Sirtuin1 and autophagy protect cells from fluoride-induced cell stress

AbstractSirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase functioning in the regulation of metabolism, cell survival and organismal lifespan. Active SIRT1 regulates autophagy during cell stress, including calorie restriction, endoplasmic reticulum (ER) stress and oxidative stress. Previously, we reported that fluoride induces ER-stress in ameloblasts responsible for enamel formation, suggesting that ER-stress plays a role in dental fluorosis. However, the molecular mechanism of how cells respond to fluoride-induced cell stress is unclear. Here, we demonstrate that fluoride activates SIRT1 and initiates autophagy to protect cells from fluoride exposure. Fluoride treatment of ameloblast-derived cells (LS8) significantly increased Sirt1 expression and induced SIRT1 phosphorylation resulting in the augmentation of SIRT1 deacetylase activity. To demonstrate that fluoride exposure initiates autophagy, we characterized the expression of autophagy related genes (Atg); Atg5, Atg7 and Atg8/LC3 and showed that both their transcript and protein levels were significantly increased following fluoride treatment. To confirm that SIRT1 plays a protective role in fluoride toxicity, we used resveratrol (RES) to augment SIRT1 activity in fluoride treated LS8 cells. RES increased autophagy, inhibited apoptosis, and decreased fluoride cytotoxicity. Rats treated with fluoride (0, 50, 100 and 125ppm) in drinking water for 6weeks had significantly elevated expression levels of Sirt1, Atg5, Atg7 and Atg8/LC3 in their maturation stage enamel organs. Increased protein levels of p-SIRT1, ATG5 and ATG8/LC3 were present in fluoride-treated rat maturation stage ameloblasts. Therefore, the SIRT1/autophagy pathway may play a critical role as a protective response to help prevent dental fluorosis

Experience with the Vibrant Soundbridge RW-Coupler for round window Vibroplasty with tympanosclerosis

Usage of the Vibrant Soundbridge (VSB) with round window (RW)-Coupler placement at the RW has been shown to successfully treat mixed hearing loss. Coupling between the VSB's floating mass transducer (FMT) and the RW membrane is difficult in the case of sclerosis in the RW and drilling down the bony lip until the RW membrane can be seen completely can possibly induce a perilymphatic fistula. A 68-year-old woman who had bilateral mixed hearing loss with sclerosis in the RW due to tympanosclerosis underwent a RW-Vibroplasty with a RW-Coupler. Speech discrimination scores in quiet and noise and functional gain with the VSB with RW-Coupler were better than those using a conventional hearing aid. The results of the present case have shown the feasibility of implanting a VSB with RW-Coupler in patients with mixed hearing loss due to tympanosclerosis.ArticleACTA OTO-LARYNGOLOGICA. 132(6):676-682 (2012)journal articl

Patients with CDH23 mutations and the 1555A > G mitochondrial mutation are good candidates for electric acoustic stimulation (EAS)

Conclusions: CDH23 mutations and the 1555A>G mitochondrial mutation were identified among our series of electric acoustic stimulation (EAS) patients, confirming that these genes were important in hearing loss with involvement of high frequency. Successful hearing preservation as well as good outcomes from EAS indicated that patients with this combination of mutations are good candidates for EAS. Objectives: Screening for gene mutations that possibly cause hearing loss involving high frequency was performed to identify the responsible genes in patients with EAS. In addition to a review of the genetic background of the patients with residual hearing loss, the benefit of EAS for patients with particular gene mutations was evaluated. Methods: Eighteen patients (15 late-onset, 3 early-onset) with residual hearing who had received EAS were included in this study. Genetic analysis was performed to identify GJB2, CDH23, SLC26A4, and the 1555 mitochondrial mutations. Results: Three early-onset patients had CDH23 mutations. One late-onset patient had the 1555 A>G mitochondrial mutation.ArticleACTA OTO-LARYNGOLOGICA. 132(4):377-384 (2012)journal articl

Achievement of hearing preservation in the presence of an electrode covering the residual hearing region

Conclusions: With full insertion with a long electrode, hearing preservation can be achieved even in the presence of a long electrode covering the residual hearing region. Objectives: Advances in developing new atraumatic concepts of electrode design as well as surgical technique have enabled hearing preservation after cochlear implantation surgery, and EAS (electric acoustic stimulation) accompanied with hearing preservation is a new trend for patients with residual hearing at the lower frequencies. However, full insertion with a long/medium electrode and hearing preservation is still a challenging field that calls for discussion. Method: In this study, round window insertion, an atraumatic electrode, and dexamethasone administration were used and atraumaticity (hearing preservation and conservation of vestibular function) was evaluated with full insertion of the electrode. Results: Postoperative evaluation after full insertion of the electrodes showed that hearing at low frequencies was well preserved in all five cases. Combined postoperative imaging with the referential tonotopic map confirmed achievement of full insertion and indicated the corresponding frequencies and the depth of the electrode. Achievement of atraumaticity of round window insertion in the present cases was confirmed from the viewpoint of the minimal drilling time as well as the preserved vestibular function.ArticleACTA OTO-LARYNGOLOGICA. 131(4):405-412 (2011)journal articl

A Case of Necrotizing Sialometaplasia of the Hard Palate Treated with Tranexamic Acid and Sodium Azulene Sulfonate

Necrotizing sialometaplasia is a benign lesion affecting the minor salivary glands of the hard palate. This lesion may be clinically and histopathologically confused with malignant lesions. A case of a 47-year-old man who presented with necrotizing sialometaplasia on the left side of the hard palate is herein reported. A biopsy was performed, and the condition was diagnosed based on immunohistochemistry. The lesion receded following treatment with tranexamic acid and sodium azulene sulfonate. The symptom of painful swelling on the hard palate subsided within 10 days. The palatal lesion had disappeared completely 4 months later

Suppressive effects of 2-methacryloyloxyethyl phosphorylcholine (MPC)-polymer on the adherence of Candida species and MRSA to acrylic denture resin

Objectives: The effects of 2-methacryloyloxyethyl phosphorylcholine (MPC)-polymer on the adherence of microorganisms such as non-Candida albicans Candida (NCAC) and methicillin-resistant Staphylococcus aureus (MRSA), frequently detected in oral infections in immunocompromised and/or elderly people, to denture resin material, are still unclear. Here, we report the effects of MPC-polymer on the adherence of C. albicans, NCAC, and MRSA to acrylic denture resin. Methods: Sixteen strains of C. albicans, seven strains of C. glabrata, two strains of C. tropicalis, one strain of C. parapsilosis, and six strains of MRSA were used. We cultured the fungal/bacterial strains and examined the cell growth and adherence of fungi/bacteria to mucin-coated acrylic denture resin plates (ADRP) with or without MPC-polymer coating, by scanning electron microscopy. The cell surface hydrophobicity of the fungal/bacterial strains was measured by the adsorption to hydrocarbons. Results: MPC-polymer did not affect the growth of all strains of Candida species and MRSA, but significantly suppressed adherence to ADRP in most strains of C. albicans and all strains of NCAC and MRSA. A significant positive correlation was found between cell hydrophobicity and the reduction rates of microbial adherence to ADRP treated with 5% of MPC-polymer. Conclusions: MPC-polymer treatment for acrylic resin material suppresses the adherence of C. albicans, NCAC and MRSA via their hydrophilicity interaction. Clinical significance: The application of MPC-polymer for denture hygiene is potent to prevent oral candidiasis, denture stomatitis and opportunistic infection, caused by Candida species and MRSA, via suppressing the adherence of those fungus/bacteria