Author
C. Allievi
Bio: C. Allievi is an academic researcher. The author has contributed to research in topics: Urine & Excretion. The author has an hindex of 4, co-authored 5 publications receiving 95 citations.
Topics: Urine, Excretion, Mass spectrometry, Thromboxane-A synthase, Thermospray
Papers
More filters
TL;DR: The absence of salsolinol in the urine of one subject after Madopar administration seems to indicate that the biological system(s) involved in the reduction of the C = N bond in 1,2-dehydrosalsol can be missing or not, or poorly, functional in some individuals, and suggests that there is no alternative pathway for the formation of salolinol for healthy volunteers.
Abstract: The R enantiomer of salsolinol was detected in the urine of two out of six healthy subjects, whereas 1,2-dehydrosalsolinol was present in the urine of all the subjects. (S)-salsolinol was never detected. Administration of Madopar for 7 days resulted in the presence of large amounts of (R)- and (S)-salsolinol in the urine of five out of the six subjects, the urinary excretion of 1,2-dehydrosalsolinol being generally not markedly increased.
65 citations
TL;DR: In this article, a high performance liquid chromatographic mass spectrometric method with thermospray ionization for the determination of concentrations of exemestane (6-methylenandrosta-1,4-diene-3,17-dione, FCE 24304) in human plasma has been developed.
Abstract: A high performance liquid chromatographic mass spectrometric method with thermospray ionization for the determination of concentrations of exemestane (6-methylenandrosta-1,4-diene-3,17-dione, FCE 24304) in human plasma has been developed. The sensitivity of the method allowed the determination of exemestane concentrations as low as 1 ng ml−1. A suitable internal standard was used for quantification. The intra-day precision (relative standard deviation, R.S.D.) ranged from 16.3% near to the lower limit of quantification to 0.3% close to the upper end of the calibration graph. The mean accuracy of the method was found to be 97.8% (R.S.D.=7%). Unlike a previously developed gas chromatographic/mass spectrometic method, the new method proved to be suitable for the determination of unchanged drug plasma levels in exemestane-treated subjects.
15 citations
TL;DR: Milacemide appears to be the first non-polyamine xenobiotic in the metabolism of which PAO participates, and two FAD-dependent amine-oxidizing enzymes, MAO and PAO, contribute to the metabolism.
Abstract: 1. It has previously been established that monoamine oxidase (MAO)-B participates in the metabolism of milacemide [2-(pentylamino)acetamide]. Furthermore, in rats, inhibition of FAD-dependent polyamine oxidase (PAO) was found to decrease the urinary excretion of two milacemide metabolites, termed UK1 and UK2. 2. Using gas chromatography-mass spectrometry, UK1 was identified as oxamic acid and UK2 as 2-hydroxyacetamide, confirming that PAO is involved in the metabolism of milacemide. 3. Thus, two FAD-dependent amine-oxidizing enzymes, MAO and PAO, contribute to the metabolism of milacemide. Milacemide appears to be the first non-polyamine xenobiotic in the metabolism of which PAO participates.
9 citations
TL;DR: The urine concentrations of free salsolinol were determined in six healthy volunteers, using a gas chromatographic-mass spectrometric method with electron-capture negative-ion chemical ionization after derivatization with pentafluoropropionyl anhydride.
7 citations
Journal Article•
TL;DR: The metabolites of 5,6-dihydro-7-(1H-imidazol-1-yl)-naphthalene-2-carboxylic acid, FCE 22178, were investigated in urine of rats and healthy volunteers after a single oral dose of 10 mg/kg and 400 mg, respectively, of the tritium-labeled drug as discussed by the authors.
Abstract: The metabolites of 5,6-dihydro-7-(1H-imidazol-1-yl)-naphthalene-2-carboxylic acid, FCE 22178, a new thromboxane synthase inhibitor, were investigated in urine of rats and healthy volunteers after a single oral dose of 10 mg/kg and 400 mg, respectively, of the tritium-labeled drug. Cumulative urinary excretion of radioactivity after 4 days amounted to 64.6% and 91.0% of the dose in rat and humans, respectively. Urinary fractions of 0-24 hr, accounting for 61.8% and 79.5% of the dose, were analyzed by radio-HPLC with direct injection. Following incubation with beta-glucuronidase both in the presence and absence of saccharo-1,4-beta-lactone, a specific inhibitor of this enzyme, a metabolite was identified as a glucuronoconjugate of FCE 22178. The recovery of the glucuronide in the rat and man amounted to approximately 30% and almost 100% of urinary radioactivity, respectively. Control incubations showed a complete deglucuronidation in the case of rat urine compared with less than 10% in human urine. Addition of saccharo-1,4-beta-lactone abolished this phenomenon, suggesting the presence of an endogenous beta-glucuronidase in rat urine. Further identification of the only metabolite present in human urine by tandem MS analysis confirmed the structure of the acyl glucuronide of FCE 22178.
2 citations
Cited by
More filters
TL;DR: Interestingly, even long-term inactivation of PAO did not provoke behavioral changes in experimental animals, despite considerable changes in polyamine metabolism, however, PAO inactivation improves the growth-inhibitory effects of inhibitors of polyamine biosynthetic enzymes and the antitumoral effects of some structural analogs of the polyamines.
Abstract: Polyamine oxidase (PAO) is a FAD-dependent enzyme with a molecular mass of about 62 kDa, present with high activity in most tissues of vertebrates Structural requirements of a substrate for PAO are two positively charged amino groups, separated by a short carbon chain and an alkyl substituent on one or both nitrogen atoms Spermine and the monoacetyl derivatives N1-acetylspermine and N1-acetylspermidine appear to be the natural substrates Spermidine is only poorly oxidized by PAO Using O2, the substrates are oxidatively cleaved by PAO to form equimolar amounts of an amine, an aldehyde and hydrogen peroxide PAO is an integral part of the polyamine interconversion cycle, a major intracellular regulatory system, which contributes to the maintenance of polyamine homeostasis in non-proliferating cells, including brain cells Selective inactivators were used as tools in the elucidation of the functions of PAO Interestingly, even long-term inactivation of PAO did not provoke behavioral changes in experimental animals, despite considerable changes in polyamine metabolism PAO inactivation, however, improves the growth-inhibitory effects of inhibitors of polyamine biosynthetic enzymes and the antitumoral effects of some structural analogs of the polyamines
133 citations
TL;DR: The isolation and characterization of a novel enzyme, which enantio-selectively synthesizes (R)salsolinol from dopamine and acetaldehyde is reported, and the possible function of this enzyme under physiological and pathological conditions in the brain is discussed.
130 citations
TL;DR: The results demonstrate the selective cytotoxicity of NM(R)Sal to the dopamine neurons in the substantia nigra, and the possible involvement of this 6,7-dihydroxy-isoquinoline in the pathogenesis of Parkinson's disease is discussed.
122 citations
TL;DR: Apoptosis induced by inhibitors of mitochondrial complex I is probably mediated by permeability pore opening and collapse of the mitochondrial membrane potential, and this observation may allow the development of novel neuroprotective strategies in disorders that may involve mitochondrial dysfunction and apoptotic cell death.
114 citations
TL;DR: Dopamine and structurally related catecholamines in the presence of hydrogen peroxide are oxidized in vitro by xanthine oxidase producing the corresponding melanin pigments, and the kinetic parameters of the reaction are calculated.
109 citations