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Sample records for absolute metabolite concentrations

  1. Absolute concentration determination of phosphorus metabolites in the Langendorff-perfused rabbit heart by phosphorus-31 nuclear magnetic resonance

    SciTech Connect

    Gard, J.K.

    1984-01-01

    The concentrations of mobile high energy phosphorus metabolites and intracellular pH of Langendorff-perfused rabbit heart have been determined under control and reduced flow conditions. Absolute concentration determination was accomplished by Lorentzian lineshape analysis after development of hexachlorocyclotriphosphazene as an external intensity standard. Hearts were demonstrated to be biochemically and physiologically competent during control perfusion periods and compromised during reduced flow conditions by independent hemodynamic and metabolic measurements coincident with the NMR experiment. Reduction in perfusate flow from 20 mL/min to 5.0 mL/min (25% flow) or 2.5 mL/min (12.5% flow) demonstrated a fall in phosphocreatine and adenosine triphosphate concentrations, a rise in cytosolic inorganic phosphate concentrations, and drops in pH. Subsequent recovery upon reflow was observed. The derived values for the free concentration of ADP were very close to the reported values of the Michaelis constant for respiratory stimulation, implicating a regulatory role for this molecule in cellular respiration. Strong evidence that the creating kinase reaction was in equilibrium in the 25% flow study was seen. The NMR observable correlated closely with myocardial performance and biochemical indices of metabolic function, and supported the use of phosphocreatine as an indicator of current metabolic integrity.

  2. Measurement of absolute concentrations of individual compounds in metabolite mixtures by gradient-selective time-zero 1H-13C HSQC with two concentration references and fast maximum likelihood reconstruction analysis.

    PubMed

    Hu, Kaifeng; Ellinger, James J; Chylla, Roger A; Markley, John L

    2011-12-15

    Time-zero 2D (13)C HSQC (HSQC(0)) spectroscopy offers advantages over traditional 2D NMR for quantitative analysis of solutions containing a mixture of compounds because the signal intensities are directly proportional to the concentrations of the constituents. The HSQC(0) spectrum is derived from a series of spectra collected with increasing repetition times within the basic HSQC block by extrapolating the repetition time to zero. Here we present an alternative approach to data collection, gradient-selective time-zero (1)H-(13)C HSQC(0) in combination with fast maximum likelihood reconstruction (FMLR) data analysis and the use of two concentration references for absolute concentration determination. Gradient-selective data acquisition results in cleaner spectra, and NMR data can be acquired in both constant-time and non-constant-time mode. Semiautomatic data analysis is supported by the FMLR approach, which is used to deconvolute the spectra and extract peak volumes. The peak volumes obtained from this analysis are converted to absolute concentrations by reference to the peak volumes of two internal reference compounds of known concentration: DSS (4,4-dimethyl-4-silapentane-1-sulfonic acid) at the low concentration limit (which also serves as chemical shift reference) and MES (2-(N-morpholino)ethanesulfonic acid) at the high concentration limit. The linear relationship between peak volumes and concentration is better defined with two references than with one, and the measured absolute concentrations of individual compounds in the mixture are more accurate. We compare results from semiautomated gsHSQC(0) with those obtained by the original manual phase-cycled HSQC(0) approach. The new approach is suitable for automatic metabolite profiling by simultaneous quantification of multiple metabolites in a complex mixture. PMID:22029275

  3. TE = 32 ms vs TE = 100 ms echo‐time 1H‐magnetic resonance spectroscopy in prostate cancer: Tumor metabolite depiction and absolute concentrations in tumors and adjacent tissues

    PubMed Central

    Basharat, Meer; Morgan, Veronica A.; Parker, Chris; Dearnaley, David; deSouza, Nandita M.

    2015-01-01

    Purpose To compare the depiction of metabolite signals in short and long echo time (TE) prostate cancer spectra at 3T, and to quantify their concentrations in tumors of different stage and grade, and tissues adjacent to tumor. Materials and Methods First, single‐voxel magnetic resonance imaging (MRI) spectra were acquired from voxels consisting entirely of tumor, as defined on T 2‐weighted and diffusion‐weighted (DW)‐MRI and from a biopsy‐positive octant, at TEs of 32 msec and 100 msec in 26 prostate cancer patients. Then, in a separate cohort of 26 patients, single‐voxel TE = 32 msec MR spectroscopy (MRS) was performed over a partial‐tumor region and a matching, contralateral normal‐appearing region, defined similarly. Metabolite depiction was compared between TEs using Cramér‐Rao lower bounds (CRLB), and absolute metabolite concentrations were calculated from TE = 32 msec spectra referenced to unsuppressed water spectra. Results Citrate and spermine resonances in tumor were better depicted (had significantly lower CRLB) at TE = 32 msec, while the choline resonance was better depicted at TE = 100 msec. Citrate and spermine concentrations were significantly lower in patients of more advanced stage, significantly lower in Gleason grade 3+4 than 3+3 tumors, and significantly lower than expected from the tumor fraction in partial‐tumor voxels (by 14 mM and 4 mM, respectively, P < 0.05). Conclusion Citrate and spermine resonances are better depicted at short TE than long TE in tumors. Reduction in these concentrations is related to increasing tumor stage and grade in vivo, while reductions in the normal‐appearing tissues immediately adjacent to tumor likely reflect tumor field effects. J. Magn. Reson. Imaging 2015;42:1086–1093. PMID:26258905

  4. Metabolite concentrations, fluxes and free energies imply efficient enzyme usage.

    PubMed

    Park, Junyoung O; Rubin, Sara A; Xu, Yi-Fan; Amador-Noguez, Daniel; Fan, Jing; Shlomi, Tomer; Rabinowitz, Joshua D

    2016-07-01

    In metabolism, available free energy is limited and must be divided across pathway steps to maintain a negative ΔG throughout. For each reaction, ΔG is log proportional both to a concentration ratio (reaction quotient to equilibrium constant) and to a flux ratio (backward to forward flux). Here we use isotope labeling to measure absolute metabolite concentrations and fluxes in Escherichia coli, yeast and a mammalian cell line. We then integrate this information to obtain a unified set of concentrations and ΔG for each organism. In glycolysis, we find that free energy is partitioned so as to mitigate unproductive backward fluxes associated with ΔG near zero. Across metabolism, we observe that absolute metabolite concentrations and ΔG are substantially conserved and that most substrate (but not inhibitor) concentrations exceed the associated enzyme binding site dissociation constant (Km or Ki). The observed conservation of metabolite concentrations is consistent with an evolutionary drive to utilize enzymes efficiently given thermodynamic and osmotic constraints. PMID:27159581

  5. Familial resemblance for serum metabolite concentrations.

    PubMed

    Draisma, Harmen H M; Beekman, Marian; Pool, René; van Ommen, Gert-Jan B; Adamski, Jerzy; Prehn, Cornelia; Vaarhorst, Anika A M; de Craen, Anton J M; Willemsen, Gonneke; Slagboom, P Eline; Boomsma, Dorret I

    2013-10-01

    Metabolomics is the comprehensive study of metabolites, which are the substrates, intermediate, and end products of cellular metabolism. The heritability of the concentrations of circulating metabolites bears relevance for evaluating their suitability as biomarkers for disease. We report aspects of familial resemblance for the concentrations in human serum of more than 100 metabolites, measured using a targeted metabolomics platform. Age- and sex-corrected monozygotic twin correlations, midparent-offspring regression coefficients, and spouse correlations in subjects from two independent cohorts (Netherlands Twin Register and Leiden Longevity Study) were estimated for each metabolite. In the Netherlands Twin Register subjects, who were largely fasting, we found significant monozygotic twin correlations for 121 out of 123 metabolites. Heritability was confirmed by midparent-offspring regression. For most detected metabolites, the correlations between spouses were considerably lower than those between twins, indicating a contribution of genetic effects to familial resemblance. Remarkably high heritability was observed for free carnitine (monozygotic twin correlation 0.66), for the amino acids serine (monozygotic twin correlation 0.77) and threonine (monozygotic twin correlation 0.64), and for phosphatidylcholine acyl-alkyl C40:3 (monozygotic twin correlation 0.77). For octenoylcarnitine, a consistent point estimate of approximately 0.50 was found for the spouse correlations in the two cohorts as well as for the monozygotic twin correlation, suggesting that familiality for this metabolite is explained by shared environment. We conclude that for the majority of metabolites targeted by the used metabolomics platform, the familial resemblance of serum concentrations is largely genetic. Our results contribute to the knowledge of the heritability of fasting serum metabolite concentrations, which is relevant for biomarker research. PMID:23985338

  6. Absolute determination of local tropospheric OH concentrations

    NASA Technical Reports Server (NTRS)

    Armerding, Wolfgang; Comes, Franz-Josef

    1994-01-01

    Long path absorption (LPA) according to Lambert Beer's law is a method to determine absolute concentrations of trace gases such as tropospheric OH. We have developed a LPA instrument which is based on a rapid tuning of the light source which is a frequency doubled dye laser. The laser is tuned across two or three OH absorption features around 308 nm with a scanning speed of 0.07 cm(exp -1)/microsecond and a repetition rate of 1.3 kHz. This high scanning speed greatly reduces the fluctuation of the light intensity caused by the atmosphere. To obtain the required high sensitivity the laser output power is additionally made constant and stabilized by an electro-optical modulator. The present sensitivity is of the order of a few times 10(exp 5) OH per cm(exp 3) for an acquisition time of a minute and an absorption path length of only 1200 meters so that a folding of the optical path in a multireflection cell was possible leading to a lateral dimension of the cell of a few meters. This allows local measurements to be made. Tropospheric measurements have been carried out in 1991 resulting in the determination of OH diurnal variation at specific days in late summer. Comparison with model calculations have been made. Interferences are mainly due to SO2 absorption. The problem of OH self generation in the multireflection cell is of minor extent. This could be shown by using different experimental methods. The minimum-maximum signal to noise ratio is about 8 x 10(exp -4) for a single scan. Due to the small size of the absorption cell the realization of an open air laboratory is possible in which by use of an additional UV light source or by additional fluxes of trace gases the chemistry can be changed under controlled conditions allowing kinetic studies of tropospheric photochemistry to be made in open air.

  7. Absolute Quantification of Human Liver Phosphorus-Containing Metabolites In Vivo Using an Inhomogeneous Spoiling Magnetic Field Gradient

    PubMed Central

    Bashir, Adil; Gropler, Robert; Ackerman, Joseph

    2015-01-01

    Purpose Absolute concentrations of high-energy phosphorus (31P) metabolites in liver provide more important insight into physiologic status of liver disease compared to resonance integral ratios. A simple method for measuring absolute concentrations of 31P metabolites in human liver is described. The approach uses surface spoiling inhomogeneous magnetic field gradient to select signal from liver tissue. The technique avoids issues caused by respiratory motion, chemical shift dispersion associated with linear magnetic field gradients, and increased tissue heat deposition due to radiofrequency absorption, especially at high field strength. Methods A method to localize signal from liver was demonstrated using superficial and highly non-uniform magnetic field gradients, which eliminate signal(s) from surface tissue(s) located between the liver and RF coil. A double standard method was implemented to determine absolute 31P metabolite concentrations in vivo. 8 healthy individuals were examined in a 3 T MR scanner. Results Concentrations of metabolites measured in eight healthy individuals are: γ-adenosine triphosphate (ATP) = 2.44 ± 0.21 (mean ± sd) mmol/l of wet tissue volume, α-ATP = 3.2 ± 0.63 mmol/l, β-ATP = 2.98 ± 0.45 mmol/l, inorganic phosphates (Pi) = 1.87 ± 0.25 mmol/l, phosphodiesters (PDE) = 10.62 ± 2.20 mmol/l and phosphomonoesters (PME) = 2.12 ± 0.51 mmol/l. All are in good agreement with literature values. Conclusions The technique offers robust and fast means to localize signal from liver tissue, allows absolute metabolite concentration determination, and avoids problems associated with constant field gradient (linear field variation) localization methods. PMID:26633549

  8. Maternal and Infant Urinary Phthalate Metabolite Concentrations: Are They Related?

    PubMed Central

    Sathyanarayana, S; Calafat, Antonia Maria; Liu, Fan; Swan, Shanna Helen

    2008-01-01

    Background Phthalates are synthetic chemicals that are ubiquitous in our society and may have adverse health effects in humans. Detectable concentrations of phthalate metabolites have been found in adults and children, but no studies have examined the relationship between maternal and infant phthalate metabolite concentrations. Objective We investigated the relationship between maternal and infant urinary phthalate metabolite concentrations. Methods We measured nine phthalate metabolites in urine samples from 210 mother/infant pairs collected on the same study visit day (1999–2005) and obtained demographic history from questionnaires. Using multivariate linear regression analyses, we examined the degree to which maternal urine phthalate metabolite concentration predicted infant phthalate metabolite concentration. All analyses were adjusted for infant age, creatinine concentration, and race. Results Correlation coefficients between phthalate metabolite concentrations in the urine of mothers and their infants were generally low but increased with decreasing age of infant. In multivariate analyses, mother’s phthalate metabolite concentrations were significantly associated with infants’ concentrations for six phthalate metabolites: monobenzyl phthalate, monoethyl phthalate, monoisobutyl phthalate, and three metabolites of di(2-ethylhexyl) phthalate: mono(2-ethylhexyl) phthalate, mono(2-ethyl-5-hydroxy-hexyl) phthalate and mono(2-ethyl-5-oxo-hexyl) phthalate (p-values for all coefficients <0.05). Discussion Mother’s urine phthalate metabolite concentration is significantly associated with infant urine phthalate metabolite concentration for six phthalate metabolites. It is plausible that shared exposures to phthalates in the immediate surrounding environment accounted for these relationships, but other unidentified sources may also contribute to infants’ phthalate exposures. This study indicates the importance of further identifying infant phthalate exposures

  9. Absolute Quantification of Individual Biomass Concentrations in a Methanogenic Coculture

    PubMed Central

    2014-01-01

    Identification of individual biomass concentrations is a crucial step towards an improved understanding of anaerobic digestion processes and mixed microbial conversions in general. The knowledge of individual biomass concentrations allows for the calculation of biomass specific conversion rates which form the basis of anaerobic digestion models. Only few attempts addressed the absolute quantification of individual biomass concentrations in methanogenic microbial ecosystems which has so far impaired the calculation of biomass specific conversion rates and thus model validation. This study proposes a quantitative PCR (qPCR) approach for the direct determination of individual biomass concentrations in methanogenic microbial associations by correlating the native qPCR signal (cycle threshold, Ct) to individual biomass concentrations (mg dry matter/L). Unlike existing methods, the proposed approach circumvents error-prone conversion factors that are typically used to convert gene copy numbers or cell concentrations into actual biomass concentrations. The newly developed method was assessed and deemed suitable for the determination of individual biomass concentrations in a defined coculture of Desulfovibrio sp. G11 and Methanospirillum hungatei JF1. The obtained calibration curves showed high accuracy, indicating that the new approach is well suited for any engineering applications where the knowledge of individual biomass concentrations is required. PMID:24949269

  10. Quantitation of normal metabolite concentrations in six brain regions by in-vivoH-MR spectroscopy.

    PubMed

    Minati, Ludovico; Aquino, Domenico; Bruzzone, Maria Grazia; Erbetta, Alessandra

    2010-07-01

    This study examined the concentrations of brain metabolites visible to in-vivo(1)H-Magnetic Resonance Spectroscopy ((1)H-MRS) at 1.5 T in a sample of 28 normal subjects. Quantitation was attempted for inositol compounds, choline units, total creatine and N-acetyl moieties, using open-source software. Six brain regions were considered: frontal and parietal white matter, medial temporal lobe, thalamus, pons and cerebellum. Absolute concentrations were derived using tissue water as an internal reference and using an external reference; metabolite signal intensity ratios with respect to creatine were also calculated. The inter-individual variability was smaller for absolute concentrations (internal reference) as compared to that for signal intensity ratios. Significant regional variability in concentration was found for all metabolites, indicating that separate normative values are needed for different brain regions. The values obtained in this study can be used as reference in future studies, provided the same methodology is followed; it is confirmed that despite unsuccessful attempts in the past, smaller coefficients of variation can indeed be obtained through absolute quantification. PMID:20927223

  11. Absolute Quantification of Matrix Metabolites Reveals the Dynamics of Mitochondrial Metabolism.

    PubMed

    Chen, Walter W; Freinkman, Elizaveta; Wang, Tim; Birsoy, Kıvanç; Sabatini, David M

    2016-08-25

    Mitochondria house metabolic pathways that impact most aspects of cellular physiology. While metabolite profiling by mass spectrometry is widely applied at the whole-cell level, it is not routinely possible to measure the concentrations of small molecules in mammalian organelles. We describe a method for the rapid and specific isolation of mitochondria and use it in tandem with a database of predicted mitochondrial metabolites ("MITObolome") to measure the matrix concentrations of more than 100 metabolites across various states of respiratory chain (RC) function. Disruption of the RC reveals extensive compartmentalization of mitochondrial metabolism and signatures unique to the inhibition of each RC complex. Pyruvate enables the proliferation of RC-deficient cells but has surprisingly limited effects on matrix contents. Interestingly, despite failing to restore matrix NADH/NAD balance, pyruvate does increase aspartate, likely through the exchange of matrix glutamate for cytosolic aspartate. We demonstrate the value of mitochondrial metabolite profiling and describe a strategy applicable to other organelles. PMID:27565352

  12. Localized phosphorus spectroscopy in vivo: Quantitation of metabolite concentrations

    NASA Astrophysics Data System (ADS)

    Wylezinska-Arridge, Marzena Malgorzata

    This project was dedicated to the investigation of the factors that may affect absolute quantitation in localized 31P MRS and if possible to the improvement of the accuracy of both localization and quantification. Three aspects have been looked at: 1) the acquisition /localization technique used; 2) the strategy used for conversion of signal amplitude/peak areas into concentrations; and 3) methods for MRS signal processing and analysis. With respect to the first aspect, image selected in vivo spectroscopy (ISIS) and point resolved spectroscopy (PRESS), were considered. Aspects of ISIS localization, including relaxation effects during inversion and excitation adiabatic pulses, and uniformity of spin excitation across the "in vivo" 31P spectral range, were investigated using simulation. In order to reduce the chemical shift displacement error in ISIS, a new adiabatic pulse for spin inversion, has been designed and experimentally verified. For PRESS, the performance of the selective 90[degrees] and 180[degrees] pulses was investigated experimentally and using simulations. The consequences of nonideal flip angles on T1 measurements based on two PRESS experiments were analyzed. Effects of amplitude and phase modulation of the ATP signal during the PRESS sequence were analyzed using product-operator formalism for an AMX system. A tissue substitute material, with known metabolite concentrations and simulating the 31P spectrum obtained from neonatal brain, has been developed for testing quantitation accuracy. The manufacture, physical properties and chemical stability of a material has been presented. The following calibration protocols have been experimentally verified: use of water as an internal concentration reference (ICR), and use of a standard phantom as an external concentration reference (ECR). A modified ECR protocol using the tissue substitute material as a reference, has been suggested to deal with problems related to off-resonance effects. This protocol has

  13. Non-invasive quantification of brain glycogen absolute concentration

    PubMed Central

    van Heeswijk, Ruud B.; Xin, Lijing; Laus, Sabrina; Frenkel, Hanne; Lei, Hongxia; Gruetter, Rolf

    2009-01-01

    The only currently available method to measure brain glycogen in vivo is 13C NMR spectroscopy. Incorporation of 13C-labeled glucose (Glc) is necessary to allow glycogen measurement, but might be affected by turnover changes. Our aim was to measure glycogen absolute concentration in the rat brain by eliminating label turnover as variable. The approach is based on establishing an increased, constant 13C isotopic enrichment (IE). 13C-Glc infusion is then performed at the IE of brain glycogen. As glycogen IE cannot be assessed in vivo, we validated that it can be inferred from that of N-acetyl-aspartate IE in vivo: After [1-13C]-Glc ingestion, glycogen IE was 2.2 ± 0.1 fold that of N-acetyl-aspartate (n = 11, R2 = 0.77). After subsequent Glc infusion, glycogen IE equaled brain Glc IE (n = 6, paired t-test, p = 0.37), implying isotopic steady-state achievement and complete turnover of the glycogen molecule. Glycogen concentration measured in vivo by 13C NMR (mean ± SD: 5.8 ± 0.7 μmol/g) was in excellent agreement with that in vitro (6.4 ± 0.6 μmol/g, n = 5). When insulin was administered, the stability of glycogen concentration was analogous to previous biochemical measurements implying that glycogen turnover is activated by insulin. We conclude that the entire glycogen molecule is turned over and that insulin activates glycogen turnover. PMID:19013831

  14. Bio-generation of stable isotope-labeled internal standards for absolute and relative quantitation of phase II drug metabolites in plasma samples using LC-MS/MS.

    PubMed

    Li, Pei; Li, Zi; Beck, Wayne D; Callahan, Patrick M; Terry, Alvin V; Bar-Peled, Maor; Bartlett, Michael G

    2015-05-01

    Quantification of drug metabolites in biological samples has been of great interest in current pharmaceutical research, since metabolite concentrations and pharmacokinetics can contribute to a better understanding of the toxicity of drug candidates. Two major categories of Phase II metabolites, glucuronide conjugates and glutathione conjugates, may cause significant drug toxicity and therefore require close monitoring at early stages of drug development. In order to achieve high precision, accuracy, and robustness, stable isotope-labeled (SIL) internal standards (IS) are widely used in quantitative bioanalytical methods using liquid chromatography and tandem mass spectrometry (LC-MS/MS), due to their capability of compensating for matrix effects, extraction variations and instrument response fluctuations. However, chemical synthesis of SIL analogues of Phase II metabolites can often be very difficult and require extensive exploratory research, leading to higher cost and significant delays in drug research and development. To overcome these challenges, we have developed a generic method which can synthesize SIL analogues of Phase II metabolites from more available SIL parent drugs or SIL conjugation co-factors, using in vitro biotransformation. This methodology was successfully applied to the bio-generation of SIL glucuronide conjugates and glutathione conjugates. The method demonstrated satisfactory performance in both absolute quantitation and assessment of relative exposure coverage across species in safety tests of drug metabolites (MIST). This generic technique can be utilized as an alternative to chemical synthesis and potentially save time and cost for drug research and development. PMID:25804729

  15. A simple and accurate protocol for absolute polar metabolite quantification in cell cultures using quantitative nuclear magnetic resonance.

    PubMed

    Goldoni, Luca; Beringhelli, Tiziana; Rocchia, Walter; Realini, Natalia; Piomelli, Daniele

    2016-05-15

    Absolute analyte quantification by nuclear magnetic resonance (NMR) spectroscopy is rarely pursued in metabolomics, even though this would allow researchers to compare results obtained using different techniques. Here we report on a new protocol that permits, after pH-controlled serum protein removal, the sensitive quantification (limit of detection [LOD] = 5-25 μM) of hydrophilic nutrients and metabolites in the extracellular medium of cells in cultures. The method does not require the use of databases and uses PULCON (pulse length-based concentration determination) quantitative NMR to obtain results that are significantly more accurate and reproducible than those obtained by CPMG (Carr-Purcell-Meiboom-Gill) sequence or post-processing filtering approaches. Three practical applications of the method highlight its flexibility under different cell culture conditions. We identified and quantified (i) metabolic differences between genetically engineered human cell lines, (ii) alterations in cellular metabolism induced by differentiation of mouse myoblasts into myotubes, and (iii) metabolic changes caused by activation of neurotransmitter receptors in mouse myoblasts. Thus, the new protocol offers an easily implementable, efficient, and versatile tool for the investigation of cellular metabolism and signal transduction. PMID:26898303

  16. Urinary concentrations of PAH and VOC metabolites in marijuana users

    PubMed Central

    Wei, Binnian; Alwis, K. Udeni; Li, Zheng; Wang, Lanqing; Valentin-Blasini, Liza; Sosnoff, Connie S.; Xia, Yang; Conway, Kevin P.; Blount, Benjamin C.

    2016-01-01

    Background Marijuana is seeing increased therapeutic use, and is the world’s third most-popular recreational drug following alcohol and tobacco. This widening use poses increased exposure to potentially toxic combustion by-products from marijuana smoke and the potential for public health concerns. Objectives To compare urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs) among self-reported recent marijuana users and nonusers, while accounting for tobacco smoke exposure. Methods Measurements of PAH and VOC metabolites in urine samples were combined with questionnaire data collected from participants in the National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2012 in order to categorize participants (≥18 years) into exclusive recent marijuana users and nonusers. Adjusted geometric means (GMs) of urinary concentrations were computed for these groups using multiple regression analyses to adjust for potential confounders. Results Adjusted GMs of many individual monohydroxy PAHs (OH-PAHs) were significantly higher in recent marijuana users than in nonusers (p < 0.05). Urinary thiocyanate (p < 0.001) and urinary concentrations of many VOC metabolites, including metabolites of acrylonitrile (p < 0.001) and acrylamide (p < 0.001), were significantly higher in recent marijuana users than in nonusers. Conclusions We found elevated levels of biomarkers for potentially harmful chemicals among self-identified, recent marijuana users compared with nonusers. These findings suggest that further studies are needed to evaluate the potential health risks to humans from the exposure to these agents when smoking marijuana. PMID:26690539

  17. Urinary phthalate metabolite concentrations and blood glucose levels during pregnancy

    PubMed Central

    Robledo, Candace A.; Peck, Jennifer D.; Stoner, Julie; Calafat, Antonia M.; Carabin, Hélène; Cowan, Linda; Goodman, Jean R.

    2016-01-01

    Purpose To examine associations between phthalate metabolite urinary concentrations during early pregnancy and blood glucose levels obtained at the time of screening for gestational diabetes mellitus (GDM). Methods Upon initiation of prenatal care, women with a mean gestational age of 12.8 weeks were recruited for a study of environmental chemical exposures (n = 110) and provided a spot urinary specimen. Blood glucose concentrations (mg/dl) were obtained from the electronic medical record for those patients who did not experience a pregnancy loss and did not transfer care to another facility prior to glucose screening (n = 72). Urinary concentrations of nine phthalate metabolites and creatinine were measured at the US Centers for Disease Control and Prevention. Associations between tertiles of phthalate metabolites concentrations and blood glucose levels were estimated using linear regression. Results Compared to pregnant women in the lowest concentration tertile, women with the highest urinary concentrations (≥3rd tertile) of mono-iso-butyl phthalate (tertile: ≥15.3 μg/l, β = −18.3, 95% CI: −35.4, −1.2) and monobenzyl phthalate (tertile: ≥30.3 μg/l, β = −17.3, 95% CI: −34.1, −0.4) had lower blood glucose levels at the time of GDM screening after adjustment for urinary creatinine and demographic covariates. Conclusion Because maternal glucose levels increase during pregnancy to provide adequate nutrition for fetal growth and development, these findings may have implications for fetal health. However, given the limitations of our study, findings should be interpreted cautiously. PMID:25726127

  18. Steady-State Metabolite Concentrations Reflect a Balance between Maximizing Enzyme Efficiency and Minimizing Total Metabolite Load

    PubMed Central

    Amador-Noguez, Daniel; Haraldsdóttir, Hulda S.; Milo, Ron; Rabinowitz, Josh; Liebermeister, Wolfram; Shlomi, Tomer

    2013-01-01

    Steady-state metabolite concentrations in a microorganism typically span several orders of magnitude. The underlying principles governing these concentrations remain poorly understood. Here, we hypothesize that observed variation can be explained in terms of a compromise between factors that favor minimizing metabolite pool sizes (e.g. limited solvent capacity) and the need to effectively utilize existing enzymes. The latter requires adequate thermodynamic driving force in metabolic reactions so that forward flux substantially exceeds reverse flux. To test this hypothesis, we developed a method, metabolic tug-of-war (mTOW), which computes steady-state metabolite concentrations in microorganisms on a genome-scale. mTOW is shown to explain up to 55% of the observed variation in measured metabolite concentrations in E. coli and C. acetobutylicum across various growth media. Our approach, based strictly on first thermodynamic principles, is the first method that successfully predicts high-throughput metabolite concentration data in bacteria across conditions. PMID:24086517

  19. Quantitation of normal metabolite concentrations in six brain regions by in-vivo 1H-MR spectroscopy

    PubMed Central

    Minati, Ludovico; Aquino, Domenico; Bruzzone, Maria Grazia; Erbetta, Alessandra

    2010-01-01

    This study examined the concentrations of brain metabolites visible to in-vivo 1H-Magnetic Resonance Spectroscopy (1H-MRS) at 1.5 T in a sample of 28 normal subjects. Quantitation was attempted for inositol compounds, choline units, total creatine and N-acetyl moieties, using open-source software. Six brain regions were considered: frontal and parietal white matter, medial temporal lobe, thalamus, pons and cerebellum. Absolute concentrations were derived using tissue water as an internal reference and using an external reference; metabolite signal intensity ratios with respect to creatine were also calculated. The inter-individual variability was smaller for absolute concentrations (internal reference) as compared to that for signal intensity ratios. Significant regional variability in concentration was found for all metabolites, indicating that separate normative values are needed for different brain regions. The values obtained in this study can be used as reference in future studies, provided the same methodology is followed; it is confirmed that despite unsuccessful attempts in the past, smaller coefficients of variation can indeed be obtained through absolute quantification. PMID:20927223

  20. Behavior of Multiclass Pesticide Residue Concentrations during the Transformation from Rose Petals to Rose Absolute.

    PubMed

    Tascone, Oriane; Fillâtre, Yoann; Roy, Céline; Meierhenrich, Uwe J

    2015-05-27

    This study investigates the concentrations of 54 multiclass pesticides during the transformation processes from rose petal to concrete and absolute using roses spiked with pesticides as a model. The concentrations of the pesticides were followed during the process of transforming the spiked rose flowers from an organic field into concrete and then into absolute. The rose flowers, the concrete, and the absolute, as well as their transformation intermediates, were analyzed for pesticide content using gas chromatography/tandem mass spectrometry. We observed that all the pesticides were extracted and concentrated in the absolute, with the exception of three molecules: fenthion, fenamiphos, and phorate. Typical pesticides were found to be concentrated by a factor of 100-300 from the rose flowers to the rose absolute. The observed effect of pesticide enrichment was also studied in roses and their extracts from four classically phytosanitary treated fields. Seventeen pesticides were detected in at least one of the extracts. Like the case for the spiked samples in our model, the pesticides present in the rose flowers from Turkey were concentrated in the absolute. Two pesticides, methidathion and chlorpyrifos, were quantified in the rose flowers at approximately 0.01 and 0.01-0.05 mg kg(-1), respectively, depending on the treated field. The concentrations determined for the corresponding rose absolutes were 4.7 mg kg(-1) for methidathion and 0.65-27.25 mg kg(-1) for chlorpyrifos. PMID:25942486

  1. Characterisation of the Metabolites of 1,8-Cineole Transferred into Human Milk: Concentrations and Ratio of Enantiomers

    PubMed Central

    Kirsch, Frauke; Buettner, Andrea

    2013-01-01

    1,8-Cineole is a widely distributed odorant that also shows physiological effects, but whose human metabolism has hitherto not been extensively investigated. The aim of the present study was, thus, to characterise the metabolites of 1,8-cineole, identified previously in human milk, after the oral intake of 100 mg of this substance. Special emphasis was placed on the enantiomeric composition of the metabolites since these data may provide important insights into potential biotransformation pathways, as well as potential biological activities of these substances, for example on the breastfed child. The volatile fraction of the human milk samples was therefore isolated via Solvent Assisted Flavour Evaporation (SAFE) and subjected to gas chromatography-mass spectrometry (GC-MS). The absolute concentrations of each metabolite were determined by matrix calibration with an internal standard, and the ratios of enantiomers were analysed on chiral capillaries. The concentrations varied over a broad range, from traces in the upper ng/kg region up to 40 µg/kg milk, with the exception of the main metabolite α2-hydroxy-1,8-cineole that showed concentrations of 100–250 µg/kg. Also, large inter- and intra-individual variations were recorded for the enantiomers, with nearly enantiomerically pure α2-hydroxy- and 3-oxo-1,8-cineole, while all other metabolites showed ratios of ~30:70 to 80:20. PMID:24957890

  2. Brain metabolite concentrations across cortical regions in healthy adults

    PubMed Central

    Bracken, Bethany K.; Jensen, J. Eric; Prescot, Andrew P.; Cohen, Bruce M.; Renshaw, Perry F.; Öngür, Dost

    2010-01-01

    Magnetic resonance spectroscopy (MRS) can provide in vivo information about metabolite levels across multiple brain regions. This study used MRS to examine concentrations of N-acetylaspartate (NAA), a marker of neuronal integrity and function, and choline (Cho) which is related to the amount of cell membrane per unit volume, in anterior cingulate cortex (ACC) and parieto-occipital cortex (POC) in healthy individuals. Data were drawn from two experiments which examined glutamatergic and GABAergic signaling in schizophrenia and bipolar disorder. After controlling for gray matter percentages, NAA/Creatine (Cr) was 18% higher in POC than in ACC (p<0.001); Cho/Cr was 46% lower in POC than in ACC (p<0.001). There was an effect of study (p<0.001 for both metabolites), but no region by study interaction (NAA p=0.101, Cho p=0.850). Since NAA is localized to the intracellular space, these data suggest that ACC neuronal compartment is reduced as compared with POC, or that there is a lower concentration of NAA per cell in the ACC than POC, or both. Since elevated Cho suggests more cell membrane per unit volume, reduced NAA in ACC appears to be coupled with increases in overall cell membrane compartment. These findings are consistent with a number of previous studies using proton MRS which found increasing NAA and decreasing Cho moving caudally, and with post mortem anatomical studies which found neurons in more widely spaced bundles in ACC when compared to parietal and occipital cortices. MRS may be a useful tool for studying physical properties of the living human brain. PMID:21081116

  3. Metabolite

    MedlinePlus

    A metabolite is any substance produced during metabolism (digestion or other bodily chemical processes). The term metabolite may also refer to the product that remains after a drug is broken down (metabolized) by the body.

  4. In situ measurement of leaf chlorophyll concentration: analysis of the optical/absolute relationship.

    PubMed

    Parry, Christopher; Blonquist, J Mark; Bugbee, Bruce

    2014-11-01

    In situ optical meters are widely used to estimate leaf chlorophyll concentration, but non-uniform chlorophyll distribution causes optical measurements to vary widely among species for the same chlorophyll concentration. Over 30 studies have sought to quantify the in situ/in vitro (optical/absolute) relationship, but neither chlorophyll extraction nor measurement techniques for in vitro analysis have been consistent among studies. Here we: (1) review standard procedures for measurement of chlorophyll; (2) estimate the error associated with non-standard procedures; and (3) implement the most accurate methods to provide equations for conversion of optical to absolute chlorophyll for 22 species grown in multiple environments. Tests of five Minolta (model SPAD-502) and 25 Opti-Sciences (model CCM-200) meters, manufactured from 1992 to 2013, indicate that differences among replicate models are less than 5%. We thus developed equations for converting between units from these meter types. There was no significant effect of environment on the optical/absolute chlorophyll relationship. We derive the theoretical relationship between optical transmission ratios and absolute chlorophyll concentration and show how non-uniform distribution among species causes a variable, non-linear response. These results link in situ optical measurements with in vitro chlorophyll concentration and provide insight to strategies for radiation capture among diverse species. PMID:24635697

  5. Measurements of absolute concentrations of NADH in cells using the phasor FLIM method

    PubMed Central

    Ma, Ning; Digman, Michelle A.; Malacrida, Leonel; Gratton, Enrico

    2016-01-01

    We propose a graphical method using the phasor representation of the fluorescence decay to derive the absolute concentration of NADH in cells. The method requires the measurement of a solution of NADH at a known concentration. The phasor representation of the fluorescence decay accounts for the differences in quantum yield of the free and bound form of NADH, pixel by pixel of an image. The concentration of NADH in every pixel in a cell is obtained after adding to each pixel in the phasor plot a given amount of unmodulated light which causes a shift of the phasor towards the origin by an amount that depends on the intensity at the pixel and the fluorescence lifetime at the pixel. The absolute concentration of NADH is obtained by comparison of the shift obtained at each pixel of an image with the shift of the calibrated solution. PMID:27446681

  6. Absolute Quantitation of Water and Metabolites in the Human Brain. I. Compartments and Water

    NASA Astrophysics Data System (ADS)

    Ernst, T.; Kreis, R.; Ross, B. D.

    A method is presented to determine the compartmentation of a localized region in the human brain in terms of CSF, tissue water, and an NMR-invisible rest, using a PRESS or STEAM sequence. Discrimination between CSF and tissue water is based on differences in their T2 relaxation times. The NMR-invisible compartment is assessed using an external standard. The composition of three regions in the human brain is determined. The CSF content of specific regions can be used to quantify cortical atrophy. The method provides a means for measuring the water content of brain tissue in vivo with a precision of 1.5%. After appropriate corrections, the results are in close agreement with biochemical values. The method has major applications in localized quantitative spectroscopy. The compartmentation model can be used to correct for the CSF content of the selected volume and to properly define and interconvert all major concentration units.

  7. Absolute tracer dye concentration using airborne laser-induced water Raman backscatter

    NASA Technical Reports Server (NTRS)

    Hoge, F. E.; Swift, R. N.

    1981-01-01

    The use of simultaneous airborne-laser-induced dye fluorescence and water Raman backscatter to measure the absolute concentration of an ocean-dispersed tracer dye is discussed. Theoretical considerations of the calculation of dye concentration by the numerical comparison of airborne laser-induced fluorescence spectra with laboratory spectra for known dye concentrations using the 3400/cm OH-stretch water Raman scatter as a calibration signal are presented which show that minimum errors are obtained and no data concerning water mass transmission properties are required when the laser wavelength is chosen to yield a Raman signal near the dye emission band. Results of field experiments conducted with an airborne conical scan lidar over a site in New York Bight into which rhodamine dye had been injected in a study of oil spill dispersion are then indicated which resulted in a contour map of dye concentrations, with a minimum detectable dye concentration of approximately 2 ppb by weight.

  8. Concentrations of Phthalate Metabolites in Milk, Urine, Saliva, and Serum of Lactating North Carolina Women

    PubMed Central

    Hines, Erin P.; Calafat, Antonia M.; Silva, Manori J.; Mendola, Pauline; Fenton, Suzanne E.

    2009-01-01

    Background Phthalates are ubiquitous in the environment, but concentrations in multiple media from breast-feeding U.S. women have not been evaluated. Objectives The objective of this study was to accurately measure and compare the concentrations of oxidative monoester phthalate metabolites in milk and surrogate fluids (serum, saliva, and urine) of 33 lactating North Carolina women. Methods We analyzed serum, saliva, urine, and milk for the oxidative phthalate metabolites mono(3-carboxypropyl) phthalate, mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethyl-5-oxohexyl) phthalate using isotope-dilution high-performance liquid chromatography tandem mass spectroscopy. Because only urine lacks esterases, we analyzed it for the hydrolytic phthalate monoesters. Results We detected phthalate metabolites in few milk (< 10%) and saliva samples. MECPP was detected in > 80% of serum samples, but other metabolites were less common (3–22%). Seven of the 10 urinary metabolites were detectable in ≥ 85% of samples. Monoethyl phthalate had the highest mean concentration in urine. Metabolite concentrations differed by body fluid (urine > serum > milk and saliva). Questionnaire data suggest that frequent nail polish use, immunoglobulin A, and fasting serum glucose and triglyceride levels were increased among women with higher concentrations of urinary and/or serum phthalate metabolites; motor vehicle age was inversely correlated with certain urinary phthalate concentrations. Conclusions Our data suggest that phthalate metabolites are most frequently detected in urine of lactating women and are less often detected in serum, milk, or saliva. Urinary phthalate concentrations reflect maternal exposure and do not represent the concentrations of oxidative metabolites in other body fluids, especially milk. PMID:19165392

  9. Novel rapid liquid chromatography tandem masspectrometry method for vemurafenib and metabolites in human plasma, including metabolite concentrations at steady state.

    PubMed

    Vikingsson, Svante; Strömqvist, Malin; Svedberg, Anna; Hansson, Johan; Höiom, Veronica; Gréen, Henrik

    2016-08-01

    A novel, rapid and sensitive liquid chromatography tandem-mass spectrometry method for quantification of vemurafenib in human plasma, that also for the first time allows for metabolite semi-quantification, was developed and validated to support clinical trials and therapeutic drug monitoring. Vemurafenib was analysed by precipitation with methanol followed by a 1.9 min isocratic liquid chromatography tandem masspectrometry analysis using an Acquity BEH C18 column with methanol and formic acid using isotope labelled internal standards. Analytes were detected in multireaction monitoring mode on a Xevo TQ. Semi-quantification of vemurafenib metabolites was performed using the same analytical system and sample preparation with gradient elution. The vemurafenib method was successfully validated in the range 0.5-100 μg/mL according to international guidelines. The metabolite method was partially validated owing to the lack of commercially available reference materials. For the first time concentration levels at steady state for melanoma patients treated with vemurafenib is presented. The low abundance of vemurafenib metabolites suggests that they lack clinical significance. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26683023

  10. Urinary phthalate metabolite concentrations among workers in selected industries: a pilot biomonitoring study.

    PubMed

    Hines, Cynthia J; Nilsen Hopf, Nancy B; Deddens, James A; Calafat, Antonia M; Silva, Manori J; Grote, Ardith A; Sammons, Deborah L

    2009-01-01

    Phthalates are used as plasticizers and solvents in industrial, medical and consumer products; however, occupational exposure information is limited. We sought to obtain preliminary information on occupational exposures to diethyl phthalate (DEP), di-n-butyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP) by analyzing for their metabolites in urine samples collected from workers in a cross-section of industries. We also obtained data on metabolites of dimethyl phthalate (DMP), benzylbutyl phthalate (BzBP), di-isobutyl phthalate and di-isononyl phthalate. We recruited 156 workers in 2003-2005 from eight industry sectors. We assessed occupational contribution by comparing end-shift metabolite concentrations to the US general population. Evidence of occupational exposure to DEHP was strongest in polyvinyl chloride (PVC) film manufacturing, PVC compounding and rubber boot manufacturing where geometric mean (GM) end-shift concentrations of DEHP metabolites exceeded general population levels by 8-, 6- and 3-fold, respectively. Occupational exposure to DBP was most evident in rubber gasket, phthalate (raw material) and rubber hose manufacturing, with DBP metabolite concentrations exceeding general population levels by 26-, 25- and 10-fold, respectively, whereas DBP exposure in nail-only salons (manicurists) was only 2-fold higher than in the general population. Concentrations of DEP and DMP metabolites in phthalate manufacturing exceeded general population levels by 4- and >1000-fold, respectively. We also found instances where GM end-shift concentrations of some metabolites exceeded general population concentrations even when no workplace use was reported, e.g. BzBP in rubber hose and rubber boot manufacturing. In summary, using urinary metabolites, we successfully identified workplaces with likely occupational phthalate exposure. Additional work is needed to distinguish occupational from non-occupational sources in low-exposure workplaces. PMID:18948546

  11. Contribution of Network Connectivity in Determining the Relationship between Gene Expression and Metabolite Concentration Changes

    PubMed Central

    Zelezniak, Aleksej; Sheridan, Steven; Patil, Kiran Raosaheb

    2014-01-01

    One of the primary mechanisms through which a cell exerts control over its metabolic state is by modulating expression levels of its enzyme-coding genes. However, the changes at the level of enzyme expression allow only indirect control over metabolite levels, for two main reasons. First, at the level of individual reactions, metabolite levels are non-linearly dependent on enzyme abundances as per the reaction kinetics mechanisms. Secondly, specific metabolite pools are tightly interlinked with the rest of the metabolic network through their production and consumption reactions. While the role of reaction kinetics in metabolite concentration control is well studied at the level of individual reactions, the contribution of network connectivity has remained relatively unclear. Here we report a modeling framework that integrates both reaction kinetics and network connectivity constraints for describing the interplay between metabolite concentrations and mRNA levels. We used this framework to investigate correlations between the gene expression and the metabolite concentration changes in Saccharomyces cerevisiae during its metabolic cycle, as well as in response to three fundamentally different biological perturbations, namely gene knockout, nutrient shock and nutrient change. While the kinetic constraints applied at the level of individual reactions were found to be poor descriptors of the mRNA-metabolite relationship, their use in the context of the network enabled us to correlate changes in the expression of enzyme-coding genes to the alterations in metabolite levels. Our results highlight the key contribution of metabolic network connectivity in mediating cellular control over metabolite levels, and have implications towards bridging the gap between genotype and metabolic phenotype. PMID:24762675

  12. Release of adenine nucleotide metabolites by toxic concentrations of cardiac glycosides.

    PubMed

    Bernauer, W

    1994-01-01

    In isolated perfused guinea-pig hearts the effect of toxic concentrations of cardiac glycosides on the release of the adenine nucleotide metabolites adenosine, inosine, hypoxanthine, xanthine, and uric acid was investigated. Digoxin concentrations of 0.03-1 mumol.l-1 produced moderate to severe tachyarrhythmias. Large amounts of metabolites were released by concentrations of 0.1 mumol.l-1, and higher. Occurrence of glycoside-induced ventricular fibrillation was associated with a particularly high release. Metabolite release was also obtained when fibrillation was elicited electrically in normal control hearts, or in hearts receiving simultaneously a marginally toxic digoxin concentration (0.03 mumol.l-1). Digoxin-induced tachyarrhythmias and metabolite release were almost completely prevented by a high potassium concentration in the coronary perfusion fluid (8.1 mmol.l-1). The antiarrhythmic effect was also obtained with lidocaine (60 mumol.l-1), but the release was only partially antagonized. Similar results concerning arrhythmias and metabolite release as with digoxin were obtained with ouabain. The findings suggest that the decrease in myocardial ATP observed in glycoside-intoxicated heart preparations is partly due to the loss of nucleotide precursor substances. Moreover, it appears likely that liberated adenosine in the interstitium of severely intoxicated heart preparations reaches pharmacologically effective concentrations. PMID:7826306

  13. Vinyl flooring in the home is associated with children's airborne butylbenzyl phthalate and urinary metabolite concentrations.

    PubMed

    Just, Allan C; Miller, Rachel L; Perzanowski, Matthew S; Rundle, Andrew G; Chen, Qixuan; Jung, Kyung Hwa; Hoepner, Lori; Camann, David E; Calafat, Antonia M; Perera, Frederica P; Whyatt, Robin M

    2015-01-01

    Prior studies have shown that vinyl flooring as well as the vinyl-softening plasticizers butylbenzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP) are associated with asthma and airway inflammation. Although DEHP exposure is primarily dietary, whether home vinyl flooring contributes to indoor air and urinary metabolite concentrations for these two phthalates is unclear. Exposures to BBzP and DEHP were examined in a prospective birth cohort of New York City children (n=239) using: (i) visual observation of potential phthalate containing flooring, (ii) a 2-week home indoor air sample, and (iii) concurrent urinary metabolites in a subset (n=193). The category "vinyl or linoleum" flooring was observed in 135 (56%) of monitored rooms; these rooms had statistically significantly higher indoor air geometric mean concentrations of BBzP (23.9 ng/m(3)) than rooms with wood or carpet flooring (10.6 ng/m(3)). Children from homes with "vinyl or linoleum" flooring also had significantly higher urinary BBzP metabolite concentrations than other children. Indoor air BBzP and urinary metabolite concentrations were correlated positively (Spearman's rho 0.40). By contrast, indoor air DEHP was not associated with flooring type nor with its urinary metabolite concentrations. Vinyl flooring in the home may be an important source of children's exposure to BBzP via indoor air. PMID:25690585

  14. Absolute quantitative autoradiography of low concentrations of (/sup 125/I)-labeled proteins in arterial tissue

    SciTech Connect

    Schnitzer, J.J.; Morrel, E.M.; Colton, C.K.; Smith, K.A.; Stemerman, M.B.

    1987-12-01

    We developed a method for absolute quantitative autoradiographic measurement of very low concentrations of (/sup 125/I)-labeled proteins in arterial tissue using Kodak NTB-2 nuclear emulsion. A precise linear relationship between measured silver grain density and isotope concentration was obtained with uniformly labeled standard sources composed of epoxy-embedded gelatin containing glutaraldehyde-fixed (/sup 125/I)-albumin. For up to 308-day exposures of 1 micron-thick tissue sections, background grain densities ranged from about two to eight grains/1000 micron 2, and the technique was sensitive to as little as about one grain/1000 micron 2 above background, which correspond to a radioactivity concentration of about 2 x 10(4) cpm/ml. A detailed statistical analysis of variability was performed and the sum of all sources of variation quantified. The half distance for spatial resolution was 1.7 micron. Both visual and automated techniques were employed for quantitative grain density analysis. The method was illustrated by measurement of in vivo transmural (/sup 125/I)-low-density lipoprotein (( /sup 125/I)-LDL) concentration profiles in de-endothelialized rabbit thoracic aortic wall.

  15. Variability and Predictors of Urinary Concentrations of Phthalate Metabolites during Early Childhood

    PubMed Central

    2015-01-01

    The variability and predictors of urinary concentrations of phthalate metabolites in preschool-aged children have not been thoroughly examined. Additionally, the impact of temporal changes in the use and restriction of phthalates in children’s products has not been assessed. Our objective was to identify demographic, behavioral, and temporal predictors of urinary phthalate metabolite concentrations in young children. Between 2004 and 2011, we collected up to five urine samples from each of 296 children participating in a prospective birth cohort during annual study visits at ages 1–5 years. We used linear mixed models to calculate intraclass correlation coefficients (ICCs), a measure of within-individual reproducibility, and identify demographic predictors of urinary phthalate metabolites. We used multivariable linear regression to examine cross-sectional relationships between food packaging or personal care product use and phthalate metabolites measured at age 5 years. Across annual measurements, monoethyl phthalate exhibited the least variation (ICC = 0.38), while di-2-ethylhexyl phthalate (ΣDEHP) metabolites exhibited the most variation (ICC = 0.09). Concentrations changed with age, suggesting age-related changes in phthalate exposure and perhaps metabolism. Our findings suggest that fast food consumption may be a source of butylbenzyl phthalate and di-isononyl phthalate (DiNP) exposure, and some personal care products may be sources of diethyl phthalate exposure. Concentrations of ΣDEHP metabolites decreased over the study period; however, concentrations of DiNP metabolites increased. This finding suggests that manufacturer practices and regulations, like the Consumer Product Safety Improvement Act of 2008, may decrease DEHP exposure, but additional work characterizing the nature and toxicity of replacements is critically needed. PMID:24977926

  16. Phthalate metabolites in urine of Chinese young adults: Concentration, profile, exposure and cumulative risk assessment.

    PubMed

    Gao, Chong-Jing; Liu, Li-Yan; Ma, Wan-Li; Ren, Nan-Qi; Guo, Ying; Zhu, Ning-Zheng; Jiang, Ling; Li, Yi-Fan; Kannan, Kurunthachalam

    2016-02-01

    Phthalates are widely used in consumer products. People are frequently exposed to phthalates due to their applications in daily life. In this study, 14 phthalate metabolites were analyzed in 108 urine samples collected from Chinese young adults using high-performance liquid chromatography-tandem mass spectrometry. The total concentrations of 14 phthalate metabolites ranged from 71.3 to 2670 ng/mL, with the geometric mean concentration of 306 ng/mL. mBP and miBP were the two most abundant compounds, accounting for 48% of the total concentrations. Principal component analysis suggested two major sources of phthalates: one dominated by the DEHP metabolites and one by the group of mCPP, mBP and miBP metabolites. The estimated daily intakes of DMP, DEP, DBP, DiBP and DEHP were 1.68, 2.14, 4.12, 3.52 and 1.26-2.98 μg/kg-bw/day, respectively. In a sensitivity analysis, urinary concentration and body weight were the most influential variables for human exposure estimation. Furthermore, cumulative risk for hazard quotient (HQ) and hazard index (HI) were evaluated. Nearly half of Chinese young adults had high HI values exceeding the safe threshold. This is the first study on the occurrence and human exposure to urinary phthalate metabolites with Chinese young adults. PMID:26575634

  17. Parent and Metabolite Opioid Drug Concentrations in Unintentional Deaths Involving Opioid and Benzodiazepine Combinations.

    PubMed

    Fields, Marcia D; Abate, Marie A; Hu, Lan; Long, D Leann; Blommel, Matthew L; Haikal, Nabila A; Kraner, James C

    2015-07-01

    Effects of benzodiazepines on postmortem opioid parent and parent/metabolite blood concentration ratios were determined for fentanyl-, hydrocodone-, methadone-, or oxycodone-related accidental deaths. These opioids are partially metabolized by the CYP3A4 enzyme system, which is also affected by diazepam and alprazolam. Opioid/metabolite combinations examined were as follows: fentanyl/norfentanyl, hydrocodone/dihydrocodeine, methadone/EDDP, and oxycodone/oxymorphone. Parent opioid concentrations were analyzed for 877 deaths. Parent/metabolite concentration ratios were analyzed for 349 deaths, excluding cases with co-intoxicants present known to interfere with opioid elimination. Alprazolam in combination with diazepam significantly decreased median hydrocodone concentrations by 48% (p = 0.01) compared to hydrocodone alone. The methadone parent/metabolite concentration ratio was reduced by 35% in the presence of diazepam compared to methadone alone (p = 0.03). Benzodiazepines did not statistically significantly affect fentanyl or oxycodone concentrations. Possible factors affecting opioid concentrations and possible toxicity development, including any differential effects on specific opioids, should continue to be explored. PMID:26223761

  18. Absolute quantitation of phosphorus metabolites in the cerebral cortex of the newborn human infant and in the forearm muscles of young adults using a double-tuned surface coil

    NASA Astrophysics Data System (ADS)

    Cady, Ernest B.

    The application of a double-tuned surface coil with strong coupling for both 31P and 1H to the in vivo measurement of metabolite concentrations by NMR spectroscopy is demonstrated. It is shown that sample loading, although important for a coil tuned to a single frequency, does not necessarily have a significant effect on absolute quantitation results if the coil is strongly coupled to the sample for both nuclei. For the coil used in the present study, the spectrometer calibration coefficient is almost independent of loading and the 1H and 31P flip angles at the coil center produced by fixed length pulses could be arranged to be nearly equal over a range of loading conditions. In seven normal infants, of gestational plus postnatal age 35 to 37 weeks, the cerebral cortex nucleotide triphosphate concentration was 3.7 ± 0.6 m M/liter wet (mean ± SD). Metabolite concentrations were low in the cerebral cortex of a severely birth asphyxiated infant. The adenosine triphosphate concentration in the resting, fresh forearm muscles of six young adults was 6.3 ± 0.8 m M/liter wet.

  19. Choline intake and genetic polymorphisms influence choline metabolite concentrations in human breast milk and plasma123

    PubMed Central

    Fischer, Leslie M; da Costa, Kerry Ann; Galanko, Joseph; Sha, Wei; Stephenson, Brigitte; Vick, Julie; Zeisel, Steven H

    2010-01-01

    Background: Choline is essential for infant nutrition, and breast milk is a rich source of this nutrient. Common single nucleotide polymorphisms (SNPs) change dietary requirements for choline intake. Objective: The aim of this study was to determine whether total choline intake and/or SNPs influence concentrations of choline and its metabolites in human breast milk and plasma. Design: We gave a total of 103 pregnant women supplemental choline or a placebo from 18 wk gestation to 45 d postpartum and genotyped the women for 370 common SNPs. At 45 d postpartum, we measured choline metabolite concentrations in breast milk and plasma and assessed the dietary intake of choline by using a 3-d food record. Results: On average, lactating women in our study ate two-thirds of the recommended intake for choline (Adequate Intake = 550 mg choline/d). Dietary choline intake (no supplement) correlated with breast-milk phosphatidylcholine and plasma choline concentrations. A supplement further increased breast-milk choline, betaine, and phosphocholine concentrations and increased plasma choline and betaine concentrations. We identified 5 SNPs in MTHFR that altered the slope of the intake–metabolite concentration relations, and we identified 2 SNPs in PEMT that shifted these curves upward. Individuals who shared sets of common SNPs were outliers in plots of intake–metabolite concentration curves; we suggest that these SNPs should be further investigated to determine how they alter choline metabolism. Conclusion: Total intake of choline and genotype can influence the concentrations of choline and its metabolites in the breast milk and blood of lactating women and thereby affect the amount of choline available to the developing infant. This study was registered at clinicaltrials.gov as NCT00678925. PMID:20534746

  20. Serum concentrations of tamoxifen and its metabolites increase with age during steady-state treatment.

    PubMed

    Lien, Ernst A; Søiland, Håvard; Lundgren, Steinar; Aas, Turid; Steen, Vidar M; Mellgren, Gunnar; Gjerde, Jennifer

    2013-09-01

    It has been suggested that the concentrations of tamoxifen and its demethylated metabolites increase with age. We measured the serum concentrations of the active tamoxifen metabolites, 4OHtamoxifen (4OHtam), 4-hydroxy-N-desmethyltamoxifen (4OHNDtam, Endoxifen), tamoxifen and its demethylated metabolites. Their relations to age were examined. One hundred fifty-one estrogen receptor and/or progesterone receptor positive breast cancer patients were included. Their median (range) age was 57 (32-85) years. Due to the long half-life of tamoxifen, only patients treated with tamoxifen for at least 80 days were included in the study in order to insure that the patients had reached steady-state drug levels. Tamoxifen and its metabolites were measured by liquid chromatography-tandem mass spectrometry. Their serum concentrations were related to the age of the patients. To circumvent effects of cytochrome (CYP) 2D6 polymorphisms we also examined these correlations exclusively in homozygous extensive metabolizers. The concentrations of 4OHNDtam, tamoxifen, NDtam (N-desmethyltamoxifen), and NDDtam (N-desdimethyltamoxifen) were positively correlated to age (n = 151, p = 0.017, 0.045, 0.011, and 0.001 respectively). When exclusively studying the CYP2D6 homozygous extensive metabolizers (n = 86) the correlation between 4OHNDtam and age increased (p = 0.008). Up to tenfold inter-patient variation in the serum concentrations was observed. The median (inter-patient range) concentration of 4OHNDtam in the age groups 30-49, 50-69, and >69 years were 65 (24-89), 116 (25-141), and 159 (26-185) ng/ml, respectively. We conclude that the serum concentrations of 4OHNDtam (endoxifen), tamoxifen, and its demethylated metabolites increase with age during steady-state tamoxifen treatment. This may represent an additional explanation why studies on the effects of CYP2D6 polymorphisms on outcome in tamoxifen-treated breast cancer patients have been inconsistent. The observed high inter-patient range

  1. Structural transformation of lignan compounds in rat gastrointestinal tract; II. Serum concentration of lignans and their metabolites.

    PubMed

    Nose, M; Fujimoto, T; Nishibe, S; Ogihara, Y

    1993-04-01

    Serum concentrations of arctiin, tracheloside, and their metabolites formed in the gastrointestinal tract were investigated in the rat. Arctiin or tracheloside was not detected in the serum after oral administration (200 mg/kg). In regard to their metabolites, each metabolite 1 (AM1, TM1), their genuine genins, appeared in the serum, and the serum concentration of arctiin metabolite 1 (AM1) reached its peak at 4 h and that of tracheloside metabolite 1 (TM1) reached its peak at 8 h. On the other hand, both metabolites 2 (AM2, TM2), which each possess a catechol moiety as reported previously, were not found in the serum. Now, we have studied the detection of their metabolites in the rat large intestinal contents after oral administration. It was revealed that all metabolites reported previously were certainly formed in rat gastrointestinal tract in vivo. Thus, we presumed a possibility that metabolite 2 was converted into metabolite 1 through C-3" methylation by catechol-O-methyltransferase (COMT) in rat liver. Each metabolite 2 was incubated with rat liver cytosol in the presence of S-adenosyl-L-methionine. It was proved that metabolite 2 was rapidly converted into metabolite 1 within 3 min. We suggest that arctiin or tracheloside was transformed to at least two metabolites in the gastrointestinal tract, and after absorption from the intestine, metabolite 2 was converted into metabolite 1 through methylation by COMT in the liver, and arctiin and tracheloside existed as metabolite 1, the genuine genin, in the blood stream. PMID:8387675

  2. Concentrations of phthalates and DINCH metabolites in pooled urine from Queensland, Australia.

    PubMed

    Gomez Ramos, M J; Heffernan, A L; Toms, L M L; Calafat, A M; Ye, X; Hobson, P; Broomhall, S; Mueller, J F

    2016-03-01

    Dialkyl phthalate esters (phthalates) are ubiquitous chemicals used extensively as plasticizers, solvents and adhesives in a range of industrial and consumer products. 1,2-Cyclohexane dicarboxylic acid, diisononyl ester (DINCH) is a phthalate alternative introduced due to a more favourable toxicological profile, but exposure is largely uncharacterised. The aim of this study was to provide the first assessment of exposure to phthalates and DINCH in the general Australian population. De-identified urine specimens stratified by age and sex were obtained from a community-based pathology laboratory and pooled (n=24 pools of 100). Concentrations of free and total species were measured using online solid phase extraction isotope dilution high performance liquid chromatography tandem mass spectrometry. Concentrations ranged from 2.4 to 71.9ng/mL for metabolites of di(2-ethylhexyl)phthalate, and from <0.5 to 775ng/mL for all other metabolites. Our data suggest that phthalate metabolites concentrations in Australia were at least two times higher than in the United States and Germany; and may be related to legislative differences among countries. DINCH metabolite concentrations were comparatively low and consistent with the limited data available. Ongoing biomonitoring among the general Australian population may help assess temporal trends in exposure and assess the effectiveness of actions aimed at reducing exposures. PMID:26760715

  3. Nuclear magnetic resonance spectroscopy as a quantitative tool to determine the concentrations of biologically produced metabolites: implications in metabolites in safety testing.

    PubMed

    Espina, Robert; Yu, Linning; Wang, Jianyao; Tong, Zeen; Vashishtha, Sarvesh; Talaat, Rasmy; Scatina, JoAnn; Mutlib, Abdul

    2009-02-01

    Nuclear magnetic resonance (NMR) spectroscopy has traditionally been considered as an indispensable tool in elucidating structures of metabolites. With the advent of Fourier transform (FT) spectrometers, along with improvements in software and hardware (such as high-field magnets, cryoprobes, versatile pulse sequences, and solvent suppression techniques), NMR is increasingly being considered as a critical quantitative tool, despite its lower sensitivity as compared to mass spectrometry. A specific quantitative application of NMR is in determining the concentrations of biologically isolated metabolites, which could potentially be used as reference standards for further quantitative work by liquid chromatography/mass spectrometry. With the recent demands from regulatory agencies on quantitative information on metabolites, it is proposed that NMR will play a significant role in strategies aimed at addressing metabolite coverage in toxicological species. Traditionally, biologically isolated metabolites have not been considered as a way of generating "reference standards" for further quantitative work. However, because of the recent FDA guidance on safety testing of metabolites, one has to consider means of authenticating and quantitating biologically or nonbiologically generated metabolites. 1H NMR is being proposed as the method of choice, as it is able to be used as both a qualitative and a quantitative tool, hence allowing structure determination, purity check, and quantitative measurement of the isolated metabolite. In this publication, the application of NMR as a powerful and robust analytical technique in determining the concentrations of in vitro or in vivo isolated metabolites is discussed. Furthermore, to demonstrate the reliability and accuracy of metabolite concentrations determined by NMR, validation and cross-validation with gravimetric and mass spectrometric methods were conducted. PMID:18980340

  4. Measurement of absolute minority species concentration and temperature in a flame by the photothermal deflection spectroscopy technique.

    PubMed

    Li, Yunjing; Gupta, Rajendra

    2003-04-20

    It is experimentally demonstrated that absolute concentrations of minority species in flames can be measured by the photothermal deflection spectroscopy (PTDS) technique. In addition, the PTDS signal simultaneously yields the flame temperature the measurement point. Absolute concentration profiles of OH have been measured in a flat-flame burner with methane as fuel. The PTDS measurements agree well with those obtained independently by the absorption technique. The flame temperature measurements by PTDS are also in good agreement with those obtained by the Boltzmann distribution among the rotational levels of OH. PMID:12716166

  5. Comparison of DDT and its metabolites concentrations in cow milk from agricultural and industrial areas.

    PubMed

    Kuba, Jarosław; Tomza-Marciniak, Agnieszka; Pilarczyk, Bogumiła; Tarasewicz, Natalia; Pilarczyk, Renata; Ligocki, Marek

    2015-01-01

    The risk of pesticidal intoxication in humans is severe, especially because of the strongly negative impact on human health. The consequences of the exposure to these substances may include cancerogenesis or endocrine abnormalities resulting for example in decreased fertility. Therefore, the aim of our study was to evaluate the content of dichlorodiphenyltrichloroethane (DDT) and its metabolites in cow milk from two regions of Poland, varying by level of industrialization. Samples were collected from agricultural (n = 25) and industrial (n = 25) areas, and the concentrations of DDT and its metabolites were evaluated by gas chromatography. Residues of DDT were detected in all the milk samples tested, mostly in the samples from the agricultural area, where a total DDT median concentration reached 0.336 μg L(-1). In the milk samples from the industrial area, the median concentration was lower, at 0.131 μg L(-1). 4,4'-DDT was the main metabolite, constituting 83% of total DDT metabolites. Although none of the samples exceeded the level above which they should be considered dangerous, the results showed that the problem of DDT had not diminished and so should be constantly monitored. PMID:25421622

  6. Chemically Polymerized Polypyrrole for On-Chip Concentration of Volatile Breath Metabolites

    PubMed Central

    Strand, Nicholas; Bhushan, Abhinav; Schivo, Michael; Kenyon, Nicholas J.; Davis, Cristina E.

    2009-01-01

    A wide range of metabolites are measured in the gas phase of exhaled human breath, and some of these biomarkers are frequently observed to be up- or down-regulated in certain disease states. Portable breath analysis systems have the potential for a wide range of applications in health diagnostics. However, this is currently limited by the lack of concentration mechanisms to enhance trace metabolites found in the breath to levels that can be adequately recorded using miniaturized gas-phase sensors. In this study we have created chip-based polymeric pre-concentration devices capable of absorbing and desorbing breath volatiles for subsequent chemical analysis. These devices appear to concentrate chemicals from both environmental air samples as well as directly from exhaled human breath, and these devices may have applications in lab-on-a-chip-based environmental and health monitoring systems. PMID:20161533

  7. Determinants of relative and absolute concentration indices: evidence from 26 European countries

    PubMed Central

    2013-01-01

    Introduction The aim of publicly-provided health care is generally not only to produce health, but also to decrease variation in health by socio-economic status. The aim of this study is to measure to what extent this goal has been obtained in various European countries and evaluate the determinants of inequalities within countries, as well as cross-country patterns with regard to different cultural, institutional and social settings. Methods The data utilized in this study provides information on 440,000 individuals in 26 European countries and stem from The European Union Statistics on Income and Living Conditions (EU-SILC) collected in 2007. As measures of income-related inequality in health both the relative concentration indices and the absolute concentration indices are calculated. Further, health inequality in each country is decomposed into individual-level determinants and cross-country comparisons are made to shed light on social and institutional determinants. Results Income-related health inequality favoring the better-off is observed for all the 26 European countries. In terms of within-country determinants inequality is mainly explained by income, age, education, and activity status. However, the degree of inequality and contribution of each determinant to inequality varies considerably between countries. Aggregate bivariate linear regressions show that there is a positive association between health-income inequality in Europe and public expenditure on education. Furthermore, a negative relationship between health-income inequality and income inequality was found when individual employee cash income was used in the health-concentration measurement. Using that same income measure, health-income inequality was found to be higher in the Nordic countries than in other areas, but this result is sensitive to the income measure chosen. Conclusions The findings indicate that institutional determinants partly explain income-related health inequalities across

  8. Absolute nutrient concentration measurements in cell culture media: (1)H q-NMR spectra and data to compare the efficiency of pH-controlled protein precipitation versus CPMG or post-processing filtering approaches.

    PubMed

    Goldoni, Luca; Beringhelli, Tiziana; Rocchia, Walter; Realini, Natalia; Piomelli, Daniele

    2016-09-01

    The NMR spectra and data reported in this article refer to the research article titled "A simple and accurate protocol for absolute polar metabolite quantification in cell cultures using q-NMR" [1]. We provide the (1)H q-NMR spectra of cell culture media (DMEM) after removal of serum proteins, which show the different efficiency of various precipitating solvents, the solvent/DMEM ratios, and pH of the solution. We compare the data of the absolute nutrient concentrations, measured by PULCON external standard method, before and after precipitation of serum proteins and those obtained using CPMG (Carr-Purcell-Meiboom-Gill) sequence or applying post-processing filtering algorithms to remove, from the (1)H q-NMR spectra, the proteins signal contribution. For each of these approaches, the percent error in the absolute value of every measurement for all the nutrients is also plotted as accuracy assessment. PMID:27331118

  9. Positive association between concentration of phthalate metabolites in urine and microparticles in adolescents and young adults.

    PubMed

    Lin, Chien-Yu; Hsieh, Chia-Jung; Lo, Shyh-Chyi; Chen, Pau-Chung; Torng, Pao-Ling; Hu, Anren; Sung, Fung-Chang; Su, Ta-Chen

    2016-01-01

    Di-(2-ethylhexyl) phthalate (DEHP) has been used worldwide in various products for many years. In vitro studies have shown that exposure to DEHP and its metabolite mono(2-ethylhexyl) phthalate (MEHP) induces endothelial cell apoptosis. Moreover, exposure to DEHP had been linked to cardiovascular risk factors and cardiovascular diseases in epidemiological studies. Circulating microparticles have been known to be indicators of vascular injury. However, whether DEHP or its metabolites are independently associated with microparticles in humans remains unknown. From 2006 to 2008, we recruited 793 subjects (12-30years) from a population-based sample to participate in this cardiovascular disease prevention examination. Each participant was subjected to interviews and biological sample collection to determine the relationship between concentrations of DEHP metabolites MEHP, mono(ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethly-5-oxoheyl) phthalate in urine and concentrations of endothelial microparticles (CD62E and CD31+/CD42a-), platelet microparticles (CD62P and CD31+/CD42a+), and CD14 in serum. Multiple linear regression analysis revealed that an ln-unit increase in MEHP concentration in urine was positively associated with an increase in serum microparticle counts/μL of 0.132 (±0.016) in CD31+/CD42a- (endothelial apoptosis marker), 0.117 (±0.023) in CD31+/CD42a+ (platelet apoptosis marker), and 0.026 (±0.007) in CD14 (monocyte, macrophage, and neutrophil activation marker). There was no association between DEHP metabolite concentration and CD62E or CD62P. In conclusion, a higher MEHP concentration in urine was associated with an increase in endothelial and platelet microparticles in this cohort of adolescents and young adults. Further studies are warranted to clarify the causal relationship between exposure to DEHP and atherosclerosis. PMID:27104673

  10. A new quantification method for assessing plasma concentrations of pemetrexed and its polyglutamate metabolites.

    PubMed

    Stoop, Marcel P; Visser, Sabine; van Dijk, Evert; Aerts, Joachim G J V; Stricker, Bruno H; Luider, Theo M

    2016-09-01

    Currently no quantification method exists for potentially therapeutically relevant polyglutamate metabolites of the drug pemetrexed which is used for the treatment of lung carcinoma patients. We developed and tested an LC-MS/MS-based analytical assay that uses isotope-labeled internal standards to quantify pemetrexed and its (poly)glutamate metabolites in clinical human plasma samples of lung carcinoma patients. UHPLC chromatography and triple quadrupole mass spectrometry showed an LLOQ of 0.2nmol/L for pemetrexed and an LLOQ of 0.5nmol/L for the two metabolites (one glutamate and two glutamate moieties covalently bound to the pemetrexed molecule, for which no other quantification methods have previously been published). The recoveries for PMTX and its metabolites ranged between 30% and 67%. Precision and accuracy at a concentration of 20nmol/L for all four analytes was well below 15% CV. The precision (RSD) in the biological replicates of the separate days (within-run precision) as well as the reproducibility over several days (between-run precision), tested in the range of 5-250nmol/L, were all below 15%. Autosampler, benchtop and freeze-thaw cycle stability of the analytes was also demonstrated. To illustrate the new assay in a relevant biological context, concentrations of pemetrexed and the two metabolites were quantified in plasma samples of lung carcinoma patients treated with pemetrexed. The assay is straightforward, relatively easy to perform, and has potential for use in therapeutic drug monitoring in non-small cell lung carcinoma patients. PMID:27209449

  11. Methimazole increases the plasma concentrations of the albendazole metabolites of netobimin in sheep.

    PubMed

    Lanusse, C E; Prichard, R K

    1992-03-01

    The influence of methimazole (MTZ) on the pharmacokinetics of netobimin (NTB) and its metabolites was investigated in adult sheep. NTB zwitterion suspension was administered at 20 mg kg-1 by intraruminal injection either alone or with simultaneous administration of MTZ intramuscularly at 1.5 mg kg-1. Blood samples were taken serially over a 120-h period and plasma was analysed by HPLC for NTB, albendazole (ABZ), albendazole sulphoxide (ABZSO), and albendazole sulphone (ABZSO2). NTB parent drug showed fast absorption, low area under the plasma concentration-time curve (AUC) and was rapidly removed from plasma after both treatments. The presence of MTZ did increase significantly the ABZ AUC (138 per cent) and mean residence time (MRT) (86 per cent). Concomitant treatment with MTZ resulted in a notably higher ABZSO plasma profile with significantly longer elimination half-life (t1/2 beta) (390 per cent) and MRT (252 per cent) and with significantly higher AUC (95 per cent). Also, MTZ induced significant increases in ABZSO2 t1/2 beta, AUC, and MRT. We have demonstrated a pharmacokinetic interaction between MTZ and NTB metabolites. MTZ may alter the liver biotransformation of ABZ metabolites which results in pronounced changes in the disposition kinetics of anthelmintically active metabolites. PMID:1550912

  12. Urinary phthalate metabolite concentrations among men with inflammatory bowel disease on mesalamine therapy

    PubMed Central

    Hait, Elizabeth J; Calafat, Antonia M.; Hauser, Russ

    2014-01-01

    Background Phthalates, a family of compounds used in a variety of consumer products, are reproductive and developmental toxicants in experimental animals. One of these phthalates, dibutyl phthalate (DBP), is an inactive ingredient in the coating of Asacol. Aim To determine if men with inflammatory bowel disease taking Asacol have higher urinary concentrations of monobutyl phthalate (MBP), a metabolite of DBP, compared to the general population in the United States. Methods Five patients at the Massachusetts General Hospital Crohn’s and Colitis Center, taking at least 800 mg of Asacol three times a day, provided one spot urine sample. Urinary MBP and other phthalate metabolite concentrations were measured by using online solid phase extraction coupled with isotope dilution high-performance liquid chromatography tandem mass spectrometry. Results In four of the five men, the urinary concentrations of MBP (9888 ng/mL, 12,308 ng/mL, 10,124 ng/mL, and 41,590 ng/mL) and of a minor DBP metabolite, mono(3-carboxypropyl) phthalate (MCPP, 116.4 ng/mL, 163.4 ng/mL 72.6 ng/mL, 5604 ng/mL) were orders of magnitude higher than the background concentrations among the US general population. One subject missed his morning Asacol dose and had urinary MBP concentrations (17.5 ng/mL) similar to background levels. Conclusion We confirmed that men with inflammatory bowel disease taking Asacol have urinary concentrations of MBP and MCPP much higher than background levels. PMID:25392847

  13. Maternal buprenorphine dose, placenta buprenorphine, and metabolite concentrations and neonatal outcomes.

    PubMed

    Concheiro, Marta; Jones, Hendreé E; Johnson, Rolley E; Choo, Robin; Shakleya, Diaa M; Huestis, Marilyn A

    2010-04-01

    Buprenorphine is approved as pharmacotherapy for opioid dependence in nonpregnant patients in multiple countries and is currently under investigation for pregnant women in the United States and Europe. This research evaluates the disposition of buprenorphine, opiates, cocaine, and metabolites in five term placentas from a US cohort. Placenta and matched meconium concentrations were compared, and relationships among maternal buprenorphine dose, placenta concentrations, and neonatal outcomes after controlled administration during gestation were investigated. Buprenorphine and/or metabolites were detected in all placenta specimens and were uniformly distributed across this tissue (coefficient of variation less than 27.5%, four locations), except for buprenorphine in three placentas. In two of these, buprenorphine was not detected in some locations and in the third placenta was totally absent. Median (range) concentrations were 1.6 ng/g buprenorphine (not detected to 3.2), 14.9 ng/g norbuprenorphine (6.2-24.2), 3 ng/g buprenorphine-glucuronide (1.3-5.0), and 14.7 ng/g norbuprenorphine-glucuronide (11.4-25.8). Placenta is a potential alternative matrix for detecting in utero buprenorphine exposure, but at lower concentrations (15- to 70-fold) than in meconium. Statistically significant correlations were observed for mean maternal daily dose from enrollment to delivery and placenta buprenorphine-glucuronide concentration and for norbuprenorphine-glucuronide concentrations and time to neonatal abstinence syndrome onset and duration, for norbuprenorphine/norbuprenorphine-glucuronide ratio and maximum neonatal abstinence syndrome score, and newborn length. Analysis of buprenorphine and metabolites in this alternative matrix, an abundant waste product available at the time of delivery, may be valuable for prediction of neonatal outcomes for clinicians treating newborns of buprenorphine-exposed women. PMID:20216119

  14. Arsenic Species in Chicken Breast: Temporal Variations of Metabolites, Elimination Kinetics, and Residual Concentrations

    PubMed Central

    Liu, Qingqing; Peng, Hanyong; Lu, Xiufen; Zuidhof, Martin J.; Li, Xing-Fang; Le, X. Chris

    2016-01-01

    Background: Chicken meat has the highest per capita consumption among all meat types in North America. The practice of feeding 3-nitro-4-hydroxyphenylarsonic acid (Roxarsone, Rox) to chickens lasted for more than 60 years. However, the fate of Rox and arsenic metabolites remaining in chicken are poorly understood. Objectives: We aimed to determine the elimination of Rox and metabolites from chickens and quantify the remaining arsenic species in chicken meat, providing necessary information for meaningful exposure assessment. Methods: We have conducted a 35-day feeding experiment involving 1,600 chickens, of which half were control and the other half were fed a Rox-supplemented diet for the first 28 days and then a Rox-free diet for the final 7 days. We quantified the concentrations of individual arsenic species in the breast meat of 229 chickens. Results: Rox, arsenobetaine, arsenite, monomethylarsonic acid, dimethylarsinic acid, and a new arsenic metabolite, were detected in breast meat from chickens fed Rox. The concentrations of arsenic species, except arsenobetaine, were significantly higher in the Rox-fed than in the control chickens. The half-lives of elimination of these arsenic species were 0.4–1 day. Seven days after termination of Rox feeding, the concentrations of arsenite (3.1 μg/kg), Rox (0.4 μg/kg), and a new arsenic metabolite (0.8 μg/kg) were significantly higher in the Rox-fed chickens than in the control. Conclusion: Feeding of Rox to chickens increased the concentrations of five arsenic species in breast meat. Although most arsenic species were excreted rapidly when the feeding of Rox stopped, arsenic species remaining in the Rox-fed chickens were higher than the background levels. Citation: Liu Q, Peng H, Lu X, Zuidhof MJ, Li XF, Le XC. 2016. Arsenic species in chicken breast: temporal variations of metabolites, elimination kinetics, and residual concentrations. Environ Health Perspect 124:1174–1181; http://dx.doi.org/10.1289/ehp

  15. Urinary phthalate metabolite concentrations among pregnant women in Northern Puerto Rico: Distribution, temporal variability, and predictors

    PubMed Central

    Cantonwine, David E.; Cordero, José F.; Rivera-González, Luis O.; Del Toro, Liza V. Anzalota; Ferguson, Kelly K.; Mukherjee, Bhramar; Calafat, Antonia M.; Crespo, Noe; Jiménez-Vélez, Braulio; Padilla, Ingrid Y.; Alshawabkeh, Akram N.; Meeker, John D.

    2013-01-01

    Background Phthalate contamination exists in the North coast karst aquifer system in Puerto Rico. In light of potential health impacts associated with phthalate exposure, targeted action for elimination of exposure sources may be warranted, especially for sensitive populations such as pregnant women. However, information on exposure to phthalates from a variety of sources in Puerto Rico is lacking. The objective of this study was to determine concentrations and predictors of urinary phthalate biomarkers measured at multiple times during pregnancy among women living in the Northern karst area of Puerto Rico. Methods We recruited 139 pregnant women in Northern Puerto Rico and collected urine samples and questionnaire data at three separate visits (18±2 weeks, 22±2 weeks, and 26±2 weeks of gestation). Urine samples were analyzed for eleven phthalate metabolites: mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-hydroxyhexyl phthalate, mono-2-ethyl-5-oxohexyl phthalate, mono-2-ethyl-5-carboxypentyl phthalate, mono-ethyl phthalate (MEP), mono-n-butyl phthalate, mono-benzyl phthalate, mono-isobutyl phthalate, mono-3-carboxypropyl phthalate (MCPP), mono carboxyisononyl phthalate (MCNP), and mono carboxyisooctyl phthalate (MCOP). Results Detectable concentrations of phthalate metabolites among pregnant women living in Puerto Rico was prevalent, and metabolite concentrations tended to be higher than or similar to those measured in women of reproductive age from the general US population. Intraclass correlation coefficients ranged from very weak (MCNP; 0.05) to moderate (MEP; 0.44) reproducibility among all phthalate metabolites. We observed significant or suggestive positive associations between urinary phthalate metabolites concentrations and water usage/storage habits (MEP, MCNP, MCOP), use of personal care products (MEP), and consumption of certain food items (MCPP, MCNP, and MCOP). Conclusions To our knowledge this is the first study to report concentrations

  16. Interactions of valproic acid with carbamazepine and its metabolites' concentrations, concentrations ratios, and level/dose ratios in epileptic children.

    PubMed

    Liu, H; Delgado, M R; Browne, R H

    1995-02-01

    In two groups of epileptic children receiving carbamazepine (CBZ) therapy with or without valproic acid (VPA) comedication, we investigate the drug interactions of VPA on serum CBZ and its metabolites' concentrations, concentration ratios, and level/dose ratios. Serum total and free CBZ-10, 11-epoxide (CBZ-E) concentrations are significantly increased in patients taking CBZ plus VPA, together with higher CBZ-E/CBZ concentration ratios and CBZ-E level/dose ratios. These results reflect the accumulation of CBZ-E. The decreased concentration ratios of trans-10, 11-dihydroxy-10, 11-dihydro-CBZ (CBZ-H)/CBZ-E observed in patients taking CBZ plus VPA suggest an inhibition in the biotransformation from CBZ-E to CBZ-H. Significant negative correlations are found between serum VPA level and CBZ-H/CBZ-E concentration ratios, indicating that the inhibition of CBZ-E hydrolysis by VPA may depend on the concentration of VPA (total or free CBZ-H/CBZ-E concentration ratio = [formula: see text], respectively). VPA concentration also shows significant positive correlations with CBZ-E and CBZ level/dose ratios. Patients taking CBZ plus VPA have significant higher free fractions of CBZ and CBZ-E than do patients on CBZ alone, suggesting a protein-binding displacement by VPA. PMID:8665529

  17. Citalopram and escitalopram plasma drug and metabolite concentrations: genome-wide associations

    PubMed Central

    Ji, Yuan; Schaid, Daniel J; Desta, Zeruesenay; Kubo, Michiaki; Batzler, Anthony J; Snyder, Karen; Mushiroda, Taisei; Kamatani, Naoyuki; Ogburn, Evan; Hall-Flavin, Daniel; Flockhart, David; Nakamura, Yusuke; Mrazek, David A; Weinshilboum, Richard M

    2014-01-01

    Aims Citalopram (CT) and escitalopram (S-CT) are among the most widely prescribed selective serotonin reuptake inhibitors used to treat major depressive disorder (MDD). We applied a genome-wide association study to identify genetic factors that contribute to variation in plasma concentrations of CT or S-CT and their metabolites in MDD patients treated with CT or S-CT. Methods Our genome-wide association study was performed using samples from 435 MDD patients. Linear mixed models were used to account for within-subject correlations of longitudinal measures of plasma drug/metabolite concentrations (4 and 8 weeks after the initiation of drug therapy), and single-nucleotide polymorphisms (SNPs) were modelled as additive allelic effects. Results Genome-wide significant associations were observed for S-CT concentration with SNPs in or near the CYP2C19 gene on chromosome 10 (rs1074145, P = 4.1 × 10−9) and with S-didesmethylcitalopram concentration for SNPs near the CYP2D6 locus on chromosome 22 (rs1065852, P = 2.0 × 10−16), supporting the important role of these cytochrome P450 (CYP) enzymes in biotransformation of citalopram. After adjustment for the effect of CYP2C19 functional alleles, the analyses also identified novel loci that will require future replication and functional validation. Conclusions In vitro and in vivo studies have suggested that the biotransformation of CT to monodesmethylcitalopram and didesmethylcitalopram is mediated by CYP isozymes. The results of our genome-wide association study performed in MDD patients treated with CT or S-CT have confirmed those observations but also identified novel genomic loci that might play a role in variation in plasma levels of CT or its metabolites during the treatment of MDD patients with these selective serotonin reuptake inhibitors. PMID:24528284

  18. Selecting reference concentrations for fish biliary PAH metabolites for stream ecological exposure assessment

    SciTech Connect

    Lin, E.L.C.; Cormier, S.M.; Subramanian, B.; Williams, D.; Wulfeck, K.; Detmer, S.; Lowry, M.E.

    1995-12-31

    Reference concentrations for two types of biliary PAH metabolites were empirically determined for two species of fish. Bile from white sucker and common carp were collected from streams in Ohio having poor to excellent condition based on a modified index of biotic integrity (MIBI). PAH were measured using fixed wavelength fluorescence with excitation/emission pairs at 290/335 nm for naphthalene-type (NAPH) and 380/430 nm for benzo[a]pyrene-type (B[a]P) metabolites. Exposures to PAH were estimated for petroleum sources with NAPH and from combustion sources with B[a]P. Three criteria were used to select reference concentrations. Site criteria were: an MIBI score of at least 30, relatively low median values of biliary PAH concentration, and low statistical variation. The median reference values selected were 0.5 {micro}g B[a]P/mg protein and 50 pg NAPH/mg protein for white sucker and 0.5 {micro}g B[a]P/mg protein and 90 {micro}g NAPH/mg protein for common carp. Of the 28 sites sampled with white sucker in 1993, 68% exceeded the reference value for NAPH and 32% for B[a]P. Of the 22 sites sampled with carp, 68% exceeded the value for NAPH and 41% for B[a]P. Likewise, more sites with MIBI scores between 30 and 60 exceeded the NAPH reference than the B[a]P reference concentration.

  19. Ketamine Metabolites Enantioselectively Decrease Intracellular D-Serine Concentrations in PC-12 Cells

    PubMed Central

    Singh, Nagendra S.; Rutkowska, Ewelina; Plazinska, Anita; Khadeer, Mohammed; Moaddel, Ruin; Jozwiak, Krzysztof; Bernier, Michel; Wainer, Irving W.

    2016-01-01

    D-Serine is an endogenous NMDA receptor co-agonist that activates synaptic NMDA receptors modulating neuronal networks in the cerebral cortex and plays a key role in long-term potentiation of synaptic transmission. D-serine is associated with NMDA receptor neurotoxicity and neurodegeneration and elevated D-serine concentrations have been associated with Alzheimer’s and Parkinsons’ diseases and amyotrophic lateral sclerosis. Previous studies have demonstrated that the ketamine metabolites (rac)-dehydronorketamine and (2S,6S)-hydroxynorketamine decrease intracellular D-serine concentrations in a concentration dependent manner in PC-12 cells. In the current study, PC-12 cells were incubated with a series of ketamine metabolites and the IC50 values associated with attenuated intracellular D-serine concentrations were determined. The results demonstrate that structural and stereochemical features of the studied compounds contribute to the magnitude of the inhibitory effect with (2S,6S)-hydroxynorketamine and (2R,6R)-hydroxynorketamine displaying the most potent inhibition with IC50 values of 0.18 ± 0.04 nM and 0.68 ± 0.09 nM. The data was utilized to construct a preliminary 3D-QSAR/pharmacophore model for use in the design of new and more efficient modulators of D-serine. PMID:27096720

  20. In situ TDLAS measurement of absolute acetylene concentration profiles in a non-premixed laminar counter-flow flame

    NASA Astrophysics Data System (ADS)

    Wagner, S.; Klein, M.; Kathrotia, T.; Riedel, U.; Kissel, T.; Dreizler, A.; Ebert, V.

    2012-06-01

    Acetylene (C2H2), as an important precursor for chemiluminescence species, is a key to understand, simulate and model the chemiluminescence and the related reaction paths. Hence we developed a high resolution spectrometer based on direct Tunable Diode Laser Absorption Spectroscopy (TDLAS) allowing the first quantitative, calibration-free and spatially resolved in situ C2H2 measurement in an atmospheric non-premixed counter-flow flame supported on a Tsuji burner. A fiber-coupled distributed feedback diode laser near 1535 nm was used to measure several absolute C2H2 concentration profiles (peak concentrations up to 9700 ppm) in a laminar non-premixed CH4/air flame ( T up to 1950 K) supported on a modified Tsuji counter-flow burner with N2 purge slots to minimize end flames. We achieve a fractional optical resolution of up to 5×10-5 OD (1 σ) in the flame, resulting in temperature-dependent acetylene detection limits for the P17e line at 6513 cm-1 of up to 2.1 ppmṡm. Absolute C2H2 concentration profiles were obtained by translating the burner through the laser beam using a DC motor with 100 μm step widths. Intercomparisons of the experimental C2H2 profiles with simulations using our new hydrocarbon oxidation mechanisms show excellent agreement in position, shape and in the absolute C2H2 values.

  1. Association between Circulating Vitamin D Metabolites and Fecal Bile Acid Concentrations.

    PubMed

    Jacobs, Elizabeth T; Haussler, Mark R; Alberts, David S; Kohler, Lindsay N; Lance, Peter; Martínez, María Elena; Roe, Denise J; Jurutka, Peter W

    2016-07-01

    Although hydrophobic bile acids have been demonstrated to exhibit cytotoxic and carcinogenic effects in the colorectum, ursodeoxycholic acid (UDCA) has been investigated as a potential chemopreventive agent. Vitamin D has been shown to play a role in both bile acid metabolism and in the development of colorectal neoplasia. Using a cross-sectional design, we sought to determine whether baseline circulating concentrations of the vitamin D metabolites 25(OH)D and 1,25(OH)2D were associated with baseline fecal bile acid concentrations in a trial of UDCA for the prevention of colorectal adenoma recurrence. We also prospectively evaluated whether vitamin D metabolite concentrations modified the effect of UDCA on adenoma recurrence. After adjustment for age, sex, BMI, physical activity, and calcium intake, adequate concentrations of 25(OH)D (≥30 ng/mL) were statistically significantly associated with reduced odds for high levels of total [OR, 0.61; 95% confidence interval (CI), 0.38-0.97], and primary (OR, 0.61; 95% CI, 0.38-0.96) bile acids, as well as individually with chenodeoxycholic acid (OR, 0.39; 95% CI, 0.24-0.63) and cholic acid (OR, 0.56; 95% CI, 0.36-0.90). No significant associations were observed for 1,25(OH)2D and high versus low fecal bile acid concentrations. In addition, neither 25(OH)D nor 1,25(OH)2D modified the effect of UDCA on colorectal adenoma recurrence. In conclusion, this is the first study to demonstrate an inverse relationship between circulating levels of 25(OH)D and primary fecal bile acid concentrations. These results support prior data demonstrating that vitamin D plays a key role in bile acid metabolism, and suggest a potential mechanism of action for 25(OH)D in colorectal cancer prevention. Cancer Prev Res; 9(7); 589-97. ©2016 AACR. PMID:27138789

  2. Analytical chiral separation of the stereoisomers of a novel carbonic anhydrase inhibitor and its deethylated metabolite, and the assignment of absolute configuration of the human metabolite and chiral degradation products.

    PubMed

    Matuszewski, B K; Constanzer, M L; Kiganda, M

    1994-03-01

    Several approaches to the separation of four stereoisomers, 1-4, of a novel, topically active, carbonic anhydrase inhibitor, 1, with two chiral centers in the molecule and four isomers, 5-8, of its chiral metabolite, 5, were evaluated. These methods include nonchiral derivatization followed by separation on chiral stationary phases (CSPs) and chiral derivatization and separation on nonchiral columns and on CSPs. Baseline separation of stereoisomers 1-4 was achieved in less than 15 min after chiral derivatization with (S)-(+)-1-(1-naphthyl)ethyl isocyanate (NEIC) and chiral chromatography on a (R)-N-(3,5-dinitrobenzoyl)phenyl glycine (DNBPG) column under normal phase (NP) conditions. Similarly, isomers 5-8 were baseline separated in less than 20 min after derivatization with NEIC and chromatography on nonchiral (nitrophenyl) and chiral [(S)-(3,5-dinitrobenzoyl)leucine; DNBL] columns in series under the same NP chromatographic conditions. Only partial separation of the diastereomeric derivatives was observed on a variety of nonchiral columns. In addition, all other direct and indirect chiral separation approaches gave only partial separation of at least two stereoisomers within the group of 1-4 or 5-8. The details of chiral separations using various methods and separation (alpha) and capacity factors (k') of the derivatized isomers 1-8 on a series of chiral and nonchiral columns are presented. Using these methods, the absolute configuration of the human metabolite of 1 was established as S1S2 (5), and the heat (HD) and light (LD) degradation products of 1 as R1S2 (3) and S1S2 (5), respectively. PMID:8008715

  3. Concentrations of nandrolone metabolites in urine after the therapeutic administration of an ophthalmic solution.

    PubMed

    Avois, Lidia; Mangin, Patrice; Saugy, Martial

    2007-05-01

    Nandrolone, an anabolic steroid, is used for the treatment of several diseases and is available in various pharmaceutical formulations. The most widely used pharmaceutical formulation is Deca-Durabolin, but other products, such as Keratyl eye drops solution, are also currently administered. Nandrolone is one of the most abused anabolic steroid in sports. Analyses for this anabolic steroid according to the World Anti-Doping Agency (WADA) protocol are based on the identification of the nandrolone two main urinary metabolites which, in humans, are glucuronides of 19-norandrosterone and 19-noretiocholanolone. A positive cut off limit of 2 ng/mL has been set by the anti-doping code for the first metabolite, 19-norandrosterone. In this preliminary study, an eye drops solution (Keratyl) containing a therapeutic dose of a nandrolone sodium sulphate was administered to several male volunteers during 3 days and urines were collected during 3 weeks. Surprisingly, contrary to all expectations, the urinary concentrations measured in urines reached 450 ng/mL and 70 ng/mL for norandrosterone and noretiocholanolone, respectively. Moreover, concentration levels near to 2 ng/mL were found, more than 2 weeks after the last administration, depending on individual metabolism. Inter-variability as well as intra-variability of nandrolone excretion kinetic, regarding this particular administration mode, were also evaluated. Quantification of nandrolone metabolites was performed by GC-MS. The method was previously validated in terms of specificity, precision, linearity, LOD, LOQ, robustness, accuracy and the expanded uncertainty was also evaluated. PMID:17391892

  4. Faecal corticosterone metabolite concentrations are not a good predictor of habitat suitability for common gartersnakes

    PubMed Central

    Halliday, William D.; Gilmour, Kathleen M.; Blouin-Demers, Gabriel

    2015-01-01

    Measuring habitat suitability is important in conservation and in wildlife management. Measuring the abundance or presence–absence of a species in various habitats is not sufficient to measure habitat suitability because these metrics can be poor predictors of population success. Therefore, having some measure of population success is essential in assessing habitat suitability, but estimating population success is difficult. Identifying suitable proxies for population success could thus be beneficial. We examined whether faecal corticosterone metabolite (fCM) concentrations could be used as a proxy for habitat suitability in common gartersnakes (Thamnophis sirtalis). We conducted a validation study and confirmed that fCM concentrations indeed reflect circulating corticosterone concentrations. We estimated abundance, reproductive output and growth rate of gartersnakes in field and in forest habitat and we also measured fCM concentrations of gartersnakes from these same habitats. Common gartersnakes were more abundant and had higher reproductive outputs and higher growth rates in field habitat than in forest habitat, but fCM concentrations did not differ between the same two habitats. Our results suggest either that fCM concentrations are not a useful metric of habitat suitability in common gartersnakes or that the difference in suitability between the two habitats was too small to induce changes in fCM concentrations. Incorporating fitness metrics in estimates of habitat suitability is important, but these metrics of fitness have to be sensitive enough to vary between habitats. PMID:27293731

  5. Tamoxifen metabolite concentrations, CYP2D6 genotype, and breast cancer outcomes.

    PubMed

    Madlensky, L; Natarajan, L; Tchu, S; Pu, M; Mortimer, J; Flatt, S W; Nikoloff, D M; Hillman, G; Fontecha, M R; Lawrence, H J; Parker, B A; Wu, A H B; Pierce, J P

    2011-05-01

    We explored whether breast cancer outcomes are associated with endoxifen and other metabolites of tamoxifen and examined potential correlates of endoxifen concentration levels in serum including cytochrome P450 2D6 (CYP2D6) metabolizer phenotype and body mass index (BMI). Concentration levels of tamoxifen, endoxifen, 4-hydroxytamoxifen (4OH-tamoxifen), and N-desmethyltamoxifen (ND-tamoxifen) were measured from samples taken from 1,370 patients with estrogen receptor (ER)-positive breast cancer who were participating in the Women's Healthy Eating and Living (WHEL) Study. We tested these concentration levels for possible associations with breast cancer outcomes and found that breast cancer outcomes were not associated with the concentration levels of tamoxifen, 4-hydroxytamoxifen, and ND-tamoxifen. For endoxifen, a threshold was identified, with women in the upper four quintiles of endoxifen concentration appearing to have a 26% lower recurrence rate than women in the bottom quintile (hazard ratio (HR) = 0.74; 95% confidence interval (CI), (0.55-1.00)). The predictors of this higher-risk bottom quintile were poor/intermediate metabolizer genotype, higher BMI, and lower tamoxifen concentrations as compared with the mean for the cohort as a whole. This study suggests that there is a minimal concentration threshold above which endoxifen is effective against the recurrence of breast cancer and that ~80% of tamoxifen takers attain this threshold. PMID:21430657

  6. Noninvasive imaging of absolute PpIX concentration distribution in nonmelanoma skin tumors at pre-PDT

    NASA Astrophysics Data System (ADS)

    Sunar, Ulas; Rohrbach, Daniel; Morgan, Janet; Zeitouni, Natalie

    2013-03-01

    Photodynamic Therapy (PDT) has proven to be an effective treatment option for nonmelanoma skin cancers. The ability to quantify the concentration of drug in the treated area is crucial for effective treatment planning as well as predicting outcomes. We utilized spatial frequency domain imaging for quantifying the accurate concentration of protoporphyrin IX (PpIX) in phantoms and in vivo. We correct fluorescence against the effects of native tissue absorption and scattering parameters. First we quantified the absorption and scattering of the tissue non-invasively. Then, we corrected raw fluorescence signal by compensating for optical properties to get the absolute drug concentration. After phantom experiments, we used basal cell carcinoma (BCC) model in Gli mice to determine optical properties and drug concentration in vivo at pre-PDT.

  7. Lincomycin at Subinhibitory Concentrations Potentiates Secondary Metabolite Production by Streptomyces spp.

    PubMed Central

    Imai, Yu; Sato, Seizo; Tanaka, Yukinori; Ochi, Kozo

    2015-01-01

    Antibiotics have either bactericidal or bacteriostatic activity. However, they also induce considerable gene expression in bacteria when used at subinhibitory concentrations (below the MIC). We found that lincomycin, which inhibits protein synthesis by binding to the ribosomes of Gram-positive bacteria, was effective for inducing the expression of genes involved in secondary metabolism in Streptomyces strains when added to medium at subinhibitory concentrations. In Streptomyces coelicolor A3(2), lincomycin at 1/10 of its MIC markedly increased the expression of the pathway-specific regulatory gene actII-ORF4 in the blue-pigmented antibiotic actinorhodin (ACT) biosynthetic gene cluster, which resulted in ACT overproduction. Intriguingly, S. lividans 1326 grown in the presence of lincomycin at a subinhibitory concentration (1/12 or 1/3 of its MIC) produced abundant antibacterial compounds that were not detected in cells grown in lincomycin-free medium. Bioassay and mass spectrometry analysis revealed that some antibacterial compounds were novel congeners of calcium-dependent antibiotics. Our results indicate that lincomycin at subinhibitory concentrations potentiates the production of secondary metabolites in Streptomyces strains and suggest that activating these strains by utilizing the dose-response effects of lincomycin could be used to effectively induce the production of cryptic secondary metabolites. In addition to these findings, we also report that lincomycin used at concentrations for markedly increased ACT production resulted in alteration of the cytoplasmic protein (FoF1 ATP synthase α and β subunits, etc.) profile and increased intracellular ATP levels. A fundamental mechanism for these unique phenomena is also discussed. PMID:25819962

  8. Bisphenol A and phthalate metabolite urinary concentrations: Daily and across pregnancy variability

    PubMed Central

    Fisher, Mandy; Arbuckle, Tye E; Mallick, Ranjeeta; LeBlanc, Alain; Hauser, Russ; Feeley, Mark; Koniecki, Diane; Ramsay, Tim; Provencher, Gilles; Bérubé, René; Walker, Mark

    2015-01-01

    Phthalates and bisphenol A (BPA) are high production volume and ubiquitous chemicals that are quickly metabolized in the body. Traditionally, studies have relied on single spot urine analyses to assess exposure; ignoring variability in concentrations throughout a day or over a longer period of time. We compared BPA and phthalate metabolite results from urine samples collected at five different time points. Participants (n=80) were asked to collect all voids in a 24 h period on a weekday and then again on a weekend before 20 weeks of pregnancy. During the second and third trimesters and in the postpartum period, single spot urines were collected. Variability over time in urinary concentrations was assessed using intraclass correlation coefficients (ICCs) and the sensitivity to correctly classify a single sample as high or low versus the geometric mean (GM) of all samples was calculated. We found low reproducibility and sensitivity of BPA and all phthalate metabolites throughout pregnancy and into the postpartum period but much higher reproducibility within a day. Time of day when the urine was collected was a significant predictor of specific gravity adjusted exposure levels. We concluded that, if the interest is in average exposures across pregnancy, maternal/fetal exposure estimation may be more accurate if multiple measurements, collected across the course of the entire pregnancy, rather than a single spot measure, are performed. PMID:25248937

  9. Selecting reference concentrations for fish biliary PAH metabolites for stream ecological exposure assessment

    SciTech Connect

    Lin, E.L.C.; Cormier, S.M.; Subramanian, B.; Williams, D.; Wulfeck, K.; Detmer, S.; Lowry, M.E.

    1995-12-31

    Reference concentrations for two types of biliary polycyclic aromatic hydrocarbon (PAH) metabolites were empirically determined for two species of fish. Bile from white sucker and common carp were collected from streams in Ohio having poor to excellent conditions based on a modified index of biotic integrity (mIBI). PAH were measured using fixed wavelength fluorescence with excitation/emission pairs at 290/335 nm for naphthalene-type (NAPH) and 380/430 nm for benzo[a]pyrene-type (B[a]P) metabolites. Exposures to PAH`s were estimated for petroleum sources with NAPH and from combustion sources with B[a]P. Three criteria were used to select reference concentrations. Site criteria were: an mIBI score of at least 30; relatively low median values of biliary PAH concentration; and low statistical variation. The median reference values selected were 0.5 {micro}g B[a]P/mg protein and 50 {micro}g NAPH/mg protein for white suckers and 0.5 {micro}g B[a]P/mg protein and 90 {micro}g NAPH/mg protein for common carp. Of the 28 sites sampled with white sucker in 1993, 68% exceeded the reference value for NAPH and 32% for B[a]P. Of the 22 sites sampled with carp, 68% exceeded the value for NAPH and 41% for B[a]P. Likewise, more sites with mIBI scores between 30 and 60 exceeded the NAPH reference than the B[a]P reference concentration.

  10. Couples’ Urinary Bisphenol A and Phthalate Metabolite Concentrations and the Secondary Sex Ratio

    PubMed Central

    Bae, Jisuk; Kim, Sungduk; Kannan, Kurunthachalam; Buck Louis, Germaine M.

    2015-01-01

    With limited research focusing on non-persistent chemicals as exogenous factors affecting human sex selection, this study aimed to evaluate the association of urinary bisphenol A (BPA) and phthalate metabolite concentrations with the secondary sex ratio (SSR), defined as the ratio of male to female live births. The current analysis is limited to singleton live births (n=220, 43.9%) from the Longitudinal Investigation of Fertility and the Environment (LIFE) Study, which enrolled couples upon discontinuing contraception and followed while trying for pregnancy and through delivery those achieving pregnancy. Using modified Poisson regression models accounting for potential confounders, we estimated the relative risks (RRs) of a male birth per standard deviation change in the log-transformed maternal, paternal, and couple urinary BPA and 14 phthalate metabolite concentrations (ng/mL) measured upon enrollment. When maternal and paternal chemical concentrations were modeled jointly, paternal BPA (RR, 0.77; 95% confidence interval [CI], 0.62–0.95) and mono-isobutyl phthalate (RR, 0.82; 95% CI, 0.67–1.00) were significantly associated with a female excess. Contrarily, maternal BPA (RR, 1.16; 95% CI, 1.03–1.31), mono-isobutyl phthalate (RR, 1.28; 95% CI, 1.06–1.54), mono-benzyl phthalate (RR, 1.31; 95% CI, 1.08–1.58), and mono-n-butyl phthalate (RR, 1.24; 95% CI, 1.01–1.51) were significantly associated with a male excess. These findings underscore varying patterns for the SSR in relation to parental exposures. Given the absence of previous investigation, these partner-specific associations of non-persistent chemicals with the SSR need future corroboration. PMID:25677702

  11. Couples' urinary bisphenol A and phthalate metabolite concentrations and the secondary sex ratio.

    PubMed

    Bae, Jisuk; Kim, Sungduk; Kannan, Kurunthachalam; Buck Louis, Germaine M

    2015-02-01

    With limited research focusing on non-persistent chemicals as exogenous factors affecting human sex selection, this study aimed to evaluate the association of urinary bisphenol A (BPA) and phthalate metabolite concentrations with the secondary sex ratio (SSR), defined as the ratio of male to female live births. The current analysis is limited to singleton live births (n=220, 43.9%) from the Longitudinal Investigation of Fertility and the Environment (LIFE) Study, in which couples discontinuing contraception with the intention of becoming pregnant were enrolled and followed while trying for pregnancy and through delivery for those achieving pregnancy. Using modified Poisson regression models accounting for potential confounders, we estimated the relative risks (RRs) of a male birth per standard deviation change in the log-transformed maternal, paternal, and couple urinary BPA and 14 phthalate metabolite concentrations (ng/mL) measured upon enrollment. When maternal and paternal chemical concentrations were modeled jointly, paternal BPA (RR, 0.77; 95% confidence interval [CI], 0.62-0.95) and mono-isobutyl phthalate (RR, 0.82; 95% CI, 0.67-1.00) were significantly associated with a female excess. Contrarily, maternal BPA (RR, 1.16; 95% CI, 1.03-1.31), mono-isobutyl phthalate (RR, 1.28; 95% CI, 1.06-1.54), mono-benzyl phthalate (RR, 1.31; 95% CI, 1.08-1.58), and mono-n-butyl phthalate (RR, 1.24; 95% CI, 1.01-1.51) were significantly associated with a male excess. These findings underscore varying patterns for the SSR in relation to parental exposures. Given the absence of previous investigation, these partner-specific associations of non-persistent chemicals with the SSR need future corroboration. PMID:25677702

  12. Gas concentration effects on secondary metabolite production by plant cell cultures.

    PubMed

    Linden, J C; Haigh, J R; Mirjalili, N; Phisaphalong, M

    2001-01-01

    One aspect of secondary metabolite production that has been studied relatively infrequently is the effect of gaseous compounds on plant cell behavior. The most influential gases are believed to be oxygen, carbon dioxide and other volatile hormones such as ethylene and methyl jasmonate. Organic compounds of interest include the promising antimalarial artemisinin (known as "qing hao su" in China where it has been a folk remedy for centuries) that is produced by Artemisia annua (sweet wormwood) and taxanes used for anticancer therapy that are produced by species of Taxus (yew). The suspension cultures of both species were grown under a variety of dissolved gas conditions in stoppered culture flasks and under conditions of continuous headspace flushing with known gas mixtures. An analysis is presented to show the culture conditions are such that equilibrium between the culture liquid and gas head-space is assured. The growth rate of the cells and their production rates of artemisinin and paclitaxel were determined. These and other parameters are correlated as functions of the gas concentrations. Interdependence of ethylene and methyl jasmonate is also explored with respect to regulation of secondary metabolite formation. PMID:11729755

  13. Free and total urinary phthalate metabolite concentrations among pregnant women from the Healthy Baby Cohort (HBC), China.

    PubMed

    Zhu, Yingshuang; Wan, Yanjian; Li, Yuanyuan; Zhang, Bin; Zhou, Aifen; Cai, Zongwei; Qian, Zhengmin; Zhang, Chuncao; Huo, Wenqian; Huang, Kai; Hu, Jie; Cheng, Lu; Chang, Huailong; Huang, Zheng; Xu, Bing; Xia, Wei; Xu, Shunqing

    2016-03-01

    Total urinary phthalate metabolites (the free plus glucuronidated forms) have been frequently measured in the general population. However, data are limited on the free forms which may be more bioactive, especially for sensitive population such as pregnant women. Here the data gap was addressed by measuring concentrations of free and total forms of six phthalate metabolites in 293 urine samples from pregnant women at delivery, who were randomly selected from the prospective Healthy Baby Cohort (HBC), China. We observed detectable concentrations of the total amount of phthalate metabolites in all urine samples. The geometric mean (GM) urinary concentrations of free and total mono-butyl phthalate (MBP) (5.20, 54.49ng/mL) were the highest, followed by mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) (4.52, 7.27ng/mL). For most of phthalate metabolites, urinary concentrations were significantly higher in women who were nulliparous. Significantly higher concentrations of mono-ethyl phthalate (MEP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) were found in women who had higher educational level. To our knowledge, this is the first study to report the free and total forms of phthalate metabolites among pregnant women in China. The results suggest that exposure characteristics may be related to parity and education. PMID:26722670

  14. Vinyl flooring in the home is associated with children’s airborne butylbenzyl phthalate and urinary metabolite concentrations

    PubMed Central

    Just, Allan C.; Miller, Rachel L.; Perzanowski, Matthew S.; Rundle, Andrew G.; Chen, Qixuan; Jung, Kyung Hwa; Hoepner, Lori; Camann, David E.; Calafat, Antonia M.; Perera, Frederica P.; Whyatt, Robin M.

    2015-01-01

    Prior studies have shown that vinyl flooring, as well as the vinyl-softening plasticizers butylbenzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP), are associated with asthma and airway inflammation. While DEHP exposure is primarily dietary, whether home vinyl flooring contributes to indoor air and urinary metabolite concentrations for these two phthalates is unclear. Exposures to BBzP and DEHP were examined in a prospective birth cohort of New York City children (n=239) using: (1) visual observation of potential phthalate containing flooring, (2) a two-week home indoor air sample, and (3) concurrent urinary metabolites in a subset (n=193). The category “vinyl or linoleum” flooring was observed in 135 (56%) of monitored rooms; these rooms had statistically significantly higher indoor air geometric mean concentrations of BBzP (23.9 ng/m3) than rooms with wood or carpet flooring (10.6 ng/m3). Children from homes with “vinyl or linoleum” flooring also had significantly higher urinary BBzP metabolite concentrations than other children. Indoor air BBzP and urinary metabolite concentrations were correlated positively (Spearman’s rho 0.40). By contrast, indoor air DEHP was not associated with flooring type nor with its urinary metabolite concentrations. Vinyl flooring in the home may be an important source of children’s exposure to BBzP via indoor air. PMID:25690585

  15. Cerebrospinal fluid monoamine metabolite concentrations as intermediate phenotypes between glutamate-related genes and psychosis.

    PubMed

    Andreou, Dimitrios; Söderman, Erik; Axelsson, Tomas; Sedvall, Göran C; Terenius, Lars; Agartz, Ingrid; Jönsson, Erik G

    2015-09-30

    Glutamate-related genes have been associated with schizophrenia, but the results have been ambiguous and difficult to replicate. Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) are the major degradation products of the monoamines dopamine, serotonin and noradrenaline, respectively, and their concentrations in the cerebrospinal fluid (CSF), mainly HVA, have been associated with schizophrenia. In the present study, we hypothesized that CSF HVA, 5-HIAA and MHPG concentrations represent intermediate phenotypes in the association between glutamate-related genes and psychosis. To test this hypothesis, we searched for association between 238 single nucleotide polymorphisms (SNPs) in ten genes shown to be directly or indirectly implicated in glutamate transmission and CSF HVA, 5-HIAA and MHPG concentrations in 74 patients with psychotic disease. Thirty-eight nominally significant associations were found. Further analyses in 111 healthy controls showed that 87% of the nominal associations were restricted to the patients with psychosis. Some of the psychosis-only-associated SNPs found in the d-amino acid oxidase activator (DAOA) and the kynurenine 3-monooxygenase (KMO) genes have previously been reported to be associated with schizophrenia. The present results suggest that CSF monoamine metabolite concentrations may represent intermediate phenotypes in the association between glutamate-related genes and psychosis. PMID:26142836

  16. Tamoxifen Metabolite Concentrations, CYP2D6 Genotype and Breast Cancer Outcomes

    PubMed Central

    Madlensky, Lisa; Natarajan, Loki; Tchu, Simone; Pu, Minya; Mortimer, Joanne; Flatt, Shirley W.; Nikoloff, D. Michele; Hillman, Grantland; Fontecha, Marcel R.; Lawrence, H. Jeffrey; Parker, Barbara A.; Wu, Alan H.B.; Pierce, John P.

    2011-01-01

    We explored whether breast cancer outcomes are associated with endoxifen and other metabolites of tamoxifen, and to examine potential correlates of endoxifen concentrations including CYP2D6 metabolizer phenotype and body mass index (BMI). Tamoxifen, endoxifen, 4-hydroxytamoxifen and N-desmethyltamoxifen concentrations were measured from 1370 estrogen receptor positive breast cancer patients participating in the Women’s Healthy Eating and Living (WHEL) Study, and tested for associations with breast cancer outcomes. Breast cancer outcomes were not associated with tamoxifen, 4-hydroxytamoxifen or N-desmethyltamoxifen concentrations. For endoxifen, a threshold was identified suggesting that women in the upper four quintiles of endoxifen had a 26% lower recurrence rate than women in the bottom quintile. (HR=0.74; 95% CI, [0.55, 1.00]). Predictors of membership in this higher risk bottom quintile were poor/intermediate metabolizer genotype, higher BMI, and low tamoxifen concentrations. This study suggests a minimal threshold at which endoxifen is effective against breast cancer recurrence, which 80% of tamoxifen-takers achieve. PMID:21430657

  17. Nitric oxide metabolite concentrations in maternal plasma decrease during parturition: possible transient down-regulation of nitric oxide synthesis.

    PubMed

    Nanno, H; Sagawa, N; Itoh, H; Matsumoto, T; Terakawa, K; Mori, T; Itoh, H; Nakao, K

    1998-06-01

    To elucidate the possible involvement of nitric oxide (NO) in parturition, we measured the maternal plasma concentrations of the NO metabolites, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and guanosine 3',5'-cyclic phosphate (cGMP) in pregnant women at various gestational ages including those at vaginal and elective Caesarean deliveries. The plasma cGMP and NO metabolite concentrations at vaginal delivery were significantly lower than those of the pregnant women in the third trimester of pregnancy. These concentrations remained low until 4 h after delivery but returned 24 h after delivery to values similar to those of the non-pregnant women. Such suppressions of plasma cGMP and NO metabolite concentrations were not observed in the women who underwent elective Caesarean section before the onset of labour. Moreover, no significant changes were observed in the plasma ANP and BNP concentrations at the time of vaginal and Caesarean deliveries, except that a slight but significant elevation of the plasma ANP concentration was observed 1 h after Caesarean delivery. In conclusion, the plasma concentrations of cGMP and NO metabolites significantly decreased at vaginal delivery but not at Caesarean delivery. These changes were independent of the plasma ANP and BNP concentrations, suggesting the possible down-regulation of maternal NO synthesis during parturition. PMID:9665345

  18. Effect of Heat Stress on Concentrations of Faecal Cortisol Metabolites in Dairy Cows.

    PubMed

    Rees, A; Fischer-Tenhagen, C; Heuwieser, W

    2016-06-01

    The negative impact of heat stress on health and productivity of dairy cows is well known. Heat stress can be quantified with the temperature-humidity index (THI) and is defined as a THI ≥ 72. Additionally, animal welfare is affected in cows living under heat stress conditions. Finding a way to quantify heat stress in dairy cows has been of increasing interest over the past decades. Therefore, the objective of this study was to evaluate concentrations of faecal glucocorticoid metabolites [i.e. 11,17-dioxoandrostanes (11,17-DOA)] as an indirect stress parameter in dairy cows without heat stress (DOA 0), with heat stress on a single day (acute heat stress, DOA 1) or with more than a single day of heat stress (chronic heat stress, DOA 2). Cows were housed in five farms under moderate European climates. Two statistical approaches (approach 1 and approach 2) were assessed. Using approach 1, concentrations of faecal 11,17-DOA were compared among DOA 0, DOA 1 and DOA 2 samples regardless of their origin (i.e. cow, unpaired comparison with a one-way anova). Using approach 2, a cow was considered as its own control; that is 11,17-DOA was treated as a cow-specific factor and only paired samples were included in the analysis for this approach (paired comparison with t-tests). In approach 1 (p = 0.006) and approach 2 (p = 0.038), 11,17-DOA values of cows under acute heat stress were higher compared to those of cows without heat stress. Our results also indicate that acute heat stress has to be considered as a confounder in studies measuring faecal glucocorticoid metabolites in cows to evaluate other stressful situations. PMID:27091101

  19. Gender, season and management affect fecal glucocorticoid metabolite concentrations in captive goral (Naemorhedus griseus) in Thailand.

    PubMed

    Khonmee, Jaruwan; Brown, Janine L; Rojanasthien, Suvichai; Aunsusin, Anurut; Thumasanukul, Dissakul; Kongphoemphun, Adisorn; Siriaroonrat, Boripat; Tipkantha, Wanlaya; Punyapornwithaya, Veerasak; Thitaram, Chatchote

    2014-01-01

    Chinese goral (Naemorhedus griseus) are a threatened species in Thailand and the focus of captive breeding for possible reintroduction. However, little is known of their biology or what factors in the captive environment affect welfare. Our objective was to determine the impact of gender, season, and management on goral adrenal activity. We hypothesized that differences in fecal glucocorticoid concentrations would be related to animal density. Fecal samples were collected 3 days/week for 1 year from 63 individuals (n = 32 males, 31 females) at two facilities that house the majority of goral in Thailand: Omkoi Wildlife Sanctuary (Omkoi), an off-exhibit breeding center that houses goral in individual pens (16 pens; n = 8 males, 8 females) and in small family groups (8 pens; n = 8 males, 8 females); and the Chiang Mai Night Safari (NS), a zoo that maintains 31 goral (n = 17 males, 14 females) in one large pen. Glucocorticoid metabolite concentrations were higher in male than female goral at Omkoi throughout the year, and there was a seasonal effect on adrenal activity (p<0.05). Goral at Omkoi and NS were used to test the effect of animal density on fecal glucocorticoid excretion of goral housed in similar-sized enclosures. Overall, the highest levels were found at NS (n = 31 adults/pen; 27 m2 per animal) compared to Omkoi (n = 2 adults/pen; 400 m2 per animal) (p<0.05). Overall findings support our hypothesis that animal density and aspects of the captive environment impact adrenal steroid activity in captive goral. In addition, gender and season also had significant effects on glucocorticoid metabolite production. Potential stressors pertaining to the welfare of this species were identified, which will guide future efforts to improve management and create self-sustaining and healthy populations of this threatened species. PMID:24637886

  20. Gender, Season and Management Affect Fecal Glucocorticoid Metabolite Concentrations in Captive Goral (Naemorhedus griseus) in Thailand

    PubMed Central

    Khonmee, Jaruwan; Brown, Janine L.; Rojanasthien, Suvichai; Aunsusin, Anurut; Thumasanukul, Dissakul; Kongphoemphun, Adisorn; Siriaroonrat, Boripat; Tipkantha, Wanlaya; Punyapornwithaya, Veerasak; Thitaram, Chatchote

    2014-01-01

    Chinese goral (Naemorhedus griseus) are a threatened species in Thailand and the focus of captive breeding for possible reintroduction. However, little is known of their biology or what factors in the captive environment affect welfare. Our objective was to determine the impact of gender, season, and management on goral adrenal activity. We hypothesized that differences in fecal glucocorticoid concentrations would be related to animal density. Fecal samples were collected 3 days/week for 1 year from 63 individuals (n = 32 males, 31 females) at two facilities that house the majority of goral in Thailand: Omkoi Wildlife Sanctuary (Omkoi), an off-exhibit breeding center that houses goral in individual pens (16 pens; n = 8 males, 8 females) and in small family groups (8 pens; n = 8 males, 8 females); and the Chiang Mai Night Safari (NS), a zoo that maintains 31 goral (n = 17 males, 14 females) in one large pen. Glucocorticoid metabolite concentrations were higher in male than female goral at Omkoi throughout the year, and there was a seasonal effect on adrenal activity (p<0.05). Goral at Omkoi and NS were used to test the effect of animal density on fecal glucocorticoid excretion of goral housed in similar-sized enclosures. Overall, the highest levels were found at NS (n = 31 adults/pen; 27 m2 per animal) compared to Omkoi (n = 2 adults/pen; 400 m2 per animal) (p<0.05). Overall findings support our hypothesis that animal density and aspects of the captive environment impact adrenal steroid activity in captive goral. In addition, gender and season also had significant effects on glucocorticoid metabolite production. Potential stressors pertaining to the welfare of this species were identified, which will guide future efforts to improve management and create self-sustaining and healthy populations of this threatened species. PMID:24637886

  1. Parent and Metabolite Opioid Drug Concentrations in Unintentional Deaths Involving Opioid and Benzodiazepine Combinations*†‡

    PubMed Central

    Fields, Marcia D.; Abate, Marie A.; Hu, Lan; Long, D. Leann; Blommel, Matthew L.; Haikal, Nabila A.; Kraner, James C.

    2016-01-01

    Effects of benzodiazepines on postmortem opioid parent and parent/metabolite blood concentration ratios were determined for fentanyl-, hydrocodone-, methadone-, or oxycodone-related accidental deaths. These opioids are partially metabolized by the CYP3A4 enzyme system, which is also affected by diazepam and alprazolam. Opioid/metabolite combinations examined were as follows: fentanyl/norfentanyl, hydrocodone/dihydrocodeine, methadone/EDDP, and oxycodone/oxymorphone. Parent opioid concentrations were analyzed for 877 deaths. Parent/metabolite concentration ratios were analyzed for 349 deaths, excluding cases with co-intoxicants present known to interfere with opioid elimination. Alprazolam in combination with diazepam significantly decreased median hydrocodone concentrations by 48% (p = 0.01) compared to hydrocodone alone. The methadone parent/metabolite concentration ratio was reduced by 35% in the presence of diazepam compared to methadone alone (p = 0.03). Benzodiazepines did not statistically significantly affect fentanyl or oxycodone concentrations. Possible factors affecting opioid concentrations and possible toxicity development, including any differential effects on specific opioids, should continue to be explored. PMID:26223761

  2. Aging effect on plasma metabolites and hormones concentrations in riding horses

    PubMed Central

    Kawasumi, K.; Yamamoto, M.; Koide, M.; Okada, Y.; Mori, N.; Yamamoto, I.; Arai, T.

    2015-01-01

    Age effects on plasma metabolites, hormone concentrations, and enzyme activities related to energy metabolism were investigated in 20 riding horses. Animals were divided into two groups: Young (3-8 years) and aged (11-18 years). They were clinically healthy, and not obese. Plasma adiponectin (ADN) concentrations in aged horses were significantly lower than those in young horses (mean±SE, 6.5±1.3 µg mL-1 vs, 10.9±1.7 µg mL-1, Mann-Whitney U test, respectively; P=0.0233). Plasma non-esterified fatty acid levels and Insulin and malondialdehyde concentrations in aged group tended to increase compared to those in young group although there were not significant differences statistically. In aged group, malate dehydrogenase/lactate dehydrogenase (M/L) ratio, which is considered an energy metabolic indicator, did not change significantly compared to that in young group. Present data suggest that aging may negatively affect nutrition metabolism, but not induce remarkable changes in M/L ratio in riding horses. PMID:26623382

  3. Aging effect on plasma metabolites and hormones concentrations in riding horses.

    PubMed

    Kawasumi, K; Yamamoto, M; Koide, M; Okada, Y; Mori, N; Yamamoto, I; Arai, T

    2015-01-01

    Age effects on plasma metabolites, hormone concentrations, and enzyme activities related to energy metabolism were investigated in 20 riding horses. Animals were divided into two groups: Young (3-8 years) and aged (11-18 years). They were clinically healthy, and not obese. Plasma adiponectin (ADN) concentrations in aged horses were significantly lower than those in young horses (mean±SE, 6.5±1.3 µg mL(-1) vs, 10.9±1.7 µg mL(-1), Mann-Whitney U test, respectively; P=0.0233). Plasma non-esterified fatty acid levels and Insulin and malondialdehyde concentrations in aged group tended to increase compared to those in young group although there were not significant differences statistically. In aged group, malate dehydrogenase/lactate dehydrogenase (M/L) ratio, which is considered an energy metabolic indicator, did not change significantly compared to that in young group. Present data suggest that aging may negatively affect nutrition metabolism, but not induce remarkable changes in M/L ratio in riding horses. PMID:26623382

  4. Follicular fluid and urinary concentrations of phthalate metabolites among infertile women and associations with in vitro fertilization parameters.

    PubMed

    Du, Yao-Yao; Fang, Yue-Li; Wang, Yi-Xin; Zeng, Qiang; Guo, Na; Zhao, Hua; Li, Yu-Feng

    2016-06-01

    Evidence from toxicological studies has demonstrated that phthalates can lead to reduced fertility through effects on folliculogenesis, oocyte maturation and embryonic development, but human data are limited. Concentrations of eight phthalate metabolites in 110 follicular fluid (FF) and urine samples collected from 112 women attending an infertility clinic in Wuhan, China were quantified, and correlations between paired matrices were explored. Associations between metabolite concentrations and in vitro fertilization (IVF) parameters were evaluated with multivariable models. Six metabolites were detected in >72.73% of the FF samples. MEHP and MBP were the dominant metabolites with a median level of 2.80 and 2.05ng/mL, respectively. Significant correlations between the two matrices, urine and FF, were found for MEP (rs=0.44), and MBP (rs=0.22). FF and urinary metabolite concentrations were not associated with any IVF parameters. However, given the prevalence of phthalates exposure, further work is needed to elucidate the potential hazard on female reproduction. PMID:27067915

  5. Anthocyanins and their gut metabolites reduce the adhesion of monocyte to TNFα-activated endothelial cells at physiologically relevant concentrations.

    PubMed

    Krga, Irena; Monfoulet, Laurent-Emmanuel; Konic-Ristic, Aleksandra; Mercier, Sylvie; Glibetic, Maria; Morand, Christine; Milenkovic, Dragan

    2016-06-01

    An increasing number of evidence suggests a protective role of dietary anthocyanins against cardiovascular diseases. Anthocyanins' extensive metabolism indicates that their metabolites could be responsible for the protective effects associated with consumption of anthocyanin-rich foods. The aim of this work was to investigate the effect of plasma anthocyanins and their metabolites on the adhesion of monocytes to TNFα-activated endothelial cells and on the expression of genes encoding cell adhesion molecules. Human umbilical vein endothelial cells (HUVECs) were exposed to circulating anthocyanins: cyanidin-3-arabinoside, cyanidin-3-galactoside, cyanidin-3-glucoside, delphinidin-3-glucoside, peonidin-3-glucoside, anthocyanin degradation product: 4-hydroxybenzaldehyde, or to their gut metabolites: protocatechuic, vanillic, ferulic and hippuric acid, at physiologically-relevant concentrations (0.1-2 μM) and time of exposure. Both anthocyanins and gut metabolites decreased the adhesion of monocytes to HUVECs, with a magnitude ranging from 18.1% to 47%. The mixture of anthocyanins and that of gut metabolites also reduced monocyte adhesion. However, no significant effect on the expression of genes encoding E-selectin, ICAM1 and VCAM1 was observed, suggesting that other molecular targets are involved in the observed effect. In conclusion, this study showed the potency of anthocyanins and their gut metabolites to modulate the adhesion of monocytes to endothelial cells, the initial step in atherosclerosis development, under physiologically-relevant conditions. PMID:26873533

  6. Non-invasive monitoring of stress hormones in the bat Eptesicus isabellinus - Do fecal glucocorticoid metabolite concentrations correlate with survival?

    PubMed

    Kelm, Detlev H; Popa-Lisseanu, Ana G; Dehnhard, Martin; Ibáñez, Carlos

    2016-01-15

    Chronic stress may negatively impact fitness and survival in wildlife. Stress hormone analysis from feces is a non-invasive tool for identifying stressors and deducing about individual and population level fitness. Although many bat populations are endangered, fecal stress hormone analysis has not been established in bats as a method for focusing conservation efforts. The isabelline serotine bat, Eptesicus isabellinus, is exposed to human disturbance as its roosts are mostly found in anthropogenic structures. Moreover, this bat is host to various diseases and survival rates between colonies may vary significantly. To validate the analysis of fecal glucocorticoid metabolites, we applied an adrenocorticotropic hormone (ACTH) challenge and tested four different enzyme immunoassays (EIA) for measuring glucocorticoid concentrations. Cortisol and its metabolites showed the highest increase in blood and feces after the ACTH challenge, but corticosterone and its metabolites also increased significantly. Baseline fecal cortisol metabolite (FCM) concentrations did not increase until 1.5h after the animals were captured, which is a convenient time lag for sample collection from captured animals. We furthermore compared baseline FCM concentrations between five colonies of E. isabellinus in Andalusia, Spain, and tested for their correlation with survival rates. FCM concentrations did not vary between colonies, but FCM levels increased with the animals' age. FCM analysis may prove a useful tool for identifying bat colonies that experience uncommon environmental stress. However, inter-individual variation in hormone secretion, due to factors such as age, may require additional information to properly interpret differences in hormone concentrations. PMID:26673871

  7. In vivo MRS and MRSI: Performance analysis, measurement considerations and evaluation of metabolite concentration images

    NASA Astrophysics Data System (ADS)

    Vikhoff-Baaz, Barbro

    2000-10-01

    The doctoral thesis concerns development, evaluation and performance of quality assessment methods for volume- selection methods in 31P and 1H MR spectroscopy (MRS). It also contains different aspects of the measurement procedure for 1H MR spectroscopic imaging (MRSI) with application on the human brain, image reconstruction of the MRSI images and evaluation methods for lateralization of temporal lobe epilepsy (TLE). Two complementary two-compartment phantoms and evaluation methods for quality assessment of 31P MRS in small-bore MR systems were presented. The first phantom consisted of an inner cube inside a sphere phantom where measurements with and without volume selection where compared for various VOI sizes. The multi-centre showed that the evaluated parameters provide useful information of the performance of volume-selective MRS at the MR system. The second phantom consisted of two compartments divided by a very thin wall and was found useful for measurements of the appearance and position of the VOI profile in specific gradient directions. The second part concerned 1H MRS and MRSI of whole-body MR systems. Different factors that may degrade or complicate the measurement procedure like for MRSI were evaluated, e.g. the volume selection performance, contamination, susceptibility and motion. Two interpolation methods for reconstruction of MRSI images were compared. Measurements and computer simulations showed that Fourier interpolation correctly visualizes the information inherent in the data set, while the results were dependent on the position of the object relative the original matrix using Cubic spline interpolation. Application of spatial filtering may improve the image representation of the data. Finally, 1H MRSI was performed on healthy volunteers and patients with temporal lobe epilepsy (TLE). Metabolite concentration images were used for lateralization of TLE, where the signal intensity in the two hemispheres were compared. Visual analysis of the

  8. A non-invasive diffuse reflectance calibration-free method for absolute determination of exogenous biochemicals concentration in biological tissues

    NASA Astrophysics Data System (ADS)

    Lappa, Alexander V.; Kulikovskiy, Artem N.; Busarov, Oleg G.

    2014-03-01

    The paper presents a new method for distant non-destructive determination of concentration of light absorbing admixtures in turbid media. In particular, it is intended for non-invasive in vivo control of accumulation in patient tissues of various biochemicals introduced to the patients for chemotherapy, photodynamic therapy or diagnostics. It is require that the admixture absorption spectrum should have a clearly marked peak in the wavelength region where the pure medium one varies regularly. Fluorescence of admixtures is not required. The method uses the local diffuse reflectance spectroscopy with optical fiber probe including one emitting and two reading There are several features in the method: the value to be determined is absolute concentration of admixtures; the method needs no calibration measurements on phantoms; it needs no reference measurements on sample with zero admixture concentration; it uses a two parametric kinetic light propagation model and original algorithms to resolve direct and inverse tasks of radiation transport theory. Experimental testing passed with tissue equivalent phantoms and different admixtures, including a chlorine photosensitizer, showed accuracy under 10% in all cases.

  9. Personal care product use and urinary phthalate metabolite and paraben concentrations during pregnancy among women from a fertility clinic

    PubMed Central

    Braun, Joe M.; Just, Allan C.; Williams, Paige L.; Smith, Kristen W.; Calafat, Antonia M.; Hauser, Russ

    2014-01-01

    Parabens and phthalates are potential endocrine disruptors frequently used in personal care/beauty products, and the developing fetus may be sensitive to these chemicals. We measured urinary butyl-paraben (BP), methyl-paraben (MP), propyl-paraben (PP), mono-n-butyl phthalate (MBP), and monoethyl phthalate (MEP) concentrations up to three times in 177 pregnant women from a fertility clinic in Boston MA. Using linear mixed models, we examined the relationship between self-reported personal care product use in the previous 24 hours and urinary paraben and phthalate metabolite concentrations. Lotion, cosmetic, and cologne/perfume use were associated with the greatest increases in the molar sum of phthalate metabolite and paraben concentrations, although the magnitude of individual biomarker increases varied by product used. For example, women who used lotion had BP concentrations 111% higher (95% confidence interval [CI]:41%, 216%) than non-users, while their MBP concentrations were only 28% higher (CI:2%, 62%). Women using/cologne/perfume had MEP concentrations 167% (CI:98%, 261%) higher than non-users, but BP concentrations were similar. We observed a monotonic dose-response relationship between the total number of products used and urinary paraben and phthalate metabolite concentrations. These results suggest that questionnaire data may be useful for assessing exposure to a mixture of chemicals from personal care products during pregnancy. PMID:24149971

  10. Personal care product use and urinary phthalate metabolite and paraben concentrations during pregnancy among women from a fertility clinic.

    PubMed

    Braun, Joe M; Just, Allan C; Williams, Paige L; Smith, Kristen W; Calafat, Antonia M; Hauser, Russ

    2014-01-01

    Parabens and phthalates are potential endocrine disruptors frequently used in personal care/beauty products, and the developing fetus may be sensitive to these chemicals. We measured urinary butyl-paraben (BP), methyl-paraben, propyl-paraben, mono-n-butyl phthalate (MBP), and monoethyl phthalate (MEP) concentrations up to three times in 177 pregnant women from a fertility clinic in Boston, MA. Using linear mixed models, we examined the relationship between self-reported personal care product use in the previous 24 h and urinary paraben and phthalate metabolite concentrations. Lotion, cosmetic, and cologne/perfume use were associated with the greatest increases in the molar sum of phthalate metabolite and paraben concentrations, although the magnitude of individual biomarker increases varied by product used. For example, women who used lotion had BP concentrations 111% higher (95% confidence interval (CI): 41%, 216%) than non-users, whereas their MBP concentrations were only 28% higher (CI: 2%, 62%). Women using cologne/perfume had MEP concentrations 167% (CI: 98%, 261%) higher than non-users, but BP concentrations were similar. We observed a monotonic dose-response relationship between the total number of products used and urinary paraben and phthalate metabolite concentrations. These results suggest that questionnaire data may be useful for assessing exposure to a mixture of chemicals from personal care products during pregnancy. PMID:24149971

  11. Easy Absolute Values? Absolutely

    ERIC Educational Resources Information Center

    Taylor, Sharon E.; Mittag, Kathleen Cage

    2015-01-01

    The authors teach a problem-solving course for preservice middle-grades education majors that includes concepts dealing with absolute-value computations, equations, and inequalities. Many of these students like mathematics and plan to teach it, so they are adept at symbolic manipulations. Getting them to think differently about a concept that they…

  12. Phosphate metabolite concentrations and ATP hydrolysis potential in normal and ischaemic hearts

    PubMed Central

    Wu, Fan; Zhang, Eric Y; Zhang, Jianyi; Bache, Robert J; Beard, Daniel A

    2008-01-01

    To understand how cardiac ATP and CrP remain stable with changes in work rate – a phenomenon that has eluded mechanistic explanation for decades – data from 31phosphate-magnetic resonance spectroscopy (31P-MRS) are analysed to estimate cytoplasmic and mitochondrial phosphate metabolite concentrations in the normal state, during high cardiac workstates, during acute ischaemia and reactive hyperaemic recovery. Analysis is based on simulating distributed heterogeneous oxygen transport in the myocardium integrated with a detailed model of cardiac energy metabolism. The model predicts that baseline myocardial free inorganic phosphate (Pi) concentration in the canine myocyte cytoplasm – a variable not accessible to direct non-invasive measurement – is approximately 0.29 mm and increases to 2.3 mm near maximal cardiac oxygen consumption. During acute ischaemia (from ligation of the left anterior descending artery) Pi increases to approximately 3.1 mm and ATP consumption in the ischaemic tissue is reduced quickly to less than half its baseline value before the creatine phosphate (CrP) pool is 18% depleted. It is determined from these experiments that the maximal rate of oxygen consumption of the heart is an emergent property and is limited not simply by the maximal rate of ATP synthesis, but by the maximal rate at which ATP can be synthesized at a potential at which it can be utilized. The critical free energy of ATP hydrolysis for cardiac contraction that is consistent with these findings is approximately −63.5 kJ mol−1. Based on theoretical findings, we hypothesize that inorganic phosphate is both the primary feedback signal for stimulating oxidative phosphorylation in vivo and also the most significant product of ATP hydrolysis in limiting the capacity of the heart to hydrolyse ATP in vivo. Due to the lack of precise quantification of Piin vivo, these hypotheses and associated model predictions remain to be carefully tested experimentally. PMID:18617566

  13. Effects of supplemental feeding and aggregation on fecal glucocorticoid metabolite concentrations in elk

    USGS Publications Warehouse

    Forristal, Victoria E.; Creel, Scott; Taper, Mark L.; Scurlock, Brandon M.; Cross, Paul C.

    2012-01-01

    Habitat modifications and supplemental feeding artificially aggregate some wildlife populations, with potential impacts upon contact and parasite transmission rates. Less well recognized, however, is how increased aggregation may affect wildlife physiology. Crowding has been shown to induce stress responses, and increased glucocorticoid (GC) concentrations can reduce immune function and increase disease susceptibility. We investigated the effects of supplemental feeding and the aggregation that it induces on behavior and fecal glucocorticoid metabolite concentrations (fGCM) in elk (Cervus elaphus) using observational and experimental approaches. We first compared fGCM levels of elk on supplemental feedgrounds to neighboring elk populations wintering in native habitats using data from 2003 to 2008. We then experimentally manipulated the distribution of supplemental food on feedgrounds to investigate whether more widely distributed food would result in lower rates of aggression and stress hormone levels. Contrary to some expectations that fed elk may be less stressed than unfed elk during the winter, we found that elk on feedgrounds had fecal GC levels at least 31% higher than non-feedground populations. Within feedgrounds, fGCM levels were strongly correlated with local measures of elk density (r2 = 0.81). Dispersing feed more broadly, however, did not have a detectable effect on fGCM levels or aggression rates. Our results suggest that increases in aggregation associated with winter feedgrounds affects elk physiology, and the resulting increases in fGCM levels are not likely to be mitigated by management efforts that distribute the feed more widely. Additional research is needed to assess whether these increases in fGCMs directly alter parasite transmission and disease dynamics.

  14. Concentration distribution of the marijuana metabolite Delta9-tetrahydrocannabinol-9-carboxylic acid and the cocaine metabolite benzoylecgonine in the department of defense urine drug-testing program.

    PubMed

    Jemionek, John F; Copley, Curtis L; Smith, Michael L; Past, Marilyn R

    2008-01-01

    Urine drug testing has been employed for punitive purposes by the Department of Defense since December 1981 (Memorandum 62884, Deputy Secretary of Defense Frank C. Carlucci). Federal Workplace Drug Testing Programs were initiated in response to Executive Order 12564 issued on September 15, 1986, that required Drug-Free Federal Workplaces be established. In their respective programs, a positive urine drug test may be referred to a military court martial or to an administrative board. To address safety and insurance requirements, the testing of civilians has expanded beyond Federal Programs to include pre-employment and post-accident urine drug testing. During adjudication, an Expert Toxicologist may be asked to opine what can be discerned from the concentration of drug or drug metabolite found in the urine. Little can be opined with certainty from a positive urine drug test as to the amount of drug ingested, when the drug was ingested, and in most instances, whether the individual felt the effects of the drug, or was under the influence of the drug found in the urine. What may be useful to both the Expert and to the Trier-of-Facts is the frequency that a particular urine drug concentration is encountered in positive drug tests. The finding that 50% of all positive marijuana and cocaine urine metabolite concentrations in the military testing program over the three-year period of October 1, 2004 through September 30, 2007, are below a median value of 65 and 968 ng/mL, respectively, provide reference points. A median drug concentration combined with the percentile or frequency that a particular urine drug concentration occurs may provide evaluative information for a determination of the facts and the outcome of judicial or administrative proceedings. This may be especially useful to jurors when the concentration of marijuana or cocaine metabolite is perceptibly low. The information would also be applicable to medical review officers, medical examiners, drug treatment

  15. Software-assisted serum metabolite quantification using NMR.

    PubMed

    Jung, Young-Sang; Hyeon, Jin-Seong; Hwang, Geum-Sook

    2016-08-31

    The goal of metabolomics is to analyze a whole metabolome under a given set of conditions, and accurate and reliable quantitation of metabolites is crucial. Absolute concentration is more valuable than relative concentration; however, the most commonly used method in NMR-based serum metabolic profiling, bin-based and full data point peak quantification, provides relative concentration levels of metabolites and are not reliable when metabolite peaks overlap in a spectrum. In this study, we present the software-assisted serum metabolite quantification (SASMeQ) method, which allows us to identify and quantify metabolites in NMR spectra using Chenomx software. This software uses the ERETIC2 utility from TopSpin to add a digitally synthesized peak to a spectrum. The SASMeQ method will advance NMR-based serum metabolic profiling by providing an accurate and reliable method for absolute quantification that is superior to bin-based quantification. PMID:27506360

  16. Predictors of Urinary Bisphenol A and Phthalate Metabolite Concentrations in Mexican Children

    PubMed Central

    Lewis, Ryan C.; Meeker, John D.; Peterson, Karen E.; Lee, Joyce M.; Pace, Gerry G.; Cantoral, Alejandra; Téllez-Rojo, Martha Maria

    2013-01-01

    Exposure to endocrine disrupting chemicals such as bisphenol A (BPA) and phthalates is prevalent among children and adolescents, but little is known regarding important sources of exposure at these sensitive life stages. In this study, we measured urinary concentrations of BPA and nine phthalate metabolites in 108 Mexican children aged 8–13 years. Associations of age, time of day, and questionnaire items on external environment, water use, and food container use with specific gravity-corrected urinary concentrations were assessed, as were questionnaire items concerning the use of 17 personal care products in the past 48-hr. As a secondary aim, third trimester urinary concentrations were measured in 99 mothers of these children, and the relationship between specific gravity-corrected urinary concentrations at these two time points was explored. After adjusting for potential confounding by other personal care product use in the past 48-hr, there were statistically significant (p <0.05) positive associations in boys for cologne/perfume use and monoethyl phthalate (MEP), mono(3-carboxypropyl) phthalate (MCPP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and in girls for colored cosmetics use and mono-n-butyl phthalate (MBP), mono(2-ethylhexyl) phthalate (MEHP), MEHHP, MEOHP, and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), conditioner use and MEP, deodorant use and MEP, and other hair products use and MBP. There was a statistically significant positive trend for the number of personal care products used in the past 48-hr and log-MEP in girls. However, there were no statistically significant associations between the analytes and the other questionnaire items and there were no strong correlations between the analytes measured during the third trimester and at 8–13 years of age. We demonstrated that personal care product use is associated with exposure to multiple phthalates in children. Due to rapid development

  17. Plasma concentrations of cortisol and PGF2α metabolite in Danish sows during mating, and intrauterine and conventional insemination

    PubMed Central

    Norrby, Mattias; Madsen, Mads T; Alexandersen, Charlotte Borg; Kindahl, Hans; Madej, Andrzej

    2007-01-01

    Background The aims of the present work was to study whether there are any relationships between cortisol and PG-metabolite in mated sows or inseminated with the intrauterine technique and compare these to changes occurring in conventionally inseminated sow. Methods Thirty three crossbred sows (Danish Landrace × Danish Large White) were fitted with jugular vein catheters through vena auricularis from one of the ears. The sows were randomly divided into three groups (Boar-, IUI- and AI-group) and blood samples were collected before, during and after service. In a final evaluation only 25 sows that became pregnant and farrowed piglets at full term were used. Results Cortisol concentrations increased in all groups but Boar-group (n = 8) had a significantly higher cortisol during 10 to 20 min after service than sows in AI-group (n = 8). In mated sows cortisol concentrations peaked at 15 minutes after service. The Boar-group (n = 8) showed no ascending PG-metabolite levels during the whole experiment, while both IUI- and AI-groups (n = 9 and n = 8, respectively) had a 2.5-fold increase in PG-metabolite 15 minutes after service. Conclusion In conclusion, mating of sows by a boar results in a greater increase of cortisol than AI and without an elevation of PG-metabolite levels, which was seen in both the inseminated groups. It was also demonstrated that IUI-group had an earlier significant increase of PG-metabolite levels than sows inseminated conventionally. Further investigation using different semen extenders or even different type of insemination catheters might be helpful in understanding the reason for an immediate increase of PG-metabolite after insemination but not after mating. PMID:18053237

  18. Concentrations of dimethylaniline and other metabolites in milk and tissues of dairy cows treated with lidocaine.

    PubMed

    Hoogenboom, Ron L A P; Zuidema, Tina; Essers, Martien; van Vuuren, Ad M; van Wikselaar, Piet G; van Eijkeren, Jan C H; Mengelers, Marcel J B; Zeilmaker, Marco J; Bulder, Astrid S

    2015-01-01

    Lidocaine is a topical anaesthetic drug used in dairy cows for laparotomy (caesarean section, abomasal displacement). Because there are no registered drugs for this indication, it can be applied under the so-called Cascade rules (off-label use), with the restriction that the off-label withdrawal periods of 7 days for milk and 28 days for meat are taken into account. In animals, lidocaine is rapidly metabolised into various metabolites, one being 2,6-dimethylaniline (DMA) which is reported to possess carcinogenic and mutagenic properties and detected also in milk. To investigate whether the off-label withdrawal periods are long enough to exclude the presence of lidocaine and DMA, and potential other metabolites, in edible products, a study was performed with eight dairy cows treated with lidocaine by injection in the abdominal muscles. At various time points blood samples, milk and urine were collected. Four animals were slaughtered 3.5 h after treatment, the other four after 48.5 h. The injection site, meat, liver and kidney were analysed for levels of lidocaine, DMA, monoethylglycinexylidide (MEGX) and 3-OH-lidocaine. It was shown that DMA is an important metabolite in dairy cows and can be detected in both meat and milk. In addition, also MEGX, 3-OH-lidocaine and three other metabolites were identified and to some extent quantified. These metabolites were 4-OH-lidocaine, lidocaine-N-oxide and 4-hydroxy-DMA. The latter compound was the most important metabolite in urine. However, levels in milk and meat decreased rapidly after the application. Overall, it can be concluded that the off-label withdrawal times of 7 and 28 days for milk and meat, respectively, guarantee the absence of detectable levels of lidocaine and metabolites. PMID:26118443

  19. Urinary Phthalate Metabolite Concentrations and Reproductive Outcomes among Women Undergoing in Vitro Fertilization: Results from the EARTH Study

    PubMed Central

    Hauser, Russ; Gaskins, Audrey J.; Souter, Irene; Smith, Kristen W.; Dodge, Laura E.; Ehrlich, Shelley; Meeker, John D.; Calafat, Antonia M.; Williams, Paige L.

    2015-01-01

    Background: Evidence from both animal and human studies suggests that exposure to phthalates may be associated with adverse female reproductive outcomes. Objective: We evaluated the associations between urinary concentrations of phthalate metabolites and outcomes of assisted reproductive technologies (ART). Methods: This analysis included 256 women enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2004–2012) who provided one to two urine samples per cycle before oocyte retrieval. We measured 11 urinary phthalate metabolites [mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), monoethyl phthalate (MEP), monocarboxyisooctyl phthalate (MCOP), monocarboxyisononyl phthalate (MCNP), and mono(3-carboxypropyl) phthalate (MCPP)]. We used generalized linear mixed models to evaluate the association of urinary phthalate metabolites with in vitro fertilization (IVF) outcomes, accounting for multiple IVF cycles per woman. Results: In multivariate models, women in the highest as compared with lowest quartile of MEHP, MEHHP, MEOHP, MECPP, ΣDEHP (MEHP + MEHHP + MEOHP + MECPP), and MCNP had lower oocyte yield. Similarly, the number of mature (MII) oocytes retrieved was lower in the highest versus lowest quartile for these same phthalate metabolites. The adjusted differences (95% CI) in proportion of cycles resulting in clinical pregnancy and live birth between women in the fourth versus first quartile of ΣDEHP were –0.19 (–0.29, –0.08) and –0.19 (–0.28, –0.08), respectively, and there was also a lower proportion of cycles resulting in clinical pregnancy and live birth for individual DEHP metabolites. Conclusions: Urinary concentrations of DEHP metabolites were inversely associated with oocyte yield, clinical pregnancy

  20. Effect of repeated administration of antidepressant drugs on the serum and brain concentration of testosterone and its metabolites.

    PubMed

    Przegaliński, E; Warchoł-Kania, A; Budziszewska, B; Jaworska, L

    1987-01-01

    A repeated oral treatment (twice daily, for 21 consecutive days) with 10 mg/kg of antidepressants imipramine, amitriptyline, citalopram, mianserin affects the level of testosterone and its metabolites (5 alpha-dihydrotestosterone and estradiol-17 beta) in the serum and brain structures (cerebral cortex, hypothalamus). Citalopram and mianserin increased significantly the serum testosterone concentration, while imipramine and amitriptyline reduced the concentration of 5 alpha-dihydrotestosterone. In the cerebral cortex a reduction in 5 alpha-dihydrotestosterone after imipramine, and in the hypothalamus a decrease in testosterone level after amitriptyline were observed. None of the investigated drugs influenced estradiol-17 beta concentration in the serum or in the brain. PMID:3503989

  1. Concentration of metabolites from low-density planktonic communities for environmental metabolomics using nuclear magnetic resonance spectroscopy.

    PubMed

    Everroad, R Craig; Yoshida, Seiji; Tsuboi, Yuuri; Date, Yasuhiro; Kikuchi, Jun; Moriya, Shigeharu

    2012-01-01

    Environmental metabolomics is an emerging field that is promoting new understanding in how organisms respond to and interact with the environment and each other at the biochemical level. Nuclear magnetic resonance (NMR) spectroscopy is one of several technologies, including gas chromatography-mass spectrometry (GC-MS), with considerable promise for such studies. Advantages of NMR are that it is suitable for untargeted analyses, provides structural information and spectra can be queried in quantitative and statistical manners against recently available databases of individual metabolite spectra. In addition, NMR spectral data can be combined with data from other omics levels (e.g. transcriptomics, genomics) to provide a more comprehensive understanding of the physiological responses of taxa to each other and the environment. However, NMR is less sensitive than other metabolomic techniques, making it difficult to apply to natural microbial systems where sample populations can be low-density and metabolite concentrations low compared to metabolites from well-defined and readily extractable sources such as whole tissues, biofluids or cell-cultures. Consequently, the few direct environmental metabolomic studies of microbes performed to date have been limited to culture-based or easily defined high-density ecosystems such as host-symbiont systems, constructed co-cultures or manipulations of the gut environment where stable isotope labeling can be additionally used to enhance NMR signals. Methods that facilitate the concentration and collection of environmental metabolites at concentrations suitable for NMR are lacking. Since recent attention has been given to the environmental metabolomics of organisms within the aquatic environment, where much of the energy and material flow is mediated by the planktonic community, we have developed a method for the concentration and extraction of whole-community metabolites from planktonic microbial systems by filtration. Commercially

  2. Postmortem Brain and Blood Reference Concentrations of Alprazolam, Bromazepam, Chlordiazepoxide, Diazepam, and their Metabolites and a Review of the Literature.

    PubMed

    Skov, Louise; Holm, Karen Marie Dollerup; Johansen, Sys Stybe; Linnet, Kristian

    2016-09-01

    To interpret postmortem toxicology results, reference concentrations for non-toxic and toxic levels are needed. Usually, measurements are performed in blood, but because of postmortem redistribution phenomena this may not be optimal. Rather, measurement in the target organ of psychoactive drugs, the brain, might be considered. Here we present reference concentrations of femoral blood and brain tissue of selected benzodiazepines (BZDs). Using LC-MS/MS, we quantified alprazolam, bromazepam, chlordiazepoxide, diazepam, and the metabolites desmethyldiazepam, oxazepam and temazepam in postmortem femoral blood and brain tissue in 104 cases. BZDs were judged to be unrelated to the cause of death in 88 cases and contributing to death in 16 cases. No cases were found with cause of death solely attributed to BZD poisoning. All BZDs investigated tended to have higher concentrations in brain than in blood with median brain-blood ratios ranging from 1.1 to 2.3. A positive correlation between brain and blood concentrations was found with R(2) values from 0.51 to 0.95. Our reported femoral blood concentrations concur with literature values, but sparse information on brain concentration was available. Drug-metabolite ratios were similar in brain and blood for most compounds. Duplicate measurements of brain samples showed that the pre-analytical variation in brain (5.9%) was relatively low, supporting the notion that brain tissue is a suitable postmortem specimen. The reported concentrations in both brain and blood can be used as reference values when evaluating postmortem cases. PMID:27416838

  3. Method for determining molar concentrations of metabolites in complex solutions from two-dimensional 1H-13C NMR spectra.

    PubMed

    Lewis, Ian A; Schommer, Seth C; Hodis, Brendan; Robb, Kate A; Tonelli, Marco; Westler, William M; Sussman, Michael R; Markley, John L

    2007-12-15

    One-dimensional (1D) (1)H nuclear magnetic resonance (NMR) spectroscopy is used extensively for high-throughput analysis of metabolites in biological fluids and tissue extracts. Typically, such spectra are treated as multivariate statistical objects rather than as collections of quantifiable metabolites. We report here a two-dimensional (2D) (1)H-(13)C NMR strategy (fast metabolite quantification, FMQ, by NMR) for identifying and quantifying the approximately 40 most abundant metabolites in biological samples. To validate this technique, we prepared mixtures of synthetic compounds and extracts from Arabidopsis thaliana, Saccharomyces cerevisiae, and Medicago sativa. We show that accurate (technical error 2.7%) molar concentrations can be determined in 12 min using our quantitative 2D (1)H-(13)C NMR strategy. In contrast, traditional 1D (1)H NMR analysis resulted in 16.2% technical error under nearly ideal conditions. We propose FMQ by NMR as a practical alternative to 1D (1)H NMR for metabolomics studies in which 50-mg (extract dry weight) samples can be obtained. PMID:17985927

  4. Effects of Forage:Concentrate Ratio on Growth Performance, Ruminal Fermentation and Blood Metabolites in Housing-feeding Yaks

    PubMed Central

    Chen, G. J.; Song, S. D.; Wang, B. X.; Zhang, Z. F.; Peng, Z. L.; Guo, C. H.; Zhong, J. C.; Wang, Y.

    2015-01-01

    The objective of this study was to determine the effect of forage: concentrate ratio (F:C) on growth performance, ruminal fermentation and blood metabolites of housing-feeding yaks. Thirty-two Maiwa male yaks (initial body weight = 207.99±3.31 kg) were randomly assigned to four dietary treatments (8 yaks per treatment). Experimental diets were: A, B, C, D which contained 70:30, 60:40, 50:50 and 40:60 F:C ratios, respectively. Dry matter intake and average daily gain in yaks fed the C and D diets were greater (p<0.05) than yaks fed the A and B diets. No differences were found in ruminal NH3-N, total volatile fatty acids, acetate, butyrate, valerate, and isovalerate concentrations. The propionate concentration was increased (p<0.05) in the C and D groups compared with the A and B diets. In contrast, the acetate to propionate ratio was decreased and was lowest (p<0.05) in the C group relative to the A and B diets, but was similar with the D group. For blood metabolites, no differences were found in serum concentrations of urea-N, albumin, triglyceride, cholesterol, low density lipoprotein, alanine aminotransferase, and aspartate aminotransferase (p>0.05) among treatments. Treatment C had a higher concentration of total protein and high density lipoprotein (p<0.05) than A and B groups. In addition, there was a trend that the globulin concentration of A group was lower than other treatments (p = 0.079). Results from this study suggest that increasing the level of concentrate from 30% to 50% exerted a positive effect on growth performance, rumen fermentation and blood metabolites in yaks. PMID:26580441

  5. Responses of metabolites in soybean shoot apices to changing atmospheric carbon dioxide concentrations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soybean seedlings were grown in controlled environment chambers with chamber air CO2 partial pressures of 38 (ambient) and 72 (elevated) Pa. Samples were collected 21 to 24 days after sowing by harvesting five or six apices from the main shoot and from lateral branches on a single plant. Metabolit...

  6. Influence of age and caloric restriction on liver glycolytic enzyme activities and metabolite concentrations in mice.

    PubMed

    Hagopian, Kevork; Ramsey, Jon J; Weindruch, Richard

    2003-03-01

    The influence of caloric restriction (CR) from 2 months of age on the activities of liver glycolytic enzymes and metabolite levels was studied in young and old mice. Livers were sampled 48 h after the last scheduled feeding time. Old mice on CR showed significant decreases in the activities of all the enzymes studied, except for aldolase, triosephosphate isomerase and phosphoglycerate mutase, which were unchanged. The metabolites glucose, glucose-6-phosphate, fructose-6-phosphate, pyruvate and lactate were lower while fructose-1,6-bisphosphate, glyceraldehyde-3-phosphate, dihydroxyacetone phosphate, 3-phosphoglycerate and phosphoenolpyruvate were increased in old CR. Young mice on CR also showed reduced enzyme activities, except for aldolase, triosephosphate isomerase and enolase which were unchanged when compared with young controls. The metabolites glucose, glucose-6-phosphate, fructose-6-phosphate and pyruvate were decreased when compared with young controls, while phosphoenolpyruvate was increased. Ketone bodies increased (65%) in old, but not young, CR mice while fructose-2,6-bisphosphate decreased in both young (22%) and old CR (28%) mice. The results indicate that decreased hepatic glucose levels in CR mice are associated with decreased enzyme activities but not a uniform decrease in metabolite levels. Increased ketone body levels indicate increased utilization of non-carbohydrate fuels while decreased fructose-2,6-bisphosphate level suggests its importance in the control of glycolysis in CR. PMID:12581789

  7. Identification, quantification, and relative concentrations of carotenoids and their metabolites in human milk and serum.

    PubMed

    Khachik, F; Spangler, C J; Smith, J C; Canfield, L M; Steck, A; Pfander, H

    1997-05-15

    Thirty-four carotenoids, including 13 geometrical isomers and eight metabolites, in breast milk and serum of three lactating mothers have been separated, identified, quantified, and compared by high-performance liquid chromatography (HPLC)-photodiode array (PDA) detection-mass spectrometry (MS). Among the metabolites were two oxidation products of lycopene and four of lutein/ zeaxanthin. In addition, two metabolites of lutein, formed as a result of dehydration of this dihydroxycarotenoid under acidic conditions similar to those of the stomach, have also been identified in plasma and breast milk. The oxidative metabolites of lycopene with a novel five-membered-ring end group have been identified as epimeric 2,6-cyclolycopene-1,5-diols by comparison of their HPLC-UV/visible-MS profiles with those of fully characterized (1H- and 13C-NMR spectroscopy) synthetic compounds. The HPLC procedures employed also detected vitamin A, two forms of vitamin E (gamma- and alpha-tocopherol), and two non-carotenoid food components, i.e., piperine and caffeine, in serum and breast milk. PMID:9164160

  8. Absolute measurement of cerebral optical coefficients, hemoglobin concentration and oxygen saturation in old and young adults with near-infrared spectroscopy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We present near-infrared spectroscopy measurement of absolute cerebral hemoglobin concentration and saturation in a large sample of 36 healthy elderly (mean age, 85 ± 6 years) and 19 young adults (mean age, 28 ± 4 years). Non-invasive measurements were obtained on the forehead using a commercially a...

  9. Determinants of Arsenic Metabolism: Blood Arsenic Metabolites, Plasma Folate, Cobalamin, and Homocysteine Concentrations in Maternal–Newborn Pairs

    PubMed Central

    Hall, Marni; Gamble, Mary; Slavkovich, Vesna; Liu, Xinhua; Levy, Diane; Cheng, Zhongqi; van Geen, Alexander; Yunus, Mahammad; Rahman, Mahfuzar; Pilsner, J. Richard; Graziano, Joseph

    2007-01-01

    Background In Bangladesh, tens of millions of people have been consuming waterborne arsenic for decades. The extent to which As is transported to the fetus during pregnancy has not been well characterized. Objectives We therefore conducted a study of 101 pregnant women who gave birth in Matlab, Bangladesh. Methods Maternal and cord blood pairs were collected and concentrations of total As were analyzed for 101 pairs, and As metabolites for 30 pairs. Maternal urinary As metabolites and plasma folate, cobalamin, and homocysteine levels in maternal cord pairs were also measured. Household tube well–water As concentrations exceeded the World Health Organization guideline of 10 μg/L in 38% of the cases. Results We observed strong associations between maternal and cord blood concentrations of total As (r = 0.93, p < 0.0001). Maternal and cord blood arsenic metabolites (n = 30) were also strongly correlated: in dimethylarsinate (DMA) (r = 0.94, p < 0.0001), monomethylarsonate (r = 0.80, p < 0.0001), arsenite (As+3) (r = 0.80, p < 0.0001), and arsenate (As+5) (r = 0.89, p < 0.0001). Maternal homocysteine was a strong predictor of %DMA in maternal urine, maternal blood, and cord blood (β = −6.2, p < 0.02; β = −10.9, p < 0.04; and β = −13.7, p < 0.04, respectively). Maternal folate was inversely associated with maternal blood As5+ (β = 0.56, p < 0.05), and maternal cobalamin was inversely associated with cord blood As5+ (β = −1.2, p < 0.01). Conclusions We conclude that exposure to all metabolites of inorganic As occurs in the prenatal period. PMID:17938743

  10. Caffeine metabolites are inhibitors of the nuclear enzyme poly(ADP-ribose)polymerase-1 at physiological concentrations.

    PubMed

    Geraets, Liesbeth; Moonen, Harald J J; Wouters, Emiel F M; Bast, Aalt; Hageman, Geja J

    2006-09-28

    The activity of the nuclear enzyme poly(ADP-ribose)polymerase-1 (E.C.2.4.2.30), which is highly activated by DNA strand breaks, is associated with the pathophysiology of both acute as well as chronic inflammatory diseases. PARP-1 overactivation and the subsequent extensive turnover of its substrate NAD+ put a large demand on mitochondrial ATP-production. Furthermore, due to its reported role in NF-kappaB and AP-1 mediated production of pro-inflammatory cytokines, PARP-1 is considered an interesting target in the treatment of these diseases. In this study the PARP-1 inhibiting capacity of caffeine and several metabolites as well as other (methyl)xanthines was tested using an ELISA-assay with purified human PARP-1. Caffeine itself showed only weak PARP-1 inhibiting activity, whereas the caffeine metabolites 1,7-dimethylxanthine, 3-methylxanthine and 1-methylxanthine, as well as theobromine and theophylline showed significant PARP-1 inhibiting activity. Further evaluation of these compounds in H2O2-treated A549 lung epithelial and RF24 vascular endothelial cells revealed that the decrease in NAD+-levels as well as the formation of the poly(ADP-ribose)polymer was significantly prevented by the major caffeine metabolite 1,7-dimethylxanthine. Furthermore, H2O2-induced necrosis could be prevented by a high dose of 1,7-dimethylxanthine. Finally, antioxidant effects of the methylxanthines could be ruled out with ESR and measurement of the TEAC. Concluding, caffeine metabolites are inhibitors of PARP-1 and the major caffeine metabolite 1,7-dimethylxanthine has significant PARP-1 inhibiting activity in cultured epithelial and endothelial cells at physiological concentrations. This inhibition could have important implications for nutritional treatment of acute and chronic inflammatory pathologies, like prevention of ischemia-reperfusion injury or vascular complications in diabetes. PMID:16870158

  11. The concentration of plasma metabolites varies throughout reproduction and affects offspring number in wild brown trout (Salmo trutta).

    PubMed

    Gauthey, Zoé; Freychet, Marine; Manicki, Aurélie; Herman, Alexandre; Lepais, Olivier; Panserat, Stéphane; Elosegi, Arturo; Tentelier, Cédric; Labonne, Jacques

    2015-06-01

    In wild populations, measuring energy invested in the reproduction and disentangling investment in gametes versus investment in reproductive behavior (such as intrasexual competition or intersexual preference) remain challenging. In this study, we investigated the energy expenditure in brown trout reproductive behavior by using two proxies: variation in weight and variation of plasma metabolites involved in energy production, over the course of reproductive season in a semi natural experimental river. We estimated overall reproductive success using genetic assignment at the end of the reproductive season. Results show that triglycerides and free fatty acid concentrations vary negatively during reproduction, while amino-acids and glucose concentrations remain stable. Decrease in triglyceride and free fatty acid concentrations during reproduction is not related to initial concentration levels or to weight variation. Both metabolite concentration variations and weight variations are correlated to the number of offspring produced, which could indicate that gametic and behavioral reproductive investments substantially contribute to reproductive success in wild brown trout. This study opens a path to further investigate variations in reproductive investment in wild populations. PMID:25666363

  12. Blood vitamin D(3) metabolite concentrations of adult female bearded dragons (Pogona vitticeps) remain stable after ceasing UVb exposure.

    PubMed

    Oonincx, D G A B; van de Wal, M D; Bosch, G; Stumpel, J B G; Heijboer, A C; van Leeuwen, J P T M; Hendriks, W H; Kik, M

    2013-07-01

    Vitamin D deficiency can lead to several health problems collectively called metabolic bone disease (MBD). One commonly kept reptile species prone to develop MBD if managed incorrectly is the bearded dragon (Pogona vitticeps). This study aimed to determine the extent to which adult female bearded dragons fed a diet low in vitamin D can use stored vitamin D and its metabolites to maintain plasma 25(OH)D(3) and 1,25(OH)(2)D(3) concentrations after discontinuing UVb exposure. Blood samples of healthy adult female bearded dragons, exposed to UVb radiation for over 6 months were collected (day 0) after which UVb exposure was discontinued for 83 days and blood was collected. Blood plasma was analysed for concentrations of total Ca, total P, ionized Ca, uric acid, 25(OH)D(3) and 1,25(OH)(2)D(3). There was no significant change in plasma 25(OH)D(3) and 1,25(OH)(2)D(3) concentrations during the study. While total Ca and P in whole blood was found to significantly decrease over time (P < 0.0088 and 0.0016, respectively), values were within the reference range. Plasma ionized Ca tended (P = 0.0525) to decrease during the study. Adult female bearded dragons, previously exposed to UVb, are able to maintain blood vitamin D metabolite concentrations when UVb exposure is discontinued for a period of up to 83 days. PMID:23648288

  13. Tamoxifen dose and serum concentrations of tamoxifen and six of its metabolites in routine clinical outpatient care.

    PubMed

    Jager, N G L; Rosing, H; Schellens, J H M; Linn, S C; Beijnen, J H

    2014-02-01

    A sensitive and selective HPLC-MS/MS assay was used to analyze steady-state serum concentrations of tamoxifen, N-desmethyltamoxifen (E)-endoxifen, (Z)-endoxifen, N-desmethyl-4'-hydroxytamoxifen, 4-hydroxytamoxifen, and 4'-hydroxytamoxifen to support therapeutic drug monitoring (TDM) in patients treated with tamoxifen according to standard of care. When the (Z)-endoxifen serum concentration was below the predefined therapeutic threshold concentration of 5.9 ng/mL, the clinician was advised to increase the tamoxifen dose and to collect another serum sample. Paired serum samples from patients at one dose level at different time points during the tamoxifen treatment were used to assess the intra-patient variability. A total of 251 serum samples were analyzed, obtained from 205 patients. Of these patients, 197 used 20 mg tamoxifen per day and 8 patients used 10 mg/day. There was wide variability in tamoxifen and metabolite concentrations within the dosing groups. The threshold concentration for (Z)-endoxifen was reached in one patient (12 %) in the 10 mg group, in 153 patients (78 %) in the 20 mg group, and in 26 (96 %) of the patients who received a dose increase to 30 or 40 mg/day. Dose increase from 20 to 30 or 40 mg per day resulted in a significant increase in the mean serum concentrations of all analytes (p < 0.001). The mean intra-patient variability was between 10 and 20 % for all analytes. These results support the suitability of TDM for optimizing the tamoxifen treatment. It is shown that tamoxifen dose is related to (Z)-endoxifen exposure and increasing this dose leads to a higher serum concentration of tamoxifen and its metabolites. The low intra-patient variability suggests that only one serum sample is needed for TDM, making this a relatively noninvasive way to optimize the patient's treatment. PMID:24390246

  14. Concentrations of Urinary Phthalate Metabolites Are Associated with Increased Waist Circumference and Insulin Resistance in Adult U.S. Males

    PubMed Central

    Stahlhut, Richard W.; van Wijngaarden, Edwin; Dye, Timothy D.; Cook, Stephen; Swan, Shanna H.

    2007-01-01

    Background Phthalates impair rodent testicular function and have been associated with anti-androgenic effects in humans, including decreased testosterone levels. Low testosterone in adult human males has been associated with increased prevalence of obesity, insulin resistance, and diabetes. Objectives Our objective in this study was to investigate phthalate exposure and its associations with abdominal obesity and insulin resistance. Methods Subjects were adult U.S. male participants in the National Health and Nutrition Examination Survey (NHANES) 1999–2002. We modeled six phthalate metabolites with prevalent exposure and known or suspected antiandrogenic activity as predictors of waist circumference and log-transformed homeostatic model assessment (HOMA; a measure of insulin resistance) using multiple linear regression, adjusted for age, race/ethnicity, fat and total calorie consumption, physical activity level, serum cotinine, and urine creatinine (model 1); and adjusted for model 1 covariates plus measures of renal and hepatic function (model 2). Metabolites were mono-butyl phthalates (MBP), mono-ethyl phthalate (MEP), mono-(2-ethyl)-hexyl phthalate (MEHP), mono-benzyl phthalate (MBzP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP). Results In model 1, four metabolites were associated with increased waist circumference (MBzP, MEHHP, MEOHP, and MEP; p-values ≤ 0.013) and three with increased HOMA (MBP, MBzP, and MEP; p-values ≤ 0.011). When we also adjusted for renal and hepatic function, parameter estimates declined but all significant results remained so except HOMA-MBP. Conclusions In this national cross-section of U.S. men, concentrations of several prevalent phthalate metabolites showed statistically significant correlations with abdominal obesity and insulin resistance. If confirmed by longitudinal studies, our findings would suggest that exposure to these phthalates may contribute to the population

  15. Microbial Successions and Metabolite Changes during Fermentation of Salted Shrimp (Saeu-Jeot) with Different Salt Concentrations

    PubMed Central

    Lee, Se Hee; Jung, Ji Young; Jeon, Che Ok

    2014-01-01

    To investigate the effects of salt concentration on saeu-jeot (salted shrimp) fermentation, four sets of saeu-jeot samples with 20%, 24%, 28%, and 32% salt concentrations were prepared, and the pH, bacterial and archaeal abundances, bacterial communities, and metabolites were monitored during the entire fermentation period. Quantitative PCR showed that Bacteria were much more abundant than Archaea in all saeu-jeot samples, suggesting that bacterial populations play more important roles than archaeal populations even in highly salted samples. Community analysis indicated that Vibrio, Photobacterium, Psychrobacter, Pseudoalteromonas, and Enterovibrio were identified as the initially dominant genera, and the bacterial successions were significantly different depending on the salt concentration. During the early fermentation period, Salinivibrio predominated in the 20% salted samples, whereas Staphylococcus, Halomonas, and Salimicrobium predominated in the 24% salted samples; eventually, Halanaerobium predominated in the 20% and 24% salted samples. The initially dominant genera gradually decreased as the fermentation progressed in the 28% and 32% salted samples, and eventually Salimicrobium became predominant in the 28% salted samples. However, the initially dominant genera still remained until the end of fermentation in the 32% salted samples. Metabolite analysis showed that the amino acid profile and the initial glycerol increase were similar in all saeu-jeot samples regardless of the salt concentration. After 30–80 days of fermentation, the levels of acetate, butyrate, and methylamines in the 20% and 24% salted samples increased with the growth of Halanaerobium, even though the amino acid concentrations steadily increased until approximately 80–107 days of fermentation. This study suggests that a range of 24–28% salt concentration in saeu-jeot fermentation is appropriate for the production of safe and tasty saeu-jeot. PMID:24587230

  16. Microbial successions and metabolite changes during fermentation of salted shrimp (saeu-jeot) with different salt concentrations.

    PubMed

    Lee, Se Hee; Jung, Ji Young; Jeon, Che Ok

    2014-01-01

    To investigate the effects of salt concentration on saeu-jeot (salted shrimp) fermentation, four sets of saeu-jeot samples with 20%, 24%, 28%, and 32% salt concentrations were prepared, and the pH, bacterial and archaeal abundances, bacterial communities, and metabolites were monitored during the entire fermentation period. Quantitative PCR showed that Bacteria were much more abundant than Archaea in all saeu-jeot samples, suggesting that bacterial populations play more important roles than archaeal populations even in highly salted samples. Community analysis indicated that Vibrio, Photobacterium, Psychrobacter, Pseudoalteromonas, and Enterovibrio were identified as the initially dominant genera, and the bacterial successions were significantly different depending on the salt concentration. During the early fermentation period, Salinivibrio predominated in the 20% salted samples, whereas Staphylococcus, Halomonas, and Salimicrobium predominated in the 24% salted samples; eventually, Halanaerobium predominated in the 20% and 24% salted samples. The initially dominant genera gradually decreased as the fermentation progressed in the 28% and 32% salted samples, and eventually Salimicrobium became predominant in the 28% salted samples. However, the initially dominant genera still remained until the end of fermentation in the 32% salted samples. Metabolite analysis showed that the amino acid profile and the initial glycerol increase were similar in all saeu-jeot samples regardless of the salt concentration. After 30-80 days of fermentation, the levels of acetate, butyrate, and methylamines in the 20% and 24% salted samples increased with the growth of Halanaerobium, even though the amino acid concentrations steadily increased until approximately 80-107 days of fermentation. This study suggests that a range of 24-28% salt concentration in saeu-jeot fermentation is appropriate for the production of safe and tasty saeu-jeot. PMID:24587230

  17. Effects of natural environmental conditions on faecal glucocorticoid metabolite concentrations in jaguars (Panthera onca) in Belize.

    PubMed

    Mesa-Cruz, J Bernardo; Brown, Janine L; Kelly, Marcella J

    2014-01-01

    In situ studies that rely on non-invasive faecal hormone monitoring are subject to problems due to potential changes in hormone concentrations in samples exposed to field conditions. In this study, we conducted an environmental validation for measurement of faecal glucocorticoid metabolites (FGMs) in jaguars (Panthera onca). We collected fresh faeces (e.g. no older than 8 h) from jaguars (six males and four females), housed at the Belize Zoo, and exposed them randomly to two environmental conditions: shade and sun. A control (first sub-sample) was immediately frozen, after which sub-samples were frozen daily over a 5 day period in both the dry and wet seasons. We quantified FGMs using a cortisol enzyme immunoassay (EIA) and a corticosterone radioimmunoassay (RIA), both capable of identifying relevant metabolites. Results indicated that FGMs assessed with the cortisol EIA were stable for 5 days during the dry season but for <1 day during the wet season, while FGMs assessed with the corticosterone RIA were stable for 5 days during both the dry and wet seasons. Exposure of jaguar faeces to sun or shade had no effect on FGM concentrations, despite significant differences in weather parameters. Analysis of faecal morphology proved unreliable in identifying faecal age. We conclude that the corticosterone RIA is suitable for assessing FGMs in free-ranging Belizean jaguars by surveying the same transects every 3-4 days in both seasons. The cortisol EIA can be used during the dry season, but there are possible shifts in metabolite immunoactivity in wet conditions. Assessment of adrenal activity in jaguars ranging areas of varying human disturbance is a timely application of this methodology in Belize. PMID:27293660

  18. Effects of natural environmental conditions on faecal glucocorticoid metabolite concentrations in jaguars (Panthera onca) in Belize

    PubMed Central

    Mesa-Cruz, J. Bernardo; Brown, Janine L.; Kelly, Marcella J.

    2014-01-01

    In situ studies that rely on non-invasive faecal hormone monitoring are subject to problems due to potential changes in hormone concentrations in samples exposed to field conditions. In this study, we conducted an environmental validation for measurement of faecal glucocorticoid metabolites (FGMs) in jaguars (Panthera onca). We collected fresh faeces (e.g. no older than 8 h) from jaguars (six males and four females), housed at the Belize Zoo, and exposed them randomly to two environmental conditions: shade and sun. A control (first sub-sample) was immediately frozen, after which sub-samples were frozen daily over a 5 day period in both the dry and wet seasons. We quantified FGMs using a cortisol enzyme immunoassay (EIA) and a corticosterone radioimmunoassay (RIA), both capable of identifying relevant metabolites. Results indicated that FGMs assessed with the cortisol EIA were stable for 5 days during the dry season but for <1 day during the wet season, while FGMs assessed with the corticosterone RIA were stable for 5 days during both the dry and wet seasons. Exposure of jaguar faeces to sun or shade had no effect on FGM concentrations, despite significant differences in weather parameters. Analysis of faecal morphology proved unreliable in identifying faecal age. We conclude that the corticosterone RIA is suitable for assessing FGMs in free-ranging Belizean jaguars by surveying the same transects every 3–4 days in both seasons. The cortisol EIA can be used during the dry season, but there are possible shifts in metabolite immunoactivity in wet conditions. Assessment of adrenal activity in jaguars ranging areas of varying human disturbance is a timely application of this methodology in Belize. PMID:27293660

  19. Urinary metabolite concentrations of organophosphorous pesticides, bisphenol A, and phthalates among pregnant women in Rotterdam, the Netherlands: The Generation R Study

    PubMed Central

    Ye, Xibiao; Pierik, Frank H.; Hauser, Russ; Duty, Susan; Angerer, Jürgen; Park, Melissa M.; Burdorf, Alex; Hofman, Albert; Jaddoe, Vincent W.V.; Mackenbach, Johan P.; Steegers, Eric A.P.; Tiemeier, Henning; Longnecker, Matthew P.

    2008-01-01

    Concern about potential health impacts of low level exposures to organophosphorus (OP) pesticides, bisphenol A (BPA), and phthalates among the general population is increasing. We measured levels of six dialkyl phosphate (DAP) metabolites of OP pesticides, a chlorpyrifos-specific metabolite (3,5,6-trichloro-2-pyridinol, TCPy), BPA, and fourteen phthalate metabolites in urine samples of 100 pregnant women from the Generation R study, the Netherlands. The unadjusted and creatinine-adjusted concentrations were reported, and compared to National Health and Nutrition Examination Survey and other studies. In general, these metabolites were detectable in the urine of the women from the Generation R study and compared with other groups, they had relatively high level exposures to OP pesticides and several phthalates but similar exposure to BPA. The median concentrations of total dimethyl (DM) metabolites was 264.0 nmol/g creatinine (Cr) and of total DAP was 316.0 nmol/g Cr. The median concentration of mono-ethyl phthalate (MEP) was 222.0 µg/g Cr; the median concentrations of mono-isobutyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP) were above 50 µg/g Cr. The median concentrations of the three secondary metabolites of di-2-ethylhexyl phthalate (DEHP) were greater than 20 µg/g Cr. The data indicate that the Generation R study population provides a wide distribution of selected environmental exposures. Reasons for the relatively high levels and possible health effects need investigation. PMID:18774129

  20. Does superficial fat affect metabolite concentrations determined by MR spectroscopy with water referencing?

    PubMed

    Kyathanahally, S P; Fichtner, N D; Adalid, V; Kreis, R

    2015-11-01

    It has recently been reported in this journal that local fat depots produce a sizable frequency-dependent signal attenuation in magnetic resonance spectroscopy (MRS) of the brain. If of a general nature, this effect would question the use of internal reference signals for quantification of MRS and the quantitative use of MRS as a whole. Here, it was attempted to verify this effect and pinpoint the potential causes by acquiring data with various acquisition settings, including two field strengths, two MR scanners from different vendors, different water suppression sequences, RF coils, localization sequences, echo times, and lipid/metabolite phantoms. With all settings tested, the reported effect could not be reproduced, and it is concluded that water referencing and quantitative MRS per se remain valid tools under common acquisition conditions. PMID:26423456

  1. Neurotransmitter and their metabolite concentrations in different areas of the HPRT knockout mouse brain.

    PubMed

    Tschirner, Sarah K; Gutzki, Frank; Schneider, Erich H; Seifert, Roland; Kaever, Volkhard

    2016-06-15

    Lesch-Nyhan syndrome (LNS) is characterized by uric acid overproduction and severe neurobehavioral symptoms, such as recurrent self-mutilative behavior. To learn more about the pathophysiology of the disease, we quantified neurotransmitters and their metabolites in the cerebral hemisphere, cerebellum and the medulla oblongata of HPRT knockout mice, an animal model for LNS, in comparison to the corresponding wild-type. Our analyses included l-glutamate, 4-aminobutanoic acid (GABA), acetylcholine, serotonin, 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine, l-normetanephrine, epinephrine and l-metanephrine and were conducted via high performance liquid chromatography (HPLC) coupled to tandem mass spectrometry (MS/MS). Among these neurotransmitter systems, we did not find any abnormalities in the HPRT knockout mouse brains. On one side, this might indicate that HPRT deficiency most severely affects dopamine signaling, while brain functioning based on other neurotransmitters is more or less spared. On the other hand, our findings may reflect a compensating mechanism for impaired purine salvage that protects the brain in HPRT-deficient mice but not in LNS patients. PMID:27206901

  2. Assessment of Pregnancy Status of Asian Elephants (Elephas maximus) by Measurement of Progestagen and Glucocorticoid and Their Metabolite Concentrations in Serum and Feces, Using Enzyme Immunoassay (EIA)

    PubMed Central

    KAJAYSRI, Jatuporn; NOKKAEW, Weerapun

    2013-01-01

    ABSTRACT The study was to find patterns of progestagen (progesterone and its metabolite) and glucocorticoid and their metabolite concentrations in serum and feces of pregnant Asian elephants (Elephas maximus). The 5 female Asian domestic elephants were naturally mated until pregnancy. After that, blood and feces samples were collected monthly during pregnancy for progestagen, glucocorticoid and their metabolites analysis by enzyme immunoassay (EIA). The results showed the serum progestagen concentration during gestation was 2.11 ± 0.60 to 18.44 ± 2.28 ng/ml. Overall, serum progestagen concentration rose from the 1st month to reach peak in the 11th month, after which it declined to its lowest level in the 22nd month of pregnancy. Fecal progestagen concentration varied from 1.18 ± 0.54 to 3.35 ± 0.45 µg/g during pregnancy. In general, fecal progestagen concentration increased from the 1st month to its highest level in the 12th month. After this, it declined reaching its lowest point in the 22nd month of pregnancy. Glucocorticoid hormones and their metabolite concentrations both in serum and feces fluctuated from low to medium throughout almost the entire pregnancy period and then rapidly increased around the last week before calving. Our study suggests that this profile of progestagen and glucocorticoid hormones and their metabolite concentration levels in serum and feces can be used to assess the pregnancy status of Asian elephants. If serum and fecal progestagen concentrations were found in very low levels and glucocorticoid and their metabolite concentrations were found in very high levels, it was indicated that the cow elephant would calve within 7 days. PMID:24257195

  3. Health benefits of vitamins and secondary metabolites of fruits and vegetables and prospects to increase their concentrations by agronomic approaches.

    PubMed

    Poiroux-Gonord, Florine; Bidel, Luc P R; Fanciullino, Anne-Laure; Gautier, Hélène; Lauri-Lopez, Félicie; Urban, Laurent

    2010-12-01

    Fruits and vegetables (FAVs) are an important part of the human diet and a major source of biologically active substances such as vitamins and secondary metabolites. The consumption of FAVs remains globally insufficient, so it should be encouraged, and it may be useful to propose to consumers FAVs with enhanced concentrations in vitamins and secondary metabolites. There are basically two ways to reach this target: the genetic approach or the environmental approach. This paper provides a comprehensive review of the results that have been obtained so far through purely agronomic approaches and brings them into perspective by comparing them with the achievements of genetic approaches. Although agronomic approaches offer very good perspectives, the existence of variability of responses suggests that the current understanding of the way regulatory and metabolic pathways are controlled needs to be increased. For this purpose, more in-depth study of the interactions existing between factors (light and temperature, for instance, genetic factors × environmental factors), between processes (primary metabolism and ontogeny, for example), and between organs (as there is some evidence that photooxidative stress in leaves affects antioxidant metabolism in fruits) is proposed. PMID:21067179

  4. Cerebrospinal fluid concentrations of hypoxanthine, xanthine, uridine and inosine: high concentrations of the ATP metabolite, hypoxanthine, after hypoxia.

    PubMed Central

    Harkness, R A; Lund, R J

    1983-01-01

    CSF obtained for clinical purposes from newborn, children and adults has been analysed by high pressure liquid chromatography for hypoxanthine, xanthine, inosine, uridine and urate. Large rises in hypoxanthine and to a lesser extent xanthine occur for about 24 h after hypoxia. High concentrations were associated with later evidence of brain damage or subsequent death. Changes in CSF could be independent of those in plasma. Small or negligible rises were associated with localised and generalised infections including bacterial meningitis, fits, or both. Marked and rapid rises were found after death. These estimations may "predict" the extent of brain damage or brain death. PMID:6681617

  5. Phimosis in male dromedary camels: Clinical findings and changes in the hemogram, nitric oxide metabolites, and testosterone concentrations.

    PubMed

    Ali, Ahmed; Derar, Derar; Al-Sobyil, Fahd A; Zeitoun, Moustafa M; Hassanein, Khaled M A; Al-Howas, Abdella

    2016-06-01

    The objectives of this study were to elucidate the clinical findings in male dromedary camels with phimosis (PHI, n = 43) and to investigate the association of this syndrome with the hemogram, nitric oxide metabolites (NOMs), and testosterone concentrations. History and signalment were obtained, and a breeding soundness examination was performed. The penis was exteriorized after administration of a pudendal nerve block. Abnormal masses obtained from the prepuce and penis were prepared for histopathology. Blood samples for hemogram assessment were taken from the diseased animals and from 10 healthy control males. Total nitrates/nitrites were determined in sera using the Griess assay. Testosterone was estimated in sera using ELISA. Phimosis associated with detectable pathologic lesions, mainly including ulcerative posthitis and lacerated glans penis, was present in 34 (79.1%) of the 43 cases (PHI-P), whereas the remaining nine (20.9%) of the 43 cases had no noticeable lesions (PHI-N). The PHI-P group showed higher leukocyte counts (P = 0.001), especially neutrophils (P = 0.0001), and greater NOM concentrations (P = 0.002) than the PHI-N and control groups. However, testosterone concentrations did not differ among groups. In conclusion, PHI in the male dromedary camels was mainly associated with ulcerative posthitis and laceration of the glans penis. The presence of pathologic lesions in cases with PHI was associated with leukocytosis, neutrophilia, and high NOM concentrations. PMID:26879996

  6. Diagnosing pregnancy in free-ranging dugongs using fecal progesterone metabolite concentrations and body morphometrics: a population application.

    PubMed

    Burgess, Elizabeth A; Lanyon, Janet M; Brown, Janine L; Blyde, David; Keeley, Tamara

    2012-05-15

    Assessing reproductive status and monitoring reproductive rates is important in the effective management of vulnerable marine mammal species such as the dugong (Dugong dugon). Knowledge of the reproductive physiology of this species is limited, and determining reproductive parameters (e.g., sexual maturation, pregnancy, and reproductive senescence) has been restricted by a lack of non-lethal methods for assessing reproductive status in free-ranging individuals. The aim of this study was to develop a method to identify pregnant individuals in a wild dugong population. Using an enzymeimmunoassay, we quantified concentrations of fecal progesterone metabolites (fP) in 322 dugongs, including confirmed pregnant females (n=10), presumed non-pregnant adult females (n=25), juvenile females (n=24), subadult females (n=41), adult females of unknown pregnancy state (n=63), and males of all sizes (n=159). External body morphometrics of each dugong were measured, and confirmation of pregnancy in adult female dugongs was determined by ultrasonography or observation of subsequent neonates. Concentrations of fP were different between sexes and reproductive size classes (P<0.001), and ∼30-fold higher in confirmed pregnant dugongs (2017-7760 ng/g) compared to presumed non-pregnant females (30-221 ng/g), juvenile females (29-195 ng/g), and males (24-261 ng/g) (P<0.001). Body measures of maximum and anal girths, and teat length were all greater in confirmed pregnant females than presumed non-pregnant females (all P<0.05). We evaluated a Discriminant Function Analysis (DFA) to provide a model for predicting pregnant and non-pregnant dugongs. Cross-validated results showed that the DFA correctly classified 100% of pregnant and non-pregnant females using fP concentrations, body length, fineness ratio (an index of body shape), and teat length (a female reproductive trait). Using the DFA model, we classified the pregnancy status of all female dugongs and identified a total of 30 females

  7. Monoamine metabolite concentrations in lumbar cerebrospinal fluid of patients with histologically verified Alzheimer's dementia.

    PubMed Central

    Palmer, A M; Sims, N R; Bowen, D M; Neary, D; Palo, J; Wikstrom, J; Davison, A N

    1984-01-01

    Concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxy indoleacetic acid (5-HIAA) and homovanillic acid (HVA) were determined in lumbar cerebrospinal fluid (CSF) from control subjects and patients of both presenile and senile age with histologically verified Alzheimer's dementia. CSF HVA increased with age in control but not in Alzheimer patients. HVA and 5-HIAA in the CSF of presenile Alzheimer patients was lower than that of age matched control subjects. PMID:6204017

  8. Effect of postpartum propylene glycol allocation to over-conditioned Holstein cows on concentrations of milk metabolites.

    PubMed

    Bjerre-Harpøth, Vibeke; Storm, Adam C; Vestergaard, Mogens; Larsen, Mogens; Larsen, Torben

    2016-05-01

    The objective of the study was to investigate the effect of propylene glycol (PG) allocation on concentrations of milk metabolites with potential use as indicators of glucogenic status in high yielding postpartum dairy cows. At time of calving, nine ruminally cannulated Holstein cows were randomly assigned to ruminal dosing of 500 g/d tap water (CON, n = 4) or 500 g/d PG (PPG, n = 5). The PG was given with the morning feeding week 1-4 postpartum (treatment period) and cows were further followed during week 5-8 postpartum (follow-up period). All cows were fed the same postpartum diet. Milk samples were obtained at each milking (3 times/d) in the treatment period, and at morning milking during the follow-up period. Weekly blood samples were obtained from -4 to +8 weeks relative to calving and daily blood samples from -7 until +7 d relative to calving. The main effect of PG allocation was an increased glucogenic status, e.g. visualised by a prompt marked increase in blood fructosamine. During the treatment period, milk concentration of free glucose tended to be greater, whereas milk concentrations of isocitrate and BHBA were lower for PPG compared with CON. It is proposed that the ratio between free glucose and isocitrate in milk may be a potential biomarker for glucogenic status in the vulnerable early postpartum period. We will pursue this issue in the future. PMID:27032705

  9. Pharmacokinetics and endometrial tissue concentrations of enrofloxacin and the metabolite ciprofloxacin after i.v. administration of enrofloxacin to mares.

    PubMed

    Papich, M G; Van Camp, S D; Cole, J A; Whitacre, M D

    2002-10-01

    Enrofloxacin was administered i.v. to five adult mares at a dose of 5 mg/kg. After administration, blood and endometrial biopsy samples were collected at regular intervals for 24 h. The plasma and tissue samples were analyzed for enrofloxacin and the metabolite ciprofloxacin by high-pressure liquid chromatography. In plasma, enrofloxacin had a terminal half-life (t(1/2)), volume of distribution (area method), and systemic clearance of 6.7 +/- 2.9 h, 1.9 +/- 0.4 L/kg, and 3.7 +/- 1.4 mL/kg/min, respectively. Ciprofloxacin had a maximum plasma concentration (Cmax) of 0.28 +/- 0.09 microg/mL. In endometrial tissue, the enrofloxacin Cmax was 1.7 +/- 0.5 microg/g, and the t(1/2) was 7.8 +/- 3.7 h. Ciprofloxacin Cmax in tissues was 0.15 +/- 0.04 microg/g and the t(1/2) was 5.2 +/- 2.0 h. The tissue:plasma enrofloxacin concentration ratios (w/w:w/v) were 0.175 +/- 0.08 and 0.47 +/- 0.06 for Cmax and AUC, respectively. For ciprofloxacin, these values were 0.55 +/- 0.13 and 0.58 +/- 0.31, respectively. We concluded that plasma concentrations achieved after 5 mg/kg i.v. are high enough to meet surrogate markers for antibacterial activity (Cmax:MIC ratio, and AUC:MIC ratio) considered effective for most susceptible gram-negative bacteria. Endometrial tissue concentrations taken from the mares after dosing showed that enrofloxacin and ciprofloxacin both penetrate this tissue adequately after systemic administration and would attain concentrations high enough in the tissue fluids to treat infections of the endometrium caused by susceptible bacteria. PMID:12423224

  10. Concentrations of the urinary pyrethroid metabolite 3-phenoxybenzoic acid in farm worker families in the MICASA study

    SciTech Connect

    Trunnelle, Kelly J.; Bennett, Deborah H.; Ahn, Ki Chang; Schenker, Marc B.; Tancredi, Daniel J.; Gee, Shirley J.; Stoecklin-Marois, Maria T.; Hammock, Bruce D.

    2014-05-01

    Indoor pesticide exposure is a growing concern, particularly from pyrethroids, a commonly used class of pesticides. Pyrethroid concentrations may be especially high in homes of immigrant farm worker families who often live in close proximity to agricultural fields, and are faced with poor housing conditions, causing higher pest infestation and more pesticide use. We investigate exposure of farm worker families to pyrethroids in a study of mothers and children living in Mendota, CA within the population-based Mexican Immigration to California: Agricultural Safety and Acculturation (MICASA) Study. We present pyrethroid exposure based on an ELISA analysis of urinary metabolite 3-phenoxybenzoic acid (3PBA) levels among 105 women and 103 children. The median urinary 3PBA levels (children=2.56 ug/g creatinine, mothers=1.46 ug/g creatinine) were higher than those reported in population based studies for the United States general population, but similar to or lower than studies with known high levels of pyrethroid exposure. A positive association was evident between poor housing conditions and the urinary metabolite levels, showing that poor housing conditions are a contributing factor to the higher levels of 3PBA seen in the urine of these farm worker families. Further research is warranted to fully investigate sources of exposure. - Highlights: • We investigate exposure of farm worker families to pyrethroids. • We present pyrethroid exposure based on an ELISA analysis of urinary 3PBA levels. • 3PBA levels were higher than those reported for the U.S. general population. • Poor housing conditions may be associated with pyrethroid exposure.

  11. Mapping the microvascular and the associated absolute values of oxy-hemoglobin concentration through turbid media via local off-set diffuse optical imaging

    NASA Astrophysics Data System (ADS)

    Chen, Chen; Klämpfl, Florian; Stelzle, Florian; Schmidt, Michael

    2014-11-01

    An imging resolution of micron-scale has not yet been discovered by diffuse optical imaging (DOI), while a superficial response was eliminated. In this work, we report on a new approach of DOI with a local off-set alignment to subvert the common boundary conditions of the modified Beer-Lambert Law (MBLL). It can resolve a superficial target in micron scale under a turbid media. To validate both major breakthroughs, this system was used to recover a subsurface microvascular mimicking structure under an skin equivalent phantom. This microvascular was included with oxy-hemoglobin solution in variant concentrations to distiguish the absolute values of CtRHb and CtHbO2 . Experimental results confirmed the feasibility of recovering the target vascular of 50 µm in diameter, and graded the values of the concentrations of oxy-hemoglobin from 10 g/L to 50 g/L absolutely. Ultimately, this approach could evolve into a non-invasive imaging system to map the microvascular pattern and the associated oximetry under a human skin in-vivo.

  12. Concentration-dependent effects of resveratrol and metabolites on the redox status of human erythrocytes in single-dose studies.

    PubMed

    Pignitter, Marc; Schueller, Katharina; Burkon, Alexander; Knorr, Verena; Esefelder, Laura; Doberer, Daniel; Wolzt, Michael; Somoza, Veronika

    2016-01-01

    Dietary trans-resveratrol (RES) is rapidly metabolized into sulfated and glucuronated conjugates in humans. This study focused on the in vitro determination of the antioxidant capacity of RES and its main physiological metabolites and on its relevance in vivo. In vitro, RES, RES-3-O-sulfate (R3S) and 3-O-glucuronide (R3G) showed antioxidant activities at a concentration of 1mM when compared to Trolox using an assay in which the antioxidant inhibits iron-induced linoleic acid oxidation: 0.87±0.08mM Trolox equivalents (TE) for RES, 0.52±0.01mM TE for R3S and 0.36±0.02mM TE for R3G. At a concentration of 1μM, compounds promoted linoleic acid peroxidation (RES -0.30±0.09mM TE, R3S -0.48±0.05mM TE and R3G -0.57±0.07mM TE). To elucidate whether these effects were reflected in vivo, total antioxidant capacity, reactive oxygen species (ROS), conjugated fatty acid dienes (CD), superoxide dismutase (SOD) and catalase (CAT) activities were determined in human plasma and erythrocytes over 24h, after oral intake of either 0.05g RES as piceid or 5g RES. Oral administration of RES did not show an impact on total antioxidant capacity, ROS or CD. However, enzymatic activities of ROS scavenging SOD and CAT were significantly lower after high-dose compared to low-dose administration of RES (P<.03 and P<.01). In conclusion, in healthy subjects, neither 0.05g nor 5g RES changed blood oxidative state, although our in vitro data point to a prooxidative activity of low concentrations of RES and its metabolites, which could be important in vivo for individuals with compromised antioxidant defense capacity. PMID:26454510

  13. Effect of bovine ABCG2 Y581S polymorphism on concentrations in milk of enrofloxacin and its active metabolite ciprofloxacin.

    PubMed

    Otero, J A; García-Mateos, D; de la Fuente, A; Prieto, J G; Álvarez, A I; Merino, G

    2016-07-01

    The ATP-binding cassette transporter G2 (ABCG2) is involved in the secretion of several drugs into milk. The bovine Y581S ABCG2 polymorphism increases the secretion into milk of the fluoroquinolone danofloxacin in Holstein cows. Danofloxacin and enrofloxacin are the fluoroquinolones most widely used in veterinary medicine. Both enrofloxacin (ENRO) and its active metabolite ciprofloxacin (CIPRO) reach milk at relatively high concentrations. The aim of this work was to study the effect of the bovine Y581S ABCG2 polymorphism on in vitro transport as well as on concentrations in plasma and in milk of ENRO and CIPRO. Experiments using cells overexpressing bovine ABCG2 showed the effects of ABCG2 on the transport of CIPRO, demonstrating more efficient in vitro transport of this antimicrobial by the S581 variant as compared with the Y581 variant. Animal studies administering 2.5mg/kg of ENRO subcutaneously to Y/Y 581 and Y/S 581 cows revealed that concentrations in plasma of ENRO and CIPRO were significantly lower in Y/S animals. Regardless of the genotype, the antimicrobial profile in milk after the administration of ENRO was predominantly of CIPRO. With respect to the genotype effects on the amounts of drugs present in milk, AUC0-24 values were more than 1.2 times higher in Y/S cows for ENRO and 2.2 times for CIPRO, indicating a greater capacity of Y581S to transfer these drugs into milk. These results emphasize the clinical relevance of this polymorphism as a factor affecting the concentrations in plasma and in milk of drugs of importance in veterinary medicine. PMID:27157572

  14. Relationships between metabolite and IGF1 concentrations with fertility and production outcomes following left abomasal displacement.

    PubMed

    Lyons, N A; Cooke, J S; Wilson, S; van Winden, S C; Gordon, P J; Wathes, D C

    2014-06-28

    Left displacement of the abomasum (LDA) is an important periparturient disorder of dairy cows. This study evaluated differences in metabolic parameters between case-control pairs of cows (n=67) from 24 farms, and related these to outcomes in fertility and production. Cows with an assisted delivery were ×3 more likely to develop LDA, and affected cows tended to have had a longer dry period. At recruitment, cows with LDA tended to be in lower body condition accompanied by significantly higher circulating concentrations of β-hydroxybutyrate (BHB), non-esterified fatty acid (NEFA) and glucose and lower IGF1. Overall culling rate for all cows in the subsequent lactation was 22.5 per cent. Cows with LDA were not at increased odds of being culled but they produced, on average, 2272 l less milk and tended to have longer intervals to conception. Considering all cows irrespective of LDA status, the mean IGF1 level at recruitment was the only measured parameter associated with subsequent risk of culling (culled 11.7 ng/ml, not culled 23.5 ng/ml; P=0.005). Our findings support previous work indicating that poor insulin sensitivity through an uncoupling of the somatotrophic axis may be an important factor associated with LDA. Improved nutritional management of dry cows should reduce the incidence of both LDA and culling. PMID:24696444

  15. Effect of digestible methionine + cystine concentration on performance, egg quality and blood metabolites in laying hens.

    PubMed

    Akbari Moghaddam Kakhki, R; Golian, A; Zarghi, H

    2016-06-01

    The estimation of sulphur amino acid requirement is a vital key to providing appropriate nutrition in poultry. The estimation of amino acid requirement depends on what production parameter is taken into consideration for optimisation. A complete randomised block design was performed with 5 treatments and 6 replicates of 8 Hy-line layers (W-36) each from 32 to 44 weeks of age. The blocks were made to have a replicate of each treatment. The dietary treatments were consisted of 5 concentrations of digestible sulphur amino acid (DSAA) at 5.1, 5.6, 6.1, 6.6 and 7.1 (g/kg). Egg production, egg mass, egg weight and feed conversion ratio (FCR) were significantly affected by an increase in DSAA intake. However, feed intake, egg component yield, Haugh unit, specific gravity, eggshell thickness, egg protein and dry matter (DM) were not altered by DSAA intake. A significant increment in plasma high-density lipoprotein was concomitant with a reduction in low-density lipoprotein when DSAA intake was increased. However, triglyceride, cholesterol, uric acid and total protein in plasma were not affected by DSAA intake. The DSAA requirements estimated by the linear broken-line model to optimise egg production, egg mass, egg weight and FCR were 678, 673, 641 and 656 mg/bird.d in the whole experimental period, respectively. The DSAA requirement estimated by the quadratic broken-line model to optimise egg production, egg mass, egg weight and FCR were 4.71%, 7.87%, 8.73% and 7.62% higher than those estimated by linear broken-line fit model in the whole experimental period, respectively. PMID:27074313

  16. Absolute concentration of free volume-type defects in ultrafine-grained Fe prepared by high-pressure torsion

    PubMed Central

    Oberdorfer, Bernd; Lorenzoni, Bernd; Unger, Katrin; Sprengel, Wolfgang; Zehetbauer, Michael; Pippan, Reinhard; Würschum, Roland

    2010-01-01

    A maximum excess volume ΔV/V ≈ 1.9 × 10−3 in ultrafine-grained Fe prepared by high-pressure torsion is determined by measurements of the irreversible length change upon annealing employing a high-resolution differential dilatometer. Since dislocations and equilibrium-type grain boundaries cannot fully account for the observed released excess volume, the present study yields evidence for a high concentration of free volume-type defects inherent to nanophase materials, which is considered to be the main source of their particular properties, such as strongly enhanced diffusivities. PMID:21785571

  17. Pharmacokinetics of Cocaine and Metabolites in Human Oral Fluid and Correlation with Plasma Concentrations following Controlled Administration

    PubMed Central

    Scheidweiler, Karl B.; Kolbrich Spargo, Erin A.; Kelly, Tamsin L.; Cone, Edward J.; Barnes, Allan J.; Huestis, Marilyn A.

    2011-01-01

    Oral fluid is an attractive alternative matrix for drug testing, with a non-invasive and directly observed collection, but there are few controlled cocaine administration studies to guide interpretation. Materials and Methods While residing on a closed research unit for up to 10 weeks under constant medical supervision, 19 participants were administered 75 mg/70 kg subcutaneous cocaine and 14 received 150mg/70 kg. The disposition of cocaine, benzoylecgonine (BE) and ecgonine methyl ester (EME) into oral fluid was determined by gas chromatography-mass spectrometry for 0.08–48h after administration. Results In oral fluid collected by citric acid candy stimulated expectoration, cocaine first appeared in oral fluid 0.08–0.32h after dosing and was rapidly eliminated with half-lives of 1.1–3.8h. BE and EME were first detected 0.08–1.0h after dosing, with longer half-lives of 3.4–13.8 (BE) and 2.4–15.5h (EME) (p<0.05). Oral fluid and plasma concentrations were significantly correlated for cocaine, BE and EME (p<0.0001). There were no significant differences (p>0.05) in first and last detection times with the 8 μg/L cutoff proposed by the Substance Abuse and Mental Health Services Administration or the 10 μg/L cutoff from the European initiative, Driving Under the Influence of Drugs, Alcohol and Medicines. Metabolite:cocaine ratios increased after cocaine administration, potentially helpful for interpreting time of last use. Comparison of oral fluid collection via citric acid candy stimulated expectoration, citric acid treated Salivette® and neutral cotton Salivette® devices did not reveal significant differences between devices for areas under the curve for cocaine, BE or EME (p>0.05). Discussion and Conclusion These results provide additional evidence for interpreting cocaine and metabolite concentrations in oral fluid and oral fluid’s usefulness as an alternative matrix for drug testing. PMID:20814350

  18. High-throughput assay for simultaneous quantification of the plasma concentrations of morphine, fentanyl, midazolam and their major metabolites using automated SPE coupled to LC-MS/MS.

    PubMed

    Ghassabian, Sussan; Moosavi, Seyed Mojtaba; Valero, Yarmarly Guerra; Shekar, Kiran; Fraser, John F; Smith, Maree T

    2012-08-15

    A rapid LC-MS/MS assay method for simultaneous quantification of morphine, fentanyl, midazolam and their major metabolites: morphine-3-β-D-glucuronide (M3G), morphine-6-β-D-glucuronide (M6G), norfentanyl, 1'-hydroxymidazolam (1-OH-MDZ) and 4-hydroxymidazolam (4-OH-MDZ) in samples of human plasma has been developed and validated. Robotic on-line solid phase extraction (SPE) instrumentation was used to elute the eight analytes of interest from polymeric SPE cartridges to which had been added aliquots (150 μL) of human plasma and aliquots (150 μL) of a mixture of two internal standards, viz. morphine-d3 (200 ng/mL) and 1'-hydroxymidazolam-d5 (50 ng/mL) in 50 mM ammonium acetate buffer (pH 9.25). Cartridges were washed using 10% methanol in ammonium acetate buffer, pH 9.25 (1 mL, 2 mL/min) before elution with mobile phase comprising 0.1% formic acid in water (A) and acetonitrile (B) with a flow rate of 0.6 mL/min using an 11.5 min run time. The analytes were separated on a C18 X-Terra® analytical column. The linear concentration ranges were 0.5-100 ng/mL for fentanyl, norfentanyl and midazolam; 1-200 ng/mL for 4-hydroxymidazolam, 2.5-500 ng/mL for 1'-hydroxymidazolam and 3.5-700 ng/mL for morphine, M3G, and M6G. The method showed acceptable within-run and between-run precision (relative standard deviation (RSD) and accuracy <20%) for quality control (QC) samples spiked at concentrations of 80% and 50% of the ULOQ, 3 times higher than the LLOQ, and also at the LLOQ. Furthermore, analytes were stable in samples (after mixing with internal standard) for at least 48 h in the autosampler (except for 4-hydroxymidazolam which decreased by 22% after 24 h), 5 h at room temperature and after three cycles of freeze and thaw. No autosampler carry-over was observed and the absolute recovery (the area ratio of analyte in plasma relative to that in ammonium acetate buffer 50 mM, pH 9.25) was in the range 40% (midazolam) to 110% (morphine). The assay was applied successfully to

  19. A PILOT STUDY OF GLOBAL POSITION SYSTEM/GEOGRAPHICAL INFORMATION SYSTEM MEASUREMENT OF RESIDENTIAL PROXIMITY TO AGRICULTURE FIELDS AND URINARY ORGANOPHOSPHATE METABOLITE CONCENTRATIONS IN TODDLERS

    EPA Science Inventory

    A pilot study of global position system/geographical information system measurement of residential proximity to agricultural fields and urinary organophosphate metabolite concentrations in toddlers

    Michael O. Royster1, Elizabeth D. Hilborn1, Dana Barr2, Cara L. Carty1, Sco...

  20. Soy isoflavone metabolism in cats compared with other species: urinary metabolite concentrations and glucuronidation by liver microsomes.

    PubMed

    Redmon, Joanna M; Shrestha, Binu; Cerundolo, Rosario; Court, Michael H

    2016-01-01

    1. Soybean is a common source of protein in many pet foods. Slow glucuronidation of soy-derived isoflavones in cats has been hypothesized to result in accumulation with adverse health consequences. Here, we evaluated species' differences in soy isoflavone glucuronidation using urine samples from cats and dogs fed a soy-based diet and liver microsomes from cats compared with microsomes from 12 other species. 2. Significant concentrations of conjugated (but not unconjugated) genistein, daidzein and glycitein, and the gut microbiome metabolites, dihydrogenistein and dihydrodaidzein, were found in cat and dog urine samples. Substantial amounts of conjugated equol were also found in cat urine but not in dog urine. 3. β-Glucuronidase treatment showed that all these compounds were significantly glucuronidated in dog urine while only daidzein (11%) and glycitein (37%) showed any glucuronidation in cat urine suggesting that alternate metabolic pathways including sulfation predominate in cats. 4. Glucuronidation rates of genistein, daidzein and equol by cat livers were consistently ranked within the lowest 3 out of 13 species' livers evaluated. Ferret and mongoose livers were also ranked in the lowest four species. 5. Our results demonstrate that glucuronidation is a minor pathway for soy isoflavone metabolism in cats compared with most other species. PMID:26366946

  1. The influence of the corpus luteum on metabolites composition of follicular fluid from different sized follicles and their relationship to serum concentrations in dairy cows.

    PubMed

    Shabankareh, Hamed Karami; Kor, Nasroallah Moradi; Hajarian, Hadi

    2013-08-01

    The presence of corpus luteum may have a local effect on metabolite composition of follicular fluid (FF) and could indirectly influence follicular development and oocyte quality. The purpose of this study was to examine the influence of the corpus luteum on metabolite composition of follicular fluid (FF), harvested from different-sized follicles and the relationship between metabolite composition of FF to blood serum in dairy cows. Ovaries and blood samples were collected from 30 female adult Holstein Friesian cows, 4-7 years old, with clinically normal reproductive tracts. The animals were in the diestrus stage and selected post mortem. The ovaries collected were classified based on the presence and absence of corpus luteum (CL(+/-)). Visible follicles on the surface of the ovaries were classified into (i) small (3-5mm), (ii) medium (6-9 mm) and (iii) large (10-20mm) based on their diameter. Follicular fluid was aspirated from follicles with different sizes in CL(+) and CL(-) ovaries. Blood and FF samples were analyzed for various biochemical constituents including glucose, cholesterol, triglyceride, total protein, albumin and globulin. The results showed that serum concentration of glucose, cholesterol and triglyceride was significantly different (p≤0.05) in FF from follicles of different size categories. Differences between various follicle size categories in CL(-) ovaries were only significant for concentrations of glucose, cholesterol and triglyceride. FF concentration of glucose and cholesterol in the same follicle size categories in CL(+) ovaries was significantly lower than that of CL(-) ovaries. These results indicate that levels of the biochemical metabolites in serum and FF differ significantly. In addition, FF concentrations of biochemical metabolites were related to follicular size and to the presence or absence of corpus luteum. PMID:23890803

  2. A general method for the calculation of absolute trace gas concentrations in air and breath from selected ion flow tube mass spectrometry data

    NASA Astrophysics Data System (ADS)

    Spanel, Patrik; Dryahina, Kseniya; Smith, David

    2006-03-01

    A complete description is presented of a numerical method that allows the calculation, in real time, of absolute concentrations of trace gases, including volatile organic compounds and water vapour, from selected ion flow tube mass spectrometry, SIFT-MS, data. No assumptions are made concerning the SIFT-MS instrument size or its configuration and thus the calculation can be applied to the currently available, relatively large instruments and the anticipated new generation of smaller SIFT-MS instruments. This numerical method clearly distinguishes those parameters that are obviously specific to a particular instrument, including flow tube geometry, degree of mass discrimination in the analytical mass spectrometer and flow tube reaction time, from general fundamental processes, in particular the differential diffusive loss of ions along the flow tube that is dependent on the properties of those ions involved in the determination of the concentrations of particular trace gases. The essential reaction and transport kinetics are outlined, which describe the formation and loss of the product ions formed in the chemical ionisation of the trace gases by the precursor ions. A generalised calculation of the required ionic diffusion coefficients is introduced with options either for their accurate determination from the molecular geometry of ions or for less accurate but simpler estimates obtained using just the ionic mass. Based on the above ideas, a straightforward calculation sequence is shown to determine trace gas concentrations by SIFT-MS, and its utility demonstrated by an example of the analysis of acetone in exhaled breath.

  3. Absolute Zero

    NASA Astrophysics Data System (ADS)

    Donnelly, Russell J.; Sheibley, D.; Belloni, M.; Stamper-Kurn, D.; Vinen, W. F.

    2006-12-01

    Absolute Zero is a two hour PBS special attempting to bring to the general public some of the advances made in 400 years of thermodynamics. It is based on the book “Absolute Zero and the Conquest of Cold” by Tom Shachtman. Absolute Zero will call long-overdue attention to the remarkable strides that have been made in low-temperature physics, a field that has produced 27 Nobel Prizes. It will explore the ongoing interplay between science and technology through historical examples including refrigerators, ice machines, frozen foods, liquid oxygen and nitrogen as well as much colder fluids such as liquid hydrogen and liquid helium. A website has been established to promote the series: www.absolutezerocampaign.org. It contains information on the series, aimed primarily at students at the middle school level. There is a wealth of material here and we hope interested teachers will draw their student’s attention to this website and its substantial contents, which have been carefully vetted for accuracy.

  4. Use of 1 alpha-hydroxyvitamin D3 to prevent bovine parturient paresis. VI. Concentrations of vitamin D metabolites and vitamin D3 equivalence in milk.

    PubMed

    Bar, A; Sachs, M; Perlman, R

    1986-11-01

    Concentration of vitamin D metabolites was determined in the milk of control and 1 alpha-hydroxyvitamin D3-injected (700 micrograms) cows that calved 36 to 43 h after treatment. Milk samples were taken 60 h after calving. Concentrations of vitamin D, 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D in milk of the control cows were 372 +/- 24, 264 +/- 68, 68 +/- 26, and 21 +/- 3 ng/L, respectively. Concentrations of vitamin D metabolites in the milk of the treated cows did not differ significantly from those of controls. Concentration of 1 alpha-hydroxyvitamin D3 in milk of treated cows was less than 20 ng/L. In a second experiment, cows were injected twice, at 72-h intervals, with 350 micrograms 1 alpha-hydroxyvitamin D3. Milk was taken 60 h after parturition from cows that calved 37 to 60 h after the second injection. The vitamin D3 equivalence of the milk was 40 +/- 3 IU/L. Results indicate that injection of 700 micrograms 1 alpha-hydroxyvitamin D3 did not affect the concentration of vitamin D metabolites or the vitamin D3 equivalence of milk taken 60 h after calving. PMID:3027149

  5. Corticosterone metabolite concentrations in greater sage-grouse are positively associated with the presence of cattle grazing

    USGS Publications Warehouse

    Jankowski, M.D.; Russell, R.E.; Franson, J. Christian; Dusek, R.J.; Hines, M.K.; Gregg, M.; Hofmeister, Erik K.

    2014-01-01

    The sagebrush biome in the western United States is home to the imperiled greater sage-grouse (Centrocercus urophasianus) and encompasses rangelands used for cattle production. Cattle grazing activities have been implicated in the range-wide decline of the sage-grouse, but no studies have investigated the relationship between the physiological condition of sage-grouse and the presence of grazing cattle. We sampled 329 sage-grouse across four sites (two grazed and two ungrazed) encompassing 13 600 km2 during the spring and late summer–early autumn of 2005 to evaluate whether demographic factors, breeding status, plasma protein levels, and residence in a cattle-grazed habitat were associated with the stress hormone corticosterone. Corticosterone was measured in feces as immunoreactive corticosterone metabolites (ICM). Males captured during the lekking season exhibited higher ICM levels than all others. Prenesting female sage-grouse captured in a grazed site had higher ICM levels than those in ungrazed sites and prenesting female plasma protein levels were negatively correlated with ICM concentrations. With the use of a small-scale spatial model, we identified a positive correlation between cattle pat count and sage-grouse ICM levels. Our model indicated that ICM levels increased by 2.60 ng · g−1 dry feces for every increase in the number of cow pats found in the vicinity. Management practices will benefit from future research regarding the consistency and mechanism(s) responsible for this association and, importantly, how ICM levels and demographic rates are related in this species of conservation concern.

  6. Quantitative measurements of one-dimensional OH absolute concentration profiles in a methane/air flat flame by bi-directional laser-induced fluorescence

    NASA Astrophysics Data System (ADS)

    Yu, Xin; Yang, Zhen; Peng, Jiang-Bo; Zhang, Lei; Ma, Yu-Fei; Yang, Chao-Bo; Li, Xiao-Hui; Sun, Rui

    2015-11-01

    The one-dimensional (1D) spatial distributions of OH absolute concentration in methane/air laminar premixed flat flame under different equivalence ratios at atmospheric pressure are investigated by using bi-directional laser-induced fluorescence (LIF) detection scheme combined with the direct absorption spectroscopy. The effective peak absorption cross section and the average temperature at a height of 2 mm above the burner are obtained by exciting absorption on the Q1(8) rotational line in the A2Σ+ (ʋ‧ = 0) ← X2Π (ʋ″ = 0) at 309.240 nm. The measured values are 1.86×10-15 cm2 and 1719 K, respectively. Spatial filtering and frequency filtering methods of reducing noise are used to deal with the experimental data, and the smoothing effects are also compared using the two methods. The spatial distribution regularities of OH concentration are obtained with the equivalence ratios ranging from 0.8 to 1.3. The spatial resolution of the measured result is 84 μm. Finally, a comparison is made between the experimental result of this paper and other relevant study results. Project supported by the National Key Scientific Instrument and Equipment Development Projects of China (Grant No. 2012YQ040164), the National Natural Science Foundation of China (Grant Nos. 61275127 and 91441130), the China Postdoctoral Science Foundation (Grant No. 2014M560262), and the Postdoctoral Fellowship in Heilongjiang Province, China (Grant No. LBH-Z14074).

  7. Absolute Summ

    NASA Astrophysics Data System (ADS)

    Phillips, Alfred, Jr.

    Summ means the entirety of the multiverse. It seems clear, from the inflation theories of A. Guth and others, that the creation of many universes is plausible. We argue that Absolute cosmological ideas, not unlike those of I. Newton, may be consistent with dynamic multiverse creations. As suggested in W. Heisenberg's uncertainty principle, and with the Anthropic Principle defended by S. Hawking, et al., human consciousness, buttressed by findings of neuroscience, may have to be considered in our models. Predictability, as A. Einstein realized with Invariants and General Relativity, may be required for new ideas to be part of physics. We present here a two postulate model geared to an Absolute Summ. The seedbed of this work is part of Akhnaton's philosophy (see S. Freud, Moses and Monotheism). Most important, however, is that the structure of human consciousness, manifest in Kenya's Rift Valley 200,000 years ago as Homo sapiens, who were the culmination of the six million year co-creation process of Hominins and Nature in Africa, allows us to do the physics that we do. .

  8. Effect of prepartal and postpartal dietary fat level on performance and plasma concentration of metabolites in transition dairy cows.

    PubMed

    Karimian, M; Khorvash, M; Forouzmand, M A; Alikhani, M; Rahmani, H R; Ghaffari, M H; Petit, H V

    2015-01-01

    The objective of this study was to determine the effects of 2 levels of dietary fat (low and high) offered during the prepartal and postpartal periods on dry matter intake (DMI), plasma concentration of metabolites, and milk yield and composition. Twenty-four Holstein dry cows were assigned on d 21 relative to expected parturition date to 1 of 4 treatments in a 2×2 factorial arrangement of 2 levels of fat fed during the prepartal period and 2 levels of fat fed during the postpartal period: prepartal low fat and postpartal low fat (LF-LF), prepartal low fat and postpartal high fat (LF-HF), prepartal high fat and postpartal low fat (HF-LF), or prepartal high fat and postpartal high fat (HF-HF). Prepartal and postpartal LF diets contained no fat supplement. Prepartal HF diets contained 1.60% calcium salts of soybean oil. The proportion of calcium salts of soybean oil was increased to 1.70% of DM for the first 21 d of lactation and to 2.27% of DM from d 21 to 56 of lactation in the HF diet. Diets were fed for ad libitum intake from d 21 before calving until d 56 of gestation. Prepartal DMI was lower for cows fed the HF diet compared with those fed the LF diet (12.6 vs. 16.2kg/d). Postpartum, cows fed the HF-HF and HF-LF diets had, respectively, the lowest and highest DMI, although no significant differences existed between HF-LF and LF-LF. Net energy intake was higher for cows fed the postpartal HF diets compared with those fed the LF diets. Prepartal fat level had no effect on net energy intake. Cows offered the prepartal HF diet had higher milk yield when offered the postpartal LF diet compared with those offered the postpartal HF diet and no effect of the postpartal fat level was detected when cows were fed the prepartal LF diet. Milk composition was similar among treatments. Plasma cholesterol concentration postpartum was higher for cows fed the prepartal LF diet than for those fed the prepartal HF diet (5.16 vs. 3.74mmol/L) and postpartal fat level had no effect

  9. Effect of heat stress on the serum concentrations of free amino acids and some of their metabolites in growing pigs.

    PubMed

    Morales, A; Cota, S E M; Ibarra, N O; Arce, N; Htoo, J K; Cervantes, M

    2016-07-01

    Exposure to heat stress (HS) may affect the intestinal epithelia of pigs, resulting in impaired digestive and absorptive capacity. The serum concentration (SC) of free AA in pigs can be used as indicators of their availability. This study was conducted with 12 crossbred (Landrace × Hampshire × Duroc) pigs (29.0 ± 2.8 kg initial BW) distributed into 2 groups to analyze the SC of free AA and some AA metabolites in pigs exposed to HS conditions. The treatments were pigs housed under natural HS conditions in a room with no ambient temperature control (23.6 to 37.6°C, HS) and pigs housed at thermoneutral conditions (24 ± 2°C), feed restricted to a level similar to that of their HS counterparts. All pigs received a wheat-soybean meal diet. Blood samples were collected at both the absorptive (2.5 h after a meal) and postabsorptive (10.0 h after a meal) phase. At the absorptive phase, the SC of free Arg, Leu, Lys, Phe, Thr, and Trp were lower ( < 0.05) and the SC of His, Val, Ala, Pro, Ser, and Tyr tended to be lower ( < 0.10) in HS pigs. At the postabsorptive phase, the SC of free Arg, His, Met, Asn, Gln, and Tyr were higher ( < 0.05) but the SC of Ala was lower ( < 0.01) and the SC of Pro tended to be lower ( < 0.10) in HS pigs. The absorptive SC of carnosine, ornithine (Orn), and Tau were lower ( < 0.05) and of citrulline (Cit), cystathionine, and urea tended to be lower ( < 0.10) in HS pigs. The postabsorptive SC of 3-methyl-His, homo-Cys, OH-Lys, and OH-Pro increased ( = 0.05) and of Cit tended to increase ( = 0.10) but that of carnosine and sarcosine ( < 0.05) decreased in HS pigs. The results of this study show a marked and differential effect of HS on the SC of AA. These data indicate that HS negatively affects the digestive and absorptive capacity of pigs and that the metabolism of some AA is modified in pigs to counteract the negative effects of the HS. PMID:27482670

  10. (31)P-MRS of healthy human brain: ATP synthesis, metabolite concentrations, pH, and T1 relaxation times.

    PubMed

    Ren, Jimin; Sherry, A Dean; Malloy, Craig R

    2015-11-01

    The conventional method for measuring brain ATP synthesis is (31)P saturation transfer (ST), a technique typically dependent on prolonged pre-saturation with γ-ATP. In this study, ATP synthesis rate in resting human brain is evaluated using EBIT (exchange kinetics by band inversion transfer), a technique based on slow recovery of γ-ATP magnetization in the absence of B1 field following co-inversion of PCr and ATP resonances with a short adiabatic pulse. The unidirectional rate constant for the Pi → γ-ATP reaction is 0.21 ± 0.04 s(-1) and the ATP synthesis rate is 9.9 ± 2.1 mmol min(-1)  kg(-1) in human brain (n = 12 subjects), consistent with the results by ST. Therefore, EBIT could be a useful alternative to ST in studying brain energy metabolism in normal physiology and under pathological conditions. In addition to ATP synthesis, all detectable (31)P signals are analyzed to determine the brain concentration of phosphorus metabolites, including UDPG at around 10 ppm, a previously reported resonance in liver tissues and now confirmed in human brain. Inversion recovery measurements indicate that UDPG, like its diphosphate analogue NAD, has apparent T1 shorter than that of monophosphates (Pi, PMEs, and PDEs) but longer than that of triphosphate ATP, highlighting the significance of the (31)P-(31)P dipolar mechanism in T1 relaxation of polyphosphates. Another interesting finding is the observation of approximately 40% shorter T1 for intracellular Pi relative to extracellular Pi, attributed to the modulation by the intracellular phosphoryl exchange reaction Pi ↔ γ-ATP. The sufficiently separated intra- and extracellular Pi signals also permit the distinction of pH between intra- and extracellular environments (pH 7.0 versus pH 7.4). In summary, quantitative (31)P MRS in combination with ATP synthesis, pH, and T1 relaxation measurements may offer a promising tool to detect biochemical alterations at early stages of brain dysfunctions and diseases

  11. Differences in the metabolite profiles of spinach (Spinacia oleracea L.) leaf in different concentrations of nitrate in the culture solution.

    PubMed

    Okazaki, Keiki; Oka, Norikuni; Shinano, Takuro; Osaki, Mitsuru; Takebe, Masako

    2008-02-01

    The nitrogen (N) status of a plant determines the composition of its major components (amino acids, proteins, carbohydrates and organic acids) and, directly or indirectly, affects the quality of agricultural products in terms of their calorific value and taste. Although these effects are guided by changes in metabolic pathways, no overall metabolic analysis has previously been conducted to demonstrate such effects. Here, metabolite profiling using gas chromatography-mass spectrometry (GC-MS) was used to evaluate the effect of N levels on spinach tissue, comparing two cultivars that differed in their ability to use N. Wide variation in N content was observed without any distinct inhibition of growth in either cultivar. Principal component analysis (PCA) and self-organizing mapping (SOM) were undertaken to describe changes in the metabolites of mature spinach leaves. In PCA, the first component accounted for 44.5% of the total variance, the scores of which was positively correlated with the plant's N content, and a close relationship between metabolite profiles and N status was observed. Both PCA and SOM revealed that metabolites could be broadly divided into two types, correlating either positively or negatively with plant N content. The simple and co-coordinated metabolic stream, containing both general and spinach-specific aspects of plant N content, will be useful in future research on such topics as the detection of environmental effects on spinach through comprehensive metabolic profiling. PMID:18089581

  12. Under proper control, oxidation of proteins with known chemical structure provides an accurate and absolute method for the determination of their molar concentration.

    PubMed

    Guermant, C; Azarkan, M; Smolders, N; Baeyens-Volant, D; Nijs, M; Paul, C; Brygier, J; Vincentelli, J; Looze, Y

    2000-01-01

    Oxidation at 120 degrees C of inorganic and organic (including amino acids, di- and tripeptides) model compounds by K(2)Cr(2)O(7) in the presence of H(2)SO(4) (mass fraction: 0.572), Ag(2)SO(4) (catalyst), and HgSO(4) results in the quantitative conversion of their C-atoms into CO(2) within 24 h or less. Under these stressed, well-defined conditions, the S-atoms present in cysteine and cystine residues are oxidized into SO(3) while, interestingly, the oxidation states of all the other (including the N-) atoms normally present in a protein do remain quite unchanged. When the chemical structure of a given protein is available, the total number of electrons the protein is able to transfer to K(2)Cr(2)O(7) and thereof, the total number of moles of Cr(3+) ions which the protein is able to generate upon oxidation can be accurately calculated. In such cases, unknown protein molar concentrations can thus be determined through straightforward spectrophotometric measurements of Cr(3+) concentrations. The values of molar absorption coefficients for several well-characterized proteins have been redetermined on this basis and observed to be in excellent agreement with the most precise values reported in the literature, which fully assesses the validity of the method. When applied to highly purified proteins of known chemical structure (more generally of known atomic composition), this method is absolute and accurate (+/-1%). Furthermore, it is well adapted to series measurements since available commercial kits for chemical oxygen demand (COD) measurements can readily be adapted to work under the experimental conditions recommended here for the protein assay. PMID:10610688

  13. Growth of Pseudomonas sp. TX1 on a wide range of octylphenol polyethoxylate concentrations and the formation of dicarboxylated metabolites.

    PubMed

    Lin, Yi-Wen; Guo, Gia-Luen; Hsieh, Hsiao-Cheng; Huang, Shir-Ly

    2010-04-01

    Pseudomonas sp. TX1, is able to use octylphenol polyethoxylates (OPEO(n), or Triton X-100; average n = 9.5) as a sole carbon source. It can grow on 0.05-20% of OPEO(n) with a specific growth rate of 0.34-0.44 h(-1). High-performance liquid chromatography-mass spectrometer analysis of OPEO(n) degraded metabolites revealed that strain TX1 was able to shorten the ethoxylate chain and produce octylphenol (OP). Furthermore, formation of the short carboxylate metabolites, such as carboxyoctylphenol polyethoxylates (COPEO(n), n = 2, 3) and carboxyoctylphenol polyethoxycarboxylates (COPEC(n), n = 2, 3) began at the log stage, while octylphenol polyethoxycarboxylates (OPEC(n), n = 1-3) was formed at the stationary phase. All the short-ethoxylated metabolites, OPEO(n), OPEC(n), COPEO(n), and COPEC(n), accumulated when the cells were in the stationary phase. This study is the first to demonstrate the formation of COPEO(n) and COPEC(n) from OPEO(n) by an aerobic bacterium. PMID:20044249

  14. Brain metabolite concentrations are associated with illness severity scores and white matter abnormalities in very preterm infants

    PubMed Central

    Card, Dallas; Nossin-Manor, Revital; Moore, Aideen M.; Raybaud, Charles; Sled, John G.; Taylor, Margot J.

    2016-01-01

    Background Magnetic resonance spectroscopy allows for the noninvasive study of brain metabolism and therefore may provide useful information about brain injuries. We examined the associations of brain metabolite ratios in very preterm infants with white matter lesions and overall health status at birth. Methods Spectroscopy data were obtained from 99 very preterm infants (born ≤32wk gestation) imaged shortly after birth and from 67 of these infants at term-equivalent age. These data were processed using LC Model. Multiple regression was used to examine the association of metabolite ratios with focal non cystic white matter lesions visible on conventional magnetic resonance imaging (MRI) and with at-birth illness severity scores. Results Within 2wk of birth, the ratio of N-acetylaspartate + N-acetylaspartylglutamate to creatine + phosphocreatine was significantly lower in those infants showing white matter abnormalities on conventional MRI. Increased lactate to creatine + phosphocreatine and lactate to glycerophosphocholine + phosphocholine ratios were significantly associated with increasing severity of Clinical Risk Index for Babies II and Apgar scores taken at 1 and 5min after birth. Conclusion Both overall health status at birth and white matter injury in preterm neonates are reflected in metabolite ratios measured shortly after birth. Long-term follow-up will provide additional insight into the prognostic value of these measures. PMID:23575877

  15. Simulation of Human Plasma Concentrations of Thalidomide and Primary 5-Hydroxylated Metabolites Explored with Pharmacokinetic Data in Humanized TK-NOG Mice.

    PubMed

    Nishiyama, Sayako; Suemizu, Hiroshi; Shibata, Norio; Guengerich, F Peter; Yamazaki, Hiroshi

    2015-11-16

    Plasma concentrations of thalidomide and primary 5-hydroxylated metabolites including 5,6-dihydroxythalidomide and glutathione (GSH) conjugate(s) were investigated in chimeric mice with highly "humanized" liver cells harboring cytochrome P450 3A5*1. Following oral administration of thalidomide (100 mg/kg), plasma concentrations of GSH conjugate(s) of 5-hydroxythalidomide were higher in humanized mice than in controls. Simulation of human plasma concentrations of thalidomide were achieved with a simplified physiologically based pharmacokinetic model in accordance with reported thalidomide concentrations. The results indicate that the pharmacokinetics in humans of GSH conjugate and/or catechol primary 5-hydroxylated thalidomide contributing in vivo activation can be estimated for the first time. PMID:26492539

  16. Urinary Concentrations of Phthalate Metabolites and Bisphenol A and Associations with Follicular-Phase Length, Luteal-Phase Length, Fecundability, and Early Pregnancy Loss

    PubMed Central

    Jukic, Anne Marie; Calafat, Antonia M.; McConnaughey, D. Robert; Longnecker, Matthew P.; Hoppin, Jane A.; Weinberg, Clarice R.; Wilcox, Allen J.; Baird, Donna D.; Calafat, Antonia M.; McConnaughey, D. Robert; Longnecker, Matthew P.; Hoppin, Jane A.; Weinberg, Clarice R.; Wilcox, Allen J.; Baird, Donna D.

    2015-01-01

    Background Certain phthalates and bisphenol A (BPA) show reproductive effects in animal studies and potentially affect human ovulation, conception, and pregnancy loss. Objectives We investigated these chemicals in relation to follicular- and luteal-phase lengths, time to pregnancy, and early pregnancy loss (within 6 weeks of the last menstrual period) among women attempting pregnancy. Methods Women discontinuing contraception provided daily first-morning urine specimens and recorded days with vaginal bleeding for up to 6 months. Specimens had previously been analyzed for estrogen and progesterone metabolites and human chorionic gonadotropin. A total of 221 participants contributed 706 menstrual cycles. We measured 11 phthalate metabolites and BPA in pooled urine from three specimens spaced throughout each menstrual cycle. We analyzed associations between chemical concentrations and outcomes using linear mixed models for follicular- and luteal-phase lengths, discrete-time fecundability models for time to pregnancy, and logistic regression for early pregnancy loss. Results Higher concentrations of monocarboxyoctyl phthalate (MCOP) were associated with shorter luteal phase [2nd tertile vs. 1st tertile: –0.5 days (95% CI: –0.9, –0.1), 3rd vs. 1st: –0.4 days (95% CI: –0.8, 0.01), p = 0.04]. BPA was also associated with shorter luteal phase [2nd vs. 1st: –0.8 days (95% CI: –1.2, –0.4), 3rd vs. 1st: –0.4 days (95% CI: –0.8, 0.02), p = 0.001]. Conclusions BPA and MCOP (or its precursors) were associated with shorter luteal phase. Menstrual cycle–specific estimates of urinary BPA and phthalate metabolites were not associated with detrimental alterations in follicular-phase length, time to pregnancy, or early pregnancy loss, and in fact, DEHP [di(2-ethylhexyl) phthalate] metabolites {MEOHP [mono(2-ethyl-5-oxohexyl) phthalate] and ΣDEHP} were associated with reduced early loss. These findings should be confirmed in future human studies. Citation Jukic

  17. Adding Sarcosine to Antipsychotic Treatment in Patients with Stable Schizophrenia Changes the Concentrations of Neuronal and Glial Metabolites in the Left Dorsolateral Prefrontal Cortex.

    PubMed

    Strzelecki, Dominik; Podgórski, Michał; Kałużyńska, Olga; Stefańczyk, Ludomir; Kotlicka-Antczak, Magdalena; Gmitrowicz, Agnieszka; Grzelak, Piotr

    2015-01-01

    The glutamatergic system is a key point in pathogenesis of schizophrenia. Sarcosine (N-methylglycine) is an exogenous amino acid that acts as a glycine transporter inhibitor. It modulates glutamatergic transmission by increasing glycine concentration around NMDA (N-methyl-d-aspartate) receptors. In patients with schizophrenia, the function of the glutamatergic system in the prefrontal cortex is impaired, which may promote negative and cognitive symptoms. Proton nuclear magnetic resonance (¹H-NMR) spectroscopy is a non-invasive imaging method enabling the evaluation of brain metabolite concentration, which can be applied to assess pharmacologically induced changes. The aim of the study was to evaluate the influence of a six-month course of sarcosine therapy on the concentration of metabolites (NAA, N-acetylaspartate; Glx, complex of glutamate, glutamine and γ-aminobutyric acid (GABA); mI, myo-inositol; Cr, creatine; Cho, choline) in the left dorso-lateral prefrontal cortex (DLPFC) in patients with stable schizophrenia. Fifty patients with schizophrenia, treated with constant antipsychotics doses, in stable clinical condition were randomly assigned to administration of sarcosine (25 patients) or placebo (25 patients) for six months. Metabolite concentrations in DLPFC were assessed with 1.5 Tesla ¹H-NMR spectroscopy. Clinical symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS). The first spectroscopy revealed no differences in metabolite concentrations between groups. After six months, NAA/Cho, mI/Cr and mI/Cho ratios in the left DLPFC were significantly higher in the sarcosine than the placebo group. In the sarcosine group, NAA/Cr, NAA/Cho, mI/Cr, mI/Cho ratios also significantly increased compared to baseline values. In the placebo group, only the NAA/Cr ratio increased. The addition of sarcosine to antipsychotic therapy for six months increased markers of neurons viability (NAA) and neurogilal activity (mI) with simultaneous improvement

  18. Adding Sarcosine to Antipsychotic Treatment in Patients with Stable Schizophrenia Changes the Concentrations of Neuronal and Glial Metabolites in the Left Dorsolateral Prefrontal Cortex

    PubMed Central

    Strzelecki, Dominik; Podgórski, Michał; Kałużyńska, Olga; Stefańczyk, Ludomir; Kotlicka-Antczak, Magdalena; Gmitrowicz, Agnieszka; Grzelak, Piotr

    2015-01-01

    The glutamatergic system is a key point in pathogenesis of schizophrenia. Sarcosine (N-methylglycine) is an exogenous amino acid that acts as a glycine transporter inhibitor. It modulates glutamatergic transmission by increasing glycine concentration around NMDA (N-methyl-d-aspartate) receptors. In patients with schizophrenia, the function of the glutamatergic system in the prefrontal cortex is impaired, which may promote negative and cognitive symptoms. Proton nuclear magnetic resonance (1H-NMR) spectroscopy is a non-invasive imaging method enabling the evaluation of brain metabolite concentration, which can be applied to assess pharmacologically induced changes. The aim of the study was to evaluate the influence of a six-month course of sarcosine therapy on the concentration of metabolites (NAA, N-acetylaspartate; Glx, complex of glutamate, glutamine and γ-aminobutyric acid (GABA); mI, myo-inositol; Cr, creatine; Cho, choline) in the left dorso-lateral prefrontal cortex (DLPFC) in patients with stable schizophrenia. Fifty patients with schizophrenia, treated with constant antipsychotics doses, in stable clinical condition were randomly assigned to administration of sarcosine (25 patients) or placebo (25 patients) for six months. Metabolite concentrations in DLPFC were assessed with 1.5 Tesla 1H-NMR spectroscopy. Clinical symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS). The first spectroscopy revealed no differences in metabolite concentrations between groups. After six months, NAA/Cho, mI/Cr and mI/Cho ratios in the left DLPFC were significantly higher in the sarcosine than the placebo group. In the sarcosine group, NAA/Cr, NAA/Cho, mI/Cr, mI/Cho ratios also significantly increased compared to baseline values. In the placebo group, only the NAA/Cr ratio increased. The addition of sarcosine to antipsychotic therapy for six months increased markers of neurons viability (NAA) and neurogilal activity (mI) with simultaneous improvement

  19. Staphylococcus aureus Alpha-Toxin Mediates General and Cell Type-Specific Changes in Metabolite Concentrations of Immortalized Human Airway Epithelial Cells

    PubMed Central

    Gierok, Philipp; Harms, Manuela; Richter, Erik; Hildebrandt, Jan-Peter; Lalk, Michael; Mostertz, Jörg; Hochgräfe, Falko

    2014-01-01

    Staphylococcus aureus alpha-toxin (Hla) is a potent pore-forming cytotoxin that plays an important role in the pathogenesis of S. aureus infections, including pneumonia. The impact of Hla on the dynamics of the metabolome in eukaryotic host cells has not been investigated comprehensively. Using 1H-NMR, GC-MS and HPLC-MS, we quantified the concentrations of 51 intracellular metabolites and assessed alterations in the amount of 25 extracellular metabolites in the two human bronchial epithelial cell lines S9 and 16HBE14o− under standard culture conditions and after treatment with sub-lethal amounts (2 µg/ml) of recombinant Hla (rHla) in a time-dependent manner. Treatment of cells with rHla caused substantial decreases in the concentrations of intracellular metabolites from different metabolic pathways in both cell lines, including ATP and amino acids. Concomitant increases in the extracellular concentrations were detected for various intracellular compounds, including nucleotides, glutathione disulfide and NAD+. Our results indicate that rHla has a major impact on the metabolome of eukaryotic cells as a consequence of direct rHla-mediated alterations in plasma membrane permeability or indirect effects mediated by cellular signalling. However, cell-specific changes also were observed. Glucose consumption and lactate production rates suggest that the glycolytic activity of S9 cells, but not of 16HBE14o− cells, is increased in response to rHla. This could contribute to the observed higher level of resistance of S9 cells against rHla-induced membrane damage. PMID:24733556

  20. Measurement of C-reactive protein and prostaglandin F2α metabolite concentrations in differentiation of canine pyometra and cystic endometrial hyperplasia/mucometra.

    PubMed

    Enginler, S O; Ateş, A; Diren Sığırcı, B; Sontaş, B H; Sönmez, K; Karaçam, E; Ekici, H; Evkuran Dal, G; Gürel, A

    2014-08-01

    Canine pyometra is a dioestrus period disease in which systemic inflammatory response syndrome (SIRS) is a common outcome due to the response of the body to the bacterial infection. The purpose of this study was i) to differentiate canine pyometra and cystic endometrial hyperplasia (CEH)/mucometra by measuring serum C-reactive protein (CRP) and prostaglandin F2α metabolite (PGFM) concentrations in blood and ii) to compare serum concentrations of CRP and PGFM in bitches with a pathological uterus (pyometra or CEH/mucometra) to concentrations in bitches with a healthy uterus. Mean CRP concentrations were found significantly higher (p < 0.001) in dogs with pyometra compared to those with CEH/mucometra or healthy uterus. However, no statistical difference could be detected between the groups for mean PGFM concentrations. Mean white blood cell count (WBC), alkaline phosphatase (ALP) and total protein concentrations were found significantly higher (p < 0.001) in dogs with pyometra. Escherichia coli was the most frequently isolated microorganism from dogs with pyometra (64.3%). Edwardsiella spp. was detected in a single case of pyometra for the first time. In conclusion, our results demonstrate that serum CRP concentrations were increased in dogs with pyometra and thus we conclude that serum CRP concentration but not PGFM might be useful as a marker to differentiate a case of CEH/mucometra from pyometra in female dogs. To the authors' knowledge, this is the first report in which Edwardsiella spp. has been isolated in the canine uterus. PMID:24889379

  1. Concentrations of Monoamines and Their Metabolites in Blood Plasma and Some Brain Structures of Mice, Participated in a Space Flight on the Aircraft BION-M1

    NASA Astrophysics Data System (ADS)

    Shtemberg, Andrey; Kudrin, Vladimir

    The purpose of this work was to study the possible disturbances of monoamines concentration and their metabolites in some structures of mouse brain and blood plasma caused by the influence of space flight. The forty eight C57BL/6 mice were divided into the following groups : basal control - animals , which together with a group of space flight arrived at Baykonur and then were returned to Moscow; the first space flight group - animals who spent 30 days in space, BION-M1 - board and decapitated 12 hours after the landing; animal house control to the first space flight group; second space flight group - animals who spent 30 days in space, aboard the BION-M1, and then recovered at ground conditions for 7 days; animal house control to the second space flight group; space flight imitation group - spent 30 days on board at ground model of BION-M1; animal house control to the imitation group. In all animals concentration of HA, DA, 5 -HT and their metabolites DOPAC, HVA, 3 -MT, 5 - HIAA in plasma and in the prefrontal cortex, hypothalamus, striatum and hippocampus were studied. In the blood plasma of first space flight group the concentrations of DOPAC were significantly higher compared to animal house control. The most significant changes were observed in the second space flight group, in those animals which recovered after the flight. There was a significant increase in the concentration of HA and A in blood plasma relative to the basal control and increased concentration of HA and the DOPAC/DA ratio relative to the first space flight group. No significant changes were observed in the hippocampus. In the first space flight group there was observed an increase in concentration of HA and DOPAC in the hypothalamus relative to controls. Seven days after rest concentrations of monoamines and their metabolites were significantly enhanced relative to the control and the first space flight groups. In physiology and pharmacology there is a process called as withdrawal effect

  2. The Effects of Thyme and Cinnamon Essential Oils on Performance, Rumen Fermentation and Blood Metabolites in Holstein Calves Consuming High Concentrate Diet

    PubMed Central

    Vakili, A. R.; Khorrami, B.; Mesgaran, M. Danesh; Parand, E.

    2013-01-01

    Essential oils have been shown to favorably effect in vitro ruminal fermentation, but there are few in vivo studies that have examined animal responses. The objective of this study was to evaluate the effects of thyme (THY) and cinnamon (CIN) essential oils on feed intake, growth performance, ruminal fermentation and blood metabolites in feedlot calves fed high-concentrate diets. Twelve growing Holstein calves (213±17 kg initial BW) were used in a completely randomized design and received their respective dietary treatments for 45 d. Treatments were: 1-control (no additive), 2-THY (5 g/d/calf) and 3-CIN (5 g/d/calf). Calves were fed ad libitum diets consisting of 15% forage and 85% concentrate, and adapted to the finishing diet by gradually increasing the concentrate ratio with feeding a series of transition diets 5 wk before the experiment started. Supplementation of THY or CIN did not affect DMI and ADG, and feed efficiency was similar between treatment groups. There were no effects of additives on ruminal pH and rumen concentrations of ammonia nitrogen and total VFA; whereas molar proportion of acetate and ratio of acetate to propionate decreased, and the molar proportion of propionate increased with THY and CIN supplementation. Rumen molar concentration of butyrate was significantly increased by adding CIN compared to control; but no change was observed with THY compared with control group. No effects of THY, or CIN were observed on valerate, isobutyrate or isovalerate proportions. Plasma concentrations of glucose, cholesterol, triglyceride, urea-N, β-hydroxybutyrate, alanine aminotransferase and aspartate aminotransferase were not changed by feeding THY or CIN. Results from this study suggest that supplementing a feedlot finishing diet with THY or CIN essential oil might be useful as ruminal fermentation modifiers in beef production systems, but has minor impacts on blood metabolites. PMID:25049871

  3. Dietary administration of sodium arsenite to rats: Relations between dose and urinary concentrations of methylated and thio-metabolites and effects on the rat urinary bladder epithelium

    SciTech Connect

    Suzuki, Shugo; Arnold, Lora L.; Pennington, Karen L.; Chen, Baowei; Naranmandura, Hua; Le, X. Chris; Cohen, Samuel M.

    2010-04-15

    Based on epidemiological data, chronic exposure to high levels of inorganic arsenic in drinking water is carcinogenic to humans, inducing skin, urinary bladder and lung tumors. In vivo, inorganic arsenic is metabolized to organic methylated arsenicals including the highly toxic dimethylarsinous acid (DMA{sup III}) and monomethylarsonous acid (MMA{sup III}). Short-term treatment of rats with 100 mug/g trivalent arsenic (As{sup III}) as sodium arsenite in the diet or in drinking water induced cytotoxicity and necrosis of the urothelial superficial layer, with increased cell proliferation and hyperplasia. The objectives of this study were to determine if these arsenic-induced urothelial effects are dose responsive, the dose of arsenic at which urothelial effects are not detected, and the urinary concentrations of the arsenical metabolites. We treated female F344 rats for 5 weeks with sodium arsenite at dietary doses of 0, 1, 10, 25, 50, and 100 ppm. Cytotoxicity, cell proliferation and hyperplasia of urothelial superficial cells were increased in a dose-responsive manner, with maximum effects found at 50 ppm As{sup III}. There were no effects at 1 ppm As{sup III}. The main urinary arsenical in As{sup III}-treated rats was the organic arsenical dimethylarsinic acid (DMA{sup V}). The thio-metabolites dimethylmonothioarsinic acid (DMMTA{sup V}) and monomethylmonothioarsinic acid (MMMTA{sup V}) were also found in the urine of As{sup III}-treated rats. The LC{sub 50} concentrations of DMMTA{sup V} for rat and human urothelial cells in vitro were similar to trivalent oxygen-containing arsenicals. These data suggest that dietary As{sup III}-induced urothelial cytotoxicity and proliferation are dose responsive, and the urothelial effects have a threshold corresponding to the urinary excretion of measurable reactive metabolites.

  4. The benzene metabolite para-benzoquinone is genotoxic in human, phorbol-12-acetate-13-myristate induced, peripheral blood mononuclear cells at low concentrations.

    PubMed

    Westphal, Götz Alexander; Bünger, Jürgen; Lichey, Nadine; Taeger, Dirk; Mönnich, Angelika; Hallier, Ernst

    2009-07-01

    Benzene is one of the most prominent occupational and environmental pollutants. The substance is a proven human carcinogen that induces hematologic malignancies in humans, probably at even low doses. Yet knowledge of the mechanisms leading to benzene-induced carcinogenesis is still incomplete. Benzene itself is not genotoxic. The generation of carcinogenic metabolites involves the production of oxidized intermediates such as catechol, hydroquinone and para-benzoquinone (p-BQ) in the liver. Further activation to the ultimate carcinogenic intermediates is most probably catalyzed by myeloperoxidase (MPO). Yet the products of the MPO pathway have not been identified. If an oxidized benzene metabolite such as p-BQ was actually the precursor for the ultimate carcinogenic benzene metabolite and further activation proceeds via MPO mediated reactions, it should be possible to activate p-BQ to a genotoxic compound in vitro. We tested this hypothesis with phorbol-12-acetate-13-myristate (PMA) activated peripheral blood cells exposed to p-BQ, using the cytokinesis-block micronucleus test. Addition of 20-28 ng/ml PMA caused a significant increase of micronuclei at low and non-cytotoxic p-BQ concentrations between 0.04 and 0.2 microg/ml (0.37-1.85 microM). Thus with PMA or p-BQ alone no reproducible elevation of micronuclei was seen up to toxic concentrations. PMA and p-BQ induce micronuclei when administered jointly. Our results add further support to the hypothesis that MPO is a key enzyme in the activation of benzene. PMID:19212761

  5. Vitamin D expenditure is not altered in pregnancy and lactation despite changes in vitamin D metabolite concentrations

    PubMed Central

    Jones, Kerry S; Assar, Shima; Prentice, Ann; Schoenmakers, Inez

    2016-01-01

    Pregnancy and lactation are associated with changes in vitamin D and calcium metabolism but the impact of these changes on vitamin D expenditure is unknown. We measured plasma 25(OH)D3 half-life with a stable-isotope tracer and investigated relationships with vitamin D metabolites in pregnant, lactating and ‘non-pregnant, non-lactating’ (NPNL) women. Vitamin D metabolites, vitamin D binding protein (DBP), PTH and 25(OH)D3 half-life were measured in third-trimester pregnant women (n22) and repeated during lactation 12 weeks post-partum (n14) and twice in NPNL women (n23 and n10, respectively) in rural Gambia where calcium intakes are low with little seasonality in UVB-exposure. 25(OH)D3 half-life was not significantly different between groups (mean(SD): 20.6(6.8), 22.6(7.7), 18.0(4.7) and 17.7(9.5) days in pregnant, lactating and NPNL women, respectively). Plasma 25(OH)D3, 1,25(OH)2D, and DBP were higher in pregnancy, and calculated free-25(OH)D3 and PTH were lower (P < 0.05). In lactation, 25(OH)D3 and 24,25(OH)2D3 were lower compared to pregnant (P < 0.001, P = 0.02) and NPNL women (P = 0.04, P = 0.07). Significant associations were observed between half-life and 25(OH)D3 (+ve) in pregnancy, and in all groups between 25(OH)D3 and free-25(OH)D3 (+ve) and PTH and 25(OH)D3 (−ve) (P < 0.0001). These data suggest that adaptive changes in pregnancy and lactation occur that prevent pronounced changes in vitamin D expenditure. PMID:27222109

  6. Vitamin D expenditure is not altered in pregnancy and lactation despite changes in vitamin D metabolite concentrations.

    PubMed

    Jones, Kerry S; Assar, Shima; Prentice, Ann; Schoenmakers, Inez

    2016-01-01

    Pregnancy and lactation are associated with changes in vitamin D and calcium metabolism but the impact of these changes on vitamin D expenditure is unknown. We measured plasma 25(OH)D3 half-life with a stable-isotope tracer and investigated relationships with vitamin D metabolites in pregnant, lactating and 'non-pregnant, non-lactating' (NPNL) women. Vitamin D metabolites, vitamin D binding protein (DBP), PTH and 25(OH)D3 half-life were measured in third-trimester pregnant women (n22) and repeated during lactation 12 weeks post-partum (n14) and twice in NPNL women (n23 and n10, respectively) in rural Gambia where calcium intakes are low with little seasonality in UVB-exposure. 25(OH)D3 half-life was not significantly different between groups (mean(SD): 20.6(6.8), 22.6(7.7), 18.0(4.7) and 17.7(9.5) days in pregnant, lactating and NPNL women, respectively). Plasma 25(OH)D3, 1,25(OH)2D, and DBP were higher in pregnancy, and calculated free-25(OH)D3 and PTH were lower (P < 0.05). In lactation, 25(OH)D3 and 24,25(OH)2D3 were lower compared to pregnant (P < 0.001, P = 0.02) and NPNL women (P = 0.04, P = 0.07). Significant associations were observed between half-life and 25(OH)D3 (+ve) in pregnancy, and in all groups between 25(OH)D3 and free-25(OH)D3 (+ve) and PTH and 25(OH)D3 (-ve) (P < 0.0001). These data suggest that adaptive changes in pregnancy and lactation occur that prevent pronounced changes in vitamin D expenditure. PMID:27222109

  7. Disruption of OsSULTR3;3 reduces phytate and phosphorus concentrations and alters the metabolite profile in rice grains.

    PubMed

    Zhao, Haijun; Frank, Thomas; Tan, Yuanyuan; Zhou, Chenguang; Jabnoune, Mehdi; Arpat, A Bulak; Cui, Hairui; Huang, Jianzhong; He, Zuhua; Poirier, Yves; Engel, Karl-Heinz; Shu, Qingyao

    2016-08-01

    Two low phytic acid (lpa) mutants have been developed previously with the aim to improve the nutritional value of rice (Oryza sativa) grains. In the present study, the impacts of lpa mutations on grain composition and underlying molecular mechanisms were investigated. Comparative compositional analyses and metabolite profiling demonstrated that concentrations of both phytic acid (PA) and total phosphorus (P) were significantly reduced in lpa brown rice, accompanied by changes in other metabolites and increased concentrations of nutritionally relevant compounds. The lpa mutations modified the expression of a number of genes involved in PA metabolism, as well as in sulfate and phosphate homeostasis and metabolism. Map-based cloning and complementation identified the underlying lpa gene to be OsSULTR3;3. The promoter of OsSULTR3;3 is highly active in the vascular bundles of leaves, stems and seeds, and its protein is localized in the endoplasmic reticulum. No activity of OsSULTR3;3 was revealed for the transport of phosphate, sulfate, inositol or inositol 1,4,5 triphosphate by heterologous expression in either yeast or Xenopus oocytes. The findings reveal that OsSULTR3;3 plays an important role in grain metabolism, pointing to a new route to generate value-added grains in rice and other cereal crops. PMID:27110682

  8. A Yeast Metabolite Extraction Protocol Optimised for Time-Series Analyses

    PubMed Central

    Sasidharan, Kalesh; Soga, Tomoyoshi; Tomita, Masaru; Murray, Douglas B.

    2012-01-01

    There is an increasing call for the absolute quantification of time-resolved metabolite data. However, a number of technical issues exist, such as metabolites being modified/degraded either chemically or enzymatically during the extraction process. Additionally, capillary electrophoresis mass spectrometry (CE-MS) is incompatible with high salt concentrations often used in extraction protocols. In microbial systems, metabolite yield is influenced by the extraction protocol used and the cell disruption rate. Here we present a method that rapidly quenches metabolism using dry-ice ethanol bath and methanol N-ethylmaleimide solution (thus stabilising thiols), disrupts cells efficiently using bead-beating and avoids artefacts created by live-cell pelleting. Rapid sample processing minimised metabolite leaching. Cell weight, number and size distribution was used to calculate metabolites to an attomol/cell level. We apply this method to samples obtained from the respiratory oscillation that occurs when yeast are grown continuously. PMID:22952947

  9. DHFR 19-bp Deletion and SHMT C1420T Polymorphisms and Metabolite Concentrations of the Folate Pathway in Individuals with Down Syndrome

    PubMed Central

    Mendes, Cristiani Cortez; Raimundo, Aline Maria Zanchetta de Aquino; Oliveira, Luciana Dutra; Zampieri, Bruna Lancia; Marucci, Gustavo Henrique; Biselli, Joice Matos; Goloni-Bertollo, Eny Maria; Eberlin, Marcos Nogueira; Haddad, Renato; Riccio, Maria Francesca; Vannucchi, Hélio; Carvalho, Valdemir Melechco

    2013-01-01

    Background: Down syndrome (DS) results from the presence and expression of three copies of the genes located on chromosome 21. Studies have shown that, in addition to overexpression of the Cystathionine β-synthase (CBS) gene, polymorphisms in genes involved in folate/homocysteine (Hcy) metabolism may also influence the concentrations of metabolites of this pathway. Aim: Investigate the association between Dihydrofolate reductase (DHFR) 19-base pair (bp) deletion and Serine hydroxymethyltransferase (SHMT) C1420T polymorphisms and serum folate and plasma Hcy and methylmalonic acid (MMA) concentrations in 85 individuals with DS. Methods: Molecular analysis of the DHFR 19-bp deletion and SHMT C1420T polymorphisms was performed by polymerase chain reaction (PCR) by difference in the size of fragments and real-time PCR allelic discrimination, respectively. Serum folate was quantified by chemiluminescence and plasma Hcy and MMA by liquid chromatography–tandem mass spectrometry. Results: Individuals with DHFR DD/SHMT TT genotypes presented increased folate concentrations (p=0.004) and the DHFR II/SHMT TT genotypes were associated with increased MMA concentrations (p=0.008). In addition, the MMA concentrations were negatively associated with age (p=0.04). Conclusion: There is an association between DHFR DD/SHMT TT and DHFR II/SHMT TT combined genotypes and folate and MMA concentrations in individuals with DS. PMID:23421317

  10. Effects of partial replacement of barley grain with beet pulp on performance, ruminal fermentation and plasma concentration of metabolites in transition dairy cows.

    PubMed

    Shahmoradi, A; Alikhani, M; Riasi, A; Ghorbani, G R; Ghaffari, M H

    2016-02-01

    The objective of this study was to determine the effect of partial replacement of barley grain with beet pulp (BP) on dry matter intake (DMI), ruminal fermentation, plasma concentration of metabolites and milk yield of transition dairy cows. Twenty-four multiparous Holstein cows [735 ± 26 kg of body weights and 3.5 ± 0.05 of body condition score (BCS)] were used in a randomized complete block design. Cows were assigned randomly on day 28 relative to expected parturition date to one of three treatments containing (i) 0% BP, (ii) 25% BP or (iii) 50% BP substituted for barley grain on a DM basis. During the pre-partum period, DMI and energy intake were greater (P < 0.01) in cows fed the BP diet compared with cows fed the barley grain diet. During the post-partum period, substituting BP for barley grain caused a response in DMI and energy intake, with the highest amount for the 25% BP diet and lowest for the 50% BP diet (P < 0.01). Milk yield was lowest (P < 0.01) for 50% BP diet than the other treatments. During the post-partum period, cows fed the 50% BP diets had greater rumen pH, molar proportion of butyrate and acetate: propionate ratio (P < 0.01) in the rumen compared with cows fed the 0% BP diets. In addition, cows fed the BP diets had greater (P < 0.01) plasma β-hydroxybutyrate and lower plasma glucose (P < 0.05) and blood urinary nitrogen (BUN) (P < 0.01) concentrations than cows fed the barley grain diets. Results showed that substituting BP for barley grain was effective in increasing DMI, but it did not have a significant effect on net energy balance during the post-partum period. However, replacing BP for barley grain at 50% had adverse effects on DMI, milk yield and metabolic status, as indicated by key blood metabolite concentrations. PMID:25816899

  11. Plasma and ear tissue concentrations of enrofloxacin and its metabolite ciprofloxacin in dogs with chronic end-stage otitis externa after intravenous administration of enrofloxacin.

    PubMed

    Cole, Lynette K; Papich, Mark G; Kwochka, Kenneth W; Hillier, Andrew; Smeak, Daniel D; Lehman, Amy M

    2009-02-01

    The purpose of this study was to measure the concentrations of enrofloxacin and its metabolite ciprofloxacin following intravenous administration of enrofloxacin in the plasma and ear tissue of dogs with chronic end-stage otitis undergoing a total ear canal ablation and lateral bulla osteotomy. The goals were to determine the relationship between the dose of enrofloxacin and the concentrations of enrofloxacin and ciprofloxacin, and determine appropriate doses of enrofloxacin for treatment of chronic otitis externa and media. Thirty dogs were randomized to an enrofloxacin-treatment group (5, 10, 15 or 20 mg kg(-1)) or control group (no enrofloxacin). After surgical removal, ear tissue samples (skin, vertical ear canal, horizontal ear canal, middle ear) and a blood sample were collected. Concentrations of enrofloxacin and ciprofloxacin in the plasma and ear tissue were measured by high performance liquid chromatography. Repeated measures models were applied to log-transformed data to assess dosing trends and Pearson correlations were calculated to assess concentration associations. Ear tissue concentrations of enrofloxacin and ciprofloxacin were significantly (P < 0.05) higher than plasma concentrations. Each 5 mg kg(-1 )increase in the dose of enrofloxacin resulted in a 72% and 37% increase in enrofloxacin and ciprofloxacin concentrations, respectively. For bacteria with an minimal inhibitory concentration of 0.12-0.15 or less, 0.19-0.24, 0.31-0.39 and 0.51-0.64 microg mL(-1), enrofloxacin should be dosed at 5, 10, 15 and 20 mg kg(-1), respectively. Treatment with enrofloxacin would not be recommended for a bacterial organism intermediate or resistant in susceptibility to enrofloxacin since appropriate levels of enrofloxacin would not be attained. PMID:19152587

  12. Effects of dietary vitamin D3 on concentrations of vitamin D and its metabolites in blood plasma and milk of dairy cows.

    PubMed

    McDermott, C M; Beitz, D C; Littledike, E T; Horst, R L

    1985-08-01

    To determine the effect of supplemental dietary vitamin D3 on concentration of vitamin D and its metabolites in milk, 20 Holstein cows were assigned to four groups and fed either 0, 10,000, 50,000, or 250,000 IU of vitamin D3/d beginning approximately 2 wk prepartum and continuing through wk 12 of lactation. Samples of blood plasma and milk were assayed for concentrations of vitamin D, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D. Only the daily dosage of 250,000 IU caused significant increases of concentrations of vitamin D or 25-hydroxyvitamin D in plasma. Concentrations of vitamin D and 25-hydroxyvitamin D in milk were approximately equal and averaged .2 ng/ml. Little 1,25-dihydroxyvitamin D and no 24,25-dihydroxyvitamin D could be detected in milk from any of the four treatment groups. Cows fed 250,000 IU of vitamin D3/d produced milk containing 54 IU of vitamin D activity per liter, whereas unsupplemented cows produced milk containing 17 IU/L. Oral supplementation with up to 250,000 IU of vitamin D3/d does not increase effectively vitamin D activity of milk. PMID:2995465

  13. Comparison of concentrations and profiles of polycyclic aromatic hydrocarbon metabolites in bile of fishes from offshore oil platforms and natural reefs along the California coast

    USGS Publications Warehouse

    Gale, Robert W.; Tanner, Michael J.; Love, Milton S.; Nishimoto, Mary M.; Schroeder, Donna M.

    2012-01-01

    To determine the environmental consequences of decommissioning offshore oil platforms on local and regional fish populations, contaminant loads in reproducing adults were investigated at seven platform sites and adjacent, natural sites. Specimens of three species (Pacific sanddab, Citharichthys sordidus; kelp rockfish, Sebastes atrovirens; and kelp bass, Paralabrax clathratus) residing at platforms and representing the regional background within the Santa Barbara Channel and within the San Pedro Basin were collected. Some of the most important contaminant classes related to oil operations are polycyclic aromatic hydrocarbons (PAHs) because of their potential toxicity and carcinogenicity. However, acute exposure cannot be related directly to PAH tissue concentrations because of rapid metabolism of the parent chemicals in fish; therefore, PAH metabolites in bile were measured, targeting free hydroxylated PAHs (OH-PAHs) liberated by enzymatic hydrolysis of the bound PAH glucuronides and sulfates. An ion-pairing method was developed for confirmatory analysis that targeted PAH glucuronides and sulfates. Concentrations of hydroxylated PAHs in all samples (76 fish from platforms and 64 fish from natural sites) were low, ranging from less than the limits of detection (5 to 120 nanograms per milliliter bile; 0.03 to 42 nanograms per milligram protein) to a maximum of 320 nanograms per milliliter bile (32 nanograms per milligram protein). A previously proposed dosimeter of PAH exposure in fish, 1-hydroxypyrene, was not detected at any platform site. Low concentrations of 1-hydroxypyrene were detected in 3 of 12 kelp rockfish collected from a natural reef site off Santa Barbara. The most prevalent OH-PAH, 2-hydroxyfluorene, was detected at low concentrations in seven fish of various species; of these, four were from two of the seven platform sites. The greatest concentrations of 2-hydroxyfluorene were found in three fish of various species from Platform Holly and were only

  14. Teaching Absolute Value Meaningfully

    ERIC Educational Resources Information Center

    Wade, Angela

    2012-01-01

    What is the meaning of absolute value? And why do teachers teach students how to solve absolute value equations? Absolute value is a concept introduced in first-year algebra and then reinforced in later courses. Various authors have suggested instructional methods for teaching absolute value to high school students (Wei 2005; Stallings-Roberts…

  15. Plasma cortisol and faecal cortisol metabolites concentrations in stereotypic and non-stereotypic horses: do stereotypic horses cope better with poor environmental conditions?

    PubMed Central

    2013-01-01

    Background Stereotypic behaviours, i.e. repetitive behaviours induced by frustration, repeated attempts to cope and/or brain dysfunction, are intriguing as they occur in a variety of domestic and captive species without any clear adaptive function. Among the different hypotheses, the coping hypothesis predicts that stereotypic behaviours provide a way for animals in unfavourable environmental conditions to adjust. As such, they are expected to have a lower physiological stress level (glucocorticoids) than non-stereotypic animals. Attempts to link stereotypic behaviours with glucocorticoids however have yielded contradictory results. Here we investigated correlates of oral and motor stereotypic behaviours and glucocorticoid levels in two large samples of domestic horses (NStudy1 = 55, NStudy2 = 58), kept in sub-optimal conditions (e.g. confinement, social isolation), and already known to experience poor welfare states. Each horse was observed in its box using focal sampling (study 1) and instantaneous scan sampling (study 2). Plasma samples (collected in study 1) but also non-invasive faecal samples (collected in both studies) were retrieved in order to assess cortisol levels. Results Results showed that 1) plasma cortisol and faecal cortisol metabolites concentrations did not differ between horses displaying stereotypic behaviours and non-stereotypic horses and 2) both oral and motor stereotypic behaviour levels did not predict plasma cortisol or faecal cortisol metabolites concentrations. Conclusions Cortisol measures, collected in two large samples of horses using both plasma sampling as well as faecal sampling (the latter method minimizing bias due to a non-invasive sampling procedure), therefore do not indicate that stereotypic horses cope better, at least in terms of adrenocortical activity. PMID:23289406

  16. Effect of light intensity and wavelength on concentration of plant secondary metabolites in the leaves of Flourensia cernua

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flourensia cernua (tarbush) is a shrub that has encroached into grasslands in many areas of the northern Chihuahuan Desert and contains high levels of carbon-based secondary compounds. Concentrations of secondary compounds are affected by numerous biotic and abiotic influences, including amount and ...

  17. Feed restriction and realimentation in Holstein-Friesian bulls: II. Effect on blood pressure and systemic concentrations of metabolites and metabolic hormones.

    PubMed

    Keogh, K; Waters, S M; Kelly, A K; Wylie, A R G; Sauerwein, H; Sweeney, T; Kenny, D A

    2015-07-01

    The objective of this study was to evaluate the endocrine response and metabolic rate in Holstein–Friesian bulls during restricted feeding and realimentation. Sixty bulls were allocated to 1 of 2 feeding regimes: 1) restricted feed allowance (RES; n = 30) or 2) ad libitum feeding (ADLIB; n = 30) for 125 d (Period 1). The bulls in both treatment groups were then offered ad libitum access to feed for a further 55 d (Period 2). Five and 4 blood samples were collected during periods 1 (n = 60) and 2 (n = 30), respectively. Plasma samples were assayed for hormones and metabolites including insulin, IGF-1, leptin, thyroid hormones, albumin, β-hydroxy butyrate (BHB), creatinine, glucose, NEFA, total protein, triglycerides, and urea. Blood pressure measurements were determined on all animals at the beginning and end of each period as an indicator of metabolic rate. During Period 1, RES bulls gained 0.6 kg/d whereas ADLIB bulls grew at 1.9 kg/d. Following realimentation in Period 2, RES bulls displayed accelerated growth, gaining 2.5 kg/d compared with 1.4 kg/d for ADLIB bulls (P < 0.001). Treatment × period interactions (P < 0.05) were evident for all plasma analytes assayed. During Period 1, RES bulls had lower concentrations of glucose and insulin, reflecting their lower feed intake. Adipose and protein tissue mobilization was evident through greater concentrations of triglycerides, NEFA, BHB, creatinine, albumin, and total protein in RES animals in Period 1. Additionally, the effect of restricted feeding on growth was apparent through lower concentrations of IGF-1. A lower metabolic rate was also apparent through lower concentrations of thyroid hormones and fewer beats per minute in RES bulls during Period 1. During the initial stage of realimentation in Period 2, IGF-1, insulin, thyroid hormones, creatinine, glucose, total protein, and triglycerides followed the same pattern as per Period 1 with divergence maintained between RES and ADLIB bulls (P < 0.05), whereas

  18. Environmental concentrations of the cocaine metabolite benzoylecgonine induced sublethal toxicity in the development of plants but not in a zebrafish embryo-larval model.

    PubMed

    García-Cambero, J P; García-Cortés, H; Valcárcel, Y; Catalá, M

    2015-12-30

    Several studies have found cocaine and its main active metabolite benzoylecgonine (BE) in the aquatic environment and drinking water, derived from its consumption by humans as well as the inability of water treatment processes to eliminate it. A few studies have already investigated the ecotoxicology of BE to aquatic invertebrates, but none has still addressed the effects of BE on aquatic vertebrates or vascular plants. The goal of this publication is to provide information on the toxicity of environmental concentrations of BE during animal and vascular plant development, in order to contribute to a better understanding of the potential risk of this substance for the environment. BE induced alterations in mitochondrial activity and DNA levels of fern spores at environmental concentrations (1 ng L(-1)), which could disrupt gametophyte germination. However, BE at concentrations ranging from 1 ng L(-1) to 1 mg L(-1) did not disturb morphogenesis, hatching, heartbeat rate or larval motility in a zebrafish embryo-larval model. Adverse effects on ferns agree with the allelophathic role described for alkaloids and their unspecific interference with plant germination. Therefore, the anthropogenic dispersion of alkaloid allelochemicals may pose a risk for biodiversity and irrigated food production that should be further investigated. PMID:26340554

  19. Too low to kill: concentration of the secondary metabolite ranunculin in buttercup pollen does not affect bee larval survival.

    PubMed

    Sedivy, Claudio; Piskorski, Rafal; Müller, Andreas; Dorn, Silvia

    2012-08-01

    Growing evidence suggests that the freely accessible pollen of some plants is chemically protected against pollen-feeding flower visitors. For example, a diet of pollen from buttercup plants (Ranunculus) recently was shown to have a deleterious effect on developing larvae of several bee species not specialized on Ranunculus. Numerous Ranunculus species contain ranunculin, the glucosyl hydrate form of the highly reactive and toxic lactone protoanemonin, that causes the toxicity of these plants. We tested whether the presence of ranunculin is responsible for the lethal effects of R. acris pollen on the larvae of two bee species that are not Ranunculus specialists. To investigate the effect on bee larval development, we added ranunculin to the pollen provisions of the Campanula specialist bee Chelostoma rapunculi and the Asteraceae specialist bee Heriades truncorum, and allowed the larvae to feed on these provisions. We quantified ranunculin in pollen of R. acris and in brood cell provisions collected by the Ranunculus specialist bee Chelostoma florisomne. We demonstrated that although ranunculin was lethal to both tested bee species in high concentrations, the concentration in the pollen of R. acris was at least fourfold lower than that tolerated by the larvae of C. rapunculi and H. truncorum in the feeding experiments. Ranunculin concentration in the brood cells of C. florisomne was on average even twentyfold lower than that in Ranunculus pollen, suggesting that a mechanism different from ranunculin intoxication accounts for the larval mortality reported for bees not specialized on Ranunculus pollen. PMID:22711029

  20. Concentrations of phthalate metabolites in breast milk in Korea: estimating exposure to phthalates and potential risks among breast-fed infants.

    PubMed

    Kim, Sunmi; Lee, Jangwoo; Park, Jeongim; Kim, Hai-Joong; Cho, Geumjoon; Kim, Gun-Ha; Eun, So-Hee; Lee, Jeong Jae; Choi, Gyuyeon; Suh, Eunsook; Choi, Sooran; Kim, Sungjoo; Kim, Young Don; Kim, Sung Koo; Kim, Su Young; Kim, Seunghyo; Eom, Soyong; Moon, Hyo-Bang; Kim, Sungkyoon; Choi, Kyungho

    2015-03-01

    Phthalates have been associated with endocrine disruption and developmental effects in many experimental and epidemiological studies. Developing infants are among the most susceptible populations to endocrine disruption. However, limited information is available on phthalate exposure and its associated risks among breast-fed newborn infants. In the present study, breast milk samples were collected from 62 lactating mothers at 1 month post-partum from four cities of Korea in 2012 and were evaluated for six phthalate metabolites (mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), mono(2-ethyl-hexyl) phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and monoethyl phthalate (MEP)). MEP was detected in all breast milk samples, with a median concentration of 0.37 μg/L, and MiBP, MnBP and MEHP were detected in 79-89% of samples, with median concentrations of 1.10, 1.70, and 2.08 μg/L, respectively. However, MEHHP and MEOHP, the oxidized forms of di-ethyl-hexyl phthalate (DEHP), were detected in only one sample. For exposure assessment, the levels of phthalate diesters were estimated based on the parent:metabolite ratios in the breast milk that are reported elsewhere. For risk assessment, the endocrine-related toxicity of the monoester was assumed to be the same as that of its diester form. Median daily intake estimates of phthalates, including both monoester and diester forms, through breast milk consumption ranged between 0.91 and 6.52 μg/kg body weight (bw) for DEHP and between 0.38 and 1.43 μg/kg bw for di-n-butyl phthalate (DnBP). Based on the estimated daily intake, up to 8% of infants exceeded the reference dose of anti-androgenicity (RfD AA) for DEHP, and 6% of infants exceeded the tolerable daily intake (TDI) for DnBP. Breast milk MiBP and MnBP concentrations showed significant positive associations with maternal consumption of whipped cream or purified water. Considering vulnerability of

  1. Vitamin D Metabolites and Their Association with Calcium, Phosphorus, and PTH Concentrations, Severity of Illness, and Mortality in Hospitalized Equine Neonates

    PubMed Central

    Kamr, Ahmed M.; Dembek, Katarzyna A.; Reed, Stephen M.; Slovis, Nathan M.; Zaghawa, Ahmed A.; Rosol, Thomas J.; Toribio, Ramiro E.

    2015-01-01

    Background Hypocalcemia is a frequent abnormality that has been associated with disease severity and outcome in hospitalized foals. However, the pathogenesis of equine neonatal hypocalcemia is poorly understood. Hypovitaminosis D in critically ill people has been linked to hypocalcemia and mortality; however, information on vitamin D metabolites and their association with clinical findings and outcome in critically ill foals is lacking. The goal of this study was to determine the prevalence of vitamin D deficiency (hypovitaminosis D) and its association with serum calcium, phosphorus, and parathyroid hormone (PTH) concentrations, disease severity, and mortality in hospitalized newborn foals. Methods and Results One hundred newborn foals ≤72 hours old divided into hospitalized (n = 83; 59 septic, 24 sick non-septic [SNS]) and healthy (n = 17) groups were included. Blood samples were collected on admission to measure serum 25-hydroxyvitamin D3 [25(OH)D3], 1,25-dihydroxyvitamin D3 [1,25(OH) 2D3], and PTH concentrations. Data were analyzed by nonparametric methods and univariate logistic regression. The prevalence of hypovitaminosis D [defined as 25(OH)D3 <9.51 ng/mL] was 63% for hospitalized, 64% for septic, and 63% for SNS foals. Serum 25(OH)D3 and 1,25(OH) 2D3 concentrations were significantly lower in septic and SNS compared to healthy foals (P<0.0001; P = 0.037). Septic foals had significantly lower calcium and higher phosphorus and PTH concentrations than healthy and SNS foals (P<0.05). In hospitalized and septic foals, low 1,25(OH)2D3 concentrations were associated with increased PTH but not with calcium or phosphorus concentrations. Septic foals with 25(OH)D3 <9.51 ng/mL and 1,25(OH) 2D3 <7.09 pmol/L were more likely to die (OR=3.62; 95% CI = 1.1-12.40; OR = 5.41; 95% CI = 1.19-24.52, respectively). Conclusions Low 25(OH)D3 and 1,25(OH)2D3 concentrations are associated with disease severity and mortality in hospitalized foals. Vitamin D deficiency may

  2. LC-MS/MS for the simultaneous analysis of arachidonic acid and 32 related metabolites in human plasma: Basal plasma concentrations and aspirin-induced changes of eicosanoids.

    PubMed

    Shinde, Dhananjay D; Kim, Kwon-Bok; Oh, Kyung-Suk; Abdalla, Nagi; Liu, Kwang-Hyeon; Bae, Soo Kyung; Shon, Ji-Hong; Kim, Ho-Sook; Kim, Dong-Hyun; Shin, Jae Gook

    2012-12-12

    Eicosanoids play an important role in various biological responses and can be used as biomarkers for specific diseases. Therefore, we developed a highly selective, sensitive, and robust liquid chromatography-tandem mass spectrometric method to measure arachidonic acid and its 32 metabolites in human plasma. Sample preparation involved solid phase extraction, which efficiently removed sources of interference present in human plasma. Chromatographic separation was performed using a Luna C(8)-column with 0.5mM ammonium formate buffer and acetonitrile as the mobile phase under gradient conditions. Detection was performed using tandem mass spectrometry equipped with an electrospray ionization interface in negative ion mode. The matrix did not affect the reproducibility and reliability of the assay. All analytes showed good linearity over the investigated concentration range (r>0.997). The validated lower limit of quantitation for the analytes ranged from 10 to 400pg/mL. Intra- and inter-day precision (RDS%) over the concentration ranges for all eicosanoids were within 16.8%, and accuracy ranged between 88.1 and 108.2%. This assay was suitable for the determination of basal plasma levels of eicosanoids and the evaluation of effect of aspirin on eicosanoid plasma levels in healthy subjects. PMID:23217314

  3. Accurate and absolute diffusion measurements of Rhodamine 6G in low-concentration aqueous solutions by the PGSE-WATERGATE sequence

    NASA Astrophysics Data System (ADS)

    Majer, G.; Zick, K.

    2015-04-01

    A pulsed field gradient spin-echo nuclear magnetic resonance (NMR) sequence with solvent suppression (PGSE-WATERGATE) was applied to accurately measure the diffusion coefficients of Rhodamine 6G (Rh6G) in low-concentration aqueous solutions. Three samples with Rh6G concentrations of CRh6G = 1, 4.5, and 25 μM were investigated. The precise determination of the diffusion coefficients in this low-concentration range was made possible by using a cryogenically cooled NMR probe and by the effective solvent suppression of the PGSE-WATERGATE sequence. The present results bridge the gap between diffusion data measured by fluorescence correlation spectroscopy in the single molecule limit and diffusivities obtained by pulsed field gradient NMR (PFG-NMR) without solvent suppression at higher concentrations. To further extend the concentration range, the diffusion coefficient of Rh6G was also measured on a sample with CRh6G = 410 μM by PFG-NMR. The overall concentration dependence of the Rh6G diffusion at 25 °C is discussed in terms of dimerization of the Rh6G molecules. The concentration-dependent monomer/dimer proportion is deduced from the diffusion data.

  4. Accurate and absolute diffusion measurements of Rhodamine 6G in low-concentration aqueous solutions by the PGSE-WATERGATE sequence

    SciTech Connect

    Majer, G.; Zick, K.

    2015-04-28

    A pulsed field gradient spin-echo nuclear magnetic resonance (NMR) sequence with solvent suppression (PGSE-WATERGATE) was applied to accurately measure the diffusion coefficients of Rhodamine 6G (Rh6G) in low-concentration aqueous solutions. Three samples with Rh6G concentrations of C{sub Rh6G} = 1, 4.5, and 25 μM were investigated. The precise determination of the diffusion coefficients in this low-concentration range was made possible by using a cryogenically cooled NMR probe and by the effective solvent suppression of the PGSE-WATERGATE sequence. The present results bridge the gap between diffusion data measured by fluorescence correlation spectroscopy in the single molecule limit and diffusivities obtained by pulsed field gradient NMR (PFG-NMR) without solvent suppression at higher concentrations. To further extend the concentration range, the diffusion coefficient of Rh6G was also measured on a sample with C{sub Rh6G} = 410 μM by PFG-NMR. The overall concentration dependence of the Rh6G diffusion at 25 °C is discussed in terms of dimerization of the Rh6G molecules. The concentration-dependent monomer/dimer proportion is deduced from the diffusion data.

  5. Elevated temperatures increase leaf senescence and root secondary metabolite concentrations in the understory herb Panax quinquefolius (Araliaceae).

    PubMed

    Jochum, Gera M; Mudge, Kenneth W; Thomas, Richard B

    2007-05-01

    The response of understory species to elevated temperatures is not well understood but is important because these plants are highly sensitive to their growth conditions. Three-year-old plants of Panax quinquefolius, an understory herb endemic to the eastern deciduous forests of North America, were grown in a greenhouse at 25/20°C (day/night) or 30/25°C for one growing season and analyzed each month. Plants grown at high temperatures had an early onset of leaf senescence and therefore accumulated less carbon. From May to July, P. quinquefolius grown at high temperatures had decreased photosynthesis (52%), stomatal conductance (60%), and root and total biomass (33% and 28%, respectively) compared to plants grown at low temperatures. As P. quinquefolius prepared to overwinter, plants grown at high temperatures had less root biomass (53%) than plants in low temperatures. The amount of storage-root ginsenosides was unaffected by temperature, and differences in storage root size may explain why plants grown at high temperatures had greater concentrations of storage root ginsenosides (49%) than plants grown at low temperatures. Panax quinquefolius is clearly sensitive to a 5°C increase in temperature, and therefore other understory species may be negatively impacted by future increases in global temperature. PMID:21636451

  6. Eosinophil count - absolute

    MedlinePlus

    Eosinophils; Absolute eosinophil count ... the white blood cell count to give the absolute eosinophil count. ... than 500 cells per microliter (cells/mcL). Normal value ranges may vary slightly among different laboratories. Talk ...

  7. Effects of essential oils, yeast culture and malate on rumen fermentation, blood metabolites, growth performance and nutrient digestibility of Baluchi lambs fed high-concentrate diets.

    PubMed

    Malekkhahi, M; Tahmasbi, A M; Naserian, A A; Danesh Mesgaran, M; Kleen, J L; Parand, A A

    2015-04-01

    The experiment was conducted to evaluate the effects of dietary supplementation with a mixture of essential oils (MEO), yeast culture (YC) and malate on performance, nutrient digestion, rumen fermentation and blood metabolites of lambs fed high-concentrate growing diets. For this purpose, twenty Baluchi lambs (17.3 ± 0.5 kg body weight and 3 months old) were randomly assigned to four dietary treatments in a completely randomized design with five lambs per treatment. The treatment groups were as follows: (i) control: basal diet without any additive, (ii) basal diet plus 400 mg/day MEO (thymol, carvacrol, eugenol, limonene and cinnamaldehyde), (iii) basal diet with 4 g/day YC and (iv) basal diet plus 4 g/day malate. No differences between the dietary treatments were observed in dry matter intake, average daily gain or feed conversion ratio (p > 0.05). Compared with control and malate treatment, lambs fed MEO and YC had an improved crude protein digestibility (p < 0.05). Yeast culture significantly increased (p > 0.05) cell wall digestibility compared to the other treatments. No differences were observed between treatments with respect to nitrogen balance or ruminal pH and ammonia concentrations (p > 0.05). No differences were observed between treatments with respect to ruminal total volatile fatty acid concentration and molar proportions of acetate, butyrate and valerate. Molar proportion of propionate was higher (p < 0.05) for YC and malate compared to control and MEO. Plasma glucose concentration was higher (p < 0.05) in lambs fed YC and malate than in lambs fed the control or the MEO diet. Blood concentration of triglycerides significantly decreased when feeding the MEO and YC diets (p < 0.05). It was concluded that YC may be more useful as a feed additive for manipulation of rumen fermentation in lambs fed with high-concentrate diets than MEO and malate, because YC enhanced crude protein and cell wall digestibility, ruminal molar proportion

  8. First-Trimester Urine Concentrations of Phthalate Metabolites and Phenols and Placenta miRNA Expression in a Cohort of U.S. Women

    PubMed Central

    LaRocca, Jessica; Binder, Alexandra M.; McElrath, Thomas F.; Michels, Karin B.

    2015-01-01

    Background There is increasing concern that early-life exposure to endocrine-disrupting chemicals (EDCs) can influence the risk of disease development. Phthalates and phenols are two classes of suspected EDCs that are used in a variety of everyday consumer products, including plastics, epoxy resins, and cosmetics. In utero exposure to EDCs may affect disease propensity through epigenetic mechanisms. Objective The objective of this study was to determine whether prenatal exposure to multiple EDCs is associated with changes in miRNA expression of human placenta, and whether miRNA alterations are associated with birth outcomes. Methods Our study was restricted to a total of 179 women co-enrolled in the Harvard Epigenetic Birth Cohort and the Predictors of Preeclampsia Study. We analyzed associations between first-trimester urine concentrations of 8 phenols and 11 phthalate metabolites and expression of 29 candidate miRNAs in placenta by qRT-PCR. Results For three miRNAs—miR-142-3p, miR15a-5p, and miR-185—we detected associations between Σphthalates or Σphenols on expression levels (p < 0.05). By assessing gene ontology enrichment, we determined the potential mRNA targets of these microRNAs predicted in silico were associated with several biological pathways, including the regulation of protein serine/threonine kinase activity. Four gene ontology biological processes were enriched among genes significantly correlated with the expression of miRNAs associated with EDC burden. Conclusions Overall, these results suggest that prenatal phenol and phthalate exposure is associated with altered miRNA expression in placenta, suggesting a potential mechanism of EDC toxicity in humans. Citation LaRocca J, Binder AM, McElrath TF, Michels KB. 2016. First-trimester urine concentrations of phthalate metabolites and phenols and placenta miRNA expression in a cohort of U.S. women. Environ Health Perspect 124:380–387; http://dx.doi.org/10.1289/ehp.1408409 PMID:26090578

  9. Sub-anesthetic concentrations of (R,S)-ketamine metabolites inhibit acetylcholine-evoked currents in α7 nicotinic acetylcholine receptors

    PubMed Central

    Moaddel, Ruin; Abdrakhmanova, Galia; Kozak, Joanna; Jozwiak, Krzysztof; Toll, Lawrence; Jimenez, Lucita; Rosenberg, Avraham; Tran, Thao; Xiao, Yingxian; Zarate, Carlos A.; Wainer, Irving W.

    2012-01-01

    The effect of the (R,S)-ketamine metabolites (R,S)-norketamine, (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)- hydroxynorketamine on the activity of α7 and α3β4 neuronal nicotinic acetylcholine receptors was investigated using patch-clamp techniques. The data indicated that (R,S)-dehydronorketamine inhibited acetylcholine-evoked currents in α7-nicotinic acetylcholine receptor, IC50 = 55 ± 6 nM, and that (2S,6S)-hydroxynorketamine, (2R,6R)-hydroxynorketamine and (R,S)-norketamine also inhibited α7-nicotinic acetylcholine receptor function at concentrations ≤1μM, while (R,S)-ketamine was inactive at these concentrations. The inhibitory effect of (R,S)-dehydronorketamine was voltage-independent and the compound did not competitively displace selective α7-nicotinic acetylcholine receptor ligands [125I]-α-bungarotoxin and [3H]-epibatidine indicating that (R,S)-dehydronorketamine is a negative allosteric modulator of the α7-nicotinic acetylcholine receptor. (R,S)-Ketamine and (R,S)-norketamine inhibited (S)-nicotine-induced whole-cell currents in cells expressing α3β4-nicotinic acetylcholine receptor, IC50 3.1 and 9.1μM, respectively, while (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)-hydroxynorketamine were weak inhibitors, IC50 >100μM. The binding affinities of (R,S)-dehydronorketamine, (2S,6S)-hydroxynorketamine and (2R,6R)-hydroxynorketamine at the NMDA receptor were also determined using rat brain membranes and the selective NMDA receptor antagonist [3H]-MK-801. The calculated Ki values were 38.95 μM for (S)-dehydronorketamine, 21.19 μM for (2S,6S)-hydroxynorketamine and > 100 μM for (2R,6R)-hydroxynorketamine. The results suggest that the inhibitory activity of ketamine metabolites at the α7-nicotinic acetylcholine receptor may contribute to the clinical effect of the drug. PMID:23183107

  10. Metabolite and ionic composition of follicular fluid from different-sized follicles and their relationship to serum concentrations in dairy cows.

    PubMed

    Leroy, J L M R; Vanholder, T; Delanghe, J R; Opsomer, G; Van Soom, A; Bols, P E J; de Kruif, A

    2004-02-01

    Metabolic changes in blood serum may be reflected in the biochemical composition of follicular fluid and could indirectly influence oocyte quality. The purpose of this study was to examine the biochemical composition of follicular fluid harvested from different-sized follicles and its relationship with that of blood serum in dairy cattle. Following slaughter, blood samples were collected from dairy cows n=30 and follicular fluid aspirated from three size classes of non-atretic follicles (<4 mm, 6-8 mm and >10 mm diameter). Samples remained independent between cows and between size classes within cows. Serum and follicular fluid samples were assayed using commercial clinical and photometric chemistry assays for ions (sodium, potassium and chloride) and metabolites (glucose, beta-hydroxybutyrate (beta-OHB), lactate, urea, total protein, triglycerides, non-esterified fatty acids (NEFA) and total cholesterol). Results showed that follicular fluid concentrations of glucose, beta-OHB and total cholesterol increased from small to large follicles and decreased for potassium, chloride, lactate, urea and triglycerides. There was a significant concentration gradient for all variables between their levels in serum and follicular fluid (P<0.05). Significant correlations were observed for chloride (r=0.40), glucose (r=0.56), beta-OHB (r=0.85), urea (r=0.95) and total protein (r=0.60) for all three follicle size classes and for triglycerides (r=0.43), NEFA (r=0.50) and total cholesterol (r=0.42) for large follicles (P<0.05). The results from the present study suggest that the oocyte and the granulosa cells of dairy cows grow and mature in a biochemical environment that changes from small to large follicles. Furthermore, the significant correlation between the composition of serum and follicular fluid for the above-mentioned metabolites suggests that metabolic changes in serum levels will be reflected in the follicular fluid and, therefore, may affect the quality of both the

  11. Short communication: serum and tissue concentrations of vitamin D metabolites in beef heifers after buccal dosing of 25-hydroxyvitamin D3.

    PubMed

    Rivera, J D; Bachman, S E; Hubbert, M E; Branine, M E; Horst, R L; Williams, S N; Galyean, M L

    2005-04-01

    Sixteen crossbred (British x Continental; average un-shrunk body weight = 507.9 kg; SD = 45.6 kg) beef heifers fed a steam-flaked corn-based finishing diet with melengestrol acetate (0.4 mg/heifer daily) included to suppress estrus were used in a completely random design to evaluate the efficacy of buccal administration of 0, 10, 100, or 1000 mg of 25-hydroxyvitamin D3, (25-OH D3). Serum Ca, P, Mg, 25-OH D3, 1,25-dihydroxyvitamin D [1,25-(OH)2 D3], albumin, and protein were measured 24 h before dosing (-24 h), at dosing (0 h), and 6 and 24 h after dosing, after which the cattle were slaughtered at a commercial facility. Samples of kidneys, liver, longissimus lumborum, and triceps brachii were collected and evaluated for concentrations of 1,25-(OH)2 D3. With -24 and 0 h as baseline covariates, a significant time x treatment interaction was observed for serum 25-OH D3 and Ca concentrations, but not for serum 1,25-(OH)2 D3. Supplemental 25-OH D3 doses of 100 and 1000 mg significantly increased serum 25-OH D3 at 24 h after dosing, 1,25-(OH)2 D3 at 6 and 24 h after dosing, and serum Ca at 24 h after dosing. Similarly, buccal dosing of 1000 mg of supplemental 25-OH D3 significantly increased (approximately 2- to 3-fold) concentrations of 1,25-(OH)2 D3 in the kidney, liver, and longissimus lumborum relative to the other 3 treatments but not in triceps brachii. Serum albumin, protein, P, and Mg were not affected by treatment. Based on these results, buccal administration of 100 and 1000 mg 25-OH D3 increased vitamin D3 metabolites in serum and tissues, and it should be an effective method of delivering the vitamin. PMID:15778304

  12. Characterizing concentrations of diethylene glycol and suspected metabolites in human serum, urine, and cerebrospinal fluid samples from the Panama DEG mass poisoning

    PubMed Central

    SCHIER, J. G.; HUNT, D. R.; PERALA, A.; MCMARTIN, K. E.; BARTELS, M. J.; LEWIS, L. S.; MCGEEHIN, M. A.; FLANDERS, W. D.

    2015-01-01

    Context Diethylene glycol (DEG) mass poisoning is a persistent public health problem. Unfortunately, there are no human biological data on DEG and its suspected metabolites in poisoning. If present and associated with poisoning, the evidence for use of traditional therapies such as fomepizole and/or hemodialysis would be much stronger. Objective To characterize DEG and its metabolites in stored serum, urine, and cerebrospinal fluid (CSF) specimens obtained from human DEG poisoning victims enrolled in a 2006 case-control study. Methods In the 2006 study, biological samples from persons enrolled in a case-control study (42 cases with new-onset, unexplained AKI and 140 age-, sex-, and admission date-matched controls without AKI) were collected and shipped to the Centers for Disease Control and Prevention (CDC) in Atlanta for various analyses and were then frozen in storage. For this study, when sufficient volume of the original specimen remained, the following analytes were quantitatively measured in serum, urine, and CSF: DEG, 2-hydroxyethoxyacetic acid (HEAA), diglycolic acid, ethylene glycol, glycolic acid, and oxalic acid. Analytes were measured using low resolution GC/MS, descriptive statistics calculated and case results compared with controls when appropriate. Specimens were de-identified so previously collected demographic, exposure, and health data were not available. The Wilcoxon Rank Sum test (with exact p-values) and bivariable exact logistic regression were used in SAS v9.2 for data analysis. Results The following samples were analyzed: serum, 20 case, and 20 controls; urine, 11 case and 22 controls; and CSF, 11 samples from 10 cases and no controls. Diglycolic acid was detected in all case serum samples (median, 40.7 mcg/mL; range, 22.6 – 75.2) and no controls, and in all case urine samples (median, 28.7 mcg/mL; range, 14 – 118.4) and only five (23%) controls (median,

  13. Taurine and vitamin E supplementations have minimal effects on body composition, hepatic lipids, and blood hormone and metabolite concentrations in healthy Sprague Dawley rats

    PubMed Central

    Allen, Portia S; Brown, Andrew W; Brown, Michelle M Bohan; Hsu, Walter H; Beitz, Donald C

    2015-01-01

    Background As prescriptions for off-label pharmaceutical use and autonomous administration of over-the-counter nutraceuticals become mainstream, thorough assessments of these compounds are warranted. Objective To determine the effects of gemfibrozil, rosiglitazone, metformin, taurine, and vitamin E on body composition, hepatic lipids, and metabolic hormone and blood metabolite concentrations in a healthy, outbred rat cohort. Methods Male Sprague Dawley rats were fed a purified 10 kcal% from fat diet for 56 days and assigned to diet alone (control) or diet plus oral administration of gemfibrozil (34 mg/kg), metformin (500 mg/kg), rosiglitazone (3 mg/kg), taurine (520 mg/kg), or vitamin E (200 mg/kg). Results Rosiglitazone administration resulted in a 56% increase in carcass adiposity, cautioning potential prescriptive off-label use. Taurine supplementation had no adverse effects on evaluated parameters. A modest but significant increase in liver triacylglycerol content was observed with vitamin E supplementation compared with control (Δ 17.2 g triacylglycerol/100 g liver lipid). Conclusions The evaluated pharmaceuticals had effects in a healthy population similar to the reported effects in their target population and the nutraceuticals had minimal effects on the measured physiological parameters. PMID:26752960

  14. Concentrations of progesterone, a metabolite of PGF2α, prolactin, and luteinizing hormone during development of idiopathic persistent corpus luteum in mares.

    PubMed

    Ginther, O J; Baldrighi, J M; Castro, T; Wolf, C A; Santos, V G

    2016-04-01

    In experiment 1, daily blood samples were available from Days 0 to 20 (Day 0 = ovulation) in mares with an interovulatory interval (IOI, n = 5) and in mares that developed idiopathic persistent corpus luteum (PCL, n = 5). The PCL was confirmed by maintenance of progesterone (P4) concentration until end of the experiment (Day 20). Significant interactions of group and day revealed the novel findings that luteinizing hormone (LH) was lower (P < 0.05) in the PCL group than that in the IOI group on Days 0 to 4, and prolactin was lower (P < 0.05) on Days 1, 4, 6, and 7. In experiment 2, treatment with a gonadotropin-releasing hormone antagonist (n = 6) significantly reduced LH on Days 1 to 6 compared with the controls (n = 6) but did not support the hypothesis that low LH during the postovulatory period increases the frequency of PCL. In experiment 3, P4, PGFM (a PGF2α metabolite), and prolactin concentrations on Days 12 to 20 from 2 reported experiments were combined to increase the number of mares with an IOI (n = 11) or a PCL (n = 11). An abrupt and complete decrease in P4 (luteolysis) began on Day 13 in the IOI group compared with a gradual and partial P4 decline after Day 12 in the PCL group. Concentrations of PGFM and prolactin were lower (P < 0.05) in the PCL group than those in the IOI group on the day at the end of the most pronounced decrease in P4. The PCL mares were subgrouped into those with an abrupt but incomplete P4 decrease (partial luteolysis; n = 5) at the expected time and those without partial luteolysis (n = 6). There were no significant differences between the 2 subgroups in concentrations of PGFM and prolactin, but on a tentative basis (P < 0.10), the concentration of PGFM seemed more focused on the day of the most pronounced decrease in P4 in the subgroup with partial luteolysis. Results for PCL compared with IOI indicated (1) postovulatory LH and prolactin were lower, (2) treatment to reduce postovulatory LH did not increase the incidence

  15. Identification, quantification, spatiotemporal distribution and genetic variation of major latex secondary metabolites in the common dandelion (Taraxacum officinale agg.).

    PubMed

    Huber, Meret; Triebwasser-Freese, Daniella; Reichelt, Michael; Heiling, Sven; Paetz, Christian; Chandran, Jima N; Bartram, Stefan; Schneider, Bernd; Gershenzon, Jonathan; Erb, Matthias

    2015-07-01

    The secondary metabolites in the roots, leaves and flowers of the common dandelion (Taraxacum officinale agg.) have been studied in detail. However, little is known about the specific constituents of the plant's highly specialized laticifer cells. Using a combination of liquid and gas chromatography, mass spectrometry and nuclear magnetic resonance spectrometry, we identified and quantified the major secondary metabolites in the latex of different organs across different growth stages in three genotypes, and tested the activity of the metabolites against the generalist root herbivore Diabrotica balteata. We found that common dandelion latex is dominated by three classes of secondary metabolites: phenolic inositol esters (PIEs), triterpene acetates (TritAc) and the sesquiterpene lactone taraxinic acid β-D-glucopyranosyl ester (TA-G). Purification and absolute quantification revealed concentrations in the upper mgg(-1) range for all compound classes with up to 6% PIEs, 5% TritAc and 7% TA-G per gram latex fresh weight. Contrary to typical secondary metabolite patterns, concentrations of all three classes increased with plant age. The highest concentrations were measured in the main root. PIE profiles differed both quantitatively and qualitatively between plant genotypes, whereas TritAc and TA-G differed only quantitatively. Metabolite concentrations were positively correlated within and between the different compound classes, indicating tight biosynthetic co-regulation. Latex metabolite extracts strongly repelled D. balteata larvae, suggesting that the latex constituents are biologically active. PMID:25682510

  16. Absolute nuclear material assay

    DOEpatents

    Prasad, Manoj K.; Snyderman, Neal J.; Rowland, Mark S.

    2012-05-15

    A method of absolute nuclear material assay of an unknown source comprising counting neutrons from the unknown source and providing an absolute nuclear material assay utilizing a model to optimally compare to the measured count distributions. In one embodiment, the step of providing an absolute nuclear material assay comprises utilizing a random sampling of analytically computed fission chain distributions to generate a continuous time-evolving sequence of event-counts by spreading the fission chain distribution in time.

  17. Absolute nuclear material assay

    DOEpatents

    Prasad, Manoj K.; Snyderman, Neal J.; Rowland, Mark S.

    2010-07-13

    A method of absolute nuclear material assay of an unknown source comprising counting neutrons from the unknown source and providing an absolute nuclear material assay utilizing a model to optimally compare to the measured count distributions. In one embodiment, the step of providing an absolute nuclear material assay comprises utilizing a random sampling of analytically computed fission chain distributions to generate a continuous time-evolving sequence of event-counts by spreading the fission chain distribution in time.

  18. Quantitating Metabolites in Protein Precipitated Serum Using NMR Spectroscopy

    PubMed Central

    2015-01-01

    Quantitative NMR-based metabolite profiling is challenged by the deleterious effects of abundant proteins in the intact blood plasma/serum, which underscores the need for alternative approaches. Protein removal by ultrafiltration using low molecular weight cutoff filters thus represents an important step. However, protein precipitation, an alternative and simple approach for protein removal, lacks detailed quantitative assessment for use in NMR based metabolomics. In this study, we have comprehensively evaluated the performance of protein precipitation using methanol, acetonitrile, perchloric acid, and trichloroacetic acid and ultrafiltration approaches using 1D and 2D NMR, based on the identification and absolute quantitation of 44 human blood metabolites, including a few identified for the first time in the NMR spectra of human serum. We also investigated the use of a “smart isotope tag,” 15N-cholamine for further resolution enhancement, which resulted in the detection of a number of additional metabolites. 1H NMR of both protein precipitated and ultrafiltered serum detected all 44 metabolites with comparable reproducibility (average CV, 3.7% for precipitation; 3.6% for filtration). However, nearly half of the quantified metabolites in ultrafiltered serum exhibited 10–74% lower concentrations; specifically, tryptophan, benzoate, and 2-oxoisocaproate showed much lower concentrations compared to protein precipitated serum. These results indicate that protein precipitation using methanol offers a reliable approach for routine NMR-based metabolomics of human blood serum/plasma and should be considered as an alternative to ultrafiltration. Importantly, protein precipitation, which is commonly used by mass spectrometry (MS), promises avenues for direct comparison and correlation of metabolite data obtained from the two analytical platforms to exploit their combined strength in the metabolomics of blood. PMID:24796490

  19. Changes in gene expression in human renal proximal tubule cells exposed to low concentrations of S-(1,2-dichlorovinyl)-L-cysteine, a metabolite of trichloroethylene

    SciTech Connect

    Lock, Edward A. . E-mail: e.lock@ljmu.ac.uk; Barth, Jeremy L.; Argraves, Scott W.; Schnellmann, Rick G.

    2006-10-15

    Epidemiology studies suggest that there may be a weak association between high level exposure to trichloroethylene (TCE) and renal tubule cell carcinoma. Laboratory animal studies have shown an increased incidence of renal tubule carcinoma in male rats but not mice. TCE can undergo metabolism via glutathione (GSH) conjugation to form metabolites that are known to be nephrotoxic. The GSH conjugate, S-(1,2-dichlorovinyl)glutathione (DCVG), is processed further to the cysteine conjugate, S-(1,2-dichlorovinyl)-L-cysteine (DCVC), which is the penultimate nephrotoxic species. We have cultured human renal tubule cells (HRPTC) in serum-free medium under a variety of different culture conditions and observed growth, respiratory control and glucose transport over a 20 day period in medium containing low glucose. Cell death was time- and concentration-dependent, with the EC{sub 5} for DCVG being about 3 {mu}M and for DCVC about 7.5 {mu}M over 10 days. Exposure of HRPTC to sub-cytotoxic doses of DCVC (0.1 {mu}M and 1 {mu}M for 10 days) led to a small number of changes in gene expression, as determined by transcript profiling with Affymetrix human genome chips. Using the criterion of a mean 2-fold change over control for the four samples examined, 3 genes at 0.1 {mu}M DCVC increased, namely, adenosine kinase, zinc finger protein X-linked and an enzyme with lyase activity. At 1 {mu}M DCVC, two genes showed a >2-fold decrease, N-acetyltransferase 8 and complement factor H. At a lower stringency (1.5-fold change), a total of 63 probe sets were altered at 0.1 {mu}M DCVC and 45 at 1 {mu}M DCVC. Genes associated with stress, apoptosis, cell proliferation and repair and DCVC metabolism were altered, as were a small number of genes that did not appear to be associated with the known mode of action of DCVC. Some of these genes may serve as molecular markers of TCE exposure and effects in the human kidney.

  20. Absolute biological needs.

    PubMed

    McLeod, Stephen

    2014-07-01

    Absolute needs (as against instrumental needs) are independent of the ends, goals and purposes of personal agents. Against the view that the only needs are instrumental needs, David Wiggins and Garrett Thomson have defended absolute needs on the grounds that the verb 'need' has instrumental and absolute senses. While remaining neutral about it, this article does not adopt that approach. Instead, it suggests that there are absolute biological needs. The absolute nature of these needs is defended by appeal to: their objectivity (as against mind-dependence); the universality of the phenomenon of needing across the plant and animal kingdoms; the impossibility that biological needs depend wholly upon the exercise of the abilities characteristic of personal agency; the contention that the possession of biological needs is prior to the possession of the abilities characteristic of personal agency. Finally, three philosophical usages of 'normative' are distinguished. On two of these, to describe a phenomenon or claim as 'normative' is to describe it as value-dependent. A description of a phenomenon or claim as 'normative' in the third sense does not entail such value-dependency, though it leaves open the possibility that value depends upon the phenomenon or upon the truth of the claim. It is argued that while survival needs (or claims about them) may well be normative in this third sense, they are normative in neither of the first two. Thus, the idea of absolute need is not inherently normative in either of the first two senses. PMID:23586876

  1. Consumption of both low and high (-)-epicatechin apple puree attenuates platelet reactivity and increases plasma concentrations of nitric oxide metabolites: a randomized controlled trial.

    PubMed

    Gasper, Amy; Hollands, Wendy; Casgrain, Amelie; Saha, Shikha; Teucher, Birgit; Dainty, Jack R; Venema, Dini P; Hollman, Peter C; Rein, Maarit J; Nelson, Rebecca; Williamson, Gary; Kroon, Paul A

    2014-10-01

    We hypothesised that consumption of flavanol-containing apple puree would modulate platelet activity and increase nitric oxide metabolite status, and that high flavanol apple puree would exert a greater effect than low flavanol apple puree. 25 subjects consumed 230 g of apple puree containing 25 and 100mg epicatechin (low and high flavanol apple puree, respectively) and aspirin (75 mg) in random order. Measurements were made at baseline, acutely after treatment (2, 6 and 24 h), and after 14 d of treatment. Low flavanol apple puree significantly attenuated ADP and epinephrine-induced integrin-β3 expression 2 h and 6 h after consumption and ADP and epinephrine-induced P-selectin expression within 2h of consumption. High flavanol apple puree attenuated epinephrine and ADP-induced integrin-β3 expression after 2 and 6h. ADP and epinephrine-induced integrin-β3 expression was significantly attenuated 2, 6 and 24 h after consumption of aspirin, whilst 14 d aspirin consumption attenuated collagen-induced P-selectin expression only. The plasma total nitric oxide metabolite conc. was significantly increased 6h after consumption of both low and high flavanol apple purees. In conclusion, consumption of apple purees containing ⩾25 or 100 mg flavanols transiently attenuated ex vivo integrin-β3 and P-selectin expression and increased plasma nitric oxide metabolite conc. in healthy subjects, but the effect was not enhanced for the high flavanol apple puree. PMID:24929184

  2. The absolute path command

    SciTech Connect

    Moody, A.

    2012-05-11

    The ap command traveres all symlinks in a given file, directory, or executable name to identify the final absolute path. It can print just the final path, each intermediate link along with the symlink chan, and the permissions and ownership of each directory component in the final path. It has functionality similar to "which", except that it shows the final path instead of the first path. It is also similar to "pwd", but it can provide the absolute path to a relative directory from the current working directory.

  3. The absolute path command

    Energy Science and Technology Software Center (ESTSC)

    2012-05-11

    The ap command traveres all symlinks in a given file, directory, or executable name to identify the final absolute path. It can print just the final path, each intermediate link along with the symlink chan, and the permissions and ownership of each directory component in the final path. It has functionality similar to "which", except that it shows the final path instead of the first path. It is also similar to "pwd", but it canmore » provide the absolute path to a relative directory from the current working directory.« less

  4. Volatile Metabolites

    PubMed Central

    Rowan, Daryl D.

    2011-01-01

    Volatile organic compounds (volatiles) comprise a chemically diverse class of low molecular weight organic compounds having an appreciable vapor pressure under ambient conditions. Volatiles produced by plants attract pollinators and seed dispersers, and provide defense against pests and pathogens. For insects, volatiles may act as pheromones directing social behavior or as cues for finding hosts or prey. For humans, volatiles are important as flavorants and as possible disease biomarkers. The marine environment is also a major source of halogenated and sulfur-containing volatiles which participate in the global cycling of these elements. While volatile analysis commonly measures a rather restricted set of analytes, the diverse and extreme physical properties of volatiles provide unique analytical challenges. Volatiles constitute only a small proportion of the total number of metabolites produced by living organisms, however, because of their roles as signaling molecules (semiochemicals) both within and between organisms, accurately measuring and determining the roles of these compounds is crucial to an integrated understanding of living systems. This review summarizes recent developments in volatile research from a metabolomics perspective with a focus on the role of recent technical innovation in developing new areas of volatile research and expanding the range of ecological interactions which may be mediated by volatile organic metabolites. PMID:24957243

  5. Pitfalls and advantages of different strategies for the absolute quantification of N-acetyl aspartate, creatine and choline in white and grey matter by 1H-MRS.

    PubMed

    Malucelli, E; Manners, D N; Testa, C; Tonon, C; Lodi, R; Barbiroli, B; Iotti, S

    2009-12-01

    This study extensively investigates different strategies for the absolute quantitation of N-acetyl aspartate, creatine and choline in white and grey matter by (1)H-MRS at 1.5 T. The main focus of this study was to reliably estimate metabolite concentrations while reducing the scan time, which remains as one of the main problems in clinical MRS. Absolute quantitation was based on the water-unsuppressed concentration as the internal standard. We compared strategies based on various experimental protocols and post-processing strategies. Data were obtained from 30 control subjects using a PRESS sequence at several TE to estimate the transverse relaxation time, T(2), of the metabolites. Quantitation was performed with the algorithm QUEST using two different metabolite signal basis sets: a whole-metabolite basis set (WhoM) and a basis set in which the singlet signals were split from the coupled signals (MSM). The basis sets were simulated in vivo for each TE used. Metabolites' T(2)s were then determined by fitting the estimated signal amplitudes of the metabolites obtained at different TEs. Then the absolute concentrations (mM) of the metabolites were assessed for each subject using the estimated signal amplitudes and either the mean estimated relaxation times of all subjects (mean protocol, MP) or the T(2) estimated from the spectra derived from the same subject (individual protocol, IP). Results showed that MP represents a less time-consuming alternative to IP in the quantitation of brain metabolites by (1)H-MRS in both grey and white matter, with a comparable accuracy when performed by MSM. It was also shown that the acquisition time might be further reduced by using a variant of MP, although with reduced accuracy. In this variant, only one water-suppressed and one water-unsuppressed spectra were acquired, drastically reducing the duration of the entire MRS examination. However, statistical analysis highlights the reduced accuracy of MP when performed using Who

  6. Correlating absolute concentrations of gas-phase species determined by microwave, Fourier transform infrared, and atomic absorption spectroscopies to properties of silicon dioxide films deposited in an electron cyclotron resonance reactor

    NASA Astrophysics Data System (ADS)

    Cornett, Mary Jezl

    Three different gas-phase absorption spectroscopies (microwave, FTIR, and silicon atomic absorption) were used simultaneously during the plasma enhanced chemical vapor deposition of SiO2 and fluorinated SiO 2 films using an ECR deposition reactor. With these spectroscopic techniques, absolute concentrations of a large number of species present in these deposition plasmas were determined. A new ECR system with multiple diagnostic ports on the same horizontal plane, and incorporating an electrostatic chuck, rf-bias, and He-backside cooling, was constructed to facilitate these studies. Correlations to the quality of the resulting films were made using ellipsometry, FTIR, XPS, and wet etch rate techniques. The systems investigated were SiH 4/O2/Ar, SiH4/SiF4/O2 and TEOS/O2 plasmas. The SiH4/O2 plasmas are found to contain less water than previously expected (under our detection limit of 0.1 mTorr). The molecular fragment SiO was monitored as a function of power, pressure, oxygen flow, and argon flow at densities between 3.7 × 109 and 1.3 × 10-11 cm-3 in this system. Silicon atoms were detected at densities between 5.1 × 109 and 5.8 × 1010 cm -3. The decomposition of SiF4 is investigated and is shown to occur at a constant rate of about 98% in pure SiF4/O 2 plasmas. This dissociation rate is enhanced when silane is added. Water and HF are generated in large quantities when SiH4 and SiF 4 are both present in the system, and reach their maximum concentrations at the SiF4/SiH4 ratio where the film quality appears to be the best. Fluorine incorporation into SiOF films result in a consistent decrease in index of refraction values. No SiO molecules were detected in SiH4/SiF4/O2 chemistries (<5 × 10 9 cm-3). Plasmas employing TEOS/O2 chemistries show large concentrations of CO, CO2 and H2O. Larger organic molecules (ethanol, acetaldehyde, methanol, formaldehyde, and formic acid) are also present in these plasmas, totaling about 9% of the species present under most

  7. Antileishmanial Metabolites from Geosmithia langdonii

    PubMed Central

    2015-01-01

    Antileishmanial bioassay guided fractionation of Geosmithia langdonii has resulted in the isolation and identification of two new compounds (1 and 2) together with 10 known compounds (3–12). The structures of the isolated metabolites were elucidated based on comprehensive 1D and 2D NMR spectroscopic data as well as mass spectrometry. The absolute configuration at C4, C5, and C6 of 2 was determined as R using a modified Mosher esterification method and NOESY correlations. The extracts and the isolated metabolites were evaluated for their antileishmanial activities. Compounds 3, 9, 11, and 12 were found to be active against Leishmania donovani with IC50 values of 6.9, 3.3, 8.5, and 9.2 μM, respectively, while compounds 1, 5, and 10 showed lower activities against L. donovani with IC50 values of 13.0, 47.3, and 34.0 μM, respectively. PMID:25084548

  8. NMR high-resolution magic angle spinning rotor design for quantification of metabolic concentrations

    NASA Astrophysics Data System (ADS)

    Holly, R.; Damyanovich, A.; Peemoeller, H.

    2006-05-01

    A new high-resolution magic angle spinning nuclear magnetic resonance technique is presented to obtain absolute metabolite concentrations of solutions. The magnetic resonance spectrum of the sample under investigation and an internal reference are acquired simultaneously, ensuring both spectra are obtained under the same experimental conditions. The robustness of the technique is demonstrated using a solution of creatine, and it is shown that the technique can obtain solution concentrations to within 7% or better.

  9. Absolute bioavailability and regional absorption of ticagrelor in healthy volunteers

    PubMed Central

    Teng, Renli; Maya, Juan

    2014-01-01

    Objective Ticagrelor is a direct-acting, reversibly-binding, oral P2Y12 receptor antagonist. It demonstrates predictable, linear pharmacokinetics. Two studies were undertaken to further elucidate the absolute bioavailability of ticagrelor and its regional absorption in the gastrointestinal (GI) tract. Design and methods In two open-label, randomized, cross-over studies, 12 volunteers received a single dose of ticagrelor: oral 90 mg and 15 mg IV (Study 1); or 100 mg oral suspension vs 100 mg immediate release (IR) tablet (Study 2). After the initial cross-over period in Study 2, patients received 100 mg suspension delivered to specific sites in the GI tract using an Enterion capsule. In both studies, plasma concentrations of ticagrelor and AR-C124910XX were measured following administration of each formulation. Results The mean absolute bioavailability of ticagrelor was 36% (95% confidence interval = 30–42%). Metabolite:parent ratios were higher after oral administration, compared with IV administration (maximum plasma concentration [Cmax] = 0.356 and 0.037; area under the plasma concentration-time curves [AUC] = 0.530 and 0.173, respectively). Following oral administration of the 100 mg IR tablet, the AUC and Cmax of ticagrelor were 78% and 58%, respectively, of those following oral administration of the 100 mg suspension. Exposure to ticagrelor decreased the further down the GI tract it was released: mean Cmax for ticagrelor was 91%, 68%, and 13% that for the oral suspension when released in the proximal small bowel, distal small bowel and ascending colon, respectively; mean AUCs were 89%, 73%, and 32%, respectively. Conclusion The mean absolute bioavailability of ticagrelor was 36% and the proportion of ticagrelor absorbed decreased the further down the GI tract it was released: the mean AUC for ticagrelor was 89% (proximal small bowel), 73% (distal small bowel), and 32% (ascending colon) that of the mean AUC for the orally

  10. Absolute quantification of carnosine in human calf muscle by proton magnetic resonance spectroscopy

    NASA Astrophysics Data System (ADS)

    Özdemir, Mahir S.; Reyngoudt, Harmen; DeDeene, Yves; Sazak, Hakan S.; Fieremans, Els; Delputte, Steven; D'Asseler, Yves; Derave, Wim; Lemahieu, Ignace; Achten, Eric

    2007-12-01

    Carnosine has been shown to be present in the skeletal muscle and in the brain of a variety of animals and humans. Despite the various physiological functions assigned to this metabolite, its exact role remains unclear. It has been suggested that carnosine plays a role in buffering in the intracellular physiological pHi range in skeletal muscle as a result of accepting hydrogen ions released in the development of fatigue during intensive exercise. It is thus postulated that the concentration of carnosine is an indicator for the extent of the buffering capacity. However, the determination of the concentration of this metabolite has only been performed by means of muscle biopsy, which is an invasive procedure. In this paper, we utilized proton magnetic resonance spectroscopy (1H MRS) in order to perform absolute quantification of carnosine in vivo non-invasively. The method was verified by phantom experiments and in vivo measurements in the calf muscles of athletes and untrained volunteers. The measured mean concentrations in the soleus and the gastrocnemius muscles were found to be 2.81 ± 0.57/4.8 ± 1.59 mM (mean ± SD) for athletes and 2.58 ± 0.65/3.3 ± 0.32 mM for untrained volunteers, respectively. These values are in agreement with previously reported biopsy-based results. Our results suggest that 1H MRS can provide an alternative method for non-invasively determining carnosine concentration in human calf muscle in vivo.

  11. Electronic Absolute Cartesian Autocollimator

    NASA Technical Reports Server (NTRS)

    Leviton, Douglas B.

    2006-01-01

    An electronic absolute Cartesian autocollimator performs the same basic optical function as does a conventional all-optical or a conventional electronic autocollimator but differs in the nature of its optical target and the manner in which the position of the image of the target is measured. The term absolute in the name of this apparatus reflects the nature of the position measurement, which, unlike in a conventional electronic autocollimator, is based absolutely on the position of the image rather than on an assumed proportionality between the position and the levels of processed analog electronic signals. The term Cartesian in the name of this apparatus reflects the nature of its optical target. Figure 1 depicts the electronic functional blocks of an electronic absolute Cartesian autocollimator along with its basic optical layout, which is the same as that of a conventional autocollimator. Referring first to the optical layout and functions only, this or any autocollimator is used to measure the compound angular deviation of a flat datum mirror with respect to the optical axis of the autocollimator itself. The optical components include an illuminated target, a beam splitter, an objective or collimating lens, and a viewer or detector (described in more detail below) at a viewing plane. The target and the viewing planes are focal planes of the lens. Target light reflected by the datum mirror is imaged on the viewing plane at unit magnification by the collimating lens. If the normal to the datum mirror is parallel to the optical axis of the autocollimator, then the target image is centered on the viewing plane. Any angular deviation of the normal from the optical axis manifests itself as a lateral displacement of the target image from the center. The magnitude of the displacement is proportional to the focal length and to the magnitude (assumed to be small) of the angular deviation. The direction of the displacement is perpendicular to the axis about which the

  12. ABSOLUTE POLARIMETRY AT RHIC.

    SciTech Connect

    OKADA; BRAVAR, A.; BUNCE, G.; GILL, R.; HUANG, H.; MAKDISI, Y.; NASS, A.; WOOD, J.; ZELENSKI, Z.; ET AL.

    2007-09-10

    Precise and absolute beam polarization measurements are critical for the RHIC spin physics program. Because all experimental spin-dependent results are normalized by beam polarization, the normalization uncertainty contributes directly to final physics uncertainties. We aimed to perform the beam polarization measurement to an accuracy Of {Delta}P{sub beam}/P{sub beam} < 5%. The absolute polarimeter consists of Polarized Atomic Hydrogen Gas Jet Target and left-right pairs of silicon strip detectors and was installed in the RHIC-ring in 2004. This system features proton-proton elastic scattering in the Coulomb nuclear interference (CNI) region. Precise measurements of the analyzing power A{sub N} of this process has allowed us to achieve {Delta}P{sub beam}/P{sub beam} = 4.2% in 2005 for the first long spin-physics run. In this report, we describe the entire set up and performance of the system. The procedure of beam polarization measurement and analysis results from 2004-2005 are described. Physics topics of AN in the CNI region (four-momentum transfer squared 0.001 < -t < 0.032 (GeV/c){sup 2}) are also discussed. We point out the current issues and expected optimum accuracy in 2006 and the future.

  13. Serum concentrations of vitamin D metabolites, vitamins A and E, and carotenoids in six canid and four ursid species at four zoos.

    PubMed

    Crissey, S; Ange, K; Slifka, K; Bowen, P; Stacewicz-Sapuntzakis, M; Langman, C; Sadler, W; Ward, A

    2001-01-01

    Nutritional status for six captive canid species (n=34) and four captive ursid species (n=18) were analyzed. The species analyzed included: African wild dog (Lycaon pictus), arctic fox (Alopex lagopus), gray wolf (Canis lupus), maned wolf (Chrysocyon brachyurus), Mexican wolf (Canis lupus baleiyi), red wolf (Canis rufus), brown bear (Ursus arctos), polar bear (Ursus maritimus), spectacled bear (Tremarctos ornatus), and sun bear (Ursus malayanus). Diet information was collected for these animals from each participating zoo (Brookfield Zoo, Fort Worth Zoo, Lincoln Park Zoological Gardens, and North Carolina Zoological Park). The nutritional composition of the diet for each species at each institution met probable dietary requirements. Blood samples were collected from each animal and analyzed for vitamin D metabolites 25(OH)D and 1,25(OH)(2)D, vitamin A (retinol, retinyl stearate, retinyl palmitate), vitamin E (alpha-tocopherol and gamma-tocopherol) and selected carotenoids. Family differences were found for 25(OH)D, retinol, retinyl stearate, retinyl palmitate and gamma-tocopherol. Species differences were found for all detectable measurements. Carotenoids were not detected in any species. The large number of animals contributing to these data, provides a substantial base for comparing the nutritional status of healthy animals and the differences among them. PMID:11137448

  14. Implication of steady state concentrations of nitrite and nitrate metabolites of nitric oxide in plasma and whole blood in healthy human subjects.

    PubMed

    Himeno, Mariko; Ishibashi, Takaharu; Nakano, Shigeru; Furuya, Keisuke; Yoshida, Junko; Kigoshi, Toshikazu; Uchida, Kenzo; Nishio, Matomo

    2004-09-01

    1. The aim of the present study was to determine whether the steady state NOx concentration reflects NOx formation in vivo. 2. A NO3- load study was performed after achieving NOx steady state. Chronological changes in NOx concentrations in plasma and whole blood samples from nine healthy subjects were determined by the HPLC-Griess system and NOx concentrations in erythrocytes were estimated as a possible NOx compartment influential in regulating plasma NOx concentrations. 3. Analysis was performed using the first-order one-compartment open model and the NOx formation rate was subsequently calculated. 4. The mean (+/-SEM) steady state NOx concentration of plasma (15.5 +/- 1.6 micromol/L), whole blood (12.8 +/- 1.2 micromol/L) and erythrocytes (11.9 +/- 0.7 micromol/L) did not correlate with the NOx formation rate in the compartments (0.50 +/- 0.05, 0.61 +/- 0.04 and 0.91 +/- 0.17 micromol/kg per h, respectively), whereas a significant correlation was found between the steady state NOx concentration and NOx elimination rate (Kel) in plasma (r=-0.69; P=0.04) and whole blood (r=-0.79; P=0.01). 5. Although there was no direct correlation between steady state NOx concentrations and serum creatinine levels, the correlation between half-life and serum creatinine levels was significant (plasma: r=0.60, P=0.02; whole blood: r=0.49, P=0.04). 6. Plasma NOx concentrations correlated significantly with erythrocyte NOx concentrations (r=0.92, P <0.01; erythrocyte NOx=0.66 x plasma NOx). 7. The results of the present study indicate that NOx does not accumulate excessively into erythrocytes at steady state and during a NO3- load and that the steady state NOx concentration in whole blood and plasma preferentially implies NOx elimination (mainly depending on renal function) rather than NOx formation. PMID:15479165

  15. Implants as absolute anchorage.

    PubMed

    Rungcharassaeng, Kitichai; Kan, Joseph Y K; Caruso, Joseph M

    2005-11-01

    Anchorage control is essential for successful orthodontic treatment. Each tooth has its own anchorage potential as well as propensity to move when force is applied. When teeth are used as anchorage, the untoward movements of the anchoring units may result in the prolonged treatment time, and unpredictable or less-than-ideal outcome. To maximize tooth-related anchorage, techniques such as differential torque, placing roots into the cortex of the bone, the use of various intraoral devices and/or extraoral appliances have been implemented. Implants, as they are in direct contact with bone, do not possess a periodontal ligament. As a result, they do not move when orthodontic/orthopedic force is applied, and therefore can be used as "absolute anchorage." This article describes different types of implants that have been used as orthodontic anchorage. Their clinical applications and limitations are also discussed. PMID:16463910

  16. Absolute Equilibrium Entropy

    NASA Technical Reports Server (NTRS)

    Shebalin, John V.

    1997-01-01

    The entropy associated with absolute equilibrium ensemble theories of ideal, homogeneous, fluid and magneto-fluid turbulence is discussed and the three-dimensional fluid case is examined in detail. A sigma-function is defined, whose minimum value with respect to global parameters is the entropy. A comparison is made between the use of global functions sigma and phase functions H (associated with the development of various H-theorems of ideal turbulence). It is shown that the two approaches are complimentary though conceptually different: H-theorems show that an isolated system tends to equilibrium while sigma-functions allow the demonstration that entropy never decreases when two previously isolated systems are combined. This provides a more complete picture of entropy in the statistical mechanics of ideal fluids.

  17. Arsenate Impact on the Metabolite Profile, Production, and Arsenic Loading of Xylem Sap in Cucumbers (Cucumis sativus L.)

    PubMed Central

    Uroic, M. Kalle; Salaün, Pascal; Raab, Andrea; Feldmann, Jörg

    2012-01-01

    Arsenic uptake and translocation studies on xylem sap focus generally on the concentration and speciation of arsenic in the xylem. Arsenic impact on the xylem sap metabolite profile and its production during short term exposure has not been reported in detail. To investigate this, cucumbers were grown hydroponically and arsenate (AsV) and DMA were used for plant treatment for 24 h. Total arsenic and arsenic speciation in xylem sap was analyzed including a metabolite profiling under AsV stress. Produced xylem sap was quantified and absolute arsenic transported was determined. AsV exposure had a significant impact on the metabolite profile of xylem sap. Four m/z values corresponding to four compounds were up-regulated, one compound down-regulated by AsV exposure. The compound down-regulated was identified to be isoleucine. Furthermore, AsV exposure had a significant influence on sap production, leading to a reduction of up to 96% sap production when plants were exposed to 1000 μg kg−1 AsV. No difference to control plants was observed when plants were exposed to 1000 μg kg−1 DMA. Absolute arsenic amount in xylem sap was the lowest at high AsV exposure. These results show that AsV has a significant impact on the production and metabolite profile of xylem sap. The physiological importance of isoleucine needs further attention. PMID:22536187

  18. An in vivo microdialysis characterization of the transient changes in the interstitial dialysate concentration of metabolites and cytokines in human skeletal muscle in response to insertion of a microdialysis probe.

    PubMed

    Carson, Brian P; McCormack, William G; Conway, Clare; Cooke, John; Saunders, Jean; O'Connor, William T; Jakeman, Philip M

    2015-02-01

    Skeletal muscle has recently been described as an endocrine organ, capable of releasing cytokines and regulators of metabolism. Microdialysis of the interstitial space of skeletal muscle enables analysis of the release of such cytokines. The purpose of this study was to determine the transient changes in concentration of metabolites and cytokines in human skeletal muscle in a 7h period following the insertion of a microdialysis probe. In total, sixteen microdialysis catheters were inserted into the vastus lateralis of male participants (age 26.2±1.35y, height 180.8±3.89cm, mass 83.9±3.86kg, BMI 25.7±0.87kgm(-2), body fat 26.1±3.0%). Serial samples were analyzed by micro-enzymatic and multiplexed immunoassay. Muscle interstitial glucose and lactate levels remained stable throughout, amino acid concentrations stabilized after 2.5h, however, insertion of a microdialysis catheter induced a 29-fold increase in peak IL-6 (p<0.001) and 35-fold increase in peak IL-8 concentrations (p<0.001) above basal levels 6h post insertion. In contrast to stable amino acid, glucose and lactate concentrations after 2h, commonly reported markers of tissue homeostasis in in vivo microdialysis, the multi-fold increase in IL-6 and IL-8 following insertion of a microdialysis catheter is indicative of a sustained disturbance of tissue homeostasis. PMID:25528289

  19. [Absolute bioavailability of a special sustained-release acetylsalicylic acid formulation].

    PubMed

    Lücker, P W; Swoboda, M; Wetzelsberger, N

    1989-03-01

    Absolute Bioavailability of a Special Acetylsalicylic Acid Sustained Release Formulation. The absolute bioavailability of an acetylsalicylic acid (ASA) sustained release formulation (Contrheuma retard), containing 300 mg ASA as initial dose and 350 mg in a retard formulation, was determined in comparison to a standard ASA solution for intravenous administration in a two-treatment, two-period cross-over trial with 6 healthy male volunteers by comparing the areas under the plasma-fluctuation-time curves of the primary metabolite. In addition, it was examined by comparison of the mean times after administration of both formulations, whether the test formulation meets the requirements of a sustained release formulation. The investigations led to the following results: The absolute bioavailability of the test formulation was 95%. The statistical comparison of the areas under the concentration-time courses allowed no decision (neither for equivalence nor difference). The maximal concentration of SA after intravenous administration of the standard formulation was reached after 0.4 h on an average and amounted to 62 micrograms/ml. After oral administration of the test formulation, a mean concentration maximum of 28 micrograms/ml was calculated, which had been reached after about 2 h. The differences are statistically significant. The mean time for SA was 6 h after the standard formulation, whereas after administration of the test compound, a mean of 11.5 h was calculated. 24 h following administration, the concentration of SA was 1.3 micrograms/ml after intravenous administration of the standard formulation and 5.5 micrograms/ml after administration of the test formulation. These differences, too, are statistically significant. From the comparison of the mean time for SA, a retard factor of 1.9 was calculated. PMID:2757664

  20. Use of 1 alpha-hydroxyvitamin D3 in prevention of bovine parturient paresis. 8. Maternal and neonatal plasma calcium, parathyroid hormone, and vitamin D metabolites concentrations.

    PubMed

    Bar, A; Striem, S; Perlman, R; Sachs, M

    1988-10-01

    Thirteen Israeli Friesian cows (3.71 average calvings) in the second or later lactation, fed a daily diet containing 90 g of Ca and 50 g of P, were injected once intramuscularly with 700 micrograms 1 alpha-hydroxy-vitamin D3 in order to investigate its placental transfer and its subsequent metabolism in the neonate. The injection of the vitamin 96 to 24 h before calving slightly increased plasma Ca at parturition, whereas uninjected controls displayed a prominent hypo-calcemia. On the 10th and 20th d after calving, difference in the plasma Ca concentration of the two groups was not significant. At parturition, plasma parathyroid hormone concentration was significantly higher and plasma 1,25-dihydroxyvitamin D lower in the control than in the treated cows. At parturition the plasma concentrations of Ca, parathyroid hormone, hydroxyproline, and 24,25-hydroxyvitamin D were higher in the calves than in their dams. Plasma concentrations of 25-hydroxyvitamin D were markedly higher and 1,25-hydroxyvitamin D was slightly higher in cows than in their offsprings. PMID:3204189

  1. Does Long-Term High Fat Diet Always Lead to Smaller Hippocampi Volumes, Metabolite Concentrations, and Worse Learning and Memory? A Magnetic Resonance and Behavioral Study in Wistar Rats

    PubMed Central

    Setkowicz, Zuzanna; Gaździńska, Agata; Osoba, Joanna J.; Karwowska, Karolina; Majka, Piotr; Orzeł, Jarosław; Kossowski, Bartosz; Bogorodzki, Piotr; Janeczko, Krzysztof; Wyleżoł, Mariusz; Gazdzinski, Stefan P.

    2015-01-01

    Background Obesity is a worldwide epidemic with more than 600 million affected individuals. Human studies have demonstrated some alterations in brains of otherwise healthy obese individuals and elevated risk of neurodegenerative disease of old age; these studies have also pointed to slightly diminished memory and executive functions among healthy obese individuals. Similar findings were obtained in animal models of obesity induced by high fat diet. On the other hand, low carbohydrate high fat diets are currently promoted for losing weight (e.g., Atkin’s style diets). However, the long-term effects of such diets are not known. Additionally, high fat diets leading to (mild) ketonemia were shown to improve brain function in elderly humans and in some animal models. Aim To evaluate the hypothesis that long-term use of a high fat diet was associated with decreases in spatial memory, smaller hippocampi and hippocampi metabolite concentrations in Wistar rats. Methods Twenty five male Wistar rats were put on high fat diet (HFD; 60% calories from fat, 30% from carbohydrates) on their 55th day of life, while 25 control male rats (CONs) remained on chow. Adequate levels of essential nutrients were provided. Both groups underwent memory tests in 8-arm radial maze at 3rd, 6th, 9th, and 12th month. 1H magnetic resonance spectroscopy was employed to measure concentrations of tNAA (marker of neuronal integrity) at one month and one year, whereas MRI was used to evaluate hippocampal volumes. Results Obese rats (OBRs) consumed similar amount of calories as CONs, but less proteins. However, their protein intake was within recommended amounts. Throughout the experiment OBRs had statistically higher concentrations of blood ketone bodies than CONs, but still within normal values. At post-mortem assessment, OBRs had 38% larger fat deposits than CONs (p<0.05), as evaluated by volume of epididymis fat, an acknowledged marker of fat deposits in rats. Contrary to our expectations, OBRs had

  2. Performance, egg quality traits, and serum metabolite concentrations of laying hens affected by dietary supplemental chromium picolinate and vitamin C under a heat-stress condition.

    PubMed

    Torki, Mehran; Zangeneh, Samira; Habibian, Mahmood

    2014-02-01

    A 3 × 2 factorial experiment consisting three levels (0, 200, and 400 μg/kg) of chromium (chromium picolinate) and two levels (0 and 250 mg/kg) of vitamin C was employed to evaluate the effects of these dietary supplements on performance, egg quality traits, and serum biochemical parameters of heat-stressed laying hens (Lohmann LSL-Lite) from 66 to 74 weeks of age. Feed intake increased when birds were given either 400 μg/kg chromium or 250 mg/kg vitamin C (P < 0.05), but the birds that received both chromium and vitamin C consumed feed similar to those that received only chromium. Dietary treatments had no effect on egg production, egg mass, egg volume, feed conversion ratio, and body mass (P > 0.05). The birds that fed on diet with chromium or vitamin C produced eggs with higher shell mass and thickness compared to the control. Both eggshell mass and thickness decreased when vitamin C and chromium were supplemented simultaneously, and birds given the diet supplemented with 400 μg/kg chromium and 250 mg/kg vitamin C had eggshell mass and thickness similar to those of the control group. The serum concentration of chromium increased due to increasing level of dietary chromium (P < 0.05). The birds that received diet with chromium and vitamin C had higher serum concentrations of chromium compared to those that received only chromium (P < 0.05). Similarly, the hens that received chromium and vitamin C had higher serum concentrations of calcium and phosphorus compared to the hens fed with other treatments (P < 0.05). The birds given with supplemental chromium exhibited lower serum glucose, total cholesterol, and triglycerides concentrations but higher serum albumin and total protein concentrations compared to the other groups (P < 0.05). PMID:24347228

  3. Absolute neutrino mass measurements

    SciTech Connect

    Wolf, Joachim

    2011-10-06

    The neutrino mass plays an important role in particle physics, astrophysics and cosmology. In recent years the detection of neutrino flavour oscillations proved that neutrinos carry mass. However, oscillation experiments are only sensitive to the mass-squared difference of the mass eigenvalues. In contrast to cosmological observations and neutrino-less double beta decay (0v2{beta}) searches, single {beta}-decay experiments provide a direct, model-independent way to determine the absolute neutrino mass by measuring the energy spectrum of decay electrons at the endpoint region with high accuracy.Currently the best kinematic upper limits on the neutrino mass of 2.2eV have been set by two experiments in Mainz and Troitsk, using tritium as beta emitter. The next generation tritium {beta}-experiment KATRIN is currently under construction in Karlsruhe/Germany by an international collaboration. KATRIN intends to improve the sensitivity by one order of magnitude to 0.2eV. The investigation of a second isotope ({sup 137}Rh) is being pursued by the international MARE collaboration using micro-calorimeters to measure the beta spectrum. The technology needed to reach 0.2eV sensitivity is still in the R and D phase. This paper reviews the present status of neutrino-mass measurements with cosmological data, 0v2{beta} decay and single {beta}-decay.

  4. Absolute neutrino mass measurements

    NASA Astrophysics Data System (ADS)

    Wolf, Joachim

    2011-10-01

    The neutrino mass plays an important role in particle physics, astrophysics and cosmology. In recent years the detection of neutrino flavour oscillations proved that neutrinos carry mass. However, oscillation experiments are only sensitive to the mass-squared difference of the mass eigenvalues. In contrast to cosmological observations and neutrino-less double beta decay (0v2β) searches, single β-decay experiments provide a direct, model-independent way to determine the absolute neutrino mass by measuring the energy spectrum of decay electrons at the endpoint region with high accuracy. Currently the best kinematic upper limits on the neutrino mass of 2.2eV have been set by two experiments in Mainz and Troitsk, using tritium as beta emitter. The next generation tritium β-experiment KATRIN is currently under construction in Karlsruhe/Germany by an international collaboration. KATRIN intends to improve the sensitivity by one order of magnitude to 0.2eV. The investigation of a second isotope (137Rh) is being pursued by the international MARE collaboration using micro-calorimeters to measure the beta spectrum. The technology needed to reach 0.2eV sensitivity is still in the R&D phase. This paper reviews the present status of neutrino-mass measurements with cosmological data, 0v2β decay and single β-decay.

  5. Effect of dietary sugar concentration and sunflower seed supplementation on lactation performance, ruminal fermentation, milk fatty acid profile, and blood metabolites of dairy cows.

    PubMed

    Razzaghi, A; Valizadeh, R; Naserian, A A; Mesgaran, M Danesh; Carpenter, A J; Ghaffari, M H

    2016-05-01

    Previous research has shown that both sunflower seed (SF) and sucrose (SC) supplementation can result in variation in milk fat concentration and composition, possibly due to altered fermentation patterns and biohydrogenation of fatty acids in the rumen. The objective of this study was to determine the effects of different sugar concentrations with or without SF supplementation on lactation performance, ruminal fermentation, and milk fatty acid profile in lactating dairy cows. Eight multiparous Holstein dairy cows (body weight=620±15kg, 60±10 d in milk, mean ± standard deviation) were randomly assigned to treatments in a replicated 4×4 Latin square design with a 2×2 factorial arrangement of treatments. Each 21-d period consisted of a 14-d diet adaptation period and 7-d collection period. Dairy cows were fed 1 of the following 4 diets: (1) no additional SC without SF supplementation (NSC-SF), (2) no additional SC with SF supplementation (NSC+SF), (3) SC without SF supplementation (SC-SF), and (4) SC with SF supplementation (SC+SF). The diets contained the same amount of forages (corn silage and alfalfa hay). Four isonitrogenous and isoenergetic diets were formulated by replacing corn grain with SC and SF and balanced using change in proportions of canola meal and sugar beet pulp. No interaction was detected between SC and SF supplementation with respect to dry matter intake, milk yield, and composition. A tendency was found for an interaction between inclusion of SC and SF on energy-corrected milk with the highest amount in the SC-SF diet. Ruminal pH and the molar proportion of acetate were affected by SC inclusion, with an increase related to the SC-SF diet. Diets containing SF decreased the concentrations of short-chain fatty acids (4:0 to 10:0) and medium-chain fatty acids (12:0 to 16:0) in milk fat. The addition of SC tended to decrease the concentration of total trans-18:1. These data provide evidence that exchanging SC for corn at 4% of dietary dry matter

  6. Effect of extruded linseeds alone or in combination with fish oil on intake, milk production, plasma metabolite concentrations and milk fatty acid composition in lactating goats.

    PubMed

    Bernard, L; Leroux, C; Rouel, J; Delavaud, C; Shingfield, K J; Chilliard, Y

    2015-05-01

    Based on the potential benefits for long-term human health, there is interest in developing sustainable nutritional strategies for lowering medium-chain saturated fatty acids (FA) and increasing specific unsaturated FA in ruminant milk. Dietary supplements of extruded linseeds (EL), fish oil (FO) or a mixture of EL and FO increase cis-9,trans-11 CLA and long-chain n-3 polyunsaturated FA in bovine milk. Supplements of FO cause milk fat depression in lactating cows, but information for dairy goats is limited. A total of 14 Alpine goats were used in a replicated 3×3 Latin square with 28-days experimental periods to examine the effects of EL alone or in combination with FO on animal performance, milk fat synthesis and milk FA composition. Treatments comprised diets based on natural grassland hay supplemented with no additional oil (control), 530 of EL or 340 g/day of EL and 39 g/day of FO (ELFO). Compared with the control, ELFO tended (P=0.08) to lower milk fat yield, whereas EL increased (P<0.01) milk fat content and yield (15% and 10%, respectively). Relative to EL, ELFO decreased (P<0.01) milk fat content and yield (19% and 17%, respectively). Relative to the control and ELFO, EL decreased (P<0.05) milk 10:0 to 16:0 and odd- and branched-chain FA content and increased 18:0, cis-18:1, trans-13 18:1 (and their corresponding ∆-9 (desaturase products), trans-12,cis-14 CLA, cis-13,trans-15 CLA, cis-12,trans-14 CLA and trans-11,cis-13 CLA and 18:3n-3 concentrations. ELFO was more effective for enriching (P<0.05) milk cis-9, trans-11 CLA and trans-11 18:1 concentrations (up to 5.4- and 7.1-fold compared with the control) than EL (up to 1.7- and 2.5-fold increases). Furthermore, ELFO resulted in a substantial increase in milk trans-10 18:1 concentration (5.4% total FA), with considerable variation between individual animals. Relative to the control and EL, milk fat responses to ELFO were characterized by increases (P<0.05) in milk trans-16:1 (Δ9 to 11), trans-18:1 (Δ6

  7. Snapping Turtles (Chelydra serpentina) from Canadian Areas of Concern across the southern Laurentian Great Lakes: Chlorinated and brominated hydrocarbon contaminants and metabolites in relation to circulating concentrations of thyroxine and vitamin A.

    PubMed

    Letcher, Robert J; Lu, Zhe; de Solla, Shane R; Sandau, Courtney D; Fernie, Kimberly J

    2015-11-01

    The metabolites of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), as well as other halogenated phenolic contaminants (HPCs) have been shown to have endocrine-disrupting properties, and have been reported with increasing frequency in the blood of wildlife, and mainly in mammals and birds. However, little is known about the persistence, accumulation and distribution of these contaminants in long-lived freshwater reptiles. In the present study, in addition to a large suite of chlorinated and brominated contaminants, metabolites and HPCs, we assessed and compared hydroxylated (OH) PCBs and OH-PBDEs relative to PCBs and PBDEs, respectively, in the plasma of adult male common snapping turtles (Chelydra serpentina). Blood samples were collected from 62 snapping turtles (2001-2004) at 12 wetland sites between the Detroit River and the St. Lawrence River on the Canadian side of the Laurentian Great Lakes of North America. Turtles were sampled from sites designated as Areas of Concern (AOCs) and from a relatively clean reference site in southern Georgian Bay (Tiny Marsh), Lake Huron. Plasma concentrations of Σ46PCB (10-340 ng/g wet weight (ww)) and Σ28OH-PCB (3-83 ng/g ww) were significantly greater (p<0.05) in turtles from the Turkey Creek and Muddy Creek-Wheatley Harbour sites in Lake Erie compared with the reference site turtles. The HPC, pentachlorophenol (PCP), had a mean concentration of 9.6±1.1 ng/g ww. Of the 28 OH-CB congeners screened for, 4-OH-CB187 (42±7 ng/g ww) was the most concentrated of all HPCs measured. Of the 14 OH-BDE congeners examined, four (4'-OH-BDE17, 3-OH-BDE47, 5-OH-BDE47 and 4'-OH-BDE49) were consistently found in all plasma samples. p,p'-DDE was the most concentrated of the 18 organochlorine pesticides (OCPs) examined. The mean concentrations of circulating total thyroxine (TT4), dehydroretinol and retinol in the plasma of the male snapping turtles regardless of sampling site were 5.4±0.3, 81±4.7 and 291±13

  8. Quantitative proton MRS of cerebral metabolites in laminin alpha2 chain deficiency.

    PubMed

    Brockmann, Knut; Dechent, Peter; Bönnemann, Carsten; Schreiber, Gudrun; Frahm, Jens; Hanefeld, Folker

    2007-07-01

    Congenital muscular dystrophy (CMD) due to merosin (laminin alpha2 chain) deficiency is an autosomal recessively inherited disorder characterized by severe muscular weakness and hypotonia from birth on. Brain involvement is the rule and characterized by variable T2 hyperintensities of white matter which appears swollen on cranial MRI. The pathophysiology of these white matter changes is not clear. In five patients with laminin alpha2 deficient CMD we performed short-echo time localized proton MRS with determination of absolute metabolite concentrations in grey and white matter. In affected white matter, a consistent pattern of metabolites was detected comprising reduced concentrations of N-acetylaspartate and N-acetylaspartylglutamate, creatine, and phosphocreatine, and to a milder degree of choline-containing compounds. In contrast, concentrations of myo-inositol were in the normal range. Spectra of cortical and subcortical grey matter were normal. The observed metabolite profile is consistent with white matter edema, that is reduced cellular density, and relative astrocytosis. This interpretation is in line with the hypothesis that laminin alpha2 deficiency results in leakage of fluids across the blood-brain barrier and a histopathological report of astrocytic proliferation in CMD. PMID:17174499

  9. Absolute cavity pyrgeometer

    DOEpatents

    Reda, Ibrahim

    2013-10-29

    Implementations of the present disclosure involve an apparatus and method to measure the long-wave irradiance of the atmosphere or long-wave source. The apparatus may involve a thermopile, a concentrator and temperature controller. The incoming long-wave irradiance may be reflected from the concentrator to a thermopile receiver located at the bottom of the concentrator to receive the reflected long-wave irradiance. In addition, the thermopile may be thermally connected to a temperature controller to control the device temperature. Through use of the apparatus, the long-wave irradiance of the atmosphere may be calculated from several measurements provided by the apparatus. In addition, the apparatus may provide an international standard of pyrgeometers' calibration that is traceable back to the International System of Units (SI) rather than to a blackbody atmospheric simulator.

  10. Effect of exogenous estradiol on plasma concentrations of somatotropin, insulin-like growth factor-I, insulin-like growth factor binding protein activity, and metabolites in ovariectomized Angus and Brahman cows.

    PubMed

    Simpson, R B; Chase, C C; Spicer, L J; Carroll, J A; Hammond, A C; Welsh, T H

    1997-11-01

    To determine the effect of breed and estradiol-17 beta on selected hormones and metabolites, ovariectomized (> or = 3 mo) Angus (n = 14) and Brahman (n = 12) cows were paired by age and body weight and randomly assigned as either nonimplanted controls (CON) or implanted with estradiol (E2) for 45 d. After Day 7 and through Day 42, plasma concentration of somatotropin was greater for E2 than CON cows (treatment x day, P < 0.05). During an intensive blood sampling on Day 36, E2 cows tended (P < 0.10) to have greater somatotropin pulse amplitudes than CON cows, but other parameters of somatotropin release were not affected (P > 0.10) by E2 treatment. The effect of breed was apparent on Day 36 as Brahman cows had greater (P < 0.05) somatotropin pulse amplitude, basal secretion, and mean concentration than Angus cows. Overall, plasma concentration of IGF-I was greater (P < 0.01) for E2 than CON cows (158.3 vs. 104.2 ng/ml) and was greater for Brahman than Angus cows (164.1 vs. 98.4 ng/ml). However, there was a trend (P < 0.10) for a treatment x breed x day interaction for IGF-I (i.e., the magnitude of increase in IGF-I concentration was greater in E2-Angus than E2-Brahman cows). After Day 7 and through Day 42, total plasma IGF binding protein (IGFBP) activity was greater (P < 0.01) for E2 than CON cows. Ligand blotting revealed at least five forms of IGFBP activity, and E2 cows had greater (P < 0.05) binding activity of IGFBP-3 and the 30- and 32-kDa IGFBP than CON cows. Brahman cows had greater (P < 0.05) IGFBP-3 and the 32-kDa IGFBP than Angus cows. After Day 14 and through Day 42, concentration of urea nitrogen (PUN) was greater (P < 0.001) for CON than E2 cows (treatment x day, P < 0.001). Brahman had greater (P < 0.01) PUN than Angus cows (16.6 vs. 14.2 mg/dl). Plasma concentration of glucose was greater (P < 0.01) for E2 than CON cows (78.9 vs. 76.4 mg/dl) but was not affected (P > 0.10) by breed. In summary, these data suggest that some, but not all, of the

  11. Absolute Identification by Relative Judgment

    ERIC Educational Resources Information Center

    Stewart, Neil; Brown, Gordon D. A.; Chater, Nick

    2005-01-01

    In unidimensional absolute identification tasks, participants identify stimuli that vary along a single dimension. Performance is surprisingly poor compared with discrimination of the same stimuli. Existing models assume that identification is achieved using long-term representations of absolute magnitudes. The authors propose an alternative…

  12. Be Resolute about Absolute Value

    ERIC Educational Resources Information Center

    Kidd, Margaret L.

    2007-01-01

    This article explores how conceptualization of absolute value can start long before it is introduced. The manner in which absolute value is introduced to students in middle school has far-reaching consequences for their future mathematical understanding. It begins to lay the foundation for students' understanding of algebra, which can change…

  13. A snapshot of plasma metabolites in first-episode schizophrenia: a capillary electrophoresis time-of-flight mass spectrometry study

    PubMed Central

    Koike, S; Bundo, M; Iwamoto, K; Suga, M; Kuwabara, H; Ohashi, Y; Shinoda, K; Takano, Y; Iwashiro, N; Satomura, Y; Nagai, T; Natsubori, T; Tada, M; Yamasue, H; Kasai, K

    2014-01-01

    Few biomarkers have been known that can easily measure clinical conditions in mental illnesses such as schizophrenia. Capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) is a new method that can measure ionized and low-molecular-weight metabolites. To explore global metabolomic alterations that characterize the onset of schizophrenia and identify biomarkers, we profiled the relative and absolute concentrations of the plasma metabolites from 30 patients with first-episode schizophrenia (FESZ, four drug-naïve samples), 38 healthy controls and 15 individuals with autism spectrum disorders using CE-TOFMS. Five metabolites had robust changes (increased creatine and decreased betaine, nonanoic acid, benzoic acid and perillic acid) in two independent sample sets. Altered levels of these metabolites are consistent with well-known hypotheses regarding abnormalities of the homocysteine metabolism, creatine kinase-emia and oxidative stress. Although it should be considered that most patients with FESZ received medication, these metabolites are candidate biomarkers to improve the determination of diagnosis, severity and clinical stages, especially for FESZ. PMID:24713860

  14. Effect of different concentrations of ginger root powder and its essential oil on growth performance, serum metabolites and antioxidant status in broiler chicks under heat stress.

    PubMed

    Habibi, R; Sadeghi, Gh; Karimi, A

    2014-01-01

    1. This study was carried out to evaluate the impact of ginger (Zingiber officinale) feed supplementation on growth performance, antioxidant status, carcass characteristics and blood parameters in broiler chicks under conditions of heat stress (32 ± 2ºC for 8 h per d). 2. A total of 336 d-old male broiler chicks (Cobb-500) were randomly assigned to one of 6 dietary groups representing: basal diet with no supplement as control, basal diet containing 100 mg/kg vitamin E as positive control, basal diets containing either 7.5 or 15 g/kg of ginger root powder, and diets containing 75 or 150 mg/kg of ginger essential oil. 3. The results indicated that at 22 d of age, the group receiving 7.5 g/kg of ginger root powder experienced significantly increased body weight (BW) and body weight gain (BWG) compared to the control group. There were no significant difference among the diet groups regarding BW, BWG, feed intake (FI) or feed conversion ratio (FCR) at 42 and 49 d of age. 4. The inclusion of powder and essential oil of ginger in broiler diets did not affect carcass characteristics and blood parameters of the chickens. However, in the group receiving 150 mg/kg ginger essential oil, the total superoxide dismutase (TSOD) activity in liver increased compared to the control group. Malondialdehyde (MDA) concentrations in liver also decreased in the groups receiving ginger powder and essential oil compared to that in the control group. There were no significant difference between experimental groups regarding glutathione peroxidise (Gpx), TSOD and catalase (CAT) enzymes in red blood cells. All dietary groups increased total antioxidant capacity (TAC) and decreased MDA concentration in serum compared to the control group. 5. The results of this study suggest that ginger powder and essential oils may be a suitable replacement for synthetic antioxidants in broiler diets. Results also suggest that ginger powder might be better than extracted essential oil for improving

  15. Improved Strategies and Optimization of Calibration Models for Real-time PCR Absolute Quantification

    EPA Science Inventory

    Real-time PCR absolute quantification applications rely on the use of standard curves to make estimates of DNA target concentrations in unknown samples. Traditional absolute quantification approaches dictate that a standard curve must accompany each experimental run. However, t...

  16. Dependence of negative-mode electrospray ionization response factors on mobile phase composition and molecular structure for newly-authenticated neutral acylsucrose metabolites.

    PubMed

    Ghosh, Banibrata; Jones, A Daniel

    2015-10-01

    Authentic standards of known concentrations serve as references for accurate absolute quantification of plant metabolites using liquid chromatography/mass spectrometry (LC/MS). However, often such standards are not commercially available or not amenable for custom syntheses. Despite the widespread use of electrospray ionization for metabolite analyses, the fundamentals needed for reliable prediction of molecular response factors have yet to be explored in detail for analytes that lack ionized functional groups. In order to lay a foundation for quantifying unknown neutral plant metabolites in absence of authentic standards, sub-milligram quantities of purified homologous acylsucrose metabolites were authenticated by subjecting each to basic hydrolysis and quantifying the sucrose product using stable-isotope dilution ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) with multiple reaction monitoring (MRM). Once authenticated, molar response factors of [M + formate](-) ions for the acylsucrose metabolites were determined at different mobile phase compositions ranging from 40%-80% acetonitrile, and demonstrated relationships of response factors with mobile phase composition and metabolite structural features including nonpolar surface areas, the length of the longest acyl chain, and the number of hydroxyl groups. This approach was employed to calculate predicted response factors for three authenticated acylsucroses based on mean values for all isomers with a common number of total acyl carbon atoms. Absolute UHPLC-MS quantification was performed on these three metabolites in an extract from leaves of the wild tomato Solanum habrochaites LA1777, yielding deviations of 26%, 6.7%, and 7.3% from values established using compound-specific response factors. PMID:26331907

  17. Airborne concentrations, skin contamination, and urinary metabolite excretion of polycyclic aromatic hydrocarbons among paving workers exposed to coal tar derived road tars

    SciTech Connect

    Jongeneelen, F.J.; Scheepers, P.T.; Groenendijk, A.; Van Aerts, L.A.; Anzion, R.B.; Bos, R.P.; Veenstra, S.J.

    1988-12-01

    The exposure of surface dressing workers to polycyclic aromatic hydrocarbons (PAH) was studied. Four different paving sites, at which coal tar-containing binders were applied, were selected as work sites with high exposure levels of PAH. Breathing zone airborne particulates, contamination of the skin with PAH, and 1-hydroxypyrene in urine of the workers involved in chip sealing were determined. Substantial concentrations of cyclohexane-soluble airborne particulate matter were found (GM = 0.2 mg/m3, n = 28). Skin contamination was determined using two different methods: with exposure pads and by hand washing. Pads were mounted on several parts of the body: wrist, elbow, neck, shoulder, and ankle. The pads located on the wrist appeared to be the most contaminated (pyrene: GM = 22 ng/1.77 cm2, n = 40). The end-of-shift hand washing showed that the hands of the workers were contaminated with PAH (pyrene: GM = 70 micrograms, n = 35). Preshift hand washing showed far lower, but detectable, quantities of PAH on workers' hands (pyrene: GM = 5 micrograms, n = 35). Enhanced levels of urinary 1-hydroxypyrene among the workers were found. The highest levels were found in the end-of-shift urine samples. Correlations between the pyrene exposure variables were studied. Significant positive correlations were found between pyrene on the wrist pad versus end-of-shift urinary 1-hydroxypyrene; between pyrene on the hands versus end-of-shift urinary 1-hydroxypyrene; and between the two different skin contamination variables.

  18. Effect of L- or DL-methionine Supplementation on Nitrogen Retention, Serum Amino Acid Concentrations and Blood Metabolites Profile in Starter Pigs.

    PubMed

    Tian, Q Y; Zeng, Z K; Zhang, Y X; Long, S F; Piao, X S

    2016-05-01

    The objective of the current study was to evaluate the effect of supplementation of either L-methionine (L-Met) or DL-methionine (DL-Met) to diets of starter pigs on nitrogen (N) balance, metabolism, and serum amino acid profile. Eighteen crossbred (Duroc×Landrace×Yorkshire) barrows weighing 15.45±0.88 kg were randomly allotted to 1 of 3 diets with 6 pigs per treatment. The diets included a basal diet (Met-deficient diet) containing 0.24% standardized ileal digestibility Met with all other essential nutrients meeting the pig's requirements. The other two diets were produced by supplementing the basal diet with 0.12% DL-Met or L-Met. The experiment lasted for 18 days, consisting of a 13-day adaptation period to the diets followed by a 5-day experimental period. Pigs were fed ad libitum and free access to water throughout the experiment. Results showed that the supplementation of either L-Met or DL-Met improved N retention, and serum methionine concentration, and decreased N excretion compared with basal diet (p<0.01). The N retention of pigs fed diets supplemented with the same inclusion levels of DL-Met or L-Met were not different (p>0.05). In conclusion, on equimolar basis DL-Met and L-Met are equally bioavailable as Met sources for starter pigs. PMID:26954214

  19. Effect of L- or DL-methionine Supplementation on Nitrogen Retention, Serum Amino Acid Concentrations and Blood Metabolites Profile in Starter Pigs

    PubMed Central

    Tian, Q. Y.; Zeng, Z. K.; Zhang, Y. X.; Long, S. F.; Piao, X. S.

    2016-01-01

    The objective of the current study was to evaluate the effect of supplementation of either L-methionine (L-Met) or DL-methionine (DL-Met) to diets of starter pigs on nitrogen (N) balance, metabolism, and serum amino acid profile. Eighteen crossbred (Duroc×Landrace×Yorkshire) barrows weighing 15.45±0.88 kg were randomly allotted to 1 of 3 diets with 6 pigs per treatment. The diets included a basal diet (Met-deficient diet) containing 0.24% standardized ileal digestibility Met with all other essential nutrients meeting the pig’s requirements. The other two diets were produced by supplementing the basal diet with 0.12% DL-Met or L-Met. The experiment lasted for 18 days, consisting of a 13-day adaptation period to the diets followed by a 5-day experimental period. Pigs were fed ad libitum and free access to water throughout the experiment. Results showed that the supplementation of either L-Met or DL-Met improved N retention, and serum methionine concentration, and decreased N excretion compared with basal diet (p<0.01). The N retention of pigs fed diets supplemented with the same inclusion levels of DL-Met or L-Met were not different (p>0.05). In conclusion, on equimolar basis DL-Met and L-Met are equally bioavailable as Met sources for starter pigs. PMID:26954214

  20. Absolute oral bioavailability of ciprofloxacin.

    PubMed

    Drusano, G L; Standiford, H C; Plaisance, K; Forrest, A; Leslie, J; Caldwell, J

    1986-09-01

    We evaluated the absolute bioavailability of ciprofloxacin, a new quinoline carboxylic acid, in 12 healthy male volunteers. Doses of 200 mg were given to each of the volunteers in a randomized, crossover manner 1 week apart orally and as a 10-min intravenous infusion. Half-lives (mean +/- standard deviation) for the intravenous and oral administration arms were 4.2 +/- 0.77 and 4.11 +/- 0.74 h, respectively. The serum clearance rate averaged 28.5 +/- 4.7 liters/h per 1.73 m2 for the intravenous administration arm. The renal clearance rate accounted for approximately 60% of the corresponding serum clearance rate and was 16.9 +/- 3.0 liters/h per 1.73 m2 for the intravenous arm and 17.0 +/- 2.86 liters/h per 1.73 m2 for the oral administration arm. Absorption was rapid, with peak concentrations in serum occurring at 0.71 +/- 0.15 h. Bioavailability, defined as the ratio of the area under the curve from 0 h to infinity for the oral to the intravenous dose, was 69 +/- 7%. We conclude that ciprofloxacin is rapidly absorbed and reliably bioavailable in these healthy volunteers. Further studies with ciprofloxacin should be undertaken in target patient populations under actual clinical circumstances. PMID:3777908

  1. A comprehensive study of the relation between serum concentrations, concentration ratios, and level/dose ratios of carbamazepine and its metabolites with age, weight, dose, and clearances in epileptic children.

    PubMed

    Liu, H; Delgado, M R

    1994-01-01

    We made a comprehensive study of the relation between age, weight, carbamazepine (CBZ) dose, total clearance (TC), and intrinsic clearance (IC) and concentrations, concentration ratios, and level/dose ratios of CBZ, carbamazepine-10,11-epoxide (CBZ-E) and trans-10,11-dihydroxy-10,11- dihydro-carbamazepine (CBZ-H) in a group of epileptic children receiving CBZ monotherapy. Body weight and age showed negative correlations with TC, IC, CBZ dose, and CBZ-E/CBZ and CBZ-H/CBZ concentration ratios, and had positive relation with CBZ, CBZ-E, and CBZ-H level/dose ratios. These results indicate decreased CBZ metabolism with patient maturity. Correlations between CBZ dose with TC, IC, and the concentration ratios of CBZ-E/CBZ, CBZ-H/CBZ-E, and CBZ-H/CBZ were positive. CBZ dose also had negative associations with CBZ and CBZ-E level/dose ratios, indicating dose-dependent autoinduction of CBZ metabolism. Our data suggest that weight, age, and CBZ dose have less influence on epoxide-hydrolase activities than on epoxidase activities. The CBZ-E/CBZ concentration ratio can be used as an indicator of the degree of autoinduction of CBZ metabolism, even in patients receiving CBZ monotherapy. PMID:7988515

  2. Antimicrobial and Antiinsectan Phenolic Metabolites of Dalea searlsiae

    PubMed Central

    2015-01-01

    Continued interest in the chemistry of Dalea spp. led to investigation of Dalea searlsiae, a plant native to areas of the western United States. Methanol extractions of D. searlsiae roots and subsequent chromatographic fractionation afforded the new prenylated and geranylated flavanones malheurans A–D (1–4) and known flavanones (5 and 6). Known rotenoids (7 and 8) and isoflavones (9 and 10) were isolated from aerial portions. Structure determination of pure compounds was accomplished primarily by extensive 1D- and 2D-NMR spectroscopy. The absolute configurations of compounds 1–5, 7, and 8 were assigned using electronic circular dichroism spectroscopy. Antimicrobial bioassays revealed significant activity concentrated in the plant roots. Compounds 1–6 exhibited MICs of 2–8 μg/mL against Streptococcus mutans, Bacillus cereus, and oxacillin-sensitive and -resistant Staphylococcus aureus. Aerial metabolites 7–10 were inactive against these organisms, but the presence of 7 and 8 prompted investigation of the antiinsectan activity of D. searlsiae metabolites toward the major crop pest Spodoptera frugiperda (fall armyworm). While compounds 1–10 all caused significant reductions in larval growth rates, associated mortality (33–66%) was highest with flavanone 4 and rotenoids 7 and 8. These findings suggest a differential allocation of antimicrobial and antiinsectan plant resources to root and aerial portions of the plant, respectively. PMID:24761805

  3. Concentrations of Insulin Glargine and Its Metabolites During Long-Term Insulin Therapy in Type 2 Diabetic Patients and Comparison of Effects of Insulin Glargine, Its Metabolites, IGF-I, and Human Insulin on Insulin and IGF-I Receptor Signaling

    PubMed Central

    Varewijck, Aimee J.; Yki-Järvinen, Hannele; Schmidt, Ronald; Tennagels, Norbert; Janssen, Joseph A.M.J.L.

    2013-01-01

    We investigated 1) the ability of purified glargine (GLA), metabolites 1 (M1) and 2 (M2), IGF-I, and NPH insulin to activate the insulin receptor (IR)-A and IR-B and IGF-I receptor (IGF-IR) in vitro; 2) plasma concentrations of GLA, M1, and M2 during long-term insulin therapy in type 2 diabetic patients; and 3) IR-A and IR-B activation in vitro induced by serum from patients treated with GLA or NPH insulin. A total of 104 patients (age 56.3 ± 0.8 years, BMI 31.4 ± 0.5 kg/m2, and A1C 9.1 ± 0.1% [mean ± SE]) were randomized to GLA or NPH insulin therapy for 36 weeks. Plasma concentrations of GLA, M1, and M2 were determined by liquid chromatography–tandem mass spectrometry assay. IR-A, IR-B, and IGF-IR autophosphorylation was induced by purified hormones or serum by kinase receptor activation assays. In vitro, M1 induced comparable IR-A, IR-B, and IGF-IR autophosphorylation (activation) as NPH insulin. After 36 weeks, M1 increased from undetectable (<0.2 ng/mL) to 1.5 ng/mL (0.9–2.1), while GLA and M2 remained undetectable. GLA dose correlated with M1 (r = 0.84; P < 0.001). Serum from patients treated with GLA or NPH insulin induced similar IR-A and IR-B activation. These data suggest that M1 rather than GLA mediates GLA effects and that compared with NPH insulin, GLA does not increase IGF-IR signaling during long-term insulin therapy in type 2 diabetes. PMID:23569175

  4. LC-MS/MS method for the determination of nine antidepressants and some of their main metabolites in oral fluid and plasma. Study of correlation between venlafaxine concentrations in both matrices.

    PubMed

    de Castro, A; Concheiro, M; Quintela, O; Cruz, A; López-Rivadulla, M

    2008-09-10

    In this paper, a fast, sensitive and selective LC-MS/MS method is described for the simultaneous determination of amitriptyline, imipramine, clomipramine, fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram and venlafaxine, as well as some of their main metabolites (nortriptyline, desipramine, norclomipramine and norfluoxetine), in oral fluid and plasma. The sample (0.2 mL) was extracted with an automated solid-phase extraction system (ASPEC XL), using mixed mode OASIS MCX cartridges. Chromatographic separation was performed in a Sunfire C18 IS column (20 mmx2.1 mm, 3.5 microm), using a gradient of acetonitrile and ammonium formate (pH 3; 2 mM) as mobile phase, which allowed the elution of all the compounds in less than 5 min. The method has been fully validated in both specimens. This method was initially applied to the analysis of oral fluid and plasma samples from patients on antidepressant treatment in order to assess for which compounds it was likely to find a good correlation between both matrices. The best results were obtained for venlafaxine, so the study was extended for this compound, comparing the ratio between oral fluid and plasma concentrations (ROF/PL) in five patients on venlafaxine treatment when both samples were collected simultaneously on four different occasions. An important inter and intraindividual variability was found in oral fluid concentrations for 150 mg dose (mean=287.5 ng/m, range 58.8-531.2 ng/mL) and for 75 mg dose (mean=186.3 ng/mL, range=82.1-289.2 ng/mL). R(OF/PL) was calculated for each patient on the four different occasions, showing also a high variability (CV=24.2-69.6%). PMID:18602787

  5. Higher body weight patients on clopidogrel maintenance therapy have lower active metabolite concentrations, lower levels of platelet inhibition, and higher rates of poor responders than low body weight patients.

    PubMed

    Wagner, Henrik; Angiolillo, Dominick J; Ten Berg, Jurrien M; Bergmeijer, Thomas O; Jakubowski, Joseph A; Small, David S; Moser, Brian A; Zhou, Chunmei; Brown, Patricia; James, Stefan; Winters, Kenneth J; Erlinge, David

    2014-01-01

    Body weight is a predictor of clopidogrel response. However, no prospective studies have compared pharmacodynamic (PD) and pharmacokinetic (PK) data based on body weight. We compared PD and PK effects of clopidogrel 75 mg in low body weight (LBW, <60 kg) and higher body weight (HBW, ≥60 kg) patients with stable coronary artery disease. LBW (n = 34, 56.4 ± 3.7 kg) and HBW (n = 38, 84.7 ± 14.9 kg) aspirin-treated patients received clopidogrel 75 mg for 10-14 days. The area under the concentration-time curve of active metabolite (Clop-AM) calculated through the last quantifiable concentration up to 4 h postdose, AUC(0-tlast), was calculated by noncompartmental methods. Light transmission aggregometry (LTA) (maximum platelet aggregation and inhibition of platelet aggregation to 20 μM adenosine diphosphate (ADP), and residual platelet aggregation to 5 μM ADP), VerifyNow(®) P2Y12 reaction units (PRU), and vasodilator-associated stimulated phosphoprotein phosphorylation platelet reactivity index (VASP-PRI) were performed. Mean AUC(0-tlast) was lower in HBW than LBW patients: 12.8 versus 17.9 ng h/mL. HBW patients had higher platelet reactivity as measured by LTA (all p ≤ 0.01), PRU (207 ± 68 vs. 152 ± 57, p < 0.001), and VASP-PRI (56 ± 18 vs. 39 ± 17, p < 0.001). More HBW patients exhibited high on-treatment platelet reactivity (HPR) using PRU (35 vs. 9%) and VASP-PRI (65 vs. 27%). Body weight correlated with PRU and VASP-PRI (both p < 0.001), and inversely with log transformed AUC(0-tlast) (p < 0.001). In conclusion, HBW patients had lower levels of Clop-AM, and higher platelet reactivity and rates of HPR than LBW subjects, contributing to their suboptimal response to clopidogrel. PMID:24043374

  6. Testing the quasi-absolute method in photon activation analysis

    SciTech Connect

    Sun, Z. J.; Wells, D.; Starovoitova, V.; Segebade, C.

    2013-04-19

    In photon activation analysis (PAA), relative methods are widely used because of their accuracy and precision. Absolute methods, which are conducted without any assistance from calibration materials, are seldom applied for the difficulty in obtaining photon flux in measurements. This research is an attempt to perform a new absolute approach in PAA - quasi-absolute method - by retrieving photon flux in the sample through Monte Carlo simulation. With simulated photon flux and database of experimental cross sections, it is possible to calculate the concentration of target elements in the sample directly. The QA/QC procedures to solidify the research are discussed in detail. Our results show that the accuracy of the method for certain elements is close to a useful level in practice. Furthermore, the future results from the quasi-absolute method can also serve as a validation technique for experimental data on cross sections. The quasi-absolute method looks promising.

  7. Urinary metabolites of diisodecyl phthalate in rats.

    PubMed

    Kato, Kayoko; Silva, Manori J; Wolf, Cynthia; Gray, L Earl; Needham, Larry L; Calafat, Antonia M

    2007-07-01

    Diisodecyl phthalate (DiDP) is an isomeric mixture of phthalates with predominantly 10-carbon branched-dialkyl chains, widely used as a plasticizer for polyvinyl chloride. The extent of human exposure to DiDP is unknown in part because adequate biomarkers of exposure to DiDP are not available. We identified several major metabolites of DiDP in urine of adult female Sprague-Dawley rats after a single oral administration of DiDP (300 mg/kg). These metabolites can potentially be used as biomarkers of exposure to DiDP. The metabolites extracted from urine were chromatographically resolved and identified by their chromatographic behavior and full scan negative ion electrospray ionization mass spectrum. The identity of metabolites with similar molecular weights was further examined in accurate mass mode. For some metabolites, unequivocal identification was done using authentic standards. Among these were the hydrolytic monoester of DiDP, monoisodecyl phthalate (MiDP), detected as a minor metabolite, and one omega oxidation product of MiDP, mono(carboxy-isononyl) phthalate (MCiNP), which was the most abundant urinary metabolite. We also tentatively identified other secondary metabolites of MiDP, mono(hydroxy-isodecyl) phthalate, mono(oxo-isodecyl) phthalate, mono(carboxy-isoheptyl) phthalate, mono(carboxy-isohexyl) phthalate, mono(carboxy-isopentyl) phthalate, mono(carboxy-isobutyl) phthalate, and mono(carboxy-ethyl) phthalate. Oxidative metabolites of diisoundecyl phthalate (DiUdP) and diisononyl phthalate (DiNP) were also detected suggesting the presence of DiUdP and DiNP in the DiDP formulation. The urinary concentrations of all these metabolites gradually decreased in the 4 days following the administration of DiDP. MCiNP and other DiDP secondary metabolites are more abundant in urine than MiDP, suggesting that these oxidative products are better biomarkers for DiDP exposure assessment than MiDP. Additional research on the toxicokinetics of these metabolites is needed

  8. Transplacental transport of netobimin metabolites in ewes.

    PubMed

    Cristofol, C; Carretero, A; Fernandez, M; Navarro, M; Sautet, J; Ruberte, J; Arboix, M

    1995-01-01

    Neither netobimin (NTB) nor its metabolite albendazole (ABZ) were found in plasma after an oral administration of 20 mg/kg of NTB to pregnant ewes during the last third of gestation. ABZ metabolites, albendazole sulphoxide (ABZSO) and albendazole sulphone (ABZSO2) were found in plasma 30 min and 2 h, respectively, after administration. The maximal plasma concentration (Cmax) of ABZSO was detected at 11.6 +/- 1.0 h and for ABZSO2 at 16.5 +/- 2.3 h. The plasma levels of the latter remained constant for 36 h, and decreased as ABZSO was removed from the blood. Jugular plasma levels of both metabolites did not differ significantly from those observed in the ovarian vein, suggesting that there were no exchanges between foetal and placental tissues. Both metabolite concentrations were similar in the umbilical vein and artery and in the amniotic and allantoic fluids, their values were half the maternal plasma concentration, leading to the conclusion that there was transplacental movement of metabolites. Both metabolites reached the foetus and could be responsible for the teratogenicity of NTB in sheep. PMID:8751036

  9. Pharmacokinetic study of harmane and its 10 metabolites in rat after intravenous and oral administration by UPLC-ESI-MS/MS.

    PubMed

    Li, Shuping; Teng, Liang; Liu, Wei; Cheng, Xuemei; Jiang, Bo; Wang, Zhengtao; Wang, Chang-Hong

    2016-09-01

    Context The β-carboline alkaloid harmane is widely distributed in common foods, beverages and hallucinogenic plants. Harmane exerts potential in therapies for Alzheimer's and depression diseases. However, little information on its dynamic metabolic profiles and pharmacokinetics in vivo is currently available. Objective This study investigates the dynamic metabolic profiles and pharmacokinetic properties of harmane and its metabolites in rats in vivo. Materials and methods A highly selective, sensitive and rapid ultra-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) method was developed and well-validated for simultaneous quantitative determination of harmane and its uncertain endogenous metabolite harmine, as well as for semiquantitative determination of 10 harmane metabolites in rats after intravenous injection and oral administration of harmane at 1.0 and 30.0 mg/kg, respectively. Results The calibration curves of harmane and harmine showed excellent linearity within the concentration range of 1-2000 ng/mL with acceptable accuracy, precision, selectivity, recovery, matrix effect and stability. Ten metabolites, including harmane but not harmine, were detected and identified after intravenous and oral administration of harmane. The absolute bioavailability of harmane following an oral dose was 19.41 ± 3.97%. According to the AUC0-t values of all the metabolites, the metabolic levels of phase II metabolites were higher than those of phase I metabolites, and the sulphation pathways were the dominant metabolic routes for harmane in both routes of administration. Discussion and conclusion The pharmacokinetic properties of harmane and its 10 metabolites in rats were determined. Sulphate conjugation was the predominant metabolic process of harmane in rats. PMID:26730489

  10. NMR identification of endogenous metabolites interacting with fatted and non-fatted human serum albumin in blood plasma: Fatty acids influence the HSA-metabolite interaction

    NASA Astrophysics Data System (ADS)

    Jupin, Marc; Michiels, Paul J.; Girard, Frederic C.; Spraul, Manfred; Wijmenga, Sybren S.

    2013-03-01

    Metabolites and their concentrations are direct reporters on body biochemistry. Thanks to technical developments metabolic profiling of body fluids, such as blood plasma, by for instance NMR has in the past decade become increasingly accurate enabling successful clinical diagnostics. Human Serum Albumin (HSA) is the main plasma protein (˜60% of all plasma protein) and responsible for the transport of endogenous (e.g. fatty acids) and exogenous metabolites, which it achieves thanks to its multiple binding sites and its flexibility. HSA has been extensively studied with regard to its binding of drugs (exogenous metabolites), but only to a lesser extent with regard to its binding of endogenous (non-fatty acid) metabolites. To obtain correct NMR measured metabolic profiles of blood plasma and/or potentially extract information on HSA and fatty acids content, it is necessary to characterize these endogenous metabolite/plasma protein interactions. Here, we investigate these metabolite-HSA interactions in blood plasma and blood plasma mimics. The latter contain the roughly twenty metabolites routinely detected by NMR (also most abundant) in normal relative concentrations with fatted or non-fatted HSA added or not. First, we find that chemical shift changes are small and seen only for a few of the metabolites. In contrast, a significant number of the metabolites display reduced resonance integrals and reduced free concentrations in the presence of HSA or fatted HSA. For slow-exchange (or strong) interactions, NMR resonance integrals report the free metabolite concentration, while for fast exchange (weak binding) the chemical shift reports on the binding. Hence, these metabolites bind strongly to HSA and/or fatted HSA, but to a limited degree because for most metabolites their concentration is smaller than the HSA concentration. Most interestingly, fatty acids decrease the metabolite-HSA binding quite significantly for most of the interacting metabolites. We further find