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At least 1,585 records · Page 88

Enkephalin inhibition of angiotensin-stimulated release of oxytocin and vasopressin

The effect of intracerebroventricular (ICV) pretreatment with 100 ng/5 microliter leucine(5)-enkephalin (LE) on the increase in plasma oxytocin (OT) and vasopressin (VP) caused by ICV injection of 10, 50, or 100 ng/5 microliter of angiotensin II (AII) is investigated experimentally in conscious adult male Sprague-Dawley rats; the effects of water-deprivation dehydration and lactation/suckling (in female rats) are also studied. An OT radioimmunoassay (RIA) with a sensitivity of 800 fg/ml (described in detail) and the VP RIA technique of Keil and Severs (1977) are employed. Administration of AII or dehydration for 48 or 72 h cause a significant increase in OT and VP without affecting the ratio, while lactation and suckling increase OT only. LE pretreatment inhibits significantly but does not suppress the AII-stimulated OT-VP response.

Keil, L. C.↗

Purification and cultivation of human pituitary growth hormone secreting cells

A multiphase study was conducted to examine the properties of growth hormone cells. Topics investigated included: (1) to determine if growth hormone (GH) cells contained within the rat pituitary gland can be separated from the other hormone producing cell types by continuous flow electrophoresis (CFE); (2) to determine what role, if any, gravity plays in the electrophoretic separation of GH cells; (3) to compare in vitro GH release from rat pituitary cells previously exposed to microgravity conditions vs release from cells not exposed to microgravity; (4) to determine if the frequency of different hormone producing pituitary cell types contained in cell suspensions can be quantitated by flow cytometry; and (5) to determine if GH contained within the human post mortem pituitary gland can be purified by CFE. Specific experimental procedures and results are included.

Hymer, W. C.↗

Mammalian Gravity Receptors: Structure and Metabolism

Calcium metabolism in mammalian gravity receptors is examined. To accomplish this objective it is necessary to study both the mineral deposits of the receptors, the otoconia, and the sensory areas themselves, the saccular and utricular maculas. The main focus was to elucidate the natures of the organic and inorganic phases of the crystalline masses, first in rat otoconia but more recently in otoliths and otoconia of a comparative series of vertebrates. Some of the ultrastructural findings in rat maculas, however, have prompted a more thorough study of the organization of the hair cells and innervation patterns in graviceptors.

Ross, M. D.↗

The Role of Vitamin D in the Bone Changes Associated with Simulated Weightlessness

The role of vitamin D in the change in bone metabolism was examined. The serum concentrations in rats sacrificed after 2, 5, 7, 10, 12 and 15 days of suspension was measured. Between days 1 and 5 of suspension and then gradually decreased towards normal between days 5 and 15. The time course of the changes in the circulating concentrations of 1,25(OH)2D and 24,25(OH)2D mirror almost precisely the changes in bone metabolism. The relationship between the changes in vitamin D metabolism and bone metabolism is investigated. Whether the bone changes are due to the change in serum concentration of 1,25(OH)2D or the changes in bone formation causing a reduction in Ca flux out of the serum pool and thereby suppressing 1,25(OH)2D production is examined. It is found that suspension had no effect on hormone concentration in the 1,25(OH)2D infused animals. Nevertheless, both vehicle and 1,25(OH)2D infused suspended rats exhibited the same reduction in bone mineral, and uptake of (45)Ca. It is suggested that the transitory reduction in circulating 1,25(OH)2D during suspension is not likely to cause the abnormalities in bone metabolism but rather that the changes in bone metabolism are primary and cause the fall in serum 1,25(OH)2D concentration. This supports the hypothesis that the metabolic abnormalities in bone associated with simulated weightlessness are due to the direct effect of unweighting on the bone.

Halloran, B. P.↗

Effects of Muscle Atrophy on Motor Control: Cage-size Effects

Two populations of male Sprague-Dawley rats were raised either in conventional minimum-specification cages or in a larger cage. When the animals were mature (125 to 150 d), the physiological status of the soleus (SOL) and extensor digitorum longus (EDL) muscles of the small- and large-cage animals were compared. Analysis of whole-muscle properties including the performance of the test muscle during a standardized fatigue test in which the nerve to the test muscle was subjected to supramaximal intermittent stimulation shows: (1) the amplitude, area, mean amplitude, and peak-to-peak rate of the compound muscle action potential decreased per the course of the fatigue test; (2) cage size did not affect the profile of changes for any of the action-potential measurements; (3) changes exhibited in the compound muscle action potential by SOL and EDL were substantially different; and (4) except for SOL of the large-cage rats, there was a high correlation between all four measures of the compound muscle action potential and the peak tetanic force during the fatigue test; i.e., either the electrical activity largely etermines the force profile during the fatigue test or else contractile-related activity substantially affects the compound muscle action potential.

Stuart, D. G.↗

Neural Mechanism by which Gravitational Stimuli and Stress Affect the Secretion of Renin and Other Hormones

The serotonin-releasing drug p-chloroamphetamine (PCA), as well as L-propranolol and chloriasondamine were used in a study which established that the pathway from the hypothalamus to the kidneys is sympathetic. Which hypothalamic nuclei mediate the response to PCA is being investigated experiments are being conducted to determine a readily reproducible psychological stimulus to renin secretion that can be used in rats. The effects of equithesin, urethane, and inactin on plasma renin activity were examined in preparation for tilting experiments. The relation of vasopressin-secreting neurons in the brain sem to PCA response was explored in Brattleboro rats that are congenitally unable to produce vasopressin in their hypothalami.

Ganong, W. F.↗

The role of 1,25-dihydroxyvitamin D in the inhibition of bone formation induced by skeletal unloading

Skeletal unloading results in osteopenia. To examine the involvement of vitamin D in this process, the rear limbs of growing rats were unloaded and alterations in bone calcium and bone histology were related to changes in serum calcium (Ca), inorganic phosphorus (P sub i), 25-hydroxyvitamin D (25-OH-D), 24,25-dihydroxyvitamin D (24,25(OH)2D and 1,25-dihydroxyvitamin D (1,25(OH)2D. Acute skeletal unloading induced a transitory inhibition of Ca accumulation in unloaded bones. This was accompanied by a transitory rise in serum Ca, a 21% decrease in longitudinal bone growth (P 0.01), a 32% decrease in bone surface lined with osteoblasts (P .05), no change in bone surface lined with osteoclasts and a decrease in circulating (1,25(OH)2D. No significant changes in the serum concentrations of P sub i, 25-OH-D or 24,25(OH)2D were observed. After 2 weeks of unloading, bone Ca stabilized at approximately 70% of control and serum Ca and 1,25(OH)2D returned to control values. Maintenance of a constant serum 1,25(OH)2D concentration by chronic infusion of 1,25(OH)2D (Alza osmotic minipump) throughout the study period did not prevent the bone changes induced by acute unloading. These results suggest that acute skeletal unloading in the growing rat produces a transitory inhibition of bone formation which in turn produces a transitory hypercalcemia.

Halloran, B. P.↗

Response of amino acids in hindlimb muscles to recovery from hypogravity and unloading by tail-cast suspension

Concentrations of glutamine, glutamate, aspartate (+ asparagine) and alanine were compared in hindlimb muscles of SL-3 and ground control rats. Alanine was lower in the soleus of flown rats but not of suspended animals, with no response in other muscles except a slight increase in the unloaded plantaris. With recovery, alanine in the soleus was elevated. Since no differences in alanine metabolism were found by isolated muscle, changes in muscle alanine are probably due to altered body use of this amino acid leading to varied plasma levels.

Tischler, M. E.↗

Responses of skeletal muscle to unloading, a review

Suspension models were used to study muscle response to reduced activity. During 6 days of tail casting, the soleus (SOL) atrophies while the extensor digitorum longus grows relatively normally. After discounting those changes in both muscles due primarily to increased secretion of adrenal hormones, the following conclusions regarding the specific responses of the SOL could be drawn: (1) Atrophy is probably due primarily to increased protein degradation; (2) Decreased synthesis of glutamine may result from reduced availability of ammonia due to diminished use of ATP; (3) Greater muscle glycogen seems to reflect an increased response to insulin of glucose uptake which leads to greater glucose metabolism; and (4) Faster catabolism of branched-chain amino acids can be attributed to enhanced flux through ketoacid dehydrogenase. Studies by others using tail casted suspended rats showed in the SOL: (1) a gradual switch from type 1 to type 2 fibers; (2) increased acid protease activity; and (3) altered muscle function and contractile duration. Using harness suspended rats, others showed in the SOL: (1) significant atrophy; (2) increased numbers of glucocorticoid receptors; and (3) no change in muscle fatigability.

Tischler, M. E.↗

Electrophoretic separation of kidney and pituitary cells on STS-8

Specific secretory cells were separated from suspensions of cultured primary human embryonic cells and rat pituitary cells in microgravity conditions, with an objective of isolating the subfractions of kidney cells that produce the largest amount of urakinase, and the subfractions of rat pituitary cells that secrete growth hormones (GH), prolactin (PRL), and other hormones. It is inferred from the experimental observations that the surface charge distributions of the GH-containing cells differ from those of the PRL-containing cells, which is explained by the presence of secretory products on the surface of pituitary cells. For kidney cells, the electrophoretic mobility distributions in flight experiments were spread more than the ground controls.

Morrison, D. R.↗

Development and testing of a mouse simulated space flight model

The development and testing of a mouse model for simulating some aspects of weightlessness that occur during space flight, and the carrying out of immunological flight experiments on animals was discussed. The mouse model is an antiorthostatic, hypokinetic, hypodynamic suspension model similar to the one used with rats. It is shown that this murine model yield similar results to the rat model of antiorthostatic suspension for simulating some aspects of weightlessness. It is also shown that mice suspended in this model have decreased interferon-alpha/beta production as compared to control, nonsuspended mice or to orthostatically suspended mice. It is suggested that the conditions occuring during space flight could possibly affect interferon production. The regulatory role of interferon in nonviral diseases is demonstrated including several bacterial and protozoan infections indicating the great significance of interferon in resistance to many types of infectious diseases.

Sonnenfeld, G.↗

Animal studies on Spacelab-3

The flight of two squirrel monkeys and 24 rates on Spacelab-3 was the first mission to provide hand-on maintenance on animals in a laboratory environment. With few exceptions, the animals grew and behaved normally, were free of chronic stress, and differed from ground controls only for gravity-dependent parameters. One of the monkeys exhibited symptoms of space sickness similar to those observed in humans, which suggests squirrel monkeys may be good models for studying the space-adaptation syndrome. Among the wide variety of parameters measured in the rats, most notable was the dramatic loss of muscle mass and increased fragility of long bones. Other interesting rat findings were those of suppressed interferon production by spleen cells, defective release of growth hormone by somatotrophs, possible dissociation of circadian pacemakers, changes in hepatic lipid and carbohydrate metabolism, and hypersensitivity of marrow cells to erythopoietin. These results portend a strong role for animals in identifying and elucidating the physiological and anatomical responses of mammals to microgravity.

Schatte, C.↗

The temporal response of bone to unloading

Rats were suspended by their tails with the forelimbs bearing the weight load to simulate the weightlessness of space flight. Growth in bone mass ceased by 1 week in the hindlimbs and lumbar vertebrae in growing rats, while growth in the forelimbs and cervical vertebrae remained unaffected. The effects of selective skeletal unloading on bone formation during 2 weeks of suspension was investigated using radio iostope incorporation (with Ca-45 and H-3 proline) and histomorphometry (with tetracycline labeling). The results of these studies were confirmed by histomorphometric measurements of bone formation using triple tetracycline labeling. This model of simulated weightlessness results in an initial inhibition of bone formation in the unloaded bones. This temporary cessation of bone formation is followed in the accretion of bone mass, which then resumes at a normal rate by 14 days, despite continued skeletal unloading. This cycle of inhibition and resumption of bone formation has profound implication for understanding bone dynamics durng space flight, immobilization, or bed rest and offers an opportunity to study the hormonal and mechanical factors that regulate bone formation.

Globus, R. K.↗

Responses of skeletal muscle to unloading - A review

Suspension models were used to study muscle response to reduced activity. During 6 days of tail casting, the soleus (SOL) atrophies while the extensor digitorum longus grows relatively normally. After discounting those changes in both muscles due primarily to increased secretion of adrenal hormones, the following conclusions regarding the specific responses of the SOL could be drawn: (1) Atrophy is probably due primarily to increased protein degradation; (2) Decreased synthesis of glutamine may result from reduced availability of ammonia due to diminished use of ATP; (3) Greater muscle glycogen seems to reflect an increased response to insulin of glucose uptake which leads to greater glucose metabolism; and (4) Faster catabolism of branched-chain amino acids can be attributed to enhanced flux through ketoacid dehydrogenase. Studies by others using tail casted suspended rats showed in the SOL: (1) a gradual switch from type 1 to type 2 fibers; (2) increased acid protease activity; and (3) altered muscle function and contractile duration. Using harness suspended rats, others showed in the SOL: (1) significant atrophy; (2) increased numbers of glucocorticoid receptors; and (3) no change in muscle fatigability.

Tischler, M. E.↗

Bone loss during simulated weightlessness - Is it glucocorticoid mediated?

Elevating the hindquarters of a rat by the tail unweights the hind limbs but maintains normal weight-bearing by the forelimbs. This maneuver leads to a decrease in bone mass and calcium content in the unweighted bones (e.g., tibia and L1 vertebra), but not in the normally weighted bones (e.g., humerus and mandible). Potentially, the stress of the maneuver, mediated by increased glucocorticoid production and secretion, could explain the decreased bone formation, rather than the skeletal unweighting per se. To test this possibility, the effects of adrenalectomy on the response of bone to the unweighting of the hind limbs of normal rats were evaluated.

Bikle, D. D.↗

Responses of amino acids in hindlimb muscles to recovery from hypogravity and unloading by tail-cast suspension

Amino acids were assayed in muscles from rats exposed to 7 days of hypogravity and 12 h of gravity (F) or 6 days of suspension with (R) or without (H) 12 h of loading. In these groups, lower aspartate was common only to the soleus (SOL) relative to control muscles, the smallest difference being in group R. This difference in aspartate for F and H, but not for R, correlated with lower malate suggesting diminution of citric acid cycle intermediates. The R SOL value was increased over the H SOL. Therefore desite 12 h of loading, the F SOL was more comparable to the H SOL. The role of stress in preventing recovery of the F SOL was apparent from the ratios of glutamine/glutamate. Synthesis of glutamine is enhanced by glucocorticoids and is reflected by an increased ratio. In 5 of the 6 F muscles studied, this ratio was greater than in controls. In contrast, the ratio in all R muscles was similar to controls and showed recovery from the values in H muscles. Hence the post-flight treatment of F rats may have produced additional stress. Despite this stress, in some respects the SOL responses to hypogravity were similar to its responses to unloding by suspension.

Tischler, M. E.↗

Osteocalcin as an indicator of bone metabolism during spaceflight

The effect of microgravity on osteocalcin (OC) is investigated in rats flown on Spacelab 3. Serum, Ca, Pi, total protein, alkaline phosphatase, and OC contents, and the breaking strength of the humerus of control and Spacelab rats are calculated; the procedures utilized for these analyses are described. It is detected that the OC is reduced, and the serum and alkaline phosphatase are unaffected by microgravity.

Patterson-Buckendahl, P. E.↗

Role of carbonic anhydrase in bone - Partial inhibition of disuse atrophy of bone by parenteral acetazolamide

The effectiveness of orally and subcutaneously administered acetazolamide sodium in preventing denervation-induced bone loss in rats is examined. Male Sprague-Dawley rats were treated with acetazolamide either orally by incorporation of 0.2, 0.5, or 1.5 percent concentrations in their diet for 15 days, or subcutaneously by either injection of 0.5 ml/rat of a solution containing either 20 or 100 mg/ml of the drug twice daily for 15 days or by continuous infusion of 5, 50, 500, or 1000 mg/ml of acetazolamide sodium for 8 days using an osmotic minipump. The effects of acetazolamide on body weight, food consumption, and plasma calcium content are evaluated. It is observed that parenteral administration is equally effective as oral administration in partially preventing denervation-induced bone mass changes. The data reveal that approximately 50 percent protection occurs with daily doses of 1094, 129, and 8 mg/kg body weight for the oral, subcutaneous injection, and subcutaneous infusion methods, respectively.

Kenny, A. D.↗