三种消毒剂对体检中心物体表面消毒效果与使用成本的比较研究

目的对3种消毒剂在体检中心物体表面消毒的消毒效果及使用成本进行比较,为体检中心优选合适的物体表面消毒方式提供依据。方法分别使用I型复合双链季铵盐卫生湿巾、500mg/L含氯消毒剂、75%乙醇擦拭消毒健康体检中心采血台、彩超机和乳腺红外线诊断仪的表面,在消毒前、消毒后即刻、消毒后30min及1h分别对各区域进行棉拭子涂抹采样及培养。结果受检物体表面细菌菌落数采血台为(78.4±6.2)cfu/cm2,彩超机为(36.2±2.1)cfu/cm2,乳腺红外线诊断仪为(45.9±3.0)cfu/cm2。3种消毒剂消毒后各时间点采样菌落数与消毒前比较,差异有统计学意义(均P0.01)。I型复合双链季铵盐卫生湿巾消毒效果在消毒后即刻、消毒后30min及1h优于500mg/L含氯消毒剂、75%乙醇(P0.05,P0.01);每次消毒成本I型复合双链季铵盐卫生湿巾最低。结论 3种消毒剂对各监测表面均有良好的消毒效果,但I型复合双链季铵盐卫生湿巾的消毒持续效果优于其他两种,且使用成本低,使用方便、侵蚀性小,适用于体检中心物表消毒。     

华蟾素注射液配伍复方斑蝥胶囊对膀胱癌荷瘤小鼠瘤体的生长抑制作用

目的：探讨华蟾素注射液配伍复方斑蝥胶囊对膀胱癌荷瘤小鼠瘤体的生长抑制作用。方法建立膀胱癌荷瘤小鼠模型,随机分为空白对照组、对照组及实验组,肿瘤生长1周时开始给药,实验组给予华蟾素注射液及复方斑蝥胶囊,对照组给予注射用吡柔比星,并设空白对照（仅用生理盐水）,给药量均以临床常用量为标准,给药4周后处死裸鼠,分别测量、记录瘤体重量。结果空白对照组、对照组、实验组的平均瘤重（6.82±1.034 g、4.79±0.973 g、3.08±1.129 g ）,对照组、实验组抑制率分别为31.89％、50.47％,对照组、实验组抑制率差异具有统计学意义（ P＜0．05）。结论对照组、实验组对膀胱癌均具有抑制作用,且实验组较对照组对膀胱癌荷瘤小鼠瘤体生长抑制作用更明显。     

Exploring isoxazoles and pyrrolidinones decorated with the 4,6‐dimethoxy‐1,3,5‐triazine unit as human farnesyltransferase inhibitors

Unprecedented triazinyl‐isoxazoles were afforded via an effective cycloaddition reaction between nitrile oxides and the scarcely described 2‐ethynyl‐4,6‐dimethoxy‐1,3,5‐triazine as dipolarophile. The biological evaluation of the newly synthesized compounds showed that the inhibition of human farnesyltransferase by zinc complexation could be improved with triazine‐isoxazole moieties. The replacement of the isoxazole unit by a pyrrolidin‐2‐one was detrimental to the inhibitory activity while the pyrrolidin‐2‐thione derivatives conserved the biological potential. The potential of selected compounds to disrupt protein farnesylation in Chinese hamster ovary (CHO) cells transfected with pEGFP‐CAAX was also evaluated.     

One-shot NMR analysis of microbial secretions identifies highly potent proteasome inhibitor

Natural products represent valuable lead structures for drug discovery. However, for most bioactive compounds no cellular target is yet identified and many substances predicted from genome analysis are inaccessible due to their life stage-dependent biosynthesis, which is not reflected in common isolation procedures. In response to these issues, an NMR-based and target-directed protease assay for inhibitor detection of the proteasome was developed. The methodology is suitable for one-shot identification of inhibitors in conglomerates and crude culture broths. The technique was applied for analysis of the different life stages of the bacterium Photorhabdus luminescens, which resulted in the isolation and characterization of cepafungin I (CepI), the strongest proteasome inhibitor described to date. Its biosynthesis is strictly regulated and solely induced by the specific environmental conditions determined by our methodology. The transferability of the developed technique to other drug targets may disclose an abundance of novel compounds applicable for drug development.     

浓台氏液对口腔铸造用银铟合金的腐蚀性的初步研究

目的:通过体外浸泡实验观察口腔铸造用银铟合金与浓台氏液发生腐蚀反应后表面形貌及粗糙度的变化,考察不同腐蚀反应时间浓台氏液对银铟合金的腐蚀情况。方法:制作口腔修复铸造用银铟合金测试件,对照组不与浓台氏液接触,实验组浸入浓台氏液发生腐蚀反应,反应时间分别为5sec、10sec、15sec、30sec、1min、5min、10min、30min,以扫描电子显微镜观察试件表面形貌,再以粗糙度仪检测试件表面粗糙度,应用SPSS16.0统计软件对各组合金样本粗糙度值做统计学检验。结果:扫描电子显微镜结果显示:浓台氏液对银铟合金的腐蚀是在整个金属表面上均匀进行的,且腐蚀产物有随腐蚀时间的增加而增加的趋势。试件表面粗糙度检测结果显示:各试验组表面粗糙度值与电镜观察到的材料表面腐蚀程度一致,随腐蚀时间的增加而有增加的趋势。统计结果显示:5sec、10sec组与对照组两两相比粗糙度差异有统计学意义(P<0.05),而10min组、15sec、30sec、1min组、5min、10min组、30min组两两相比粗糙度均无显著差异(P>0.05)。结论:浓台氏液与银铟合金的腐蚀反应特征为均匀腐蚀。腐蚀产物和表面粗糙度有随腐蚀时间的增加而增加的趋势。表面粗糙度与腐蚀时间不呈线性增长关系,具体表现为表面粗糙度10min到达较高水平,后在30min内随时间的增加,浓台氏液对银铟合金表面的腐蚀基本稳定。     

TEAS复合药物全麻行控制性降压后胃血流的变化

目的:探讨经皮穴位电刺激(transcutaneous electrical acupoint stimulation,TEAS)复合药物全麻行控制性降压至不同血压水平的胃血流变化,从而明确针药复合麻醉的胃保护机制.方法:54只,♂,比格犬随机分为9组:单纯全麻组、60%对照组、60%实验组、50%对照组、50%实验组、40%对照组、40%实验组、30%对照组、30%实验组,每组6只,后8组动物均以异氟醚联合硝普钠行控制性降压,将动脉血压降至60%、50%、40%、30%基础平均动脉血压水平并维持60min,单纯全麻组不行控制性降压.实验组采用TEAS干预处理,采用激光多普勒组织血流仪监测不同水平相应时间点胃表面血流的变化.结果:在行控制性降压至目标低血压水平(T0)时,所有对照组胃血流均显著低于各自基础水平(P<0.05),而60%实验组、50%实验组胃血流未明显降低,在维持10min(T1)时,除50%实验组外,其他各控压组胃血流均显著低于各自基础水平和同期单纯全麻组水平(P<0.05),50%实验组与同水平对照组相比有显著统计学差异(P<0.05),在血压回升阶段,50%、30%、40%实验组胃血流先后恢复至基础水平和同期单纯全麻组水平,而同水平对照组未明显恢复.结论:轻度控压时(尤其是50%水平),TEAS的胃保护效应明显.重度控压时(尤其是30%水平),TEAS基本无保护效应,但在血压回升结束时,TEAS可促进胃血流的较快恢复.     

Excitation Patterns of Standard and Steered Partial Tripolar Stimuli in Cochlear Implants

Current steering in partial tripolar (pTP) mode has been shown to improve pitch perception and spectral resolution with cochlear implants (CIs). In this mode, a fraction (σ) of the main electrode current is returned within the cochlea and steered between the basal and apical flanking electrodes (with a proportion of α and 1 − α, respectively). Pitch generally decreases when α increases from 0 to 1, although the salience of pitch change varies across CI users. This study aimed to identify the mechanism of pitch changes with pTP-mode current steering and the factors contributing to the intersubject variability in pitch-ranking sensitivity. The electrical fields were measured for steered pTP stimuli on the same main electrode with α = 0, 0.5, and 1 in five implanted ears using electrical field imaging (EFI). The related excitation patterns were also measured physiologically using evoked compound action potential (ECAP) and psychophysically using psychophysical forward masking (PFM). Consistent with the pitch-ranking results in this study, the EFI, ECAP, and PFM centroids shifted apically with increasing α. An apical shift was also observed for the PFM peak but not for the EFI or ECAP peak. The pattern width was similar with different α values within a given measure (e.g., EFI, ECAP, or PFM), but the ECAP patterns were broader than the EFI and PFM patterns, possibly because ECAP was measured with smaller σ values than EFI and PFM. The amount of pattern shift with α depended on σ (i.e., the total amount of current used for steering) but was not correlated with the pitch-ranking sensitivity across subjects. The results revealed that the pitch changes elicited by pTP-mode current steering were not only driven by the shifts of excitation centroid.     

Prediction of Human Brain Penetration of P-glycoprotein and Breast Cancer Resistance Protein Substrates Using In Vitro Transporter Studies and Animal Models

Four P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrates with human cerebrospinal fluid (CSF) concentrations and preclinical neuropharmacokinetics were used to assess in vitro–in vivo extrapolation of brain penetration in preclinical species and the ability to predict human brain penetration. Unbound brain (C_b,u), unbound plasma (C_p,u), and CSF compound concentrations (C_CSF) were measured in rats and nonhuman primates (NHPs), and the unbound partition coefficients (C_b,u/C_p,u and C_CSF/C_p,u) were used to assess brain penetration. The results indicated that for P-gp and BCRP dual substrates, brain penetration was severally impaired in all species. In comparison, for P-gp substrates that are weak or non-BCRP substrates, improved brain penetration was observed in NHPs and humans than in rats. Overall, NHP appears to be more predictive of human brain penetration for P-gp substrates with weak or no interaction with BCRP than rat. Although C_CSF does not quantitatively correspond to C_b,u for efflux transporter substrates, it is mostly within 3-fold higher of C_b,u in rat and NHP, suggesting that C_CSF can be used as a surrogate for C_b,u. Taken together, a holistic approach including both in vitro transporter and in vivo neuropharmacokinetics data enables a better estimation of human brain penetration of P-gp/BCRP substrates.