Exploration of the binding mode of indanesulfonamides as selective inhibitors of human carbonic anhydrase type VII by targeting Lys 91

Convulsions are common neurological disorders in clinical medicine and are triggered by several mechanisms. The enhancement of neuronal excitability can be related, among other factors, to GABAergic depolarization. Carbonic anhydrase (CA) VII contributes to this electrophysiological behavior by providing bicarbonate anion, which can mediate current through channels coupled to GABA(A) receptors. Among the cytosolic CAs, the mechanism of action and inhibition of CA VII is less understood. We present herein the pharmacological evaluation of both enantiomers of an indanesulfonamide compound substituted by a pentafluorophenyl moiety against CA VII and five other human CA isoforms to evaluate their selectivity. The investigated compounds are powerful inhibitors of hCA VII, with K(i) values in the range of 1.7-3.3 nM, but their selectivity needs to be improved. A molecular modeling study was conducted to rationalize the structure-activity relationships and provide useful insight into the future design of selective hCA VII inhibitors.     

Theory and experiments of transport at channel microband electrodes under laminar flows. 1. Steady-state regimes at a single electrode

Integration of microelectrodes in microfluidic devices has attracted significant attention during the past years, in particular for analytical detections performed by direct or indirect electrochemical techniques. In contrast there is a lack of general theoretical treatments of the difficult diffusion-convection problems which are borne by such devices. In this context, we investigated the influence of the confining effect and hydrodynamic conditions on the steady-state amperometric responses monitored at a microband electrode embedded within a microchannel. Several convective-diffusive mass transport regimes were thus identified under laminar flow on the basis of numerical simulations performed as a function of geometrical and hydrodynamic parameters. A rationalization of these results has been proposed by establishing a zone diagram describing all the limiting and intermediate regimes. Concentration profiles generated by the electrode across the microchannel section were also simulated according to the experimental conditions. Their investigation allowed us to evaluate the thickness of the diffusive-convective layer probed by the electrode as well as the distance downstream from which the solution becomes again homogeneous across the whole microchannel section. Experimental checks of the theoretical principles delineated here have validated the present results. Experiments were performed at microband electrodes integrated in microchannels with aqueous solutions of ferrocene methanol under pressure-driven flow.     

Inhibition of polyphenoloxidase activity by mixtures of heated cysteine derivatives with carbonyl compounds

It had previously been shown that soluble Maillard reaction products (MRP) made from thiol compounds and glucose or fructose contained powerful inhibitors of various fruit and vegetable polyphenoloxidase (PPO) activity. In MRP from cysteine and glucose, the amount of hydroxymethylfurfural (HMF) formed increased with the increase in glucose concentration (0-1 M), particularly under acidic (pH 2) conditions. Using model mixtures containing a preheated cysteine-derived compound and a carbonyl component, especially HMF, furfural and benzaldehyde, we showed that the neoformed compounds produced exhibited a stronger inhibitory potency toward PPO activity of eggplant, apple, and mushroom than former MRP. Optimal reaction conditions for the formation of inhibitory compounds when HMF reacted with preheated cysteine were investigated. It was found that a reactants molar ratio of 1:1 and a reaction time exceeding 1 h were the most efficient reaction conditions to generate inhibitory compounds. The stability of the newly formed products, evaluated during storage, showed that their inhibitory potency was globally kept at 4, 21, and 37 degrees C for 72 h but was unstable when stored at -20 degrees C and lost when exposed to UV radiations for 24 h.     

Is plasma vitamin C an appropriate biomarker of vitamin C intake? A systematic review and meta-analysis

Background  

As the primary source of dietary vitamin C is fruit and to some extent vegetables, the plasma level of vitamin C has been considered a good surrogate or predictor of vitamin C intake by fruit and vegetable consumption. The purpose of this systematic review was to investigate the relationship between dietary vitamin C intakes measured by different dietary methods and plasma levels of vitamin C.     

Binding of pulmonary surfactant proteins to carbon nanotubes; potential for damage to lung immune defense mechanisms

Potential pulmonary toxicity of carbon nanotubes is a research area that has received considerable attention. Surfactant proteins A and D (SP-A and SP-D) are collectin proteins that are secreted by airway epithelial cells in the lung. They play an important role in first-line defense against infection within the lung. The aim of this study was to investigate the interaction between carbon nanotubes and proteins contained in lung surfactant. By using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), Western Blotting, a novel technique of affinity chromatography based on carbon nanotube-Sepharose matrix [1] and electron microscopy data it was shown that SP-A and SP-D selectively bind to carbon nanotubes. The binding was Ca²⁺-ion dependent, and was variable between batches of nanotubes. It was therefore likely to be mediated by surface impurities or chemical modifications of the nanotubes. Chronic level exposure to carbon nanotubes may result in sequestration of SP-D and SP-A. Absence of these proteins in knockout mice leads to susceptibility to lung infection and emphysema.     

Comparison of microwave and thermal cure of an epoxy/amine matrix

An investigation was carried out into the effect ofa microwave cure on an epoxy prepolymer with a cycloaliphatic diamine mixture, as compared to a standard thermal cure. The microwave waveguide and process (propagation mode TE₀₁) were adjusted to obtain large homogeneous samples. The extent of reaction, x, was measured during the microwave processing by size exclusion chromatography and differential scanning calorimetry. A good estimate of x was found using a modified DiBenedetto equation correlating x and the glass transition temperature T_g. The homogeneity of the samples was checked during the last steps of cure, showing the efficiency of the microwave processing and waveguide. The influence of the nature of the mold (metallic or dielectric) on the reaction kinetic was also investigated. Samples cured by both thermal and microwave processing were characterized by dynamic and static mechanical properties and then compared with those of fully crosslinked networks, i.e., postcured at a high temperature.     

Dietary Lipid Intake only Partially Influences Variance in Serum Phospholipid Fatty Acid Composition in Adolescents: Impact of Other Dietary Factors

The present study aimed to assess the correlation between food and fatty acid (FA) intake and the serum phospholipid (PL) FA status in European adolescents and explored the percentage of variation in serum PL FA that could be attributed to dietary habits. Participants included 528 adolescents recruited in the HELENA Study. Dietary intake was assessed by two, self-administered, non-consecutive 24-h recalls. PL FA concentrations were measured in fasting venous serum samples. Reduced rank regressions were applied to examine the combined effect of food intakes. Results indicated that the variance in serum PL FA in adolescents, that could be explained by diet varied from 7.0 % for MUFA to 14.2 % for n-3FA. The variance in the long-chain n-3FA was mainly explained by fish intake but also by coffee and tea consumption. In conclusion this study indicated that dietary intake influences the serum PL FA status to a limited amount but that also other factors interfere. However, dietary intake is important as it is among those factors that could be modified. Furthermore, the results suggest that the overall dietary habits should be considered instead of only the consumption of single foods or nutrients, as the medium of the food or concomitant intake of foods and nutrients might interact and as such influence absorption or metabolism.     

Catalytic Transfer Dehydrogenation of Geraniol to Geranial Over Palladium and Copper Supported Catalysts

Dehydrogenation of geraniol into geranial in the presence of a hydrogen acceptor (alkene) was studied. Supported palladium catalysts were not suitable for this transformation, but supported copper catalysts showed promising results at 150 °C; selectivity to the expected geranial was strongly dependent on the support and the calcinations/reduction procedure (>50 % in the presence of Mg–La hydrotalcite-supported copper).     

New Intumescent Formulations of Fire-retardant Polypropylene—Discussion of the Free Radical Mechanism of the Formation of Carbonaceous Protective Material During the Thermo-oxidative Treatment of the Additives

The study compares five new intumescent additive mixtures and a carbonizing additive system with the ammonium polyphosphate–pentaerythritol system and additive formulations previously developed in laboratory in terms of fire retardancy of polypropylene-based formulations. The mixture of diammonium pyrophosphate and polyols produced by agrochemical industry xylitol and d-sorbitol (carbonization agent) are FR additive mixtures of interest for polyolefins. Moreover, the FR performance of the mixture of ammonium polyphosphate and polyamide-6 is reported. It is proposed that boric acid salts have to be developed as precursors for carbonization catalytic species. A thermal analysis study shows that FR performances and amounts of carbonaceous materials resulting from the thermal degradation of the additive mixtures are not related. An additional compilation of previous spectroscopic studies by the laboratory confirms that the intumescent process results from the formation of polyaromatic species and that FR systems maintain acidic species in a relatively high temperature range. An ESR study discusses the presence of π radicals in the protective coating formed using the additive systems. It provides information on the size of the carbonaceous structures in the materials and the presence of crystalline phases in the coating. Finally, the participation of free radicals in the formation of chemical bonds between the materials produced from the additives and the products of the degradation of the polymer is discussed.