Kazuhiko Nario

Effects of intravenous administration of prostaglandin E1 and lipo-prostaglandin E1 on cochlear blood flow in guinea pigs

Abstract Prostaglandin E1 (PGE1), a vasodilator and an inhibitor of platelet aggregation, has been used for the treatment of idiopathic sudden sensorineural hearing loss, despite the fact that its effectiveness has not been proven. Furthermore, it is rapidly metabolized in the lungs, which makes it difficult to use clinically. In an attempt to prevent this, PGE1 was coated with a 0.2-µg lipid microsphere produced by beans; this was designated lipo-PGE1. This coating protects PGE1 from being rapidly metabolized. In this study, the effectiveness of the intravenous administration of lipo-PGE1 was compared with that of PGE1 by investigating the effects on systemic blood pressure (SBP) and cochlear blood flow (CBF) in guinea pigs with normal ears. The results of both drugs showed a dose-dependent decrease in SBP and the maintenance of CBF despite the decrease in SBP. However, no significant increase in CBF was observed for either drug. In comparing the effects of PGE1 and lipo-PGE1, no obvious differences in the effects on SBP and CBF were observed in this study.

The effect of protein kinase C stimulator and inhibitor on cochlear potentials in the guinea pig

To determine a possible role of protein kinase C (PKC) in the cochlear, the effects of a PKC stimulator (phorbol-12-myristate-13-acetate; PMA), an inactive analogue of PKC stimulator (4 alpha-phorbol-12,13-didecanoate; 4 alpha-PDD) and a PKC inhibitor (D-sphingosine) on cochlear potentials were examined in the guinea pig. The perilymphatic perfusion with PMA (3 x 10(-6) M) produced an increase in compound action potential (CAP) amplitude and no change in N1 latency, the amplitudes of negative summating potential (-SP), cochlear microphonics (CM) and endocochlear potential (EP). The perfusion with 4 alpha-PDD (3 x 10(-6) M) did not change the sound-evoked cochlear potentials and the EP. The perfusion with D-sphingosine (10(-5) M) produced a decrease in CAP amplitude and no change in N1 latency and the amplitudes of -SP, CM and EP. The results suggest that PKC may be involved in the mechanism underlying the CAP generation.

Chronic invasive sinus and intracerebral aspergillosis controlled by combination therapy with micafungin and a daily dose of 400 mg itraconazole oral solution

Chronic invasive aspergillosis of the sinus is frequently fatal in the absence of early surgical and chemotherapeutic intervention because of its invasion of vascular tissue. We attempted to control a case of inoperable invasive aspergillosis of the sinus with micafungin and itraconazole oral solution. We prescribed a daily oral dose of 400 mg of itraconazole, which is twice the usual dose, and monitored the serum concentration of the drug. Finally, we were able to control the spread of the lesion. This case indicates that combination therapy with micafungin and a daily dose of 400 mg itraconazole oral solution is an alternative treatment strategy for inoperable invasive aspergillosis of the sinus.

The action of substance P methyl ester on cochlear potentials in the guinea pig

The action of the substance P agonist, substance P methyl ester (SPME) on cochlear potentials was examined in the guinea pig. Previous studies have shown that SPME is a selective agonist for neurokinin 1(NKI) receptor. Perfusion with SPME at a concentration of more than 10-6M produced an increase in the amplitudes of the compound action potential and negative summating potential in a dose-dependent manner. N1 latency showed a tendency to be shortened, but this change was not significant. Amplitudes of the cochlear microphonics and endocochlear potential remained unchanged. Substance P fragment 7–11, an inactive analogue, produced no changes in the cochlear potentials. In contrast, the substance P antagonist [D-Pro2,D-Trp7,9]-SP blocked the action of SPME on the cochlear potentials. These results suggest that substance P may modulate neurotransmission through NK1 receptors in the cochlea.

The effect of adenosine on cochlear potentials in the guinea pig

The effect of adenosine on cochlear potentials was examined in the guinea pig. Perilymphatic perfusion with 10−4 M adenosine produced a significant decrease in the amplitudes of cochlear microphonics, negative summating potential (-SP) and compound action potential (CAP) and significant prolongation of N1 latency with no change in the endocochlear potential. The decreases in the amplitudes of -SP and CAP caused by adenosine were dose-dependent. Perilymphatic perfusion with an inactive analogue, 8-bromoadenosine, produced no changes in the cochlear potentials. The A1-receptor agonist, 2-chloroadenosine, produced a similar change in cochlear potentials to adenosine, while no changes were produced by the A2-receptor agonist ,5′-(N-ethylcarboxamido)-adenosine. These results suggest that adenosine may have a modulatory function through an Al receptor in the cochlea.

Endolymphatic space size in patients with Meniere’s disease and healthy controls

Abstract Conclusions: The incident ratios of cochlear and/or vestibular endolymphatic hydrops (EH) were significantly higher in the affected ears of patients with Meniere’s disease (MD) than in the ears of healthy controls. There were no significant differences between controls and the contralateral ears of MDs. Objectives: The aim was to compare the incidence ratios of EH between unilateral/bilateral MD and controls using 3T magnetic resonance imaging (MRI) with intravenous gadolinium. Methods: A total of 41 patients were diagnosed with MD: 32 with unilateral MD (uMD) and nine with bilateral MD (bMD). Fifteen healthy volunteers were enrolled as controls. The patients underwent 3T MRI 4 h after intravenous injection of gadolinium. Results: Cochlear EH was present in 3.3% of 30 ears of 15 controls, 6.3% of 32 contralateral (contra) ears of 32 uMDs, 62.5% of 32 affected ears of 32 uMDs, and 55.6% of 18 affected ears of nine bMDs. Vestibular EH was observed in 6.7% of control ears, 3.1% of contra-uMD ears, 65.6% of affected uMD ears, and in 55.6% of affected bMD ears. Either cochlear or vestibular EH was present in 10.0% of control ears, 6.3% of contra-uMD ears, 81.3% of affected uMD ears, and 44.4% of affected bMD ears.

Cardiac mechanical and electrophysiologic modulations of guinea-pig by caffeine and thapsigargin

1. The effects of caffeine and thapsigargin on the contractile force and the action potential in guinea-pig papillary muscles were examined. 2. Caffeine (1 to 10 mM) initially increased contractile force in a concentration-dependent manner. Subsequently, 1 mM caffeine decreased it as compared with precaffeine level (but not significantly). At 5 mM or 10 mM, caffeine also decreased contractile force, but the decrease was still positive as compared with control level. 3. Exchange to low [Ca]o (0.9 mM) or high [K]o (8 mM) decreased steady-state value during exposure to 1 mM caffeine. Addition of 1 microM thapsigargin (TG) decreased the steady-state value during exposure to 1 mM caffeine, but enhanced it with 5 mM and 10 mM caffeine. TG (1 microM) alone increased the force. 4. In electrophysiologic, studies, caffeine shortened the action potential duration (APD) in a concentration-dependent manner. In the presence of caffeine (1 mM), high [K]o shortened APD and decreased the action potential amplitude and resting potential. 5. These results suggest that in the presence of caffeine and/or thapsigargin calcium overload might not occur in the left ventricular papillary muscles of the guinea-pig heart.

Effect of Endoplasmic Ca2+-ATPase Inhibitors on Cochlear Potentials in the Guinea-pig

The effect of endoplasmic Ca2+-ATPase inhibitors on cochlear potentials was examined in the guinea-pig. Perilymphatic perfusion with thapsigargin (10[-6] M) produced a significant decrease in the amplitudes of cochlear microphonics, negative summating potential and compound action potential, and a significant prolongation of N1 latency with no change in the endocochlear potential. These changes were all dose dependent. Another endoplasmic Ca2+-ATPase inhibitor, cyclopiazonic acid (10[-5] M), produced the same effects as thapsigargin on cochlear potentials. These results suggest that endoplasmic Ca2+-ATPase inhibitors may have inhibitory functions on cochlear potentials.

Neurovascular compression syndrome with Meniere's disease—a report of the treatment of a patient with microvascular decompression

Neurovascular compression syndrome(NVCS) is currently regarded as one of the causes of disabling positional vertigo (DPV). A 59-year-old man visited our hospital on December 15, 1993. The neuro-otological examination suggested that the patient had Menières disease and he was treated with conservative medication. However, the patient continued to suffer definite vertigo attacks, as well as a fluctuation in his hearing. A consultation and discussion lead us to believe the patient was also suffering from NVCS. We planned the microvascular decompression surgery. After surgery, the patient stopped suffering from vertigo attacks but his audiogram showed severe fluctuation in sensorineural hearing levels. It was concluded that the present patient had been suffering from NVCS combined with Menières disease.

Inner Ear Blood Flow in the Rat after Unilateral Arterial Occlusion in the Vertebrobasilar Arterial System

It is generally accepted that certain kinds of vertigo and hearing disturbances are caused by blood flow insufficiency in the vertebrobasilar arterial system. Using the microsphere method we investigated whether unilateral vertebral artery or unilateral posterior inferior cerebellar artery occlusion could cause an imbalance between right and left inner ear blood flow in rats. We also studied the differential vulnerability between blood flow in the cochlea and in the ampullae of the three semicircular canals. We counted the numbers of microspheres distributed to the cochlea (CO) and microspheres distributed to three ampullae of semicircular canals (SC) under a microscope with the surface preparation method. The results were as follows: i) no imbalances were observed between bilateral CO or SC even in animals with arterial occlusion, and ii) the CO/SCs of animals with arterial occlusion were not significantly different from that of the control animals. These findings suggest that total inner ear blood flow over a certain period of time was even between the ears bilaterally even in animals with arterial occlusion. The blood flow in the ampullae of the three semicircular canals was not more or less affected by arterial occlusion than the blood flow in the cochlea.