Analgesic Effects of Dexmedetomidine in Vincristine-Evoked Painful Neuropathic Rats

Dexmedetomidine, which is a selective α2-adrenoceptor agonist, was recently introduced into clinical practice for its analgesic properties. The purpose of this study was to evaluate the effects of dexmedetomidine in a vincristine-evoked neuropathic rat models. Sprague-Dawley rats were injected intraperitoneally with vincristine or saline (0.1 mg/kg/day) using a 5-day-on, 2-day-off schedule for 2 weeks. Saline and dexmedetomidine (12.5, 25, 50, and 100 µg/kg) were injected to rats developed allodynia 14 days after vincristine injection, respectively. We evaluated allodynia at before, 15, 30, 60, 90, 120, 180, and 240 min, and 24 hr after intraperitoneal drug (normal saline or dexmedetomidine) injection. Saline treatment did not show any differences for all the allodynia. Maximal paw withdrawal thresholds to mechanical stimuli were 3.0 ± 0.4, 9.1 ± 1.9, 13.0 ± 3.6, 16.6 ± 2.4, and 24.4 ± 1.6 g at saline, 12.5, 25, 50, and 100 µg/kg dexmedetomidine injection, respectively. Minimal withdrawal frequency to cold stimuli were 73.3 ± 4.2, 57.1 ± 6.8, 34.3 ± 5.7, 20.0 ± 6.2, and 14.3 ± 9.5 g at saline, 12.5, 25, 50, and 100 µg/kg dexmedetomidine injection, respectively. Dexmedetomidine shows a dose-dependent antiallodynic effect on mechanical and cold stimuli in vincristine-evoked neuropathic rat models (P < 0.05).     

两种化疗方案超选择动脉灌注治疗颅内恶性肿瘤的疗效及并发症比较

目的：比较表阿霉素（组）、长春新碱（组）分别联合卡铂、VP16超选择动脉灌注化疗治疗脑恶性肿瘤的疗效及并发症。方法：超选择动脉灌注化疗治疗脑恶性肿瘤30例，随机使用表阿霉素（组）、长春新碱（组）分别联合卡铂、VP16治疗并比较其疗效。结果：两组有效率（CR＋PR）分别为55．6％（10／18）和58．3％（7／12）(P＞0．05），均无严重并发症。结论：两组联合治疗方案的疗效相当，但表阿霉素组脱发更为明显，且价格昂贵，临床应用受一定限制。     

Sensorineural hearing loss associated with vincristine treatment

Summary We describe a 64-year-old patient with multiple myeloma who developed a sudden sensorineural hearing loss shortly after receiving chemotherapy with vincristine. Ototoxicity is not a known side effect of this drug. It would be of interest to perform repeated audiograms on patients receiving vincristine, in order to appreciate the actual ototoxicity of this drug.     

Degradation kinetics of vincristine sulphate and vindesine sulphate in aqueous solutions

The degradation kinetics of the antineoplastic drugs, vincristine and vindesine, have been studied in the pH range from − 2 up to 11 at 80°C. A stability-indicating HPLC system with UV detection was utilized for the analysis of vincristine and vindesine in the reaction solutions. The influences of external factors (e.g. pH, buffer concentrations, ionic strength and temperature) on the degradation rate have been studied systematically. The relationship between pH and log k_obs was modelled by using a non-linear least-squares curve-fitting computer program. From this plot thepK_a values of vindesine have been calculated. This plot also showed that vincristine was most stable at pH 4.8 and vindesine at pH 1.9.     

NGF prevention of neurotoxicity induced by cisplatin, vincristine and taxol depends on toxicity of each drug and NGF treatment schedule:: In vitro study of adult rat sympathetic ganglion explants

The simultaneous administration of nerve growth factor (NGF) has been found to prevent experimental neuropathies induced by anti-cancer drugs such as cisplatin, vincristine and taxol. However, it is clinically important to know whether NGF is beneficial once the neuropathy is already manifest. We established a bioassay system to examine the preventive effects of NGF in various treatment schedules. NGF significantly prevented the inhibition of neurite outgrowth by vincristine and taxol regardless of treatment schedules. The pre-treatment and co-treatment schedules were effective against cisplatin, but the post-treatment schedule was not. With regard to the neurite and nerve cell population densities, only the cisplatin group treated with NGF showed lower values than the control. These results indicate that NGF-treatment is effective for the toxic sympathetic nerve injury induced by vincristine and taxol regardless of the treatment schedule, but is not protective against cisplatin-induced nerve cell injury.     

Studies on the use of antimitotic drugs entrapped within liposomes and of their action on a human glioma cell line

The optimal conditions have been determined for producing the maximum incorporation within liposomes of two cell cycle-specific antimitotic drugs (bleomycin and vincristine) used in the treatment of human cerebral gliomas. Under these conditions the subsequent rate of release of these two drugs was studied in vitro. Neither cell fusion nor endocytosis could be demonstrated between liposomes of the size distribution used in these experiments (0.1-15 micron) and a human glioma cell line (U.251-MG) using a variety of marker techniques. Dose-response curves were similar for the two drugs whether free or entrapped within liposomes when applied to this cell line. These results suggest that drugs entrapped within liposomes may be useful as a potential depot preparation in the treatment of human gliomas.     

Vincristine-induced dermal toxicity is significantly reduced when the drug is given in liposomes

 A problem associated with the intravenous delivery of vincristine concerns drug extravasation at the site of injection or infusion. This can result in extensive local soft-tissue damage. A new formulation of vincristine has recently been developed based on encapsulation of the drug in liposomes. The liposomal drug is somewhat less toxic and substantially more efficacious than free drug. The studies described here assessed, using a murine model of drug extravasation, whether vincristine encapsulation in liposomes influences drug-induced dermal toxicity. It was shown that subcutaneous injection of vincristine in liposomes does not result in the gross skin necrosis and ulceration observed following injection of free drug. Histological analysis of the dermal tissue surrounding the injection site suggests that free drug induces a pronounced inflammatory reaction as judged by the presence of infiltrating leukocytes. In contrast, the liposomal formulation of vincristine engenders a mild prolonged inflammatory condition. These toxicological studies were correlated with an evaluation of drug retention at the site of administration. It was shown using radiolabelled vincristine as a drug marker, that free vincristine is rapidly eliminated from the injection site. In contrast, the level of drug at the site of injection was far greater when the drug was given in liposomal form. Received: 13 December 1994 / Accepted: 14 May 1995     

The labelling index of marrow myeloblasts: A predictive test for relapse of acute non-lymphoblastic leukemia

The ³HTdR labelling index of the marrow myeloblasts (MLI) was determined serially throughout complete remission (CR) of adult acute non-lymphoblastic leukemia (ANLL). 110 marrow samples were examined during 28 phases of CR obtained in 23 ANLL patients. The MLI was found to be between 20 and 66 in 100 determinations. An MLI below 20% was not found in well established complete remission but did occur near the end of 8 out of 20 CRs, 5–12 weeks (mean 7.6) before the reappearance of leukemic blasts in the marrow as judged by conventional microscopic examination. In those cases, the mean MLI was 13.2 (range 6–18). An MLI below 20% appears to be a reliable and early predictor of relapse of AML and permits the investigation of the clinical benefit of treating incipient relapse.     

阿霉素和长春新碱对pRb-胃癌细胞株的影响

目的：探索一种对Rb基因表达异常之胃癌细胞的化疗方案。方法：用Rb-CMV质粒转染Rb表达阴性的胃癌AGS细胞株，然后将25ng/ml阿霉素和100ng/ml长春新碱序贯加入两组细胞，应用MTT、流式细胞技术来测定转染前后此细胞株对序贯用药后的活性及细胞周期变化。结果：预先作用的阿霉素使Rb阳性胃癌AGS细胞阻滞于细胞周期的G1／S期，而不影响Rb阴性胃癌AGS细胞增殖。阿霉素和长春新碱序贯用药对Rb阴性胃癌AGS细胞有显著细胞毒性作用，而对Rb阳性胃癌AGS细胞的毒性作用轻微。结论：由于绝大多数正常组织的Rb是正常表达，而在胃癌中表达大多是阴性，故此联合用药有望用于Rb表达阴性胃癌的治疗。