Failed Neuroprotection of Combined Inhibition of L-Type and ASIC1a Calcium Channels with Nimodipine and Amiloride

Effective pharmacological neuroprotection is one of the most desired aims in modern medicine. We postulated that a combination of two clinically used drugs—nimodipine (L-Type voltage-gated calcium channel blocker) and amiloride (acid-sensing ion channel inhibitor)—might act synergistically in an experimental model of ischaemia, targeting the intracellular rise in calcium as a pathway in neuronal cell death. We used organotypic hippocampal slices of mice pups and a well-established regimen of oxygen-glucose deprivation (OGD) to assess a possible neuroprotective effect. Neither nimodipine (at 10 or 20 µM) alone or in combination with amiloride (at 100 µM) showed any amelioration. Dissolved at 2.0 Vol.% dimethyl-sulfoxide (DMSO), the combination of both components even increased cell damage (p = 0.0001), an effect not observed with amiloride alone. We conclude that neither amiloride nor nimodipine do offer neuroprotection in an in vitro ischaemia model. On a technical note, the use of DMSO should be carefully evaluated in neuroprotective experiments, since it possibly alters cell damage.     

Phylloquinone (vitamin K1) and dihydrophylloquinone content of fats and oils

Assessment of vitamin K (VK) dietary intakes has been limited by the incompleteness of VK food composition data for the U.S. food supply, particularly for VK-rich oils. The phylloquinone (VK-1) and 2′,3′-dihydrophylloquinone (dK) concentrations of margarines and spreads (n=43), butter (n=4), shortening (n=4), vegetable oils (n=6), and salad dressings (n=24) were determined by RP-HPLC with fluorescence detection. Each sample represented a composite of units or packages obtained from 12 or 24 outlets, which were geographically representative of the U.S. food supply. Butter, which is derived from animal fat sources, had less VK-1 compared to vegetable oil sources. The VK-1 and dK of the margarines and spreads increased with fat content and the degree of hydrogenation, respectively. In some margarines or spreads and in all shortenings, the dK concentrations were higher than the corresponding VK-1 concentrations. As the fat content of salad dressings increased, the VK-1 concentrations also increased. Fat-free foods had <1 μg/100 g of either form of the vitamin. No dK was detected in the salad dressings or oils tested. Some margarines, spreads, and salad dressings may be significant sources of vitamin K in the U.S. food supply.     

Wet spun fibers from solutions of cellulose in an ionic liquid with suspended carbon nanoparticles

Wet spun fibers from solutions of dissolving pulp in 1‐ethyl‐3‐methylimidazolium acetate (EmimAc) with up to 50 wt % (based on cellulose) suspended carbon black and graphene nanoplatelets particles were studied. Carbon fillers were dispersed by simple shearing in a Couette type mixer and the resulting spin dope was extruded into a hot water coagulation bath from a single hole spinneret. Microstructure, mechanical properties, and electrical conductivity were assessed as a function of filler loading and discussed in comparison to melt spun fibers with similar fillers. The coagulation process and subsequent drying of wet spun fibers was found to produce a significant microporosity, more so the higher the filler loading. The electrical percolation threshold was quite high in the wet spun fibers and relatively modest values of conductivity were obtained with regard to the high filler loadings. Carbon black was found to be superior to graphene nanoplatelets. This was related to flow‐induced orientation effects. The mechanical properties of the carbon‐filled fibers were found to be similar or lower compared to the pure cellulose fibers because of low interfacial interactions and formation of microporosity. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41417.     

Effects of Enantiomeric Blend of Verbenone on Response ofIps paraconfusus to Naturally Produced Aggregation Pheromone in the Laboratory

The aggregation pheromone produced by maleIps paraconfusus (Coleoptera: Scolytidae) tunneling in Monterey pine,Pinus radiata, logs was trapped on Porapak Q. A concentration of an extract of trapped volatiles that attracted beetles was determined in the laboratory through a concentration–response analysis of walking behavior of males and females. The interruptant effects of four concentrations of verbenone on response to a constant concentration of this naturally produced aggregation pheromone were tested with males and females. Independent of its enantiomeric composition [99.5% (S)-(–), 93.1 % (S)-(–), and 98.3% (R)-(+)], verbenone significantly reduced the percentage of females (but not males) reaching the attractant source. However, when the time required for beetles of both sexes taken together to reach the attractant source was considered, verbenone of higher enantiomeric purity had a greater effect on beetle behavior. Solutions of 99.5% (S)-(–)- and 98.3% (R)-(+)-verbenone increased the time required for beetles to reach the attractive source when compared to 93.1% (S)-(–)-verbenone. When pooled across enantiomeric blends, increasing concentrations of verbenone resulted in slower responses in beetles that reached the attractant source within 2 min. Males and females did not respond to verbenone alone.     

Morphologically dependent alternating‐current and direct‐current breakdown strength in silica–polypropylene nanocomposites

In this article, we report the synthesis of a new bimodal surface ligand morphology on silica nanoparticles. Combining grafting‐to and grafting‐from approaches, in this study, we demonstrated the efficacy of anthracene surface modification for improving the dielectric breakdown strength (DBS) under alternating‐current and direct‐current conditions and that of a matrix‐compatible polymer brush for controlling the nanofiller (NF) dispersion. Ligand‐modified spherical colloidal SiO₂ nanoparticles (～14 nm in diameter) were mixed into polypropylene, and the resulting dispersion was improved over the unmodified particles, as shown with transmission electron microscopy. The results suggest that the electronic structure of the anthracene‐modified particle surface was critical to the improvement in DBS. In addition, the DBS of the composite was shown to depend on the dispersion state of the filler and the mode of stress; this indicated that the individually dispersed nanoparticles were not necessarily the optimal morphology for all stress conditions. Additionally, the precise nature of the matrix‐compatible brush was less important than the NF dispersion it produced. The bimodal grafted architectural design has provided a promising solution for the control of the dispersion and surface properties, especially for high‐molecular‐weight polymer matrices. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44347.     

Acceleration of kinetic monte carlo simulations of free radical copolymerization: A hybrid approach with scaling

Kinetic Monte Carlo (KMC) has been widely used in the simulation of polymeric reactions. The power of KMC is highlighted by its ability to keep track of the length and sequence of every radical or polymer chain, while it is computationally more expensive than deterministic kinetic models. This paper introduces an acceleration method that significantly reduces the computational cost of KMC simulations, while keeping the same features as the full kinetic Monte Carlo simulations. Case studies are used to demonstrate the general applicability of this method to free radical copolymerization. © 2017 American Institute of Chemical Engineers AIChE J, 63: 4013–4021, 2017     

Catalyst Screening through Quantum Chemical Calculations and Microkinetic Modeling: Hydrolysis of Carbon Dioxide

Quantum chemical calculations are emerging as an effective way to screen catalysts for particular applications. In this contribution, we demonstrate the power of density functional theory to study CO₂ hydrolysisby six carbonic anhydrase mimics, evaluating thermodynamic and kinetic parameters at the mechanistic level. A microkinetic model was then built based on the kinetics and thermodynamics calculated from first principles. The intrinsic reaction rate constant was calculated from the results of the microkinetic model and compared with experimental data. Overall, the rate constants were in good agreement with experimental values, except for zinc-tri and complex b, which were overestimated. This was ascribed to their ineffective complexation with Zn²⁺. How the reaction rate constants vary with time was also investigated. From 0 to 12 ms, the rate constants of complexes a and d decreased to 50 and 67% of their initial values, respectively; the rate constants of complexes b and f2 were almost invariant with time; the rate constant of complex f1 showed an unusual double sigmoidal shape. The pK_a values of these six carbonic anhydrase mimics as well as three additional mimics were calculated. A correlation between pK_a values and the binding free energy of OH-was obtained by fitting data from five zinc(II) aza-macrocyclic complexes. The reaction rate constants were found to increase linearly with the pK_a value, indicating CO₂ adsorption is the rate-limiting step.