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  • 1
    Digitale Medien
    Digitale Medien
    s.l. : American Chemical Society
    Journal of medicinal chemistry 35 (1992), S. 3705-3713 
    ISSN: 1520-4804
    Quelle: ACS Legacy Archives
    Thema: Chemie und Pharmazie
    Materialart: Digitale Medien
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  • 2
    ISSN: 1520-6882
    Quelle: ACS Legacy Archives
    Thema: Chemie und Pharmazie
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1471-4159
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: An endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol, was found to induce apoptosis in human dopaminergic SH-SY5Y cells by step-wise activation of apoptotic cascade; collapse in mitochondrial membrane potential, ΔΨm, activation of caspases, and fragmentation of DNA. Recently, accumulation of gylceraldehyde-3-phosphate dehydrogenase (GAPDH) in nuclei was proposed to play an important role in apoptosis. In this paper, involvement of GAPDH in apoptosis induced by N-methyl(R)salsolinol was studied. The isoquinoline reduced ΔΨm within 3 h, as detected by a fluorescence indicator, JC-1, then after 16 h incubation, GAPDH accumulated in nuclei by detection with immunostaining. To clarify the role of GAPDH in apoptotic process, a stable cell line of Bcl-2 overexpressed SH-SY5Y cells was established. Overexpression of Bcl-2 prevented the decline in ΔΨm and also apoptotic DNA damage induced by N-methyl(R)salsolinol. In Bcl-2 transfected cells, nuclear translocation of GAPDH was also completely suppressed. In addition, a novel antiparkinsonian drug, rasagiline, prevented nuclear accumulation of GAPDH induced by N-methyl(R)salsolinol in control cells. These results suggest that GAPDH may accumulate in nuclei as a consequence of signal transduction, which is antagonized by anti-apoptotic Bcl-2 protein family and rasagiline. The results are discussed in concern to intracellular mechanism underlying anti-apoptotic function of rasagiline analogues.
    Materialart: Digitale Medien
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  • 4
    ISSN: 1573-6903
    Schlagwort(e): Brofaromine ; bulimia nervosa ; melatonin, biogenic amine ; acid metabolites
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Brofaromine, a selective and reversible inhibitor of monoamine oxidase-A (MAO-A) was given to 19 women while 17 received placebo for 8 weeks. All met DSM III-R criteria for bulimia nervosa, a psychiatric disorder in which uncontrolled overeating episodes are accompanied by purging activities and extreme concerns about body shape and weight. The following indices were measured: plasma and urinary phenylacetic acid (PAA), homovanillic acid (HVA), vanillylmandellic acid (VMA); plasma tryptamine (T), β phenylethylamine (PE), and 5-hydroxyindoleacetic acid (5-HIAA) and urinary 6-sulphatoxymelatonin (aMT6s). PE levels remained the same but T showed a trend toward elevation over time. Twenty-four hour levels of urinary aMT6s in BN patients were higher at week 4 when compared to baseline and week 8. There was a significant reduction in plasma VMA and HVA over time during treatment with brofaromine and both plasma HVA and VMA were significantly lower for the brofaromine group compared to placebo at week 4. Plasma 5-HIAA was significantly higher for the brofaromine group after 8 weeks when compared to placebo. Urinary VMA decreased significantly from baseline to week 4 with a partial elevation at 8 weeks. Urinary VMA was also significantly lower in patients on brofaromine at week 4. This study verifies that brofaromine complies with predicted MAO-A inhibiting patterns in a clinical population.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Neurochemical research 2 (1977), S. 495-506 
    ISSN: 1573-6903
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Through use of the high-resolution double-focusing mass spectrometer, copper has been identified in various regions of the mouse, rat, guinea pig, rabbit, and human brain. The procedure depends on converting the copper (in ashed tissue) to its chloride salt, followed by derivatization with tetraphenylporphyrin (TPP) to yield a TPP chelate. After chromatographic separation, this chelate is assessed in the mass spectrometer by the integrated-ion-current procedure. Deuterated metal TPP chelates and the rare stable isotope65Cu were used as internal standards. Whole brain values obtained were as follows: mouse, 6.67±0.16 (mean±SEM) μg/g wet weight of tissue; rat, 1.06±0.05; guinea pig, 5.40±0.63; and rabbit, 7.52±0.76. In the rat, the cerebellum contained the highest concentration (1.25 μg/g), and the striatum the lowest (0.70 μg/g). In the human brain, the cortex (gray) and the striatum were relatively the highest copper-containing regions, with the cerebellum (white) being the lowest.
    Materialart: Digitale Medien
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  • 6
    ISSN: 1573-4919
    Schlagwort(e): cardiac ; sarcoplasmic reticulum ; phospholamban ; calcium transport ; protein kinase ; phosphatase
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie , Medizin
    Notizen: Abstract The calcium transport mechanism of cardiac sarcoplasmic reticulum (SR) is regulated by a phosphoregulatory mechanism involving the phosphorylation-dephosphorylation of an integral membrane component, termed phospholamban. Phospholamban, a 27,000 Da proteolipid, contains phosphorylation sites for three independent protein kinases: 1) cAMP-dependent, 2) Ca2+-calmodulin-dependent, and 3) Ca2+-phospholipid-dependent. Phosphorylation of phospholamban by any one of these kinases is associated with stimulation of the calcium transport rates in isolated SR vesicles. Dephosphorylation of phosphorylated phospholamban results in the reversal of the stimulatory effects produced by the protein kinases. Studies conducted on perfused hearts have shown that during exposure to beta-adrenergic agents, a good correlation exists between the in situ phosphorylation of phospholamban and the relaxation of the left ventricle. Phosphorylation of phospholamban in situ is also associated with stimulation of calcium transport rates by cardiac SR, similar to in vitro findings. Removal of beta-adrenergic agents results in the reversal of the inotropic response and this is associated with dephosphorylation of phospholamban. These findings indicate that a phospho-regulatory mechanism involving phospholamban may provide at least one of the controls for regulation of the contractile properties of the myocardium.
    Materialart: Digitale Medien
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  • 7
    Digitale Medien
    Digitale Medien
    Chichester : Wiley-Blackwell
    Biological Mass Spectrometry 14 (1987), S. 207-211 
    ISSN: 0887-6134
    Schlagwort(e): Chemistry ; Analytical Chemistry and Spectroscopy
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: Eight normal subjects ingested 125 mg of p-tyramine-β,β-2H2 hydrochloride and the 3 h and following 21 h urine collections were analysed by mass spectrometry with selected ion monitoring for the deuterated metabolites: free and conjugated p-tyramine-β,β-2H2, free p-octopamine-β-2H1, free and conjugated p-hydroxyphenylacetic acid-α-2H1 and -α,α-2H2, and free p-hydroxymandelic acid-α-2H1. These metabolites accounted for 72% of the ingested label, of which conjugated p-tyramine and free p-hydroxyphenylacetic acid constituted 90%. Approximately 50% of the total deuterated tyramine and 70% of the total deuterated p-hydroxyphenylacetic acid were excreted in the first three hours, although there was considerable variation between individuals. The presence of a small amount of p-hydroxyphenylacetic acid-α-2H1 suggests that some exchange of deuterium occurred at the intermediate p-hydrophenylacetaldehyde stage.These results, based as they are on metabolites labelled with the stable isotope deuterium, ought to be more reliable than earlier studies in which unlabelled tyramine was ingested with the resultant metabolites, indistinguishable from their endogenous metabolic counterparts, being measured by fluorimetry or gas chromatography.
    Zusätzliches Material: 1 Ill.
    Materialart: Digitale Medien
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  • 8
    ISSN: 0887-6134
    Schlagwort(e): Chemistry ; Analytical Chemistry and Spectroscopy
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: The gas chromatographic and mass spectrometric properties of the methyl, trifluorethyl, pentafluoropropyl and hexafluoroisopropyl esters of the pentafluoropropionyl and heptafluorobutyryl derivatives of twelve important acidic metabolites of biogenic amines have been investigated. The optimum derivatization conditions for the different classes of metabolites have been established and the byproducts formed in some of the derivatizations have been identified. Under certain derivatizing conditions, back-exchange of deuterium in the labelled internal standards was observed. No single derivative appears to be ideally suitable for the simultaneous quantitative analysis by GC/MS of all twelve metabolites, so extracts of plasma and urine were split and a combination of the methyl or trifluoroethyl esters of the pentafluoropropionyl derivatives were used.
    Zusätzliches Material: 2 Ill.
    Materialart: Digitale Medien
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  • 9
    ISSN: 1052-9306
    Schlagwort(e): Chemistry ; Analytical Chemistry and Spectroscopy
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: An ultrasensitive method capable of detection and quantification of β-phenylethylamine in 1 ml of human plasma has been developed using gas chromatography/electron capture negative ion mass spectrometry. Phenylethylamine and tetra-deutero phenylethylamine internal standard in plasma were acetylated, extracted into organic solvent and then further acylated with pentafluorobenzoyl chloride. The N-acetyl-N-pentafluorobenzoyl-phenylethylamines were detected by high-resolution single ion monitoring of the molecular ions. Normal plasma levels were found to be 41.5 ± 10.7 pg ml-1, in accordance with results of a previous high-performance liquid chromatographic method.
    Zusätzliches Material: 5 Ill.
    Materialart: Digitale Medien
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  • 10
    Digitale Medien
    Digitale Medien
    Chichester : Wiley-Blackwell
    Biological Mass Spectrometry 6 (1979), S. 149-156 
    ISSN: 0306-042X
    Schlagwort(e): Chemistry ; Analytical Chemistry and Spectroscopy
    Quelle: Wiley InterScience Backfile Collection 1832-2000
    Thema: Chemie und Pharmazie
    Notizen: The 5-dimethyl-, diethyl-, dibutyl-, and dipentyl-aminonaphthalene-1-sulfonyl (dansyl, ethansyl, propansyl, bansyl and pentansyl resectively) derivatives of tyramine and other biogenic amines were prepared and their mass spectra recoded. The relative intensity of the largest unique ion increased with increasing length of the alkyl group. Several O-alkyl-N-propansyl- and N,O-dialkyl-N-propansyl-, bansyl- and pentansyl-tyramines were also synthesized and their mass spectra recorded. Dimethylbansyl- and dimethylpentansyltyramines exhibited the largest unique ions in their mass spectra and the greatest sensitivity in quantitation by the integrated ion current method. Procedures for preparing these derivatives in amounts ranging from nanograms to milligrams are presented and their thin-layer chromatographic behavior in three solvent systems is described.
    Zusätzliches Material: 5 Ill.
    Materialart: Digitale Medien
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