一类新型的四氢异喹啉类PPARα/γ受体激动剂的设计、合成与活性研究

为得到更高效的PPAR(过氧化物酶体增殖激活受体)α/γ受体激动剂,设计合成了新型的四氢异喹啉类化合物,通过1H NMR、HR-MS对化合物结构进行了确证,并测定了化合物的体外PPARα/γ受体激动活性。其中化合物8a具有PPARα/γ双受体激动活性,其PPARα/γ受体激动活性与阳性对照品WY14643、罗格列酮相比活性更强。     

Characterization and quantification of the triterpenoids in different parts of Xanthoceras sorbifolia by HPLC-ESI-MS

Two new triterpenoid glycosides, sorbifoside A (2) and B (3), were isolated from the husks of Xanthoceras sorbifolia along with two known saponins (1, 5). Their structures were established on the basis of 1D and 2D NMR data. A simple and sensitive assay was developed for the simultaneous determination of 6 triterpenoids (1-6, including two triterpenoid aglycones) in X. sorbifolia based on high performance liquid chromatography-mass spectrometry (HPLC-MS) coupled to an electrospray ionization (ESI) interface. The analytes were detected by positive ESI ionization mode and quantified by selected ion monitoring (SIM). All the linear regressions were acquired with r2>0.998. The precisions were evaluated by intra- and inter-day tests, and the relative standard deviation (RSD) values were within the range of 2.0-2.8% and 1.7-2.9%, respectively. The recoveries for the quantified compounds were observed over the range of 95.3-104.7% with RSD values less than 4.6%. The method developed was successfully applied for simultaneous quantification of the six triterpenoids in X. sorbifolia, and our results showed that the contents of triterpenoids in different parts of X. sorbifolia varied significantly.     

替米沙坦片在中国健康男性志愿者中的人体药物动力学

目的 研究19名健康男性志愿者服用替米沙坦片后的药动学特征,为该药进行临床研究及合理用药提供依据.方法 19名健康男性志愿者采用单次给药方案,口服海南赛力克药业有限公司生产的替米沙坦片40 mg.应用HPLC-MS法测定服药后不同时间点替米沙坦的血药浓度,并使用DAS ver 2.0程序对所得的药动学数据进行药动学参数求算.结果 单次服用替米沙坦40 mg后,其主要药物动力学参教如下:Cmax为(312.7±279.7)μg/L,AUC0-48为(1477.4±927.4)μg/(h·L),Tmax为(1.4±0.7)h,t1/2为(13.9±8.1)h.结论 替米沙坦片半衰期较长,且药动学参数在个体间的差异性很大,因此临床使用本品时需注意个体化给药.     

伊布利特与普罗帕酮对新发房颤转复的疗效对比

目的评价静注伊布利特与普罗帕酮转复持续时间〈90d的心房颤动（房颤）的有效性及安全性。方法选择2008年6月—2010年6月,符合条件的房颤患者42例。随机进入伊布利特组（21例）和普罗帕酮组（20例）。二组分别在心电、血压监测下,同时建立静脉通路,伊布利特组首剂1mg,如无效,10min后再给予1mg;普罗帕酮组首剂70mg,如无效,10min后再给予35mg。结果伊布利特组房颤转复率为85.7%,明显高于普罗帕酮组46.7%（P〈0.05）。伊布利特组发生连发室性期前收缩1例;普罗帕酮组发生低血压3例,窦性停搏1例。结论与普罗帕酮相比,伊布利特对房颤的转复有明显优势,二药虽均有不良反应但经对症治疗可好转。     

腹腔积液穿刺道腹壁结节活检术诊断隐性癌(附4例报告)

腹腔积液穿刺脱落细胞检查是诊断恶性肿瘤的常用方法.特别是对未发现原发病灶的隐性癌的诊断更具意义.恶性腹腔积液反复病理检查找到恶性细胞,阳性率40%～60%,我院2005-2006年收治高度怀疑恶性肿瘤引起腹腔积液患者4例,反复腹腔积液穿刺检查脱落细胞,均未查到癌细胞,通过腹腔积液穿刺道腹壁结节活检明确诊断为恶性肿瘤,现报告如下.     

电针百会穴对慢性应激抑郁模型大鼠HPA轴的影响

[目的]揭示针灸治疗抑郁症的作用机理。[方法]SD雄性大鼠32只,随机分为正常对照组、模型组、百会穴电针组、百会穴埋线组,每组8只。采用慢性轻度不可预见性应激刺激结合孤养的方法造模,大鼠共接受21天各种不同的刺激。造模同时电针组、百会穴埋线组分别给予电针、埋线等不同疗法干预。造模结束后通过观察下丘脑-垂体-肾上腺皮质轴的变化,判断针刺对其的干预作用。[结果]经过治疗,电针组与模型组相比,血清CRH、CORT和ACTH含量显著降低(P0.01);而埋线组与模型组相比,血清CRH和ACTH也明显降低(P0.01),但是CORT含量无显著性差异。[结论]百会穴电针疗法及埋线疗法均可拮抗HPA轴功能的亢进,并且电针疗效优于埋线疗效。     

牙根管马达仪治疗根尖周炎的技术研究

目的探讨根管马达仪治疗根尖周炎的临床应用价值。方法178例200颗患牙经根管马达仪直接治疗,1次治疗5s,2～3次为1疗程。结果200颗患牙采用根管马达仪治疗时间短,疗效显著。结论牙根管马达仪治疗根尖周炎,使患者的病牙得以保留,减轻疼痛,延长牙齿寿命。     

新型醒脑静大鼠鼻腔及静脉注射给药后龙脑的药代动力学研究

目的:研究新型醒脑静中艾片有效成分龙脑在大鼠鼻腔给药和静注给药后的药代动力学。方法:醒脑静静注给药剂量为12 mg.kg-1,鼻腔给药剂量为150 mg.kg-1。采用气相色谱法测定血中龙脑的浓度,以Kinetica 4.4软件计算药代动力学参数。结果:鼻腔给药醒脑静滴鼻液后,艾片有效成分龙脑能迅速进入血液中,生物利用度可达83%。结论:鼻腔给药后龙脑能迅速而较完全地吸收进入体循环。     

High vancomycin minimum inhibitory concentration is a predictor of mortality in meticillin-resistant Staphylococcus aureus bacteraemia

Failure of vancomycin in the treatment of meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia has been reported despite full susceptibility of the organism to vancomycin. A retrospective observational cohort study including 137 patients with MRSA bacteraemia was performed at two centres in South Korea during 2009-2010. A total of 137 patients with MRSA bacteraemia receiving vancomycin therapy were enrolled during the study period. Isolates from 13 (9.5%) of the 137 patients had minimum inhibitory concentrations (MICs) ≥1 μg/mL. The 30-day cumulative survival was 53.8% for patients infected with isolates having a MIC≥1 μg/mL and 79.8% for patients infected with isolates having a MIC<1 μg/mL (log-rank test, P=0.026). Vancomycin MIC≥1 μg/mL [hazard ratio (HR)=7.0, 95% confidence interval (CI) 2.2-22.1; P=0.001], nosocomial acquisition of bacteraemia (HR=5.4, 95% CI 1.4-20.1; P=0.013), rapidly fatal underlying diseases (HR=20.5, 95% CI 3.9-106.4; P<0.001), presentation with septic shock (HR=8.4, 95% CI 3.0-23.3; P<0.001), presence of complicated infections (HR=5.6, 95% CI 2.0-15.8; P=0.001) and persistent MRSA bacteraemia for ≥3 days (HR=4.2, 95% CI 1.4-12.7; P=0.012) were independent predictors of 30-day mortality in patients with MRSA bacteraemia. In patients with high Pitt bacteraemia scores (Pitt score ≥2), the delay in initiation of vancomycin therapy was significantly different between non-survivors and survivors (2.4 days vs. 1.1 days; P=0.012). Vancomycin MIC≥1 μg/mL had a significant impact on mortality of patients with MRSA bacteraemia. These findings support early consideration of alternative anti-MRSA agents in patients with MRSA bacteraemia who have high vancomycin MICs as well as prompt initiation of anti-MRSA treatment in patients with MRSA bacteraemia, especially those with high Pitt scores.     

外周血白细胞与糖尿病肾病进展关系的研究

将473例肌酐正常的2型糖尿病肾病（DN）患者根据尿白蛋白／肌酐分为微量白蛋白尿组（DNl组,246例）和大量白蛋白尿组（DN2组,227例）,结果显示,DN2组WBC、单核细胞、CRP较DNl组显著增加[（6．8±1．7）×109／L比（6．3±1．5）×109／L,（0．49±0．23）×109／L比（0．32±0．21）×109／L,（4．1±1．1）mg／L比（1．7±0．3）mg／L,均P〈0．05]。多元线性回归分析显示,WBC、单核细胞、LDL—C和淋巴细胞是尿白蛋白／肌酐升高的独立影响因素。