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At least 451 records · Page 25

Prostacyclin-induced hyperthermia - Implication of a protein mediator

The mechanism of the prostacyclin-linked hyperthermia is studied in rabbits. Results show that intracerebroventricular administration of prostacyclin (PGI2) induces dose-related hyperthermia at room temperature (21 C), as well as at low (4 C) and high (30 C) ambient temperatures. It is found that this PGI2-induced hyperthermia is not mediated by its stable metabolite 6-keto prostaglandin F-1(alpha). Only one of the three anion transport systems, the liver transport system, appears to be important to the central inactivation of pyrogen, prostaglandin E2, and PGI2. Phenoxybenzamine and pimozide have no thermolytic effect on PGI2-induced hyperthermia, while PGI2 still induces hyperthermia after norepinephrine (NE) and dopamine levels are depleted by 6-hydroxydopamine. Indomethacin and SC-19220 (a PG antagonist) do not antagonize PGI2 induced hyperthermia, while theophylline does not accentuate the PGI2-induced hyperthermia. However, the hyperthermic response to PGI2 is attenuated by central administration of the protein synthesis inhibitor, anisomycin. It is concluded that PGI2-induced hyperthermia is not induced by NE, dopamine, or cyclic AMP, but rather that a protein mediator is implicated in the induction of fever by PG12.

Kandasamy, S. B.↗

Peptide and non-peptide opioid-induced hyperthermia in rabbits

The intracerebroventricular administration of prototype nonpeptide opioid receptor (mu, kappa, and sigma) agonists, morphine, ketocyclazocine, and N-allyl-normetazocine was found to induce hyperthermia in rabbits. The similar administration of peptide opioids like beta-endorphin (BE), methionine-enkephalin (ME), and its synthetic analogue D-ala2-methionine-enkephalinamide (DAME) was also found to cause hyperthermia. Results indicate that only the liver-like transport system is important to the ventricular inactivation of BE and DAME. Prostaglandins and norepinephrine were determined not to be involved in peptide and nonpeptide opioid-induced hyperthermia. In addition, cAMP was not required since a phosphodiesterase inhibitor, theophylline, did not accentuate the hyperthermia due to peptide and nonpeptide opioids. Naloxone-sensitive receptors were found to be involved in the induction of hyperthermia by morphine, BE, ME, and DAME since naloxone attenuated them. However, the hyperthermic response to ketocyclazocine and N-allyl-normetazocine was not antagonized by naloxone.

Kandasamy, S. B.↗

Effects of simulated increased gravity on the rate of aging of rats - Implications for the rate of living theory of aging

It was found that the rate of aging of 17 month old rats which had been exposed to 3.14 times normal gravity in an animal centrifuge for 8 months was larger than that of the controls as determined by the apparently elevated lipofuscin content in heart and kidney, reduced numbers and increased size of mitochondria of heart tissue, and inferior liver mitochondria respiration. Steady-state food intake per day per kg body weight, which is presumably proportional to rate of living or specific basal metabolic expenditure, was found to be about 18 percent higher than in the controls after an initial 2 month adaptation period. Although half of the centrifuged animals lived only a little shorter than the controls (average about 343 vs. 364 days on the average, statistically nonsignificant), the remaining half (longest survivors) lived on the centrifuge an average of 520 days (range 483-572) compared to an average of 574 days (range 502-615) for the controls, computed from the onset of centrifugation, or 11 percent shorter. These findings indicate that a moderate increase of the level of basal metabolism of young adult rats adapted to hypergravity compared to controls in normal gravity is accompanied by a roughly similar increase in the rate of organ aging and reduction of survival, in agreement with Pearl's (1928) rate of living theory of aging, previously experimentally demonstrated only in poikilotherms.

Economos, A. C.↗

Effects of suspension on tissue levels of glucocorticoid receptors

Differential muscle responses can be simulated by hypokinetic/hypodynamic (H/H) suspension of rats with complete unloading of the hindlimb muscles. Since mechanism(s) underlying these atrophic effects were not clearly elucidated, experiments were initiated to investigate a possible role for glucocorticoids in the physiological and biochemical responses to H/H. The principal objective was to assess the potential for alterations in peripheral responsiveness to glucocorticoids in response to H/H. Studies have initially focused on the determination of tissue levels of glucocorticoid receptors as one index of hormonal sensitivity at the cellular level. Four hindlimb muscles (soleus, gastrocnemius, plantaris and EDL), previously demonstrated to exhibit differential responses to H/H, were investigated. Receptor levels in other glucocorticoid sensitive tissues (heart, liver, and kidney) were determined. Male rats (180-200g) were suspended for 7 or 14 days, sacrificed by cervical dislocation, and the tissues excised.

Steffen, J. M.↗

Distribution of fluids in the body of the centrifuged rat

The effects of exposure to an elevated g-level throughout the period of rapid growth is investigated in a comparison of a group of female Sprague-Dawley rats centrifuged as adults with other groups centrifuged for prolonged intervals starting shortly after weaning. The fluid-solid composition of total body, heart, liver, gut, skin, and muscle for both study groups is compared with that of a control group. None of the changes as a result of centrifugation were truly persistent. The only increases in mass associated with centrifugation and the only responses to centrifugation per se were observed in the skin values.

Pitts, G. C.↗

The unresponsiveness of the immune system of the rat to hypergravity

The immune response in rats exposed to simulated hypergravity (2.1 G and 3.1 G) by chronic centrifugation was assessed. Rats were immunized with sheep red blood cells (SRBC), either on the day of initial exposure to hypergravity (hyper-G), or after being centrifuged for 28 d and remaining on the centrifuge thereafter. Pair-fed and ad libitum fed noncentrifuged controls were used. Although there were some alterations in leukocyte counts, hyper-G did not systematically affect the primary or secondary anti-SRBC response, hematocrits, or the sizes of the liver, spleen, kidneys, thymus, or adrenal glands. The immune system is thus remarkably homeostatic under hypergravity conditions which do affect other physiologic parameters.

Scibetta, S. M.↗

Causes of the triglyceride-lowering effect of exercise training in rats

Studies conducted with human subjects and laboratory animals have consistently shown a reduction in serum triglyceride (TG) in exercise-trained subjects. The obtained data have suggested that this decrease was due to a reduction in hepatic TG secretion. The present investigation, which was conducted with rats trained to attain a high level of spontaneous running activity, provides support for the earlier results. In addition, insights are obtained regarding the mechanism by which exercise lowers TG levels. Since the liver accounts for the vast majority of endogenous very low density lipoprotein (VLDL)-TG secretion, the fall in TG secretion rate seen in exercise-trained (ET) rats must be due to a reduction in hepatic TG secretion.

Mondon, C. E.↗

Purification and Cultivation of Human Pituitary Growth Hormones Secreting Cells

The rat and human pituitary gland contains a mixture of hormone producing cell types. The separation of cells which make growth hormone (GH) is attempted for the purpose of understanding how the hormone molecule is made within the pituitary cell; what form(s) it takes within the cell; and what form(s) GH assumes as it leaves the cell. Since GH has a number of biological targets (e.g., muscle, liver, bone), the assessment of the activities of the intracellular/extracellular GH by new and sensitive bioassays. GH cells contained in the mixture was separated by free flow electrophoresis. These experiments show that GH cells have different electrophoretic mobilities. This is relevant to NASA since a lack of GH could be a prime causative factor in muscle atrophy. Further, GH has recently been implicated in the etiology of motion sickness in space. Continous flow electrophoresis experiment on STS-8 showed that GH cells could be partially separated in microgravity. However, definitive cell culture studies could not be done due to insufficient cell recoveries.

Hymer, W. C.↗

Interactions of the interferon system with cellular metabolism

The results of studies concerning the interaction of the interferon (Inf) system with the activities of carcinogens, tumor promoters, and cytochrome P-450 are presented. The results show that the addition of a tumor promoter (TPA or 4-O-methyl-TPA) to a tissue culture enhances virus-induced Inf-gamma production, suggesting a potential value of tumor promoters in the biosynthesis of commercial Inf. On the other hand, the carcinogens were reported to inhibit the induction of Inf-alpha/beta in cultured cells and in intact animals (with no effect on the administered or preformed Inf). The demonstration of a correlation between the carcinogenic potential of a compound and its inhibitive effect on Inf production suggests a possible use of the Inf production assay in the evaluation of the carcinogenicity of chemicals. In addition, it was shown that the induction of Inf-alpha/beta as well as the administration of this Inf depresses the levels of rat liver cytochrome P-450 which is responsible for binding lipophilic drugs, steroids, and carcinogens, thus increasing the toxicity of the respective chemical.

Sonnenfeld, Gerald↗

Comparison of bioseparation methods for microgravity experiments

The efficiency of the 1-g version of the continuous-flow electrophoresis (CFE) system flown on Space Shuttle missions is compared with the efficiency of a commercial CFE for separating living cells (human kidney, liver, and pituitary-gland cells and T-lymphocytes). In addition, the CFE system and a reciprocal isoelectric focusing (RIEF) system are compared with respect to protein pyrification efficiency. Correlations were made among electrophoretic mobilities (EPMs), secretory functions of cells, and input sample concentrations. A significant reduction in mean and range EPM was observed when input sample concentrations exceeded a low threshohold. This effect was not observed in microgravity experiments conducted at sample concentrations three times greater than the threshold for the controls. Comparison of CFE and RIEF methods showed that there are apparent advantages for each method depending on the product. For example, RIEF purification of urokinase removed more protein impurities, but focused the enzyme at a pH different than the enzyme's known isoelectric point.

Morrison, Dennis R.↗

Cosmos 1887 - Science overview

Twenty two groups of U.S. investigators participated in joint studies of ten male rats flown on the Cosmos 1887 biosatellite. A summary of these studies embracing skeletal muscle, bone, endocrine, neural, intestinal, metabolic, immunology, cardiac, and gonadal investigations is presented. Three general objectives of the rat experiments are outlined - verification of previous observations of the biological responses to microgravity; clarification of the effects of microgravity on both the tissues investigated and the measurements performed; and relation of biological responses to flight duration. It is concluded that the first objective is met fully and the second with a varying degree of success. The confounding effects of overshooting the designated landing site and delayed recovery of the animals largely precluded meeting the last objective. It is also noted that investigations were performed for the first time on brain and spinal cord enzymes, a neurotransmitter, transmitter receptors, hypothalamic regulatory factors, pineal metabolites, atrial granules, liver histology, and jejunal mitotic rate in spaceflight animals.

Grindeland, R. E.↗

Binding of alpha-fetoprotein by immobilized monoclonal antibodies during episodes of zero-gravity obtained by parabolic flight

Alpha-fetoprotein (AFP), a single-chain polypeptide which is synthesized by the liver and yolk sac of the human fetus, provided a model ligand for assessing the effects of microgravity on ligand binding to surface-immobilized model receptor molecules. Monoclonal antibodies, used as receptors for AFP, were immobilized by covalent attachment to latex microparticles. Zero gravity environment was obtained by parabolic flight aboard NASA 930, a modified KC-135 aircraft. Buring the onset of an episode of zero gravity, ligand and receptor were mixed. Timed incubation (20 s) was terminated by centrifugation, the supernatant removed, and microparticies were assessed for bound AFP by immunochemical methods. The extent of binding was not influenced by microgravity, when compared with 1-G controls, which suggests that aberrant cellular activities observed in microgravity are not the simple expression of altered macromolecular interactions.

Spooner, Brian S.↗

Three-dimensional structure of human serum albumin

The binding locations to human serum albumin (HSA) of several drug molecules were determined at low resolution using crystallographic methods. The principal binding sites are located within subdomains IIA and IIIA. Preliminary studies suggest that an approach to increasing the in vivo efficacy of drugs which are rendered less effective or ineffective by virtue of their interaction with HSA, would be the use of competitive displacement in drug therapies and/or the development of a general inhibitor to the site within subdomain IIIA. These findings also suggest that the facilitated transfer of various ligands across organ/circulatory interfaces such as liver, kidney, and brain may be associated with binding to the IIIA subdomain.

Carter, Daniel C.↗

Effect of chemical form of selenium on tissue glutathione peroxidase activity in developing rats

The hypothesis that the stage of development of rats may affect the availability of various forms of selenium for the activity of glutathione peroxidase (GSHPx) in the rat was experimentally investigated. One experiment evaluated the availability of selenium as selenite or selenomethionine for GSPHx activity during three developmental states in rats: fetus and 7-day old and 14-day old nursing pups. In all tissues studied, GSHPx activity was highest in the 14-day-old pups whose dams were in the selenomethionine group. Rat pups given intraperitoneal selenite had higher liver and kidney GSHPx activity than pups given the same amount of selenium as intraperitoneal selenomethionine. In a second experiment, all dams were fed the same basal diet and pups were weaned to diets containing one of two levels of selenium and one of three forms of selenium (selenite, selenomethionine, or selenocystine). The results also supported the hypothesis these dietary forms of selenium are differentially available for GSHPx activity.

Lane, Helen W.↗

Space research on organs and tissues

The effects of microgravity on various physiological systems are reviewed focusing on muscle, bone, cardiovascular, pulmonary, neurovestibular, liver, and endocrine systems. It is noted that certain alterations of organs and tissues caused by microgravity are not reproducible in earth-bound animal or human models. Thus space research on organs and tissues is essential for both validating the earth-bound models used in laboratories and studying the adaptations to weightlessness which cannot be mimicked on earth.

Tischler, Marc E.↗

The role of pyridoxine as a countermeasure for in-flight loss of lean body mass

Ground based and in flight research has shown that humans, under conditions of microgravity, sustain a loss of lean body tissue (protein) and changes in several biological processes including, reductions in red blood cell mass, and neurotransmitters. The maintenance of muscle mass, the major component of lean body mass, is required to meet the needs of space station EVAs. Central to the biosynthesis of amino acids, the building blocks of protein, is pyridoxine (vitamin B-6). Muscle mass integrity requires the availability of vitamin B-6 for protein metabolism and neurotransmitter synthesis. Furthermore, the formation of red blood cells require pyridoxine as a cofactor in the biosynthesis of hemoglobin, a protein that carries oxygen to tissues. In its active form, pyridoxal-5'-phosphate (PLP), vitamin B-6 serves as a link between amino acid and carbohydrate metabolism through intermediates of glycolysis and the tricarboxylic acid cycle. In addition to its role in energy metabolism, PLP is involved in the biosynthesis of hemoglobin and neurotransmitter which are necessary for neurological functions. Alterations in pyridoxine metabolism may affect countermeasures designed to overcome some of these biochemical changes. The focus of this research is to determine the effects of microgravity on the metabolic utilization of vitamin B-6, integrating nutrition as an integral component of the countermeasure (exercise) to maintain lean body mass and muscle strength. The objectives are: 1) to determine whether microgravity effects the metabolic utilization of pyridoxine and 2) to quantitate changes in B-6 vitamer distribution in tissue and excreta relative to loss of lean body tissue. The rationale for this study encompasses the unique challenge to control biochemical mechanisms effected during space travel and the significance of pyridoxine to maintain and counter muscle integrity for EVA activities. This experiment will begin to elucidate the importance of biochemical interactions between micronutrients and the homeostasis condition of biological processes in the space environment. To address this research topic a simulated microgravity model has been developed. The experiment uses radioisotopically labelled pyridoxine administered as an oral dose to rats which are maintained by tail suspension to simulate a microgravity environment. At the termination of the study, liver, muscle, blood and urine are collected and analyzed by reverse phase high pressure liquid chromatography to determine the quantity and distribution of the B-6 vitamers in tissue and excreta relative to lean body tissue loss. Earlier studies, published by this investigator, have shown that differences in vitamer distribution among samples from experimental versus control subjects indicate changes in metabolic utilization and storage of vitamin B-6.

Gilbert, Joyce A.↗

Fuzzy neural network methodology applied to medical diagnosis

This paper presents a technique for building expert systems that combines the fuzzy-set approach with artificial neural network structures. This technique can effectively deal with two types of medical knowledge: a nonfuzzy one and a fuzzy one which usually contributes to the process of medical diagnosis. Nonfuzzy numerical data is obtained from medical tests. Fuzzy linguistic rules describing the diagnosis process are provided by a human expert. The proposed method has been successfully applied in veterinary medicine as a support system in the diagnosis of canine liver diseases.

Gorzalczany, Marian B.↗

Space research on organs and tissues

Studies in space on various physiological systems have and will continue to provide valuable information on how they adapt to reduced gravitational conditions, and how living in a 1 g (gravity) environment has guided their development. Muscle and bone are the most notable tissues that respond to unweighting caused by lack of gravity. The function of specific muscles and bones relates directly to mechanical loading, so that removal of 'normal forces' in space, or in bedridden patients, causes dramatic loss of tissue mass. The cardiovascular system is also markedly affected by reduced gravity. Adaptation includes decreased blood flow to the lower extremities, thus decreasing the heart output requirement. Return to 1 g is associated with a period of reconditioning due to the deconditioning that occurs in space. Changes in the cardiovascular system are also related to responses of the kidney and certain endocrine (hormone-producing) organs. Changes in respiratory function may also occur, suggesting an effect on the lungs, though this adaptation is poorly understood. The neurovestibular system, including the brain and organs of the inner ear, must adapt to the disorientation caused by lack of gravity. Preliminary findings have been reported for liver. Additionally, endocrine organs responsible for release of hormones such as insulin, growth hormone, glucocorticoids, and thyroid hormone may respond to spaceflight.

Tischler, Marc E.↗