The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform
Lance S. Terada - One of the best experts on this subject based on the ideXlab platform.
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suppression of rabbit myocardial xanthine dehydrogenase activity by an Endogenous Compound
Journal of Molecular and Cellular Cardiology, 1994Co-Authors: Lance S. TeradaAbstract:Xanthine dehydrogenase (XDH) is an important precursor to the oxygen radical producing enzyme xanthine oxidase (XO). We found that the apparent activity of rabbit myocardial XDH increased from 2 ± 1 to 50 ± 3 μU/g (P<0.05) following extraction of tissue homogenate with butanol. Further studies suggested that the basis for this observation was a high molecular weight Compound which consumes the XDH cofactor, NAD+. Addition of myocardial homogenate to exogenous NAD+ resulted in depletion of NAD+ and concomitant formation of an additional Compound (peak A). Both NAD+ consumption and peak A formation were abrogated by prior extraction of homogenate with butanol. Separation of myocardial homogenate by Sephadex chromatography revealed a high molecular weight Compound which suppressed activity of purified milk XDH but not xanthine oxidase (XO). This activity co-eluted with the ability of myocardial homogenate to consume added NAD+ and form peak A. The NAD+-consuming activity was heat and acid-labile. In addition, nicotinamide was both a product and an inhibitor of the NADase activity, consistent with the existence of a previously described myocardial glycohydrolase. Extraction of tissue with butanol may be necessary to detect low levels of XDH activity in vitro.
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Suppression of Rabbit Myocardial Xanthine Dehydrogenase Activity by an Endogenous Compound
Journal of molecular and cellular cardiology, 1994Co-Authors: Lance S. TeradaAbstract:Xanthine dehydrogenase (XDH) is an important precursor to the oxygen radical producing enzyme xanthine oxidase (XO). We found that the apparent activity of rabbit myocardial XDH increased from 2 ± 1 to 50 ± 3 μU/g (P
Benjamin F Cravatt - One of the best experts on this subject based on the ideXlab platform.
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an Endogenous sleep inducing Compound is a novel competitive inhibitor of fatty acid amide hydrolase
Bioorganic & Medicinal Chemistry Letters, 1998Co-Authors: Matthew P Patricelli, Dale L Boger, Jean E Patterson, Benjamin F CravattAbstract:Abstract 2-Octyl γ-bromoacetoacetate (OγBr), an Endogenous Compound originally isolated from human cerebrospinal fluid (CSF), has previously been demonstrated to increase REM sleep duration in cats. Based on the chemical structure of OγBr and its reported sleep-inducing effects, we synthesized OγBr along with chemically related analogs and tested these Compounds as inhibitors of fatty acid amide hydrolase (FAAH), a brain enzyme that degrades neuromodulatory fatty acid amides. OγBr was found to competitively inhibit FAAH activity with IC 50 and K i values of 2.6 μM and 0.8 μM, respectively [for the ( R )-enantiomer of OγBr ( 1 )]. A set of synthetic analogs of OγBr was examined to define the structural features required for FAAH inhibition and inhibitor potencies were assessed at pH 9.0 (near the pH optimum of FAAH) and pH 7.0. Interestingly, at pH 7.0 the γ-halo β-keto ester inhibitors proved to be significantly more potent than the trifluoromethyl ketone of oleic acid, one of the most potent FAAH inhibitors described to date. This study supports the possibility that OγBr may be a physiological regulator of FAAH activity and fatty acid amide levels in vivo. Additionally, the characterization of γ-halo β-keto esters as powerful FAAH inhibitors near physiological pH may aid in future studies of the enzymology and biological properties of FAAH.
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structure determination of an Endogenous sleep inducing lipid cis 9 octadecenamide oleamide a synthetic approach to the chemical analysis of trace quantities of a natural product
Journal of the American Chemical Society, 1996Co-Authors: Benjamin F Cravatt, Richard A Lerner, Dale L BogerAbstract:The pursuit of Endogenous sleep-inducing substances has been the focus of an extensive, complicated body of research. Several Compounds, including Δ-sleep-inducing peptide and prostaglandin D2, have been suggested to play a role in sleep induction, and yet, the molecular mechanisms of this physiological process remain largely unknown. In recent efforts, the cerebrospinal fluid of sleep-deprived cats was analyzed in search of Compounds that accumulated during sleep deprivation. An agent with the chemical formula C18H35NO was found to cycle with sleep−wake patterns, increasing in concentration with sleep deprivation and decreasing in amount upon recovery sleep. Since the material was generated in minute quantities and only under the special conditions of sleep deprivation, efforts to isolate sufficient material for adequate characterization, structure identification, and subsequent detailed evaluation of its properties proved unrealistic. With the trace amounts of the impure Endogenous Compound available, e...
D Guinta - One of the best experts on this subject based on the ideXlab platform.
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sodium oxybate reduces pain fatigue and sleep disturbance and improves functionality in fibromyalgia results from a 14 week randomized double blind placebo controlled study
Pain, 2011Co-Authors: Jon I Russell, Andrew J Holman, Todd J Swick, Sarah Alvarezhorine, Grace Y Wang, D GuintaAbstract:Abstract This 14-week, phase 3, double-blind, randomized, controlled trial evaluated sodium oxybate (SXB) 4.5 and 6 g per night versus placebo in patients with fibromyalgia (FM). SXB is the sodium salt of γ-hydroxybutyrate (GHB). GHB is an Endogenous Compound, synthesized from γ-aminobutyric acid (GABA) and found broadly in the central nervous system and body. Among 548 randomized patients, a ⩾30% reduction in pain was experienced by 54.2% and 58.5% of patients treated with SXB 4.5 and 6 g, respectively, versus 35.2% for placebo with a 100-mm Visual Analog Scale (VAS) ( P P P P = 0.003 and P = 0.001 for 4.5 and 6 g per night, respectively). On the Short-Form 36 Health Survey, SXB-related improvement was significant on the Physical, but not the Mental, Component Scale. The proportion of patients who reported a global improvement of “much” or “very much” better on the Patient Global Impression of Change was significantly greater in both SXB groups versus placebo ( P
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sodium oxybate reduces pain fatigue and sleep disturbance and improves functionality in fibromyalgia results from a 14 week randomized double blind placebo controlled study
Pain, 2011Co-Authors: Jon I Russell, Andrew J Holman, Todd J Swick, Sarah Alvarezhorine, Grace Y Wang, D GuintaAbstract:This 14-week, phase 3, double-blind, randomized, controlled trial evaluated sodium oxybate (SXB) 4.5 and 6g per night versus placebo in patients with fibromyalgia (FM). SXB is the sodium salt of γ-hydroxybutyrate (GHB). GHB is an Endogenous Compound, synthesized from γ-aminobutyric acid (GABA) and found broadly in the central nervous system and body. Among 548 randomized patients, a ≥30% reduction in pain was experienced by 54.2% and 58.5% of patients treated with SXB 4.5 and 6g, respectively, versus 35.2% for placebo with a 100-mm Visual Analog Scale (VAS) (P<0.001 for both comparisons). Relative to placebo, both SXB doses significantly reduced fatigue (with a 100-mm VAS; P<0.001) and sleep disturbance (with the Jenkins Sleep Scale; P<0.001), and resulted in significant improvements in function as measured by the FM Impact Questionnaire (P=0.003 and P=0.001 for 4.5 and 6 g per night, respectively). On the Short-Form 36 Health Survey, SXB-related improvement was significant on the Physical, but not the Mental, Component Scale. The proportion of patients who reported a global improvement of "much" or "very much" better on the Patient Global Impression of Change was significantly greater in both SXB groups versus placebo (P<0.001). Headache, nausea, dizziness, vomiting, diarrhea, anxiety, and sinusitis were the most commonly reported adverse events, with an incidence at least twice that of placebo. These results expand the evidence from previous clinical trials suggesting that SXB is effective and safe in FM.
Andrés H. Thomas - One of the best experts on this subject based on the ideXlab platform.
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Photochemical formation of a fluorescent thymidine-pterin adduct in DNA
Dyes and Pigments, 2019Co-Authors: Sandra Estébanez, Carolina Lorente, Maira Gaspar Tosato, Miguel A. Miranda, M. Luisa Marin, Virginie Lhiaubet-vallet, Andrés H. ThomasAbstract:Abstract The photochemistry of the DNA biomacromolecule is an issue of paramount importance as it is part of the etiology of skin cancer development, being ultraviolet sunlight radiation the most relevant environmental carcinogen. Herein, we demonstrate the potential of pterin, an Endogenous Compound, to form covalent adduct under UVA irradiation with a short thymine oligomer as well as with the whole DNA polymer. Our approach is based on the spectroscopic features of pterin, which allow, by monitoring specific absorption or emission wavelengths, the following-up of the covalent binding. The results are confirmed by HPLC coupled with mass spectrometry, revealing the attachment of one or two pterin units to the homothymine 5-mer oligonucleotide. Altogether the findings point toward the role of pterin as Endogenous sensitizer and genotoxic Compound.
Dale L Boger - One of the best experts on this subject based on the ideXlab platform.
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an Endogenous sleep inducing Compound is a novel competitive inhibitor of fatty acid amide hydrolase
Bioorganic & Medicinal Chemistry Letters, 1998Co-Authors: Matthew P Patricelli, Dale L Boger, Jean E Patterson, Benjamin F CravattAbstract:Abstract 2-Octyl γ-bromoacetoacetate (OγBr), an Endogenous Compound originally isolated from human cerebrospinal fluid (CSF), has previously been demonstrated to increase REM sleep duration in cats. Based on the chemical structure of OγBr and its reported sleep-inducing effects, we synthesized OγBr along with chemically related analogs and tested these Compounds as inhibitors of fatty acid amide hydrolase (FAAH), a brain enzyme that degrades neuromodulatory fatty acid amides. OγBr was found to competitively inhibit FAAH activity with IC 50 and K i values of 2.6 μM and 0.8 μM, respectively [for the ( R )-enantiomer of OγBr ( 1 )]. A set of synthetic analogs of OγBr was examined to define the structural features required for FAAH inhibition and inhibitor potencies were assessed at pH 9.0 (near the pH optimum of FAAH) and pH 7.0. Interestingly, at pH 7.0 the γ-halo β-keto ester inhibitors proved to be significantly more potent than the trifluoromethyl ketone of oleic acid, one of the most potent FAAH inhibitors described to date. This study supports the possibility that OγBr may be a physiological regulator of FAAH activity and fatty acid amide levels in vivo. Additionally, the characterization of γ-halo β-keto esters as powerful FAAH inhibitors near physiological pH may aid in future studies of the enzymology and biological properties of FAAH.
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structure determination of an Endogenous sleep inducing lipid cis 9 octadecenamide oleamide a synthetic approach to the chemical analysis of trace quantities of a natural product
Journal of the American Chemical Society, 1996Co-Authors: Benjamin F Cravatt, Richard A Lerner, Dale L BogerAbstract:The pursuit of Endogenous sleep-inducing substances has been the focus of an extensive, complicated body of research. Several Compounds, including Δ-sleep-inducing peptide and prostaglandin D2, have been suggested to play a role in sleep induction, and yet, the molecular mechanisms of this physiological process remain largely unknown. In recent efforts, the cerebrospinal fluid of sleep-deprived cats was analyzed in search of Compounds that accumulated during sleep deprivation. An agent with the chemical formula C18H35NO was found to cycle with sleep−wake patterns, increasing in concentration with sleep deprivation and decreasing in amount upon recovery sleep. Since the material was generated in minute quantities and only under the special conditions of sleep deprivation, efforts to isolate sufficient material for adequate characterization, structure identification, and subsequent detailed evaluation of its properties proved unrealistic. With the trace amounts of the impure Endogenous Compound available, e...