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At least 1,765 records · Page 98
All sourcesNASA NTRSDOE OSTI
NASA NTRS2002

Water and Energy Dietary Requirements and Endocrinology of Human Space Flight

Fluid and energy metabolism and related endocrine changes have been studied nearly from the beginning of human space flight in association with short- and long-duration flights. Fluid and electrolyte nutrition status is affected by many factors including the microgravity environment, stress, changes in body composition, diet, exercise habits, sleep cycles, and ambient temperature and humidity conditions. Space flight exposes astronauts to all these factors and consequently poses significant challenges to establishing dietary water, sodium, potassium, and energy recommendations. The purpose of this article is to review the results of ground-based and space flight research studies that have led to current water, electrolyte, and energy dietary requirements for humans during space flight and to give an overview of related endocrinologic changes that have been observed in humans during short- and long-duration space flight.

short duration↗
NASA NTRS2002

The vestibulosympathetic reflex in humans: neural interactions between cardiovascular reflexes

1. Over the past 5 years, there has been emerging evidence that the vestibular system regulates sympathetic nerve activity in humans. We have studied this issue in humans by using head-down rotation (HDR) in the prone position. 2. These studies have clearly demonstrated increases in muscle sympathetic nerve activity (MSNA) and calf vascular resistance during HDR. These responses are mediated by engagement of the otolith organs and not the semicircular canals. 3. However, differential activation of sympathetic nerve activity has been observed during HDR. Unlike MSNA, skin sympathetic nerve activity does not increase with HDR. 4. Examination of the vestibulosympathetic reflex with other cardiovascular reflexes (i.e. barorereflexes and skeletal muscle reflexes) has shown an additive interaction for MSNA. 5. The additive interaction between the baroreflexes and vestibulosympathetic reflex suggests that the vestibular system may assist in defending against orthostatic challenges in humans by elevating MSNA beyond that of the baroreflexes. 6. In addition, the further increase in MSNA via otolith stimulation during isometric handgrip, when arterial pressure is elevated markedly, indicates that the vestibulosympathetic reflex is a powerful activator of MSNA and may contribute to blood pressure and flow regulation during dynamic exercise. 7. Future studies will help evaluate the importance of the vestibulosympathetic reflex in clinical conditions associated with orthostatic hypotension.

Review↗
NASA NTRS2002

Influence of vestibular activation on respiration in humans

The purpose of this study was to determine the effects of the semicircular canals and otolith organs on respiration in humans. On the basis of animal studies, we hypothesized that vestibular activation would elicit a vestibulorespiratory reflex. To test this hypothesis, respiratory measures, arterial blood pressure, and heart rate were measured during engagement of semicircular canals and/or otolith organs. Dynamic upright pitch and roll (15 cycles/min), which activate the otolith organs and semicircular canals, increased respiratory rate (Delta2 +/- 1 and Delta3 +/- 1 breaths/min, respectively; P < 0.05). Dynamic yaw and lateral pitch (15 cycles/min), which activate the semicircular canals, increased respiration similarly (Delta3 +/- 1 and Delta2 +/- 1, respectively; P < 0.05). Dynamic chair rotation (15 cycles/min), which mimics dynamic yaw but eliminates neck muscle afferent, increased respiration (Delta3 +/- 1; P < 0.05) comparable to dynamic yaw (15 cycles/min). Increases in respiratory rate were graded as greater responses occurred during upright (Delta5 +/- 2 breaths/min) and lateral pitch (Delta4 +/- 1) and roll (Delta5 +/- 1) performed at 30 cycles/min. Increases in breathing frequency resulted in increases in minute ventilation during most interventions. Static head-down rotation, which activates otolith organs, did not alter respiratory rate (Delta1 +/- 1 breaths/min). Collectively, these data indicate that semicircular canals, but not otolith organs or neck muscle afferents, mediate increased ventilation in humans and support the concept that vestibular activation alters respiration in humans.

NASA Discipline Neuroscience↗
NASA NTRS2001

Radiation transport modeling and assessment to better predict radiation exposure, dose, and toxicological effects to human organs on long duration space flights

NASA is very interested in improving its ability to monitor and forecast the radiation levels that pose a health risk to space-walking astronauts as they construct the International Space Station and astronauts that will participate in long-term and deep-space missions. Human exploratory missions to the moon and Mars within the next quarter century, will expose crews to transient radiation from solar particle events which include high-energy galactic cosmic rays and high-energy protons. Because the radiation levels in space are high and solar activity is presently unpredictable, adequate shielding is needed to minimize the deleterious health effects of exposure to radiation. Today, numerous models have been developed and used to predict radiation exposure. Such a model is the Space Environment Information Systems (SPENVIS) modeling program, developed by the Belgian Institute for Space Aeronautics. SPENVIS, which has been assessed to be an excellent tool in characterizing the radiation environment for microelectronics and investigating orbital debris, is being evaluated for its usefulness with determining the dose and dose-equivalent for human exposure. Thus far. the calculations for dose-depth relations under varying shielding conditions have been in agreement with calculations done using HZETRN and PDOSE, which are well-known and widely used models for characterizing the environments for human exploratory missions. There is disagreement when assessing the impact of secondary radiation particles since SPENVIS does a crude estimation of the secondary radiation particles when calculating LET versus Flux. SPENVIS was used to model dose-depth relations for the blood-forming organs. Radiation sickness and cancer are life-threatening consequences resulting from radiation exposure. In space. exposure to radiation generally includes all of the critical organs. Biological and toxicological impacts have been included for discussion along with alternative risk mitigation methods--shielding and anti-carcinogens. c 2001. Elsevier Science Ltd. All rights reserved.

STS-91 Shuttle Project↗
NASA NTRS2001

Rejoining of isochromatid breaks induced by heavy ions in G2-phase normal human fibroblasts

We reported previously that exposure of normal human fibroblasts in G2 phase of the cell cycle to high-LET radiation produces a much higher frequency of isochromatid breaks than exposure to gamma rays. We concluded that an increase in the production of isochromatid breaks is a signature of initial high-LET radiation-induced G2-phase damage. In this paper, we report the repair kinetics of isochromatid breaks induced by high-LET radiation in normal G2-phase human fibroblasts. Exponentially growing human fibroblasts (AG1522) were irradiated with gamma rays or energetic carbon (290 MeV/nucleon), silicon (490 MeV/nucleon), or iron (200 MeV/nucleon) ions. Prematurely condensed chromosomes were induced by calyculin A after different postirradiation incubation times ranging from 0 to 600 min. Chromosomes were stained with Giemsa, and aberrations were scored in cells at G2 phase. G2-phase fragments, the result of the induction of isochromatid breaks, decreased quickly with incubation time. The curve for the kinetics of the rejoining of chromatid-type breaks showed a slight upward curvature with time after exposure to 440 keV/microm iron particles, probably due to isochromatid-isochromatid break rejoining. The formation of chromatid exchanges after exposure to high-LET radiation therefore appears to be underestimated, because isochromatid-isochromatid exchanges cannot be detected. Increased induction of isochromatid breaks and rejoining of isochromatid breaks affect the overall kinetics of chromatid-type break rejoining after exposure to high-LET radiation.

NASA Center JSC↗
NASA NTRS1990

Medical considerations for extending human presence in space

The prospects for extending the length of time that humans can safely remain in space depend partly on resolution of a number of medical issues. Physiologic effects of weightlessness that may affect health during flight include loss of body fluid, functional alterations in the cardiovascular system, loss of red blood cells and bone mineral, compromised immune system function, and neurosensory disturbances. Some of the physiologic adaptations to weightlessness contribute to difficulties with readaptation to Earth's gravity. These include cardiovascular deconditioning and loss of body fluids and electrolytes; red blood cell mass; muscle mass, strength, and endurance; and bone mineral. Potentially harmful factors in space flight that are not related to weightlessness include radiation, altered circadian rhythms and rest/work cycles, and the closed, isolated environment of the spacecraft. There is no evidence that space flight has long-term effects on humans, except that bone mass lost during flight may not be replaced, and radiation damage is cumulative. However, the number of people who have spent several months or longer in space is still small. Only carefully-planned experiments in space preceded by thorough ground-based studies can provide the information needed to increase the amount of time humans can safely spend in space.

Review, Tutorial↗
NASA NTRS2001

Influence of respiratory motor neurone activity on human autonomic and haemodynamic rhythms

Although humans hold great advantages over other species as subjects for biomedical research, they also bring major disadvantages. One is that among the many rhythmic physiological signals that can be recorded, there is no sure way to know which individual change precedes another, or which change represents cause and which represents effect. In an attempt to deal with the inherent complexity of research conducted in intact human subjects, we developed and used a structural equation model to analyse responses of healthy young men to pharmacological changes of arterial pressure and graded inspiratory resistance, before and after vagomimetic atropine. Our model yielded a good fit of the experimental data, with a system weighted R2 of 0.77, and suggested that our treatments exerted both direct and indirect influences on the variables we measured. Thus, infusions of nitroprusside and phenylephrine exerted all of their direct effects by lowering and raising arterial pressure; the changes of R-R intervals, respiratory sinus arrhythmia and arterial pressure fluctuations that these drugs provoked, were indirect consequences of arterial pressure changes. The only direct effect of increased inspiratory resistance was augmentation of arterial pressure fluctuations. These results may provide a new way to disentangle and understand responses of intact human subjects to experimental forcings. The principal new insight we derived from our modelling is that respiratory gating of vagal-cardiac motor neurone firing is nearly maximal at usual levels of arterial pressure and inspiratory motor neurone activity.

Non-NASA Center↗
NASA NTRS1999

Estimate of the frequency of true incomplete exchanges in human lymphocytes exposed to 1 GeV/u Fe ions in vitro

PURPOSE: To study the frequency of true incomplete exchanges induced by high-LET radiation. MATERIALS AND METHODS: Human lymphocytes were exposed to 1 GeV/u Fe ions (LET = 140 keV/microm). Chromosome aberrations were analysed by a fluorescence in situ hybridization using a combination of whole-chromosome-specific probes and human telomere probes. Chromosomes 1, 3 and 4 were investigated. RESULTS: The percentage of incomplete exchanges was between 23 and 29% if telomere signals were not considered. The percentage decreased to approximately 10% after ruling out false incomplete exchanges containing telomere signals. The final estimation of true incomplete exchanges was <10%. CONCLUSION: Within a degree of uncertainty, the percentage of true incomplete exchanges in 1 GeV/u Fe ion-irradiated human lymphocytes was similar to that induced by gamma rays.

NASA Center JSC↗
NASA NTRS2001

Interaction between vestibulosympathetic and skeletal muscle reflexes on sympathetic activity in humans

Evidence from animals indicates that skeletal muscle afferents activate the vestibular nuclei and that both vestibular and skeletal muscle afferents have inputs to the ventrolateral medulla. The purpose of the present study was to investigate the interaction between the vestibulosympathetic and skeletal muscle reflexes on muscle sympathetic nerve activity (MSNA) and arterial pressure in humans. MSNA, arterial pressure, and heart rate were measured in 17 healthy subjects in the prone position during three experimental trials. The three trials were 2 min of 1) head-down rotation (HDR) to engage the vestibulosympathetic reflex, 2) isometric handgrip (IHG) at 30% maximal voluntary contraction to activate skeletal muscle afferents, and 3) HDR and IHG performed simultaneously. The order of the three trials was randomized. HDR and IHG performed alone increased total MSNA by 46 +/- 16 and 77 +/- 24 units, respectively (P < 0.01). During the HDR plus IHG trial, MSNA increased 142 +/- 38 units (P < 0.01). This increase was not significantly different from the sum of the individual trials (130 +/- 41 units). This finding was also observed with mean arterial pressure (sum = 21 +/- 2 mmHg and HDR + IHG = 22 +/- 2 mmHg). These findings suggest that there is an additive interaction for MSNA and arterial pressure when the vestibulosympathetic and skeletal muscle reflexes are engaged simultaneously in humans. Therefore, no central modulation exists between these two reflexes with regard to MSNA output in humans.

NASA Discipline Neuroscience↗
NASA NTRS2000

Dynamic resetting of the human circadian pacemaker by intermittent bright light

In humans, experimental studies of circadian resetting typically have been limited to lengthy episodes of exposure to continuous bright light. To evaluate the time course of the human endogenous circadian pacemaker's resetting response to brief episodes of intermittent bright light, we studied 16 subjects assigned to one of two intermittent lighting conditions in which the subjects were presented with intermittent episodes of bright-light exposure at 25- or 90-min intervals. The effective duration of bright-light exposure was 31% or 63% compared with a continuous 5-h bright-light stimulus. Exposure to intermittent bright light elicited almost as great a resetting response compared with 5 h of continuous bright light. We conclude that exposure to intermittent bright light produces robust phase shifts of the endogenous circadian pacemaker. Furthermore, these results demonstrate that humans, like other species, exhibit an enhanced sensitivity to the initial minutes of bright-light exposure.

Non-NASA Center↗
NASA NTRS2000

Interaction of the vestibular system and baroreflexes on sympathetic nerve activity in humans

Muscle sympathetic nerve activity (MSNA) is altered by vestibular otolith stimulation. This study examined interactive effects of the vestibular system and baroreflexes on MSNA in humans. In study 1, MSNA was measured during 4 min of lower body negative pressure (LBNP) at either -10 or -30 mmHg with subjects in prone posture. During the 3rd min of LBNP, subjects lowered their head over the end of a table (head-down rotation, HDR) to engage the otolith organs. The head was returned to baseline upright position during the 4th min. LBNP increased MSNA above baseline during both trials with greater increases during the -30-mmHg trial. HDR increased MSNA further during the 3rd min of LBNP at -10 and -30 mmHg (Delta32% and Delta34%, respectively; P < 0.01). MSNA returned to pre-HDR levels during the 4th min of LBNP when the head was returned upright. In study 2, MSNA was measured during HDR, LBNP, and simultaneously performed HDR and LBNP. The sum of MSNA responses during individual HDR and LBNP trials was not significantly different from that observed during HDR and LBNP performed together (Delta131 +/- 28 vs. Delta118 +/- 47 units and Delta340 +/- 77 vs. Delta380 +/- 90 units for the -10 and -30 trials, respectively). These results demonstrate that vestibular otolith stimulation can increase MSNA during unloading of the cardiopulmonary and arterial baroreflexes. Also, the interaction between the vestibulosympathetic reflex and baroreflexes is additive in humans. These studies indicate that the vestibulosympathetic reflex may help defend against orthostatic challenges in humans by increasing sympathetic outflow.

NASA Discipline Neuroscience↗
NASA NTRS2000

Physiological effects of light on the human circadian pacemaker

The physiology of the human circadian pacemaker and its influence and on the daily organization of sleep, endocrine and behavioral processes is an emerging interest in science and medicine. Understanding the development, organization and fundamental properties underlying the circadian timing system may provide insight for the application of circadian principles to the practice of clinical medicine, both diagnostically (interpretation of certain clinical tests are dependent on time of day) and therapeutically (certain pharmacological responses vary with the time of day). The light-dark cycle is the most powerful external influence acting upon the human circadian pacemaker. It has been shown that timed exposure to light can both synchronize and reset the phase of the circadian pacemaker in a predictable manner. The emergence of detectable circadian rhythmicity in the neonatal period is under investigation (as described elsewhere in this issue). Therefore, the pattern of light exposure provided in the neonatal intensive care setting has implications. One recent study identified differences in both amount of sleep time and weight gain in infants maintained in a neonatal intensive care environment that controlled the light-dark cycle. Unfortunately, neither circadian phase nor the time of day has been considered in most clinical investigations. Further studies with knowledge of principles characterizing the human circadian timing system, which governs a wide array of physiological processes, are required to integrate these findings with the practice of clinical medicine.

Review, Tutorial↗
NASA NTRS2000

Fluid flow releases fibroblast growth factor-2 from human aortic smooth muscle cells

This study tested the hypothesis that fluid shear stress regulates the release of fibroblast growth factor (FGF)-2 from human aortic smooth muscle cells. FGF-2 is a potent mitogen that is involved in the response to vascular injury and is expressed in a wide variety of cell types. FGF-2 is found in the cytoplasm of cells and outside cells, where it associates with extracellular proteoglycans. To test the hypothesis that shear stress regulates FGF-2 release, cells were exposed to flow, and FGF-2 amounts were measured from the conditioned medium, pericellular fraction (extracted by heparin treatment), and cell lysate. Results from the present study show that after 15 minutes of shear stress at 25 dyne/cm(2) in a parallel-plate flow system, a small but significant fraction (17%) of the total FGF-2 was released from human aortic smooth muscle cells. FGF-2 levels in the circulating medium increased 10-fold over medium from static controls (P<0.01). A 50% increase in FGF-2 content versus control (P<0.01) was found in the pericellular fraction (extracted by heparin treatment). Furthermore, a significant decrease in FGF-2 was detected in the cell lysate, indicating that FGF-2 was released from inside the cell. Cell permeability studies with fluorescent dextran were performed to examine whether transient membrane disruption caused FGF-2 release. Flow cytometry detected a 50% increase in mean fluorescence of cells exposed to 25 dyne/cm(2) versus control cells. This indicates that the observed FGF-2 release from human aortic smooth muscle cells is likely due to transient membrane disruption on initiation of flow.

Non-NASA Center↗
NASA NTRS2000

Color M-mode Doppler flow propagation velocity is a preload insensitive index of left ventricular relaxation: animal and human validation

OBJECTIVES: To determine the effect of preload in color M-mode Doppler flow propagation velocity (v(p)). BACKGROUND: The interpretation of Doppler filling patterns is limited by confounding effects of left ventricular (LV) relaxation and preload. Color M-mode v(p) has been proposed as a new index of LV relaxation. METHODS: We studied four dogs before and during inferior caval (IVC) occlusion at five different inotropic stages and 14 patients before and during partial cardiopulmonary bypass. Left ventricular (LV) end-diastolic volumes (LV-EDV), the time constant of isovolumic relaxation (tau), left atrial (LA) pre-A and LV end-diastolic pressures (LV-EDP) were measured. Peak velocity during early filling (E) and v(p) were extracted by digital analysis of color M-mode Doppler images. RESULTS: In both animals and humans, LV-EDV and LV-EDP decreased significantly from baseline to IVC occlusion (both p < 0.001). Peak early filling (E) velocity decreased in animals from 56 +/- 21 to 42 +/- 17 cm/s (p < 0.001) without change in v(p) (from 35 +/- 15 to 35 +/- 16, p = 0.99). Results were similar in humans (from 69 +/- 15 to 53 +/- 22 cm/s, p < 0.001, and 37 +/- 12 to 34 +/- 16, p = 0.30). In both species, there was a strong correlation between LV relaxation (tau) and v(p) (r = 0.78, p < 0.001, r = 0.86, p < 0.001). CONCLUSIONS: Our results indicate that color M-mode Doppler v(p) is not affected by preload alterations and confirms that LV relaxation is its main physiologic determinant in both animals during varying lusitropic conditions and in humans with heart disease.

Non-NASA Center↗
NASA NTRS1999

Alterations of p53 in tumorigenic human bronchial epithelial cells correlate with metastatic potential

The cellular and molecular mechanisms of radiation-induced lung cancer are not known. In the present study, alterations of p53 in tumorigenic human papillomavirus-immortalized human bronchial epithelial (BEP2D) cells induced by a single low dose of either alpha-particles or 1 GeV/nucleon (56)Fe were analyzed by PCR-single-stranded conformation polymorphism (SSCP) coupled with sequencing analysis and immunoprecipitation assay. A total of nine primary and four secondary tumor cell lines, three of which were metastatic, together with the parental BEP2D and primary human bronchial epithelial (NHBE) cells were studied. The immunoprecipitation assay showed overexpression of mutant p53 proteins in all the tumor lines but not in NHBE and BEP2D cells. PCR-SSCP and sequencing analysis found band shifts and gene mutations in all four of the secondary tumors. A G-->T transversion in codon 139 in exon 5 that replaced Lys with Asn was detected in two tumor lines. One mutation each, involving a G-->T transversion in codon 215 in exon 6 (Ser-->lle) and a G-->A transition in codon 373 in exon 8 (Arg-->His), was identified in the remaining two secondary tumors. These results suggest that p53 alterations correlate with tumorigenesis in the BEP2D cell model and that mutations in the p53 gene may be indicative of metastatic potential.

Non-NASA Center↗
NASA NTRS1999

Stability, precision, and near-24-hour period of the human circadian pacemaker

Regulation of circadian period in humans was thought to differ from that of other species, with the period of the activity rhythm reported to range from 13 to 65 hours (median 25.2 hours) and the period of the body temperature rhythm reported to average 25 hours in adulthood, and to shorten with age. However, those observations were based on studies of humans exposed to light levels sufficient to confound circadian period estimation. Precise estimation of the periods of the endogenous circadian rhythms of melatonin, core body temperature, and cortisol in healthy young and older individuals living in carefully controlled lighting conditions has now revealed that the intrinsic period of the human circadian pacemaker averages 24.18 hours in both age groups, with a tight distribution consistent with other species. These findings have important implications for understanding the pathophysiology of disrupted sleep in older people.

NASA Discipline Regulatory Physiology↗
NASA NTRS1999

Enhanced protein electrophoresis technique for separating human skeletal muscle myosin heavy chain isoforms

Talmadge and Roy (J. Appl. Physiol. 1993, 75, 2337-2340) previously established a sodium dodecyl sulfate - polyacrylamide gel electrophoresis (SDS-PAGE) protocol for separating all four rat skeletal muscle myosin heavy chain (MHC) isoforms (MHC I, IIa, IIx, IIb); however, when applied to human muscle, the type II MHC isoforms (Ila, IIx) are not clearly distinguished. In this brief paper we describe a modification of the SDS-PAGE protocol which yields distinct and consistent separation of all three adult human MHC isoforms (MHC I, IIa, IIx) in a minigel system. MHC specificity of each band was confirmed by Western blot using three monoclonal IgG antibodies (mAbs) immunoreactive against MHCI (mAb MHCs, Novacastra Laboratories), MHCI+IIa (mAb BF-35), and MHCIIa+IIx (mAb SC-71). Results provide a valuable SDS-PAGE minigel technique for separating MHC isoforms in human muscle without the difficult task of casting gradient gels.

NASA Center JSC↗
NASA NTRS1997

Induction of cyclo-oxygenase-2 mRNA by prostaglandin E2 in human prostatic carcinoma cells

Prostaglandins are synthesized from arachidonic acid by the enzyme cyclo-oxygenase. There are two isoforms of cyclooxygenases: COX-1 (a constitutive form) and COX-2 (an inducible form). COX-2 has recently been categorized as an immediate-early gene and is associated with cellular growth and differentiation. The purpose of this study was to investigate the effects of exogenous dimethylprostaglandin E2 (dmPGE2) on prostate cancer cell growth. Results of these experiments demonstrate that administration of dmPGE2 to growing PC-3 cells significantly increased cellular proliferation (as measured by the cell number), total DNA content and endogenous PGE2 concentration. DmPGE2 also increased the steady-state mRNA levels of its own inducible synthesizing enzyme, COX-2, as well as cellular growth to levels similar to those seen with fetal calf serum and phorbol ester. The same results were observed in other human cancer cell types, such as the androgen-dependent LNCaP cells, breast cancer MDA-MB-134 cells and human colorectal carcinoma DiFi cells. In PC-3 cells, the dmPGE2 regulation of the COX-2 mRNA levels was both time dependent, with maximum stimulation seen 2 h after addition, and dose dependent on dmPGE2 concentration, with maximum stimulation seen at 5 microg ml(-1). The non-steroidal anti-inflammatory drug flurbiprofen (5 microM), in the presence of exogenous dmPGE2, inhibited the up-regulation of COX-2 mRNA and PC-3 cell growth. Taken together, these data suggest that PGE2 has a specific role in the maintenance of human cancer cell growth and that the activation of COX-2 expression depends primarily upon newly synthesized PGE2, perhaps resulting from changes in local cellular PGE2 concentrations.

Non-NASA Center↗