No abstract

Development of hypesthesia, a loss of sensitivity to stimulation, is associated with impaired regeneration of peripheral sensory fibers, in which Schwann cells play a key role by secreting nerve growth factor (NGF). Recent clinical trials indicated that an inhibitor of aldose reductase (AR), the ratelimiting enzyme in the polyol pathway, significantly improved hypesthesia in diabetic patients. The fact that AR is localized in Schwann cells led us to investigate the role of the polyol pathway in NGF production of isolated Schwann cells. Among various endogenous factors examined, increased production of NGF was demonstrated in the cells treated with neurotrophin-3 (NT-3) for 24 h. NT-3-induced NGF production was significantly suppressed when cells were cultured in the medium containing high glucose. In these cells, the levels of glutathione (GSH) and cAMP-response element binding protein (CREB) were reduced, whereas the level of activated nuclear factor-jB (NF-jB) was elevated. These changes were abolished when an AR inhibitor fidarestat was included in the medium. NT-3-induced NGF production was further attenuated in the cells treated with an inhibitor of GSH synthesis. Together, the enhanced polyol pathway activity under highglucose conditions seems to elicit reduced NT-3-induced NGF production in Schwann cells. Enhanced oxidative stress linked to the polyol pathway activity may mediate this process.

For the sound localization, an interaural difference is important. To obtain the desired localization, it is necessary to use a head-related transfer function (refer to HRTF), which is defined as the transfer function between a sound source and a surface of the ear drum. In our previous work, as far as in the case of reproducing the virtual sound source in the horizontal plane, it is confirmed to be capable of remarkable localization by using the numeric data calculated by a rigid sphere head model instead of a dummy head microphone. However, it is necessary to solve the problem of the front back confusion and the sound localization of the vertical plane. For that, it might be essential to add the pinna information to the rigid sphere model, to examine how each part of the pinna is related to the localization.