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Biomedical subjects

O Beck

Publications and source records attributed to O Beck.

At least 109 records · Page 6Linked to original sources

Measurement of 5-hydroxytryptophol and 5-hydroxyindoleacetic acid in human and rat brain and plasma.

The levels of 5-hydroxyindoleacetic acid (5-HIAA) and free and total 5-hydroxytryptophol (5-HTOL) in human and rat brain regions and plasma were determined by a specific capillary column gas chromatographic--mass spectrometric method. The human brains were obtained 2-3 hours post mortem, and the levels of 5-HIAA were in the range of 0.48-31.3 nmoles/g in the regions investigated. The levels of free and total 5-HTOL were 10.9-387 pmoles/g and 14.5-821 pmoles/g, respectively. The ratio of total 5-HTOL to 5-HIAA was in the range of 0.6-5.5%. In human plasma the levels of free and total 5-HTOL were 0.9 +/- 0.3 and 2.9 +/- 0.8 pmoles/ml +/- S.E.M., respectively. In regions of rat brain, the 5-HIAA levels ranged from 0.37-2.84 nmoles/g. Free and total 5-HTOL were in the range of 11.4-56.1 and 16.2-77.1 pmoles/g, respectively. The ratio of total 5-HTOL and 5-HIAA ranged from 2.3-5.1%. Higher levels of 5-HIAA and 5-HTOL occurred in the rat pineal gland. In rat plasma the levels of free and total 5-HTOL were 1.34 +/- 0.06 and 21.6 +/- 1.6 pmoles/ml +/- S.E.M., respectively.

Aged↗

5-hydroxytryptophol in human cerebrospinal fluid: conjugation, concentration gradient, relationship to 5-hydroxyindoleacetic acid, and influence of hereditary factors.

The serotonin metabolite 5-hydroxytryptophol was studied in human cerebrospinal fluid. A minor fraction (approximately 13%) was found in conjugated form from which it was liberated by treatment with sulphatase containing beta-glucuronidase activity. A concentration gradient of 5-hydroxytryptophol concentration was shown on lumbar tapping and the concentration in ventricular CSF was about 2.5 times higher than that in lumbar CSF. 5-Hydroxytryptophol and 5-hydroxyindoleacetic acid concentrations were significantly correlated in healthy, psychotic, and depressed subjects, but not in alcoholics. 5-Hydroxytryptophol concentrations in CSF of psychotic and depressed subjects were not different from those of healthy controls (4.22 pmol/ml +/- 0.15, SEM). In healthy subjects, hereditary factors seemed to have little influence on the CSF level of 5-hydroxytryptophol.

Adolescent↗

Occurrence of 6-hydroxy-1-methyl-1,2,3,4-tetrahydro-beta-carboline in tissues and body fluids of rat.

A capillary column gas chromatographic-mass spectrometric method was used to identify and quantitate 6-hydroxy-1-methyl-1,2,3,4-tetrahydro-beta-carboline (6OMTHBC) in rat. The excretion rate in urine was 0.73 +/- 0.20 nmoles per 24 hr and in faeces 0.18 +/- 0.03 nmoles per 24 hr. In urine, about 90% of the 6OMTHBC was in a conjugated form, whereas in faeces most (approximately 75%) of the 6OMTHBC was in a free form. The compound was detectable in liver (11.1 +/- 3.6 pmoles/g), kidney (2.1 +/- 0.9 pmoles/g) and plasma (0.52 +/- 0.15 pmoles/ml), but not in brain (less than 0.3 pmoles/g). When 6OMTHBC was injected to rats, 75% of the injected amount was excreted in urine during the first 10 hr. The plasma level of 6OMTHBC declined with a half-life of 1.5 hr.

Animals↗

Presence of formaldehyde in biological media and organic solvents: artifactual formation of tetrahydro-beta-carbolines.

A gas chromatography-mass spectrometry method is described for the identification and quantitation of 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline (6OHTHBC). During the analysis of 6OHTHBC in human platelets, the artifactual formation of 6OHTHBC was observed and shown to be due to the presence of formaldehyde in both organic solvents and in platelet homogenates. Formaldehyde was facilely removed from the organic solvent via a Pictet-Spengler reaction; however, removal from tissue homogenates was not possible by using conventional aldehyde-trapping agents. The solution of these problems and their consequences for persons attempting to establish the in vivo presence of tetrahydro-beta-carbolines or biochemically study tissue preparations are discussed.

Blood Platelets↗

Tryptophan levels in human cerebrospinal fluid after acute and chronic ethanol consumption.

The essential amino acid tryptophan was measured in human cerebrospinal fluid by a fluorometric high-performance liquid chromatographic method. Acute ethanol consumption (80 g) by healthy volunteers lead to a decrease in tryptophan levels during intoxication. After intoxication no difference from base levels was evident. Following ingestion of a higher dose (120 g) the mean levels of tryptophan remained unchanged. Alcoholics were found to have elevated tryptophan levels in the cerebrospinal fluid as compared to healthy subjects even after abstention from ethanol for several weeks.

Adolescent↗

Identification and measurement of 6-hydroxy-1-methyl-1,2,3,4-tetrahydro-beta-carboline by gas chromatography-mass spectrometry.

A glass capillary gas chromatographic-mass spectrometric method for the analysis of 6-hydroxy-1-methyl-1,2,3,4-tetrahydro-beta-carboline in urine, plasma and blood platelets was developed. The method involves the use of a deuterated analogue as internal standard, addition of semicarbazide, extraction with methylene chloride and formation of pentafluoropropionyl derivatives. The 6-hydroxy-1-methyl-1,2,3,4-tetrahydro-beta-carboline was found to occur in the urine of controls and alcoholics as both the free and conjugated compound. In the controls the mean level of free and conjugated 60MTHBC was 75 +/- 20 nmole/l. When intoxicated, the alcoholics had a statistically higher excretion rate of the conjugate(s) than the controls. The compound was not detectable in blood platelets or plasma.

Adult↗

5-hydroxytryptophol in the cerebrospinal fluid and urine of alcoholics and healthy subjects.

The serotonin metabolite 5-hydroxytryptophol was determined in cerebrospinal fluid and urine of alcoholics and healthy subjects, by a glass capillary gas chromatographic-mass spectrometric method. The urinary excretion rate (14.6 +/- 2.9 pmoles/mumoles creatinine) and urine (109 +/- 20 pmoles/ml) and cerebrospinal fluid (4.12 +/- 0.21 pmoles/ml) concentrations in healthy subjects were established. Only 1% of the 5-hydroxytryptophol in urine occurred in free form. Ethanol ingestion (80, 120 g) by healthy subjects lead to a 20--100-fold increase in the urinary excretion rate of 5-hydroxytryptophol. In cerebrospinal fluid the increase was about 60%. Alcoholics had increased urinary excretion rates and cerebrospinal fluid levels during intoxication, which were in the same range as in intoxicated healthy subjects. During recovery from intoxication, the 5-hydroxytryptophol level in alcoholics decreased, but the CSF levels were still higher than in healthy subjects.

Adult↗

Concentration of 5-methoxyindoles in the human pineal gland.

The pineal gland concentration of the four 5-methoxyindoles: melatonin, 5-methoxytryptamine, 5-methoxytryptophol and 5-methoxyindole-3-acetic acid, were measured by gas chromatography-mass spectrometry. The pineal glands were obtained from 11 subjects 2-3 hours post mortem. The concentration of 5-methoxytryptophol ranged from 4-93 pmoles/g, 5-methoxyindole-3-acetic acid from 79-560 pmoles/g and melatonin from 24-6860 pmoles/g. 5-methoxytryptamine was present only in trace amounts (0-12 pmoles/g). A variation over time of these compounds was not evident from the data obtained.

5-Methoxytryptamine↗

5-Methoxyindoles in pineal gland of cow, pig, sheep and rat.

The occurrence and concentration of the four 5-methoxyindoles: 5-methoxtryptamine, 5-methoxytryptophol, 5-methyoxyindole-3-acetic acid and melatonin in the pineal gland of pig, cow, sheep and rat was investigated. The analytical method involved the use of deuterated analogues as internal standards and capillary column gas chromatography - mass spectrometry. The analyses of pineal glands obtained during the morning hours revealed the presence of 5-methoxyindole-3-acetic acid and melatonin in nmoles/g and 5-methyoxytryptophol and 5-methoxytryptamine in pmoles/g amounts in pig, cow and sheep. In Wistar and Sprague-Dawley strain of rat, melatonin was present at a concentration of about 0.5 pmoles/pineal, a level which was elevated more than five times by treatment with a monoamine oxidase inhibitor. 5-Methoxytryptamine was found at a concentration of about 0.03 pmoles/pineal, and was elevated by monoamine oxidase inhibition.

5-Methoxytryptamine↗

In vivo formation of 5-methoxytryptamine from melatonin in rat.

Deacetylation of melatonin to 5-methoxytryptamine (5-MT) in vitro and in vivo was investigated in rat liver and brain tissue, using a gas chromatographic--mass spectrometric 5-MT assay method. In vitro incubation of liver but not brain (hypothalamic, Mesencephalic) slices with melatonin led to a concentration-dependent formation of small amounts of 5-MT; the conversion being 0.3--0.8%. In vivo administration of melatonin resulted in a dose-dependent formation of 5-MT in small quantities in the liver. The time course showed a peak maximum within 0.5 h, with a rapid decline; the half-life being about 1 h. 5-MT could be detected in both the blood and the hypothalamus after in vivo injection of melatonin. The time course of 5-MT in the blood was similar to that in the liver, but 5-MT could only be detected in the hypothalamus after large doses shortly after the melatonin injection. MAO had to be inhibited both in the in vitro and in vivo experiments in order to recover 5-MT, indicating that formed 5-MT is normally rapidly metabolised by MAO. It is concluded that a small fraction of melatonin can be converted to 5-MT by deacetylation (by aryl acylamidase) in the liver in vivo, constituting a minor pathway. Such a pathway could not be demonstrated in the brain. Trace amounts of 5-MT previously reported to be present in various tissues could originate from deacetylation of melatonin in the liver and possibly some other peripheral organs known to contain the deacetylating enzyme. The present results indicate that peripherally formed 5-MT, a psychoactive compound, is unlikely to have any effect on brain function under normal circumstances.

5-Methoxytryptamine↗

Concentration of serotonin metabolites in the cerebrospinal fluid from alcoholics before and during disulfiram therapy.

The levels of 5-hydroxytryptophol and 5-hydroxyindoleacetic acid were measured in the cerebrospinal fluid before and after one week of disulfiram treatment (400 mg/day) from ten male hospitalized alcoholic patients. The disulfiram treatment induced elevated (P less than 0.001) levels of 5-hydroxytryptophol. The levels were higher than in a control group, both before (P less than 0.01) and after (P less than 0.001) the treatment. No effects on the levels of 5-hydroxyindoleacetic acid were noted. The results indicate an altered serotonin metabolism in alcoholics, which is further potentiated by disulfiram treatment.

Alcoholism↗