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Fix Joseph A. Alexander Jose Cortese Margot Engle Karen Leppert Paula Repta A. J. 《Pharmaceutical research》1990,7(4):384-387
Short-chain alkyl esters of L-dopa were administered to rats and mice via oral and rectal routes. Plasma L-dopa esters and L-dopa were determined in the systemic and portal circulation by HPLC. A comparison of isopropyl, butyl, and 4-hydroxybutyl esters of L-dopa demonstrated significantly higher levels of the esters in both systemic and portal blood samples following rectal administration than following oral administration. In most cases, oral administration resulted in nondetectable (<0.01 µg/ml) levels of the esters in plasma. Correspondingly, the plasma levels of L-dopa itself were consistently higher following rectal administration. At very high oral doses (500 mg L-dopa equivalents/kg body weight), systemic plasma levels of the butyl ester could be detected (1.25 µg/ml at 10 min), which might indicate saturation of the esterase activity of the small intestine. These studies indicate that the systemic availability of L-dopa from short-chain alkyl esters of L-dopa may be best optimized by rectal administration, which avoids the relatively high esterase activity characteristic of the small intestine. 相似文献
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S C Jameson C Rada R Lorenzi A G Diamond G W Butcher J C Howard 《Transplantation proceedings》1990,22(6):2510-2511
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J R Voelker D M Jameson D C Brater 《The Journal of pharmacology and experimental therapeutics》1989,250(3):772-778
Diuretic resistance to furosemide in the nephrotic syndrome (NS) may result from binding of drug to filtered albumin within the renal tubule. In buffer solutions intended to partially mimic the luminal environment of the distal nephron during the NS, we examined several chemical properties to determine their effect on furosemide-albumin binding equilibria. Dissociation constants were obtained by measuring furosemide's quenching of human serum albumin's intrinsic tryptophan fluorescence over ranges of pH, ionic strength (IS) and osmolarity. Neither pH nor osmolarity significantly affected binding; however, incremental increases in IS between 0.0 and 1.0 produced increases in Kd from 0.65 +/- 0.05 to 34.38 +/- 1.72 microM, resulting in a 5- and 28-fold increase in the unbound furosemide fraction when the furosemide-albumin concentrations were 3.0:5.0 and 10.0:45.0 microM, respectively. Our results indicate that human serum albumin contains one high affinity binding site for furosemide that is sensitive to IS. Because of changes in the concentrations of reactants as well as IS that can occur in nephron segments distal to furosemide's site of action, we conclude that the amount of unbound (i.e., pharmacologically active) drug in voided urine will not necessarily correspond to the amount at the active site. To clinically assess the pharmacodynamic consequence of protein binding in the NS, changes in the concentration of the reactants and IS in the distal nephron must be minimized so that the unbound furosemide measured in voided urine will accurately reflect the amount at the drug's active site. 相似文献
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Image fusion of bone SPECT and CT - a specific diagnostic method in oral and maxillofacial surgery] 总被引:1,自引:0,他引:1
Denys John Loeffelbein Marco Rainer Kesting Eckhart Mielke Margot Jonas Frank H?lzle Klaus-Dietrich Wolff 《Mund-, Kiefer- und Gesichtschirurgie》2007,11(1):33-41
OBJECTIVE: The aim of this study was to evaluate the benefit of image fusion of CT (computertomography) and bone SPECT (single photon emission computed tomography) in diagnosis of head and neck cancer. METHODS AND PATIENTS: Computer based image fusion has been applied in 39 patients with suspected cancer in the oromaxillofacial region following CT and SPECT without any further hazard for the patients. Afterwards image fusion was set in comparision to simultaneously evaluation of CT and SPECT and histological findings. RESULTS: In 5 out of 39 patients SPECT/CT image fusion obtained more precise anatomical findings in tumour expansion than simultaneously evaluation of CT and SPECT. CONCLUSION: For planning of surgical and radiation therapy of oral and maxillofacial cancer, image fusion of CT/SPECT provides efficient and plastical diagnostic imaging. Particularly in complex anatomical regions like maxilla or base of the skull image fusion could be an additional device, if simultaneous evaluation of CT and SPECT is not clear. 相似文献
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Chronic food restriction has been shown to enhance glucose metabolism in adipocytes from lean Zucker rats at 10, 26, and 52 weeks of age compared to ad libitum-fed lean rats. Only adipocytes from food restricted 10-week-old obese rats demonstrated this response. In this study, lean and obese rats were food restricted from 5 until 14 weeks of age to determine the age at which adipocytes from obese rats were no longer affected by this intervention. Effects of 1 week of refeeding were also determined. When the rats were killed, body weights were highest in control rats followed by restricted/refed and then restricted rats within each genotype. Epididymal pad weights of lean rats were resistant to dietary intervention, while those of obese-restricted and obese-restricted/refed rats weighed less than pads of obese-control rats. Retroperitoneal pad weight was lowered by food restriction in both genotypes; but only that of lean-restricted/refed rats totally recovered with refeeding. Adipocytes of lean-restricted rats had the highest conversion of glucose to CO2. Glyceride-glycerol production was higher in obese compared to lean rats, but restricted rats had elevated conversion of glucose to fatty acids. In general, these results indicate that by 14 weeks of age obese Zucker rats no longer respond to food restriction with an elevated rate of glucose metabolism in adipocytes. 相似文献
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