Mechanism of action and initial evaluation of a membrane active all-D-enantiomer antimicrobial peptidomimetic

Development of therapy against infections caused by antibiotic-resistant pathogens is a major unmet need in contemporary medicine. In previous work, our group chemically modified an antimicrobial peptidomimetic motif for targeted applications against cancer and obesity. Here, we show that the modified motif per se is resistant to proteolytic degradation and is a candidate antiinfective agent. We also show that the susceptibility of microorganisms to the drug is independent of bacterial growth phase. Moreover, this peptidomimetic selectively interferes with the integrity and function of the microbial surface lipid bilayer, data indicative that bacterial death results from membrane disruption followed by dissipation of membrane potential. Finally, we demonstrate two potential translational applications: use against biofilms and synergy with antibiotics in use. In summary, we introduce the mechanism of action and the initial evaluation of a prototype drug and a platform for the development of D-enantiomer antimicrobial peptidomimetics that target bacterial membranes of certain Gram-negative problem pathogens with promising translational applications.     

牡丹江市正常成人尿液红、白细胞定量分析参考值调查

目的尿液沉渣分析红、白细胞由传统的定性报告方式改为定量分析(××/μl).由于使用的检查方法不同,其参考值也不一样,国内目前尚未有统一的参考值,为使牡丹江市有一个统一的判断标准.方法我们对1109名健康成人其中男性591人,女性518人进行尿中红细胞及白细胞的参考值调查.方法采用国内的专用尿沉渣计数板,显微镜下计数.对体检者在统一时间清晨7点钟留取尿液20～30毫升,按统一操作规程进行操作,对不同性别的人群进行参考值的调查.结果男性红细胞x是1.12,S是1.42,95%可信界限0～3.96,参考值范围0～4/μl;男性白细胞x是1.84,是S 2.05,95%可信界限0～5.94,参考值范围0～6/μl.女性红细胞x是2.46,S是3.26,95%可信界限0～8.98,参考值范围0～9/μl;女性白细胞x是2.25,S是3.82,95%可信界限0～9.89,参考值范围0～10/μl.结论通过1109名正常成人尿液红细胞及白细胞含量的调查,建立了牡丹江市的参考值.     

Growth of the uterus

BACKGROUND: The pattern of growth of the uterus was examined by ultrasound examinations of 358 girls who attended a paediatric endocrine outpatient department but were shown not to have any endocrine defect. METHOD: The uterus was measured in length and width at the cervix and at the fundus (cm). Endometrial thickness was measured (mm). Scans were divided by Tanner breast stage and the dimensions compared by one way analysis of variance (ANOVA, with the Student Newman Keuls post hoc test). RESULTS: There was an increase in uterine length, diameter of the fundus, and endometrial thickness at each breast stage from 1 to 5 (ANOVA, p < 0.05), and in the diameter of the cervix with each breast stage from 1 to 4 (ANOVA, p < 0.05). The ratio of the fundus to the cervix increased from 0.95 to 1.29 between breast stages 1 and 4. CONCLUSION: The onset of puberty is marked by an increase in the dimensions of the uterus and in endometrial thickness, but also by a change in the shape of the uterus from a tubular to a pear shaped organ.