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David Steed - One of the best experts on this subject based on the ideXlab platform.
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Values for Urinary Free Cortisol during Treatment with Amino-Glutethimide for Cushing’sSyndrome
2016Co-Authors: Karl W. Schmitt, James Hanlon, Roger Juselius, Ph. D, David SteedAbstract:Of the chemical tests used, we found that values for urinary free cortisol had the best clinical correla-tion and were the most sensitive indicator of cortisol secretion in a patient with Gushing’s syndrome who was treated with amino-Glutethimide. Amino-Glutethimide (“Elipten”) may be used to suppress adrenal function of patients with Cushing’s syndrome who are poor surgical risks. Associated with amino-Glutethimide therapy for Cushing’s syndrome is the problem of which test(s) to use in helping assess treatment. Plasma cortisol, cortisol secretion rate, urinary 17-hydroxycorticoste-roids, urinary 17-ketogenic steroids, and urinary 17-ketosteroids have been discussed in the literature, and all have their limitations (1-3). The determi-nation of urinary free cortisol to follow a patient’s progress has not been previously investigated. The present report discusses the usefulness of various tests, including urinary free cortisol, in a patient with Cushing’s syndrome during amino-Glutethimide therapy. Materials and Methods Urinary 17-OHCS2 and 17-KS were determined by modifications of the Porter-Silber (4) and Zimmer-mann (5) procedures, respectively, PC by the fluoro-metric method of Mattingly (6), and UFC by a mod-ification of the method of Beardwell et al. (7). The modified procedure for UFC included a car-bon tetrachloride pre-extraction and the use of a Flo-risil slurry-dispensing bottle, shaker, and crushed ice-water bath for temperature control to obtain greater precision, thus facilitating definition of a hy
Karl W. Schmitt - One of the best experts on this subject based on the ideXlab platform.
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Values for Urinary Free Cortisol during Treatment with Amino-Glutethimide for Cushing’sSyndrome
2016Co-Authors: Karl W. Schmitt, James Hanlon, Roger Juselius, Ph. D, David SteedAbstract:Of the chemical tests used, we found that values for urinary free cortisol had the best clinical correla-tion and were the most sensitive indicator of cortisol secretion in a patient with Gushing’s syndrome who was treated with amino-Glutethimide. Amino-Glutethimide (“Elipten”) may be used to suppress adrenal function of patients with Cushing’s syndrome who are poor surgical risks. Associated with amino-Glutethimide therapy for Cushing’s syndrome is the problem of which test(s) to use in helping assess treatment. Plasma cortisol, cortisol secretion rate, urinary 17-hydroxycorticoste-roids, urinary 17-ketogenic steroids, and urinary 17-ketosteroids have been discussed in the literature, and all have their limitations (1-3). The determi-nation of urinary free cortisol to follow a patient’s progress has not been previously investigated. The present report discusses the usefulness of various tests, including urinary free cortisol, in a patient with Cushing’s syndrome during amino-Glutethimide therapy. Materials and Methods Urinary 17-OHCS2 and 17-KS were determined by modifications of the Porter-Silber (4) and Zimmer-mann (5) procedures, respectively, PC by the fluoro-metric method of Mattingly (6), and UFC by a mod-ification of the method of Beardwell et al. (7). The modified procedure for UFC included a car-bon tetrachloride pre-extraction and the use of a Flo-risil slurry-dispensing bottle, shaker, and crushed ice-water bath for temperature control to obtain greater precision, thus facilitating definition of a hy
Herbert L. Bonkovsky - One of the best experts on this subject based on the ideXlab platform.
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Synergistic induction of δ-aminolevulinate synthase by Glutethimide and iron: relationship to the synergistic induction of heme oxygenase
Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1991Co-Authors: Edward Earl Cable, John F. Healey, Yvonne J. Greene, Chheng-orn Evans, Herbert L. BonkovskyAbstract:Abstract Relationships between activities of δ-aminolevulinate synthase and heme oxygenase, respectively the rate-limiting enzymes of heme biosynthesis and degradation, have been studied in chick embryo liver cell cultures following exposure of the cultures to Glutethimide and iron, a combination known to produce a synergistic induction of both enzymes. In time-course experiments, synergistic induction of heme oxygenase activity by Glutethimide and iron preceded that of δ-aminolevulinate synthase by 4 h. Effects of selective inhibitors of both heme synthesis and degradation have also been studied with respect to effects on δ-aminolevulinate synthase and heme oxygenase activities. The synergistic induction of heme oxygenase by Glutethimide and iron appears to be dependent upon cellular heme synthesis because addition of inhibitors of heme biosynthesis, 4,6-dioxoheptanoic acid or N-methylmesoporphyrin abolishes this synergistic induction. Exposure of cultures to tin-mesoporphyrin, a potent inhibitor of heme oxygenase, prevented the synergistic induction of δ-aminolevulinate synthase produced by Glutethimide and iron, or, when added after induction was already established, promptly halted any further induction. These results suggest that the level of activity of heme oxygenase can reciprocally modulate intracellular heme levels and thus activity of δ-aminolevulinate synthase.
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Mechanism of synergistic induction of hepatic heme oxygenase by Glutethimide and iron: Studies in cultured chick embryo liver cells
Biochemical and Biophysical Research Communications, 1990Co-Authors: Edward Earl Cable, John F. Healey, Yvonne J. Greene, Chheng-orn Evans, Herbert L. BonkovskyAbstract:Heme oxygenase, the rate controlling enzyme for heme catabolism, is inducible by a variety of treatments, some of which induce by a heme-dependent mechanism and others by a heme-independent mechanism. This work shows that, in cultured chick embryo liver cells, synergistic induction of heme oxygenase by iron, added with the phenobarbital-like drug, Glutethimide was heme-dependent. Addition of an inhibitor of heme biosynthesis abolished the synergistic induction of heme oxygenase providing evidence for the heme-dependent mechanism of induction. Glutethimide and iron appeared to induce at the transcriptional level since both heme oxygenase mRNA and protein levels correlate with changes in heme oxygenase activity.
H M Schiebel - One of the best experts on this subject based on the ideXlab platform.
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Investigation of the stereoselective in vitro biotransformation of Glutethimide by high-performance liquid chromatography and capillary electrophoresis.
Journal of chromatography. B Biomedical sciences and applications, 1997Co-Authors: C Weinz, G Blaschke, H M SchiebelAbstract:Due to our interest in drugs with a glutarimide structure, we reinvestigated the stereoselectivity of the in vitro biotransformation of the chiral hypnotic-sedative drug Glutethimide. Glutethimide enantiomers were separated on a preparative scale by HPLC on cellulose tris(4-methylbenzoate) as chiral stationary phase. The enantiomeric purity was higher than 99%. A reversed-phase HPLC method was developed to determine the metabolites of Glutethimide. After incubations with rat liver microsomes both enantiomers formed 5-hydroxyGlutethimide as the main metabolite, as well as additional metabolites, of which some were formed stereoselectively. Mass spectrometry of the unknown metabolites indicated a hydroxylation in the ethyl side chain for two of the metabolites. A third metabolite was tentatively identified as desethylGlutethimide.
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Investigation of the stereoselective in vitro biotransformation of Glutethimide by high-performance liquid chromatography and capillary electrophoresis
Journal of Chromatography B: Biomedical Sciences and Applications, 1997Co-Authors: C Weinz, G Blaschke, H M SchiebelAbstract:Abstract Due to our interest in drugs with a glutarimide structure, we reinvestigated the stereoselectivity of the in vitro biotransformation of the chiral hypnotic-sedative drug Glutethimide. Glutethimide enantiomers were separated on a preparative scale by HPLC on cellulose tris(4-methylbenzoate) as chiral stationary phase. The enantiometric purity was higher than 99%. A reversed-phase HPLC method was developed to determine the metabolites of Glutethimide. After incubations with rat liver microsomes both enantiomers formed 5-hydroxyGlutethimide as the main metabolite, as well as additional metabolites, of which some were formed stereoselectivity. Mass spectrometry of the unknown metabolites indicated a hydroxylation in the ethyl side chain for two of the metabolites. A third metabolite was tentatively identified as desethylgutethimide.
Krzysztof Bajdor - One of the best experts on this subject based on the ideXlab platform.
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Vibrational spectroscopy of Glutethimide—from isolated molecule to solid state
Journal of Molecular Structure, 1999Co-Authors: Krzysztof Bajdor, Magdalena Glice, Andrzej Leś, Ludwik Adamowicz, Robert KołosAbstract:Abstract The IR and Raman spectra of Glutethimide (3-ethyl-3-phenyl-2,6-piperidinedione) were obtained for both monomers and dimers in solution and matrix environment. The IR and Raman spectra were also obtained for the crystalline Glutethimide. The spectral assignments were made based on quantum chemical theoretical calculations with the use of RHF and DFT methods and using isotopically labelled derivatives. The Raman spectra seem to be of limited use to study the intermolecular interactions of cyclic imides. The dominant species in diluted solutions of CCl 4 , CS 2 and CHCl 3 solutions were the Glutethimide monomers. The dimer formation appeared at higher concentration about 0.2% in CCl 4 and CS 2 and 1% in CHCl 3 . In CH 3 CN solution no dimers were formed. The band corresponding to the ν (N–H) stretching vibration was selected as a diagnostic band reflecting hydrogen bonding interactions of Glutethimide with the solution, matrix and crystalline environment.
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vibrational spectroscopy of Glutethimide from isolated molecule to solid state
Journal of Molecular Structure, 1999Co-Authors: Krzysztof Bajdor, Magdalena Glice, Andrzej Leś, Ludwik Adamowicz, Robert KolosAbstract:Abstract The IR and Raman spectra of Glutethimide (3-ethyl-3-phenyl-2,6-piperidinedione) were obtained for both monomers and dimers in solution and matrix environment. The IR and Raman spectra were also obtained for the crystalline Glutethimide. The spectral assignments were made based on quantum chemical theoretical calculations with the use of RHF and DFT methods and using isotopically labelled derivatives. The Raman spectra seem to be of limited use to study the intermolecular interactions of cyclic imides. The dominant species in diluted solutions of CCl 4 , CS 2 and CHCl 3 solutions were the Glutethimide monomers. The dimer formation appeared at higher concentration about 0.2% in CCl 4 and CS 2 and 1% in CHCl 3 . In CH 3 CN solution no dimers were formed. The band corresponding to the ν (N–H) stretching vibration was selected as a diagnostic band reflecting hydrogen bonding interactions of Glutethimide with the solution, matrix and crystalline environment.