Changes In Calcium Metabolism Research Articles

Correlation of kinetics and absorption of 47Ca with estrogen and hormonal ovarian function in postmenopause

The relationship between the metabolism of 47 Ca bone kinetics and intestinal absorption with estrogen and hormonal ovarian function in physiologic and artificial postmenopause has been studied. The augmented exchangeable pool of calcium in bone is related to the duration of postmenopause and estradiol values. The time from menopause/oophorectomy includes all changes occurring in postmenopause, so other undefined factors, besides estrogens, are seemingly indispensable for postmenopausal changes of calcium kinetics. The diminished calcium absorption and augmented exchangeable pool of calcium correlate only with the absence of ovaries and not with estrogen levels in physiologic and artificial postmenopause. It seems that the total hormonal and especially ovarian function in postmenopause cannot be neglected, and although estrogens are important, they are not the sole etiologic factor in postmenopausal changes in calcium metabolism.

Increased calmodulin in cultured skin fibroblasts from patients with cystic fibrosis

We have found that the content of an endogenous calcium-binding protein, calmodulin, is greater in cystic fibrosis fibroblasts than in normal cells. Homogenate preparations from CF fibroblasts contained 2.4 ± 0.2 ng calmodulin/μg protein while normal fibroblasts contained 1.5 ± 0.1 ng calmodulin/μg protein. Cyclic AMP phosphodiesterase activity, however, was the same in cystic fibrosis and normal fibroblasts. The increased calmodulin in cystic fibrosis cells could be involved in the changes in calcium metabolism and cyclic AMP production found in these cells.

Effects of a cation exchange resin on intestinal calcium absorption and urinary calcium in calcium stone formers.

The effect on the urinary excretion of calcium of an oral cation exchange resin without phosphorus was studied in healthy control subjects and patients with recurrent calcium lithiasis under out-patient conditions. An immediate reduction of intestinal calcium absorption and urinary calcium excretion was found in five control subjects and in one patient after ingestion of resin, whereas calcium excretion remained unchanged in all other patients during long-term treatment. In addition, signs of mild transitory hyperparathyroidism together with an increase in intestinal calcium transport were observed during treatment. It is suggested that intraluminal binding of calcium ions to the resin leads to substantial changes in calcium metabolism with the result that urinary calcium excretion returns to pre-treatment values.

Interrelations of calcium-regulating hormones during normal pregnancy.

Profound changes in calcium metabolism occur during pregnancy. The mother has to make available extra calcium for fetal requirements while ensuring that her plasma and bone calcium concentrations are satisfactorily maintained. In a cross-sectional study plasma concentrations of the major calcium-regulating hormones--namely, calcitonin, parathyroid hormone, 25-hydroxyvitamin D (25-OHD), and 1,25-dihydroxyvitamin D (1,25-(OH)2D)--were measured to establish their interrelations during normal pregnancy. The major changes observed were increases in the circulating concentrations of 1,25-(OH)2D and calcitonin. Concentrations of parathyroid hormone and 25-OHD remained within the normal range. The increased concentrations of 1,25-(OH)2D enable the increased physiological need for calcium to be met by enhancing intestinal absorption of this element. The simultaneous rise in calcitonin opposes the bone-resorbing activities of 1,25-(OH)2D, thereby protecting the integrity of the maternal skeleton. Maternal calcium homeostasis is thus maintained yet the requirements of the fetus are fulfilled.

Seasonality of Cardiovascular Disease Mortality and the Possible Protective Effect of Ultra-violet Radiation

Previous studies suggested that cardiovascular disease (CVD) seasonality is due to variations in temperature or respiratory disease prevalence. Another mechanism might be that the seasonal variation in ultra-violet (UV) radiation is responsible for the seasonality of CVD. An hypothesis is put forward that UV radiation, by increasing body levels of vitamin D, protects against CVD by decreasing the risk of thrombus formation. This hypothesis might explain the seasonal variations in CVD mortality and morbidity which decrease in summer, the higher CVD mortality in higher latitudes, and the inverse relationship between altitude and CVD mortality. It is speculated that this mechanism might involve a direct effect of vitamin D on the platelet, or might be mediated by a change in calcium metabolism.

The effect of photoperiod on female reproductive activity and growth of the freshwater pulmonate snailLymnaea stagnaliskept under laboratory breeding conditions

At a Long Day photoperiod (LD = 16 h light, 8 h dark) egg laying of snails kept under laboratory breeding conditions started 2 weeks earlier than in animals kept at Medium Day (MD = 12 h light, 12 h dark) or Short Day (SD = 8 h light, 16 h dark) photoperiods. At the end of the experimental period of 24 weeks the total number of egg masses produced by the LD animals had been 6 and 10 times higher than that of the MD and the SD animals, respectively, while the mean size (number of eggs) of the egg masses of the LD snails was only 30 and 10% larger. The high ovipository activity of the LD animals was reflected in the proportional wet weights of the female accessory sex organs, which tended to be larger. The energy metabolism of the LD animals had been clearly affected as was apparent from the metabolic drain to the female reproductive activity and a change in calcium metabolism, which reflects changes in energy metabolism. Growth of the LD snails, measured as the increase in body wet weight and in shell heig...

Effect of hydrochlorothiazide on 1,25-dihydroxyvitamin D3-induced changes in calcium metabolism in experimental hypoparathyroidism in rats.

1. Chronic administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] can normalize plasma calcium in human hypoparathyroidism and in thyroparathyroidectomized animals. The effect of 1,25(OH)2D3 on plasma calcium is associated with an increase in urinary calcium excretion. In an attempt to prevent this increase thyroparathyroidectomized rats receiving 1,25(OH)2D3 were also treated with hydrochlorothiazide for 9-11 days. 2. Calcium clearance studies show that hydrochlorothiazide stimulated the tubular reabsorption of calcium in thyroparathyroidectomized rats treated with 1,25(OH)2D3. 3. Calcium balance and kinetic studies indicated that hydrochlorothiazide decreased 1,25(OH)2D3-induced hypercalciuria in thyroparathyroidectomized rats. Hydrochlorothiazide did not affect the 1,25(OH)2D3-induced increase in plasma calcium. The hypocalciuric effect of hydrochlorothiazide was not associated with significant changes in calcium deposition into or release from bone. 4. In thyroparathyroidectomized rats treated with 1,25(OH)2D3 the hypocalciuric effect of hydrochlorothiazide was associated with a fall in intestinal calcium absorption. Overall, the calcium balance was unaffected. 5. Thus it appears that hydrochlorothiazide reduces the 1,25(OH)2D3-induced hypercalciuria in parathyroid hormone-deficient animals by decreasing intestinal calcium absorption. Despite the decreased absorption, hydrochlorothiazide does not reduce the 1,25(OH)2D3-induced increase in plasma calcium.

Calcitonin in extrathyroidal tissues of man.

Prior studies have demonstrated detectable immunoreactive calcitonin in the serum and urine of totally thyroidectomized humans, suggesting that the hormone may be secreted by extrathyroidal tissues. Accordingly, a study of the immunoreactive calcitonin content of human tissues was undertaken, utilizing autopsy material from 23 patients. Significant amounts of calcitonin were found in many extrathyroidal tissues, ranging up to 40 ng/g wet weight. The hormone was detectable with two antibodies having different region specificities for calcitonin. Gel filtration and subsequent radioimmunoassay demonstrated that extrathyroidal tissue has calcitonin fractions of the same molecular size and charge characteristics as do the serum and thyroid. The finding of large amounts of extrathyroidal calcitonin may explain why thyroidectomy in man is not accompanied by marked changes in calcium metabolism.

High-dose methaqualone inhibits platelet aggregation

Soon after methaqualone (Quaalude) became popular as a "street" hypnotic drug, it became obvious that serious hemorrhages occurred in many people who used it. Initially some clinicians postulated that this resulted from an increased vascular permeability and drug-induced changes in calcium metabolism. Now a Canadian pharmacologist, Donald G. Mills, PhD, from the University of Western Ontario reports that in toxic doses methaqualone may lead to a defect of platelet function. This may partly explain the bleeding associated with the drug, which increasingly is being used both as a recreational and suicidal agent. In his experiments Mills studied human and rabbit blood platelets. The human platelets were incubated with methaqualone for nine minutes and then mixed with either collagen or adenosine diphosphate (ADP), both of which normally induce aggregation. The rabbits first received injections of methaqualone; blood samples were then drawn 30 and 60 minutes after drug injection. Next, platelet-rich plasma

Kinetic parameters of calcium metabolism and femur morphometry in rats. II. Influence of ovariectomy and dietary calcium.

The purpose of this work was to determine changes in calcium metabolism in the bone of adult rats caused by the deficiency of oestrogen hormones and a moderately low calcium intake.

The effect of theophylline on amine-induced cardiac cyclic AMP and cardiac contractile force

In the isolated electrically driven rat atria, theophylline (5 X 10(-4)M) produced a small but significant increase in cyclic AMP content which was prevented by reserpine pretreatment. Theophylline was also found to exert a direct contractile effect, unrelated to cyclic AMP, in atria obtained from reserpine-pretreated animals. The norepinephrine inotropic response was attenuated after 3 min, enhanced after 15 min, and abolished after 60 min of exposure to theophylline (5 X 10(-4) M). The maximum phenylephrine inotropic response was not significantly changed after 15 min of exposure to theophylline; however, there was a slight shift to the left of the phenylephrine dose-response curve. The effect of theophylline on cyclic AMP appeared to be additive with the norepinephine and phenylephrine responses. The effect of theophylline on amine-induced cardiac cyclic AMP and contractile force showed no correlation between the contractile and the cyclic AMP effects at the different times tested. It is concluded that the inotropic effects of theophylline in rat atria are not mediated through cyclic AMP; instead, the methylxanthines may exert their effects on the heart through changes in calcium metabolism.

A 47calcium kinetic model with two bone compartments

A linear 4-compartment model is proposed for the analysis of 47Ca kinetics. Analysis was made by parameter fitting, using a digital computer. The 47Ca kinetics measured in the calcaneus, used as a bone aliquot, could be integrated in the analysis. It was possible to define and to measure two pools of bone calcium: the pool of rapidly exchangeable calcium and that of the fixed calcium in bone. New parameters were the fixed bone calcium pool and the rate of calcium turnover between rapidly exchangeable bone calcium and soft tissue calcium. This rate of rapid bone calcium exchange is expected to reflect the regulation of the serum calcium concentration and of bone formation. The kinetics determined in a healthy subject agreed in general with the physiology of calcium metabolism. The pathological results in one patient with hyper- and one with pseudohypoparathyroidism correctly illustrated the known changes in calcium metabolism in these diseases. In conclusion, our model of 47Ca kinetics and its analysis by parameter fitting, appear to be valid and applicable for clinical investigation.

The hypercalcaemic syndrome in rats bearing the Walker carcinosarcoma 256.

The strain of Walker carcinosarcoma 256 described induces hypercalcaemia, hyperphosphataemia and hyperuraemia in tumour bearing rats. Changes in calcium and phosphorus excretion are observed as well as accompanying calcification of soft tissue organs and loss of bone calcium. These changes in calcium metabolism disappear after removal of the tumour, so that long-range action of the tumour can be stated. The results are discussed in comparison with three other animal models of tumour dependent hypercalcaemia.

Role of calcium and cyclic adenosine 3',5'-monophosphate in the antilipolytic effect of tolbutamide and glibenclamide.

Tolbutamide (1 mM) and glibenclamide (0.1 mM) reduced lipolysis due to adrenaline, noradrenaline, isoprenaline, glucagon, and ACTH, whereas theophylline-induced glycerol production was only marginally affected. Furthermore, the effect of dibutyryl cyclic AMP on lipolysis was markedly decreased by low concentrations of both drugs. The antilipolytic action of glibenclamide and, to a smaller degree, of tolbutamide was highly dependent on the calcium concentration in the incubation medium used after preparation of fat cells in the absence of calcium. In the presence of isoprenaline as a lipolytic agent the antilipolytic effect of glibenclamide was progressively enhanced by raising the calcium concentration up to 1.2 mM. Howver, further elevation of calcium to 2.4 mM resulted in a loss of antilipolytic effect. Basal cyclic AMP levels of isolated fat cells were increased twofold by glibenclamide or tolbutamide. In contrast to the effect of glibenclamide, cyclic AMP levels in the presence of isoprenaline were further increased by tolbutamide. Low Km cyclic AMP phosphodiesterase of fat cells was inhibited by tolbutamide as well as by glibenclamide. The results indicate that the antilipolytic action of sulfonylurea drugs is closely related to changes in calcium metabolism but independent of cyclic AMP levels.

Pseudogout after parathyroidectomy.

Four cases of acute arthritis developed after parathyroidectomy, and pseudogout was suspected in each patient. All patients demonstrated typical chondrocalcinosis in radiographs of knees and wrists, and acute polyarticular arthritis developed in these affected joints. Intracellular rhomboidal crystals with weakly positive birefringence were characteristic of fluid obtained from the affected joints in two patients. The episode of acute pseudogout in these four cases, three of whom had no previous history of symptomatic joint diseases, indicates a possible relation between the changes in calcium metabolism after parathyroidectomy and the development of acute pseudogout.

Studies of fluoride and calcium metabolism in patients with osteoporosis

Studies of fluoride and calcium metabolism were made under constant metabolic conditions in three patients with osteoporosis during the intake of sodium fluoride. The dose of sodium fluoride ranged from 88 to 100 mg/day, given for two and a half to three months. Fluoride, calcium, phosphorus and nitrogen balances were measured in control studies and during the intake of sodium fluoride. The intake of sodium fluoride resulted in a very high retention of fluoride, the fluoride balances ranging from +11.2 to +17.7 mg/day. The only change in calcium metabolism was a gradual decrease in urinary calcium during the intake of sodium fluoride, whereas the fecal calcium, the intestinal absorption of calcium, the endogenous fecal calcium and the retention of intravenously infused calcium remained unchanged. The changes in phosphorus metabolism corresponded to those in calcium metabolism. Studies of fluoride and calcium metabolism were made under constant metabolic conditions in three patients with osteoporosis during the intake of sodium fluoride. The dose of sodium fluoride ranged from 88 to 100 mg/day, given for two and a half to three months. Fluoride, calcium, phosphorus and nitrogen balances were measured in control studies and during the intake of sodium fluoride. The intake of sodium fluoride resulted in a very high retention of fluoride, the fluoride balances ranging from +11.2 to +17.7 mg/day. The only change in calcium metabolism was a gradual decrease in urinary calcium during the intake of sodium fluoride, whereas the fecal calcium, the intestinal absorption of calcium, the endogenous fecal calcium and the retention of intravenously infused calcium remained unchanged. The changes in phosphorus metabolism corresponded to those in calcium metabolism.

Calcium metabolism in atrial tissue during frequency potentiation and paired stimulation

In order to study whether the application of paired stimuli and also the occurrence of frequency potentiation were accompanied by changes in calcium metabolism, the uptake and release of45Ca and also the total tissue Ca were studied in guinea pig isolated left auricles, subjected to either single or paired stimulation at different basic frequencies.

A Critical Analysis of Calcium Kinetics in Metastatic Cancer

SummaryStudies on the kinetics of calcium metabolism were carried out in 12 women with advanced breast cancer and in 7 patients with miscellaneous metastatic bone cancers. Each subject was injected i.v. with either 45Ca or 47Ca and followed by determining the time-course of the plasma specific activity, the activity excreted in urine and faeces, as well as the stable calcium excreted in urine. The kinetic analysis was based on a mammillary three-compartment model. In five premenopausal oophorectomized women the accretion rate and the daily urinary excretion of calcium were increased. The trend of the dianges indicated both loss of oestrogenic and increase in pituitary activity. Of 7 postmenopausal women, calcium kinetics was normal in five and abnormal in two patients. There was hypophosphataemia, low calciuria and high albeit normal accretion rate in one whereas in the other patient a high plasma phosphate concentration, moderate hypercalciuria and a markedly lowered accretion rate was observed. The remaining 7 patients had rather normal kinetics: the accretion rate was always normal and the daily urinary calcium was sometimes abnormal. The changes of calcium metabolism occurred whether the cancer process was arrested, improved or progressed. The data of this study evidence against the idea that disturbances in the kinetics of calcium are simply a matter of the extent and the activity of bone métastasés and show that they are influenced by the endocrine milieu.

Changes in metabolism of calcium, phosphorus and uric acid after oral administration of chlorothiazide

The effects of chlorothiazide, administered orally in a dose of 500 mg. every 12 hours for a period of 15 days were studied in 9 normal volunteers. Chlorothiazide had negligible effects on urinary flow. The serum concentration of calcium and phosphorus did not change significantly following the oral administration of chlorothiazide. An increase in serum uric acid was observed in all cases. The glomerular filtration rate and the urinary excretion of calcium and uric acid decreased. The plasma lactic acid tended to increase. The interpretation of these results is discussed.

CALCIUM METABOLISM IN STATES OF DEPRESSION.

We have previously demonstrated, in small groups of patients receiving either electric convulsive treatments or imipramine therapy, changes in calcium metabolism associated with recovery from states of depression (5, 7). Other investigators have also reported somewhat unusual changes in calcium physiology among depressed patients or during the administration of antidepressant therapies. These include low cerebrospinal fluid calcium levels (4), changes in blood calcium during electric convulsive treatments (10), and alterations in bound and ionized fractions of blood calcium during imipramine therapy (3). It is the purpose of this report to describe and discuss the changes in urinary calcium excretion in the relatively large series of patients we have now acquired.