BjMT2, a metallothionein type-2 from Brassica juncea, may effectively remove excess lead from erythrocytes and kidneys of rats

The remedial effects of a plant metallothionein type-2 were observed from lead (Pb) injured rats. BjMT2 from Brassica juncea was expressed in Escherichia coli and purified by affinity chromatography, a purified BjMT2 protein was obtained which strongly reacted with the thiol reagent MBB (monobromobimane). The profiles of erythrocytes, renal tubules and glomerulus of kidney of rats suffered pathological changes from excess Pb were evidently improved by supplying the BjMT2. Quantitative analysis showed that the content of Pb and the amount of leukocytes in blood were significantly declined after supplying BjMT2 to rats. The results indicated that the BjMT2 may have the potential function to decrease Pb toxicification in rate organs and tissues.     

罗格列酮对小鼠急性肝衰竭的保护作用及其机制

罗格列酮为过氧化物酶增殖物活化受体- γ(PPAR-γ)的合成型配体,对PPAR-γ有高度选择性.研究表明肝组织也有PPAR-γ的表达,且PPAR-γ的功能状态与脂肪肝、肝脏炎症与纤维化,甚至肝癌的发生有密切关系.     

甜菜碱对载脂蛋白E~(-/-)小鼠动脉粥样硬化发生过程中铜锌超氧化物岐化酶基因甲基化及表达的影响

目的 检测栽脂蛋白E-/-小鼠动脉粥样硬化发生过程中肝脏铜锌超氧化物岐化酶基因启动子区CpG岛甲基化及其表达状态,探讨甜菜碱对动脉粥样硬化的作用及其可能的机刺.方法 将正常的C57BL/6J小鼠作为正常对照组,同品系载脂蛋白E-/-小鼠分为模型组、1%、2%和4%甜菜碱组.用油红O染色法检测小鼠主动脉窦脂质斑块面积,应用甲基化特异性聚合酶链反应检测肝脏钢锌超氧化物岐化酶基因甲基化,荧光定量逆转录聚合酶链反应检测铜锌超氧化物岐化酶mRNA表达,免疫组织化学检测其蛋白表达.结果 饲养至14周,2%和4%甜菜碱组小鼠主动脉窦脂质斑块面积明显少于模型组(P<0.05);各组铜锌超氧化物岐化酶基因CpG岛甲基化状态差异无显著性(P>0.05);各时间段正常对照组铜锌超氧化物岐化酶mBNA表达均高于模型组,7周时1%甜菜碱组mRNA表达高于2%和4%甜菜碱组,14周时1%甜菜碱组mRNA表达高于模型组和2%甜菜碱组;各时间段正常对照组铜锌超氧化物歧化酶蛋白表迭均高于模型组、1%、2%和4%甜菜碱组(P<0.05),但模型组、1%、2%和4%甜菜碱组间无显著性差异.结论 铜锌超氧化物岐化酶基因可能没有参与动脉粥样硬化过程中DNA甲基化的异常改变,补充甜菜碱可以增加肝脏铜锌超氧化物岐化酶mBNA表达,改善载脂蛋白E>-/-小鼠的脂质沉积,减少主动脉窦粥样斑块面积.     

心血管事件年和日周期节律的临床研究

目的 探讨心血管事件的年和日周期节律.方法 记录10年间5837例急诊患者心血管疾病事件发生的时间和月平均气温,分析月平均气温与心血管事件的关系.结果 急性心肌梗死、心绞痛、急性左心衰竭、高血压危象、猝死以冬春寒冷季节及季节交替时发病率最高,发病率与月平均气温显著负相关(P<0.005～0.001).清晨和上午心血管事件发病率较高.结论 心血管事件的发生具有明显的年和日周期节律;寒冷是心血管事件的重要危险因素,清晨和上午为发病的高峰时段.     

PPARα contributes to colonic protection in mice with DSS-induced colitis

Inflammatory bowel disease (IBD) is characterized by repeated chronic inflammation of the gastrointestinal tract. We have used the complementary model of colonic inflammation to examine the roles of peroxisome proliferator-activated receptor α (PPARα) in colonic inflammation and thus its possible role in IBD. We characterized an innate immune-mediated model of colitis induced by dextran sulfate sodium (DSS). Mice with DSS-induced colitis were injected with Wy-14643 (2 mg/kg) as a PPARα agonist every day from day 0 to day 5. We show that mice given Wy-14643 were less susceptible to experimental acute colitis induced by DSS, and this decreased susceptibility was correlated with decreased production of IFNγ, IL-1β, IL-6, and TNF-α. Our findings suggest that PPARα has a role in controlling colonic inflammation and mucosal tissue homeostasis.     

注射用头孢哌酮／他唑巴坦的体外抗菌活性研究

目的：评价头孢哌酮／他唑巴坦（4：1和8：1）、头孢哌酮／舒巴坦（1：1和2：1）的抑酶增效作用,并比较同类复方制剂在临床常用量时的体外抗菌效果。方法：采用琼脂二倍稀释法对409株临床分离株进行药物敏感测定。结果：头孢哌酮／他唑巴坦（4：1和8：1）、头孢哌酮／舒巴坦（1：l和2：1）联合应用对金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌等革兰阳性菌的MIC50／MIC90均较头孢哌酮钠单用时降低2～4倍。对大肠埃希菌（包括产ESBLs）、肺炎克雷伯菌（包括产（ESBLs）、铜绿假单胞菌、阴沟肠杆菌、鲍曼不动杆菌等革兰阴性杆菌的MIC50／MIC90分别较头孢哌酮钠单用时降低2～64倍和2～8倍,尤其对产ESBLs的大肠埃希菌和肺炎克雷伯菌其MIC50／MIC990也分别降低8～32倍和2—8倍。同类复方制剂对上述革兰阳性菌和革兰阴性杆菌的MIC50／MIC90在临床常用量的1／256—1／65536倍,MIC50和MIC90较按常规试验配比组分别降低3～33倍和4～87倍。结论：头孢哌酮与他唑巴坦或舒巴坦联合应用可不同程度地提高头孢哌酮的体外抗菌活性,头孢哌翮／他唑巴坦4：1和8：1的体外抗菌活性基本相当,均优于头孢哌酮／舒巴坦1：1和2：1。4种同类复方制剂的体外抗菌活性,注射用头孢哌酮／他唑巴坦亦优于注射用头孢哌酮／舒巴坦。     

Identification and characterization of noncalcemic, tissue-selective, nonsecosteroidal vitamin D receptor modulators

Vitamin D receptor (VDR) ligands are therapeutic agents for the treatment of psoriasis, osteoporosis, and secondary hyperparathyroidism. VDR ligands also show immense potential as therapeutic agents for autoimmune diseases and cancers of skin, prostate, colon, and breast as well as leukemia. However, the major side effect of VDR ligands that limits their expanded use and clinical development is hypercalcemia that develops as a result of the action of these compounds mainly on intestine. In order to discover VDR ligands with less hypercalcemia liability, we sought to identify tissue-selective VDR modulators (VDRMs) that act as agonists in some cell types and lack activity in others. Here, we describe LY2108491 and LY2109866 as nonsecosteroidal VDRMs that function as potent agonists in keratinocytes, osteoblasts, and peripheral blood mononuclear cells but show poor activity in intestinal cells. Finally, these nonsecosteroidal VDRMs were less calcemic in vivo, and LY2108491 exhibited more than 270-fold improved therapeutic index over the naturally occurring VDR ligand 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in an in vivo preclinical surrogate model of psoriasis.