Antimalarial activity of new water-soluble dihydroartemisinin derivatives. 3. Aromatic amine analogues

A series of artemisinin (1) derivatives containing bromo and heterocyclic or aromatic amine functions was prepared in the search for analogues with good water solubility and high antimalarial activity. Treatment of dihydroartemisinin (2a) with boron trifluoride etherate at room temperature gave the key intermediate, 9,10-dehydrodihydroartemisinin (3), which, on reaction with bromine, gave the dibromide 4. The latter was condensed with amines in anhydrous CH2Cl2 at less than -10 degrees C to give the desired products in 25-55% yield. The new derivatives, tested in vitro against Plasmodium falciparum, were found to be more effective against W-2 than D-6 clones and were not cross-resistant with existing antimalarials. Compound 6b, 3-fluoroaniline derivative, was the most active of the series, with the IC50 less than or equal to 0.16 ng/mL, making it several fold more potent than 1. However, no significant in vivo antimalarial activity against Plasmodium berghei was observed in any of the new compounds tested.     

Genetic determinants of statin intolerance

Background  

Statin-related skeletal muscle disorders range from benign myalgias – such as non-specific muscle aches or joint pains without elevated serum creatinine kinase (CK) concentration – to true myositis with >10-fold elevation of serum CK, to rhabdomyolysis and myoglobinuria. The genetic basis of statin-related muscle disorders is largely unknown. Because mutations in the COQ2 gene are associated with severe inherited myopathy, we hypothesized that common, mild genetic variation in COQ2 would be associated with inter-individual variation in statin intolerance. We studied 133 subjects who developed myopathy on statin monotherapy and 158 matched controls who tolerated statins without incident or complaint.     

Ergebnisse der strukturierten Konsensuskonferenz „Bild gebende Verfahren in der Unfallchirurgie“ und Methodik zur Messung der Akzeptanz unter Tagungsteilnehmern

Existing knowledge and present experience relating to the indications for imaging techniques in trauma surgery were summarised, screened and considered in different ways by representatives of various professional scientific bodies, with the aim of finding what procedures should be implemented as the primary examination techniques after a careful clinical examination when particular posttraumatic situations affecting the knee, foot, ankle, or hand were found. In the course of an interdisciplinary consensus conference the evidence-based recommendations prepared by a panel were discussed and modified, giving rise to statements on the suitability of the given imaging techniques in 28 different clinical situations immediately after a clinical examination, based on scientific evidence and medical consensus. The degree of consensus was measured and carefully documented. These statements were transformed into decision algorithms and presented to doctors working in accident and emergency medicine during a conference on trauma surgery, with the aim of.measuring the acceptance of the statements among those attending the trauma surgery meeting. The remarks made by the participants during the discussion and the results of the acceptance measurements clearly show the need for further discussion among experts.     

Agilent 2100 Bioanalyzer在基因差异表达研究中的应用

目的：观察Agilent2100 Bioanalyzer芯片分析系统（以下简称Bioanalyzer）在基因差异表达研究中的应用。方法：应用限制性显示技术分别从正常和热休克处理后的酿酒酵母细胞中分离出cDNA片段，然后再用Bioanalyzer和传统的琼脂糖凝胶电泳技术对RD-PCR产物进行检测分析。结果：Bioanalyzer能更快速、敏感地分离和显示差异表达的基因片段，并且通过对差异片段进行定量比较，发现了数个表达有明显差异的基因片段。结论：Bioanalyzer在基因差异表达研究中具有重要的应用价值。     

几种杀虫剂对印鼠客蚤的毒力测定

本文报告用罐头瓶药膜法和点滴法对实验室饲养的3日龄未吸血印鼠客蚤为试验对象,测试了溴氰菊酯、滴滴畏、久效磷、磷胺、喹硫磷、倍硫磷半数致死量(LD_(50))和半数致死浓度(LC_(50))。结果以溴氰菊酯和喹硫磷的LC_(50)值较低,磷胺和滴滴畏的数值较高,LD_(50)以溴氰菊酯和倍硫磷毒力较强,磷胺和久效磷次之,雌雄个体差异不明显。     

肠腔侧侧分流术治疗门静脉高压症的体会

本文报道了肠系膜上静脉与下腔静脉侧侧分流术7例,并介绍了手术的体会,认为应解剖、暴露肠系膜上静脉“外科干”与相应平面的下腔静脉,清除两者间的增生组织,缩短两者的间距,才易取得手术成功。本术既可使门静脉压下降适中,又对门静脉向肝血流干扰较小,且对组织损伤较轻。