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Biomedical subjects

L Oreland

Publications and source records attributed to L Oreland.

At least 37 records · Page 2Linked to original sources

Monoamine oxidase B in brains from patients with Alzheimer's disease: a biochemical and autoradiographical study.

In vitro quantitative autoradiography using [3H]L-deprenyl, an irreversible and preferential inhibitor of monoamine oxidase B, was performed to investigate the localization of the enzyme in brains from senile dementia of Alzheimer type and control cases. Brains from three male patients with the clinical diagnosis of senile dementia of Alzheimer type and from three male control patients, without any known clinical history of neurological disorder, were obtained at autopsy. Cryosections of 100 microns thickness were mounted on gelatinized glass plates and dried over desiccant for one week at -20 degrees C. The sections were incubated with 10 nM [3H]L-deprenyl for 1 h and then exposed to film for four weeks. The autoradiographs were analysed by computer-assisted densitometry. Monoamine oxidase-B activities were also estimated in 1% homogenates from 10 different regions, using 10 microM beta-[ethyl-14C]phenylethylamine, in order to study the consonance between the autoradiographical and biochemical techniques. Both [3H]L-deprenyl binding and monoamine oxidase-B activities in senile dementia of Alzheimer type were higher than in the controls in all brain regions studied. The increase was highest in the white matter (about 70%) and in the order of 20-50% in the various gray matter regions. A high correlation coefficient (r approximately 0.9) was obtained between [3H]L-deprenyl binding and monoamine oxidase-B activity, both in the senile dementia of Alzheimer type and in the control brains.

Aged

Personality traits and platelet monoamine oxidase activity in alcoholic women.

Twenty-nine women, sent to an inpatient treatment facility for rehabilitation and social training after treatment for heavy alcohol abuse, were compared with 29 female students of pharmacy or medicine with regard to platelet monoamine oxidase (MAO) activity and extraversion-impulsivity and anxiety-proneness personality traits. The alcoholic females were found to have slightly lower platelet MAO activity than the controls, the difference being considerably smaller than that previously found between male alcoholics and male controls. The personality pattern of the female alcoholics is in line with that previously found in alcoholic males. Thus, the female alcoholics were characterized by high anxiety proneness, impulsive acting-out behaviour, sensation seeking, social withdrawal, and a hostile attitude.

Alcoholism

Peripheral serotonergic markers in patients with suicidal behavior.

Peripheral serotonergic parameters were studied in 17 patients with a history of suicidal behavior and in 17 age- and sex-matched healthy controls. Serotonin2 receptor function in platelets, measured as serotonin-induced [32P]phosphatidylinositol 4,5-bisphosphate hydrolysis, was significantly higher in patients than in age- and sex-matched controls. Increased serotonin2 receptor transduction was not correlated to psychiatric diagnosis, drug treatment or a history of violent suicide attempt. Monoamine oxidase activity was lower in platelets from patients with a history of suicidal behavior than in controls. In addition, whole blood serotonin was analyzed but no significant alterations were found in blood from patients.

Adult

Platelet monoamine oxidase activity in type 1 and type 2 alcoholism.

Earlier studies have identified at least two distinct subtypes of alcoholism. Type 2 is characterised by high heritability, early onset, frequent social complications and mixed misuse. With regard to temperament, the type 2 alcoholics score high in impulsiveness and sensation-seeking behaviour. Type 1 alcoholics have a later onset, lower degree of heritability and rarely there is misuse of illegal drugs. In the present study, 37 type 1 and 62 type 2 male alcoholics were compared with 36 male controls with regard to platelet monoamine oxidase (MAO) activity, which is a stable biological marker, inversely correlated to personality traits such as impulsiveness and sensation seeking. The platelet MAO activity was found to be lower in type 2 alcoholics when compared both with healthy controls and with type 1 alcoholics. Also, the type 1 alcoholics had lower platelet MAO activity than the controls. The result confirms a previous study and validates the subclassification of alcoholism according to the type 1 and 2 concept. This should be of value for future studies concerning etiology, epidemiology, treatment and prevention of alcoholism.

Alcoholism

Monoamine oxidase, dopamine and Parkinson's disease.

Four aspects about monoamine oxidase (MAO; E.C. 1.4.3.4) are of obvious interest in relation to Parkinson's disease and its treatment with the irreversible and selective MAO-B inhibitor L-deprenyl and are discussed in this review: 1) To what extent the two forms of MAO are of importance for the deamination of dopamine and to what degree MAO localised inside and outside of dopaminergic nerve terminals contributes 2) The kinetics of the MAO-protein, i.e. the rate of recovery of MAO after irreversible inhibition. 3) To what extent MAO may be changed as a consequence of the pathophysiological processes. 4) To what extent MAO may be involved as a force in the pathophysiological processes.

Animals

Turnover of monoamine oxidase B (MAO-B) in pig brain by positron emission tomography using 11C-L-deprenyl.

Positron emission tomography (PET) was applied to investigate the rate of turnover of pig brain MAO-B. For this purpose 11C-L-deprenyl was used as an irreversible ligand, which bind stoichiometrically to the enzyme. A tracer dose of 11C-L-deprenyl was injected and PET scans performed to obtain baseline deprenyl binding. A high dose of unlabelled deprenyl was then administered to inhibit the enzyme and tracer doses of 11C-L-deprenyl, with subsequent PET analyses, were given at 0, 2, 7, 21 and 42 days. The half-life for the turnover rate calculated was found to be 6.5 days.

Animals

Visualization of brain monoamine oxidase B (MAO-B) in dementia of Alzheimer's type by means of large cryosection autoradiography: a pilot study.

Quantitative autoradiography, using 3H-deprenyl, was applied to study the regional localization of MAO-B in large cryosections from 3 control brains and 3 brains from patients with Alzheimer's disease (AD). High 3H-L-deprenyl binding was found in e.g. basal ganglia, cingulate gyrus, and insula cortex. Temporal cortex, parietal cortex, occipital cortex and various nuclei of the thalamus, showed moderate density, while low binding was observed in e.g. white matter. When the brains from the controls were compared with those with AD, the mean values for 3H-deprenyl binding was higher in the latter group, however, more generalised than previously reported.

Aged

Effect of reserpine on the brain uptake of carbon 11 methamphetamine and its N-propagyl derivative, deprenyl.

The enantiomers of methamphetamine (MAMP) and its N-propagyl derivative, deprenyl, were labelled with carbon 11, and the tissue distribution of these labelled compounds in mice was studied. Both enantiomers of 11C-MAMP rapidly entered into the brain and then disappeared according to a single exponential curve. The enantiomers of 11C-deprenyl were also rapidly distributed to various organs in the same manner. With regard to elimination, however, a stereoselective, long-term retention of radioactivity in the brain, heart and lung, due to its irreversible binding with monoamine oxidase B, was observed for L-11C-deprenyl. In reserpinized mice, the initial brain uptake of both the L and D forms of 11C-MAMP was significantly decreased. On the other hand, the brain uptake of both enantiomers of 11C-deprenyl was slightly increased by pretreatment with reserpine. A significant and non-stereoselective elevation of the lung uptake of 11C-deprenyl was also seen in reserpinized mice. In addition, both the relative tissue distribution and ratios of radioactivity in the brain compared with blood or heart at 1 and 5 min after the injection of 11C-labelled methanol in mice were not changed by reserpine. These results indicate that the transport or binding processes of these amines rather than the blood flow might be altered by reserpine. There would be an important role of the pKa values of amines in both processes. The reduction of brain uptake as well as the change in ratio between brain and heart of L-11C-MAMP in reserpinized mice 1 min after injection were reversed by treatment with amphetamine in a dose-related manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Clinical characteristics of female alcoholics with low platelet monoamine oxidase activity.

The aim of the present study was to see if female alcoholics had low platelet MAO activity and whether there was a correlation between low MAO activity in female alcoholics and specific clinical characteristics often observed in type II male alcoholics. In earlier studies, male alcoholics have been subdivided into type I and type II alcoholics. Type II alcoholics were characterized by early onset, a high frequency of depression and alcoholism in first degree relatives, a high frequency of drug abuse and social complications, sensation seeking behavior, extraversion, impulsive sensation seeking psychopathy, and low platelet MAO activity. In the present series it was demonstrated that the female alcoholics had significantly lower platelet MAO activities than the female healthy volunteers. The subgroup of female alcoholics with low platelet MAO activity, however, did not differ from female alcoholics with normal platelet MAO activity in the same way as male alcoholics with low platelet MAO activity have been shown to differ from male alcoholics with normal platelet activity. They did not have early onset, higher frequency of depression or alcoholism in their first degree relatives, nor more social complications than the female alcoholics with normal platelet MAO activity. Furthermore, they did not differ from the female alcoholics with normal platelet MAO activity in any personality trait covered by the Karolinska Scales of Personality (KSP).

Adult

Monoamine oxidase in platelets and brains of non-psychiatric and non-neurological geriatric patients.

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.

Age Factors

The inhibition of rat brain monoamine oxidase-B by J-508 (N-methyl-N-propargyl-(1-indanyl)-ammonium hydrochloride), and its use for the titration of this enzyme form.

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.

Alkynes

Brain monoamine oxidase activity after chronic ethanol treatment of rats.

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.

Administration, Oral

Changes in psychopathology in relation to EEG variables and visual averaged evoked responses (V.AER) in schizophrenic patients treated with penfluridol or thiothixene.

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.

Adult

Neurophysiological measures and visual averaged evoked responses in psychiatric patients. Relationship to monoamine oxidase activity in platelets.

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.

Adult

Monoamine oxidase activity in gamma-irradiated rat brains.

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.

Animals

Low platelet monoamine oxidase activity in human alcoholics.

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.

Alcoholism