Vagal damage enhances polyneuropathy pain: additive effect of two algogenic mechanisms

While the major pain generation in polyneuropathy is in the somatic peripheral nerves, pathologies at visceral nerves might be involved as well. Decreased vagal afferent activity is known to disinhibit pain perception, and therefore might contribute to pain in polyneuropathy. In this study we explored this potential contribution by employing a rat model of vincristine (VCR)-induced pain after sub-diaphragmatic vagotomy (SDV). Forty rats were divided into 4 groups: VCR, SDV, VCR + SDV and controls. Each rat underwent a variety of pain-related behavioral tests including assessment of spontaneous pain, allodynia and hyperalgesia to thermal and mechanical stimuli. We found that VCR + SDV rats had enhanced painful neuropathy compared to VCR alone, expressed as: (1) earlier development of central sensitization: at the first week in rats that underwent SDV + VCR (p < 0.0001) and only at the second week in rats injected with VCR alone (p < 0.0001), (2) increased incidence of spontaneous pain behavior (p = 0.0036), (3) spreading of the spontaneous pain behavior to the forelimbs, (4) higher mechanical dynamic allodynia (tendency, p = 0.08) and (5) augmentation of the response to repetitive painful and non-painful mechanical stimuli (p < 0.001). Thus, decreased vagal activity aggravates both the severity and the time course of painful polyneuropathy. Therefore, the two mechanisms add to each other in generating the pain picture.     

柔红霉素长春新碱体外对人急性髓系白血病细胞株的相互作用

目的：观察柔红霉素、长春新碱联合应用在体外对人急性髓系白血病细胞株（HL－60）的相互作用。方法：采用MTT法，利用中效原理判断联合用药的效果。结果；两种药物单用及联合应用时随着药物剂量增加，其效应也增加。两药大剂量合用时为拮抗效应，较小剂量合用时为协同效应。两药合用时（除最小剂量外）与先用柔红霉素24小时或先用长春新碱24小时比较P＜0．01；小剂量合用时先用柔红霉素24小时与先用长春新碱24小时比较P＞0．05。两药合用时浓度变化会影响合用效应。结论：柔红霉素与长春新碱合用时大剂量为拮抗，较小剂量为协同；合用效应大小与两种药物浓度比例有关；与给药先后次序无关，同时给药效果好。     

Vincristine in steroid-resistant nephrotic syndrome

The therapeutic response to vincristine was examined in seven children (aged 2–15 years) with corticosteroid-resistant (CR) nephrotic syndrome (NS) with focal and segmental glomerulosclerosis (FGS). Five were also resistant to cyclophosphamide. Vincristine was given weekly (1.5 mg/m² intravenously) for 8 weeks. Simultaneously, prednisone (60 mg/m² per day, orally) was given for 4 weeks and then gradually tapered. Two of these patients had a complete and stable remission; in five no benefit was observed. It was not possible to identify any characteristics to predict the response to vincristine. Although there is a case for trying vincristine therapy in CR NS with FGS, the results of this study are not encouraging and a better understanding of its action and indications is necessary.     

糖尿病兔肾小管间质损伤标志物变化及长春新碱的干预作用

目的 观察糖尿病兔肾小管间质损伤标志物变化及长春新碱对其影响。方法 日本大白兔随机分成正常对照组（C组）、糖尿病组（DM组）、糖尿病长春新碱治疗组（DV组）；耳缘静注射四氧嘧啶造成兔糖尿病模型，DV组每周予一次长春新碱耳缘静脉注射；胰岛素控制DM组、DV组血糖16.0-25.0 mmol/L.第8周、第12周时分别测各组半数兔血糖、肾重、体重、尿视黄醇结合蛋白（RBP）、N-乙酰-β-D-氨基葡萄糖苷酶（NAG）。结果 给药后72h DV组、DM组血糖明显升高形成稳定糖尿病模型；第8周、第12周时，DV组体重明显高于DM组（P〈0.05）、肾重/体重值明显2低于DM组（P〈0.05）,DM组尿RBP、NAG明显高于对照组（P〈0.05）,DV组尿RBP、NAG均明显低于DM组（P〈0.05）.结论 糖尿病兔早期存在肾小管间质损伤，长春新碱可减轻糖尿病兔肾小管间质损伤，降低肾重/体重值。     

从CX3CR1通路探讨天麻素对化疗痛的作用机制

目的 探讨天麻素对化疗药物诱导的神经病理性疼痛的抑制作用及其机制. 方法 根据痛阈值大小筛选出合格的SD大鼠50只,采用随机数字表法分为5组:对照组、模型组、天麻素30 mg/kg组、天麻素60 mg/kg组、天麻素120 mg/kg组,每组10只.用隔日腹腔注射长春新碱(125 μg/kg)的方法建立化疗药物诱导的神经病理性疼痛动物模型(对照组大鼠除外),建模后第9天开始,继续腹腔注射长春新碱(125 μg/kg),并开始采用不同剂量的天麻素治疗后3组大鼠.对照组和模型组用生理盐水(腹腔注射,5 mL/kg)同步对照.治疗1周后(建模后第16天)分别用Electronicvonfrey测痛仪和热刺痛仪再次测定大鼠机械刺激痛阈值和热刺激痛阈值.Western blotting法检测脊髓CX3CR1蛋白和磷酸化p38MAPK蛋白表达,ELISA法检测脊髓TNF-α蛋白表达. 结果 与对照组比较,模型组大鼠机械痛阈值和热痛阈值明显降低,差异有统计学意义(P＜0.05),脊髓CX3CR1蛋白、p-p38MAPK蛋白和TNF-α蛋白表达显著升高,差异有统计学意义(P＜0.05);与模型组比较,天麻素60 mg/kg组、120 mg/kg组大鼠机械痛阈值与热痛阈值有不同程度的升高,差异有统计学意义(P＜0.05),脊髓CX3CR1蛋白、p-p38MAPK蛋白和TNF-α蛋白表达有不同程度的降低,差异有统计学意义(P＜0.05). 结论 天麻素能够抑制化疗痛大鼠机械痛阈值和热痛阈值,其发挥作用的机制可能与其抑制大鼠脊髓小胶质细胞活化通路中的CX3CR1、p-p38MAPK蛋白,进而减少炎性细胞因子TNF-α的表达相关.     

A case of thrombotic thrombocytopenic purpura in an adult treated with vincristine

 The case of a woman with thrombotic thrombocytopenic purpura refractory to prolonged treatment with plasma exchange and steroid treatment is described. The addition of vincristine yielded a complete response, which has been maintained for 9 months up to the time of this report. Received: May 29, 1998 / Accepted: September 11, 1998     

抗癌药1,2:5,6-二去水卫矛醇与长春新碱联合用药的实验研究

去水卫矛醇(DAG)与长春新碱(VCR)联合使用,对小鼠淋巴细胞白血病L₁₂₁₀有协同疗效,疗效强度决定于给药方案和剂量。先给DAG,24 h后给VCR,协同疗效最高。DAG剂量是影响疗效的主要因素,最佳剂量为3.0 mg/kg。琼脂扩散合试验亦证明二药有方案依赖性协同作用。二药合用对小鼠骨髓干细胞仅有微弱的协同杀灭作用。     

Severe vincristine toxicity in combination with itraconazole

We report two patients with acute lymphoblastic leukaemia (ALL) who were entered into the current MRC adult ALL trial (UKALL XII) in whom unusually severe vincristine induced neurotoxicity developed. This appeared to be the result of an interaction with itraconazole suspension.     

Cytotoxic Effects of Vitamin A in Combination with Vincristine, Daunorubicin and 6-Thioguanine upon Cells from Lymphoblastic Leukemic Patients

We studied whether isotretinoin potentiated the effects of vincristine (VCR), daunorubicin (DNR), and 6-thioguanine (6-TG) against cells obtained from 24 patients with acute lymphoblastic leukemia (ALL). Treatment with 5 μg /ml isotretinoin alone resulted in a leukemic cell survival of 82%± 28.1%. So isotretinoin is toxic to ALL cells. Dose-response curves were obtained for VCR, DNR and 6-TG in the presence and absence of isotretinoin Isotretinoin showed additive leukemic cell kills in combination with VCR and DNR, When corrected for cell kill by isotretinoin alone, it appeared that isotretinoin did not significantly enhance leukemic cell kills by VCR, DNR and 6-TG. No differences were found between samples from patients at initial diagnosis and at relapse with respect to cell kill by isotretinoin alone and with respect to a possible synergistic effect of isotretinoin and the cytostatic drugs. It is concluded that isotretinoin has additive antileukemic effects in combination with VCR or DNR. However, isotretinoin does not potentiate the antileukemic effects of VCR, DNR and 6-TG against leukemic cells obtained from patients with ALL.     

硫酸长春新碱在0.9%氯化钠注射液中的稳定性研究

本文用紫外分光光度法对硫酸长春新碱在０．９％氯化钠注射液中的稳定性，按经典恒温加速试验法进行了动力学实验研究，结果表明，硫酸长春新碱的降解为一级反应。２５℃，３２℃时硫酸长春新碱的有效期ｔ０．９分别为１２．５１ｈ，８．８６ｈ。为临床合理用药提供了确切的数据。