Mineralocorticoid Receptor Antagonists—Use in Chronic Kidney Disease

Mineralocorticoid receptor antagonists (MRA) are drugs with a potentially broad spectrum of action. They have been reported to have healing effects in many diseases, such as chronic heart failure, hypertension, or nephrotic syndrome. Numerous studies suggest that mineralocorticoid receptor activation is pathogenic and a progression factor of chronic kidney disease (CKD); however, results of studies on the use of MRA in the treatment of CKD are inconclusive. Current guidelines recommend against the use of MRA in patients with advanced CKD. Although, there is growing interest on their use in this population due to treatment benefits. In this review, we summarize studies which were purposed to evaluate the impact of MRA therapy on CKD patients. Despite many benefits of this treatment e.g., reducing cardiovascular mortality or alleviating proteinuria, steroidal MRA (such as spironolactone or eplerenone) have a low safety profile. They often lead to hyperkalemia complications which are dangerous in patients with CKD, and diabetic nephropathy, especially in hemodialysis patients. Studies on recently developed nonsteroidal MRA showed that they have fewer side effects. In our review, we discuss steroidal and nonsteroidal MRA treatment effects on the estimated glomerular filtration rate (eGFR), proteinuria, the cardiovascular system, and hyperkalemia in CKD patients. We present new content and recent publications in this field.     

Biodegradable Amphoteric Surfactants in Titration-Ultrasound Formulation of Oil-in-Water Nanoemulsions: Rational Design,Development, and Kinetic Stability

Amphoteric amphiphilic compounds, due to their unique properties, may represent a group of safe and biocompatible surface-active agents for effective colloidal stabilization of nanoformulations. For this reason, the aim of this work was to develop and characterize the oil-in-water nanoemulsions based on two betaine-derived surfactants with high biodegradability, i.e., cocamidopropyl betaine and coco-betaine. In the first step, we investigated ternary phase diagrams of surfactant-oil-water systems containing different weight ratios of surfactant and oil, as the betaine-type surfactant entity (S), linoleic acid, or oleic acid as the oil phase (O), and the aqueous phase (W) using the titration-ultrasound approach. All the received nanoemulsion systems were then characterized upon droplets size (dynamic light scattering), surface charge (electrophoretic light scattering), and morphology (transmission electron as well as atomic force microscopy). Thermal and spinning tests revealed the most stable compositions, which were subjected to further kinetic stability analysis, including turbidimetric evaluation. Finally, the backscattering profiles revealed the most promising candidate with a size <200 nm for potential delivery of active agents in the future cosmetic, pharmaceutical, and biomedical applications.     

Comparative Antiseizure Analysis of Diverse Natural Coumarin Derivatives in Zebrafish

Coumarins are a well-known group of plant secondary metabolites with various pharmacological activities, including antiseizure activity. In the search for new antiseizure drugs (ASDs) to treat epilepsy, it is yet unclear which types of coumarins are particularly interesting as a systematic analysis has not been reported. The current study performed behavioral antiseizure activity screening of 18 different coumarin derivatives in the larval zebrafish pentylenetetrazole (PTZ) model using locomotor measurements. Activity was confirmed for seven compounds, which lowered seizure-like behavior as follows: oxypeucedanin 38%, oxypeucedanin hydrate 74%, notopterol 54%, nodakenetin 29%, hyuganin C 35%, daphnoretin 65%, and pimpinellin 60%. These coumarins, together with nodakenin, underwent further antiepileptiform analysis by local field potential recordings from the zebrafish opticum tectum (midbrain). All of them, except for nodakenetin, showed pronounced antiepileptiform activity, decreasing PTZ-induced elevation in power spectral density (PSD) by 83–89% for oxypeucedanin, oxypeucedanin hydrate, and notopterol, 77% for nodakenin, 26% for nodakenetin, 65% for hyuganin C, 88% for daphnoretin, and 81% for pimpinellin. These data demonstrate the potential of diverse coumarin scaffolds for ASD discovery. Finally, the structural differences between active and inactive coumarins were investigated in silico for oxypeucedanin hydrate and byacangelicin for their interaction with GABA-transaminase, a hypothetical target.     

Palm Oil-Rich Diet Affects Murine Liver Proteome and S-Palmitoylome

Palmitic acid (C16:0) is the most abundant saturated fatty acid in animals serving as a substrate in synthesis and β-oxidation of other lipids, and in the modification of proteins called palmitoylation. The influence of dietary palmitic acid on protein S-palmitoylation remains largely unknown. In this study we performed high-throughput proteomic analyses of a membrane-enriched fraction of murine liver to examine the influence of a palm oil-rich diet (HPD) on S-palmitoylation of proteins. HPD feeding for 4 weeks led to an accumulation of C16:0 and C18:1 fatty acids in livers which disappeared after 12-week feeding, in contrast to an accumulation of C16:0 in peritoneal macrophages. Parallel proteomic studies revealed that HPD feeding induced a sequence of changes of the level and/or S-palmitoylation of diverse liver proteins involved in fatty acid, cholesterol and amino acid metabolism, hemostasis, and neutrophil degranulation. The HPD diet did not lead to liver damage, however, it caused progressing obesity, hypercholesterolemia and hyperglycemia. We conclude that the relatively mild negative impact of such diet on liver functioning can be attributed to a lower bioavailability of palm oil-derived C16:0 vs. that of C18:1 and the efficiency of mechanisms preventing liver injury, possibly including dynamic protein S-palmitoylation.     

Impact of the addition of dolomite to cream-firing clays on the technological and color properties of sintered ceramics

Sintered ceramics, represented by ceramic tiles or clinker bricks, are widely used in the building materials industry due to their technological properties and visual qualities. The topic of color changing of ceramic materials from cream-firing clays with the use of mineral additives has not been addressed to date. The aim of the paper was to investigate the effect of granulation of dolomite additives to ceramic masses based on cream-firing Borkowice clay on the color and properties of fired ceramic materials. The paper proposes that grain size of mineral additive affects the color of sintered ceramics. In order to confirm this hypothesis, a number of experiments were performed, consisting of determination of the color and technological properties of ceramic materials. The conducted tests showed that the color and technological properties of sintered ceramics are influenced by the grain size of the additives used.     

The effect of La2O3 and CeO2 modifiers on properties of Ni–Al catalysts for LNG prereforming

Ni/La–Al₂O₃ and Ni/Ce–Al₂O₃ catalysts with a small amount of promoters intended for prereforming of LNG were characterized by XRF, N₂ adsorption-desorption, XRD, H₂ chemisorption, HRTEM and XPS. The catalytic activity was evaluated in methane steam reforming both in the kinetic and diffusion regime, at temperatures characteristic of pre-reforming. Carbonaceous deposit was analysed by TPO-MS method. The nature and location of the coke were studied by HRTEM.La or Ce addition into Ni–Al system causes the increase of the active surface area of Ni by enhancing its dispersion. Studies at kinetic regime have shown that the promoted catalysts have almost twice the activity than reference Ni–Al catalyst. This effect was not confirmed by measurements in the diffusion regime on whole catalyst tablets. Almost identical textural properties of catalysts and diffusive limitations related to them but not the catalytic properties of the material itself appeared to be crucial factors. The presence of La (but not Ce) causes a significant increase in resistance to coking.     

Zinc(II) Complexes of Amino Acids as New Active Ingredients for Anti-Acne Dermatological Preparations

Zinc compounds have a number of beneficial properties for the skin, including antimicrobial, sebostatic and demulcent activities. The aim of the study was to develop new anti-acne preparations containing zinc–amino acid complexes as active ingredients. Firstly, the cytotoxicity of the zinc complexes was evaluated against human skin fibroblasts (1BR.3.N cell line) and human epidermal keratinocyte cell lines, and their antimicrobial activity was determined against Cutibacterium acnes. Then, zinc complexes of glycine and histidine were selected to create original gel formulations. The stability (by measuring pH, density and viscosity), microbiological purity (referring to PN-EN ISO standards) and efficacy of the preservative system (according to Ph. Eur. 10 methodology) for the preparations were evaluated. Skin tolerance was determined in a group of 25 healthy volunteers by the patch test. The preparations containing zinc(II) complexes with glycine and histidine as active substances can be topically used in the treatment of acne skin due to their high antibacterial activity against C. acnes and low cytotoxicity for the skin cells. Dermatological recipes have been appropriately composed; no irritation or allergy was observed, and the preparations showed high microbiological purity and physicochemical stability.     

Polymerized ionic liquids-based hydrogels with intrinsic antibacterial activity: Modern weapons against antibiotic-resistant infections

In this study, the inherent antibacterial activity of 11 different polymerized ionic liquids (PILs)-based hydrogels as well as their corresponding monomers was examined in an extensive screening. The methicillin-resistant Staphylococcus aureus Xen 30 (MRSA Xen 30) and Pseudomonas aeruginosa Xen 5 (P. aeruginosa Xen 5) were chosen as test microorganisms. Both are typical representatives of gram-positive and gram-negative bacteria, respectively. Six of the 11 tested monomers were able to eradicate more than 80% of P. aeruginosa Xen 5 cells in suspension. Unfortunately, the anionic, neutral and zwitterionic representatives lost their function after polymerization. However, the cationic gels retained their antibacterial activity with nearly 100% eradication of selected microorganisms - even at the smallest amount tested. Bactericidal activity against gram-positive MRSA Xen 30 was high when the bacteria were treated with the imidazolium-based monomers. Five of the tested compounds showed rather limited bactericidal activity <50% killed bacteria. The weak antibacterial activities could be significantly increased by crosslinking them to three-dimensional networks. As a result, all the hydrogels possessed strong killing efficiencies of at least 68% and were able to maintain this activity even at low hydrogel volume fractions. These findings are very promising for the development of new antibacterial materials for medical applications, for example, stent coatings.     

Strongly basic anion exchanger Lewatit MonoPlus SR-7 for acid,reactive, and direct dyes removal from wastewaters

The strongly basic anion exchanger Lewatit MonoPlus SR-7 (SR-7) of polystyrene matrix was applied for removal of the textile dyes such as C.I. Acid Orange 7 (AO7), C.I. Reactive Black 5 (RB5), and C.I. Direct Blue 71 (DB71). The dyes sorption on SR-7 was examined based on the initial dye concentration, phase contact time, type of additives and their concentrations, and solution pH. The equilibrium and kinetic characteristics of the dyes uptake by SR-7 followed the Langmuir isotherm model and the pseudo-second-order model. The dyes sorption in the column system was also investigated.