Maria Rossato

Conhecimento da anatomia da orelha de cobaias e ratos e sua aplicação na pesquisa otológica básica

O uso de mostras animais e importante na pesquisa otologica e o conhecimento da anatomia de sua orelha permite sua utilizacao adequada. OBJETIVO: Estudar a anatomia da orelha da cobaia e do rato por microscopia optica de luz (MOL) e microscopia eletronica de varredura (MEV) e suas vantagens anatomicas na pesquisa otologica basica. MATERIAL E METODO: Os ossos temporais, as bulas timpânicas e cocleas de tres cobaias e ratos albinos foram fotografados e analisados ao MOL e MEV. RESULTADOS: O rato nao e tao simples de manipular como a cobaia, e frequentemente apresenta otite media. O rato apresenta uma juncao fragil da bula timpânica, duas e meia espiras na coclea e a membrana timpânica nao veda todo o conduto auditivo externo. A cobaia possui uma bula inteirica, martelo e bigorna fundidos e tres e meia espiras na coclea. Pela MEV a cobaia e o rato possuem Membrana Tectoria, Membrana de Raissner e o Orgao de Corti. As Celulas de Hensen estao presentes somente na cobaia. CONCLUSAO: A cobaia foi considerada de facil manipulacao para a microdisseccao, pelo tamanho e rigidez do osso temporal, e para experimentos cirurgicos envolvendo o estribo, janela oval e a membrana timpânica. Pela MEV nota-se semelhanca entre cobaia e rato, podendo ambos serem utilizados em estudos da orelha interna.

Gentamicin Attenuates Gentamicin-Induced Ototoxicity - Self-Protection

Aminoglycoside antibiotics cause considerable toxicity to the inner ear. A progressive hearing loss at high frequencies resulted from the loss of hair cells in the base of the cochlea and a constant preoccupation with finding a treatment that protects against their toxic effects. A self-protection phenomenon to high ototoxic doses of gentamicin is proposed in this paper. Thirty-eight adult guinea pigs with normal hearing were tested using Preyers reflex and the distortion product otoacoustic emission (DPOAE) test, and their cochleae were analyzed by scanning electron microscopy. To the four groups investigated, group I (control) and group II (low dose, 10 mg/kg/day for 30 days) showed a normal DPOEA and normal outer hair cells; group III (high dose, 160 mg/kg/day for 10 days) showed the absence of DPOEA and damage to the outer hair cells; and group IV (low dose, 10 mg/kg/day for 30 days followed by a high dose of 160 mg/kg/day for 10 days) showed a normal DPOEA and normal outer hair cells. These results demonstrate that there was a considerable self-protection phenomenon by gentamicin.

Ototoxicidade da cisplatina e otoproteção pelo extrato de ginkgo biloba às células ciliadas externas: estudo anatômico e eletrofisiológico

Cisplatina e uma potente droga antineoplasica, largamenteutilizada para o tratamento do câncer, tanto em adultos quantoem criancas. Dentre seus efeitos colaterais, a ototoxicidade seapresenta como um dos mais importantes e leva a perda auditivairreversivel, bilateral, para as altas frequencias (4KHz#8KHz). Es-tudos tem tentado identificar drogas que, associadas a cisplatinapossam atuar como otoprotetores. Sabe-se que o mecanismo daototoxicidade pela cisplatina esta relacionado a alteracoes nosmecanismos antioxidantes das celulas ciliadas, principalmente ascelulas ciliadas externas da coclea.

Otoproteção da amifostina aos efeitos ototóxicos da cisplatina: estudo em cobaias albinas por emissões otoacústicas produtos de distorção e microscopia eletrônica de varredura

Cisplatin is an antineoplastic drug for cancer treatment in children and adults. The side effects of cisplatin ototoxicity are significant: irreversible bilateral hearing damage to high frequencies (4 kHz - 8 kHz). Reports recognize some drugs that are associated with cisplatin to obtain an otoprotector effect. The ototoxicity mechanisms of cisplatin are related to injury of hair cell oxidation mechanism, especially of outer hair cells. AIM: Using otoacoustic emissions distortion products (DPOEA) and scanning electron microscopy we intended to verify the action of amifostine, a radioprotective drug that has well known antioxidant characteristics and otoprotector effects to cisplatin injury. STUDY DESIGN: Experimental. MATERIAL AND METHODS: We used an experimental guinea pig model. The study was performed as follows: group 1: 6 animals, 12 ears, cisplatin 8.0 mg/Kg/day (IP), 3 days. Group 2: 6 animals, 12 ears, amifostine 100 mg/Kg/day (IP) and after 90 minutes, cisplatin 8.0 mg/Kg/day (IP), 3 days and group 3: 3 animals, 6 ears, amifostine 100 mg/Kg/day (IP), 3 days. RESULTS: DPOEA were present before and after treatment in groups 2 and 3. The normal cilium architecture of outer hair cells was supported in all cochlear turns in groups 2 and 3. We concluded that amifostine has a potential otoprotector effect against cisplatin ototoxicity and could be used in clinical trials.

Self-Protection against Aminoglycoside Ototoxicity in Guinea Pigs

BACKGROUND: Amikacin is a semisynthetic aminoglycoside. It acts against most of the microbial species. Amikacin limitation of the therapeutic application is the ototoxicity which promotes permanent lesions in the cochlear system. Aminoglycoside antibiotics have ototoxic potential. The target cells are preferentially the outer hair cells in the cochlear basal turns. Amynoglicoside antibiotics can quelate iron forming a complex with oxidate properties and promotes the formation of free radicals. Responsible for production of lesions in the hair cells. OBJECTIVE: The objective of the present investigation was to determine whether the use of the aminoglycoside amikacin at small doses may lead to the occurrence of some types of resistance to or protection against ototoxicity of the drug by analyzing lesions to the organ of Corti by scanning electron microscopy. METHODS: The study was conducted on 31 guinea pigs that were divided into 4 groups, amikacin was administered intramuscularly. The groups consisted of: group A = control group: 5 animals (10 cochleae); group B = 5 animals (10 cochleae), amikacin 20 mg/kg/day for 30 days; group c = 7 animals (13 cochleae), amikacin 400 mg/kg/day for 12 days; group d = 14 animals (26 cochleae) amikacin 20 mg/kg/day for 30 days, followed by 400 mg/kg/day for 12 days. Histological studies were performed by scanning electron microscopy. Three cochleae were excluded. RESULTS: In groups A and B, the cells were normal in all cochleae, in group C there were extensive lesions of the 2 more basal turns, and in group D there was a significant reduction of lesions in the 2 more basal turns compared with group C, which had received the ototoxic dose of amikacin alone. CONCLUSION: We conclude that the non-ototoxic dose of amikacin administered before the ototoxic dose of the same antibiotic had a statistically significant protective effect on the 2 more basal turns of the guinea pig cochlea.

[Amifostine otoprotection to cisplatin ototoxicity: a guinea pig study using otoacoustic emission distortion products (DPOEA) and scanning electron microscopy].

UNLABELLED Cisplatin is an antineoplastic drug for cancer treatment in children and adults. The side effects of cisplatin ototoxicity are significant: irreversible bilateral hearing damage to high frequencies (4 kHz - 8 kHz). Reports recognize some drugs that are associated with cisplatin to obtain an otoprotector effect. The ototoxicity mechanisms of cisplatin are related to injury of hair cell oxidation mechanism, especially of outer hair cells. AIM Using otoacoustic emissions distortion products (DPOEA) and scanning electron microscopy we intended to verify the action of amifostine, a radioprotective drug that has well known antioxidant characteristics and otoprotector effects to cisplatin injury. STUDY DESIGN Experimental. MATERIAL AND METHODS We used an experimental guinea pig model. The study was performed as follows: group 1: 6 animals, 12 ears, cisplatin 8.0 mg/Kg/day (IP), 3 days. Group 2: 6 animals, 12 ears, amifostine 100 mg/Kg/day (IP) and after 90 minutes, cisplatin 8.0 mg/Kg/day (IP), 3 days and group 3: 3 animals, 6 ears, amifostine 100 mg/Kg/day (IP), 3 days. RESULTS DPOEA were present before and after treatment in groups 2 and 3. The normal cilium architecture of outer hair cells was supported in all cochlear turns in groups 2 and 3. We concluded that amifostine has a potential otoprotector effect against cisplatin ototoxicity and could be used in clinical trials.

Ototoxicity and otoprotection in the inner ear of guinea pigs using gentamicin and amikacin: ultrastructural and functional aspects

UNLABELLED Ototoxicity is still a challenge to medicine. The discovery of self-protecting endogenous mechanisms of the outer hair cells associated with their functional and ultra-structural assessment methods has opened new horizons in the understanding and controlling of these mechanisms. AIM this paper aimed at establishing whether or not underdoses of gentamicin could protect the inner ear against the harmful effects of amikacin, based on these protection mechanisms and determine if the otoacoustic emission amplitudes could be associated with the level of hair cell integrity. MATERIALS AND METHODS Experimental study. We used 31 guinea pigs. They were injected with saline solution, gentamicin and amikacin, alone and in combinations -intramuscular injections - during 12, 30 and 42 days. The otoacoustic emissions were recorded in the beginning and at the end of the experiment, comparing it with the cochlear integrity study carried out by electron microscopy. RESULTS gentamicin underdoses did not protect the inner ear against amikacin toxicity; the reduction in otoacoustic emissions was strongly associated with an increase in hair cell lesions. CONCLUSION these findings help understand inner ear otoprotection and ototoxicity. Establishing the correlation between the emissions amplitude an cell integrity plays an important role in the follow up of hair cell damage, with possible monitoring of ototoxicity caused by drugs in humans.

Ototoxicidade e otoproteção em orelha interna de cobaias utilizando gentamicina e amicacina: aspectos ultra-estruturais e funcionais

A ototoxicidade ainda e um desafio para medicina. A descoberta dos mecanismos endogenos autoprotetores das celulas ciliadas externas associados a metodos de avaliacao funcional e ultra-estrutural das mesmas abriu nova perspectiva no entendimento e controle destes mecanismos. OBJETIVO: O trabalho objetivou determinar se subdoses de gentamicina protegia contra ototoxicidade da amicacina baseado nestes mecanismos e determinar se a amplitude das emissoes otoacusticas teria correlacao com grau de integridade das celulas ciliadas. MATERIAL E METODO: Estudo experimental. Utilizando 31 cobaias, administrou-se soro fisiologico, gentamicina e amicacina, isoladamente e associadas, via intramuscular, por 12, 30 e 42 dias. Pesquisa de emissoes otoacusticas foi realizada no inicio e final do experimento, comparado com estudo da integridade coclear, por microscopia eletronica. RESULTADOS: Subdoses de gentamicina nao protegeram a orelha interna contra toxicidade da amicacina; diminuicoes da amplitude das emissoes otoacusticas apresentaram forte correlacao com aumento de lesoes das celulas ciliadas. CONCLUSAO: Os achados contribuem para o entendimento dos mecanismos de ototoxicidade e otoprotecao da orelha interna. A determinacao da correlacao entre amplitude de emissoes e integridade celular tem grande importância no acompanhamento das lesoes de celulas ciliadas, com possivel aplicacao no monitoramento de ototoxicidade por drogas em humanos.

Histological evaluation of maxillary sinus mucosa after functional endoscopic sinus surgery.

Background This study was performed to evaluate the histological changes of the maxillary sinus mucosa of patients with chronic rhinosinusitis (CRS) after functional endoscopic sinus surgery (FESS). Methods In a cohort study, biopsy specimens were collected from the maxillary sinus of patients submitted for FESS. One year after surgery, patients were clinically reassessed. Patients showing recurrence of disease (group 1) required a revision surgery, through which a second biopsy specimen was collected. Patients showing a favorable clinical response (group 2) were submitted to an outpatient maxillary biopsy through the previous opened middle meatus antrostomy. Biopsy material from four cadavers was used as control. The histological and electron microscope findings were analyzed. Results At the initial surgery, patients presented many histopathological alterations, such as an inflammatory process infiltrating the submucosa, atypical respiratory epithelium with an important increase in goblet cells, metaplasia, or mixed epithelium. Group 1 patients persisted with the same alterations 1 year later, but ciliary dysmorphy was more accentuated. Group 2 patients presented a predominantly pseudostratified epithelium, but some areas contained an increased number of goblet cells and a reduction in the number of ciliated cells. Conclusion Recovery of the maxillary sinus mucosa of patients with CRS, observed by electron and light microscopy, was incomplete 1 year after endoscopic surgery, even in nonsymptomatic patients; nevertheless, these alterations were more important in symptomatic patients than in asymptomatic patients.

Analysis of the cytoprotective effect of amifostine on the irradiated inner ear of guinea pigs: an experimental study

UNLABELLED Radiation can cause damage to the inner ear, from a simple hearing loss all the way to profound deafness. Amifostine is a cytoprotective substance extensively used during radio-chemotherapy for malignant tumors. AIM the objective of the present investigation was to establish the antioxidant and radioprotective effects of amifostine on the organ of Corti of albino guinea pigs irradiated in the head and neck region. MATERIALS AND METHODS An experimental study conducted on four groups of guinea pigs were used; One group received only amifostine, one group was submitted to a single dose of 350 cGy and the other two were similarly irradiated but received amifostine doses of 100 or 200 mg/kg. All animals were slaughtered 30 days after the experiment, their bullae were removed and the damaged outer hair cells were counted. RESULT The extent of injury was lower in the outer hair cells of the two groups treated with amifostine compared to the group that was only irradiated. There was no difference between the group treated with 100 and 200 mg/kg of amifostine. The group that received only amifostine had no cochlear damage. CONCLUSION Amifostine is an effective cytoprotective substance in the Organ of Corti of irradiated guinea pigs.