15 research outputs found

    Association between COMT genotype and fMRI activation during painful stimulation in frontal brain areas.

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    <p>Significant correlations were observed for both stimulus conditions within the dorsolateral prefrontal cortex (DLPFC; A,B). Furthermore, the posterior parietal cortex (PPC; C) and the lateral globus pallidus (LGP; D) also displayed significant correlation during both conditions. Statistics and regression lines for group means are shown in gray (all 50 subjects), black (BPD), and dashed (Control), respectively; significant Pearson product moment correlation * p<0.05, ** p<0.01, *** p<0.001, versus r = 0.</p

    Brain areas activated in response to subjectively adjusted heat pain correlate with COMT val158met polymorphism.

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    <p>During subjectively similar intense heat pain perception (individual temperature in BPD 43°C in healthy controls), posterior parietal cortex (A), lateral globus pallidus (LGP; B) and the posterior cingulate cortex (PPC; C) displayed significant correlation with COMT-polymorphism. Labelling as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0023658#pone-0023658-g002" target="_blank">Fig. 2</a>,* p<0.05.</p

    Patients suffering from BPD are less heat pain sensitive independent of the <i>val158met</i> polymorphism.

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    <p>(A) Genotype distribution of the <i>val158met</i> polymorphism in healthy controls (open) and BPD patients (filled bars) do not differ. (B) Heat pain perception was markedly reduced in BPD. Dose-response function in the pretest session (circles) and stimulus temperatures applied during fMRI (squares) did significantly differ between controls and BPD (ns p>0.4; * p<0.05; ** p<0.01; *** p<0.001, students t-test).</p

    Radiofluorinated <i>N</i>‑Octanoyl Dopamine ([<sup>18</sup>F]F-NOD) as a Tool To Study Tissue Distribution and Elimination of NOD in Vitro and in Vivo

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    To mitigate pretransplantation injury in organs of potential donors, <i>N</i>-octanoyl dopamine (NOD) treatment might be considered as it does not affect hemodynamic parameters in braindead (BD) donors. To better assess optimal NOD concentrations for donor treatment, we report on the fast and facile radiofluorination of the NOD-derivative [<sup>18</sup>F]­F-NOD [<sup>18</sup>F]<b>5</b> for in vivo assessment of NOD’s elimination kinetics by means of PET imaging. [<sup>18</sup>F]<b>5</b> was synthesized in reproducibly high radiochemical yields and purity (>98%) as well as high specific activities (>20 GBq/μmol). Stability tests showed no decomposition of [<sup>18</sup>F]<b>5</b> over a period of 120 min in rat plasma. In vitro, low cell association was found for [<sup>18</sup>F]<b>5</b>, indicating no active transport mechanism into cells. In vivo, [<sup>18</sup>F]<b>5</b> exhibited a fast blood clearance and a predominant hepatobiliary elimination. As these data suggest that also NOD might be cleared fast, further pharmacokinetic evaluation is warranted

    Radiofluorinated <i>N</i>‑Octanoyl Dopamine ([<sup>18</sup>F]F-NOD) as a Tool To Study Tissue Distribution and Elimination of NOD in Vitro and in Vivo

    No full text
    To mitigate pretransplantation injury in organs of potential donors, <i>N</i>-octanoyl dopamine (NOD) treatment might be considered as it does not affect hemodynamic parameters in braindead (BD) donors. To better assess optimal NOD concentrations for donor treatment, we report on the fast and facile radiofluorination of the NOD-derivative [<sup>18</sup>F]­F-NOD [<sup>18</sup>F]<b>5</b> for in vivo assessment of NOD’s elimination kinetics by means of PET imaging. [<sup>18</sup>F]<b>5</b> was synthesized in reproducibly high radiochemical yields and purity (>98%) as well as high specific activities (>20 GBq/μmol). Stability tests showed no decomposition of [<sup>18</sup>F]<b>5</b> over a period of 120 min in rat plasma. In vitro, low cell association was found for [<sup>18</sup>F]<b>5</b>, indicating no active transport mechanism into cells. In vivo, [<sup>18</sup>F]<b>5</b> exhibited a fast blood clearance and a predominant hepatobiliary elimination. As these data suggest that also NOD might be cleared fast, further pharmacokinetic evaluation is warranted

    Histology (H&E stain) of proximal tubule segment S3 (pars recta) on day 1 and day 5.

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    <p>On day 1 there are no significant differences between the groups (left H&E stains). Cellular swelling, tubular epithelial necrosis and apoptosis are detectable at segment S3 at the pars recta of proximal tubules in all groups (see arrows). At day 5 (right H&E stains) in NaCl and DA groups revealed cellular debris in the tubular lumen, apoptosis, necrosis, shedding of the proximal tubule brush border with intraluminal calcifications and desquamation of cells (see arrows). In contrast in the NOD group proximal tubules show marginal calcifications and less destruction of epithelial cell lining with marked repopulation of tubular epithelial cells.</p

    TRPV1 expression in human cultured PTEC.

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    <p><b>A.</b> Human PTECs were marked with DAPI and stained with a primary anti-TRPV1 antibody (giunea-pig polyclonal serum); omission of a primary antibody served as negative control (<b>B</b>). <b>C.</b> In addition TRPV1 was assessed in lysates of unstimulated (1) or TNF-α stimulated PTECs (2) by Western blotting. TRPV1 transfected HEK cells (3) were used as positive control to indicate the molecular weight of TRPV1.</p

    NOD activates TRPV1 in DRG neurons.

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    <p><b>A.</b> Increases in free intracellular calcium in response to repetitive application of NOD displayed marked tachyphylaxis from stimulus to stimulus (grey trace). Application of the competitive TRPV1 antagonist capsazepine before and during the 2<sup>nd</sup> stimulus (CPZ; black trace) abolished the NOD response. <b>B.</b> Mean change in intracellular calcium by NOD in cells challenged with (filled bars; n = 4) and without CPZ during the second stimulus (open bars; n = 5) indicated the specificity of NOD at TRPV1. The threshold for a significant response is indicated by the dotted line (*p<0.05, ***p<0.001 vehicle versus CPZ, student’s unpaired t-test).</p
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