肝素钠细菌内毒素检查法的建立

目的: 建立肝素钠原料药的细菌内毒素检查方法.方法: 通过干扰评价试验,证明肝素钠对细菌内毒素检查有抑制作用,使用稀释剂(I)适当补充二价阳离子,对样品作适当稀释,以消除其干扰抑制作用.结果: 补充适量的二价阳离子可以消除干扰作用.结论: 肝素钠原料药可以建立细菌内毒素检查法.     

浅论企业药品召回管理规范的制定

结合中美史克公司召回康泰克的经验,浅谈企业药品召回管理规范的制定.     

Oxalate-induced ceramide accumulation in Madin-Darby canine kidney and LLC-PK1 cells

BACKGROUND: Oxalate exposure produces oxidant stress in renal epithelial cells leading to death of some cells and adaptation of others. The pathways involved in these diverse actions remain unclear, but appear to involve activation of phospholipase A2 (PLA2) and redistribution of membrane phospholipids. The present studies examined the possibility that oxalate actions may also involve increased accumulation of ceramide, a lipid-signaling molecule implicated in a variety of pathways, including those leading to apoptotic cell death. METHODS: Ceramide accumulation was examined in renal epithelial cells from pig kidney (LLC-PK1 cells) and from dog kidney [Madin-Darby canine kidney (MDCK cells)] using the diacylglycerol kinase assay. Sphingomyelin degradation was assessed by monitoring the disappearance of 3H-sphingomyelin from cells that had been prelabeled with [3H]-choline. The effects of oxalate were compared with those of other oxidants (peroxide, xanthine/xanthine oxidase), other organic acids (formate and citrate), and a known activator of sphingomyelinase in these cells [tumor necrosis factor-alpha (TNF-alpha)]. Separate studies determined whether oxalate-induced accumulation of ceramide could be blocked by pretreatment with antioxidants [Mn (III) tetrakis (1-methyl-4-pyridyl) porphyrin (Mn TMPyP, a superoxide dismutase mimetic) or N-acetylcysteine (NAC; an antioxidant)], with an inhibitor of ceramide synthase [fumonisin B1 (FB1)] or with an inhibitor of PLA2 [arachidonyl trifluoromethylketone (AACOCF3)]. RESULTS: Oxalate exposure produced a significant time- and concentration-dependent increase in cellular ceramide. A reciprocal decrease in 3H-sphingomyelin was observed under these conditions. Increases in cellular ceramide levels were also observed after treatment with other oxidants (hydrogen peroxide, and xanthine/xanthine oxidase), activators of sphingomyelinase (TNF-alpha), exogenous sphingomyelinase, or arachidonic acid. Formate produced similar (albeit smaller) effects, and citrate did not. The oxidant-induced increases in ceramide were attenuated by pretreatment with NAC (a glutathione precursor) and MnTMPyP (a superoxide dismutase mimetic), suggesting a role for cellular redox states. The oxalate-induced increase in ceramide was also attenuated by pretreatment with AACOCF3, suggesting a role for PLA2. Pretreatment with FB1 produced a small but statistically insignificant attenuation of the response to oxalate. CONCLUSIONS: Oxalate exposure produces a marked accumulation of ceramide in renal epithelial cells by a process that is redox sensitive and mediated in part by activation of PLA2. Since cellular sphingomyelin decreased as ceramide increased, it seems likely that oxalate actions are mediated, at least in part, by an increase in sphingomyelinase activity, although alterations in ceramide synthase are also possible. Further study is required to define the steps involved in oxalate actions and to determine the extent to which ceramide signaling mediates oxalate actions.     

Trace element levels in drinking water and cognitive function among elderly Chinese

The relation between trace element levels in drinking water and cognitive function was investigated in a population-based study of elderly residents (n = 1,016) in rural China in 1996-1997. Cognitive function was measured using a Chinese translation of the Community Screening Interview for Dementia. A mixed effects model was used to evaluate the effect of each of the elements on cognitive function while adjusting for age, sex, and educational level. Several of the elements examined had a significant effect on cognitive function when they were assessed in a univariate context. However, after adjustment for other elements, many of these results were not significant. There was a significant quadratic effect for calcium and a significant zinc-cadmium interaction. Cognitive function increased with calcium level up to a certain point and then decreased as calcium continued to increase. Zinc showed a positive relation with cognitive function at low cadmium levels but a negative relation at high levels.     

那法瑞林长效制剂对大鼠垂体功能影响

 目的:观察国产那法瑞林(nafarelin )长效制剂的长效作用及对大鼠垂体功能影响，并探讨其作用部位。方法:采用大鼠间质细胞睾酮 (RICT)法检测血清LH(luteinizing hormone)生物活性水平。结果:那法瑞林长效制剂在体内的持续释药时间为((40.0±6.8)d。单次理植3周后大鼠血LH的周期性分泌高峰及激发高峰均消失。预先理植长效制剂组大鼠血LH在切除双侧卵巢后变化不明显。结论:那法瑞林长效制剂确有长效作用，其通过作用于垂体而抑制大鼠垂体功能。     

THE HUMORAL ANTITUMOR RESPONSES INDUCED BY IL-4 GENE-MODIFIED TUMOR VACCINE

ＴＨＥＨＵＭＯＲＡＬＡＮＴＩＴＵＭＯＲＲＥＳＰＯＮＳＥＳＩＮＤＵＣＥＤＢＹＩＬ４ＧＥＮＥＭＯＤＩＦＩＥＤＴＵＭＯＲＶＡＣＣＩＮＥ１ＹｕＹｉｚｈｉ于益芝ＣａｏＸｕｅｔａｏ２曹雪涛ＺｈａｎｇＭｉｎｇｈｕｉ张明徽ＬｅｉＨｏｎｇ雷虹ＴａｏＱｕｎ陶群Ｄｅｐ...     

GM-CSF/IL-4基因修饰的瘤苗不同的免疫途径诱导不同免疫反应的观察

对细胞因子基因修饰瘤苗的研究表明,IL-2、IL-4、IFN-γ、GM-CSF等一系列细胞因子基因以不同载体转入肿瘤细胞制成瘤苗后皮下免疫小鼠,均可增强机体抗肿瘤免疫力,其机制可能是由于瘤苗分泌的细胞因子促进了免疫细胞对肿瘤抗原的识别、提呈及对肿瘤细胞的杀伤能力.有文献报道,逆转录病毒介导的GM-CSF和IL-4共同转染瘤苗可以有效激发机体抗肿瘤免疫力,为探讨不同途径瘤苗免疫后机体的免疫反应,我们采用皮下、腹腔、脾内、静脉四种途径接种GM-CSF、IL-4基因双重转染的小鼠红白血病细胞FBL-3瘤苗,发现免疫途径不同,所激发的免疫应答类型不同,诱导机体生成的免疫力不同,提示某些瘤苗应用时应选择适当的免疫途径.     

自身免疫性感音神经性聋的内耳代谢与电生理研究

为探讨自身免疫性感音神经性聋（ＡＳＨＬ）的内耳病理生理学机制，采用听觉电生理技术和酶组织化学方法，观察ＡＳＨＬ模型动物的内耳生理功能与组织内主要酶活性的变化。结果示：听视经复合动作电位和耳蜗微音器电位阈值明显升高，内淋巴电位（包括负相）幅值均有不同程度的降低，并与血管纹和内淋巴囊局部组织内Ｎａ＾＋－Ｋ＾＋－ＡＴＰ酶和琥珀酸脱氢酶活性改变之间的相关性。表明自身免疫性内耳损伤，进而造成组织内相关酶代谢     

新生儿窒息多脏器血流动力学研究

目的研究新生儿窒息多脏器损伤的机理，提供早期诊断方法。方法应用美国Ｕｌｔｒａｍａｒｋ－９型彩色超声诊断仪及丹麦ＡＢＬ－５００型血气分析仪等，对新生儿窒息全身性多脏器血流动力学变化进行有对照组的前瞻性研究。结果（１）窒息新生儿脑、肾上腺、肾、肝、脾、胃及肠道等各脏器血液灌流量均减少，尤以舒张期为甚；但各脏器减少的程度不一致。（２）肺动脉压力与阻力增高，严重者可致持续胎儿循环，是病情严重的标志。（３）心脏功能障碍是缺氧缺血性心肌损伤的结果，窒息性心功能障碍表现为舒张功能首先受累，而收缩功能障碍则右室重于左室。（４）低氧血症是新生儿窒息各脏器损伤的病理生理基础，且低氧血症的程度与各脏器血流速度减慢的程度呈高度正相关（ｒ＝０．９３～０．９８，Ｐ均＜０．０１），与左室射血分数降低的程度呈高度正相关（ｒ＝０．９１，Ｐ＜０．０１），与肺动脉压力增高的程度呈高度负相关（ｒ＝－０．９７，Ｐ＜０．０１）。ＱＴ离散度是评价新生儿缺氧缺血性心肌损伤特异而敏感的指标。结论血流动力学紊乱是新生儿窒息各脏器损伤的主要原因，肺动脉压升高是新生儿窒息的重要病理生理变化。超声检测各脏器血流动力学变化，可用于新生儿窒息多脏器损伤的早期诊断