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Biomedical subjects

M Sandler

Publications and source records attributed to M Sandler.

At least 217 records · Page 12Linked to original sources

Dopamine oxidation and its inhibition by (-)-deprenyl in man.

Dopamine is predominantly oxidized by a (-)-deprenyl sensitive form of MAO in the human striatum, and (-)-deprenyl, acting at some suitably low selective inhibitory concentration may, therefore, be of benefit in Parkinson's disease. 10(-6)M was the most effective (-)-deprenyl concentration in vitro for discriminating between the inhibition of MAO A and B. The correlation between the A/B ratio present in different human brain regions and the sensitivity of dopamine oxidation to 10(-6)M deprenyl was 0.84 (p<0.001). This suggests that all dopamine oxidation can be accounted for by the joint contribution of MAO A and B and that it is unnecessary to postulate a special form of the enzyme which metabolizes dopamine. In the brain, the striatum has the highest proportion of MAO B, and in several cortical regions, relatively more dopamine is oxidized by MAO A. In other human tissues also the deprenyl sensitivity of dopamine oxidation correlated with the known A/B ratio, the placenta, lung and jejeunum having the lowest sensitivity and being the richest in MAO A. Km values for dopamine for MAO A and B are similar, 130 and 140 uM respectively, so that the proportion oxidized by the two forms should not vary with substrate concentration.

Blood Platelets↗

Tele-Methylhistamine is a specific MAO B substrate in man.

Tele-methylhistamine, the first metabolite of histamine in tissues which lack diamine oxidase, is shown to be a substrate for human MAO B. Human liver homogenates were incubated with 3H-tele-methylhistamine and the products separated using thin-layer chromatography. The major product was 3-methylimidazoleacetic acid, the oxidatively deaminated metabolite of tele-methylhistamine. The reaction was inhibited by low concentrations of (-)deprenyl, the specific MAO B inhibitor. Tele-methylhistamine was also found to inhibit competitively the oxidation of phenylethlamine, but not that of 5-hydroxytryptamine, providing further evidence that it is oxidized by MAO B itself and not a related enzyme. This finding implies that (-)deprenyl and other MAO inhibitors used clinically may interfere with histamine metabolism.

Binding, Competitive↗

Amine oxidase histochemistry of the human uterus during the menstrual cycle.

The enzymes monoamine oxidase A (MAO A), monoamine oxidase B (MAO B) and benzylamine oxidase (BzAO) have been locaized histochemically in the human uterus during various phases of the menstrual cycle. The results show a large increase in MAO A activity in th endometrial gland cells in the secretory phase of the cycle. MAO B activity was found in both endometrium and myometrium but did not show a cyclical variations in activity. BzAO was localized primarily in the tunica media of the myometrial blood vessels. These observations have been supported by parallel biochemical assay.s

Benzylamine Oxidase↗

The inhibition of tyramine oxidation and the tyramine hypertensive response ("cheese effect") may be independent phenomena.

Although the selective monoamine oxidase (MAO) inhibitor, (-)-deprenyl, substantially inhibits tyramine-oxidizing ability in the pig, intravenous tyramine challenge after pretreatment with this drug failed to produce the characteristic pressor response ("cheese effect") associated with other irreversible MAO inhibitors. Conversely, pretreatment with the tyramine oxidation-sparing selective MAO inhibitor, clorgyline, followed by intravenous tyramine, paradoxically resulted in a profound pressor response. We suggest that the action of standard MAO-inhibiting drugs may be compounded of two separate actions, usually associated but, in fact, unreleated.

Animals↗

Decreased urinary output of conjugated tyramine is associated with lifetime vulnerability to depressive illness.

In a group of normal pregnant women whose psychiatric histories were unknown, those with the lowest output of urinary tyramine (free plus conjugated) after an oral tyramine load had a significantly higher lifetime incidence of depressive illness compared with those with the highest output. as none of the women were suffering from depression at the time of tyramine loading, it seems likely that this decreased excretion of tyramine is associated in some way with vulnerability to depressive illness, whether puerperal or nonpuerperal.

Chronic Disease↗

Further light on the tyramine test in depression.

In studies of post-partum women, the oral tyramine loading test is shown to be of predictive value in identifying those subjects with a lifetime history of depressive illness. The cause of the decreased output of conjugated tyramine, after tyramine ingestion, is still unclear. Some possible mechanisms have been under scrutiny.

Affective Disorders, Psychotic↗

A predictive study of post-partum depression: some predisposing characteristics.

Postnatal depression was investigated by the antenatal screening of a sample of women for factors that might be predictive of later disturbance. The women were assessed when they were 36 weeks pregnant on anxiety, hostility, and locus of control. Predictions were tested by assessing depression 6 weeks after birth. Both high anxiety and high hostility were positively associated with postnatal depression. Intropunitiveness was not significantly related to subsequent depression. The most depressed women were those who had been the more extrapunitive as well as the more hostile. Women who perceived themselves as less in control of their lives were likely to rate high on depression postnatally, as were younger women. There were indications that some women may have been experiencing depression before the birth. Depression was not significantly associated with parity, gravidity, race, social class or marital status.

Adaptation, Psychological↗

Platelet monoamine oxidase activity in megaloblastic anaemia.

Platelet monoamine oxidase activity has been measured in 17 patients with megaloblastic anaemia due to either vitamin B12 or folate deficiency, and in 20 healthy subjects. There was a highly significant increase in patients compared with controls. In two patients, platelet activity decreased following successful treatment. A significant correlation between platelet activity and the severity of bone marrow megaloblastic change, assessed by the deoxyuridine suppression test and bone marrow morphology, was also observed. If the change in activity also occurs in the nervous system, this may contribute to the mental disturbance associated with vitamin B12 or folate deficiency.

Anemia, Macrocytic↗

Separation and quantification of urinary di- and polyamines by gas chromatography with electron capture detection.

A sensitive and specific gas chromatographic assay procedure employing electron capture detection has been developed for the assay of free and total di- and polyamines in human urine. Urine samples, hydrolysed with hydrochloric acid where necessary for the measurement of total amine output, were evaporated to dryness and, after the residues had been taken up in water, purified successively on Porapak Q and Dowex 50 X2 columns. Following evaporation of eluate, pentafluoropropionyl derivatives were made and analysed gas chromatographically using temperature programming. Di- and polyamines can be measured accurately at the picomole level and normal urinary output values calculated using this method agree well with those noted by other workers.

Chromatography, Gas↗

Urinary 4-hydroxy-3-methoxyphenylglycol is not a predictor for clinical response to amitriptyline in depressive illness.

The urinary excretion of 4-hydroxy-3-methoxyphenylglycol was compared in a group of 23 depressive patients and 27 control subjects of similar age. There was no difference between patients and controls although female controls excreted less than males. After 6 weeks' treatment with 150 mg daily of amitriptyline there was no correlation between therapeutic response and pretreatment urinary excretion value.

Amitriptyline↗