Effects of acute fluoride intoxication on rats.
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Biomedical subjects
Publications and source records attributed to L Singer.
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During the treatment of a manic depressive patient, the authors reported some lithium toxicity signs, as lithium carbonate (3 X 300 mg p.d.) and phenylbutazone suppository (3 X 250 mg/p.d.) were associated, this last medication being prescribed for a phlebitis. Lithiemia increased from .70 to 1,44 mEq/l., the lithiemia clearance falling from 10 ml to 5 ml/mn/1.73 m2) and the lithium tubular reabsorption percentage increasing from 85 to 94% (standard rates: 77.4 +/- 1.3%). In a second time, a rat experimentation corroborated these findings: phenylbutazone treatment (100 mg/kg/p.o. for five days) resulted in a lithium tubular reabsorption increase. It seems that the association of lithium carbonate with phenylbutazone should be avoided. The authors point out the risk of prescribing lithium and pyrazolic by-products as phenylbutazone, which are potentially nephrotoxic.
One man and 2 women, aged 67, 63 and 68 years, observed for 8, 6, and 2 years, developed a classical postoperative malignant glaucoma. After a second operation, the use of atropine drops was continued for 2 years in one case, whereas in the other 2 cases miotics and later acetazolamide (Diamox) were necessary in order to maintain normal intraocular pressure. All 3 patients refused a preventive operation in the fellow eye and the use of miotics proved both necessary and effective in maintaining normal intraocular pressure, normal visual acuity, and normal visual fields.
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The effects of fluoride intake on the serum lipids of guinea pigs were determined in animals provided with either high or low levels of fat in their diet and fluoride in their drinking water. Evidence of the difference in fluoride intake were reflected by serum fluoride contents. The results suggest that, in guinea pigs receiving excess dietary cholesterol, an inadequate fluoride intake is reflected in increased serum cholesterol. Fluoride intake also influence the serum triglyceride levels, but the direction of the response was dependent on the amount of dietary fat. Serum free fatty acids and phospholipids were not influenced by fluoride intake.
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To investigate the effect of fluoride on the mobilization of skeletal magnesium and on kidney calcification during magnesium depletion, male Holtzman rats were fed a magnesium-sufficient diet (400 ppm of magnesium) and drinking water containing either 0, 50 or 100 ppm of fluoride for a 20-day period prior to the initiation of magnesium deficiency. The high fluoride regimen resulted in a 100-fold increase in the fluoride content of the skeleton. On day 20 magnesium depletion was initiated by feeding the animals a diet containing 12 ppm of magnesium. Over a 4-week period of magnesium deprivation, a 26% decrease of the total magnesium in the humeri was observed. Fluoride exerted a significant effect in retarding the mobilization of skeletal magnesium. Four weeks of magnesium deficiency was associated with a decreased rate of skeletal mineral accretion and with an increase in the kidney calcium content. The decreased rate of mineral accretion was accentuated by the administration of fluoride during the deficiency state. While fluoride exerted an initial protective effect on calcinosis of the kidneys, the overall effect of the administration of fluoride during magnesium deficiency was to promote calcification of the kidneys rather than to prevent it.
The adjustments in total fluoride concentration in plasma, bones, liver, and muscle were examined when rats were given a diet of very low fluoride content following a dietary regimen of elevated fluoride intake. The animals received a diet containing 34 ppm of fluoride and water with 50 ppm added fluoride in the 28-day initial period and in the depletion period they were given a diet containing only 0.21 ppm of fluoride and distilled water. The findings indicated a 12-fold increase in the fluoride content of the humeri after 28 days of high-flurodie intake with a greater increment by the epiphyses than by the diaphyses. During 21 days of the depletion period the skeletal fluoride was reduced by only 7.7% indicating a marked retention of fluoride during processes of bone remodeling and growth. The plasma, muscle, and liver total fluoride contents were significantly increased at the end of the period of high-fluoride intake, but these concentrations were found to be restored to base-line levels in 3-7 days of the depletion period. By comparison of the distribution of total fluoride with injected radiofluoride between tissue and plasma waters, it was concluded that muscle and liver contain bound fluoride that does not exchange completely with ionic fluoride.
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Thromboembolic complications secondary to psychiatric therapy are known but relatively rare. Four pulmonary embolisms happening in a few months' time in our services have lead us to reconsider the incidence of psychotropes on thrombogenesis, and more particularly on the aggregability of blood-platelets. We have found hyperaggregability curves for a significant number of cases in patients undergoing treatment in comparison with reference patients undergoing no treatment. We have tried to explain the difference in the results of works concerning the aggregability of blood-platelets and psychotropes by problems of dosage and of level of action of these medications and of their metabolites, the effects often oposite for a limit dose, the danger of extrapolating in vivo the results found in vitro, finally the complexity and numerous unknown elements in the working of aggregation of blood-platelets.
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The effect of magnesium deficiency on phosphatase activity and bone composition was determined in the femora of young rats. In the right distal metaphysis the acid and alkaline phosphatase activities were decreased in magnesium-deficient rats, and the activity of bone alkaline phosphatase in the incubation mixture after adding magnesium was significantly greater in the magnesium-deficient than in the control rats. In the left distal metaphysis the water content was significantly lower in the magnesium-deficient rats at the fifth week but not at the third week. Conversely, the ash content of metaphyseal bone was significantly increased in magnesium-deficient rats at the fifth week, but not at the third week. The magnesium and phosphorus contents were abnormally low in the deficient bone at both periods. The calcium content was increased in the deficient bone at the third week, but not at the fifth week.
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