EPITHELIAL PERMEABILITY; THE EFFECTS OF AGE AND ALCOHOL

口腔粘膜为口腔提供了保护性衬里， 微生物、毒素和抗原的进入。 此功能 通过表面细胞间渗透屏障进行， 主要是脂质，限制了水溶性物质的渗透。 口腔的不同区域表现出不同的渗透性。 这 与某些口腔疾病的发生频率有关，包括 癌前病变和恶性病变，其病因可能涉及 渗透的物质，如酒精和烟草成分从 粘膜表面。 这些病变中的许多在老年人中更常见， 这就提出了屏障功能如何随年龄变化的问题。 的 拟议中的研究将检查障碍的假定起源 角化和非角化中的膜包衣颗粒组分 口腔上皮 然后，它将检查组成和功能， 通过脂质分析和渗透性测量确定，在不同的 来自不同年龄个体的人口腔粘膜区域。 最后， 它将研究长期摄入酒精对脂质的影响， 烟草致癌物的含量、组成和渗透性 （亚硝基去甲烟碱）的作用。 使用方法以 将使用的方法包括组织分离、脂质提取、薄层层析、 色谱分析、结构表征和渗透性 体外测量。 将从猪和人中获得组织 尸体解剖 将使用大鼠作为动物模型。 这是第一个试图描述 口腔上皮屏障，并检查年龄对 人体组织中屏障的结构和功能。 它还将努力 对酒精和烟草之间已知协同作用的解释 口腔癌的病因。 这些研究很重要，因为 渗透性屏障在各种疾病病因学中的可能作用 口腔粘膜病变和由于增加的易感性， 老年人对这种疾病。 对所提问题的回答将有助于 治疗，并可能导致预防策略。

The oral mucosa provides a protective lining for the oral cavity, limiting the entry of microorganisms, and toxins and antigens. This function is carried out by a superficial intercellular permeability barrier, composed largely of lipid, that limits penetration of water soluble substances. Different regions of the oral cavity show different permeabilities. This has been associated with the frequency of certain oral disease, including premalignant and malignant lesions, the etiology of which may involve the penetration of substances such as alcohol and tobacco components from the mucosal surface. Many of these lesions are more common in the elderly, which raises the question of how barrier function changes with age. The proposed research will examine the putative origin of the barrier components from membrane-coating granules in keratinized and nonkeratinized oral epithelia. It will then examine composition and function, as determined by lipid analysis and permeability measurements, in different regions of human oral mucosa from individuals of different ages. Finally, it will examine the effects of chronic alcohol ingestion on the lipid content, composition and permeability to a tobacco carcinogen (nitrosonornicotine) of oral mucosa in an animal model. The techniques to be used will include tissue fractionation, lipid extraction, thin layer chromatographic analysis and structural characterization and permeability measurements in vitro. Tissues will be obtained from pig and from human autopsies. Rats will be used as an animal model. This represents the first study to attempt to characterize the origin of the barrier in oral epithelium and to examine the effects of age on the structure and function of the barrier in human tissue. It will also seek explanations for the known synergy between alcohol and tobacco in the etiology of oral cancer. Such studies are important in view of the possible role of the permeability barrier in the etiology of a variety of oral mucosal lesions and because of the increased susceptibility of the elderly to such lesions. Answers to the questions posed will facilitate therapy and may lead to preventive strategies.