Trauma-Induced Vestibular Dysfunction: Improved Repair Under Local Treatment With α1-Antitrypsin.

AIM: To characterize vestibular recovery in a mouse model of unilateral labyrinthotomy under local AAT and dexamethasone treatment. BACKGROUND: Alpha1-antitrypsin (AAT) is a circulating tissue-protective molecule that rises during inflammatory conditions and promotes inflammatory resolution. Its local concentration in human perilymph inversely correlates with the severity of inner ear dysfunction; concomitantly, mice that overexpress AAT and undergo inner ear trauma rapidly restore vestibular function. Locally applied AAT has yet to be examined in this context, nor has it been directly compared with anti-inflammatory corticosteroid treatment. METHODS: Wild-type mice C57BL/6 underwent a unilateral inner ear injury. Nine microliters of saline, clinical-grade AAT (180 µg/site), dexamethasone (4 mg/site), or both were applied locally on Days 0, 1, and 2 (n = 5/group). Vestibular function was assessed for 7 days. An in vitro human epithelial gap closure assay was performed using A549 cells in the presence of AAT and/or dexamethasone. RESULTS: Upon labyrinthotomy, all groups displayed severe vestibular dysfunction. Saline-treated mice showed the longest impairment. That group and the dexamethasone group displayed partial to no recovery, while AAT-treated mice exhibited complete recovery within 7 days; at this time point, dexamethasone-treated mice exhibited 50% recovery. Objective vestibular testing showed similar outcomes. In vitro, cotreatment with AAT and dexamethasone resulted in a gap closure dynamic that was superior to AAT alone at 6 h and superior to DEX alone at 48 h. CONCLUSION: Locally applied AAT treatment is superior to locally applied dexamethasone in promoting vestibular recovery in vivo. Ongoing studies are exploring the potential advantages of AAT combined with early low-dose dexamethasone therapy.

Local Alpha1-Antitrypsin Accelerates the Healing of Tympanic Membrane Perforation in Mice.

BACKGROUND: Most tympanic membrane (TM) perforations heal spontaneously, but 10%-20% remain chronic and might lead to impaired hearing and recurrent middle ear infections. Alpha1-antitrypsin (AAT) is a circulating tissue-protective protein that is elevated under inflammatory conditions and is currently indicated for genetic AAT deficiency. Recently, AAT has been shown to promote tissue remodeling and inflammatory resolution. OBJECTIVE: This study aimed to examine the effects of local clinical-grade AAT treatment on tissue repair in a mouse model of acute traumatic TM perforation. METHODS: Wild-type mice underwent unilateral TM perforation and were either left untreated or treated locally with human AAT (9 × 10-3 mL at 20 mg/mL on days 0, 1, and 2; n = 15/group). The perforations were evaluated macroscopically on a serial basis. Mice were sacrificed on various days post-injury, and TMs were excised for gene analysis by RT-PCR. RESULTS: There were no adverse reactions in hAAT-treated ears throughout the study period. Compared with untreated animals, TM closure occurred earlier in the treated group (days until full closure, median: 4 and 9, respectively). According to gene expression analysis, VEGF, TGFß, and collagen-5A1 were induced earlier in AAT-treated mice (day 4-5 compared with day 9). Additionally, IL-10 expression levels were higher and IL-6 levels were lower in treated versus untreated mice. CONCLUSION: A local tissue environment rich in AAT promotes early tissue repair in a perforated TM model both macroscopically and molecularly. Studies are underway to examine TM functionality and recombinant AAT formulations for micro-dosing in the format of a single local application. LEVEL OF EVIDENCE: NA Laryngoscope, 134:3802-3806, 2024.

Comparison of instability resistance training, traditional resistance training and plyometric training on athletic performance parameters.

OBJECTIVES: The objective of the study was to compare traditional resistance, instability resistance, and plyometric training methods on measures of athletic performance in healthy subjects. METHODS: Sixty five healthy, physically active male students were randomly assigned to the following groups: traditional resistance training (RT, n=22), instability training (IT, n=22), and plyometric training (PLY, n=21).Athletic performance parameters were assessed pre- and post-training using chair squat test, standing stork test, shuttle run test, t-test, and vertical jump test. RESULTS: General linear univariate model with baseline as covariate (ANCOVA) was used for analyzing the change in outcome from baseline to post-treatment. Statistically significant improvement was observed in all the athletic performance parameters in all three groups after seven weeks of training (p-value<0.05). The highest change in chair squat test was reported for RT compared to IT (p-value<0.001) and PLY (p-value<0.001). The change in standing stork test among the IT group was substantially higher than that among RT (p-value=0.007) but did not significantly differ from that among the PLY (p-value=0.27). No statistically significant difference was observed in post-test values of vertical jump test among three groups. The highest change in t-test and shuttle run test was reported for PLY compared to IT (p-value<0.001) and RT (p-value<0.001). CONCLUSIONS: Based on the findings of this study, it is suggested that IT and PLY can be included with traditional RT to improve various aspects of athletic performance in healthy physically active individuals. The current study will give an insight to athletes, coaches, and trainers regarding utilization of appropriate training methods in enhancing athletic performance. However, further research is required to establish the effectiveness.