An Overview,Advantages and Therapeutic Potential of Nonpeptide Positive Allosteric Modulators of Glucagon-Like Peptide-1 Receptor

Due to uncomfortable injection regimens of peptidic agonists of glucagon-like peptide-1 receptor (GLP-1R), orally available nonpeptide positive allosteric modulators (PAMs) of GLP-1Rs are foreseen as the possible future mainstream therapy for type 2 diabetes. Herein, current GLP-1R PAMs are reviewed. Based on the effectiveness and in silico predicted physicochemical properties, pharmacokinetics, and toxicity, possible candidates for further development as oral drugs were selected. The suggestion is that GLP-1R PAMs might be used orally alone or in combination with dipeptidyl peptidase-4 (DPP-4) inhibitors, which could offer an optimal treatment option next to metformin monotherapy in type 2 diabetes mellitus, or in a wider spectrum of indications. Quercetin acts as a GLP-1R PAM and DPP-4 inhibitor, and therefore, might be considered as a pioneering agent with a dual mechanism of action, in terms of GLP-1R positive allosteric modulation and DPP-4 inhibition for potentiating GLP-1 dependent effects.     

The contribution of fractal nature to BaTiO3-ceramics microstructure analysis

The structure of BaTiO₃ based materials can be controlled by using different technological parameters and different additives. In this paper, microstructure and dielectrical properties of Er₂O₃ doped BaTiO₃-ceramics, sintered from 1320 °C to 1380 °C have been investigated. Microstructural investigations were carried out using scanning electron microscope equipped with energy dispersive spectrometer. Grain size distribution was determined by quantitative metallography method.The new correlation between microstructure and dielectric properties of doped BaTiO₃-ceramics, based on fractal geometry and contact surface probability, has been developed. Using the fractals and statistics of the grains contact surface, a reconstruction of microstructure configurations, as grains shapes or intergranular contacts, has been successfully done. Obtained results indicated that fractal analysis and statistics model for contact surfaces of different shapes were very important for the prognosis of BaTiO₃-ceramics microstructure and dielectric properties.The morphology of ceramics grains pointed out the validity of developing new structure analytical methods, based on different grains’ shape geometries. The grains contact model based on ellipsoidal geometry is presented as new modeling tool for structure research of BaTiO₃-ceramics materials. The directions of possible materials properties prognosis are determined according to the correlations synthesis-structure-property.The statistical approach to the investigation of BaTiO₃-ceramic grains concerning the relationship between the temperature and the area of the contact surface is also introduced.     

Dark-field microscopy studies of single metal nanoparticles: understanding the factors that influence the linewidth of the localized surface plasmon resonance

This article provides a review of our recent Rayleigh scattering measurements on single metal nanoparticles. Two different systems will be discussed in detail: gold nanorods with lengths between 30 and 80 nm, and widths between 8 and 30 nm; and hollow gold-silver nanocubes (termed nanoboxes or nanocages depending on their exact morphology) with edge lengths between 100 and 160 nm, and wall thicknesses of the order of 10 nm. The goal of this work is to understand how the linewidth of the localized surface plasmon resonance depends on the size, shape, and environment of the nanoparticles. Specifically, the relative contributions from bulk dephasing, electron-surface scattering, and radiation damping (energy loss via coupling to the radiation field) have been determined by examining particles with different dimensions. This separation is possible because the magnitude of the radiation damping effect is proportional to the particle volume, whereas, the electron-surface scattering contribution is inversely proportional to the dimensions. For the nanorods, radiation damping is the dominant effect for thick rods (widths greater than 20 nm), while electron-surface scattering is dominant for thin rods (widths less than 10 nm). Rods with widths in between these limits have narrow resonances-approaching the value determined by the bulk contribution. For nanoboxes and nanocages, both radiation damping and electron-surface scattering are significant at all sizes. This is because these materials have thin walls, but large edge lengths and, therefore, relatively large volumes. The effect of the environment on the localized surface plasmon resonance has also been studied for nanoboxes. Increasing the dielectric constant of the surroundings causes a red-shift and an increase in the linewidth of the plasmon band. The increase in linewidth is attributed to enhanced radiation damping.     

Effect of commercial or depurinized milk on rat liver growth-regulatory kinases,nuclear factor-kappa B,and endonuclease in experimental hyperuricemia: Comparison with allopurinol therapy

Hyperuricemia is a biochemical hallmark of gout, renal urate lithiasis, and inherited purine disorders, and may be a result of enormous ATP breakdown or purine release as a result of cardiovascular disease, hypertension, kidney disease, eclampsia, obesity, metabolic syndrome, psoriasis, tumor lysis syndrome, or intense physical training. The beneficial role of dairy products on hyperuricemia management and prevention is well documented in the literature. The primary aim of our experimental study was to examine the effect of milk dietary regimen (commercial 1.5% fat UHT milk or patented depurinized milk) compared with allopurinol therapy on experimental hyperuricemia induced by oxonic acid in rats. Principal component analysis was applied on a data set consisting of 11 variables for 8 different experimental groups. Among the 11 parameters measured (plasma uric acid and the liver parameters NFκB-p65, Akt kinase/phospho-Akt kinase, ERK kinase/phospho-ERK kinase, IRAK kinase/phospho IRAK kinase, p38/phospho-p38, and DNase), Akt/phospho Akt and ERK/phospho-ERK signaling were extracted as the most discriminating. We also compared the content of various potentially toxic compounds (sulfur compounds, ketones, aldehydes, alcohols, esters, carboxylic acids, and phthalates) in untreated commercial milk and depurinized milk. Of all the compounds investigated in this study that were observed in commercial milk (24 volatile organic compounds and 4 phthalates), 6 volatile organic compounds were not detected in depurinized milk. For almost all of the other compounds, significant decreases in concentration were observed in depurinized milk compared with commercial milk. In conclusion, a depurinized milk diet may be recommended in nutritional treatment of primary and secondary hyperuricemia to avoid uric acid and other volatile, potentially toxic compounds that may slow down liver regeneration and may induce chronic liver diseases.     

Short communication: Effect of commercial or depurinized milk diet on plasma advanced oxidation protein products,cardiovascular markers,and bone marrow CD34 stem cell potential in rat experimental hyperuricemia

Cardiovascular repair and myocardial contractility may be improved by migration of bone marrow stem cells (BMSC) and their delivery to the site of injury, a process known as BMSC homing. The aim of our study was to examine the dietary effect of a newly patented depurinized milk (DP) that is almost free of uric acid and purine and pyrimidine compounds compared with a standard commercial 1.5% fat UHT milk diet or allopurinol therapy in rat experimental hyperuricemia. Bone marrow stem cell potential (BMCD34⁺, CD34-postive bone marrow cells), plasma oxidative stress parameters [advanced oxidation protein products, AOPP) and thiobarbituric acid reactive substances (TBARS)], myocardial damage markers [creatine phosphokinase (CPK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH)], plasma cholesterol, and high-density lipoprotein cholesterol were investigated. The DP milk diet significantly increased the number of BMCD34⁺ stem cells compared with commercial UHT milk. Allopurinol given alone also increased the number of BMCD34⁺. Hyperuricemia caused a significant increase in all plasma enzyme markers for myocardial damage (CPK, LDH, and AST). A cardioprotective effect was achieved with allopurinol but almost equally with DP milk and more than with commercial milk. Regarding plasma AOPP, TBARS, and cholesterol levels, the most effective treatment was DP milk. In conclusion, the protective role of a milk diet on cardiovascular function may be enhanced through the new depurinized milk diet, which may improve cardiovascular system function via increased bone marrow stem cell regenerative potential, decreased plasma oxidative stress parameters, and decreased levels of myocardial damage markers and cholesterol. New dairy technology strategies focused on eliminating harmful milk compounds should be completely nontoxic. Novel milk products should be tested for their ability to improve tissue repair and function.     

The influence of talc as a nucleation agent on the nonisothermal crystallization and morphology of isotactic polypropylene: The application of the Lauritzen–Hoffmann,Avrami, and Ozawa theories

A new method is proposed, which can be used to analyze the influence of different additives and fillers on the nonisothermal crystallization of polymers. The composites of talc in isotactic polypropylene (i‐PP) were prepared using a corotating twin‐screw extruder. The compounds were subsequently dried and injection molded. PP morphology and talc dispersion were visualized using optical microscopy and computed tomography. Wide‐angle X‐ray scattering and small‐angle X‐ray scattering measurements provided an insight into the crystal structure of PP. The data obtained from nonisothermal DSC measurements were fitted to the Avrami model for the nonisothermal case. The calculated Avrami's exponent (n), which takes into account the influence of talc on the nucleation and growth of the PP crystals, was used in the combination of Lauritzen–Hoffman and Ozawa models to calculate the nucleation parameter (K_g). A good agreement was found between the model predictions and literature values. The examination shows that the developed model extension gives an expected trend in the case of i‐PP filled with talcs from the same origin but with different particle sizes. Furthermore, it is shown that delaminated talc with a higher specific surface is more efficient in nucleation of i‐PP. Thus, the introduced model extension could be a useful tool for comparing of nucleation ability of different additives in the crystallization of polymers. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Nucleation parameter and size distribution of critical nuclei for nonisothermal polymer crystallization: The influence of the cooling rate and filler

The nucleation parameter K_g of filled PP, HDPE, and PA6 is determined through nonisothermal DSC measurements. A novel method is proposed for the determination of the size distribution of critical nuclei, where the most commonly found fraction was obtained as a peak value. The models are tested at different cooling rates and different filler loadings. K_g varies up to a certain cooling rate and afterwards remains constant. The introduction of talc in PP and HDPE facilitates nucleation and thus reduces K_g. An opposite trend occurs upon the addition of bentonite in PA6. The changes of K_g and are reflected on sample morphology, as confirmed with SAXS. The ratio between the final crystal thickness and amounts to approx. 2 and thus agrees well with the one listed in literature. The simple linear correlations of the obtained K_g are established with Young's modulus and yield stress. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41433.     

Vibrational response of Au-Ag nanoboxes and nanocages to ultrafast laser-induced heating

Time-resolved spectroscopy has been used to investigate the vibrational properties of hollow cubic nanoparticles: Au-Ag nanoboxes and nanocages. In these experiments, laser-induced heating was used to coherently excite the breathing vibrational modes of the particle. The vibrational periods scale with the edge length of the particle and the nanocages and nanoboxes showing equivalent responses despite a large difference in their morphology. The measured vibrational periods are compared to finite element calculations, where the particles are modeled as a hollow cube, with the principle crystal axes parallel to the sides of the cube. Very good agreement is obtained between the calculations and the experimental data, with the experimental frequencies being slightly lower than the calculated values (by approximately 7%). These results demonstrate the importance of accurately modeling the particles in order to interpret experimental data.     

Tesla’s Fountain – Modeling and simulation in ceramics technology

In this paper, we present Tesla’s Fountain in ceramics technology reconstruction from basic 3D model, simulation of the engine, light and fluids till the real materialization. As the one of the most important model purposes, we enrich this solution by additional multicolor lights. All of this elements are designed based on Tesla’s original patent no. 1,113,716, US patent office, granted Oct,13. In this model we applied ceramics technology based on ceramic materials casting and sintering. At the time when the patent was granted, the metal materials science and technologies were more advanced than the ceramics technology and applications. We performed all materials characteristics analyses and preparation steps based on the one author’s patent no. 46121, Serbia patent office, granted 21.12.1991. This is one original two patents solution with complete new over-bridging by the state-of-the-art computer modeling and simulation technology.