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An exploratory pilot study of mechanisms of action within normative feedback for adult drinkers

Alexis Kuerbis, Frederick J. Muench, Rufina Lee, Juan Pena, Lisa Hail
<span title="2016-06-21">2016</span> <i title="PeerJ"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/eyfkjqp7sva5bbnwatk5zazi7q" style="color: black;">PeerJ</a> </i> &nbsp;
Background. Normative feedback (NF), or receiving information about one's drinking compared to peer drinking norms, is one of the most widely used brief interventions for prevention and intervention for hazardous alcohol use. NF has demonstrated predominantly small but significant effect sizes for intention to change and other drinking related outcomes. Identifying mechanisms of action may improve the effectiveness of NF; however, few studies have examined NF's mechanisms of action,
more &raquo; ... among adults. Objective. This study is an exploratory analysis of two theorized mechanisms of NF: discrepancy (specifically personal dissonance—the affective response to feedback) and belief in the accuracy of feedback. Method. Using Amazon's Mechanical Turk, 87 men (n = 56) and women (n = 31) completed an online survey during which they were asked about their perceptions about their drinking and actual drinking behaviors. Then participants were provided tailored NF and evaluated for their reactions. Severity of discrepancy was measured by the difference between one's estimated percentile ranking of drinking compared to peers and actual percentile ranking. Surprise and worry reported due to the discrepancy were proxies for personal dissonance. Participants were also asked if they believed the feedback and if they had any plans to change their drinking. Mediation analyses were implemented, exploring whether surprise, worry, or belief in the accuracy of feedback mediated severity of discrepancy's impact on plan for change. Results. Among this sample of adult drinkers, severity of discrepancy did not predict plan for change, and personal dissonance did not mediate severity of discrepancy. Severity of discrepancy was mediated by belief in the accuracy of feedback. In addition, viewing one's drinking as a problem prior to feedback and post-NF worry both predicted plan for change independently. Conclusions. Results revealed that NF may not work to create personal dissonance through discrepancy, but belief in the accuracy of feedback may be important. It appears the more one believes the feedback, the more one makes a plan for change, suggesting practitioners should be mindful of how information within feedback is presented. Findings also indicate NF may work by validating a preexisting perception that drinking is a problem instead of creating concern related to discrepancy where none existed. Limitations regarding generalizability are discussed.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.7717/peerj.2114">doi:10.7717/peerj.2114</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/27366638">pmid:27366638</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC4924138/">pmcid:PMC4924138</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/btxudh6hnrenfejq35ms5vzk2q">fatcat:btxudh6hnrenfejq35ms5vzk2q</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20180723174640/https://peerj.com/preprints/2030.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/4b/45/4b453662615f371232035f6ef39f0879ec0d3055.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.7717/peerj.2114"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> Publisher / doi.org </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924138" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

Fishing for Isotopes: Capturing Beryllium-7 from Brookhaven LINAC Isotope Producer's 300 gallons of Cooling Water

Jonathan Fitzsimmons, Lisa Muench, Cathy S. Cutler
<span title="2018-03-16">2018</span> <i title="American Chemical Society (ACS)"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/5bauvlie4bfghm76pih4uwnmve" style="color: black;">ACS Omega</a> </i> &nbsp;
The ability of capturing metals and/or radionuclides from large amounts of water is important for radioisotope waste treatment and environmental cleanup. We have developed an approach that rapidly optimizes the capturing of radioisotopes in large-volume aqueous environments. The approach was scaled up to capture beryllium-7 from 300 gallons of cooling water associated with a linear accelerator. Solid supports with the functional groups sulfonic acid, iminodiacetate, pyridine amine, pyridine
more &raquo; ... e acid, or quaternary amine were incubated in the cooling water for 1 week. One sulfonic acid solid support was able to capture 2.1 mCi of Be-7. Subsequent studies with the sulfonic acid solid support focused on the uptake over time of Be-7, scale-up of capturing Be-7, and subsequent purification of Be-7. The uptake over time of Be-7 was found to be linear in the first 24 h, with an equation of Y = 4.11X (% uptake/time (h)) (R 2 = 0.998). The uptake of Be-7 reached the maximum at 24 h and was identical to the uptake at 168 h. To purify Be-7, the optimal purification approach was to release the Be-7 from the solid support with 10 M HCl, which could be immediately passed through an AG1 resin to remove radioimpurities. The radiopurity of the purified Be-7 was greater than 99%, and this method was used to purify 65 mCi of the isotope.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1021/acsomega.7b01757">doi:10.1021/acsomega.7b01757</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/31458580">pmid:31458580</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC6641255/">pmcid:PMC6641255</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/mafnitdj5reujews42sxd4j4ji">fatcat:mafnitdj5reujews42sxd4j4ji</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20210527141110/http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC6641255&amp;blobtype=pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/4c/f8/4cf8b0f6b1e555e06ed07e3fbb5b8ba86ff659ca.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1021/acsomega.7b01757"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> acs.org </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6641255" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

Acute myeloid leukemia cells are targeted by the naturally occurring CXCR4 antagonist EPI-X4 [article]

Lisa Marie Kaiser, Mirja Harms, Daniel Sauter, Vijay P.S. Rawat, Mirco Glitscher, Eberhard Hildt, Konstanze Doehner, Hartmut Doehner, Jan Muench, Christian Buske
<span title="2021-03-11">2021</span> <i title="Cold Spring Harbor Laboratory"> bioRxiv </i> &nbsp; <span class="release-stage" >pre-print</span>
The G protein-coupled receptor (GPCR) and chemokine receptor CXCR4 plays an essential role in tumor initiation and maintenance. This is exemplified in acute myeloid leukemia (AML), where CXCL12-mediated CXCR4 signaling plays a pivotal role for the crosstalk between leukemic stem cells and their microenvironmental niche. Despite the key role of CXCR4 in cancer, surprisingly little is known about endogenous mechanisms that specifically target CXCR4 and dampen its activity. Here, we demonstrate
more &raquo; ... t the naturally occurring peptide and CXCR4 antagonist EPI-X4 and its optimized derivatives effectively blocks CXCL12-mediated migration of AML cells towards a CXCL12 gradient and impairs growth of AML cells in vitro and in vivo in contrast to normal hematopoietic stem and progenitor cells. This anti-leukemic activity of EPI-X4 was accompanied by suppression of CXCR4-mediated MAPK signaling. Of note, EPI-X4 suppressed metabolic pathways and induced depletion of intracellular nicotinamide phosphoribosyltransferase (iNAMPT) in AML cells, linking anti-CXCR4 activity to shifts in NAD+ metabolism.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1101/2021.03.11.434944">doi:10.1101/2021.03.11.434944</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/cmgnga3t65cyroumavmhepive4">fatcat:cmgnga3t65cyroumavmhepive4</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20210717233125/https://www.biorxiv.org/content/biorxiv/early/2021/03/25/2021.03.11.434944.full.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/a8/2f/a82fbe19bb67efa58e42cfb360047803a62ecc93.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1101/2021.03.11.434944"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> biorxiv.org </button> </a>

CXCR4 signaling is counteracted by the naturally occurring CXCR4 antagonist EPI-X 4 in Waldenstrom Macroglobulinemia [article]

Lisa Marie Kaiser, Mirja Harms, Daniel Sauter, Vijay PS Rawat, Mirco Glitscher, Eberhard Hildt, Daniel Tews, Zachary Hunter, Jan Muench, Christian Buske
<span title="2020-10-19">2020</span> <i title="Cold Spring Harbor Laboratory"> bioRxiv </i> &nbsp; <span class="release-stage" >pre-print</span>
CXCR4 expression and downstream signaling have been identified as key factors in malignant hematopoiesis. Thus, up to 40% of all patients with Waldenstrom Macroglobulinemia carry an activating mutation of CXCR4 that leads to a more aggressive clinical course and inferior outcome upon treatment with the Bruton's tyrosine kinase inhibitor ibrutinib. Nevertheless, little is known about physiological mechanisms counteracting CXCR4 signaling in hematopoietic neoplasms. Recently, the endogenous human
more &raquo; ... peptide EPI-X4 was identified as a natural CXCR4 antagonist that effectively blocks CXCL12-mediated receptor internalization and suppresses the migration and invasion of cancer cells towards a CXCL12 gradient. Here, we demonstrate that EPI-X4 efficiently impairs growth of WM cells in vitro and in vivo and blocks their migration towards CXCL12. The CXCR4 inhibitory activity of EPI-X4 is accompanied by decreased expression of genes involved in MAPK signaling and energy metabolism. Notably, the anti-WM activity of EPI-X4 could be further augmented by the rational design of EPI-X4 derivatives showing higher binding affinity to CXCR4. In summary, these data demonstrate that a naturally occurring anti-CXCR4 peptide is able to interfere with WM growth, and that optimized derivatives of EPI-X4 may represent a promising approach in suppressing growth promoting CXCR4 signaling in WM.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1101/2020.10.19.344812">doi:10.1101/2020.10.19.344812</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/22bi3iaoxzdcbcngtokbj5hx5e">fatcat:22bi3iaoxzdcbcngtokbj5hx5e</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20201211070214/https://www.biorxiv.org/content/biorxiv/early/2020/10/19/2020.10.19.344812.full.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/14/b6/14b6409066880e01bd34c91551537deea7be4a78.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1101/2020.10.19.344812"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> biorxiv.org </button> </a>

Nicotine Blocks Brain Estrogen Synthase (Aromatase): In Vivo Positron Emission Tomography Studies in Female Baboons

Anat Biegon, Sung-Won Kim, Jean Logan, Jacob M. Hooker, Lisa Muench, Joanna S. Fowler
<span title="">2010</span> <i title="Elsevier BV"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/z5ukx73avrb57kufzzr36timya" style="color: black;">Biological Psychiatry</a> </i> &nbsp;
Hooker, Lisa Muench, and Joanna S. Fowler. 2010. Nicotine blocks brain estrogen synthase (aromatase): In vivo positron emission tomography studies in female baboons.  ... 
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1016/j.biopsych.2010.01.004">doi:10.1016/j.biopsych.2010.01.004</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/20188349">pmid:20188349</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC2904480/">pmcid:PMC2904480</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/voknwfzz5jdrnbxpl2c6ckuc3q">fatcat:voknwfzz5jdrnbxpl2c6ckuc3q</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20190426164634/https://dash.harvard.edu/bitstream/handle/1/12111433/Hooker_Nicotine.pdf;jsessionid=00C0E30B8ACCEB05024B32439C0031BD?sequence=1" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/92/ff/92ff699455ee711fc621fd71c2a9ae08638ab3c6.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1016/j.biopsych.2010.01.004"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> elsevier.com </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904480" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

Synthesis and positron emission tomography studies of carbon-11-labeled imatinib (Gleevec)

Kun-Eek Kil, Yu-Shin Ding, Kuo-Shyan Lin, David Alexoff, Sung Won Kim, Colleen Shea, Youwen Xu, Lisa Muench, Joanna S. Fowler
<span title="">2007</span> <i title="Elsevier BV"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/oanaz6u6wrhhrm4y4mb75gquqe" style="color: black;">Nuclear Medicine and Biology</a> </i> &nbsp;
Introduction-Imatinib mesylate (Gleevec) is a well known drug for treating chronic myeloid leukemia and gastrointestinal stromal tumors. Its active ingredient, imatinib ([4-[(4-methyl- , blocks the activity of several tyrosine kinases. Here we labeled imatinib with carbon-11 as a tool for determining the drug distribution and pharmacokinetics of imatinib, and we carried out positron emission tomography (PET) studies in baboons. Methods-[N-11 C-methyl]imatinib was synthesized from [ 11 C]methyl
more &raquo; ... odide and norimatinib was synthesized by the demethylation of imatinib (isolated from Gleevec tablets) according to a patent procedure [Collins JM, Klecker RW Jr, Anderson LW. Imaging of drug accumulation as a guide to antitumor therapy. US Patent 20030198594A1, 2003]. Norimatinib was also synthesized from the corresponding amine and acid. PET studies were carried out in three baboons to measure pharmacokinetics in the brain and peripheral organs and to determine the effect of a therapeutic dose of imatinib. Log D and plasma protein binding were also measured. Results-[N-11 C-methyl]imatinib uptake in the brain is negligible (consistent with P-glycoproteinmediated efflux); it peaks and clears rapidly from the heart, lungs and spleen. Peak uptake and clearance occur more slowly in the liver and kidneys, followed by accumulation in the gallbladder and urinary bladder. Pretreatment with imatinib did not change uptake in the heart, lungs, kidneys and spleen, and increased uptake in the liver and gallbladder. Conclusions-[N-11 C-methyl]imatinib has potential for assessing the regional distribution and kinetics of imatinib in the human body to determine whether the drug targets tumors and to identify other organs to which the drug or its labeled metabolites distribute. Paired with tracers such as 2deoxy-2-[ 18 F]fluoro-D-glucose ( 18 FDG) and 3′-deoxy-3′-[ 18 F]fluorothymidine ( 18 FLT), [N-11 Cmethyl]imatinib may be a useful radiotracer for planning chemotherapy, for monitoring response to treatment and for assessing the role of drug pharmacokinetics in drug resistance.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1016/j.nucmedbio.2006.11.004">doi:10.1016/j.nucmedbio.2006.11.004</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/17307123">pmid:17307123</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC2866181/">pmcid:PMC2866181</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/jjy7n6xbc5fkbnc56b3bxcxzdq">fatcat:jjy7n6xbc5fkbnc56b3bxcxzdq</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20191203210316/http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC2866181&amp;blobtype=pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/38/34/3834b2882ec69636302288e21dc2a41a328a133a.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1016/j.nucmedbio.2006.11.004"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> elsevier.com </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866181" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

A pilot study of online feedback for adult drinkers 50 and older: Feasibility, efficacy, and preferences for intervention

Alexis N. Kuerbis, Lisa Hail, Alison A. Moore, Frederick J. Muench
<span title="">2017</span> <i title="Elsevier BV"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/k2opzqyoxva63al5vmczwyxace" style="color: black;">Journal of Substance Abuse Treatment</a> </i> &nbsp;
., 2015; Kuerbis, Muench, Lee, Pena, & Hail, 2016) , which found online NF to be ineffective in reducing drinking or planning for change.  ... 
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1016/j.jsat.2017.04.004">doi:10.1016/j.jsat.2017.04.004</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/28476264">pmid:28476264</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC5959034/">pmcid:PMC5959034</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/thlidlwj4jfqraspoan7p6oufu">fatcat:thlidlwj4jfqraspoan7p6oufu</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20200503052435/http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC5959034&amp;blobtype=pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/a3/2a/a32a0b2efb20476a4ebaabd84057d7f75501e120.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1016/j.jsat.2017.04.004"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> elsevier.com </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959034" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

Therapeutic doses of buspirone block D3 receptors in the living primate brain

Sung Won Kim, Joanna S. Fowler, Phil Skolnick, Lisa Muench, Yeona Kang, Colleen Shea, Jean Logan, Dohyun Kim, Pauline Carter, Payton King, David Alexoff, Nora D. Volkow
<span title="2014-03-28">2014</span> <i title="Oxford University Press (OUP)"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/t7zhumcn45gvdefswsettbaxjm" style="color: black;">International Journal of Neuropsychopharmacology</a> </i> &nbsp;
Dopamine D 3 receptor (D 3 R) antagonists may be effective medications for multiple substance use disorders (SUDs). However, no selective D 3 R antagonists are currently available for clinical testing. Buspirone, originally characterized as a 5-HT 1A partial agonist and used as an anxiolytic, also binds to D 3 R and D 4 R with high affinity, with lower affinity to D 2 R, and interferes with cocaine reward. Here we used PET with [ 11 C]PHNO (D 3 R-preferring radioligand), [ 11 C]raclopride (D 2
more &raquo; ... /D 3 R radioligand) and [ 11 C]NNC-112 (D 1 R radioligand) to measure occupancy of oral and parenteral buspirone in the primate brain. Intramuscular buspirone (0.19 and 0.5 mg/kg) blocked both [ 11 C]PHNO and [ 11 C]raclopride binding to striatum, exhibiting high occupancy (50-85%) at 15 min and rapid wash-out over 2-6 h. In contrast, oral buspirone (3 mg/kg) significantly blocked [ 11 C]PHNO binding in D 3 -rich regions (globus pallidum and midbrain) at 3 h, but had minimal effects on [ 11 C]raclopride binding (28-37% at 1 h and 10% at 3 h). Buspirone did not block [ 11 C]NNC-112. Our findings provide evidence that i.m. buspirone blocks D 3 R and D 2 R, whereas oral buspirone is more selective towards D 3 R blockade in vivo, consistent with extensive first pass metabolism and supporting the hypothesis that its metabolites (5-and 6′-hydroxybuspirone) merit evaluation for treating SUDs. They also indicate that for oral buspirone to achieve greater than 80% sustained D 3 R occupancy, as might be needed to treat addiction, higher doses (at least three-fold) than those used to treat anxiety (maximal 60 mg) will be required. Nonetheless, based on previous clinical studies, these doses would be safe and well tolerated.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1017/s1461145714000194">doi:10.1017/s1461145714000194</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/24679922">pmid:24679922</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/w6n76jmhjvgz7ab7kr7xu7x4pu">fatcat:w6n76jmhjvgz7ab7kr7xu7x4pu</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20170901012852/https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/ijnp/17/8/10.1017_S1461145714000194/1/17-8-1257.pdf?Expires=1504257178&amp;Signature=GF76~c2JgWWnCFXICjXcVvXUg-2LL97Bt6okpbVPmdtgclKxjIFalmAe3bImf6BCuJFob0rzuNyzSrE4HIcfCcxQf2v2z19AgqFle7g7iQ9OOT3wYproVXrfzYjeekwscF6s57XnDOUVg3mu1Qx3kzWvzsLirc3jUcH4Ooh3whkz75Qb3baBA8DC9MRNcxtDG1VG64FOTcV3gqbCr0mMmVCAFe7KThsdhyEPMuaQtd4hc0lLBYuqGwTAUaz2rqTtdTulJTAZ28Cgsg7hSBPHS9FsoJpAvqn2c71dwkvQ66Sy491Y9t50UoEY4Zs81iuSZIRkvWvgi9cgYnashh-2~A__&amp;Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/17/d9/17d9f60bdf6d36177e2989b30b38e48ca7b1ac00.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1017/s1461145714000194"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> Publisher / doi.org </button> </a>

Therapeutic doses of buspirone block D3 receptors in the living primate brain – CORRIGENDUM

Sung Won Kim, Joanna S. Fowler, Phil Skolnick, Lisa Muench, Yeona Kang, Colleen Shea, Jean Logan, Dohyun Kim, Pauline Carter, Payton King, David Alexoff, Nora D. Volkow
<span title="2014-06-26">2014</span> <i title="Oxford University Press (OUP)"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/t7zhumcn45gvdefswsettbaxjm" style="color: black;">International Journal of Neuropsychopharmacology</a> </i> &nbsp;
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1017/s1461145714000881">doi:10.1017/s1461145714000881</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/ycs3zcyczjar5i5r5cefbebqoe">fatcat:ycs3zcyczjar5i5r5cefbebqoe</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20180729151723/https://watermark.silverchair.com/17-8-1354.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAakwggGlBgkqhkiG9w0BBwagggGWMIIBkgIBADCCAYsGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMHDK2-ykDu8FxJZPSAgEQgIIBXFXiPZmQIthpNAHvlou9tGtv8pyGOFxQvrIiEf73x2cqfFPNutnjLdS-uLct0aFx0yequDTAu5gqHX7Y72dMHEa3ObqC3NGJM3r7EBEkgaJptafCB3TcDZur9CbO5m4o6NDd24KmoLedCKEMymFSV9jesDQLAKA5DNg7Qyi9KlYoPTrR9-pPlIVbGIKgz2VbaQPYHNh-JIh0EbzlVMrB4cg8ihTTwOo2Vxoa3En56KdeSV4BBG_EuRHoa8LRsr82Y05Hid4j1b29q9Bdok72_7SOd1OlmLSUrGoqLDuO2jqHszPqZEPBOFz4SJB-kmfvbgTiTiH3ihqCX-S5uPX1ezQ8KXi5OB7f7MVw_ASUUfA14aCAUsjJcwvN8KZI8YWTdMIj9_K8qjdJK9TpgiNtIUFe3hca8wu1mvn6LdIB_g4Z51OE9tcNVATAEM9fESenq8_fuZ7nFVy3G72ICg" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/29/ea/29ead805381613312fc246318ed4953e7d970a3d.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1017/s1461145714000881"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> Publisher / doi.org </button> </a>

Radionuclide labeling and evaluation of candidate radioligands for PET imaging of histone deacetylase in the brain

Young Jun Seo, Lisa Muench, Alicia Reid, Jinzhu Chen, Yeona Kang, Jacob M. Hooker, Nora D. Volkow, Joanna S. Fowler, Sung Won Kim
<span title="">2013</span> <i title="Elsevier BV"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/k7ofkw67pzd37psjlg42n4cezm" style="color: black;">Bioorganic &amp; Medicinal Chemistry Letters</a> </i> &nbsp;
Positron emission tomography SAHA Brain Epigenetics Brain permeability a b s t r a c t Histone deacetylases (HDACs) regulate gene expression by inducing conformational changes in chromatin. Ever since the discovery of a naturally occurring HDAC inhibitor, trichostatin A (TSA) stimulated the recent development of suberoylanilide (SAHA, Zolinza Ò ), HDAC has become an important molecular target for drug development. This has created the need to develop specific in vivo radioligands to study
more &raquo; ... etic regulation and HDAC engagement for drug development for diseases including cancer and psychiatric disorders. 6-([ 18 F]Fluoroacetamido)-1-hexanoicanilide ([ 18 F]FAHA) was recently developed as a HDAC substrate and shows moderate blood-brain barrier (BBB) permeability and specific signal (by metabolic trapping/or deacetylation) but rapid metabolism. Here, we report the radiosynthesis of two carbon-11 labeled candidate radiotracers (substrate-and inhibitor-based radioligand) for HDAC and their evaluation in non-human primate brain. PET studies showed very low brain uptake and rapid metabolism of both labeled compounds but revealed a surprising enhancement of brain penetration by F for H substitution when comparing one of these to [ 18 F]FAHA. Further structural refinement is needed for the development of brain-penetrant, metabolically stable HDAC radiotracers and to understand the role of fluorine substitution on brain penetration. Published by Elsevier Ltd. Gene expression is regulated, in part, through enzyme catalyzed epigenetic modifications targeting both the DNA and its associated histone proteins. 1 For example, histone acetyl transferases (HATs) catalyze the acetylation of the lysine residues of histone proteins removing the positive charge and rendering the DNA more accessible to transcription initiation complexes and RNA polymerase. In contrast, histone deacetylases (HDACs) typically catalyze the hydrolysis of the acetyl groups from lysine residues of histone proteins condensing the chromatin and repressing gene expression. 2 Because the folding process induced by the deacetylation of histones represses the expression of genes which are involved in critical metabolic processes such as apoptosis, cell-cycle arrest and differentiation, HDAC has become an important molecular target in drug development. [3] [4] [5] [6] The discovery of a naturally occurring HDAC inhibitor, trichostatin A (TSA, Fig. 1) , 7,8 an antifungal antibiotic with anticancer activity, has stimulated the development of inhibitors of HDAC including Vorinostat (SAHA, Fig. 1 ) which was recently approved by FDA for the treatment of cutaneous T cell lymphoma (CTCL) and other cancers. 9 HDAC inhibitors are also of interest in the study and treatment of a number of CNS disorders including depression, addiction and neurodegenerative diseases. 4, 10, 11 In fact, valproic acid, a class I HDAC inhibitor, 6 is one of the most widely used and effective antiseizure medications, which we recently showed its poor blood-brain barrier (BBB) penetration explaining the high doses needed for therapeutic efficacy. 12 For this reason, the development of brain penetrant radiotracers for positron emission tomography (PET) imaging of HDAC in the brain would advance the study of this important epigenetic marker as well as the measurement of target engagement during HDAC inhibitor therapy. Only a handful of HDAC active compounds including HDAC inhibitor drugs have been radiolabeled with either F-18 (t 1/2 : 110 min) or C-11 (t 1/2 : 20.4 min) and evaluated for specificity for 0960-894X/$ -see front matter Published by Elsevier Ltd. http://dx.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1016/j.bmcl.2013.10.038">doi:10.1016/j.bmcl.2013.10.038</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/24210501">pmid:24210501</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC4007514/">pmcid:PMC4007514</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/gah42v7ejbhe7f2llbopoghhui">fatcat:gah42v7ejbhe7f2llbopoghhui</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20190501105924/https://dash.harvard.edu/bitstream/handle/1/33471147/Hooker_Radionucleotide.pdf;jsessionid=FCD960B099095C4A072C7E2F7D461DAC?sequence=1" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/93/6f/936fd5d87589640083c1462c317d6458fd9fbd22.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1016/j.bmcl.2013.10.038"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> elsevier.com </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4007514" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

Blockade of the brain histamine H3 receptor by JNJ-39220675: preclinical PET studies with [11C]GSK189254 in anesthetized baboon

Jean Logan, Nicholas I. Carruthers, Michael A. Letavic, Steven Sands, Xiaohui Jiang, Colleen Shea, Lisa Muench, Youwen Xu, Pauline Carter, Payton King, Joanna S. Fowler
<span title="2012-05-22">2012</span> <i title="Springer Nature"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/476xkwimnredro3yrtvqfs2ujq" style="color: black;">Psychopharmacology</a> </i> &nbsp;
Rationale The preclinical characterization of a series of aryloxypyridine amides has identified JNJ-39220675 ((4cyclobutyl-1,4-diazepan-1-yl)(6-(4-fluorophenoxy)pyridin-3-yl)methanone) as a high-affinity histamine H 3 receptor antagonist and a candidate for further drug development particularly in the treatment of alcohol-related behaviors. Objective This study measured brain histamine H 3 receptor blockade by JNJ-39220675 (1 mg/kg) in the female baboon. Methods Positron emission tomography
more &raquo; ... ing and [ 11 C] GSK189254, a reversible high-affinity radiotracer with specificity for the histamine H 3 receptor, was used to measure histamine H 3 receptor availability at baseline and after i.v. and oral administration of JNJ-39220675 (1 mg/kg) in the anesthetized baboon. Histamine H 3 receptor availability was estimated as the total distribution volume (V T ) in brain regions. The sensitivity of [ 11 C]GSK189254 binding to injected mass and carryover effects was determined. Results JNJ-39220675 produces robust (ca. 90 %) blockade of [ 11 C]GSK189254 binding after i.v. and oral administration. After oral administration of JNJ-39220675 (1 mg/kg), the fractional receptor occupancy was >0.9 at 90 min with a slight increase from 90 to 240 min. Similar to prior studies in humans, V T was highly sensitive to the mass of GSK189254 with ED 50 estimated to be 0.16 μg/kg. Conclusions The robust blockade of binding of [ 11 C] GSK189254 by JNJ-39220675 demonstrates that this compound readily penetrates the blood-brain barrier and occupies the histamine H 3 receptor after oral administration at low plasma concentrations (∼1 ng/cc) supporting further drug development for alcohol addiction and other disorders. This study corroborates prior reports of the high sensitivity of [ 11 C]GSK189254 to injected mass at doses >0.1 μg/kg.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1007/s00213-012-2733-x">doi:10.1007/s00213-012-2733-x</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/22614669">pmid:22614669</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC3456925/">pmcid:PMC3456925</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/xe5lbwdhh5hjbo6h27vh6ggvsm">fatcat:xe5lbwdhh5hjbo6h27vh6ggvsm</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20171017160249/http://publisher-connector.core.ac.uk/resourcesync/data/Springer-OA/pdf/af7/aHR0cDovL2xpbmsuc3ByaW5nZXIuY29tLzEwLjEwMDcvczAwMjEzLTAxMi0yNzMzLXgucGRm.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/d5/b7/d5b7fd5d164fd45f1106c1fcb41e9e2ed75c4972.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1007/s00213-012-2733-x"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> springer.com </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3456925" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

Image-Guided Synthesis Reveals Potent Blood-Brain Barrier Permeable Histone Deacetylase Inhibitors

Young Jun Seo, Yeona Kang, Lisa Muench, Alicia Reid, Shannon Caesar, Logan Jean, Florence Wagner, Edward Holson, Stephen J. Haggarty, Philipp Weiss, Payton King, Pauline Carter (+4 others)
<span title="2014-05-21">2014</span> <i title="American Chemical Society (ACS)"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/qaga5yeaebadtf3qgiktiul5nq" style="color: black;">ACS Chemical Neuroscience</a> </i> &nbsp;
Recent studies have revealed that several histone deacetylase (HDAC) inhibitors, which are used to study/treat brain diseases, show low blood-brain barrier (BBB) penetration. In addition to low HDAC potency and selectivity observed, poor brain penetrance may account for the high doses needed to achieve therapeutic efficacy. Here we report the development and evaluation of highly potent and blood-brain barrier permeable HDAC inhibitors for CNS applications based on an image-guided approach
more &raquo; ... ing the parallel synthesis and radiolabeling of a series of compounds based on the benzamide HDAC inhibitor, MS-275 as a template. BBB penetration was optimized by rapid carbon-11 labeling and PET imaging in the baboon model and using the imaging derived data on BBB penetration from each compound to feed back into the design process. A total of 17 compounds were evaluated, revealing molecules with both high binding affinity and BBB permeability. A key element conferring BBB penetration in this benzamide series was a basic benzylic amine. These derivatives exhibited 1-100 nM inhibitory activity against recombinant human HDAC1 and HDAC2. Three of the carbon-11 labeled aminomethyl benzamide derivatives showed high BBB penetration (∼0.015%ID/cc) and regional binding heterogeneity in the brain (high in thalamus and cerebellum). Taken together this approach has afforded a strategy and a predictive model for developing highly potent and BBB permeable HDAC inhibitors for CNS applications and for the discovery of novel candidate molecules for small molecule probes and drugs.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1021/cn500021p">doi:10.1021/cn500021p</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/24780082">pmid:24780082</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC4102966/">pmcid:PMC4102966</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/6yhbcqshwff5bjz2noxfkt3k7e">fatcat:6yhbcqshwff5bjz2noxfkt3k7e</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20170508083537/http://pubs.acs.org/doi/pdf/10.1021/cn500021p" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/14/17/14174d0ec6424c12816af4d27da8b2c8592d7344.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1021/cn500021p"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> acs.org </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102966" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

Reinvestigation of the synthesis and evaluation of [N-methyl-11C]vorozole, a radiotracer targeting cytochrome P450 aromatase

Sung Won Kim, Anat Biegon, Zachary E. Katsamanis, Carolin W. Ehrlich, Jacob M. Hooker, Colleen Shea, Lisa Muench, Youwen Xu, Payton King, Pauline Carter, David L. Alexoff, Joanna S. Fowler
<span title="">2009</span> <i title="Elsevier BV"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/oanaz6u6wrhhrm4y4mb75gquqe" style="color: black;">Nuclear Medicine and Biology</a> </i> &nbsp;
We reinvestigated the synthesis of [N-methyl-11 C]vorozole, a radiotracer for aromatase, and discovered the presence of an N-methyl isomer which was not removed in the original purification method. Herein we report the preparation and positron emission tomography (PET) studies of pure [N-methyl-11 C]vorozole. Methods: Norvorozole was alkylated with [ 11 C]methyl iodide as previously described and also with unlabeled methyl iodide. A highperformance liquid chromatography (HPLC) method was
more &raquo; ... ed to separate the regioisomers. Nuclear magnetic resonance (NMR) spectroscopy ( 13 C and 2D-nuclear Overhauser effect spectroscopy NMR) was used to identify and assign structures to the N-methylated products. Pure [N-methyl-11 C]vorozole and the contaminating isomer were compared by PET imaging in the baboon. Results: Methylation of norvorozole resulted in a mixture of isomers (1:1:1 ratio) based on new HPLC analysis using a pentafluorophenylpropyl bonded silica column, in which vorozole coeluted one of its isomers under the original HPLC conditions. Baseline separation of the three labeled isomers was achieved. The N-3 isomer was the contaminant of vorozole, thus correcting the original assignment of isomers. PET studies of pure [N-methyl-11 C]vorozole with and without the contaminating N-3 isomer revealed that only [Nmethyl-11 C]vorozole binds to aromatase. [N-methyl-11 C]Vorozole accumulated in all brain regions with highest accumulation in the aromatase-rich amygdala and preoptic area. Accumulation was blocked with vorozole and letrozole consistent with reports of some level of aromatase in many brain regions. Conclusions: The discovery of a contaminating labeled isomer and the development of a method for isolating pure [N-methyl-11 C]vorozole combine to provide a new scientific tool for PET studies of the biology of aromatase and for drug research and development.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1016/j.nucmedbio.2008.12.013">doi:10.1016/j.nucmedbio.2008.12.013</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/19324278">pmid:19324278</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC3693459/">pmcid:PMC3693459</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/pt6qqtuokfbrpmuh5dvl6s5hcy">fatcat:pt6qqtuokfbrpmuh5dvl6s5hcy</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20170211195648/https://www.bnl.gov/tcp/uploads/files/BSA09-12j.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/55/6f/556f1ee1c2f7455ab4bc5706052209f4e4e6c867.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1016/j.nucmedbio.2008.12.013"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="external alternate icon"></i> elsevier.com </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693459" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>

Production of platinum radioisotopes at Brookhaven Linac Isotope Producer (BLIP)

Suzanne V. Smith, Elizabeth McCutchan, Gülhan Gürdal, Christopher Lister, Lisa Muench, Michael Nino, Alexandro Sonzogni, Michal Herman, Gustavo Nobre, Chris Cullen, Thomas Chillery, Partha Chowdury (+9 others)
<span title="">2017</span> <i title="EDP Sciences"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/oduy4e4fvfhovftixyndrlkomi" style="color: black;">EPJ Web of Conferences</a> </i> &nbsp;
The accelerator production of platinum isotopes was investigated at the Brookhaven Linac Isotope Producer (BLIP). In this study high purity natural platinum foils were irradiated at 53.2, 65.7, 105.2, 151.9, 162.9 and 173.3.MeV. The irradiated foils were digested in aqua regia and then converted to their hydrochloride salt with concentrated hydrochloric acid before analyzing by gamma spectrometry periodically for at least 10 days post end of bombardment. A wide range of platinum (Pt), gold (Au)
more &raquo; ... and iridium (Ir) isotopes were identified. Effective cross sections at BLIP for were compared to literature and theoretical cross sections determined using Empire-3.2. The majority of the effective cross sections (<70 MeV) confirm those reported in the literature. While the absolute values of the theoretical cross sections were up to a factor of 3 lower, Empire 3.2 modeled thresholds and maxima correlated well with experimental values. Preliminary evaluation into a rapid separation of Pt isotopes from high levels of Ir and Au isotopes proved to be a promising approach for large scale production. In conclusion, this study demonstrated that with the use of isotopically enriched target material accelerator production of selected platinum isotopes is feasible over a wide proton energy range.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1051/epjconf/201714609029">doi:10.1051/epjconf/201714609029</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/rvesktud7vajfh7ijzfwrudpou">fatcat:rvesktud7vajfh7ijzfwrudpou</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20180719010845/https://www.epj-conferences.org/articles/epjconf/pdf/2017/15/epjconf-nd2016_09029.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/f6/90/f69075d56222c73f49eeb60f7252844e0868db20.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1051/epjconf/201714609029"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> Publisher / doi.org </button> </a>

Fast uptake and long-lasting binding of methamphetamine in the human brain: Comparison with cocaine

Joanna S. Fowler, Nora D. Volkow, Jean Logan, David Alexoff, Frank Telang, Gene-Jack Wang, Christopher Wong, Yeming Ma, Aarti Kriplani, Kith Pradhan, David Schlyer, Millard Jayne (+8 others)
<span title="">2008</span> <i title="Elsevier BV"> <a target="_blank" rel="noopener" href="https://fatcat.wiki/container/sa477uo7lveh7hchpikpixop5u" style="color: black;">NeuroImage</a> </i> &nbsp;
Methamphetamine is one of the most addictive and neurotoxic drugs of abuse. It produces large elevations in extracellular dopamine in the striatum through vesicular release and inhibition of the dopamine transporter. In the U.S. abuse prevalence varies by ethnicity with very low abuse among African Americans relative to Caucasians, differentiating it from cocaine where abuse rates are similar for the two groups. Here we report the first comparison of methamphetamine and cocaine pharmacokinetics
more &raquo; ... in brain between Caucasians and African Americans along with the measurement of dopamine transporter availability in striatum. Methamphetamine's uptake in brain was fast (peak uptake at 9 min) with accumulation in cortical and subcortical brain regions and in white matter. Its clearance from brain was slow (except for white matter which did not clear over the 90 min) and there was no difference in pharmacokinetics between Caucasians and African Americans. In contrast cocaine's brain uptake and clearance were both fast, distribution was predominantly in striatum and uptake was higher in African Americans. Among individuals, those with the highest striatal (but not cerebellar) methamphetamine accumulation also had the highest dopamine transporter availability suggesting a relationship between METH exposure and DAT availability. Methamphetamine's fast brain uptake is consistent with its highly reinforcing effects, its slow clearance with its longlasting behavioral effects and its widespread distribution with its neurotoxic effects that affect not only striatal but also cortical and white matter regions. The absence of significant differences between Caucasians and African Americans suggests that variables other than methamphetamine pharmacokinetics and bioavailability account for the lower abuse prevalence in African Americans.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1016/j.neuroimage.2008.07.020">doi:10.1016/j.neuroimage.2008.07.020</a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/18708148">pmid:18708148</a> <a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC2606665/">pmcid:PMC2606665</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/zugsj7i5yrgbfjxzequdqm2ndq">fatcat:zugsj7i5yrgbfjxzequdqm2ndq</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20100710133957/http://tauruspet.med.yale.edu/staff/edm42/papers/summer-journal-club/NeuroImage_Fowler_2008.pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/fe/bd/febd538778f5fd393fbe1f24a54e78909dfc11fd.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1016/j.neuroimage.2008.07.020"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> elsevier.com </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2606665" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>
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