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At least 163 records · Page 9

Reduction of blood serum cholesterol

By feeding a human subject as the sole source of sustenance a defined diet wherein the carbohydrate consists substantially entirely of glucose, maltose or a polysaccharide of glucose, the blood serum cholesterol level of the human subject is substantially reduced. If 25 percent of the carbohydrate is subsequently supplied in the form of sucrose, an immediate increase from the reduced level is observed. The remainder of the defined diet normally includes a source of amino acids, such as protein or a protein hydrolysate, vitamins, minerals and a source of essential fatty acid.

Winitz, M.↗

Microbial metabolism and dynamic changes in the electrical conductivity of soil solutions - A method for detecting extraterrestrial life

Experiments are reported which show that measuring metabolic activity in soil solutions by means of dynamic changes in electrical conductivity, water-soluble Ca, or water-soluble Mg is a feasible life detection method. The addition of 0.5% glucose solutions to 12 different air-dried soils always resulted in increases in all three of these parameters. The kinetics and magnitude of these changes for at least two and usually all three of the parameters over a 14-day period were clearly distinguishable from the changes in heat-sterilized controls or unsterilized controls without added glucose. In general, maximal values were achieved more rapidly under aerobic than under anaerobic incubation.

Silverman, M. P.↗

Factors affecting the palmitoyl-coenzyme A desaturase of Saccharomyces cerevisiae

The activity and stability of the palmitoyl-coenzyme A (CoA) desaturase complex of Saccharomyces cerevisiae was influenced by several factors. Cells, grown nonaerobically and then incubated with glucose, either in air or under N2, showed a marked increase in desaturase activity. Cycloheximide, added during such incubations, prevented the increase in activity, suggesting de novo synthesis. The stability of the desaturase from cells grown nonaerobically was affected by subsequent treatment of the cells; enzyme from freshly harvested cells, or from cells that were then shaken under nitrogen, readily lost activity upon washing or during density gradient analysis, whereas aerated cells, in the presence or absence of glucose, yielded stable enzyme preparations. The loss of activity in nonaerobic preparations could be reversed by adding soluble supernatant from these homogenates and could be prevented by growing the cells in the presence of palmitoleic acid and ergosterol, but not with several other lipids tested.

Klein, H. P.↗

Effect of exercise on the pseudodiabetes of bed rest

The effect of intensive isotonic exercise and isometric exercise (with its low metabolic rate) during bed rest on plasma insulin and glucose tolerance test was investigated. The subjects were seven healthy men, 19 to 22 years in age, 166 to 188 cm in height, and 62.40 to 103.80 kg in weight; maximal oxygen uptakes ranged from 3.36 to 4.38 liters/min. It appears that bed-rest-induced glucose intolerance is diminished with increasing energy expenditure during both bed rest and recovery.

Greenleaf, J. E.↗

Increased gluconeogenesis in hyper-G stressed rats

The role of gluconeogenesis in the altered carbohydrate metabolism in rats exposed to hyper-G stress is investigated. The blood levels of the substrates and hormones involved in gluconeogenesis were determined in rats exposed to 3.1 G for various time periods (0.25 to 24 hr). It is found that hyper-G stressed rats showed an immediate increase in plasma glucose at the onset of centrifugation which persisted throughout all the exposure periods. A substantial part of the initial rise in blood glucose is attributed to an increased rate of gluconeogenesis. An increase in liver glycogen deposition was observed in centrifuged rats as early as 0.50 hr exposure time, with progressively larger amounts accumulated as the exposure time was extended to 24 hr. It is concluded that the increase in gluconeogenic activity of hyper-G stressed rats is due to an increase in the mobilization of gluconeogenic substrates from perpheral tissues to the liver as a result of increases in circulating catecholamines and glucagon.

Daligcon, B. C.↗

Effect of confinement in small space flight size cages on insulin sensitivity of exercise-trained rats

The effect of confinement in small cages (simulating the size to be used in future space Shuttle missions) on insulin sensitivity was studied in rats having an increased insulin sensitivity due to exercise training prior to confinement. Oral glucose tolerance tests (OGTT) were given to both control and exercise-trained rats before and after placement in the small cages for 7 days. The insulin resistance was assessed by the product of the area of the insulin and glucose curves of the OGTT (IG index). Results show that the values obtained before confinement were one-half as high in exercise-trained rats as those in control rats, reflecting an increased sensitivity to insulin with exercise training. After 7 days confinement, the IG index was found to be not significantly different from initial values for both control and exercise-trained rats. These findings suggest that increased insulin sensitivity in exercise-trained rats persists 7 days after cessation of running activity. The data also indicate that exercise training, before flight, may be beneficial in minimizing the loss of insulin sensitivity expected with decreased use of gravity dependent muscles during exposure to hypogravity in space flight.

Mondon, C. 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.↗

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.↗

Carbon isotopic fractionation in heterotrophic microbial metabolism

Differences in the natural-abundance carbon stable isotopic compositions between products from aerobic cultures of Escherichia coli K-12 were measured. Respired CO2 was 3.4 percent depleted in C-13 relative to the glucose used as the carbon source, whereas the acetate was 12.3 percent enriched in C-13. The acetate C-13 enrichment was solely in the carboxyl group. Even though the total cellular carbon was only 0.6 percent depleted in C-13, intracellular components exhibited a significant isotopic heterogeneity. The protein and lipid fractions were -1.1 and -2.7 percent, respectively. Aspartic and glutamic acids were -1.6 and +2.7 percent, respectively, yet citrate was isotopically identical to the glucose. Probable sites of carbon isotopic fractionation include the enzyme, phosphotransacetylase, and the Krebs cycle.

Blair, N.↗

Evaluation of the endogenous glucocorticoid hypothesis of denervation atrophy

The effects are studied of the oral administration of RU38486, a potent selective glucocorticoid antagonist, on muscle weight, non-collagen protein content, and selected enzyme activities (choline acetyltransferase, glucose 6-phosphate dehydrogenase, and glutamine synthetase) following denervation of rat skeletal muscle. Neither decreases in muscle weight, protein content, and choline acetyltransferase activity, nor increases in the activities of glucose 6-phosphate dehydrogernase and glutamine synthetase were affected by RU38486. These data do not support the hypothesis that denervation atrophy results from enhanced sensitivity of muscle to endogenous glucocorticoids.

Konagaya, Masaaki↗

Time course of the response of carbohydrate metabolism to unloading of the soleus

The time course of the response of carbohydrate metabolism to unloading was studied in the soleus muscle of rats subjected to tail-cast suspension. In the fresh soleus, 12 hours of unloading led to higher concentrations of glycogen and lower activity ratios of both glycogen synthase and glycogen phosphorylase. These changes were still evident on day three. Thereafter, the increased glycogen concentration apparently diminished the activity ratio of glycogen synthase, leading to a subsequent fall in the total glycogen content after day one. After 24 hours of unloading, when no significant atrophy was detectable, there was no differential response to insulin for in vitro glucose metabolism. On day three, the soleus atrophied significantly and displayed a greater sensitivity to insulin for most of these parameters compared to the weight-bearing control muscle. However, insulin sensitivity for glycogen synthesis was unchanged. These results showed that the increased sensitivity to insulin of the unloaded soleus is associated with the degree of muscle atrophy, likely due to an increased insulin binding capacity relative to muscle mass. This study also showed that insulin regulation of glucose uptake and of glycogen synthesis is affected differentially in the unloaded soleus muscle.

Henriksen, Erik J.↗

Effect of body weight gain on insulin sensitivity after retirement from exercise training

The effect of the body-weight gain after retirement from an exercise-training program on the retained increase in insulin sensitivity elicited by the training was investigated in exercise-trained (ET) rats. Insulin sensitivity was assessed by oral glucose tolerance and insulin suppression tests immediately after training and during retirement. Results show that, compared with sedentary controls, exercise training enhanced insulin-induced glucose uptake, but the enhanced sensitivity was gradually lost with the end of running activity until after seven days of retirement, when it became equal to that of controls. This loss of enhanced sensitivity to insulin was associated with an accelerated gain in body weight beginning one day after the start of retirement. However, those animals that gained weight only at rates similar to those of control rats, retained their enhanced sensitivity to insulin.

Dolkas, Constantine B.↗

Cellular responses to low-gravity: Pilot studies on suborbital rockets and orbiting spacecraft

The allocated funding supported, in part, experiments conducted on two Consort sounding rockets and five Shuttle flights. The primary parameters investigated were signal transduction in response to various mediators, cellular differentiation and metabolism in microgravity, and effect of microgravity on cytoskeletal morphology. Achievements include: demonstration of effect of spaceflight on the actin cytoskeleton in mouse osteoblasts and frog cells; confirmation that the T cell receptor-mediated signal transduction pathway in T lymphocytes is not affected by low-gravity compared to non-TCR-mediated stimulation (Con-A) which classically does not promote proliferative response; indication that microgravity may allow separation of proliferative signaling and secretory function in lymphocytes; demonstration that T lymphocytes and bone cells utilized less glucose indicating a shift in metabolism and confirming Spacelab results with WI-38 cells which used significantly less glucose, during spaceflight; confirmation that activation of human splenic B cells with a number of different mediators is not affected during spaceflight; demonstration of increased prostaglandin synthesis during reduced bone cell growth suggesting an effect of microgravity on prostaglandin-induced mitogenesis. The funding contributed significantly to the database described above and resulted in submission of six collaborative abstracts in 1993 (five to the ASGSB Annual Meeting and one to the ASCB Annual Meeting). Two abstracts were presented at the 1992 ASGSB Annual Meeting in Tucson. In addition, several peer reviewed papers are being generated and data will be included as background in preparation of future proposals, which hopefully will allow us to continue this type of extremely productive collaborative research.

Lewis, Marian L.↗

Soybean cotyledon starch metabolism is sensitive to altered gravity conditions

We have demonstrated that etiolated soybean seedlings grown under the altered gravity conditions of clinorotation (1 rpm) and centrifugation (5xg) exhibit changes in starch metabolism. Cotyledon starch concentration was lower (-28%) in clinorotated plants and higher (+24%) in centrifuged plants than in vertical control plants. The activity of ADP-glucose pyrophosphorylase in the cotyledons was affected in a similar way, i.e. lower (-37%) in the clinorotated plants and higher (+22%) in the centrifuged plants. Other starch metabolic enzyme activities, starch synthase, starch phosphorylase and total hydrolase were not affected by the altered gravity treatments. We conclude that the observed changes in starch concentrations were primarily due to gravity-mediated differences in ADP-glucose pyrophosphorylase activity.

Brown, C. S.↗

Skeletal muscle satellite cells cultured in simulated microgravity

Satellite cells are postnatal myoblasts responsible for providing additional nuclei to growing or regenerating muscle cells. Satellite cells retain the capacity to proliferate and differentiate in vitro and therefore provide a useful model to study postnatal muscle development. Most culture systems used to study postnatal muscle development are limited by the two-dimensional (2-D) confines of the culture dish. Limiting proliferation and differentiation of satellite cells in 2-D could potentially limit cell-cell contacts important for developing the level of organization in skeletal muscle obtained in vivo. Culturing satellite cells on microcarrier beads suspended in the High-Aspect-Ratio-Vessel (HARV) designed by NASA provides a low shear, three-dimensional (3-D) environment to study muscle development. Primary cultures established from anterior tibialis muscles of growing rats (approximately 200 gm) were used for all studies and were composed of greater than 75 % satellite cells. Different inoculation densities did not affect the proliferative potential of satellite cells in the HARV. Plating efficiency, proliferation, and glucose utilization were compared between 2-D flat culture and 3-D HARV culture. Plating efficiency (cells attached - cells plated x 100) was similar between the two culture systems. Proliferation was reduced in HARV cultures and this reduction was apparent for both satellite cells and non-satellite cells. Furthermore, reduction in proliferation within the HARV could not be attributed to reduced substrate availability since glucose levels in media from HARV and 2-D cell culture were similar. Morphologically, microcarrier beads within the HARVS were joined together by cells into three-dimensional aggregates composed of greater than 10 beads/aggregate. Aggregation of beads did not occur in the absence of cells. Myotubes were often seen on individual beads or spanning the surface of two beads. In summary, proliferation and differentiation of satellite cells on microcarrier beads within the HARV bioreactor results in a three dimensional level of organization that could provide a more suitable model to study postnatal muscle development.

Molnar, Greg↗

Application of Rotating Wall Vessel (RWV) Cell Culture for Pancreas Islet Cell Transplantation

Type I insulin-dependent diabetes mellitus (IDDM) remains a major cause of morbidity and mortality in both pediatric and adult populations, despite significant advances in medical management. While insulin therapy treats symptoms of acute diabetes, it fails to prevent chronic complications such as microvascular disease, blindness, neuropathy, and chronic renal failure. Strict control of blood glucose concentrations delays but does not prevent the onset and progression of secondary complications. Although, whole pancreas transplantation restores physiological blood glucose levels, a continuous process of allograft rejection causes vascular and exocrine-related complications. Recent advances in methods for isolation and purification of pancreatic islets make transplantation of islet allografts an attractive alternative to whole pancreas transplantation. However, immunosuppressive drugs are necessary to prevent rejection of islet allografts and many of these drugs are known to be toxic to the islets. Since auto-transplants of isolated islets following total pancreatectomy survive and function in vivo, it is apparent that a major obstacle to successful clinical islet transplantation is the immunogenicity of the islet allografts.

Rutzky, Lynne P.↗

Drinking-Induced Plasma Vasopressin and Norepinephrine Changes in Dehydrated Humans

After 24-h water deprivation, five men (23-41 yr; 78 +/- 3.6 kg) consumed, within 4.0-6.2 min, 12 mL/kg of one of six fluid formulations (16.5 C) once a week over a period of 6 weeks: water, hypotonic saline (0.045% Na(+)), isotopic saline (0.36%, Na(+)), hypertonic glucose 9 7%, glucose), and two commercial mildly hypertonic 9.7% carbohydrate drinks. Blood samples were drawn 5 min before and: 3, 9, 15, 30, and 70 min after completion of drinking. Ingestion induced no significant change in plasma Na(+), K(+), osmotic, or protein concentrations, blood pressure; or heart rate. Plasma volume (PV) was increases (P <0.05) between 30-70 min with isotonic saline and the two commercial drinks. Ingestion induced a decrease in plasma AVP (PAVP) at 3 min, which was maximal (P < 0.05) at 15 min with all drinks. Thus, the act of drinking, independent of the composition or osmolality of the fluid absorbed, leads to a prompt inhibition of PAVP secretion in man. With the exception of rehydration with isotonic saline, this prompt response was followed by a long lasting inhibition of PAVP. There was no change in PRA, plasma aldosterone, atrial natriuretic peptide, or epinephrine, but an increase in plasma norepinephrine occurred immediately after ingestion, which suggests, like that for PAVP depression, a drinking-stimulate neural mechanism.

Geelen, Ghislaine↗

NASA Rodent Foodbar: Long Term Effects in Swiss Webster Mice

Swiss Webster male and female mice (150 of each) were fed NASA Rodent Foodbar for more than 110 days to test the diet's nutritional adequacy for use in future long-term studies aboard the International Space Station. Mice were grouped three to a cage (one cage = one sample) and cages were assigned to either Foodbar or Purina Chow #5001 (control) diet groups. Body weights, food intake, and water intake were obtained throughout the study. There were no significant differences in body weights between male Foodbar fed and Chow fed males (p=0.58), and at 15 weeks into the female mouse study there appear to be no significant body weight differences. Both male and female Foodbar fed groups consumed more food and less water than their Chow controls, both factors thought to be attributable to the high moisture content of the Foodbars (26% versus 10% for Chow). All differences in gross food and water consumption had p-values of less than 0.01. When food and water intake were adjusted for the moisture content in the food, both male and female Foodbar fed animals consumed less food, but still had a lower water intake rate than their controls. (p is less than 0.01). Preliminary analysis on blood samples from male and female halfway point dissections suggests differences in glucose and fat metabolism. In both male and female Foodbar fed animals, blood glucose values were significantly lower (p is less than 0.01) but there were no significant differences in cholesterol levels (p=0.51). In Foodbar fed females, triglycerides were significantly higher (p is less than 0.01). These data suggest that Foodbars allow for normal growth in Swiss Webster mice, but affect some blood chemistry parameters.

Santiago, D. L.↗