GROWTH FACTORS IN DRUG INDUCED GINGIVAL OVERGROWTH

三组药物可导致牙龈过度生长。它们是：(1) 苯妥英(PHT)，一种抗惊厥药物；(2)环孢素(CS)， 免疫抑制剂；和(3)硝苯地平(普罗卡地平)和相关的钙 用于治疗心血管疾病的通道阻滞剂。 对于较大的牙周组织来说，牙龈过度生长既会毁容，也会导致功能障碍 所有年龄段的患者数量。这一数字可能还会增加。 因为没有药物可以取代PHT和CS的使用 硝苯地平正在增加。这给美国带来了一个严重的问题 在那里这三种药物都被广泛使用。只有PHT和CS将成为 在拟议的试点研究中进行了调查。 这项研究提案的目标是为 对某些药物，如苯妥英钠和安非他明 CS可引起牙龈过度生长。工作假说是 这些药物刺激牙龈结缔组织的某些细胞 合成和分泌过量的通常使用的生长因子 用于修复牙床磨损和伤口。假设将是 通过以下具体目标进行测试： 1.测定正常人血清三种生长因子水平 牙周炎； 2.确定这三种生长因子的水平是否 在PHT和CS诱导的牙龈过度生长中升高；以及 3.确定PHT和CS是否刺激血管紧张素原的合成和分泌 这三种生长因子在人结缔组织细胞中的表达 细胞培养的受控环境。 待研究的生长因子有：血小板衍生生长因子， 转化生长因子β1和白介素1β。研究方法： 分析将包括：(1)RNA逆转录聚合酶链 反应分析法定量测定药物中各生长因子的mRNA 暴露在培养中的细胞、正常牙龈和牙龈过度生长的细胞；以及 (2)药物暴露细胞分泌生长因子的放射免疫测定 在培养中，正常牙龈和药物诱导的牙龈过度生长。数据 这项初步研究将为今后的研究提供基础 这种与药物有关的现象涉及的细胞机制。

Three groups of drugs induce gingival overgrowth. They are: (1) phenytoin (PHT), an anticonvulsant; (2) cyclosporin (CS), an immunosuppressant; and (3) nifedipine (Procardia R) and related calcium channel blockers used for the treatment of cardiovascular disorders. Gingival overgrowth is both disfiguring and dysfunctional for a large number of patients of all age groups. The number is likely to increase because no drug is foreseen to replace PHT and the use of CS and nifedipine is increasing. This presents a significant problem in the US where all three of these drugs are widely used. Only PHT and CS will be investigated in the proposed pilot study. The goal of this research proposal is to provide a foundation for investigations into the mechanisms whereby certain drugs, such as PHT and CS induce excessive growth of the gingiva. The working hypothesis is that these drugs stimulate certain cells of the gingival connective tissue to synthesize and secrete excessive amounts of growth factors normally used in the repair of gingival attrition and wounds. The hypothesis will be tested by the following specific aims: 1. To determine the levels of three growth factors in normal human gingiva; 2. To determine whether or not the levels of these three growth factors are elevated in PHT and CS-induced gingival overgrowth; and 3. To determine if PHT and CS stimulate the synthesis and secretion of these three growth factors by human connective tissue cells in the controlled environment of cell culture. The growth factors to be studied are: platelet-derived growth factor, transforming growth factor beta1 and interleukin-1beta. The methods of analysis will include: (1) RNA reverse transcription-polymerase chain reaction analysis to quantify the mRNA for each growth factor in drug- exposed cells in culture, normal gingiva and in gingiva overgrowth; and (2) radioimmunoassay of the secreted growth factors by drug-exposed cells in culture, normal gingiva and drug-induced gingival overgrowth. Data derived from this pilot study will provide a basis for future studies on the cellular mechanisms involved in this drug-related phenomenon.