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.     

Combination of nuclear magnetic resonance spectroscopy and nonlinear methods to analyze the copolymerization of phosphonic acid derivatives

We demonstrate in this study that the combination of modern inline monitoring methods [here: inline nuclear magnetic resonance (NMR)] with simulations gains more exact and profound kinetic results than previously used methods like linearization without that combination. The ¹H-NMR spectroscopic data (more than 100 data points) are used to construct the copolymerization diagram. The reactivity ratios are obtained applying the van Herks nonlinear least square method. The examination of the radical copolymerization of 2-hydroxyethyl methacrylate (HEMA) with (2-{[2-(ethoxycarbonyl)prop-2-en-1-yl]oxy}ethyl) phosphonic acid (ECPPA) as important adhesive monomer used in dentistry yields reactivity ratios of r_HEMA = 1.83; r_ECPPA = 0.42. The copolymerization diagram reflects nonideal, non-azeotropic copolymerization. The sequence distribution of the obtained by Monte Carlo simulation indicates the generation of statistical copolymers. As an important finding, it is demonstrated that the repeating units responsible for etching and adhesion are arranged over the whole polymer chain, which is necessary to achieve proper functionality. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 48256.     

Age and gender differences in cardiac reactivity and subjective emotion responses to emotional autobiographical memories.

This research reports age and gender differences in cardiac reactivity and subjective responses to the induction of autobiographical memories related to anger, fear, sadness, and happiness. Heart rate (HR) and subjective state were assessed at baseline and after the induction of each emotion in 113 individuals (61 men, 52 women; 66% European American, 34% African American) ranging in age from 15 to 88 years (M = 50.0; SD = 20.2). Cardiac reactivity was lower in older individuals; however, for anger and fear, these age effects were significantly more pronounced for the women than the men. There were no gender differences in subjective responses, however, suggesting that the lower cardiac reactivity found among older people is dependent on gender and the specific emotion assessed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Efficient allylation of cellulose in dimethyl sulfoxide/tetrabutylammonium fluoride trihydrate

The cellulose solvent dimethyl sulfoxide (DMSO)/tetrabutylammonium fluoride trihydrate (TBAF) was successfully applied as reaction medium for the synthesis of allyl cellulose by conversion of the polymer with allyl chloride in the presence of solid NaOH. Samples with degree of substitution from 0.50 to 2.98 were accessible by varying the molar ratio anhydroglucose unit:allyl chloride:NaOH and reaction time. DMSO/TBAF was found to be an efficient reaction medium for the preparation of highly functionalized samples from spruce sulfite pulp with degree of polymerization of about 500 even in a scale of 50 g. The allyl cellulose samples were characterized by means of FTIR- and NMR spectroscopy. Size exclusion chromatography revealed negligible polymer degradation during synthesis and purification of the samples.     

A Multinomial Model of Event-Based Prospective Memory.

Prospective memory is remembering to perform an action in the future. The authors introduce the 1st formal model of event-based prospective memory, namely, a multinomial model that includes 2 separate parameters related to prospective memory processes. The 1st measures preparatory attentional processes, and the 2nd measures retrospective memory processes. The model was validated in 4 experiments. Manipulations of instructions to place importance on either the prospective memory task or the background task (Experiments 1 and 2) and manipulations of distinctiveness of prospective memory targets (Experiment 2) had expected effects on model parameters, as did a manipulation of the difficulty of prospective memory target encoding (Experiments 3 and 4). An alternative model was also evaluated. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Machining of reproducible flaws corresponding to fatigue cracks for fracture mechanics tests of components and welded joints

In connection with the analysis and the development of failure concepts in fracture mechanics for quasistatic loaded components and elastic-plastic behaviour of the material, tests are also carried out with welded and/or complex shaped specimens or structures. Thereby the difficulty arises of generating reproducible flaws in the form of fatigue precracks in definite positions in the components, respectively in the welded joint. It is reported exemplarily about experiments on different CT25 and CCT specimens and on a pressure vessel which contained a fatigue pre-crack, a 0.2 mm saw cut or notches with notch root radius ≤ ≥ 0.1 mm as flaws. The comparison of the results with regard to J-integral at initiation of stable crack, J_i, and J_R curves shows that under certain conditions the 0.2 mm saw cut (notch root radius ≤ ≤ 0.02 mm) is a useful alternative, if reproducible generation of a fatigue pre-crack will not be successful or too expensive. The tests were carried out on StE 460 and on a welded joint of this steel at 25 ± 2°C.     

Multigigabit transmission through rain in a dual polarizationfrequency reuse system: an experimental study

An experimental terrestrial link was set up for the purpose of evaluating very-high-data-rate communications in dual-polarization frequency reuse systems. Possible applications are in the field of satellite communications. Two 3.2-Gb/s signals using staggered quadriphase shift keying (SQPSK) were transmitted on opposite senses of circular polarization over a 7-km path located in Crane rain region D3. Performance degradation of the demodulator as a function of cross-polarization discrimination (XPD) was evaluated and found to closely match simulation predictions. However, the relationship between XPD and rain attenuation was found to be more complex than thought previously, displaying a relatively slowly varying hysteresis effect as well as significant interactions with characteristics of the receive antenna. The latter effect suggests that careful control of antenna characteristics may be required if such high-data-rate techniques are to be employed in space-ground links     

Polycyclic Aromatic Hydrocarbons Activate the Aryl Hydrocarbon Receptor and the Constitutive Androstane Receptor to Regulate Xenobiotic Metabolism in Human Liver Cells

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants produced by incomplete combustion of organic matter. They induce their own metabolism by upregulating xenobiotic-metabolizing enzymes such as cytochrome P450 monooxygenase 1A1 (CYP1A1) by activating the aryl hydrocarbon receptor (AHR). However, previous studies showed that individual PAHs may also interact with the constitutive androstane receptor (CAR). Here, we studied ten PAHs, different in carcinogenicity classification, for their potential to activate AHR- and CAR-dependent luciferase reporter genes in human liver cells. The majority of investigated PAHs activated AHR, while non-carcinogenic PAHs tended to activate CAR. We further characterized gene expression, protein abundancies and activities of the AHR targets CYP1A1 and 1A2, and the CAR target CYP2B6 in human HepaRG hepatoma cells. Enzyme induction patterns strongly resembled the profiles obtained at the receptor level, with AHR-activating PAHs inducing CYP1A1/1A2 and CAR-activating PAHs inducing CYP2B6. In summary, this study provides evidence that beside well-known activation of AHR, some PAHs also activate CAR, followed by subsequent expression of respective target genes. Furthermore, we found that an increased PAH ring number is associated with AHR activation as well as the induction of DNA double-strand breaks, whereas smaller PAHs activated CAR but showed no DNA-damaging potential.     

New inhibitors of the Tat-TAR RNA interaction found with a "fuzzy" pharmacophore model

TAR RNA is a potential target for AIDS therapy. Ligand-based virtual screening was performed to retrieve novel scaffolds for RNA-binding molecules capable of inhibiting the Tat-TAR interaction, which is essential for HIV replication. We used a "fuzzy" pharmacophore approach (SQUID) and an alignment-free pharmacophore method (CATS3D) to carry out virtual screening of a vendor database of small molecules and to perform "scaffold-hopping". A small subset of 19 candidate molecules were experimentally tested for TAR RNA binding in a fluorescence resonance energy transfer (FRET) assay. Both methods retrieved molecules that exhibited activities comparable to those of the reference molecules acetylpromazine and chlorpromazine, with the best molecule showing ten times better binding behavior (IC50 = 46 microM). The hits had molecular scaffolds different from those of the reference molecules.