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At least 775 records · Page 43
All sourcesNASA NTRSDOE OSTI
NASA NTRS1994

Prostanoid-induced expression of matrix metalloproteinase-1 messenger ribonucleic acid in rat osteosarcoma cells

Individual prostanoids have distinct potencies in activating intracellular signaling pathways and regulating gene expression in osteoblastic cells. The E-series prostaglandins (PGs) are known to stimulate matrix metalloproteinase-1 (MMP-1) synthesis and secretion in certain rodent and human osteoblastic cells, yet the intracellular events involved remain unclear. To further characterize this response and its signal transduction pathway(s), we examined prostanoid-induced expression of the MMP-1 gene in the rat osteoblastic osteosarcoma cell line UMR 106-01. Northern blot analysis demonstrated that prostaglandin E2 (PGE2) and PGE1 were very potent stimulators (40-fold) of MMP-1 transcript abundance, PGF2 alpha and prostacyclin were weak stimulators (4-fold), and thromboxane-B2 had no effect. The marked increase in MMP-1 transcript abundance after PGE2 treatment was first detected at 2 h, became maximal at 4 h, and persisted beyond 24 h. This response was dose dependent and elicited maximal and half-maximal effects with concentrations of 10(-6) and 0.6 x 10(-7) M, respectively. Cycloheximide, a protein synthesis inhibitor, completely blocked this effect of PGE2, suggesting that the expression of other genes is required. Nuclear run-on experiments demonstrated that PGE2 rapidly activates MMP-1 gene transcription, with a maximal increase at 2-4 h. The second messenger analog, 8-bromo-cAMP, mimicked the effects of PGE2 by stimulating a dose-dependent increase in MMP-1 messenger RNA (mRNA) levels, with a maximal effect quantitatively similar to that observed with PGE2. Thus, in UMR 106-01 cells, different prostanoids have distinct potencies in stimulating MMP-1 mRNA abundance. Our data suggest that PGE2 stimulation of MMP-1 synthesis is due to activation of MMP-1 gene transcription and a subsequent marked increase in MMP-1 mRNA abundance. This effect is dependent on de novo protein synthesis and is mimicked by protein kinase-A activation.

NASA Discipline Musculoskeletal↗
NASA NTRS1994

Mechanical stimulation of skeletal muscle cells mitigates glucocorticoid-induced decreases in prostaglandin production and prostaglandin synthase activity

The glucocorticoid dexamethasone (Dex) induces a decline in protein synthesis and protein content in tissue cultured, avian skeletal muscle cells, and this atrophy is attenuated by repetitive mechanical stretch. Since the prostaglandin synthesis inhibitor indomethacin mitigated this stretch attenuation of muscle atrophy, the effects of Dex and mechanical stretch on prostaglandin production and prostaglandin H synthase (PGHS) activity were examined. In static cultures, 10(-8) M Dex reduced PGF2 alpha production 55-65% and PGE2 production 84-90% after 24-72 h of incubation. Repetitive 10% stretch-relaxations of non-Dex-treated cultures increased PGF2 alpha efflux 41% at 24 h and 276% at 72 h, and increased PGE2 production 51% at 24 h and 236% at 72 h. Mechanical stimulation of Dex-treated cultures increased PGF2 alpha production 162% after 24 h, returning PGF2 alpha efflux to the level of non-Dex-treated cultures. At 72 h, stretch increased PGF2 alpha efflux 65% in Dex-treated cultures. Mechanical stimulation of Dex-treated cultures also increased PGE2 production at 24 h, but not at 72 h. Dex reduced PGHS activity in the muscle cultures by 70% after 8-24 h of incubation, and mechanical stimulation of the Dex-treated cultures increased PGHS activity by 98% after 24 h. Repetitive mechanical stimulation attenuates the catabolic effects of Dex on cultured skeletal muscle cells in part by mitigating the Dex-induced declines in PGHS activity and prostaglandin production.

NASA Discipline Musculoskeletal↗
NASA NTRS1994

Temporal changes in sarcomere lesions of rat adductor longus muscles during hindlimb reloading

Focal sarcomere disruptions were previously observed in adductor longus muscles of rats flown approximately two weeks aboard the Cosmos 1887 and 2044 biosatellite flights. These lesions, characterized by breakage and loss of myofilaments and Z-line streaming, resembled damage induced by unaccustomed exercise that includes eccentric contractions in which muscles lengthen as they develop tension. We hypothesized that sarcomere lesions in atrophied muscles of space flow rats were not produced in microgravity by muscle unloading but resulted from muscle reloading upon re-exposure to terrestrial gravity. To test this hypothesis, we examined temporal changes in sarcomere integrity of adductor longus muscles from rats subjected to 12.5 days of hindlimb suspension unloading and subsequent reloading by return to vivarium cages for 0, 6, 12, or 48 hours of normal weightbearing. Our ultrastructural observations suggested that muscle unloading (0 h reloading) induced myofibril misalignment associated with myofiber atrophy. Muscle reloading for 6 hours induced focal sarcomere lesions in which cross striations were abnormally widened. Such lesions were electron lucent due to extensive myofilament loss. Lesions in reloaded muscles showed rapid restructuring. By 12 hours of reloading, lesions were moderately stained foci and by 48 hours darkly stained foci in which the pattern of cross striations was indistinct at the light and electron microscopic levels. These lesions were spanned by Z-line-like electron dense filamentous material. Our findings suggest a new role for Z-line streaming in lesion restructuring: rather than an antecedent to damage, this type of Z-line streaming may be indicative of rapid, early sarcomere repair.

Non-NASA Center↗
NASA NTRS1994

Influence of antiorthostatic suspension on resistance to murine Listeria monocytogenes infection

The present study was designed to evaluate the influence of antiorthostatic suspension, a ground-based modeling system employed to simulate certain aspects of weightlessness that occur during space flight, on the capacity of mice to resist infection with the facultative intracellular bacterial pathogen Listeria monocytogenes. Female BDF1 mice were suspended by the tail in the orthostatic or antiorthostatic position and were infected with a sublethal dose of virulent L. monocytogenes at various times during the suspension. It was found that suspension did not influence the kinetics of bacterial growth in vivo if the infection was started concurrently with the suspension. However, mice that were antiorthostatically suspended 2, 4, or 7 days before the onset of infection exhibited an enhanced capacity to eliminate the challenge infection. Suspending mice on day 2 of the infection did not alter the kinetics of bacterial growth. Finally, the enhancement of resistance to the primary Listeria infection was accompanied by failure of the mice to generate long-term protective immunological memory to the challenge organism. Collectively, these results indicate that the stress of antiorthostatic suspension can influence the capacity of mice to resist bacterial infection.

NASA Discipline Regulatory Physiology↗
NASA NTRS1993

Alterations in skeletal muscle related to impaired physical mobility: an empirical model

The objective of this investigation was to study impaired physical mobility and the resulting skeletal muscle atrophy. An animal model was used to study morphological adaptations of the soleus and plantaris muscles to decreased loading induced by hindlimb suspension of an adult rat for 7, 14, and 28 consecutive days. Alterations in weight, skeletal muscle growth, and changes in fiber type composition were studied in synergistic plantar flexors of the rat hindlimb. Body weight and the soleus muscle mass to body mass ratio demonstrated significant progressive atrophy over th 28-day experimental period with the most significant changes occurring in the first 7 days of hindlimb suspension. Hindlimb suspension produced atrophy of Type I and Type IIa muscle fibers as demonstrated by significant decreases in fiber cross-sectional area (micron 2). These latter changes account for the loss of contractile force production reported in the rat following hindlimb unloading. When compared to traditional models of hindlimb suspension and immobilization, the ISC model produces a less severe atrophy while maintaining animal mobility and health. We conclude that it is the preferred animal model to address nursing questions of impaired physical mobility.

Non-NASA Center↗
NASA NTRS1993

Gender differences in endocrine responses to posture and 7 days of -6 degrees head-down bed rest

Endocrine regulation of fluids and electrolytes during 7 days of -6 degrees head-down bed rest (HDBR) was compared in male (n = 8) and, for the first time, female (n = 8) volunteers. The subjects' responses to quiet standing for 2 h before and after HDBR were also tested. In both sexes, diuresis and natriuresis were evident during the first 2-3 days of HDBR, resulting in a marked increase in the urinary Na(+)-to-K+ ratio and significant Na+ retention on re-ambulation. After the 1st day of HDBR, plasma renin activity (PRA) was increased relative to aldosterone (Aldo), plasma volume was decreased, and the renal response to Aldo appeared to be appropriate. Circulating levels of arginine vasopressin, cortisol, and ACTH were unchanged during HDBR. Plasma testosterone decreased slightly on day 2 of HDBR in males. The ratio of early morning ACTH to cortisol was lower in females than in males because ACTH was lower in females. Urinary cortisol increased and remained elevated throughout the HDBR in males only. There were no gender differences in the responses to 7 days of HDBR, except those in the pituitary-adrenal system; those differences appeared unrelated to the postural change. The provocative cardiovascular test of quiet standing before and after HDBR revealed both sex differences and effects of HDBR. There were significant sex differences in cardiovascular responses to standing before and after HDBR. Females had greater PRA and Aldo responses to standing before HDBR and larger Aldo responses to standing after HDBR than males.(ABSTRACT TRUNCATED AT 250 WORDS).

NASA Discipline Number 14-10↗
NASA NTRS1993

cAMP levels in fast- and slow-twitch skeletal muscle after an acute bout of aerobic exercise

The present study examined whether exercise duration was associated with elevated and/or sustained elevations of postexercise adenosine 3',5'-cyclic monophosphate (cAMP) by measuring cAMP levels in skeletal muscle for up to 4 h after acute exercise bouts of durations that are known to either produce (60 min) or not produce (10 min) mitochondrial proliferation after chronic training. Treadmill-acclimatized, but untrained, rats were run at 22 m/min for 0 (control), 10, or 60 min and were killed at various postexercise (0, 0.5, 1, 2, and 4 h) time points. Fast-twitch white and red (quadriceps) and slow-twitch (soleus) muscles were quickly excised, frozen in liquid nitrogen, and assayed for cAMP with a commercial kit. Unexpectedly, cAMP contents in all three muscles were similar to control (nonexercise) at most (21 of 30) time points after a single 10- or 60-min run. Values at 9 of 30 time points were significantly different from control (P < 0.05); i.e., 3 time points were significantly higher than control and 6 were significantly less than control. These data suggest that the cAMP concentration of untrained skeletal muscle after a single bout of endurance-type exercise is not, by itself, associated with exercise duration.

NASA Discipline Musculoskeletal↗
NASA NTRS1993

Echocardiograms during six hours of bedrest at head-down and head-up tilt and during space flight

Left ventricular end-diastolic volume increased after 4 1/2 to 6 hours of space flight, but was significantly decreased after 5 to 6 days of space flight. To determine the role of acute gravitational effects in this phenomenon, responses to a 6-hour bedrest model of 0 gravity (G; 5 degrees head-down tilt) were compared with those of fractional gravity loads of 1/6 G, 1/3 G, and 2/3 G by using head-up tilts of 10 degrees, 20 degrees, and 42 degrees, respectively. On 4 different days, six healthy male subjects were tilted at one of the four angles for 6 hours. Cardiac dimensions and volumes were determined from two-dimensional and M-mode echocardiograms in the left lateral decubitus position at control (0), 2, 4, and 6 hours. Stroke volume decreased with time (P < .05) for all tilt angles when compared with control. Ejection fraction (EF) at -5 degrees was greater than at +20 degrees and +42 degrees (not significant); EF at +10 degrees was greater than at +42 degrees (not significant). For the tilt angles of -5 degrees, +10 degrees, and +20 degrees, mean heart rate decreased during the first 2 hours, and returned to control or was slightly elevated above control (+20 degrees) by 6 hours (not significant). At the +42 degrees angle of tilt, heart rate was increased above control at hours 2, 4, and 6. There were no significant differences in cardiac output at any time point for any tilt angle.(ABSTRACT TRUNCATED AT 250 WORDS).

Flight Experiment↗
NASA NTRS1993

Skeletal unloading decreases production of 1,25-dihydroxyvitamin D

The plasma concentration of 1,25-dihydroxyvitamin D [1,25(OH)2D] decreases during skeletal unloading and increases when normal weight bearing is restored. To determine whether these changes in plasma 1,25(OH)2D reflect changes in production, metabolic clearance, or both we measured the kinetics of 1,25(OH)2D metabolism in rats whose skeletons were normally loaded, unloaded, or reloaded after a period of nonweight bearing. Skeletal unloading produced a transient but striking fall in the production (-73%) and plasma concentration (-72%) of 1,25(OH)2D without having a significant effect (< 20%) on metabolic clearance. Skeletal reloading returned production to normal. Bone formation predictably decreased during unloading and returned to normal after return to weight bearing. No consistent changes in blood ionized calcium, plasma immunoreactive parathyroid hormone (irPTH), or plasma phosphorus occurred. These data suggest that the changes in plasma 1,25-(OH)2D associated with changes in skeletal weight bearing primarily reflect changes in 1,25(OH)2D production. The data provide no evidence that the changes in 1,25(OH)2D production are a consequence of changes in blood ionized calcium, plasma irPTH, or phosphorus.

Non-NASA Center↗
NASA NTRS1993

Influence of recreational activity and muscle strength on ulnar bending stiffness in men

Bone bending stiffness (modulus of elasticity [E] x moment of inertia [I]), a measure of bone strength, is related to its mineral content (BMC) and geometry and may be influenced by exercise. We evaluated the relationship of habitual recreational exercise and muscle strength to ulnar EI, width, and BMC in 51 healthy men, 28-61 yr of age. BMC and width were measured by single photon absorptiometry and EI by mechanical resistance tissue analysis. Maximum biceps strength was determined dynamically (1-RM) and grip strength isometrically. Subjects were classified as sedentary (S) (N = 13), moderately (M) (N = 18), or highly active (H) (N = 20) and exercised 0.2 +/- 0.2; 2.2 +/- 1.3; and 6.8 +/- 2.3 h.wk-1 (P < 0.001). H had greater biceps (P < 0.0005) and grip strength (P < 0.05), ulnar BMC (P < 0.05), and ulnar EI (P = 0.01) than M or S, who were similar. Amount of activity correlated with grip and biceps strength (r = 0.47 and 0.49; P < 0.001), but not with bone measurements, whereas muscle strength correlated with both EI and BMC (r = 0.40-0.52, P < 0.005). EI also correlated significantly with both BMC and ulnar width (P < 0.0001). Ulnar width and biceps strength were the only independent predictors of EI (r2 = 0.67, P < 0.0001). We conclude that levels of physical activity sufficient to increase arm strength influence ulnar bending stiffness.

NASA Discipline Musculoskeletal↗
NASA NTRS1993

Time-resolved tryptophan fluorescence in photosynthetic reaction centers from Rhodobacter sphaeroides

Tryptophan fluorescence of reaction centers isolated from Rhodobacter sphaeroides, both stationary and time-resolved, was studied. Fluorescence kinetics were found to fit best a sum of four discrete exponential components. Half of the initial amplitude was due to a component with a lifetime of congruent to 60 ps, belonging to Trp residues, capable of efficient transfer of excitation energy to bacteriochlorophyll molecules of the reaction center. The three other components seem to be emitted by Trp ground-state conformers, unable to participate in such a transfer. Under the influence of intense actinic light, photooxidizing the reaction centers, the yield of stationary fluorescence diminished by congruent to 1.5 times, while the number of the kinetic components and their life times remained practically unchanged. Possible implications of the observed effects for the primary photosynthesis events are considered.

NASA Program Exobiology↗
NASA NTRS1993

Temporal expression and immunogold localization of Plodia interpunctella granulosis virus structural proteins

Monospecific antisera were produced against four structural proteins (VP12, VP17, VP31, and granulin) of the Plodia interpunctella granulosis virus using polypeptides derived by sodium dodecyl sulfate-polyacrylamide gel electrophoresis or acid extraction. The antisera were shown to be specific on immunoblots of SDS-PAGE separated granulosis virus and were further used to detect structural proteins in infected fat body lysates. Immunoblots of fat body lysates from early stages of infection indicated that VP12, VP17, VP31, and granulin were expressed by 2.5 days post-infection. Immunogold labeling of the virus using the monospecific antisera and electron microscopy confirmed earlier reports that granulin is located in the protein matrix, V17 is an envelope protein, and VP31 is a capsid protein.

Non-NASA Center↗
NASA NTRS1993

Human performance and physiological function during a 24-hr exposure to 1% bromotrifluoromethane (Halon 1301)

Performance and physiological measurements were obtained from four pairs of men exposed for 24 hr to 1% (10,000 ppm) Halon 1301 (bromotrifluoromethane, CBrF3) and to air with order counterbalanced using a double-blind protocol. Cognitive and motor performance was assessed before, during, and after the exposures using seven scales of the Automated Portable Testing System, which produced 13 measures of performance. Halon inhalation induced decrements in 2 of the 13 measures, but actual and estimated magnitudes of the decrements were no greater than 5% of baseline values. Physiological data were obtained before, during, and after the exposures from clinical chemistry analyses of blood and urine samples, pulmonary function tests, and monitoring of vital signs. Significant change during Halon inhalation was observed for 6 of the 52 variables assessed; however, all physiological values remained within clinically acceptable limits. No cardiovascular effects were noted. This study demonstrated that exposure to 1% Halon 1301 for 24 hr can produce minor disturbance of central nervous system function as assessed by cognitive tasks.

Randomized Controlled Trial↗
NASA NTRS1993

Renal and cardiovascular responses to water immersion in trained runners and swimmers

The purpose of this study was to determine if fluid-electrolyte, renal, hormonal, and cardiovascular responses during and after multi-hour water immersion were associated with aerobic training. Additionally, we compared these responses in those who trained in a hypogravic versus a 1-g environment. Seventeen men comprised three similarly aged groups: six long-distance runners, five competitive swimmers, and six untrained control subjects. Each subject underwent 5 h of immersion in water [mean (SE)] 36.0 (0.5) degrees C to the neck. Immediately before and at each hour of immersion, blood and urine samples were collected and analyzed for sodium (Na), potassium, osmolality, and creatinine (Cr). Plasma antidiuretic hormone and aldosterone were also measured. Hematocrits were used to calculate relative changes in plasma volume (% delta Vpl). Heart rate response to submaximal cycle ergometer exercise (35% peak oxygen uptake) was measured before and after water immersion. Water immersion induced significant increases in urine flow, Na clearance (CNa), and a 3-5% decrease in Vpl. Urine flow during immersion was greater (P < 0.05) in runners [2.4 (0.4) ml.min-1] compared to controls [1.3 (0.1) ml.min-1]. However, % delta Vpl, CCr, CNa and CH2O during immersion were not different (P > 0.05) between runners, swimmers, and controls. After 5 h of immersion, there was an increase (P < 0.05) in submaximal exercise heart rate of 9 (3) and 10 (3) beats.min-1 in both runners and controls, respectively, but no change (P > 0.05) was observed in swimmers.(ABSTRACT TRUNCATED AT 250 WORDS).

Running/physiology↗
NASA NTRS1992

Effectiveness and duration of intramuscular antimotion sickness medications

Motion sickness inhibits gastric motility, making the oral route ineffective for medications. The intramuscular route is an effective alternative. The rotating chair was used to produce the M 111 level of motion sickness on the Graybiel Symptom Scale. The intramuscular medications given 30 minutes before rotation were compared with placebo (saline, 1 mL) for effectiveness and duration in increasing the number of tolerated head movements. Average placebo number of head movements was 294. Promethazine 25 mg increased head movements by 78% (P < .05), with a duration of 12 hours. Scopolamine 0.2 mg increased head movements by 91% (P < .05), with a duration of 4 hours. The effect of caffeine 250 mg and ephedrine 25 mg was not significant. When combined with scopolamine, ephedrine produced an 32% additive effect. Scopolamine 0.08 mg, 0.1 mg, and 0.2 mg and also promethazine 12.5 mg and 25 mg were significant (P < .05). Promethazine appears to be the drug of choice for intramuscular use because of a longer duration and a high level of effectiveness. Scopolamine was of high effectiveness, but had a duration of 4 hours. It was eight times as potent by the intramuscular as by the oral route.

Non-NASA Center↗
NASA NTRS1992

Association of sleep-wake habits in older people with changes in output of circadian pacemaker

Many elderly people complain of disturbed sleep patterns but there is not evidence that the need to sleep decreases with age; it seems rather that the timing and consolidation of sleep change. We tried to find out whether there is a concurrent change in the output of the circadian pacemaker with age. The phase and amplitude of the pacemaker's output were assessed by continuous measurement of the core body temperature during 40 h of sustained wakefulness under constant behavioural and environmental conditions. 27 young men (18-31 years) were compared with 21 older people (65-85 years; 11 men, 10 women); all were healthy and without sleep complaints. The mean amplitude of the endogenous circadian temperature oscillation (ECA) was 40% greater in young men than in the older group. Older men had a lower mean temperature ECA than older women. The minimum of the endogenous phase of the circadian temperature oscillation (ECP) occurred 1 h 52 min earlier in the older than in the young group. Customary bedtimes and waketimes were also earlier in the older group, as was their daily alertness peak. There was a close correlation between habitual waketime and temperature ECP in young men, which may lose precision with age, especially among women. These findings provide evidence for systematic age-related changes in the output of the human circadian pacemaker. We suggest that these changes may underlie the common complaints of sleep disturbance among elderly people. These changes could reflect the observed age-related deterioration of the hypothalamic nuclei that drive mammalian circadian rhythms.

Non-NASA Center↗
NASA NTRS1992

Electrophysiology of the mammillary complex in vitro. II. Medial mammillary neurons

1. The electrophysiological properties of guinea pig medial mammillary body (MMB) neurons were studied using an in vitro slice preparation. 2. The neurons (n = 80) had an average resting potential of -57 +/- 5.5 (SD) mV, an input resistance of 176 +/- 83 M omega, and a spike amplitude of 58 +/- 15.7 mV. Most of the neurons were silent at rest (n = 52), but some fired spontaneous single spikes (n = 16) or spike bursts (n = 14). 3. The main electrophysiological characteristic of MMB neurons was the ability to generate Ca(2+)-dependent regenerative events, which resulted in very robust burst responses. However, this regenerative event was not the same for all neurons, ranging from typical low-threshold Ca2+ spikes (LTSs) to intermediate-threshold plateau potentials (ITPs). 4. The ITPs were distinct from the LTSs in that they lasted > or = 100 ms and were not inactivated at membrane potentials at or positive to -55 mV. 5. Some cells with a prominent ITP and no LTS (n = 36) displayed repetitive, usually rhythmic, bursting (n = 14). This ITP could be powerful enough to maintain rhythmic membrane potential oscillations after pharmacological block of Na+ conductances. 6. A group of 32 MMB neurons displayed complex bursting that was generated by activation of both LTSs and ITPs. This was established on the basis of their distinct time- and voltage-dependent characteristics. In a group of neurons (n = 14), the burst responses were exclusively generated by an LTS; however, a Ca(2+)-dependent plateau potential contributed to the generation of rebound-triggered oscillatory firing. 7. In addition to the Ca(2+)-dependent LTS and/or ITP, MMB neurons always displayed high-threshold Ca2+ spikes after reduction of K+ conductances with tetraethylammonium. 8. MMB neurons display one of the richer varieties of voltage-dependent Ca2+ conductances so far encountered in mammalian CNS. We propose that the very prominent endogenous bursting and oscillatory properties of MB neurons allow this nuclear complex to function as an oscillatory relay for the transmission of low-frequency rhythmic activities throughout the limbic circuit.

NASA Discipline Neuroscience↗