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      Increased dopamine content in lymphocytes from high-dose L-Dopa-treated Parkinson's disease patients.

      Neuroimmunomodulation
      3,4-Dihydroxyphenylacetic Acid, metabolism, Adult, Aged, Antiparkinson Agents, pharmacology, Dopamine, Dose-Response Relationship, Drug, Electrophoresis, Capillary, Female, Humans, Levodopa, Lymphocytes, drug effects, immunology, Male, Middle Aged, Neuroimmunomodulation, Parkinson Disease, drug therapy, Up-Regulation

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          Abstract

          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. Catecholamine levels of PBLs were measured using capillary electrophoresis in healthy controls and PD patients receiving different doses of L-dihydroxyphenylalanine (L-Dopa). 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). 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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          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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