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Biomedical subjects

P Riederer

Publications and source records attributed to P Riederer.

At least 487 records · Page 27Linked to original sources

Dopamine metabolism in human brain: effect of monoamine oxidase inhibition in vitro by (-)deprenyl and (+) and (-) tranylcypromine.

The effects of the monoamine oxidase inhibitors (-)deprenyl and (+)-and (-)tranylcypromine on dopamine oxidation in human caudate have been investigated. Oxidation of dopamine has been found to exhibit both (-)deprenyl-sensitive and -insensitive components. The tranylcypromine isomers are both more sensitive towards dopamine than 5-hydroxytryptamine oxidation, (+) isomer being the more effective of the two. These results are discussed in terms of the in vivo action of the drugs and their therapeutic value.

Aged↗

Benign and malignant types of Parkinson's disease: clinical and patho-physiological characterization.

Parkinson's disease (P.D.) is characterized by two different types, a benign form found in 85% of patients and a malignant type in 15%. Computer tomography shows malignant patients, in the end stage of the disease process, to exhibit hydrocephalus internus and externus. Such patients exhibit early EEG-deterioration and pharmacotoxic psychosis. The application of neuroleptics to patients with P.D. is associated with an increase in the urinary excretion of acidic metabolites especially of 5-hydroxyindoleacetic acid. It is suggested, that this treatment might also be a useful therapeutic approach to optimizing the residual neuronal function in Parkinson's disease.

Aged↗

Oral and parenteral nutrition with L-Valine: mode of action.

The intravenous application of the branched chain amino acid L-valine to patients with hepatic coma resulted in a specific drop of tryptophan, serotonin and 5-hydroxyindole acetic acid. Clinical improvement of hepatic encephalopathy and of the underlying neurotransmitter (serotonin) and ammonia derangements by administration of L-valine suggest a possible role of this competitive amino acid on intermediary metabolism and ammonia detoxification.

Aged↗

L-dopa competes with tyrosine and tryptophan for human brain uptake.

Tyrosine and tryptophan have been assayed spectrofluorometrically in postmortem human brain areas of patients with Parkinson's disease treated orally with or without 3,4-dihydroxyphenylalanine (L-dopa) plus the peripherally acting decarboxylase inhibitor benserazide. Tyrosine as well as tryptophan decrease significantly after treatment with L-dopa, thus showing a competitive action of L-dopa to other aromatic amino acids on human brain uptake. It is suggested that some of the side effects of L-dopa treatment in Parkinson's disease are due to a disturbance in the brain and neural uptake of other, specially aromatic and branched-chain amino acids. An influence of L-dopa administration on protein synthesis also cannot be excluded.

Aged↗

The distribution and metabolism of L-tryptophan in healthy probands under dietary conditions.

Oral administration of 500 mg or 1,500 mg of L-tryptophan (TRP) respectively to healthy probands resulted in a significant increase in free and bound TRP in plasma 2 hours after consumption. Serotonin and 5-hydroxyindole-3-acetic acid (5-HIAA) also demonstrate a significant increase in plasma, while tyrosine shows no changes. However, a competitive reciprocity exists between the uptake of tryptophan and tyrosine because TRP increases significantly in the platelets after administration, and tyrosine is reduced. The concentration of serotonin also decreases, an effect which also indicates a competitive reciprocity between tryptophan and serotonin uptake. Hence, the platelet may be employed as a (neuronal) model for the study of mechanisms of amino acid transport through membranes and the factors by which they are influenced. Studies on metabolites of biogenic amines in urine, that is, indole-3-acetic acid (IAA), 5-HIAA, homovanillic acid (HVA), and vanillylmandelic acid (VMA) showed significant increase in IAA, 5-HIAA, and HVA after administration of 1,500 mg TRP. The increased concentration of HVA is traced to synthesis of serotonin in dopaminergic neurons, which leads to temporary secretion of dopamine, and subsequently, HVA.

Adult↗

[The combined treatment of Parkinson's disease with L-dopa plus decarboxylase inhibitors (carbidopa, benserazide) (author's transl)].

An open cross-over study of 20 patients with Parkinson's disease performed with two drugs containing L-dopa and a peripheral aromatic amino acid decarboxylase inhibitor (benserazide, carbidopa) confirmed the conclusions reached in other clinical trials that this combined treatment of Parkinson's disease is the most effective form of drug therapy available at present. With both drugs, Madopar or Sinemet, an optimum therapeutic result was obtained with relatively small doses of L-dopa (the reduction in L-dopa dosage amounting to about 80%). A loss of efficacy with both drugs, which has observed during long-term treatment of patients with Parkinson's disease, could be avoided by switching the patients from Sinemet to Madopar and vice versa. Determination of L-dopa in the plasma demonstrated that with either drug similar plasma levels of L-dopa were achieved during clinically effective treatment.

Aged↗

Effects of post-mortem storage on synaptic 5-HT binding and uptake in mammalian brain.

Synaptosomes and synaptic membranes were isolated from rat brain after various storage times and temperatures of the tissue. Synaptosomal 5-HT uptake was diminished by about 20% within the first hour after decapitation. No significant change in the incorporation rate was observed for the seven proceeding hours if the brains were stored at room temperature. After an initial decrease of about 15%, 5-HT incorporation remained constant for at least 24 hours if the tissue was stored at 4 degrees C. Electron micrographs showed that nerve endings were highly disrupted by freezing and thawing of the brains.--The capacity of high affinity 5-HT binding to the microsomal synaptic membrane fraction decreased with the first hour by about 13% to 120--130 fmoles 5-HT/mg protein and remained almost constant for the next eight hours. Freezing at --80 degrees C of whole brain or of isolated membranes did not affect 5-HT receptor interaction.--The capacity of specific 5-HT binding to membranes isolated from human post-mortem brain was comparable to that found with synaptic membranes from rat brain. In contrast to the control values, a significant decrease in 5-HT binding was observed in membrane fractions isolated from brain after cerebral insult.

Animals↗

Regional brain studies on indoles and tyrosine in Mongolian gerbils during nutrition with artificial mixtures high in branched chain amino acids compared to a protein rich diet.

Up till now evidence is lacking regarding the regional distribution of indoles, like tryptophan (TRP), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) as well as tyrosine (TYR) in the brains of Mongolian gerbils. Therefore using a microdissection technique and pooling regional brain samples, it can be shown that there is a regional distribution of 5-HT and 5-HIAA in the brain of Mongloian gerbils which is highest in the raphe + reticular formation system followed by the rest of the brainstem and lenticular nuclei. A longterm fast (22 hours) increases TRP and 5-HIAA but not 5-HT, indicating an increase in the turnover rate of 5-HT. Brain TYR and TRP are only slightly increased after a protein rich diet, whereas 5-HT and 5-HIAA are not changed. Artificial nutrition with amino acid mixtures highly concentrated with branched chain amino acids lead to a decrease of TYR and TRP as well as 5-HT and 5-HIAA. Competing amino acid as well as inhibition of 5-HT synthesis is suggested to be responsible for these effects. Mongolian gerbils show higher brain values of TRP and lower ones of TYR in comparison with other species of mice. In peripheral organs, specially in the liver and lung, similar effects are observable. However, the changes are only mild in comparison to that observed in the brain. Moreover, TYR and TRP are significantly increased in peripheral organs after a protein rich diet.

Amino Acids, Branched-Chain↗

Distinction between benign and malignant type of Parkinson's disease.

Clinical data demonstrate that there is a significant difference between at least two types of idiopathic Parkinsonian patients; a benign type of Parkinson's disease and a malignant type. They can be distinguished by the time course of a disability-score, independent of the duration of the disease. The benign cases respond very well to L-Dopa (Madopar) treatment and show a long lasting (7 years) drop in the disability, whereas the improvement of disability in the malignant cases is much smaller and lasts for about one year, followed by an increase of disability. The duration of the disease is 12,5 +/- 0,4 years in the benign type but only 4,0 +/- 0,3 years in the malignant type. Akinetic crises, off-phases, hyperkinetic crises and toxic deliria after Madopar treatment can be observed later in the benign than in the malignant cases. These results suggest that the degeneration of the dopaminergic nigrostriatal system occurs much more rapidly in malignant cases than in benign cases of Parkinson's disease.

Dose-Response Relationship, Drug↗

Brain monoamines in human cerebral infarcts. A preliminary study.

Dopamine (DA), serotonin (5-HT), and 5-hydroxyindole acetic aced (5-HIAA) were assayed spectrofluorometrically in various brain regions of 8 human patients who died after acute and old cerebral infarction. In both recent and older infarct a total depletion of DA and 5-HT was associated with slight reduction of DA and 5-HT levels in remote nonischemic areas and various nuclei of both the injured and contralateral hemispheres. 5-HIAA was significantly reduced in acute ischemic necrosis, while the perifocal edema zone showed considerable accumulation of both 5-HT and 5-HIAA. The degradation zone surrounding old infarcts showed a mild decrease of both 5-HT and 5-HIAA, indicating normalization of K-HT metabolism and turnover after decrease of cerebral edema. These preliminary data which confirm previous findings in experimental cerebral ischemia and infarct indicate that disorders of brain monoamine metabolism are contributing to the development of postischemic brain damage and the complicating cerebral edema.

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