顶空-气相色谱/质谱联用法检测饮用水中的氯仿和四氯化碳

目的:自来水厂消毒工艺过程中产生的氯仿、四氯化碳对人的健康有严重的危害,需建立灵敏度高的检测方法监测饮用水中的氯仿和四氯化碳。方法:建立了顶空采样用质谱作为检测器并采用选择离子监测的方法检测饮用水中的氯仿和四氯化碳。结果:氯仿和四氯化碳浓度在0~80μg/L范围内,线性较好,相关系数分别为0.9993和0.9991;氯仿的最低检出浓度为0.05μg/L,四氯化碳的最低检出浓度为0.03μg/L,跟国标方法相比降低了两个数量级,灵敏度大大提高。结论:实验表明本方法操作简单,准确度和精密度较高均符合检测要求,回收率范围93.6%~106.4%,RSD为5.0%~7.5%之间。     

Recent developments in cell-based assays and stem cell technologies for botulinum neurotoxin research and drug discovery

Botulinum neurotoxins (BoNTs) are exceptionally potent inhibitors of neurotransmission, causing muscle paralysis and respiratory failure associated with the disease botulism. Currently, no drugs are available to counter intracellular BoNT poisoning. To develop effective medical treatments, cell-based assays provide a valuable system to identify novel inhibitors in a time- and cost-efficient manner. Consequently, cell-based systems including immortalized cells, primary neurons and stem cell-derived neurons have been established. Stem cell-derived neurons are highly sensitive to BoNT intoxication and represent an ideal model to study the biological effects of BoNTs. Robust immunoassays are used to quantify BoNT activity and play a central role during inhibitor screening. In this review, we examine recent progress in physiologically relevant cell-based assays and high-throughput screening approaches for the identification of both direct and indirect BoNT inhibitors.     

Overexpansion of the SAPIEN 3 Transcatheter Heart Valve: An Ex Vivo Bench Study

Objectives

This study assessed the effect of overexpansion beyond labeled size (diameter) of transcatheter heart valves through an ex vivo bench study.

苯甲吗啉类药物的代谢及代谢产物的研究

本文报道苯甲吗啉类药物的气相色谱与气质联用检测方法。用HP-5890A气相色谱仪、氮专属性检测器,对服药后不同时间排尿中原型药及主要代谢产物,以内标法定量测定,绘制尿累积排泄曲线.醚提取物用三氟醋酐衍生化、气相色谱、气质联用分析比较衍生化前后保留时间及质谱数据,鉴定主要代谢产物苯甲吗啉,微量代谢产物去甲麻黄素、去甲伪麻黄素、麻黄素和伪麻黄素,方法灵敏、结果可靠,适用于此类药物的临床监测与运动员尿样检测。     

Role of two adjacent cytoplasmic tyrosine residues in MRP1 (ABCC1) transport activity and sensitivity to sulfonylureas

The human ATP-binding cassette (ABC) protein MRP1 causes resistance to many anticancer drugs and is also a primary active transporter of conjugated metabolites and endogenous organic anions, including leukotriene C(4) (LTC(4)) and glutathione (GSH). The sulfonylurea receptors SUR1 and SUR2 are related ABC proteins with the same domain structure as MRP1, but serve as regulators of the K(+) channel Kir6.2. Despite their functional differences, the activity of both SUR1/2 and MRP1 can be blocked by glibenclamide, a sulfonylurea used to treat diabetes. Residues in the cytoplasmic loop connecting transmembrane helices 15 and 16 of the SUR proteins have been implicated as molecular determinants of their sensitivity to glibenclamide and other sulfonylureas. We have now investigated the effect of mutating Tyr(1189) and Tyr(1190) in the comparable region of MRP1 on its transport activity and sulfonylurea sensitivity. Ala and Ser substitutions of Tyr(1189) and Tyr(1190) caused a > or =50% decrease in the ability of MRP1 to transport different organic anions, and a decrease in LTC(4) photolabeling. Kinetic analyses showed the decrease in GSH transport was attributable primarily to a 10-fold increase in K(m). In contrast, mutations of these Tyr residues had no major effect on the catalytic activity of MRP1. Furthermore, the mutant proteins showed no substantial differences in their sensitivity to glibenclamide and tolbutamide. We conclude that MRP1 Tyr(1189) and Tyr(1190), unlike the corresponding residues in SUR1, are not involved in its differential sensitivity to sulfonylureas, but nevertheless, may be involved in the transport activity of MRP1, especially with respect to GSH.     

Discrepancies in vessel sizing between angiography and intravascular ultrasound varies according to the vessel evaluated

Background/objectives

Quantitative coronary analysis (QCA) of the coronary artery and stent size may be influenced by anatomical location in relation to both calibration point and the X-ray tube. The impact of this phenomenon on lesion assessment is undetermined.

Methods

In total, 427 consecutive patients who underwent PCI with intravascular ultrasound (IVUS)-guidance were enrolled. The minimum stent diameter (MSD) was measured using QCA (MSD_QCA) and IVUS (MSD_IVUS) analysis. We used reference objects positioned at a different height from the X-ray source to validate our approach.

Results

A statistically positive moderate correlation was observed between MSD_QCA and MSD_IVUS (r = 0.649, p = 0.001). The mean MSD_QCA and MSD_IVUS were 3.04 ± 0.49 mm and 2.68 ± 0.47 mm respectively. The difference between MSD_QCA and MSD_IVUS of > 0.75 mm was more frequently observed in the LCx rather than in the LAD (7.4% in the LAD vs. 24.3% in the LCx, p = 0.001). The discrepancy between the MSD_QCA and MSD_IVUS for the LCx was larger than for the LAD, and tended to be larger than for the RCA (13.3% vs. 18.5%, p = 0.05 and 18.5% vs. 14.5%, p = 0.17). A discrepancy > 20% was more frequently observed in the small (≤ 2.5 mm) than in the large MSD_IVUS group (52.7% vs. 25.1%, p = 0.001). This discrepancy was more common in the LCx than in the LAD or RCA (48.6% vs. 30.9% vs. 31.2%, p = 0.03).

Conclusions

Assessment of the MSD_QCA is more likely to overestimate in the LCx than in the LAD, particularly when the MSD_IVUS is < 2.5 mm. Therefore, we should be less aggressive in oversizing balloons and stents based on QCA for the LCx or small vessel intervention.     

A Unified Approach for Assessing Agreement for Continuous and Categorical Data

Abstract

In simultaneous testing for noninferiority and superiority, Morikawa and Yoshida (Morikawa, T., Yoshida, M. (1995 Morikawa, T. and Yoshida, M. 1995. A useful testing strategy in phase III trials: Combined test of superiority and test of equivalence. J. Biopharmaceutical Statistics, 5: 297–306. [Taylor &; Francis Online] , [Google Scholar]). A useful testing strategy in phase III trails: Combined test of superiority and test of equivalence. J. Biopharmaceutical Statistics 5:297–306) argue that multiplicity adjustment is not necessary by using the closed testing (CT) principle. In fact, using the same argument, no multiplicity adjustment is necessary in simultaneous testing of any number of nested null hypotheses. However, simultaneous testing of many nested null hypotheses is problematic in a confirmatory trial because such simultaneous testing is similar to post-hoc specification of the null hypothesis. Thus, simultaneous testing for noninferiority and superiority may be viewed as an initial step towards exploratory analysis and may be best used cautiously in confirmatory evaluation.     

Comparison between a new multiplex electrochemiluminescence assay and the WHO reference enzyme-linked immunosorbent assay to measure serum antibodies against pneumococcal serotype-specific polysaccharides

Background

Two electrochemiluminescence (ECL) assays were developed which, together, can simultaneously measure serum antibodies against pneumococcal capsular polysaccharides (PnPS) for 17 serotypes. The assays were validated for the 13 PnPS included in the 13-valent pneumococcal conjugate vaccine (PCV13). As recommended by the World Health Organization (WHO), we compared the ECL assays with the WHO reference enzyme-linked immunosorbent assay (ELISA) and derived a threshold corresponding to the 0.35?µg/mL threshold established for the WHO reference ELISA for the non-inferiority comparison and licensure of new PCVs against invasive pneumococcal disease.

Hematopoietic stem cell transplantation for CD40 ligand deficiency: Results from an EBMT/ESID-IEWP-SCETIDE-PIDTC study

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