hearing loss exposure to toxins

Loss of sensory hair cells from exposure to certain licit drugs (e.g., aminoglycoside antibiotics, platinum-based chemotherapy agents) can result in permanent hearing loss. Here we ask if allosteric activation of the hepatocyte growth factor (HGF) cascade via Dihexa, a small molecule drug candidate, can protect hair cells from aminoglycoside toxicity. Unlike native HGF, Dihexa is chemically stable and blood-brain barrier permeable. As a synthetic HGF mimetic, it forms a functional ligand by dimerizing with endogenous HGF to activate the HGF receptor and downstream signaling cascades...

OBJECTIVE: To propose an etiology for a syndrome of bilateral vestibular hypofunction and sound and/or pressure-evoked eye movements with normal hearing thresholds. DESIGN: Retrospective case series. SETTING: Tertiary care referral center. PATIENTS: Four patients with bilateral vestibular hypofunction, sound and/or pressure-evoked nystagmus and normal hearing thresholds were identified over a 3-year period. No evidence of other known vestibular disorders was identified...

The different cell types within the cochlea may have a specific contribution to the pathological changes during metabolism failure, which may provide clues for developing novel strategies for inner ear therapy. In order to evaluate activity-correlated cell death during metabolism failure in the cochlea, 3-nitropropionic acid was used to irreversibly inhibit the respiratory chain. Dose-response of the cochlear cells to 3-nitropropionic acid was analyzed in vitro. 3-Nitropropionic acid was administered onto the round window of guinea pigs...

CONCLUSION: Brain-derived neurotrophic factor (BDNF) protects the inner ear from PaExoA (exotoxin A from Pseudomonas aeruginosa)-induced sensory neural hearing loss when administered 12 h after exotoxin, but not after 72 h. OBJECTIVE: BDNF is a peptide in the neurotrophin family with protective effects against noise-induced hair cell loss and toxic inner ear damage following exposure to cisplatin. The exotoxin A (PaExoA) from P. aeruginosa, the most common microorganism in chronic suppurative otitis media, induces sensorineural hearing loss in rats...

CONCLUSION: Brain-derived neurotrophic factor (BDNF) can prevent auditory brainstem response (ABR) threshold shift changes caused by Pseudomonas aeruginosa exotoxin A (PaExoA). OBJECTIVE: Peptides of the neurotrophin family are known to prevent neuronal death during embryonic development by interacting with specific membrane receptors. The purpose of this study was to investigate whether a single dose of BDNF is an effective protectant against toxic effects of PaExoA-induced ABR threshold shifts...

OBJECTIVES: Reports of an association between antineutrophil cytoplasmic antibodies (ANCA) and autoimmune neutropenia have rarely included cases of proven vasculitis. A case of ANCA-associated vasculitis (AAV) with recurrent neutropenia is described and relevant literature on the association between ANCA, neutropenia, and vasculitis is reviewed. METHODS: Longitudinal clinical assessments and laboratory findings are described in a patient with AAV and recurrent episodes of profound neutropenia from December 2008 to October 2010...

Hepatic encephalopathy (HE) is a challenging clinical complication of liver dysfunction with a wide spectrum of neuropsychiatric abnormalities that range from mild disturbances in cognitive function and consciousness to coma and death. The pathogenesis of HE in cirrhosis is complex and multifactorial, but a key role is thought to be played by circulating gut-derived toxins of the nitrogenous compounds, most notably ammonia. Therapeutic treatment options for HE are currently limited and have appreciable risks and benefits associated with their use...

Congenital sensorineural hearing loss (SNHL) is common. In the Western world, the incidence is 1-3 per 1000 live births. The aetiology encompasses genetic and non-genetic factors accounting for 55 % and 45 % of cases, respectively. Reports that describe the contribution of intrauterine infection to the occurrence of congenital SNHL are limited, and comparative analysis of the different pathogens is lacking. Lipopolysaccharide (LPS), a product of bacteriolysis, has been demonstrated to be associated with inner ear damage in experimental studies...

Inner ear sensory hair cell death is observed in the majority of hearing and balance disorders, affecting the health of more than 600 million people worldwide. While normal aging is the single greatest contributor, exposure to environmental toxins and therapeutic drugs such as aminoglycoside antibiotics and antineoplastic agents are significant contributors. Genetic variation contributes markedly to differences in normal disease progression during aging and in susceptibility to ototoxic agents. Using the lateral line system of larval zebrafish, we developed an in vivo drug toxicity interaction screen to uncover genetic modulators of antibiotic-induced hair cell death and to identify compounds that confer protection...

OBJECTIVES: Occupational noise-induced hearing loss (ONIHL) describes an acquired hearing deficiency directly attributable to excessive workplace noise exposure. Data suggest that excessive noise attributes to approximately 37% of all adult causes of hearing loss and remains a significant contributor to employment-related morbidity internationally. Typically insidiously-acquired, often without frank progressive symptomatology, regional medical agencies continue to struggle with this potentially debilitating condition...

CONCLUSION: Our findings suggest that edaravone can protect against cochlear damage caused by Pseudomonas aeruginosa exotoxin A (PaExoA). OBJECTIVE: To analyze the protective effect of a free radical scavenger, edaravone, against the ototoxicity resulting from exposure of the middle ear to PaExoA. MATERIAL AND METHODS: In nine groups of albino rats the following solutions were instilled either via the tympanic membrane into the round window niche [intratympanically (i...

Mitochondrial dysfunction in the cochlea is thought to be an important cause of sensorineural hearing loss. Recently, we have established a novel rat model with acute hearing impairment caused by exposure to the mitochondrial toxin 3-nitropropionic acid (3-NP) to analyze the mechanism of cochlear mitochondrial dysfunction. Both permanent and temporary threshold shifts were observed in this model depending on the amount of 3-NP used to induce hearing impairment. In this study, we demonstrate cochlear morphological changes in the permanent threshold shift model...

OBJECTIVE: To ascertain whether the severity of toxin-related hearing loss and the interval between instillation of toxin and surgical trauma affect hearing recovery capacity following semicircular canal (SCC) surgery in the rat. MATERIAL AND METHODS: Twelve rats were injected with Pseudomonas aeruginosa exotoxin A (PaExoA). Auditory brainstem responses (ABRs) were measured 72 h and 3 weeks later. Depending on the severity of hearing loss, the rats were divided into two groups: those with moderate (Group A; n = 6) and severe (Group B; n = 6) hearing loss...

OBJECTIVE: The protective effect of brain-derived neurotrophic factor (BDNF) against the ototoxicity resulting from exposure of Pseudomonas aeruginosa exotoxin A (PaExoA) to the middle ear was analyzed. The combined effect of BDNF and N(G)-nitro-L-arginine methyl ester (L-NAME) was also investigated. MATERIAL AND METHODS: Six groups of albino rats were instilled through the tympanic membrane into the round window niche with the following solutions: saline; PaExoA; BDNF; L-NAME; PaExoA + BDNF; and PaExoA + BDNF + L-NAME...

Red tides are formed from blooms of marine algae. Among them, the dinoflagellate ( Karenia brevis) that is responsible for Florida red tides can release many types of natural toxins, which cause massive kills of marine animals, including endangered species, and threaten human health. This study was to investigate whether or not a neurotoxin, brevetoxin-3, purified from Florida red tides affects hearing sensitivity of a teleost fish, the goldfish ( Carassius auratus). LD(50) of the goldfish that were intraperitoneally injected with brevetoxin-3 was 0...

The auditory and nonauditory effects of noise can be quite profound, affecting approximately 15 to 20 million Americans. As with most occupational toxins, recognition and careful assessment of noise exposure are the foundation on which preventive measures and treatment are based. Dosimeters can measure noise exposure over specific time periods. Pure tone air conduction audiometric monitoring should be performed on an annual basis in workers at risk for significant noise exposure. Occupational infectious disease involves far more than hepatitis and tuberculosis...

One group of Sprague-Dawley rats (group A, n = 6) was treated by instilling Pseudomonas aeruginosa exotoxin A (PaExoA), and another (group B, n = 6) treated similarly with Haemophilus influenzae type b endotoxin (HiBEndo). In group A a 20 dB hearing loss was observed, predominantly in the high-frequency region, which was reversible within 1 month. In group B no significant hearing impairment was noted. Between 1 and 6 months later, the lateral and posterior semicircular canals (SCCs) were ablated unilaterally...

Electrophysiological changes were studied in the albino rat following instillation of Pseudomonas aeruginosa exotoxin A into the middle ear cavity through the tympanic membrane. Hearing threshold was measured by a burst-elicited, frequency-specific auditory brainstem response (ABR) technique prior to exposure, then 24 and 48 h, 5 days, 2 and 4 weeks after the toxin instillation. A single dose (1 microgram/20 microliters) of Pseudomonas aeruginosa exotoxin A raised the ABR threshold over the whole frequency range, by 5-25 dB, particularly in the high tones...

Epidemiologic studies document that work in the agricultural sector is associated with many occupational health hazards. Exposure to organic dusts and airborne microorganisms and their toxins may lead to respiratory disorders. The burden of exposure-related chronic bronchitis, asthma, hypersensitivity pneumonitis, organic-dust toxic syndrome, and chronic airflow limitation can be diminished by appropriate preventive measures. The contribution of exposures to agricultural chemicals to cancers and neurodegenerative disorders is being investigated...

Middle ear permeability after instillation of staphylococcal pyrogenic exotoxin was studied in each of 12 cats, 6 of them with otitis media induced by obstructing their eustachian tubes. This is the first report that there is passage of toxin to the perilymph, cerebrospinal fluid and blood not only in diseased ears, but also in normal controls, 25 min and 12 h after exposure of the middle ear cavity and round window membrane to toxin. The data suggest a pathophysiological explanation for the association of otitis media and sensorineural hearing loss and/or endolymphatic hydrops; potentially both entities can be caused by exotoxins...