-Hydroperoxy diethyl peroxide, an unusual natural compound isolated from an ascidian (Phallusia mammillata): acute toxicity in DDY mice

-Hydroperoxy diethyl peroxide, a novel compound found in the tunic of ascidians, has two peroxide moieties per molecule. Since ascidians are a widely served food item in Japan, human exposure to this compound potentially exists in the seafood preparation industries. No toxicological data have so far been published on this compound, and so we determined the intraperitoneal 6-day LD₅₀ in mice and conducted histopathological examinations. The 6-day LD₅₀, was found to be 199 mg/kg with 95% confidence limits of 126–314 mg/kg. Histopathological examination revealed necrosis induced in a variety of cells that had been directly exposed to the compound. These cells included hepatocytes, parenchymal pancreatic cells and fat cells. It is concluded that direct contact with this compound is likely to elicit cellular necrosis of various organs. The specific toxicological effects are probably dependent on the route of exposure.     

大剂量卡铂化疗的药物毒性观察

6例肺癌患者接受了大剂量卡铂并自体骨髓移植治疗 ,卡铂剂量从 5 60～ 1375 mg/ m2 ,5例加用 VP～ 1630 0 mg,1例并用 MMC6mg和 VCR2 mg;主要毒性反应为白细胞、中性粒细胞、血小板减少和脱发 ( WHO毒性反应 ～ 级 )其次是贫血、皮肤粘膜出血、呕吐和可逆性肝功能损害 ,口腔粘膜溃疡及轻度发烧各 2例 ,一过性蛋白尿、室上性心动过速和便秘各 1例 ,尿素氮和肌酐未见升高 ;全部患者骨髓均获解救 ,从自体骨髓回输到骨髓造血功能重建成功平均 2 6.67( 17～ 32 )天     

天冬胶作为血管栓塞剂毒性实验的初步报告

目的:从其毒性和相关特性方面研究天冬胶作为血管栓塞剂的可行性。方法:昆明小鼠腹腔注射天冬胶后观察外貌行为、食物消耗、体重情况。最后检测WBC、血小板、RBC和Hb浓度;测定血清ALT、肌酐和尿素氮浓度。病理检查心、肝、肾、脾、脑、腹膜、生精组织及腹壁肌肉。大腿肌肉注射天冬胶的小鼠1、3、7 d后各处死,取局部肌肉标本送病理检查。结果:1.仅实验组给药后第1天反应稍差及食量显著低于对照组(P<0.001)外,第2天起各组外貌行为无异常、食量无显著差异(均P>0.05)。2.各组小鼠的体重随时间而增加,除实验组2于实验1周后增长速度显著低于实验组1(P<0.02)和对照组(P<0.001)外,其他无显著差异。3.各组血WBC、血小板、RBC、Hb及血清ALT、肌酐和尿素氮浓度无显著差别。4.仅1个实验组小鼠肝脏内可见多灶性淋巴细胞和其他炎症细胞浸润区,其他组肝脏表现正常。实验组腹膜出现少许慢性炎症细胞的浸润和间皮细胞的增生。其他均无病理改变。大腿肌肉内仅见少许残留异物,无病理改变。结论:天冬胶使用安全、生物相容性较好,作为血管栓塞剂有较好的前景。     

The chemosensitizer cyclosporin A enhances the toxic side-effects of doxorubicin in the rat

the feasibility of using chemosensitizers in the circumvention of P-glycoprotein-mediated multidrug resistance has been shown in many studies. We recently reported on the chemosensitizing effect of cyclosporin A (CsA) on doxorubicin in a rat solid tumour model. Using the same experimental design we investigated the side-effects of the combination treatment. During the 35-day experiment doxorubicin treatment caused dose-dependent weight loss, which was enhanced by combination treatment with CsA. The main doxorubicin-related side-effects were myelosuppression (transient leucopenia and thrombopenia) and nephrotoxicity. Damage to the kidney was severe, leading to a nephrotic syndrome and resulting in ascites, pleural effusion, hypercholesterolaemia and hypertriglyceridaemia. These toxicities were enhanced by the addition of the chemosensitizer CsA. Mild doxorubicin-related cardiomyopathy and minimal hepatotoxicity were seen on histological examination. There were no signs of enhanced toxicity of the combination treatment in tissues with known high expression levels of P-glycoprotein, like the liver, adrenal gland and large intestine. CsA had a low toxicity profile, as it only caused a transient rise in bilirubin. In conclusion, the chemosensitizer CsA enhanced the side-effects of the anticancer drug doxorubiein without altering the toxicity pattern. There was no evidence of a therapeutic gain by adding CsA to doxorubicin, compared to single-agent treatment with doxorubicin in 25%–33% higher doses, because of the enhanced toxicity of the combination treatment.Abbreviations CsA cyclosporin A - DOX doxorubicin - MDR multidrug resistance - PBS phosphate-buffered saline This work was supported by the Dr Daniël den Hoed Foundation, Rotterdam, The Netherlands     

消毒剂敌菲特的研究

经全面考察研究,敌菲特缓释消毒灭菌剂具有良好的消毒灭菌效果,对细菌繁殖体、病毒和细菌芽孢均可完全灭活;即使在—20℃低温条件下,对枯黑变种芽孢仍具很好的杀灭效果。此外,该消毒剂基本克服了氯制剂对金属腐蚀性的缺陷;原药性能基本稳定。     

Culturable and nonculturable bacterial symbionts in the toxic benthic dinoflagellate Ostreopsis lenticularis.

The toxic benthic dinoflagellate Ostreopsis lenticularis hosts a variety of symbiont bacterial flora. Laboratory cultured Ostreopsis clones require the presence of symbiotic Pseudomonas/Alteromonas bacterial strains for growth and toxicity development. Three culturable bacterial strains associated with Ostreopsis were identified as Pseudomonas/Alteromonas strain 1, Pseudomonas/Alteromonas strain 2 and Acinetobacter. Denaturing gradient gel electrophoresis (DGGE) analyses of extracted Ostreopsis associated bacterial DNAs indicated that there were three culturable and four non-culturable associated bacterial strains. The results presented here are the first report of the presence of unculturable bacterial symbionts in a toxic benthic dinoflagellate. Ostreopsis lost toxicity when exposed to elevated temperatures in the field and laboratory culture and subsequently recovered toxicity at reduced temperatures. Ostreopsis associated culturable Pseudomonas/Alteromonas bacterial strains were significantly reduced in dinoflagellate cultures exposed to elevated temperatures. The decreased toxicity of O. lenticularis exposed to elevated temperatures and their subsequent recovery of toxicity in periods of reduced thermal stress may have resulted from the effects of elevated temperature on the spectrum of culturable and unculturable bacterial species interacting with their Ostreopsis host.     

甲基叔丁基醚无铅汽油肾脏毒性的实验研究

目的：了解甲基叔丁基醚（MTBE）无铅汽油对肾脏的毒性及毒作用机制。方法：昆明种小鼠经呼吸道静式染毒，MTBE无铅汽油22．9、11．4及2．3g/m^3每天一次，连续2h，共22d亚急性染毒。日立－7150型全自动生化仪检测血清中尿素氮（BUN）、肌酐（Cr）含量；肾组织均浆中丙二醛（MDA）和超氧化物歧化酶（SOD）含量分别用荧光法，邻苯三酚自氧化固定时间法测定；电镜观察肾皮质区超微结构的变化，结果：22.9g/m^3染毒组雌性小鼠血清中BUN含量与阴性对照组间比较差异有显著性（P＜0．05）；电镜观察到22.9g/m^3染色毒对照组雌雄性小鼠的肾小球基底膜，肾小管细胞线粒体及绒毛均未见显著异常改变。结论：MTBE无铅汽油对肾小球的滤过功能有一定的影响，雌性小鼠可能更为敏感。     

Polyether toxin analysis of the top minnow (Poecilia vitatta)

A detailed toxicity analysis was performed on the top minnow utilizing the stick‐enzyme immunoassay (S‐EIA), the mouse bioassay, the guinea pig atrium assay and fluorometric HPLC. The S‐EIA test indicated 96% of the samples tested contained polyether toxins. Mice injected with acetone extractions from top minnow displayed symptoms of toxicity while the guinea pig atrium assay demonstrated the presence of a polar, Na⁺ channel inhibitor.