Over-expression of heat shock protein 27 attenuates doxorubicin-induced cardiac dysfunction in mice

Background：Oxidative stress and myocyte apoptosis are thought to play an important role in the pathogenesis, progression and prognosis of heart failure（HF）. Heat shock protein 27 （Hsp27） has been found to confer resistance to oxidative stress in cultured cells; however, the role of Hsp27 in in-vivo hearts remains to be determined. Aim：To investigate the effects of Hsp27 over- expression on doxorubicin-induced HF. Methods and Results：Transgenic mice （TG） with cardiac specific over-expression of Hsp27 and their wild type littermates （WT） were challenged with doxorubicin （25 mg/kg, IP） to induce HE＇ At day 5, TG mice had significantly improved cardiac function and viability and decreased loss of heart weight following doxorubicin exposure compared with WT. In another parallel experiment, doxorubicin-induced increased levels of reactive oxygen species, protein carbonylation, apoptosis and morphologic changes were detected in the mitochondria in WT hearts, whereas these effects were markedly attenuated in TG hearts. In addition, upregulation of heat shock protein 70 and heme oxygenase-1 was present in the TG hearts after doxorubicin stimulation in comparison to WT hearts. Conclusion：These findings indicate that Hsp27 may play a key role in resistance to doxorubicin-induced cardiac dysfunction. （c）2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.     

Optimum use of a spacer device

Nedocromil sodium given by the Fisonair spacer should be inhaled immediately. Multiple actuations into the spacer should be avoided. Delay of 20 seconds before sampling reduced the amount of drug available for inhalation in the respirable range by 81%. Placing two actuations into the spacer reduced the amount of drug available by 47%.     

6β－乙酰氧基去甲托烷呼吸抑制效应

６β－乙酰氧基去甲托烷（６β－ａｃｅｔｏｘｙｎｏｒｔｒｏｐａｎｅ，６β－ＡＮ）是一种新型Ｍ２受体激动剂，兔１０ｕｇ·ｋｇ－１ｉｖ，犬２，５，２０ｕｇ·ｋｇ－１ｉｖ均导致呼吸频率、潮气量、每分通气量明显减少（Ｐ＜０．０５或０．０１），呈剂量依赖关系。ｐＯ２降低，ｐＣＯ２升高。较小剂量给兔０．５，１．０，２．０，４．０ｕｇ·ｋｇ－１ｉｖａ和犬０．２５，０．５，１．０ｕｇ·ｋｇ－１ｉｖａ亦产生与静脉给药相似的呼吸抑制效应。ＡＦ－ＤＸ１１６能拮抗６β－ＡＮ的呼吸抑制作用，ＰＺ则与６β－ＡＮ产生协同作用。表明６β－ＡＮ有呼吸抑制作用，并可能与其激动呼吸中枢Ｍ２受体有关。     

中药大黄质量的化学模式识别

本文用PRIMA法对大黄属(Rheum)6种植物的29个样品的质量进行了化学模式识别研究。以泻下药理实验的结果佐证、核对。根据35维HPLC数据或16维UV数据,与SIMCA法、Bayes判别法、非线性映照法(NLM)等模式识别法比较,PRIMA法具有计算速度快、适用范围广的特点,比植物形态学方法的正确率高。本文还根据一阶导数紫外光谱提供的数据,简化了化学模式识別法鉴定中药大黄的操作步骤。     

Anemoside A3 Enhances Cognition through the Regulation of Synaptic Function and Neuroprotection

Compounds that have the ability to both strengthen synaptic function and facilitate neuroprotection are valuable cognitive enhancers that may improve health and quality of life, as well as retard age-related cognitive deterioration. Medicinal plants are an abundant source of potential cognitive enhancers. Here we report that anemoside A3 (AA3) isolated from Pulsatilla chinensis modulates synaptic connectivity in circuits central to memory enhancement. AA3 specifically modulates the function of AMPA-type glutamate receptors (AMPARs) by increasing serine phosphorylation within the GluA1 subunit, which is a modification required for the trafficking of GluA1-containing AMPARs to synapses. Furthermore, AA3 administration activates several synaptic signaling molecules and increases protein expressions of the neurotrophin brain-derived neurotrophic factor and monoamine neurotransmitters in the mouse hippocampus. In addition to acting through AMPARs, AA3 also acts as a non-competitive NMDA receptor (NMDAR) modulator with a neuroprotective capacity against ischemic brain injury and overexcitation in rats. These findings collectively suggest that AA3 possesses a unique ability to modulate the functions of both AMPARs and NMDARs. Concordantly, behavioral studies indicate that AA3 not only facilitates hippocampal long-term potentiation but also enhances spatial reference memory formation in mice. These multifaceted roles suggest that AA3 is an attractive candidate for further development as a cognitive enhancer capable of alleviating memory dysfunctions associated with aging and neurodegenerative diseases.     

Randomized prospective trial comparing the native prothrombin antigen with the prothrombin time for monitoring oral anticoagulant therapy

The dosage of the anticoagulant warfarin sodium is based upon the prolongation of the prothrombin time into an optimal therapeutic range. We have developed a new assay for the native prothrombin antigen that measures the fully gamma-carboxylated prothrombin using a radioimmunoassay. Based on preliminary data that indicated that the native prothrombin antigen predicted both bleeding and thrombotic complications more accurately than the prothrombin time in patients anticoagulated with warfarin sodium, we have performed a randomized prospective trial comparing the complication rate in warfarin-treated patients monitored with the native prothrombin antigen or the prothrombin time. Patients with indications for anticoagulation were randomized to be monitored by the native prothrombin antigen (therapeutic range, 12 to 24 micrograms/mL) or the prothrombin time index (therapeutic range, 1.5 to 2.0). Of the prothrombin time group (N = 80), seven (8.8%) had bleeding or thrombotic complications, with a complication rate of 9.5%/patient-year. In the native prothrombin antigen group (N = 76), one subject (1.3%) had a bleeding complication. The complication rate per patient-year was 1.5%. These results indicate an 85% reduction in the complication rate of the native prothrombin antigen group compared with the complication rate of the prothrombin time group. This difference is statistically significant by the Fisher exact test (P = .037) and by Kaplan Meier survival analysis (P = .040). This study suggests that the use of the native prothrombin antigen assay has the potential to decrease the complications associated with anticoagulation therapy with warfarin sodium.