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  • Catechol-O-methyltransferase inhibitor  (1)
  • Keywords: Caspase-1, caspase-3, tumor necrosis factor receptor R1 (p55), Parkinson's disease, brain.  (1)
  • L-dopa  (1)
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 6 (1993), S. 211-214 
    ISSN: 1435-1463
    Keywords: Amino acid ; L-dopa ; Parkinson's disease ; rat ; rotation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studied the effect of amino acid load on L-dopa-induced rotational behavior in rats with unilateral lesion of the nigrostriatal pathway. Pretreatment of rats with an ingestion of high concentration of amino acids significantly reduced the number of rotations induced by subcutaneously injected L-dopa. These results provide the experimental basis for clinical observations that dietary protein affects the response to L-dopa in parkinsonian patients.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1435-1463
    Keywords: Catechol-O-methyltransferase inhibitor ; 3-O-methyldopa ; levodopa ; Parkinson's disease ; tolcapone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of tolcapone, a catechol-O-methyltransferase inhibitor, on the bioavailability and efficacy of levodopa were evaluated in 12 patients with Parkinson's disease (PD), 8 of whom showed signs of daily motor fluctuations (wearing-off phenomenon). Motor disabilities were assessed in 12 patients at 7 time points before and after the chronic administration of tolcapone using the Unified Parkinson's Disease Rating Scale (UPDRS). The UPDRS score was improved at all points of determination. Eight patients with wearing-off phenomenon on levodopa showed symptomatic improvement on the combination. The area under the curve (AUC) for levodopa increased by 34% (p=0.0059) after the administration of tolcapone. The elimination half-life (T1/2) of levodopa was significantly prolonged by 81% (p=0.0001) after the treatment. The AUC of 3-O-methyldopa, a metabolite of levodopa, was decreased by 79% (p=0.0001) and the Cmax (maximum concentration) was also decreased by 80% after the administration (p=0.0001) of tolcapone. The combination of tolcapone and levodopa was well tolerated. Our findings suggest that tolcapone improves the pharmacokinetics of levodopa in plasma and motor symptoms of fluctuating PD patients. It is suggested that tolcapone may be a useful drug adjunct to levodopa in treating patients with PD with wearing-off phenomena.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1435-1463
    Keywords: Keywords: Caspase-1, caspase-3, tumor necrosis factor receptor R1 (p55), Parkinson's disease, brain.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. The activities of caspase-1 and caspase-3 were measured by use of fluoropeptides as substrates for the first time in the brain (substantia nigra, caudate nucleus, putamen, cerebellum, and frontal cortex) from control and parkinsonian patients. The activities of caspases in the brain were significantly higher in the substantia nigra from parkinsonian patients than those in the brain from control patients (p 〈 0.01). However, the activities of caspases in the caudate nucleus, putamen, cerebellum, and frontal cortex showed no significant difference between parkinsonian and control patients. The tumor necrosis factor (TNF) receptor R1 (TNF-R1, p55) level was also elevated in the substantia nigra of the parkinsonian brain in comparison with that of controls (p 〈 0.05). Since both caspases and TNF-R1 may play important roles in apoptotic cell death through TNF-α-induced signaling pathway, our present data suggest the presence of a proapoptotic environment in the substantia nigra of parkinsonian brain, probably inducing vulnerability of neurons and glias towards a variety of noxious factors.
    Type of Medium: Electronic Resource
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