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At least 829 records · Page 46

Noninvasive markers of bone metabolism in the rhesus monkey: normal effects of age and gender

Measurement of bone turnover in conditions such as osteoporosis has been limited by the need for invasive iliac bone biopsy to reliably determine parameters of bone metabolism. Recent advances in the area of serum and urinary markers of bone metabolism have raised the possibility for noninvasive measurements; however, little nonhuman primate data exist for these parameters. The purpose of this experiment was to define the normal range and variability of several of the newer noninvasive bone markers which are currently under investigation in humans. The primary intent was to determine age and gender variability, as well as provide some normative data for future experiments in nonhuman primates. Twenty-four rhesus macaques were divided into equal groups of male and female according to the following age groupings: 3 years, 5-10 years, 15-20 years, and > 25 years. Urine was collected three times daily for a four-day period and measured for several markers of bone turnoverm including pyridinoline (PYD), deoxypyrodinoline (DPD), hydroxyproline, and creatinine. Bone mineral density measurements of the lumbar spine were performed at the beginning and end of the study period. Serum was also obtained at the time of bone densitometry for measurement of osteocalcin levels by radioimmunoassay. There were no significant differences in bone mineral density, urine PYD, or urine DPD based on gender. Bone density was lowest in the youngest animals, peaked in the 15-20-year group, but again decreased in the oldest animals. The osteocalcin, PYD, and DPD levels followed an inversely related pattern to bone density. The most important result was the relative age insensitivity of the ratio of PYD:DPD in monkeys up to age 20 years. Since bone density changes take months or years to become measurable and iliac biopsies are invasive, the PYD/DPD marker ratio may have important implications for rapid noninvasive measurement of the effects of potential treatments for osteoporosis in the non-human primate model.

NASA Discipline Musculoskeletal↗

Clinical models of cardiovascular regulation after weightlessness

After several days in microgravity, return to earth is attended by alterations in cardiovascular function. The mechanisms underlying these effects are inadequately understood. Three clinical disorders of autonomic function represent possible models of this abnormal cardiovascular function after spaceflight. They are pure autonomic failure, baroreflex failure, and orthostatic intolerance. In pure autonomic failure, virtually complete loss of sympathetic and parasympathetic function occurs along with profound and immediate orthostatic hypotension. In baroreflex failure, various degrees of debuffering of blood pressure occur. In acute and complete baroreflex failure, there is usually severe hypertension and tachycardia, while with less complete and more chronic baroreflex impairment, orthostatic abnormalities may be more apparent. In orthostatic intolerance, blood pressure fall is minor, but orthostatic symptoms are prominent and tachycardia frequently occurs. Only careful autonomic studies of human subjects in the microgravity environment will permit us to determine which of these models most closely reflects the pathophysiology brought on by a period of time in the microgravity environment.

Review, Tutorial↗

The dynamic contributions of the otolith organs to human ocular torsion

We measured human ocular torsion (OT) monocularly (using video) and binocularly (using search coils) while sinusoidally accelerating (0.7 g) five human subjects along an earth-horizontal axis at five frequencies (0.35, 0.4, 0.5, 0.75, and 1.0 Hz). The compensatory nature of OT was investigated by changing the relative orientation of the dynamic (linear acceleration) and static (gravitational) cues. Four subject orientations were investigated: (1) Y-upright-acceleration along the interaural (y) axis while upright; (2) Y-supine-acceleration along the y-axis while supine; (3) Z-RED-acceleration along the dorsoventral (z) axis with right ear down; (4) Z-supine-acceleration along the z-axis while supine. Linear acceleration in the Y-upright, Y-supine and Z-RED orientations elicited conjugate OT. The smaller response in the Z-supine orientation appeared disconjugate. The amplitude of the response decreased and the phase lag increased with increasing frequency for each orientation. This frequency dependence does not match the frequency response of the regular or irregular afferent otolith neurons; therefore the response dynamics cannot be explained by simple peripheral mechanisms. The Y-upright responses were larger than the Y-supine responses (P < 0.05). This difference indicates that OT must be more complicated than a simple low-pass filtered response to interaural shear force, since the dynamic shear force along the interaural axis was identical in these two orientations. The Y-supine responses were, in turn, larger than the Z-RED responses (P < 0.01). Interestingly, the vector sum of the Y-supine responses plus Z-RED responses was not significantly different (P = 0.99) from the Y-upright responses. This suggests that, in this frequency range, the conjugate OT response during Y-upright stimulation might be composed of two components: (1) a response to shear force along the y-axis (as in Y-supine stimulation), and (2) a response to roll tilt of gravitoinertial force (as in Z-RED stimulation).

NASA Discipline Neuroscience↗

An optimized index of human cardiovascular adaptation to simulated weightlessness

Prolonged exposure to weightlessness is known to produce a variety of cardiovascular changes, some of which may influence the astronaut's performance during a mission. In order to find a reliable indicator of cardiovascular adaptation to weightlessness, we analyzed data from nine male subjects after a 24-hour period of normal activity and after a period of simulated weightlessness produced by two hours in a launch position followed by 20 hours of 6 degrees head-down tilt plus pharmacologically induced diuresis (furosemide). Heart rate, arterial pressure, thoracic fluid index, and radial flow were analyzed. Autoregressive spectral estimation and decomposition were used to obtain the spectral components of each variable from the subjects in the supine position during pre- and post-simulated weightlessness. We found a significant decrease in heart rate power and an increase in thoracic fluid index power in the high frequency region (0.2-0.45 Hz) and significant increases in radial flow and arterial pressure powers in the low frequency region (<0.2 Hz) in response to simulated weightlessness. However, due to the variability among subjects, any single variable appeared limited as a dependable index of cardiovascular adaptation to weightlessness. The backward elimination algorithm was then used to select the best discriminatory features from these spectral components. Fisher's linear discriminant and Bayes' quadratic discriminant were used to combine the selected features to obtain an optimal index of adaptation to simulated weightlessness. Results showed that both techniques provided improved discriminant performance over any single variable and thus have the potential for use as an index to track adaptation and prescribe countermeasures to the effects of weightlessness.

NASA Discipline Number 14-10↗

Fundamental relations between short-term RR interval and arterial pressure oscillations in humans

BACKGROUND: One of the principal explanations for respiratory sinus arrhythmia is that it reflects arterial baroreflex buffering of respiration-induced arterial pressure fluctuations. If this explanation is correct, then elimination of RR interval fluctuations should increase respiratory arterial pressure fluctuations. METHODS AND RESULTS: We measured RR interval and arterial pressure fluctuations during normal sinus rhythm and fixed-rate atrial pacing at 17.2+/-1.8 (SEM) beats per minute greater than the sinus rate in 16 healthy men and 4 healthy women, 20 to 34 years of age. Measurements were made during controlled-frequency breathing (15 breaths per minute or 0.25 Hz) with subjects in the supine and 40 degree head-up tilt positions. We characterized RR interval and arterial pressure variabilities in low-frequency (0.05 to 0.15 Hz) and respiratory-frequency (0.20 to 0.30 Hz) ranges with fast Fourier transform power spectra and used cross-spectral analysis to determine the phase relation between the two signals. As expected, cardiac pacing eliminated beat-to-beat RR interval variability. Against expectations, however, cardiac pacing in the supine position significantly reduced arterial pressure oscillations in the respiratory frequency (systolic, 6.8+/-1.8 to 2.9 +/-0.6 mm Hg2/Hz, P=.017). In contrast, cardiac pacing in the 40 degree tilt position increased arterial pressure variability (systolic, 8.0+/-1.8 to 10.8 +/-2.6, P=.027). Cross-spectral analysis showed that 40 degree tilt shifted the phase relation between systolic pressure and RR interval at the respiratory frequency from positive to negative (9 +/-7 degrees versus -17+/-11 degrees, P=.04); that is, in the supine position, RR interval changes appeared to lead arterial pressure changes, and in the upright position, RR interval changes appeared to follow arterial pressure changes. CONCLUSIONS: These results demonstrate that respiratory sinus arrhythmia can actually contribute to respiratory arterial pressure fluctuations. Therefore, respiratory sinus arrhythmia does not represent simple baroreflex buffering of arterial pressure.

NASA Discipline Cardiopulmonary↗

Immune responses in humans after 60 days of confinement

A confinement experiment in a normobaric diving chamber was undertaken to better understand the effect of confinement and isolation on human psychology and physiology. Pre- and postconfinement blood samples were obtained from four test subjects and control donors to analyze immune responses. No modification in the levels of CD2+, CD3+, CD4+, CD8+, CD19+, and CD56+ cells was observed after confinement. Mitogen-induced T-lymphocyte proliferation and interleukin-2 receptor expression were not altered significantly. Whole blood interferon-alpha and gamma-induction and plasma cortisol levels were also unchanged, as was natural killer cell activity. These data suggest that in humans, no specific components of the immune response are affected by a 2-month isolation and confinement of a small group.

NASA Discipline Number 18-10↗

Skeletal muscle satellite cells

Evidence now suggests that satellite cells constitute a class of myogenic cells that differ distinctly from other embryonic myoblasts. Satellite cells arise from somites and first appear as a distinct myoblast type well before birth. Satellite cells from different muscles cannot be functionally distinguished from one another and are able to provide nuclei to all fibers without regard to phenotype. Thus, it is difficult to ascribe any significant function to establishing or stabilizing fiber type, even during regeneration. Within a muscle, satellite cells exhibit marked heterogeneity with respect to their proliferative behavior. The satellite cell population on a fiber can be partitioned into those that function as stem cells and those which are readily available for fusion. Recent studies have shown that the cells are not simply spindle shaped, but are very diverse in their morphology and have multiple branches emanating from the poles of the cells. This finding is consistent with other studies indicating that the cells have the capacity for extensive migration within, and perhaps between, muscles. Complexity of cell shape usually reflects increased cytoplasmic volume and organelles including a well developed Golgi, and is usually associated with growing postnatal muscle or muscles undergoing some form of induced adaptive change or repair. The appearance of activated satellite cells suggests some function of the cells in the adaptive process through elaboration and secretion of a product. Significant advances have been made in determining the potential secretion products that satellite cells make. The manner in which satellite cell proliferative and fusion behavior is controlled has also been studied. There seems to be little doubt that cellcell coupling is not how satellite cells and myofibers communicate. Rather satellite cell regulation is through a number of potential growth factors that arise from a number of sources. Critical to the understanding of this form of control is to determine which of the many growth factors that can alter satellite cell behavior in vitro are at work in vivo. Little work has been done to determine what controls are at work after a regeneration response has been initiated. It seems likely that, after injury, growth factors are liberated through proteolytic activity and initiate an activation process whereby cells enter into a proliferative phase. After myofibers are formed, it also seems likely that satellite cell behavior is regulated through diffusible factors arising from the fibers rather than continuous control by circulating factors.(ABSTRACT TRUNCATED AT 400 WORDS).

NASA Program Space Biology↗

A diminished aortic-cardiac reflex during hypotension in aerobically fit young men

We compared the aortic-cardiac baroreflex sensitivity in eight average fit (AF: VO2max = 44.7 +/- 1.3 ml.kg-1 x min-1) and seven high fit (HF: VO2max = 64.1 +/- 1.7 ml.min-1 x kg-1) healthy young men during hypotension elicited by steady state sodium nitroprusside (SN) infusion. During SN mean arterial pressure (MAP) was similarly decreased in AF (-12.6 +/- 1.0 mm Hg) and HF (-12.1 +/- 1.1 mm Hg). However, the increases in heart rate (HR) were less (P < 0.023) in HF (15 +/- 3 bpm) than AF (25 +/- 1 bpm). When sustained neck suction (NS, -22 +/- 1 torr in AF and -20 +/- 1 torr in HF, P > 0.05) was applied to counteract the decreased carotid sinus transmural pressure during SN, thereby isolating the aortic baroreceptors, the increased HR remained less (P < 0.021) in HF (8 +/- 2 bpm) than AF (16 +/- 2 bpm). During both SN infusion and SN+NS, the calculated gains (i.e., delta HR/delta MAP) were significantly greater in AF (2.1 +/- 0.3 and 1.3 +/- 0.2 bpm.mm Hg-1) than HF (1.2 +/- 0.2 and 0.6 +/- 0.2 bpm.mm Hg-1). However, the estimated carotid-cardiac baroreflex sensitivity (i.e., the gain difference between the stage SN and SN + NS) was not different between AF (0.7 +/- 0.2 bpm.mm Hg-1) and HF (0.6 +/- 0.1 bpm.mm Hg-1). These data indicated that the aortic-cardiac baroreflex sensitivity during hypotension was significantly diminished with endurance exercise training.

NASA Discipline Number 14-10↗

Potentiation by choline of basal and electrically evoked acetylcholine release, as studied using a novel device which both stimulates and perfuses rat corpus striatum

We examined the release of acetylcholine (ACh) and dopamine (DA) using a novel probe through which striatal neurons could be both superfused and stimulated electrically in both anesthetized and freely moving awake animals. Optimal stimulation parameters for eliciting ACh release from cholinergic neurons differed from those required for eliciting DA release from dopaminergic terminals: at 0.6 ms pulse duration, 20 Hz and 200 microA, ACh release increased to 357 +/- 30% (P < 0.01) of baseline and was blocked by the addition of tetrodotoxin (TTX). Pulse durations of 2.0 ms or greater were required to increase DA release. Unlike ACh release, DA release showed no frequency dependence above 5 Hz. The maximal evoked releases of ACh and DA were 556 +/- 94% (P < 0.01) and 254 +/- 38% (P < 0.05) of baseline, respectively. Peripheral administration of choline (Ch) chloride (30-120 mg/kg) to anesthetized animals caused dose-related (r = 0.994, P < 0.01) increases in ACh release; basal release rose from 117 +/- 7% to 141 +/- 5% of initial baseline levels (P < 0.05) and electrically evoked ACh release rose from 386 +/- 38% to 600 +/- 34% (P < 0.01) in rats given 120 mg/kg. However, Ch failed to affect basal or evoked DA release although neostigmine (10 microM) significantly elevated basal DA release (from 36.7 fmol/10 min to 71.5 fmol/10 min; P < 0.05). In awake animals, Ch (120 mg/kg) also elevated both basal (from 106 +/- 7% to 154 +/- 17%; P < 0.05) and electrically evoked (from 146 +/- 13 to 262 +/- 16%; P < 0.01) ACh release.(ABSTRACT TRUNCATED AT 250 WORDS).

NASA Program Space Physiology and Countermeasures↗

Evidence for reduced cancellous bone mass in the spontaneously hypertensive rat

The histomorphometric changes in the proximal tibial metaphysis and epiphyseal growth plate and midtibial shaft of 26-week-old spontaneously hypertensive rats (SHR) compared with those of the corresponding normotensive Wistar-Kyoto (WKY) rats were studied. A decrease in body weight, growth plate thickness, and longitudinal growth rate of the proximal tibial epiphysis, trabecular bone volume, trabecular thickness and number, the number of osteoblasts and osteoprogenitor cells per millimeter square surface of the proximal tibial metaphysis, periosteal and endocortical apposition rate and bone formation rate of the tibial diaphysis were observed in the SHR. Additionally, systolic blood pressure, the number of osteoclasts per millimeter square surface and average number of nuclei per osteoclast of the proximal tibial metaphysis were significantly increased. Thus, osteoclastic activity is dominant over osteoblastic and chondroblastic activity in the SHR that results in a cancellous bone deficit in the skeleton. It will require additional work to ascertain the underlying cause for this condition as several factors in the SHR with a potential for causing this change are present, including elevated parathyroid hormone (PTH), depressed 1,25-(OH)2D3, low calcium absorption, reduced body weight (reduced loading) elevated blood pressure and possibly other direct cell differences in the mutant strain. At present elevated PTH and adaptation to underloading from reduced weight are postulated to be a likely cause, but additional studies are required to test this interpretation.

NASA Discipline Musculoskeletal↗

Three dimensional eye movements of squirrel monkeys following postrotatory tilt

Three-dimensional squirrel monkey eye movements were recorded during and immediately following rotation around an earth-vertical yaw axis (160 degrees/s steady state, 100 degrees/s2 acceleration and deceleration). To study interactions between the horizontal angular vestibulo-ocular reflex (VOR) and head orientation, postrotatory VOR alignment was changed relative to gravity by tilting the head out of the horizontal plane (pitch or roll tilt between 15 degrees and 90 degrees) immediately after cessation of motion. Results showed that in addition to post rotatory horizontal nystagmus, vertical nystagmus followed tilts to the left or right (roll), and torsional nystagmus followed forward or backward (pitch) tilts. When the time course and spatial orientation of eye velocity were considered in three dimensions, the axis of eye rotation always shifted toward alignment with gravity, and the postrotatory horizontal VOR decay was accelerated by the tilts. These phenomena may reflect a neural process that resolves the sensory conflict induced by this postrotatory tilt paradigm.

NASA Program Space Physiology and Countermeasures↗

Cytoplasm-to-myonucleus ratios following microgravity

The cytoplasmic volume-to-myonucleus ratio in the tibialis anterior and gastrocnemius muscles of juvenile rats after 5.4 days of microgravity was studied. Three groups of rats (n = 8 each) were used. The experimental group (space rats) was flown aboard the space shuttle Discovery (NASA, STS-48), while two ground-based groups, one hindlimb suspended (suspended rats), one non-suspended (control), served as controls. Single fibre analysis revealed a significant decrease in cross-sectional area (microns2) in the gastrocnemius for both the space and the suspended rats; in the tibialis anterior only the suspended rats showed a significant decrease. Myonuclei counts (myonuclei per mm) in both the tibialis anterior and gastrocnemius were significantly increased in the space rats but not in the suspended rats. The mean myonuclear volume (individual nuclei: microns3) in tibialis anterior fibres from the space rats, and in gastrocnemius fibres from both the space and the suspended rats, was significantly lower than that in the respective control group. Estimation of the total myonuclear volume (microns3 per.mm), however, revealed no significant differences between the three groups in either the tibialis anterior or gastrocnemius. The described changes in the cross-sectional area and myonuclei numbers resulted in significant decreases in the cytoplasmic volume-to-myonucleus ratio (microns3 x 10(3)) in both muscles and for both space and suspended rats (tibialis anterior; 15.6 +/- 0.6 (space), 17.2 +/- 1.0 (suspended), 20.8 +/- 0.9 (control): gastrocnemius; 13.4 +/- 0.4 (space) and 14.9 +/- 1.1 (suspended) versus 18.1 +/- 1.1 (control)). These results indicate that even short periods of unweighting due to microgravity or limb suspension result in changes in skeletal muscle fibres which lead to significant decreases in the cytoplasmic volume-to-myonucleus ratio.

NASA Discipline Cell Biology↗

Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain

Estrogen deficiency induced bone loss is associated with increased bone turnover in rats and humans. The respective roles of increased bone turnover and altered balance between bone formation and bone resorption in mediating estrogen deficiency-induced cancellous bone loss was investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in the distal femur. However, cancellous bone was preferentially lost in the metaphysis, a site that normally experiences low strain energy. No bone loss was observed in the epiphysis, a site experiencing higher strain energy. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased and decreased in long bones of ovariectomized rats by treadmill exercise and functional unloading, respectively. Functional unloading was achieved during orbital spaceflight and following unilateral sciatic neurotomy. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing loading accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in the unloaded and prevented loss in the loaded limb following unilateral sciatic neurotomy in part by reducing indices of bone turnover. These results suggest that estrogen regulates the rate of bone turnover, but the overall balance between bone formation and bone resorption is influenced by prevailing levels of mechanical strain.

STS-62 Shuttle Project↗

The Living With a Star Space Environment Testbed Program

NASA has initiated the Living with a Star (LWS) Program to develop the scientific understanding to address the aspects of the Connected Sun-Earth system that affects life and society. The Program Architecture includes science missions, theory and modeling and Space Environment Testbeds (SET). This current paper discusses the Space Environment Testbeds. The goal of the SET program is to improve the engineering approach to accomodate and/or mitigate the effects of solar variability on spacecraft design and operations. The SET Program will infuse new technologies into the space programs through collection of data in space and subsequent design and validation of technologies. Examples of these technologies are cited and discussed.

Barth, Janet↗

The laboratory telerobotic manipulator program

New opportunities for the application of telerobotic systems to enhance human intelligence and dexterity in the hazardous environment of space are presented by the NASA Space Station Program. Because of the need for significant increases in extravehicular activity and the potential increase in hazards associated with space programs, emphasis is being heightened on telerobotic systems research and development. The Laboratory Telerobotic Manipulator (LTM) program is performed to develop and demonstrate ground-based telerobotic manipulator system hardware for research and demonstrations aimed at future NASA applications. The LTM incorporates traction drives, modularity, redundant kinematics, and state-of-the-art hierarchical control techniques to form a basis for merging the diverse technological domains of robust, high-dexterity teleoperations and autonomous robotic operation into common hardware to further NASA's research.

Herndon, J. N.↗