Simultaneous detection of heterocyclic aromatic amines and acrylamide in thermally processed foods by magnetic solid-phase extraction combined with HPLC-MS/MS based on cysteine-functionalized covalent organic frameworks.

Acrylamide (AA) and heterocyclic aromatic amines (HAAs), as classic hazards produced during food thermal processing, have been widely concerned, but because of their polarity difference, it is very difficult to detect these contaminants simultaneously. Herein, novel cysteine (Cys)-functionalized magnetic covalent organic frameworks (Fe3O4@COF@Cys) were synthesized via a thiol-ene click strategy and then used as adsorbents for magnetic solid-phase extraction (MSPE). Benefiting from the hydrophobic properties of COFs and the modification of hydrophilic Cys, AA and HAAs could be enriched simultaneously. Then, a rapid and reliable method based on MSPE coupled with HPLC-MS/MS was developed for the simultaneous detection of AA and 5 HAAs in thermally processed foods. The proposed method showed good linearity (R2 ≥ 0.9987) with satisfactory limits of detection (0.012-0.210 µg kg-1) and recoveries (90.4-102.8%). Actual sample analysis showed that the levels of AA and HAAs in French fries were affected by frying time and temperature, water activity of samples, content and type of reaction precursors, and reuse of oils.

Effects of smoking on the severity and transmission of pulmonary tuberculosis: A hospital-based case control study.

Introduction: There is a high incidence of both smoking and tuberculosis (TB) in China. This study examined the risk factors for severe pulmonary TB (PTB) and positive tubercle bacilli in sputum. Methods: We conducted a retrospective case-control study in a tertiary hospital from January 2017 to December 2018 (n = 917). The clinical and biological characteristics of patients were collected, and univariable and multivariable logistic regression analyses were performed to assess the factors associated with smoking in terms of the severity and transmission of PTB. Results: Positive tubercle bacilli in sputum and severe PTB were much higher in smoking patients. Together with nutrition status, heavy smoking exhibited a 284% greater risk in severe PTB. Positive tubercle bacilli in sputum was significantly associated with hypoproteinemia and smoking regardless of the status, duration, and degree. Conclusion: Because cigarette smoking was strongly and inversely associated with hypoproteinemia, we conclude that smoking plays a critical role in the severity and transmission of PTB. Smoking cessation interventions should be employed to prevent severe PTB and decrease the transmission of PTB.

HMGB1 accumulation in cytoplasm mediates noise-induced cochlear damage.

Damage-associated molecular pattern molecules (DAMPs) play a critical role in mediating cochlear cell death, which leads to noise-induced hearing loss (NIHL). High-mobility group box 1 (HMGB1), a prototypical DAMP released from cells, has been extensively studied in the context of various diseases. However, whether extracellular HMGB1 contributes to cochlear pathogenesis in NIHL and the potential signals initiating HMGB1 release from cochlear cells are not well understood. Here, through the transfection of the adeno-associated virus with HMGB1-HA-tag, we first investigated early cytoplasmic accumulation of HMGB1 in cochlear hair cells after noise exposure. We found that the cochlear administration of HMGB1-neutralizing antibody immediately after noise exposure significantly alleviated hearing loss and outer hair cells (OHCs) death induced by noise exposure. In addition, activation of signal transducer and activators of transcription 1 (STAT1) and cellular hyperacetylation were verified as potential canonical initiators of HMGB1 cytoplasmic accumulation. These findings reveal the adverse effects of extracellular HMGB1 on the cochlea and the potential signaling events mediating HMGB1 release in hair cells, indicating multiple potential pharmacotherapeutic targets for NIHL.

Case report: Successful management of Parvimonas micra pneumonia mimicking hematogenous Staphylococcus aureus pneumonia.

Parvimonas micra is an anaerobic Gram-positive coccus frequently found in the oral cavity and gastrointestinal tract, but rarely in the lung. Therefore, pneumonia caused by P. micra is also rare. Although there are some reports of P. micra related pneumonia due to aspiration or blood-borne infection with definite remote infection source, there are no reported cases of hematogenous P. micra pneumonia in healthy adults lacking a remote source of infection. Herein, we described the intact disease of P. micra-related pneumonia mimicking hematogenous Staphylococcus aureus pneumonia in terms of chest imagery and diagnosed via metagenomic next-generation sequencing (mNGS). Interestingly, there was no clear remote pathogenic source identified in the patient. Microbiome analysis revealed dysbiosis of the oral flora possibly related to poor oral hygiene and a long history of smoking. The patient was treated with moxifloxacin for 3 months. Ultimately, computed tomography (CT) of the chest showed total resolution of the lung lesion. Clinicians need to update the etiology of community-acquired pneumonia. When antibiotic therapy is not effective, pathogen examination becomes very important. New methods of pathogen detection such as mNGS should be employed to this end. For the treatment of P. micra pneumonia, no standardized course of treatment was reported. Imaging absorption of lung infections may provide a more objective guidance for the duration of antibiotics in P. micra pneumonia.

Heterocyclic aromatic amines induce Neuro-2a cells cytotoxicity through oxidative stress-mediated mitochondria-dependent apoptotic signals.

Heterocyclic aromatic amines (HAAs) are a class of hazardous compounds produced in food thermal processing. These compounds raise concerns because they have mutagenic and carcinogenic properties. However, the neurotoxicity of these compounds has received limited attention. Here, the toxic effects of three HAAs, i.e. 9H-pyrido[3,4-b]indole (Norharman), 1-methyl-9H-pyrido[3,4-b]indole (Harman), and 2-amino-3-methylimidazole[4,5-f]quinoline (IQ) were investigated in Neuro-2a cells model. The results showed that the survival rate of cells decreased in a dose-dependent manner and apoptosis occurred after exposure to the three HAAs for 24 h and 48 h. Their neurotoxicity was ranked as Harman > Norharman > IQ. Further, treatment of Harman, Norharman, or IQ at 50 and 100 µM for 48 h led to intracellular REDOX imbalance, which was manifested as increased ROS and malondialdehyde (MDA) levels, decreased GSH/GSSG ratio, and reduced SOD and CAT activities. Moreover, Norharman and Harman up-regulated the expression level of nuclear factor erythroid 2-related factor 2 (Nrf2), as well as the mRNA levels of Heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoredutase1 (NQO1), while IQ had no significant effect on the levels of Nrf2, HO-1, and NQO1. Additionally, Harman, Norharman, or IQ exposure significantly reduced mitochondrial membrane potential and intracellular ATP levels and up-regulated the levels of apoptosis-related genes and proteins. Collectively, our finding suggested that HAAs were neurotoxic, with mechanisms related to induction of oxidative stress and mitochondrial dysfunction.

Simultaneous Determination of Five Coumarins in Peucedanum Decursivum Radix by UPLC.

OBJECTIVE: To establish an ultra-high performance liquid chromatography (UPLC) method for simultaneous determination of umbelliferonel, nodakenin, psoralen, xanthotoxin and bergapten contents in Peucedanum decursivum Radix. METHODS: The analysis was achieved on a Symmetry®C18 column (4.6 mm × 250 mm, 5 µm), with acetonitrile and water as the mobile phase in gradient elution mode. The column temperature was maintained at 30°C, with flow rate 1.0 mL·min-1. The injection volume of sample was 10 µL. The ultraviolet detection wavelength was set at the maximum absorption wavelength 325 nm for umbelliferonel and nodakenin, 259 nm for psoralen, xanthotoxin and bergapten, respectively. RESULTS: The five kinds of coumarins in Peucedanum decursivum Radix were separated well and the linear relation was obtained (R2 ≥ 0.9998). The average recoveries were 101.31, 105.27, 90.85, 106.42 and 90.19%, respectively, with Relative standard deviation (RSD) 3.07, 3.17, 1.62, 2.53 and 4.54%, respectively. CONCLUSIONS: The established method was accurate and feasible, which could be used as the basis of quality control of Peucedanum decursivum Radix.

Identifying genetic risk variants associated with noise-induced hearing loss based on a novel strategy for evaluating individual susceptibility.

BACKGROUND: The overall genetic profile for noise-induced hearing loss (NIHL) remains elusive. Herein we proposed a novel machine learning (ML) based strategy to evaluate individual susceptibility to NIHL and identify the underlying genetic risk variants based on a subsample of participants with extreme phenotypes. METHODS: Five features (age, sex, cumulative noise exposure [CNE], smoking, and alcohol drinking status) of 5,539 shipbuilding workers from large cross-sectional surveys were included in four ML classification models to predict their hearing levels. The area under the curve (AUC) and prediction accuracy were exploited to evaluate the performance of the models. Based on the prediction error of the ML models, the NIHL-susceptible group (n=150) and NIHL-resistant group (n=150) with a paradoxical relationship between hearing levels and features were separately screened, to identify the underlying variants associated with NIHL risk using whole-exome sequencing (WES). Subsequently, candidate risk variants were validated in an additional replication cohort (n=2108), followed by a meta-analysis. RESULTS: With 10-fold cross-validation, the performances of the four ML models were robust and similar, with average AUCs and accuracies ranging from 0.783 to 0.798 and 73.7% to 73.8%, respectively. The phenotypes of the NIHL-susceptible and NIHL-resistant groups were significantly different (all p<0.001). After WES analysis and filtering, 12 risk variants contributing to NIHL susceptibility were identified and replicated. The meta-analyses showed that the A allele of CDH23 rs41281334 (odds ratio [OR]=1.506, 95% confidence interval [CI]=1.106-2.051) and the C allele of WHRN rs12339210 (OR=3.06, 95% CI=1.398-6.700) were significantly associated with increased risk of NIHL after adjustment for confounding factors. CONCLUSIONS: This study revealed two genetic variants in CDH23 rs41281334 and WHRN rs12339210 that associated with NIHL risk, based on a promising approach for evaluating individual susceptibility using ML models.

Volume quantification of endolymphatic hydrops in patients with vestibular schwannoma.

OBJECTIVE: The origin of vestibular symptoms in patients with vestibular schwannoma (VS) is uncertain. We used intratympanic gadolinium-enhanced magnetic resonance imaging (MRI) to confirm the labyrinthine lesions in patients with VS and to explore the features of endolymphatic hydrops (EH) in these patients. METHODS: In total, 66 patients diagnosed with unilateral VS were enrolled in this study and underwent intratympanic gadolinium-enhanced MRI. The borders of the vestibule and endolymph were mapped on the axial MRI images, and the area and volume of vestibule and endolymph were automatically calculated using Osirix software, and the area and volume percentage of vestibular endolymph were obtained. RESULTS: The area and volume percentages of vestibular endolymph on the affected side were significantly larger than those on the healthy side (both p < 0.001). Using Kendall's W test, we found that the area and volume percentages of vestibular endolymph on the affected side were consistent (p < 0.001), but the consistency was moderate (k = 0.574). The healthy side was also consistent (p < 0.001), and the degree of consistency was moderate (k = 0.444). We used 19.1% as the cut-off point to distinguish the presence or absence of vestibular EH; that is, the volume percentage of vestibular endolymph that was more than 19.1% were defined as the subgroup with hydrops, while the subgroup without hydrops included patients with a baseline level below 19.1%. No volume classification for vestibular EH was proposed. Based on this standard, 11/66 (16.7%) of the patients with VS in this study had vestibular EH. CONCLUSIONS: The volume percentage of the vestibular endolymph was more accurate than the area percentage for assessing vestibular EH. Using 19.1% as the cut-off point to distinguish the presence or absence of vestibular EH, we found that 16.7% of patients with VS had varying degrees of vestibular EH. We believe that the vestibular symptoms in patients with VS may originate from the peripheral lesions.

[Development of novel drug carrier via round window membrane].

As isolated anatomical position, limited labyrinthine artery supply, and blood-labyrinth barrier hampers systemic drug delivery to the inner ear. The efficient concentration of drug treatment is unsatisfactory and there's possible side effects after systemic administration. Intratympanic injection of drug can bypass the blood-labyrinth and permeated to the hair cells or synaptic area via the round-or oval window of the cochlea. Efficacy and safety of pharmacotherapy has become increasingly relied on the inner ear delivery carrier system. The goal of this review focus on the anatomical barrier that need to be overcome in the intratympanic applications, the improvement of drug retention and specific targets, and the safety of novel drug carriers, these emerging strategies of local drug delivery promise novel and better guidance for the clinical application.

XIAP inhibits gentamicin-induced hair cell damage and ototoxicity through the caspase-3/9 pathway.

Gentamicin (GM), an aminoglycoside antibiotic, is one commonly used clinical drugs with ototoxic side effects. One of the most principal mechanisms of its ototoxicity is that GM can activate caspase-mediated cell death pathways in the cochlea. Since the anti-apoptotic protein known as X-linked Inhibitor of Apoptosis Protein (XIAP) has been reported to directly bind to activated caspase protein and inhibit their activities, we hypothesized that it might protect cochlea hair cells from GM ototoxicity. To evaluate this hypothesis, postnatal day 2-3 (P2-3) transgenic (TG) mice, in which XIAP gene is over-expressed under a pure C57BL/6J genetic background was constructed. We first extracted the cochlea tissue of normal mice and treated them with different concentrations of GM, and the number of hair cells were observed to determine the concentration of GM used in subsequent experiments. Next, we used Western Blot experiment to examine the effect of GM on XIAP protein expression in normal mouse cochlea, and then Western Blot and RT-PCR experiments were used to identify the transgenic mice. Finally, immunofluorescence assays were used to detect the effect of GM on the expression of caspase protein and verify the protective effect of XIAP. We found that GM at a concentration of 0.5 mM significantly affected the function of cochlea hair cells, up-regulating the expression of cleaved-caspase-3 and cleaved-caspase-9 protein but down-regulating XIAP protein. In the cochlea tissues of TG mice, this effect of GM was suppressed, and the destruction of hair cells was significantly reduced, and the cleaved-caspase-3 and cleaved-caspase-9 proteins were significantly suppressed. These results suggested that XIAP reduces GM-induced ototoxicity and caspase-3/9 pathway is associated with this process.

Coagulation States in Patients With Sudden Sensorineural Hearing Loss Evaluated by Thromboelastography.

OBJECTIVE: The state of coagulation is controversial in patients with sudden sensorineural hearing loss (SSNHL). We used thromboelastography (TEG) to explore the relationships between blood coagulation parameters and SSNHL pathogenesis and recovery. STUDY DESIGN: Prospective study. SETTING: Affiliated Sixth People's Hospital, Shanghai Jiao Tong University. METHODS: A total of 104 newly diagnosed patients with SSNHL and 29 matched healthy controls were recruited. Hearing assessments, TEG, and conventional coagulation tests (CCTs) were performed, followed by standard treatments and follow-up. RESULTS: The TEG parameters of patients with SSNHL were in the normal range, but the group exhibited a significantly prolonged kinetic time (K; P = .004) and a smaller angle (P = .003) as compared with the controls. After grouping the patients with SSNHL according to audiograms and comparing them in pairs, we found that the differences were significant only when controls were compared with patients with low-frequency SSNHL (K, P = .023; angle, P = .04) and flat-type SSNHL (K, P = .017; angle, P = .014). Logistic regression analysis showed that neither TEG nor CCT parameters significantly affected hearing improvement after SSNHL treatment. CONCLUSIONS: Although the K value and angle were significantly increased and significantly reduced, respectively, in the test group as compared with the control group, the state of coagulation in patients with SSNHL was still within the normal range. No CCT or TEG coagulation parameters (except the angle) differed significantly among patients in each group according to hearing recovery status, which suggested that the coagulation status does not determine the prognosis of patients with SSNHL.

[Evaluation of the validity and reliability of the Chinese version of Glasgow Benefit Inventory].

Objective:To evaluate the validity and reliability of the Chinese version of Glasgow Benefit Inventory. Method:Using the Chinese version of Glasgow benefit inventory（C-GBI） to evaluate how the otorhinolaryngological（ORL） interventions have altered the quality of life of 98 cases of ORL department and analyze the validity and reliability of the test results, which is assessed by content validity, construct validity, internal consistency and split-half reliability. Result:The results show that the C-GBI has 3 dimensions and 18 items. The content validity of C-GBI is acceptable. Three factors were extracted by exploratory factor analysis. Since item No. 10 matched Factor 3 in error, we decided to delete it after discussions. After this adjustment, exploratory factor analysis yielded with an three-factor solution, explaining 70.32% of the total variance and the loading coefficient for each of the 17 C-GBI questions is above 0.4. The results also show good convergent validity and discriminant validity. Reliability using Cronbach α, Spearman-Brown and Guttman Split-Half was higher than 0.6 for total score and its three subscales of the adjusted C-GBI. Conclusion:After deleting one item of the C-GBI which matched factor in error, we found that the adjusted C-GBI shows good reliability and validity. It can help Chinese clinicians evaluate how the ORL interventions have altered the health status of patients.

Prevalence of High Jugular Bulb across Different Stages of Adulthood in A Chinese Population.

Pulsatile tinnitus, ear fullness, vertigo, hearing disorders, and vestibular dysfunction have been found to be related to high jugular bulb. Anatomical variation in this region also affects surgical planning and approaches. Therefore, knowledge on the detailed anatomy of the high jugular bulb is critical for middle ear and lateral skull base surgery. Prevalence of high jugular bulb is uncertain as data are usually derived from temporal bone specimens and patient reports from hospitals. Therefore, a community-based epidemiological study is necessary to understand the significance of high jugular bulb anatomy. Here, we report a cross-sectional study to characterize the prevalence of high jugular bulb and jugular bulb size using a 3.0 T magnetic resonance imaging. Furthermore, we studied the relationship between the prevalence of high jugular bulb and age-related changes. We enrolled 4539 permanent residents (9078 ears) from two communities in the Shanghai region who underwent magnetic resonance imaging between 2007 and 2011. We divided participants into four subgroups according to age: 35-44 (early middle age), 45-54 (middle age), 55-64 (late middle age), and 65-75 (late adulthood) years. We found that the overall prevalence of high jugular bulb was 14.5% in a Chinese population. There was a higher prevalence of high jugular bulb on the right side and especially in women (both p < 0.001). The occurrence of high jugular bulb was higher in the early middle age group and gradually decreased with age, but was still present in the late adulthood group (p = 0.039). These findings provide useful information on the prevalence of high jugular bulb in a Chinese population and the distribution in age groups, suggesting that high jugular bulb should be considered, even in those without ear disorders. This work serves as a foundation for further research on the relationship between jugular bulb changes and disease symptoms.

De Novo Mutation of m.3243A>G together with m.16093T>C Associated with Atypical Clinical Features in a Pedigree with MIDD Syndrome.

BACKGROUND: The syndrome of maternally inherited diabetes and deafness (MIDD) is typically caused by the m.3243A>G mutation and widely considered maternally inherited. In our study, we aimed to investigate the heredity way of the m.3243A>G among pedigrees with MIDD and discover novel mitochondrial DNA mutations related to atypical clinical phenotypes. METHODS: Heteroplasmy levels of the m.3243A>G mutation in peripheral blood, saliva, and urine sediment of 31 individuals from 10 unrelated pedigrees were measured by pyrosequencing. Clinical evaluations including endocrinological, audiological, and magnetic resonance imaging (MRI) examinations, mitochondrial function evaluation in peripheral blood mononuclear cells (PBMCs), and whole mitochondrial DNA (mtDNA) sequencing were performed among the spontaneous mutant pedigrees. RESULTS: Among the 10 unrelated MIDD pedigrees, we found that the de novo m.3243A>G mutation occurred in the family 1957 (F1957). The proband (F1957-II-1) and her son (F1957-III-1) both manifested diabetes with mild bilateral sensorineural hearing loss (SNHL) and abnormal brain MRI, and F1957-III-1 also complained of severe nausea and vomiting. Mitochondrial function evaluation in PBMCs revealed an increased level of ROS generation and decreased levels of ATP and mitochondrial membrane potential (ΔΨm) in the two m.3243A>G carriers. Whole mtDNA sequencing also revealed a de novo heteroplasmic substitution at m.16093T>C in both the proband and her son. CONCLUSIONS: Our study showed that de novo m.3243A>G mutation accompanied by other point mutations may occur in the very early embryonic or germ cell stage without maternal inheritance, bringing about both typical and atypical clinical features.

Successful management of isolated pulmonary Langerhans cell histiocytosis in a 50-year-old man with early diagnosis using transbronchial cryobiopsy: A case report.

RATIONALE: Isolated pulmonary Langerhans cell histiocytosis (PLCH) is rare in adults. The gold standard diagnosis requires surgical lung biopsy. However, few cases have been diagnosed with transbronchial cryobiopsy (TBCB) sampling in the early stages of the disease, particularly in China. PRESENTING CONCERNS: A 50-year-old man was referred for dry cough and exertional dyspnea of more than 1 week. High-resolution computed tomography (HRCT) of the chest revealed symmetric nodules and cyst lesions with upper lobe infiltrate. Further history taking indicated that he had smoked 20 cigarettes per day for more than 30 years. Therefore, PLCH was highly suspected. However, he refused surgical lung biopsy, and TBCB was attempted to complete diagnosis. DIAGNOSIS: Emission computed tomography excluded the possibility of extrapulmonary involvements, and pathological findings supported the diagnosis of isolated PLCH. INTERVENTIONS: Smoking cessation and prednisone treatment were used for patient management. OUTCOMES: The symptoms receded with significant improvement of chest HRCT during 2-months of follow-up. LESSONS: Early diagnosis contributes to the prognosis of isolated PLCH in adults, and TBCB may be an alternative to conventional surgical lung biopsy for pathological diagnosis of PLCH.

Changes in tinnitus after vestibular schwannoma surgery.

We designed a prospective study to evaluate changes in tinnitus after vestibular schwannoma (VS) surgery. Subjects included 41 patients who were diagnosed with a VS and underwent translabyrinthine microsurgery (TLM) between January 2015 and May 2016. All patients underwent related examinations and were asked to answer the Tinnitus Handicap Inventory (THI) scale and a visual analog scale (VAS) of tinnitus severity both pre- and postoperatively. Of the 41 patients, 31 (75.6%) suffered from tinnitus before surgery. Microsurgery was associated with an overall decrease in tinnitus (p < 0.001). There was a significant improvement in THI and VAS scores after surgery (p = 0.001 and p = 0.005, respectively). The decrease in THI scores in the low-frequency group was significantly larger than that of the mid- and high-frequency groups after surgery (p = 0.034 and p = 0.001, respectively). The loudness of tinnitus decreased significantly after surgery (p = 0.031). Tinnitus in patients with VS improved after TLM. Patients with mid-/high-frequency tinnitus and louder tinnitus preoperatively seemed to have a worse prognosis than those with low-frequency and quieter tinnitus.

Effects of bone marrow-derived mesenchymal stem cells transfected with survivin on pulmonary fibrosis in mice.

The aim of the present study was to investigate the effects of bone marrow-derived mesenchymal stem cells (BMSCs) transfected with survivin on lung fibrosis in mice. Mice with bleomycin-induced pulmonary fibrosis were allocated at random to group A, B or C, and injected with 1×106 survivin gene-expressing BMSCs, 1×106 BMSCs or normal saline, respectively. A total of 6 mice were sacrificed from each group on days 7, 14 and 28 after treatment. The extent of alveolitis and pulmonary fibrosis was assessed and the apoptotic rates of the BMSCs and survivin-expressing BMSCs were detected. The content of surfactant protein A (SP-A) in the lung and hydroxyproline (Hyp) in the serum was measured. The mRNA expression levels of transforming growth factor (TGF)-ß1 and matrix metalloproteinase (MMP)-9 in the lung tissue of the mice was detected. Furthermore, the protein expression levels of caspase-3 and -9 were detected. The apoptotic rates of the BMSCs (group B) and survivin-expressing BMSCs (group A) were 14.466±1.953 and 7.718±0.493%, respectively. The degree of lung fibrosis in groups A and B was reduced compared with that in group C. The hydroxyproline content in groups A and B was reduced compared with that in group C, and the SP-A content in groups A and B was increased compared with that in group C. The mRNA expression levels of TGF-ß1 in group A were reduced compared with those in group B, and the levels in group B were reduced compared with those in group C. By contrast, the mRNA expression levels of MMP-9 in group A were increased compared with those in groups B and C, and the levels in group B were increased compared with those in group A. The expression levels of caspase-3 and -9 in group A were elevated compared with those in groups B and C. In conclusion, BMSCs are effective in preventing bleomycin-induced lung fibrosis, and survivin may enhance the protective effects of BMSCs.

Assessment of the potential ototoxicity of high-dose celecoxib, a selective cyclooxygenase-2 inhibitor, in rats.

OBJECTIVE: To evaluate the potential ototoxicity of high-dose celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor. STUDY DESIGN: Prospective animal study. SETTING: Laboratory. METHODS: Twenty adult male Sprague Dawley rats were divided into 2 groups for hearing and tinnitus tests, respectively. The auditory brain-stem response (ABR) and the gap prepulse inhibition of acoustic startle (GPIAS) were used as indicators of hearing loss and tinnitus, respectively, and were measured before and at 2, 4, 6, 8, 12, 24, and 48 hours after administration of celecoxib (2 g/kg) via gavage. RESULTS: ABR threshold and wave III latencies did not increase significantly at any frequency following celecoxib administration, at any time point (P > .05). GPIAS remained below 30% after celecoxib, from a baseline of 20.03% ± 3.62%; no change was significant. CONCLUSION: High-dose celecoxib (2 g/kg), a selective COX-2 inhibitor, did not cause hearing loss or tinnitus in Sprague Dawley rats within 48 hours of administration. Further studies are needed to explore the roles played by COX-related mechanisms when nonselective COX inhibitors induce ototoxicity.