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61.
62.
安吉复口服液的耐缺氧,耐低温和抗疲劳作用 总被引:2,自引:0,他引:2
采用缺氧、寒冷和负重游泳等方法,观察了安吉复口服液(0.025、0.1和0.4mg·kg~(-1),ig,qd×14d)对小鼠的耐缺氧、耐低温及抗疲劳作用.结果表明,安吉复口服液0.1、0.4mg·kg~(-1)可延长KCN中毒小鼠的存活时间及延长小鼠在寒冷环境中存活时间,而0.4mg·kg~(-1)可延长常压缺氧条件下小鼠存活时间及延长小鼠负重游泳时间. 相似文献
63.
Summary The aim of this study was to investigate imipramine-induced alterations of cytochrome P-450 and to determine whether prolonged concomitant administration of imipramine and lithium results in a pharmacokinetic interaction.Male Wistar rats received imipramine (10 mg/kg i. p.) at 12 h intervals or lithium chloride (100 mg/kg in drinking water) or they were treated with the combination of these drugs for 2 weeks. The long term treatment with imipramine produced a very complex alteration of cytochrome P-450: imipramine increased the level of the cytochrome, but it decreased the rate of its own aromatic hydroxylation in position 2. The rate of N-demethylation in the side chain was not changed. Consequently, in the case of both hydroxylation and demethylation, calculated molecular activities were decreased to 48% and 70% respectively. This differential change in activities corresponded well to the observed decrease of absorption in difference spectra (type I) produced in microsomes by imipramine. Carbamazepine-induced type I difference spectra were also decreased by imipramine pretreatment, but to a lesser extent. In contrast, hexobarbital type I binding was increased by imipramine treatment while type II difference spectra produced by metyrapone were not affected. The preliminary SDS-PAGE analysis of cytochrome P-450 isoenzymes of control and imipramine treated rats showed that the investigated antidepressant markedly intensified a protein band at 50.11 kD while bands at 51.28 kD, 56.20 kD and 56.88 kD were less intensive. These results indicate that the alteration of cytochrome P-450 by imipramine treatment is not only of quantitative but also of qualitative character. Lithium alone given to rats affected neither the concentration of cytochrome P-450 in microsomal protein nor the rate of imipramine metabolism in vitro. Lithium given jointly with imipramine reduced imipramine-induced elevation of cytochrome P-450. This, however, did not cause any change in the rate of imipramine metabolism in vitro and accordingly in imipramine pharmacokinetics in vivo. The concentration of lithium in the blood plasma tended to increase by concurrent administration of imipramine.Send offprint requests to K. J. Netter at the above address 相似文献
64.
H. Fuder S. Stiegler N. Wetzelsberger G. Wieckhorst R. Lange & P. W. Lücker 《British journal of clinical pharmacology》1997,44(6):527-530
Aims Concomitant administration of magnesium hydroxide may affect the rate or extent of absorption of non-steroidal anti-inflammatory drugs. In order to find out whether or not buffering modifies the pharmacokinetics of ketoprofen, plasma concentration-time courses resulting from oral administration of unbuffered formulations were compared with those of buffered formulations.
Methods Two groups of 12 healthy and young male subjects were included in two randomized cross-over studies and received single oral doses of ketoprofen 12.5 or 25 mg, respectively, given as tablets which were either unbuffered or buffered with magnesium hydroxide/citrate. Ketoprofen enantiomers in plasma were determined by h.p.l.c. up to 24 h post-dose.
Results Maximum plasma concentrations ( Cmax ) of both the (R)- and (S)-enantiomer, observed after administration of the buffered formulations (12.5 and 25 mg), were higher compared with the unbuffered tablets by about 50–80%. The area under concentration-time data (AUC) was unaffected, and, hence, C max /AUC was increased by buffering. Time to C max ( t max ) and mean residence time (MRT) tended to be or was shortened by buffering.
Conclusions It is concluded that buffering of two ketoprofen formulations with magnesium hydroxide/citrate enhanced the concentration maximum by increasing the rate of absorption and leaving AUC unaffected. 相似文献
Methods Two groups of 12 healthy and young male subjects were included in two randomized cross-over studies and received single oral doses of ketoprofen 12.5 or 25 mg, respectively, given as tablets which were either unbuffered or buffered with magnesium hydroxide/citrate. Ketoprofen enantiomers in plasma were determined by h.p.l.c. up to 24 h post-dose.
Results Maximum plasma concentrations ( C
Conclusions It is concluded that buffering of two ketoprofen formulations with magnesium hydroxide/citrate enhanced the concentration maximum by increasing the rate of absorption and leaving AUC unaffected. 相似文献
65.
Elizabeth E. Epstein Barbara S. McCrady Linda S. Hirsch 《Alcoholism, clinical and experimental research》1997,21(3):547-556
Current knowledge about alcohol and marital functioning is limited by restrictive sample selection, inattention to the literature on individual-based alcoholic subtypes, and lack of research linking individual differences among alcoholics to marital functioning. The present study was designed to study marital functioning of alcoholics in light of current alcohol typologies. Subjects were part of a larger study on conjoint treatment of alcoholic males and their female partners. Four typologies—including Type 1/2, In-Home/Out-of-home, SteadyIEpisodic, and EarlyILate Onset—were tested for replicability and discriminant validity before linking them to marital functioning. Discriminant validity was found only for the Early (59%)-versus Late (41 %)-Onset typology; thus, further analyses linked only this typology with marital functioning. At baseline, Early-Onset couples reported more marital instability, and the females in these couples were more distressed. During treatment, Early-Onset couples reported higher daily marital satisfaction than Late-Onset couples. Regardless of age of onset, males reported higher marital satisfaction than their spouses during treatment, but their satisfaction did not increase during treatment. Female partners' marital satisfaction increased during treatment. Female partners of Late-Onset males reported particularly low marital satisfaction during treatment. Parsing the sample according to the early-/late-onset typology yielded different predictors of marital satisfaction for males and females within each subtype. For female partners of Early-Onset alcoholics, psychological distress unrelated to her pattner's drinking severity was most associated with her own marital satisfaction, whereas marital adjustment of female partners of Late-Onset alcoholics was most associated with the male's level of perceptual accuracy regarding her needs. This pattern was reversed for the males; marital adjustment of Early-Onset alcoholics was most associated with his partner's perceptual accuracy of his needs, whereas marital functioning of Late-Onset alcoholics was best accounted for by his own psychological distress. 相似文献
66.
Characterization of the human cytochrome P450 enzymes involved in the metabolism of dihydrocodeine 总被引:1,自引:0,他引:1
L. C. Kirkwood R. L. Nation & A. A. Somogyi 《British journal of clinical pharmacology》1997,44(6):549-555
Aims Using human liver microsomes from donors of the CYP2D6 poor and extensive metabolizer genotypes, the role of individual cytochromes P-450 in the oxidative metabolism of dihydrocodeine was investigated.
Methods The kinetics of formation of N- and O -demethylated metabolites, nordihydrocodeine and dihydromorphine, were determined using microsomes from six extensive and one poor metabolizer and the effects of chemical inhibitors selective for individual P-450 enzymes of the 1A, 2A, 2C, 2D, 2E and 3A families and of LKM1 (anti-CYP2D6) antibodies were studied.
Results Nordihydrocodeine was the major metabolite in both poor and extensive metabolizers. Kinetic constants for N -demethylation derived from the single enzyme Michaelis-Menten model did not differ between the two groups. Troleandomycin and erythromycin selectively inhibited N -demethylation in both extensive and poor metabolizers. The CYP3A inducer, α-naphthoflavone, increased N -demethylation rates. The kinetics of formation of dihydromorphine in both groups were best described by a single enzyme Michaelis-Menten model although inhibition studies in extensive metabolizers suggested involvement of two enzymes with similar K m values. The kinetic constants for O -demethylation were significantly different in extensive and poor metabolizers. The extensive metabolizers had a mean intrinsic clearance to dihydromorphine more than ten times greater than the poor metabolizer. The CYP2D6 chemical inhibitors, quinidine and quinine, and LKM1 antibodies inhibited O -demethylation in extensive metabolizers; no effect was observed in microsomes from a poor metabolizer.
Conclusions CYP2D6 is the major enzyme mediating O -demethylation of dihydrocodeine to dihydromorphine. In contrast, nordihydrocodeine formation is predominantly catalysed by CYP3A. 相似文献
Methods The kinetics of formation of N- and O -demethylated metabolites, nordihydrocodeine and dihydromorphine, were determined using microsomes from six extensive and one poor metabolizer and the effects of chemical inhibitors selective for individual P-450 enzymes of the 1A, 2A, 2C, 2D, 2E and 3A families and of LKM1 (anti-CYP2D6) antibodies were studied.
Results Nordihydrocodeine was the major metabolite in both poor and extensive metabolizers. Kinetic constants for N -demethylation derived from the single enzyme Michaelis-Menten model did not differ between the two groups. Troleandomycin and erythromycin selectively inhibited N -demethylation in both extensive and poor metabolizers. The CYP3A inducer, α-naphthoflavone, increased N -demethylation rates. The kinetics of formation of dihydromorphine in both groups were best described by a single enzyme Michaelis-Menten model although inhibition studies in extensive metabolizers suggested involvement of two enzymes with similar K
Conclusions CYP2D6 is the major enzyme mediating O -demethylation of dihydrocodeine to dihydromorphine. In contrast, nordihydrocodeine formation is predominantly catalysed by CYP3A. 相似文献
67.
68.
组织扩张术皮肤胶原的代谢改变 总被引:4,自引:0,他引:4
目的:研究常规扩张(ITE)和持续快速扩张(CTE)对皮肤胶原代谢的影响。方法用白色小家猪制作组织扩张术动物模型,用Gordeladze法测定血清和扩张组织的羟脯氨酸(HP)含量,藻酸盐印模材膜片法测量标记区面积;光镜测量真皮厚度。结果:ITE组血清HP含量升高,0.8倍,CTE组升高1.2倍,ITE和CTE组皮肤含量与正常皮肤相同,组织中HP总量均明显升高,持续扩张皮瓣组(CTEF)术后4wk皮 相似文献
69.
R. Berkels A. Bertsch T. Zuther S. Dhein K. Stockklauser P. Rsen R. Rsen 《European journal of haematology》1997,58(5):307-313
Abstract: We tried to characterize the porcine platelet nitric oxide (NO) synthase and its L-arginine (L-arg)/NO metabolism. Using RT-PCR we could show a constitutive endothelial NOS (ecNOS) and an inducible NOS (iNOS) similar mRNA in platelets. The NOS protein could be evidenced by an ecNOS specific antibody which also bound in platelets. This finding could be confirmed by Western blot showing an ecNOS in the membrane but not the cytosolic fraction; iNOS protein could not be detected. Using NADPH-diaphorase staining we could show NO synthase in preactivated platelets but not in resting platelets, indicating that the platelet NOS may be activated during platelet activation/aggregation. Porcine L-arg plasma levels (9.31 × 10–5 mol/l ± 10%) could be shown to be in the same range as human plasma levels. Moreover, we could show that the NO precursor L-arg and hydroxy-L-arginine (OHarg) concentration dependently inhibited collagen induced platelet aggregation. Summarizing these results confirm the existence of and further characterize porcine platelet NO synthases. 相似文献
70.
Eduardo E. Castilla María Luísa Martínez-Frías 《American journal of medical genetics. Part A》1995,58(2):106-112
Congenital “healed” cleft lip (CHCL) is an unusual anomaly including a paramedian “scar” of the upper lip, which appears as if a typical cleft lip has been corrected in utero. The CHCL is frequently associated with an ipsilateral notch in the vermilion, and “collapsed” nostril. Twenty-five CHCL cases are presented, eighteen of which were an isolated malformation found among the 3,950,715 births examined in two similar birth defect registries: ECEMC in Spain and ECLAMC in Latin America. Like open cleft lip, of which it seems to be a variant, CHCL is most frequently seen among males (14/18 isolated cases), it preferentially affects the left side (10/18 cases), and it segregated together with cleft lip in one family. The five CHCL cases with other congenital anomalies included: two cases with hydrocephalus, two VACTERL associations, and one atypical oblique facial cleft infant with single umbilical artery. CHCL may result from a defective fusion of the frontonasal and maxillary processes (before week 7 of embryonic life), or from a spontaneously repaired open cleft lip, later on. In either way, these cases heal with a visible scar, and the pre-occurrence of CHCL in two families suggests a familial predisposition to this phenomenon. © 1995 Wiley-Liss, Inc. 相似文献