Characterization of the anticonvulsant profile of isonicotinic acid benzylamide in various experimental seizure models in mice

This study focused on the evaluation of anticonvulsant properties of isonicotinic acid benzylamide (iso-Nic-BZA) in numerous experimental seizure models (maximal electroshock [MES]-, bicuculline [BIC]-, pentylenetetrazole [PTZ]-, pilocarpine [PILO]-, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA]-, kainic acid [KA]- and N-methyl-d-aspartic acid [NMDA]-induced seizures). Moreover, acute adverse-effect profile of the agent with respect to impairment of motor coordination was assessed in animals subjected to the chimney test. The evaluation of time-course and dose-response relationships for iso-Nic-BZA provided evidence that the compound produced the peak to maximum antielectroshock action and acute adverse effects at 5min after its systemic (i.p.) administration. Iso-Nic-BZA exerted a clear-cut anticonvulsant action against maximal electroshock-induced seizures in mice and its ED(50) value was 70.6 (56.4-88.4)mg/kg. The assessment of acute adverse effects in the chimney test revealed that the agent produced acute neurotoxic effects and its TD(50) value was 135.6 (108.8-169.0)mg/kg. Additionally, iso-Nic-BZA showed the anticonvulsant activity in numerous chemically-induced seizures (AMPA-, BIC-, KA-, and PTZ-evoked clonic convulsions), remaining virtually ineffective (at doses up to 200mg/kg) in PILO- and NMDA-induced seizures in mice. Based on this study, one can conclude that iso-Nic-BZA due to the short time to peak of its maximum anticonvulsant effects (5min after its i.p. administration), deserves more attention as a potential antiepileptic drug for patients in status epilepticus.     

Vascular endothelial growth factor in systemic lupus erythematosus: relationship to disease activity,systemic organ manifestation,and nailfold capillaroscopic abnormalities

Introduction: The aim of the study was to evaluate whether vascular endothelial growth factor (VEGF) serum level is associated with systemic organ involvement, microvascular changes as determined by nailfold capillaroscopy, and disease activity of systemic lupus erythematosus (SLE). Materials and Methods: Serum levels of VEGF were determined by an enzyme-linked immunosorbent assay in 47 SLE patients and in 30 healthy controls. Nailfold capillaroscopy was performed in all patients and healthy subjects. Results: Morphological changes were observed by nailfold capillaroscopy in 45 of 47 (95.7%) SLE patients. Mild capillary changes were found in 16 (34%), moderate in 21 (44.7%), and severe in 8 (17%) SLE patients. All patients with systemic organ involvement showed severe or moderate changes in nailfold capillaroscopy. In comparison with the control group, a higher serum concentration of VEGF in SLE patients was demonstrated (p<0.05). Furthermore, significant differences in VEGF serum concentration between SLE patients with systemic involvement and controls were found (p<0.01). Comparison between patients with active and inactive SLE according to SLEDAI score showed a significantly higher concentration of VEGF in the sera of patients with active SLE (p<0.01). The SLE patients with severe and moderate changes in nailfold capillaroscopy showed significantly higher VEGF serum levels than SLE patients with mild changes (p<0.05) or healthy controls (p<0.01). Moreover, the VEGF serum level correlated significantly with ESR (r=0.580, p<0.0001) and CRP (r=0.512, p<0.005). Conclusions: Our data suggest that VEGF serum level may be a useful marker of disease activity and internal organ involvement in SLE patients. Abnormalities in nailfold capillaroscopy may reflect the extent of microvascular involvement and are associated with systemic manifestation in SLE.     

Visfatin serum concentration is associated with cardiac allograft vasculopathy in heart transplant recipients

Cardiac allograft vasculopathy (CAV) still is one of the most important limiting factors of long‐term survival following heart transplant (HT). This study aimed to investigate the association between proinflammatory adipokine‐visfatin and the incidence of CAV in HT recipients. After HT, 182 patients who had a follow‐up visit at the Transplantation Clinic between 2016 and 2017 were analyzed. The median age was 60.5 years, and 76.4% were men. The incidence of CAV was 54.9%. According to the multivariable proportional hazard regression analysis, visfatin level (1.795 [1.539‐2.094]; P < .001) was significantly associated with CAV, and statin use was protective against CAV (0.504 [0.32‐0.793]; P = .003). The area under the receiver operating characteristic curve indicated an excellent discriminatory power of visfatin (0.9548 [0.9281‐0.9816]) for CAV detection. The cutoff value of 5.42 ng/mL for visfatin yielded a sensitivity of 89% and specificity of 91%. This is the first study to demonstrate that visfatin serum concentrations are independently associated with the incidence of CAV in HT recipients. Visfatin allows for simple and cheap detection of CAV given its excellent discriminatory ability and high sensitivity and specificity. In addition, we have found an independent association between the statin use and a lower risk of CAV.     

Effects of Various Types of Expandable Graphite and Blackcurrant Pomace on the Properties of Viscoelastic Polyurethane Foams

We investigated the effect of the type and amount of expandable graphite (EG) and blackcurrant pomace (BCP) on the flammability, thermal stability, mechanical properties, physical, and chemical structure of viscoelastic polyurethane foams (VEF). For this purpose, the polyurethane foams containing EG, BCP, and EG with BCP were obtained. The content of EG varied in the range of 3–15 per hundred polyols (php), while the BCP content was 30 php. Based on the obtained results, it was found that the additional introduction of BCPs into EG-containing composites allows for an additive effect in improving the functional properties of viscoelastic polyurethane foams. As a result, the composite containing 30 php of BCP and 15 php of EG with the largest particle size and expanded volume shows the largest change in the studied parameters (hardness (H) = 2.65 kPa (+16.2%), limiting oxygen index (LOI) = 26% (+44.4%), and peak heat release rate (pHRR) = 15.5 kW/m² (−87.4%)). In addition, this composite was characterized by the highest char yield (m₆₀₀ = 17.9% (+44.1%)). In turn, the change in mechanical properties is related to a change in the physical and chemical structure of the foams as indicated by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) analysis.     

Manufacturing Elements with Small Cross-Sections of 17-4 PH Steel (1.4542) with the Application of the DMLS Additive Manufacturing Method

The application of direct metal laser sintering renders it possible to manufacture models with complex geometries. However, there are certain limits to the application of this method connected with manufacturing thin-walled cuboidal elements, as well as cylinders and holes with small diameters. The principal objective of the research was to determine the accuracy of manufacturing geometries with small cross-sections and the possibility of application in heat exchangers that are radiators with radially arranged ribs. To that end, four specimens were designed and manufactured; their geometries of representations assumed for the purpose of research (analysis) changed dimensions within the following scope: 10–0.1 mm. The specimens to be applied in the research were manufactured with 17-4 PH stainless steel (1.4542) with the application of 3D-DMLS printing and an EOS M270 printer. The measurement of accuracy was performed with the application of an optical stereomicroscope (KERN OZL-466). In addition to that, research into the chemical composition of the material, as well as the size of spherical agglomerates, was conducted with the application of a scanning electron microscope. The analysis of the chemical composition was conducted as well (after the sintering process). The analysis of the results based on the values received by means of measurements of the manufactured geometries was divided into three parts. Based on this, it is possible to conclude that the representation of models manufactured with the application of DMLS was comparable with the assumptions, and that the deviations between a nominal dimension and that received in the course of the research were within the following scope: 0–0.1 mm. At the final stage of research and based on the received results, two heat exchangers were manufactured.     

The Influence of Mechanical Alloying and Plastic Consolidation on the Resistance to Arc Erosion of the Ag–Re Composite Contact Material

The article presents the influence of mechanical alloying and plastic consolidation on the resistance to arc erosion of the composite Ag–Re material against the selected contact materials. The following composites were selected for the tests: Ag90Re10, Ag95Re5, Ag99Re1 (bulk chemical composition). Ag–Re materials were made using two methods. In the first, the materials were obtained by mixing powders, pressing, sintering, extrusion, drawing, and die forging, whereas, in the second, the process of mechanical alloying was additionally used. The widely available Ag(SnO₂)10 and AgNi10 contact materials were used as reference materials. The reference AgNi10 material was made by powder metallurgy in the process of mixing, pressing, sintering, extrusion, drawing, and die forging, while the Ag(SnO₂)10 composite was obtained by spraying AgSniBi alloy with water, and then the powder was pressed, oxidized internally, sintered, extruded into wire, and drawn and die forged. The tests of electric arc resistance were carried out for loads with direct current (DC) and alternating current (AC). For alternating current (I = 60 A, U = 230 V), 15,000 switching cycles were made, while, for constant current 50,000 (I = 10 A, U = 550 V). A positive effect of the mechanical alloying process and the addition of a small amount of rhenium (1% by mass) on the spark erosion properties of the Ag–Re contact material was found. When DC current of 10 A was used, AgRe1 composite was found to be more resistant than commonly used contact materials (AgNi10 and Ag(SnO₂)10).     

The Unique Binding Mode of Laulimalide to Two Tubulin Protofilaments

Laulimalide, a cancer chemotherapeutic in preclinical development, has a unique binding site located on two adjacent β‐tubulin units between tubulin protofilaments of a microtubule. Our extended protein model more accurately mimics the microtubule environment, and together with a 135 ns molecular dynamics simulation, identifies a new binding mode for laulimalide, which differs from the modes presented in work using smaller protein models. The new laulimalide–residue interactions that are computationally revealed explain the contacts observed via independent mass shift perturbation experiments. The inclusion of explicit solvent shows that many laulimalide–tubulin interactions are water mediated. The new contacts between the drug and the microtubule structure not only improve our understanding of laulimalide binding but also will be essential for efficient derivatization and optimization of this prospective cancer chemotherapy agent. Observed changes in secondary protein structure implicate the S7–H9 loop (M–loop) and H1′–S2 loop in the mechanism by which laulimalide stabilizes microtubules to exert its cytotoxic effects.     

Uniformity of Thermoluminescence and Optically Stimulated Luminescence Signals Over the Length of Doped LiMgPO4 Crystal Rods Grown by Micro-Pulling-Down Method

The purpose of this work was to systematically assess the distribution of thermoluminescence (TL) and optically stimulated luminescence (OSL) properties along the length of crystals grown by the micro-pulling-down method, in relation to the microstructure and distribution of activators. We analyzed lithium magnesium phosphate (LiMgPO₄; LMP) crystals doped with terbium (Tb; 0.8 mol%) or with a combination of thulium (Tm; 0.8 mol% or 1.2 mol%) and boron (B; 10 mol%). Crystals of several centimeters in length and 3 mm in diameter were cut into 20–40 slices, depending on length. For each sample, TL glow curves and OSL decay curves were examined. Optical microscopy and scanning electron microscopy were used to assess the microstructure and elemental composition of several selected samples. Two-dimensional TL readouts were performed to identify the areas with higher and lower signal emission. Our study showed that there may be significant differences not only in LMP sensitivity along the crystal’s axis but also on the surface of the slice. The distribution of activators varies depending on the type of crystals and strongly affects luminescence properties.