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In a program of studies of disuse osteoporosis, fluoride balances were determined in healthy men during ambulation and then during bed rest for 6 to 17 wk. Control subjects ingested basal diets containing 0.4 mg fluoride per day, whereas experimental subjects received 10-mg fluoride supplements in divided doses with meals. Fluoride and calcium were measured in diets, urine, and feces. Serum analyses included calcium and ionic fluoride. Fluoride balances during both phases were uniformly negative in control subjects (mean -0.46 mg/day) but uniformly positive in supplement subjects (mean +2.58 mg/day). Calcium balances were markedly negative during bed rest in both groups. Serum fluoride concentrations increased proportionally to fluoride intake, averaging 0.016 ppm in the controls and 0.045 ppm in the supplement subjects. The supplement of 10 mg fluoride daily did not protect against bed rest-induced calcium loss, or cause any clinical or laboratory abnormality in any subject.

Anion channels have been found in the plasma membrane of the outer and inner segment of the isolated retinal rod by means of the patch voltage-clamp technique. The permeability of the channels for different anions follows a sequence: Cl- greater than F- greater than NO3- greater than propionate; the channel conductance in the fully open state is 200 +/- 30 pS measured in 108 mM NaCl. The non-linear character of the current-voltage relationship at membrane potentials from -40 to -20 mV suggests that these anion channels may be involved in receptor potential generation through an electrogenic mechanism.

The mixing efficiency for two gases of different gaseous diffusivity, helium (He) and sulphur hexafluoride (SF6) have been studied in anaesthetised dogs, closed and open chested, with and without the heart beating. Equilibration of He and SF6 was studied during rebreathing at frequency of 0.5 Hz and a tidal volume of either 0.3 or 0.5 L. Circulation and gas exchange were taken over by a complete heart and lung bypass circuit during the periods when the heart was stopped. The number of breaths required to reach 99% equilibration (n99) ranged from 4 to 14 for He and from 6 to 17 for SF6. There was no significant change in mixing efficiency in any situation. Stopping the heart increased the n99 for He by only 0.4 +/- 11% (1 SD) (n = 21). Opening the chest increased n99 by 1.4 +/- 13% with the heart beating and 2.5 +/- 19% with the heart stopped. The n99 for SF6 was 30 +/- 22% higher than that for He with the chest closed with or without the heart beating. This increased to 37% with the chest opened but was not altered by stopping the heart. The findings for the final phase equilibration rate constant were similar. We conclude that the beating action of the heart does not affect gas mixing in the lungs in the tidal breathing range.

The parallel effects of the anion transport inhibitor DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonate) on net chloride flow and on chloride exchange suggest that a major portion of net chloride flow takes place through the anion exchange system. The "slippage" model postulates that the rate of net anion flow is determined by the movement of the unloaded anion transport site across the membrane. Both the halide selectivity of net anion flow and the dependence of net chloride flux on chloride concentration over the range of 75 to 300 mM are inconsistent with the slippage model. Models in which the divalent form of the anion exchange carrier or water pores mediate net anion flow are also inconsistent with the data. The observations that net chloride flux increases with chloride concentration and that the DIDS-sensitive component tends to saturate suggest a model in which net anion flow involves "transit" of anions through the diffusion barriers in series with the transport site, without any change in transport site conformation such as normally occurs during the anion exchange process. This model is successful in predicting that the anion exchange inhibitor NAP-taurine, which binds to the modifier site and inhibits the conformational change, has less effect on net chloride flow than on chloride exchange.

A model relating caries to surface enamel fluoride and plaque has been derived by exploratory data analyses. Since the model was obtained a posteriori, it is best viewed in qualitative terms as a hypothesis for future testing. The model prompts a re-evaluation of expectations relative to the effects of surface enamel apatitic fluoride, and a consideration that the effectiveness of a given measure of fluoride may vary as a function of inherent challenge. Thus, further studies are needed, aimed at quantifying the parameters of resistance and challenge, and characterizing the relationship between them.

Universal water fluoridation will have a positive impact on the oral health of the nation. The ultimate goal is to have every individual's teeth last a lifetime. Fluoridation of community water supplies provides the best cost containment public health measure known for improving the dental health of the nation's citizens.

This section of the meeting has been devoted to enamel crystal chemistry and its behavior during formation and demineralization. In dealing with calcified tissues of any type we are looking at a crystalline formation with the most diverse range of properties which one could choose for its purpose. The size, shape, and intercrystalline binding give mechanical strength, cutting ability, and flexibility where necessary.

This study examined the role of cyclic AMP in the phosphaturic response to parathyroid hormone in vitamin D-deficient rats. Infusion of purified bovine parathyroid hormone (13.3 mug/h) into control, D-fed, or D-deficient, thyroparathyroidectomized rats produced a sixfold increase in renal phosphate and cyclic AMP excretion in D-fed rats, but only a two- to threefold increase in both parameters in D-deficient animals. Intravenous injection of parathyroid hormone over the dosage range from 1-50 mug/kg resulted in a dose-dependent increase in phosphate and cyclic AMP excretion with both D-fed and D-deficient thyroparathyroidectomized rats. However, the D-deficient rats responded to these injections of parathyroid hormone with a two- to threefold increase in both renal phosphate and cyclic AMP excretion at the highest dose of 50 mug/kg, whereas the D-fed animals' response was 35-fold and 11-fold over control excretion levels of phosphate and cyclic AMP, respectively. To directly examine the role of the renal cortical adenylate cyclase system in the blunted phosphaturic and urinary cyclic AMP responses to parathyroid hormone in D-deficient rats, we prepared a plasma membrane fraction enriched in this enzyme activity from the renal cortex of D-fed and D-deficient thyroparathyroidectomized rats. The renal cortical adenylate cyclase of D-deficient rats showed significantly (P less than 0.001) less activation by parathyroid hormone over the hormone concentration range from 0.3 to 7.0 mug/ml than was observed with the enzyme prepared from D-fed animals. Basal adenylate cyclase activity and the fluoride-stimulated enzyme activity were not altered by the state of D-deficiency. These experiments demonstrate that the blunted phosphaturic response to parathyroid hormone observed in D-deficient rats is associated with the reduced responsiveness of the renal cortical adenylate cyclase to the hormone. Moreover, the defect in the renal membrane adenylate cyclase system appears to be localized at the level of PTH binding to membrane receptors or, alternatively, at the level of transmission of the hormone-receptor binding signal to the catalytic moiety of this membrane enzyme.

Certain hormones regulate the activity of their target cells by stimulating adenyl cyclase, which is an enzyme located within the target cell's plasma membrane. Adenyl cyclase catalyzes the formation of cyclic AMP, which is released into the cell and modulates cell functions. In this communication the characteristics of adenyl cyclase are reviewed. The coupling between hormone receptors and this enzyme is discussed as is the ability of agents such as hormones, ATP, magnesium, calcium, guanine nucleotides and prostaglandins to alter cyclase activity. Several diseases that result from derangements of the adenyl cyclase system are known and the molecular bases for these diseases are discussed in this review.