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Biomedical subjects

E Jellum

Publications and source records attributed to E Jellum.

At least 109 records · Page 6Linked to original sources

Urinary metabolites of chloroprocaine studied by combined gas chromatography--mass spectrometry.

The purpose of this study was to identify the metabolic pathway of 2-chloro-4-aminobenzoic acid (CABA), a primary metabolite of chloroprocaine. Urine was collected from 4 healthy, pregnant women following the epidural administration of 600 mg chloroprocaine. The urinary metabolites were extracted with ether and identified and quantitatively estimated with a gas chromatography--mass spectrometry instrument. The analysis showed that CABA is converted to N-acetyl-CABA and subsequently excreted in the urine.

Anesthetics, Local↗

The cerebral lesions in a patient with generalized glutathione deficiency and pyroglutamic aciduria (5-oxoprolinuria).

The clinical and pathologic features of a male patient with generalized glutathione deficiency and pyroglutamic aciduria are presented. The patient died at the age of 28 years. He was mentally retarded from infancy and developed progressive tremor, retardation of movement, and ataxia as from the age of 16. Neuropathologic examination of the brain disclosed a selective atrophy of the granule cell layer of the cerebellum and focal lesions in the visual cortex and the thalamus. The type and distribution of the lesions resembled those seen after mercury intoxication. However, in our patient the damage was probably caused by the lack of protection of glutathione against oxidative damage in the brain. Possible treatment of this rare metabolic disorder might include external supply of an antioxidant, e.g., a thiol capable of penetrating the blood brain barrier.

Adult↗

Biochemical composition of suction blister fluid determined by high resolution multicomponent analysis (capillary gas chromatography--mass spectrometry and two-dimensional electrophoresis).

The biochemical composition of blister fluid was compared with serum and with blister fluid from erythematous lesions induced by ultraviolet irradiation. By using glass capillary gas chromatography--mass spectrometry over 100 metabolites were determined and with the aid of two-dimensional high resolution electrophoresis (the ISO-DALT system) several hundred protein spots were seen. The results show that the suction blister fluid qualitatively have a serum-like pattern but that the concentration of each compound was smaller than in serum. Also in suction blisters raised on erythematous reactions induced by ultraviolet light the same pattern was seen. The content of sodium, potassium and chloride was the same in suction blisters raised on erythematous and normal skin as that of serum.

Blister↗

Fate of the gold and the thiomalate part after intramuscular administration of aurothiomalate to mice.

Double isotope-labelled aurothiomalate (195Au-14C-thiomalate) has been administered to mice, and the excretory fate and tissue distribution have been studied. The results show that the gold and the thiomalate separate in vivo resulting in protein-bound gold and release of free thiomalate. About half of this thiol is excreted in the urine during the first day, and the remaining half is bound to tissue membranes and cells. Although thiomalate penetrates cellular membranes slowly in vitro. the compound is found in all organs, mostly in the liver and the kidneys, after administration of aurothiomalate. Separation of the gold moiety from its thiol carrier also takes place in man. This explains the finding of free thiomalate in the urine of patients receiving aurothiomalate intramuscularly. As thiomalate has now been shown to possess penicillamine-like biological activities it is suggested that at least part of the antirheumatic effects of aurothiomalate may be due to the thiol carrier being released in the body.

Animals↗

The effect of penicillamine and 2,3-dimercaptosuccinic acid on urinary excretion and tissue distribution of gold.

In order to study interactions in vivo between Au+ and SH-containing agents, groups of mice were given 35 mumol/kg of radiolabelled [195Au] thiomalate (Myocrisin) intramuscularly. The administration of Myocrisin is known to result in protein-bound gold and free thiomalate (mercaptosuccinate). High doses of dimercaptosuccinate (1 mmol/kg daily) increased the urinary excretion of radiolabelled gold [195Au] for several days. Treatment for 7 days with 1 mmol/kg of penicillamine or dimercaptosuccinate reduced the blood and kidney levels of gold to 30--50% of the controls. The oral administration of penicillamine in high doses, 1--10 mmol/kg, increased significantly the urinary excretion of [195Au] the first day after the Myocrisin injection, but on the subsequent days the radio-metal excretion was unaffected by the treatment. A lower dose level of penicillamine (0.3 mmol/kg daily) gave rise to only a small and insignificant increase in the urinary excretion of gold. The present results indicate that penicillamine at low clinical doses is an inefficient chelator of gold, while high doses (presumably comparable to about 1 200 mg daily in humans) may mobilize certain amounts of the metal deposits.

Animals↗

A variant form of 2-methyl-3-hydroxybutyric and 2-methylacetoacetic aciduria.

A new case of assumed beta-ketothiolase deficiency, excreting 2-methyl-3-hydroxybutyrate and tiglylglycine is described in a 15-year-old boy. The patient presented with episodes of metabolic acidosis following intercurrent infections in the early childhood. After the age of 7 years he has had periods of headache, but no acidotic episodes have occurred even during infections. Systematic dietary treatment has not been instituted, and the patient is physically and mentally normal. This indicates a mild variant of the beta-ketothiolase deficiency. Diagnosis of the condition may be obscured by large quantities of ordinary ketone bodies, and requires gas chromatographic and mass spectrometric techniques.

Acetoacetates↗

Gold and thiol compounds in the treatment of rheumatoid arthritis: excretory fate and tissue distribution of thiomalate in relation to gold after administration of myocrisin (auro-thiomalate).

Double isotope-labelled auro thiomalate (Au195-C14-thiomalate) has been administered to mice and rats, and the excretory fate and tissue distribution have been studied. The results show that the gold and the thiomalate separate in vivo resulting in protein-bound gold and release of free thiomalate. About half of this thiol is excreted in the urine during the first day and the remaining half is taken up by the tissues. Thiomalate penetrates cellular membranes poorly, but is able to interact slowly with proteins (mixed disulphide formation). Part of the thiomalate which remains in the body is membrane bound. In contrast to penicillamine little thiomalate remains in circulation a few hours after administration. Gas chromatography--mass spectrometry has been used to search for the presence of free thiomalate in rheumatoid arthritis patients on Myocrisin (auro thiomalate) therapy. Thiomalate was found in their urine, but not in serum and synovial fluid 20 hours after administration. As thiomalate is released in the body after administration of Myocrisin. the question arises whether this thiol, like penicillamine, may have a beneficial effect in the treatment of rheumatoid arthritis.

Animals↗

Capillary column gas chromatography--mass spectrometry in studies on rheumatoid arthritis.

A method is described for determining the organic acid profile of synovial fluid. The method requires 50--100 microgram of sample and involves ion exchange for isolation of the acids followed by combined capillary column gas chromatography--mass spectrometry. Normal synovial fluid and synovial fluid from patients with rheumatoid arthritis show a similar qualitative pattern of acids (mainly fatty acids) resembling the pattern found in serum. The concentrations of the organic acids in the abnormal synovial fluids are 5--10 times higher than those in the fluid from the normal joints. In patients receiving treatment with gold thiomalate, free thiomalate was excreted in the urine. The release of this thiol upon gold therapy is of consequence for the further understanding of the mechanism of action of certain drugs against rheumatoid arthritis.

Arthritis, Rheumatoid↗

Methylmalonic/beta-hydroxy-n-valeric aciduria due to methylmalonyl-CoA mutase deficiency.

A patient with methylmalonic and beta-hydroxy-n-valeric aciduria, apparently due to deficiency of methylmalonyl-CoA mutase, is described. The excretion of beta-hydroxy-n-valerate did not parallel that of beta-hydroxypropionate and methylmalonate but was observed, together with beta-keto-n-valerate, only during ketosis. beta-Hydroxy-n-valerate excretion thus correlates primarily not with the pool size of propionyl-CoA but with that of acetyl-CoA, and may occur during ketosis in any disorder causing accumulation of propionyl-CoA.

Amino Acid Metabolism, Inborn Errors↗

Monosaccharides and monosaccharide derivatives in human seminal plasma.

Gas chromatography--mass spectrometry with an on-line data system was used to identify monosaccharides and monosaccharide derivatives in human seminal plasma. The carbohydrates were converted into the methoxime-trimethylsilyl derivatives before separation in open tubular glass capillary columns coated with SE-30. Twenty-one different compounds were detected in the seminal fluid, of which twelve have not been recognized before. Seventeen of the monosaccharides have previously been identified in urine. Similar patterns of sugars were found both in fertile and infertile individuals, including one with azoospermia. The compounds identified are, with the possible exception of D-ribose, present as free monosaccharides at the time of ejaculation, and they do not seem to be preformed by spermatozoa.

Chromatography, Gas↗

Studies on the metabolism of 2,4'-isobutylphenylpropionic acid (ibuprofen) by gas chromatography and mass spectrometry. Dialysis fluid, a convenient medium for studies on drug metabolism.

2,4'-Isobutylphenylpropionic acid (ibuprofen) has previously been demonstrated to yield four urinary metabolites, formed by omega 1-, omega 2- and omega 3-hydroxylation and by a further oxidation of the primary alcohol of the omega 1-hydroxylated metabolite to a carboxyl group. By synthesis and gas chromatography--mass spectrometry the suggested structure of the omega 3-hydroxylated metabolite was verified in the present study. Moreover, a new metabolite, 2,4'-carboxyphenylpropionic acid, was demonstrated to be present in substantial amounts in dialysis fluid from a nephrectomized patient. In such patients ingested drugs cannot be excreted in the urine, but are metabolized to end products. Thus, dialysis fluid may be a convenient medium for studies on drug metabolism.

Chemical Phenomena↗

Chromatographic profile of high boiling point organic acids in human urine.

The profile of high boiling point organic acids in urine samples from both normal subjects and patients suspected of having some form of metabolic disorder has been determined by combined gas chromatography-mass spectrometry. Fifteen different compounds eluting after hippuric acid have been identified, including two, cinnamoylglycine and acetyltributylcitrate, which have not been recognised previously. Relative retention times and abbreviated mass spectra of the identified compounds are presented.

Acids↗

Do penicillamine and Myocrisin act the same way in rheumatoid arthritis?

Our observations, as well as similarities between penicillamine and Myocrisin in clinical action and side effects in RA make it not unreasonable to think that thiomalate may have a penicillamine-like effect. Only a controlled clinical trial with thiomalate in RA can provide an answer to this question.

Animals↗

Organic acid profiles of human tissue biopsies by capillary gas chromatography-mass spectrometry.

A method is described to determine the organic acid content of tissue specimens comparable in size to those obtainable by closed biopsy. The method involves solvent extraction of tissue homogenates followed by analysis of trimethylsilyl derivatives of the organic acids by combined capillary gas chromatography-mass spectrometry. Organic acid profiles of human liver, pancreas, kidney and muscle are shown.

Acids↗

Profiling of human body fluids in healthy and diseased states using gas chromatography and mass spectrometry, with special reference to organic acids.

This review summarizes recent advances in the application of gas chromatography and mass spectrometry to the study of human diseases. Emphasis is placed upon the organic acid profiles of the various body fluids. Methods for sample work-up prior to separation and mass spectrometric analysis are reviewed, and artifacts and pitfalls are discussed. Organic acid profiles, obtained with packed or capillary columns attached to mass spectrometers with or without computer systems, have led to the discovery of new normal metabolites, new metabolic disorders, and to new knowledge about a number of other diseases. Stable isotopes and gas chromatography--mass spectrometry are suitable for quantitative analysis of many compounds in the body fluids, and well suited for investigation of metabolic pathways.

Adult↗