1例冠心病伴2型糖尿病患者服用阿托伐他汀钙引发的思考

通过考察1例冠心病伴2型糖尿病患者服用他汀类药物治疗效果,研究阿托伐他汀在糖尿病患者中使用的合理性。患者入院时饭后血糖高达14.76 mmol/L,血糖监控表显示患者在22日中餐前,23日早餐、中餐前血糖均跃7 mmol/L,患者空腹血糖控制不佳,23日临床药师与医生查房建议患者加大甘精胰岛素用量,晚上皮下注射甘精胰岛素加至20 U,24日晚餐前后血糖仍跃7 mmol/L,血糖控制不佳。由此可知,本例患者应用他汀药物可能会导致患者血糖异常,但相对心血管不良风险,本例使用阿托伐他汀是合理的。     

皮下注射低分子肝素钙预防烧伤植皮后深静脉血栓形成的效果评价

目的：评估皮下注射低分子肝素钙对预防烧伤植皮后深静脉血栓(DVT)形成的效果。方法选取2013年1月~2014年12月本院收治的79例烧伤后需植皮的患者,其中皮下注射低分子肝素钙预DVT患者41例设为治疗组。植皮术后仅使用红外线治疗仪照射,硫酸镁热敷,活动肌肉组织等基础措施的38例为对照组。统计血浆D-二聚体(D-dimer)浓度、血小板计数、植皮成活率、创面愈合时间、感染病例数、组织器官出血病例数和DVT形成数等指标。结果治疗组术后第3、7、11、15 d的血浆D-dimer浓度均低于对照组(P<0.05);对照组的血栓形成率为10.5%,明显高于治疗组的0(P<0.05);两组术前1 d的D-dimer浓度、血小板计数,植皮成活率、创面愈合时间、感染及出血发生率差异无统计学意义(P>0.05)。结论皮下注射低分子肝素钙对预防烧伤植皮术后患者DVT形成有一定的临床意义。     

Induction of Suicidal Erythrocyte Death by Cantharidin

The natural phosphoprotein phosphatase inhibitor cantharidin, primarily used for topical treatment of warts, has later been shown to trigger tumor cell apoptosis and is thus considered for the treatment of malignancy. Similar to apoptosis of tumor cells, erythrocytes may undergo eryptosis, a suicidal cell death characterized by cell shrinkage and translocation of cell membrane phosphatidylserine to the erythrocyte surface. Signaling of eryptosis includes increase of cytosolic Ca²⁺-activity ([Ca²⁺]_i), ceramide, oxidative stress and dysregulation of several kinases. Phosphatidylserine abundance at the erythrocyte surface was quantified utilizing annexin-V-binding, cell volume from forward scatter, [Ca²⁺]_i from Fluo3-fluorescence, ceramide from antibody binding, and reactive oxidant species (ROS) from 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence. A 48 h treatment of human erythrocytes with cantharidin significantly increased the percentage of annexin-V-binding cells (≥10 μg/mL), significantly decreased forward scatter (≥25 μg/mL), significantly increased [Ca²⁺]_i (≥25 μg/mL), but did not significantly modify ceramide abundance or ROS. The up-regulation of annexin-V-binding following cantharidin treatment was not significantly blunted by removal of extracellular Ca²⁺ but was abolished by kinase inhibitor staurosporine (1 μM) and slightly decreased by p38 inhibitor skepinone (2 μM). Exposure of erythrocytes to cantharidin triggers suicidal erythrocyte death with erythrocyte shrinkage and erythrocyte membrane scrambling, an effect sensitive to kinase inhibitors staurosporine and skepinone.     

Induction of Suicidal Erythrocyte Death by Nelfinavir

The HIV protease inhibitor, nelfinavir, primarily used for the treatment of HIV infections, has later been shown to be effective in various infectious diseases including malaria. Nelfinavir may trigger mitochondria-independent cell death. Erythrocytes may undergo eryptosis, a mitochondria-independent suicidal cell death characterized by cell shrinkage and phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include oxidative stress and increase of cytosolic Ca²⁺-activity ([Ca²⁺]_i). During malaria, accelerated death of infected erythrocytes may decrease parasitemia and thus favorably influence the clinical course of the disease. In the present study, phosphatidylserine abundance at the cell surface was estimated from annexin V binding, cell volume from forward scatter, reactive oxidant species (ROS) from 2'',7''-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, and [Ca²⁺]_i from Fluo3-fluorescence. A 48 h treatment of human erythrocytes with nelfinavir significantly increased the percentage of annexin-V-binding cells (≥5µg/mL), significantly decreased forward scatter (≥2.5µg/mL), significantly increased ROS abundance (10 µg/mL), and significantly increased [Ca²⁺]_i (≥5 µg/mL). The up-regulation of annexin-V-binding following nelfinavir treatment was significantly blunted, but not abolished by either addition of the antioxidant N-acetylcysteine (1 mM) or removal of extracellular Ca²⁺. In conclusion, exposure of erythrocytes to nelfinavir induces oxidative stress and Ca²⁺ entry, thus leading to suicidal erythrocyte death characterized by erythrocyte shrinkage and erythrocyte membrane scrambling.     

马尔可夫模型评价三种磷结合剂治疗高磷血症的研究

目的：评价碳酸钙、碳酸镧和盐酸司维拉姆三者在治疗高磷血症方面的经济性。方法：通过构建马尔可夫模型进行成本效果评价。结果：碳酸镧降磷效果最好,盐酸司维拉姆次之,碳酸钙最差,但考虑成本之后碳酸钙为最优方案。结论：在3倍人均GDP为支付阈值的条件下碳酸钙是最具有成本效果优势的方案。     

Structural and Binding Studies of SAP-1 Protein With Heparin

SAP-1 is a low molecular weight cysteine protease inhibitor (CPI) which belongs to type-2 cystatins family. SAP-1 protein purified from human seminal plasma (HuSP) has been shown to inhibit cysteine and serine proteases and exhibit interesting biological properties, including high temperature and pH stability. Heparin is a naturally occurring glycosaminoglycan (with varied chain length) which interacts with a number of proteins and regulates multiple steps in different biological processes. As an anticoagulant, heparin enhances inhibition of thrombin by the serpin antithrombin III. Therefore, we have employed surface plasmon resonance (SPR) to improve our understanding of the binding interaction between heparin and SAP-1 (protease inhibitor). SPR data suggest that SAP-1 binds to heparin with a significant affinity (K_D = 158 nm ). SPR solution competition studies using heparin oligosaccharides showed that the binding of SAP-1 to heparin is dependent on chain length. Large oligosaccharides show strong binding affinity for SAP-1. Further to get insight into the structural aspect of interactions between SAP-1 and heparin, we used modelled structure of the SAP-1 and docked with heparin and heparin-derived polysaccharides. The results suggest that a positively charged residue lysine plays important role in these interactions. Such information should improve our understanding of how heparin, present in the reproductive tract, regulates cystatins activity.