Hough Ear Institute

Tinnitus is the perception of sound in the absence of external acoustic stimulation. Being one of the most common diseases of the ear, it has a global prevalence ranging from 4.1 to 37.2%. To date, it has been difficult to treat tinnitus as its pathophysiology is poorly understood and there are limited treatment options. To investigate the effect of OKN-007 (also known as HPN-07), a nitrone-based investigational drug, in combination with oral N-acetylcycsteine (NAC), for the treatment of hearing loss and chronic tinnitus under an individual expanded access protocol. We report the case of a patient who presented with left-sided ear fullness, mild tinnitus, and mild high frequency sensorineural hearing loss with 100% word recognition. A large enhancing mass seen on MRI revealed a vestibular schwannoma. He underwent subtotal resection of the tumor resulting in a moderate-to-profound sensorineural hearing loss and catastrophic tinnitus. The patient was treated with intravenous OKN-007 at 60 mg/kg dosed three times per week and oral NAC 2500 mg twice daily. Post-treatment audiometric testing revealed an average of 16.66 dB in hearing threshold improvement in three frequencies (125, 250 and 500 Hz) with residual hearing in the affected left ear. His tinnitus loudness matching improved from 90 dB to 19 dB post-treatment. His Tinnitus Handicap Inventory improved from 86/100 (Catastrophic) to 40/100 (Moderate). He also experienced improvements in sleep, concentration, hearing, and emotional well-being, and reported significantly decreased levels of tinnitusrelated distress. This case report highlights the feasibility and therapeutic potential of the combination of OKN-007 and NAC in treating hearing loss and tinnitus that warrants further investigation.

This paper will discuss the design challenges and solutions associated with the rehabilitation and replacement of the Del City Pipeline in Central Oklahoma. These challenges included tight development corridors along portions of the existing pipeline, the need for a specialty trenchless technology, unique service requirements, and a variety of project stakeholders. Ultimately, the pipeline was determined to be replaced in sections via an open-cut parallel pipeline and rehabilitated in other sections utilizing a compressed-fit high-density polyethylene (HDPE) liner. This paper will also discuss the steps undertaken during construction to ensure a successful project and the lessons learned.

BackgroundSudden sensorineural hearing loss (SSNHL) is currently treated with a combination of drugs, predominantly with glucocorticoids (GCs). However, the mechanisms of action of GCs in SSNHL are unknown. This study aimed to analyze the role of endoplasmic reticulum stress (ERS) in SSNHL pathogenesis and prognosis.Material/MethodsIn this study, we evaluated the expression and activation status of the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-C/EBP homologous protein (CHOP) pathway in peripheral blood mononuclear cells (PBMCs) from patients with SSNHL and compared them with those in healthy controls. We also compared differences in expression of activating transcription factor 4 (ATF4) and CHOP before and after glucocorticoid treatment in patients with improved and unimproved SSNHL.ResultsTreatment with GCs significantly improved hearing in 55% of patients with SSNHL. Levels of phosphorylated PERK (p-PERK) and phosphorylated eukaryotic initiation factor 2α were increased in PBMCs from patients with SSNHL compared with healthy controls. ATF4 and CHOP expression were also significantly elevated. After treatment, the amount of ATF4 and CHOP proteins in PBMCs in the patients whose SSNHL improved was significantly reduced compared with the levels measured before treatment in all patients with SSNHL. The expression of the ATF4 and CHOP proteins in PBMCs in the unimproved group, however, was not significantly changed relative to pretreatment levels.ConclusionsERS may play a significant role in the pathogenesis of SSNHL, and the responsiveness of the condition to GC-mediated mitigation of ERS may be one of the key factors that affect patient prognosis.

Glucocorticoids have been used to treat hearing loss and vestibular dysfunction for many years. However, some reports have indicated that a subset of patients with these disorders exhibit glucocorticoid insensitivity or resistance. A reduction in histone deacetylase 2 (HDAC2) activity and expression has been reported to play a critical role in glucocorticoid resistance. Here, we investigated the protective effects of aminophylline on HDAC2 expression and glucocorticoid sensitivity in lipopolysaccharide (LPS)-induced sudden sensorineural hearing loss in guinea pigs. We assessed hearing recovery in LPS-applied guinea pigs, which were either left untreated or were systemically treated with either dexamethasone, aminophylline, or a combination of the two. We utilized fluorescence microscopy and enzyme-linked immunosorbent assay to analyze the distribution patterns of HDAC2 and detect its levels in the cochlea. We used hematoxylin-eosin staining to examine cochlear histopathological changes. In the absence of treatment, significant hearing loss was detected in LPS-exposed animals. A synergistic effect was observed between aminophylline and dexamethasone in maintaining HDAC2 expression levels, preventing hearing loss in LPS-exposed animals and reducing cochlear damage. This study indicates that aminophylline can restore glucocorticoid sensitivity, which provides a new approach to treating patients with hearing disorders who are refractory to glucocorticoids.

This study has summarized the development of Docetaxel (DOC) loaded nanocapsules (NCs) intended for breast cancer (BC) therapy. These NCs are composed of a lipid core to encapsulate the hydrophobic DOC and a polymeric shell for surface functionalization. DOC was efficiently encapsulated within the oily core of NCs. The critical role of stabilizers on NCs stealthiness and anticancer drug efficacy was investigated. The potential impact of surface chemistry on the cytotoxicity and phagocytic clearance of NCs for a subsequent improvement of the efficacy of DOC in BC treatment was explored. The in vitro cell culture studies in cancer cell lines showed a significant enhancement of the cytotoxicity of DOC due to its high loading within the NCs. Interestingly, the NCs were stable during storage and could be efficiently transformed into powder form using freeze-drying method. It is also hypothesized that DOC-loaded hyaluronic acid (HA) grafted oily core NCs can enhance the drug cytotoxicity and uptake in CD44 expressing BC cells (MDA-MB 231). These novel nanostructures hold the promise to support the potential clinical application and cost-effectiveness of innovative nanotherapeutics in cancer therapy.

Electrocochleography measures in humans were examined to determine factors affecting results. Retrospective study. Analysis was performed on data from 479 patients seen from 1998 to 2002 who underwent electrocochleography with a tympanic membrane electrode. Measures from click evoked electrocochleography (the summating potential to action potential ratio [SP/AP]) were compared with tone evoked electrocochleography (the SP amplitude). Findings indicate a strong correlation between click and tone measures if the AP from click measures was over 1 microV (P <.001), but no significant correlation between these measures if the AP was under 1 microV. Results were also analyzed with respect to patient hearing sensitivity and final diagnosis. Tympanic membrane electrocochleography is more efficacious when the AP from click stimulation is over 1 microV.