Larry J. Ream

The effects of short-term fluoride ingestion on bone formation and resorption in the rat femur

SummaryThe femurs from rats given 120 ppm fluoride in their drinking water for 4 weeks were examined with histological, histochemical, and radiographic methods. Blood removed from the rats prior to sacrifice was analyzed for calcium, phosphorus, and alkaline phosphatase. Results of this study indicated that the ingestion of fluoride produced wide osteoid seams on the periosteal surface of the femoral diaphysis within 4 weeks. The increase in osteoid appeared to be due to an increase in the number of osteoid-producing cells (osteoblasts) along with a subsequent delay in the mineralization of this tissue. The metabolic activity of osteoblasts did not appear to be affected since the intracellular production of acid and alkaline phosphatase was not inhibited. However, due to the high concentration of fluoride ingested, abnormal collagen deposition and a change in bone mineral may have combined to cause a delay in osteoid mineralization. Mineralization was also delayed in the distal femoral epiphyseal plate resulting in an increase in the number of hypertrophied cells. Resorption of metaphyseal trabecular bone, presumably formed prior to fluoride administration, was increased causing a reduction in the amount of trabeculae extending into the shaft of the femur. Concurrent with these changes in bone, the serum levels of calcium, phosphorus, and alkaline phosphatase remained within normal ranges.

A Rapid, Noninvasive Method for Evaluation of Total Menstrual Loss

Three types of packages containing enough sanitary supplies for one menstrual period were weighed and distributed to 100 subjects to determine adequacy of supplies and compliance to protocol. Returned packages were then reweighed to determine total menstrual loss. No subject used all the supplies in her package; therefore, packages contents were deemed ample. 7 subjects added their own purchased products to their packages; since added products were specified by name, weight corrections were easily made. 2 subjects lost unused supplies which were specified, and weight corrections were made accordingly. Evaporative loss from sealed and stored and frequently opened packages was measured. 100 g distilled water were added to contents inside 60 packages which were sealed and set aside 7 days. Average loss from these packages was 0.65 +/- 0.57 g. 5 g water were added to 60 packages 4 times daily for 5 days (100 g total). Then packages were set aside for 2 days and weighed on day 7. Average loss from these packages was 1.25 +/- 0.85 g. The combination of storage plus frequent opening resulted in an average loss of 1.90 +/- 0.87 g. Thus, the direct-weight method permits recovery of 97-98% of sample.

Effect of Small Doses of Aspirin and Acetaminophen on Total Menstrual Loss and Pain of Cramps and Headache

90 women participated in a 4-month study. During the first 2 periods, they took no pain relievers whatsoever; during their last 2 periods they took 2 X 325 mg aspirin, acetaminophen or an identically packaged placebo every 4 h to total 8 tablets during the first 24 h of their periods beginning with spotting. For statistical analysis, periods 1 and 2 were combined and averaged, then compared with periods 3 and 4 combined and averaged. Total menstrual loss in grams, number of days of flow, and pain of cramps and headaches were analyzed by MANOVA for each of the three treatment groups. An ANOVA for each of these variables as well as for daily menstrual loss for the first 3 menstrual days was also performed. The MANOVA for all variables by the three treatment groups failed to show any significant differences. Similarly, ANOVAs for the individual variables failed to indicate significant differences except for the variable pain of cramps (p = 0.0072). The Duncans Multiple Range Test for pain of cramps showed that the average pain for the placebo group was higher than for either the aspirin or the acetaminophen group, although the means for these two groups were not significantly different. These results indicate that neither aspirin nor acetaminophen in the doses given alter either total menstrual loss or the pattern of loss during the first 3 menstrual days. However, both preparations were found to be more effective than placebo in reducing pain of cramps.

Fluoride ingestion during multiple pregnancies and lactations: microscopic observations on bone of the rat

SummaryFemale rats were given 150 ppm fluoride in the drinking water during three successive pregnancy and lactation periods; the femoral diaphyses were then examined for morphological alterations by light and scanning electron microscopy to determine the influence of fluoride ingestion during multiple pregnancies and lactations. The periosteal surface was dominated by areas of woven bone formation with some prolonged resting areas around osteocyte lacunae. The endosteal surface consisted mainly of areas of active bone resorption with some areas of bone formation. The interior of the cortex was characterized by numerous resorption cavities and remodeling in secondary Haversian systems. Fluoride, by the nature of its incorporation into bone crystals and by its direct cytotoxic effect on bone resorbing cells, reduces the availability of calcium from bone. It appears that fluoride ingestion during lactation created a heightened state of calcium homeostatic stress. As a result, bone mineral was mobilized by resorption of the endosteal surface and by cavitation of the interior of the cortex. Secondary hyperparathyroidism is thought to play an integral part in an attempt to maintain calcium homeostasis.

Ultrastructural observations on the mechanism of secretion in the rat parathyroid after fluoride ingestion.

SummaryThe secretory mechanism of the parathyroid glands of fluoride treated rats is evaluated ultrastructurally and compared to that of control rats. The principal difference between the two groups of rats concerns the rate of activity of the chief cells of the gland. In the control animals, these cells are predominantly inactive. In the fluoride-treated rats, they exhibit a more active stage of the secretory cycle. The active chief cells in rats treated with fluoride contain increased numbers of secretory granules. These granules are released into the perivascular spaces within cytoplasmic projections suggesting an apocrine-like mechanism for the secretion of parathyroid hormone. Secretory granules are observed free in the perivascular spaces and within the cytoplasm of capillary endothelial cells in the parathyroid glands.

Do aspirin and acetaminophen affect total menstrual loss

Two commonly taken over-the-counter analgesics, aspirin and acetaminophen, were compared for: effect on total menstrual loss, effect on total days of menstruation, and effect in reduction of pain due to headaches and/or menstrual cramps. Drugs were administered during a 4-month study according to a double-blind format. During the first 2 months, subjects ingested no drugs whatsoever during their menstrual periods. During the second 2 months, subjects ingested aspirin, acetaminophen, or placebo at the rate of two 325-mg tablets every 4 h to total 8 tablets per day during the first 3 days of their menstrual periods. Statistical analysis of the first 2 periods compared to the last 2 showed no differences in total menstrual weights. The number of days of menstruation in the placebo group was significantly lower (p = 0.0137) than in its own control or in the other groups. Neither analgesic showed a significant reduction in pain due to headache or cramps, although acetaminophen appeared to be slightly more effective than aspirin in reducing menstrual cramps.

Glycogen accumulation in the parathyroid gland of the rat after fluoride ingestion

SummaryThe parathyroid glands of young male rats given 150 ppm fluoride in their drinking water for 10 weeks were examined by transmission electron microscopy. As a result of fluoride ingestion, the parathyroid chief cells of the experimental animals accumulated glycogen in excess of that seen in control animals given distilled drinking water for the same time period. In the majority of active chief cells, glycogen granules were diffusely spread throughout the cytoplasm as single granules or in small deposits. Large aggregations of glycogen granules were also seen within intercellular spaces. Accompanying the increase in glycogen was a rise in the number and development of the organelles associated with protein synthesis and secretion. The accumulation of glycogen is similar to that in hyperparathyroidism caused by chronic stimulation and prolonged secretory activity of the parathyroid gland. The results of this study suggest that increased amounts of glycogen occur in hyperactive chief cells of the parathyroid in response to the ingestion of large doses of fluoride.

Bone morphology of weanling rats from dams subjected to fluoride

SummaryFemurs of weanling rats from third-pregnancy litters of dams given 150 ppm fluoride in the drinking water were examined by light- and scanning-electron microscopy. Under the conditions of the experimental procedure, no pathological changes were seen in the femurs as a result of maternal ingestion of fluoride. These results indicate that the amount of fluoride crossing the placenta and mammary gland was insufficient to produce significant morphological changes in the bones of 3-week-old rats.

The Effect of an H1 Blocker, Chlorpheniramine Maleate, on Total Menstrual Loss

50 subjects participated in a 4-month study of the effects of an antihistamine on total menstrual loss. During the first 2 periods, no drugs were given; during the last 2 periods, an antihistamine or a placebo was administered according to a double-blind format. The menstrual weights of the first 2 months were averaged and compared with averages from the last 2 months combined. The treated group showed an average decrease in menstrual loss of 11.30 g compared to a decrease of 0.98 g in the placebo group. While the difference in means was not statistically significant, the variance between the 2 groups was significant (p = 0.0002), indicating that the antihistamine, chlorpheniramine maleate, was effective in reducing menstrual loss in certain individuals, but that the effect was neither uniform nor universal.

Umbilical Vessels of Spontaneously Hypertensive Rats

SummaryUmbilical vessels of spontaneously hypertensive rats, control strain Wistar-Kyoto rats and rats treated with α-methyldopa were compared using the scanning electron microscope and light microscope. Observations with the scanning electron microscope revealed that the venous endothelial cells were relatively flat, giving the luminal surface of the vein a smooth appearance. The nuclear region of the fusiform arterial endothelial cells was responsible for the bumpy appearance of the luminal surface of the artery. Microvilli were a consistent feature of the endothelium in both umbilical vessels. There was no consistant pattern of distribution or density of microvilli within either vessel, but microvilli were more abundant on the luminal surface of the artery than in the vein. The luminal surface of some endothelial cells of the artery had long straight processes which crossed several cells before terminating. Light microscopic observations revealed that the endothelial cells and cells of the tunica intima and media contained an abundance of glycogen. The same layers stained sparsely for acid glycosaminoglycans. Maternal hypertension and treatment of spontaneously hypertensive rats with the antihypertensive drug, α-methyldopa, did not result in significant morphological alterations of either the endothelium or tunica media of the umbilical blood vessels.