大学院医学系研究科

This study investigated the potential of adalimumab (ADA), a monoclonal antibody targeting TNF-alfa, to protect the inner ear from intense sound exposure, given that inflammatory cytokines, including TNF-alfa, are linked to hearing loss in acoustic disorders. In this study, adalimumab was administered to mice, and its effect on the inner ear was assessed. We examined the translocation of ADA to the inner ear and its ototoxicity and impact on acoustic exposure. The results showed that adalimumab partially reached the cochlea after administration but increased the susceptibility to acoustic exposure, resulting in higher hair cell loss in the inner ear. While TNF-alfa had been considered a potential therapeutic target, the results suggested that excessive TNF-alfa suppression could harm the inner ear. We acknowledged some limitations, such as the use of adalimumab instead of an anti-mouse TNF-alfa antibody and the need to explore the suppression of other cytokines for better inner ear protection. In conclusion, adalimumab administration was found to increase the inner earʼs susceptibility to acoustic exposure, potentially leading to more significant hair cell damage, possibly due to excessive TNF-alfa suppression

Vestibular hair cells are susceptible to damage from various stimuli such as infections, ischemia, and certain therapeutic drugs, including aminoglycoside antibiotics and the antineoplastic agent cisplatin. In mammals, damage to the vestibular hair cells is permanent. This study aimed to evaluate the protective effects of nobiletin (NOB) against aminoglycoside-induced hair cell death using utricles collected from adult mice. The utricles removed from CBA/N mice were assigned to eight groups according to the dose of NOB and the administration or not of neomycin. Hair cells in the utricles were counted by double labeling with calmodulin and calbindin. NOB inhibited hair cell death in utricles exposed to neomycin. The protective effect of NOB on hair cells in the utricles was also suggested to have resulted from the inhibition of the production and accumulation of 4-hydroxy-2-nonenal, the final product of lipid peroxide aldehyde. NOB suppressed neomycin-induced hair cell death. The principle of hair cell protection from aminoglycoside-induced hair cell death suggests that NOB inhibits reactive oxygen species formation in the utricles exposed to neomycin.

Objective: The objective was to explore the potential existence and nature of the relationship between serum of uric acid (SUA) and serum uric acid to serum creatinine ratio (SUA/SCr) with reduced estimated glomerular filtration rate (eGFR) in patients with non-alcoholic fatty liver disease (NAFLD). Methods: A cross-sectional study was conducted among apparently healthy subjects with NAFLD (n=485). The association between tertiles of SUA and SUA/SCr with reduced eGFR (n=56) were investigated after adjustments for potentially relevant confounders. Also, the diagnostic performances of SUA and SUA/SCr were evaluated with the receiver operating characteristic (ROC) curve analysis. Results: In the adjusted models, SUA showed a significant positive association with reduced eGFR in the highest tertile (OR 5.65, 95% CI 2.48-12.86, p<0.001), and SUA/SCr, in the lowest tertile (4.21, 95% CI 1.76-10.07, p=0.001). The ROC curve analysis did not reveal any significant difference between the corresponding values of area under the curve for SUA and SUA/SCr (0.70 and 0.67, respectively; p=0.521). Conclusions: We revealed significant and independent associations of elevated SUA and reduced SUA/SCr with kidney function decline in NAFLD. However, the clinical utility of these two biomarkers seemed to be limited for the mentioned purpose and needs further investigations.

Benign paroxysmal positional vertigo (BPPV) is the most common vertigo disease and is more likely to occur in perimenopausal women, suggesting an association with osteoporosis. Since otoconia are primarily composed of calcium carbonate, abnormal calcium metabolism may lead to otoconia dislocation. However, the detailed mechanism is currently unknown. In this study, we investigated the effects of drugs (cadmium and dexamethasone) that cause abnormal calcium metabolism on otolith formation in zebrafish larvae. Here, otolith size was clearly reduced in the cadmium group, and the calcium content of the larvae was also markedly reduced. In contrast, in the dexamethasone group, which also had a lower calcium content than the control group, otolith size increased. Our results suggest that, as in bone, calcium metabolism influences the repeated dissolution and recrystallization of otoliths and maintains homeostasis in response to calcium concentrations in the endolymphatic fluid.

Abstract Background: Expanding nursing workload is a worldwide problem. However, any nursing workload assessment (NWA) tool requires complicated analyses of the nursing job profile. To determine the imbalance in time assignments across all nursing operations and to reduce nursing workload, a nursing job survey was conducted. Methods: A total of 25 major job categories, common to all hospital wards, were identified, and an NWA tool was developed for efficient analyses to feature easy/flexible entry of the time spent for each job category and real-time visual profiling of job time allocation. The profile could be divided by job categories, wards, shifts, and years. Results: From the preliminary analyses, undesirable time allocation was revealed in several job categories, especially the time for recording and other nonessential nursing operations. Using the analytical functions of the NWA tool between 2014 and 2016, a series of corrective measures were successfully taken to many job categories, and they were found to be effective. Consequently, excessive overtime workload was reduced from 125 min/day/nurse in 2014 to 100 and 100 min/day/ nurse in 2015 and 2016, respectively. Conclusion: Notable improvements in nursing workload and time allocation for attentive patient care could be achieved employing the novel user-aimed NWA tool.