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Biomedical subjects

G B Steventon

Publications and source records attributed to G B Steventon.

31 records · Page 2Linked to original sources
PubMed1991

Hereditary variation of liver enzymes involved with detoxification and neurodegenerative disease.

Enzymes involved with the metabolic transformation of xenobiotics have recently been studied in patients with the neurodegenerative diseases, Alzheimer's disease, Parkinson's disease and motor neurone disease. Defects were detected in sulphur pathways and also, in the case of Parkinson's disease, in monoamine oxidase B. The possibility exists that the ability to cope safely with endogenous and exogenous substances which have neurotoxic properties is important in the pathogenesis of these diseases. Potentially such individuals could be identified preclinically and these diseases postponed by reduction in the load of toxin or modification of the relevant enzymic activity.

Animals↗
PubMed1990

Plasma cysteine and sulphate levels in patients with motor neurone, Parkinson's and Alzheimer's disease.

Elevated plasma cysteine to sulphate ratios were found in patients with Motor neurone disease (MND), Parkinson's disease (PD) and Alzheimer's disease (AD). Cysteine and sulphate were measured by colourimetric methods. Following recent discovery of a defect in sulphoxidation and sulphation of xenobiotics in these diseases, this finding confirms that endogenous sulphur metabolism is disturbed. The mean cysteine:sulphate ratios (x 10(3] in fasting early morning plasma were 506, 521 and 477 for MND, PD and AD whereas it was 96 for normal controls (P less than 0.001). This excess of cysteine thiol groups may interfere with neural protein function. The deficiency of sulphate ions may lead to reduced xenobiotic detoxification.

Adult↗
PubMed1990

Xenobiotic metabolism in Alzheimer's disease.

Using 5 methods, we assessed the ability of patients with a clinical diagnosis of Alzheimer's disease (AD) to handle xenobiotics. Patients with AD, compared with controls, have reduced sulfoxidation of the probe drug S-carboxymethyl-L-cysteine; they also form less of the sulfate conjugate of acetaminophen. In addition, they have lower activity of the enzyme thiolmethyltransferase. In contrast, the capacity to oxidize debrisoquin and to acetylate sulfamethazine was normal. These findings suggest that a major risk factor for the development of AD is a skewed capacity for xenobiotic metabolism especially of compounds containing sulfur.

Acetaminophen↗
PubMed1990

Metabolism of low-dose paracetamol in patients with chronic neurological disease.

1. Low dose (500 mg) paracetamol (acetaminophen) was administered to patients with Parkinson's disease, motor neurone disease and to age-matched controls. 2. At this low dose level the controls excreted proportionately more sulphate and less glucuronide conjugate than has been reported for administration of 1000 mg of paracetamol. 3. Both groups of patients with chronic neurological disease excreted decreased amounts of paracetamol sulphate (control mean 11.2 +/- 5.4% dose; Parkinson's disease 3.9 +/- 3.7%; motor neurone disease, 5.0 +/ 4.1%). 4. The mean ratio of excretion of paracetamol sulphate/paracetamol glucuronide was 5.6 +/- 11.7 in controls, but 1.1 +/- 1.7 and 1.2 +/- 1.7 in Parkinson's disease and motor neurone disease respectively. These differences are statistically significant (p less than 0.001).

Acetaminophen↗
PubMed1989

S-methylation in motorneuron disease and Parkinson's disease.

Thiolmethyltransferase activity has been measured in newly diagnosed, untreated patients with idiopathic Parkinson's disease and motorneuron disease, and in normal volunteers. In Parkinsonian patients, mean thiolmethyltransferase activity was low (300 U/mg protein [SD 96]) compared with that in controls (947 [409]), whereas activity was high in patients with motorneuron disease (2077 [825]).

Adult↗
PubMed1989

Platelet monoamine oxidase-B activity in Parkinson's disease.

Platelet MAO-B levels have been investigated in seventeen consecutively diagnosed and previously untreated patients with idiopathic Parkinson's disease using the non-hydroxylated catecholamine, beta-phenylethylamine, as substrate. Patients with Parkinson's disease had MAO-B activity levels that were considerably higher than sex and age matched normal controls or patients with Motor neurone disease or Myasthenia gravis.

Adult↗
PubMed1989

Xenobiotic metabolism in Parkinson's disease.

We studied 68 patients with Parkinson's disease (PD) with probe drugs to determine whether a defect in metabolism might be an etiologic factor and found no difference between patients and controls in their ability to form the 4-hydroxy metabolite of debrisoquin. However, using S-carboxymethyl-L-cysteine, 63.2% (43/68) of PD patients had reduced S-oxidation capacity, while 35.3% (24/68) produced no sulfoxides (controls, 35.2% and 2.5%). When we studied acetaminophen (paracetamol) metabolism, only 29.6% of PD patients excreted greater than 5% of the dose as the sulfate conjugate; the corresponding figure for controls was 83.9%. These results suggest a deficiency in detoxication pathways involving sulfur metabolism. PD patients may be unusually susceptible to exogenous or even endogenous toxins.

Acetaminophen↗
PubMed1987

Ethanol-induced inhibition of pinocytosis and proteolysis in rat yolk sac in vitro.

Pinocytic capture of 125I-labelled polyvinylpyrrolidone and of formaldehyde-denatured 125I-labelled bovine serum albumin by 17.5-day rat visceral yolk sacs incubated in vitro was rapidly and strongly inhibited by low concentrations (0.01 and 0.05%, v/v) of ethanol. The induced inhibition of pinocytosis was readily reversible, but a marked lag was observed before ethanol-exposed tissue regained its full proteolytic capacity towards the exogenous protein. These observations suggest that the acute administration of ethanol to a pregnant rat may give rise to concentrations of ethanol in the maternal blood and/or uterine fluid that induce dysfunction of the yolk sac. In late gestation such inhibition of yolk-sac function may interfere with the transfer of passive immunity across the yolk sac. If similar dysfunction is induced earlier in gestation, in the period before the chorioallantoic placenta is functional, this could cause a transient period of inhibition of histiotrophic nutrition that may be important to the pathogenic mechanism of action of ethanol as a teratogen.

Animals↗