Juen-Haur Hwang

Effects of C-phycocyanin and Spirulina on Salicylate-Induced Tinnitus, Expression of NMDA Receptor and Inflammatory Genes

Effects of C-phycocyanin (C-PC), the active component of Spirulina platensis water extract on the expressions of N-methyl D-aspartate receptor subunit 2B (NR2B), tumor necrosis factor–α (TNF-α), interleukin-1β (IL-1β), and cyclooxygenase type 2 (COX-2) genes in the cochlea and inferior colliculus (IC) of mice were evaluated after tinnitus was induced by intraperitoneal injection of salicylate. The results showed that 4-day salicylate treatment (unlike 4-day saline treatment) caused a significant increase in NR2B, TNF-α, and IL-1β mRNAs expression in the cochlea and IC. On the other hand, dietary supplementation with C-PC or Spirulina platensis water extract significantly reduced the salicylate-induced tinnitus and down-regulated the mRNAs expression of NR2B, TNF-α, IL-1β mRNAs, and COX-2 genes in the cochlea and IC of mice. The changes of protein expression levels were generally correlated with those of mRNAs expression levels in the IC for above genes.

Tetrandrine and Caffeine Modulated Cell Cycle and Increased Glioma Cell Death via Caspase-Dependent and Caspase-Independent Apoptosis Pathways

Viability, cell cycle distribution, and expressions of eukaryotic translation initiation factor-2α (eIF-2α), cyclin D1, poly(ADP-ribose) polymerase 1 (PARP-1), and apoptosis-inducing factor (AIF) of RT-2 glioma cells were assayed under treatment of tetrandrine and caffeine for 48 h. The results showed that cell viability decreased significantly under treatment with tetrandrine (5 μM) alone or under combined treatment with tetrandrine (5 μM) and caffeine (0.5 or 1 mM). The ratio of RT-2 cells at sub G1 and G0/G1 stages increased significantly during combined treatment of tetrandrine (5 μM) and caffeine (0.5, 1 mM). The ratio of phospharylated eIF-2α to dephospharylated eIF-2α increased, whereas cyclin D1 decreased significantly under combined treatment of tetrandrine (5 μM) and caffeine (1 mM). The cleaved PARP-1 to PARP-1 ratio was elevated significantly under treatment of 5 μM tetrandrine alone, and combined treatment of 5 μM tetrandrine and caffeine (0.5, 1 mM). The expression levels of AIF increased significantly under treatment of 5 μM tetrandrine alone or 1 mM caffeine alone, and combined treatment of 5 μM tetrandrine and caffeine (0.5, 1 mM). In conclusion, tetrandrine and caffeine could induce glioma cell death possibly via increasing eIF-2α phospharylation, decreasing cyclin-D1 expression, and increasing caspase-dependent and -independent apoptosis pathways.

Risk of tinnitus in patients with sleep apnea: A nationwide, population‐based case control study

To investigate the risk of tinnitus in patients with sleep disturbance or sleep apnea.

Risks of peripheral arterial occlusive disease in patients with obstructive sleep apnoea: a population-based case–control study

This study aimed to evaluate the risk of peripheral arterial occlusive disease (PAOD) in patients with obstructive sleep apnoea (OSA) using a nationwide claim database in Taiwan.

Association of Tinnitus and Other Cochlear Disorders With a History of Migraines

Importance A headache is a symptom of a migraine, but not all patients with migraine have headaches. It is still unclear whether a migraine might increase the risk of cochlear disorders, even though a migraine does not occur concurrently with cochlear disorders. Objective To investigate the risk of cochlear disorders for patients with a history of migraines. Design, Setting, and Participants This study used claims data from the Taiwan Longitudinal Health Insurance Database 2005 to identify 1056 patients with migraines diagnosed between January 1, 1996, and December 31, 2012. A total of 4224 controls were also identified from the same database based on propensity score matching. Statistical analysis was performed from January 23, 1996, to December 28, 2012. Main Outcomes and Measures The incidence rate of cochlear disorders (tinnitus, sensorineural hearing impairment, and/or sudden deafness) was compared between the cohorts by use of the Kaplan-Meier method. The Cox proportional hazards regression model was also used to examine the association of cochlear disorders with migraines. Results Of the 1056 patients with migraines, 672 were women and 384 were men, and the mean (SD) age was 36.7 (15.3) years. Compared with the nonmigraine cohort, the crude hazard ratio for cochlear disorders in the migraine cohort was 2.83 (95% CI, 2.01-3.99), and the adjusted hazard ratio was 2.71 (95% CI, 1.86-3.93). The incidence rates of cochlear disorders were 81.4 (95% CI, 81.1-81.8) per 1 million person-years for the migraine cohort and 29.4 (95% CI, 29.2-29.7) per 1 million person-years for the nonmigraine cohort. The cumulative incidence of cochlear disorders in the migraine cohort (12.2%) was significantly higher than that in the matched nonmigraine cohort (5.5%). Subgroup analysis showed that, compared with the nonmigraine cohort, the adjusted hazard ratios in the migraine cohort were 3.30 (95% CI, 2.17-5.00) for tinnitus, 1.03 (95% CI, 0.17-6.41) for sensorineural hearing impairment, and 1.22 (95% CI, 0.53-2.83) for sudden deafness. Conclusions and Relevance In this population-based study, the risk of cochlear disorders, especially for tinnitus, was found to be significantly higher among patients with a history of migraines. This finding may support the presence and/or concept of “cochlear migraine.”

Effects of Spirulina on the functions and redox status of auditory system in senescence-accelerated prone-8 mice

To our knowledge, the effects of Spirulina platensis water extract (SP) on hearing function have not yet been reported. This study investigated the effects of SP on the function and redox status of the auditory system. Auditory brainstem responses and redox status were compared between two groups of 3-month-old senescence-accelerated prone-8 (SAMP8) mice: the control group was fed a normal diet, and the experimental group was fed a normal diet with oral supplementation of SP for 6 weeks. Compared with the control group, the experimental group had significantly lower hearing thresholds according to auditory brainstem responses measured using click sounds and 8-kHz tone burst sound stimulation at the end of this study. The experimental group had a shorter I-III interval of auditory brainstem responses with 16-kHz tone burst stimulation than the control group that was of borderline significance. Additionally, the experimental group had significantly higher mRNA expression of the superoxide dismutase and catalase genes in the cochlea and brainstem and significantly higher mRNA expression of the glutathione peroxidase gene in the cochlea. Further, the experimental group had significantly lower malondialdehyde levels in the cochlea and brainstem than the control group. However, tumor necrosis factor–α mRNA expression was not significantly different between the control and experimental groups. SP could decrease hearing degeneration in senescence-accelerated prone-8 mice possibly by increasing superoxide dismutase, catalase, and glutathione peroxidase gene expression and decreasing damage from oxidative stress in the cochlea and brainstem.

Risk of Sudden Sensorineural Hearing Loss in Patients with Common Preexisting Sensorineural Hearing Impairment: A Population-Based Study in Taiwan

Objective The role of preexisting sensorineural hearing impairment on the risk for sudden sensorineural hearing loss (SSHL) is still unclear. In this study, we aimed to assess the risk of SSHL in patients with common preexisting sensorineural hearing impairment using population-based data. Methods A population-based case-control study design was used to analyze claims data between January 2001 and December 2011 obtained from the Taiwan National Health Insurance Research Database. The cases consisted of 514 patients with SSHL and the controls were frequency matched to 2,570 cases by sex, 10-year age group, and year of index date. Common sensorineural hearing impairments were retrospectively assessed in the cases and controls. Associations between sensorineural hearing impairment and risk of SSHL were evaluated using unconditional univariate and multivariate logistic regression analyses. Results The mean age for the 3,084 study subjects was 53.1 years (standard deviation, S.D. = 15.6). Of the 514 cases, 49 (9.5%) had sensorineural hearing impairment while only 44 (1.7%) of the 2,570 controls had the same condition. Univariate logistic regression analyses indicated that preexisting sensorineural hearing impairment was significantly associated with SSHL (odds ratio, OR = 6.05, p < 0.001). Other comorbidities including hypertension, diabetes mellitus, and hyperlipidemia also showed significant associations with SSHL. Similar results were obtained when the association between SSHL and sensorineural hearing impairment was adjusted with either all the covariates (adjusted OR = 6.22, p < 0.001) or with only those selected using a backward elimination procedure (adjusted OR = 6.20, p < 0.001). Conclusions Results from this population-based case-control study revealed that common sensorineural hearing impairment might be a novel risk factor for SSHL.

Incidence of Vestibular Schwannoma in Taiwan from 2001 to 2012: A Population-Based National Health Insurance Study:

Objectives: Vestibular schwannomas, also known as acoustic neuromas, are slow-growing tumors that may lead to asymmetric hearing loss, unilateral tinnitus, and vertigo. Population-based data are lacking regarding the incidence of vestibular schwannoma in Asian populations. The aim of this study was to investigate the incidence of vestibular schwannoma in Taiwan using data from a population-based health claim database. Subjects and Methods: Patients aged 20 years and over with incident cases of vestibular schwannoma between January 1, 2001, and December 31, 2012, were identified from the Longitudinal Health Insurance Database 2000 of the National Health Insurance Research Database (NHIRD), Taiwan, based on the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code 225.1. Only those patients who had received a magnetic resonance imaging scan prior to the diagnosis of vestibular schwannoma were considered as definitive cases. Results: 206 cases of vestibular schwannoma were identified during the interval 2001 to 2012. The overall annual incidence was 2.66 per 100 000 persons (95% confidence interval, 2.32-3.05). The annual incidence rate varied throughout the study period, ranging from 1.74 to 3.72 per 100 000 persons. The highest incidence rate of 4.86 per 100 000 persons was observed in the age group of 60 to 69 years. Conclusions: Based on data from the NHIRD in Taiwan for the years 2001 to 2012, the average annual incidence rate of vestibular schwannoma was found to be 2.66 per 100 000 persons.

The association between tinnitus and the risk of ischemic cerebrovascular disease in young and middle-aged patients: A secondary case-control analysis of a nationwide, population-based health claims database

Background Tinnitus and ischemic cerebrovascular disease (ICVD) may share common pathophysiologic mechanisms. Nevertheless, no studies have investigated whether tinnitus is associated with a higher risk of ICVD. The aim of this study was to evaluate the risk of ICVD among young and middle-aged patients with tinnitus. Methods Using the Taiwan’s National Health Insurance Research Database, we identified 3,474 patients 20–45 years old with incident ICVD diagnosed between January 1, 2000 and December 31, 2010 and 17,370 controls, frequency matched on age interval, sex, and year of the index date. Risk of ICVD associated with tinnitus was assessed using multiple logistic regression analyses. Results Tinnitus was significantly associated with a higher risk of incident ICVD among young and middle-aged patients (adjusted odds ratio [OR] 1.66, 95% confidence interval [CI] 1.34–2.04), adjusting for sex, age, and comorbidities. In addition, sex-stratified analysis showed that the associations were significant in both male (adjusted OR 1.55, 95% CI 1.16–2.07) and female patients (adjusted OR 1.77, 95% CI 1.30–2.41). Furthermore, tinnitus was significantly associated with a higher risk of ICVD in the 20.0–29.9 years (adjusted OR 4.11, 95% CI 1.98–8.52) and 30.0–39.9 years (adjusted OR 2.19, 95% CI 1.57–3.05) age groups, but not in the 40.0–45.0 years age group. Conclusions Tinnitus could be a novel risk factor or clinical indicator for young ischemic stroke, and further investigations are warranted.

Tinnitus Is Associated with a Higher Risk of Benign Brain Tumors: A Nationwide, Population-Based Secondary Cohort Study of Young and Middle-Aged Adults

Background: It remains unclear whether tinnitus is associated with a higher risk of benign or malignant brain tumors in humans. Therefore, the aim of this secondary study was to investigate the risk of brain tumors in adult with tinnitus using data from a nationwide health claims research database. Methods: Patients aged 20–50 years who were newly diagnosed with tinnitus were identified from the Taiwan’s National Health Insurance Research Database and they served as the study cohort. A comparison cohort was formed by using patients without tinnitus from the same database with frequency matching (4: 1) by 10-year age interval and gender to the patients in the tinnitus cohort. Cox proportional hazards models were used to calculate the adjusted hazard ratios (AHR) for benign and malignant brain tumors in patients with tinnitus, adjusting for age, gender, and comorbidities. Results: There were 15,819 patients in the tinnitus cohort and 63,276 in the comparison cohort. A significantly higher proportion of patients with tinnitus had benign brain tumor (p = 0.003) and all 11 comorbid conditions (p < 0.001) compared to those without tinnitus. Cox proportional hazards regression analysis performed on the basis of age, gender, and the 11 comorbidities revealed that tinnitus was independently associated with a higher risk for benign brain tumor (AHR 1.65, 95% CI 1.24–2.20, p = 0.001) and but not with malignant brain tumors (AHR 1.66, 95% CI 0.93–2.94, p = 0.085). Conclusions: Findings from this secondary cohort analysis indicated that tinnitus is associated with a higher risk of benign brain tumors.