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Biomedical subjects

J Adline

Publications and source records attributed to J Adline.

8 recordsLinked to original sources
PubMed1997

Accumulation of manganese in the brain of mice after intravenous injection of manganese-based contrast agents.

Because the manganese-based contrast agents used in magnetic, resonance imaging are unstable in vivo, some concern exists about the potential toxicity coming from the Mn2+ released by the complexes. This potential problem arises because the manganese is known to accumulate in the brain of people intoxicated by this metal (manganism): this central accumulation leads to neurological disorders (i.e., parkinsonism-like syndrome). The aim of this study was to assess the amount of Mn found in the brain after administration of MnCl2 or different chelates of Mn in normal mice as well as in mice with impaired biliary elimination. Male NMRI mice received an intravenous injection in a caudal vein of 5 mumol/kg of 54Mn compounds as MnCl2, manganese-diethylenetriaminepentaacetate (Mn-DTPA), or manganese-dipyridoxal diphosphate (Mn-DPDP). The radiolabeled complexes (1:1) were prepared by direct chelation (Mn-DTPA) or transchelation of preformed complex (Mn-DPDP), and the radiochemical purity was assessed by paper chromatography. The mice were killed at various times post-exposure (0-3 months), and the radioactivity present in the organs was determined by gamma counting. For each compound analyzed in the present study, we observed an accumulation of Mn (0.25-0.3% of the amount injected/g of tissue) in the mouse brain, reaching a plateau after 24 h, while the Mn content in the liver was decreasing with time. The amount of Mn accumulated in the brain remained unchanged 1 month later, but decreased to 40% of the maximum amount 3 months after the exposure. In mice whose bile ducts had been ligated 24 h before the administration of the manganese compound, we observed, 1 week after the injection, an amount of manganese accumulated in the brain 2 times higher than in normal mice.

Animals↗
PubMed1996

The uptake of Mn-DPDP by hepatocytes is not mediated by the facilitated transport of pyridoxine.

Manganese-dipyridoxal diphosphate (Mn-DPDP) is a liver-selective contrast agent selectively taken up by the hepatocytes. Because of the analogy of structure with pyridoxine (vitamin B6), it was previously suggested that this compound can be selectively taken up by the facilitated transport of vitamers B6. To understand the uptake mechanism, an in vivo binding study was performed based on a competition between 54Mn-DPDP and pyridoxine on the one hand, and Mn-DPDP and [3H]pyridoxine on the other. We found that the [3H]pyridoxine levels in the liver were not significantly different 5 min after intravenous administration of several doses of Mn-DPDP (5 nmol/kg to 50 mumol/kg): 5.0 +/- 0.3% of the injected dose/g tissue. The content of 54Mn (administered as 54Mn-DPDP) in the liver was not affected by a saturation dose of pyridoxine (1 mmol/kg) and was found to be constant (+/- 10% of the injected dose/g tissue) for 60 min. These experiments showed that the uptake of Mn-DPDP is not mediated by the transporter of pyridoxine.

Animals↗
PubMed1988

Rapid and precise micro-methods for quantitating active components in commercial bone scintigraphy kits--II. Diphosphonates.

Two parallel, independent micro-methods for diphosphonate determination are presented. These procedures are based on the interference of diphosphonate with the formation of cation-morin (3,5,7,2',4'-pentahydroxyflavone) complexes. In the spectrophotometric method, a change of the absorbance of thorium-morin complex is used as a measure of diphosphonate concentration. In the fluorimetric method, a decrease of the fluorescence of aluminium-morin complex is used. Both methods: (1) quantitate methylene-diphosphonate in the range of 5-40 x 10(-9) M with a coefficient of variation of less than 1%; (2) are specific and interference-free in commercial kits control; (3) are operative with other diphosphonates; and (4) are adaptable to the analysis of chromatographic eluents.

Bone and Bones↗
PubMed1979

Stereochemical aspects of the metabolism of 5-(4'-fluorophenyl)-5-phenylhydantoin in the rat.

Racemic 5-(4'-fluorophenyl)-5-phenylhydantoin was synthesized to examine its metabolism in rat. This compound differs from the antiepileptic agent 5,5-diphenylhydantoin in that the normal site of hydroxylation in 5,5-diphenylhydantoin is blocked on one of the phenyl groups by a fluorine atom. The 4'-fluoro analogue gives a major metabolite, which was isolated and identified as (R)-(-)-5-(4'-fluorophenyl)-5-(4'-hydroxyphenyl)hydantoin of 37% enantiomeric purity. The absolute configuration and enantiomeric purity of the metabolite was determined by chemical conversion to (S)-(-)-5-(4'-hydroxyphenyl)-5-phenylhydantoin. A second metabolite of the catechol type, possibly as a mixture of 5-(3',4'-dihydroxyphenyl)-5-(4'-fluorophenyl)hydantoin, and the corresponding O-3'-methyl derivative was detected by gas chromatography-mass spectrometry after methylation.

Animals↗
PubMedDate not supplied

Evidence for an arene oxide-NIH shift pathway in the metabolic conversion of phenytoin to 5-(4-hydroxyphenyl)-5-phenylhydantoin in the rat and in man.

To determine whether the hydroxylation of 5,5-diphenylhydantoin (DPH) to 5-(4-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) occurs by an arene oxide-NIH shift process, racemic 5-(4-deuteriophenyl)-5-phenylhydantoin (p-2H-DPH) was subjected to in vivo metabolic experiments in the rat and in man. After enzymatic hydrolysis of the urine, para-hydroxylated metabolites were separated by HPLC. Deuterium retention in the isolated metabolites determined by gas chromatography-mass spectrometry, was 68-72%. The results are interpreted as the predominance of an arene oxide-NIH shift pathway in those two metabolic systems. Induction of rats with phenobarbital or 3-methylcholanthrene showed no effect on the value of deuterium retention.

Adult↗
PubMedDate not supplied

Evidence for an arene-3,4-oxide as a metabolic intermediate in the meta- and para-hydroxylation of phenytoin in the dog.

To investigate the potential involvement of an arene oxide-NIH shift pathway in the meta- and para-hydroxylation of phenytoin, (R,S)-5-(2-deuteriophenyl)-5-phenylhydantoin (2-2H-DPH), (R,S)-5-(3-deuteriophenyl)-5-phenylhydantoin (3-2H-DPH), and (R,S)-5-(4-deuteriophenyl)-5-phenylhydantoin (4-2H-DPH) were subjected to in vivo metabolic experiments in the dog. After enzymatic hydrolysis of the urine, meta- and para-hydroxy metabolites were isolated by HPLC and deuterium retentions were determined by GC/MS. The metahydroxy metabolites had 100, 52, and 80-82% retained of their initial deuterium content after oral administration of (R,S)-2-, 3-, and 4-2H-DPH, respectively. Similarly, in the case of the para-hydroxy metabolites, the percentages of deuterium retained were 100, 92, and 71-72%. These results exclude the intermediacy of a DPH-2,3-oxide in the production of meta-hydroxy metabolites but are consistent with the existence of DPH-3,4-oxide as intermediate in the production of both meta- and para-hydroxy metabolites. The stereoselectivity of the meta- and para-hydroxylation has been determined by GC/MS analyses of the urinary metabolites after administration of (R)-5-(3-deuteriophenyl)-5-phenylhydantoin [(R)-3-2H-DPH], and the measurements are in agreement with previous determinations in the literature obtained by optical methods. The overall results of 2H retention are compared with those obtained in the rabbit, rat, and man.

Animals↗