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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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At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2001

Quantitation of promethazine and metabolites in urine samples using on-line solid-phase extraction and column-switching

A chromatographic method for the quantitation of promethazine (PMZ) and its three metabolites in urine employing on-line solid-phase extraction and column-switching has been developed. The column-switching system described here uses an extraction column for the purification of PMZ and its metabolites from a urine matrix. The extraneous matrix interference was removed by flushing the extraction column with a gradient elution. The analytes of interest were then eluted onto an analytical column for further chromatographic separation using a mobile phase of greater solvent strength. This method is specific and sensitive with a range of 3.75-1400 ng/ml for PMZ and 2.5-1400 ng/ml for the metabolites promethazine sulfoxide, monodesmethyl promethazine sulfoxide and monodesmethyl promethazine. The lower limits of quantitation (LLOQ) were 3.75 ng/ml with less than 6.2% C.V. for PMZ and 2.50 ng/ml with less than 11.5% C.V. for metabolites based on a signal-to-noise ratio of 10:1 or greater. The accuracy and precision were within +/- 11.8% in bias and not greater than 5.5% C.V. in intra- and inter-assay precision for PMZ and metabolites. Method robustness was investigated using a Plackett-Burman experimental design. The applicability of the analytical method for pharmacokinetic studies in humans is illustrated.

NASA Center JSC↗
NASA NTRS2008

Focused Metabolite Profiling for Dissecting Cellular and Molecular Processes of Living Organisms in Space Environments

Regulatory control in biological systems is exerted at all levels within the central dogma of biology. Metabolites are the end products of all cellular regulatory processes and reflect the ultimate outcome of potential changes suggested by genomics and proteomics caused by an environmental stimulus or genetic modification. Following on the heels of genomics, transcriptomics, and proteomics, metabolomics has become an inevitable part of complete-system biology because none of the lower "-omics" alone provide direct information about how changes in mRNA or protein are coupled to changes in biological function. The challenges are much greater than those encountered in genomics because of the greater number of metabolites and the greater diversity of their chemical structures and properties. To meet these challenges, much developmental work is needed, including (1) methodologies for unbiased extraction of metabolites and subsequent quantification, (2) algorithms for systematic identification of metabolites, (3) expertise and competency in handling a large amount of information (data set), and (4) integration of metabolomics with other "omics" and data mining (implication of the information). This article reviews the project accomplishments.

Source record↗
NASA NTRSDate not supplied

Separation of isobaric Amino Acids and Small Molecule Metabolites Using Multipass Ion Mobility Analysis

Amino acids along with small molecule metabolites are important biomarkers for the study and detection of diseases that are initially analyzed in untargeted omics fashion. Amino acids and many metabolites are isomeric, and their specific form can have a significant impact on biological function. Chromatographic separation of isomers is challenging, and they cannot be resolved by mass spectrometry alone. Ion mobility is a technique that allows the separation of ions based on their size, shape, and charge. Here we present the results of the separation of isobaric amino acids and small molecule metabolites using a system that allows for multi-pass ion mobility separation which, in turn, enhances the ion mobility resolution of the separation. Amino acid standards and small molecule metabolites commercially available were infused directly into a SELECT SERIES™ Cyclic™ IMS system. Solutions of individual and mixture of the isobaric species were used and the mobility conditions were optimized for multiple passes for each corresponding set of isobaric species. Both ionization polarities and various solvent adducts were tested to provide the best signal intensity and separation. Amino acids such as leucine and isoleucine have previously been separated with ion mobility in a system with lower ion mobility resolution (SYNAPT™ G2 mass spectrometer) rendering about 90% of valley and mobility resolution of around 40 Ω/ΔΩ. With the enhanced ion mobility resolution using the cyclic IMS technique we have obtained almost complete separation of those amino acids rendering a valley of about 10% after 15 passes. For this case, the mobility resolution is around 250 Ω/ΔΩ. Another example is the separation of glucose-6-phosphate from glucose-1-phosphate, and fructose-6phosphate which were separated after 10 passes. For this case, the mobility resolution is around 205 Ω/ΔΩ.

Hernando J Olivos↗
NASA NTRS1978

Experiment requirements: Vitamin D metabolites and bone demineralization, Spacelab 2, experiment no. 1

As a contribution toward an understanding of the molecular basis of bone loss, mineral imbalance, and increasing fecal calcium under conditions of prolonged space flight, the blood levels of biologically active vitamin D metabolites of flight crew members will be quantitatively measured. Prior to the mission, the refinement of existing and the development of new techniques for the assay of all vitamin D metabolites will provide an arsenal of methods suitable for a wide range of metabolite levels. In terms of practical application, the analysis of human and animal plasma samples, Spacelab crew plasma samples, and flight hardware are envisioned.

Schnoes, H. K.↗
NASA NTRS1992

Synergistic action of the benzene metabolite hydroquinone on myelopoietic stimulating activity of granulocyte/macrophage colony-stimulating factor in vitro

The effects of in vitro pretreatment with benzene metabolites on colony-forming response of murine bone marrow cells stimulated with recombinant granulocyte/macrophage colony-stimulating factor (rGM-CSF) were examined. Pretreatment with hydroquinone (HQ) at concentrations ranging from picomolar to micromolar for 30 min resulted in a 1.5- to 4.6-fold enhancement in colonies formed in response to rGM-CSF that was due to an increase in granulocyte/macrophage colonies. The synergism equaled or exceeded that reported for the effects of interleukin 1, interleukin 3, or interleukin 6 with GM-CSF. Optimal enhancement was obtained with 1 microM HQ and was largely independent of the concentration of rGM-CSF. Pretreatment with other authentic benzene metabolites, phenol and catechol, and the putative metabolite trans, trans-muconaldehyde did not enhance growth factor response. Coadministration of phenol and HQ did not enhance the maximal rGM-CSF response obtained with HQ alone but shifted the optimal concentration to 100 pM. Synergism between HQ and rGM-CSF was observed with nonadherent bone marrow cells and lineage-depleted bone marrow cells, suggesting an intrinsic effect on recruitment of myeloid progenitor cells not normally responsive to rGM-CSF. Alterations in differentiation in a myeloid progenitor cell population may be of relevance in the pathogenesis of acute myelogenous leukemia secondary to drug or chemical exposure.

NASA Discipline Environmental Health↗
NASA NTRS1973

Hypoxia, an adjunct in helium-cold hypothermia - Sparing effect on hepatic and cardiac metabolites.

Investigation of the effect of hypoxia on the depletion of metabolites that occurs in helium-aided induction of hypothermia. Hypoxic slowing of the heart of a hamster while exposed to cold helox is demonstrated. An attempt is made to evaluate the relative importance of cardiac slowing and limitation of thermogenesis in determining the effect of hypoxia. In explanation of the results presented, it is suggested that hypoxia limits the energy expenditure by the heart during induction.

Anderson, G. L.↗
NASA NTRS1974

Automated analysis of oxidative metabolites

An automated system for the study of drug metabolism is described. The system monitors the oxidative metabolites of aromatic amines and of compounds which produce formaldehyde on oxidative dealkylation. It includes color developing compositions suitable for detecting hyroxylated aromatic amines and formaldehyde.

Furner, R. L.↗
NASA NTRS2004

Microminiature Monitor for Vital Electrolyte and Metabolite Levels of Astronauts

Ions, such as proton (pH) and potassium, play a crucial role in body fluids to maintain proper basic functioning of cells and tissues. Metabolites, such as glucose, control the energy available to the entire human body in normal as well as stress situations, and before, during, and after meals. These molecules diffuse easily between blood in the capillaries and the interstitial fluid residing between cells and tissues. We have developed and approach to monitoring of critical ions (called electrolytes) and glucose in the interstitial fluid under the human skin. Proton and potassium levels sensed using optode technology that translates the respective ionic concentrations into variable colors of corresponding ionophore/dye/polymeric liquid membranes. Glucose is monitored indirectly, by coupling through immobilized glucose oxidase with local pH that is then detected using a similar color scheme. The monitor consists of a tiny plastic bar, 100-200 microns wide and 1-2 mm long, placed just under the skin, with color changing spots for each analyte as well as blanks. The colors are read and translated into concentration values by a CCD camera. Direct optical coupling between the in vivo sensing bar and the ex vivo detector device requires no power, and thus eliminates the need for wires or optical fibers crossing the skin. The microminiature bar penetrates the skin easily and painlessly, so that astronauts could insert it themselves. The approach is fully compatible with telemetry in space, and thus, in vivo clinical data will be available real time in the Earth based command center once the device is fully developed. The information provided can be used for collecting hitherto unavailable vital data on clinical effects of space travel. Managing clinical emergencies in space with the sensor already in place should also become much more efficient than without a continuous monitor, as is currently the case. Civilian applications may include better glucose control of patients with moderate to severe diabetes: a growing health problem in the US and World-wide.

Tohda, Koji↗
NASA NTRS2004

High Salt Intake Promotes Urinary Loss of Vitamin D Metabolites by Dahl Salt-Sensitive Rats in a Space Flight Model

Vitamin D metabolism in the Dahl salt-sensitive (S) rat, a model of salt-induced hypertension, differs from that in the Dahl salt-resistant (R) rat. We have demonstrated that female S rats are more vulnerable than female R rats to decreases in plasma 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D (1,25-(OH)2D) concentrations during hind limb unloading (a space flight model). We report here on the response of the vitamin D endocrine system of S and R rats to hind limb unloading during high salt intake. Dahl female rats (9.7-week-old) were tail-suspended (hind limb unloaded) for 28 days, while fed a diet containing twice the salt in standard rat chow (2 % sodium chloride). Control rats were fed the same diet, but were not hind limb unloaded. Vitamin D metabolites were analyzed by HPLC and radioimmunoassay kits from Diasorin.

Thierry-Palmer, M.↗
NASA NTRS1974

Effect of 14 days of bed rest on urine metabolite excretion and plasma enzyme levels

After 1 week of ambulatory base-line measurement, a group of 8 men 19-26 years of age remained continuously recumbent for 14 days. Studies were continued for 1 week following the prolonged recumbency. Urine excretion rates for a number of constituents were determined 2 days before bed rest, on day 14 of bed rest, and day 6 after bed rest. Blood plasma samples were also obtained at these times, and analyzed for several enzymes. On day 14 of bed rest significant increases were observed in urine excretion of total osmotically-active substances, magnesium, calcium, phosphate, creatinine, hydroxyproline, and 17-OH corticosteroids. A decrease occurred in urinary glucose excretion. Plasma levels of alkaline phosphatase and LDH-3 were depressed, while plasma GPT was elevated. Many of these changes persisted on day 6 after bed rest, and are interpreted as concomitants of the disuse atrophy of the musculoskeletal system that characterizes prolonged bed rest and weightlessness.

Pace, N.↗
NASA NTRS1982

Analysis of volatile metabolites in biological fluids as indicators of prodromal disease condition

The volatile profile cannot be defined as a single class of substances, rather it is a broad spectrum of materials of different polarities characterized by having a boiling-point in the low to medium range (up to approximately 300 C) and the fact that the compounds are suitable for gas chromatography without derivatization. The organic volatile profiles are very complex mixtures of metabolic byproducts, intermediates, and terminal products of enzymatic degradations composed mainly of alcohols, ketones, aldehydes, pyrazines, sulfides, isothiocyanates, pyrroles, and furans. The concentration of organic volatiles in biological fluids covers a wide range with many important components present at trace levels. The complexity of the organic volatile fraction requires the use of capillary columns for their separation.

Zlatkis, A.↗
NASA NTRS1988

Vitamin D metabolites and bioactive parathyroid hormone levels during Spacelab 2

The effect of an 8-day space flight (Spacelab mission 2) on plasma levels of the vitamin D and parathyroid hormones is investigated experimentally in four crew members. The results are presented in tables and graphs and briefly characterized. Parathyroid hormone levels remained normal throughout the flight, whereas vitamin D hormone levels increased significantly on day 1 but returned to normal by day 7.

Morey-Holton, Emily R.↗
NASA NTRS1993

Control of cell cycle by metabolites of prostaglandin D2 through a non-cAMP mediated mechanism

The dehydration products of PGD2, 9-deoxy-9 prostaglandin D2(PGJ2), 9-deoxy-delta 9, delta 12, delta 13 dehydroprostaglandin D2 (delta 12 PGJ2), and PGA2 all contain an unsaturated cyclopentenone structure which is characteristic of prostaglandins which effectively inhibit cell growth. It has been suggested that the action of the inhibitory prostaglandins may be through a cAMP mechanism. In this study, we use S49 wild type (WT) and adenylate cyclase variant (cyc-) cells to show that PGD2 and PGJ2 are not acting via a cyclic AMP mechanism. First, the increase in cyclic AMP in wild type S-49 cells is not proportional to its effects on DNA synthesis. More importantly, when S-49 cyc- cells were exposed to PGJ2, the adenylate cyclase (cyc-) mutant had decreased DNA synthesis with no change in its nominal cAMP content. Short-term (2 hours or less) exposure of the cyc- cells to prostaglandin J2 caused an inhibition of DNA synthesis. PGJ2 caused cytolysis at high concentrations. Long-term exposure (>14 hrs) of the cells to PGJ2, delta 12PGJ2 or delta 12, delta 14PGJ2 caused a cell cycle arrest in G1 demonstrating a cell cycle specific mechanism of action for growth inhibition by naturally occurring biological products independent of cAMP.

NASA Discipline Cell Biology↗