Determination of thyreostat residues from bovine matrices using high-performance liquid chromatography

High-performance liquid chromatography (HPLC) methodologies were evaluated for the detection and quantification of thyreostatic drug residues in cattle serum and thyroid tissue. The paper details a protocol, using a simple ethyl acetate extraction for the determination of thiouracil, tapazole, methyl thiouracil, propyl thiouracil and phenyl thiouracil in thyroid tissue. Using two sequential HPLC injections, and quantitative analysis, in two steps, all five thyreostats were detectable at concentrations greater than 2.45-4.52 ng/g. Modifications to a published method for detection of thyreostatic residues in serum involving the addition of mercaptoethanol and a freezing step are described. The modifications improved sensitivity and allowed detection of the five thyreostats at levels greater than 16.98-35.25 ng/ml. Young bulls were treated with thyreostats to demonstrate the validity of the methodologies described. Administered thyreostats were not absorbed equally by the test animals and the compounds were not all detected in the serum samples removed at 7 days following drug withdrawal. These experiments indicate the necessity to be able to detect thyreostat residues in a variety of matrices. (C) 1998 Elsevier Science B.V. All rights reserved.

A Novel Selective Muscarinic Acetylcholine Receptor Subtype 1 Antagonist Reduces Seizures without Impairing Hippocampus-Dependent Learning

Previous studies suggest that selective antagonists of specific subtypes of muscarinic acetylcholine receptors (mAChRs) may provide a novel approach for the treatment of certain central nervous system (CNS) disorders, including epileptic disorders, Parkinson's disease, and dystonia. Unfortunately, previously reported antagonists are not highly selective for specific mAChR subtypes, making it difficult to definitively establish the functional roles and therapeutic potential for individual subtypes of this receptor subfamily. The M 1 mAChR is of particular interest as a potential target for treatment of CNS disorders. We now report the discovery of a novel selective antagonist of M-1 mAChRs, termed VU0255035 [N-(3-oxo-3-(4-(pyridine-4-yl)piperazin-1-yl)propyl)benzo[c][1,2,5]thiadiazole-4-sulfonamide]. Equilibrium radioligand binding and functional studies demonstrate a greater than 75-fold selectivity of VU0255035 for M-1 mAChRs relative to M-2-M-5. Molecular pharmacology and mutagenesis studies indicate that VU0255035 is a competitive orthosteric antagonist of M-1 mAChRs, a surprising finding given the high level of M-1 mAChR selectivity relative to other orthosteric antagonists. Whole-cell patch-clamp recordings demonstrate that VU0255035 inhibits potentiation of N-methyl-D-aspartate receptor currents by the muscarinic agonist carbachol in hippocampal pyramidal cells. VU0255035 has excellent brain penetration in vivo and is efficacious in reducing pilocarpine-induced seizures in mice. We were surprised to find that doses of VU0255035 that reduce pilo-carpine-induced seizures do not induce deficits in contextual freezing, a measure of hippocampus-dependent learning that is disrupted by nonselective mAChR antagonists. Taken together, these data suggest that selective antagonists of M-1 mAChRs do not induce the severe cognitive deficits seen with nonselective mAChR antagonists and could provide a novel approach for the treatment certain of CNS disorders.

Dry gel conversion of organosilane templated mesoporous silica: from amorphous to crystalline catalysts for benzene oxidation

Mesoporous silica grown using [3-(trimethoxysilyl)propyl]octadecyldimethylammonium chloride as the mesoporogen in the presence of Fe and Al is X-ray amorphous, but contains very small domains with features of MFI zeolite as evidenced by IR and Raman spectroscopy. When applied as a catalyst, this amorphous sample shows good performance in the selective oxidation of benzene using nitrous oxide. Addition of tetrapropylammonium as structure directing agent to the as-synthesized mesoporous silica and subsequent dry gel conversion results in the formation of hierarchical Fe/ZSM-5 zeolite. During dry gel conversion the wormhole mesostructure of the initial material is completely lost. A dominant feature of the texture after crystallization is the high interconnectivity of micropores and mesopores. Substantial redistribution of low-dispersed Fe takes place during dry gel conversion towards highly dispersed isolated Fe species outside the zeolite framework. The catalytic performance in the oxidation of benzene to phenol of these highly mesoporous zeolites is appreciably higher than that of the parent material.

Hierarchical zeolites prepared by organosilane templating: A study of the synthesis mechanism and catalytic activity

The crystallization of hierarchical ZSM-5 in the presence of the organosilane octadecyl-dimethyl-(3-trimethoxysilyl-propyl)-ammonium chloride as the mesoporogen was investigated as a function of time and temperature. The synthesis by this method proceeds in two steps. The rapid formation of a predominantly amorphous disordered mesoporous aluminosilicate precursor phase is followed by the formation of globular highly mesoporous zeolite particles involving dissolution of the precursor phase. It is difficult to completely convert the initial phase into the final hierarchical zeolite. This limits the amount of aluminium built into the MFI network and the resulting Bronsted acidity. In the presence of iron, more crystalline hierarchical zeolite is obtained. These Fe-containing zeolites are excellent catalysts for the selective oxidation of benzene to phenol. Their hierarchical pore structure leads to higher reaction rates due to increased mass transfer and increased catalyst longevity despite more substantial coke formation. (C) 2011 Elsevier B.V. All rights reserved.

On the Performances of Ionic Liquid-Based Electrolytes for Li-NMC Batteries

Herein, the N-butyl-N-methylpyrrolidinium bis(fluorosulfonyl)amide and the N-propyl-N-methylpyrrolidinium bis(fluorosulfonyl)amide room temperature ionic liquids, combined with the lithium bis(trifluoromethanesulfonyl)amide salt, are investigated as electrolytes for Li/LiNi1/3Mn1/3Co1/3O2 (Li/NMC) batteries. To conduct this study, volumetric properties, ionic conductivity and viscosity of the pure ionic liquids and selected electrolytes were firstly determined as a function of temperature and composition in solution. These data were then compared with those measured in the case of the standard alkyl carbonate-based electrolyte: e.g. the EC/PC/3DMC + 1 mol·L−1 LiPF6. The compatibility of the selected electrolytes with the lithium electrode was then investigated by following the evolution of Li/electrolyte interfaces through impedance measurements. Interestingly, the impedances of the investigated Li/electrolyte interfaces were found to be more than three times lower than that measured using the standard electrolyte. Finally, electrochemical performances of the ionic liquid-based electrolytes were investigated using galvanostatic charge and discharge and cyclic voltammetry of each Li/NMC cell. Using these electrolytes, each tested Li cell reaches up to 145 mA·h·g−1 at C/10 and 110 mA·h·g−1 at C with a coulombic efficiency close to 100 %.

The use of water soluble mucoadhesive gels for the intravesical delivery of epirubicin to the bladder for the treatment of non-muscle invasive bladder cancer

Objectives: To develop an epirubicin-loaded, water-soluble mucoadhesive gels that have the correct rheological properties to facilitate their delivery into the bladder via a catheter, while allowing for their spread across the bladder wall with limited expansion of the bladder and increasing the retention of epirubicin in the bladder and flushing with urine.

Methods: Epirubicin-loaded hydroxyl ethyl cellulose (HEC) and hydroxy propyl methyl cellulose (HPMC) gels were manufactured and tested for their rheological properties. Their ability to be pushed through a catheter was also assessed as was their in-vitro drug release, spreading in a bladder and retention of epirubicin after flushing with simulated urine.

Key findings: Epirubicin drug release was viscosity-dependent. The 1 and 1.5% HEC gels and the 1, 1.5 and 2% HPMC gels had the correct viscosity to be administered through a model catheter and spread evenly across the bladder wall under the pressure of the detrusor muscle. The epirubicin-loaded gels had an increased retention time in the bladder when compared with a standard intravesical solution of epirubicin, even after successive flushes with simulated urine.

Conclusion: The increased retention of epirubicin in the bladder by the HEC and HPMC gels warrant further investigation, using an in-vivo model, to assess their potential for use as treatment for non-muscle-invasive bladder cancer.

Acoustic and Volumetric Properties of Diluted Solutions of Water in Ionic Liquids

Herein, we report the densities and speeds of sound in binary mixtures of three hydrophobic and one hydrophilic ionic liquids: 1-butyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide, [C4mim][NTf2], 1-butyl-1-methylpyrrolidinium bis[(trifluoromethyl)sulfonyl]imide, [C4mpyr][NTf2], 1-propyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide, [C3mim][NTf2] and 1-ethyl-3-methylimidazolium thiocyanate, [C2mim][SCN], with water at 298.15 K and 0.1 MPa. The concentration range of water, which encompassed relatively small values well below the saturation point, is often regarded as an impurity for hydrophobic ionic liquids. On the basis of experimental results the molar volume, adiabatic molar compressibility, partial molar volume and apparent molar volume, as well as, partial molar and apparent molar isentropic compressibility properties were then calculated. Interesting results are obtained using the solutions based on the hydrophilic [C2mim][SCN], since these mixtures are characterized by relatively low density and high values of speed of sound. Furthermore, the partial molar volumes and partial molar adiabatic compressibilities of water in solution with [C2mim][SCN] are the lowest among the investigated in mixtures with ionic liquids. However, in the case of the hydrophobic ionic liquid solutions, only small differences are observed for molar adiabatic compressibilities with the change of the cation structure, i.e. for water + [C4mim][NTf2] or + [C4mpyr][NTf2]. A more pronounced difference has been observed for the partial molar compressibility of water in solutions with these two ionic liquids.

An Ultrasonic Relaxation Study of 1-Alkyl-3-Methylmidazolium-Based Room Temperature Ionic Liquids: Probing the Role of Alkyl Chain Length in the Cation

Ultrasound absorption spectra of four 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide were determined as a function of the alkyl chain length on the cation from 1-propyl- to 1-hexyl- from 293.15 to 323.15 K at ambient pressure. Herein, the ultrasound absorption measurements were carried out using a standard pulse technique within a frequency range from 10 to 300 MHz. Additionally the speed of sound, density and viscosity have been measured. The presence of strong dissipative processes during the ultrasound wave propagation was found experimentally, i.e. relaxation processes in the megahertz range were observed for all compounds over the whole temperature range. The relaxation spectra (both relaxation amplitude and relaxation frequency) were shown to be dependent on the alkyl side chain length of the 1-alkyl-3-methylimidazolium ring. In most cases, a single Debye model described the absorption spectra very well. However, a comparison of the determined spectra with the spectra of a few other imidazolium-based ionic liquids reported in the literature (in part recalculated in this work) shows that the complexity of the spectra increases rapidly with the elongation of the alkyl chain length on the cation. This complexity indicates that both the volume viscosity and the shear viscosity are involved in relaxation processes even in relatively low frequency ranges. As a consequence, the sound velocity dispersion is present at relatively low megahertz frequencies.