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  • 1
    Electronic Resource
    Electronic Resource
    Increased CNS uptake and enhanced antinociception of morphine-6-glucuronide in rats after inhibition of P-glycoprotein (2002)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 83 (2002), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Morphine-6-glucuronide (M6G) is a substrate of P-glycoprotein (P-gp), which forms an outward transporter at the blood–brain barrier. Inhibition of P-gp may therefore be expected to cause increased CNS uptake of M6G. We directly assessed the spinal concentrations of M6G and its antinociceptive effects in rats following pharmacological inhibition of P-gp. Spinal cord tissue concentrations of M6G were assessed by microdialysis with probes transversally implanted through the dorsal horns of the spinal cord at level L4. Ten rats received M6G intravenously (0.018 mg/kg loading dose plus 0.00115 mg/kg/min for an 8-h infusion), five of them together with PSC833 to inhibit P-gp (32-h infusion, starting 24 h before the addition of M6G). Antinociceptive effects were explored by means of formalin tests. After having obtained evidence for enhanced CNS uptake and antinociception of M6G in the presence of PSC833, additional behavioural experiments were performed in another 32 rats to assess the dose dependency of the antinociceptive effects of M6G either with or without PSC833 in comparison with both PSC833 alone and placebo. Inhibition of P-gp increased the M6G concentrations in the spinal cord approximately three-fold whereas the plasma concentrations were increased only by a factor of 1.4, which resulted in a more than doubled spinal cord/plasma concentration ratio (from 0.08 ± 0.03 for M6G alone to 0.17 ± 0.08 for M6G plus PSC833). Antinociceptive effects of M6G were significantly enhanced by inhibition of P-gp. Inhibition of P-gp alters the transport of M6G across the blood–brain barrier, resulting in enhanced spinal cord uptake and enhanced antinociception.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2002.01177.x
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  • 2
    Electronic Resource
    Electronic Resource
    Effects of selective COX-1 and -2 inhibition on formalin-evoked nociceptive behaviour and prostaglandin E2 release in the spinal cord (2001)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 79 (2001), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Nociception evoked prostaglandin (PG) release in the spinal cord considerably contributes to the induction of hyperalgesia and allodynia. To evaluate the relative contribution of cyclooxygenase-1 (COX-1) and COX-2 in this process we assessed the effects of the selective COX-1 inhibitor SC560 and the selective COX-2 inhibitor celecoxib on formalin-evoked nociceptive behaviour and spinal PGE2 release. SC560 (10 and 20 mg/kg) significantly reduced the nociceptive response and completely abolished the formalin-evoked PGE2 raise. In contrast, celecoxib (10 and 20 mg/kg) was ineffective in both regards, i.e. the flinching behaviour was largely unaltered and the formalin-induced PGE2 raise as assessed using microdialysis was only slightly, not significantly reduced. This suggests that the formalin-evoked rapid PG release was primarily caused by COX-1 and was independent of COX-2. Mean free spinal cord concentrations of celecoxib during the formalin assay were 32.0 ± 4.5 nm, thus considerably higher than the reported IC50 for COX-2 (3–7 nm). Therefore, the lack of efficacy of celecoxib is most likely not to be a result of poor tissue distribution. COX-2 mRNA and protein expression in the spinal cord were not affected by microdialysis alone but the mRNA rapidly increased following formalin injection and reached a maximum at 2 h. COX-2 protein was unaltered up to 4 h after formalin injection. The time course of COX-2 up-regulation suggests that the formalin-induced nociceptive response precedes COX-2 protein de novo synthesis and may therefore be unresponsive to COX-2 inhibition. Considering the results obtained with the formalin model it may be hypothesized that the efficacy of celecoxib in early injury evoked pain may be less than that of unselective NSAIDs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2001.00613.x
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  • 3
    Electronic Resource
    Electronic Resource
    VERTICAL HETEROGENEITY AND MOVEOUT IN THE ONE-DIMENSIONAL MEDIUM (1987)
    Oxford, UK : Blackwell Publishing Ltd
    Geophysical prospecting 35 (1987), S. 0 
    Details
    ISSN: 1365-2478
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Geosciences , Physics
    Notes: Since the important contributions of Dürbaum and Dix, 30 years ago, velocity profile estimation procedures on horizontally layered and vertically heterogeneous media from seismic probing data have been based largely on hyperbolic moveout models and RMS and stacking velocity concepts. Re-examination of the fundamentals reveals that quantitative velocity heterogeneity and canonical valocity profiles have been implicit factors for moveout modelling and for profile inversion in the use of the Dix procedure. Heterogeneity h is the ratio (and vRMS the geometric or harmonic mean) of the path-average and time-average velocities for a raypath or, in a more restricted sense, for the normal ray belonging to a velocity profile. The canonical profile for a given velocity profile or profile segment is a moveout-equivalent monotonically increasing ramp-like profile.The ramp or constant gradient in depth is the simplest velocity profile approximator which can explicitly accommodate velocity heterogeneity. A ramp model structure is detailed which facilitates moveout simulation and model parameter estimation, and the parametric effects are explored. The horizontal offset range is quantified for which this model can give good moveout approximations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2478.1987.tb00845.x
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  • 4
    Electronic Resource
    Electronic Resource
    Biochemical Analysis of Bone Compacta in Osteogenesis Imperfecta (1988)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 543 (1988), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1988.tb55322.x
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  • 5
    Electronic Resource
    Electronic Resource
    Inheritance of the sesquiterpenes longipinenone and hydroxy-longipinenone within the Achillea millefolium complex (Compositae) (2001)
    Oxford, UK : Blackwell Publishing Ltd
    Plant breeding 120 (2001), S. 0 
    Details
    ISSN: 1439-0523
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Three selfing and 13 crossing experiments between tetraploid individuals of Achillea ceretanica, Achillea collina, Achillea distans ssp.‘styriaca’ Saukel (ined.), and Achillea pratensis (Achillea millefolium complex, Compositae), five F1 crosses, three backcrosses and one further selfing experiment were carried out in order to study the inheritance of longipinenone (1) and its hydroxyl derivative (2). From these crossings, 1294 plants were studied by qualitative thin layer chromatography. Progenies from parent and F1 plants without longipinenones (0-type, ll) uniformly contained none of these two sesquiterpenes. All other crossing experiments showed typical segregation patterns of 0-type, L-type (longipinenone (1) without hydroxylongipinenone, L.hh) and H-type (hydroxy-longipinenone (2) and occasionally longipinenone, L.H.) in the ratio of 1 : 1 and 1 : 3. According to these results both derivatives are under dominant genetic control regulated by genes L and H, whereby hydroxylation takes place after synthesis of longipinenone (1).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1439-0523.2001.00603.x
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  • 6
    Electronic Resource
    Electronic Resource
    Mice transgenic for exon 1 of Huntington's disease: properties of cholinergic and dopaminergic pre-synaptic function in the striatum (2003)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 85 (2003), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In Huntington's disease (HD), neuronal loss is most prominent in the striatum leading to emotional, cognitive and progressive motor dysfunction. The R6/2 mice, transgenic for exon 1 of the HD gene, develop a neurological phenotype with similarities to these features of HD. In striatal tissue, electrically evoked release of tritiated acetylcholine (ACh) and dopamine (DA) were compared in wild-type (WT) and R6/2 mice. In R6/2 mice, the evoked release of ACh, its M2 autoreceptor-mediated maximum inhibition and its dopamine D2 heteroreceptor-mediated maximum inhibition was diminished to 51%, 74% and 87% of controls, respectively. Also, the activities of choline acetyltransferase and of synaptosomal high-affinity choline uptake decreased progressively with age in these mice. In the DA release model, however, electrical stimulation elicited equal amounts of [3H]-DA both in WT and R6/2 mice. Moreover, high-affinity DA uptake into striatal slices was similar in WT and R6/2 mice. In order to confirm these findings in vivo, intrastriatal levels of extracellular DA were measured by intracerebral microdialysis in freely moving mice: striatal DA levels were found to be equal in WT and R6/2 mice. In conclusion, in the transgenic R6/2 mice changes occur mainly in striatal cholinergic neurones and their pre-synaptic modulation, but not in the dopaminergic afferent terminals. Whether similar events also contribute to the pathogenesis of HD in humans has to be established.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2003.01704.x
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