高效液相色谱法测定人血浆中阿莫西林浓度及药代动力学

高效液相色谱法测定人血浆中阿莫西林浓度及药代动力学谭力周继红罗楠袁倚盛（南京军区南京总医院中心仪器分析科，南京２１０００１）阿莫西林（ａｍｏｘｉｃｉｌｉｎ）为β内酰胺类抗生素，其抗菌谱广，口服受食物影响小，对大多数病人耐受性良好，因而在临床上得以广泛...     

Cost-effectiveness of human papillomavirus testing after treatment for cervical intraepithelial neoplasia

OBJECTIVE: To compare current cytological follow up of women treated for high-grade cervical intraepithelial neoplasia (CIN) with follow up by high-risk human papillomavirus (HPV) testing together with cytology. DESIGN: A cost-effectiveness modelling study. SETTING: Gynaecology clinics in the Netherlands. POPULATION: Women treated for high-grade CIN. METHODS: A Markov model was developed to compare six follow-up strategies with HPV testing with current cytological follow up at 6, 12, and 24 months. Model parameter estimation was based on three Dutch follow-up studies and a Dutch population-based screening cohort. MAIN OUTCOME MEASURES: The number of CIN2/3 cases missed after 5 years follow up, the number of diagnostic procedures, and costs involved. RESULTS: Strategies with adjunct HPV testing were more effective than current follow up (reduction in missed CIN2/3 cases 32-77%, corresponding to a number needed to treat of 192-455) and less inconvenient (reduction in repeat smears 28-65%). A particularly attractive strategy was HPV testing alone at 6 months and both HPV and cytological testing at 24 months after treatment. This strategy yielded a high detection rate of post-treatment CIN, did not lead to an increase in colposcopy rate, and was 49 Euro per woman cheaper than the current strategy. CONCLUSIONS: Our model supports the use of high-risk HPV testing for monitoring women treated for high-grade CIN.     

抗胆碱药3-(2-苯基-2-环戊基-2-羟基-乙氧基)奎宁环烷的立体化学和构效关系

研究了强效抗胆碱药dl-3-(2-苯基-2-环戊基-2-羟基-乙氧基)-奎宁环烷的四个光学异构体的两种不对称合成方法,用HPLC检测了异构体含量,讨论了构效关系。     

ADAMTS-4 activity on a proteoglycan vs. a polypeptide is controlled by the ancillary domains

Introduction In combination with the catalytic domain, the ancillary domains of the ADAMTS' are proposed to regulate activity via interactions with sulfated GAGs, the extracellular matrix (ECM) and cell surface. Interactions with both GAGs and the ECM have been attributed to the thrombospondin (TSP) type 1 motifs and spacer region ( Kuno and Matsushima 1998 ; Flannery et al. 2002 ). ADAMTS‐1, ‐4 and ‐5, all undergo cleavage within their respective spacer regions ( Flannery et al. 2002 ; Rodriguez‐Manzaneque et al. 2000 ; Georgiadis et al. 2002 ), an event which has been reported to increase activity towards the interglobular domain of aggrecan and decrease the heparin affinity of ADAMTS‐4 ( Flannery et al. 2002 ; Gao et al. 2002 ). Materials and methods V5‐ and His‐tagged recombinant human ADAMTS‐4 constructs terminating after the catalytic (?DTS), disintegrin‐like (?TS), TSP (?S) or spacer region (Full) were expressed in High‐Five cells. Proteoglycanase activities of the resultant proteins were assayed with solution digests of aggrecan and a polyacrylamide‐entrapped aggrecan particle assay. Proteolytic activity was measured using a novel, nonglycosylated, reporter substrate assay. Results All forms of ADAMTS‐4 were active to varying degrees in the reporter substrate assay. Digestion of aggrecan in solution digests was apparent in all proteins with the exception of the catalytic domain in isolation (?DTS). Activity towards aggrecan decreased with increasing truncation of the protein. Discussion Removal of the cysteine‐rich‐spacer domain and further C‐terminal truncations decrease the activity of ADAMTS‐4 towards aggrecan, whilst the proteolytic activity remains intact. Cleavages releasing the ancillary domains of ADAMTS' may therefore alter the catalytic activity of these enzymes against proteoglycans and also nonglycosylated polypeptides. More information is required about potential substrates for the processed forms of ADAMTS‐4.     

苯丙胺诱发小鼠激怒反应及其机制

苯丙胺15mg/kg ip能诱发小鼠激怒反应,使小鼠出现攻击和殴斗行为。强安定药、弱安定药和利血平有明显拮抗效果。镇静剂如巴比妥类、抗胆碱药及抗肾上腺素药均无拮抗作用。金刚胺、左旋多巴和阿扑吗啡均能增强苯丙胺的激怒效应。因苯丙胺激怒小鼠的方法简便易行,可作为筛选抗精神病药的动物模型。苯丙胺产生激怒作用的机制与增强多巴胺能神经的功能有关,推测可能是促进边缘系统多巴胺释放的结果。