Project: Research project

Project Details


The long-term objective of this project is to increase our understanding of
the fundamental features of the metabolism and biologic effects of fluoride
with special emphasis on the influence of acid-base status. During the
first 12 years of this project, it has been learned that urinary pH is a
major determinant of the rate of fluoride removal from the body. The
distribution of fluoride between the major fluid compartments of the body
has been found to be a function of the magnitude and direction of
transmembrane pH gradients. Other studies have clarified the mechanism of
fluoride absorption from the GI tract, provided evidence against the
concept of fluoride homeostasis and new insights into the effect of growth
and development on the pharmacokinetics of fluoride. The proposed studies
for the next grant period deal with several aspects of fluoride metabolism
and disturbances in amelogenesis. It has been found that hypobaric hypoxia
(simulated high altitude) increases the retention of fluoride and that it
causes disturbances in enamel mineralization that resemble fluorosis. The
physiologic basis of these effects will be studied with emphasis on renal
function, the metabolism of calcium, phosphorus and fluoride and the
characteristics of calcified tissues. The hypothesis that the
mineralization defects caused by hypobaric hypoxia and fluoride share the
same basic mechanism will undergo initial testing. It has also been
learned that acidosis produced by chronic ammonium chloride administration
is associated with defects in enamel mineralization. It is not clear
whether the defects are caused by acidosis per se or by elevated levels of
ammonium ion. Experiments are proposed to identify the etiologic factor.
Several aspects of the metabolism and toxicity of MFP will be studied and
compared to those of sodium fluoride. This and toxicity of MFP will be
studied and compared to those of sodium fluoride. This research is timely
and of clinical importance because of the increasingly widespread use of
MFP in dentistry and medicine. Finally, the use of a novel lucite chamber
will permit highly controlled studies of the effects of sodium fluoride or
MFP on the structure and function of the gastric mucosa, a target organ for
the adverse effects of fluoride. The cytoprotectant PGE2 and the inhibitor
of prostaglandin synthesis, indomethacin, will be used in these studies to
more fully understand the underlying mechanism and possibly suggest new
approaches to prevent or reduce the unwanted side effects.
StatusNot started


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