passage, rate of chewing (kr) and two lag times. An inverse relationship was found between kr and sp.gr. The kr was higher for 5 mm than that for 2 mm particles. In contrast, kp was greatest for particles of sp.gr. 1.34, with higher kp for 2 mm than for 5 mm particles. Rates of passage and rumination (kp, kr) were higher for buffaloes than for cattle. Rumination time was related to kr, most highly (r2 0.96) with kr of 2 mm, 1.10 sp.gr. particles. Fragmentation of 5 mm particles by rumination tended to increase the rate of passage from the rumen. Ruminal passage rates of Yb and Cr markers were poorly correlated with each other and with kp of any of the plastic markers. Reanalysis of published data from plastic particle studies supported the relationships between sp.gr., size, kp and kr.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗