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Biomedical subjects

S M Aquilonius

Publications and source records attributed to S M Aquilonius.

At least 55 records · Page 3Linked to original sources
PubMed1992

Increased binding of 3H-L-deprenyl in spinal cords from patients with amyotrophic lateral sclerosis as demonstrated by autoradiography.

The present investigation has applied quantitative autoradiography and histochemistry to study the regional distribution of MAO-B and its relation to the number of cells in respective regions. L-deprenyl binds irreversibly and quantitatively to the B-form of monoamine oxidase, MAO, and is an ideal 3H-ligand to measure the MAO-B enzyme protein in tissues by means of in vitro autoradiography. The investigation is performed on spinal sections from five controls and five cases with amyotrophic lateral sclerosis (ALS) on cervical, thoracic and lumbar level. The highest density of 3H-L-deprenyl binding was found around the central canal (lamina X). MAO-B was markedly increased (up to 2.5 times of values in controls) specifically in regions of neurodegeneration e.g. motor neuron laminae and corticospinal tracts. There was a high correlation between glial cell count and 3H-L-deprenyl binding with a relation indicating enhanced MAO-B protein in glial cells within areas of neurodegeneration. In contrast the increased microglial cell number in ALS did not show any correlation with 3H-L-deprenyl binding.

Aged↗
PubMed1992

Receptor alterations in manganese intoxicated monkeys.

The density of four different receptors and one marker of dopamine uptake sites were analyzed in monkey brains after manganese exposure (0.1 g manganese per month during 26 months, a dose comparable to that workers might inhale in dusty environments) by means of quantitative receptor autoradiography. The binding of 3H-mazindol to the dopamine uptake sites was reduced by 75% in both the head of the caudate nucleus and putamen, while it remained unchanged in the other regions analyzed. The binding of the D1 receptor ligand 3H-SCH 23,390 was reduced about 45% in the same areas as mazindol binding, while the density of D2 receptors was unaffected. The muscarinic acetylcholine receptors as well as GABAA receptors remained also unchanged in all brain areas analyzed after manganese exposure. Thus the dopaminergic neurons must be considered to be vulnerable to manganese concentrations attainable in the work environment. Our results also indicate that postsynaptic structures containing D1 receptors are sensitive while cells containing D2 receptors are either spared or compensated for by up-regulation of the number of receptors on remaining sites.

Animals↗
PubMed1992

Manganese induced brain lesions in Macaca fascicularis as revealed by positron emission tomography and magnetic resonance imaging.

A series of positron emission tomography scans was made on two monkeys during a 16-month period when they received manganese(IV)oxide by subcutaneous injection. The distribution of [11C]-nomifensine uptake, indicating dopamine terminals, was followed in both monkey brains. The brain distributions of [11C]-raclopride, demonstrating D2 dopamine receptors, and [11C]-L-dopa, as a marker of dopamine turnover, were followed in one monkey each. The monkeys developed signs of poisoning namely unsteady gait and hypoactivity. The [11C]-nomifensine uptake in the striatum was reduced with time and reached a 60% reduction after 16 months exposure. This supports the suggestion that dopaminergic nerve endings degenerate during manganese intoxication. The [11C]-L-dopa decarboxylation was not significantly altered indicating a sparing of [11C]-L-dopa decarboxylation during manganese poisoning. A transient decrease of [11C]-raclopride binding occurred but at the end of the study D2-receptor binding had returned to starting values. The magnetic resonance imaging (MRI) revealed that the manganese accumulated in the globus pallidus, putamen and caudate nucleus. There were also suggestions of gliosis/edema in the posterior limb of the internal capsule. MRI might be useful to follow manganese intoxication in humans as long as the scan is made within a few months of exposure to manganese, i.e. before a reversal of the manganese accumulation.

Animals↗
PubMed1992

Monoamine oxidase-B in motor cortex: changes in amyotrophic lateral sclerosis.

The occurrence of monoamine oxidase-B in cerebral cortex and white matter in brains from three patients with the diagnosis of amyotrophic lateral sclerosis and three controls was quantified by means of an autoradiographical method. [3H]L-Deprenyl, an irreversible and selective monoamine oxidase-B inhibitor, was used as ligand and the autoradiographs were analysed by computer-assisted densitometry. In both amyotrophic lateral sclerosis and control cerebral cortex, lamina I showed the highest, laminae II and III intermediate, laminae IV, V and VI the lowest [3H]L-deprenyl binding. White matter showed about one-third of the binding in the cortex. Amyotrophic lateral sclerosis cases showed significantly higher binding of [3H]L-deprenyl in all the cortex laminae of the pre- and postcentral gyri. There was no difference in the binding between the amyotrophic lateral sclerosis cases and the controls in area 7 of the occipital cortex, an area which is relatively spared in amyotrophic lateral sclerosis.

Aged↗
PubMed1992

Cerebral uptake and utilization of therapeutic [beta-11C]-L-DOPA in Parkinson's disease measured by positron emission tomography. Relations to motor response.

Cerebral uptake and utilization of levodopa was measured in eight patients with idiopathic Parkinson's disease (PD) by [beta-11C]-L-DOPA and positron emission tomography (PET). By adding pharmacological doses of unlabelled levodopa to the radioactive solution it was possible to evaluate the clinical effect simultaneously with the cerebral kinetics of the drug. Additionally, in two of the patients with advanced PD, investigations with the dopamine re-uptake blocker [11C]-(+)-nomifensine and PET were carried out to get a measure of the density of striatal dopaminergic nerve-terminals. The brain uptake of [beta-11C]-L-DOPA was inversely correlated to the sum of large neutral amino acids in plasma. In the eight PD patients studied with [beta-11C]-L-DOPA striatal k3, which reflects the ability for striatal tissue to decarboxylate the tracer by the action of aromatic L-amino acid decarboxylase (AADC), was decreased 35% compared to healthy subjects. It was demonstrated that, in the patients with advanced PD and motor fluctuations on oral L-DOPA medication, reversal of parkinsonian symptoms occurred at very low striatal tissue dopamine concentrations. In the two very advanced patients studied with [11C]-(+)-nomifensine the striatal binding of the tracer was 50% reduced.

Aged↗
PubMed1992

Estimation of regional cerebral utilization of [11C]-L-3,4-dihydroxy-phenylalanine (DOPA) in the primate by positron emission tomography.

The intracerebral kinetics of [11C]-labelled L-3,4-dihydroxyphenylalanine, L-DOPA, was investigated in rhesus monkeys by positron emission tomography (PET). Through the labelling of the L-DOPA molecule in different positions and observation of a series of pharmacological challenges it was possible to establish that the kinetic conversion of the radiotracer in the striatum represents the process of decarboxylation to [11C]-labelled dopamine. The rate constant for this process can be estimated using a two-compartment model. The use of [11C]-L-DOPA and PET will thus provide a possibility for in vivo studies of blood-brain barrier transport of the amino acid as well as for the estimation of the ability for brain tissue to decarboxylate the tracer by the action of aromatic L-amino acid decarboxylase.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1992

No re-expression of high-affinity nerve growth factor binding sites in spinal motor neurons in amyotrophic lateral sclerosis.

Autoradiographic studies of high-affinity nerve growth factor binding sites in the cervical human spinal cord revealed a high density of binding sites in the dorsal horn and in the tract of Lissauer, which is in agreement with investigations in nonprimates. Very low or no binding was found in the motor neuron areas of controls as well as in amyotrophic lateral sclerosis cases, which indicates that the degeneration of motor neurons in this disease is not accompanied by re-expression of high-affinity nerve growth factor receptors.

Aged↗
PubMed1991

Quantitative localization of human brain monoamine oxidase B by large section autoradiography using L-[3H]deprenyl.

The distribution of monoamine oxidase B (MAO-B) in the human brain was studied by quantitative autoradiography using L-[3H]deprenyl as a ligand. Two postmortem brains from patients without any known neurological diseases were used in this study. Cryosections of 100 microns thickness were taken on tape/paper and transferred to gelatinized glass plates. The sections were incubated with 10 nM L-[3H]deprenyl for 1 h and exposed to a film at 4 degrees C for 4 weeks. The autoradiograms were analyzed by computerized densitometry. High L-[3H]deprenyl binding was observed in caudate nucleus, putamen, cingulate gyrus and insula cortex. Moderate to low binding was seen in globus pallidus, temporal and parietal cortex and in various thalamus nuclei. Occipital cortex showed the lowest binding among the cortex regions and white matter the lowest among all the regions studied. All the regions in case 2 (aged 67) showed higher degree of binding when compared with case 1 (aged 58), which is in agreement with previous results showing an increase in MAO-B activity with age. When the specific binding of L-[3H]deprenyl was plotted against the MAO-B activities estimated biochemically in punches from the same areas, a high positive correlation was found.

Adult↗
PubMed1991

What has PET told us about Parkinson's disease?

From 1983, when dopaminergic structures were visualized for the first time in the human brain by positron emission tomography (PET) and onwards about 120 PET studies on Parkinsons disease have been listed in MEDLINE. With 18F-fluorodopa presynaptic dopamine insufficiency can be demonstrated in PD. By using 11C-nomifensine the dopamine reuptake sites can be visualized with PET. These results indicate that the striatal dopaminergic terminals are relatively preserved in PD as compared to the extreme reductions of dopamine in this region post mortem. Radiolabelled D2-agonists indicate a slight increase in these binding sites in de novo PD and no marked reduction in more advanced disease. 11C-selegiline have been used to demonstrate the intracerebral MAO-B inhibition by therapeutic doses of this drug. 11C-L-dopa and PET have demonstrat the rapid striatal decarboxylation of therapeutic doses of L-dopa also in advanced PD and a rough estimate of the striatal dopamine concentration inducing an "on-response" has been obtained. These contributions of PET to PD research are discussed in the article.

Animals↗
PubMed1990

[Injection of botulinum toxin as a new treatment of torticollis].

Thirty patients with spasmodic torticollis were injected with Botulinum A toxin into sternomastoid and posterior neck muscles. Neurophysiological investigation showed neuromuscular transmission in the sternomastoid muscle to be impaired already within the first day after injection of 50 U toxin. Signs of denervation were discernible after seven days, and of reinnervation after two weeks. As assessed by 'blind' ratings of videotapes, 78 per cent of the patients improved, as compared with the figure of 87 per cent based on clinical evaluation. When injections were repeated every third month, there was a tendency for symptomatic effects to increase with time. Side effects were mild and transient. Thus local injections of botulinum toxin would seem to be the treatment of choice in this form of dystonia.

Adult↗
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

Clinical pharmacokinetics of intravenous and oral 9-amino-1,2,3,4-tetrahydroacridine, tacrine.

The pharmacokinetics of 9-amino-1,2,3,4-tetrahydroacridine; tacrine, THA, was studied after intravenous administration and following the first and last oral doses of a seven week clinical trial involving 8 patients with amyotrophic lateral sclerosis, ALS. Two surgical patients given intravenous THA for reversal of postoperative sedation were also included. Plasma concentration of THA and in some cases the metabolite, 1-hydroxy-THA, were assayed using a selective and sensitive method with high performance liquid chromatography. After an intravenous dose of 30 mg THA, the plasma concentrations were fitted to a two-compartment model. Plasma clearance showed a threefold interindividual variation with a mean of 2.42 l.h-1. Volume of distribution, V alpha varied 100-680 l with a mean of 349 l. The plasma half-lives of distribution and elimination were 1.8 and 98.2 min, respectively. Oral bioavailability showed large interindividual differences and ranged 6-36% in the four subjects studied. After seven weeks treatment with oral THA, plasma concentrations immediately prior to medication were below 10 ng/ml in three patients and above 100 ng/ml in two patients. At the same occasion the plasma metabolite concentrations considerably exceeded those of THA. THA medication was associated with side effects in the majority of the patients.

Administration, Oral↗
PubMed1990

Pharmacokinetics and effects of levodopa in advanced Parkinson's disease.

Five patients with severe Parkinson's disease were characterized with respect to their pharmacokinetic and pharmacodynamic responses to levodopa given: orally, intravenously (three different infusion rates) and intraduodenally. The best therapeutic infusion rate in the intravenous study was used for the intraduodenal infusion of levodopa. A lag time between plasma concentration and effect following oral administration was seen in three of the five patients and this disequilibrium was estimated as the rate constant Ke0 using model-independent analysis. The plasma concentration-effect relationship was similar for the three modes of administration and in all patients the therapeutic plasma concentration for full mobility was greater than 4-5 micrograms.ml-1. The disequilibrium half-life for development of effect after oral administration was calculated to be about 30 min. The patients remained clinically stable during the period of the intraduodenal infusion.

Administration, Oral↗