Lennart Krook

Calcium homeostasis and bone pathology in magnesium deficient rats.

SummaryCalcium homeostasis and bone pathology were studied in weanling rats fed a low (70 ppm) magnesium diet for 2–21 days. The rats developed significant, progressive hypercalcemia after 6 days on the diet. The increase in blood calcium was accompanied by progressive hypoactivity of the parathyroid gland (PTG), as determined by histologic and morphometric analyses. Thus hyperactivity of the PTG could not have been responsible for the hypercalcemia observed.Histologic examination of femora and humeri from magnesium-deficient rats showed progressive subperiosteal hyperplasia, consisting of undifferentiated osteoprogenitor cells and fibrous tissue, after 7 days of deficiency. The presence of unmineralized osteoid tissue in the metaphyses indicated that mineralization was not proceeding normally. The alterations in differentiation of osteoprogenitor cells, together with the failure of mineralization, resulted in significantly lower rates of bone formation (as measured by fluorochrome labeling) in the magnesium-deficient rats. Basophilic cementing lines and inactive osteocytes in the cortices of bones from magnesium-deficient rats indicated that bone resorption was also severely reduced in magnesium deficiency. We postulate that bone magnesium depletion (66% by day 21) has a direct negative effect on osteoblastic and osteocytic activity, and may explain, in part, the decreased responsiveness of bone to parathyroid hormone (PTH) that has been observed in magnesium-deficient animals.

Ultimobranchial Tumor of the Thyroid and Pheochromocytoma in the Bull

An ultimobranchial tumor of the thyroid and a phcochromocytoma occurred in a bull. The thyroid tumor contained amyloid. The occurrence of ultimobranchial tumor of the thyroid and phcochromocytoma was established in a large series of bovine necropsies and the co-existance of these tumors in the bull was highly significant; neither occurred in the cow.

The Effects of Phenylbutazone on the Morphology and Prostaglandin Concentrations of the Pyloric Mucosa of the Equine Stomach

Phenylbutazone, a nonsteroidal anti-inflammatory drug known to produce gastric ulcers, was administered intravenously (13.46 mg/kg body weight) daily to 12 horses. Horses were euthanatized daily after 24,48,72, and 96 hours following the initial injection. Eight untreated horses served as controls. Small multifocal pyloric erosions were seen after 24 hours and then progressed in severity over time. The erosions were characterized by sloughing of the surface epithelium, subepithelial bleb formation, necrosis of the lamina propria, degeneration of the walls of subsurface capillaries, and microthrombosis of the capillaries of the pyloric mucosa. Large numbers of neutrophils with abundant fibrin and cellular debris were present at the erosion sites. Eroded pyloric mucosa and adjacent macroscopically intact mucosa were examined ultrastructurally. In both the mac-roscopically eroded mucosa and multifocally in the adjacent macroscopically uneroded mucosa, there was cellular swelling of the endothelium, pericytes, and smooth muscle cells of arterioles. In capillaries and post-capillary venules, the endothelium ranged from swollen to lysed and necrotic. Extensive extravasation of erythrocytes and edema were seen. These lesions were not seen in the control horses. Phenylbutazone produces a microvascular injury that is associated with the formation of pyloric erosions in horses. The pyloric mucosa of six horses was assayed for prostacyclin and prostaglandin E2 at 48 and 96 hours following the initial injection. There was no statistically significant difference between prostaglandin concentrations in the mucosa of control and treated horses. It was concluded that there was little correlation between pyloric mucosal prostaglandin concentrations and pyloric erosions after 48 hours.

Humeral skeletal development and plasma constituent changes in fetuses of ewes maintained on a low calcium diet from 60 days of gestation.

SummaryThe objective of this study was to evaluate the effects of a long-term, low-calcium diet on fetal calcium metabolism and fetal skeleton skeleton development in ewes. Eleven pregnant sheep were assigned to two groups, fed either a diet low in calcium (0.26% total dry matter) or normal in calcium (0.8% total dry matter) for 2 months, starting at 60 days gestational age. The ewes fed the low calcium diet showed lower plasma levels of calcium and higher plasma levels of hydroxyproline, parathyroid hormone, and 1,25 (OH)2D compared with the ewes fed the normal calcium diet. There were no differences in these variables between the two groups of fetuses. These observations suggest that the plasma components of calcium homeostasis measured in the fetal lamb in the present study are independent of the ewe and are not significantly affected by the presence of lowere maternal calcium for many weeks during pregnancy. Despite the ability of the fetus of the ewe on the low calcium diet to maintain relatively normal circulating plasma components of calcium homeostasis, long-term maternal hypocalcemia delayed fetal skeletal ossification as shown by histological examination of the fetal humerus. The fetal humerus from low calcium-fed ewes showed a lower proportion of bone versus cartilage (45.6±5.9 versus 57.4±4.6%, mean ±SD) lower ash content (15.4±1.5 versus 17.4±1.0%), and lower specific gravity (1.19±0.2 versus 1.22±0.02) (P<0.05) than the humerus from fetuses of normal calcium-fed ewes. This study shows that the long-term calcium intake of the ewe does affect fetal skeletal development, despite a lack of observable effects on fetal plasma concentrations of calcium or known calcium regulating hormones such as 1,25(OH)2D or parathyroid hormone.

Osteochondrosis in fetuses of ewes overfed calcium.

SummaryEwes were fedad libitum (up to maximum of 2.5 kg/day) a complete feed containing either 1.52% calcium (High Ca) or 0.59% calcium (Normal Ca) on a dry matter basis from day 50 of pregnancy, and the fetuses were removed at 133–135 days. Thyroid C cells, identified by indirect immunofluorescence, were more numerous (P<0.001) and plasma levels of 24,25-dihydroxycholecalciferol [24,25(OH)2D] were higher (P<0.09) in fetuses of High Ca ewes. These fetuses also had retarded cartilage differentiation in the proximal humeral epiphysis and metaphysis as well as transverse trabeculation in the epiphysis. These entities are two of the hallmarks of osteochondrosis. It was shown that feeding high dietary calcium to pregnant ewes caused osteochondrosis in their fetuses. Hypercalcitoninism and/or an adverse effect of supraphysiological levels of 24,25-dihydroxycholecalciferol may have been contributory to the skeletal abnormalities.

Nutritional secondary hyperparathyroidism in the animal kingdom: report of two cases

This report describes two cases of marked bone loss (osteopenia) occurring in a 9-week-old German shepherd puppy and in a 6-month-old tiger. In both cases the animals were fed a diet which was exclusively boneless meat. The diets in both cases contained approximately 40 mg of calcium and 1000 mg of phosphorus per pound resulting in both calcium deficiency and phosphorus excess, resulting in a phosphorus-to-calcium ratio of 25:1, well beyond the amounts known to cause marked loss of bone experimentally. This has been termed nutritional secondary hyperparathyroidism (NSH). Both animals presented with severe bone pain, difficulty in ambulation, and difficulty in chewing food. Radiographs showed marked osteopenia and spontaneous fractures. Both responded clinically and radiographically to calcium supplementation and a diet with an appropriate phosphorus-to-calcium ratio. The importance of calcium and phosphorus in the human diet is briefly discussed.

Effect of calcium depletion and subsequent repletion on parathyroids, parafollicular (C) cells and bone in the growing pig

SummaryThe ultrastructure of the chief cells of the parathyroid gland and thyroid parafollicular (C) cells and the morphology of bone in calcium depletion and subsequent repletion were examined in young growing pigs. A low calcium diet resulted in osteopenia, increased removal of the cartilaginous core, osteoclasia and osteocytic osteolysis. Subsequent repletion quickly returned bone to normal. In pigs fed the low calcium diet, there was a marked depletion of secretory granules but a striking increase in the number of microtubules in chief cells. Increasing the calcium content of the diet to normal quickly returned the ultrastructural appearance of chief cells to apparent normal. In the initial response to calcium repletion, chief cells exhibited large number of lysosomes and occasionally prominent paracrystalloid bodies. Electron microscopic examination of parafollicular (C) cells of the thyroid gland failed to reveal differences in ultrastructure between test and control pigs. These findings support the view that bone resorption following calcium deficiency may be the result of a secondary hyperparathyroidism rather than of calcium deficiency per se.

Nutritional Hepatic Necrosis in Beef Cattle “Sawdust Liver”:

A histologic examination of spontaneous cases of sawdust livers in cattle indicated that the focal liver necrosis was an expression of vitamin E-selenium deficiency. The condition was reproduced in Hereford steers by feeding a diet rich in polyunsaturated fatty acids and poor in protein, vitamin E. and selenium. Lesions also occurred in the kidney, heart, skeletal muscled and pylorus. Addition of dictary protein or injection of selenium partially prevented the condition. Cellular anoxia with formation of hyalinc bodies in the liver and kidney was considered to be the common denominator of the degenerative changes. Due to the relatively mild tissue changes, plasma GOT and OCT determinations were found to be of no diagnostic value.

Milk production of cows exposed to industrial fluoride pollution

Milk sales records for a dairy herd showed that milk production did not decrease during the first 4 yr of exposure of cows to fluoride pollution from an aluminum plant. During the next 3 yr milk production decreased, but not significantly. From yr 8 of exposure there was a significant decrease, which persisted through yr 19, when the dairy operation was terminated. From yr 15 through yr 19, the milk yield averaged less than 60% of the expected value.

Fluoride in the bone and diet of fin whales, Balaenoptera physalus

Abstract Bone samples were taken from fin whales Balaenoptera physalus from the North Atlantic to examine the relationship between fluoride concentration in skeletal tissue and age, sex, body length and anatomic location. By the use of an ion-selective electrode, the fluoride concentration in these samples were found to be higher than that normally occurring in any mammalian species, ranging from 4340 to 18 570 ppm. The positive correlation observed with age, along with high fluoride concentrations found in krill taken from the stomachs of these whales, indicated a probable bioaccumulation of fluoride from dietary sources. These results confirmed and extended earlier findings that bone tissue in fin whales naturally contains very high concentrations of fluoride and indicate that this baleen whale is tolerant to a significant extent of the high fluoride concentrations found in krill.