Preconditioning by ultra-low dose of tramadol reduces the severity of tramadol-induced seizure: Contribution of glutamate receptors.

Tramadol, a weak agonist of mu-opioid receptors, causes seizure via several mechanisms. Preconditioning has been purposed to reduce the epileptic seizures in animal models of epilepsy. The preconditioning effect of tramadol on seizure is not studied yet. This study was designed to evaluate the preconditioning effect of ultra-low dose of tramadol on the seizures induced by tramadol at high dose. Furthermore, regarding the critical role of glutamate signaling in the pathogenesis of epilepsy, the effect of preconditioning on some glutamate signaling elements was also examined. Male Wistar rats received tramadol (2 mg/kg, i.p) or normal saline (1 mL/kg, i.p) in preconditioning and control groups, respectively. After 4 days, the challenging tramadol dose (150 mg/kg) was injected to all rats. Epileptic behaviors were recorded during 50 min. The expression of Norbin (as a regulator of metabotropic glutamate receptor 5), Calponin3 (as a regulator of excitatory synaptic markers), NR1 (NMDA receptor subunit 1) and GluR1 (AMPA receptor subunit 1) was measured in hippocampus, prefrontal cortex (PFC) and amygdala. Preconditioning decreased the number and duration of tremors and tonic-clonic seizures. Norbin, Calponin3, NR1 and GluR1 expression were decreased in hippocampus, and preconditioning had no effect on them. In contrast, it increased Norbin expression in PFC and amygdala, and attenuated NR1 and GluR1 upregulation following tramadol at high dose. These findings indicated that preconditioning by ultra-low dose of tramadol protected the animals against seizures following high dose of tramadol mediated, at least in part, by Norbin up regulation, and NR1 and GluR1 down regulation.

Bactericidal dental nanocomposites containing 1,2,3-triazolium-functionalized POSS additive prepared through thiol-ene click polymerization.

OBJECTIVE: Deterioration of mechanical strength for the dental composite containing ionic bactericidal compounds restricts the widespread utilization of this class of useful materials. This problem is originated from the reduction of the intermolecular interaction of polymeric network due to plasticization effect of absorbed water molecules penetrated between the chain segments. The main goal of this study is the synthesis of the highly efficient bactericidal additive with low hydrophilicity and consequently the least adverse effect on the final mechanical strength of the dental composite. METHODS: The bactericidal 1, 2, 3-triazolium functional groups were chemically anchored on the surface of hydrophobic POSS nanoparticles (Triazolium-POSS) and incorporated into a dental restorative system composed of a ternary thiol-allyl ether-methacrylate resin and glass fillers. A similar system was also prepared, in which the POSS additive was replaced with quaternized dimethyl aminoethyl methacrylate monomer (DMAEMA-BC). The chemical structure of POSS derivatives was evaluated by 1HNMR and FTIR spectra. The water uptake of dental composites was evaluated at days 1 and 14 after immersion into water. The bactericidal activity of composite specimens against Streptococcus mutans (ATCC 35668) was determined based on ASTM E 2180 - 07. The flexural properties of samples were investigated through three-point bending assay and the shrinkage-strain of photo-cured resins was measured using the bonded-disk technique. The degree of conversion (DC %) of methacrylate functions was followed by FTIR spectroscopy. MTT assay was performed to investigate the cytocompatibility of samples. RESULTS: Regardless of the partial increase in water uptake for Triazolium-POSS-containing sample, this parameter was much favor than the composite made from DMAEMA-BC. Therefore, the lower decline in flexural properties was recorded under the wet condition for the former system. Incorporation of Triazolium-POSS had no significant effect on shrinkage strain and cytocompatibility of composite specimen, meanwhile, a higher degree of conversion of methacrylate functional groups was recorded. The Triazolium-POSS-containing nano composite showed significantly higher bactericidal activity against Streptococcus mutans than another studied model system. SIGNIFICANCE: The new derivative of bactericidal POSS nanoparticles decorated with 1, 2, 3-Triazolium moieties is a highly efficient bactericidal compound. If Triazolium-POSS is incorporated into a proper dental resin formulation, it can provide a strong bactericidal activity for dental materials; in the meantime, it leads to minimum deterioration of their mechanical strength due to its low water uptake.

Guanidine hydrochloride embedded polyurethanes as antimicrobial and absorptive wound dressing membranes with promising cytocompatibility.

Preparation and assessments of novel absorptive wound dressing materials with efficient antimicrobial activity as well as very good cytocompatibility were described in this work. An amine terminated poly(hexamethylene guanidine hydrochloride) was prepared and used as curing agent of different epoxy-terminated polyurethane prepolymers. The structures of prepared materials were elucidated by evaluation of their (1)H NMR and FTIR spectra. The recorded tensile strength of membranes confirmed the excellent dimensional stability of the film type dressings even at fully hydrated conditions. Therefore, these dressings could protect the wound bed from external forces during the healing period. The structurally optimized dressing membranes could preserve the desired moist environment over the wounded area, as a result of their balanced equilibrium, water absorption and water vapor transmission rate. Therefore, a very good condition for stimulation of self-healing of wound bed was attained. Also, owing to the presence of guanidine hydrochloride moieties embedded into the structure of dressings, efficient antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans were detected. In vitro cytotoxicity assay of the prepared dressings revealed cytocompatibility of these materials against fibroblast cells. Therefore, they could support cell growth and proliferation at the wounded area.