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At least 1,351 records · Page 75

Changes in renal function and fluid and electrolyte regulation in space flight

The cephalad fluid redistribution resulting from weightlessness has a number of physiologic consequences. Plasma volume is reduced soon after weightlessness is reached, and red blood cell mass reduction follows. Plasma atrial natriuretic peptide, which inhibits aldosterone secretion, was elevated during space flight while plasma aldosterone was below preflight levels. Serum sodium was also reduced and potassium was elevated. Antidiuretic hormone (ADH) was markedly elevated at almost all measurement times in the first eight days of flight, but plasma volume did not return to preflight levels.

Leach, C. S.↗

Ethylene-Vapor Optrodes

Porous optical fibers include sensing regions filled with reagents. Optical-fiber chemical sensors (optrodes) developed to measure concentrations of ethylene in air in enclosed artificial plant-growth environments. Such measurements needed because ethylene acts as plant-growth hormone affecting growth at concentrations less than or equal to 20 parts per billion. Optrodes small, but exhibit sensitivities comparable to those of larger instruments. Operated safely in potentially explosive atmospheres and neither cause, nor susceptible to, electrical interference at suboptical frequencies.

Tabacco, Mary Beth↗

Effect of hemorrhage on cardiac output, vasopressin, aldosterone, and diuresis during immersion in men

The purpose of this research was to test the hypotesis that a reduction in blood volume would attenuate or eliminate immersion-induced increases in cardiac output (Q(sub co)) and urine excretion, and to investigate accompanying vasoactive and fluid-electrolyte hormonal responses. Eight men (19-23 yr) were supine during a 2-hr control period in air, and then sat for 5-hr test periods in air at 20 C (dry control, DC); water at 34.5 C (wet control, WC); and water (34.5 C) after hemorrhage (WH) of 14.8 plus or minus 0.3 percent of their blood volume. Blood volume was -11.6 plus or minus 0.6 percent at immersion (time 0). Mean (bar-X hrs 1-5) Q(sub co) was unchanged in WC (5.3 plus or minus 0.01 l/min) and in WH (4.5 plus or minus 0.1 l/min), but decreased (P less than 0.05) in DC to 3.6 plus or minus 0.1 l/min. Mean urine excretion rates were 1.0 plus or minus 0.2 ml/min for DC and 1.1 plus or minus 0.2 ml/min for WH; both were lower (P less than 0.05) than that for WC of 2.0 plus or minus 0.4 ml/min. Plasma (Na+) and (Osm) were unchanged in all experiments. Mean plasma vasopressin (PVP) (bar-X hrs 1-5) was 1.1 plus or minus 0.1 pg/ml in WC, and higher (P less than 0.05) in DC (2.1 plus or minus 0.2 pg/ml)and WH (2.1 plus or minus 0.1 pg/ml); it was unchanged during air and water test periods. Thus, hemorrhage attenuated the immersion-induced increase in Q(sub co), eliminated the WC diuresis, maintained plasma renin activity and PVP at DC levels and did not change immersion-induced aldosterone suppression; the osmotic diuresis during control immersion is apparently not due to either aldosterone suppression or vasopressin suppression.

Greenleaf, J. E.↗

Large scale crystallization of protein pharmaceuticals in microgravity via temperature change

The major objective of this research effort is the temperature driven growth of protein crystals in large batches in the microgravity environment of space. Pharmaceutical houses are developing protein products for patient care, for example, human insulin, human growth hormone, interferons, and tissue plasminogen activator or TPA, the clot buster for heart attack victims. Except for insulin, these are very high value products; they are extremely potent in small quantities and have a great value per gram of material. It is feasible that microgravity crystallization can be a cost recoverable, economically sound final processing step in their manufacture. Large scale protein crystal growth in microgravity has significant advantages from the basic science and the applied science standpoints. Crystal growth can proceed unhindered due to lack of surface effects. Dynamic control is possible and relatively easy. The method has the potential to yield large quantities of pure crystalline product. Crystallization is a time honored procedure for purifying organic materials and microgravity crystallization could be the final step to remove trace impurities from high value protein pharmaceuticals. In addition, microgravity grown crystals could be the final formulation for those medicines that need to be administered in a timed release fashion. Long lasting insulin, insulin lente, is such a product. Also crystalline protein pharmaceuticals are more stable for long-term storage. Temperature, as the initiation step, has certain advantages. Again, dynamic control of the crystallization process is possible and easy. A temperature step is non-invasive and is the most subtle way to control protein solubility and therefore crystallization. Seeding is not necessary. Changes in protein and precipitant concentrations and pH are not necessary. Finally, this method represents a new way to crystallize proteins in space that takes advantage of the unique microgravity environment. The results from two flights showed that the hardware performed perfectly, many crystals were produced, and they were much larger than their ground grown controls. Morphometric analysis was done on over 4,000 crystals to establish crystal size, size distribution, and relative size. Space grown crystals were remarkably larger than their earth grown counterparts and crystal size was a function of PCF volume. That size distribution for the space grown crystals was a function of PCF volume may indicate that ultimate size was a function of temperature gradient. Since the insulin protein concentration was very low, 0.4 mg/ml, the size distribution could also be following the total amount of protein in each of the PCF's. X-ray analysis showed that the bigger space grown insulin crystals diffracted to higher resolution than their ground grown controls. When the data were normalized for size, they still indicated that the space crystals were better than the ground crystals.

Long, Marianna M.↗

Measuring the metastatic potential of cancer cells

Cancer cells must secrete proteolytic enzymes to invade adjacent tissues and migrate to a new metastatic site. Urokinase (uPA) is a key enzyme related to metastasis in cancers of the lung, colon, gastric, uterine, breast, brain, and malignant melanoma. A NASA technology utilization project has combined fluorescence microscopy, image analysis, and flow cytometry, using fluorescent dyes, and urokinase-specific antibodies to measure uPA and abnormal DNA levels (related to cancer cell proliferation) inside the cancer cells. The project is focused on developing quantitative measurements to determine if a patient's tumor cells are actively metastasizing. If a significant number of tumor cells contain large amounts of uPA (esp. membrane-bound) then the post-surgical chemotherapy or radiotherapy can be targeted for metastatic cells that have already left the primary tumor. These analytical methods have been applied to a retrospective study of biopsy tissues from 150 node negative, stage 1 breast cancer patients. Cytopathology and image analysis has shown that uPA is present in high levels in many breast cancer cells, but not found in normal breast. Significant amounts of uPA also have been measured in glioma cell lines cultured from brain tumors. Commercial applications include new diagnostic tests for metastatic cells, in different cancers, which are being developed with a company that provides a medical testing service using flow cytometry for DNA analysis and hormone receptors on tumor cells from patient biopsies. This research also may provide the basis for developing a new 'magic bullet' treatment against metastasis using chemotherapeutic drugs or radioisotopes attached to urokinase-specific monoclonal antibodies that will only bind to metastatic cells.

Morrison, Dennis R.↗

STS-46 Space Shuttle mission report

The STS-46 Space Shuttle Program Mission Report contains a summary of the Orbiter, External Tank (ET), Solid Rocket Booster/Redesigned Solid Rocket Motor (SRB/RSRM), and the Space Shuttle main engine (SSME) subsystem performance during the forty-ninth flight of the Space Shuttle Program, and the twelfth flight of the Orbiter vehicle Atlantis (OV-104). In addition to the Atlantis vehicle, the flight vehicle consisted of the following: an ET, designated ET-48 (LWT-41); three SSME's, which were serial numbers 2032, 2033, and 2027 in positions 1, 2, and 3, respectively; and two SRB's which were designated BI-052. The lightweight/redesigned SRM's that were installed in each SRB were designated 360W025A for the left RSRM and 360L025B for the right RSRM. The primary objective of this flight was to successfully deploy the European Retrievable Carrier (EURECA) payload and perform the operations of the Tethered Satellite System-1 (TSS-1) and the Evaluation of Oxygen Interaction with Material 3/Thermal Energy Management Processes 2A-3 (EOIM-3/TEMP 2A-3). The secondary objectives of this flight were to perform the operations of the IMAX Cargo Bay Camera (ICBC), Consortium for Material Development in Space Complex Autonomous Payload-2 and 3 (CONCAP-2 and CONCAP-3), Limited Duration Space Environment Candidate Materials Exposure (LDCE), Pituitary Growth Hormone Cell Function (PHCF), and Ultraviolet Plume Instrumentation (UVPI). In addition to summarizing subsystem performance, this report also discusses each Orbiter, ET, SSME, SRB, and RSRM in-flight anomaly in the applicable section of the report. Also included in the discussion is a reference to the assigned tracking number as published on the Problem Tracking List. All times are given in Greenwich mean time (G.m.t.) as well as mission elapsed time (MET).

Fricke, Robert W.↗

Beta-endorphin and arginine vasopressin following stressful sensory stimuli in man

This experimentation partially defines, for the first time, the response of beta-endorphin (ENDO) in man during tests designed to elicit nausea and motion sickness. These responses are similar to those associated with arginine vasopressin (AVP) and adreno-corticotropin (ACTH) to the extent that all hormones rise in response to motion sickness (p less than 0.003). Repeated exposure diminished motion-induced release of ENDO (p less than 0.005) and AVP (p less than 0.004) despite a three-fold increase in resistance to motion stimuli. Higher post-stress levels of AVP (p less than 0.04) and ACTH (p less than 0.02) were correlated with greater resistance to motion sickness. These data support the hypothesis that release of AVP is a significant link between stressful motion and motion-induced nausea and other autonomic system changes. Further, resistant individual apparently can tolerate higher peripheral levels of AVP before nausea results. Peripheral release of ENDO and ACTH may follow release of AVP; however, given the extensive and complex functional interactions that exist between AVP and the opiate systems, it is not yet possible to define a clear role for ENDO in the etiology of motion sickness.

Kohl, Randall L.↗

Development of lower body negative pressure as a countermeasure for orthostatic intolerance

Exposure to prolonged (1-4 hr) lower body negative pressure (LBNP) is a countermeasure against postflight orthostatic intolerance which is used in the Soviet space program and planned for use in the American space program. LBNP in combination with fluid-loading is believed to act by promoting a transient positive fluid balance resulting in an increase in vascular, as well as extravascular fluid. Inflight LBNP also may provide beneficial orthostatic effects by restoring baroreceptor reflex functions and/or lower body venous compliance. Current research efforts at the Johnson Space Center are directed toward increasing the effectiveness and efficiency of the LBNP and saline countermeasure. A promising avenue may involve combining pharmacologic agents, such as inhaled anti-diuretic hormone, or mineralocorticoids, with mechanical stimuli such as LBNP.

Fortney, Suzanne M.↗

Metabolic changes observed in astronauts

Results of medical experiments with astronauts reveal rapid loss of volume (2 l) from the legs and a transient early increase in left ventricular volume index. These findings indicate that, during space flight, fluid is redistributed from the legs toward the head. In about 2 days, total body water decreases 2 to 3 percent. Increased levels of plasma renin activity and antidiuretic hormone while blood sodium and plasma volume are reduced suggest that space flight-associated factors are influencing the regulatory systems. In addition to fluid and electrolyte loss, Skylab astronauts lost an estimated 0.3 kg of protein. Endocrine factors, including increased cortisol and thyroxine and decreased insulin, are favorable for protein catabolism. The body appears to adapt to weightlessness at some physiologic cost. Readaptation to earth's gravity at landing becomes another physiologic challenge.

Leach, Carolyn S.↗

Altered cell function in microgravity

The paper overviews published results from investigations of changes in basic biological parameters taking place as a result of spaceflight exposure. These include changes in the rates of the DNA, mRNA, and protein biosyntheses; changes in the growth rate of an organism; and alterations in the cytoskeleton structure, differentiation, hormone accumulation, and collagen matrix secretion. These results, obtained both in complex biological organisms and on cultured cells, suggest that a basic cellular function is influenced and changed by microgravity. Many of the above mentioned changes are also found to take place in aging cells.

Hughes-Fulford, Millie↗

Melatonin in human preovulatory follicular fluid

Melatonin, the major hormone of the pineal gland, has antigonadotrophic activity in many mammals and may also be involved in human reproduction. Melatonin suppresses steroidogenesis by ovarian granulosa and luteal cells in vitro. To determine if melatonin is present in the human ovary, preovulatory follicular fluids (n = 32) from 15 women were assayed for melatonin by RIA after solvent extraction. The fluids were obtained by laparoscopy or sonographically controlled follicular puncture from infertile women undergoing in vitro fertilization and embryo transfer. All patients had received clomiphene citrate, human menopausal gonadotropin, and hCG to stimulate follicle formation. Blood samples were obtained by venipuncture 30 rain or less after follicular aspiration. All of the follicular fluids contained melatonim, in concentrations substantially higher than those in the corresponding serum. A positive correlation was found between follicular fluid and serum melatonin levels in each woman; these observations indicate that preovulatory follicles contain substantial amounts of melatonin that may affect ovarian steroidogenesis.

Brzezinski, Amnon↗

Body fluid alterations during head-down bed rest in men at moderate altitude

To determine the effects of hypoxia on fluid balance responses to simulated zero-gravity, measurements were made in six subjects before and during -5 deg continuous head-down bed rest (HDBR) over 8 d at 10,678 ft. The same subjects were studied again at this altitude without HDBR as a control (CON) using a cross-over design. During this time, they maintained normal upright day-time activities, sleeping in the horizontal position at night. Fluid balance changes during HDBR in hypoxia were more pronounced than similar measurements previously reported from HDBR studies at sea level. Plasma volume loss was slightly greater and the diuresis and natriuresis were doubled in magnitude as compared to previous studies in normoxia and sustained for 4 d during hypoxia. These changes were associated with an immediate but transient rise in plasma atrial natriuretic peptide (ANP) to day 4 of 140 percent in HDBR and 41 percent in CON (p less than 0.005), followed by a decline towards baseline. Differences were less striking between HDBR and CON for plasma antidiuretic hormone and aldosterone, which were transiently reduced by HDBR. Plasma catecholamines showed a similar pattern to ANP in both HDBR and CON, suggesting that elevated ANP and catecholamines together accounted for the enhanced fluid shifts with HDBR during hypoxia.

Loeppky, J. A.↗

Melatonin in human preovulatory follicular fluid

Melatonin, the major hormone of the pineal gland, has antigonadotrophic activity in many mammals and may also be involved in human reproduction. Melatonin suppresses steroidogenesis by ovarian granulosa and luteal cells in vitro. To determine if melatonin is present in the human ovary, preovulatory follicular fluids (n = 32) from 15 women were assayed for melatonin by RIA after solvent extraction. The fluids were obtained by laparoscopy or sonographically controlled follicular puncture from infertile women undergoing in vitro fertilization and embryo transfer. All patients had received clomiphene citrate, human menopausal gonadotropin, and hCG to stimulate follicle formation. Blood samples were obtained by venipuncture 30 min or less after follicular aspiration. All of the follicular fluids contained melatonin, in concentrations (35.6 plus or minus 4.8 (plus or minus SEM) pg/mL) substantially higher than those in the corresponding serum (10.0 plus or minus 1.4 pg/mL). A positive correlation was found between follicular fluid and serum melatonin levels in each woman (r = 0.770; P less than 0.001). These observations indicate that preovulatory follicles contain substantial amounts of melatonin that may affect ovarian steroidogenesis.

Brzezinski, Amnon↗

Effect of prolonged LBNP and saline ingestion on plasma volume and orthostatic responses during bed rest

Orthostatic intolerance remains a significant problem following space flight despite frequent use of the saline fluid-loading countermeasure and volitional use of an anti-gravity suite during reentry and landing. The purpose of this project is to examine the plasma volume (PV), endocrine, and orthostatic responses of bedrested subjects following 2-hr and 4-hr treatments of lower body negative pressure (LBNP) and saline ingestion. Ten healthy men were randomly assigned into 2 groups. Group A underwent a 4-hr LBNP/saline treatment on best rest day 5 and the 2-hr treatment on day 11. Group B underwent the 2-hr treatment on day 6 and the 4-hr treatment on day 10. Blood volume was determined before and after bed rest using radiolabelling. Changes in PV between measurements were calculated from changes in hematocrit and estimated red cell volume. Urinary excretion of anti-diuretic hormone (ADH) and aldosterone (ALD) were measured each day during the study. Orthostatic responses were measured using a ramp LBNP protocol before bed rest, before each treatment, and 24 hours after each treatment. Both 2-hr and 4-hr treatments resulted in a restoration of PV to pre-bed rest levels which persisted at least 24 hours. This increase in PV was associated with significant increases in urinary excretion of ADH and ALD. Twenty-four hours after the 4-hr treatment, the heart rate and pulse pressure response to LBNP were significantly lower and stroke volumes during LBNP were increased. Twenty-four hours after the 2-hr treatment, there was no evidence of improvement in orthostatic responses. These results suggest that a countermeasure which simply restores PV during space flight may not be sufficient for restoring orthostatic responses.

Fortney, Suzanne M.↗

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

Endocrine regulation of fluids and electrolytes during seven days of 6 deg 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 hr 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/K ratio and significant Na retention on reambulation. After the first day of HDBR, plasma renin activity (PRA) was increased relative to aldosterone, plasma volume was decreased, and the renal response to aldosterone appeared to be appropriate. Circulating levels of arginine vasopressin (AVP), cortisol, and ACTH were unchanged during HDBR. Plasma testosterone decreased slightly on day 2 of HDBR in males. The ratio of AM 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 day 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 bed rest 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 aldosterone responses to standing before bedrest and larger aldosterone responses to standing after HDBR than males. Cardiovascular responses to standing before and after bedrest differed markedly: arterial pressure and heart rates increased with standing before HDBR, by contrast, arterial pressure decreased, with greater increases in heart rates after HDBR. In both sexes, all hormonal responses to standing were greater after HDBR. The results show clearly that similar responses to standing as well as to HDBR occur in both sexes, but that females exhibit greater PRA and aldosterone responses than males.

Vernikos, J.↗

Clinical physiology of bed rest

Maintenance of optimal health in humans requires the proper balance between exercise, rest, and sleep as well as time in the upright position. About one-third of a lifetime is spent sleeping; and it is no coincidence that sleeping is performed in the horizontal position, the position in which gravitational influence on the body is minimal. Although enforced bed rest is necessary for the treatment of some ailments, in some cases it has probably been used unwisely. In addition to the lower hydrostatic pressure with the normally dependent regions of the cardiovascular system, body fuid compartments during bed rest in the horizontal body position, and virtual elimination of compression on the long bones of the skeletal system during bed rest (hypogravia), there is often reduction in energy metabolism due to the relative confinement (hypodynamia) and alteration of ambulatory circadian variations in metabolism, body temperature, and many hormonal systems. If patients are also moved to unfamiliar surroundings, they probably experience some feelings of anxiety and some sociopsychological problems. Adaptive physiological responses during bed rest are normal for that environment. They are attempts by the body to reduce unnecessary energy expenditure, to optimize its function, and to enhance its survival potential. Many of the deconditioning responses begin within the first day or two of bed rest; these early responses have prompted physicians to insist upon early resumption of the upright posture and ambulation of bedridden patients.

Greenleaf, John E.↗

Amphibian fertilization and development in microgravity

During the year before launch, female frogs will be tested every 3 months for the quantity and quality of eggs produced. Two weeks or more prior to launch, male and female frogs will be transported to the John F. Kennedy Space Center (KSC). During the few weeks before launch, groups will be periodically tested for egg quality to assure that the frogs have adapted to the KSC laboratory environment. About 27 hours before launch, four females will be placed in a damp foam-lined box, called the Adult Frog Box (AFB), through which 100 cc/min of air wil be circulated. The AFB will be lowered into the Spacelab and loaded into the Frog Environmental Unit (FEU) during the final pre-launch preparations. A sperm suspension, for use in flight to fertilize the eggs, will also be prepared and loaded during the pre-launch period. The sperm suspension, together with a kit of syringes containing Human Chorionic Gonadotropin (HCG), will be stored in a refrigerator aboard the shuttle until needed in flight. On the first day of flight, the AFB will be transferred from the FEU to the General Purpose Work Station (GPWS), which is a type of glove box specially designed to allow the crew to use chemicals and biological materials during the flight without contaminating the shuttle/Spacelab environment. Inside the GPWS the four adult frogs will be injected with the HCG hormone and returned to the FEU. Approximately 16 hours after injection, ovulation should have taken place and 15 to 20 eggs from each frog will be placed on each of two egg baskets and covered with sperm for 10 minutes. The egg baskets are inserted into acrylic egg chambers and 50 ml of 'pond water' (20 percent strength Modified Ringers solution (is added. One of the chambers from each frog will be placed on a centrifuge within the FEU and rotated to simulate normal terrestrial gravity (1 g). The remaining chambers are incubated under microgravity conditions within the FEU. Forty minutes after fertilization, the four chambers exposed to 1 g will be removed and observed within the GPWS using a dissecting microscope and camera system. On the basis of egg rotation and egg appearance, the 'best' and 'second best' frogs will be selected to contribute additional eggs. Using the two best frogs, 22 egg chambers will be loaded with eggs and fertilized. Eleven chambers wil be incubated at microgravity and eleven will be incubated on the centrifuge. At various times during the flight, chambers will be removed from the FEU and transferred to the GPWS where a formaldehyde-based fixative will be injected in order to preserve important developmental stages for in depth study following the flight. Five of the 22 chambers plus the eight fertilization test chambers will be returned to Earth with live tadpoles. The swimming behavior of these free swimming tadpoles will be examined within several hours of landing and some will be fixed for a detailed analysis of their inner ear, the otolity, the animals 'balance system.' Lychakov and Vinikov reported an increase in otolith size in tadpoles that developed (but were not fertilized) in space. Live tadpoles from the SL-J flight will be raised through metamorphsis for studies of maturation including an analysis of the effects of space flight on their ability to produce normal progency. Following the flight, the fixed embryos will be serially sectioned and stained using procedures that were developed for this experiment. The embroys fixed at the 2-4 cell stage will be examined for the distribution of cytoplasmic contents, including the various classes of yolk platelets, and the location and shape of the cleavage furrows. The gastrulae will be assessed for the normality of the complex cellular rearrangements that constitute blastopore formation and involution, i.e., the differentiation of the embryo into its specialized body parts. Using a new procedure, the gastrulae will be bleached which will enable the initial sperm entry point (SEP) to be located. The correlation between the SEP and the dorsal lip of the blastopore will be determined. Under normal terrestrial conditions it was shown that the SEP typically is located on the side of the egg opposite the future dorsal side of the embryo. The neurulae will be examined for the normality and completeness of the neural plate and archenteron expansion. The tadpole stages will be used to study the allometry and morphology of the various organ systems.

Souza, Kenneth A.↗

Strategies for enhancing catecholamine-mediated neurotransmission

Major findings made during this project period included the following observations: changes in tyrosine availability do affect brain dopamine release, as assessed by in vivo microdialysis, but that neuronal feedback mechanisms limit the durations of this effect except when dopaminergic neurotransmission has been deficient; the circulating hormone TRH markedly stimulates brain dopamine release, an effect probably mediated by its diketopiperazine metabolite; the amount of circulating L-dopa which enters the brain is both enhanced by carbohydrate consumption and suppressed by protein intake (both nutritional effects can be damaging, inasmuch as a sudden rush of L-dopa into the brain can facilitate dyskinesias, while the inhibition of brain L-dopa uptake by proteins suppresses its conversion to brain dopamine; an appropriate mixture of dietary proteins and carbohydrates can obviate both effects); serotonin release from superfused hypothalamic slices is a linear function of available tryptophan levels throughout the normal dynamic range; the daily rhythm in plasma melatonin levels is abnormal both in the sudden infant death syndrome and in women with secondary amenorrhea; tyrosine can potentiate the anorectic effects of widely-used sympathomimetic drugs; newly-described COMT inhibitors can enhance brain dopamine release in vivo; and a cell culture system, based on Y-79 (retinoblast) cells, exists in which melatonin reliably suppresses dopamine release.

Wurtman, Richard J.↗