THE SEPARATE AND SYNERGISTIC EFFECTS OF AMPAR ANTAGONISTS ON THE TRANSITION OF CORTICAL NETWORKS TO EPILEPTIFORM ACTIVITY

Οι περιπτώσεις των φαρμακοανθεκτικών κρίσεων και κατ’ επέκταση της επιληψίας είναι σημαντικά υψηλή στα παιδιά, αλλά η υποκείμενη αιτιολογία για την ανθεκτικότητα τους στην αντιεπιληπτική θεραπεία παραμένει αόριστη. Πρωταρχικοί συντελεστές στην εγγενή ευαισθησία των επιληπτικών κρίσεων του ανώριμου εγκεφάλου είναι οι υποδοχείς ΑΜΡΑ, οι οποίοι αντιπροσωπεύουν ιδανικούς στόχους για την ανάπτυξη νέων αντιεπιληπτικών φαρμάκων για τις περιπτώσεις ανθεκτικών παιδιατρικών συνδρόμων. Συγκεκριμένα, το δεκανοϊκό οξύ, ένα κύριο συστατικό της κετογονικής δίαιτας τριγλυκεριδίων μεσαίας αλυσίδας και το perampanel, ένα πρόσφατα εγκεκριμένο αντισπασμωδικό, έχουν αποδειχθεί ότι παρέχουν ισχυρή ανεξάρτητη καθώς και συνεργιστική αντιεπιληπτική δράση μέσω αναστολής των υποδοχέων ΑΜΡΑ. Ωστόσο, δεν είναι ακόμη γνωστό εάν αυτές οι ενώσεις μπλοκάρουν τους υποδοχείς ΑΜΡΑ συνολικά στον εγκέφαλο και κατά τη διάρκεια των κρίσιμων αναπτυξιακών μεταβάσεων. Εδώ, παρουσιάζουμε ένα ex vivo μοντέλο ενδογενούς δραστηριότητας νεοφλοιώδους δικτύου σε φέτες εγκεφάλου ποντικιών πριν και μετά τον απογαλακτισμό τους, ώστε να διερευνήσουμε την επίδραση των αναπτυξιακών αλλαγών στη δημιουργία και την εξάπλωση επιληπτικών κρίσεων, καθώς και τη φαρμακοευαισθησία της παροξυσμικής δραστηριότητας σε αυτούς τους φαρμακολογικούς παράγοντες. Τα δεδομένα μας υποστήριξαν την ύπαρξη συγκεκριμένων ηλικιακών μοτίβων επιληπτικής δραστηριότητας στις αναπτυξιακές μεταβάσεις από την πρώιμη έως την παιδική ηλικία. Το δεκανοϊκό οξύ εμφάνισε υψηλότερη δράση σε σύγκριση με το perampanel, το οποία απέτυχε να τερματίσει τις επαγόμενες από 0-Mg2 + επιληπτικές κρίσεις σε κλινικά σχετικές συγκεντρώσεις. Αυτά τα αποτελέσματα υποδηλώνουν ότι η ανάπτυξη ανθεκτικότητας σε ορισμένα φάρμακα μπορεί να είναι ένα εγγενές χαρακτηριστικό του ανώριμου ιστού ή συγκεκριμένων εγκεφαλικών δικτύων.The incidence of drug-resistant seizures and epilepsy is considerably high in children, but the underlying etiology for their refractoriness to antiepileptic treatment remains elusive. As primary contributors to the inherent seizure susceptiveness of the immature brain, AMPA receptors represent unique targets for the development of novel antiepileptic drugs for intractable pediatric syndromes. Specifically, decanoic acid, a main constituent of the medium chain triglyceride ketogenic diet, and perampanel, a recently approved anticonvulsant, has been shown to provide strong separate and synergistic antiseizure action through sufficient AMPA receptor inhibition. However, it is unknown yet whether these compounds block AMPA receptors globally across the brain and during critical developmental transitions. Here, we present an ex vivo model of endogenous neocortical network activity from brain slice preparations of pre- and post-wining mice to explore the impact of developmental changes on seizure generation and spread, as well as on the pharmacosensitivity of paroxysmal activity to these two pharmacological agents. Our data supported the existence of age-specific patterns of epileptiform activity in the developmental transitions from early to late childhood. Decanoic acid displayed a higher potency compared to perampanel, which failed to terminate 0-Mg2+ induced epileptiform discharges at clinically relevant concentrations. These results denote that the development of resistance to certain drugs may be an intrinsic characteristic of immature tissue or specific brain networks

Lamellar Tetragonal Symmetry of Amphiphilic Thermotropic Ionic Liquid Crystals in the Framework of Other Closely Related Highly Ordered Structures

An overview of the chemical compounds forming the rare smectic T phases is presented with references to the historical context. Thermodynamics (transition temperatures, enthalpies) along with the factors (stereochemical constraints, electrostatic interactions, aliphatic chain stacking, intermolecular forces) contributing to the adoption of tetragonal scaffolds are also discussed. Characteristic optical microscopy textures and X-ray diffraction patterns are presented. In parallel, a comparison of the geometrical parameters such as distances between atoms, molecular areas, volumes, and lattice parameters with the closest two-dimensional and three-dimensional organizations, is performed

Lamellar Tetragonal Symmetry of Amphiphilic Thermotropic Ionic Liquid Crystals in the Framework of Other Closely Related Highly Ordered Structures

An overview of the chemical compounds forming the rare smectic T phases is presented with references to the historical context. Thermodynamics (transition temperatures, enthalpies) along with the factors (stereochemical constraints, electrostatic interactions, aliphatic chain stacking, intermolecular forces) contributing to the adoption of tetragonal scaffolds are also discussed. Characteristic optical microscopy textures and X-ray diffraction patterns are presented. In parallel, a comparison of the geometrical parameters such as distances between atoms, molecular areas, volumes, and lattice parameters with the closest two-dimensional and three-dimensional organizations, is performed

Dendritic Polymers as Promising Additives for the Manufacturing of Hybrid Organoceramic Nanocomposites with Ameliorated Properties Suitable for an Extensive Diversity of Applications

As the field of nanoscience is rapidly evolving, interest in novel, upgraded nanomaterials with combinatory features is also inevitably increasing. Hybrid composites, offer simple, budget-conscious and environmental-friendly solutions that can cater multiple needs at the same time and be applicable in many nanotechnology-related and interdisciplinary studies. The physicochemical idiocrasies of dendritic polymers have inspired their implementation as sorbents, active ingredient carriers and templates for complex composites. Ceramics are distinguished for their mechanical superiority and absorption potential that render them ideal substrates for separation and catalysis technologies. The integration of dendritic compounds to these inorganic hosts can be achieved through chemical attachment of the organic moiety onto functionalized surfaces, impregnation and absorption inside the pores, conventional sol-gel reactions or via biomimetic mediation of dendritic matrices, inducing the formation of usually spherical hybrid nanoparticles. Alternatively, dendritic polymers can propagate from ceramic scaffolds. All these variants are covered in detail. Optimization techniques as well as established and prospected applications are also presented

Catalytic Neutralization of Water Pollutants Mediated by Dendritic Polymers

Radially polymerized dendritic compounds are nowadays an established polymer category next to their linear, branched, and cross-linked counterparts. Their uncommon tree-like architecture is characterized by adjustable internal cavities and external groups. They are therefore exceptional absorbents and this attainment of high concentrations in their interior renders them ideal reaction media. In this framework, they are applied in many environmentally benign implementations. One of the most important among them is water purification through pollutant decomposition. Simple and composite catalysts and photo-catalysts containing dendritic polymers and applied in water remediation will be discussed jointly with some unconventional solutions and prospects

Hydrophilic Antimicrobial Coatings for Medical Leathers from Silica-Dendritic Polymer-Silver Nanoparticle Composite Xerogels

Hybrid organic-inorganic (dendritic polymer-silica) xerogels containing silver nanoparticles (Ag Nps) were developed as antibacterial leather coatings. The preparation method is environmentally friendly and is based on two biomimetic reactions. Silica gelation and spontaneous Ag Nps formation were both mediated by hyperbranched poly (ethylene imine) (PEI) scaffolds of variable Mw (2000–750,000). The formation of precursor hydrogels was monitored by dynamic light scattering (DLS). The chemical composition of the xerogels was assessed by infrared spectroscopy (IR) and energy-dispersive X-ray spectroscopy (EDS), while the uniformity of the coatings was established by scanning electron microscopy (SEM). The release properties of coated leather samples and their overall behavior in water in comparison to untreated analogs were investigated by Ultraviolet-Visible (UV-Vis) spectroscopy. Antibacterial activity was tested against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, and antibiofilm properties against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Acinetobacter baumannii, and Enterococcus faecalis, while the SARS-CoV-2 clinical isolate was employed for the first estimation of their antiviral potential. Toxicity was evaluated using the Jurkat E6.1 cell line. Finally, water-contact angle measurements were implemented to determine the enhancement of the leather surface hydrophilicity caused by these composite layers. The final advanced products are intended for use in medical applications

Hydrophilic Antimicrobial Coatings for Medical Leathers from Silica-Dendritic Polymer-Silver Nanoparticle Composite Xerogels

Hybrid organic-inorganic (dendritic polymer-silica) xerogels containing silver nanoparticles (Ag Nps) were developed as antibacterial leather coatings. The preparation method is environmentally friendly and is based on two biomimetic reactions. Silica gelation and spontaneous Ag Nps formation were both mediated by hyperbranched poly (ethylene imine) (PEI) scaffolds of variable Mw (2000–750,000). The formation of precursor hydrogels was monitored by dynamic light scattering (DLS). The chemical composition of the xerogels was assessed by infrared spectroscopy (IR) and energy-dispersive X-ray spectroscopy (EDS), while the uniformity of the coatings was established by scanning electron microscopy (SEM). The release properties of coated leather samples and their overall behavior in water in comparison to untreated analogs were investigated by Ultraviolet-Visible (UV-Vis) spectroscopy. Antibacterial activity was tested against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, and antibiofilm properties against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Acinetobacter baumannii, and Enterococcus faecalis, while the SARS-CoV-2 clinical isolate was employed for the first estimation of their antiviral potential. Toxicity was evaluated using the Jurkat E6.1 cell line. Finally, water-contact angle measurements were implemented to determine the enhancement of the leather surface hydrophilicity caused by these composite layers. The final advanced products are intended for use in medical applications