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Relevant bibliographies by topics / Labelled Metabolites

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Academic literature on the topic 'Labelled Metabolites'

Author: Grafiati

Published: 6 September 2023

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Journal articles on the topic "Labelled Metabolites"

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Matei, Lidia, Cristian Postolache, and Corneliu Podina. "Preparation of3H-labelled testosterone metabolites." Journal of Labelled Compounds and Radiopharmaceuticals 50, no. 5-6 (2007): 442–43. http://dx.doi.org/10.1002/jlcr.1184.

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Dhuguru, Jyothi, and Marie E. Migaud. "1-(4-Aminobutyl)guanidine." Molbank 2022, no. 4 (October 9, 2022): M1463. http://dx.doi.org/10.3390/m1463.

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Isotope labelling of otherwise endogenous metabolites has emerged as a powerful approach to study metabolism-related biological processes, when used in conjunction with nuclear magnetic resonance or chromatography-supported mass spectrometry. Given the advantages of metabolite tracing in uncovering metabolic pathways, there is always a need to develop new methods to generate isotopically labelled compounds. In this direction, we developed a new synthetic route to access the labelled agmatine. To access labelled agmatine, we developed a two-step method that includes the treatment of labelled cyanamide with N-Boc-1,4-butanediamine, followed by a BOC deprotection. Structural confirmation was achieved by 1DNMR, 2DNMR and IR spectroscopy. This isotopologue of agmatine can be very helpful to study the pharmacokinetics and bio-distribution of this neurotransmitter and its metabolites in vitro and in vivo or used as an internal standard in mass spectrometry measurements.

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Vollmer, K. O., W. Klemisch, and A. von Hodenberg. "High Performance Liquid Chromatography Coupled with Radioactivity Detection: A Powerful Tool for Determining Drug Metabolite Profiles in Biological Fluids." Zeitschrift für Naturforschung C 41, no. 1-2 (February 1, 1986): 115–25. http://dx.doi.org/10.1515/znc-1986-1-218.

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Abstract High performance liquid chromatography coupled with continuous radioactivity detection represents an advancement in drug metabolism research. Using radioactive substances labelled in biologically stable positions, all metabolites can be specifically detected by radioactivity measurement. Thus no clean-up of biological fluids is required prior to HPLC. This can prevent artefact formation from unstable metabolites, reduces recovery problems and facilitates quantitation. Separation of highly polar and unpolar metabolites is possible in a single chromatographic run using gradient elution and reversed phase materials. This technique is also well-suited for preparative isolation and purification of metabolites for subsequent structure elucidation. Various metabolite profiles of drugs labelled with carbon-14 or tritium are shown. Metabolites of the following drugs are presented: norfenefrine, etozolin, thymoxamine, naloxone, and levobunolol. We review the general methodology and report our experience with this technique. In principle, this technique may be useful for all biological systems in which tracer techniques are applied.

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Feng, Shixia, and Mahmoud A. Elsohly. "Synthesis of [2H6]-labelled metabolites of cannabinoids." Journal of Labelled Compounds and Radiopharmaceuticals 43, no. 7 (2000): 655–62. http://dx.doi.org/10.1002/1099-1344(200006)43:7<655::aid-jlcr350>3.0.co;2-t.

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Shyadehi, Akbar Z., and John J. Harding. "Synthesis of tritium-labelled metabolites of ibuprofen." Journal of Labelled Compounds and Radiopharmaceuticals 42, no. 3 (March 1999): 207–13. http://dx.doi.org/10.1002/(sici)1099-1344(199903)42:3<207::aid-jlcr210>3.0.co;2-5.

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Heinkele, Georg, Ute Hofmann, Joachim Opitz, and Thomas E. Mürdter. "Syntheses of2H-labelled dihydropyrimidinediones and their metabolites." Journal of Labelled Compounds and Radiopharmaceuticals 44, no. 1 (January 2001): 7–11. http://dx.doi.org/10.1002/jlcr.426.

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Krais, Annette, Christina Andersen, Axel Eriksson, Eskil Johnsson, Jörn Nielsen, Joakim Pagels, Anders Gudmundsson, Christian Lindh, and Aneta Wierzbicka. "Excretion of Urinary Metabolites of the Phthalate Esters DEP and DEHP in 16 Volunteers after Inhalation and Dermal Exposure." International Journal of Environmental Research and Public Health 15, no. 11 (November 9, 2018): 2514. http://dx.doi.org/10.3390/ijerph15112514.

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Phthalate esters are suspected endocrine disruptors that are found in a wide range of applications. The aim of this study was to determine the excretion of urinary metabolites in 16 individuals after inhalation and/or dermal exposure to 100–300 µg/m3 of deuterium-labelled diethyl phthalate (D4-DEP) and bis(2-ethylhexyl) phthalate (D4-DEHP). Dermal exposure in this study represents a case with clean clothing acting as a barrier. After inhalation, D4-DEP and D4-DEHP metabolites were excreted rapidly, though inter-individual variation was high. D4-DEP excretion peaked 3.3 h (T½ of 2.1 h) after combined inhalation and dermal exposure, with total excreted metabolite levels ranging from 0.055 to 2.351 nmol/nmol/m3 (nmol of urinary metabolites per phthalates air concentration in (nmol/m3)). After dermal exposure to D4-DEP, metabolite excretion peaked 4.6 h (T½ of 2.7 h) after exposure, with excreted metabolite levels in between 0.017 and 0.223 nmol/nmol/m3. After combined inhalation and dermal exposure to D4-DEHP, the excretion of all five analysed metabolites peaked after 4.7 h on average (T½ of 4.8 h), and metabolite levels ranged from 0.072 to 1.105 nmol/nmol/m3 between participants. No dermal uptake of particle phase D4-DEHP was observed. In conclusion, the average excreted levels of metabolites after combined inhalation and dermal exposure to D4-DEP was three times higher than after combined exposure to D4-DEHP; and nine times higher than after dermal exposure of D4-DEP. This study was made possible due to the use of novel approaches, i.e., the use of labelled phthalate esters to avoid the background concentration, and innovative technique of phthalate generation, both in the particle and the gas phase.

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Mehrsheikh, Mohammad E., Lane A. Clizbe, Harbhajan Singh, and Wr Purdum. "Syntheses of 14C-labelled monoacidic metabolites of dithiopyr." Journal of Labelled Compounds and Radiopharmaceuticals 29, no. 1 (January 1991): 9–13. http://dx.doi.org/10.1002/jlcr.2580290103.

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Bergin, Julie A., Ryan A. Bragg, Nick Bushby, John R. Harding, Angela Jordan, David A. Killick, and Claire L. Silcock. "Synthesis of isotopically labelled AZD3409 and its metabolites." Journal of Labelled Compounds and Radiopharmaceuticals 50, no. 5-6 (2007): 426–27. http://dx.doi.org/10.1002/jlcr.1175.

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Seidel, D., P. Brehmer, Y. Schoof, U. Weinberg, and M. Nowakowski. "Synthesis of [14C]-labelled vardenafil hydrochloride and metabolites." Journal of Labelled Compounds and Radiopharmaceuticals 46, no. 11 (2003): 1019–32. http://dx.doi.org/10.1002/jlcr.736.

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Dissertations / Theses on the topic "Labelled Metabolites"

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Hess, Jeremy P. "Synthesis of isotopically labeled substrates, lipid peroxidation products, and a novel metabolite, 2-(aminomethyl)malonate, for use in metabolic research." Case Western Reserve University School of Graduate Studies / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1586521864090244.

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Book chapters on the topic "Labelled Metabolites"

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Morris, P. G., R. S. Badar-Goffer, M. J. W. Prior, and H. S. Bachelard. "Proton Observation of 13C-Labelled Metabolites." In Magnetic Resonance Scanning and Epilepsy, 235–40. Boston, MA: Springer US, 1994. http://dx.doi.org/10.1007/978-1-4615-2546-2_43.

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Nakanishi, Tomoko M. "Visualization of 14C-labeled Gas Fixation in a Plant." In Novel Plant Imaging and Analysis, 169–89. Singapore: Springer Singapore, 2021. http://dx.doi.org/10.1007/978-981-33-4992-6_5.

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AbstractWe targeted not only the elements we can supply to the nutrient solution but also carbon dioxide gas to visualize the fixation process and the movement of assimilated carbon in a plant. This is another highlight of our study using real-time RI imaging systems (RRIS). The interesting result was that the route of assimilated carbon was different depending on where the fixation took place. In Arabidopsis, most of the metabolites after photosynthesis were transferred to the tip of the main internode and roots when 14CO2 gas was fixed and photosynthates were produced at rosette leaves, whereas most of the metabolites moved to the tip of the branch internode and hardly moved down to the roots when 14CO2 gas was supplied to the aboveground parts of the plant other than rosette leaves. Interestingly, it was possible to visualize and trace which tissue performed the fixation of 14CO2 gas, i.e., carbon could be traced from the fixation site in tissue to tissue formation. However, especially in the case of 14C imaging, image analysis should be carefully performed because of the self-absorption of the β-rays in tissue. To image 14CO2 gas fixation in larger samples, approximately 50 cm in height, a plastic scintillator was introduced, and the assimilation process of the gas was visualized for rice and maize.

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Vogel, G. "Purification of 125Iodine-Labeled Tyrosylated Human Parathyroid Hormone Fragment (Residues 44–68), Optimized by Reverse-Phase High-Performance Liquid Chromatography." In Calcium Regulating Hormones, Vitamin D Metabolites, and Cyclic AMP Assays and Their Clinical Application, 116–26. Berlin, Heidelberg: Springer Berlin Heidelberg, 1990. http://dx.doi.org/10.1007/978-3-662-00406-7_9.

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Ronald Lawrence, James, Gwendoline Joan Baxter, and John Robert Paterson. "Salicylic Acid Sans Aspirin in Animals and Man." In Drug Repurposing - Hypothesis, Molecular Aspects and Therapeutic Applications. IntechOpen, 2020. http://dx.doi.org/10.5772/intechopen.91706.

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Analyses in non-aspirin takers finding salicylic acid (SA) and hydroxylated metabolites in serum also SA and salicyluric acid (SU) in urine led to a re-evaluation of dietary sources of salicylates. Fruit and vegetable sources explained higher levels found in drug-free vegetarians, which overlapped with those from patients on low dose aspirin. That drug’s chemo-protective action in cancer is, at least partially, attributable to its principal metabolite, SA—which we believe contributes to the benefits of a vegetarian diet. However, diet is unlikely to be the sole source of the circulating salicylate found in aspirin-free animals and man. We adduced evidence for its persistence in prolonged fasting and biosynthesis in vivo from labelled benzoic acid. We review the roles, defined and potential, of SA in the biosphere. Emphasis on the antiplatelet effect of aspirin in man has detracted from the likely pivotal role of SA in many potential areas of bioregulation—probably as important in animals as in plants. In this expanding field, some aspirin effects, mediated by apparently conserved receptors responding to SA, are discussed. The perspectives revealed may lead to re-evaluation of the place of salicylates in therapeutics and potentially improve formulations and drug delivery systems.

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"Synthesis of Dietary Phenolic Metabolites and Isotopically Labeled Dietary Phenolics." In Flavonoids and Related Compounds, 253–300. CRC Press, 2012. http://dx.doi.org/10.1201/b11872-17.

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"SYNTHESES OF LABELED SIDE CHAINS OF VITAMIN D METABOLITES AND ANALOGS." In Vitamin D, 74–75. De Gruyter, 1988. http://dx.doi.org/10.1515/9783110846713.74.

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MANKOFF, DAVID A., MICHAEL M. GRAHAM, and ANTHONY F. SHIELDS. "A Graphical Method of Determining Tracer Influx Constants in the Presence of Labeled Metabolites." In Quantification of Brain Function Using PET, 312–16. Elsevier, 1996. http://dx.doi.org/10.1016/b978-012389760-2/50063-3.

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Antshel, Kevin M. "Cognitive and Behavioral Manifestations of Classical Galactosemia." In Cognitive and Behavioral Abnormalities of Pediatric Diseases. Oxford University Press, 2010. http://dx.doi.org/10.1093/oso/9780195342680.003.0040.

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An autosomal recessive group of disorders, galactosemia is caused by a deficiency of one of four enzymes: galactose mutarotase (GALM), galactokinase (GALK), galactose-1-phosphate uridyltransferase (GALT), and UDP-galactose epimerase (GALE) (Holton et al. 2001). Galactose-1-phosphate uridyltransferase deficiency is clearly the most prevalent of these four and is labeled classical galactosemia. All of the information provided in this chapter refers to classical galactosemia. These four enzymes metabolize galactose to glucose. Lacking one of these enzymes, galactose accumulates in individuals with galactosemia. Treatment involves a galactose-restricted diet and, with this diet, the normally high levels of galactose that are excreted in the urine return to normal (Jakobs et al. 1995). Endogenous production of galactose, however, amounting to 1 g/day in adults, has been suggested to be a major cause of the substantial disease morbidity (Schadewaldt et al. 2004). Thus, even with strict dietary elimination of galactose, the human body produces galactose endogenously. Also due to the GALT deficiency, galactose-1-phosphate cannot be further metabolized and begins to accumulate in red blood cells and other cells and tissues. Unlike the normalization of urinary galactose excretion, galactose-1-phosphate concentrations remain elevated even with dietary treatment relative to healthy comparison subjects (Holton et al. 2001). In addition, if untreated, significantly elevated concentrations of galactitol are detected in plasma, as well as in urine in individuals with galactosemia. With treatment, plasma galactitol and the urinary excretion of galactitol decrease, yet still remain above the upper limit of normal (Jakobs et al. 1995). Thus, the pathophysiology of galactosemia is manifold and involves elevations of galactose, galactose-1-phosphate, and galactitol. Screening for galactosemia is part of newborn screening programs in all 50 states and most countries worldwide. A positive screen will be followed up with measurement of galactose-1-phosphate uridyltransferase activity in red blood cells. If done before the fifth day of life, neonatal screening can prevent acute morbidity and mortality, yet does not change the long-term outcomes of significant disease morbidity (Schweitzer-Krantz 2003).

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Chowdhury, S. K., VS Gopaul, N. Blumenkrantz, R. Zhong, K. M. Kulmatycki, and K. B. Alton. "Chapter 11 Detection and characterization of highly polar metabolites by lc-ms: proper selection of lc column and use of stable isotope-labeled drug to study metabolism of ribavirin in rats." In Identification and Quantification of Drugs, Metabolites and Metabolizing Enzymes by LC-MS, 277–93. Elsevier, 2005. http://dx.doi.org/10.1016/s1464-3456(05)80013-4.

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Krawielitzki, E., R. Schadereit, and U. Herrmann. "Suitability of different ¹⁵N-labelled compounds as tracers for the labelling of organisms and for studies of protein- and amino acid metabolisms / Eignung verschiedener ¹⁵N-Verbindungen als Tracer für Körpermarkierung und für Untersuchungen des Protein- und Aminosäuremetabolismus." In August 1986, 262–69. De Gruyter, 1986. http://dx.doi.org/10.1515/9783112523360-002.

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Conference papers on the topic "Labelled Metabolites"

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Von Gerichten, Johanna, Annette Holland, Barbara Fielding, Elizabeth Miles, and Graham Burdge. "α-Linolenic acid metabolism in human CD3+ T cells favours oxylipin production over polyunsaturated fatty acid synthesis." In 2022 AOCS Annual Meeting & Expo. American Oil Chemists' Society (AOCS), 2022. http://dx.doi.org/10.21748/asgv6871.

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The essential dietary fatty acid α-linolenic acid (ALA) can be converted into anti-inflammatory 18 carbon oxylipins or into longer chain n€‘3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The partitioning of ALA between these alternative metabolic fates is not understood. To address this, peripheral blood CD3+ T cells from healthy volunteers (18-30 years; n=10) were cultured for 48h, with or without concanavalin A (10µg/ml) in 10% (v/v) pooled donor plasma with low ALA (20 µM) or high ALA (40 µM) concentrations (1:10 [13C]€‘labelled/unlabelled). [13C]ALA metabolites were detected either by GC-isotope ratio mass spectrometry for intracellular PUFA or by LC-MS/MS for oxylipins in cell culture supernatant. The ratio of the labelled metabolites hydroxyoctatrienoic acid ([13C]HOTrE) and dihydroxyoctadecaenoic acid ([13C]DiHODE) to [13C]ALA were 1.8±0.2 / 7.2±1.1 and 0.9±0.2 / 4.3±0.6 for low / high ALA, respectively, compared to the eicosatrienoic acid ([13C]20:3n€‘3) to [13C]ALA ratio of 0.002±0.0001 / 0.02±0.003 in stimulated T cells. Results from unstimulated cells were similar. Furthermore, oxylipins from all PUFA precursors were analysed in the culture supernatant of the T cells. The ratio of oxylipin concentrations in high compared to low ALA cultures was 1.4±0.1 for EPA-derived dihydroxyeicosatetraenoic acid (DiHETE), 5.6±0.9 for DHA-derived dihydroxydocosapentaenoic acid (DiHDPE), 7.9±2.7 for resolvin RvE1 and 2.0±0.3 for resolvin RvD1. The total oxylipin profile was not altered significantly by mitogen stimulation. These findings show that ALA is used primarily by T cells for constitutive production of anti-inflammatory lipid mediators rather than synthesis of longer chain PUFA. Further, ALA addition changes the secreted oxylipins towards a less-inflammatory profile. This has implications for understanding the effects of dietary PUFA on immune function.

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Setty, B. N. Y., M. Berger, and M. J. Stuart. "13-HYDROXY-9,11-OCTADECADIENOIC ACID (13-HOD) INCREASES PROSTACYCLIN PRODUCTION IN ENDOTHELIAL CELLS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643948.

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Recently, endothelial cells (ECs) have been shown to generate a potent vascular chemorepellant factor. This metabolite, 13-HOD is reported to be the major lipoxygenase product produced in microgram amounts in ECs (JBC 260:16056, 1985). We have studied the effect of 13-HOD on EC arachidonic acid (AA) metabolism, and report modulation of both AA release and conversion to prostacyclin. Using fetal bovine aortic ECs, 13-HOD stimulated prostacyclin production (RIA for 6KPGF1α ) by 40±13% (1SE), and 51±09% at 10 and 30μM (P<0.05; n=5). When the time-course of this effect was evaluated, 13-HOD (30μM) significantly enhanced the time-dependent release of 6KPGF1α by 31 to 51% between 5 and 120 min. (P<0.05 to 0.01; n=5). In [14C]AA labeled cells, this compound modulated both AA release and its subsequent conversion. In 5 paired experiments, 13-HOD (30μM) enhanced the release of AA from membrane phospholipids (9065±0553 cpm/well in controls vs 10738±1725 in 13-HOD treated cells; PC0.01). Analysis of cellular phospholipids revealed a significant decrease in [14C]phosphatidylethanolamine (62312±3963 cpm/well in controls vs 56959±4104 in 13-HOD treated cells; P<0.02). No significant changes were seen in the levels of phosphatidyl-choline, -serine, -inositol, or phosphatidic acid. Production of [14C]prostacyclin was stimulated by 56±16% (P<0.01 ), while total cyclooxygenase metabolites increased by 28±8% (P<0.01), suggesting effects on both cyclooxygenase and prostacyclin synthetase. 13-HOD, the major vascular product of linoleic acid enhances both AA release and metabolism, thus demonstrating an intimate hemostatic interaction between the metabolic products of these two polyunsaturated fatty acids in endothelial cells.

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Patscheke, H., K. Stegmeier, W. Hornberger, Ch Staiger, and G. Neugebauer. "INHIBITION OF PLATELET ACTIVATION BY THE NOVEL THROMBOXANE RECEPTOR ANTAGONIST BM 13.505." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643469.

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The effects of BM 13.505 (4-[2-(4-Chlorobenzenesulfonylami-no)ethyl]-benzene acetic acid = BM) on human washed platelets and platelet-rich plasma (PRP) were studied in vitro and after oral application in 10 male volunteers ex vivo/in vitro. BM inhibited the shape change, aggregation and (1H)serotonin release when the platelets were activated by agents that stimulate via the thromboxane Az/prostaglandin H2 (TXA2/PGH2) receptor. Such agonists were collagen, methyl mercury chloride (methyl-Hg), arachidonic acid and the PGH2 analogue U 46,619. BM was 9 times more potent an inhibitor than sulotroban (= BM 13.177). The slope of the Schild plot for U 46,619-induced shape change was close to unity, which is consistent with competitive antagonism. The pA2 -value in PRP was 6.5. BM did not inhibit the primary platelet activation induced by ADP, PAF or serotonin in aspirin-treated platelets, indicating that the inhibition by BM was specific for the platelet TXA2/PGH2 receptor. BM also suppressed platelet activation by PGH2 which accumulated when the platelets were stimulated by collagen, methyl-Hg or arachidonic acid in the presence of the thromboxane synthase inhibitor dazoxiben. At concentrations beyond about 600 times the apparent KD (200 μM in PRP and 10 μM in washed platelets), BM induced a transient shape change. This effect was inhibited by sulotroban and might indicate a slight intrinsic activity of BM. BM 10 μM exerted no effect on the formation of 14C-labelled TXB2, PGE2, PGD2, PGF2α , HHT and 12-HETE from 14C-labelled arachidonic in washed platelet suspensions, irrespective of whether exogenous or endogenous (by methyl-Hg mobilized) arachidonic acid was metabolized. Volunteers who received 7 oral doses of 400 mg in 12 hour intervals reached peak plasma concentrations between 9.5 and 45 pM 1 hour after dosage. The bleeding time was prolonged by 90 %. Platelet activation by collagen, methyl-Hg and U 46,619 was inhibited for at least 9 hours after a single dose. No objective and subjective side effects were observed in any of the subjects. Thus, BM 13.505 is a specific, we11-tolerated and long-acting TXA2/PGH2 receptor antagonist. (Supported by the DFG, Grant Pa-263).

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Maurice, D. H., and R. J. Haslam. "ROLES OF cAMP AND cGMP IN THE SYNERGISTIC INHIBITORY EFFECTS OF NITROVASODILATORS AND PGE1 ON PLATELET AGGREGATION AND DEGRANULATION." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644533.

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Washed rabbit platelets labelled with [14C]5-HT and suspended in a modified Tyrode’s solution were used in this study. Incubation of the platelets with 0.1, 1 and 10 μM sodium nitro-prusside (SNP) for 30 s inhibited aggregation induced by 10 nM platelet-activating factor by 7, 13 and 45% and the release of [14C]5-HT by 16, 30 and 45%, respectively. In combination with 0.02 μM PGE1, which had little effect alone (7% inhibitions), these concentrations of SNP caused 58, 90 and 100% inhibitions of aggregation and 60, 73 and 81% inhibitions of [14C]5-HT release. Thus, SNP and PGE1 acted synergisti-cally. The changes in [3H]cGMP and [3H]cAMP caused by these compounds were measured in platelets labelled by preincubation with [3H]guanine and [3H]adenine. [3H]cGMP (initially 0.01% of platelet [3H]GTP) increased by amounts equivalent to 0.02, 0.10 and 0.63% of [3H]GTP with 0.1, 1 and 10 μM SNP. PGE1 had no effects on platelet [3H]cGMP. The above SNP concentrations also increased [3H]cAMP by amounts equivalent to 0.01, 0.02 and 0.04% of platelet [3H]ATP (basal value 0.02%). However, in the presence of 0.02 μM PGE1, 0.1, 1 and 10 μM SNP increased [3H]cAMP by amounts equivalent to 0.13, 0.26 and 0.39% of platelet [3H]ATP. Both with and without PGE1, 10 μM SIN-1 (the active metabolite of molsidomine) had effects similar to those of 1 μM SNP. Thus, the synergistic actions of PGE-, and SNP or SIN-1 on platelet function correlated with increases in [3H]cAMP, not [3H]cGMP. Preincubation of the platelets for 30 s with 200 μM 2∲,5∲-dideoxy-adenosine (an inhibitor of adenylate cyclase) reduced the above increases in [3H]cAMP and inhibitions of platelet reactions by about 60%, without affecting [3H]cGMP levels. Addition of specific inhibitors of platelet cAMP phosphodiesterase (e.g. cilostamide) enhanced the actions of PGE1 in a manner similar to SNP but had little effect on the actions of SNP. The results show that the nitrovasodilators studied have effects on platelet function and [3H]cAMP similar to those of inhibitors of cAMP phosphodiesterase, suggesting that their actions may be mediated by increases in cAMP caused by an effect of cGMP on the platelet cGMP-inhibited cAMP phosphodiesterase. (HSFO Grant T443H)

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Reports on the topic "Labelled Metabolites"

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Borch, Thomas, Yitzhak Hadar, and Tamara Polubesova. Environmental fate of antiepileptic drugs and their metabolites: Biodegradation, complexation, and photodegradation. United States Department of Agriculture, January 2012. http://dx.doi.org/10.32747/2012.7597927.bard.

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Abstract:

Many pharmaceutical compounds are active at very low doses, and a portion of them regularly enters municipal sewage systems and wastewater-treatment plants following use, where they often do not fully degrade. Two such compounds, CBZ and LTG, have been detected in wastewater effluents, surface waters, drinking water, and irrigation water, where they pose a risk to the environment and the food supply. These compounds are expected to interact with organic matter in the environment, but little is known about the effect of such interactions on their environmental fate and transport. The original objectives of our research, as defined in the approved proposal, were to: Determine the rates, mechanisms and products of photodegradation of LTG, CBZ and selected metabolites in waters exposed to near UV light, and the influence of DOM type and binding processes on photodegradation. Determine the potential and pathways for biodegradation of LTG, CBZ and selected metabolites using a white rot fungus (Pleurotusostreatus) and ADP, and reveal the effect of DOM complexation on these processes. Reveal the major mechanisms of binding of LTG, CBZ and selected metabolites to DOM and soil in the presence of DOM, and evaluate the effect of this binding on their photodegradation and/or biodegradation. We determined that LTG undergoes relatively slow photodegradation when exposed to UV light, and that pH affects each of LTG’s ability to absorb UV light, the efficiency of the resulting reaction, and the identities of LTG’sphotoproducts (t½ = 230 to 500 h during summer at latitude 40 °N). We observed that LTG’sphotodegradation is enhanced in the presence of DOM, and hypothesized that LTG undergoes direct reactions with DOM components through nucleophilic substitution reactions. In combination, these data suggest that LTG’s fate and transport in surface waters are controlled by environmental conditions that vary with time and location, potentially affecting the environment and irrigation waters. We determined that P. ostreatusgrows faster in a rich liquid medium (glucose peptone) than on a natural lignocellulosic substrate (cotton stalks) under SSF conditions, but that the overall CBZ removal rate was similar in both media. Different and more varied transformation products formed in the solid state culture, and we hypothesized that CBZ degradation would proceed further when P. ostreatusand the ᵉⁿᶻʸᵐᵃᵗⁱᶜ ᵖʳᵒᶠⁱˡᵉ ʷᵉʳᵉ ᵗᵘⁿᵉᵈ ᵗᵒ ˡⁱᵍⁿⁱⁿ ᵈᵉᵍʳᵃᵈᵃᵗⁱᵒⁿ. ᵂᵉ ᵒᵇˢᵉʳᵛᵉᵈ ¹⁴C⁻Cᴼ2 ʳᵉˡᵉᵃˢᵉ ʷʰᵉⁿ ¹⁴C⁻ᶜᵃʳᵇᵒⁿʸˡ⁻ labeled CBZ was used as the substrate in the solid state culture (17.4% of the initial radioactivity after 63 days of incubation), but could not conclude that mineralization had occurred. In comparison, we determined that LTG does not degrade in agricultural soils irrigated with treated wastewater, but that P. ostreatusremoves up to 70% of LTG in a glucose peptone medium. We detected various metabolites, including N-oxides and glycosides, but are still working to determine the degradation pathway. In combination, these data suggest that P. ostreatuscould be an innovative and effective tool for CBZ and LTG remediation in the environment and in wastewater used for irrigation. In batch experiments, we determined that the sorption of LTG, CBZ and selected metabolites to agricultural soils was governed mainly by SOM levels. In lysimeter experiments, we also observed LTG and CBZ accumulation in top soil layers enriched with organic matter. However, we detected CBZ and one of its metabolites in rain-fed wheat previously irrigated with treated wastewater, suggesting that their sorption was reversible, and indicating the potential for plant uptake and leaching. Finally, we used macroscale analyses (including adsorption/desorption trials and resin-based separations) with molecular- level characterization by FT-ICR MS to demonstrate the adsorptive fractionation of DOM from composted biosolids by mineral soil. This suggests that changes in soil and organic matter types will influence the extent of LTG and CBZ sorption to agricultural soils, as well as the potential for plant uptake and leaching.

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