Comparative study in the rat of the actions of different types of stress on the release of 5-HT in raphe nuclei and forebrain areas

The effects of several stress procedures on the release of 5-HT in the dorsal and median raphe nuclei (DRN and MRN, respectively) and in forebrain structures of the rat brain innervated by both nuclei have been studied using intracerebral microdialysis. Handling for 30 sec, a saline injection and forced swimming for 5 min elevated significantly the 5-HT output in the MRN. The 5-HT output in the DRN was also enhanced by a saline injection. With regard to the forebrain structure examined, handling and forced swimming increased dialysate 5-HT in the amygdala. The injection of saline induced a slight, but significant, elevation of 5-HT in the medial prefrontal cortex. In contrast, the outflow of 5-HT was significantly reduced in the ventral hippocampus and medial prefrontal cortex following forced swimming and this effect persisted well beyond the cessation of the swim session. These results indicate that the efflux of 5-HT in the MRN appears to respond to different forms of stress, whereas that in the DRN only increases after the injection of saline. The release of 5-HT in the forebrain structures is also dependent on the type of stress procedure and the region studied.     

The interpretation of X-ray photoelectron spectra of pyrolized S-containing carbonaceous materials

Theoretical models and ab initio Hartree-Fock wavefunctions have been used to investigate the S(2p) core level binding energies (BE), of pyrolized S-containing, carbonaceous materials. Comparison between experimental and calculated data for thiophene permits the accuracy of the present approach to be established. A systematic study of different situations demonstrates that, in these materials, non-oxidized S atoms can show peaks at very high BE relative to the C(1s) peak at 285.0 eV. This study confirms that the peak at 164.1 eV corresponds to ‘thiophenic’ S atoms. On the other hand, it shows that the peaks at higher BE could correspond to S atoms replacing C atoms in three-coordinated structures of graphene layers, in agreement with the arguments suggested in the experimental works. The energetic similarity between the two peaks at very high BE makes it difficult to differentiate between them, although the results of the present study seem to suggest that the peak at experimental BE ≈ 166 eV could correspond to S atoms coordinated to two C and one H atoms at the edge of graphene layers, while the peak at ≈ 169 eV would correspond to S atoms replacing C atoms in inner positions of the graphene layers, and it is bonded to three C atoms.     

Asymmetric Intermolecular Mizoroki-Heck Reaction: From Phosphine/Phosphinite-Nitrogen to Phosphite-Nitrogen Ligands

This review discusses the latest developments in ligand design for the Pd-catalyzed asymmetric intermolecular Mizoroki-Heck reaction, from the successful phosphine/phosphinite-nitrogen ligands to the recently reported phosphite-nitrogen ligands. The presence of a biaryl phosphite group offers several advantages as a ligand scaffold for this process.     

Inroads to Predict in Vivo Toxicology-An Introduction to the eTOX Project

There is a widespread awareness that the wealth of preclinical toxicity data that the pharmaceutical industry has generated in recent decades is not exploited as efficiently as it could be. Enhanced data availability for compound comparison ("read-across"), or for data mining to build predictive tools, should lead to a more efficient drug development process and contribute to the reduction of animal use (3Rs principle). In order to achieve these goals, a consortium approach, grouping numbers of relevant partners, is required. The eTOX ("electronic toxicity") consortium represents such a project and is a public-private partnership within the framework of the European Innovative Medicines Initiative (IMI). The project aims at the development of in silico prediction systems for organ and in vivo toxicity. The backbone of the project will be a database consisting of preclinical toxicity data for drug compounds or candidates extracted from previously unpublished, legacy reports from thirteen European and European operation-based pharmaceutical companies. The database will be enhanced by incorporation of publically available, high quality toxicology data. Seven academic institutes and five small-to-medium size enterprises (SMEs) contribute with their expertise in data gathering, database curation, data mining, chemoinformatics and predictive systems development. The outcome of the project will be a predictive system contributing to early potential hazard identification and risk assessment during the drug development process. The concept and strategy of the eTOX project is described here, together with current achievements and future deliverables.     

Vitrification and further structural relaxation in the isothermal curing of an epoxy resin

Isothermal curing of an epoxy resin based on diglycidyl ether of bisphenol A, using a hardener derived from phthalic anhydride, has been performed at curing temperatures between 30 and 130°C. Samples were cured isothermally at various intervals of time and analyzed by differential scanning calorimetry (DSC), the glass transition temperature T_g, and the conversion degree being determined by the residual enthalpy technique. The vitrification phenomenon and a further structural relaxation process, occurring at curing temperatures (T_c) lower than the maximum T_g (109°C), at which T_g equalizes T_c, have been studied at curing temperatures between 30 and 100°C. The structural relaxation process is analyzed by the endothermic peak that appears superposed on T_g in dynamic DSC scans. The area of this peak (Q) is a measure of the recovery enthalpy, and thus of the extent of the relaxation process. This process begins at higher curing times (t_c) when T_c decreases because the vitrification of the system starts later. Both the enthalpy recovery (Q) and the temperature of the endothermic peak (T_m) increase with the annealing time (t_a), calculated as the difference between t_c and the time in which vitrification occurs, and tend to have a limiting value due to the fact that the system loses mobility when the free volume decreases during its asymptotic approach toward the metastable equilibrium state. Furthermore, the dependence of Q and T_m on t_a at different T_c shows that the relaxation process in partially cured resins depends on the conversion degree of the system and consequently on the crosslinking density of the network.     

Dealumination–aging pattern of REUSY zeolites contained in fluid cracking catalysts

The evolution of the properties of a REUSY zeolite contained in a fluid cracking catalyst was investigated under laboratory steam deactivation procedures and in age fractions of the corresponding equilibrium catalyst (Ecat). The aging pattern, defined by the evolution of the zeolite surface area (ZSA) related to the decrease of the unit cell size (UCS), was similar between lab-steamed zeolites and Ecat fractions. A sharp drop in ZSA occurred at ca. 2.430 nm UCS. A study done by FT-IR spectroscopy suggested that zeolite dealumination initially took place more extensively on the sodalite cages and double six-member rings (D6R) of the structure and that the final collapse of the zeolite framework occurred through destruction of the 12-member rings (12M). This can be explained by a crystal fracture and break down process and disassembling of the sodalite cages in the faujasite structure. NH₃ microcalorimetry showed that strong acid sites in faujasites are destroyed by steam aging, but this effect does not lead to a reduction in the cracking activity of the Ecat form. The microactivity test (MAT) showed that the specific activity declined sharply at 2.430 nm UCS. Differences in product selectivity were related to the extent of damage of the zeolite, extra-framework alumina and mesoporosity. While further aging canceled the effect attributed to extra-framework alumina differences attributed to mesoporosity increased.     

Stabilization of Telomeric I‐Motif Structures by (2′S)‐2′‐Deoxy‐2′‐C‐Methylcytidine Residues

G‐quadruplexes and i‐motifs are tetraplex structures present in telomeres and the promoter regions of oncogenes. The possibility of producing nanodevices with pH‐sensitive functions has triggered interest in modified oligonucleotides with improved structural properties. We synthesized C‐rich oligonucleotides carrying conformationally restricted (2′S)‐2′‐deoxy‐2′‐C‐methyl‐cytidine units. The effect of this modified nucleoside on the stability of intramolecular i‐motifs from the vertebrate telomere was investigated by UV, CD, and NMR spectroscopy. The replacement of selected positions of the C‐core with C‐modified residues induced the formation of stable intercalated tetraplexes at near‐neutral pH. This study demonstrates the possibility of enhancing the stability of the i‐motif by chemical modification.     

Kinetics of the liquid phase dehydration of 1‐octanol to di‐n‐octyl ether on Amberlyst 70

The kinetics of the liquid phase dehydration of 1‐octanol to di‐n‐octyl ether (DNOE) over Amberlyst 70 was studied at 413–453 K. Mechanistic rate models assuming water and 1‐octanol adsorbed on the resin, and the free sites fraction negligible, were selected from 1‐octanol dehydration experiments. Next, the influence of DNOE, water, and 1,4‐dioxane (solvent) concentration was evaluated. DNOE and 1,4‐dioxane do not affect significantly the reaction rate, while water inhibits it strongly. Water effect was quantified by splitting the rate constant into a “true one” and a correction factor related to the fraction of active sites blocked by water. The best kinetic model stemmed from an Eley‐Rideal mechanism with water adsorbed onto the resin and DNOE released directly to the liquid phase, with a correction factor for water inhibitory effect based on a Freundlich isotherm‐like function; activation energy being 110 ± 5 kJ·mol^?1, in line with literature data on homologous reactions. © 2017 American Institute of Chemical Engineers AIChE J, 63: 3966–3978, 2017     

Thermosensitive fibres of lyocell/poly(N‐isopropylacrylamide): multiparametric analysis for studying the graft copolymerization

The thermosensitive properties of the hydrogel poly(N‐isopropylacrylamide) (pNIPAAm) together with the good mechanical properties of lyocell fibres make a combination of the two to be thought of as a smart textile. In the present study the optimal values of various parameters that control the grafting process of pNIPAAm onto lyocell fibres were determined considering the influence of the interaction between them. The copolymerization of pNIPAAm hydrogel onto lyocell fibres was performed in aqueous acidic medium using cerium(IV) as initiator. An experimental design was planned in order to study the effect of the interactions between some variables that affect the kinetics of the graft copolymerization: the cerium(IV) initiator concentration, the N‐isopropylacrylamide (NIPAAm) monomer concentration and the liquor fibre‐to‐bath ratio. The results show that the interaction between the concentrations of NIPAAm and the initiator significantly affects the degree of grafting (DG), the optimum values being 1250 and 12.25 mmol L^?1, respectively. In contrast, the liquor ratio parameter shows no significant interaction with the other two variables studied, meaning that it acts independently but showing a proportional relationship with respect to the DG obtained. In addition, the presence of pNIPAAm in the copolymer obtained was confirmed by Fourier transform infrared spectral analysis. Moreover, the water sorption capacity, depending on the temperature, of the lyocell/pNIPAAm copolymer was studied, with an increase being observed when the DG is higher than 60% and also increasing with the temperature.© 2012 Society of Chemical Industry