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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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29 records · Page 2

Opposing actions of dibutyryl cyclic AMP and GMP on temperature in conscious guinea-pigs

It is shown that the intracerebroventricular administration of dibutyryl cyclic AMP (Db-cAMP) induced hyperthermia in guinea pigs which was not mediated through prostaglandins or norepinephrine since a prostaglandin synthesis inhibitor and an alpha-adrenergic receptor blocking agent did not antagonize the hyperthermia. However, the hyperthermic response to Db-cAMP was attenuated by the central administration of a beta-adrenergic receptor antagonist, which indicates that cAMP may be involved, through beta-adrenergic receptors, in the central regulation of heat production and conservation. The central administration of Db-cGMP produced hypothermia which was not mediated via histamine H1 or H2 receptors and serotonin. The antagonism of hypothermia induced by Db-cGMP and acetylcholine + physostigmine by central administration of a cholinergic muscarine receptor antagonist and not by a cholinergic nicotinic receptor antagonist suggests that cholinoceptive neurons and endogenous cGMP may regulate heat loss through cholinergic muscarine receptors. It is concluded that these results indicate a regulatory role in thermoregulation provided by a balance between opposing actions of cAMP and cGMP in guinea pigs.

Kandasamy, S. B.↗

Presynaptic elements involved in the maintenance of the neuromuscular junction

Alterations in the neuromuscular junction were observed in rats preceding loss of muscle mass. In view of the possibility that these alterations involve changes in the secretion of myotrophic agents by presynaptic motor neurons, an investigation was undertaken to characterize a neuronall factor which is thought to be involved in the initiation and maintenance of cholinergic synapses. This factor, which is secreted into the incubation medium by NG108-15 neuroblastoma x glioma hybrid cells, induces the aggregation of nicotinic acetylcholine receptors on primary cultures of rat hindlimb myotubes. Previous attempts to purify this factor failed. Extensive washing of the NG108-15 cells with hepes-buffered salt solution followed by short (4 hour) collection times resulted in the collection of incubation medium containing maximal aggregation activity with as little as 5 ug secreted protein per ml of fresh medium. A three-fold increase in specific activity was obtained after anion exchange chromatography.

Burrows, G. H.↗

Disuse Induced Changes in the Cholinergic System of Sciatic Nerve and Slow and Fast Twitch Muscle of Rats

Hindlimb suspension was used as a model of disuse in experiments studing the effects of reduced muscle activity on AChE and its molecular forms, choline acetyltransferase and nicotinic receptor binding in innervated slow and fast muscle. The weight of SOL was reduced to 64% within one week and continued to decrease progressively up to the third week when the weight was reduced to 40% as compared to controls. EDL showed a significant decrease in its weight only at the end of three weeks hypokinesia when it was reduced to 71% of control. Biochemical and histochemical findings are summarized. From these data and from morphological findings it is evident that some properties of skeletal muscles are strongly dependent on patterns and level of loadbearing and on motor unit activiy. With suspension-induced disuse, the usually slow SOL appeared to change its characteristics such as fiber type distribution and AChE activity to one that more resembled a faster muscle. It is important to note that hypokinesia induced changes either physiological, biochemical or morphological, are totally reversible as the induced changes returned to control levels within a week after cessation of disuse.

Dettbarn, W. D.↗

Changes in the cholinergic system of rat sciatic nerve and skeletal muscle following suspension induced disuse

Muscle disused induced changes in the cholinergic system of sciatic nerve, slow twitch soleus (SOL) and fast twitch extensor digitorum longus (EDL) muscle were studied in rats. Rats with hindlimbs suspended for 2 to 3 weeks showed marked elevation in the activity of choline acetyltransferase (ChAT) in sciatic nerve (38%), in SOL (108%) and in EDL (67%). Acetylcholinesterase (AChE) activity in SOL increased by 163% without changing the molecular forms pattern of 4S, 10S, 12S, and 16S. No significant changes in activity and molecular forms pattern of AChE were seen in EDL or in AChE activity of sciatic nerve. Nicotinic receptor binding of 3H-acetylcholine was increased in both muscles. When measured after 3 weeks of hindlimb suspension the normal distribution of type 1 fibers in SOL was reduced and a corresponding increase in type IIa and IIb fibers is seen. In EDL no significant change in fiber proportion is observed. Muscle activity, such as loadbearing, appears to have a greater controlling influence on the characteristics of the slow twitch SOL muscle than upon the fast twitch EDL muscle.

Gupta, R. C.↗

Current status of the prebiotic synthesis of small molecules

Experiments designed to simulate conditions on the primitive earth and to demonstrate how the organic compounds that made up the first living organisms were synthesized are described. Simulated atmospheres with CH4, N2, NH3, and H2O were found to be most effective for synthesis of small prebiotic molecules, although atmospheres with H2, CO, N2, and H2O, and with H2, CO2, N2, and H2O also give good yields of organic compounds provided the H2/CO and H2/CO2 ratios are above 1 and 2, respectively. The spark discharge (which is a good source of HCN) and UV light are also important. Reasonable prebiotic syntheses were worked out for the amino acids that occur in proteins (with the exception of lysine, arginine, and histidine), and for purines, pyrimidines, sugars, and nicotinic acid. Many of the molecules that have been produced in these simulated primitive-earth experiments are found in carbonaceous chondrites.

Miller, Stanley L.↗

Spectral infrared hemispherical reflectance measurements for LDEF tray clamps

This paper describes infrared hemispherical reflectance measurements (2-15 microns) that were made on 58 chromic acid anodized tray clamps retrieved from the LDEF spacecraft. These clamps were used for maintaining the experiments in place and were located at various locations about the spacecraft. Changes in reflectance of the tray clamps at these locations were compared with atomic oxygen fluxes at the same locations. A decrease in absorption band depth was seen for the surfaces exposed to space indicating that there was some surface layer erosion. In all of the surfaces measured, little evidence of contamination was observed and none of the samples showed evidence of the brown nicotine stain that was so prominent in other experiments. Total emissivity values were calculated for both exposed and unexposed tray clamp surfaces. Only small differences, usually less than 1 percent, were observed. The spectral reflectances were measured using a hemi-ellipsoidal mirror reflectometer matched with an interferometer spectrometer. The rapid scanning capability of the interferometer allowed the reflectance measurements to be made in a timely fashion. The ellipsoidal mirror has its two foci separated by 2 inches and located on the major axis. A blackbody source was located at one focus while the tray clamp samples were located at the conjugate focus. The blackbody radiation was modulated and then focused by the ellipsoid onto the tray clamps. Radiation reflected from the tray clamp was sampled by the interferometer by viewing through a hole in the ellipsoid. A gold mirror (reflectance approximately 98 percent) was used as the reference surface.

Wood, Bobby E.↗

Reduced receptor aggregation and altered cytoskeleton in cultured myocytes after space-flight

We carried out parallel experiments first on the slow clinostat and then in space-flight to examine the effects of altered gravity on the aggregation of the nicotinic acetylcholine receptors and the structure of the cytoskeleton in cultured Xenopus embryonic muscle cells. By examining the concordance between results from space flight and the clinostat, we tested whether the slow clinostat is a relevant simulation paradigm. Space-flown cells showed marked changes in the distribution and organization of actin filaments and had a reduced incidence of acetylcholine receptor aggregates at the site of contact with polystyrene beads. Similar effects were found after clinostat rotation. The sensitivity of synaptic receptor aggregation and cytoskeletal morphology suggests that in the microgravity of space cell behavior may be importantly altered.

STS-56 Shuttle Project↗

Cultured rat vascular smooth muscle cells are resistant to methylamine toxicity: no correlation to semicarbazide-sensitive amine oxidase

Methylamine (MA), a component of serum and a metabolite of nicotine and certain insecticides and herbicides, is metabolized by semicarbazide-sensitive amine oxidase (SSAO). MA is toxic to cultured human umbilical vein and calf pulmonary artery endothelial cells. Endothelial cells, which do not exhibit endogenous SSAO activity, are exposed to SSAO circulating in serum. In contrast, vascular smooth muscle cells (VSMC) do exhibit innate SSAO activity both in vivo and in vitro. This property, together with the critical localization of VSMC within the arterial wall, led us to investigate the potential toxicity of MA to VSMC. Cultured rat VSMC were treated with MA (10-5 to 1 M). In some cultures, SSAO was selectively inhibited with semicarbazide or MDL-72145 [(E)-2-(3,4-dimethoxyphenyl)-3-fluoroallylamine]. Cytotoxicity was measured via MTT, vital dye exclusion, and clonogenic assays. MA proved to be toxic to VSMC only at relatively high concentrations (LC(50) of 0.1 M). The inhibition of SSAO with semicarbazide or MDL-72145 did not increase MA toxicity, suggesting that the production of formaldehyde via tissue-bound, SSAO-mediated MA metabolism does not play a role in the minimal toxicity observed in isolated rat VSMC. The omission of fetal calf serum (FCS), which contains high SSAO activity, from media similarly showed little effect on cytotoxicity. We conclude that VSMC--in contrast to previous results in endothelial cells--are relatively resistant to MA toxicity, and SSAO does not play a role in VSMC injury by MA.

Amine Oxidase (Copper-Containing)/metabolism↗

The pressor response to water drinking in humans : a sympathetic reflex?

BACKGROUND: Water drinking increases blood pressure profoundly in patients with autonomic failure and substantially in older control subjects. The mechanism that mediates this response is not known. METHODS AND RESULTS: We studied the effect of drinking tap water on seated blood pressure in 47 patients with severe autonomic failure (28 multiple system atrophy [MSA], 19 pure autonomic failure patients [PAF]). Eleven older controls and 8 young controls served as control group. We also studied the mechanisms that could increase blood pressure with water drinking. Systolic blood pressure increased profoundly with water drinking, reaching a maximum of 33+/-5 mm Hg in MSA and 37+/-7 in PAF mm Hg after 30 to 35 minutes. The pressor response was greater in patients with more retained sympathetic function and was almost completely abolished by trimethaphan infusion. Systolic blood pressure increased by 11+/-2.4 mm Hg in elderly but not in young controls. Plasma norepinephrine increased in both groups. Plasma renin activity, vasopressin, and blood volume did not change in any group. CONCLUSIONS: Water drinking significantly and rapidly raises sympathetic activity. Indeed, it raises plasma norepinephrine as much as such classic sympathetic stimuli as caffeine and nicotine. This effect profoundly increases blood pressure in autonomic failure patients, and this effect can be exploited to improve symptoms due to orthostatic hypotension. Water drinking also acutely raises blood pressure in older normal subjects. The pressor effect of oral water is an important yet unrecognized confounding factor in clinical studies of pressor agents and antihypertensive medications.

Non-NASA Center↗

Stabilized NADH as a Countermeasure for Jet Lag

Current remedies for jet lag (phototherapy, melatonin, stimulant, and sedative medications) are limited in efficacy and practicality. The efficacy of a stabilized, sublingual form of reduced nicotin amide adenine dinucleotide (NADH, ENADAlert, Menuco Corp.) as a countermeasure for jet lag was examined. Because NADH increases cellular production of ATP and facilitates dopamine synthesis, it may counteract the effects of jet lag on cognitive functioning and sleepiness. Thirty-five healthy, employed subjects participated in this double-blind, placebo-controlled study. Training and baseline testing were conducted on the West Coast before subjects flew overnight to the East Coast, where they would experience a 3-hour time difference. Upon arrival, individuals were randomly assigned to receive either 20 mg of sublingual stabilized ADH (n=18) or identical placebo tablets (n=17). All participants completed computer-administered tests (including CogScreen7) to assess changes in cognitive functioning, mood, and sleepiness in the morning and afternoon. Jet lag resulted in increased sleepiness for over half the participants and deterioration of cognitive functioning for approximately one third. The morning following the flight, subjects experienced lapses of attention in addition to disruptions in working memory, divided attention, and visual perceptual speed. Individuals who received NADH performed significantly better on 5 of 8 cognitive and psychomotor test measures (P less than or equal to 0.5) and showed a trend for better performance on the other three measures (P less than or equal to .l0). Subjects also reported less sleepiness compared with those who received placebo. No adverse effects were observed with NADH treatment. Stabilized NADH significantly reduced jet lag-induced disruptions of cognitive functioning, was easily administered, and was found to have no adverse side effects.

Kay, Gary G.↗

Interaction of genetic predisposition and environmental factors in the pathogenesis of idiopathic orthostatic intolerance

BACKGROUND: The hemodynamic and autonomic abnormalities in idiopathic orthostatic intolerance (IOI) have been studied extensively. However, the mechanisms underlying these abnormalities are not understood. If genetic predisposition were important in the pathogenesis of IOI, monozygotic twins of patients with IOI should have similar hemodynamic and autonomic abnormalities. METHODS: We studied two patients with IOI and their identical twins. Both siblings in the first twin pair had orthostatic symptoms, significant orthostatic tachycardia, increased plasma norepinephrine levels with standing, and a greater than normal decrease in systolic blood pressure with trimethaphan infusion. RESULTS: Both siblings had a normal response of plasma renin activity to upright posture. In the second twin pair, only one sibling had symptoms of orthostatic intolerance, an orthostatic tachycardia, and raised plasma catecholamines with standing. The affected sibling had inappropriately low plasma renin activity with standing and was 8-fold more sensitive to the pressor effect of phenylephrine than the unaffected sibling. CONCLUSIONS: We conclude that in some patients, IOI seems to be strongly influenced by genetic factors. In others, however, IOI may be mainly caused by nongenetic factors. These findings suggest that IOI is heterogenous, and that both genetic and environmental factors contribute individually or collectively to create the IOI phenotype.

NASA Discipline Regulatory Physiology↗