Determination of vinca alkaloids in human plasma by liquid chromatography/atmospheric pressure chemical ionization mass spectrometry

 A sensitive assay was developed for the quantitation of vinblastine, desacetylvinblastine and vincristine using liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (LC-APCI-MS). Analyses were performed on an Ultrasphere C₁₈ microbore column using ammonium acetate as mobile phase. The calibration curves were linear across the range of 0.51–4.00 ng/ml (0.63–4.93 nM) for vinblastine, 0.74–3.93 ng/ml (0.96–5.11 nM) for desacetylvinblastine and 0.30–3.95 ng/ml (0.36–4.79 nM) for vincristine. Vinca alkaloid concentrations were measured with an accuracy and precision within 11%. This assay could be implemented to determine the plasma concentrations for pharmacokinetic studies of vinblastine, desacetylvinblastine and vincristine in conjunction with clinical trials. Received: 15 December 1995 / Accepted: 16 June 1996     

Slow infusions of vinblastine in the treatment of adult idiopathic thrombocytopenic purpura: A report on 43 cases

Summary Forty-three adult patients with idiopathic thrombocytopenic purpura (ITP) were treated by slow intravenous infusions of vinblastine. Nineteen had ITP of recent onset (i.e. of less than 6 months duration) and had contraindication to steroids (3 patients), refractoriness to steroids (6 patients) or to steroids and high dose intravenous immunoglobulins (IVIg, 10 patients). Of the 19 patients, 10 achieved complete response (CR), 2 achieved partial response (PR), 2 had minor response (MR) and the remaining 5 patients had no response (NR). Six of the complete responders remained in CR after 12 to 48 months, whereas all other responders relapsed within 3 months, in spite of maintenance therapy. Twenty-four patients had chronic ITP (i.e. of 6 months duration or more) and had showed no or only transient response to steroids and/or splenectomy, and in many of them, to other therapeutic approaches. Four achieved CR, 4 PR, 6 MR and 10 NR. All but 2 responses were shorter than 3 months, in spite of maintenance therapy. Most responses to slow infusions of vinblastine began after the first infusion. Main side effects included leukopenia in 9 patients (but with absolute neutropenia in only one) and peripheral neuropathy in 2 patients. Interval from diagnosis was the only prognostic factor of response to treatment. We conclude that slow infusions of vinblastine may be a useful approach in ITP of recent onset, when contraindication or refractoriness to steroids and/or IVIg exists. In our experience, this treatment has limited benefit in chronic ITP. In addition, it remains to be demonstrated that slow infusions of vinca alkaloids have any superiority over intravenous bolus injections of the same drugs.     

环磷酰胺与长春新碱治疗小儿激素依赖型肾病综合征的疗效比较

目的：比较环磷酰胺（cyclophosphamide,CTX）与长春新碱（vincristine,VCR）治疗小儿激素依赖型肾病综合征的临床疗效。方法：回顾性研究62例小儿激素依赖型肾病综合征,其中CTX联合泼尼松龙治疗组31例[CTX剂量3～5mg/（kg·d）],VCR联合泼尼松龙治疗组31例[VCR剂量3～5mg/（kg·d）]。对两组患儿治疗后6、12个月进行随访,比较临床疗效及毒副作用。结果：治疗后6个月随访,CTX治疗组、VCR治疗组有效缓解率分别为48.39%、83.87%。12个月随访,CTX治疗组、VCR治疗组有效缓解率分别为51.61%、87.10%。CTX治疗组合外周血白细胞减低5例（16.13%）及消化道不良反应4例（12.90%）。VCR治疗组5例（16.13%）出现较严重的腹痛。结论：小儿激素依赖型肾病综合征应用CTX或VCR联合泼尼松龙治疗取得了较好的疗效,其中VCR治疗组总有效率优于CTX组。     

Non-AIDS-related Kaposi's sarcoma: A single-institution experience

AIM: To evaluate the outcomes and potential prognostic factors in patients with non-acquired immunodeficiency syndrome (AIDS)-related Kaposi’s sarcoma (KS).METHODS: Patients with histologically proven non-AIDS-related KS treated with systemic chemotherapy were included in this retrospective analysis. In some cases, the human herpes virus 8 status was assessed by immunohistochemistry. The patients were staged according to the Mediterranean KS staging system. A multivariable model was constructed using a forward stepwise selection procedure. A P value < 0.05 was considered statistically significant, and all tests were two-sided.RESULTS: Thirty-two cases were included in this analysis. The average age at diagnosis was 70 years, with a male/female ratio of approximately 2:1. Eighty-four percent of the cases had classic KS. All patients received systemic chemotherapy containing one of the following agents: vinca alkaloid, taxane, and pegylated liposomal doxorubicin. Ten patients (31.5%) experienced a partial response, and a complete response was achieved in four patients (12.4%) and stable disease in sixteen cases (50%). Two patients (6.2%) were refractory to the systemic treatment. The median progression-free survival (PFS) was 11.7 mo, whereas the median overall survival was 28.5 mo. At multivariate analysis, the presence of nodular lesions (vs macular lesions only) was significantly related to a lower PFS (hazard ratio: 3.09; 95%CI: 1.18-8.13, P = 0.0133).CONCLUSION: Non-AIDS-related KS appears mostly limited to the skin and is well-responsive to systemic therapies. Our data show that nodular lesions may be associated with a shorter PFS in patients receiving chemotherapy.     

In vitro production of granulocyte-macrophage colony-stimulating activity by murine bone marrow and spleen following vinblastine administration in vivo

The production of granulocyte-macrophage colony-stimulating activity (CSA) by isolated murine femur shafts, non-dispersed bone marrow and spleens was assessed following administration of Vinblastine (VLB). These organs were removed from 2 h to 10 days post-VLB and allowed to condition endotoxin-free medium for 48 h. CSA activity was assessed using a soft agar cloning system. The data demonstrate that CSA elaboration was maximal 24 h post-VLB, corresponding to the nadir of bone marrow GM-CFC, and 6 h after splenic reached a minimum. No relationship between peripheral blood granulocyte count or serum endotoxin levels were observed.     

培养人淋巴细胞微核测试法检测非整倍体诱变剂的研究

直接用培养人淋巴细胞微核测试系统，采取控制化学品处理培养细胞和恢复时间，对已知非整倍体诱变剂长春新碱进行微核检测，实验结果显示，在设定的微核检测程序中，阴性对照和断裂剂丝裂霉素Ｃ未诱发微核率的显著增加（Ｐ〉０．０５）而ＶＢＬ却引起ＭＮＦ显著增加（Ｐ〈０．０１）。结果揭示培养人外周血淋巴细胞微核测试法可能成为一种新的人类化学品非整倍体诱变剂的检测方法。     

The effect of vinblastine on CFU-E IN normal and W anaemic mice

Using a plasma clot technique, we studied the comparative levels of in vitro erythroid colony forming units (CFU-E) of normal and W anaemic mice following intravenous (IV) injection of 6·25 mg/kg of vinblastine (VBL). Mice used in this study were C57B1/6J, WBB6F,₁, (+/+, WV^v/+ and W/W^v). CFU-E content was looked at on day 0, 1, 3, 5, 7 and 10 following IV VBL. The CFU-E content of bone marrow (BM) and spleen was adequate prior to VBL treatment in all four mouse strains tested. We found IV VBL resulted in a significant rebound of CFU-E production in spleens of all four mouse strains. Most CFU-E production occurred on days 7 and 10 post VBL. The total CFU-E content of BM was not significantly affected by VBL in C57B1/6J, WBB6F₁, +/+ and W^v/+ mice. However, a significant reduction of total CFU-E was seen in the BM of WBB6F₁, W/W^v mice. This plus the fact that increased CFU-E is seen in the spleen of all mouse strains including W/W^v suggests that there may be differing cellular or environmental factor(s) in different hematological organs controlling CFU-E of the W/W^v mouse.     

长春碱对RAW264.7细胞增殖和分泌一氧化氮的影响

目的:研究长春碱对RAW264.7细胞增殖和分泌一氧化氮(NO)的影响。方法:采用MTT法检测长春碱对细胞增殖的抑制作用;流式细胞术观察长春碱对细胞周期的阻断作用;Western blot法检测细胞中cyclin B1蛋白含量的变化;Griess试剂盒检测长春碱对脂多糖(LPS)刺激的细胞分泌NO的影响。结果:长春碱可抑制RAW264.7细胞的增殖,使细胞周期阻滞于G2～M期,呈浓度依赖性地降低细胞中cyclin B1的含量,并抑制LPS刺激的RAW264.7细胞的NO分泌(P<0.05或P<0.01)。结论:长春碱可能通过抑制RAW264.7细胞表达cyclin B1,使细胞周期停滞于G2～M期,从而抑制了RAW264.7细胞的增殖,影响RAW264.7细胞的生物学行为。     

Influence of long-term acute heat exposure on regional blood-brain barrier permeability, cerebral blood flow and 5-HT level in conscious normotensive young rats

Exposure of conscious young rats to 4 h heat stress at 38 degrees C in B.O.D. incubator was associated with increased blood-brain barrier (BBB) permeability in 14 brain regions studied. In the same regions cerebral flow (CBF) diminished by 4-65%, but the magnitude of flow reduction was not correlated with the degree of increased BBB permeability. On the other hand, a correlation was observed with increased plasma and brain 5-hydroxytryptamine (5-HT) levels. p-Chlorophenylalanine (p-CPA), indomethacin and diazepam pretreatment prevented both the increased BBB permeability and 5-HT levels following heat exposure. Whereas cyproheptadine and vinblastine pretreatment prevented the increased BBB permeability alone. The probable mechanism(s) underlying the BBB permeability is discussed.     

电话回访预防长春瑞滨致迟发性静脉炎探讨

目的应用电话回访进行跟踪式的健康教育预防患者出院后长春瑞滨所致的迟发性静脉炎的效果观察。方法选择我科2005年5月～2007年3月间应用长春瑞滨治疗并在治疗后2d内出院的非小细胞肺癌患者129例,建立出院登记本并留取患者的电话,在患者出院后的第2天起由责任护士主动进行电话回访,询问患者静脉情况并认真记录,提醒或告知相应的处理方法。结果有效电话回访372次,及时发现静脉炎3例,占0．8％。电话回访后出院患者的满意度调查比回访前提升了8．8％。结论应用电话回访来指导出院后的患者和家属,可有效预防长春瑞滨静脉注射后所致的迟发性静脉炎,提升了护理服务的满意度。