RESUMEN
HYPOTHESIS: In this study we tested the effect of local administration of D-methionine, sodium thiosulfate, brain-derived neurotrophic factor, and fibroblast growth factor-2 on cisplatin ototoxicity in guinea pigs to the round window membrane. BACKGROUND: Cisplatin is an important antineoplastic agent in the therapy of many malignancies. Its clinical utility is limited by severe side effects, including ototoxicity. Recent studies have shown protection against cisplatin ototoxicity in animal experiments by the systemic administration of D-methionine and sodium thiosulfate. Growth factors such as brain-derived neurotrophic factor and fibroblast growth factor-2 also have shown otoprotective effects in in vitro studies. METHODS: Osmotic pumps (Alzet) were implanted unilaterally in 30 guinea pigs. Five groups of six animals received either D-methionine, sodium thiosulfate, fibroblast growth factor-2, brain-derived neurotrophic factor, or saline 0.9%. Cisplatin was administered intraperitoneally for 5 consecutive days. Distortion product otoacoustic emissions were recorded every day. The animals were killed on day 6, and their cochleae were removed and analyzed by transmission electron microscopy. RESULTS: Compared with control animals, guinea pigs treated with D-methionine showed better otoacoustic emissions on days 3 and 4 (Mann-Whitney test, p < 0.05). The differences were not evident on days 5 and 6. Sodium thiosulfate, brain-derived neurotrophic factor, and fibroblast growth factor-2 showed no significant protective effect. CONCLUSION: Local application to the round window membrane can be used as an effective treatment in the prevention of cisplatin toxicity. Local application may avoid systemic side effects and reduce the antineoplastic effects of cisplatin.
Asunto(s)
Antineoplásicos/efectos adversos , Factor Neurotrófico Derivado del Encéfalo/administración & dosificación , Cisplatino/efectos adversos , Factor 2 de Crecimiento de Fibroblastos/administración & dosificación , Pérdida Auditiva Sensorineural/prevención & control , Metionina/administración & dosificación , Tiosulfatos/administración & dosificación , Administración Tópica , Animales , Femenino , Cobayas , Pérdida Auditiva Sensorineural/inducido químicamente , Bombas de Infusión , Emisiones Otoacústicas Espontáneas , Análisis de Regresión , Ventana RedondaRESUMEN
In order to find correlations between skin gland morphology and specific ethological features, the cutaneous glands of the foot pads of the primitive mammal the Madagascan tenrec, Echinops telfairi, were studied by histological and various histochemical methods as well as by electron microscopy. In the foot pads specific eccrine skin glands occurred consisting of coiled ducts and tubular secretory portions, the lumina of which were considerably wider than in primate sweat glands. The secretory tubules were composed of branched myoepithelial cells and glandular cells. The latter contained abundant mitochondria, large amounts of glycogen particles and few secretory granules as well as individual heterolysosomes and myelin bodies. The lateral cell membrane was marked by extensive interdigitations. The apical membranes of all glandular cells contained proteoglycans with sulfated and carboxylated groups containing N-acetyl-glucosamine, N-acetyl-galactosamine, galactose and mannose. The expression pattern of cytokeratins of the glandular epithelium was variable and showed similarities to that of the human eccrine glands. Tubulin, vinculin and actin were expressed in the glandular epithelium. The secretory cells showed positive reactions with antibodies against antimicrobial peptides and IgA. A positive reaction was observed with antibodies against the androgen receptor. The PCNA and TUNEL reactions indicated that the tubular skin glands of Echinops are made up of a slowly renewing tissue. We conclude that the glands fulfill several functions: production of a fluid-rich secretory product, which may prevent slipping of the foot pads on the substrate during running or climbing, secretion of antimicrobial peptides and proteins, and playing a role in thermoregulation.
Asunto(s)
Glándulas Ecrinas , Eulipotyphla/anatomía & histología , Animales , Proteínas del Citoesqueleto/análisis , Proteínas del Citoesqueleto/metabolismo , Glándulas Ecrinas/citología , Glándulas Ecrinas/metabolismo , Glándulas Ecrinas/ultraestructura , Pie/anatomía & histología , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Lectinas , Muramidasa/análisis , Muramidasa/metabolismo , Antígeno Nuclear de Célula en Proliferación/análisis , Receptores de Esteroides/análisis , Receptores de Esteroides/metabolismoRESUMEN
The human mammary gland undergoes a sequence of histological changes in both epithelial and stromal compartments during the menstrual cycle. Swelling and unswelling of the breast stromal tissue is a characteristic feature of the two phases of the cycle and is mediated by changes in the water content of sulfated proteoglycans in the matrix between the fibrils. In an ultrastructural study we investigated the distribution of sulfated proteoglycans identified as cupromeronic blue-positive needle-like structures and measured the distance between the dermatan sulfate-proteoglycan attachment sites at the d-bands of the collagen fibrils in the loose intralobular connective tissue and in the dense interlobular connective tissue. We characterized the dermatan sulfate proteoglycan by enzyme digestion and by immunogold-labeled antibody. In the follicular phase a relatively constant distance of 46 nm between neighboring proteoglycan attachment sites was found, while in the luteal phase the measured distances are strikingly variable and exceed the follicular value by up to 9 nm. This difference of the two cycle phases is more evident in the loose than in the dense connective tissue. Possibly the changes of the fibril-attached proteoglycans in the luteal phase reflect an influence of the higher water content of the matrix leading to a probably torsional swelling of the collagen fibril.