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The influence of arrhythmogenic substances on the E.C.G. of rats calcified by high doses of vitamin D2.

Calcification of the aorta and the coronary vessels as well as metastatic calcification of the heart muscle in the rat was produced by daily oral administration of 300,000 i.u. vitamin D2/kg for 6 consecutive days. E.C.G. tracings showed different pathological conditions. The response of the cardiovascular system to certain arrhythmogenic substances, e.g. aconitine and CaCl2 was generally reduced in comparison to non-treated rats.

Aconitine↗

Drug actions in rats with arteriosclerosis induced by toxic doses of vitamin D2.

The vascular response of isolated perfused hind legs from normal and arteriosclerotic rats to noradrenaline, ATP, PGF2 alpha and vasopressin was determined. The increase of perfusion pressure to noradrenaline and ATP was reduced and that to PGF2 alpha and vasopressin was enhanced in arteriosclerotic rats in comparison to normal animals. The results indicate that the reactivity of the vascular smooth muscle of isolated hind legs of arterioslerotic rats is not only quantitatively but also qualitatively different in comparison with normal rats.

Adenosine Triphosphate↗

Freeze-fracture study of the rat parathyroid gland under hypo- and hypercalcemic conditions, with special reference to secretory granules.

Freeze-fracture images of the parenchymal cells in the parathyroid gland of rats were observed after vitamin D2 plus calcium chloride-suppression and EGTA-activation of secretion. In cells of the suppressed glands, large bulges protruded from the Golgi cisternae, and large granules with a stalk, which are identified as storage granules, suggest that, during maturation, some storage granules may be connected by long tubules with the Golgi cisternae and supplied with secretory products from the Golgi cisternae via these tubules. In the activated glands, presumptive exocytotic and endocytotic specializations of intramembranous particles of the parenchymal cell plasma membrane were frequently observed. In addition, elevations and complementary shallow depressions of various shape and extent were occasionally encountered in the intercellular space. From their morphological characteristics it was concluded that these originated from secretory granule cores, which are discharged from the parenchymal cells into the intercellular space by exocytosis, and it was suggested that discharged granule cores may retain their spherical shape until they fuse to form a flat conglomerate.

Animals↗

Electron-microscopic studies on the relationship between the frequency of parathyroid storage granules and serum calcium levels in the rat.

In the rat parathyroid, the mean number of storage granules (NSG) per chief cell has been electron-microscopically studied and correlated with the mean serum calcium level (SCL). In animals given 4% CaCl2 plus vitamin D2 for 3 days. SCL is significantly elevated and NSG is increased. When these animals are injected with 2% EDTA, SCl is lowered to 8 mg/dl, but NSG is not affected; in those injected with 4% EDTA, however, SCL declines to a minimum (5.8 mg/dl) after 30 min, and NSG is also decreased. Control SCL are 8.9 mg/dl. These results indicate that storage granules may not be released until SCL is depressed to a certain level. In rats 3 weeks after castration, the chief cells show hyperplastic changes and SCl is at a low concentration (8.0 mg/dl). NSG, however, remains almost within control limits. Castrated animals injected with 4% EDTA show a hypocalcemia and a decrease in NSG, but NSG gradually recovers over a period of 6 h. These data suggest that storage granules can be produced even under lower calcium concentrations. It is concluded that storage granules may be constantly produced and stored, and are released only as an emergency supply of hormone.

Animals↗

Bone-resorbing activities of 24-epi-1 alpha-hydroxyvitamin D2 and 24-epi-1 alpha,25-dihydroxyvitamin D2.

Bone-resorbing activities of 24-epi-1 alpha-hydroxyvitamin D2 [24-epi-1 alpha(OH)D2], 24-epi-1 alpha,25-dihydroxyvitamin D2 [24-epi-1,25(OH)2D2], and 1 alpha,24S,25-trihydroxyvitamin D2 [1,24S,25(OH)3D2], which might be a metabolite of 24-epi-1,25(OH)2D2, were investigated. In an in vitro bone resorption test, the activity of 24-epi-1 alpha(OH)D2 was similar to that of 1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3] at 10(-9) M-10(-6) M. The activity of 24-epi-1,25(OH)2D2 was weaker than that of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] at 10(-11) M-10(-8) M. On the other hand, the activity of 1,24S,25(OH)3D2 was similar to that of 24-epi-1,25(OH)2D2 at 10(-11) M-10(-9) M. In the formation assay of osteoclast-like cells, the activity of 24-epi-1 alpha(OH)D2 was weaker than that of 1 alpha(OH)D3 at 10(-7) M. The activity of 24-epi-1,25(OH)2D2 was almost similar to that of 1,25(OH)2D3 at 10(-11) M-10(-7) M. The activity of 1,24S,25(OH)3D2 was significantly weaker than that of 24-epi-1,25(OH)2D2 at 10(-11) M-10(-9) M. In the two experiments, the potencies of 24-epi-1,25(OH)2D2 were about 100 times higher than those of 24-epi-1 alpha(OH)D2. In an in vivo/in vitro bone resorption test, the activity of 24-epi-1 alpha(OH)D2 was almost similar to those of 1 alpha(OH)D3 and 1,25(OH)2D3 and higher than those of 24-epi-1,25(OH)2D2 and 1,24S,25(OH)3D2. 24-epi-1 alpha-(OH)D2 and 1 alpha(OH)D3 were longer lasting than 24-epi-1,25(OH)2D2 and 1,25(OH)2D3 in this experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Parathyroid hormone and calcitonin levels in vitamin D deficient rickets.

In six infants aged between 5 and 8 months with vitamin D deficient rickets, we have studied blood levels of calcium (Ca), phosphorus (P), alkaline phosphatase, immunoreactive parathyroid hormone (PTH) and calcitonin (CT), as well as urinary excretion of Ca, P, hydroxyproline and cyclic AMP, both under basal conditions and during a 4h infusion of 20 mg/kg 10% Ca gluconate in normal saline. Under basal conditions all the infants had high alkaline phosphatase (range: 470--770 U.I./1); PTH (range: 620--1200 pg Eq/ml) and CT (range: 440--750 pg/ml) but two infants had hypocalcaemia and four had normocalcaemia and hypophosphataemia. The urinary Ca excretion was low whereas the urinary P, hydroxyproline and cyclic AMP excretions were high. During Ca infusion the total serum Ca and CT levels increased, while alkaline phosphatase and PTH fell. After the end of the infusion, CT levels fell perceptibly; phosphaturia, hydroxyprolinuria and cyclic AMP decreased on the day of the infusion.

Alkaline Phosphatase↗

A comparison of the effects of alfacalcidol treatment and vitamin D2 supplementation on calcium absorption in elderly women with vertebral fractures.

Although vitamin D supplementation in the frail elderly improves calcium absorption, suppresses parathyroid hormone, decreases bone loss and reduces the risk of fractures, such treatment may be ineffective in patients with vertebral osteoporosis, because of impaired vitamin D metabolism or resistance to the action of vitamin D metabolites on the bowel. We have therefore performed a randomized, single masked study comparing the effects of alfacalcidol treatment (0.25 micrograms twice daily) and vitamin D2 supplementation (500-1000 units daily) on calcium absorption and bone turnover in 46 elderly women (median age 69 years, range 64-79 years) with radiological evidence of vertebral fractures. Serum 25-hydroxyvitamin D increased significantly after 3 and 6 months of treatment with vitamin D2 (p < 0.001), but was unchanged in the group receiving alfacalcidol. Serum 1,25-dihydroxyvitamin D did not change significantly in either group over the study period. Fractional 45Ca absorption increased after 3 months of treatment with alfacalcidol (p < 0.05), but was unchanged with vitamin D2. There was also a reduction in plasma intact parathyroid hormone and serum alkaline phosphatase after 6 months of treatment with alfacalcidol (p < 0.05) which was not seen in the group receiving vitamin D2. Our study shows that vitamin D2 supplementation is ineffective in stimulating calcium absorption in elderly women with vertebral osteoporosis. By increasing calcium absorption in such patients, alfacalcidol may prove more effective than vitamin D in the management of vertebral osteoporosis.

Absorption↗

Thoughts about high chlorine peaks in X-ray microanalysis.

In X-ray microanalysis of biological tissues, high Cl-peaks are constantly observable. Higher Cl-peaks in the tissue than in the epon environment suggest that most Cl originates from the tissue. Therefore rough regional estimations of the Cl level could be possible.

Animals↗