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At least 217 records · Page 12

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NASA NTRS1998

Stress, Aging and Thirst

After growth during adolesence, total body water decreases progressively with aging from 65% of body weight to about 53% of body weight in the 70th decade; a majority of the loss occurs from the extracellular volume, from 42% to about 25%, respectively. Cellular volume also reaches equilibrium in the 70th decade at about 25% of body weight. Various stresses such as exercise, heat and attitude exposure, ad prior dehydration attenuate voluntary fluid intake (involuntary dehydration). Voluntary fluid intake appears to decrease with aging (involuntary dehydration in this sense aging can be considered as a stress. Kidney function and muscle mass (80% water) decrease somewhat with aging, and voluntary fluid intake (thirst) is also attenuated. Thirst is stimulated by increasing osmolality (hypernatremia) of the extracellular fluid and by decreased extracellular volume (mainly plasma volume) which act to increase intracellular fluid volume osmolality to activiate drinking. The latter decreases fluid compartment osmolality which ' It terminates drinking. However, this drinking mechanism seems to be attenuated with aging such that increasing plasma osmolality no longer stimulates fluid intake appropriately. Hypernatremia in the elderly has been associated all too frequently with greater incidence of bacterial infection and increased mortality. Involuntary dehydration can be overcome in young men by acclimation to an intermittent exercise-in-heat training program. Perhaps exercise training in the elderly would also increase voluntary fluid intake and increase muscle mass to enhance retention of water.

Greenleaf, John E.↗

NASA NTRS1999

Cell Culture in Microgravity: Opening the Door to Space Cell Biology

Adaptational response of human cell populations to microgravity is investigated using simulation, short-term Shuttle experiments, and long-term microgravity. Simulation consists of a clinostatically-rotated cell culture system. The system is a horizontally-rotated cylinder completely filled with culture medium. Low speed rotation results in continuous-fall of the cells through the fluid medium. In this setting, cells: 1) aggregate, 2) propagate in three dimensions, 3) synthesize matrix, 4) differentiate, and 5) form sinusoids that facilitate mass transfer. Space cell culture is conducted in flight bioreactors and in static incubators. Cells grown in microgravity are: bovine cartilage, promyelocytic leukemia, kidney proximal tubule cells, adrenal medulla, breast and colon cancer, and endothelium. Cells were cultured in space to test specific hypotheses. Cartilage cells were used to determine structural differences in cartilage grown in space compared to ground-based bioreactors. Results from a 130-day experiment on Mir revealed that cartilage grown in space was substantially more compressible due to insufficient glycosaminoglycan in the matrix. Interestingly, earth-grown cartilage conformed better to the dimensions of the scaffolding material, while the Mir specimens were spherical. The other cell populations are currently being analyzed for cell surface properties, gene expression, and differentiation. Results suggest that some cells spontaneously differentiate in microgravity. Additionally, vast changes in gene expression may occur in response to microgravity. In conclusion, the transition to microgravity may constitute a physical perturbation in cells resulting in unique gene expressions, the consequences of which may be useful in tissue engineering, disease modeling, and space cell biology.

Pellis, Neal R.↗

NASA NTRS2000

Mixing of an Airblast-atomized Fuel Spray Injected into a Crossflow of Air

The injection of a spray of fuel droplets into a crossflow of air provides a means of rapidly mixing liquid fuel and air for combustion applications. Injecting the liquid as a spray reduces the mixing length needed to accommodate liquid breakup, while the transverse injection of the spray into the air stream takes advantage of the dynamic mixing induced by the jet-crossflow interaction. The structure of the spray, formed from a model plain-jet airblast atomizer, is investigated in order to determine and understand the factors leading to its dispersion. To attain this goal, the problem is divided into the following tasks which involve: (1) developing planar imaging techniques that visualize fuel and air distributions in the spray, (2) characterizing the airblast spray without a crossflow, and (3) characterizing the airblast spray upon injection into a crossflow. Geometric and operating conditions are varied in order to affect the atomization, penetration, and dispersion of the spray into the crossflow. The airblast spray is first characterized, using imaging techniques, as it issues into a quiescent environment. The spray breakup modes are classified in a liquid Reynolds number versus airblast Weber number regime chart. This work focuses on sprays formed by the "prompt" atomization mode, which induces a well-atomized and well-dispersed spray, and which also produces a two-lobed liquid distribution corresponding to the atomizing air passageways in the injector. The characterization of the spray jet injected into the crossflow reveals the different processes that control its dispersion. Correlations that describe the inner and outer boundaries of the spray jet are developed, using the definition of a two-phase momentum-flux ratio. Cross-sections of the liquid spray depict elliptically-shaped distributions, with the exception of the finely-atomized sprays which show kidney-shaped distributions reminiscent of those obtained in gaseous jet in crossflow systems. A droplet trajectory analysis overpredicts the liquid mass penetration, and indicates a need for a more rigorous model to account for the three-dimensional mixing field induced by the jet-crossflow interaction. Nonetheless, the general procedures and criteria that are outlined can be used to efficiently assess and compare the quality of sprays formed under different conditions.

Leong, May Y.↗

NASA NTRS2001

Development of a Neutron Spectrometer to Assess Biological Radiation Damage Behind Spacecraft Materials

Astronauts who spend months and years traveling long distances in spacecraft and working on other planets will be subjected to high energy radiation of galactic and solar origin without the protection of the Earth's thick (one writer has called it buff) atmosphere and magnetic field. The lack of natural protection will allow high energy cosmic ray particles and solar protons to crash directly into relatively thin spacecraft walls and planetary atmospheres producing energetic secondary particles in these collisions. A substantial fraction of these secondaries will be neutrons that carry no electric charge and, consequently, are difficult to detect. At sea level on Earth the remaining neutrons are the result of many generations (approximately 10) of collisions, have very low energies (scientists call them thermal neutrons), and do not penetrate deeply into the human body. They do contribute to the natural background radiation seen by humans on Earth, but much of the dose is only at the surface or skin of the body. In the International Space Station or on the surface of Mars, the secondary neutrons will be the result of only one or two generations of interaction due to the thinner (about a factor of 20 compared to the Earth's atmosphere) walls or atmosphere, have considerably more energy and penetrate deeply into the human body. In addition, neutrons are substantially moderated by hydrogenous material such as water. A significant fraction of the water exists in the astronaut's body. Therefore, the neutron can not only penetrate more deeply into the body, but also be stopped there and deposit all or most of its radiation dose in organs such as the liver, spleen, kidney, etc. We hypothesize that the risk of serious cancers will be increased for the exposed humans. The portable, real time neutron spectrometer being developed by our team will monitor the environment inside spacecraft structures and on planetary surfaces. Activities supported by this grant will evaluate the neutron environment inside several candidate spacecraft materials at accelerator facilities. These experiments will enable engineers to choose the structure materials that minimize the production of secondary neutrons. With the information that the neutron energy spectrometer produces, scientists and doctors will be able to assess the increased risk of cancer and develop countermeasures. The instrument itself will include an alarm system to warn astronauts when high radiation fluxes are occurring so that they can seek shelter immediately.

Maurer, R. H.↗

NASA NTRS2001

ISS Flight 2A.2B (STS-106): Commercial Generic Bioprocessing Apparatus (CGBA) Payload BioServe Space Technologies

The two experiments housed in the Commercial Generic Bioprocessing Apparatus (CGBA) during STS-106 were designed to explore how biological processes are affected by microgravity. The first was a developmental study into the effects of microgravity on motor-neuronal growth in the fruit fly species Drosophila melanogaster and the second study was designed to characterize changes in kidney cell gene expression. The objective of the primary experiment, called NIH-B1, was to determine how gravity affects neuronal development of the D. melanogaster embryo and larvae in microgravity, specifically observing the neural connections to muscle fibers.

Stodieck, Louis↗

NASA NTRS2001

Considerations for Medical Transport from the Space Station via an Assured Crew Return Vehicle (ACRV)

In developing a permanently crewed space station, the importance of medical care has been continually reaffirmed; and the health maintenance facility (HMF) is an integral component. It has diagnostic, therapeutic, monitoring, and information management capability. It is designed to allow supportive care for: (1) non-life-threatening illnesses; e.g., headache, lacerations; (2) moderate to severe, possibly life-threatening illnesses; e.g., appendicitis, kidney stones; and (3) severe, incapacitating, life-threatening illnesses; e.g., major trauma, toxic exposure. Since the HMF will not have a general surgical capability, the need for emergency escape and recovery methods has been studied. Medical risk assessments have determined that it is impossible to accurately predict the incidence of crewmember illness/injury. A best estimate is 1:3 per work-year, with 1% of these needing an ACRV. For an eight-person crew, this means that one assured crew return vehicle (ACRV) will be used every 4 to 12 years. The ACRV would serve at least three basic objectives as: (1) a crew return if the space shuttle is unavailable; (2) an escape vehicle from a major time-critical space station emergency; and (3) a full or partial crew return vehicle for a medical emergency. The focus of this paper is the third objective for the ACRV.

Stepaniak, Philip↗

NASA NTRS2001

Effects of Cage Type and NASA Rodent Food Bar in Male Sprague-Dawley Rats

Early prototype caging for the rodent Advanced Animal Habitat (P-AAH) for the International Space Station (ISS) is currently being tested. In this five week study, effects of the wire-bottom P-AAH cages and specialized NASA rodent food bars (FB) were compared to standard vivarium cages (VIV) with corn-cob, litter-filled bottoms, and standard Purina rat chow (CH). Ninety-six male Sprague-Dawley rats were divided into four treatment groups (24 rats/treatment): Group 1) VIV+CH, Group 2) P-AAH+CH, Group 3) VIV+FB, and Group 4) P-AAH+FB. Each VIV and P-AAH cage housed three and six rats, respectively. After five weeks of treatment rats were weighed, euthanized, and blood samples were collected. Weights of liver (LIV), kidney (KID), brain (BRN), epididymal fat (EPI), and perirenal fat (PERI) were also measured. Statistical analysis to compare differences between groups was performed by standard analysis of variance procedures (ANOVA) with a significance level of pLO.05. Results indicated P-AAH housed rats had significantly lower body weights (BW), LIV weights, and LIV/BW than VIV housed rats. FB fed rats had significantly lower blood urea nitrogen (BUN) levels and LIV/BW than CH fed rats. In addition, FB fed rats had significantly higher cholesterol (CHOL) levels, EPI/BW, PERI/BW, and total fat (EPI+PERI)/BW than CH fed rats. The P-AAH+FB group had significantly lower EPI, BRN, and total fat than VIV+FB rats. VIV+FB rats had significantly higher BRN, EPI, PERI, and total fat than VIV+CH rats. Triglycerides (TG), KID, KID/BW, and BRN/BW were not significantly different among treatment groups. These findings provide valuable information regarding cage design and food bar suitability for long-term use on the ISS.

Lau, Angela↗

NASA NTRS1995

Pros and Cons of Using Water Immersion to Simulate Physiological Responses to Microgravity

Head-out water immersion (HOI) has been employed as a remedial treatment for various ills and ailments for many millennia, and total body immersion even longer as protective encapsulation for the mammalian fetus. Two discrete differences between stimuli induced by true microgravity (10(exp -4) g) and HOI are readily apparent. External water pressure on the skin and accompanying negative pressure breathing cause blood to shift headward. Secondly, the gravitational force is ever present during immersion and microgravity, but its effect is essentially neutralized during Earth orbital flight. Thus, the physiological responses to immersion should not be expected to match those during microgravity. Immersion has been used mainly to study and understand kidney function and associated cardiovascular responses for control of body fluid volume and osmotic content, with some application to and simulation of microgravity responses. There is a plethora of data from human HOI studies, but relatively few controlled data from microgravity studies. In general, it appears that physiological responses occur more quickly with water immersion than in microgravity, but this may be due to less rigorous control (voluntary and involuntary) of the preflight state of crew members. The central venous pressure-vasopressin (Gauer-Henry) reflex control for fluid balance may not be of prime importance in microgravity. Gross functions such as reduced body weight and water, level of hypovolemia, decreased isokinetic strength, and lower nitrogen balance found during immersion are qualitatively similar in microgravity, but the mechanisms controlling these and other functions are, for the most part, unclear. Only acquisition of data from well-controlled microgravity experiments will resolve this discrepancy.

Greenleaf, J. E.↗

NASA NTRS2002

Insertional Mutagenesis for Genes involved in Otic/Vestibular Development and Function in Xenopus Tropicalis

Sensitivity to gravity is essential for spatial orientation. Consequently, the gravity receptor system is one of the phylogenetically oldest sensory systems, and the special adaptations that enhance sensitivity to gravity are highly conserved. The main goal of this project is to use Xenopus (frog) to identify genes expressed during vestibular and auditory development. These studies will lead a better understanding of the molecular mechanisms involved in vestibular and auditory development and function. We are using a gene-trap approach in Xenopus tropicalis with the green fluorescent protein (GFP) gene as the transgene reporter. GFP expression occurs only when the GFP gene is correctly integrated in actively transcribed genes. Using the GFP as a tag we can easily identify and clone the mutated gene. In addition, we can study the function of the mutated gene by analyzing the defects generated by insertion of the GFP transgene. To date we have tissue specific GFP expression in X. tropicalis including expression in ear, neural tube, kidney, muscle, eyes and nose. Our transgenic animals will soon reach maturity so that we can outcross them and analyze their progeny. Our next goal is to isolate RNA from our transgenics and clone the tagged genes using RACE-PCR. Currently we are optimizing the RACE-PCR method using transgenics with crystallin GFP expression.

Torrejon, Marcela↗

NASA NTRS1992

Critical Care Dialysis System

Organon Teknika Corporation's REDY 2000 dialysis machine employs technology originally developed under NASA contract by Marquardt Corporation. The chemical process developed during the project could be applied to removing toxic waste from used dialysis fluid. This discovery led to the development of a kidney dialysis machine using "sorbent" dialysis, a method of removing urea from human blood by treating a dialysate solution. The process saves electricity and, because the need for a continuous water supply is eliminated, the patient has greater freedom.

Source record↗

NASA NTRS2003

Summary of Research Adaptions of Visceral and Cerebral Resistance Arteries to Simulated Microgravity

The proposed studies were designed address the effects of simulated microgravity on vascular smooth muscle and endothelial cell function in resistance arteries isolated from visceral tissues (spleen, mesentery and kidneys) and cerebrum. Alterations in vascular function induced by microgravity are particularly relevant to the problems of orthostatic intolerance and reduced exercise capacity experienced by astronauts upon re-entry into the earth's gravitational field. Decrements in contractile function or enhanced vasodilatory responsiveness of peripheral resistance arteries could lead to decreased peripheral resistance and orthostatic hypotension. Alternatively, augmentation of contractile function in cerebral resistance arteries could lead to increased cerebral vascular resistance and diminished perfusion of the brain. The Specific Aims and hypotheses were proposed in this grant. Following each of the Specific Aims, progress toward addressing that specific aim is presented. With the exception of Specific Aim VI (see aim for details), all aims have been experimentally addressed as proposed. The final six months of the granting period will be used for manuscript preparation; manuscripts in preparation will contain results from Specific Aims I-IV. Results from Specific Aims V and VI have been published.

Delp, Michael↗

NASA NTRS2003

Nitric oxide in microgravity-induced orthostatic intolerance: relevance to spinal cord injury

Prolonged exposure to microgravity results in cardiovascular deconditioning which is marked by orthostatic intolerance in the returning astronauts and recovering bed-ridden patients. Recent studies conducted in our laboratories at University of California, Irvine have revealed marked elevation of nitric oxide (NO) production in the kidney, heart, brain, and systemic arteries coupled with significant reduction of NO production in the cerebral arteries of microgravity-adapted animals. We have further demonstrated that the observed alteration of NO metabolism is primarily responsible for the associated cardiovascular deconditioning. Recovery from acute spinal cord injury (SCI) is frequently complicated by orthostatic intolerance that is due to the combined effects of the disruption of efferent sympathetic pathway and cardiovascular deconditioning occasioned by prolonged confinement to bed. In this presentation, I will review the nature of altered NO metabolism and its role in the pathogenesis of microgravity-induced cardiovascular deconditioning. The possible relevance of the new findings to orthostatic intolerance in patients with acute SCI and its potential therapeutic implications will be discussed.

Review↗

NASA NTRS2003

Isolation and characterization of a novel gene sfig in rat skeletal muscle up-regulated by spaceflight (STS-90)

We obtained the skeletal muscle of rats exposed to weightless conditions during a 16-day-spaceflight (STS-90). By using a differential display technique, we identified 6 up-regulated and 3 down-regulated genes in the gastrocnemius muscle of the spaceflight rats, as compared to the ground control. The up-regulated genes included those coding Casitas B-lineage lymphoma-b, insulin growth factor binding protein-1, titin and mitochondrial gene 16 S rRNA and two novel genes (function unknown). The down-regulated genes included those encoding RNA polymerase II elongation factor-like protein, NADH dehydrogenase and one novel gene (function unknown). In the present study, we isolated and characterized one of two novel muscle genes that were remarkably up-regulated by spaceflight. The deduced amino acid sequence of the spaceflight-induced gene (sfig) comprises 86 amino acid residues and is well conserved from Drosophila to Homo sapiens. A putative leucine-zipper structure located at the N-terminal region of sfig suggests that this gene may encode a transcription factor. The up-regulated expression of this gene, confirmed by Northern blot analysis, was observed not only in the muscles of spaceflight rats but also in the muscles of tail-suspended rats, especially in the early stage of tail-suspension when gastrocnemius muscle atrophy initiated. The gene was predominantly expressed in the kidney, liver, small intestine and heart. When rat myoblastic L6 cells were grown to 100% confluence in the cell culture system, the expression of sfig was detected regardless of the cell differentiation state. These results suggest that spaceflight has many genetic effects on rat skeletal muscle.

STS-90 Shuttle Project↗

NASA NTRS2002

Renal effects of fresh water-induced hypo-osmolality in a marine adapted seal

With few exceptions, marine mammals are not exposed to fresh water; however quantifying the endocrine and renal responses of a marine-adapted mammal to the infusion of fresh water could provide insight on the evolutionary adaptation of kidney function and on the renal capabilities of these mammals. Therefore, renal function and hormonal changes associated with fresh water-induced diuresis were examined in four, fasting northern elephant seal ( Mirounga angustirostris) (NES) pups. A series of plasma samples and 24-h urine voids were collected prior to (control) and after the infusion of water. Water infusion resulted in an osmotic diuresis associated with an increase in glomerular filtration rate (GFR), but not an increase in free water clearance. The increase in excreted urea accounted for 96% of the increase in osmotic excretion. Following infusion of fresh water, plasma osmolality and renin activity decreased, while plasma aldosterone increased. Although primary regulators of aldosterone release (Na(+), K(+) and angiotensin II) were not significantly altered in the appropriate directions to individually stimulate aldosterone secretion, increased aldosterone may have resulted from multiple, non-significant changes acting in concert. Aldosterone release may also be hypersensitive to slight reductions in plasma Na(+), which may be an adaptive mechanism in a species not known to drink seawater. Excreted aldosterone and urea were correlated suggesting aldosterone may regulate urea excretion during hypo-osmotic conditions in NES pups. Urea excretion appears to be a significant mechanism by which NES pups sustain electrolyte resorption during conditions that can negatively affect ionic homeostasis such as prolonged fasting.

NASA Center ARC↗

NASA NTRS2002

Continuous pH monitoring in a perfused bioreactor system using an optical pH sensor

Monitoring and regulating the pH of the solution in a bioprocess is one of the key steps in the success of bioreactor operation. An in-line optical pH sensor, based on the optical absorption properties of phenol red present in the medium, was developed and tested in this work for use in NASA space bioreactors based on a rotating wall-perfused vessel system supporting a baby hamster kidney (BHK-21) cell culture. The sensor was tested over three 30-day and one 124-day cell runs. The pH sensor initially was calibrated and then used during the entire cell culture interval. The pH reported by the sensor was compared to that measured by a fiber optically coupled Shimadzu spectrophotometer and a blood gas analyzer. The maximum standard error of prediction for all the four cell runs for development pH sensor against BGA was +/-0.06 pH unit and for the fiber optically coupled Shimadzu spectrophotometer against the blood gas analyzer was +/-0.05 pH unit. The pH sensor system performed well without need of recalibration for 124 days. Copyright 2002 Wiley Periodicals, Inc.

Bioreactors↗

NASA NTRS2002

Renal responses to plasma volume expansion and hyperosmolality in fasting seal pups

Renal responses were quantified in northern elephant seal (Mirounga angustirostris) pups during their postweaning fast to examine their excretory capabilities. Pups were infused with either isotonic (0.9%; n = 8; Iso) or hypertonic (16.7%; n = 7; Hyper) saline via an indwelling catheter such that each pup received 3 mmol NaCl/kg. Diuresis after the infusions was similar in magnitude between the two treatments. Osmotic clearance increased by 37% in Iso and 252% in Hyper. Free water clearance was reduced 3.4-fold in Hyper but was not significantly altered in Iso. Glomerular filtration rate increased 71% in the 24-h period after Hyper, but no net change occurred during the same time after Iso. Natriuresis increased 3.6-fold in Iso and 5.3-fold in Hyper. Iso decreased plasma arginine vasopressin (AVP) and cortisol acutely, whereas Hyper increased plasma and excreted AVP and cortisol. Iso was accompanied by the retention of water and electrolytes, whereas the Hyper load was excreted within 24 h. Natriuresis is attributed to increased filtration and is independent of an increase in atrial natriuretic peptide and decreases in ANG II and aldosterone. Fasting pups appear to have well-developed kidneys capable of both extreme conservation and excretion of Na(+).

NASA Center ARC↗

NASA NTRS2001

Evolution and development of the vertebrate ear

This review outlines major aspects of development and evolution of the ear, specifically addressing issues of cell fate commitment and the emerging molecular governance of these decisions. Available data support the notion of homology of subsets of mechanosensors across phyla (proprioreceptive mechanosensory neurons in insects, hair cells in vertebrates). It is argued that this conservation is primarily related to the specific transducing environment needed to achieve mechanosensation. Achieving this requires highly conserved transcription factors that regulate the expression of the relevant structural genes for mechanosensory transduction. While conserved at the level of some cell fate assignment genes (atonal and its mammalian homologue), the ear has also radically reorganized its development by implementing genes used for cell fate assignment in other parts of the developing nervous systems (e.g., neurogenin 1) and by evolving novel sets of genes specifically associated with the novel formation of sensory neurons that contact hair cells (neurotrophins and their receptors). Numerous genes have been identified that regulate morphogenesis, but there is only one common feature that emerges at the moment: the ear appears to have co-opted genes from a large variety of other parts of the developing body (forebrain, limbs, kidneys) and establishes, in combination with existing transcription factors, an environment in which those genes govern novel, ear-related morphogenetic aspects. The ear thus represents a unique mix of highly conserved developmental elements combined with co-opted and newly evolved developmental elements.

Review↗

NASA NTRS1988

Dynamic cell culture system: a new cell cultivation instrument for biological experiments in space

The prototype of a miniaturized cell cultivation instrument for animal cell culture experiments aboard Spacelab is presented (Dynamic cell culture system: DCCS). The cell chamber is completely filled and has a working volume of 200 microliters. Medium exchange is achieved with a self-powered osmotic pump (flowrate 1 microliter h-1). The reservoir volume of culture medium is 230 microliters. The system is neither mechanically stirred nor equipped with sensors. Hamster kidney (Hak) cells growing on Cytodex 3 microcarriers were used to test the biological performance of the DCCS. Growth characteristics in the DCCS, as judged by maximal cell density, glucose consumption, lactic acid secretion and pH, were similar to those in cell culture tubes.

NASA Program Flight↗