Surface charge modification decreases Pseudomonas aeruginosa adherence in vitro and bacterial persistence in an in vivo implant model.

Objective: Chronic, persistent infections complicate otologic procedures utilizing implantable devices such as cochlear implants or tympanostomy tubes. These infections are thought to be due to the establishment of microbial biofilms on implant surfaces. To address this issue, we hypothesized that surface charge modification may inhibit the formation of Pseudomonas aeruginosa biofilms on implant surfaces in vitro and in vivo.

D-amino acids do not inhibit biofilm formation.

Objective: , a known biofilm-forming organism, is an opportunistic pathogen that plays an important role in chronic otitis media, tracheitis, cholesteatoma, chronic wounds, and implant infections. Eradication of biofilm infections has been a challenge because the biofilm phenotype provides bacteria with a protective environment from the immune system and antibiotics; thus, there has been great interest in adjunctive molecules that may inhibit biofilm formation or cause biofilm dispersal. There are reports that D-amino acids may inhibit biofilms.

FleQ, a Transcriptional Activator, Is Required for Biofilm Formation In Vitro But Does Not Alter Virulence in a Cholesteatomas Model.

Hypothesis: Bacterial biofilm formation within cholesteatomas is responsible for increased persistence and tissue destruction and Pseudomonas aeruginosa deficient in biofilm formation (PAO1 ΔfleQ) are less virulent than the parent bacteria.

Background: Infected aural cholesteatomas have been demonstrated to be more destructive than uninfected cholesteatomas and infections are more persistent. The chronicity and persistence of infections within cholesteatomas may be because of the presence of biofilm formation.

QTL Mapping of Endocochlear Potential Differences between C57BL/6J and BALB/cJ mice.

We reported earlier that the endocochlear potential (EP) differs between C57BL/6J (B6) and BALB/cJ (BALB) mice, being lower in BALBs by about 10 mV (Ohlemiller et al. Hear Res 220: 10-26, 2006). This difference corresponds to strain differences with respect to the density of marginal cells in cochlear stria vascularis.

Inactivation of specific Pseudomonas aeruginosa biofilm factors does not alter virulence in infected cholesteatomas.

Hypothesis: When experimental cholesteatomas are infected with Pseudomonas aeruginosa (PA) mutants lacking factors associated with the formation of biofilms, host defenses are more effective against these strains when compared with wild-type strains (PAO1 and OPPA8) in preventing tissue destruction.

Background: Previous studies have identified biofilms within chronically infected aural cholesteatomas. These infected cholesteatomas are associated with increased tissue destruction.

Biofilm formation by otopathogenic strains of Pseudomonas aeruginosa is not consistently inhibited by ethylenediaminetetraacetic acid.

Hypothesis: Biofilm formation in otopathogenic of Pseudomonas aeruginosa (OPPA) strains is inhibited by ethylenediaminetetraacetic acid (EDTA).

Background: EDTA, a widely used chelating agent, has been shown to inhibit biofilm formation in a number of bacteria. Because EDTA may be a well-tolerated reagent to inhibit biofilm formation in cases of suppurative otitis media, we asked if it might be effective in all OPPA strains isolated from chronically infected cholesteatomas.

Nutrient-enhanced diet reduces noise-induced damage to the inner ear and hearing loss.

Oxidative stress has been implicated broadly as a cause of cell death and neural degeneration in multiple disease conditions; however, the evidence for successful intervention with dietary antioxidant manipulations has been mixed. In this study, we investigated the potential for protection of cells in the inner ear using a dietary supplement with multiple antioxidant components, which were selected for their potential interactive effectiveness. Protection against permanent threshold shift (PTS) was observed in CBA/J mice maintained on a diet supplemented with a combination of β-carotene, vitamins C and E, and magnesium when compared with PTS in control mice maintained on a nutritionally complete control diet.

Protection by low-dose kanamycin against noise-induced hearing loss in mice: dependence on dosing regimen and genetic background.

We recently demonstrated that sub-chronic low-dose kanamycin (KM, 300 mg/kg sc, 2×/day, 10 days) dramatically reduces permanent noise-induced hearing loss (NIHL) and hair cell loss in 1 month old CBA/J mice (Fernandez et al., 2010, J. Assoc.

Different cellular and genetic basis of noise-related endocochlear potential reduction in CBA/J and BALB/cJ mice.

The acute and permanent effects of noise exposure on the endocochlear potential (EP) and cochlear lateral wall were evaluated in BALB/cJ (BALB) inbred mice, and compared with CBA/J (CBA) and C57BL/6 (B6) mice. Two-hour exposure to broadband noise (4-45 kHz) at 110 dB SPL leads to a approximately 50 mV reduction in the EP in BALB and CBA, but not B6. EP reduction in BALB and CBA is reliably associated with characteristic acute cellular pathology in stria vascularis and spiral ligament.

Divergent aging characteristics in CBA/J and CBA/CaJ mouse cochleae.

Two inbred mouse strains, CBA/J and CBA/CaJ, have been used nearly interchangeably as 'good hearing' standards for research in hearing and deafness. We recently reported, however, that these two strains diverge after 1 year of age, such that CBA/CaJ mice show more rapid elevation of compound action potential (CAP) thresholds at high frequencies (Ohlemiller, Brain Res. 1277: 70-83, 2009).

Protection against noise-induced hearing loss in young CBA/J mice by low-dose kanamycin.

Animal studies indicate that a combination of kanamycin (KM) and noise produces a synergistic effect, whereby the threshold shift from the combination is greater than the sum of the shifts caused by either agent alone. Most such studies have focused on adult animals, and it has remained unclear whether younger, presumably more susceptible, animals show an even greater synergistic effect. The present study tested the hypothesis that young CBA/J mice receiving a low dose of KM (300 mg/kg, 2x/day, s.

A major effect QTL on chromosome 18 for noise injury to the mouse cochlear lateral wall.

We recently demonstrated a striking difference among inbred mouse strains in the effects of a single noise exposure, whereby CBA/J and CBA/CaJ (CBA) mice show moderate reversible reduction in the endocochlear potential (EP) while C57BL/6J (B6) mice do not (Ohlemiller, K.K., Gagnon, P.

Absence of strial melanin coincides with age-associated marginal cell loss and endocochlear potential decline.

Cochlear stria vascularis contains melanin-producing intermediate cells that play a critical role in the production of the endocochlear potential (EP) and in maintaining the high levels of K(+) that normally exist in scala media. The melanin produced by intermediate cells can be exported to the intrastrial space, where it may be taken up by strial marginal cells and basal cells. Because melanin can act as an antioxidant and metal chelator, evidence for its role in protecting the stria and organ of Corti against noise, ototoxins, and aging has long been sought.

Strial microvascular pathology and age-associated endocochlear potential decline in NOD congenic mice.

NOD/ShiLtJ (previously NOD/LtJ) inbred mice show polygenic autoimmune disease and are commonly used to model autoimmune-related type I diabetes, as well as Sjogren's syndrome. They also show rapidly progressing hearing loss, partly due to the combined effects of Cdh23ahl and Ahl2. Congenic NOD.

Genetic dependence of cochlear cells and structures injured by noise.

The acute and permanent effects of a single damaging noise exposure were compared in CBA/J, C57BL/6 (B6), and closely related strains of mice. Two hours of broadband noise (4-45 kHz) at 110 dB SPL led to temporary reduction in the endocochlear potential (EP) of CBA/J and CBA/CaJ (CBA) mice and acute cellular changes in cochlear stria vascularis and spiral ligament. For the same exposure, B6 mice showed no EP reduction and little of the pathology seen in CBA.

Temporal and genetic influences on protection against noise-induced hearing loss by hypoxic preconditioning in mice.

The protective benefits of hypoxic preconditioning (HPC) against permanent noise-induced hearing loss (NIHL) were investigated in mice. Hypoxia induced by exposure to 8% O2 for 4 h conferred significant protection against damaging broadband noise delivered 24-48 h later in male and female CBA/J (CBA) and CBA/CaJ mice. No protection was found in C57BL/6 (B6) mice, their B6.

Cellular correlates of age-related endocochlear potential reduction in a mouse model.

Age-related degeneration of cochlear stria vascularis and resulting reduction in the endocochlear potential (EP) are the hallmark features of strial presbycusis, one of the major forms of presbycusis, or age-related hearing loss (ARHL) (Schuknecht, H.F., 1964.

Apical-to-basal gradients in age-related cochlear degeneration and their relationship to "primary" loss of cochlear neurons.

The predominant conceptual framework for understanding human age-related hearing loss (ARHL, or presbycusis) holds that three different cochlear elements (organ of Corti, afferent neurons, and stria vascularis) can degenerate independently, and exert independent influences on hearing. Within this framework, temporal bones from subjects with ARHL may be classified as exemplifying sensory (referring to organ of Corti), "primary" neural (loss of afferent neurons without loss of their hair cell targets), strial, or mixed ARHL. While there is general agreement as to the types of cochlear cells most affected by aging, there is less agreement about how to classify ARHL, and whether contributions of particular structures to hearing loss can be isolated.

Cellular correlates of progressive hearing loss in 129S6/SvEv mice.

Several strains of mice hear well initially but show progressive sensorineural hearing loss. Affected cochlear cell types include all those known to be affected in human age-related hearing loss (ARHL), or presbycusis. Thus these mice have been offered as models of human ARHL.