Intoxication with high doses of the aminoglycoside antibiotic amikacin in a supranormal sensitive period in the rat induces complete destruction of the inner and outer hair cells in the organ of Corti in all turns, whereas the supporting cells remain partially preserved in the upper turns. With increasing survival time, the number of ganglion cells in the spiral ganglion decreases progressively, reaching a minimum of about 10% surviving cells after 12 months. Both type I and type II neurons are subject to retrograde degeneration, although type-II cells degenerate more slowly than type-I cells. The presence or absence of supporting cells in the organ of Corti does not seem to influence neuronal degeneration. This retrograde degeneration is similar in all animals so far studied but its time course is different from different species. Retrograde degeneration after destruction of Corti's organ is a long-lasting process and is never completed at once. This must be taken into consideration in the treatment of total deafness with electric stimulation of surviving neurons.
The serum levels of retinol, RBP (retinol-binding protein) and PALB (prealbumin) were found to be significantly lower in patients with malignant tumors of the head and neck region than in controls. In tumor tissues as well in normal laryngeal mucosa, specific binding sites for retinol and retinoic acid were found. Whereas retinol-binding (CRBP = cellular retinol-binding protein) could only be detected in a few cases, binding for retinoic acid (CRABP = cellular retinoic acid-binding protein) was present in all specimens investigated. The presence or lack of binding sites was not dependent on the actual serum retinol levels. With regard to the antineoplastic role of vitamin A, the reduced serum levels are considered as a possible factor in tumor development and growth. CRBP and CRABP are assumed to be mediating factors for the retinol and retinoic acid action. Since the presence of CRABP is a constant finding, we propose that retinoic acid and its synthetic derivatives with high affinity for CRABP could be appropriate antineoplastic drugs in these tissues.
The levels of retinol, retinol-binding protein (RBP), and prealbumin (PALB) in 53 patients with head and neck squamous cell carcinomas of various size and metastatic nature were significantly lower than in tumor-free individuals and patients suffering from premalignant lesions of the laryngeal mucosa. The levels in tumor patients remained low after tumor resection and postradiation. With regard to the possible antineoplastic role of vitamin A, the reduced plasma retinol levels are considered as a possible supporting factor in tumor development and growth. The cause of the disorder however remains unclear.
Rats were fed a vitamin-A-free diet and the cochleas of these animals were studied under the light and electron microscope. The cochlear function was tested by means of the electrocochleography. No pathologic changes could be found in the organ of Corti; the stria vascularis and the cochleas showed normal development. The recordings of the deficient rats are identical in configuration to controls, but they are shifted to higher intensities due to an otitis media found in the tested animals. These findings suggest that vitamin A does not have an important function in the inner ear.
In some squamous cell carcinomas of the otorhinolaryngologic region with different grades of differentiation, a protein was found that specifically binds vitamin A acid. In 28 of 37 tumors, the retinoic acid-binding sites were found in significant amounts, according to the authors' data. Areas with metastases showed a lower incidence of retinoic acid-binding, whereas in all normal epiglottis and vocal cord tissue specimens the binding was present. The possible significance of the protein-binding for the biologic effect of the vitamin A acid is discussed.
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