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Biomedical subjects

G Ebinger

Publications and source records attributed to G Ebinger.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1990

The effect of aging on the D1 dopamine receptors in human frontal cortex.

Dopaminergic pathways to the cerebral cortex may be involved in cognitive function. We examined the effect of aging on the D1 dopamine receptors, and their high-agonist affinity (RH) sites, in postmortem human frontal cortex (n = 32; age range, 19-88 years). With aging, there was a significant decrease in the densities of the D1 dopamine receptors, and their RH sites, in human frontal cortex. The age-related reduction of cortical dopaminergic neurotransmission might contribute to the decline in cognitive abilities of elderly persons.

Adult↗
PubMed1990

D1-dopamine receptor abnormality in frontal cortex points to a functional alteration of cortical cell membranes in Alzheimer's disease.

D1-dopamine receptors and their high-agonist affinity (RH) sites were determined in postmortem-obtained frontal cortex from seven patients with histopathologically confirmed Alzheimer's disease and from seven controls matched for sex, age, and postmortem delay. Total D1-dopamine receptor concentration was unchanged in patients with Alzheimer's disease compared with controls, but the RH sites were significantly reduced in number. Since the RH sites are thought to represent a conformational change of the receptors, induced by the interaction of agonist-bound receptor with a signal transduction protein located in the cell membrane, the reduced ratio of RH sites to total receptors suggests a functional alteration of cortical cell membranes in Alzheimer's disease. Such a cell membrane abnormality might explain why substitution therapy in Alzheimer's disease has been largely disappointing.

Aged↗
PubMed1990

Age-related changes in the human nigrostriatal dopaminergic system.

A deficiency of dopamine in the striatum may contribute to the decline in motor function associated with aging. We examined the effect of aging on the densities of the D1 and D2 dopamine receptors, their high-agonist affinity sites, and the dopamine uptake sites in postmortem human putamen (n = 32; age range, 19-88 years). With aging a steady decrease was seen in dopamine uptake sites (p less than 0.001), confirming previous morphometric and biochemical data of an age-related loss of nigrostriatal axons. In contrast, the concentrations of the D1 and D2 dopamine receptors and their high-agonist affinity sites, which are believed to represent the functionally active receptors, were not affected by the aging process. These results may have implications for the pharmacological treatment of the age-related decline in motor function.

Adult↗
PubMed1990

Human M1-, M2- and M3-muscarinic cholinergic receptors: binding characteristics of agonists and antagonists.

The muscarinic acetylcholine receptors were identified in membrane preparations from human tissues by the specific binding of 1-[benzilic-4,4'-3H] quinuclidinyl benzilate. Saturation binding isotherms of this radioligand yielded a total amount of receptors of 435 +/- 208, 159 +/- 65 and 913 +/- 89 fmol/mg protein, respectively, in the hippocampus, pons and submandibular gland. Non linear least squares analysis of competition binding studies with the antagonists pirenzepine and AF-DX 116 indicates that the majority of receptors are of the M1-type in the hippocampus (83%, high affinity for pirenzepine, intermediate affinity for AF-DX 116), the M2-type in the pons (low affinity for pirenzepine and high affinity for AF-DX 116), and the M3-type in the submandibular gland (low affinity for pirenzepine and AF-DX 116). Competition binding parameters of the agonists carbachol, arecoline, oxotremorine, pilocarpine and MCN-A-343 were compared for M1, M2 and M3 receptors in the human hippocampus, pons and submandibular gland. GTP caused a shift to the right and a steepening of the shallow agonist competition curves in the 3 tissues but did not affect the initially steep ones. This effect is explained by a GTP-mediated conversion of high- to low-agonist affinity sites. The extent of the nucleotide shift was much greater for M2 receptors as compared with M1 and M3 receptors. The GTP effect was impaired by the sulphydryl reagent N-ethylmaleimide, probably due to alkylation of GTP-binding proteins. Moreover, the reagent provoked also an increase of the agonist affinity for the uncoupled muscarinic receptors. For all agonists, this increase was more pronounced for the M2 receptors than for the M1 and M3 receptors. These findings suggest structural differences between the agonist binding sites of M1 and M3 receptors versus the M2 receptors.

Binding, Competitive↗