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Biomedical subjects

P Hartvig

Publications and source records attributed to P Hartvig.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1991

[How much does unemployment mean for the increased use of disability pensions?].

In a probably representative material of 363 applicants for a national rehabilitation or disability pension it was found that 5.2% had lost their job before becoming sick-listed and an applicant for pension, while 3.3% had had serious worries about losing their job, but had not actually done so. The author suggests that unemployment is a relatively modest factor in the marked increase in the 1980s of persons receiving a disability pension, but probably will be much more important in the 1990s.

Adult↗
PubMed1991

Central action of benserazide after COMT inhibition demonstrated in vivo by PET.

Positron emission tomography (PET) following intravenous administration of beta-[11C]-L-DOPA provides a method of assessing regional cerebral uptake and utilization of levodopa. Cerebral levodopa kinetics in the rhesus monkey were investigated after the inhibition of catechol-O-methyltransferase (COMT) with RO 40-7592, and after coadministration of the peripheral aromatic L-amino acid decarboxylase (AADC) inhibitors benserazide and carbidopa. Pretreatment with RO 40-7592 (10 mg/kg), benserazide (10 mg/kg) or carbidopa (3.5 mg/kg) did not change striatal k3, which mainly reflects the ability for the brain tissue to convert [11C]-L-DOPA to [11 C]-dopamine, although the brain's uptake of radioactivity increased substantially after pretreatment with the AADC inhibitors. When benserazide was coadministered with RO 40-7592 (10 mg/kg) a dose-dependent decrease in striatal k3 was measured with an apparent ED50 of 3 mg/kg. No such effect was indicated after pretreatment with the combination of RO 40-7592 (10 mg/kg) and carbidopa (3.5 mg/kg). The possible negative interactions of coadministration with COMT inhibitors and predominantly peripherally acting AADC inhibitors must be considered when used in the therapy of Parkinson's disease.

Animals↗
PubMed1991

Brain kinetics of L-[beta-11C]dopa in humans studied by positron emission tomography.

The in vivo dopamine precursor L-3,4-dihydroxyphenylalanine (L-DOPA) labelled with 11C in the beta position has been used for positron emission tomography studies of L-DOPA utilization in the brain. The brain uptake and kinetics of L-[11C]DOPA-derived radioactivity were studied in healthy male volunteers, and the specific utilization, i.e. decarboxylation rate of L-[11C]DOPA in different brain areas, was quantified using a brain region devoid of specific L-[11C]DOPA utilization as reference. Total uptake of L-[11C]DOPA-derived radioactivity measured in the brain varied two- to three-fold between subjects, with highest radioactivity in the striatal region. Specific utilization of L-[11C]DOPA radioactivity in the striatal region and in the prefrontal cortex varied twofold between subjects. No specific utilization was observed in other regions of the brain. The uptake of radioactivity in the brain increased dose-dependently with the simultaneous administration of unlabelled L-DOPA up to 10 mg. On the other hand, a decrease in brain radioactivity uptake was measured after pretreatment with 1 mg/kg oral L-DOPA, indicating competition for transport across the blood-brain barrier. Benserazide 0.5 mg/kg orally increased somewhat the radioactivity uptake to the brain. None of these pharmacological perturbations demonstrated any clearcut effect on specific utilization of L-[11C]DOPA. Thus, 11C-labelled L-DOPA is introduced as an alternative to the well-established L-6-[18F]fluoro-DOPA methodology in clinical studies on brain L-DOPA uptake and dopamine synthesis.

Adult↗
PubMed1991

Low brain uptake of L-[11C]5-hydroxytryptophan in major depression: a positron emission tomography study on patients and healthy volunteers.

The precursor of serotonin, L-5-hydroxytryptophan (L-5-HTP), was radiolabelled with 11C in the beta-position, yielding [beta-11C]serotonin after decarboxylation, allowing positron emission tomography studies of L-5-HTP uptake across the blood-brain barrier. We studied 8 healthy volunteers and 6 patients with histories of DSM-III major depression, 2 with repeated examinations after clinically successful treatment. We report a significantly lower uptake of [11C]5-HTP across the blood-brain barrier in depressed patients, irrespective of phase of illness. The findings emphasize that serotonin is involved in depressive pathophysiology and support earlier suggestions that the transport of 5-HTP across the blood-brain barrier is compromised in major depression.

5-Hydroxytryptophan↗
PubMed1990

Combination of positron emission tomography with liquid chromatography in neuropharmacologic research.

Positron emission tomography (PET) is an in vivo autoradiographic technique that determines the radioactive distribution and kinetics of a radiolabelled tracer in a tissue. By choice of tracer, it is possible to study physiological processes in living animals and man non-invasively. PET has certain disadvantages such as limited spatial resolution and simultaneous measurement of radiolabelled tracer with the metabolites formed. For an adequate interpretation of the data obtained, complementary techniques such as column liquid chromatography of radioactive composition in blood, plasma, urine and tissue samples have to be used. The prerequisites for any chromatographic technique used for the radioanalysis of substances are speed, high selectivity and high separation efficiency. Examples from PET studies in combination with chromatographic analysis will be given. The utilization of L-dopa in the brain constitutes several steps. Analysis by column liquid chromatography of metabolites in plasma and in monkey brain tissue will make it possible to elucidate different utilization processes of the tracer. Kinetic studies of 11C-labelled neuropeptides such as methionine-enkephalin and substance P revealed high radioactivities in the brain of monkeys. However, simultaneous determination plasma and urine radioactivities using liquid chromatography with radiochemical and photometric detection both indicated that the brain radioactivities emanated to a large extent from 11C-labelled metabolites formed in vivo. Studies with PET using radiotracers having a rapid and extensive metabolism require complementary techniques in the evaluation. High detection selectivity, by combination of photometric and radiochemical detection and rapid and efficient separation, will make liquid chromatography a most important complement in the analysis.

Chromatography, Liquid↗
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↗