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Furosemide 1-O-acyl glucuronide (Fgnd) was reversibly bound to a single class of binding sites on human serum albumin (HSA), and the binding of Fgnd decreased with increasing F concentrations, suggesting that Fgnd binds to the same warfarin binding sites on HSA as F binds. The rate of Fgnd degradation (hydrolysis and acyl migration) decreased in the presence of HSA. Although the formation of acyl migration isomers of Fgnd was slower in the presence of HSA than in its absence, hydrolysis of Fgnd to F was faster in the presence of HSA. Rapid minor irreversible binding of Fgnd to HSA within 30 min was followed by slow major irreversible binding. Slow irreversible binding of Fgnd to HSA was decreased by F, though not significantly. This suggests that major irreversible binding may proceed via reversible binding. It has been reported that acyl migration is a prerequisite for irreversible binding. Therefore, these results indicate that HSA decreases irreversible binding of Fgnd to protein by suppressing acyl migration. Furthermore, these results suggest that HSA may prevent irreversible binding of Fgnd to other proteins in the body by decreasing the concentration of reactive Fgnd in the unbound form. HSA eliminates reactive Fgnd by hydrolysis to F. Therefore, it is concluded that HSA works as a scavenger to decrease reactive compounds by reversible binding or eliminates reactive compounds by irreversible binding. 相似文献
43.
Panganiban K Jacob P Everhart ET Tisdale EC Batki SL Mendelson JE Jones RT 《Journal of analytical toxicology》1999,23(7):581-585
Recent studies have demonstrated the utility of quantitative assays for benzoylecgonine in assessing the efficacy of cocaine-dependence-treatment programs to determine if the amount of cocaine consumed has been reduced. We describe a simple gas chromatographic method for determining benzoylecgonine concentrations in urine. BZE is extracted from urine as an ion pair with tri-n-propylsulfonium ion. Injection into the heated injection port of the gas chromatograph results in thermal conversion of the ion pair to the n-propyl ester of BZE. Using the structural analogue of BZE, m-toluylecgonine, as the internal standard, the analysis is carried out on a (5% phenyl)methylpolysiloxane capillary column with nitrogen-phosphorus detection. There was a good correlation between BZE concentrations determined by gas chromatography-mass spectrometry and concentrations determined by the method described in this paper. Application to cocaine-dependence-treatment programs is discussed. 相似文献
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A comparison of the late patency rates of axillobilateral femoral and axillounilateral femoral grafts 总被引:4,自引:0,他引:4
LoGerfo FW Johnson WC Corson JD Vollman RW Weisel RD Davis RC O'Hara ET Nabseth DC Mannick JA 《Surgery》1977,81(1):33-8; discussion 38-40
A total of 130 axillofemoral grafts were peformed in 120 patients from 1966 to present; 66 were axillobilateral femoral moral and 64 were axillounilateral femoral grafts. The average patient age was 66 years. The indications for operation were occlusive disease with rest pain or gangrene in 102 patients, severe claudication four, and bypass of a thoracic aneurysm in one. The one month operative mortality rate was 8 percent (ten patients). Four deaths occurred in elderly patients operated upon as emergencies with acute aortic occlusion. In the 126 elective cases, there were six postoperative deaths (4.7 percent). Twenty thrombectomies were performed in 15 axillobilateral femoral grafts of which 15 (75 percent) were successful. In the unilateral grafts there were 25 thrombectomies in 22 grafts, of which only eight (32 percent) were successful. The 5 year patency rate by the life-table method was 74 percent for axillobilateral femoral grafts and 37 percent for axillounilateral femoral grafts. This difference in patency rates is statistically significant (p < 0.01). Average flow measured by electromagnetic flow meter in six axillobilateral femoral grafts was 621 c.c. per minute and in 11 unilateral femoral grafts was 273 c.c. per minute. We attribute the higher patency rate in axillobilateral femoral grafts to this increased flow. These data indicate that axillobilateral femoral grafts may be performed with anticipation of a 5 year patency rate comparable to that with conventional aortoiliac reconstruction and that axillobilateral femoral grafts should be performed in preference to axillounilateral femoral grafts in poor-risk patients requiring extra-anatomic bypass for aortoiliac occlusive disease. 相似文献
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Tzavara ET Valjent E Firmo C Mas M Beslot F Defer N Roques BP Hanoune J Maldonado R 《The European journal of neuroscience》2000,12(3):1038-1046
Region-specific up-regulation of the cyclic AMP pathway is considered an important molecular mechanism in the origin of the somatic manifestations of the withdrawal syndrome to known drugs of abuse. Nevertheless, the existence of a withdrawal syndrome after prolonged cannabinoid administration has long been a controversial issue. Recent studies, in different species, have shown that withdrawal to prolonged cannabinoid exposure precipitated by the cannabinoid antagonist SR141716A is characterized by physical signs underlying impairment of motor coordination. Interestingly, cannabinoid withdrawal is accompanied by an increase of adenylyl cyclase activity in the cerebellum. Here, we investigate the functional role of the cyclic AMP pathway in the cerebellum in the establishment of cannabinoid withdrawal. We show that after SR141716A precipitation of cannabinoid withdrawal, basal and calcium-calmodulin-stimulated adenylyl cyclase activities as well as active PKA in the cerebellum increase in a transient manner with a temporal profile which matches that of the somatic expression of abstinence. Selectively blocking the up-regulation of the cyclic AMP pathway in the cerebellum, by microinfusing the cyclic AMP blocker Rp-8Br-cAMPS in this region, markedly reduced both PKA activation and the somatic expression of cannabinoid withdrawal. Our results (i) directly link the behavioural manifestations of cannabinoid withdrawal with the up-regulation of the cyclic AMP pathway in the cerebellum, pointing towards common molecular adaptive mechanisms for dependence and withdrawal to most drugs of abuse; (ii) suggest a particular role for the cerebellum as a major neurobiological substrate for cannabinoid withdrawal. 相似文献
50.
目的设计并合成与环佐辛有类似的阿片受体亲和活性、在体内具有较长作用时间的3-四氢呋喃甲基苯并吗吩烷类似物。方法8-三氟甲磺酸酯-3-四氢呋喃甲基苯并吗吩烷经催化氨化制得目标物,对目标物进行受体亲和力测定。结果8-氨基及8-苯氨基化合物在体外与μ,δ和κ受体的亲和力均较相应的8-羟基化合物低。结论目标化合物的体外受体亲和力相对较低,但此结果尚不能完全说明其在体内的作用情况及其可否用于毒品成瘾的治疗。进一步研究正在进行。 相似文献