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71.
Chong-Sheng Chen Youssef Jounaidi David J Waxman 《Drug metabolism and disposition》2005,33(9):1261-1267
The anticancer prodrug ifosfamide (IFA) contains a chiral phosphorous atom and is administered in the clinic as a racemic mixture of R-IFA and S-IFA. Hepatic cytochrome P450 (P450) enzymes exhibit enantioselective preferences in the metabolism of R-IFA and S-IFA; however, the impact of this selectivity on P450-dependent anticancer activity is not known. Presently, the metabolism and cytotoxicity of R-IFA and S-IFA were determined in 9L gliosarcoma and Chinese hamster ovary tumor cells expressing an IFA-activating P450 enzyme and by in vitro steady-state kinetic analysis using cDNA-expressed P450 enzymes. Tumor cells expressing P450 enzyme CYP3A4 were the most sensitive to R-IFA cytotoxicity, whereas tumor cells expressing CYP2B1 or CYP2B6 were most sensitive to cyclophosphamide (CPA), an isomer of IFA. Correspondingly, CYP3A4-expressing cells and cDNA-expressed CYP3A4 metabolized R-IFA to yield the active, 4-hydroxylated metabolite at a 2- to 3-fold higher rate than they metabolized S-IFA or CPA. CYP2B cells and cDNA-expressed CYP2B enzymes metabolized CPA almost exclusively by 4-hydroxylation, whereas R-IFA and S-IFA were substantially converted to inactive, N-dechloroethylated metabolites. Further investigation revealed that CYP3A1, a rat enzyme, exhibited superior kinetic properties compared with the human enzyme CYP3A4, with R-IFA and S-IFA both metabolized with high catalytic efficiency by 4-hydroxylation and with a K(m) value of 200 microM, approximately 5-fold lower than CYP3A4. Based on these kinetic parameters and metabolic profiles, R-IFA is expected to exert greater anticancer activity than S-IFA or CPA against tumors that express CYP3A enzymes, whereas tumors expressing CYP2B enzymes may be more sensitive to CPA treatment. 相似文献
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John Jenn-Yenn Lu Chi-Chia Cheng Shieu-Ming Chou Chang-Bor Hor Yi-Chen Yang Hsiang-Ling Wang 《Vaccine》2009
The first universal hepatitis B vaccination program for newborns in the world was launched in Taiwan in July 1984. Most studies on the effectiveness of hepatitis B vaccination focused on the seroprevalence of HBs Ag among children under 14 years old. Only few studies focused on the seropositivity of anti-HBs among adolescents aged 15–18 years old. The present study aimed to evaluate the impact of the nationwide hepatitis B vaccination program on the immunity to HBV infection and the necessity of boost among adolescents. In this study including eight annual seroprevalence surveys from 2000 to 2007, 2342 college entrants (1589 15-year-olds in group I and 753 18-year-olds in group II) and 1851 university freshmen (18-year-olds in group III) participated. Subjects identified anti-HBs, HBs Ag and anti-HBc negative were given boost three doses of HBV vaccine. The HBs Ag seroprevalence was 11.6%, 3.5% and 1.0% for participants who were born before 1984, 1984–1986 and after 1986. The anti-HBs-seropositive rates were significantly higher in group II (83.1%) than in group I (53.0%) and group III (53.5%). All 572 participants who were seronegative for anti-HBs, HBs Ag and anti-HBc became anti-HBs-seropositive after catch-up vaccination. It is concluded that the anti-HBs-seropositive rate decreased to 50% in 15 years after vaccination, and boost vaccination was 100% effective. The necessity and age for boost among anti-HBs negative adolescents and the timing of the first immunization should be further evaluated. 相似文献
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尼麦角林是一种麦角生物碱衍生物,广泛应用于脑血管病患者认知障碍的治疗。多项临
床前研究显示,尼麦角林对于认知障碍的改善可能与以下因素有关:尼麦角林除能够改善脑循环,
促进神经递质释放外,还具有营养神经及抗氧化等作用。目前的研究认为,尼麦角林能够改善患者
卒中后抑郁相关的情绪障碍以及有效改善血管性痴呆,提高患者的日常生活能力。同时,尼麦角林具
有良好的安全性,目前暂无尼麦角林治疗导致纤维化或麦角中毒的研究报道。本文就尼麦角林在神
经系统的作用机制、临床疗效及安全性进行综述,以期为临床应用提供参考。 相似文献
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Background The incidence rate of incisional hernias after open surgery has been reported to be higher than that of port site hernias
after laparoscopic surgery. No studies have compared the costs for the health care system in treating those two types of hernia.
Methods A systematic review was conducted to obtain the baseline data, and a decision analysis model was created to simulate the occurrence
and recurrence of incisional and port site hernias.
Results The overall risk of having incisional hernias was eight-times higher than that of having port site hernias (7.4% vs 0.9%).
A cost savings of £93 per patient can be generated for the health care system in the UK. Similar results were obtained for
Germany, Italy and France.
Conclusions The additional treatment costs for incisional hernia should be taken into account when the costs of a surgery performed by
open approach are compared with by laparoscopy. 相似文献
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