Protective Effect of Plumbago zeylanica Against Cyclophosphamide-Induced Genotoxicity and Oxidative Stress in Swiss Albino Mice

Plumbago zeylanica, commonly known as white leadwort, found abundantly in the plains of Bengal and southern India, was tested for its possible in vivo protective effect against cyclophosphamide-induced genotoxicity and oxidative stress in Swiss albino mice. Pretreatment with the alcoholic root extract of Plumbago zeylanica (250 and 500 mg/kg body weight orally for 5 days) significantly reduced the frequency of micronucleated polychromatic erythrocytes (MnPCEs), increased the PCE/NCE (normochromatic erythrocyte) ratio in the bone marrow, and decreased the levels of lipid peroxidation products with concomitant changes in the status of antioxidants. Both doses of Plumbago zeylanica were effective in exerting a protective effect against cyclophosphamide-induced genotoxicity and oxidative stress.     

免疫抑制法制备单克隆抗体的研究

用马的红细胞作抗原，先用不含靶抗原的Ｍ２６红细胞和环磷酰胺免疫小鼠，而后再用含靶抗原的Ｍ１７红细胞免疫小鼠。结果显示：经用环磷酰胺抑制后，试验组产生抗非靶抗原抗体的孔数为１５孔，而对照组为１７９孔。试验组获得仅与Ｍ１７红细胞起反应的抗体为１１孔，对照组为８孔。经克隆后，结果显示：在与５５匹含靶抗原的马红细胞反应中。试验组与５２匹起反应，而对照组与４６匹起反应。在与１０１匹不含靶抗原的马红细胞反应中，试验组与３４匹起反应，而对照组与６０匹起反应。这表明，采用环磷酰胺做抑制剂的免疫抑制法，可有效的抑制抗非靶抗原抗体的产生，减少筛选的工作量，而获得的单克隆抗体（单抗）特异性要比对照组强。     

Oral Ondansetron 8 mg Twice Daily is as Effective as 8 mg Three Times Daily in the Prevention of Nausea and Vomiting Associated with Moderately Emetogenic Cancer Chemotherapy

The efficacy and safety of ondansetron 8 mg BID compared with 8 mg TID for 3 days in the prevention of nausea and vomiting in 402 patients on cyclophosphamide (≧500 mg/m²)-based chemotherapy were evaluated in a multicenter, randomized, double-blind, stratified study. The percentage of patients with no emetic episodes over the 3-day study period was 61% in the ondansetron BID group compared with 58% in the ondansetron TID group. Among patients with at least one emetic episode, the mean time to emesis was 14 hr and 17 min in the ondansetron BID group compared with 12 hr and 48 min in the ondansetron TID group. Patients' daily appetite ratings and nausea scores were not significantly different between groups. Clinical laboratory and adverse event profiles were similar between groups. This study is the first large-scale, double-blind trial to demonstrate that ondansetron 8 mg BID for 3 days, a dosing regimen that may enhance patient convenience and compliance, is as effective as ondansetron 8 mg TID for 3 days in the prevention of nausea and vomiting associated with cyclophosphamide-based chemotherapy.     

环磷酰胺冲击治疗狼疮性肾炎疗效观察

对大剂量环磷酰胺与甲基甲的松龙配合强的松冲击治疗重症狼疮性肾炎的疗效进行比较。结果表明环磷酰胺较甲基强的松龙缓解率高，稳定期长，副作用小，值得推广应用。     

复方环磷酰胺软膏的制备及质量控制

目的 研制具有治疗皮肤局部蕈样肉芽肿(MF)的外用化疗制剂，建立测定主药环磷酰胺含量的方法。方法 制备复方环磷酰胺软膏剂，建立质量标准。进行稳定性试验、刺激性试验。结果 质量标准可行，平均回收率99．36％。本制剂性质稳定，无刺激性。结论 本品处方工艺合理，质量稳定，是早期蕈样肉芽肿局部化疗的有效制剂。     

环磷酰胺冲击治疗难治性成人斯蒂尔病初探

目的探讨环磷酰胺(CTX)冲击治疗对难治性成人斯蒂尔病(AOSD)的疗效及安全性。方法对浙江大学医学院附属第一医院风湿免疫科1998～2003年收治11例难治性AOSD患者进行CTX冲击治疗,用量为500～750mg/m2。观察治疗前后患者的临床表现和实验室指标的变化。结果11例难治性AOSD患者经首次CTX冲击治疗后,72h内体温恢复正常者9例,其余2例体温于1周内恢复正常;其中5例患者于首次CTX冲击治疗后第9天、第10天、第11天、第13天出现体温再次升高,经第2次CTX冲击治疗后体温恢复正常。与治疗前相比,首次CTX冲击治疗后1周,血C反应蛋白(CRP)即显著下降(P<0.001);首次CTX冲击治疗后2周、4周、3个月时血沉(ESR)、血CRP、血白细胞计数(WBC)均显著下降(P<0.001)。所有患者经治疗后,肾上腺糖皮质激素剂量均能顺利减至较安全范围内。治疗过程中,4例患者出现恶心、呕吐,未见其他严重不良反应。结论CTX冲击疗法对此11例难治性AOSD有效且未见严重不良反应。     

Biological monitoring of hospital pharmacy personnel occupationally exposed to cytostatic drugs: urinary excretion and cytogenetics studies

For evaluation of the risk borne by hospital pharmacy personnel exposed to antineoplastic agents, the incorporation of cyclophosphamide, ifosfamide, and platinum-containing drugs was quantified by the determination of urinary concentrations. In addition, the induction of micronuclei (MN) and sister-chromatid-exchange (SCE) rates in peripheral blood lymphocytes were studied for correlation with the urinary excretion of cytostatic drugs. Cyclophosphamide and ifosfamide were determined in 24-h urine samples using gas chromatography with electron capture (detection limit 2.5 μg/l). Voltammetric analysis enabled the determination of platinum concentrations of 4 ng/l. Heparinized blood (20 ml) was drawn and lymphocytes were cultured for MN and SCE studies. In all, 13 hospital pharmacists and pharmacy technicians regularly involved in the preparation of cytostatic drugs participated in this investigation (7 persons represent a follow-up group). All subjects applied standard safety precautions, including the use of a vertical laminar air-flow hood, protective gowns, and latex gloves. On the day of urine sampling an average of 4,870 mg cyclophosphamide, 5,580 mg ifosfamide, and 504 mg platinum-containing drugs were handled. The excretion of 5 and 9 μg cyclophosphamide/1 urine was measured in two samples, respectively. An elevated level of urinary platinum was found in one pharmacist (22.3 ng/g creatinine) in comparison with a nonexposed control group. Mean frequencies of MN and SCE did not differ significantly between the drug exposed group and control group. The employees who had incorporated chemotherapeutic agents were part of the follow-up group and, thus, particularly cautious and sensitive to a possible hazard. The results emphasize the necessity of improving personal protection of hospital pharmacy personnel occupationally exposed to cytostatic drugs and support the importance of biological monitoring. In an ongoing project in our department the sources of contamination are being investigated parallel to biological monitoring so as to determine critical situations and improve personal protection. Received: 7 August 1996 / Accepted: 3 January 1997     

不同剂量环磷酰胺对小鼠免疫功能的影响

目的探索不同剂量环磷酰胺(CTX)对正常小鼠免疫功能的影响,为CTX临床应用提供实验数据。方法 C57BL/6小鼠24只,随机分为对照组、低剂量组和高剂量组,分别给生理盐水(NS)、低剂量和高剂量的CTX,检测血常规、Treg比率、T细胞和B细胞增殖功能及巨噬细胞吞噬功能、细胞增殖周期及凋亡比率。结果 RBC、WBC、PLT数量在高剂量组显著降低,对照组与低剂量组无差异;Treg占CD4+T细胞的比例在低剂量组显著下降,对照组与高剂量组无差异;T、B细胞增殖指数及巨噬细胞吞噬功能在低剂量组高于对照组和高剂量组,高剂量组低于对照组;细胞凋亡比率在高剂量组明显增加,对照组与低剂量组间无差异;高剂量组细胞阻滞在S期,对照组与低剂量组间无差异。结论低剂量CTX通过下调Treg、增强免疫细胞的功能,促进机体免疫;而高剂量CTX通过抑制DNA的复制、促进细胞凋亡和降低免疫细胞功能,使机体处于免疫抑制状态。相关数据可以为CTX的临床应用提供借鉴。     

不同免疫抑制剂及甲泼尼龙对小鼠肺间质纤维化的疗效对比

目的比较环磷酰胺、来氟米特和甲泼尼龙对博来霉素诱导的肺间质纤维化小鼠模型的疗效。方法将75只C57BL/6小鼠随机分成空白组、模型组、环磷酰胺组、来氟米特组及甲泼尼龙组(n=15)。空白组气管内注入0.9%氯化钠注射溶液0.2 m L,其余5组气管内注入博来霉素(5 mg/kg)建立肺纤维化模型,24 h后分别对空白组、模型组每日用0.2 m L 0.9%氯化钠注射溶液灌胃,药物组每日分别用环磷酰胺(50 mg/kg)、来氟米特(4 mg/kg)和甲泼尼龙灌胃(10 mg/kg)。并于造模后第7、14、28天分批处死小鼠,取小鼠肺脏评估肺泡炎程度及纤维化的程度。结果 (1)博来霉素诱导组小鼠体质量较对照组减轻(P<0.05),环磷酰胺、来氟米特组和甲泼尼龙组小鼠在第7、14、28天小鼠体质量较模型组均明显增加(P<0.05)。(2)与模型组相比,环磷酰胺组与甲泼尼龙组小鼠7天、14天时肺泡炎评分降低(P<0.05);第7天、14天、28天时纤维化评分明显降低(P<0.05)。而来氟米特组小鼠肺泡炎及纤维化评分较模型组差异无统计学意义。结论环磷酰胺和甲泼尼龙能显著降低博来霉素诱导的小鼠肺间质纤维化,减轻肺组织肺泡炎及肺纤维化程度,但来氟米特没有类似作用。     

Comparison of 2 Preparative Regimens for Stem Cell Transplantation from HLA-Matched Sibling Donors in Patients with Advanced Myelodysplastic Syndrome

The objective of this study was to compare how cyclophosphamide (CY) and oral busulfan (BU) therapies, each in combination with total body irradiation (TBI), affect the outcome of stem cell transplantation in patients with advanced myelodysplastic syndrome. This study was conducted with 31 patients who received bone marrow from an HLA-matched sibling and underwent treatment with BU-TBI (n = 18) or CY-TBI (n = 13). The incidence of acute graft-versus-host disease (GVHD) grades II to IV was higher, but not significantly, in the BU-TBI group (58.8%) than in the CY-TBI group (30.8%). However, the incidences of chronic extensive GVHD were significantly different (41.7% [CY-TBI] versus 80.0% [BU-TBI],P =.04). Trends after BU-TBI conditioning indicated a lower 3-year probability of disease-free survival (DFS) (38.1% versus 53.9%,P =.4), lower relapse rates (28.5% versus 36.4%,P =.8), and higher nonrelapse mortality rates (46.7% versus 15.4%,P =.2). After adjusting for the International Prognostic Scoring System risk group and the cytogenetic risk group, DFS in the CY-TBI group (relative risk, 9.0; 95% confidence interval, 1.5–52.5;P =.015) was found to be significantly increased compared with the BU-TBI group. Approaches to minimize transplantation-related toxicity should be pursued, and efforts other than the potentiation of the conditioning regimen should be made to reduce the likelihood of posttransplantation relapse.