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Altered activation pattern in synergistic ankle plantarflexor muscles in a reduced-gravity environment.

We investigated relative activations in the synergistic ankle plantarflexor muscles, the soleus (SOL) and medial gastrocnemius (MG), while subjects were walking in water. Ten healthy volunteers walked in water under three different load- and four different speed-conditions. The depth of water was to the axilla of each subject, which reduced about 80% of his or her body weight. The EMG activities of the SOL and MG were recorded with surface electrodes, and ground reaction forces (GRF) were measured by using a water-resistant force platform. Relations of EMG activity levels between the two muscles during the stance phase were analysed with respect to the load and walking speed. The results revealed that the SOL EMG activity was more dependent on the load than the walking speed in water, while the MG EMG activity was more dependent on the speed. Such dissociated activation of the synergistic ankle plantarflexors might be relevant to the different roles required of these muscles in functional motor tasks.

Adult↗

The location of the third cleavage plane of Xenopus embryos partitions morphogenetic information in animal quartets.

Analysis of the developmental potential of animal quartets (the set of four animal blastomeres isolated from the 8-cell stage Xenopus embryo) provided insight into the manner in which morphogenetic information is distributed along the animal-vegetal axis. Gravity treatments were employed to alter the partitioning plane. Animal quartets isolated from embryos exposed to simulated weightlessness had larger animal blastomeres, and they formed structures such as a groove and a protrusion more often than 1g-control animal quartets. Animal quartets with an unusual non-horizontal third cleavage plane were also found to have a higher frequency of protrusion formation than animal quartets with a typical horizontal cleavage plane. The increase in the frequency seen in simulated weightlessness animal quartets was not due to their increased size. Fusing two animal quartets isolated from hypergravity (3g) exposed embryos (small blastomeres and low incidence of protrusions) did not affect the frequency of protrusion formation. Molecular analyses revealed that a partial induction was associated with the protrusion formation. Transcripts of the dorsal lip specific homeobox gene, goosecoid, and alpha-cardiac actin were detectable by PCR amplification in the animal quartet with a protrusion, and alpha-cardiac actin mRNA was found by whole-mount in situ hybridization to be localized in the protrusion. Taken together, all these results are consistent with the notion that both animal and vegetal information is necessary for normal development and the partitioning of morphogenetic information into animal quartets results in gravity-dependent differential morphogenesis and gene regulation.

Actins↗

Artificial gravity as a countermeasure in long-duration space flight.

Long-duration exposure to weightlessness results in bone demineralization, muscle atrophy, cardiovascular deconditioning, altered sensory-motor control, and central nervous system reorganizations. Exercise countermeasures and body loading methods so far employed have failed to prevent these changes. A human mission to Mars might last 2 or 3 years and without effective countermeasures could result in dangerous levels of bone and muscle loss. Artificial gravity generated by rotation of an entire space vehicle or of an inner chamber could be used to prevent structural changes. Some of the physical characteristics of rotating environments are outlined along with their implications for human performance. Artificial gravity is the centripetal force generated in a rotating vehicle and is proportional to the product of the square of angular velocity and the radius of rotation. Thus, for a particular g-level, there is a tradeoff between velocity of rotation and radius. Increased radius is vastly more expensive to achieve than velocity, so it is important to know the highest rotation rates to which humans can adapt. Early studies suggested that 3 rpm might be the upper limit because movement control and orientation were disrupted at higher velocities and motion sickness and chronic fatigue were persistent problems. Recent studies, however, are showing that, if the terminal velocity is achieved over a series of gradual steps and many body movements are made at each dwell velocity, then full adaptation of head, arm, and leg movements is possible. Rotation rates as high as 7.5-10 rpm are likely feasible. An important feature of the new studies is that they provide compelling evidence that equilibrium point theories of movement control are inadequate. The central principles of equilibrium point theories lead to the equifinality prediction, which is violated by movements made in rotating reference frames.

Coriolis Force↗

Correlation of macro and micro cardiovascular function during weightlessness and simulated weightlessness.

The investigation of cardiovascular function necessarily involves a consideration of the exchange of substances at the capillary. If cardiovascular function is compromised or in any way altered during exposure to zero gravity in space, then it stands to reason that microvascular function is also modified. We have shown that an increase in cardiac output similar to that reported during simulated weightlessness is associated with a doubling of the number of post-capillary venules and a reduction in the number of arterioles by 35%. If the weightlessness of space travel produces similar changes in cardiopulmonary volume and cardiac output, a reasonable expectation is that astronauts will undergo venous neovascularization. We have developed an animal model in which to correlate microvascular and systemic cardiovascular function. The microcirculatory preparation consists of a lightweight, thermo-neutral chamber implanted around intact skeletal muscle on the back of a rat. Using this technique, the performed microvasculature of the cutaneous maximus muscle may be observed in the conscious, unanesthetized animal. Microcirculatory variables which may be obtained include venular and arteriolar numbers, lengths and diameters, single vessel flow velocities, vasomotion, capillary hematocrit anastomoses and orders of branching. Systemic hemodynamic monitoring of cardiac output by electromagnetic flowmetry, and arterial and venous pressures allows correlation of macro- and microcirculatory changes at the same time, in the same animal. Observed and calculated hemodynamic variables also include pulse pressure, heart rate, stroke volume, total peripheral resistance, aortic compliance, minute work, peak aortic flow velocity and systolic time interval. In this manner, an integrated assessment of total cardiovascular function may be obtained in the same animal without the complicating influence of anesthetics.

Animals↗

Ethylene plays multiple nonprimary roles in modulating the gravitropic response in tomato.

Ethylene is known to interact with auxin in regulating stem growth, and yet evidence for the role of ethylene in tropic responses is contradictory. Our analysis of four mutants of tomato (Lycopersicon esculentum) altered in their response to gravity, auxin, and/or ethylene revealed concentration-dependent modulation of shoot gravitropism by ethylene. Ethylene inhibitors reduce wild-type gravicurvature, and extremely low (0.0005-0.001 microliter L-1) ethylene concentrations can restore the reduced gravitropic response of the auxin-resistant dgt (diageotropica) mutant to wild-type levels. Slightly higher concentrations of ethylene inhibit the gravitropic response of all but the ethylene-insensitive nr (never-ripe) mutant. The gravitropic responses of nr and the constitutive-response mutant epi (epinastic) are slightly and significantly delayed, respectively, but otherwise normal. The reversal of shoot gravicurvature by red light in the lz-2 (lazy-2) mutant is not affected by ethylene. Taken together, these data indicate that, although ethylene does not play a primary role in the gravitropic response of tomato, low levels of ethylene are necessary for a full gravitropic response, and moderate levels of the hormone specifically inhibit gravicurvature in a manner different from ethylene inhibition of overall growth.

Ethylenes↗

Insulin resistance in PCOS.

Polycystic ovary syndrome (PCOS) is the commonest endocrinopathy affecting women of reproductive age, manifested with a variety of clinical signs, none of which is pathognomonic. The association of insulin resistance and reproductive abnormalities with clinical hyperandrogenism in a woman was first demonstrated by Achard and Thiers in the "diabetes of bearded woman." The link of PCOS with insulin resistance was subsequently established by clinical studies characterizing the profound insulin resistance in obese and lean PCOS patients. Insulin resistance, hyperinsulinemia, and beta-cell dysfunction are very common in PCOS, but are not required for the diagnosis. The numerous in vivo and in vitro data supporting the central role of insulin resistance in the pathogenesis of PCOS found a broad clinical application in the management of the syndrome, where the regulation of cycle abnormalities and the facilitation of pregnancy in obese PCOS patients was assisted by co-administration of agents such as the well-known insulin sensitizers. The documentation of the presence of insulin resistance contributed substantially to unravel several metabolic components present in the syndrome. Today our knowledge about PCOS appears to have broader health implications and to have profoundly altered our view of the gravity of this condition.

Diabetes Mellitus, Type 2↗

Cognitive impairment in Parkinson's disease.

Neuropsychologic studies on Parkinson's disease have shown an impairment of specific cognitive functions and a greater evidence of dementia. Cognitive alterations are related to the gravity of some peculiar motor symptoms of the disease and show a major role of motor disturbances in intellectual disorders. The concept of bradyphrenia and subcortical dementia still seems to be suitable to define the cognitive disorders of Parkinson's disease.

Cognition Disorders↗

[Compensatory reactions of the kidneys to orthostatic effects].

Studies of orthostatic effects on the renal hemodynamics and excretory function of the dog showed an increase in the heart rate, a fall in the arterial and venous pressure and a decline of the Na and K concentrations in the urine. The studies demonstrated that changes in the renal excretory function were a compensatory hemodynamic reaction to the gravity effect associated wtih an alteration of the body position in space.

Animals↗

[Isolated microhematuria as the manifestation of lupus nephritis].

The paper is concerned with lupus nephritis with marked microhematuria. The presence of severe morphological alterations in the kidneys, hematuria gravity correlation with that of SLE, positive effects of active immunosuppressive treatment allow one to consider hematuria as a separate clinical criterion of lupus nephritis activity. A case is reported of a female who had unusual clinical picture of the disease possibly due to high IgA in the blood and the presence of renal vasculitis.

Adolescent↗

Gravity sedimentation of leukocytes is partially independent from erythrocyte sedimentation.

Leukocyte function tests are suitable for monitoring the severity of chronic inflammatory and acute infectious diseases. The tests usually require time consuming leukocyte separation techniques while the original character of leukocytes can substantially alter. In contrast, we noted that gravity sedimentation properties of leukocytes is simple to measure and it also reflects non-specific inflammatory reactions of leukocytes. Our novel test is named leukocyte antisedimentation rate (LAR) which is measured by leukocyte counting in the upper (U) and lower (L) half of the sedimentation blood column after one-hour gravity sedimentation of the whole blood. The formula LAR=100.(U-L)/(U+L) is used to calculate the percentage of leukocytes crosses the middle line of sedimentation blood column upward during one-hour sedimentation (normal range<15%, inter-assay coefficient of variation<5%). In this study we found that in vitro pre-treatment of septic patients' blood samples with protamine, lidocaine and prednisolone decreased leukocyte antisedimentation rate in a concentration dependent manner without effecting erythrocyte sedimentation rate. Leukocyte adherence was measured by the retention rate of leukocytes in a nylon fibre column. There was a significant positive correlation between leukocyte antisedimentation rate and leukocyte adherence (p<0.01), hematocrit (p<0.05), erythrocyte sedimentation rate (p<0.05) when blood samples of 35 healthy individuals were analysed. We concluded that leukocyte antisedimentation rate in septic patients is significantly elevated comparing to healthy controls and as a bedside test it can reflect leukocyte involvement in infections. In vitro protamine, lidocaine and prednisolone pre-treatment of septic patients' blood samples indicates that leukocyte antisedimentation process is partially independent from the ongoing erythrocyte sedimentation.

Adult↗

Skeletal adaptations to alterations in weight-bearing activity: a comparison of models of disuse osteoporosis.

The removal of regular weight-bearing activity generates a skeletal adaptive response in both humans and animals, resulting in a loss of bone mineral. Human models of disuse osteoporosis, namely bed rest, spinal cord injury and exposure to micro-gravity demonstrate the negative calcium balance, alterations in biochemical markers of bone turnover and resultant loss of bone mineral in the lower limbs that occurs with reduced weight-bearing loading. The site-specific nature of the bone response is consistent in all models of disuse; however, the magnitude of the skeletal adaptive response may differ across models. It is important to understand the various manifestations of disuse osteoporosis, particularly when extrapolating knowledge gained from research using one model and applying it to another. In rats, hindlimb unloading and exposure to micro-gravity also result in a significant bone response. Bone mineral is lost, and changes in calcium metabolism and biochemical markers of bone turnover similar to humans are noted. Restoration of bone mineral that has been lost because of a period of reduced weight bearing may be restored upon return to normal activity; however, the recovery may not be complete and/or may take longer than the time course of the original bone loss. Fluid shear stress and altered cytokine activity may be mechanistic features of disuse osteoporosis. Current literature for the most common human and animal models of disuse osteoporosis has been reviewed, and the bone responses across models compared.

Adaptation, Physiological↗

[Ontogenesis of human motor-ability to control the position of the centre of gravity].

Knowledge of the basic principles of biomechanics makes it possible to understand the complex problem of ontogenesis of human movement. The ontogenesis of human motor can be characterized as acquisition of the ability to find a centre of gravity and to maintain or intentionally alter its position in space. This is made possible by intentional change of the tightness of connecting segments by controlled muscular activity and the use of external forces. The CNS controls the position of the centre of gravity via coordinated muscular activity.

Biomechanical Phenomena↗

Clinostats and bioreactors.

The environment created on Earth within a clinostat or Rotating Wall Vessel (RWV) bioreactor is often referred to as "simulated microgravity". Both devices utilize constant reorientation to effectively nullify cumulative sedimentation of particles. Neither, however, can fully reproduce the concurrent lack of structural deformation, displacement of intercellular components and/or reduced mass transfer in the extracellular fluid that occur in actual weightlessness. Parameters including density, viscosity, and even container geometry must each be considered to determine the overall gravity-dependent effects produced by either a clinostat or the RWV bioreactor; in addition, the intended application of these two devices differs considerably. A state of particle "motionlessness" relative to the surrounding bulk fluid, which is nearly analogous to the extracellular environment encountered under weightless conditions, can theoretically be achieved through clinorotation. The RWV bioreactor, on the other hand, while similarly maintaining cells in suspension as they continually "fall" through the medium under 1 g conditions, can also purposefully induce a perfusion of nutrients to and waste from the culture. A clinostat, therefore, is typically used in an attempt to reproduce the quiescent, unstirred fluid conditions achievable on orbit; while the RWV bioreactor ideally creates a low shear, but necessarily mixed, fluid environment that is optimized for suspension culture and tissue growth. Other techniques for exploring altered inertial environments, such as freefall, neutral buoyancy and electromagnetic levitation, can also provide unique insight into how gravity affects biological systems. Ultimately, all underlying biophysical principles thought to give rise to gravity-dependent physiological responses must be identified and thoroughly examined in order to accurately interpret data from flight experiments or ground-based microgravity analogs.

Acceleration↗

The effects of space flight on some rat liver enzymes regulating carbohydrate and lipid metabolism.

We have examined, in the livers of rats carried aboard the Cosmos 936 biosatellite, the activities of about 30 enzymes concerned with carbohydrate and lipid metabolism. In addition to the enzyme studies, the levels of glycogen and of the individual fatty acids in hepatic lipids were determined. Livers from flight and ground control rats at recovery (R0) and 25 days after recovery (R25) were used for these analyses. For all parameters measured, the most meaningful comparisons are those made between flight stationary (FS) and flight centrifuged (FC) animals at RQ. When these two groups of flight rats were compared at R0, statistically significant decreases in the activity levels of glycogen phosphorylase, alpha-glycerol phosphate acyl transferase, diglyceride acyl transferase, aconitase and 6-phosphogluconate dehydrogenase and an increase in the palmitoyl CoA desaturase were noted in the weightless group (FS). The significance of these findings was strengthened by the fact that all enzyme activities showing alterations at R0 returned to normal 25 days postflight. When liver glycogen and total fatty acids of the two sets of flight animals were determined, significant differences that could be attributed to reduced gravity were observed. The weightless group (FS) at R0 contained, on the average, more than twice the amount of glycogen than did the centrifuged controls (FC) and a remarkable shift in the ratio of palmitate to palmitoleate was noted. These metabolic alterations, both in enzyme levels and in hepatic constituents, appear to be characteristic of the weightless condition. Our data seem to justify the conclusion that centrifugation during flight is equivalent to terrestrial gravity.

Animals↗

Orientation and movement in unusual force environments.

A manned space mission to Mars might take as long as 1 year each way. Consequently, artificial gravity is being considered as a way of preventing the debilitating effects of long-duration exposure to microgravity on the human body. The present article discusses some of the problems associated with adapting to the rotation levels that might be used to generate artificial gravity. It also describes how exposure to background-force levels greater or less than the 1-G force of Earth gravity affects orientation and movement control. The primary emphasis of the article is that human movement and orientation control are dynamically adapted to the 1-G force background of Earth and that accommodation to altered force levels or to rotating environments requires a wide range of adaptive changes.

Adaptation, Physiological↗

Morpho-functional alterations in testicular and nervous cells submitted to modelled microgravity.

Humans, as well as other life forms, have developed on earth under the terrestrial gravitational field. Questions concerning the effect of the gravity vector changes on the animal physiology have begun to emerge only in the last decades. Physiological alterations were observed during space flights, but space-born investigations at cellular levels are still very limited. Earth-bound simulations of low gravity obtained with the 3-dimensional Random Positioning Machine are extensively utilized to explore the effects of microgravity on cell function. After only a few minutes, weightlessness affected the cytoskeleton of lymphocytes, astrocytes, neurons and testicular cells, disorganizing microtubules, intermediate filaments and microfilaments. Cell division was impaired, mitochondria were disrupted and apoptotic phenomena occurred. Expression of proteins involved in transmembrane ion and water transport were also affected. In the Leydig cells the key enzymes (3beta- and 17beta-hydroxysteroid dehydrogenases) leading to testosterone synthesis were depressed. However, after 20 h of clinorotation the cells were able to synthesize heat shock proteins that initiated protection and recovery. The cytoskeleton was again well organized, normal mitosis occurred and the percentage of apoptotic cells returned to the range of 5%, similar to the control cultures. Ion and water transmembrane proteins and steroid dehydrogenases returned to normal levels. Long-term experiments showed that low gravity induced only transient alterations in the cultured cells, which were able to adapt to the gravity vector changes and to regain normal activity. These data may explain the physiological adaptation occurring in astronauts during and after space flights.

Animals↗

Enhanced antibody production associated with altered amino acid metabolism in a hybridoma high-density perfusion culture established by gravity separation.

A high density hybridoma perfusion culture was established by separating and recycling cells from the product stream to the reactor using a simple external sedimentation-based separator-an inclined modified Erlenmeyer flask. After 3 weeks, when the optimal perfusion rate of 1.0 day-1 had been reached, viable cell density stabilized at around 10 x 10(6) cells ml-1, a level five times that obtained by simple batch culture. The efficiency of the separator was enhanced by cell flocculation. Specific antibody productivity, which was initially 0.4 micrograms 1 x 10(6) cells-1 h-1, decreased to half that value while cell density was increasing, but recovered to the initial level when the culture finally stabilized at a high cell density. During the final phase, when viable cell density and specific antibody production were high, there was a marked shift in metabolism. Consumption of the two most important substrates for energy generation, glucose and glutamine, caused their broth concentrations to decrease to 1.5 mM and 1 mM, respectively, from input medium concentrations of 25 mM and 10 mM, respectively. At the same time there was an increase in the specific production of glycine and aspartate, their broth concentrations reaching 1.5 mM and 0.02 mM, respectively. We suggest that this shift in metabolism results in enhanced production of ATP from glutamine. The specific glucose consumption and lactate production also indicate that there is a shift to more energy efficient metabolism. The mechanism whereby this leads to enhanced specific antibody production remains to be elucidated. Nevertheless, the combination of high cell density and enhanced productivity obtained with the present perfusion culture resulted in a high monoclonal antibody production-100 mg 1-1 d-1.

Amino Acids↗