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Biomedical subjects

D R Blake

Publications and source records attributed to D R Blake.

At least 181 records · Page 10Linked to original sources
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↗
PubMed1991

Skin inflammation induced by reactive oxygen species (ROS): an in-vivo model.

A model of skin inflammation induced by reactive oxygen species has been established using the hydrogen-peroxide-producing enzyme glucose oxidase. As a means of increasing the half-life of the enzyme and tissue retention polyethylene glycol (PEG) was attached. A rapid inflammatory response occurred consisting of an oedematous, non-erythemic swelling lasting at least 48 h. Histologically, there was an infiltration of the dermis by monocytes and neutrophils, collagen matrix breakdown and damage to the vascular endothelium. This response was significantly inhibited by both catalase and superoxide dismutase attached to PEG (PEG-CAT and PEG-SOD, respectively). PEG alone produced no effects. PEG-CAT was able to sustain an inhibitory effect for at least 12 h, whereas PEG-SOD significantly reduced inflammation for up to 6 h. PEG-SOD may have an exacerbatory effect over longer periods.

Animals↗
PubMed1991

Absorption of low and therapeutic doses of ferric maltol, a novel ferric iron compound, in iron deficient subjects using a single dose iron absorption test.

Ferric maltol is a novel ferric iron compound with potential use as an oral therapy for iron deficiency anaemia. Using a single, low dose iron absorption test we compared absorption of ferric maltol with absorption of ferrous sulphate in 21 iron deficient subjects. Absorption of 10 mg of ferric maltol as either aqueous solution or a single tablet compared favourably with that of an equivalent dose of ferrous sulphate. At a higher, more therapeutic dose of 60 mg elemental iron as tablets, absorption of ferric maltol appeared to be both more rapid and total absorption greater, than that seen with ferrous sulphate. We conclude that iron from ferric maltol, both at low dose and higher, more therapeutic doses, is at least as well absorbed as from ferrous sulphate. Ferric maltol is the first ferric iron formulation to be absorbed to a degree equivalent to that of ferrous iron salts and may represent a viable form of administration for ferric iron in the treatment of iron deficiency anaemia.

Adult↗
PubMed1991

Localisation of xanthine oxidase to synovial endothelium.

The presence of the xanthine oxidase enzyme system has been demonstrated in the rheumatoid synovium. This supplies a reactive oxygen species generating system to synovium that is subjected to hypoxic-reperfusion cycles (cf inflamed rheumatoid synovium). An antibody to bovine milk xanthine oxidase has been used to localise the enzyme by immunohistochemistry to synovial endothelium. This implicates the endothelial cell as playing a major part in exacerbations of synovitis, induced by radicals.

Antigens↗
PubMed1991

Inactivation of the elastase inhibitory activity of alpha 1 antitrypsin in fresh samples of synovial fluid from patients with rheumatoid arthritis.

The proteinase inhibitory ability of alpha 1 antitrypsin was measured in 23 samples of rheumatoid arthritis synovial fluid, eight osteoarthritic synovial fluids and nine normal control serum samples. For each sample a detailed kinetic analysis was performed with porcine pancreatic elastase as the target proteinase. Samples were stored for less than 24 hours at 4 degrees C before analysis, which does not significantly alter the proportion of inactive alpha 1 antitrypsin. In rheumatoid synovial fluid the elastase inhibitory ability was disproportionately depressed relative to the immunochemically determined concentrations of alpha 1 antitrypsin.

Arthritis, Rheumatoid↗
PubMed1991

Comparative study of intra-articular pressure dynamics in joints with acute traumatic and chronic inflammatory effusions: potential implications for hypoxic-reperfusion injury.

It has been proposed that the process of hypoxic-reperfusion injury contributes to the persistence of synovitis in the inflamed human joint. The generation of pathological, exercise induced, intra-articular pressure leading to occlusion of the synovial microcirculation is central to this mechanism. However, acute traumatic inflammatory joint effusions rarely result in chronic synovitis, suggesting that either the basic hypothesis is incorrect, or that joints with acute traumatic effusions show different intra-articular pressure dynamics. In this study the intra-articular pressure was measured at rest and during isometric exercise in five patients with acute traumatic joint effusions and in nine patients with chronic inflammatory joint effusions. The generation of intra-articular pressure in the patients with acute traumatic effusions was significantly lower at rest (mean 2.0 v 19.6 mm Hg) and during exercise (mean 13.7 v 222.5 mm Hg) than in the patients with chronic effusions. This was due to reflex muscular inhibition around the joint, which inhibited the pathological generation of intra-articular pressure. This difference in the ability to generate intra-articular pressure might mitigate against hypoxic-reperfusion injury in joints with acute traumatic effusions, thereby explaining the paradoxical clinical observation that patients with acute traumatic inflammatory joint effusions rarely develop chronic synovitis.

Acute Disease↗
PubMed1990

Does 3,5,dibromo-4-nitrosobenzene sulphonate spin trap superoxide radicals?

Pulse radiolysis studies show that the spin trap 3,5,dibromo-4-nitrosobenzene sulphonate (I) reacts rapidly with O2.- but the product formed is very unstable. No radicals were detected in ESR studies of solutions of I after reaction with O2.- formed by gamma-radiolysis. Evidence is presented that the stable radical observed by some, but not all workers, following exposure of I to the O2.(-)-generating xanthine/xanthine oxidase system, is produced by a peroxidatic oxidation using hydrogen peroxide formed by O2-. dismutation and that formation of this radical depends on the presence of peroxidase activity in the xanthine oxidase sample employed.

Benzenesulfonates↗