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At least 19 recordsLinked to original sources

PubMed1991

Metabolic conversion of dicarboxylic acids to succinate in rat liver homogenates. A stable isotope tracer study.

The metabolic conversion of dicarboxylic acids into succinate and other gluconeogenic intermediates in rat liver homogenates was investigated using [1,2,4-13C4]dodecanedioic acid as tracer. Isotope enrichments in 3-hydroxybutyrate, succinate, fumarate, and malate, as well as dicarboxylates (dodecanedioic, sebacic, suberic, and adipic acids) were measured with selected ion monitoring capillary column gas chromatograph-mass spectrometry. Significant enrichment in the M + 4 (four labeled carbons) ion of succinate (0.4-2.9%) was detected, unequivocally demonstrating the direct conversion of dicarboxylate into succinate. In addition, significant enrichment of the M + 2 ion of succinate was also observed. This labeled species was generated from labeled acetyl-CoA through the tricarboxylic acid cycle. The partition of acetyl-CoA into the tricarboxylic acid cycle relative to ketone body formation was higher in the beta oxidation of dicarboxylate than monocarboxylate. Therefore, in addition to the production of succinate, the beta oxidation of dodecanedioate resulted in the channeling of the acetyl-CoA produced to the tricarboxylic acid cycle instead of to acetoacetate production. The enrichments in lower chain dicarboxylates are consistent with a partial bidirectional beta oxidation of dodecanedioic acid. In addition to the expected M + 0 and M + 4 labels, significant M + 2 species were detected in suberic and adipic acids. These M + 2-labeled species were produced from the released free dicarboxylate intermediates which were then reactivated and metabolized. In these experiments, the overall succinate production was derived 4% from the direct conversion of dodecanedioic acid and 11% from the indirect route via acetyl-CoA through tricarboxylic acid.

Acetyl Coenzyme A↗

PubMed1987

Models to interpret kinetic data in stable isotope tracer studies.

In contrast to "weightless" radioactive tracers, stable isotope tracers have nonnegligible mass and are naturally present in the system, and the measured variable is a ratio of two isotopic species. These features do not allow stable isotopic tracer data analysis using straightforward analogy with radioactive tracer approaches, even though this practice is common. In this study, we present kinetic variables, models, and measurements for the analysis and interpretation of stable isotope tracer data. Assumptions and mathematical techniques for modeling the data when perturbation is both nonnegligible and negligible are discussed. Emphasis is placed on the rich information content of the dynamic portion of a stable isotope tracer curve and on the role of compartmental and noncompartmental modeling approaches for its interpretation. A presumed and commonly used analogy between the radioactive specific activity and stable isotopic enrichment is shown to be incorrect. We show that the proper analogue of specific activity is the tracer-to-tracee molar ratio. This variable is not a directly measurable one, but a formula is derived that allows its computation from the data. A method for reconstructing the time course in blood of the concentration component due to endogenous synthesis is presented. This allows measurement of the extent of the perturbation in the case where a nonweightless tracer is used. Special attention is given to data analysis originating from a multiple tracer experiment, a configuration necessary for studying more complex systems, e.g., the kinetics of interacting substrates.

3-Hydroxybutyric Acid↗

PubMed1990

Recent studies of human calcium metabolism using stable isotopic tracers.

Stable isotopes of calcium are used safely as tracers for calcium in human populations ranging in age from infants to postmenopausal women. Thermal ionization mass spectrometry is used to measure calcium isotope ratios with relative accuracies of about 1% for natural abundance ratios at precisions of about 1% relative to the mean. Perturbations of natural abundance ratios are determined for the calcium in blood, urine, and feces with a limit of detection of about 2 delta % excess. The mathematical rationale for clinical studies of fractional absorption of dietary calcium and the kinetics of calcium's internal distribution are presented.

Animals↗

PubMed1992

A mass spectrometric method for measuring glycerol levels and enrichments in plasma using 13C and 2H stable isotopic tracers.

The stable isotope tracer [1,1,2,3,3,-2H5]glycerol has been commonly used as a tracer to measure glycerol kinetics and lipolysis in vivo. The method for measuring samples using the trimethylsilyl derivative and electron impact gas chromatograph-mass spectrometry retains only three of the five deuteriums, resulting in the possibility of incorrectly identifying the whole glycerol tracer molecule. This reports preparation of glycerol as the heptafluorobutyrl derivative and measurement by negative ion chemical ionization gas chromatography-mass spectrometry to produce a derivative with an intense molecular ion that retains all five deuterium labels. Thus the heptafluorobutyrl derivative analyzed by negative ion mass spectrometry overcomes the problems associated with fragmentation and loss of the isotopic label. Glycerol concentration using a labeled internal standard can be determined in plasma with a precision of 3%. Nanomole amounts of glycerol can be analyzed for 13C or 2H enrichments with a precision of +/- 0.14 mol% excess isotope. This simple, sensitive method for measuring glycerol levels and stable isotopic enrichment in plasma uses a simple extraction procedure and requires a minimal volume of plasma (less than 300 microliters).

Adult↗

PubMed2006

Uptake and elimination of lead, zinc, and copper by caddisfly larvae (Trichoptera: Hydropsychidae) using stable isotope tracers.

Stable isotopes of Pb, Zn, and Cu were used in laboratory experiments to determine the uptake and elimination of these metals by stream-dwelling caddisfly (Trichoptera: Hydropsychidae) larvae. For Pb and Cu, larvae were exposed to environmentally realistic levels (2.5 and 4.5 microg x L(-1), respectively) of one isotope for 9 days followed by a 9-day exposure to either the same isotope, to a second stable isotope of the same metal, or to RW containing no added isotope (two phases in total). For zinc, the exposure concentration was 15 microg x L(-1), and the experiment lasted for a total of 27 (i.e., three phases) rather than 18 days to see if uptake and elimination changed during the extended time period. The uptake clearances (k(u)) determined for the various metals averaged 7.8, 1.4, and 0.6 L x g dw(-1) x d(-1) for Pb, Zn, and Cu, respectively, if the total metal concentration in the water was used in the calculations. The clearance rate constants (k(e)) were less variable, averaging 0.15 d(-1) for Pb, 0.22 d(-1) for Zn, and approximately 0.1 d(-1) for Cu and were similar in both the presence (i.e., elimination) and absence (i.e., depuration) of metal in the water. These values are also comparable with those reported in the literature for other aquatic invertebrates. The use of stable isotopes thus allowed simultaneous measurement of uptake and clearance (elimination and depuration) of these metals at environmentally realistic concentrations and could be of great benefit for determining partitioning, assimilation efficiency, and pathways of these and other metals in the environment.

Animals↗

PubMed1997

Availability of stable isotope tracers for human use.

Stable isotope tracers do not have approval for diagnostic use in humans. We assume that stable isotope tracers behave like natural compounds, because there is no evidence for the opposite despite a wide use in human studies. From this point of view, they are drugs comparable to unlabelled natural substances. Under this assumption a pharmacy is allowed to prepare isotope solutions by following the guideline for the preparation of infusion solutions using chemicals. The pharmacy has to perform tests for identification, content and purity following the U.S. pharmacopoeia or the corresponding national standard for the unlabelled drug. If these tests are passed then it can prepare the tracer solution. An approach is outlined which is designed to ensure sterility of the preparation as far as possible and an adequate pharmaceutical quality. From the regulation for the preparation we define requirements for an alternative preparation for immediate infusion by the physician.

Humans↗

PubMed2002

Partitioning and bioaccumulation of cadmium in artificial sediment systems: application of a stable isotope tracer technique.

The utility of stable isotope tracers for investigating the relationship between cadmium (Cd) partitioning in artificial sediment-water systems and Cd accumulation in a benthic detritivore (Asellus racovitzai, Isopoda) was explored. In the laboratory, Cd isotopes were applied to synthetic sediment and isotope concentrations were measured in sediment, overlying water and exposed asellids over a 10-day period. Isotope ratios measured in sediment and water were compared to ratios measured in asellids to determine whether Cd partitioning could predict metal bioaccumulation. Two different parameters which might affect Cd partitioning between the sediment and overlying water compartments were investigated: the chemical form in which Cd was added to systems, and the organic matter content of the sediment. To test the effect of chemical form on Cd partitioning, three isotopes of cadmium were individually applied to formulated sediment in varying combinations of 113Cd(NO3)2, 112Cd-humic acid (HA) 114CdSO4. The results demonstrated that chemical form did not influence partitioning, as the Cd isotope that was applied to sediment in the nitrate form exhibited similar partitioning between sediment and overlying water as the isotope that was applied in the sulfate or HA form. However, Cd isotope concentrations in overlying water were strongly related to the pattern of isotope accumulation in asellids suggesting that overlying water concentrations determined Cd bioaccumulation. In contrast, when the organic matter content of sediment was increased through the addition of Sphagnum peat moss, total Cd concentrations in overlying water and tissue were low, and there was no relationship between Cd-isotope concentrations in tissue and water. These results indicate that Cd accumulation occurred primarily from water, and factors that increase metal partitioning to sediment, such as increased sediment organic matter content, decrease Cd accumulation in asellids. The stable isotope tracer method described herein appears to be a useful technique for investigating the relationship between metal partitioning and bioaccumulation in simple sediment systems, but could also be extended to more complex systems, and used with different metals that have multiple stable isotopes.

Animals↗

PubMed2003

The use of ICPMS for stable isotope tracer studies in humans: a review.

The use of stable isotope tracers in human studies is a rapidly growing research field that benefits from the many new developments in inorganic mass spectrometric instrumentation and from the better availability of mass spectrometric techniques to nutritional scientists during the last three decades. Traditionally, thermal ionization mass spectrometry (TIMS) has been the preferred technique for these studies, but the development of new inductively coupled plasma mass spectrometric (ICPMS) techniques with better isotope-ratio measurement and interference-removal capabilities (e.g. single and multi-detector ICPMS and reaction/collision cell ICPMS) has enabled broader use of ICPMS for determination of stable isotope tracers in nutritional research. This review discusses the current and future use of ICPMS in stable isotope tracer studies in humans.

Humans↗

PubMed1992

Tracer-to-tracee ratio for analysis of stable isotope tracer data: link with radioactive kinetic formalism.

A kinetic formalism for the analysis of stable isotope transient tracer data is developed by establishing the link with the formalism available for radioactive tracer data. The crucial variable is the tracer-to-tracee ratio. By expressing the measurements in terms of this ratio, the conventional kinetic formalism used for radioactive data can be applied to estimate noncompartmental parameters using stable isotope tracer data. The tracer-to-tracee ratio also plays an important role in compartmental modeling. By considering the tracer masses in the compartments as state variables the system-experiment model can be written in a format analogous to that usually adopted for the radioactive tracer. Finally, it is shown that the tracer-to-tracee ratio also plays a role in a test of the endogenous steady-state assumption.

Animals↗

PubMed2005

A groundwater separation study in boreal wetland terrain: the WATFLOOD hydrological model compared with stable isotope tracers.

Monitoring of stable water isotopes (18O and 2H) in precipitation and surface waters in the Mackenzie River basin of northern Canada has created new opportunities for researchers to study the complex hydrology and hydroclimatology of this remote region. A number of prior studies have used stable isotope data to investigate aspects of the hydrological regime of the wetland-dominated terrain near Fort Simpson, Northwest Territories, Canada. The present paper compares estimates of groundwater contributions to streamflow derived using the WATFLOOD distributed hydrological model, equipped with a new water isotope tracer module, with the results of conventional isotope hydrograph separation for five wetland-dominated catchments along the lower Liard River. The comparison reveals highly promising agreement, verifying that the hydrological model is simulating groundwater flow contributions to total streamflow with reasonable fidelity, especially during the crucial snowmelt period. Sensitivity analysis of the WATFLOOD simulations also reveals intriguing features about runoff generation from channelized fens, which may contribute less to streamflow than previously thought.

Canada↗

PubMed2002

Simultaneous measurement of uptake and elimination of cadmium by caddisfly (Trichoptera: Hydropsychidae) larvae using stable isotope tracers.

The use of stable isotopes coupled with inductively coupled plasma-mass spectrometry provides a unique opportunity to investigate pathways of metals in aquatic invertebrates. In this study, the simultaneous uptake and elimination of cadmium (Cd) in stream-dwelling caddisfly (Trichoptera: Hydropsychidae) larvae was measured in laboratory experiments with stable isotopes of Cd. In one experiment, animals were exposed to low levels (0.5 microg/L) of 114Cd in filtered river water and uptake was measured for 9 d, followed by 9 d during which the larvae were exposed to either 114Cd, 113Cd, or filtered river water. In a second experiment, the initial exposure concentration of 114Cd varied from 0.1 to 1.6 microg/L for 5 d, followed by 5 d during which the larvae were exposed to the same respective levels of 113Cd. The purpose of the two experiments was to test whether or not elimination of 114Cd from Hydropsyche larvae was the same in the presence or absence of Cd in the water and also whether or not elimination rates were dependent on exposure concentration. The results indicated that elimination of Cd by Hydropsyche larvae (elimination rate constant approximately 0.21-0.24/d) in the presence of Cd in the water was the same as the depuration when no metal was present. Furthermore, the elimination rate was independent of exposure concentrations, ranging between 0.1 and 1.6 microg/L. Thus, the stable isotope tracer technique enabled the simultaneous measurement of uptake and elimination of Cd in hydropsychid larvae and may have the potential to facilitate the labeling of various compartments (e.g., water, sediment, and food) in the aquatic environment.

Animals↗

PubMed2006

Mineral bioavailability and metabolism determined by using stable isotope tracers.

Definitive data on mineral bioavailability in humans and animals can be obtained by using isotopic tracers. The use of stable isotope tracers to study important issues in mineral nutrition has expanded rapidly in the past two decades, particularly in human nutrition studies. Stable isotopes have a number of advantages over radioisotopes. There is no exposure to radiation with stable isotopes, and some minerals have no radioisotope that can be used satisfactorily as a tracer. Multiple stable isotopes of one mineral and isotopes of multiple minerals can be administered simultaneously or sequentially. The analytical methods of choice for stable isotopes are thermal ionization mass spectrometry and inductively coupled plasma mass spectrometry (ICPMS). Thermal ionization mass spectrometry offers the greatest precision and accuracy, but it is slower, more labor intensive, and more costly than ICPMS. Bioavailability data are critical to establishing reliable dietary mineral requirements and recommendations. Combined with a computer program for compartmental modeling, mineral kinetics can be studied, including mineral turnover, pool sizes, and transfer rates between compartments. Our laboratory conducts studies using stable isotopes of Zn, Cu, Fe, Ca, Mg, and Mo. We have studied the effect of the amount of dietary intake of minerals on bioavailability and use, pregnancy and aging, and interactions among minerals. The research resulted in establishing new dietary recommendations for Cu and Mo and developing compartmental models for these minerals. Although stable isotopes have been used more extensively to date in humans than in animals, the techniques applied to humans can be used to study a number of issues important to optimizing feeding strategies for animal production.

Animal Nutritional Physiological Phenomena↗

PubMed2004

Using isotope tracers to study metabolism: application in mouse models.

The application of isotope tracers for investigating metabolism in mice is discussed. To familiarize the reader, some basic principles regarding the use of tracer methods are outlined. Emphasis is placed on showing how investigators are using isotope tracers to study the regulation of carbohydrate, fat and/or protein turnover in vivo. Finally, some of the advantages of using labeled water (i.e., 2H(2)O and/or H(2)18O) to trace the kinetics of biological processes are considered. The background provided in this report should assist engineers in designing studies that enhance our understanding of conditions in which metabolism is altered (e.g., diabetes, cancer cachexia, failure to thrive and travel at zero-gravity).

Animals↗

PubMed2004

A dual stable isotope tracer method for the measurement of surfactant disaturated-phosphatidylcholine net synthesis in infants with congenital diaphragmatic hernia.

The aim of the study was to measure for the first time in humans surfactant disaturated-phosphatidylcholine (DSPC) net synthesis and kinetics by using a novel, dual stable isotope tracer approach. Ten infants with congenital diaphragmatic hernia [CDH; birth weight, 3.4 +/- 0.2; gestational age, 39.8 +/- 0.4 wk] and 6 age-matched control subjects with no lung disease (birth weight, 3.2 +/- 0.3 kg; gestational age, 39.1 +/- 1.1 wk), all of whom were admitted to the neonatal intensive care unit (Padua, Italy), were studied. All infants received simultaneously an intratracheal (carbon-13 di-palmitoyl-phosphatidylcholine) and an i.v. (deuterated palmitic acid) stable isotope tracer. Isotopic enrichment curves of DSPC from sequential tracheal aspirates were analyzed by mass spectrometry. DSPC kinetic data were expressed as mean +/- SEM and compared by the Mann-Whitney test. DSPC net synthesis from plasma palmitate was nearly identical in infants with CDH and control subjects (8.6 +/- 2.2 and 8.1 +/- 1.5 mg. kg(-1). d(-1); P = 0.7). DSPC apparent pool size was 36.7 +/- 7.5 and 58.5 +/- 9.1 mg/kg (P = 0.07) and half-life was 26.7 +/- 4.5 and 50.3 +/- 9.7 h (P = 0.03) in infants with CDH and control subjects, respectively. Both DSPC turnover and percentage of catabolism/recycling significantly correlated with duration of mechanical ventilation. In conclusion, the measurements of net DSPC synthesis and catabolism/recycling were reported for the first time in humans. Mean net DSPC synthesis was approximately 8 mg. kg(-1). d(-1). No significant differences were found between control subjects and infants with CDH. DSPC turnover was faster in infants with CDH, presumably reflecting an increased DSPC catabolism/recycling. Whether this may ultimately lead to a secondary surfactant deficiency in infants with CDH is still to be ascertained.

Animals↗

PubMed2000

Profiles of faecal output of rare earth elements and stable isotopic tracers of iron and zinc after oral administration.

The objectives of this study were to confirm the non-absorbability and the reproducibility of faecal excretion kinetics of orally administered rare earth elements, and to investigate the excretion profiles of rare earth elements and stable isotopic tracers of Fe and Zn to establish the extent to which rare earth element markers duplicate the behaviour of isotopic tracers. Two investigations were performed: (1) six healthy subjects consumed a solution containing five rare earth elements in amounts varying from 1 to 10 mg; (2) seven healthy subjects were given a standard solution labelled with Sm marker and (57)Fe tracer, and a meal labelled with Yb marker and (58)Fe and (70)Zn tracers. Individual faecal samples were collected and analysed to determine recoveries of rare earth elements and unabsorbed isotopic tracers. The mean values for recoveries were 94.1 (sd 4.5) % for the five rare earth elements, and 103 (sd 3.0) % and 99.8 (sd 2.8) % for Sm and Yb respectively. For Fe consumed with the solution, excretion kinetics of the rare earth element marker and unabsorbed tracers with cumulative collections of the first two and three faecal samples were identical, but endogenous excretion of Fe was significant in stools collected after the third. For Fe and Zn consumed with the meal, the excretion kinetics for the first two individual faecal samples and composites of sequential outputs were identical. Rare earth elements can be used as markers in studies of measurement of absorption. The dose of tracer required for the measurement of absorption would be reduced proportionally to the reduction of the period of faecal sampling, so that studies with stable isotopes would be more economical, thus enabling epidemiological investigations.

Administration, Oral↗

PubMed1998

Intramuscular fatty acid metabolism evaluated with stable isotopic tracers.

We evaluated the applicability of stable isotopic tracers to the study of intramuscular fatty acid metabolism by infusing both [U-13C]palmitate and [1-13C]oleate intravenously for 4 h into fasted conscious rats. Skeletal muscles were sequentially biopsied, and the concentration and 13C enrichment of fatty acids were measured by gas chromatography/combustion/isotope ratio mass spectrometry. Throughout the study, the 13C enrichment of plasma palmitate and oleate remained substantially greater than intramuscular nonesterified palmitate and oleate enrichment, which in turn was greater than intramuscular triglyceride palmitate and oleate enrichment. Fractional synthesis rates of intramuscular triglycerides in gastrocnemius and soleus were 0.267 +/- 0.075 and 0. 100 +/- 0.030/h (P = 0.04), respectively, as determined by using [U-13C]palmitate, and were 0.278 +/- 0.049 and 0.075 +/- 0.013/h (P = 0.02), respectively, by using [1-13C]oleate. We conclude that plasma free fatty acids are a source for intramuscular triglycerides and nonesterified fatty acids; the latter are likely the synthetic precursors of the former. Uniformly and singly labeled [13C]fatty acid tracers will provide an important tool to study intramuscular fatty acid and triglyceride metabolism.

Animals↗

PubMed2006

Subcutaneous infusion and capillary "finger stick" sampling of stable isotope tracer in metabolic studies.

Metabolic studies utilizing stable isotope tracer in humans have typically used intravenous tracer infusions and venous blood sampling. These studies explore subcutaneous infusion of isotope and "finger stick" capillary blood sampling to measure glucose turnover. Five subjects received simultaneous 8-h infusions of glucose labeled with isotope: [1-(13)C]glucose subcutaneously and [6,6-(2)H(2)]glucose intravenously. At regular intervals, venous and finger stick blood specimens were obtained. Finger stick blood was applied to filter paper. Substrate and isotopic steady state was reached after 7.0 h with both routes of infusion. The isotopic enrichments of finger stick and venous specimens did not differ significantly for the subcutaneously infused [1-(13)C]glucose (p = 0.33 and p = 0.23, respectively) but the finger stick [6,6-(2)H(2)]glucose enrichment was slightly higher (p < 0.03) than that of the venous sample. Using [6,6-(2)H(2)]glucose infusion and venous plasma sampling as the reference method, the [1-(13)C]glucose gave estimates of glucose R(a) that were 13% (plasma) and 17% (finger stick) lower (p < 0.001 and p < 0.02, respectively). This difference could be attributed to recycling of (13)C label. In conclusion, subcutaneous infusion and finger stick specimen collection onto filter paper represent a potential method of conducting in vivo studies of substrate metabolism outside of a hospital-based research unit.

Adult↗

PubMed1977

In-vivo measurement of glucose and alanine metabolism with stable isotopic tracers.

This report describes sensitive, precise microtechniques that allow quantification of glucose and alanine metabolism in vivo using stable isotope tracers. By combined gas chromatography--mass spectrometry and selected ion monitoring--deuterium and carbon-13 enrichment in blood glucose and alanine were measured with an error of less than 2 per cent. Estimation of glucose and alanine flux in dogs by stable isotope tracer techniques was compared with simultaneous measurements made in the same animal with conventional radiotracer dilution methods. Application of the described stable isotope methods to determination of glucose and alanine turnover as well as alanine-2,3-13C incorporation into glucose in adult men confirmed the safety and validity of these techniques for human investigation.

Alanine↗