Yoshimitsu Ohinata

Glutathione limits noise-induced hearing loss

The generation of reactive oxygen species (ROS) is thought to be part of the mechanism underlying noise-induced hearing loss (NIHL). Glutathione (GSH) is an important cellular antioxidant that limits cell damage by ROS. In this study, we investigated the effectiveness of a GSH supplement to protect GSH-deficient animals from NIHL. Pigmented guinea pigs were exposed to a 4 kHz octave band noise, 115 dB SPL, for 5 h. Group 1 had a normal diet, while groups 2, 3 and 4 were fed a 7% low protein diet (leading to lowered tissue levels of GSH) for 10 days prior to noise exposure. One hour before, immediately after and 5 h after noise exposure, subjects received either an intraperitoneal injection of 5 ml/kg body weight of 0.9% NaCl (groups 1 and 2), 0.4 M glutathione monoethyl ester (GSHE; group 3) or 0.8 M GSHE (group 4). Auditory thresholds were measured by evoked brain stem response at 2, 4, 8, 12, 16 and 20 kHz before and after noise exposure. Ten days post exposure, group 1 showed noise-induced threshold shifts of approximately 20 dB at 2, 16 and 20 kHz and 35 to 40 dB at other frequencies. Threshold shifts in group 2 were significantly greater than baseline at 2, 4, 16 and 20 kHz. GSHE supplementation in a dose-dependent fashion attenuated the threshold shifts in the low protein diet animals. Hair cell loss, as evaluated with cytocochleograms, was consistent with the auditory-evoked brainstem response results. Group 2 exhibited significantly more hair cell loss than any of the other groups; hair cell loss in group 3 was similar to that seen in group 1; group 4 showed less loss than group 1. These results indicate that GSH is a significant factor in limiting noise-induced cochlear damage. This is compatible with the notion that ROS generation plays a role in NIHL and that antioxidant treatment may be an effective prophylactic intervention.

Effects of nitric oxide synthase inhibitor on cochlear blood flow

We observed in rats the changes in cochlear blood flow (CoBF) and cutaneous blood flow of the abdominal wall (AbBF) after the administration of the NO synthase inhibitor, N-nitro-L-arginine-methyl ester (L-NAME). Ten minutes after i.v. infusion of L-NAME (0.2, 1, 5, 10 mg/kg), L-arginine, which is a substrate of NO, was infused (100 mg/kg) i.v. Employing a laser Doppler flowmeter, the changes in blood flow were recorded from the basal turn of the right cochlea or the abdominal wall and blood pressure (BP) was recorded from the left femoral artery simultaneously. Vascular conductance (VC) was calculated from CoBF/mean BP (cochlear VC) or AbBF/mean BP (abdominal VC). The findings in rats generally agreed with those in guinea pigs [Brechtelsbauer et al., Hear. Res. 77 (1994) 38-42]. Intravenous infusion of L-NAME produced a dose-dependent depression of cochlear VC at 0.2 mg/kg (-18.9), 1 mg/kg (-37.9%), 5 mg/kg (-45.8%) and 10 mg/kg (-48.3%). AbBF also decreased after infusion of L-NAME (5 mg/kg) but to a lesser degree (-41.1% in VC) with no significance compared to CoBF (5 mg/kg). Infusion of L-arginine partially reversed the CoBF decrease caused by L-NAME. The group of 0.2 mg/kg infusion of L-NAME showed the largest degree of recovery with L-arginine, while the 10 mg/kg group showed the smallest. The decrease in AbBF did not recover substantially with L-arginine, the degree being less than that of each group in the CoBF experiment. It was suggested that the NO/soluble guanylate cyclase/cGMP system is more active in the cochlear microcirculation. With the round window (RW) application of 1% L-NAME (2 microl), cochlear VC was decreased by 21.6%, which was closest to that of the 0.2 mg/kg group of L-NAME i.v. infusion. The cochlear VC depression after local application of L-NAME did not show any recovery (-0.3%) by RW application of 5% L-arginine (2 microl) 25 min after L-NAME application; a slight gradual increase was observed when a higher concentration (20%) of L-arginine was applied to the RW. We propose that i.v. infusions of L-NAME and L-arginine primarily affect the precapillary arteriole of the spiral modiolar artery which effectively regulates microcirculation as a resistance vessel, and that RW application affects the vessels of the lateral wall, not the spiral modiolar artery because of the difficulty of substance diffusion.

Effects of Hyperventilation and Hypoventilation on Cochlear Blood Flow and Endocochlear Direct-Current Potential

To understand the importance of oxygen transport to the inner ear tissue, we studied, in guinea pigs, the relationship between cochlear blood flow and endocochlear direct-current potential (EP) under different respiratory conditions. EP, a functional parameter of the stria vascularis, was recorded by a microelectrode inserted into the lateral wall of the chochlea. To measure the cochlear blood flow (CoBF), we employed laser Doppler flowmetry and recorded the flow with a probe placed on the same spot on the lateral wall. During 3 min of asphyxia, CoBF and systemic blood pressure showed irregular biphasic increases, while the EP decreased to reach a negative value. In the hypoxemia experiment, which was induced by stepwise reduction of the respiratory rate to 60%, increases in CoBF and blood pressure were evident during hypoventilation with an intermediate position of EP in the positive range. The mechanisms of these increases in two parameters are discussed from the viewpoints of sympathicotonic activity in the autonomic nervous system and the vasodilating action of CO2 during hypercapnia. In the hyperoxemia experiment, which was induced by stepwise increase in the respiratory rate to 140%, CoBF and blood pressure were found to decrease during hyperventilation with no significant change of EP. The decrease in blood pressure was considered to be due to the increase in intrathoracic pressure caused by the increased rate of artificial respiration. As for the concomitant decrease in CoBF, chemical regulation of PCO2 in the vascular bed of the lateral wall of the cochlea was thought to be a contributory factor.

Influence of hypotension on cochlear blood flow in polycythemic condition

We examined the influence of hypotension by infusion of acebutolol hydrochloride (AH), a cardioselective beta-receptor antagonist, on cochlear blood flow in guinea pigs with various hematocrit values. AH infusion lowered the mean blood pressure to almost the same degree in all animals, regardless of the hematocrit level. The degree of the concomitant decrease of CBF varied with the hematocrit, being greater in animals with a higher hematocrit. In those with the highest hematocrit CBF did not return to the initial level. From these values we calculated the O2 transport capacity after AH infusion and found it to be lower than in animals without AH infusion. The difference was greater at higher hematocrits. These findings suggest that the microcirculation of the inner ear is responsive to transient decreases of perfusion pressure at high hematocrits.

Cystic Parathyroid Adenoma. A Case Report.

Cystic parathyroid adenoma is rare. This report presents a 48-year-old female with primary hyperparathyroidism caused by cystic parathyroid adenoma.She was found to have hypercalcemia on laboratory examinations performed in the Department of Internal Medicine of our hospital during a search for the cause of her vertigo. Further examinations indicated a functioning parathyroid cyst. Ultrasonography and MRI scan showed that the cystic portion was sharply demarcated from the solid portion of the lesion in a parathyroid gland. The high level of plasma PTH decreased to normal after removal of the enlarged parathyroid gland. Histological examination demonstrated a secondary pseudocyst resulting from cystic degeneration of a parathyroid adenoma. Twenty-seven cases of functioning parathyroid cysts reported in the Japanese literature are reviewed. The clinical features and histological evidence of functioning parathyroid cyst are discussed.