Noise-induced hearing loss (NIHL) is one of the most common sensorineural hearing deficits. Recent studies have demonstrated that the pathogenesis of NIHL is closely related to ischemia-reperfusion injury of cochlea, which is caused by blood flow decrease and free radical production due to excessive noise. This suggests that protecting the cochlea from oxidative stress is an effective therapeutic approach for NIHL. NRF2 is a transcriptional activator playing an essential role in the defense mechanism against oxidative stress. To clarify the contribution of NRF2 to cochlear protection, we examined Nrf2–/– mice for susceptibility to NIHL. Threshold shifts of the auditory brainstem response at 7 days post-exposure were significantly larger in Nrf2–/– mice than wild-type mice. Treatment with CDDO-Im, a potent NRF2-activating drug, before but not after the noise exposure preserved the integrity of hair cells and improved post-exposure hearing levels in wild-type mice, but not in Nrf2–/– mice. Therefore, NRF2 activation is effective for NIHL prevention. Consistently, a human NRF2 SNP was significantly associated with impaired sensorineural hearing levels in a cohort subjected to occupational noise exposure. Thus, high NRF2 activity is advantageous for cochlear protection from noise-induced injury, and NRF2 is a promising target for NIHL prevention.
Objective: To clarify the characteristics of ankle-brachial index (ABI), toe-brachial index (TBI), and pulse volume recording (PVR) of the ankle with brachial-ankle pulse wave velocity (baPWV) in healthy young adults. Material and Methods: We analyzed ABI, TBI, baPWV, and PVR in the ankle of healthy adults aged 20 to 25 years (median, 20 years) using an automatic oscillometric device between 2002 and 2013. The ABI, baPWV, and PVR in 1282 legs of 641 subjects (301 men and 340 women) and the TBI in 474 toes of 237 subjects (117 men and 120 women) were evaluated. Results:The measured values showed no bilateral differences. ABI and baPWV were higher in men than in women, but TBI was similar in both sexes. ABI <1.0 was observed in 18.1% of the legs in men and in 25.6% in women. TBI <0.7 was observed in 16.2% of the toes in men and 19.1% in women. For ankle PVR, the % mean arterial pressure was higher in women than in men. The upstroke time was <180 ms in most subjects. Conclusions: For young people, ABI <1.0 or TBI <0.7 may not always indicate vascular abnormalities. When evaluating circulatory indexes, age and sex should be considered.Keywords: ABI, TBI, baPWV, PVR, healthy young adults indications of ABI. The cut-off value of ABI for detecting PAD has been confirmed as 0.9 with high sensitivity and specificity. 2) Moreover, ABI is a strong predictor of cardiovascular events: the normal ABI range was revised as 1.00 to 1.40, because patients with ABI ranging from 0.91 to 0.99 have been shown to be at the borderline of cardiovascular risk. 2) On the other hand, TBI measurements are more cumbersome and are limited to special institutions (e.g., vascular laboratories) using different techniques including laser Doppler flowmetry, photoplethysmography, oscillometric plethysmography, and mercury strain gauge plethysmography. Thus, basic data on a uniform technique for a large population remain limited. Although the cut-off value of TBI for detecting PAD is set at 0.6 or 0.7, there has been no global consensus. 1,[3][4][5] Although the normal standard ranges of ABI and TBI are based on data obtained mostly from middle and senior adults, [3][4][5][6] young patients with lower limb complaints such as coldness, pain, or claudication are also primarily examined by ABI and TBI measurements because PAD including Buerger disease, Raynaud disease, Takayasu arteritis, and even arteriosclerotic diseases can occur in young patients, as the prevalence of PAD is estimated to be 1.2% to 4% of people in their late 20s. 7) However, they occasionally show ABI <1.0 or TBI <0.7 despite their normal physical findings, making the diagnosis confusing.The gold standard method for ABI measurement has been the Doppler method since the 1980s, 2) but on the other hand, automated oscillometric sphygmomanometers have come into use recently. Moreover, full-automated ABI/TBI measuring devices have been developed since the late 1990s. 8,9) We have used the automated ABI/TBI measuring devices in our clinical work. The form PWV/ABI ® (Colin Co., Aichi, Jap...
In-vivo velocity profiles were recorded with a 20 MHz 80-channel pulsed Doppler ultrasound velocimeter in canine end-to-side ilio-femoral anastomotic grafts. The geometries were obtained from casts of the anastomotic region, and flow rates were measured with electromagnetic flow probes. Three cases reported here include a "standard" geometry, which was similar to previously studied in vitro models, a stenosed geometry, and a case with below average flow rate. Observed flow features include separation at the hood and toe, movement of the floor stagnation point, and skewed profiles in the proximal outflow segment. Out-of-plane curvature and lateral displacement of the anastomosis inlet appear to have a strong effect on the flow fields. In addition, compliance affects the instantaneous flow rates within the proximal and distal branches.
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