MECHANISMS OF TISSUE DESTRUCTION IN CHOLESTEATOMA

这个项目的目标是了解 中耳胆脂瘤侵蚀骨骼，损害内耳。这个 长期目标是开发控制组织的药理学方法 由于胆脂瘤造成的损伤，从而避免了消融手术。 首先，对骨吸收的机制进行研究。骨吸收 在胆脂瘤中主要是由于多核细胞的作用 破骨细胞但单核细胞也可能侵蚀骨骼。沙土鼠的骨头 将用Ca45或(H3)四环素预先标记；在80天， 会诱发胆脂瘤。当这些动物的骨头被杀死时 再吸收就会发生。未脱钙的组织切片将 放射自显影。活跃于骨吸收的细胞将被标记； 每种细胞类型对骨破坏的相对贡献将是 从标记的细胞数量推断。在他们牺牲之前，这些 标记的动物将被监测尿液中Ca45或H3的排泄情况。一个 排出的同位素增加可能是体内骨骼的准确反映 再吸收。人类和沙土鼠破骨细胞对骨的作用 胆脂瘤的吸收也将被移除并置于短期内。 文化。细胞质的活性和扩散将用 视频短片摄影。前列腺素对血管紧张素转换酶的影响 这些破骨细胞的细胞质活性将与 相同物质对生理性破骨细胞的作用。此外， 胆脂瘤中各种前列腺素的存在将用 (C14)花生四烯酸代谢物的放射层析。 因为初步研究表明，长着中耳的沙鼠 胆脂瘤有明显的毛细胞丢失，我们将评估耳蜗毛 患有胆脂瘤和不患有胆脂瘤的沙土鼠在年龄上的细胞丢失相匹配。这个 将使用空气和骨传导听性脑干来评估耳蜗 毛细胞的反应、扫描电子显微镜和传输 毛细胞和血管纹的电子显微镜。

The objective of this project is to understand the mechanisms by which middle ear cholesteatoma erodes bone and damages the inner ear. The long-term goal is to develop pharmacological methods to control tissue damage due to cholesteatoma, thereby avoiding ablative surgery. First, the mechanism of bone resorption will be studied. Bone resorption in cholesteatoma is primarily due to the action of multinucleated osteoclasts but mononuclear cells may also erode bone. The bone of gerbils will be pre-labeled with Ca45 or (H3)tetracycline; at 80 days, cholesteatomas will be induced. The animals will be killed when bone resorption occurs. Undecalcified tissue sections will be autoradiographed. Cells actively resorbing bone will be labeled; the relative contribution of each cell type to bone destruction will be inferred from the number of cells labeled. Prior to their sacrifice, these labeled animals will be monitored for urinary excretion of Ca45 or H3. An increase in excreted isotope may be an accurate in vivo reflection of bone resorption. The human and gerbilline osteoclasts responsible for bone resorption in cholesteatoma will also be removed and placed into short-term cultures. The cytoplasmic activity and spreading will be assessed using video lapse photography. The effects of prostaglandins upon the cytoplasmic activity of these osteoclasts will be compared to the effects of the same substances upon physiological osteoclasts. Additionally, the presence of various prostaglandins in cholesteatoma will be measured using radiochromatography of (C14) arachidonic acid metabolites. Since preliminary studies have shown that gerbils with middle ear cholesteatomas have marked hair cell loss, we will evaluate cochlear hair cell loss in age matched gerbils with and without cholesteatomas. The cochlea will be evaluated using air and bone conducted auditory brainstem responses, scanning electron microscopy of hair cells and transmission electron microscopy of hair cells and the stria vascularis.