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The purpose of this study was to investigate the disposition and the nephrotoxicity of 3-amino-1-hydroxypropylidene-1, 1-bisphosphonate (APD-pamidronate) in order to elucidate the mechanism of the non-linearity of the renal elimination of this drug. The fate of APD labelled with [14C]APD was studied in mice and rats for a range of doses (0.5-40 mg/kg) and indicators of renal function were monitored. In both species, the percentage of dose excreted during the first 24-h after treatment fell dramatically as a function of the dose. However, the renal burden of APD rose linearly for doses of APD below 10 mg/kg and increased non-linearly over this threshold. In contrast the concentration of APD in both bone and liver, which together account for a large proportion of the dose, appeared to increase proportionally with dose. There was no evidence, therefore, that the non-linear renal elimination of APD was due to an increased uptake of APD by tissues. Conversely, the significant fall in the renal excretion of APD was paralleled by a striking loss in body weight, and for high doses, by a fall in the creatinine clearance. An increased enzymuria suggested the loss of brush border membranes and the release of lysosomal contents by proximal tubular cells. Morphological studies confirmed this and revealed a focal proximal tubular necrosis 6 days post dosing. We conclude that the nephrotoxicity of APD accounts for the non-linear renal elimination of this drug. 相似文献
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Prior studies have shown that pneumothorax is one of the more difficult entities to diagnose with digitized radiography. This study was designed to test whether increasing resolution from 1.25 to 2.5 line pairs per millimeter (lp/mm) and image processing (edge enhancement from unsharp masking) would increase accuracy and confidence in the diagnosis of pneumothorax, as well as normal cases and other forms of lung disease. Conventional radiographs were digitized with use of a laser reader and then reformatted as film hard copy. Eleven observers read 35 cases reformatted in three different ways (1.25 lp/mm, 2.5 lp/mm, 1.25 lp/mm unsharp mask). The images with finer resolution (2.5 lp/mm) and unsharp mask images were superior to those with coarser resolution (1.25 lp/mm) for the diagnosis of pneumothorax. There was no difference in diagnostic accuracy for normal patients. For abnormalities other than pneumothorax, the unsharp mask images were significantly worse. Confidence in the diagnosis of pneumothorax and other abnormalities was highest with the finest resolution (2.5 lp/mm). 相似文献
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R Vettor C Martini L Calò S Cantaro C Macor C De Palo N Sicolo C Scandellari G Federspil 《Diabète & métabolisme》1992,18(3):213-217
Anomalies in prostaglandin (PG) synthesis have been suggested in both experimental and human diabetes mellitus; increased levels of plasma and tissue eicosanoids has been recently reported by several investigators. One step in prostaglandin synthesis is the enzymatic hydrolysis of membrane phospholipids by Phospholipase A2 (PLA2). Nevertheless the alternative pathway involving Phospholipase C must be considered. An evaluation of PLA2 activity is therefore a useful method for studying prostaglandin synthesis in the peripheral target tissues of insulin activity. We studied PLA2 activity in normal and diabetic rat muscle. Streptozotocin-induced diabetic rats showed significantly higher muscular PLA2 activity when compared with controls (3.04 x 10(-2) +/- 0.50 x 10(-2) versus 1.34 x 10(-2) +/- 0.35 x 10(-2) arachidonic acid pMol.mg protein-1.min-1 (p less than 0.01). This effect was not observed in diabetic animals successfully treated with insulin (1.78 x 10(-2) +/- 0.5 x 10(-2) versus 1.34 x 10(-2) +/- 0.35 x 10(-2) arachidonic acid pMol.mg protein-1.min-1), and a significant correlation was found between blood glucose and muscular PLA2 activity (r = 0.42; p less than 0.05). Our results clearly show that in streptozotocin-induced diabetic rats muscular PLA2 activity is significantly higher. The relationship between blood glucose levels and muscular PLA2 activity and the decrease of PLA2 activity after insulin treatment suggest that these changes may be related to a defect in insulin effect. 相似文献
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导数光谱系数倍率法测定多组分体系感冒清胶囊中盐酸吗啉胍的含量 总被引:1,自引:0,他引:1
This paper provides a basic principle and experimental technique of derivative signal multiplier spectrophotometry in multicomponent mixture. A microcomputer was used to process the spectral data measured on a manual spectrophotometer (UV-7520) for the determination of moroxydine hydrochloride in Gan Mao Qing capsules. Quantitative analysis of multicomponent mixture can be done without sample separation. The selection of optimal wavelength pairs is performed through the program with a computer. The method needs no special spectrophotometer and is simple, rapid and easy to operate. The mean recovery was 99.98 +/- 0.53% (n = 12). 相似文献
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