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Biomedical subjects

G Ebinger

Publications and source records attributed to G Ebinger.

At least 19 recordsLinked to original sources
PubMed1992

Microbore liquid chromatography with dual electrochemical detection for the determination of serotonin and 5-hydroxyindoleacetic acid in rat brain dialysates.

A microbore liquid chromatographic assay with dual electrochemical detection is described for the determination of serotonin and its metabolite 5-hydroxyindoleacetic acid in rat brain dialysates. The concentration of serotonin in these samples is usually in the low nanomolar range (fmol per 20 microliters range). To optimize separation and detection, several adaptations were made to the system with respect to the injection valve, flow-rate of the pump, connections between injector, column and detector, and cell volume of the detector. These aspects are discussed, as well as the procedure developed for optimal peak identification of serotonin and correct estimation of 5-hydroxyindoleacetic acid. The assay allows the measurement of basal serotonin release without the use of a re-uptake inhibitor added to the perfusion fluid.

Animals↗
PubMed1992

High-performance liquid chromatography with electrochemical detection for the determination of levodopa, catecholamines and their metabolites in rat brain dialysates.

A high-performance liquid chromatographic assay with electrochemical detection is described for the simultaneous determination of levodopa, 3-O-methyldopa, dopamine, dihydroxyphenylacetic acid, homovanillic acid, 3-methoxytyramine, noradrenaline, adrenaline, 3-methoxy-4-hydroxyphenylethylene glycol and 5-hydroxyindoleacetic acid in rat brain dialysates. Samples are obtained in vivo using the microdialysis technique. Microdialysis probes are placed in the brain area to be studied and neurochemicals are collected by perfusion of the probe with modified Ringer's solution. Direct injection of the dialysates allows rapid and reliable results to be obtained.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Serotonin-binding proteins in the bovine cerebral cortex: interaction with serotonin and catecholamines.

The soluble serotonin-binding proteins (SBP) present in bovine frontal cortex are very similar to those reported in rat brain. Binding of [3H]serotonin to SBP, present in ammonium sulphate-precipitated proteins from bovine cortex, requires Fe2+ but not Fe3+. In the presence of an optimal concentration of Fe2+ (0.1 mM), bovine SBP behave as a single class of non-cooperative sites for [3H]serotonin binding (Bmax = 120 +/- 12 pmol/mg protein, KD = 0.12 +/- 0.04 microM, n = 3). Binding of [3H]serotonin is decreased by nucleotides and by reagents which modify sulfhydryl groups and reduce disulfide bonds and by metal ion chelators. Serotonin analogs possessing an hydroxyl group on the indole ring and catecholamine analogs possessing an intact catechol moiety are effective competitors (Ki from 0.1 to 0.3 microM). In both cases, the aliphatic amino group does not contribute to the binding, but the affinity is strongly decreased if aromatic hydroxyl groups are methoxylated. Catecholamine-SBP interactions can also be demonstrated directly by binding experiments. Binding of [3H]dopamine is greatly enhanced by Fe2+, Cu2+ and Mn2+, but not by Fe3+. The Fe(2+)-dependent binding component of [3H]dopamine is saturable (Bmax = 279 +/- 64 pmol/mg protein, KD = 0.19 +/- 0.02 microM, n = 3), and possesses the same physicochemical properties as SBP: it elutes immediately after the void volume on a Sephacryl S100 HR (1.6 x 140 cm) gel filtration column (reflecting aggregation) and it migrates with an apparent molecular weight of 57-58 kDa on native polyacrylamide gel electrophoresis. Whereas the serotonin-storing role of SBP in serotonergic neurons has already been well documented, the present data advocate that these proteins may also possess catecholamine-storing properties.

Animals↗
PubMed1992

Idiopathic hemiparetic parkinsonism, a syndrome distinct from idiopathic parkinsonism.

Two women had a syndrome of progressive parkinsonism with ipsilateral rigidity, mild resting tremor, paresis, hyperreflexia, and an extensor plantar response. Symptoms had started 24 and 3 months after a surgical procedure in the affected limb. Neuroimaging studies were unhelpful. Both the parkinsonian features and the pyramidal tract signs responded well to dopaminergic drug treatment. We propose that the syndrome be called "idiopathic hemiparetic parkinsonism".

Adult↗
PubMed1992

Biotransformation of L-dopa in striatum and substantia nigra of rats with a unilateral, nigrostriatal lesion: a microdialysis study.

Microdialysis was used to study the biotransformation of L-DOPA in the striatum and substantia nigra of rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra. The animals were pretreated with carbidopa (50 mg/kg p.o.) for 5 days. They were anaesthetized, and microdialysis probes were implanted into the intact and denervated striatum and into the intact and lesioned substantia nigra. The biotransformation of L-DOPA (5 mg/kg i.p.) in these regions was investigated. These results were compared with those obtained after administration of a much higher dose of L-DOPA (100 mg/kg i.p.). Changes in extracellular L-DOPA, 3-O-methyldopa (3-OMD), dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were determined by HPLC with electrochemical detection. Although rats with a unilateral nigrostriatal lesion did not show rotational behaviour after 5 mg/kg L-DOPA, DA levels were increased significantly both in the intact and the denervated striatum and in the intact and the lesioned substantia nigra. This increase was most pronounced in the denervated striatum. At 100 mg/kg L-DOPA, the increases in extracellular dopamine in intact and denervated striatum were about twice as high as the increases observed at the lower dose. A similar increase was observed in the intact substantia nigra. However, in the lesioned substantia nigra there was a fourfold increase. L-DOPA, at both doses, was evenly distributed between the brain areas studied and the lesion had no effect on the uptake of the drug at the blood-brain barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Autoradiographic distribution of alpha 2 adrenoceptors, NAIBS, and 5-HT1A receptors in human brain using [3H]idazoxan and [3H]rauwolscine.

The regional distribution of [3H]idazoxan and [3H]rauwolscine was studied autoradiographically in human brain. [3H]Idazoxan binds with high affinity to alpha 2 adrenoceptors as well as to non-adrenergic sites (NAIBS). [3H]Rauwolscine, besides binding to alpha 2 adrenoceptors, also binds to 5-HT1A receptors. Both radioligands labelled the same population of alpha 2 adrenoceptors, defined as the epinephrine-displaceable binding component. The highest densities of alpha 2 adrenoceptors occur in the leptomeninges, cerebral cortex and claustrum; lower densities were visualised in the basal ganglia, thalamus, pons, substantia nigra, cerebellum and medulla oblongata; no alpha 2 adrenoceptors were detected in amygdala and nucleus ruber. NAIBS were present in all the examined brain areas, with the highest densities found in the basal ganglia and substantia nigra. The finding that certain brain regions, such as the amygdala, contained NAIBS but no detectable alpha 2 adrenoceptors, suggests that the binding sites are independent from each other. The regional distribution of 5-HT1A receptors labelled by [3H]rauwolscine is in agreement with previous studies using [3H]8-OH-DPAT.

Adult↗
PubMed1991

Central-nervous-system demyelination after immunisation with recombinant hepatitis B vaccine.

2 patients had neurological symptoms and signs, with evidence of central-nervous-system demyelination, 6 weeks after administration of recombinant hepatitis B vaccine. 1 had known multiple sclerosis but the other had no history of neurological disease; both had HLA haplotypes DR2 and B7, which are associated with multiple sclerosis. A causal link between vaccination and demyelination cannot be established from these 2 case-reports, but the time interval would fit a proposed immunological mechanism.

Adult↗
PubMed1991

Distribution of monoamines in human brain: evidence for neurochemical heterogeneity in subcortical as well as in cortical areas.

Norepinephrine, epinephrine, dopamine, serotonin and their major metabolites were measured by high-performance liquid chromatography with electrochemical detection in 49 regions of the human brain. The regional distribution of the different monoamines in the subcortical areas was similar to previous reports. We report here the distribution pattern of the 4 monoamines observed in the cerebral cortex. Regional differences in concentration were observed for norepinephrine, epinephrine and serotonin, with high concentrations in the frontal and parietal regions. However, no regional difference in dopamine concentrations was detected. The possible role of norepinephrine and serotonin as conventional transmitters, and of dopamine and epinephrine as neurotransmission modulators is discussed.

Aged↗
PubMed1991

In vivo pharmacokinetics of levodopa and 3-O-methyldopa in muscle. A microdialysis study.

In the present study in vivo microdialysis sampling coupled to high-performance liquid chromatography with electrochemical detection, was used to study the pharmacokinetics of levodopa and 3-O-methyldopa in skeletal muscle in dog, after intravenous administration of levodopa. For comparison, the pharmacokinetic parameters of both compounds were simultaneously determined in plasma using blood collection. Muscle microdialysis samples and blood were continuously collected for 4 h after the administration of levodopa (25 mg/kg). Pharmacokinetic profiles of levodopa in plasma and muscle were different. The mean Tmax value of levodopa in plasma and muscle was 0.16 h and 1.0 h, respectively. The AUC0----inf for levodopa in plasma was nearly 18-fold higher in plasma than in muscle. The 3-O-methyldopa concentration increased very rapidly after the administration of levodopa, to reach a plateau after 2.5 h and 3 h in plasma and muscle, respectively. The AUC0----4 for 3-O-methyldopa was 3.6-fold higher in plasma than in muscle. The ratio levodopa/3-O-methyldopa, reflecting the metabolic rate of levodopa, was 3.5 times higher in plasma than in muscle, at the peak value of levodopa, and then rapidly declined to values lower than 1, one hour after administration of the drug. We compared our results with literature data from postmortem studies done in rat experiments. We concluded that levodopa is not accumulating in muscle as such, but is converted to 3-O-methyldopa probably before leaving the plasma compartment.

Animals↗
PubMed1991

Clinical and pharmacokinetic comparison of oral and duodenal delivery of levodopa/carbidopa in patients with Parkinson's disease with a fluctuating response to levodopa.

The clinical effects and pharmacokinetics of orally and intraduodenally administered levodopa, in four patients with Parkinson's disease have been compared. The patients had unpredictable fluctuations in motor function and episodic unresponsiveness to single doses of levodopa. The pharmacokinetic and clinical data of these patients were compared retrospectively with those of Parkinsonian patients with fluctuations in motor performance but with preserved clinical responses to single oral doses of levodopa. There was a threshold plasma concentration of levodopa associated with the "switch on or off" effect. In addition, rapid attainment of this critical plasma concentration was associated with a quicker onset of action and a more prolonged clinical response. All the patients had delayed absorption of levodopa related to delayed and erratic gastric emptying, which contributed to the fluctuation in motor response. In contrast, the patients with fluctuating motor effects but a preserved clinical response after levodopa showed an absorption pattern comparable to that of four patients studied after duodenal delivery of levodopa. It is suggested that there is a subgroup of patients with fluctuating responses due mainly to altered peripheral pharmacokinetics of levodopa. The findings demonstrate the relevance of routine measurements of plasma levodopa in patients with Parkinson's disease in whom there are fluctuations in motor performance.

Administration, Oral↗
PubMed1991

Meningoencephalitis caused by Rickettsia conorii.

Case report of Mediterranean spotted fever in an 18 year old male heroin addict, caused by Rickettsia Conorii. The typical "tache noir" was absent. The patient developed meningoencephalitis within 5 days after onset of the systemic symptoms. Diagnosis was based on serological findings. Treatment with doxycycline led to rapid recovery without sequelae.

Adolescent↗
PubMed1991

Continuous intravenous monitoring of levodopa and 3-O-methyldopa by microdialysis and high-performance liquid chromatography with electrochemical detection.

Microdialysis, in association with ion-pair reversed-phase high-performance liquid chromatography with electrochemical detection, was applied in vitro for the determination and quantification of levodopa and 3-O-methyldopa in blank spiked plasma and blood. The method presented gave accurate results; the calibration graphs for plasma were linear over the range of the expected values for both compounds. When using a dialysis probe with a membrane length of 1.6 cm at a 5 microliters min-1 perfusion speed, the recovery rate in plasma for levodopa was 30.1% and 68.5% for 3-O-methyldopa. However, less reproducible results were obtained for plasma levodopa levels in the range of 0.5 microliter ml-1 and lower. The microdialysis technique was subsequently successfully applied for the continuous intravenous monitoring of levodopa and 3-O-methyldopa in a levodopa-treated dogs.

Animals↗
PubMed1991

Sudden hypotonic paraparesis caused by tophaceous gout of the lumbar spine.

Gouty arthritis of the axial skeleton is rare, and neurological complications due to spinal cord or nerve root compression secondary to tophaceous deposits have been seldom reported. We describe a patient with chronic gouty arthritis who developed an acute paraparesis caused by tophaceous cauda equina compression. Surgical removal of the mass resulted in complete recovery.

Arthritis, Gouty↗
PubMed1991

Increase in serum myoglobin, creatine kinase, and free fatty acids, during recovery from a paralytic attack in hypokalemic periodic paralysis.

In a patient with hypokalemic periodic paralysis (HPP), recovery from a paralytic attack, coinciding with the restoration of plasma potassium, was associated with a rise in serum myoglobin (Mb) and creatine kinase (CK). The increase of muscle proteins in serum was preceded by an increase in serum free fatty acids (FFA). An increased permeability of the sarcolemma, caused by an accumulation of FFA within the muscle cell, might underly the reflux of potassium into the circulation. This might represent a mechanism by which the paralytic attacks in HPP terminate.

Adolescent↗
PubMed1991

D1 and D2 dopamine receptors in human substantia nigra: localization and the effect of aging.

D1 and D2 receptor densities in human substantia nigra were examined by use of the specific binding of, respectively, [3H]SCH 23390 [R(+)-7-chloro-8-hydroxy-3-[3H]methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine] and [3H]spiperone. A unilateral loss of striato- and pallidonigral pathways by an infarction (n = 4) had no effect on the ipsilateral nigral D2 receptors, but reduced the ipsilateral nigral D1 receptors by 48-60% compared with the intact side. These data suggest that a substantial fraction of D1 receptors in human substantia nigra is located on terminals of striato- and/or pallidonigral neurons, whereas D2 receptors are confined to intrinsic nigral cells. We also examined the effect of aging on the D1 and D2 receptors in substantia nigra obtained from 25 postmortem human brains (age range 19-88 years). The densities of both receptor types were not affected by the aging process. Since nigrostriatal dopaminergic neurons degenerate with aging, these results suggest either that the nigral D2 receptors are up-regulated in response to a progressive depletion of dopamine in the substantia nigra or that, in contrast to the rat, they are not located on dopaminergic neurons.

Aged↗