Simultaneous quantitative analysis of ketanserin and ketanserinol in plasma by RP-HPLC with fluorescence detection

A sensitive and selective high-performance liquid chromatographic assay for the quantification of ketanserin and ketanserinol in human plasma was developed and validated. The procedure involves extraction of ketanserin and ketanserinol from plasma using an Extrelut NT-1 solid-phase extraction column. The chromatograph was equipped with a Hypersil BDS column (100 x 4.5 mm, 3 micro m particle size). Separation was performed with a mixture of acetate buffer 0.01 M, pH 4.9-methanol-acetonitrile (52:40:8, v/v/v). Detection was performed with fluorescence detection (lambda(ex) = 332 nm and lambda(em) = 410 nm). Calibration curves were linear (r(2) = 0.999) in the range 0-400 ng/mL for both ketanserin and ketanserinol. The repeatability coefficient for ketanserin and ketanserinol was 3.1 and 3.0%, respectively. The reproducibility coefficient for ketanserin and ketanserinol was 10.5 and 9.1%, respectively. The limit of quantification for both ketanserin and ketanserinol was 2.0 ng/mL. The mean recovery yield for both ketanserin and ketanserinol was 60%. In an 8 h work day approximately 60 samples, including calibration and reference standards, could be processed.     

The definition of the toxicologically relevant applicability domain for the SNAr reaction for substituted pyridines and pyrimidines

This study outlines how results from a glutathione reactivity assay (so-called in chemico data) can be used to define the applicability domain for the nucleophilic aromatic substitution (S_NAr) reaction for nitrogen-containing aromatic compounds. S_NAr is one of the six mechanistic domains that have been shown to be important in toxicological endpoints in which the ability to bind covalently to a protein is a key molecular initiating event. This study has analysed experimental data (2 h RC₅₀ values), allowing a clear and interpretable structure–activity relationship to be developed for pyridines and pyrimidines which reside within the S_NAr domain. The in-ring nitrogen(s) act as activating groups in the S_NAr reaction. The position(s) of the in-ring nitrogen(s) as well as other activating groups, especially in relationship to the leaving group, affect reactive potency. The experimentally defined applicability domain has resulted in a series of structural alerts. These results build on early work on the benzene derivatives residing in the S_NAr domain. The definition of the applicability domain for the S_NAr reaction and the resulting structural alerts are likely to be beneficial in the development of computational tools for category formation and read-across in hazard identification, and the development of adverse outcome pathways.     

Development and validation of an LC–MS/MS method for the quantification of artificial sweeteners in human matrices

Artificial sweeteners are widely used as substitutes for sugar. The sweeteners are generally considered safe, however their whereabouts during pregnancy and lactation and the effect on child development are poorly explored. There is a need for new tools to measure these substances during pregnancy and lactation. Here, we describe the development and validation of a sensitive liquid chromatography–tandem mass spectrometry method for the simultaneous quantification of acesulfame, cyclamate, saccharin and sucralose in human plasma, umbilical cord blood, amniotic fluid and breast milk. The samples were prepared by protein precipitation and separated on a Luna Omega Polar C₁₈ column (2.1 × 50 mm, 1.6 μm). Electrospray ionization in negative mode and multiple reaction monitoring were used to monitor the ion transitions. The validated concentration ranges were from 1 to 500 ng/ml (10–500 ng/ml for sucralose). Interassay precisions were all ≤15% and the accuracies were within ±15%. Stability, linearity, dilution integrity, carryover and recovery were also examined and satisfied the validation criteria. Finally, this analytical method was successfully applied on spiked samples of plasma, umbilical cord blood, amniotic fluid and breast milk, proving its suitability for use in clinical studies on artificial sweeteners, including during pregnancy and lactation.     

Noninvasive prenatal paternity testing by maternal plasma DNA sequencing in twin pregnancies

SNPs, combined with massively parallel sequencing technology, have proven applicability in noninvasive prenatal paternity testing (NIPPT) for singleton pregnancies in our previous research, using circulating cell-free DNA in maternal plasma. However, the feasibility of NIPPT in twin pregnancies has remained uncertain. As a pilot study, we developed a practical method to noninvasively determine the paternity of twin pregnancies by maternal plasma DNA sequencing based on a massively parallel sequencing platform. Blood samples were collected from 15 pregnant women (twin pregnancies at 9–18 weeks of gestation). Parental DNA and maternal plasma cell-free DNA were analyzed with custom-designed probes covering 5226 polymorphic SNP loci. A mathematical model for data interpretation was established, including the zygosity determination and paternity index calculations. Each plasma sample was independently tested against the alleged father and 90 unrelated males. As a result, the zygosity in each twin case was correctly determined, prior to paternity analysis. Further, the correct biological father was successfully identified, and the paternity of all 90 unrelated males was excluded in each case. Our study demonstrates that NIPPT can be performed for twin pregnancies. This finding may contribute to development in NIPPT and diagnosis of certain genetic diseases.     

超促排卵治疗后卵泡破裂合并官外孕一例

一名继发不孕，多囊卵巢病史的妇女接受ＨＭＧ和ＨＣＧ超促排卵治疗后，发生了并发症，即卵泡破裂出血，宫外孕，卵巢过度刺激综合征等。提示进行超促卵治疗时，必须合理使用排卵药及加强监测手段，以促证治疗的安全性。     

基于AHP-Entropy方法的科技成果转化绩效评价

科技成果的转化绩效优劣需要从多个层次、多个视角进行考核,本文从转化成果的经济效益、社会效益、环境效益和扩散效应等四个方面对科技成果转化绩效进行评价,评价体系的建立力求突出指标的精炼性和数据的可获性,借助AHP-Entropy方法并结合调查数据开展实证分析,阐述了评价方法的操作步骤且验证了评价体系的科学性和实践可行性。     

妊娠晚期羊水中微量元素测定及其与胎儿生长发育关系的研究

对１０２名足月正常妊娠第一胎的产妇妊娠晚期羊水中６种微量元素（锌、铜、锰、铁、钙、镁）首次进行了测定，并通过对出生新生儿生长发育的监测探讨其与胎儿生长发育的关系。妊娠晚期羊水中６种微量元素含量（±Ｓ／×１０－５）分别为：Ｚｎ２．２９±１．７７，Ｃｕ０．１４±０．１４，Ｍｎ０．１３±０．２３，Ｆｅ３．６９±２．７０，Ｃａ８２．５４±７４．１８，Ｍｇ１８．７１±１１．０９．男女新生儿其母羊水中微量元素含量比较无显著差异，Ｐ≥０．０５．与文献报道中期妊娠羊水中所含微量元素比较有增加趋势．６种微量元素相互关系中．与锌、钙呈正相关外，锌与铜、锰、铁、镁呈负相关．低体重组与低身长组新生儿孕母羊水中锌含量明显低于高体重组和高身长组，有显著差异，Ｐ≤０．０１．铁在高身长组含量增高，与低身长组比较有显著差异，Ｐ≤０．０５．锰于低体重组含量升高，与高体重组比较有显著差异，Ｐ≤０．０１．镁与铜于低身长组含量升高，与高身长组比较有显著差异，Ｐ分别≤０．０５与０．０１．可见高铜、高锰、高镁可致胎儿生长发育迟缓．     

Sensitivity and significance of disease outcome measures in inflammatory bowel disease

In inflammatory bowel disease (IBD), proxy measures of clinical outcome are often collected into summary indices of qualitative self-rated disease markers, clinical observations, and quantitative biochemical analyses. In Crohn's disease (CD), a frequently used index is the Crohn's disease activity index (DCAI). This index consists of six qualitative variables and two quantitative variables. The aim of this presentation is to illustrate the use of this index to calculate its range, to estimate errors in the index, its sensitivity, and the number of significant steps in the index. The measure of sensitivity of the summary index was analyzed for the signal-to-noise ratio (SNR), the reference change value (RCV) and the confidence interval (CI). If identical errors were assumed in patient self-rated health and clinically judged disease manifestations, such as tumours and fistulas, the majority of the variance of the index was caused by the self-rated experience of health, the number of days over which the individual variable was rated, and the prognostic multiplier of each variable.The range of the index has no upper limit, but can be estimated to 403 units, of which patient self-rating of well-being account for up to one-third of the summary index maximal score range. The median signal noise measure of index sensitivity was 18 SDs. The two disease classification limits of 150 units for moderate disease and 450 for severe disease on average cover an interval of limit ±41.5 units vs. ±60.5 units. In judgments on change in clinical outcome the RCV interval of steps of 121 units are valid. Conclusion: Both variance and range of the CDAI summary score are primarily decided by the self-rated experience of well-being. Variables on disease signs have a minor impact on the index. Rating of the two important outcome parameters: Self-experienced health and medical outcome would favourably be given in two individual scores.Presented at the 10th Conference Quality in the Spotlight, March 2005, Antwerp, Belgium.     

细菌性阴道病与甲硝唑治疗对妊娠结局的影响探讨

目的探讨细菌性阴道病和甲硝唑治疗对妊娠结局的影响。方法选取吉水县醪桥镇人口与计划生育服务所2014年7月至2015年7月收治的120例中晚期妊娠合并BV者,根据自愿原则分为治疗组和未治疗组(C组)。治疗组中口服用药为A组,阴道用药为B组。结果治疗组中两种不同用药方式都对妊娠合并BV患者有着显著的治疗效果,两组比较无统计学意义(P0.05);治疗组妊娠结局总不良率仅为10%,未治疗组中总不良率高达73.3%,对比差距显著,具备统计学意义(P0.05)。结论对妊娠期合并细菌性阴道病妇女使用甲硝唑治疗,对提升妊娠期妇女生活品质和降低不良妊娠风险有着关键的作用,同时具有十分重要的参考意义。