A dried blood spot assay with HPLC–MS/MS for the determination of larotrectinib in mouse blood and its application to a pharmacokinetic study

Larotrectinib is a first-generation tropomyosin kinase inhibitor, approved for the treatment of solid tumors. In this paper, we present a validated dried blood spot (DBS) method for the quantitation of larotrectinib from mouse blood using HPLC–MS/MS, which was operated under multiple reaction monitoring mode. To the DBS disc cards, acidified methanol enriched with internal standard (IS; enasidenib) was added and extracted using tert-butyl methyl ether as an extraction solvent with sonication. Chromatographic separation of larotrectinib and the IS was achieved on an Atlantis dC₁₈ column using 10 mm ammonium formate–acetonitrile (30:70, v/v) delivered at a flow-rate of 0.80 ml/min. Under these optimized conditions, the retention times of larotrectinib and the IS were ~0.93 and 1.37 min, respectively. The total run time was 2.50 min. Larotrectinib and the IS were analyzed using positive ion scan mode and parent–daughter mass to charge ion (m/z) transitions of 429.1 → 342.1 and 474.1 → 267.1, respectively, were used for the quantitation. The calibration range was 1.06–5,080 ng/ml. No matrix effect or carryover was observed. Hematocrit did not influence DBS larotrectinib concentrations. All of the validation parameters met the acceptance criteria. The applicability of the validated method was shown in a mouse pharmacokinetic study.     

T1Effects in Sequential Dynamic Susceptibility Contrast Experiments

Residual effects of an initial bolus of gadolinium contrast agent have been previously demonstrated in sequential dynamic susceptibility contrast MR experiments. While these residual effects quickly reach a saturation steady state, their etiology is uncertain, and they can lead to spurious estimates of hemodynamic parameters in activation experiments. The possible influence ofT₁effects is now investigated with experiments in whichT₁weighting is varied as well as with serial regionalT₁measurements. Little evidence for significant residualT₁effects is found, suggesting instead that susceptibility effects underlie these observations. An initial saturation dose of contrast agent minimizes this effect.     

Optical Glucose Monitoring Based on Femtosecond Two-Color Pulse Interferometry

We demonstrate the potential of femtosecond two-color pulse interferometry for in vitro optical glucose monitoring, by dispersion of the group refractive index in a glucose solution sample with respect to a red-color light and a blue-color light. By comparison with femtosecond one-color pulse interferometry, the basic performance of the present system with regard to sensitivity, quantitativeness, and tolerance to surrounding disturbances, is evaluated. The resulting accuracy and precision of glucose determination are 77 and 118mg/dl for 10-mm-sample-thickness, respectively. This near-common-path configuration of the two-color pulse light provides good stability to fluctuations of sample temperature, which is important in clinical applications. Considering the performance of femtosecond two-color pulse interferometry as an optical glucose sensor, a suitable measurement site for in vivo optical glucose monitoring is discussed.     

血压指标的聚类分析

利用353人的血压数据,运用2种不同的聚类分析方法对15个血压指标分类并挑选典型指标:一是利用SAS软件包中提供的变量聚类过程(VARCLUS过程)对指标进行裂类聚类分析;一是利用SAS中提供的样品聚类过程(CLUSTER过程)对指标进行系统聚类分析.2种方法得到了相同的结果:15个指标分成了4类,得到4个典型指标:BPR(收缩压与舒张压比值),BPP(收缩压与舒张压乘积),MAPPr(平均动脉压与脉率乘积),BPRPr(BPR与脉率乘积).     

Endoscopic Observation of Tissue by Narrowband Illumination

We propose a new illumination method for a medical endoscope: narrow band imaging (NBI), in which the spectral bandwidth of the filtered light is narrowed. To confirm how the spectral specifications of the filtered light influence a reproduced image, an experiment was conducted observing the endoscopic images of the back mucosa of a human tongue. In addition, the effect of NBI on endoscopic images was investigated through preliminary clinical tests in colonoscopy and upper gastrointestinal endoscopy. It has been shown that NBI can enhance the capillary pattern and the crypt pattern on the mucosa. These patterns are useful features for diagnosing an early cancer.     

家兔膀胱动脉的解剖学研究

用血管铸型和透明方法观察了家兔膀胱的血供情况。膀胱动脉主要起自脐动脉，沿膀胱侧缘行向膀胱顶，沿途发出１～４支基本对称的分支分布于膀胱前面，两侧膀胱动脉的分支在其表面有吻合现象。膀胱动脉及其分支均呈不同程度的弯曲或弹簧状，可能是适应膀胱生理性增大的结构基础。     

统计分析在血铅检测中的应用

该文针对河海大学幼儿园接受血铅调测的337名幼儿,以对家长问卷调查的方式,运用方差分析、假设检验及区间估计的方法对这些幼儿的血铅超标情况进行了统计分析.结果表明,虽然各年级幼儿血铅浓度无显著差异,但是大、中班幼儿(4～6岁)由于受环境铅污染机会多于小班幼儿和托班幼儿,故血铅超标率稍高;幼儿经常挑食、外出方式以助力车或摩托车为主、家长经常吸烟、家长职业性接触铅及其化合物等是血铅浓度超标的主要因素.     

对大学生不同血型行为差异性的研究

本文运用了“内田-克列别林的耐力测查表”、“内曼(Ney-mann)和科尔斯太特(Kohlstedt)的内、外向性格调查表”,对400余名大学生的血型类别进行了测量,此外还运用了A型血和B型血的凝集反应时的测定方法进行了研究。结果表明,不同血型的大学生其行为有明显差异性,给学校管理人员和学生职业选择问题提出了参考意见。     

Succinic acid adsorption from fermentation broth and regeneration

More than 25 sorbents were tested for uptake of succinic acid from aqueous solutions. The best resins were then tested for successive loading and regeneration using hotwater. The key desired properties for an ideal sorbent are high capacity, complete stable regenerability, and specificity for the product. The best resins have a stable capacity of about 0.06 g of succinic acid/g of resin at moderate concentrations (1–5 g/L) of succinic acid. Several sorbents were tested more exhaustively for uptake of succinic acid and for successive loading and regeneration using hot water. One resin, XUS 40285, has a good stable isotherm capacity, prefers succinate over glucose, and has good capacities at both acidic and neutral pH. Succinic acid was removed from simulated media containing salts, succinic acid, acetic acid, and sugar using a packed column of sorbent resin, XUS 40285. The fermentation byproduct, acetate, was completely separated from succinate. A simple hot water regeneration successfully concentrated succinate from 10 g/L (inlet) to 40–110 g/L in the effluent. If successful, this would lower separation costs by reducing the need for chemicals for the initial purification step. Despie promising initial results of good capacity (0.06 g of succinic/g of sorbent), 70% recovery using hot water, and a recovered concentration of >100 g/L, this regeneration was not stable over 10 cycles in the column. Alternative regeneration schemes using acid and base were examined. Two (XUS 40285 and XFS-40422) showed both good stable capacities for succinic acid over 10 cycles and >95% recovery in a batch operation using a modified extraction procedure combining acid and hot water washes. These resins showed comparable results with actual broth.