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  • BioMed Central  (15)
  • Institute of Physics Publishing (IOP)  (7)
  • Blackwell Science Ltd  (5)
  • 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
    Partitioning direct and indirect human-induced effects on carbon sequestration of managed coniferous forests using model simulations and forest inventories (2005)
    Oxford, UK : Blackwell Science Ltd
    Global change biology 11 (2005), S. 0 
    Details
    ISSN: 1365-2486
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Energy, Environment Protection, Nuclear Power Engineering , Geography
    Notes: Temperate forest ecosystems have recently been identified as an important net sink in the global carbon budget. The factors responsible for the strength of the sinks and their permanence, however, are less evident. In this paper, we quantify the present carbon sequestration in Thuringian managed coniferous forests. We quantify the effects of indirect human-induced environmental changes (increasing temperature, increasing atmospheric CO2 concentration and nitrogen fertilization), during the last century using BIOME-BGC, as well as the legacy effect of the current age-class distribution (forest inventories and BIOME-BGC). We focused on coniferous forests because these forests represent a large area of central European forests and detailed forest inventories were available.The model indicates that environmental changes induced an increase in biomass C accumulation for all age classes during the last 20 years (1982–2001). Young and old stands had the highest changes in the biomass C accumulation during this period. During the last century mature stands (older than 80 years) turned from being almost carbon neutral to carbon sinks. In high elevations nitrogen deposition explained most of the increase of net ecosystem production (NEP) of forests. CO2 fertilization was the main factor increasing NEP of forests in the middle and low elevations.According to the model, at present, total biomass C accumulation in coniferous forests of Thuringia was estimated at 1.51 t C ha−1 yr−1 with an averaged annual NEP of 1.42 t C ha−1 yr−1 and total net biome production of 1.03 t C ha−1 yr−1 (accounting for harvest). The annual averaged biomass carbon balance (BCB: biomass accumulation rate-harvest) was 1.12 t C ha−1 yr−1 (not including soil respiration), and was close to BCB from forest inventories (1.15 t C ha−1 yr−1). Indirect human impact resulted in 33% increase in modeled biomass carbon accumulation in coniferous forests in Thuringia during the last century. From the forest inventory data we estimated the legacy effect of the age-class distribution to account for 17% of the inventory-based sink. Isolating the environmental change effects showed that these effects can be large in a long-term, managed conifer forest.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2486.2005.00932.x
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  • 4
    Electronic Resource
    Electronic Resource
    Bites and stings of medically important venomous arthropods (1998)
    Oxford, UK : Blackwell Science Ltd
    International journal of dermatology 37 (1998), S. 0 
    Details
    ISSN: 1365-4632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-4362.1998.00455.x
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  • 5
    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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  • 6
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    Correlation between psychological stress levels and the severity of overactive bladder symptoms (2015)
    BioMed Central
    Details
    Publication Date: 2015-03-09
    Description: Background: The relationship between psychological stress and interstitial cystitis/bladder pain syndrome (IC/BPS) has been well described. Even though there is some overlapping of symptoms between overactive bladder (OAB) and IC/BPS, there have been very few studies that specifically investigated the relationship between psychological stress and urinary symptoms in OAB patients who do not have pelvic pain. Here we examined the relationship between psychological stress levels and the severity of overactive bladder (OAB) symptoms. Methods: Patients diagnosed with OAB (n=51), IC/BPS (n=27), and age-matched healthy controls (n=30) participated in a case control study that inquired about their psychological stress levels using the perceived stress scale (PSS). PSS reported by the three patient groups were compared. Among OAB patients, their responses on the PSS was correlated to OAB symptoms using the following questionnaires: 1) international consultation on incontinence – urinary incontinence (ICIQ-UI), 2) international consultation on incontinence – overactive bladder (ICIQ-OAB), 3) OAB-q short form, 4) urogenital distress inventory (UDI-6), 5) incontinence impact questionnaire (IIQ-7), 6) urgency severity scale (USS), 7) numeric rating scales of urgency symptom, and 8) frequency symptom. Spearman’s correlation tests were performed to examine the relationship between psychological stress levels and the severity of OAB symptoms. Results: OAB patients reported psychological stress levels that were as high as IC/BPS patients (median 17.0 versus 18.0, p=0.818, Wilcoxon sum rank test), and significantly higher than healthy controls (17.0, versus 7.5, p=0.001). Among OAB patients, there was a positive correlation between perceived stress levels and urinary incontinence symptoms (ICIQ-UI, Spearman’s correlation coefficient=0.39, p=0.007), and impacts on quality of life (UDI-6, IIQ-7, OAB-q quality of life subscale; Spearman’s correlation coefficient=0.32, 0.31, 0.39, and p=0.028, 0.005, 0.029, respectively). No significant correlation was observed between perceived stress levels and urgency or frequency symptoms (ICIQ-OAB, USS, numeric ratings of urgency and frequency). Conclusions: OAB patients reported psychological stress levels that were as high as IC/BPS patients, and significantly higher than healthy controls. There was a positive correlation between perceived stress levels and urinary incontinence symptoms, and its impacts on quality of life among OAB patients.
    Electronic ISSN: 1471-2490
    Topics: Medicine
    Published by BioMed Central
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  • 7
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    Medium-chain acyl-CoA dehydrogenase deficiency associated with a novel splice mutation in the ACADM gene missed by newborn screening (2015)
    BioMed Central
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    Publication Date: 2015-07-31
    Description: Background: Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common disorder of mitochondrial fatty acid β-oxidation and a target disease of newborn screening in many countries.Case presentationWe report on two siblings with mild MCAD deficiency associated with a novel splice site mutation in the ACADM gene. The younger sibling was detected by newborn screening, while the older sister was missed, but diagnosed later on by genetic family testing. Both children were found to be compound heterozygous for the common c.985A 〉 G (p.K329E) mutation and a novel splice site mutation, c.600-18G 〉 A, in the ACADM gene. To determine the biological consequence of the c.600-18G 〉 A mutation putative missplicing was investigated at RNA level in granulocytes and monocytes of one of the patients. The splice site mutation was shown to lead to partial missplicing of the ACADM pre-mRNA. Of three detected transcripts two result in truncated, non-functional MCAD proteins as reflected by the reduced octanoyl-CoA oxidation rate in both patients. In one patient a decrease of the octanoyl-CoA oxidation rate was found during a febrile infection indicating that missplicing may be temperature-sensitive. Conclusions: Our data indicate that the c.600-18G 〉 A variant activates a cryptic splice site, which competes with the natural splice site. Due to only partial missplicing sufficient functional MCAD protein remains to result in mild MCADD that may be missed by newborn screening.
    Electronic ISSN: 1471-2350
    Topics: Biology , Medicine
    Published by BioMed Central
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  • 8
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    Erratum to: ‘Identification and characterization of the bacterial etiology of clinically problematic acute otitis media after tympanocentesis or spontaneous otorrhea in German children’ (2016)
    BioMed Central
    Details
    Publication Date: 2016-03-11
    Electronic ISSN: 1471-2334
    Topics: Medicine
    Published by BioMed Central
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  • 9
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    Photon counting microstrip X-ray detectors with GaAs sensors (2018)
    Institute of Physics Publishing (IOP)
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    Publication Date: 2018-01-31
    Description: High-Z sensors are increasingly used to overcome the poor efficiency of Si sensors above 15 keV, and further extend the energy range of synchrotron and FEL experiments. Detector-grade GaAs sensors of 500 μm thickness offer 98% absorption efficiency at 30 keV and 50% at 50 keV . In this work we assess the usability of GaAs sensors in combination with the MYTHEN photon-counting microstrip readout chip developed at PSI. Different strip length and pitch are compared, and the detector performance is evaluated in regard of the sensor material properties. Despite increased leakage current and noise, photon-counting strips mounted with GaAs sensors can be used with photons of energy as low as 5 keV, and exhibit excellent linearity with energy. The charge sharing is doubled as compared to silicon strips, due to the high diffusion coefficient of electrons in GaAs.
    Electronic ISSN: 1748-0221
    Topics: Physics
    Published by Institute of Physics Publishing (IOP)
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  • 10
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    First full dynamic range calibration of the JUNGFRAU photon detector (2018)
    Institute of Physics Publishing (IOP)
    Details
    Publication Date: 2018-01-24
    Description: The JUNGFRAU detector is a charge integrating hybrid silicon pixel detector developed at the Paul Scherrer Institut for photon science applications, in particular for the upcoming free electron laser SwissFEL. With a high dynamic range, analogue readout, low noise and three automatically switching gains, JUNGFRAU promises excellent performance not only at XFELs but also at synchrotrons in areas such as protein crystallography, ptychography, pump-probe and time resolved measurements. To achieve its full potential, the detector must be calibrated on a pixel-by-pixel basis. This contribution presents the current status of the JUNGFRAU calibration project, in which a variety of input charge sources are used to parametrise the energy response of the detector across four orders of magnitude of dynamic range. Building on preliminary studies, the first full calibration procedure of a JUNGFRAU 0.5 Mpixel module is described. The calibration is validated using alternative sources of charg...
    Electronic ISSN: 1748-0221
    Topics: Physics
    Published by Institute of Physics Publishing (IOP)
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