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排序方式: 共有73条查询结果,搜索用时 875 毫秒
1.
Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-11C-verapamil and PET. 总被引:1,自引:0,他引:1
Jens P Bankstahl Claudia Kuntner Aiman Abrahim Rudolf Karch Johann Stanek Thomas Wanek Wolfgang Wadsak Kurt Kletter Markus Müller Wolfgang L?scher Oliver Langer 《Journal of nuclear medicine》2008,49(8):1328-1335
The multidrug efflux transporter P-glycoprotein (P-gp) is expressed in high concentrations at the blood-brain barrier (BBB) and is believed to be implicated in resistance to central nervous system drugs. We used small-animal PET and (R)-11C-verapamil together with tariquidar, a new-generation P-gp modulator, to study the functional activity of P-gp at the BBB of rats. To enable a comparison with human PET data, we performed kinetic modeling to estimate the rate constants of radiotracer transport across the rat BBB. METHODS: A group of 7 Wistar Unilever rats underwent paired (R)-11C-verapamil PET scans at an interval of 3 h: 1 baseline scan and 1 scan after intravenous injection of tariquidar (15 mg/kg, n = 5) or vehicle (n = 2). RESULTS: After tariquidar administration, the distribution volume (DV) of (R)-11C-verapamil was 12-fold higher than baseline (3.68 +/- 0.81 vs. 0.30 +/- 0.08; P = 0.0007, paired t test), whereas the DVs were essentially the same when only vehicle was administered. The increase in DV could be attributed mainly to an increased influx rate constant (K1) of (R)-11C-verapamil into the brain, which was about 8-fold higher after tariquidar. A dose-response assessment with tariquidar provided an estimated half-maximum effect dose of 8.4 +/- 9.5 mg/kg. CONCLUSION: Our data demonstrate that (R)-11C-verapamil PET combined with tariquidar administration is a promising approach to measure P-gp function at the BBB. 相似文献
2.
Stijn Keereweer Jeroen D. F. Kerrebijn Abrahim Al-Mamgani Aniel Sewnaik Robert J. Baatenburg de Jong Esther van Meerten 《European archives of oto-rhino-laryngology》2012,269(3):939-946
Chemoradiation (CRT) is a valuable treatment option for advanced hypopharyngeal squamous cell cancer (HSCC). However, long-term
toxicity and quality of life (QOL) is scarcely reported. Therefore, efficacy, acute and long-term toxic effects, and long-term
QOL of CRT for advanced HSCC were evaluated,using retrospective study and post-treatment quality of life questionnaires. in
a tertiary hospital setting. Analysis was performed of 73 patients that had been treated with CRT. Toxicity was rated using
the CTCAE score list. QOL questionnaires EORTC QLQ-C30, QLQ-H&N35, and VHI were analyzed. The most common acute toxic effects
were dysphagia and mucositis. Dysphagia and xerostomia remained problematic during long-term follow-up. After 3 years, the
disease-specific survival was 41%, local disease control was 71%, and regional disease control was 97%. The results indicated
that CRT for advanced HSCC is associated with high locoregional control and disease-specific survival. However, significant
acute and long-term toxic effects occur, and organ preservation appears not necessarily equivalent to preservation of function
and better QOL. 相似文献
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Mao B Abrahim A Ge Z Ellison DK Hartman R Prabhu SV Reamer RA Wyvratt J 《Journal of pharmaceutical and biomedical analysis》2002,28(6):1101-1113
Rofecoxib is a highly active and selective cyclo-oxygenase II inhibitor. A stability-indicating method for the assay of rofecoxib has been developed using reverse-phase high-performance liquid chromatography (HPLC). Stress testing of rofecoxib was conducted during the method development and validation. HPLC analysis of rofecoxib solutions stressed under alkaline and photolytic conditions revealed the presence of several degradates. Two main degradates were determined to be the cyclization product formed by photo-cyclization and the dicarboxylate formed by ring opening in the presence of base and oxygen. The identities of these degradates were confirmed by comparison of UV spectra and HPLC retention time with the independently synthesized products. The mechanistic pathways for the formation of these degradates are discussed. Further improvement of the HPLC method's ruggedness has been made based on these studies. 相似文献
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Martin Bauer Rudolf Karch Friederike Neumann Aiman Abrahim Claudia C. Wagner Kurt Kletter Markus Müller Markus Zeitlinger Oliver Langer 《European journal of clinical pharmacology》2009,65(9):941-946
Purpose The aim of this study was to assess the influence of age on the functional activity of the multidrug efflux transporter P-glycoprotein
(P-gp) at the human blood-brain barrier.
Methods Seven young (mean age: 27 ± 4 years) and six elderly (mean age: 69 ± 9 years) healthy volunteers underwent dynamic (R)-[11C]verapamil (VPM) positron emission tomography (PET) scans and arterial blood sampling. Parametric distribution volume (DV)
images were generated using Logan linearisation, and age groups were compared with statistical parametric mapping (SPM). Brain
regions that SPM analysis had shown to be most affected by age were analysed by a region of interest (ROI)-based approach
using a maximum probability brain atlas, before and after partial volume correction (PVC).
Results SPM analysis revealed significant clusters of DV increases in cerebellum, temporal and frontal lobe of elderly compared to
younger subjects. In the ROI-based analysis, elderly subjects showed significant DV increases in amygdala (+30%), insula (+26%)
and cerebellum (+25%) before PVC, and in insula (+33%) after PVC.
Conclusions Increased VPM DV values in the brains of elderly subjects suggest a decrease in cerebral P-gp function with increasing age. 相似文献