FLUORIDE REQUIREMENTS FOR THERAPEUTIC EFFICACY

描述：本提案的目标是建立预防牙釉质和根龋所需的最低氟化物浓度。由于缺乏关于“口腔环境中所需的目标氟化物浓度以优化其防龋潜力”的知识，NIDCR发布了一项计划公告（PA-01-121），指出该主题的高度优先地位。经过60年的社区饮水氟化，我们仍然不知道需要多少氟来预防龋齿。这可能是因为没有人系统地进行体外研究，在密切模拟口腔环境的条件下分离重要因素，然后在口内研究中验证这些发现。这项建议详细说明了这样一个系统的研究，以确定与氟化物预防龋齿的功效有关的重要因素及其相互作用。一个考虑到每个人的条件的预测模型将从体外研究中开发出来，然后通过口内研究进行验证。 在口腔中，氟化物以相对低且相当恒定的浓度（0.1ppm; Carey等人，1986）或来自氟化物漂洗剂、凝胶剂和牙膏，其是瞬时的并且浓度范围可高达15，000 ppm。在目标1中，使用连续流动模型来优化当始终存在稳定的低浓度氟化物时防止釉质龋所需的氟化物量。目标2的重点是在时间加权的基础上确定氟化物的量，当氟化物作为每日两次的丸剂治疗提供时，所述量是预防釉质龋所需的。认识到根牙质是与牙釉质非常不同的基质，目标3和4侧重于确定在恒定暴露（目标3）和周期性高浓度氟化物暴露（目标4）条件下预防根龋所需的氟化物治疗量。目标5将确定当蛋白质或其他选择性渗透大分子吸附在牙釉质或根牙本质表面时预防龋齿所需的氟化物量。在目标6中，将通过使用口内模型来测试用连续流动模型建立的唾液组成、唾液流量和预防龋齿所需的氟化物量之间的关系。在本目标6中，将确定氟暴露对预防龋齿的影响。总之，这些研究应该首次能够证明具有预防作用所需的最低治疗水平的氟化物。此外，该项目开发预测模型的潜力，可用于指示所需的F量作为特定环境的函数是特别重要的，因为该专业将能够适当地调整F制度。这在治疗高危人群时尤为重要。

DESCRIPTION: The goal of this proposal is to establish the minimum concentration of fluoride needed to prevent enamel and root caries. The lack of knowledge about "the target concentration of fluoride required in the oral environment to optimize its potential for caries prevention" has inspired the NIDCR to issue a program announcement (PA-01-121) indicating a high priority status for this subject. After 60 years of community water fluoridation we still do not know how much F is required to prevent caries. This may be because no one has systematically performed in vitro studies that separate the significant factors under conditions that closely mimic those of the oral environment and then validated those findings in intraoral studies. This proposal details such a systematic study to identify the significant factors and their interactions as related to the efficacy of fluoride to prevent caries. A predictive model that takes into account the conditions of each person is to be developed from in vitro studies and then validated through intraoral studies. In the mouth, fluoride originates either from the saliva at a relatively low and fairly constant concentration (0.1 ppm; Carey et al., 1986) or from fluoride rinses, gels, and dentifrices, which is transient and can range in concentration up to 15,000 ppm. In Aim 1 the continuous flow model is used to optimize the amount of fluoride that is needed to prevent enamel caries when there is a steady, low concentration of fluoride at all times. Aim 2 is focused on determining the amount of fluoride on a time-weighted basis that is required to prevent enamel caries when the fluoride is provided as a bolus treatment twice daily. Recognizing that root dentin is a very different substrate than enamel, Aims 3 and 4 are focused on determining the therapeutic amounts of fluoride required to prevent root caries under conditions of constant exposure (Aim 3) and periodic high concentration fluoride exposures (Aim 4). Aim 5 will establish the amount of fluoride required to prevent caries when proteins or other permselective macromolecules are adsorbed on the surfaces of the enamel or root dentin. In Aim 6, the relationships between saliva composition, salivary flow and the amount of fluoride required to prevent caries established with the continuous flow model will be tested by use of an intraoral model. In this Aim 6 the effect of fluoride exposure on the prevention of caries will be determined. Together these studies should, for the first time, be able to demonstrate the minimum therapeutic levels of fluoride necessary to have a prophylactic effect. Additionally, the potential of this project to develop predictive models that can be used to indicate the required amount of F as a function of a specific environment is particularly significant because the profession will be able to tailor F regimes as appropriate. This is particularly important in the treatment of populations that are at higher risk.