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排序方式: 共有454条查询结果,搜索用时 0 毫秒
1.
目的:使用体感诱发电位(SEP)对脑出血(ICH)模型进行评价,并观察ICH后不同时期脑水肿的形成过程。方法:采用脑立体定向术制备大鼠脑内囊出血的模型。观察大鼠在手术前及手术后不同时期内神经系统功能、SEP、脑组织形态学及脑组织含水量的改变。结果:与假手术组相比,实验组(6h、12h、1d、5d)、各波潜伏期延长(P<0.05),脑组织含水量增多(P<0.05);实验组(2d、3d)各波潜伏期明显延长(P<0.01),脑组织含水量明显增多(P<0.01);实验组(7d)各波潜伏期缩短(P>0.05),脑组织含水量减少(P>0.05)。脑组织形态学与神经系统功能呈现相应的改变。结论:SEP是评价脑立体定向术制备大鼠脑内囊出血模型的最客观指标,脑出血后脑水肿的形成是一个动态过程,SEP的改变与脑水肿的形成有直接的关系 相似文献
2.
Jan Willem van der Laan Robert E. Chapin Bert Haenen Abigail C. Jacobs Aldert Piersma 《Regulatory toxicology and pharmacology : RTP》2012
Reproductive toxicity testing is characterized by high animal use. For registration of pharmaceutical compounds, developmental toxicity studies are usually conducted in both rat and rabbits. Efforts have been underway for a long time to design alternatives to animal use. Implementation has lagged, partly because of uncertainties about the applicability domain of the alternatives. 相似文献
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目的:研究参麦注射液对脑出血大鼠血肿周围区缺氧诱导因子1-α(Hypoxia inducible factor 1-α,HIF1-α)表达的影响及其意义。方法:将50只SD大鼠随机分为正常组、假手术组、模型组、参麦组4组,模型组和参麦组组内又分为1、3、5、7天共4个时间点,立体定位仪定位注射胶原酶VII造大鼠脑出血模型,观察大鼠脑出血后神经病理体征改变,免疫组织化学法检测血肿周围区HIF1-α的表达,以及参麦注射液治疗后的影响。结果:与模型组相比较,参麦组大鼠神经病理体征减轻明显(P<0.01);正常组和假手术组脑组织神经细胞无HIF1-α表达,而模型组血肿周围区HIF1-α的表达1天时增多,3天时达到高峰,5天时表达下降,至7天时仍有少量表达,与模型组相比较,参麦组各时间点的HIF1-α表达要少,二者有显著性差异(P<0.01)。结论:参麦注射液可能通过促进血肿吸收、抑制血肿周围区HIF1-α表达而发挥神经保护作用。 相似文献
5.
目的 观察脑出血后不同时间出血灶周脑水肿和MMP-9表达的动态,变化,并初步探讨其关系.方法 健康雄性Wistar大鼠48只随机分成假手术组和脑出血组,大鼠尾壳核区注入自体非抗凝动脉血建市脑出血模型,采用于湿重法测量脑组织水含量,免疫组织化学方法观察术后不同时间点MMP-9的动态变化.结果 血肿形成后脑水肿产生迅速,从脑出血后3h开始增加,72h达高峰;脑出血后3h时,血肿周围组织中开始出现少量的深棕赞色MMP-9阳性染色细胞,72h达高峰,以后逐渐下降,至7d时仍维持存较高水平.结论 脑出血后出血灶周MMP-9的表达上调.脑水肿的形成与脑出血灶周MMP-9的表达上调有关. 相似文献
6.
The preweaning piglet has been found to be a valuable research model for testing ingredients used in infant formula. As part of the safety assessment, the neonates' immune system is an important component that has to be evaluated. In this study three concurrent strategies were developed to assess immune system status. The methods included (1) immunophenotying to assess circulating innate immune cell populations, (2) monitoring of circulating cytokines, particularly in response to a positive control agent, and (3) monitoring of localized gastrointestinal tissue cytokines using immunohistochemistry (IHC), particularly in response to a positive control agent. All assays were validated using white papers and regulatory guidance within a GLP environment. To validate the assays precision, accuracy and sample stability were evaluated as needed using a fit for purpose approach. In addition animals were treated with proinflammtory substances to detect a positive versus negative signal. In conclusion, these three methods were confirmed to be robust assays to evaluate the immune system and GIT-specific immune responses of preweaning piglets. 相似文献
7.
Introduction
Intracerebral hemorrhage (ICH) is a major clinical concern with anticoagulation therapy. The effect of a new oral direct FXa inhibitor, edoxaban, was determined in a rat model of ICH and compared with a direct thrombin inhibitor, melagatran, and heparin.Methods
To induce ICH, 0.1 U collagenase type VII was injected into the striatum of male Wistar rats under anesthesia with thiopental or halothane. Immediately after ICH induction, edoxaban, melagatran, or heparin were infused intravenously. Five hours after ICH induction, the brain was removed and ICH size was measured. To estimate the margin of safety, antithrombotic effects were evaluated in a rat venous thrombosis model.Results
Edoxaban at 6 mg/kg/h significantly increased ICH volume (1.8-fold) and prolonged prothrombin time (PT) 2.8-fold compared to the vehicle group. No deaths were observed with edoxaban. Melagatran at 1 mg/kg/h increased ICH volume at 1 mg/kg/h (2.8-fold) with 6.1-fold PT prolongation. At 3 mg/kg/h, all rats died due to severe ICH (3.9-fold). Heparin at both 100 and 500 U/kg/h significantly increased ICH. At 500 U/kg/h, 5 out of 8 rats died. The doses required for 50% inhibition of thrombosis of edoxaban, melagatran, and heparin were 0.045 mg/kg/h, 0.14 mg/kg/h, and 55 U/kg/h, respectively. The safety margins between antithrombotic and ICH exacerbation effects of these anticoagulants were 133, 7.1, and 1.8, respectively.Conclusion
The safety margin of edoxaban was wider than that of melagatran or heparin. These results suggest that edoxaban may be preferable from the perspective of ICH exacerbation risk. 相似文献8.
Zhu Zhang Zhen-guo Zhai Li-rong Liang Fang-fang Liu Yuan-hua Yang Chen Wang 《Thrombosis research》2014
Background and Objective
According to US Food and Drugs Administration (FDA), 2 hour recombinant tissue plasminogen activator (rt-PA) 100 mg infusion is recommended for eligible patients with acute pulmonary embolism (PE). However,there exists evidence implying that a lower dosage of rt-PA can be equally effective but potentially safer compared with rt-PA 100 mg regimen. The aim of this systematic review and meta-analysis is to assess the efficacy and safety of low dose rt-PA in the treatment of acute PE.Material and Method
We searched Pubmed, EMBASE, the Cochrane library and CBM Literature Database for randomized controlled trials (RCT) focusing on low dose rt-PA for acute PE. Outcomes were described in terms of changes of image tests and echocardiography, major bleeding events, all-cause death, and recurrence of PE.Results
Five studies (440 patients) were included, three of which compared low dose rt-PA (0.6 mg/kg, maximum 50 mg or 50 mg infusion 2 h) with standard dose (100 mg infusion 2 h). There were more major bleeding events in standard dose rt-PA group than in low dose group (OR 0.33, 95%CI 0.12-0.91;P = 0.94,I2 = 0%), while there were no statistical differences in recurrent PE or all cause mortality between these two groups. Two studies compared low dose (0.6 mg/kg, maximum 50 mg/2 min bolus or 10 mg bolus, ≤ 40 mg/2 h) with heparin. There was no significant difference in major bleeding events (OR 0.73, 95% CI 0.14-3.98;P = 0.72), recurrent PE or all cause mortality. No dose-related heterogeneity was found for all the included studies.Conclusions
The results of this meta-analysis were hypothesis-generating. Based on the limited data, our systematic review suggested that low dose rt-PA had similar efficacy but was safer than standard dose of rt-PA. In addition, compared with heparin, low dose rt-PA didn’t increase the risk of major bleeding for eligible PE patients. 相似文献9.
运用量化模型估计药品有效期是长期稳定实验的核心及新药申报中的重要节点。通过对比最新《中国药典(2015版)》中的对应规定(第IV部,9001章)与国际法规ICH Q1E中的估计方法,阐明ICH Q1E是符合国内法规的。其次,通过理论分析解释了国内与国际法规中量化模型所隐含的假设及局限性。最后,通过蒙特卡洛模拟得出有效期估计值的经验分布,表明取均值为最终有效期估计值的方法,可能比ICH Q1E中的方法更倾向于低估真实有效期,从而置制造方于不必要的劣势。 相似文献
10.
Ketsia Yekpe Bernard Bataille Ryan Gosselin Tahmer Sharkawi Jean-Sébastien Simard 《Pharmaceutical development and technology》2018,23(6):646-654
AbstractThis study applied the concept of Quality by Design (QbD) to tablet dissolution. Its goal was to propose a quality control strategy to model dissolution testing of solid oral dose products according to International Conference on Harmonization guidelines. The methodology involved the following three steps: (1) a risk analysis to identify the material- and process-related parameters impacting the critical quality attributes of dissolution testing, (2) an experimental design to evaluate the influence of design factors (attributes and parameters selected by risk analysis) on dissolution testing, and (3) an investigation of the relationship between design factors and dissolution profiles. Results show that (a) in the case studied, the two parameters impacting dissolution kinetics are active pharmaceutical ingredient particle size distributions and tablet hardness and (b) these two parameters could be monitored with PAT tools to predict dissolution profiles. Moreover, based on the results obtained, modeling dissolution is possible. The practicality and effectiveness of the QbD approach were demonstrated through this industrial case study. Implementing such an approach systematically in industrial pharmaceutical production would reduce the need for tablet dissolution testing. 相似文献