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31.
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
32.
Burkhard H. A. von Rahden Brigitte Stigler Wolfgang Weiß Hubert J. Stein 《Journal of gastrointestinal surgery》2007,11(7):945-947
Management of upper gastrointestinal bleeding because of erosion of vessels by esophageal cancer may be challenging. We present
herein the angiographic images of a 49-year-old patient who was admitted with massive bleeding from a tumor-eroded inferior
thyroid artery. Attempts to control the bleeding by means of flexible endoscopy and insertion of a Sengstaken–Blakemore tube
had failed. The diagnosis was impressively demonstrated by multislice computed tomography with intravenous contrast in the
arterial phase and multiplanar reconstructions (computed tomography angiography) and by digital subtraction angiography. The
bleeding was successfully treated with superselective catheterization and coiling of the eroded vessel. 相似文献
33.
Wolfgang Heubner 《Journal of molecular medicine (Berlin, Germany)》1940,19(46):1199-1199
Ohne Zusammenfassung 相似文献
34.
Wolfgang Junker 《European archives of psychiatry and clinical neuroscience》1940,111(1):115-128
Ohne Zusammenfassung 相似文献
35.
36.
Sibylle von Vietinghoff Wolfgang Schneider Friedrich C Luft Ralph Kettritz 《Nephrology, dialysis, transplantation》2006,21(11):3324-3326
37.
38.
The synthesis of all the four stereomers of the alkaloid woodinine ( 12a )1) is described and the stereochemical conclusions of Païs3) and Still6) are discussed. The absol. configurations of woodinine ( 12a ) and its diastereomer 8b are unequivocally deduced from the pertinent piperazinediones 16 and 17 . 相似文献
39.
In thePseudemys turtle retina five functionally distinct, electrically coupled networks of horizontal cells distribute signals in the outer plexiform layer. These networks differ significantly in their architecture, as determined by intracellular labeling with Neurobiotin after physiological recording and identification. The density of H1 horizontal cells is highest, ranging around 1800 cells/mm2 at approximately 2.3 mm eccentricity. H1 horizontal cell somata are connected via 6–10 thin, short dendrites. The H1 horizontal cell axon terminal network is composed of thick axon terminals, forming a three-dimensional, sheath-like structure. Networks of coupled H2 and H3 horizontal cells have cell densities of around 210 cells/mm2 and 350 cells/mm2 respectively, at the same eccentricity of 2.3 mm. Cell bodies are connected with 6–12 long, thin dendrites. Here we report for the first time H4 horizontal cell networks. Cell density is approximately 970 cells/mm2 at 2 mm eccentricity, and cell bodies are connected with 6–10 thin, short dendrites. General properties of passive voltage spread were compared for three of these horizontal cell networks using NeuronC. Realistic network architectures were obtained by digitizing the intracellularly labeled networks, respectively. One network obtained from coupled H1 horizontal cell bodies, one from coupled H1 horizontal cell axon terminals, and one from H2 horizontal cells were simulated. These three realistic networks were compared with an artificial, electrically coupled regular triangular network. Passive signal spread in these networks strongly depended on the exact network architecture using otherwise identical parameters. Changes in coupling strength affected signal spread in these networks differently. As in the experimental situation, changes in synaptic conductance influenced signal spread. Some principal effects of extensively coupled horizontal cells on photoreceptor signal processing were simulated with one type of photoreceptor connected by telodendria, synapsing onto an underlying triangular network and receiving feedback synapses. Under certain conditions, spatial information is coded in single photoreceptors. This was also the case in the experimental situation. In the simulation, spatial filter adjustment for optimal spatial coding in photoreceptors can be achieved by changing coupling strength in the horizontal cell network. 相似文献
40.
Theodor Leber grew up in Heidelberg as the son of a professor of Romance languages. Initially he planned to study natural sciences. Bunsen's advice led him to medicine. During his studies he succeeded in solving a competition problem posed by Helmholtz in the medical department. A short period of practical work in the eye hospital of Knapp was unsatisfactory. In Vienna with the physiologist Carl Ludwig, he was able in 1863/64, at the age of only 24 years, to demonstrate the blood circulation of the eye by color injections into the arteries and veins. Since that time the schematic drawings of his results can be found in every textbook of ophthalmology. On the occasion of the congress of the German Ophthalmological Society in Heidelberg in 1864, Theodor Leber reported on these findings and met with immense approval. In 1864–67 he followed an invitation as coworker of Liebreich to Paris; in 1867 he became A.v. Graefe's coworker in Berlin; in 1871 he moved to Göttingen, which became the first eye clinic with a laboratory for experimental investigations.The second epoch-making discovery accomplished by Leber was the detection of the fluid exchange in the eye. These results have also been confirmed by modern methods. Therefore, Theodor Leber can be called the father of experimental ophthalmology. 相似文献