Metabolic urinary profiling of alcohol hepatotoxicity and intervention effects of Yin Chen Hao Tang in rats using ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry

This paper was designed to study metabonomic characters of the hepatotoxicity induced by alcohol and the intervention effects of Yin Chen Hao Tang (YCHT), a classic traditional Chinese medicine formula for treatment of jaundice and liver disorders in China. Urinary samples from control, alcohol- and YCHT-treated rats were analyzed by ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC/ESI-QTOF-MS) in positive ionization mode. The total ion chromatograms obtained from the control, alcohol- and YCHT-treated rats were easily distinguishable using a multivariate statistical analysis method such as the principal components analysis (PCA). The greatest difference in metabolic profiling was observed from alcohol-treated rats compared with the control and YCHT-treated rats. The positive ions m/z 664.3126 (9.00 min) was elevated in urine of alcohol-treated rats, whereas, ions m/z 155.3547 (10.96 min) and 708.2932 (9.01 min) were at a lower concentration compared with that in urine of control rats, however, these ions did not indicate a statistical difference between control rats and YCHT-treated rats. The ion m/z 664.3126 was found to correspond to ceramide (d18:1/25:0), providing further support for an involvement of the sphingomyelin signaling pathway in alcohol hepatotoxicity and the intervention effects of YCHT.

Development of a rapid and validated method for investigating the metabolism of scoparone in rat using ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry

Scoparone (6,7-dimethoxycoumarin) is known to have a wide range of pharmacological properties. In this study, a rapid and validated ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC/ESI-QTof-MS) method was developed to investigate the metabolism of scoparone in rat for the first time. The new method reduced the sample handling and analytical time by three- to six-fold, and the detection limit by five- to 1000-fold, compared to published methods. Far more metabolites were detected and identified compared to published data, which were preliminarily identified as scopoletin, isoscopoletin, isofraxidin, and fraxidin, respectively, when subjected to tandem mass spectrometry analyses. It is found that the metabolic trajectory of scoparone in rat focused on phase I metabolism which is obviously different from published results, and revealed a wide range of pharmacological properties of scoparone partly attributed to the bioactivities of its metabolites.

Simultaneous determination of 6,7-dimethylesculetin and geniposide in rat plasma and its application to pharmacokinetic studies of Yin Chen Hao Tang preparation

A method for the rapid and simultaneous determination of 6,7-dimethylesculetin (CAS 120-08-1) and geniposide (CAS 24512-63-8) in rat plasma has been developed, using validated high performance liquid chromatography (HPLC) with solid phase extraction (SPE). The HPLC analysis was performed on a commercially available column (200 mm x 4.6 mm, 5 microm) with acetonitrile-methanol-0.1% aqueous formic acid as mobile phase and the UV detection at 343 nm and 238 nm for 6,7-dimethylesculetin and geniposide, respectively. The calibration curves for 6,7-dimethylesculetin and geniposide were linear over the range 0.4-25.6 microg/mL and 1.12-71.68 microg/mL, respectively. The lower limits of quantitation were 0.40 microg/ mL and 1.12 microg/mL, and the lower limits of detection were 0.06 microg/mL and 0.09 microg/ mL, respectively. The intra-day and inter-day precision for 6,7-dimethylesculetin and geniposide were < 5%, whereas the absolute recovery percentages were > 74%. A successful application of the developed HPLC analysis was demonstrated for the pharmacokinetic study of a Traditional Chinese Medicine formula of Yin Chen Hao Tang preparation.

Using natural user interfaces for collaborative process modelling in virtual environments

A demo video showing the BPMVM prototype using several natural user interfaces, such as multi-touch input, full-body tracking and virtual reality.

Improved ultra-performance liquid chromatography with electrospray ionization quadrupole-time-of-flight high-definition mass spectrometry method for the rapid analysis of the chemical constituents of a typical medical formula: Liuwei Dihuang Wan

Liuwei Dihuang Wan (LWD), a classic Chinese medicinal formulae, has been used to improve or restore declined functions related to aging and geriatric diseases, such as impaired mobility, vision, hearing, cognition and memory. It has attracted increasingly much attention as one of the most popular and valuable herbal medicines. However, the systematic analysis of the chemical constituents of LDW is difficult and thus has not been well established. In this paper, a rapid, sensitive and reliable ultra-performance liquid chromatography with electrospray ionization quadrupole time-of-flight high-definition mass spectrometry (UPLC-ESI-Q-TOF-MS) method with automated MetaboLynx analysis in positive and negative ion mode was established to characterize the chemical constituents of LDW. The analysis was performed on a Waters UPLCTM HSS T3 using a gradient elution system. MS/MS fragmentation behavior was proposed for aiding the structural identification of the components. Under the optimized conditions, a total of 50 peaks were tentatively characterized by comparing the retention time and MS data. It is concluded that a rapid and robust platform based on UPLC-ESI-Q-TOF-MS has been successfully developed for globally identifying multiple-constituents of traditional Chinese medicine prescriptions. This is the first report on systematic analysis of the chemical constituents of LDW. This article is protected by copyright. All rights reserved.

An effort towards understanding the sources of impurities in generating nanoparticles via liquid-phase methods

Generating nano-sized materials of a controlled size and chemical composition is essential for the manufacturing of materials with enhanced properties on an industrial scale, as well as for research purposes, such as toxicological studies. Among the generation methods for airborne nanoparticles (also known as aerosolisation methods), liquid-phase techniques have been widely applied due to the simplicity of their use and their high particle production rate. The use of a collison nebulizer is one such technique, in which the atomisation takes place as a result of the liquid being sucked into the air stream and injected toward the inner walls of the nebulizer reservoir via nozzles, before the solution is dispersed. Despite the above-mentioned benefits, this method also falls victim to various sources of impurities (Knight and Petrucci 2003; W. LaFranchi, Knight et al. 2003). Since these impurities can affect the characterization of the generated nanoparticles, it is crucial to understand and minimize their effect.

Simultaneous determination of aldrin, dieldrin, endrin, heptachlor, and p,p'-DDT in medicinal plant extracts using a novel high performance liquid chromatography method

A high performance liquid chromatographic method for the simultaneous determination of five organochlorine pesticides (aldrin, p,p’-DDT, dieldrin, endrin, and heptachlor) was developed. The method was used to determine the levels of these pesticides in medicinal plant samples. Analysis was carried out using a Merck LiChrospher 100 RP C18 (5 μm) column with a gradient solvent system of acetonitrile-water and PDA UV detection (224 nm). Quantification was carried out by the external standard method. The limit of detection for the utilized method was below the local legal limits (ANZFA) for similar plant materials for all 5 pesticides excepting endrin. Medicinal plant extracts were further analyzed by conventional GC-ECD and GC-NPD means using SPE and GPC cleanup as required.

High performance liquid chromatography determined alkamide levels in Australian-grown Echinacea spp.

Extracts of Echinacea spp. are widely used as therapeutic immunostimulants with such activity being attributed in part to the alkamide fractions of these plants. Using high performance liquid chromatography, the levels of 8 alkamides, including 2 tetraene alkamides (dodeca-2E, 4E, 8Z, 10E/Z-tetraenoic acid isobutylamide), were quantitatively determined in 2 Australian-grown Echinacea spp. Overall, the levels of alkamides in Australian-grown E. angustifolia were found to be comparable with levels obtained in this study and other studies for USA and European Echinacea spp. However, results obtained for one sample of E. angustifolia suggested that it may have been mislabelled and that it was most likely a sample of E. pallida. Levels of tetraene alkamides in Australian-grown E. purpurea were also similar to, if not higher, than levels which have been reported for the same species grown in Germany and the USA. Preliminary studies on the stability of alkamide compounds in E. angustifolia indicated that they are susceptible to degradation, with a 13% loss of alkamide level over 2 months. Overall, results indicate that there is considerable potential to develop Echinacea as a viable crop in Australia.

Ageing, technology anxiety and intuitive use of complex interfaces

This paper presents the outcome of a study that investigated the relationships between technology prior experience, self-efficacy, technology anxiety, complexity of interface (nested versus flat) and intuitive use in older people. The findings show that, as expected, older people took less time to complete the task on the interface that used a flat structure when compared to the interface that used a complex nested structure. All age groups also used the flat interface more intuitively. However, contrary to what was hypothesised, older age groups did better under anxious conditions. Interestingly, older participants did not make significantly more errors compared with younger age groups on either interface structures.

Galvanic replacement mediated transformation of Ag nanospheres into dendritic Au--Ag nanostructures in the ionic liquid [BMIM][BF4]

We demonstrate an unusual shape transformation of Ag nanospheres into {111}-oriented Au–Ag dendritic nanostructures by a galvanic replacement reaction in the ionic liquid (IL) 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]).

High energy states of gold and their importance in electrocatalytic processes at surfaces and interfaces

The ability of metals to store or trap considerable amounts of energy, and thus exist in a non-equilibrium or metastable state, is very well known in metallurgy; however, such behaviour, which is intimately connected with the defect character of metals, has been largely ignored in noble metal surface electrochemistry. Techniques for generating unusually high energy surface states for gold, and the unusual voltammetric responses of such states, are outlined. The surprisingly high (and complex) electrocatalytic activity of gold in aqueous media is attributed to the presence of a range of such non-equilibrium states as the vital entities at active sites on conventional gold surfaces. The possible relevance of these ideas to account for the remarkable catalytic activity of oxide-supported gold microparticles is briefly outlined.

Auto-inhibition of hydrogen gas evolution on gold in aqueous acid solution

It was demonstrated recently that dramatic changes in the redox behaviour of gold/aqueous solution interfaces may be observed following either cathodic or thermal electrode pretreatment. Further work on the cathodic pretreatment of gold in acid solution revealed that as the activity of the gold surface was increased, its performance as a substrate for hydrogen gas evolution under constant potential conditions deteriorated. The change in activity of the gold atoms at the interface, which was attributed to a hydrogen embrittlement process (the occurrence of the latter was subsequently checked by surface microscopy), was confirmed, as in earlier work, by the appearance of a substantial anodic peak at ca. 0.5 V (RHE) in a post-activation positive sweep. Changes in the catalytic activity of a metal surface reflect the fact that the structure (or topography), thermodynamic activity and electronic properties of a surface are dependent not only on pretreatment but also, in the case of the hydrogen evolution reaction, vary with time during the course of reaction. As will be reported shortly, similar (and often more dramatic) time-dependent behaviour was observed for hydrogen gas evolution on other metal electrodes.

Morphology changes and mechanistic aspects of the electrochemically-induced reversible solid-solid transformation of microcrystalline TCNQ into Co TCNQ 2-based materials (TCNQ= 7, 7, 8, 8-Tetracyanoquinodimethane)

The chemically reversible solid−solid phase transformation of a TCNQ-modified glassy carbon, indium tin oxide, or metal electrode into Co\[TCNQ]2(H2O)2 material in the presence of Co2+(aq) containing electrolytes has been induced and monitored electrochemically. Voltammetric data reveal that the TCNQ/Co\[TCNQ]2(H2O)2 interconversion process is independent of electrode material and identity of cobalt electrolyte anion. However, a marked dependence on electrolyte concentration, scan rate, and method of electrode modification (drop casting or mechanical attachment) is found. Cyclic voltammetric and double potential step chronoamperometric measurements confirm that formation of Co\[TCNQ]2(H2O)2 occurs through a rate-determining nucleation and growth process that initially involves incorporation of Co2+(aq) ions into the reduced TCNQ crystal lattice at the TCNQ|electrode|electrolyte interface. Similarly, the reverse (oxidation) process, which involves transformation of solid Co\[TCNQ]2(H2O)2 back to parent TCNQ crystals, also is controlled by nucleation−growth kinetics. The overall chemically reversible process that represents this transformation is described by the reaction:  2TCNQ0(s) + 2e- + Co2+(aq) + 2H2O \[Co(TCNQ)2(H2O)2](s). Ex situ SEM images illustrated that this reversible TCNQ/Co\[TCNQ]2(H2O)2 conversion process is accompanied by drastic size and morphology changes in the parent solid TCNQ. In addition, different sizes of needle-shaped nanorod/nanowire crystals of Co\[TCNQ]2(H2O)2 are formed depending on the method of surface immobilization.

AFM study of morphological changes associated with electrochemical solid--solid transformation of three-dimensional crystals of TCNQ to metal derivatives (metal= Cu, Co, Ni; TCNQ= tetracyanoquinodimethane)

In situ atomic force microscopy (AFM) allows images from the upper face and sides of TCNQ crystals to be monitored during the course of the electrochemical solid–solid state conversion of 50 × 50 μm2 three-dimensional drop cast crystals of TCNQ to CuTCNQ or M[TCNQ]2(H2O)2 (M = Co, Ni). Ex situ images obtained by scanning electron microscopy (SEM) also allow the bottom face of the TCNQ crystals, in contact with the indium tin oxide or gold electrode surface and aqueous metal electrolyte solution, to be examined. Results show that by carefully controlling the reaction conditions, nearly mono-dispersed, rod-like phase I CuTCNQ or M[TCNQ]2(H2O)2 can be achieved on all faces. However, CuTCNQ has two different phases, and the transformation of rod-like phase 1 to rhombic-like phase 2 achieved under conditions of cyclic voltammetry was monitored in situ by AFM. The similarity of in situ AFM results with ex situ SEM studies accomplished previously implies that the morphology of the samples remains unchanged when the solvent environment is removed. In the process of crystal transformation, the triple phase solid∣electrode∣electrolyte junction is confirmed to be the initial nucleation site. Raman spectra and AFM images suggest that 100% interconversion is not always achieved, even after extended electrolysis of large 50 × 50 μm2 TCNQ crystals.

Electrochemically-induced TCNQ/Mn TCNQ 2 (H2O) 2 (TCNQ= 7, 7, 8, 8-Tetracyanoquinodimethane) solid-solid interconversion : two voltammetrically distinct processes that allow selective generation of nanofiber or nanorod network morphologies

Unlike the case with other divalent transition metal M\[TCNQ](2)(H(2)O)(2) (M = Fe, Co, Ni) analogues, the electrochemically induced solid-solid phase interconversion of TCNQ microcrystals (TCNQ = 7,7,8,8-tetracyanoquinodimethane) to Mn\[TCNQ](2)(H(2)O)(2) occurs via two voltammetrically distinct, time dependent processes that generate the coordination polymer in nanofiber or rod-like morphologies. Careful manipulation of the voltammetric scan rate, electrolysis time, Mn(2+)((aq)) concentration, and the method of electrode modification with solid TCNQ allows selective generation of either morphology. Detailed ex situ spectroscopic (IR, Raman), scanning electron microscopy (SEM), and X-ray powder diffraction (XRD) characterization clearly establish that differences in the electrochemically synthesized Mn-TCNQ material are confined to morphology. Generation of the nanofiber form is proposed to take place rapidly via formation and reduction of a Mn-stabilized anionic dimer intermediate, \[(Mn(2+))(TCNQ-TCNQ)(2)(*-)], formed as a result of radical-substrate coupling between TCNQ(*-) and neutral TCNQ, accompanied by ingress of Mn(2+) ions from the aqueous solution at the triple phase TCNQ/electrode/electrolyte boundary. In contrast, formation of the nanorod form is much slower and is postulated to arise from disproportionation of the \[(Mn(2+))(TCNQ-TCNQ)(*-)(2)] intermediate. Thus, identification of the time dependent pathways via the solid-solid state electrochemical approach allows the crystal size of the Mn\[TCNQ](2)(H(2)O)(2) material to be tuned and provides new mechanistic insights into the formation of different morphologies.