The interaction between human platelet monoamine oxidase, its monoamine substrates and oxygen.
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Biomedical subjects
Publications and source records attributed to L Oreland.
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Monoamine oxidase (MAO) activity has previously been found to be high both in brain and in platelets in patients with Alzheimer's disease and low in patients with cycloid psychosis and suicidal behaviour and/or ethanol abuse. To establish if there is a correlation between brain and platelet MAO activities in patients without psychic disease, blood samples from patients in a geriatric ward were collected before death and from 4 different parts of the brain at autopsy. The MAO activities in platelets and brain were then estimated with different substrates. No correlation between the MAO activities in the two tissues was, however, found, regardless of the substrate used.
The interaction between rat brain monoamine oxidase-B and J-508, an analogue of L-deprenil, has been investigated. J-508 inhibits rat brain monoamine oxidase-B in a manner consistent with a 'suicide' reaction, and is so potent an inhibitor that it produces inhibition at concentrations of the same order as those of the enzyme. This property has been used to determine the nature of the changed monoamine oxidase-B activity in the corpus striatum after hemitransection of rat brain.
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Rats were given chronic treatments with ethanol in two ways: by offering 10% ethanol in water as the only liquid supply for 34 weeks and by exposing the rats to ethanol vapour during 5 h daily for 7 weeks. In this way blood ethanol levels of 1.4-2.3 and 5.5-6.9 mg/ml, respectively, were accomplished. In neither of the cases was brain monoamine oxidase activity changed. The result supports an hypothesis previously advanced that the lowered monoamine oxidase activity found in the brain of a suicide patient was not due to a direct effect of ethanol on alcoholics in the suicide group, but that the low enzyme activity reflected a low monoaminergic activity in the brains of the patients in the suicide group.
In a study of 28 schizophrenic in-patients treated with penfluridol or thiothixene, patients were followed with clinical ratings, EEG variables, the mean integrated amplitude (MIA) on both the left and right sides--both with filters with frequency ranges from 7.5 to 13.5 and 0.5 to 25 Hz--as well as its within-patient variance (WPV) on both sides and with both filters, and also with visual averaged evoked responses (V.AER). Moreover, determinations of plasma levels of the drugs were conducted in a search for possible objective measurements of the effects of the treatment, but also to try to find measurements that would make it possible to predict the outcome of treatment. MIA left/right and WPV left/right were found to be the most promising variables to follow the effect of treatment, which were correlated to factors 1 and 2 of the Mårten's S-scale. WPV left/right before treatment was correlated to changes in factor 4 of the S-scale during the trial.
In 57 consecutive patients with psychiatric disorders correlations were sought between the neurophysiological variables - amplitudes and latencies of visual averaged evoked responses (VAER), the proneness to augment or to reduce the amplitude of VAER with increasing stimulus intensity, PAR and PRI, the mean integrated amplitude (MIA) and its within patient variance (WPV) and the monoamine oxidase activity (MAO) in platelets, both with beta-fenylethylamine (MAO1) and with tryptamine (MAO2) as substrate. When multiple correlations with age occurred, a multiple regression was calculated to evaluate the relative importance of each component. MAO1 was found to be significantly correlated to Ampl. N1 and Lat. 2, 3 and 4 of VAER while MAO2 only gave a significant correlation with LaT. 4. As in earlier studies Ampl. N1 was found to be significantly correlated to the content of 5-hydroxyindoleacetic acid in liquor, these measurements seem to be the most important in psychiatric disorders where the monoaminergic systems are supposed to be disturbed.
The short-term effect of gamma-irradiation (single dose, 100 Gy = 10 000 rad) on tth monoamine oxidase activity in the rat brain was investigated. In contrast to other investigations virtually no changes in MAO-activity were found.
Platelet monoamine oxidase (MAO) activity was found to be significantly reduced in human alcoholics as compared to matched controls. A probable transitory increase in activity was observed during the abstinence phase. The low platelet MAO activity was not due to iron deficiency or to the presence of acetaldehyde. Since we have previously found a lowered MAO activity in the brains of suicide victims, especially in those with a previous history of alcohol abuse, we suggest that low platelet MAO activity reflects a primarily "weak" monoaminergic system in the CNS which causes an increased vulnerability to alcohol abuse and suicidal behaviour.
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Two methods have been employed to localize monoamine oxidase activity in the cells of rat liver, using either 2-(2'-benzothiazolyl)-5-stryl-3-(4'-phtalhydrazidyl) tetrazolium chloride (BSPT) or ferricyanide as electron acceptor. With both methods monoamine oxidase activity was found both in the inner and the outer mitochondral membrane, although the outer membrane appeared the most probable location. In addition the BSPT method but not the ferricyanide method, revealed monoamine oxidase activity in the endoplasmatic reticulum. The results obtained by the two methods have been compared and are discussed in view of available biochemical data on monoamine oxidase.
62 patients with affective disorder, 31 unipolar, 22 bipolar and 9 cycloid psychotics who had received prophylactic lithium therapy for 0,3 to 7,5 years were studied. Lithium in plasma, lithium in red blood cells (RBC) and the lithium ratio (RBC/plasma) were estimated. The lithium ratio does not seem to be of predictive value in determining for which patients prophylactic lithium therapy will succeed.
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The lithium RBC/plasma ratio was determined in 59 patients during prophylactic lithium therapy -- 10 cycloid psychotics, 28 unipolars and 21 bipolars -- as well as in 20 patients during lithium therapy in phase of illness -- 8 cycloid psychotics, 5 unipolars and 7 bipolars. The lithium ratio was found to be normally distributed both among patients in phase of remission and those in phase of illness. No differences in lithium ratio were found between patients in phase of remission and phase of illness, respectively. During prophylactic lithium therapy, no differences were found in the lithium ratio between patients in different diagnostic subgroups. In a correlation matrix, the lithium ratio was found to correlate to lithium in RBC but not to age, sex, type of illness, weight, lithium dosage, duration of treatment or level of lithium in plasma. The lithium level in RBC was determined only by the lithium level in plasma. Thus, the lithium RBC/plasma ratio does not seem to be of diagnostic value in affective disorders.
Plasma levels of penfluridol and thiothixene were studied after 4 weeks treatment in a double-blind controlled trial of 47 patients suffering from chronic schizophrenic syndromes. There was found a tenfold variation in plasma levels for penfluridol, and about a twentyfold variation for thiothixene. For penfluridol, a significant correlation between dosage and plasma level and also between dosage and changes in psychopathology as regards factor 5 in the Märtens & Jonsson S scale which comprises the items most characteristic of a schizophrenic syndrome, was found. For thiothixene, a significant correlation between plasma levels and changes in factor 5 was found. A gas-chromatographic method for penfluridol is also described.
Molecular turnover numbers of the different forms of monoamine oxidase in rat liver were estimated for serotonin, tyramine and beta-phenylethylamine by titration with irreversible inhibitors. The 'A' form was found to have a much higher turnover number for serotonin and a lower turnover number for beta-phenylethylamine than the 'B' form, while the turnover numbers for tyramine were in the same order of magnitude for both forms. The monoamine oxidase in the liver was found to have a significantly higher molecular turnover for tyramine and beta-phenylethylamine than that in the brain, heart and kidney. It was calculated that the 'A' form of monoamine oxidase amounted to about 20% and the 'B' form to about 80% of the total amount of monoamine oxidase in the rat liver mitochondrial preparation. The number of molecules per mitochondrion was also calculated.
Pig liver and pig brain mitochondrial monoamine oxidase were inhibited by increasing concentrations of clorgyline (selective inhibitor for the "A" form of monoamine oxidase) and deprenil (selective inhibitor for the "B" form of the enzyme) and the activities were then estimated with serotonin, tyramine and beta-phenylethylamine as substrates. The results indicate that both the "A" and the "B" forms are present in these tissues. Serotonin and tyramine are shown to be oxidized by both the "A" and the "B" forms of the enzyme, whereas beta-phenylethylamine appears to be oxidized almost exclusively by the "B" form. Lipid-depletion of the mitochondrial preparation from these tissues by extraction with aqueous methyl ethyl ketone eliminated almost all of the "A" form activity while most of the "B" form activity remained.
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