Adenosine Receptor Agonist HE-NECA Enhances Antithrombotic Activities of Cangrelor and Prasugrel in vivo by Decreasing of Fibrinogen Density in Thrombus

Blood platelets’ adenosine receptors (AR) are considered to be a new target for the anti-platelet therapy. This idea is based on in vitro studies which show that signaling mediated by these receptors leads to a decreased platelet response to activating stimuli. In vivo evidence for the antithrombotic activity of AR agonists published to date were limited, however, to the usage of relatively high doses given in bolus. The present study was aimed at verifying if these substances used in lower doses in combination with inhibitors of P2Y₁₂ could serve as components of dual anti-platelet therapy. We have found that a selective A_2A agonist 2-hexynyl-5’-N-ethylcarboxamidoadenosine (HE-NECA) improved the anti-thrombotic properties of either cangrelor or prasugrel in the model of ferric chloride-induced experimental thrombosis in mice. Importantly, HE-NECA was effective not only when applied in bolus as other AR agonists in the up-to-date published studies, but also when given chronically. In vitro thrombus formation under flow conditions revealed that HE-NECA enhanced the ability of P2Y₁₂ inhibitors to decrease fibrinogen content in thrombi, possibly resulting in their lower stability. Adenosine receptor agonists possess a certain hypotensive effect and an ability to increase the blood–brain barrier permeability. Therefore, the effects of anti-thrombotic doses of HE-NECA on blood pressure and the blood–brain barrier permeability in mice were tested. HE-NECA applied in bolus caused a significant hypotension in mice, but the effect was much lower when the substance was given in doses corresponding to that obtained by chronic administration. At the same time, no significant effect of HE-NECA was observed on the blood–brain barrier. We conclude that chronic administration of the A_2A agonist can be considered a potential component of a dual antithrombotic therapy. However, due to the hypotensive effect of the substances, dosage and administration must be elaborated to minimize the side-effects. The total number of animals used in the experiments was 146.     

On the Dependence of Prion and Amyloid Structure on the Folding Environment

Currently available analyses of amyloid proteins reveal the necessity of the existence of radical structural changes in amyloid transformation processes. The analysis carried out in this paper based on the model called fuzzy oil drop (FOD) and its modified form (FOD-M) allows quantifying the role of the environment, particularly including the aquatic environment. The starting point and basis for the present presentation is the statement about the presence of two fundamentally different methods of organizing polypeptides into ordered conformations—globular proteins and amyloids. The present study shows the source of the differences between these two paths resulting from the specificity of the external force field coming from the environment, including the aquatic and hydrophobic one. The water environment expressed in the fuzzy oil drop model using the 3D Gauss function directs the folding process towards the construction of a micelle-like system with a hydrophobic core in the central part and the exposure of polarity on the surface. The hydrophobicity distribution of membrane proteins has the opposite characteristic: Exposure of hydrophobicity at the surface of the membrane protein with an often polar center (as in the case of ion channels) is expected. The structure of most proteins is influenced by a more or less modified force field generated by water through the appropriate presence of a non-polar (membrane-like) environment. The determination of the proportion of a factor different from polar water enables the assessment of the protein status by indicating factors favoring the structure it represents.     

A comparison of selected quality features of the tissue and slaughter yield of wild and cultivated pikeperch<Emphasis Type="Italic"> Sander lucioperca</Emphasis> (L.)

The study focused on the comparison of carcass and fillet yields, fillet color, the content of basic components, and the fatty acid composition of tissue from cultivated and wild pikeperch. There was no variation in yield between carcasses and fillets. The brightness and redness of the color of the fillet surfaces of both types of fish were comparable, although the yellowness, chromaticity and shade of color differed. The tissue of cultivated fish had three times more fat (2.87%) than did that of wild fish; the difference was compensated for by water content. The protein and mineral component contents did not vary significantly. The total levels of saturated and monounsaturated acids in the tissue lipids in 1 g of fat varied. No differences were observed between the total amount of polyunsaturated fatty acids (PUFA), PUFAn-3, PUFAn-6, or in the n-3/n-6 proportion. One consequence of the higher fat content in cultivated pikeperch tissue was that the contents of eicosapentaenoic (EPA; 20:5n-3) and docosahexaenoic (DHA; 22:6n-3) acids per 100 g of fillet were significantly higher than in the tissue of wild pikeperch.     

Application of Molecular Dynamics Simulations in the Analysis of Cyclodextrin Complexes

Cyclodextrins (CDs) are highly respected for their ability to form inclusion complexes via host–guest noncovalent interactions and, thus, ensofance other molecular properties. Various molecular modeling methods have found their applications in the analysis of those complexes. However, as showed in this review, molecular dynamics (MD) simulations could provide the information unobtainable by any other means. It is therefore not surprising that published works on MD simulations used in this field have rapidly increased since the early 2010s. This review provides an overview of the successful applications of MD simulations in the studies on CD complexes. Information that is crucial for MD simulations, such as application of force fields, the length of the simulation, or solvent treatment method, are thoroughly discussed. Therefore, this work can serve as a guide to properly set up such calculations and analyze their results.     

Determination of (fluoro)quinolones in eggs by liquid chromatography with fluorescence detection and confirmation by liquid chromatography-tandem mass spectrometry

A multiresidue analytical procedure for determination of seven fluoroquinolones (marbofloxacin, norfloxacin as internal standard, ciprofloxacin, danofloxacin, enrofloxacin, sarafloxacin and difloxacin), and three quinolones (oxolinic acid, nalidixic acid and flumequine) in eggs is presented. The procedure is based on dispersive solid-phase extraction technique with acetonitrile as extractant. Norfloxacin and ciprofloxacin - d8 were used as internal standards to quantify the (fluoro)quinolones. Analyses were realised by LC-FLD for screening and LC-MS/MS for confirmatory purposes. The whole procedure was evaluated according to the Commission Decision 2002/657/EC. Specificity, decision limit (CCα), detection capacity (CCβ), recovery (absolute and relative), precision (repeatability and reproducibility) were determined during validation process. Recoveries (relative) for the LC-FLD screening determination ranged from 85% to 93%, repeatability and reproducibility were in the range of 5-9% to 9-16%, respectively. CCα and CCβ were 13-37 and 17-43 μg/kg pending on analite. For the LC-MS/MS confirmatory method, the relative recoveries were satisfactory (92-99%) with repeatability and reproducibility in the range of 4-7% to 6-12%, respectively. CCα and CCβ were 3-7 and 7-11 μg/kg depending on the analite. The results of both prepared methods showed these analytical procedures simple, rapid, sensitive and suitable for routine control of eggs.     

Biofunctionalized upconverting CaF<Subscript>2</Subscript>:Yb,Tm nanoparticles for <Emphasis Type="Italic">Candida albicans</Emphasis> detection and imaging

Versatile optimization of the synthesis method and composition of Yb3+ and Tm3+ co-doped CaF2 nanoparticles as well as a novel biofunctionalization method were developed and evaluated.Through multistep synthesis,the luminescence intensity of the Tm3+ activator was enhanced by more than 10-fold compared to standard one-step synthesis.The proposed methods were used to homogenously distribute the doping ions within the nanoparticle's volume and thus reduce luminescence quenching.Optimization of dopant ions concentration led to the selection of the most efficient visible and near-infrared up-converting nanoparticles,which were CaF2 doped with 10％ Yb3+ 0.05％ Tm3+ and 20％ Yb3+ 0.5％ Tm3+,respectively.To illustrate the suitability of the synthesized nanoparticles as bio-labels,a dedicated biofunctionalization method was used,and the nanoparticles were applied for labeling and imaging of Candida albicans cells.This method shows great promise because of extremely low background and high specificity because of the presence of the attached molecules.     

Coacervates as a Modern Delivery System of Hand Dishwashing Liquids

Hand dishwashing liquids can be produced in a coacervate form. Such a delivery system can be readily mixed with water and, in the initial dilution stage, may exhibit a high viscosity. This makes it feasible to formulate concentrated products which can be diluted by consumers. The surfactant concentration in the starting formulation is found to affect the possibility of producing hand dishwashing liquids in coacervate form. Hand dishwashing liquids in coacervate form are produced by the separation of the upper phase under the effect of sodium chloride, whose concentration is a key parameter. An increase in the concentration of anionic surfactants in the starting formulation, requires a slight increase in the concentration of sodium chloride to start coacervation and this results in an increase in coacervate volume. The properties of the coacervate, i.e. viscosity, washability, emulsifying power and foamability, are reported and found to be similar to those of typical commercial products.     

Enhancing gas phase Fischer-Tropsch synthesis catalyst design

This paper presents the results on the research in the development of a Fe-based catalyst with Co as a co-catalyst, and Ru and ZnO as promoters. The catalytic performance of these materials for FT synthesis was investigated in the gas phase employing a fixed bed reactor system. The Fe-Zn-K/γ-Al₂O₃ catalyst performance was used as the benchmark. The data show that by varying the process conditions (T, P, flow rate), it is possible to achieve a narrow distribution of the liquid products. The effect of co-catalysts and promoters such as K and Zn are also presented. The results from a series of Fe₄Co₁Zn_0.04 based catalysts for Fischer-Tropsch (FT) synthesis, in which the different amounts of Ru are incorporated showed that the addition of Ru suppressed the CH₄ formation at the cost of increasing the CO₂ selectivity. The newly designed catalysts showed significantly high activity towards CO conversion (>70%), along with low selectivity towards CO₂ (5-15%) and methane (ND - 3%). It is also shown that the support material plays a role in the selectivities obtained.     

A two‐level detector of short‐term unique changes in time series based on a similarity method

In the paper, a novel two‐level algorithm of time‐series change detection is presented. In the first level, to identify non‐stationary sequences in a processed signal, preliminary detection of events is performed with a short‐term prediction comparison. In the second stage, to confirm the changes detected in the first level, a similarity method aimed at identification of unique changes is employed. The detection of changes in a non‐stationary time series is discussed, implemented algorithms are described and the results produced on a sample four financial time series are shown. General conditions for implementing the proposed algorithm as an immune‐like event detector are discussed.