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991.
J H Lin M Chiba I W Chen J A Nishime F A deLuna M Yamazaki Y J Lin 《Drug metabolism and disposition》1999,27(10):1187-1193
Indinavir, a potent and specific inhibitor of HIV protease, is a known substrate of cytochrome P-450 (CYP) 3A and p-glycoprotein. The purpose of this study is to investigate and compare the inducing effect of dexamethasone (DEX) on CYP3A and p-glycoprotein in the hepatic and intestinal first-pass metabolism of indinavir in rats. Pretreatment of rats with DEX had little effect on the pharmacokinetics (Cl and T(1/2)) after i.v. administration of indinavir, whereas DEX markedly altered the peak concentration (C(max)) and bioavailability of indinavir after oral dosing. The C(max) decreased from 2.8 microM in control rats to 0.28 microM in DEX-treated rats, and bioavailability decreased from 28 to 12.4%. The decreased bioavailability after DEX pretreatment was due mainly to an increase in first-pass metabolism. Intestinal first-pass metabolism (E(G)) increased from 6% in control rats to 34% in DEX-treated rats, and hepatic first-pass metabolism (E(H)) increased from 65 to 82%. Analysis of in vitro kinetic data revealed that the increased intestinal and hepatic metabolism by DEX was attributed to an increase in the V(max), as a result of CYP3A induction, without a significant change in the K(m) values. DEX pretreatment also induced p-glycoprotein in the intestine and liver of rats. p-Glycoprotein appeared to increase the intestinal metabolism of indinavir whereas it had little effect on the hepatic metabolism of indinavir. Although it has been suggested that the role of intestinal metabolism for some drugs is quantitatively greater than that of hepatic metabolism in the overall first-pass metabolism, the contribution of intestinal metabolism to the overall first-pass metabolism of indinavir in rats is not quantitatively as important as the hepatic metabolism, regardless of DEX induction. 相似文献
992.
Curcumin, the yellow pigment in turmeric and curry, has antioxidative and anticarcinogenic activities. In this study, we investigated the pharmacokinetic properties of curcumin in mice. After i.p. administration of curcumin (0.1 g/kg) to mice, about 2.25 microg/ml of curcumin appeared in the plasma in the first 15 min. One hour after administration, the levels of curcumin in the intestines, spleen, liver, and kidneys were 177.04, 26.06, 26.90, and 7.51 microg/g, respectively. Only traces (0.41 microg/g) were observed in the brain at 1 h. To clarify the nature of the metabolites of curcumin, the plasma was analyzed by reversed-phase HPLC, and two putative conjugates were observed. Treatment of the plasma with beta-glucuronidase resulted in a decrease in the concentrations of these two putative conjugates and the concomitant appearance of tetrahydrocurcumin (THC) and curcumin, respectively. To investigate the nature of these glucuronide conjugates in vivo, the plasma was analyzed by electrospray. The chemical structures of these metabolites, determined by mass spectrometry/mass spectrometry analysis, suggested that curcumin was first biotransformed to dihydrocurcumin and THC and that these compounds subsequently were converted to monoglucuronide conjugates. Because THC is one of the major metabolites of curcumin, we studied its stability at different pH values. THC was very stable in 0.1 M phosphate buffers of various pH values. Moreover, THC was more stable than curcumin in 0.1 M phosphate buffer, pH 7.2 (37 degrees C). These results, together with previous findings, suggest that curcumin-glucuronoside, dihydrocurcumin-glucuronoside, THC-glucuronoside, and THC are major metabolites of curcumin in vivo. 相似文献
993.
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
994.
康乐霉素C与环孢素对小鼠免疫抑制作用的比较 总被引:4,自引:0,他引:4
AIM: To study inhibitory effects of kanglemycin C (Kan) on the mouse immune system, and compare with the effects of ciclosporin (Cic). METHODS: Delayed hypersensitivity (DH) and cyclophosphamide-potentiated DH induced by dinitrofluorobenzene (DNFB); heart allograft and skin allograft; hemolysin; the phagocytosis of the peritoneal macrophage. RESULTS: Kan (12.5, 25, 50 mg.kg-1.d-1, ig, 8 d) markedly inhibited DH and cyclophosphamide-potentiated DH induced by DNFB (P < 0.01), prolonged survival times of heart and skin allografts (P < 0.01), and decreased the content of hemolysin (P < 0.01), but had no significant effect on the neutral-red phagocytosis of the peritoneal macrophage (P > 0.05). CONCLUSION: Kan had marked suppressive effects on cell-mediated and humoral-mediated immune responses, but no effect on phagocytosis of macrophage. 相似文献
995.
氟伐他汀对自发性高血压大鼠阻力血管 功能的影响 总被引:7,自引:0,他引:7
AIM: To evaluate the effects of fluvastatin, a hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor, on the alterations of structure and function of resistant vessels in spontaneously hypertensive rats (SHR). METHODS: Eight-week-old male SHR were given fluvastatin 20 mg.kg-1.d-1 by gavage. Rats were decapitated at 16 wk. Wall-to-lumen area ratios (W/L) of thoracic aorta and mesenteric arteries (3rd grade branch) were assessed by morphometric assay. The effects of fluvastatin on vascular reactivity to sodium nitroprusside (SNP) and norepinephrine (NE), were studied with rings of thoracic aorta and mesenteric arteries isolated from rats. RESULTS: After 8 wk of treatment, histological examination showed that the wall-to-lumen area ratio was lower in SHRflu than that in SHR (0.44 +/- 0.09 vs 0.79 +/- 0.09, P < 0.05). EC50 of vasodilation response was much lower in SHRflu than that in SHR [(4.9 vs 190) pmol.L-1, P < 0.05], while EC50 of mesenteric artery rings from SHRflu was somewhat lower than that of SHR [(0.02 vs 0.04) nmol.L-1, P > 0.05]. In both aortic and mesenteric artery rings, EC50 of vasoconstriction in response to NE from SHRflu was higher than that of SHR [thoracic aorta: (0.20 vs 0.02) nmol.L-1, P < 0.05; mesentric arteries: (1.46 vs 0.72) nmol.L-1, P < 0.05]. CONCLUSION: Short-term treatment with fluvastatin ameliorated the vasomotoricity of resistant vessels, enhanced the sensitivity to vasodilator and depressed the sensitivity to vasoconstrictor; fluvastatin also attenuated the resistant vascular hypertrophy during the development of hypertension in SHR. 相似文献
996.
中药材珍珠的X衍射Fourier谱研究 总被引:18,自引:1,他引:17
目的:珍珠为常用名贵中药,应用粉未X衍射Fourier谱分析,建立各类珍珠的X衍射特征标记峰,对其进行鉴定。方法:西方应用粉未X衍射方法对珍珠贝科海水(天然与人工养殖)、淡水珍珠、蚌科三角帆蚌壳、珍珠未与珍珠层粉等9个榈进行了X衍射Fourier谱分析计算。结果:海水珍珠、淡水珍珠、珍珠粉与珍珠层粉中的主要成分为珍珠文石型碳酸钙;但后二者中尚含有10%以下方解石型碳酸钙。同时,获得了有别于文石矿的 相似文献
997.
Yang SS Chen CY Wei CB Lin YT 《Zhonghua Minguo wei sheng wu ji mian yi xue za zhi = Chinese journal of microbiology and immunology》1996,29(4):185-196
Several microbes were isolated from the contaminated fuel-oil in Taiwan and the microbial corrosion of aluminum alloy A356-T6 was tested by MIL-STD-810E test method. Penicillium sp. AM-F5 and Cladosporium resinac ATCC 22712 had significant adsorption and pitting on the surface of aluminum alloy, Pseudomonas acruginosa AM-B5 had weak adsorption and some precipitation in the bottom, and Candida sp. AM-Y1 had the less adsorption and few cavities formation on the surface. pH of the aqueous phase decreased 0.3 to 0.7 unit for 4 months of incubation. The corrosion of aluminum alloy was very significant in the cultures of Penicillium sp. AM-F2, Penicillium sp. AM-F5 and C. resinac ATCC 22712. The major metabolites in the aqueous phase with the inoculation of C. resinac were citric acid and oxalic acid, while succinic acid and fumaric acid were the minors. 相似文献
998.
C. -T. Yang H. -C. Lin M. -C. Lin C. -H. Wang C. -H. Lee H. -P. Kuo 《European journal of clinical pharmacology》1996,49(5):341-345
Objective: The effect of 2-adrenoceptor agonist-induced hypokalaemia on cardiac arrhythmias might be exacerbated during exercise, especially in patients with more compromised airway function.
Methods: To evaluate the effect of 2-adrenoceptor agonists on plasma potassium and cardiopulmonary function during exercise, two identical submaximal treadmill exercise tests were performed, at least 48 h apart, by 13 patients with moderate to severe COPD (11 men and 2 women, mean age 66 y, mean FEV1/FVC ratio 48.9 (2.8)%) 30 min after they had received nebulised fenoterol or salbutamol (2 mg). The experiment was done as a randomised, double-blind, crossover trial after an initial baseline study with vehicle (0.45% saline). Plasma potassium concentration, spirometry and the degree of breathlessness (Borg scale) were measured before treatment and immediately after exercise; oxygen saturation, QTc interval and cardiac rhythm were monitored continuously before, during and for 30 min after exercise.
Results: After the saline control, exercise caused an increase in Borg rating (of 4.9), a premature ventricular contractions (VPC) (2.8 beats/min), and a fall in oxygen saturation (-6.7%), but no significant change in plasma potassium (+0.04 mEq·dl–1), FEV1 or QTc interval. Inhalation of fenoterol and salbutamol did not affect QTc interval, Borg scale or VPC frequency at rest, but significantly increased the duration of exercise undertaken to reach the submaximal levels (786 s, versus 783 s) compared to the vehicle control. Following exercise, plasma potassium fell after fenoterol by 0.2 mEq·dl–1 and it increased after salbutamol by 0.1 mEq·dl–1 compared to baseline levels. Plasma potassium after exercise was significantly lower after fenoterol (3.2 mEq·dl–1) compared to the saline control (3.7 mEq · dl–1) and salbutamol (3.6 mEq · dl–1). Neither fenoterol nor salbutamol had any significant effect on the change in FEV1, oxygen saturation, Borg scale, frequency of VPCs or QTc interval during or after exercise compared to the saline control.
Conclusion: When compared to salbutamol 2 mg, fenoterol 2 mg caused more marked hypokalaemia but no significant difference in cardiopulmonary response in patients with COPD during exercise. 相似文献
999.
Chen YC Hung CC Lin SF Chang SC Hsieh WC 《International journal of antimicrobial agents》1996,7(1):69-74
The safety and efficacy of flomoxef and latamoxef were compared in the treatment of hospitalized patients with sepsis and/or Gram-negative bacteremia in a prospective, open-labelled clinical trial. Patients were randomized to receive 1 to 2 g intravenous doses of either flomoxef every 6 to 12 h, or latamoxef every 8 to 12 h. Data from 21 patients given flomoxef and 23 patients given latamoxef were included in the evaluation of efficacy. Flomoxef produced clinical cure and satisfactory microbiological responses in 85.7% and 100% of patients, respectively. These results were similar to those obtained with latamoxef (87% and 100%, respectively). In addition, no significant difference was found in mean age, sex, severity of infection, distribution of pathogens and focus of infection between the two groups. However, the flomoxef group included more patients with ultimately fatal diseases. Six patients given flomoxef and two patients given latamoxef developed superinfections caused by yeast, enterococci and Pseudomonas aeruginosa in the urinary tract. Mild and reversible adverse reactions probably related to flomoxef and latamoxef were noted in 14.3% and 13% of patients, respectively. The results of this study demonstrated that flomoxef is a safe and effective antimicrobial agent in the treatment of patients with sepsis and/or Gram-negative bacteremia. 相似文献
1000.
Is male gender a risk factor for conversion of laparoscopic into open cholecystectomy? 总被引:1,自引:0,他引:1
A. Zisman R. Gold-Deutch E. Zisman M. Negri Z. Halpern G. Lin A. Halevy 《Surgical endoscopy》1996,10(9):892-894
Background: Based on a clinical observation that the conversion rate of laparoscopic cholecystectomy (LC) to open cholecystectomy (OC) is higher in males, we decided to review our records and to verify whether a significant difference in conversion rates exists between sexes.
Methods: A retrospective study on conversion rates of elective laparoscopic cholecystectomy (LC) into open cholecystectomy (LC) in relation to gender was carried out in 329 patients: 267 females and 62 males.
Results: Our data revealed that the probability of conversion is fivefold greater in males than females, 21% vs 4.5%, respectively (p=0.0001). We attribute this striking difference to significantly more adhesions (p=0.0002) and anatomical difficulties (p=0.003) in males during LC, leading to conversion.
Conclusions: We conclude that conversion of LC to OC is more prevalent among males and is probably attributable to a greater incidence of anatomical difficulties. 相似文献