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Biomedical subjects

M J Arthur

Publications and source records attributed to M J Arthur.

71 records · Page 4Linked to original sources
PubMed1987

Reduction of ferricytochrome C may underestimate superoxide production by monocytes.

Superoxide production by stimulated phagocytes is commonly measured by reduction of ferricytochrome C, with specificity of the assay assumed if the reaction is inhibited by superoxide dismutase (SOD). Most preparations of ferricytochrome C contain a small proportion in the reduced (ferro) form, and this is also formed by the reaction of ferricytochrome C with superoxide. The generation of other reactive oxygen intermediates, such as hydrogen peroxide or hydroxyl radical, could cause oxidation of ferrocytochrome C and consequent underestimation of superoxide production. In support of this, it has been demonstrated that exogenous catalase enhanced the reduction of ferricytochrome C by phorbol myristate acetate (PMA)-stimulated human monocytes. Control experiments confirmed that this was due to enhanced detection rather than increased production of superoxide. In addition, SOD was found to promote oxidation of ferrocytochrome C by PMA-stimulated human monocytes, but this was also inhibited by catalase. These effects of catalase and SOD on ferricytochrome C reduction/ferrocytochrome C oxidation were also demonstrated when superoxide was produced independently of monocytes by a xanthine and xanthine oxidase generating system. It is concluded that the assay of superoxide, using 'SOD inhibitable' reduction of ferricytochrome C, underestimates superoxide production.

Catalase↗
PubMed1986

Corynebacterium parvum-elicited hepatic macrophages demonstrate enhanced respiratory burst activity compared with resident Kupffer cells in the rat.

We have recently demonstrated that release of oxygen-derived free radicals by activated hepatic macrophages may be involved in the pathogenesis of a rat model of liver injury induced by Corynebacterium parvum and endotoxin. In the present study we have compared the respiratory burst activity of isolated normal rat Kupffer cells with that of hepatic macrophages elicited by C. parvum. Superoxide production (O2-.) and glucose oxidation via the hexose monophosphate shunt (HMPS) were low in normal Kupffer cells, but were significantly increased (O2-. 2.1-fold, HMPS 1.7-fold) by phorbol myristate acetate, a stimulant of the respiratory burst. Corynebacterium parvum-elicited hepatic macrophages demonstrated significantly enhanced superoxide production and HMPS activity compared with normal Kupffer cells, both in the absence of specific stimuli (O2-. 3.3-fold, HMPS 5.3-fold) and after exposure to phorbol myristate acetate (O2-. 4.5-fold, HMPS 5.3-fold). These results demonstrate that normal Kupffer cells are capable of exhibiting respiratory burst activity, but this is markedly increased for hepatic macrophages elicited by an inflammatory stimulus.

Animals↗
PubMed1985

Oxygen-derived free radicals promote hepatic injury in the rat.

We have investigated the possible protective effect of superoxide dismutase and allopurinol in a rat model of mild and severe hepatic necrosis produced by Corynebacterium parvum with or without endotoxin. Histology showed a sinusoidal mononuclear cell infiltrate with multiple granulomata but variable degrees of hepatic necrosis. In the severe hepatic injury model there was a reduction in mortality, associated with a decrease in histologic and biochemical evidence of hepatic necrosis, after treatment with superoxide dismutase. This protective effect was not demonstrated with partially heat-inactivated superoxide dismutase. In the mild hepatic injury model similar trends in reduction of serum levels of hepatic enzymes were observed after treatment with both superoxide dismutase and allopurinol. These results indicate that oxygen-derived free radicals may play an important role in the pathogenesis of hepatic injury in the rat.

Alanine Transaminase↗
PubMed1985

Pharmacology of propranolol in patients with cirrhosis and portal hypertension.

Ten patients with cirrhosis and protal hypertension received an initial 20 mg oral test dose of propranolol and subsequently 160 mg of a slow release preparation, orally, each day for seven days. Protein binding, serial plasma propranolol concentrations and effects on heart rate were studied. Protein binding was slightly reduced (mean 85%, range 78.9-88.1%) compared with four normals (mean 87.9%). In patients with severe liver disease (serum albumin less than 30 g/l) propranolol remained detectable in plasma 24 hours after the single 20 mg dose and high steady state concentrations (mean 266.5 ng/ml, range 84-406) were observed during regular dosing. At steady state there was a significant correlation between log total plasma propranolol concentrations and the percentage fall in heart rate (r = 0.659, p less than 0.05). We suggest that in patients with severe liver chronic disease (serum albumin less than 30 g/l), propranolol therapy should be initiated in hospital. The starting dose should be low (20 mg of the conventional formulation tds or 80 mg of the slow release preparation daily) and that regular monitoring of the heart rate should be carried out.

Aged↗
PubMed1985

Duodenal mucosa synthesis of prostaglandins in duodenal ulcer disease.

Synthesis of prostaglandins (PGE2, PGI2 and PGF2 alpha) and thromboxane A2 was investigated in short term incubates of duodenal mucosa biopsies. Mucosa close to the ulcer site synthesised significantly less PGF2 alpha (p less than 0.001) and PGI2 (p less than 0.002) measured as its stable metabolite 6-oxo-PGF1 alpha than healthy mucosa from non-ulcer patients. In paired biopsies taken from the ulcer site and opposite the ulcer in the same patient PGF2 alpha and PGI2 syntheses were both significantly and similarly depressed when compared with normal mucosa. Synthesis of PGE2 and TxA2 (as its stable metabolite TxB2) was not different in any tissue. There is a defect in the ability of the human duodenal mucosa in duodenal ulcer disease to synthesise PGF2 alpha and PGI2; the defect is not limited to the ulcer site.

Dinoprost↗
PubMed1984

Sex differences in the metabolism of ethanol and acetaldehyde in normal subjects.

Blood ethanol and acetaldehyde concentrations were compared in normal young male and female subjects after intravenous infusion of 0.5 g of ethanol/kg body weight. After the infusion was completed, females had significantly higher mean concentrations of blood ethanol than males, but a significantly lower apparent volume of distribution (Vd) of ethanol (0.56 +/- 0.06 1/kg vs 0.68 +/- 0.17 1/kg, P less than 0.05). There were no differences in ethanol elimination rate (EER) (females 1.78 +/- 0.3 mmol h-1kg-1; males 1.87 +/- 0.41 mmol h-1kg-1). The mean value of the areas under the acetaldehyde/time curves (AUC) were significantly greater for males (88.5 +/- 26.4 mumol/1. h) than for females (58.6 +/- 31.5 mumol/1. h, P less than 0.05). Since the ethanol elimination rate was similar in both sexes, the observed differences in AUC for acetaldehyde may reflect the sex differences in metabolism of this substrate by the liver.

Acetaldehyde↗
PubMed1978

Hyperlactatemia in diabetics with retinopathy during combined sulphonylurea and phenformin therapy.

Blood lactate concentration has been measured at intervals over a twelve hour period in four maturity-onset diabetics with retinopathy treated by sulphonylurea and phenformin therapy. Despite moderately good control of blood glucose, all four patients had markedly elevated concentrations of blood lactate (12h means of 2.1-2;4 mmol/1) with concentrations greater than 3 mmol/1 at some time during the day. Hepatic function was normal in all patients and in all four patients plasma creatinine was 80-85 mumol/1, (normal range 60-125 mumol/1) so that the usual indications for not using biguanides were absent. It is concluded that diabetics with retinopathy constitute a group of patients with an increased risk of phenformin-associated lactic acidosis, and that plasma creatinine estimation may be unreliable in assessing whether patients are suitable for phenformin therapy.

Aged↗
PubMedDate not supplied

Training in academic medicine: a way forward for the new millennium. A discussion document from the Academic Medicine Committee of the Royal College of Physicians.

Three schemes are presented for discussion whereby physicians undergoing postdoctoral training can combine a period of research training with their clinical training and so enable those who wish to follow a career in academic medicine to do so, or alternatively to revert to a clinical career. The training arrangements for those wishing to take up clinical academic medicine have hitherto been uncertain and hence unattractive to some. As well as encouraging more high-calibre trainees into academic medicine, the training programmes described are intended to bring greater clarity to those responsible for academic and clinical training and to those who fund research.

Academic Medical Centers↗
PubMedDate not supplied

Hepatic lipocytes, TIMP-1 and liver fibrosis.

In progressive liver fibrosis, the rate [corrected] of extracellular collagen deposition exceeds its rate of degradation. Collagen and related proteins are synthesised in the fat-storing liver cells (lipocytes). When injured, these cells proliferate and change into myofibroblast-like cells, secreting even more collagen into the extracellular space. The degradation of collagen is accomplished by metalloproteinases, whose activity is reduced by tissue inhibitors (TIMPs). Injured lipocytes produce an excess of these inhibitors. The final result of lipocyte injury is thus progressive liver fibrosis. There is evidence that TIMPs also play a role in progressive fibrosis in other tissues.

Animals↗