RESUMEN
Abstract Introduction Riluzole (2-amino-6-trifluoromethoxy benzothiazole) is known as a neuroprotective, antioxidant, antiapoptotic agent. It may have beneficial effects on neuronal cell death due to cisplatin-induced ototoxicity. Objective To evaluate the effect of riluzole on cisplatin-induced ototoxicity in guinea pigs. Methods Twenty-four guinea pigs, studied in three groups, underwent auditory brainstem response evaluation using click and 8 kHz tone burst stimuli. Subsequently, 5 mg/kg of cisplatin were administered to all animals for 3 days intraperitoneally (i.p.) to induce ototoxicity. Half an hour prior to cisplatin, groups 1, 2 and 3 received 2 ml of saline i.p., 6 mg/kg of riluzole hydrochloride i.p., and 8 mg/kg of riluzole hydrochloride i.p., respectively, for 3 days. The auditory brainstem responses were repeated 24 hours after the last drug administration. The cochleae were analyzed by transmission electron microscopy (TEM). Results After drug administiration, for 8,000 Hz stimulus, group 1 had significantly higher threshold shifts when compared with groups 2 (p < 0.05) and 3 (p < 0.05), and there was no significant difference in threshold shifts between groups 2 and 3 (p > 0.05). Transmission electron microscopy findings demonstrated the protective effect of riluzole on the hair cells and the stria vascularis, especially in the group treated with 8 mg/kg of riluzole hydrochloride. Conclusion We can say that riluzolemay have a protective effect on cisplatin- induced ototoxicity. However, additional studies are needed to confirm these results and the mechanisms of action of riluzole.
Asunto(s)
Animales , Masculino , Potenciales Evocados Auditivos del Tronco Encefálico/efectos de los fármacos , Cisplatino/efectos adversos , Riluzol/farmacología , Pérdida Auditiva Sensorineural/inducido químicamente , Umbral Auditivo/efectos de los fármacos , Estría Vascular/efectos de los fármacos , Estría Vascular/patología , Nervio Coclear/efectos de los fármacos , Nervio Coclear/patología , Riluzol/uso terapéutico , Modelos Animales , Microscopía Electrónica de Transmisión , Cobayas , Células Ciliadas Auditivas/efectos de los fármacos , Células Ciliadas Auditivas/patología , Degeneración Nerviosa/inducido químicamenteRESUMEN
OBJECTIVE: To analyze temporal bones of deaf Dalmatian dogs from 5 days after birth to adulthood to better understand the pathogenesis of cochleosaccular dysplasia. METHODS: This is an experimental animal histopathological temporal bone study that included two groups of temporal bones. Group I consisted of 41 temporal bones from deaf Dalmatian dogs and group II of 25 temporal bones from 15 "normal" aged-matched, hearing Black Labradors. Morphometric analysis included: stria vascularis and spiral ligament area measurements, and cell counts of spiral ganglion, Scarpa's ganglion, and hair cells of saccular macula. RESULTS: The following findings were significantly less in deaf Dalmatian group compared to hearing Labradors: (1) cellular area of the stria vascularis in all cochlear turns; (2) cellular area of spiral ligament in the inferior part of the basal turn; (3) cellular density of spiral ganglion cells within segments III and IV; (4) number of Scarpa's ganglion cells; and (5) density of saccular hair cells types I and II. A borderline negative correlation was found between average density of spiral ganglion cells of segments III and IV and age in group I. Young deaf animals showed some cochlear hair cells, however in adult dogs all hair cells were replaced by supporting cells. CONCLUSION: General pattern of cochleosaccular dysplasia is variable, even when only one etiology, the genetic one, is involved. The gradual degeneration of inner ear elements in the cochleosaccular degeneration might indicate that early intervention might be crucial to stop the progression of cochleosaccular dysplasia.
Asunto(s)
Cóclea/patología , Sordera/congénito , Hueso Temporal/patología , Animales , Perros , Células Ciliadas Auditivas Internas/patología , Órgano Espiral/patología , Sáculo y Utrículo/patología , Ganglio Espiral de la Cóclea/patología , Estría Vascular/patologíaRESUMEN
OBJECTIVE: The objective of this study was to perform a morphometric analysis of a series of temporal bones with cochleosaccular dysplasia to clarify the extent of inner ear changes in this disease. STUDY DESIGN: This human temporal bone histopathologic study of a series of deaf-mute cases involves morphometric analysis, including stria vascularis and spiral ligament area measurements and spiral ganglion and hair cells counts. SUBJECTS: Thirteen temporal bones were selected from 35 with deaf mutism based on the histopathologic findings described by Scheibe. Twenty normal age-matched control subjects were used for comparisons. RESULTS: All temporal bones had the main histopathologic findings described by Scheibe, as well as severe affected stria vascularis. Seven temporal bones had cystic areas in the stria and three had concretions. Cross-sectional strial areas in temporal bones with cochleosaccular dysplasia were smaller than normal in all cochlear turns; however, no difference was found in spiral ligament cross-sectional areas. Reissner's membrane was hydropic in three temporal bones and the organ of Corti was absent in at least one cochlear turn in five. Concretions were present in the macula of seven temporal bones. Twelve temporal bones showed some level of spiral ganglion cell loss. No hair cells were observed in any temporal bone. A familial history of deafness was found in three cases. CONCLUSION: Pathologic findings were variable and limited to the saccule and scala media. The variation, perhaps, reflects the different etiologies involved in the origin of cochleosaccular dysplasia.
Asunto(s)
Enfermedades del Desarrollo Óseo/patología , Cóclea/patología , Sordera/congénito , Sáculo y Utrículo/patología , Hueso Temporal/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Estudios de Casos y Controles , Niño , Preescolar , Sordera/etiología , Femenino , Humanos , Lactante , Recién Nacido , Ligamentos/patología , Masculino , Persona de Mediana Edad , Órgano Espiral/patología , Ganglio Espiral de la Cóclea/patología , Estría Vascular/patologíaRESUMEN
The gravidarum should no longer be considered as atrech marks. There is strong evidence that they are closely related to adrenal cortical hyperactivity.In a study of 116 primigravid pregnancies it was shown that:The formation of striae gravidarum does not depend directly upon skin stretching this only influences the production of striae in the presence of a striae factor.There is a close realtion between lowered gluose tolerance in late pregnancy and the development of striase gravidarum.There is a cloise relation between acne, a sign of adrenal cortical hyperactivity and breast striae particulary as regards tine of onset.Several other clinical findings all lend support to an association between striae gravidarum and adrenal cortical hyperactivityOlive oil massage does not prevent striae gravidarum.The substance of this papaer was included in a thesis accepted by the University of Adelaide for the degree o M.D.I am grateful to Sandoz Ltd, Australia, for defraying the total expenses of this study.