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M Akiyoshi

Publications and source records attributed to M Akiyoshi.

At least 37 records · Page 2Linked to original sources

Effect of loop-diuretics on hair cells of the cochlea in guinea pigs. Histological and histochemical study.

The present study revealed the following early changes in pinna reflex and in inner ear morphology of guinea pigs treated intravenously with furosemide (100 mg/kg) or ethacrynic acid (80 mg/kg). (A) Transient loss of pinna reflex occurred in wide frequency range (20K-500 Hz) immediately after the treatment. (B) Narrowing of deeper capillary network of the stria vascularis occurred soon after the treatment. The change was reversible. (C) Outer hair cells underwent cytoplasmic swelling and marked depression of supravital reduction of Nitro-BT. These changes were reversible. (D) Relationship between these changes and functional alteration of the cochlea was discussed.

Animals↗

Audiotoxicosis in newborn guinea pigs from pregnant ones given sisomicin.

The audiotoxic effect of sisomicin was investigated in guinea pig injected intramuscularly with 6.25, 12.5, 25 and 50 mg/kg of sisomicin sulfate (potential) during weeks 1--5 or 5--9 of pregnancy, and the transplacental effect on their offspring was studied. While, in some dams the higher doses of sisomicin produced a limited effect on the pinna reflex and the outer hair cells of the organ of Corti, no such effects were noted in any of the offspring during the 3-week postnatal observation period.

Animals↗

[Animal test for evaluation of ototoxicity and safety of KW-1062 (author's transl)].

KW-1062, a new aminoglycoside antibiotic, was tested for the evaluation of audiotoxicity in administration at higher dosage and compared with the audiotoxicity of gentamicin. KW-1062 was given at dosage of 50, 100 and 150 mg/kg intramuscularly for 4 weeks to each group consisting of 10 healthy guinea pigs, respectively. Gentamicin was administered at dosage of 25, 35, 50 and 100 mg/kg in the same way as in KW-1062 to the guinea pigs. In the present study the differential frequency pinna reflex test in the frequency range from 20 kHz to 0.5 kHz was performed before and during administration of the drugs, to evaluate the audiotoxicity. Comparison of number of animal with pinna reflex loss and extent of frequency range of pinna reflex loss revealed that KW-1062 at dose of 150 mg/kg is less audiotoxic than gentamicin at 50 mg/kg and 100 mg/kg, and approximately equivalent in audiotoxicity to gentamicin at dose of 35 mg/kg.

Aminoglycosides↗

[Ototoxic effect of BB-K8 administered to pregnant guinea pigs on development of inner ear of intrauterine litters (author's transl)].

UNLABELLED: Transplacental ototoxic effects of BB-K8 on development of inner ear in intrauterine guinea pigs were evaluated by differential frequency pinna reflex test in range of 20 kHZ to 500 HZ and histopathological examination of spiral and vestibular organs in new born guinea pigs from pregnant ones given BB-K8 i.m. during gestation. MATERIALS AND METHODS: Twenty-five pregnant guinea pigs of the Hartley strain and 63 new-born guinea pigs from the pregnant ones were used in the study. Following antibiotics were given i.m. daily to the 20 pregnant guinea pigs from 7th day of gestation for 56 days. BB-K8 was given at the dose level of 100 mg/kg and 200 mg/kg, respectively. Kanamycin (KM) was administered at the dose level of 100 mg/kg and 200 mg/kg, respectively. Physiological saline solution (1.0 ml/kg) was given i.m. to the pregnant guinea pigs for 56 days. The differential frequency pinna reflex test was performed in the frequency range from 20 kHZ to 500 HZ to determine an extent of frequency of pinna reflex loss. The test was carried out before the start of administration of the antibiotics and once a week during the administration. After the last injection of the antibiotics, intravital perfusion fixation was carried out in the new born animals under anesthesia with nembutal. Histopathological examination was made in celloidin serial sections of the cochlea and vestibulum of the new born animals to observe an extent or degree of hair cell damage. RESULTS: (1) The differential frequency pinna reflex test revealed that new born guinea pigs from the pregnant ones given BB-K8 and KM respectively at the dose level of 100 mg/kg did not show occurrence of pinna reflex loss at any frequency tested. At the dose level of 200 mg/kg, BB-K8 did not result in transplacental hearing impairment in new born guinea pigs, but KM caused transplacental pinna reflex loss in the highest frequencies from 20 k to 15 kHZ in 3 of 10 animals. (2) Histopathological examination detected that unilateral incomplete loss of outer hair cells of the spiral organ confined to the basal end of cochlea was found in 3 of 13 new born guinea pigs from the pregnant ones treated with BB-K8 (100 mg/kg). In the animals, slight damage of hair cells in the vestibular organs occurred in 100%. These hair cell damages were enhanced slightly in the new born guinea pigs from the pregnant ones treated with BB-K8 (200 mg/kg) and much more in the new born ones from the pregnant ones treated with KM (100 mg/kg, 200 mg/kg). (3) These results suggest that BB-K8 has a mild potency to cause transplacental ototoxic damage in the inner ear of intrauterine guinea pigs within the pregnant ones treated for 56 days (normal gestation period approximately 70 days).

Amikacin↗

[Ototoxicity of spectinomycin (author's transl)].

Spectinomycin is an aminocyclitol antibiotic, but different in chemical structure from other aminocyclitol antibiotics such as streptomycin, kanamycin and gentamicin. Spectinomycin clinically has been proven to be highly effective in the intramuscular single-dose treatment of gonorrhea. According to NOVAK et al. (1974), all evidence from pharmacological and clinical efficacy studies to date indicates that spectinomycin is free from ototoxic effects at the dose levels recommended for single-dose treatment of gonorrhea (2 or 4 g) or repeated i.m. or i.v. doses, 8g/day. The present experimental study has been made to evaluate the ontoxocic effects of spectinomycin in Hartley strain guinea pigs given i.m. a single-high dose (800 mg/kg or 1,600 mg/kg) and repeated-slightly higher dose (80 mg/kg or 160 mg/kg daily for 4 weeks) respectively. Differential frequency pinna reflex test in frequency range from 20 KHz to 500 Hz revealed that no animals showed disappearance of pinna reflex in the frequencies tested. Histologic examination in serial celloidin sections of the cochlea and vestibulum disclosed that a few animals given a single-high dose of spectinomycin (800 mg/kg or 1,600 mg/kg) and repeated-slightly higher dose or spectinomycin (80 mg/kg daily for 4 weeks) respectively showed limited mild damage of outer hair cells in the spiral organ and of hair cells in the vestibular organ. There were histologically a few focal necrosis in the liver and scattered interstitial cell infiltration around the proximal convoluted tubules which are lined with regenerated epithelial cells in some animals given the single-high dose (800 mg/kg or 1,600 mg/kg) or repeated-slightly higher dose (80 mg/kg or 160 mg/kg daily for 4 weeks) of spectinomycin. Positive correlation between the extent of the hair cell damage and the injury of the liver and kidney was not confirmed. The present study suggests that administration of spectinomycin at the dose levels recommended for single-dose treatment of gonorrhea (2 or 4 g) most probably is free from ototoxic effect.

Animals↗

[The safety evaluation of fradiomycin-gramicidin S troches "Meiji" (author's transl)].

The troches "Meiji" contain fradiomycin (neomycin), an aminoglycoside antibiotic, and gramicidin S, and are effective against gram-negative and -positive bacteria. In this paper the safety evaluation of the troches is reported. In this study male guinea pigs of Hartley strain were used, and fradiomycin (FRM) and gramicidin S (GRMN) were administered orally for 35 days consecutively except Sunday. The PRYER'S reflex test was carried out with frequency range of 10,000 approximately 15,000 Hz before, during and after the administration. After the last administration the animals underwent vital perfusion with physiological saline and then with Wittmack's fixative. Bilateral temporal bones were removed and fixed in the same fixative for several days. Using a conventional method, serial celloidin horinzontal sections were prepared and stained with hematoxyline-eosine to observe histopathological effect of the medicines on the organs of CORTI. The results were as follows: 1) There were no remarkable differences in the treated animals from the initial states. No animal died at all the doses tested. 2) All of the guinea pigs received 10 and 50 mg/kg of FRM and 4 and 20 mg/kg of GRMN for 35 days indicated positive pinna reflex in the extensive frequency range of 10,000 approximately 15,000 Hz. There was no remarkable damage in the organ of CORTI on histopathological examination. 3) It was concluded from these results that the troches are highly safe.

Animals↗

[Evaluation of ototoxicity of amikacin (BB-K8) by animal test (author's transl)].

Seventy Hartley strain guinea pigs (350 g body weight at start of the experiment) were used. BB-K8, gentamicin (GM) and kanamycin (KM) were given to the animals intramuscularly for 28 days at following various doses: (see article) These guinea pigs underwent a differential frequency pinna reflex test in wide frequency range from 20KHz to 0.5 KHz before the administration, during the injection and after the last one. For histopathological examination of the inner ears the guinea pigs were subjected to intravital fixation with Wittmaack's fixative under nembutal general anesthesia. Blocks including the bilateral temporal bones were removed from the skulls and then fixed in the same fixative for 1 similar to 2 weeks. After routine procedure for decalcification, dehydration and celloidin embedding, horizontal serial sections of the inner ears were made and stained with hematoxylin-eosin. The differential frequency pinna relfex test in the 70 guinea pigs indicated positive pinna reflex in 90% at 20KHz and in 100% at 15, 12, 10, 8, 6, 4, 3, 2, 1 and 0.5 KHz before start of the administration. Administration of the antibiotics for 28 days occasionally resulted in the pinna reflex loss which always involved the highest frequency, 20 KHz and then was followed in relatively regular succession by 15, 12, 10, 8, 6, 4, 3, 2, 1 and 0.5 KHz (Tables 1 similar to 8). On the other hand, histopathological examination of the inner ears disclosed that the loss of the outer hair cells in the spiral organ which are the most sensitive to the ototoxic antibiotics, occurred always at the basal end of the spiral organ and then spread from there to upper portion of the spiral organ (Tables 9 similar to 16). Based on the differential frequency pinna reflex test in the wide frequency range and extensive histopathological examination of the inner ears, ototoxicity of BB-K8 is considered to be more mild than GM. However, there was not so remarkable difference in ototoxicity between BB-K8 and KM in the present experiment. The result or examination of the guinea pigs received BB-K8 at 40 mg/kg and 100 mg/kg respectively for 28 days suggests that BB-K8 at expecting clinical dose, 500 mg per day (for 28 days) may be safe from ototoxicosis in the inner ears. In the vestibular organs of the animals received BB-K8 there was no decrease in number of the hair cells.

Amikacin↗