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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
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A convenient approach to the new 2-aminobenzophenone analogue 4 is reported. Condensation reactions of 4 with ortho esters or amide acetals, respectively, followed by intramolecular cyclisations were found to provide smooth access to (4-pyridazinyl)-substituted quinolines 10, 13a,b , and the quinazoline derivative 15 . 相似文献
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Aiman A Ali 《Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics》2007,103(3):e55-e59
BACKGROUND: Because the clinicopathologic effects of takhzeen al-qat are similar to those induced by smoking, the aim of this paper was to study the oral effect of 3 bad oral habits: takhzeen al-qat and cigarette and water-pipe smoking. STUDY DESIGN: This study was done on 33 Yemeni chronic qat users grouped as heavy cigarette smokers (GI), nonsmokers (GII) and water-pipe smokers (GIII). In all cases (n = 33) 2 biopsies were taken (n = 66), one from the buccal mucosa at the chewing side and the other from a similar mucosa at the contralateral (nonexposed) side. Biopsies were prepared for routine H&E staining. RESULTS: Acanthosis appeared in 88% and 0%, abnormal rete ridges in 70% and 3%, hyperparakeratosis in 67% and 0%, and epithelial dysplasia in 30% and 0% of the chewing and nonchewing sides, respectively, in the 3 groups. Epithelial dysplasia appeared in 41% of GI and GIII (smokers) but in only 9% of GII (nonsmokers). CONCLUSIONS: Takhzeen al-qat causes distinct histopathologic changes in the oral mucosa at the side of chewing, such as acanthosis, abnormal rete ridges, and hyperparakeratosis. The association between takhzeen al-qat and cigarette or water-pipe smoking may increase the risk of epithelial dysplasia. 相似文献
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Systemic angioendotheliomatosis is a very rare malignant disease characterized by intravascular neoplastic proliferation of reticuloendothelial cells. According to the clinical features three different types of prognostic value can be distinguished: Exclusive skin involvement; Progressive skin lesions disseminating to internal organs; Aggressive and lethal type affecting primarily internal organs. Until now about 60 cases of systemic angioendotheliomatosis have been reported in the literature. Here we describe the first well-documented case with almost isolated lung involvement. The presentation of morphologic and clinical signs and differential-diagnostic considerations are followed by a critical review of the literature. 相似文献
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T Ul Haq K Munir Z Haider J Yaqoob U Usman 《Journal of Medical Imaging and Radiation Oncology》2005,49(2):140-143
Budd–Chiari syndrome (BCS) is characterized by obstruction of the hepatic venous outflow tract. Therapeutic options for BCS are limited. We report a case of a 21-year-old woman with protein S and C deficiency with gross ascites. Treatment with transjugular intrahepatic portosystemic shunt (TIPS) was attempted, which revealed occluded hepatic veins, so transcaval TIPS was performed. No serious procedure-related complication occurred. After successful shunt creation, the patient's symptoms subsided and she was discharged and followed up for 6 months. 相似文献
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Comparison of a modified adherence assay with existing assay methods for identification of enteroaggregative Escherichia coli.
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K Haider S M Faruque M J Albert S Nahar P K Neogi A Hossain 《Journal of clinical microbiology》1992,30(6):1614-1616
Localized, diffuse, and aggregative adherence patterns of Escherichia coli identified with specific DNA probes were compared in cell culture adherence assays by using the Center for Vaccine Development, Baltimore, method, the University of Texas Medical School, Houston (UTH), method, and a modified UTH method. Increasing postwash incubation time from 2 to 4 h in the modified UTH method allowed identification of enteroaggregative E. coli, which was otherwise not identified by the original UTH method. 相似文献