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Biomedical subjects

O Beck

Publications and source records attributed to O Beck.

At least 91 records · Page 5Linked to original sources
PubMed1990

Immunological screening of benzodiazepines in urine: improved detection of oxazepam intake.

Immunological screening analysis of benzodiazepines in urine using the EMIT (enzyme multipled immuno-technique) and FPIA (fluorescence polarization immunoassay) techniques does not reliably detect the intake of therapeutic doses of oxazepam. In 23 patient urine samples, in which the presence of oxazepam could be verified chromatographically, only about 50% were detected as positive in the immunoassay systems. However, when the screening procedure was modified to include a simple step of hydrolysis of urine using the enzyme beta-glucuronidase to liberate conjugated oxazepam, improved detection of oxazepam intake was achieved. With EMIT 95% and with FPIA 100% of the samples were detected as positive. Since oxazepam arises in vivo also as a metabolite of other common benzodiazepines, the modification will most likely contribute to the generally improved detection of benzodiazepines.

Adult↗
PubMed1990

Monitoring of plasma methadone: intercorrelation between immunoassay and gas chromatography-mass spectrometry.

Determination of plasma methadone is essential in connection with dose adjustments for patients participating in methadone maintenance programs. We successfully adapted the existing fluorescence polarization immunoassay (FPIA) kit intended for urinary methadone to plasma assays. A concentration interval of 50-900 ng/ml could be covered. The coefficient of variation was less than 7%, and the limit of detection below 50 ng/ml. The intercorrelation between the immunoassay and a specific gas chromatographic-mass spectrometric (GC-MS) method was studied in samples from 19 heroin addicts in methadone maintenance treatment. A total number of 97 plasma samples with a concentration range of 31-842 ng/ml were used. The slope and intercept of the regression line (CFPIA = 0.93 X CGC-MS + 15) was in good agreement with the theoretical relation (CFPIA = CGC-MS), with a coefficient of correlation of 0.978. The mean ratio, in quantitative result, between the techniques (CFPIA/CGC-MS) was 1.03 +/- 0.01 (SEM). We conclude that the immunoassay proposed in this study can be safely used in patients participating in methadone maintenance programs.

Adult↗
PubMed1988

In vitro study of the aromatic hydroxylation of 1-methyltetrahydro-beta-carboline (methtryptoline) in rat.

The incubation of 1-methyltetrahydro-beta-carboline (1-MeTHBC) with hepatocytes isolated from 3-methylcholanthrene-treated rats led to formation of the 5-, 6- and 7-hydroxylated products. The hydroxylating activity was associated with the microsomal fraction as indicated by testing different subcellular fractions. The highest activity for hydroxylating 1-MeTHBC was found in liver which was about ten times as active as lung. Only a trace amount of hydroxylating activity was present in brain and kidney tissue. Analysis using chiral gas chromatography revealed an unequal abundance of enantiomers in all three products. The formation of the 5-, 6- and 7-hydroxylated products was confirmed in vivo by analysis of 24 h urine samples after intraperitoneal administration of 1-MeTHBC to 3-methylcholanthrene-treated rats.

Animals↗
PubMed1987

5-Hydroxytryptophol and 5-hydroxyindoleacetic acid levels in rat brain: effects of various drugs affecting serotonergic transmitter mechanisms.

The effect of various pharmacological treatments on the levels of free and total 5-hydroxytryptophol (5-HTOL) and 5-hydroxyindoleacetic acid (5-HIAA) in rat brain were investigated using a gas chromatographic-mass spectrometric technique. The disappearance of 5-HTOL following monoamine oxidase (MAO) inhibition induced by pargyline was more rapid (t1/2 10-15 min) than that of 5-HIAA (t1/2 30-40 min) in all regions investigated, indicating a rapid turnover of 5-HTOL. The selective MAO-A inhibitor chlorgyline produced a more pronounced reduction of 5-HTOL than of 5-HIAA, while the MAO-B inhibitor deprenyl was without effect on both serotonin metabolites. The MAO-A inhibitor amiflamine which is selective for serotonin neurons, was also more effective in reducing free 5-HTOL levels than of 5-HIAA levels, suggesting that the formation of 5-HTOL is closely associated with serotonin neurons. Neonatal treatment with the serotonin neurotoxin 5, 7-dihydroxytryptamine (5,7-HT) led to a more pronounced reduction of 5-HTOL levels in cerebral cortex than that of 5-HIAA levels, while the increase of 5-HTOL levels in pons-medulla was more marked than of 5-HIAA levels. Probenecid treatment increased several fold both conjugated 5-HTOL and 5-HIAA levels in brain tissue. An increase was also noted for free 5-HTOL, although of less magnitude. Treatment with the serotonin receptor active agents methiothepin and d-lysergic acid diethylamide produced similar alterations of free 5-HTOL and 5-HIAA. The present results have demonstrated that free 5-HTOL has a rapid turnover in rat brain and that free 5-HTOL levels may serve as a useful index for serotonin turnover.

Animals↗
PubMed1987

Serotonin condensation product 5-hydroxymethtryptoline: evidence for in vivo formation from acetaldehyde during intoxication using deuterium labelled ethanol.

Trideuterated 5-hydroxymethtryptoline was found in the urine of rats treated with trideuterated ethanol. The combined treatment with disulfiram lead to a more than 10-fold increase in the excretion rate. The chiral analysis revealed unequal abundance of enantiomers suggesting the involvement of a stereoselective (enzymatic) mechanism in the formation 5-hydroxymethtryptoline during ethanol intoxication.

Acetaldehyde↗
PubMed1986

6-Hydroxymethtryptoline is naturally occurring in mammalian urine: identification by combined chiral capillary gas chromatography and high resolution mass spectrometry.

The tricyclic indole derivative 6-hydroxymethtryptoline (7-hydroxy-1-methyltetrahydro-beta-carboline) was identified as a normal constituent of human and cat urine. The identification was based on the correct retention time on a chiral capillary gas chromatographic column and on selected ion monitoring of the molecular ion with the mass spectrometer set at high resolving power (RP 10,000). The quantitation utilized a 13C-labeled analog as internal standard and demonstrated levels of 135 +/- 35 and 174 +/- 42 (pmol ml-1, mean +/- SEM) for the S(-) and R(+) enantiomers, respectively, in human urine. In cat urine, the levels were 203 +/- 55 and 108 +/- 44 (pmol ml-1, mean +/- SEM) for the S(-) and R(+) enantiomers, respectively. In human urine, the compound occurred predominantly in a conjugated form while in cat urine the free compound predominated. It was concluded that 6-hydroxymethtryptoline is naturally occurring in mammalian urine and that it most likely constitutes a metabolite of endogenous methtryptoline (1-methyltetrahydro-beta-carboline).

Adult↗
PubMed1986

Rapid hydroxylation of methtryptoline (1-methyltetrahydro-beta-carboline) in rat: identification of metabolites by chiral gas chromatography-mass spectrometry.

Racemic methtryptoline (1-methyltetrahydro-beta-carboline) and 5-hydroxymethtryptoline-9-carboxylic acid (6-hydroxy-1-methyltetrahydro-beta-carboline-1-carboxylic acid) were administered intraperitoneally to rats and the components of their urine was subsequently investigated by chiral gas chromatography-mass spectrometry. Methtryptoline rapidly became hydroxylated in the 5- and 6-position and excreted in urine. There was about a ninefold predominance of the S(-) enantiomer over the other in the 5-hydroxylated species, while the 6-hydroxylation produced a small excess of the R(+) enantiomer. About 75% of the injected dose of methtryptoline was recovered in the urine as 5- and 6-hydroxylated compounds during the first 24 h period, demonstrating that hydroxylation represents the major metabolic pathway. Treatment with 6-hydroxymethtryptoline-9-carboxylic acid led to a fivefold increase in the urinary excretion of 5-hydroxymethtryptoline during the first 24 h period with a predominance of the S(-)-enantiomer, indicating a much smaller conversion rate than from methtryptoline. It was concluded that hydroxylation of methtryptoline is a likely pathway for the natural formation of 5-hydroxymethtryptoline.

Animals↗
PubMed1986

5-Hydroxyindoleacetic acid and 5-hydroxytryptophol levels in rat brain: effects of ethanol, pyrazole, cyanamide and disulfiram treatment.

The two serotonin metabolites 5-hydroxyindoleacetic acid (5HIAA) and 5-hydroxytryptophol (5HTOL) were measured in two regions of rat brain (pons medulla and diencephalon) using a gas chromatographic-mass spectrometric (GC-MS) method. Acute ethanol intoxication effected an elevation of 5-hydroxytryptophol levels, while 1 week of treatment with ethanol appeared to have no effect on either metabolite when measured 24 h after the last dose. Disulfiram and cyanamide treatment produced an approximately 2-fold increase in 5-hydroxytryptophol and a slight reduction in 5-hydroxyindole-acetic acid. Pyrazole treatment produced an increase in both metabolites. This effect was, however, counteracted by the simultaneous administration of ethanol.

Animals↗
PubMed1985

Isolation and characterization of substance P, substance P 5-11, and substance K from two metastatic ileal carcinoids.

Using an antiserum directed at the COOH-terminus of tachykinins, we have examined postmortem tissue from two cases of metastatic ileal carcinoid for the presence of tachykinin-like immunoreactivity. The vast majority of the immunoreactive tachykinin-like material eluted from a Sephadex G-50 column as two peaks at positions corresponding to molecular weights of 1300 and 850. The 1300 dalton peak was resolved by reverse-phase-HPLC into two components which by Edman sequencing, amino acid analysis, and fast atom bombardment (FAB)-mass spectrometry criteria, were identified as substance P and substance K. The 850 dalton peak was also resolved on RP-HPLC into two peaks which were resistant to Edman degradation but from amino acid analysis and FAB-mass spectrometry criteria were identified as pyro-Glu-substance P 5-11 and oxidized pyro-Glu-substance P 5-11. In control experiments substance P 5-11 was converted to pyro-Glu-substance P 5-11 during the extraction procedure. Both tumors also contained a minor immunoreactive peak which eluted from a Sephadex G-50 sizing column at a position corresponding to a molecular weight of 4000 which probably represents neuropeptide K. These results suggest that beta-preprotachykinin is preferentially expressed in carcinoid tumors and that substance K may also play a role in the carcinoid syndrome.

Amino Acid Sequence↗
PubMed1985

Extractive acylation and mass spectrometric assay of 3-methoxytyramine, normetanephrine, and metanephrine in cerebrospinal fluid.

The chemical analysis of 3-methoxytyramine, normetanephrine, and metanephrine in tissues, blood, and cerebrospinal fluid is complicated by the low levels in which they occur and the amphoteric nature of the functional groups, which hampers their isolation from aqueous media. In the present report, we describe a practical and simple method for the routine isolation and derivatization of 3-methoxytyramine, normetanephrine, and metanephrine in high yield from aqueous samples like cerebrospinal fluid. The metabolites are simultaneously derivatized with pentafluoropropionic anhydride and extracted into an organic solvent. After further treatment with pentafluoropropionic anhydride under anhydrous conditions, the samples are ready for GC/MS analysis. The method is able to exploit the theoretical maximal sensitivity available in the electron capture negative-ion chemical ionization mode without any apparent losses during extraction and derivatization, giving limits of detection in the low picogram range. Mean levels of free 3-methoxytyramine, normetanephrine, and metanephrine in human cerebrospinal fluid were 3.77, 5.20, and 0.40 pmol/ml. Assay of pools of squirrel monkey, human, and canine cerebrospinal fluid with and without previous enzymatic hydrolysis demonstrated that the three metabolites occur predominantly in a conjugated form.

Acylation↗
PubMed1984

Analysis of melatonin, 5-methoxytryptophol and 5-methoxyindoleacetic acid in the pineal gland and retina of hamster by capillary column gas chromatography-mass spectrometry.

A specific capillary column gas chromatographic-mass spectrometric method was used to determine 5-methoxyindoles in the pineal gland and retina of the golden hamster during a light-dark (14:10) cycle. In the pineal gland, the mean levels of melatonin ranged from 0.15 to 2.4 pmol per gland, with a maximum in the dark. The levels of 5-methoxytryptophol and 5-methoxyindoleacetic acid were in the same range, but peaked during light. In the retina the levels of melatonin were about 100 pmol/g, and seemed not to differ between light and dark. The level of 5-methoxyindoleacetic acid were in the same range during light but were below the detection limit during dark.

Animals↗
PubMed1984

Identification of melatonin in the compound eyes of an insect, the locust (Locusta migratoria), by radioimmunoassay and gas chromatography-mass spectrometry.

Melatonin, a well-known pineal substance implicated in conveying photoperiodic information in vertebrates, appears also to be present in the compound eyes of an insect, the locust. The identification of melatonin in the eyes of an invertebrate suggests that it may be an evolutionary conservative molecule, principally involved in the time transduction of photoperiodic information in all living organisms.

Animals↗