PLGA Microspheres Containing Hydrophobically Modified Magnesium Hydroxide Particles for Acid Neutralization-Mediated Anti-Inflammation.

BACKGROUND: Poly(lactic-co-glycolic acid) (PLGA) microspheres have been actively used in various pharmaceutical formulations because they can sustain active pharmaceutical ingredient release and are easy to administer into the body using a syringe. However, the acidic byproducts produced by the decomposition of PLGA cause inflammatory reactions in surrounding tissues, limiting biocompatibility. Magnesium hydroxide (MH), an alkaline ceramic, has attracted attention as a potential additive because it has an acid-neutralizing effect. METHODS: To improve the encapsulation efficiency of hydrophilic MH, the MH particles were capped with hydrophobic ricinoleic acid (RA-MH). PLGA microspheres encapsulated with RA-MH particles were manufactured by the O/W method. To assess the in vitro cytotoxicity of the degradation products of PLGA, MH/PLGA, and RA-MH/PLGA microspheres, CCK-8 and Live/Dead assays were performed with NIH-3T3 cells treated with different concentrations of their degradation products. In vitro anti-inflammatory effect of RA-MH/PLGA microspheres was evaluated with quantitative measurement of pro-inflammatory cytokines. RESULTS: The synthesized RA-MH was encapsulated in PLGA microspheres and displayed more than four times higher loading content than pristine MH. The PLGA microspheres encapsulated with RA-MH had an acid-neutralizing effect better than that of the control group. In an in vitro cell experiment, the degradation products obtained from RA-MH/PLGA microspheres exhibited higher biocompatibility than the degradation products obtained from PLGA microspheres. Additionally, the RA-MH/PLGA microsphere group showed an excellent anti-inflammatory effect. CONCLUSION: Our results proved that RA-MH-encapsulated PLGA microspheres showed excellent biocompatibility with an anti-inflammatory effect. This technology can be applied to drug delivery and tissue engineering to treat various incurable diseases in the future.

Neuronal susceptibility to beta-amyloid toxicity and ischemic injury involves histone deacetylase-2 regulation of endophilin-B1.

Histone deacetylases (HDACs) catalyze acetyl group removal from histone proteins, leading to altered chromatin structure and gene expression. HDAC2 is highly expressed in adult brain, and HDAC2 levels are elevated in Alzheimer's disease (AD) brain. We previously reported that neuron-specific splice isoforms of Endophilin-B1 (Endo-B1) promote neuronal survival, but are reduced in human AD brain and mouse models of AD and stroke. Here, we demonstrate that HDAC2 suppresses Endo-B1 expression. HDAC2 knockdown or knockout enhances expression of Endo-B1. Conversely, HDAC2 overexpression decreases Endo-B1 expression. We also demonstrate that neurons exposed to beta-amyloid increase HDAC2 and reduce histone H3 acetylation while HDAC2 knockdown prevents Aß induced loss of histone H3 acetylation, mitochondrial dysfunction, caspase-3 activation, and neuronal death. The protective effect of HDAC2 knockdown was abrogated by Endo-B1 shRNA and in Endo-B1-null neurons, suggesting that HDAC2-induced neurotoxicity is mediated through suppression of Endo-B1. HDAC2 overexpression also modulates neuronal expression of mitofusin2 (Mfn2) and mitochondrial fission factor (MFF), recapitulating the pattern of change observed in AD. HDAC2 knockout mice demonstrate reduced injury in the middle cerebral artery occlusion with reperfusion (MCAO/R) model of cerebral ischemia demonstrating enhanced neuronal survival, minimized loss of Endo-B1, and normalized expression of Mfn2. These findings support the hypothesis that HDAC2 represses Endo-B1, sensitizing neurons to mitochondrial dysfunction and cell death in stroke and AD.

Clinical and radiographic outcomes of immediate and delayed placement of dental implants in molar and premolar regions.

PURPOSE: The purpose of this retrospective study was to determine clinical and radiographic outcomes of immediate and delayed placement of dental implants in molar and premolar regions. MATERIALS AND METHODS: Clinical and radiographic records of 116 patients who received implants in molar and premolar regions were included in this study. After implantation, patients were recalled for assessments at 1 month, 3 months, 6 months, 1 year, and every year thereafter. In addition, anatomic location, type of prosthesis, gender, stage, diameter, and length of implants were analyzed. RESULTS: Of these 116 patients, 55 were males, and 61 were females. Their mean age was 50.9 years. They received 85 immediate implants and 147 delayed implants in molar and premolar regions. Gender, type of prosthesis, stage, implant diameter, and implant length were not significantly different between the immediate placement group and the delayed placement group, although anatomic locations were significantly different between the 2 groups. Their mean follow up time after dental implantation was 3 years (range, 6 months to 9 years). Kaplan-Meier survival estimates showed 97.8% probability of survival up to 9 years in the delayed placement group and 100% probability of survival up to 8 years in the immediate placement group. There was no significant difference in implant survival according to the time of implantation. No significant difference in cervical bone loss (CBL) at the mesial or distal side was found between the 2 groups. CBL according to anatomic location, the type of prosthesis, or gender was not significantly different either between the 2 groups. However, CBL at distal side of 1-stage approach was significantly (P < .05) smaller in the delayed placement group than that in the immediate placement group. CONCLUSION: This study showed that immediate dental implantation in molar and premolar regions had good clinical and radiographic outcomes.