Biomedical subjects

L Oreland

Publications and source records attributed to L Oreland.

At least 145 records · Page 8Linked to original sources

PubMed1990

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↗

PubMed1990

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↗

PubMed1990

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↗

PubMed1990

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↗

PubMed1990

Does Swedish amateur boxing lead to chronic brain damage? 1. A retrospective medical, neurological and personality trait study.

Sweden banned professional boxing in 1969 and has also considered banning amateur boxing. We therefore analysed possible chronic brain damage in 47 former amateur boxers who started their careers after the introduction of stricter Swedish amateur boxing rules. The boxers were compared with three control groups--25 soccer players, 25 track and field athletes and 19 conscripts. All athletes were interviewed about their sports career, medical history and social variables. They then underwent a physical and a neurological examination, including a mini-mental state examination. Personality traits were investigated and related to their platelet MAO activity in the athletes as well as in the conscripts. No significant differences were found between the groups in any of the physical or neurological examinations. All had a normal mini-mental state examination. Thus, results from these test methods did not reveal any signs of chronic brain damage from Swedish amateur boxing. Neither were any significant differences found with regard to platelet MAO activity, while significant differences were found in some of the social and personality traits variables.

Adult↗

PubMed1990

Blood platelet monoamine oxidase activity, serotonin uptake and release rates in anorexia and bulimia patients and in healthy controls.

Platelet monoamine oxidase (MAO) activity, serotonin uptake rate and serotonin efflux rate have all been suggested to be markers for central serotonergic mechanisms. Platelet MAO activity is associated with certain personality traits, with low activity linked to traits such as impulsiveness, sensation-seeking and avoidance of monotony, all possible expressions of low central serotonergic activity. Low platelet serotonin uptake rate has been connected to unipolar depression and the rate of efflux, in the presence of the ATP uncoupler CCP, higher in bipolar depressives than in controls. Platelet MAO was found to be lower in 16 consecutive female inpatients fulfilling the DSM-III criteria for bulimia nervosa than in 12 female controls. Rates of serotonin uptake and efflux in the presence of CCP were, on the other hand, similar to the controls. In the controls there were no correlations between platelet MAO activity and any of the other parameters estimated. Vmax for the platelet uptake of serotonin correlated positively with the Km for the uptake, but not with any other parameter. The uninfluenced rate of efflux of serotonin correlated positively with the efflux in the presence of the ATP uncoupler CCP.

Adolescent↗

PubMed1989

Tetrahydroaminoacridine inhibits human and rat brain monoamine oxidase.

The inhibitory effects of 1,2,3,4-tetrahydro-9-aminoacridine (THA) on monoamine oxidase (MAO; EC 1.4.3.4) enzyme activities in human hippocampal and rat striatal homogenates have been studied. The activities of MAO-A and MAO-B were estimated radiochemically, in-vitro, in human hippocampus and rat striatum in the presence of various concentrations of THA with [2-14C]hydroxytryptamine binoxalate (100 microM) and beta-[ethyl-14C]phenylethylamine hydrochloride (20 microM) as substrates for the respective enzyme form. THA was found to inhibit both MAO-A and MAO-B activities reversibly and competitively, with inhibition constants (Ki) of 12.5 microM and greater than 500 microM respectively, of the rat striatal enzymes. From this it can be extrapolated that at therapeutic tissue concentrations of THA (10(-8) to 10(-6) M), more than 20% of the MAO-A activity should be inhibited. Thus it is possible that inhibition of MAO may be involved in the therapeutic action of THA in Alzheimer's disease.

Aged↗

PubMed1989

The cholinergic neurotoxin ethylcholine mustard aziridinium (AF64A) induces an increase in MAO-B activity in the rat brain.

Recently it was reported that there is an increase in monoamine oxidase B (MAO-B) activity in post-mortem brains of patients with Alzheimer's disease. It was postulated that this increase in MAO-B activity was due to gliosis associated with neuronal degeneration. The aim of the present investigation was to evaluate the effect on MAO of neuronal degeneration primarily affecting the cholinergic system. The specific cholinergic toxin AF64A (3 and 4.5 nmol) was injected bilaterally into the cerebral ventricles of rats. We then estimated MAO-A, MAO-B, dopamine (DA) uptake rates and choline acetyltransferase (ChAT) activities in hippocampus, striatum and cortex, 1, 2.5 and 4.5 weeks after the injection. Marked long-lasting reduction in ChAT activities appeared only in hippocampus, consistent with previous reports. The MAO-A activity was unchanged as were DA uptake rates. Neither was there any change in MAO-B activity found 1 week after the injection. However, a significant increase in MAO-B activity appeared after 2.5 weeks and persisted after 4.5 weeks in all 3 brain regions investigated. This result is likely to reflect progressive gliosis after cholinergic neuronal degeneration. Previous results have shown an increased MAO-B activity with age and a further accelerated increase in Alzheimer's disease. Experimentally, hemitransection and injection of kainic acid have been shown to cause a similar increase. The present results show that changes in MAO-B activity also reflect degenerative processes in brain mainly affecting the cholinergic system.

Acetylcholinesterase↗

PubMed1989

11C-labelling of dimethylphenethylamine in two different positions and biodistribution studies.

Dimethylphenethylamine (DMPA), a substrate for the B-form of the monoamine oxidase enzyme (MAO, EC 1.4.3.4), was labelled with 11C in two different positions; in the methyl group (M-DMPA) and in the phenethyl group (P-DMPA). M-DMPA was prepared by N-alkylation of methylphenethylamine with [11C]methyl iodide and P-DMPA was prepared by N-alkylation of dimethylamine with [1-11C]phenethyl iodide. The radiochemical yields were 30-35% (M-DMPA) and 10% (P-DMPA), based on [11C]carbon dioxide, with overall synthesis times of 30-35 min (M-DMPA) and 50 min (P-DMPA). The compounds were isolated by semi-preparative HPLC and the radiochemical purity was in both cases greater than 99%. The biodistributions of 11C-labelled M-DMPA [correction of M-DPMA] and P-DMPA were studied in rat brain by dissection and in the brain of a Rhesus monkey by positron emission tomography (PET).

Animals↗

PubMed1989

MPTP toxicity in relation to age, dopamine uptake and MAO-B activity in two rodent species.

The effects of single and multidose 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) treatment on mice (NMRI and C-57bl) and rats of different ages have been investigated by using the reduction of striatal dopamine uptake rate as a measure of the neurotoxic effect. The possibility that differences in MAO-B activity or in dopamine (DA) uptake rate might explain differences in MPTP toxicity between species, strains or animals of different age was investigated. Single dose MPTP treatment (45 mg/kg) had no effect on 10 day and 3 week old mice, while there was a significant reduction of DA uptake rate at the age of 12 and 40 weeks (both strains). No neurotoxicity of single dose MPTP treatment was observed in the rats, irrespective of their age. Multidose treatment with MPTP (3 x 20-45 mg/kg) caused a reduction of DA uptake rates both in the mice and in the rats at all dose regimens used. The effect of MPTP increased with increasing doses and was most pronounced in the C-57bl mice. Both DA uptake rate and monoamine oxidase B (MAO-B) activity increased with age. The increase in MAO-B activity was highest between 10 days and 3 weeks both in the mice and in the rats. Rats had higher (MAO-B) activity than the mice, while the two species had about the same DA uptake rates. No obvious correlations were found either between MAO-B activities or DA uptake rates and the neurotoxic effect of MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1988

The benzodiazepines: a pharmacological overview.

Benzodiazepines exert their effects by facilitating neurotransmission in GABAergic synapses, probably by increasing the affinity of the GABA receptor to GABA. Stimulation of GABA receptors (at least of the A type) opens chloride ion channels which inhibits the ability of the cell (e.g. monoaminergic or cholinergic) to conduct nerve impulses. The endogenous ligand for the benzodiazepine receptor is probably a peptide, which is able to induce "anxiety" in rats. Thus, if the benzodiazepines are receptor agonists, the endogenous ligand would be an antagonist. The clinical effects resulting from the above mechanism of action (anticonvulsant, muscle relaxant, anxiolytic, sedative-hypnotic and amnesic) are discussed with special attention to preoperative sedation in dental practice.

Benzodiazepines↗

PubMed1988

Low B12 levels related to high activity of platelet MAO in patients with dementia disorders. A retrospective study.

In 35 patients with Alzheimer's presenile disease (AD), 56 patients with senile dementia of the Alzheimer type (SDAT), 54 patients with vascular dementia (VD) and 10 patients with confusional states, age, vitamin B12 in serum, P-folate, B-folate and B-Hb were investigated. Platelet monoamine oxidase (MAO) and cerebrospinal fluid (CSF) levels of homovanillic acid (HVA), 5-hydroxyin-doleacetic acid and 3-methoxy-4-hydroxyphenylglycol were measured. Group differences showed that vitamin B12 levels were reduced in the group of patients with confusional states and SDAT. Five out of ten and 13 out of 56 (respectively) had vitamin B12 concentrations below the lower limit of the reference value (130 pmol/l). A negative correlation was found between B12 levels and platelet MAO activity. The findings indicate that there is a subgroup of patients with late-onset dementia that has low vitamin B12 blood concentrations. HVA levels in CSF, usually found to be reduced in AD patients, were normal in this subgroup.

Aged↗

PubMed1987

Intra- and extra-dopamine-synaptosomal localization of monoamine oxidase in striatal homogenates from four species.

MAO-A and MAO-B activities within and outside dopaminergic synaptosomes in homogenates of striatal tissue from pig, cat, rat and human brains have been studied by using a specific "low substrate concentration technique" with dopamine. It was found that within the synaptosomes, MAO-A activity predominated in all species. Outside the synaptosomes there were more pronounced differences and only in the rat did MAO-A predominate, while in the other species MAO-B predominated. When estimating MAO-A and -B activities with a conventional method the activity of MAO-B predominated in man, cat and pig. Thus, also in species where the MAO-B activity (as estimated in a conventional way) was dominating, the intrasynaptosomal deamination of dopamine was brought about mainly by MAO-A. The "low substrate concentration technique", more adequately reflects physiological conditions by taking into account the higher concentration of monoamine transmitter substrates within the monoamine neurons. With this technique it was found that in all species (with the possible exception of man) the oxidation rate was higher within than that outside the DA-synaptosomes. In man the unavoidable longer time between death and estimation of the enzyme activity may be the cause of the deviating result.

Animals↗

PubMed1987

Locus coeruleus neurons show reduced alpha 2-receptor responsiveness and decreased basal activity in spontaneously hypertensive rats.

Previous studies have indicated that brain noradrenaline (NA) neurons in spontaneously (genetically) hypertensive rats (SHR) are implicated in the development of hypertension. Thus, a number of biochemical aberrations in the metabolism of NA in the SHR brain have been detected although the data are not in total agreement. We report here experiments utilizing single cell recording techniques which show directly a reduction in neuronal activity of brain NA neurons in the locus coeruleus (LC) of SHR. This reduction develops gradually with age and in parellel with the increased blood pressure (BP), but is not altered by acute alterations in BP. The SHR were found to display an increased intraneuronal monoamine oxidase (MAO) activity as well as a specifically reduced sensitivity of inhibitory alpha 2-receptors within the LC. It is suggested that in SHR the LC system, in spite of a reduced basal activity displays increased responsiveness to sensory stimuli, a phenomenon that may contribute to the development of hypertension.

Action Potentials↗

PubMed1987

Platelet MAO in patients with idiopathic pain disorders.

Patients with idiopathic pain syndromes have been compared to healthy volunteers and patients with neurogenic pain syndromes as concerns the activity of the enzyme monoamine oxidase (MAO) in thrombocytes. In both patients with idiopathic pain syndromes and in patients with neurogenic pain syndromes an increased frequency of patients with low platelet MAO activity was found. As low platelet MAO activity has been suggested to reflect low central serotoninergic activity the results are in line with findings of reduced concentrations of the serotonin metabolite 5-HIAA in CSF in patients with idiopathic pain syndromes. The results would also give some support for the suggestion that idiopathic pain syndromes might be a variant of depressive disease.

Adult↗

PubMed1987

5-HIAA and HVA in CSF in patients with idiopathic pain disorders.

Patients with idiopathic pain syndromes were compared with healthy volunteers and with patients suffering from chronic pain syndromes of neurogenic origin, with respect to the concentrations of the metabolites 5-hydroxy-indole-acetic acid (5-HIAA) and homovanillic acid (HVA) in cerebrospinal fluid (CSF). Patients with idiopathic pain syndromes were subdivided according to the presence or absence of somatic lesions. It was found that these groups did not differ in concentrations of 5-HIAA or HVA, at least not when values were corrected for age, sex, and body height. Patients with idiopathic pain syndromes were found to have low concentrations of 5-HIAA, but not of HVA, in CSF. These differences were also obvious when the values were corrected for age, sex, and body height. As low concentrations of 5-HIAA in CSF have previously been demonstrated in patients with depressive disorders, our results support the suggestion by Blumer and Heilbronn (1982) that the idiopathic pain syndrome is a variant of depressive disease. At least the two syndromes share a common pathogenetic mechanism--a disturbance in serotonergic turnover.

Adult↗

PubMed1987

Neuropsychological correlates of platelet monoamine oxidase (MAO) activity in female and male subjects.

Platelet monoamine oxidase (MAO) activity has been found to have behavioral (psychiatric and personality) correlates and is assumed to be linked to central transmitter systems and thus presumably to neuropsychological processes. In the present study, computerized neuropsychological tests, a reaction time (RT) test and a visuo-spatial problem solving test, the Perceptual Maze Test (PMT), were given to 32 female and 29 male students, each sex group divided into three subgroups on the basis of platelet MAO activity. The tests yield measures of laterality (reaction time for left- versus right-sided stimuli) and different aspects of cognitive strategy and skill, e.g. time used for inspection of the maze, for processing the stimulus pattern, and for checking the correctness of solutions. Low MAO female subjects had shorter RTs, pronounced for left-sided stimuli, and shorter inspection times in the PMT compared to other female subjects. Low and high MAO males had difficulties in inhibiting responses, when required, and low MAO males were more rapidly prepared to respond to new stimuli after short intervals than other males. In the PMT, high MAO male subjects spent a smaller part of the total time on inspection in relation to other male groups and had more rubouts than low MAO males, whose maze solving behavior indicated higher visuo-spatial ability. The results are discussed in terms of possible neurochemical bases of impulsivity and psychopathy, and of spatial skill.

Adolescent↗

PubMed1987

Monoamine oxidase (MAO), 5-hydroxyindole acetic acid (5 HIAA) and homovanillic acid (HVA) in motor neuron disease.

Thrombocyte monoamine oxidase (MAO) activity and concentrations of 5-hydroxyindole acetic acid (5-HIAA) and homovanillic acid (HVA) in the cerebrospinal fluid (CSF) were studied in patients with motor neuron disease (MND) and healthy controls. The MAO activity in MND (n = 32) did not differ from age and sex-matched controls (n = 27) or from healthy relatives (n = 9) and no difference was found between advanced and mild cases. In an attempt to explain divergent results from other studies, the effect of storage time on analysis of platelet concentration was studied in three healthy subjects and in three patients with MND. No difference was observed between the groups. No differences were found between the MND group (n = 28) and healthy controls (n = 18) with regard to CSF levels of 5-HIAA and HVA, except for an increase of 5-HIAA among males with MND. The results of this study do not confirm earlier studies that have reported extensive changes in the variables analyzed in patients with MND.

Blood Platelets↗