Use of isotope ratio mass spectrometry to differentiate between endogenous steroids and synthetic homologues in cattle: A review

Although substantial technical advances have been achieved during the past decades to extend and facilitate the analysis of growth promoters in cattle, the detection of abuse of synthetic analogs of naturally occurring hormones has remained a challenging issue. When it became clear that the exogenous origin of steroid hormones could be traced based on the ¹³C/¹²C isotope ratio of the substances, GC/C/IRMS has been successfully implemented to this aim since the end of the past century. However, due to the costly character of the instrumental setup, the susceptibility of the equipment to errors and the complex and time consuming sample preparation, this method is up until now only applied by a limited number of laboratories. In this review, the general principles as well as the practical application of GC/C/IRMS to differentiate between endogenous steroids and exogenously synthesized homologous compounds in cattle will be discussed in detail, and will be placed next to other existing and to be developed methods based on isotope ratio mass spectrometry. Finally, the link will be made with the field of sports doping, where GC/C/IRMS has been established within the World Anti-Doping Agency (WADA) approved methods as the official technique to differentiate between exogenous and endogenous steroids over the past few years.     

A Novel Cyclodextrin-containing Glass Thermoplastic System (GTS) for Formulating Poorly Water Soluble Drug Candidates: Preclinical and Clinical Results

We present a novel solid solution/dispersion technology with glass thermoplastic properties that provide good dissolution rates and oral bioavailabilities for poorly water-soluble weak bases. In this process, a thermoplastic gum was prepared by mixing a polyhydroxy acid such as citric acid or tartaric acid with a weakly basic drug, hydroxypropyl--cyclodextrin (HP--CD) and a cellulose polymer such as hydroxypropylmethylcellulose (HPMC) in a protic solvent. Removal of the solvent gave a material which could be loaded into hard gelatin capsules. Several model compounds were processed in this manner including methylene blue and itraconazole. The resulting data indicated that dissolution properties of GTS's based on methylene blue was pH independent and rapid with 80% dissolved within 30 min. Three GTS formulations of itraconazole containing 100 mg of the drug and 500 mg of citric acid as well as various concentrations of HP--CD and HMPC were found to dissolve rapidly (100% in 45 min). One of these formulations was selected for human pharmacokinetic evaluation and demonstrated significant oral bioavailability relative to unmanipulated drug.The studies suggest that the components of the GTS provide for solubilization through complexation and reduced pH and that the cellulose polymer acts to inhibit recrystallization of the supersaturated solution formed. The rationaldevelopment of the GTS dosage form can be useful for generating acceptable formulations for poorly water-soluble drug candidates.     

Obtaining the Maximum Likelihood Estimates in Incomplete R × C Contingency Tables Using a Poisson Generalized Linear Model

Abstract

This article describes estimation of the cell probabilities in an R × C contingency table with ignorable missing data. Popular methods for maximizing the incomplete data likelihood are the EM-algorithm and the Newton-Raphson algorithm. Both of these methods require some modification of existing statistical software to get the MLEs of the cell probabilities as well as the variance estimates. We make the connection between the multinomial and Poisson likelihoods to show that the MLEs can be obtained in any generalized linear models program without additional programming or iteration loops.     

Recent Updates on the Barrier Properties of Ethylene Vinyl Alcohol Copolymer (EVOH): A Review

The gas barrier properties of ethylene vinyl alcohol copolymer (EVOH) against oxygen, carbon dioxide and water vapor have been widely investigated in relation to different material characteristics, environmental conditions and new processing technologies. Recently, EVOH is gaining more attention as a barrier material against other gases and organic substances such as aromas, flavors, fuels, chemicals (e.g., BTEX), and as a functional barrier, e.g., to avoid mineral oil migration. This review contains an update on permeability data of EVOH emphasizing its potential as a barrier material for new and versatile applications in food and pharmaceutical packaging, agriculture, construction, automotive, etc.     

Synthetic Enterobacterial Common Antigen (ECA) for the Development of a Universal Immunotherapy for Drug‐Resistant Enterobacteriaceae

All Enterobacteriaceae express a polysaccharide known as enterobacterial common antigen (ECA), which is an attractive target for the development of universally acting immunotherapies. The first chemical synthesis of ECA‐derived oligosaccharides for the development of such therapies is described. A number of synthetic challenges had to be addressed, including the development of concise synthetic procedures for unusual monosaccharides, the selection of appropriate orthogonal protecting groups, the development of stereoselective glycosylation methods, appropriate timing for the introduction of the carboxylic acid groups on the ManpNAcA moieties, and the selection of appropriate conditions for the reduction of multiple azido moieties. The synthetic compounds were employed to uncover immunodominant moieties of ECA. Furthermore, a monoclonal antibody (mAb) was developed that binds to ECA and can selectively recognize a wide range of Enterobacteriaceae species.     

A Modelling Study of Evolving Particle-laden Turbulent Pipe-flow

An Eulerian turbulent two phase flow model using kinetic theory of granular flows for the particle phase was developed in order to study evolving upward turbulent gas particle flows in a pipe. The model takes the feedback of the particles into account and its results agree well with experiments. Simulations show that the pipe length required for particle laden turbulent flow to become fully developed is up to five times longer than an unladen flow. To increase the understanding of the dependence of the development length on particle diameter a simple model for the expected development length was derived. It shows that the development length becomes shorter for increasing particle diameters, which agrees with simulations up to a particle diameter of 100 ??m. Thereafter the development length becomes longer again for increasing particle diameters because larger particles need a longer time to adjust to the velocity of the carrier phase.     

First-principles study of the magnetic exchange forces between the RuO2(110) surface and Fe tip

Magnetic exchange force microscopy (MExFM) is an important experimental technique for mapping the magnetic structure of surfaces with atomic resolution relying on the spin-dependent short-range exchange interaction between a magnetic tip and a magnetic surface. RuO₂ is a significant compound with applications in heterogeneous catalysis and electrocatalysis. It has been characterized recently as an antiferromagnetic (AFM) material, and its magnetism has been predicted somewhat surprisingly to play an important role in its catalytic properties. In the current study, we explore theoretically whether MExFM can visualize the magnetic surface structure of RuO₂. We use density functional theory (DFT) calculations to extract the exchange interactions between a ferromagnetic Fe tip interacting with an AFM RuO₂(110) surface, as a function of tip-surface distance and the position of the tip over the surface. Mimicking the MExFM experiment, these data are then used to calculate the normalized frequency shift of an oscillating cantilever tip versus the minimum tip-surface distance, and construct corrugation height line profiles. It is found that the exchange interaction between tip and surface is strongest for a parallel configuration of the spins of the tip and of the surface; it is weakest for an anti-parallel orientation. In a corrugation profile, this gives rise to a sizable height difference of 25 pm between the spin-up and spin-down Ru atoms in the RuO₂(110) surface at a normalized frequency shift =−10.12 fNm^1/2. The O atoms in the surface are not or hardly visible in the corrugation profile.