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Biomedical subjects

M Grootveld

Publications and source records attributed to M Grootveld.

At least 37 records · Page 2Linked to original sources
PubMed1991

Application of a novel 1:1 gold(I)-chromophoric thiolate complex as a spectrophotometric probe for the thiol-exchange reactions of anti-arthritic gold drugs in biological fluids.

An oligomeric 1:1 gold(I) complex of the chromophoric thiol 5-mercapto (2-nitrobenzoate) has been synthesized and applied as a spectrophotometric probe for the thiol-exchange reactions of structurally-analogous 1:1 gold(I)-thiolate drugs. For low-molecular-mass thiols, results were consistent with the initial formation of a monomeric mixed-ligand bis-thiolato gold(I) complex followed by further ligand substitution by excess thiol to produce 5-mercapto (2-nitrobenzoate) and a monomeric bis-thiolato gold(I) complex. For human serum albumin, however, the spectrophotometric changes were only consistent with the binding of gold(I) to its single cysteine residue (Cys-34) with the retention of the 5-mercapto (2-nitrobenzoate) ligand on gold(I).

Antirheumatic Agents↗
PubMed1991

A biochemical investigation of auranofin nephrotoxicity by high field proton nuclear magnetic resonance (NMR) spectroscopy.

High-field proton NMR spectroscopic analysis of urine and plasma has been employed to study the biochemical effects and nephrotoxic action of an intramuscular dose of auranofin in rats. Auranofin induced a characteristic profile of proximal tubular damage as evidenced by aminoaciduria, lactic aciduria and increased urinary acetate concentrations. In addition, ethanol was detectable in both urine and plasma obtained from auranofin-treated rats. Auranofin-mediated elevations in the plasma and urine concentrations of 3-D-hydroxybutyrate indicated an increased utilisation of fats for fuel in rats treated with this novel therapeutic agent.

Acetates↗
PubMed1991

Influence of an intravenous dose of aurothiomalate on the status of low-molecular-mass endogenous metabolites in blood plasma: a proton nuclear magnetic resonance (NMR) study.

The effect of aurothiomalate on the status of a wide range of low-molecular-mass endogenous metabolites in blood plasma obtained from animals treated with an intravenous dose of this second-line agent (150 mg/kg) has been assessed by high field proton Hahn spin-echo NMR spectroscopy. As well as modulating the effective concentrations of NMR-detectable biomolecules, aurothiomalate induces a time-dependent decrease in plasma levels of triacylglycerols with a corresponding elevation in the concentration of the ketone body 3-D-hydroxybutyrate, indicating an increased utilisation of fats for energy in rats treated with this 1:1 gold(I)-thiolate complex. These observations may reflect the toxic side-effects that are associated with aurothiomalate treatment.

3-Hydroxybutyric Acid↗
PubMed1991

Influence of disodium aurothiomalate on the activities of xanthine dehydrogenase and xanthine oxidase in endothelial cells.

The effect of aurothiomalate in modulating the conversion of xanthine dehydrogenase to its superoxide producing oxidase form in rat and human liver cytosolic preparations has been investigated. Low concentrations (10(-8)-10(-5) mol.dm-3) of this second-line agent were found to inhibit the conversion of the dehydrogenase to its corresponding oxidase form. High concentrations (10(-4) mol.dm-3), however, accelerated this conversion. It is possible that the influence of aurothiomalate on the relative proportions of xanthine dehydrogenase and xanthine oxidase is a reflection of the gold(I) blockage of critical thiol(ate) or sulphido ligands present in this enzymatic system. These effects may form the basis of aurothiomalate's anti-proliferative action on endothelial cells.

Animals↗
PubMed1991

Oxidative damage to lipids within the inflamed human joint provides evidence of radical-mediated hypoxic-reperfusion injury.

Previous work has established the existence of a pathophysiological environment within the inflamed human joint, capable of sustaining a hypoxic-reperfusion event. Using four different assay systems (two standard and two novel) applied to synovial fluid for the assessment of lipid peroxidation, a series of studies demonstrate that exercise of the inflamed human knee promotes radical-mediated lipid peroxidation within the joint. The implication for novel antioxidant therapeutic approaches to inflammatory joint disease is discussed.

Adult↗
PubMed1990

Control of oxidative damage in rheumatoid arthritis by gold(I)-thiolate drugs.

The roles of anti-arthritic gold(I)-thiolate drugs such as disodium aurothiomalate ('Myocrisin') in the modulation or promotion of oxygen radical-mediated oxidative damage in vivo are reviewed. In particular, the precise molecular mechanisms by which these novel second-line agents exert their therapeutic effects are discussed in terms of (i) the direct and indirect control of enzymes involved in the generation or scavenging of reactive oxygen species (ROS) such as superoxide ion, hydrogen peroxide and hydroxyl radical, (ii) the protection of proteins and relevant enzyme systems against attack by ROS and (iii) their direct involvement in the production (at appropriate 'target' sites) or scavenging of ROS in vivo. In addition, the role of the orally-effective gold(I)-phosphine complex auranofin in the control of oxidative damage in rheumatoid arthritis is also discussed.

Antirheumatic Agents↗
PubMed1989

Non-transferrin-bound iron in plasma or serum from patients with idiopathic hemochromatosis. Characterization by high performance liquid chromatography and nuclear magnetic resonance spectroscopy.

The nature of non-transferrin-bound iron in the plasma or serum of iron-overloaded hemochromatosis patients was studied by high performance liquid chromatography (HPLC) and high resolution nuclear magnetic resonance (NMR). 500-MHz proton Hahn spin-echo NMR spectra of plasma or serum, combined with the use of the iron chelator desferrioxamine, suggests complexation of iron ions with citrate and a possible involvement of acetate. Addition of FeCl3 to hemochromatosis samples broadened the NMR signals from citrate. HPLC analysis rigorously confirmed the presence of an iron-citrate complex in ultrafiltrates of plasma or serum studies with added FeCl3 or desferrioxamine supported this conclusion. It is proposed that non-transferrin-bound iron in the plasma of iron-overloaded patients exists largely as complexes with citrate and possibly also as ternary iron-citrate-acetate complexes. The presence of such complexes would account for the ability of non-transferrin-bound iron to be measurable by the bleomycin assay and for its rapid clearance from the circulation by the liver.

Acetates↗
PubMed1989

Binding of iron(II) ions to the pentose sugar 2-deoxyribose.

Iron(II) ions are able to form a weak complex (apparent equilibrium constant about 10(2) at pH 7.4 and 25 degrees C) with 2-deoxyribose over a range of pH values, including pH 7. Evidence for this complex formation has been obtained by spectrophotometric experiments and by studies of Fe(II) oxidation. Iron(II) ions bound to deoxyribose seem to react with H2O2, in a site-specific reaction, to form hydroxyl radicals (.OH) that immediately damage the deoxyribose molecule.

Chemical Phenomena↗
PubMed1989

Recent advances in the development of a diagnostic test for irradiated foodstuffs.

Recent advances in the development and application of diagnostic tests for irradiated foodstuffs are reviewed. Exposure of water, the major chemical constituent of most foodstuffs to a source of ionising radiation initially generates the highly reactive radical species H., .OH and e- (aq) which react very rapidly with a wide variety of biological molecules. The detection of foodstuffs subjected to irradiation processing requires the identification and/or quantification of 'unnatural' chemical species (i.e. those not usually formed by normal metabolic processes) produced by the attack of .OH radical or e- (aq) on suitable 'target' molecules. Modern methods for the analysis of a series of these 'unnatural' products arising from the interaction of radiolytically-generated .OH radical or e- (aq) with polyunsaturated fatty acids, DNA, aromatic compounds and other biologically important scavenger molecules are examined. It is concluded that the analytical test to be conducted is highly dependent on the nature of the foodstuff to be tested.

Food Analysis↗
PubMed1989

Molecular distribution of gold(I) in human blood plasma after treatment with the antiarthritic disodium aurothiomalate.

On-line separation and detection of both high- and low-molecular-weight gold species in human blood plasma treated with disodium aurothiomalate were achieved by a technique incorporating a combination of fast protein liquid chromatography with continuous monitoring of absorbance at 254 nm and eluant gold concentration by flame atomic absorption spectroscopy. The fate of gold (40 microM disodium aurothiomalate) in human blood plasma was monitored over a period of 24 h. Results obtained indicated that more than 50% of the gold is associated with a peak identified as albumin after a 5 min incubation period at 37 degrees C, and by 30 min more than 90% is found to be associated with albumin. This novel analytical combination enables the rapid, selective and sensitive determination of gold(I) and its biotransformation products (both protein--and non-protein-bound) in biological fluids.

Adult↗
PubMed1988

Aromatic hydroxylation of phenylalanine as an assay for hydroxyl radicals: application to activated human neutrophils and to the heme protein leghemoglobin.

Attack of hydroxyl radical (.OH), generated by a Fenton system at physiological pH, upon L-phenylalanine produces three isomeric tyrosines, o-tyrosine (2-hydroxyphenylalanine), m-tyrosine (3-hydroxyphenylalanine), and p-tyrosine (4-hydroxyphenylalanine). These may be separated by high-performance liquid chromatography and measured using an electrochemical detector. Since L-phenylalanine is relatively nontoxic, it is proposed that generation of these three tyrosines from phenylalanine can be used as an assay for .OH in biological systems. The use of the assay to measure .OH production by leghemoglobin (plus H2O2) and by activated human neutrophils is described. No .OH production by activated human neutrophils was observed unless a source of iron ions was added to the reaction mixture, which suggests that these cells do not release an iron "promoter" of .OH generation from superoxide and hydrogen peroxide.

Chromatography, High Pressure Liquid↗
PubMed1988

2,3-Dihydroxybenzoic acid is a product of human aspirin metabolism.

2,3-Dihydroxybenzoic acid is present in blood plasma and urine of healthy human volunteers after aspirin ingestion. Its identity has been confirmed by mass spectrometry and by electrochemical analysis. Methods for its identification and measurement are described. The concentration of 2,3-dihydroxybenzoic acid is much lower than that of 2,5-dihydroxybenzoic acid, salicylic acid or salicyluric acid.

Aspirin↗
PubMed1987

Measurement of allantoin and uric acid in human body fluids. A potential index of free-radical reactions in vivo?

Free-radical attack upon uric acid generates allantoin [Ames, Cathcart, Schwiers & Hochstein (1981) Proc. Natl. Acad. Sci. U.S.A. 78, 6858-6862]. Methods are described for the accurate measurement of uric acid and allantoin in human body fluids. The concentrations of uric acid and allantoin in human serum and synovial fluid are reported. It is suggested that measurement of changes in allantoin concentration may be a useful index of free-radical reactions taking place in vivo.

Allantoin↗