Quantification of Zonisamide in Dried Blood Spots and Dried Plasma Spots by UPLC–MS/MS: Application to Clinical Practice

In this research, a UHPLC–MS/MS method was developed and validated for the determination of zonisamide in dried plasma spots (DPS) and dried blood spots (DBS). Detection of zonisamide and internal standard, 1-(2,3-dichlorphenyl)piperazine, was carried out in ESI+ mode by monitoring two MRM transitions per analyte. Total run time, less than 2.5 min, was achieved using Acquity UPLC BEH Amide (2.1 × 100 mm, 1.7 µm particle size) column with mobile phase comprising acetonitrile–water (85:15%, v/v) with 0.075% formic acid. The flow rate was 0.225 mL/min, the column temperature was 30 °C and the injection volume was 3 µL. Desolvation temperature, desolvation gas flow rate, ion source temperature and cone gas flow rate were set by the IntelliStart software tool in combination with tuning. All of the Guthrie cards were scanned, and DPS/DBS areas were determined by the image processing tool. The influence of hematocrit values (20–60%) on accuracy and precision was evaluated to determine the range within which method for DBSs is free from Hct or dependency is within acceptable limits. The validated method was applied to the determination of zonisamide levels in DPS and DBS samples obtained from patients confirming its suitability for clinical application. Finally, the distribution of zonisamide into the red blood cells was estimated by correlating its DPS and DBS levels.     

Anomalous reactivity of thermo-bioconvective nanofluid towards oxytactic microorganisms

The peristaltic flow of a non-Newtonian nanofluid with swimming oxytactic microorganisms through a space between two infinite coaxial conduits is investigated. A variable magnetic field is applied on the flow. The bioconvection flow and heat transfer in the porous annulus are formulated, and appropriate transformations are used, leading to the non-dimensionalized ruling partial differential equation model. The model is then solved by using the homotopy perturbation scheme. The effects of the ger...     

Electrolyte Analysis in Blood Serum by Laser-Induced Breakdown Spectroscopy Using a Portable Laser

The fast and reliable analysis of electrolytes such as K, Na, Ca in human blood serum has become an indispensable tool for diagnosing and preventing diseases. Laser-induced breakdown spectroscopy (LIBS) has been demonstrated as a powerful analytical technique on elements. To apply LIBS to the quantitative analysis of electrolyte elements in real time, a self-developed portable laser was used to measure blood serum samples supported by glass slides and filter paper in this work. The partial least squares regression (PLSR) method was employed for predicting the concentrations of K, Na, Ca from serum LIBS spectra. Great prediction accuracies with excellent linearity were obtained for the serum samples, both on glass slides and filter paper. For blood serum on glass slides, the prediction accuracies for K, Na, Ca were 1.45%, 0.61% and 3.80%. Moreover, for blood serum on filter paper, the corresponding prediction accuracies were 7.47%, 1.56% and 0.52%. The results show that LIBS using a portable laser with the assistance of PLSR can be used for accurate quantitative analysis of elements in blood serum in real time. This work reveals that the handheld LIBS instruments will be an excellent tool for real-time clinical practice.     

血橙呈现“红色”的探讨

血橙因果肉颜色呈血红色而得名,血橙果肉的颜色深浅取决于花色苷的含量。该含量容易受温度、光照、空气湿度、pH等因素影响而发生变化。从果肉“红色”的形成、“红色”的深浅程度、血橙对人体健康的影响等3个方面对血橙的“红色”进行探讨,以期为读者科普血橙中蕴含的化学知识,感受化学与生活的紧密联系。     

Fatty Acid Binding to Human Serum Albumin in Blood Serum Characterized by EPR Spectroscopy

One of the functions of Human Serum Albumin (HSA) is binding and transport of fatty acids. This ability could be altered by the presence of several blood components such as toxins or peptides – which in turn alters the functionality of the protein. We aim at characterizing HSA and its fatty acid binding in native serum environment. Native ligand binding and deviations from normal function can be monitored by electron paramagnetic resonance (EPR) spectroscopy using spin labeled fatty acids (FAs). Blood serum from healthy individuals is used to examine healthy HSA in its natural physiological conditions at different loading ratios of protein to FAs. Among the EPR spectroscopic parameters (like hyperfine coupling, line shape, rotational correlation time and population of different binding sites) the rotational correlation time is found to differ significantly between binding sites of the protein, especially at loading ratios of four FAs per HSA. Although differences are observed between individual samples, a general trend regarding the dynamics of healthy HSA at different loading ratios could be obtained and compared to a reference of purified commercially available HSA in buffer.     

The Cytotoxicity of Metal Nanoparticles Depends on Their Synergistic Interactions

With a steady growth in use of engineered nanoparticles (NPs) in consumer products the unintended exposure to humans has increased. The risks associated with introduction of NPs in the environment have been widely investigated, but mostly for single type of NPs. Herein, a single NP and NP co-exposure study is reported: the cellular effects of silver and platinum NPs on the main components of the blood–brain barrier, human cerebral microvascular endothelial cells, and human primary astrocytes. The synergy is quantitatively evaluated as per the Chou–Talalay method. NP co-exposure synergistically inhibits proliferation of both cell types, to a greater extent for endothelial cells. In addition, astrocytes are more tolerant to NPs. The mechanism of synergy with short-duration incubation time points (up to 30 min) is further explored. Although intracellular trafficking studies and quantitative assessments of NP uptake does not explain the mechanisms of synergistic cytotoxicity, a proteomics analysis suggests that it arises from activation of an immune modulating response and deregulation of the extracellular matrix organization. The substantial synergetic effects in the co-exposure studies highlight the importance of this work in relation to assessment of the health risks associated with nanomaterials.     

Simultaneous determination of amitraz,chlordimeform, formetanate and metabolites in human blood by liquid chromatography tandem mass spectrometry with phospholipid‐removal pretreatment

In this study, a reliable ultra‐performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) method coupled with an easy, fast and effective sample pretreatment procedure was developed for simultaneous determination of amitraz, chlordimeform, formetanate and their metabolites in human blood. With the procedures of protein precipitation and a phospholipid‐removal step, the endogenous compound interference was significantly reduced, and matrix effects were significantly reduced. The linear ranges of matrix‐matched standard curves were from 0.5 to 1000 ng/mL with coefficients of determination >0.996. Very low limits of detection (0.05–0.12 ng/mL) and limits of quantitation (0.15–0.4 ng/mL) were achieved. Reasonable recoveries ranging from 88.1 to 103.5% were obtained. The intra‐day RSDs ranging from 3.2 to 8.6% and inter‐day RSDs ranging from 4.8 to 9.2% indicated good precision. With the introduction of a phospholipid‐removal step, the ME ranged from 90.1 to 98.5%. The established method was successfully applied to the analysis of a blood sample from a formetanate poisoning case. This method possesses the advantages of high sensitivity, reduced matrix effects and rapidity.     

Synthesis of the Core Oligosaccharides of Lipooligosaccharides from Campylobacter jejuni: A Putative Cause of Guillain–Barré Syndrome

The chemical synthesis of the highly branched core oligosaccharides of lipooligosaccharides (LOSs) found in Campylobacter jejuni, which causes Guillain–Barré syndrome by a preceding infection, is described. The target LOS mimics, consisting of eight or nine monosaccharides, were classified into three groups as key building blocks: ganglioside-core tetra-/pentasaccharides (GM1-/GD1a-like), l -glycero-d -manno-heptose-containing trisaccharides, and 3-deoxy-d -manno-2-octulosonic acid (KDO) residues. These synthetic fragments were obtained from commercially available monosaccharides. Less obtainable l -glycero-d -manno-heptose and KDO residues, as key components of the LOSs, were synthesized from p-methoxyphenyl d -mannoside and di-O-isopropylidene-protected d -mannose, respectively. The synthesis of α-KDO glycoside, as one of the most difficult stereocontrolled glycosidic constructions, was achieved by treating a 2,3-ene derivative of KDO with phenylselenyl trifluoromethanesulfonate as a suitable α-directing reagent. All synthetic blocks were constructed through a convergent synthetic route, which resulted in the first synthesis of structurally challenging LOS core glycans containing ganglioside GM1 and GD1a-core sequences.     

Gas-Generating,pH-Responsive Calcium Carbonate Hybrid Particles with Biomimetic Coating for Contrast-Enhanced Ultrasound Imaging

This work reports the fabrication of biocompatible and pH-sensitive hybrid polydopamine/bovine serum albumin/calcium carbonate (PDA/BSA/CaCO₃) particles via a rapid precipitation method. These hybrid particles generate hyperechogenic carbon dioxide bubbles upon exposure to low pH environments, making them ideal as a contrast agent and detector for tumor cells. This study also highlights the application of red blood cell membrane (RBC)-derived membranes as a biomimetic coating for PDA/BSA/CaCO₃ hybrid particles in order to modulate protein corona formation, a natural physiological response that alters tailored properties of most nanomaterials that are administered systemically. Results of this work demonstrate that the RBC membrane-coated hybrid particles are ideal for a wide range of biomedical applications, such as noninvasive multimodal imaging, photothermal and photodynamic therapy, and “personalized” drug delivery systems.