A Class of High-affinity Bicyclooctane G551D-CFTR Activators Identified by High Throughput Screening

The glycine-to-aspartic acid missense mutation at the codon 551(G551D) of the cystic fibrosis transmem-brane conductance regulator (CFTR) is one of the five most frequent cystic fibrosis (CF) mutations associated with a severe CF phenotype. To explore the feasibility of pharmacological correction of disrupted activation of CFTR chloride channel caused by G551D mutation, we developed a halide-sensitive fluorescence miniassay for G551D-CFTR in Fisher rat thyroid(FRT) epithelial cells for the discovery of novel activators of G551DCFTR. A class of bicyclooctane small molecule compounds that efficiently stimulate G551D-CFTR chloride channel activity was identified by high throughput screening via the FRT cell-based assay. This class of compounds selectively activates G551D-CFTR with a high affinity, whereas little effect of the compounds on wildtype CFTR can be seen. The discovery of a class of bicyclooctane G551D-CFTR activators will permit the analysis of structure-activity relationship of the compounds to identify ideal leads for in vivo therapeutic studies.     

Nd：YAG激光与传统手术治疗会厌囊肿的疗效比较

目的比较NdYAG激光、传统手术治疗会厌囊肿的疗效。方法对60例会厌囊肿分别采用NdYAG激光照射治疗或手术摘除治疗。结果NdYAG激光照射治疗有效率达91%,手术摘除有效率达75%。结论NdYAG激光治疗会厌囊肿优越于手术摘除。     

Activation of G551D-CFTR by Bicyclooctane Compounds Is cAMP-dependent and Exhibits Low Sensitivity to Thiazolidinone CFTR Inhibitor CFTRinh-172

The G551D-CFTR mutation causing cystic fibrosis(CF) results from a missense mutation at codon 551 (G551D) in the gene encoding of the cystic fibrosis transmembrane conductance regulator (CFTR). The G551D mutation in CFTR results in a reduced functional channel but G551D-CFTR is appropriately inserted in the apical membrane. In previous studies we discovered a class of high-affinity bicyclooctane (BCO) G551D-CFTR activators(G551DBCOS) with Kd down to 1μmol/L. In this study, we analyzed the pharmacological activation of G551D-CFTR by the G551DBCOS by means of short circuit current analysis and cell-based fluorescence quenching assay. The G551DBCOS-induced G551D-CFTR activation is cAMP-dependent and is less sensitive to thiazolidinone CFTR inhibitor CFTRinh-172. These data suggest that (1) the phosphorylation of G551D-CFTR by protein kinase A is required for the activation by G551DBCOS; (2) G551DBCOS and CFTRinh-172 may act at the same site on the G551D-CFTR molecule.     

CO2激光治疗耳廓囊肿45例

耳廓囊肿临床上较常见 ,大部分因外伤引起 ,少数原因不明。我科自 1 994年 8月至今采用CO2 激光治疗 45例效果满意。一般资料 :本组 45例 ,男性 3 0例 ,女性 1 5例 ,年龄 2 0 -6 0岁 ,病程 5 -3 0天 ,3 0例位于耳甲腔 ,4例位于舟状窝 ,6例位于三角窝 ,另外 5例囊肿较大 ,贯穿舟     

Activation of CFTR-mediated Cl- Transport by Magnolin

Magnolin is a herbal compound from Magnolia biondii Pamp. It possesses numerous biological activities. Cystic fibrosis transmembrane conductance regulator（CFTR） is an epithelial chloride channel that plays a key role in the fluid secretion of various exocrine organs. In the present study, the activation of CFTR-mediated chloride transport by magnolin is indentified and characterized. In CFTR stably transfected FRT cells, magnolin increases CFTR CI- currents in a concentration-dependent manner. The activation of magnolin on CFTR is rapid, reversible, and cAMP-dependent. Magnolin does not elevate cellular cAMP level, indicating that it activates CFTR by direct binding and interaction with CFTR protein. Magnolin selectively activates wildtype CFTR rather than mutant CFTR. Magnolin may present a novel class of therapeutic lead compound tbr the treatment of diseases associated with reduced CFTR function such as keratoconjunctivitis sicca, idiopathic chronic pancreatiti, and chronic constipation.     

CO2激光治疗耳廓假囊肿的疗效观察

1　临床资料和治疗方法我科 2 0 0 1年收治 30例患者 ,男 36例 ,占 86 6 7% ,女 4例 ,占 13 33% ,年龄 12岁至 5 5岁之间 ,病史 2到 5年 ,其中 5例曾手术切开引流及针管穿刺抽吸囊液加压包扎治疗后又复发。在患耳假性囊肿处以 2 %利多卡因局麻后 ,即用ＣＯ2 激光在囊肿表面上下灼孔 ,有利于囊液的排出 ,再用Ｈｅ -Ｎｅ激光照射 ,功率调至 30Ｗ ,距离为 2 0公分 ,照射时间为 10～ 15分钟 ,每日一次 ,7天为一疗程 ,每次照射结束用 0 5 %碘伏棉球消毒 ,使局部皮肤清洁干燥 ,适当加压包扎。2　讨论结果实践确认激光穿透性强 ,光纤维插入囊腔内…     

发卡在耳廓假性囊肿手术中的应用

耳廓假性囊肿是发生于耳廓软骨夹层的无菌性浆液性渗出病变,是耳科常见病、多发病。其治疗方法多,包括穿刺抽液,手术切除部分软骨,以及激光或微波开窗治疗等〔1〕,治疗后均需要加压包扎,包扎方式既往多采绷带卷或石膏固定,虽有疗效,但操作方法复杂,耗时,昂贵,病人不能耐受取而致疗程长,复发,局部皮肤增厚,影响美观,甚至引起化脓性软骨膜炎。     

男士春季护肤攻略精英男士细致护肤守则

男人美容四步曲 专家告诉我们，男性的皮脂腺和汗腺都比女性大，瘦肤酸度也比女性高，分泌的皮脂和汗液多，脸上和身上的毛发也粗而浓。而且男性较女性更常做些体力劳动，皮肤更容易受污染、变黑、变粗糙。因此，男性更应该对皮肤进行科学、合理的护理和保养。为他护肤应掌握以下五个要点：     

皮肤囊肿成像用高频超声换能器及扫描方法

高频超声成像具有几十微米级的纵向分辨率,适用于皮肤等人体组织的微结构成像。该文针对皮肤囊肿等凸形的人体组织内部微结构,提出了一种适用于凸形组织的非接触式弧形超声扫描成像方法,设计并制备了一款41.5 MHz的高频超声换能器。首先采用脉冲回波法对其性能进行系统表征,然后设计了凸形旋转扫描成像装置,并对凸形皮肤囊肿模型进行扫描、滤波、补偿等信号采集和处理,最终实现了高频超声成像。结果表明,此方法所用换能器纵向分辨率为50μm,能够对皮肤囊肿模型内部精细结构进行成像,这将促进相关临床医学和超声成像技术的发展。     

从腱鞘囊肿谈起—漫谈材料的触变性

从笔所患腱囊肿的治愈经历,谈材料的触变性。