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      Increased Dopamine Content in Lymphocytes from High-Dose L-Dopa-Treated Parkinson’s Disease Patients

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          Abstract

          Objectives: The intracellular (i.c.) content of dopamine and its metabolites was measured in the peripheral blood lymphocytes (PBLs) of Parkinson’s disease (PD) patients and healthy controls. Methods: Catecholamine levels of PBLs were measured using capillary electrophoresis in healthy controls and PD patients receiving different doses of L-dihydroxyphenylalanine ( L-Dopa). Results: Higher i.c. dopamine content was found in lymphocytes from PD patients receiving a high dose of L-Dopa (700 ± 30 mg/day) as compared to lymphocytes from the healthy controls (p = 0.002) and from PD patients treated with a low dose of L-Dopa (400 ± 30 mg/day) (p = 0.022). The dihydroxyphenylacetic acid to dopamine ratio was significantly lower in the high-dose L-Dopa-treated PD patients than in the controls (p = 0.013). Conclusions: These findings suggest that the dopamine content and metabolism in the peripheral lymphocytes of PD patients are influenced by L-Dopa administration. This is the first study in which a dose-related effect of L-Dopa treatment was found in lymphocytes from PD patients.

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          Most cited references 10

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          Discovery of endogenous catecholamines in lymphocytes and evidence for catecholamine regulation of lymphocyte function via an autocrine loop.

          Evidence has been obtained that catecholamines and their metabolites are present in single lymphocytes and extracts of T- and B-cell clones by use of capillary electrophoresis with electrochemical detection. Pharmacological inhibition of tyrosine hydroxylase reduces observed catecholamine levels, suggesting catecholamine synthesis by lymphocytes. Intracellular dopamine levels are shown to be increased by extra-cellular dopamine, suggesting a cellular-uptake mechanism. Furthermore, incubation with either dopamine or L-dihydroxyphenylalanine, a precursor of dopamine, results in a dose-dependent inhibition of lymphocyte proliferation and differentiation. Together, these results suggest the presence of an autocrine loop whereby lymphocytes down-regulate their own activity.
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            The Prevention of Acute Gastric Ulcer in the Rat by α-Methyldopa

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              Increase in peripheral CD4 bright+ CD8 dull+ T cells in Parkinson disease.

              Immune abnormalities are known to be involved in the pathogenesis of sporadic Parkinson disease. To examine whether abnormalities in peripheral lymphocytes exist in Parkinson disease. Immune mediators, including CD1a, CD3, CD4, CD8, CD45RO, and Fas (CD95), were examined in peripheral lymphocytes of patients by 3-color flow cytometry. Patients with Parkinson disease displayed a significantly greater population of circulating CD3+ CD4 bright+ CD8 dull+ lymphocytes than age-matched control subjects (P =.005) and patients with cerebrovascular disease (P =.002). The increase in these cells appeared to continue for at least 17 months. These T cells also expressed CD45RO and Fas, markers for activated T cells, while CD1a, a marker for thymic T cells, was negative, suggesting that these cells are mature T cells with immune activities. As CD4+ CD8+ T cells are known to increase after some specific viral infections, the continuous increase in CD4 bright+ CD8 dull+ T cells shown here may indicate postinfectious immune abnormalities that are possibly associated with the pathogenesis of this slowly progressive, multifactorial neurodegenerative disease.
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                Author and article information

                Journal
                NIM
                Neuroimmunomodulation
                10.1159/issn.1021-7401
                Neuroimmunomodulation
                S. Karger AG
                1021-7401
                1423-0216
                2005
                March 2005
                17 March 2005
                : 12
                : 2
                : 81-84
                Affiliations
                aDepartment of Neurology, University of Szeged, bNeurology Research Group of the Hungarian Academy of Sciences and University of Szeged, Szeged, Hungary; cInstitute of Clinical Neuroscience, Department of Psychiatry and Neurochemistry, Göteborg University, Sahlgrenska University Hospital Mölndal, Mölndal, dInstitute of Chemistry, Department of Analytical Chemistry, Biomedical Center, Uppsala University, Uppsala, Sweden
                Article
                83579 Neuroimmunomodulation 2005;12:81–84
                10.1159/000083579
                15785109
                © 2005 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 1, Tables: 1, References: 12, Pages: 4
                Categories
                Original Paper

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