Chronic antidepressant-like effect of EMD386088, a partial 5-HT6 receptor agonist,in olfactory bulbectomy model may be connected with BDNF and/or CREB signalling pathway

Background

The removal of the olfactory bulbs has been attributed to behavioral changes and neuroplasticity manifesting themselves among others like increases in brain neurotrophin expression and neurogenesis. Earlier data presented that EMD386088, a 5-HT₆ receptor partial agonist, exerts antidepressant-like properties after chronic administration in olfactory bulbectomy (OB) model as was it compared with amitriptyline (AMI). The aim of this study was to compare acute and chronic biochemical effects of EMD386088, administered in its antidepressant active (2.5 mg/kg) and non-active (1.25 mg/kg) doses, found in the open field test in OB rats, with those of AMI (10 mg/kg). The levels of 5-HT₆ receptor protein and selected neurotrophins in prefrontal cortex (PFC) and hippocampus (Hp) of rats have been examined.

Synthesis and structure evaluation of new complex butylarylpiperazin-1-yl derivatives

A series of arylpiperazine derivatives of 1,16-diphenyl-19-azahexacyclo-[14.5.1.0^2,15.0^3,8.0^9,14.0^17,21]docosa-2,3,5,7,8,9,11,13,14-nonaene-18,20,22-trione and 4,10-diphenyl-1H,2H,3H,5H-indeno[1,2-f]isoindole-1,3,5-trione was synthesized. The pharmacological profile of compound 4 at the 5-HT_1A receptor was measured by binding assay. The title compounds were tested in cell-based assay against the human immunodeficiency virus type-1. The X-ray crystallographic studies of derivatives 2, 6, 7, 11, 19, and 20 were presented.     

The influence of ezetimibe on classical and alternative activation pathways of monocytes/macrophages isolated from patients with hypercholesterolemia

Macrophages are crucial for the development of atherosclerotic plaques. Classically activated macrophages contribute to plaque growth and destabilization, while alternatively activated macrophages increase plaque stability. Here, we assessed the influence of ezetimibe on the activation of monocyte-derived macrophages isolated from patients with hypercholesterolemia (total cholesterol 263.4?±?12.5 mg/dl, low-density lipoprotein cholesterol 179.7?±?11.3 mg/dl, triglycerides 123.9?±?11.4 mg/dl). Cells were stimulated with 1 μg/ml lipopolysaccharide (LPS) or 1 μg/ml LPS plus 22 ng/ml ezetimibe. Control cells were left unstimulated. The expression of classical activation markers (interleukin-1β (IL-1β), nitric oxide (NO), and inducible nitric oxide synthase (iNOS)) and alternative activation markers (mannose receptor (MR) and arginase-1 (Arg1)) was determined after 48 h. The employed analytical methods included enzyme-linked immunosorbent assay, Griess reaction, real-time polymerase chain reaction, and Western blotting. LPS increased the secretion of IL-1β and NO and the expression of iNOS mRNA, iNOS protein, and Arg1 protein. It did not affect the expression of MR or Arg1 mRNA. In comparison to LPS stimulation, co-stimulation with ezetimibe decreased the secretion of IL-1β and the expression of iNOS mRNA and protein, while it increased MR mRNA and protein expression. Co-stimulation with ezetimibe did not change the secretion of NO or the expression of Arg1. The results suggest that ezetimibe in inflammatory in vitro conditions contributes to the suppression of classical and promotion of the alternative macrophage activation.     

Effects of second-generation antipsychotics on selected markers of one-carbon metabolism and metabolic syndrome components in first-episode schizophrenia patients

Purpose

Alterations in one-carbon metabolism (OCM) have been repeatedly reported in schizophrenia. However, there is a scarcity of studies addressing the effects of antipsychotics on selected OCM markers in schizophrenia and provided results are inconsistent.

Methods

We recruited 39 first-episode schizophrenia (FES) patients and determined serum profile of total homocysteine (tHcy), folate, vitamin B12, lipoproteins and glucose at baseline and after 12 weeks of treatment with second-generation antipsychotics (SGA) including olanzapine and risperidone in monotherapy.

Results

After 12 weeks of treatment, all patients had significantly higher body mass index (BMI), serum levels of total cholesterol (TC), low-density lipoproteins (LDL), triglycerides (TG) and tHcy together with significantly lower levels of folate and vitamin B12. The analysis of differences between SGA revealed the same biochemical alterations in patients treated with olanzapine as in the whole group, while those receiving risperidone had no statistically significant changes in serum folate, vitamin B12 and TG. There was a significantly higher increase in BMI and TC in patients treated with olanzapine in comparison with those treated with risperidone. Patients receiving olanzapine had a higher decrease in vitamin B12 than those assigned to the treatment with risperidone. Changes in folate, vitamin B12, tHcy and TC levels were significant only in males, even after Bonferroni correction. Multiple regression analysis revealed that changes in tHcy levels are associated with gender and baseline metabolic parameters (BMI, glucose, TC, LDL and HDL) but not with selected SGA.

Conclusions

These results indicate that SGA may influence OCM, especially in first-episode schizophrenia (FES) males.     

High-Performance Face Milling of 42CrMo4 Steel: Influence of Entering Angle on the Measured Surface Roughness,Cutting Force and Vibration Amplitude

High feed Milling is a new milling method, which allows to apply high feed rates and increase machining efficiency. The method utilizes face cutters with a very small entering angle, of about 10°–20°. Thus, the cut layer cross-section is different than in traditional milling. In order to examine the high feed milling (HFM), experimental tests were conducted, preceded by an analysis of cutting zones when milling with an HF face cutter. The face milling tests of 42CrMo4 steel with the use of an HF cutter characterized by an entering angle, dependent on axial depth of cut a_p and insert radius r values, as well as with a conventional face cutter with the entering angle of 45° were performed. The study focused on analyzing the vibration amplitude, cutting force components in the workpiece coordinate system, and surface roughness. The experimental tests proved, that when milling with constant cut layer thickness, the high feed cutter allowed to obtain twice the cutting volume in comparison with the conventional face cutter. However, higher machining efficiency resulted in an increase in cutting force components. Furthermore, the results indicate significantly higher surface roughness and higher vibration amplitudes when milling with the HF cutter.     

Hardening Slurries with Fluidized-Bed Combustion By-Products and Their Potential Significance in Terms of Circular Economy

Hardening slurries (water-bentonite-binder mixtures) constitute a well-established material used broadly, i.a., for cut-off walls in civil and water engineering. Although they usually contain Portland cement, similar to common concrete, their properties differ greatly, mostly due to a much higher water content. This characteristic of hardening slurries creates unique opportunities for the utilization of significant quantities of industrial by-products that are deemed problematic in the concrete industry. This article investigates the effect of the addition of by-products of fluidized-bed combustion of hard, brown coal and municipal sewage sludge, as well as ground granulated blast furnace slag, on the properties of slurries. Unconfined compressive strength tests, as well as mercury porosimetry, scanning electron microscopy, and X-ray diffraction analyses were performed. The results suggest that it is possible to design hardening slurry mixes of desired properties, both in liquid and solid state, containing at least 100–300 kg/m³ of industrial waste. This includes cement-free slurries based entirely on industrial by-products as binders. In addition, the analyzed slurries exhibited good chemical resistance to landfill eluates, at the same time effectively immobilizing heavy metals. It was concluded that hardening slurry technology can ensure the safe deposition of significant amounts of waste that would be otherwise difficult to manage, thus contributing to the circular economy concept.     

Thermophysical Properties of Temperature-Sensitive Paint

The complex thermophysical property of temperature-sensitive paint (TSP) research is discussed. TSP is used for visualization of the surface temperature distribution in wind tunnel aerodynamic tests. The purpose of this research was to provide reliable, experimental, thermophysical data of the paint applied as a coating. As TSP is applied as thin surface layers, investigation of its final properties is challenging and demands the application of non-standard procedures. At present, most measurements were performed on composite specimens of TSP deposed onto a thin metallic film substrate or on TSP combined with a cellulose sheet support. The studies involved gravimetric,, thermogravimetric, and microcalorimetric analyses, transversal thermal diffusivity estimation from laser flash data and in-plane effective thermal diffusivity measurements done by the temperature oscillation technique. These results were complemented with scanning electron microcopy analysis, surface characterization and the results of dilatometric measurements performed on the TSP bulk specimens obtained from liquid substrate by casting. Complex analysis of the obtained results indicated an isotropic characteristic of the thermal diffusivity of the TSP layer and provided reliable data on all measured thermophysical parameters—they were revealed to be typical for insulators. Further to presenting these data, the paper, in brief, presents the applied investigation procedures.     

Foundation Piles—A New Feature for Concrete 3D Printers

Foundation piles that are made by concrete 3D printers constitute a new alternative way of founding buildings constructed using incremental technology. We are currently observing very rapid development of incremental technology for the construction industry. The systems that are used for 3D printing with the application of construction materials make it possible to form permanent formwork for strip foundations, construct load-bearing walls and partition walls, and prefabricate elements, such as stairs, lintels, and ceilings. 3D printing systems do not offer soil reinforcement by making piles. The paper presents the possibility of making concrete foundation piles in laboratory conditions using a concrete 3D printer. The paper shows the tools and procedure for pile pumping. An experiment for measuring pile bearing capacity is described and an example of a pile deployment model under a foundation is described. The results of the tests and analytical calculations have shown that the displacement piles demonstrate less settlement when compared to the analysed shallow foundation. The authors indicate that it is possible to replace the shallow foundation with a series of piles combined with a printed wall without locally widening it. This type of foundation can be used for the foundation of low-rise buildings, such as detached houses. Estimated calculations have shown that the possibility of making foundation piles by a 3D printer will reduce the cost of making foundations by shortening the time of execution of works and reducing the consumption of construction materials.     

Edgewise Compressive Behavior of Composite Structural Insulated Panels with Magnesium Oxide Board Facings

Edgewise compression response of a composite structural insulated panel (CSIP) with magnesium oxide board facings was investigated. The discussed CSIP is a novel multifunctional sandwich panel introduced to the housing industry as a part of the wall, floor, and roof assemblies. The study aims to propose a computational tool for reliable prediction of failure modes of CSIPs subjected to concentric and eccentric axial loads. An advanced numerical model was proposed that includes geometrical and material nonlinearity as well as incorporates the material bimodularity effect to achieve accurate and versatile failure mode prediction capability. Laboratory tests on small-scale CSIP samples of three different slenderness ratios and full-scale panels loaded with three different eccentricity values were carried out, and the test data were compared with numerical results for validation. The finite element (FE) model successfully captured CSIP’s inelastic response in uniaxial compression and when flexural action was introduced by eccentric loads or buckling and predicted all failure modes correctly. The comprehensive validation showed that the proposed approach could be considered a robust and versatile aid in CSIP design.