Isopropyl Amino Acid Esters Ionic Liquids as Vehicles for Non-Steroidal Anti-Inflammatory Drugs in Potential Topical Drug Delivery Systems with Antimicrobial Activity

New derivatives of non-steroidal anti-inflammatory drugs were synthesized via conjugation with L-amino acid isopropyl esters. The characteristics of the physicochemical properties of the obtained pharmaceutically active ionic liquids were determined. It has been shown how the incorporation of various L-amino acid esters as an ion pair affects the properties of the parent drug. Moreover, the antimicrobial activity of the obtained compounds was evaluated. The proposed structural modifications of commonly used drugs indicate great potential for use in topical and transdermal preparations.     

Dual Modification of Porous Ca-P/PLA Composites with APTES and Alendronate Improves Their Mechanical Strength and Cytobiocompatibility towards Human Osteoblasts

Synthetic implants are used to treat large bone defects that are often unable to regenerate, for example those caused by osteoporosis. It is necessary that the materials used to manufacture them are biocompatible and resorbable. Polymer-ceramic composites, such as those based on poly(L-lactide) (PLLA) and calcium phosphate ceramics (Ca-P), are often used for these purposes. In this study, we attempted to investigate an innovative strategy for two-step (dual) modification of composites and their components to improve the compatibility of composite components and the adhesion between PLA and Ca-P whiskers, and to increase the mechanical strength of the composite, as well as improve osteological bioactivity and prevent bone resorption in composites intended for bone regeneration. In the first step, Ca-P whiskers were modified with a saturated fatty acid namely, lauric acid (LA), or a silane coupling agent γ-aminopropyltriethoxysilane (APTES). Then, the composite, characterized by the best mechanical properties, was modified in the second stage of the work with an active chemical compound used in medicine as a first-line drug in osteoporosis—sodium alendronate, belonging to the group of bisphosphonates (BP). As a result of the research covered in this work, the composite modified with APTES and alendronate was found to be a promising candidate for future biomedical engineering applications.     

Reduced Graphene Oxides Modulate the Expression of Cell Receptors and Voltage-Dependent Ion Channel Genes of Glioblastoma Multiforme

The development of nanotechnology based on graphene and its derivatives has aroused great scientific interest because of their unusual properties. Graphene (GN) and its derivatives, such as reduced graphene oxide (rGO), exhibit antitumor effects on glioblastoma multiforme (GBM) cells in vitro. The antitumor activity of rGO with different contents of oxygen-containing functional groups and GN was compared. Using FTIR (fourier transform infrared) analysis, the content of individual functional groups (GN/exfoliation (ExF), rGO/thermal (Term), rGO/ammonium thiosulphate (ATS), and rGO/ thiourea dioxide (TUD)) was determined. Cell membrane damage, as well as changes in the cell membrane potential, was analyzed. Additionally, the gene expression of voltage-dependent ion channels (clcn3, clcn6, cacna1b, cacna1d, nalcn, kcne4, kcnj10, and kcnb1) and extracellular receptors was determined. A reduction in the potential of the U87 glioma cell membrane was observed after treatment with rGO/ATS and rGO/TUD flakes. Moreover, it was also demonstrated that major changes in the expression of voltage-dependent ion channel genes were observed in clcn3, nalcn, and kcne4 after treatment with rGO/ATS and rGO/TUD flakes. Furthermore, the GN/ExF, rGO/ATS, and rGO/TUD flakes significantly reduced the expression of extracellular receptors (uPar, CD105) in U87 glioblastoma cells. In conclusion, the cytotoxic mechanism of rGO flakes may depend on the presence and types of oxygen-containing functional groups, which are more abundant in rGO compared to GN.     

Hypertensive Effect of Downregulation of the Opioid System in Mouse Model of Different Activity of the Endogenous Opioid System

The opioid system is well-known for its role in modulating nociception and addiction development. However, there are premises that the endogenous opioid system may also affect blood pressure. The main goal of the present study was to determine the impact of different endogenous opioid system activity and its pharmacological blockade on blood pressure. Moreover, we examined the vascular function in hyper- and hypoactive states of the opioid system and its pharmacological modification. In our study, we used two mouse lines which are divergently bred for high (HA) and low (LA) swim stress-induced analgesia. The obtained results indicated that individuals with low endogenous opioid system activity have higher basal blood pressure compared to those with a hyperactive opioid system. Additionally, naloxone administration only resulted in the elevation of blood pressure in HA mice. We also showed that the hypoactive opioid system contributes to impaired vascular relaxation independent of endothelium, which corresponded with decreased guanylyl cyclase levels in the aorta. Together, these data suggest that higher basal blood pressure in LA mice is a result of disturbed mechanisms in vascular relaxation in smooth muscle cells. We believe that a novel mechanism which involves endogenous opioid system activity in the regulation of blood pressure will be a promising target for further studies in hypertension development.     

Influence of a sorbitol‐based nucleating agent modified with silsesquioxanes on the non‐isothermal crystallization of isotactic polypropylene

This article investigates the effect of modifying the polypropylene (iPP) α‐phase nucleating agent 1,3:2,4‐bis(3,4‐dimethylbenzylidene) sorbitol (DMDBS) with tetrasilanolphenyl silsesquioxane (phPOSS). It has been proven that an increasing amount of silsesquioxane leads to differences in the crystallization behavior. What is more, it has been observed that the nucleation effect that results from the addition of sorbitol derivatives is suppressed by phPOSS activity. To understand the influence of phPOSS addition on the crystallization kinetics of PP/DMDBS/phPOSS composites that have been prepared by melt processing in a twin screw extruder, differential scanning calorimetry, rotational rheometry and Fourier transform infrared spectroscopy are performed. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40131.     

A modified oddball paradigm for investigation of neural correlates of attention: a simultaneous ERP–fMRI study

Introduction

The objective of the presented study was to develop and evaluate a P300 experimental protocol for simultaneous registration of event-related potentials (ERPs) and functional MRI (fMRI) data with continuous imaging. It may be useful for investigating attention and working memory processes in specific populations, such as children and neuropsychiatric patients.

Materials and methods

Eleven children were investigated with simultaneous ERP–fMRI. To fulfill requirements of both BOLD and electroencephalographic signal registration, a modified oddball task was used. To verify the ERP–fMRI protocol we also performed a study outside the scanner using a typical two-stimuli oddball paradigm.

Results

Localization of the P300 component of ERPs partially corresponded with fMRI results in the frontal and parietal brain regions. FMRI activations were found in: middle frontal gyrus, insula, SMA, parietal lobule, thalamus, and cerebellum. Our modified oddball task provided ERP–fMRI results with high level of significance (EEG SNR = 35, fMRI p < 0.05–Bonf.). ERPs obtained in the scanner were comparable with those registered outside the scanner, although some differences in the amplitude were noticed, mainly in the N100 component.

Conclusion

In our opinion the presented paradigm may be successfully applied for simultaneous ERP–fMRI registration of neural correlates of attention in vulnerable populations.     

The Effects of Cadmium at Low Environmental Concentrations on THP-1 Macrophage Apoptosis

Cadmium at environmental concentrations is a risk factor for many diseases, including cardiovascular and neurodegenerative diseases, in which macrophages play an important role. The aim of this study was to evaluate the effects of cadmium at low environmental (nanomolar) concentrations on apoptotic processes in THP-1(acute monocytic leukemia cells line)-derived macrophages, with special focus on mitochondrial events involved. Macrophages were incubated with various cadmium chloride (CdCl₂) solutions for 48 h at final concentrations of 5 nM, 20 nM, 200 nM and 2 µM CdCl₂. Cell viability was measured using flow cytometry. Flow cytometric measurement (annexin V/FITC (annexin V/fluorescein isothiocyanate) and PI (propidium iodide) double staining) was used to quantify the extent of apoptosis. Fluorescence and confocal microscopy were used for imaging of apoptosis process. Changes in mitochondrial membrane potential were monitored using cytofluorimetry after cell staining with JC-1(5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazol-carbocyane iodide) probe. Mitochondrial ROS (reactive oxygen species) levels were measured cytofluorimetrically after incubation of cells with mitochondrial superoxide indicator (MitoSOX) red fluorescent marker. The mRNA expression of Bcl-2 and Bax was analysed with qRT-PCR. Our study demonstrates that cadmium, even at low environmental concentrations, exerts mitochondrial toxicity in THP-1 macrophages. Forty-eight-hour exposure to very low concentrations reduces cell viability and results in cell death by apoptosis and necrosis. The decrease in mitochondrial membrane potential, increased ROS production, increased Bax and decreased Bcl-2 mRNA expression are mitochondrial events involved in cadmium-induced apoptosis.     

Morphology,structure and photowettability of TiO2 coatings doped with copper and fluorine

The work reports synthesis, structure and properties of doubly doped titanium dioxide coatings activated by ultraviolet and visible light. Copper within a concentration range of 0.4–3.4 at% and fluorine within a concentration range of 1.7–9.4 at% were introduced as dopants. The coatings were prepared with the help of radiofrequency plasma enhanced chemical vapor deposition technique with a single precursor compound providing both dopants and titanium (IV) chloride being a source of titanium. Elemental composition and chemical bonding analyses of the coatings were carried out with the help of X-ray photoelectron spectroscopy. The results indicate that both admixtures are chemically bound to the TiO₂ matrix – a notion confirmed by Fourier transform infrared spectroscopy. Phase composition studies, performed with a low angle X-ray diffraction method, revealed a presence of a threshold concentration of the dopants affecting the coatings crystallinity. Surface morphology and its topography were studied with the help of scanning electron microscopy and atomic force microscopy. Several coatings exhibited a superhydrophilic effect upon relatively short time of illumination.     

Speed limits for acid-base chemistry in aqueous solutions

Proton transfer reactions, including acid-base recombination, are commonly considered to occur 'nearly instantaneously'. However, their actual time scales may stretch far into the microsecond range, as acid-base reactions are diffusion controlled and the concentrations are low near neutral pH. The interplay of competing bases in the pH relaxation is illustrated using a model acid-base system consisting of o-nitrobenzaldehyde (oNBA) as a proton cage and acetate ions and hydroxyl ions as bases. The kinetically controlled behavior leads to highly counterintuitive states, i.e. acetate ions are transiently protonated for hundreds of nanoseconds despite the presence of a much stronger base OH-.