Carbon Radioisotopes

Publication Title: 
Molecular Vision

PURPOSE: Human eye lenses contain cells that persist from embryonic development. These unique, highly specialized fiber cells located at the core (nucleus) of the lens undergo pseudo-apoptosis to become devoid of cell nuclei and most organelles. Ostensibly lacking in protein transcriptional capabilities, it is currently believed that these nuclear fiber cells owe their extreme longevity to the perseverance of highly stable and densely packed crystallin proteins.

Author(s): 
Stewart, Daniel N.
Lango, Jozsef
Nambiar, Krishnan P.
Falso, Miranda J. S.
FitzGerald, Paul G.
Rocke, David M.
Hammock, Bruce D.
Buchholz, Bruce A.
Publication Title: 
Drug Metabolism and Disposition: The Biological Fate of Chemicals

[13-14C]Dihydroartemisinin was administered to male rats (35 micromol kg-1, iv). Within 0-1 hr and 0-5 hr of dosing, 34.8 +/- 5. 2% (mean +/- SD, N = 6) and 48.4 +/- 5.9% of the radiolabel, respectively, was recovered in bile. Only 1.1 +/- 1.2% was recovered in bladder urine after 5 hr. The biliary metabolites were identified by LC/MS. The principal metabolite (21.1 +/- 9.3% of dose) was the biologically inactive dihydroartemisinin (DHA) glucuronide.

Author(s): 
Maggs, J. L.
Madden, S.
Bishop, L. P.
O'Neill, P. M.
Park, B. K.
Publication Title: 
Malaria Journal

BACKGROUND: Dihydroartemisinin (DHA), a powerful anti-malarial drug, has been used as monotherapy and artemisinin-based combination therapy (ACT) for more than decades. So far, however, the tissue distribution and metabolic profile of DHA data are not available from animal and humans. METHODS: Pharmacokinetics, tissue distribution, mass balance, and elimination of [14C] DHA have been studieded in rats following a single intravenous administration. Protein binding was performed with rat and human plasma.

Author(s): 
Xie, Lisa H.
Li, Qigui
Zhang, Jing
Weina, Peter J.
Publication Title: 
Antimicrobial Agents and Chemotherapy

Artemisone is one of the most promising artemisinin derivatives in clinical trials. Previous studies with radiolabeled artemisinin and dihydroartemisinin have measured uptake in Plasmodium falciparum-infected erythrocytes. Uptake is much greater in infected than in uninfected erythrocytes, but the relative contributions of transport, binding, and metabolism to this process still await definition. In this study, we characterized mechanisms by which [(14)C]artemisone is taken up into uninfected and P. falciparum-infected human erythrocytes in vitro.

Author(s): 
Pooley, Sophie
Fatih, Farrah A.
Krishna, Sanjeev
Gerisch, Michael
Haynes, Richard K.
Wong, Ho-Ning
Staines, Henry M.
Publication Title: 
Drug Metabolism and Disposition: The Biological Fate of Chemicals

Neat N-methyl-2-pyrrolidone (NMP) rapidly penetrated into the skin of male Sprague-Dawley rats after in vivo and in vitro topical application. At the two topical doses tested in vivo, no steady state was observed. The maximal absorption fluxes were 10 and 20 mg/cm(2)/h for 20 microl/cm(2) and 40 microl/cm(2), respectively. Similar results were observed after in vitro topical application of neat [(14)C]NMP (25-400 microl/cm(2)) in fresh full-thickness skin.

Author(s): 
Payan, Jean-Paul
Boudry, Isabelle
Beydon, Dominique
Fabry, Jean-Paul
Grandclaude, Marie-Christine
Ferrari, Elisabeth
André, Jean-Claude
Publication Title: 
Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology

This is a pilot examination of the hypothesis that some of the effects of smoking cigarettes in humans are mediated through nicotine activation of opioid and dopamine (DA) neurotransmission. Neuroimaging was performed using positron emission tomography and the radiotracers [11C]carfentanil and [11C]raclopride, labeling mu-opioid and DA D2 receptors, respectively. Six healthy male smokers were abstinent overnight. After radiotracer administration, subjects smoked two denicotinized cigarettes, followed 45 min later by two average nicotine cigarettes.

Author(s): 
Scott, David J.
Domino, Edward F.
Heitzeg, Mary M.
Koeppe, Robert A.
Ni, Lisong
Guthrie, Sally
Zubieta, Jon-Kar
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Placebo-induced expectancies have been shown to decrease pain in a manner reversible by opioid antagonists, but little is known about the central brain mechanisms of opioid release during placebo treatment. This study examined placebo effects in pain by using positron-emission tomography with [(11)C]carfentanil, which measures regional mu-opioid receptor availability in vivo. Noxious thermal stimulation was applied at the same temperature for placebo and control conditions.

Author(s): 
Wager, Tor D.
Scott, David J.
Zubieta, Jon-Kar
Publication Title: 
Behavioural Brain Research

Functional neuroimaging studies suggest that a lateral network in the brain is associated with the sensory aspects of pain perception while a medial network is associated with affective aspects. The highest concentration of opioid receptors is in the medial network. There is significant evidence that endogenous opioids are central to the experience of pain and analgesia. We applied an integrative multimodal imaging approach during acupuncture.

Author(s): 
Dougherty, Darin D.
Kong, Jian
Webb, Megan
Bonab, Ali A.
Fischman, Alan J.
Gollub, Randy L.
Publication Title: 
Journal of Agricultural and Food Chemistry

Isoflavones have potential for preventing and treating several chronic health conditions, such as osteoporosis, cardiovascular disease, and cancer. In this study, radiolabeled isoflavones were recovered from kudzu (Pueraria lobata) root cultures after incubation with uniformly labeled (14)C-sucrose in the culture medium for 21 days. Approximately 19% of administered label was recovered in the isoflavone-rich dried extracts of kudzu root cultures (90.2 microCi/g or 3.3 MBq/g extract).

Author(s): 
Reppert, Adam
Yousef, Gad G.
Rogers, Randy B.
Lila, Mary Ann
Publication Title: 
Journal of Medicinal Food

Grape polyphenols confer potential health benefits, including prevention of neurodegenerative diseases. To determine the absorption and tissue distribution of the complex grape polyphenol mixture, (14)C-labeled polyphenols were biosynthesized by grape cell suspension cultures, during co-incubation with radioisotopically labeled sucrose, and fractionated into polyphenolic subfractions. The pharmacokinetics and distribution of grape polyphenols into blood, brain, and peripheral interstitial fluid were determined by tracking the (14)C label.

Author(s): 
Janle, Elsa M.
Lila, Mary Ann
Grannan, Michael
Wood, Lauren
Higgins, Aine
Yousef, Gad G.
Rogers, Randy B.
Kim, Helen
Jackson, George S.
Ho, Lap
Weaver, Connie M.

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