1,059 research outputs found

    Reversionary Interests in Minerals

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    Pharmacometabolomic mapping of early biochemical changes induced by sertraline and placebo.

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    In this study, we characterized early biochemical changes associated with sertraline and placebo administration and changes associated with a reduction in depressive symptoms in patients with major depressive disorder (MDD). MDD patients received sertraline or placebo in a double-blind 4-week trial; baseline, 1 week, and 4 weeks serum samples were profiled using a gas chromatography time of flight mass spectrometry metabolomics platform. Intermediates of TCA and urea cycles, fatty acids and intermediates of lipid biosynthesis, amino acids, sugars and gut-derived metabolites were changed after 1 and 4 weeks of treatment. Some of the changes were common to the sertraline- and placebo-treated groups. Changes after 4 weeks of treatment in both groups were more extensive. Pathway analysis in the sertraline group suggested an effect of drug on ABC and solute transporters, fatty acid receptors and transporters, G signaling molecules and regulation of lipid metabolism. Correlation between biochemical changes and treatment outcomes in the sertraline group suggested a strong association with changes in levels of branched chain amino acids (BCAAs), lower BCAAs levels correlated with better treatment outcomes; pathway analysis in this group revealed that methionine and tyrosine correlated with BCAAs. Lower levels of lactic acid, higher levels of TCA/urea cycle intermediates, and 3-hydroxybutanoic acid correlated with better treatment outcomes in placebo group. Results of this study indicate that biochemical changes induced by drug continue to evolve over 4 weeks of treatment and that might explain partially delayed response. Response to drug and response to placebo share common pathways but some pathways are more affected by drug treatment. BCAAs seem to be implicated in mechanisms of recovery from a depressed state following sertraline treatment

    N-Acetylcysteine Reduces Cocaine-Cue Attentional Bias and Differentially Alters Cocaine Self-Administration Based on Dosing Order

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    Background—Disrupted glutamate homeostasis is thought to contribute to cocaine-use disorder, in particular, by enhancing the incentive salience of cocaine stimuli. n-Acetylcysteine might be useful in cocaine-use disorder by normalizing glutamate function. In prior studies, n-acetylcysteine blocked the reinstatement of cocaine seeking in laboratory animals and reduced the salience of cocaine stimuli and delayed relapse in humans. Methods—The present study determined the ability of maintenance on n-acetylcysteine (0 or 2400 mg/day, counterbalanced) to reduce the incentive salience of cocaine stimuli, as measured by an attentional bias task, and attenuate intranasal cocaine self-administration (0, 30, and 60 mg). Fourteen individuals (N = 14) who met criteria for cocaine abuse or dependence completed this within-subjects, double-blind, crossover-design study. Results—Cocaine-cue attentional bias was greatest following administration of 0 mg cocaine during placebo maintenance, and was attenuated by n-acetylcysteine. Cocaine maintained responding during placebo and n-acetylcysteine maintenance, but the reinforcing effects of cocaine were significantly attenuated across both maintenance conditions in participants maintained on n-acetylcysteine first compared to participants maintained on placebo first. Conclusions—These results collectively suggest that a reduction in the incentive salience of cocaine-related stimuli during n-acetylcysteine maintenance may be accompanied by reductions in cocaine self-administration. These results are in agreement with, and link, prior preclinical and clinical trial results suggesting that n-acetylcysteine might be useful for preventing cocaine relapse by attenuating the incentive salience of cocaine cues

    Naltrexone-Bupropion Combinations Do Not Affect Cocaine Self-Administration in Humans

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    The FDA has not yet approved a pharmacotherapy for cocaine use disorder despite nearly four decades of research. This study determined the initial efficacy, safety, and tolerability of naltrexone-bupropion combinations as a putative pharmacotherapy for cocaine use disorder. Thirty-one (31) non-treatment seeking participants with cocaine use disorder completed a mixed-design human laboratory study. Participants were randomly assigned to the naltrexone conditions (i.e., 0, 50 mg/day; between-subject factor) and maintained on escalating doses of bupropion (i.e., 0, 100, 200, 400 mg/day; within-subject factor) for at least four days prior to the conduct of experimental sessions. Cocaine self-administration (IN, 0, 40, 80 mg) was then determined using a modified progressive ratio and relapse procedure. Subjective and cardiovascular effects were also measured. Cocaine produced prototypical dose-related increases in self-administration, subjective outcomes (e.g., Like Drug ), and cardiovascular indices (e.g., heart rate, blood pressure) during placebo maintenance. Naltrexone and bupropion alone, or in combination, did not significantly decrease self-administration on either procedure. Low doses of bupropion (i.e., 100 mg) blunted the effects of the cocaine on subjective measures of Like Drug and Stimulated . No unexpected adverse effects were observed with naltrexone and bupropion, alone and combined, in conjunction with cocaine. Together, these results do not support the use of these bupropion-naltrexone combinations for the treatment of cocaine use disorder. Future research should determine if novel drug combinations may decrease cocaine self-administration

    Morphology of the 12-micron Seyfert Galaxies: II. Optical and Near-Infrared Image Atlas

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    We present 263 optical and near-infrared (NIR) images for 42 Seyfert 1s and 48 Seyfert 2s, selected from the Extended 12-micron Galaxy Sample. Elliptically-averaged profiles are derived from the images, and isophotal radii and magnitudes are calculated from these. We also report virtual aperture photometry, that judging from comparison with previous work, is accurate to roughly 0.05mag in the optical, and 0.07mag in the NIR. Our B-band isophotal magnitude and radii, obtained from ellipse fitting, are in good agreement with those of RC3. When compared with the B band, V, I, J, and K isophotal diameters show that the colors in the outer regions of Seyferts are consistent with the colors of normal spirals. Differences in the integrated isophotal colors and comparison with a simple model show that the active nucleus+bulge is stronger and redder in the NIR than in the optical. Finally, roughly estimated Seyfert disk surface brightnesses are significantly brighter in B and K than those in normal spirals of similar morphological type.Comment: 17 pgs including figures; Table 2 is a separate file. Complete Figure 1 is available by contacting the authors. Accepted for publication in ApJ

    VISIR/VLT mid-infrared imaging of Seyfert nuclei: Nuclear dust emission and the Seyfert-2 dichotomy

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    Half of the Seyfert-2 galaxies escaped detection of broad lines in their polarised spectra observed so far. Some authors have suspected that these non-HBLRs contain real Sy2 nuclei without intrinsic broad line region hidden behind a dust torus. If this were true, then their nuclear structure would fundamentally differ from that of Sy2s with polarised broad lines: in particular, they would not be explained by orientation-based AGN unification. Further arguments for two physically different Sy2 populations have been derived from the warm and cool IRAS F25/F60 ratios. These ratios, however, refer to the entire host galaxies and are unsuitable to conclusively establish the absence of a nuclear dust torus. Instead, a study of the Seyfert-2 dichotomy should be performed on the basis of nuclear properties only. Here we present the first comparison between [OIII] 5007A and mid-infrared imaging at matching spatial resolution. Exploring the Seyfert-2 dichotomy we find that the distributions of nuclear mid-infrared/[OIII] luminosity ratios are indistinguishable for Sy1s and Sy2s with and without detected polarised broad lines and irrespective of having warm or cool IRAS F25/F60 ratios. We find no evidence for the existence of a population of real Sy2s with a deficit of nuclear dust emission. Our results suggest 1) that all Seyfert nuclei possess the same physical structure including the putative dust torus and 2) that the cool IRAS colours are caused by a low contrast of AGN to host galaxy. Then the Seyfert-2 dichotomy is explained in part by unification of non-HBLRs with narrow-line Sy1s and to a larger rate by observational biases caused by a low AGN/host contrast and/or an unfavourable scattering geometry.Comment: 11 pages, 6 figures, accepted by A&

    Vitamin D and subsequent all-age and premature mortality: a systematic review

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    <br>Background: All-cause mortality in the population < 65 years is 30% higher in Glasgow than in equally deprived Liverpool and Manchester. We investigated a hypothesis that low vitamin D in this population may be associated with premature mortality via a systematic review and meta-analysis.</br> <br>Methods: Medline, EMBASE, Web of Science, the Cochrane Library and grey literature sources were searched until February 2012 for relevant studies. Summary statistics were combined in an age-stratified meta-analysis.</br> <br>Results: Nine studies were included in the meta-analysis, representing 24,297 participants, 5,324 of whom died during follow-up. The pooled hazard ratio for low compared to high vitamin D demonstrated a significant inverse association (HR 1.19, 95% CI 1.12-1.27) between vitamin D levels and all-cause mortality after adjustment for available confounders. In an age-stratified meta-analysis, the hazard ratio for older participants was 1.25 (95% CI 1.14-1.36) and for younger participants 1.12 (95% CI 1.01-1.24).</br> <br>Conclusions: Low vitamin D status is inversely associated with all-cause mortality but the risk is higher amongst older individuals and the relationship is prone to residual confounding. Further studies investigating the association between vitamin D deficiency and all-cause mortality in younger adults with adjustment for all important confounders (or using randomised trials of supplementation) are required to clarify this relationship.</br&gt
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