Anemia, Hemolytic ; chemically induced ; diagnosis ; Ceftriaxone ; adverse effects ; Child ; Cochlear Implantation ; adverse effects ; Hearing Loss, Sensorineural ; surgery ; Humans ; Male ; Vestibular Aqueduct

OBJECTIVETo explore the relationship of gentamicin-induced cochlear damage with autophagy-related protein LC3, beclin1, Na(+-)K(+-)2Cl(-) cotransporter (NKCC1) mRNA and endothelin-1 (ET-1), and investigate the protective mechanism of PPTA against gentamicin-induced cochlear damage.

METHODSSixty guinea pigs were randomly divided into control group (with saline and artificial perilymph injections), model group (with gentamicin and artificial perilymph injections), concurrent treatment group (with gentamicin and PPTA injections), model control group (with artificial perilymph injection 7 days after gentamicin injection) and delayed treatment group (with PPTA injection 7 days after gentamicin injection). Saline and gentamicin (160 mg/kg) were injected intraperitoneally, and artificial perilymph and PPTA were injected into the otocysts on a daily basis for 7 consecutive days. Hearing impairment of the guinea pigs was analyzed with ABR, and the protein expressions of beclin1 and LC3 in cochlear tissue were tested. The expression of NKCC1 mRNA was detected with RT-PCR, and the expression of ET-1 was detected immunohistochemically.

RESULTSThe ABR thresholds in the model group and model control group were similar (P>0.05) , but significantly higher than those in the other 3 groups (P<0.05); the threshold was significantly lower in concurrent treatment group than in delayed treatment group (P<0.05). Compared with those in the other 4 groups, the expressions of LC3 II, beclin1, and NKCC1 mRNA were significantly increased in the model group (P<0.05); and those in delayed treatment group were significantly lower than those in the model control group (P<0.05). The expressions of ET-1 in the Corti organ, striavascularis and spiral ganglion were significantly higher in the model group but significantly lower in the control group than those in the other 4 groups; ET-1 expression was significantly lower in delayed treatment group than in the model control group.

CONCLUSIONPPTA offers protection against gantamicin-induced cochlear damage in guinea pigs by inhibiting cell autophagy and suppressing of NKCC1 and ET-1 expressions. Early intervention with PPTA produces better therapeutic effect, suggesting that gantamicin causes irreversible injury of the auditory cells.

3,4-Methylenedioxyamphetamine ; analogs & derivatives ; pharmacology ; Animals ; Apoptosis Regulatory Proteins ; metabolism ; Beclin-1 ; Cochlea ; drug effects ; Endothelin-1 ; metabolism ; Gentamicins ; adverse effects ; Guinea Pigs ; Hearing Loss ; chemically induced ; prevention & control ; Microtubule-Associated Proteins ; metabolism ; Solute Carrier Family 12, Member 2 ; metabolism

Mitochondrial DNA mutations are one of the most important causes of sensorineural hearing loss. A1555G and C1494T mutations of mitochondrial 12S rRNA gene are the molecular basis for aminoglycoside hyper- sensitivity and can lead to aminoglycoside-induced hearing loss. Primary mutations in tRNA such as tRNA(Ser(UCN))7472insC are associated with syndromic hearing loss. While other mutations such as tRNA"(Se(UCN) )G7444A were considered synergy with the primary RNA mutations, modulating the phenotypic manifestation. This review de- scribes a detailed summary of hearing loss associated with mtDNA mutations and/or aminoglycoside antibiotics, and provides the possible molecular mechanisms in deafness expression.
Aminoglycosides ; adverse effects ; Anti-Bacterial Agents ; adverse effects ; DNA, Mitochondrial ; genetics ; Hearing Loss, Sensorineural ; chemically induced ; genetics ; Humans ; Mutation ; RNA, Ribosomal ; genetics

A pregnant female taken realgar because of superstition, which caused the baby congenital deafness. Auditory test indicated that bilateral auditory brainstem response (ABR) hearing threshold level was greater than 90 dB nHL and auditory steady state response (ASSR) hearing level ranging from 0.5 kHz to 4 kHz was beyond 110 dB HL. Temporal bone CT showed that bilateral cochlear and semicircular canal malformations, with internal auditory canal broadened.
Arsenicals ; adverse effects ; Evoked Potentials, Auditory, Brain Stem ; Female ; Hearing Loss, Sensorineural ; chemically induced ; congenital ; Hearing Tests ; Humans ; Infant ; Maternal Exposure ; adverse effects ; Pregnancy ; Semicircular Canals ; pathology ; Sulfides ; adverse effects ; Temporal Bone ; pathology

OBJECTIVETo evaluate the effect of mitochondrial DNA(mtDNA) secondary mutations, haplotypes, GJB2 gene mutations on phenotype of 1494C>T mutation, and to study the molecular pathogenic mechanism of maternally transmitted aminoglycoside-induced and nonsyndromic hearing loss.

METHODSTwo Chinese Han pedigrees of maternally transmitted aminoglycoside induced and nonsyndromic hearing loss were collected. The two probands and their family members underwent clinical, genetic and molecular evaluations including audiological examinations and mutational analysis of mitochondrial genome and GJB2 gene.

RESULTSClinical evaluation revealed wide range of severity, age-at-onset and audiometric configuration of hearing impairment in matrilineal relatives in both families, for which the penetrance of hearing loss was respectively 42.9% and 28.6% when aminoglycoside-induced deafness was included. When the effect of aminoglycosides was excluded, the penetrances of hearing loss were 14.3% and 14.3%. Sequence analysis of mitochondrial genomes identified a known 12S rRNA 1494C>T mutation, in addition with distinct sets of mtDNA polymorphisms belonging to Eastern Asian haplogroups C4a1a and B4b1c, respectively.

CONCLUSIONMitochondrial 12S rRNA 1494C>T mutation probably underlie the deafness in both families. Lack of significant mutation in the GJB2 gene ruled out involvement of GJB2 in the phenotypic expression. However, aminoglycosides and other nuclear modifier genes may still modify the phenotype of the 1494C>T mutation in these families. The B4b1c is a newly identified haplogroup in aminoglycoside-induced and nonsyndromic hearing loss family carrying the 1494C>T mutation. The 1494C>T mutation seems to have occurred sporadically through evolution.

Adult ; Aminoglycosides ; adverse effects ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Connexin 26 ; Connexins ; genetics ; DNA, Mitochondrial ; genetics ; Genetic Predisposition to Disease ; Haplotypes ; Hearing Loss ; chemically induced ; genetics ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Pedigree ; Phenotype ; RNA, Ribosomal ; genetics ; Young Adult

Sodium bromate is a strong oxidant used as a neutralizing solution in hair permanents, as well as an auxiliary agent in printing and dyeing. Accidental or deliberate ingestion of bromate solution has rarely been reported in Korea. The clinical manifestations of bromate intoxication are vomiting, diarrhea, central nervous system symptoms, oliguric or non-oliguric acute kidney injury, hemolytic anemia, and deafness; most of these manifestations are reversible, with the exception of renal failure and deafness. Here, we report on two patients who demonstrated distinct clinical progressions. In the first case, a 16-year-old woman was successfully treated with hemodialysis and recovered renal function without hearing loss. However, in the second case, delayed hemodialysis resulted in persistent renal failure and hearing loss in a 77-year-old woman. This suggests that emergency therapeutic measures, including hemodialysis, should be taken as soon as possible, as the rapid removal of bromate may be essential to preventing severe intoxication and its sequelae.
Acute Kidney Injury/*chemically induced/therapy ; Adolescent ; Aged ; Bromates/*toxicity ; Fatal Outcome ; Female ; Hearing Loss ; Humans ; Kidney Failure, Chronic/*therapy ; Renal Dialysis ; Sodium Compounds/*toxicity

The aim of the present study was to assess the ototoxicity of kanamycin sulfate (KM) in adult rats and its underlying mechanism. Forty male Sprague-Dawley rats (6-7 weeks old) were randomly divided into the experimental group and the control group. The animals in the experimental group were injected subcutaneously with KM (500 mg/kg per day) for two weeks, and the control group received equal volume of normal saline. To assess the ototoxicity of KM, the auditory brainstem response (ABR) was recorded to monitor the changes in hearing thresholds, and the density of spiral ganglion cells (SGCs) and morphology of cochlea were observed using surface preparations and frozen sections of cochlea. The results showed that the hearing threshold of rats in the experimental group was elevated by more than 60 dB across all the frequencies two weeks after the first administration of KM. And in the experimental group, the density of SGCs became lower, and organ of Corti suffered loss of hair cells. The loss of outer hair cells (OHCs) was more severe than that of inner hair cells (IHCs), correlated with the density decrease of SGCs. We conclude that the ototoxicity of KM in the adult rats was apparent and the underlying mechanism is associated with the loss of SGCs and hair cells.
Animals ; Cochlea ; drug effects ; pathology ; Evoked Potentials, Auditory, Brain Stem ; drug effects ; Hair Cells, Auditory, Outer ; cytology ; drug effects ; pathology ; Hearing Loss ; chemically induced ; physiopathology ; Kanamycin ; toxicity ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spiral Ganglion ; pathology ; physiology ; ultrastructure

The aim of this study was to determine the effects of transplanted neural differentiated human mesenchymal stem cells (hMSCs) in a guinea pig model of auditory neuropathy. In this study, hMSCs were pretreated with a neural-induction protocol and transplanted into the scala tympani of the guinea pig cochlea 7 days after ouabain injury. A control model was made by injection of Hanks balanced salt solution alone into the scala tympani of the guinea pig cochlea 7 days after ouabain injury. We established the auditory neuropathy guinea pig model using 1 mM ouabain application to the round window niche. After application of ouabain to the round window niche, degeneration of most spiral ganglion neurons (SGNs) without the loss of hair cells within the organ of Corti and increasing the auditory brain responses (ABR) threshold were found. After transplantation of neural differentiated hMSCs, the number of SGNs was increased, and some of the SGNs expressed immunoreactivity with human nuclear antibody under confocal laser scanning microscopy. ABR results showed mild hearing recovery after transplantation. Based on an auditory neuropathy animal model, these findings suggest that it may be possible to replace degenerated SGNs by grafting stem cells into the scala tympani.
Animals ; Cardiotonic Agents/toxicity ; Cochlea/drug effects/pathology ; Disease Models, Animal ; Female ; Guinea Pigs ; Hearing Loss, Central/chemically induced/pathology/*therapy ; Humans ; *Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/*cytology ; Neurogenesis ; Ouabain/toxicity ; Spiral Ganglion/pathology ; Transplantation, Heterologous

OBJECTIVETo study the effect of the mitochondrial 12S rRNA mutations on aminoglycoside-induced and nonsyndromic hearing loss, to carry out the clinical and molecular characterization of five Han Chinese pedigrees with maternally transmitted aminoglycoside-induced and nonsyndromic hearing loss.

METHODSFive pedigrees of maternally transmitted aminoglycoside-induced and nonsyndromic hearing loss were collected, genomic DNA was extracted, and complete mitochondrial genomes and the gap junction protein beta 2 (GJB2) gene were amplified and sequenced.

RESULTSClinical evaluation revealed a wide range of severity, age-at-onset and audiometric configuration of hearing impairment in the matrilineal relatives in these families. The penetrance rates of hearing loss in these pedigrees were 17.6%, 50.0%, 66.7%, 31.3% and 23.1%, with an average of 37.7%, when aminoglycoside-induced deafness was included. Sequence analysis of the complete mitochondrial genomes in these pedigrees identified the known 1555A>G mutation and distinct sets of mitochondrial DNA(mtDNA) polymorphisms belonging to Eastern Asian haplogroups D4b2b, B4c1b1, F3, C1 and D5a, respectively. Of these variants, ND1 L89T and CO3 A200T mutations resided at the highly conservative regions. However, there were no functionally significant mutations in tRNAs and rRNAs or secondary known mutations. No hearing loss related GJB2 gene mutation was observed.

CONCLUSIONThe lack of significant mutation in the ruled out the possible involvement of GJB2 in the phenotypic expression of the 1555A>G mutation in those affected subjects. However, aminoglycosides, mtDNA variations and other nuclear modifier genes may play an important role in the phenotypic manifestation of the 1555A>G mutation in these Chinese families.

Adult ; Amino Acid Sequence ; Aminoglycosides ; adverse effects ; Animals ; Asian Continental Ancestry Group ; genetics ; Child ; Child, Preschool ; China ; ethnology ; Connexin 26 ; Connexins ; chemistry ; genetics ; DNA Mutational Analysis ; Ethnic Groups ; genetics ; Female ; Hearing Loss, Sensorineural ; chemically induced ; genetics ; Humans ; Inheritance Patterns ; genetics ; Male ; Molecular Sequence Data ; Mothers ; Pedigree ; Young Adult

In this article, current status of noise exposure in workplaces, trend of workers with noise-induced hearing loss (NIHL), and prevalence of NIHL in workers by industry and job category in Korea were reviewed. In addition, trends of research on the audiological effects such as hearing loss from noise and occupational hearing loss from non-noise in Korea were addressed through reports in industrial audiology. Though noise exposure level has improved, noise still shows the highest rate of cases exceeding exposure limit among workplace hazards. NIHL is the most common occupational disease except work-related disease such as musculoskeletal disorders and cerebrovascular diseases, and NIHL prevalence is thought to be much higher than reported in official publications. Noise affecting hearing comes from various sources such as workplaces, military settings, areas with exposure to high noise, and specific noise sources. There is also occupational hearing loss by non-noise including chemicals such as organic solvents and heavy metals, barotrauma, and trauma due to welding spark. Noise affects daily life through audiological effects such as hearing loss and tinnitus, non-audiological physical effects (e.g., cardiovascular), and psychosocial and behavioral effects. Development of systematic and comprehensive hearing conservation programs for lowering the noise level in workplaces and preventing the NIHL, and preparation of technological, administrative system for its settlement at workplace are urgently needed.
Hearing Loss/*chemically induced ; Hearing Loss, Noise-Induced/*epidemiology ; Humans ; Noise, Occupational/*adverse effects ; Occupational Diseases/chemically induced/*epidemiology/*etiology ; Occupational Exposure/adverse effects ; Prevalence ; Republic of Korea/epidemiology ; Tinnitus/epidemiology