环磷酰胺对家兔血液流变性的影响

观察抗肿瘤药物环磷酰胺（ＣＴＸ）对家兔血液流变性的影响。结果显示：ＣＴＸ给药组（１０只）多项血液流变学指标明显异常，与正常对照组（８只）比较具有显著性差异（Ｐ＜０．０５～０．００１），标志着ＣＴＸ有引起高粘滞血症的作用。提示：恶性肿瘤病人应用ＣＴＸ后，可加重原有的高粘滞血症。这一结果可作为肿瘤化疗并用活血化瘀及抗凝治疗的依据     

重症狼疮肾炎患者血清TNF-α与sTNF-R水平及甲泼尼龙与环磷酰胺双冲击治疗对其的影响

目的探讨重症狼疮肾炎(SLN)患者血清肿瘤坏死因子!(TNF-!)、可溶性肿瘤坏死因子受体(sTNF-R)的水平、sTNF-R/TNF-!比值及甲泼尼龙(MP)与环磷酰胺(CTX)双冲击治疗对其的影响。方法采用双抗体夹心酶联免疫吸附试验(ELISA)检测35名健康人(正常对照组)和38例SLN患者经MP与CTX双冲击治疗前后血清TNF-!、sTNF-RⅠ、sTNF-RⅡ的水平;抗双链DNA抗体采用ELISA法测定;抗核抗体采用间接免疫荧光法检测;补体C3、C4含量采用速率散射比浊法测定。结果SLN患者血清中TNF-!、sTNF-RⅠ、sTNF-RⅡ水平及TNF-!/sTNF-RⅠ、TNF-!/sTNF-RⅡ比值均显著高于正常对照组(P<0.01),且sTNF-RⅡ增高幅度明显高于sTNF-RⅠ(P<0.01),TNF-!、sTNF-RⅠ、sTNF-RⅡ水平与系统性红斑狼疮疾病活动指数(SLEDAI)评分、抗核抗体、抗双链DNA抗体、血沉、24h尿蛋白定量、血尿素氮(BUN)、血肌酐(Scr)呈显著正相关(P<0.05或P<0.01),与补体C3、C4、内生肌酐清除率(Ccr)呈显著负相关(P<0.05或P<0.01);sTNF-RⅠ与sTNF-RⅡ之间呈显著正相关(P<0.01)。MP与CTX双冲击治疗能显著降低SLN患者血清TNF-!、sTNF-RⅠ、sTNF-RⅡ水平及sTNF-RⅠ/TNF-!、sTNF-RⅡ/TNF-!比值(P<0.01)。结论TNF-!、sTNF-R参与了SLN的发病过程,血清TNF-!、sTNF-RⅠ、sTNF-RⅡ在一定程度上可反映SLN患者肾脏损害程度、病情轻重。动态观察血清TNF-!、sTNF-RⅠ、sTNF-RⅡ水平及sTNF-R/TNF-!比值,有助于判断SLN的狼疮活动、治疗效果及预后。MP与CTX双冲击疗法可能通过抑制SLN患者单核/巨噬细胞、T细胞产生TNF-!而发挥治疗作用。     

环磷酰胺对睾丸组织端粒酶活性表达的影响及意义

目的通过环磷酰胺对大鼠睾丸组织中端粒酶活性影响的研究,探讨端粒酶活性在环磷酰胺导致生精功能损害中的意义。方法选取9d龄雄性Wistar大鼠,给予大、中、小剂量环磷酰胺后24h、4周、8周分别采集睾丸标本,采用TRAP-ELISA法检测睾丸组织中端粒酶活性的变化。结果①用药后24h、4周、8周,各实验组睾丸组织中端粒酶活性均较对照组显著降低(P<0.01);②随时间的增加,对照组虽有逐渐下降趋势,但各时段差异无显著性意义(P>0.05),而各实验组不但有明显的下降,且4周、8周较24h有显著降低(P<0.01);③各实验组同一时期比较,端粒酶活性均随CTX剂量增加而逐渐下降,其中,大、中剂量组与小剂量组比较均显著降低(P<0.01),CTX剂量与端粒酶活性负相关。结论环磷酰胺在损害生精功能的同时,也诱导睾丸组织端粒酶活性下调,并与剂量负相关,且有明显远期效应,提示环磷酰胺所致睾丸生精功能损害可能与其端粒酶活性持续性降低有关。     

Effect of adjuvant disease in rats on cyclophosphamide and isophosphamide metabolism

After the injection of a variety of arthritogenic adjuvants into male Wistar rats, hepatic activation of cyclophosphamide and isophosphamide is rapidly and profoundly depressed. This selective injury is largely reversible with phenobarbital and principally restricted to the liver microsomal protein fraction, which demethylates aminopyrine and N, N-dimethylaniline and generates “alkylating metabolites” from cyclophosphamide in vitro. Evidence is presented, based upon both metabolite excretion studies and the duration of hexabarbital-induced hypnosis, that this phenomenon is not an artifact in vitro and must be seriously considered in evaluating both the efficacy of potential anti-arthritic drugs against the rat adjuvant arthritis and their toxicity in these arthritic animals. A quantitative separation of two pathological responses to the same adjuvant may be obtained: (1) in Buffalo rats, whose liver metabolism may be profoundly impaired while they suffer minimal (or no) arthritis after being inoculated with adjuvants which are truly arthritogenic in other rat strains; (2) with Mycobacterium tuberculosis dispersed in methyl oleate, which induces minimal arthritis in Wistar rats, but nevertheless impairs their liver metabolism over a prolonged period (14 days or more). Drug metabolism appeared to be normal in rats with two other immunologically mediated “inflammatory diseases” (graft vs host disease and allergic encephalomyelitis) and in other rodents examined after adjuvant inoculations. A novel bioassay for cyclophosphamide and isophosphamide metabolites is described which utilizes their ability to prevent grafted rat lymphocytes from initiating a graft vs host reaction in tolerant recipient rats. At least four alkylating metabolites of cyclophosphamide were found in rat bile and tentatively identified by thin-layer chromatography. The possible error in relying on changes in urinary excretion (rather than biliary excretion) of drug metabolites as a guide to changes in hepatic xenobiotic metabolism is discussed.     

Anticancer system created by acrolein and hydroxyl radical generated in enzymatic oxidation of spermine and other biochemical reactions

A hypothesis suggesting the existence of a ubiquitous physiological anticancer system created by two highly reactive oxidative stress inducers with anticancer properties, acrolein and hydroxyl radical, is reported in this communication. Both components can originate separately or together in several biochemical interactions, among them, the enzymatic oxidation of the polyamine spermine, which appear to be their main source. The foundations of this hypothesis encompass our initial search for growth-inhibitors or anticancer compounds in biological material leading to the isolation of spermine, a polyamine that became highly cytotoxic through the generation of acrolein, when enzymatically oxidized. Findings complemented with pertinent literature data by other workers and observed anticancer activities by sources capable of producing acrolein and hydroxyl radical. This hypothesis obvious implication: spermine enzymatic oxidations or other biochemical interactions that would co-generate acrolein and hydroxyl radical, the anticancer system components, should be tried as treatments for any given cancer. The biochemical generation of acrolein observed was totally unexpected, since this aldehyde was known; as a very toxic and highly reactive xenobiotic chemical produced in the pyrolysis of fats and other organic material, found as an atmospheric pollutant, in tobacco smoke and car emissions, and mainly used as a pesticide or aquatic herbicide. Numerous studies on acrolein, considered after our work a biological product, as well, followed. In them, acrolein widespread presence, its effects on diverse cellular proteins, such as, growth factors, and its anticancer activities, were additionally reported. Regarding hydroxyl radical, the second component of the proposed anticancer system, and another cytotoxic product in normal cell metabolism, it co-generates with acrolein in several biochemical interactions, occurrences suggesting that these products might jointly fulfill some biological role. Furthermore, hydroxyl radical shares with phosphoramide mustard, anticancer activities and many similar effects against DNA, including the production of damages resulting in mutagenesis and carcinogenesis, facts that led us to consider this radical, a biological counterpart of phosphoramide mustard. A physiological system involving acrolein and hydroxyl radical, consequently, will be expected to produce effects similar to those from acrolein and phosphoramide mustard, the main anticancer metabolites from the widely used drug, cyclophosphamide.     

吗替麦考酚酯与环磷酰胺联合泼尼松治疗儿童紫癜性肾炎疗效对比

目的:对比分析吗替麦考酚酯与环磷酰胺联合泼尼松治疗儿童紫癜性肾炎的临床疗效及不良反应.方法:将55例紫癜性肾炎患儿随机分为观察组(31例)和对照组(24例),观察组给予吗替麦考酚酯联合泼尼松治疗,对照组给予环磷酰胺联合泼尼松治疗.观察比较两组患儿治疗前后实验室检查指标、完全缓解率及不良反应.结果:两组24h尿蛋白定量、血清白蛋白在治疗后2周均显著改善(P＜0.05),且随着治疗时间的延长,24h尿蛋白逐渐减少,血清白蛋白水平逐渐升高.观察组尿红细胞计数在治疗后1个月显著降低(P＜0.05),对照组尿红细胞计数在治疗后3个月显著降低(P＜0.05).两组总胆固醇、甘油三酯在治疗后6个月显著降低(P＜0.05).观察组完全缓解率90.32％明显高于对照组的63.64％,差异显著(P＜0.05).治疗组不良反应明显低于对照组,但差异无统计学意义(P＞0.05).结论:吗替麦考酚酯联合泼尼松治疗儿童紫癜性肾炎的疗效显著优于环磷酰胺联合泼尼松,且不良反应少,值得临床推广.     

SBPS对CTX增效减毒作用及其免疫学机制的研究

目的探讨半枝莲多糖(SBPS)对化疗药物环磷酰胺(CTX)的增效减毒作用及其机制。方法采用移植性H22肝癌小鼠,随机分为阴性对照组,CTX处理组,CTX+SBPS联合用药组。连续给药10 d后,测定其抑瘤率、白细胞数、吞噬指数和IL-2活性。结果SBPS能提高CTX的抑瘤率,减轻CTX的毒副作用,提高单核吞噬细胞功能和IL-2及TNF-α的活性。结论SBPS对化疗药物CTX具有明显的增效减毒作用,其机制可能是通过增强机体的免疫功能而实现的。     

针刺、艾灸膈俞穴对低白细胞模型大鼠白细胞及骨髓造血功能的调节作用

目的　研究针刺或艾灸膈俞穴对低白模型大鼠提升白细胞和增强骨髓增殖功能的作用。方法　选用Wister大鼠为实验对象,用环磷酰胺(CTX)腹腔注射造成白细胞减少及免疫功能抑制模型,分组处理后,在不同时相进行白细胞计数,并计数骨髓有核细胞数,以评估针刺或艾灸膈俞穴的升白及增强骨髓造血功能的作用。结果　针刺、艾灸膈俞穴及常规西药治疗均可显著提升白细胞、增加骨髓有核细胞计数,且艾灸膈俞穴组疗效优于针刺膈俞穴组及常规西药对照组(P<0. 05)。结论　艾灸膈俞穴可明显提升低白模型大鼠外周血白细胞数和骨髓有核细胞计数。     

黄芪和当归不同配伍提取物对造模小鼠白细胞的影响

目的：观察黄芪和当归不同配伍提取物对造模小鼠白细胞的影响。方法：选用环磷酰胺造成小鼠白细胞减少模型，灌服不同配比黄芪和当归提取物，测定小鼠白细胞计数。结果：黄芪当归5：1提取物能明显升高模型小鼠的白细胞计数，使白细胞数量恢复到正常水平（P〈0．01）。结论：黄芪当归5：1提取物能有效抑制环磷酰胺所造成的小鼠白细胞下降。     

BC369治疗多发性骨髓瘤的临床研究

作者作用生物制ＢＣ３６９（Ｂｉｏｌｇｉｃａｌｓ３６９）对１４例多发性骨髓瘤（Ｍｕｌｔｉｐｌｅ Ｍｙｅｌｏｍａ，ＭＭ）进行治疗。临床资料统计：完全缓解（ＣＲ）４例，部分缓解（ＰＲ）３例，总有效（ＣＲ＋ＰＲ）率为５０％（７／１４）；完全缓解（ＣＲ）病例数占总胶效率（ＣＲ＋ＰＲ）病例数的５７．１％（４／７）。结果提示ＢＣ３６９对多发性骨髓瘤（ＭＭ）有较好的治疗作用。