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  • 1
    ISSN: 0378-4347
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Chromatography B: Biomedical Sciences and Applications 380 (1986), S. 379-385 
    ISSN: 0378-4347
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 90 (1992), S. 145-150 
    ISSN: 1435-1463
    Keywords: OPCA ; continuous dopaminergic stimulation ; dopaminergica ; dysphagia ; dysarthria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Four patients with sporadic olivopontocerebellar atrophy (OPCA) and severe signs of Parkinsonism received continuous subcutaneous lisuride infusion via a small external pump. All 4 patients benefitted from this treatment: 3 showed an overall improvement in motor performance, in 1 patient mainly dysphagia and dysarthria improved. Therapeutic benefit lasted for at least 6 months of follow up. With a daily dose of 1.0 mg of subcutaneous lisuride, treatment limitations were reached in the form of dysphagia, probably due to oropharyngeal dystonia. Subcutaneous lisuride infusion should be taken into consideration in OPCA patients with signs of Parkinsonism if oral dopaminergic treatment has failed earlier on.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1435-1463
    Keywords: COMT-inhibition ; MAO-inhibition ; NGF ; free radicals ; neurodegenerative disorders
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Neurotrophic factors, like e.g. nerve growth factor (NGF), neurotrophin 3 (NT-3) or brain-derived neurotrophic factor (BDNF) promote the survival and function of neurones in the peripheral and central nervous system. Dopamine or other biogenic amines induce the biosynthesis of neurotrophic factors in glial and neuronal cells. Therefore inhibition of enzymes, like the extraneuronal and neuronal located MAO or the predominantly glial situated COMT, which both metabolize catecholamines, may induce an increased biosynthesis of neurotrophic factors. Due to clinical studies especially MAO-B-inhibitors appear to slow the progression of neurological deficits in Parkinson's disease and the cognitive decline in Alzheimer's disease. On the one hand inhibition of COMT alone may also slow the metabolisation of biogenic amines in glial cells and may consequently induce synthesis of neurotrophic factors in glial cells. But on the other hand in vivo and in vitro studies show, that COMT-inhibitors may intensify the metabolisation of catecholamines in neurones by MAO, what may cause an enhanced generation of free radicals. This increase of free radicals may induce lipid peroxidation of membranes and therefore cause accelerated neuronal and glial cell death. For that reason we conclude, that centrally active COMT-inhibitors may only be used together with MAO-inhibitors in the neuroprotective treatment of neurodegenerative disorders. Medical treatment with both inhibitors will have to be performed very carefully due to cytotoxic effects of high catecholamine levels on neuronal and glial cells and due to possible prolongation or potentiation of the activity of several noradrenergic drugs in the periphery.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 107 (2000), S. 113-119 
    ISSN: 1435-1463
    Keywords: Keywords: Tolcapone, levodopa, pharmacokinetics.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. No significant increase of the maximum concentration (Cmax) of levodopa after addition of catechol-O-methyltransferase inhibitor tolcapone occurred in previous pharmacokinetic studies predominantly on healthy volunteers. We compared pharmacokinetics of levodopa in plasma before and after addition of tolcapone in 13 treated parkinsonian subjects under standardized conditions. We found a significant increase of Cmax of levodopa after the addition of tolcapone. This may represent one cause for the occurrence of dyskinesia previously early in the course of treatment with tolcapone.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 7 (1994), S. 13-19 
    ISSN: 1435-1463
    Keywords: Parkinson's disease ; colour vision ; colour discrimination ; Farnsworth ; Munsell 100 Hue Test ; L-Dopa
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In recent studies disorders of colour vision in Parkinsonian patients have been demonstrated. Up to now, the influence of dopaminergic treatment on those phenomena remains unclear. We therefore performed a colour vision test (Farnsworth-Munsell 100 Hue Test) in 19 patients with Parkinson's disease before and aater the oral application of the morning dose of L-dopa. The colour discrimination was significantly improved after the ingestion of L-Dopa. There was no different effect of L-Dopa on the blue-yellow or red-green axis of colour vision. The morphological structures responsible for these colour vision disturbances are unknown, but it can be concluded that the dopamine deficiency in Parkinson's disease is not restricted to the basal ganglia but may involve the visual system as well.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 67 (1986), S. 105-112 
    ISSN: 1435-1463
    Keywords: β h-endorphin ; cerebrospinal fluid ; high-performance liquid chromatography ; substance P
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A reversed-phase high-performance liquid chromatography procedure combined with radioimmunoassay (rp-HPLC-RIA) is presented. It makes possible the quantitative determination of the neuropeptides,β-endorphin and substance P, in small volumes of cerebrospinal fluid (CSF). The concentration-dependence of the recovery of the method is demonstrated and the effect of free silanol groups of the stationary phase on the recovery is discussed. CSF was shown to contain 9.6±1.1fmolβ h-endorphin and 12.0±0.9 fmol substance P per ml.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 103 (1996), S. 717-727 
    ISSN: 1435-1463
    Keywords: Levodopa ; parkinsonian therapy ; pharmacokinetics of levodopa ; sustained-release levodopa
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Motor fluctuations and dyskinesias in Parkinsonian patients may be at least partially due to fluctuations of levodopa plasma concentrations. Sustained-release (SR) formulations of levodopa may present a promising, effective solution of this problem. Therefore we performed a 4-fold, crossover double-blind trial with a new SR preparation, tested in healthy volunteers (Gerlach et al., 1988) before, in 12 Parkinsonian subjects. Two different dosages of the pure new levodopa SR-preparation, a composition of 70% SR and 30% levodopa immediate release (IR) and a conventional IR levodopa preparation were compared by their pharmacokinetic behaviour and their clinical effects. The relative bioavailability of levodopa in plasma was 69% for the combination of SR and IR levodopa release, for the pure SR formulations (100mg levodopa) 54% and (200 mg levodopa) 55%, compared to the 100% of the standard form of IR release of 100 mg levodopa. In contrast to the conventional IR formulation the pharmacokinetic behaviour of the SR preparations showed no initial sharp peak, but more continuous and longer maintaining plasma concentrations of levodopa. Due to the small numbers of cases and the missing homogenity of the selected patients no statistical significant differences between the four preparations regarding the clinical response were observed. But the described pharmacokinetic behaviour gives hope, that these newly developed SR-preparations may lead to progress in the treatment of Parkinson's disease (prolongation of dosage intervals, reduction of motor fluctuations).
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1435-1463
    Keywords: Parkinson's disease ; bromocriptine ; L-DOPA ; levodopa ; motor fluctuations ; adverse effects ; early combination therapy ; long-term treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Long-term levodopa treatment in Parkinson's disease is typically associated with “motor side effects” consisting in dyskinesias and/or fluctuations in motility referred to as the on-off phenomena. The main objective of this prospective, randomized, multi-centre study was to determine to what extent the development of such complications could be prevented by partial substitution of levodopa monotherapy (L-DOPA/benserazide) by bromocriptine in patients with early symptoms of the disease. The basic trial population included 674 newly diagnosed Parkinsonian patients that were randomly allocated to monotherapy with levodopa or a combination therapy based upon a nearly 40% replacement of levodopa by bromocriptine. The two target regimens had to be consistently maintained for 42 months. Parkinsonian symptoms were assessed by means of the Webster rating scale, the Hoehn and Yahr scale, and the Zung Self-Rating Depression scale. Motor side effects and adverse events were recorded at each regular clinic visit. Neurological symptoms improved and stabilized in a similar manner during treatment with both regimens throughout the study period. Motor side effects were observed in more patients on levodopa alone than on combination therapy (28.8 vs 20%; p=0.008). According to Kaplan-Meier estimates the cumulative probability of experiencing motor side effects was 0.43 on monotherapy, compared to 0.28 on combination therapy, which was equal to a one third reduction of risk (p=0.025). In regard to motor side effects, the degree of substitution of levodopa proved relevant: patients with 〉50% substitution by bromocriptine exhibited half the risk observed in those with 〈30% (p=0.045). The overall burden of motor side effects, as reflected by a sum score based upon the relevance, the severity and the extent of motor dysfunction, was also significantly less on combination therapy (p=0.046). In conclusion, partial substitution of levodopa by bromocriptine (〉30%) as first-line treatment of Parkinson's disease proves active in the prophylaxis of levodopa associated motor side effects. Early combination therapy therefore extends the period of optimal disease control.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1435-1463
    Keywords: Keywords: Early-onset parkinsonism ; PARK 2 ; parkin ; Parkinson's disease.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. Recently a mutation in the parkin gene has been identified as the cause for an autosomal-recessively inherited form of early onset Parkinson's disease (EOPD). The disease causing minimal deletion has been defined as a homozygous exon 4 loss in the parkin gene among Japanese patients. We investigated 140 sporadic and familial EOPD patients of German ancestry for the exon 4 deletion in the parkin gene. None of our patients exhibited a homo-zygous deletion of exon 4, suggesting a minor role of this mutation for EOPD in Caucasians. Nevertheless a detailed mutation analysis is warranted to explore the overall significance of mutations in the parkin gene in EOPD.
    Type of Medium: Electronic Resource
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