Project: Research project

Project Details


The long-term objective of this grant is to increase our understanding of
the fundamental features of fluoride metabolism with special emphasis on
the impact of acid-base status on the overall process. During the first
six years of grant-related work, it has been learned that urine pH is a
major determinant of the rate of fluoride removal from the body. Changes
in this variable are reflected in the amount of fluoride retained in the
plasma, soft tissues, bones and teeth. It is now evident that the
distribution of fluoride between the extracellular and intracellular fluids
of some tissues is a function of the magnitude of the transcellular pH
gradient. These findings have contributed to our understanding of the
cariostatic effect of fluoride and have suggested new ways to alter the
amount of fluoride in the body generally or in selected tissues. The
studies proposed for the next three years will expand on these findings.
The influnce of the acidity of solutions contained in the stomach on the
rate of fluoride absorption, peak plasma levels, the time course of plasma
fluoride levels, and on tissue fluoride concentrations and fluoride balance
will be determined. The effects of the rate of gastric acid secretion on
these variables will also be determined in both acute and chronic studies.
Studies on the possibility of "active" fluoride transport by the intestine
will be done using the everted sac technique. The possible involvement of
plasma fluoride levels in the regulation of fluoride absorption from the GI
tract, as claimed in the literature, will be tested. In an effort to
better understand the damaging effects of high fluoride levels on the
gastric mucosa, the ability of gastric mucosal cells to accumulate fluoride
will be determined. In addition, further studies on the mechanism of
fluoride distribution between plasma and red blood cells will be done using
imposed PH gradients and specific inhibitors of the red cell anion
transport system. The influence of the acid-base status of the gravid
animal on the fluoride levels of neonatal tissues will be determined.
Finally, the interplay between the renal and extrarenal clearances of
fluoride will be evaluated in terms of the age of the animal and the dosage
schedule suing pharmacokinetic techniques.
Effective start/end date7/1/823/31/95


  • Medicine(all)
  • Dentistry(all)