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Biomedical subjects

M Sandler

Publications and source records attributed to M Sandler.

At least 199 records · Page 11Linked to original sources
PubMed1981

Human platelet phenolsulphotransferase: separate control of the two forms and activity range in depressive illness.

Human phenolsulphotransferase exists in two forms, one specific for dopamine and tyramine, termed "M" and one for phenol, termed "P". In this study we have shown that these two forms are under separate control by correlating their activities in different individuals using different substrates. There was a highly significant correlation between the activities with dopamine, p-tyramine and 4-hydroxy-3-methoxyphenylglycol, but no significant correlation between the activities with any of these three substrates and that with phenol. Neither age nor sex had any effect on platelet phenolsulphotransferase "M" or "P" activities. Nor was there any significant correlation between platelet monoamine oxidase activity and phenolsulphotransferase "M" or "P" activities. Human platelet phenolsulphotransferase "M" was found to be unstable at temperatures above 35 degree C and it lost substantial activity when stored deep frozen in isotonic saline. However it was stable for up to four months when stored in isotonic sucrose or 10 mmol/l phosphate buffer (pH 7.4). Phenolsulphotransferase "M" amd "P" activities were measured in platelets from depressed patients of a diagnostic type characterized by low output of tyramine-O-sulphate after oral tyramine loading but their enzyme activities were not different from those in two control groups.

Arylsulfotransferase↗
PubMed1981

Sulphate conjugation of biologically active monoamines and their metabolites by human platelet phenolsulphotransferase.

The substrate specificity of phenosulphotransferase in human platelets has been studied using a wide range of biogenic amines and their metabolites. Substantially differing activities were observed at 30 mumol/l; the enzyme was more active towards the catecholamines and their alcoholic metabolites than the corresponding acids (with the exception of 3,4-dihydroxyphenylacetic acid which did not appear to be a substrate) and the relative order was not changed by dialysis to remove possible low molecular mass inhibitors. However, most of the V values were similar to each other, reflecting a large variation if Km values, ranging from 0.3 mumol/l for 3-methoxytyramine to 3700 mumol/l for 4-hydroxy-3-methoxymandelic acid. All substrates showed substrate inhibition. Dopamine, noradrenaline and adrenaline all had a high affinity for the enzyme, with Km values of 3.0, 5.0 and 2.7 mumol/l respectively. These values are considerably lower than those for monoamine oxidase and the relative importance of oxidation and sulphoconjugation of these amines in vivo may be concentration dependent. Human platelet phenolsulphotransferase appears different from the rat enzyme, but similar to that described by others in human brain. The platelet should be a useful source of enzyme for clinical studies.

Arylsulfotransferase↗
PubMed1981

Brain monoamine oxidase activity in schizophrenics and controls.

Postmortem samples of caudate nucleus and frontal cortex from schizophrenic, schizophrenic-like, and control subjects were examined for monoamine oxidase activity using dopamine, phenylethylamine, and 5-hydroxytryptamine as substrates. There were no significant differences between the diagnostic groups with any of the three substrates. Neither was there a difference between the sexes, nor a consistent relationship of enzyme activity to age.

Aged↗
PubMed1981

Increased platelet monoamine oxidase activity in affective disorders.

Platelet monoamine oxidase activity was determined in 52 unipolar depressive patients, 26 patients with bipolar affective disorder and 48 controls using phenylethylamine as substrate. Unipolar depressive patients of either sex and bipolar depressive women showed significantly higher platelet MAO activity than controls. Women had higher activity than men. Neither age nor serum lithium level correlated with enzyme activity and there was no significant change in activity after the institution of lithium treatment.

Adult↗
PubMed1981

Is the failure of (-)deprenyl, a selective monoamine oxidase B inhibitor, to alleviate depression related to freedom from the cheese effect?

The selective monoamine oxidase (MAO) B inhibitor (-)deprenyl failed to produce any greater benefit than placebo in a limited double-blind trial conducted in depressive patients. Its relative freedom from the so-called cheese effect was confirmed, however, in drug-treated patients challenged IV with tyramine. There is evidence to suggest that this cheese effect, a facilitated tyramine-induced hypertensive response, is pharmacologically distinct from MAO inhibition proper. Thus, it is conceivable that its central counterpart, an enhanced noradrenaline release due to the access of traces of tyramine to the CNS, is a prerequisite for any therapeutic benefit obtainable with the MAO-inhibitory drugs in general.

Blood Pressure↗
PubMed1981

The specific activity of platelet monoamine oxidase varies with platelet count during severe exercise and noradrenaline infusion.

During severe exercise or noradrenaline infusion in healthy male volunteers, the platelet count first rose and then fell. Platelet monoamine oxidase activity per unit protein rose and fell in parallel and the correlation with the platelet count was highly significant (P less than 0.001). The increase in observed specific monoamine oxidase activity might be due to the release of a population of platelets with higher specific activity, and the decrease to their selective removal.

Adult↗
PubMed1981

Urinary MAO inhibitor in psychiatric illness.

Normal human urine contains an endogenous monoamine oxidase inhibitor. We have now investigated its activity in urine samples from psychiatric patients in various diagnostic categories. Significantly higher values were observed in alcoholics recently withdrawn from ethanol, compared with controls. Inhibitory activity was not specifically related to primary affective disorders. Inhibitor output may be positively related to certain symptom clusters rather than to disease entities (i.e. alcohol withdrawal, agitation, and hyperkinesis). Significantly lower inhibitor output was also found in a small group of patients with chronic schizophrenia.

Adolescent↗
PubMed1981

Human platelet monoamine oxidase activity in health and disease: a review.

The most readily available source of monoamine oxidase in man is the platelet, although only the B form of the enzyme is represented in this site. Platelet activity is higher in women than in men. The enzyme activity is generally stable and is partly under genetic control. There is some evidence that individuals with low activity have a higher psychiatric morbidity than those with high activity. Despite some negative studies, the consensus of publication dealing with schizophrenia, migraine, and alcoholism find that mean platelet monoamine oxidase activity in the patient group is lower than in the controls. Values are raised in unipolar depression. Technical differences, or patient or control group heterogeneity, might well account for the absence of unanimity in the literature. A considerable degree of overlap between patient and control values, whatever the clinical diagnosis, appears to be the standard finding. Apart from these neuropsychiatric disturbances, platelet monoamine oxidase activity is raised in megaloblastic anaemia and reduced in iron deficiency anaemia. Although altered enzyme activity values may be linked to abnormal platelet populations in some of the haematological disorders discussed, in general the causes of abnormal platelet monoamine oxidase activity are unknown.

Adolescent↗
PubMed1981

Nomifensine: effect in Parkinsonian patients not receiving levodopa.

A clinical trial using the anti-depressant nomifensine in Parkinsonism is reported. Eighteen subjects not receiving levodopa participated. The drug had a small, but significant anti-Parkinsonian effect. No troublesome side effects were encountered. In the treatment of Parkinsonism, nomifensine may be considered as an alternative to amantadine or anticholinergics, especially where depression is an added feature.

Aged↗
PubMed1981

Platelet monoamine oxidase activity and headache.

Mean platelet monoamine oxidase activity was reduced compared with control values in groups of headache-free male (but not female) patients suffering from classical migraine and from tension headache. Mean activity in male cluster patients, headache free, both during acute and quiescent phases of their illness, was also notably reduced. Retesting some migraine subjects after up to four years, showed that low activity may be a persistent feature: the correlation coefficient for repeated assays was 0.91 (p less than 0.01). There was no relationship between platelet monoamine oxidase activity and history of dietary migraine. A subgroup of headache patients with permanently low monoamine oxidase activity values may have been defined.

Blood Platelets↗
PubMed1981

Failure to induce reactive hypoglycaemia by drinking a starch-based alcohol beverage (sorghum beer).

Alcohol is a well-recognised cause of fasting hypoglycaemia but may also provoked reactive hypoglycaemia when drunk together with a carbohydratee mixer. In this study the ability of sorghum beer (an 'in-built' alcohol-starch beverage widely enjoyed in Southern Africa) to induce reactive hypoglycaemia was compared with "gin and tonic' in eight non-obese health African men. After an overnight fast, each subject drank, in random sequence on their different occasions, 2 litres of sorghum beer (carbohydrat content approximately 5% and alcohol concentration 2.24 g/dl-2.8% v/v), the same volume of a control solution providing a similar carbohydrate load, or a gin and standard tonic water mixture. No evidence of reactive hypoglycaemia was apparent during the 5 hours after the beginning of the sorghum beer tolerance tests, despite a mean peak blood alcohol level reaching 80 mg/dl. both the peak and total plasma insulin responses were significantly reduced (p less than or equal to 0.05) when compared to the brisk responses elicited by the carbohydrate solution alone and the gin and tonic drinks, with consequent hypoglycaemia. These data suggest that African home-brews are not potent causes of reactive hypoglycaemia, although they may be implicated in the development of ethanol-induced hypoglycaemia in the fasting state.

Adult↗
PubMed1981

Tranylcypromine isomers and Parkinson's disease: new aspects of an old drug.

The tranylcypromine stereoisomers have been investigated in a series of comparative trials in Parkinsons' disease and the results indicate that doses below 3 mg/day, of the (+)-isomer in particular, are effective as adjuvant anti-parkinsonian therapy. Biochemical results, monitoring platelet monoamine oxidase (MAO) activity and plasma concentrations of drugs and phenylethylamine, an MAO substrate, showed such low doses of the (+)-isomer to inhibit MAO without inducing the hypertensive reaction sometimes observed at higher dosage. These findings, along with the observation of substantial pharmacokinetic differences between the two isomers are discussed, particularly in relation to reports on their efficacy in depressive illness.

Humans↗