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  • 1
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] In multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) the cytokines tumour necrosis factor-α (TNF), lymphotoxin-α (LT), and interferon-gamma (IFN-γ) are of central pathogenetic importance. A therapy capable of stopping neurological ...
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 5 (1993), S. 101-106 
    ISSN: 1435-1463
    Keywords: Budipine ; NMDA receptor ; Parkinson's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Budipine (1-t-butyl-4,4-diphenylpiperidine) is a novel antiparkinsonian agent. Its clinical efficacy has been proven in double-blind placebo-controlled trials. The mechanism of action of budipine, however, is unknown. Budipine selectively increased the threshold of N-methyl-D-aspartate (NMDA)-induced seizures in mice. Similar to known specific NMDA antagonist, budipine depressed polysynaptic spinal reflexes in mice, but had no consistent effect on spinal monosynaptic reflexes. In receptor binding experiments, budipine displaced thienylcyclohexylpiperidyl-3,4-[3H]-(n) ([3H]-TCP) from its binding site with an IC50 of 36 μM suggesting that budipine acts as a non-competitive NMDA antagonist with moderate receptor affinity. It is concluded that the newly discovered NMDA antagonistic action of budipine is at least partly responsible for its antiparkinsonian activity. Our findings are additional evidence for the hypothesis that NMDA antagonists may be useful in the treatment of Parkinson's disease (PD).
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1435-1463
    Keywords: L-Dopa ; CPP ; NMDA ; antagonist ; NBQX ; AMPA antagonist ; MPTP ; common marmosets ; locomotor activity ; Parkinsonism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Degeneration of dopaminergic nigrostriatal neurons in Parkinson's disease results in an overactivity of excitatory glutamatergic projections from the subthalamic nucleus to the output nuclei of the basal ganglia resulting in rigidity and akinesia. In theory pharmacological blockade of these overactive systems should improve parkinsonian symptomatology. The selective AMPA-antagonist NBQX and the competitive NMDA-antagonist CPP are not effective in animal models of Parkinson's disease when given alone but ameliorate parkinsonian symptomatology and stimulate locomotor activity when co-administered with a threshold dose of L-Dopa. These synergistic effects are seen in the MPTP-treated (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) common marmoset and the rat with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra. Therefore competitive NMDA and non-NMDA antagonists may offer a new therapeutic strategy for the treatment of Parkinson's disease.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 1 (1989), S. 147-147 
    ISSN: 1435-1463
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1912
    Keywords: Key words [3H]-Acetylcholine release ; Rat ; caudatoputamen ; Cholinergic interneurons ; Glycine ; receptors ; Serine ; Strychnine ; Ethanol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present study acute effects of ethanol on [3H]-acetylcholine ([3H]-ACh) release induced by activation of strychnine-sensitive glycine receptors in superfused slices of rat caudatoputamen were investigated. The glycine-evoked [3H]-ACh release (lg EC50 = –4.10, CI95 = [–4.14, –4.05]) was inhibited by strychnine in a competitive manner (pA2 = 6.86, CI95 = [6.61, 7.08]). Release of [3H]-ACh could also be induced by L-serine. L-serine was less potent than glycine (lg EC50 = –2.61, CI95 = [–2.69, –2.52]). Both glycine and L-serine showed similar maximum effects (Emax(glycine) = 1.34, CI95 = [1.24, 1.45]; Emax(L-serine) = 1.19, CI95 = [1.09, 1.32]). Ethanol at concentrations of 2‰ (= 34 mM) and 4‰ (= 68 mM) inhibited glycine-evoked [3H]-ACh release in a manner like the competitive antagonist strychnine, however with lower potency. The pA2 of ethanol was 1.19, CI95 = [0.85, 1.41], at 2‰ [v/v] and 1.51, CI95 = [1.19, 1.78] at 4‰ ethanol. Similar to its action on glycine-evoked [3H]-ACh release, ethanol at 4‰ [v/v] also inhibited L-serine-evoked transmitter release in a competitive-like fashion (pA2 = 0.83, CI95 = [–0.15, 1.18]). We conclude, that strychnine-sensitive glycine receptors, mediating [3H]-ACh release in the rat caudatoputamen, might represent a new site of action of ethanol.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 356 (1997), S. 838-845 
    ISSN: 1432-1912
    Keywords: Key words GFR ; Urinary dopamine ; Sodium ; excretion ; l-DOPA ; l-Tyrosine ; Tyrosine hydroxylase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present study the renal response to intravenous infusion of the catecholamine precursors l-dihydroxyphenylalanine (l-DOPA) or l-tyrosine was investigated in thiopentone sodium-anaesthetized Sprague-Dawley rats. Glomerular filtration rate (GFR) was assessed by renal clearance of inulin, urinary concentration of dopamine (UDAV) by HPLC and sodium excretion (UNaV) by flame photometry. We found that basal UDAV was 6.5 ± 0.5 pmol/min per 100 g body weight (mean ± SEM). Intravenous infusion of l-tyrosine at 0.1–3.0 μmol/min dose dependently enhanced UDAV (17 ± 3 to 144 ± 14 pmol/ min respectively) with higher doses of l-tyrosine resulting in no further increase in UDAV. Compared with l-tyrosine administration significantly lower doses of l-DOPA (0.07 to 35 nmol/min) caused increases in UDAV which were orders of magnitude higher (18 ± 1 to 7800 ± 470 pmol/min, respectively) and did not show saturation characteristics. GFR did not change in response to l-tyrosine or l-DOPA infusion. No variations in urinary flow rate or in UNaV could be observed which were significantly correlated to changes in UDAV. In contrast, intravenous infusion of dopamine at a dose of 6 nmol/min significantly increased GFR by 35 ± 6.2% and urinary flow rate by over 2-fold. Immunohistochemistry with light microscopy revealed no tyrosine hydroxylase in the kidney. Therefore, dopamine synthesis in the tubular cells mainly depends on the renal supply of l-DOPA. The unchanged GFR and UNaV in spite of large variations of UDAV argue against the hypothesis that intratubular dopamine plays a functional role in the regulation of hemodynamics or sodium transport in the kidney. Renal dopamine excretion may rather represent an effective pathway for the elimination of catecholamine precursors from the plasma.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0533
    Keywords: Key words Parkinson’s disease ; Apoptosis ; Bcl-2 ; Bax ; Bcl-x
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied the substantia nigra of three Parkinson’s disease (PD) patients and three age-matched individuals by in situ DNA-end labeling (ISEL) and immunohistochemistry for the apoptosis regulating proteins Bcl-2, Bax and Bcl-x on 50 consecutive sections per patient. No melanin-containing cell was identified with typical apoptotic changes in either patient or control substantia nigra. With prolonged reaction-time the terminal transferase-mediated DNA-end labeling revealed a signal in 2.0 ± 1.2% melanin-containing cells in PD compared to 1.3 ± 1.1% in control. This difference did nor reach statistical significance and no condensation or margination of the chromatin was evident. No significant changes of any of the apoptosis regulating proteins were apparent in PD substantia nigra. These findings do not support the hypothesis that apoptosis plays a central role in the pathogenesis of PD.
    Type of Medium: Electronic Resource
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