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11.
SI Chowdhury BJ Lee D Mosier JH Sur FA Osorio G Kennedy ML Weiss 《Canadian Metallurgical Quarterly》1997,117(4):295-310
CI-994 (acetyldinaline) is an orally active anticancer drug currently in Phase 1 clinical trials. To assess its preclinical toxicity, CI-994 was administered orally as suspensions to Wistar rats (10/sex/dose) and in capsules to beagle dogs (3/sex/dose) once daily for two weeks. Doses were 1.5, 5, and 15 mg/kg for rats (9, 30, and 90 mg/m2, respectively), and 0.5, 2, and 5 mg/kg for dogs (10, 40, and 100 mg/m2, respectively). Systemic exposure was dose-proportional based on toxicokinetic analysis in dogs. Severe clinical signs and mortality occurred at the highest dose in both species beginning on Day 10. Neutropenia, lymphocytopenia, thrombocytopenia, lymphoid depletion, bone marrow hypocellularity, and testicular degeneration were observed in both species, primarily at the mid- and high-doses. Despite continued treatment, neutrophil counts in dogs returned to control levels in Week 2. Other microscopic findings in rats included splenic hematopoietic depletion at all doses and epithelial cell necrosis in various tissues at 15 mg/kg. Additional bone marrow changes in dogs involved myeloid and megakaryocyte hyperplasia at 2 mg/kg and abnormal myeloid and megakaryocyte maturation at 2 and 5 mg/kg. Except for the testicular effects in both species, all changes were reversible within a 4-week (rat) or 9-week (dog) recovery period. The results of these studies show that target organ effects of CI-994 principally involve tissues with rapidly dividing cell populations and that bone marrow suppression is the dose-limiting toxicity. CI-994 also seems to interfere with the release and/or maturation of cells in the bone marrow. 相似文献
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介绍摩托车起动电机的安装设计原则和方法,安装误差的形成与计算,以及达到安装设计要求的工艺保证措施,同时还分析了在检测和加工中所存在的一些做法。 相似文献
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The final stage in the production of a radiotherapy treatment plan must always be an independent check that the linear accelerator settings given on the plan do in fact deliver the required dose distribution. A tool is described that enables rapid checking of diaphragm settings in relation to the patient. 相似文献
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SI Vataev GP Dem'ianenko ES Titkov GA Oganesian 《Canadian Metallurgical Quarterly》1996,32(4):434-439
The wakefulness-sleep cycle characteristics changes in Wistar line rats after unilateral lesions of the neuronal elements of the caudate nucleus head with kainic acid (at sparing the conducting ways going through this structure) were studied. It was shown that in 4 days after acid injection the share of the active wakefulness and light slow-wave sleep is significantly increased, whereas the percentage of the passive wakefulness, deep slow-wave stage, and paradoxal sleep (up to 80%) is reduced. The wakefulness-sleep cycle in rats is completely normalized on the 7th day after injection. The obtained data allow to consider the caudate nucleus as a modulator for wakefulness-sleep cycle, that is the structure involved in the motive activity regulation. 相似文献
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阐述了5052合金铸轧坯料生产时冷隔缺陷产生的机理,结合超型FATA—HUNTERΦ1003×1850mm机多年的生产实践经验,提出了消除铸轧冷隔缺陷的措施。 相似文献