Changes In Calcium Metabolism Research Articles

Calcium metabolism and osmoregulation during sexual maturation of river running Atlantic salmon

As Atlantic salmon return from the ocean to undertake the anadromous spawning migration up the river of origin, profound changes in calcium metabolism and osmoregulation take place. Using tartrate resistant acid phosphatase as a marker, scale osteoclast activity was found to increase throughout sexual maturation and spawning migration. Thus, the participation of osteoclasts in the elevated scale resorption observed during this phase is established. As calcium was simultaneously accumulated in the female gonads, it is proposed that the scales are resorbed in order to provide calcium for the growing ovaries. Plasma oestradiol-17β levels were elevated in females during sexual maturation, and had decreased at the time of spawning. Plasma testosterone levels were similar in males and females during the first part of the upriver migration, but had increased in males and decreased in females at spawning. In addition to the role of these sex steroids in the gonadal growth, their possible involvement in the increased scale resorption during this phase is discussed. Plasma growth hormone and thyroxine levels were elevated in both sexes at spawning, with the triiodothyronine/thyroxine (T3/T4) ratio declining sharply, indicating possible roles for these hormones in the maturational process. The relatively low gill Na+, K+-ATPase activity of salmon caught in the estuary implies that the fish had already adapted to a hypoosmotic environment. During the upriver migration, the gill Na+, K+-ATPase activity decreased further, indicating that the hypoosmoregulatory ability was suppressed further during sexual maturation and spawning migration.

Role of calciotrophic hormones in calcium mobilization of lactation

The postpartum period can be a time when profound changes in calcium metabolism and bone mineral density (BMD) occur, particularly in association with lactation. We investigated the hypothesis that calciotrophic hormones [1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, and parathyroid hormone (PTH)] are different by lactation practice or hormone status [PTH-related peptide (PTHrP), estradiol, and prolactin] and have a potential role in the bone loss and recovery associated with lactation. 1,25-Dihydroxyvitamin D, 25-hydroxyvitamin D, PTH, femoral BMD, PTHrP, prolactin, estradiol, and bone turnover markers were measured at 2 wk and at 2, 4, 6, 12, and 18 mo postparturition in 115 postpartum women aged 20-40 y (parity: 0-1). Lumbar spine BMD was measured at 2 wk and at 6, 12, and 18 mo during the postpartum period. PTH, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D concentrations were nonlinear across the 18-mo postpartum period. Between baseline and 18 mo postparturition, PTH and 1,25-dihydroxyvitamin D concentrations did not decline, while there was a substantial decline in 25-hydroxyvitamin D concentrations. PTH, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D concentrations did not differ by lactation practice or by PTHrP, estradiol, or prolactin status. These classic calciotrophic hormones were not associated with concentrations of bone turnover markers or changes in BMD in lactating women. In summary, patterns of change in calciotrophic hormones (PTH, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D) in the 18-mo postpartum period appeared to be independent of PTHrP, estradiol, prolactin, or lactation status and were not associated with bone turnover markers. These data do not support the hypothesis that these three calciotrophic hormones are a central part of the calcium mobilization associated with the bone loss of lactation.

PDGF-Stimulated Calcium Influx Changes During In Vitro Cell Transformation

Platelet Derived Growth Factor (PDGF)-stimulated intracellular calcium signals were obtained from preneoplastic clones derived from C3H 10T1/2 mouse fibroblasts during a four-week transformation assay. By the end of the assay, when transformed colonies of cells were becoming apparent, the PDGF-stimulated calcium signal had reduced significantly. In addition, whole-cell patch-clamp electrophysiology measurements indicated a marked reduction in expression of T-type calcium channels. These observations demonstrate that PDGF-induced calcium metabolism changes as initiated cells progress to the transformed phenotype.

Inhibition by fenamates of calcium influx and proliferation of human lymphocytes.

1. Flufenamic and tolfenamic acids have recently been shown to inhibit receptor-mediated calcium influx in human neutrophils. The present work was designed to study the effects of these two nonsteroidal anti-inflammatory drugs on human peripheral blood lymphocyte activation. 2. Peripheral blood mononuclear cells (PBMNCs; containing 90% lymphocytes) were stimulated by mitogen concanavalin A (Con A) or by a combination of an inhibitor of microsomal Ca(2+)-adenosine triphosphatase thapsigargin (TG) and phorbol myristate acetate (PMA). The effects of the two fenamates on cell proliferation were compared with respective changes in calcium metabolism. 3. Flufenamic and tolfenamic acids (10-100 microM) inhibited both Con A and TG + PMA-induced [3H]-thymidine incorporation in a dose-dependent manner. At the same concentration range, the two fenamates inhibited the increase in intracellular free calcium concentration induced by Con A or TG + PMA. This effect was due to inhibition of calcium influx whereas calcium release from intracellular stores remained unaltered. 4. The inhibition of divalent cation influx was confirmed by showing that fenamates inhibited TG + PMA-induced Mn2+ influx. 5. The inhibitory effects of fenamates on PBMNC proliferation and Ca2+ influx were qualitatively similar with those of SK&F 96365, an earlier known inhibitor of receptor-mediated calcium entry. Ketoprofen, a chemically different prostaglandin synthetase inhibitor did not show similar suppressive effects on PBMNCs. 6. The data suggest that flufenamic and tolfenamic acids suppress proliferation of human peripheral blood lymphocytes by a mechanism which involves inhibition of Ca2+ influx and is not related to inhibition of prostanoid synthesis.

Aging and cardiovascular disease: a summary of the Eighth Münster International Arteriosclerosis Symposium.

This unique symposium focused on the remarkable increase in the older population that is occurring in many countries of the world. The international experts spoke on the effects of aging on cardiovascular disease, which is by far the most prominent cause of morbidity and mortality in the elderly. The program highlighted some of the most prominent changes that occur in the elderly and influence the toll that cardiovascular disease takes. The program was divided into four sessions: (1) the effects of aging on some of the cardiovascular risk factors; (2) the effects of aging on the heart muscle; (3) reports on recent studies of the effects of aging on morphology and function of the conduction system; and (4) a session featuring outstanding authorities on aging and the elastin, collagen, and calcium of the vessel wall, all of which are frequently added to the artery wall during aging. The speakers were carefully selected from top scholars in England, Germany, Finland, France, Italy, Japan, and the United States. Professor W.H. Hauss, who pioneered the development of the Institute for Arteriosclerosis Research at the University of Munster, Germany, and is now in his 80s, opened the symposium and introduced four prominent officials in health, education, and other German government posts, who added their words of welcome. The first session was chaired by Professor G. Assmann, who is the current director of the Arteriosclerosis Research Institute in Munster, Germany. He gave the opening presentation on genetic determinants of life expectancy, a subject on which he is a world authority. He began his presentation with a brief description of the very large PROCAM study of more than 35 000 individuals, two thirds of whom are male, being carried out at the University of Munster Arteriosclerosis Institute in Westphalia. This long-term study of the natural history …

LUNG TUMOURS IMMUNOREACTIVE FOR PARATHYROID HORMONE RELATED PEPTIDE: ANALYSIS OF SERUM CALCIUM LEVELS AND TUMOUR TYPE

Secretion by tumours of parathyroid hormone-related peptide (PTHrP) in quantities sufficient to raise circulating levels results in the syndrome of humoral hypercalcaemia of malignancy (HHM). Since HHM is commonly associated with squamous carcinoma of lung and rarely with adenocarcinoma or lung neuroendocrine tumours, immunopositivity was related to tumour type, to assess whether this difference was due to a low general incidence of PTHrP expression in the latter two groups. Seventy-six of 82 tumours were immunopositive: 22 of 22 squamous carcinomas, 21 of 25 small cell lung carcinomas, 14 of 15 carcinoids, and 19 of 20 adenocarcinomas. These data confirm and extend previous observations on squamous and neuroendocrine tumours but are in contrast with previous findings in adenocarcinoma, which have suggested that only a small proportion of cases express the peptide. They suggest that the differences in incidence of HHM in the various tumour types are due to patterns of secretion, rather than differences in expression of PTHrP. The second aim of this study was therefore to assess whether tumours immunopositive for PTHrP, but not associated with HHM, might secrete PTHrP at levels which might result in more subtle changes in calcium metabolism. Preoperative calcium levels were analysed in a series of 56 patients with immunopositive lung tumours of all types. One small cell carcinoma was associated with hypercalcaemia, but there was no evidence of any other alteration in serum calcium. These data indicate that the majority of tumours expressing PTHrP do not secrete it in amounts sufficient to alter calcium metabolism.

LUNG TUMOURS IMMUNOREACTIVE FOR PARATHYROID HORMONE RELATED PEPTIDE: ANALYSIS OF SERUM CALCIUM LEVELS AND TUMOUR TYPE

Secretion by tumours of parathyroid hormone-related peptide (PTHrP) in quantities sufficient to raise circulating levels results in the syndrome of humoral hypercalcaemia of malignancy (HHM). Since HHM is commonly associated with squamous carcinoma of lung and rarely with adenocarcinoma or lung neuroendocrine tumours, immunopositivity was related to tumour type, to assess whether this difference was due to a low general incidence of PTHrP expression in the latter two groups. Seventy-six of 82 tumours were immunopositive: 22 of 22 squamous carcinomas, 21 of 25 small cell lung carcinomas, 14 of 15 carcinoids, and 19 of 20 adenocarcinomas. These data confirm and extend previous observations on squamous and neuroendocrine tumours but are in contrast with previous findings in adenocarcinoma, which have suggested that only a small proportion of cases express the peptide. They suggest that the differences in incidence of HHM in the various tumour types are due to patterns of secretion, rather than differences in expression of PTHrP. The second aim of this study was therefore to assess whether tumours immunopositive for PTHrP, but not associated with HHM, might secrete PTHrP at levels which might result in more subtle changes in calcium metabolism. Preoperative calcium levels were analysed in a series of 56 patients with immunopositive lung tumours of all types. One small cell carcinoma was associated with hypercalcaemia, but there was no evidence of any other alteration in serum calcium. These data indicate that the majority of tumours expressing PTHrP do not secrete it in amounts sufficient to alter calcium metabolism.

Morpho-densitometry of bone using a trigonometric function

When long bone is considered to be a tube-like structure filled up with a homogenous material, single-directional densitometry of it separately shows cortical and medullary bone mass using a trigonometric function at any given section. Both bone masses can be differentiated from each other using the values of peak bone density and central bone density. This densitometry is based on the two-dimensional structure of long bone. This principle can be universally applied to skeletal disorders including osteoporosis, metabolic bone disorders, and bone tumors in which the mineral content is altered. Dynamic changes in calcium metabolism can be analyzed serially without any invasion at low cost.

Urinary excretion of deoxypyridinolin during treatment with pamidronate in post-menopausal osteoporosis

This longitudinal study evaluated bone turnover and the interrelationship between changes in bone biomarkers and habitual dietary calcium intake during pregnancy in a group of women ranging widely with regard to dietary calcium intake. Thirty-nine healthy pregnant and 30 nonpregnant women were studied. Calcium, phosphorus, 1α,25-dihydroxyvitamin D (1,25diHOD), bone alkaline phosphatase (bALP), carboxyterminal propeptides of type I procollagen (PICP) and carboxyterminal telopeptides of type I collagen (βCTX and ICTP) were measured in serum and calcium, and creatinine and aminoterminal telopeptide (NTX) were determined in urine. Serum calcium and phosphorus did not change but the urinary Ca/Creat ratio and 1,25diHOD increased throughout pregnancy (P < 0.001 and P < 0.0001, respectively). Serum b-ALP and PICP increased during the last two trimesters (P < 0.0001 and P < 0.001, respectively). All studied bone resorption markers increased compared to nonpregnant values throughout pregnancy. The highest increment was observed in the third trimester. The level of significance decreased as follows: βCTX > NTX >ICTP. Serum 1,25 diHOD versus calcium intake showed a positive and significant correlation (r = 0.51, P < 0.02). A negative correlation between the absolute change in βCTX, NTX, and b-ALP between the third and second trimester and calcium intake at the end of pregnancy was observed in pregnant women who did not cover adequately calcium intake requirements (r = −0.47, P < 0.03; r = −0.41, P < 0.05; and r = −0.43, P < 0.05, respectively). These results suggest that skeletal response to pregnancy may not be entirely independent of maternal calcium intake, especially in women with usually low calcium intake. In summary, not only hormonal changes in calcium metabolism that occur during pregnancy but also other considerations, such as low dietary calcium intake, may lead to an increment in the biological activity of the skeleton. Additional studies must be conducted to confirm our findings and to gain a better understanding of skeletal response to a low calcium intake during pregnancy.

Changes in calcium metabolism from late pregnancy to puerperium and vertebral bone mineral density in early puerperium

Changes in calcium metabolism from late pregnancy to puerperium and vertebral bone mineral density in early puerperium

Age-related changes of calcium metabolism and bone density of a novel spontaneously osteoporosis rats

Age-related changes of calcium metabolism and bone density of a novel spontaneously osteoporosis rats

The diagnostic validity of urinary free pyridinolines to identify women at risk of osteoporosis

The urinary excretion of pyridinolines either in the free form or linked to different peptide fragments of type I collagen are intensively studied as new biochemical markers of bone resorption. In the present study we compared the urinary excretion of free pyridinoline (F-Pyr) determined by enzyme-linked immunosorbent assay (ELISA) (Collagen Crosslinks Kit, Metra Biosystems) to pyridinoline (Pyr), and deoxypyridinoline (D-Pyr) determined by high performance liquid chromatography (HPLC) in early postmenopausal women treated with either hormone replacement therapy or placebo and in healthy age-matched premenopausal women. Other markers of bone metabolism were included for comparison. Compared with the premenopausal women, the postmenopausal women had significantly increased values of the biochemical parameters. F-Pyr, Pyr, D-Pyr, and T-Pyr (= Pyr + D-Pyr) decreased during hormone therapy. D-Pyr correlated with the rate of bone loss, whereas this was not the case for F-Pyr. The correlations between the markers yielded r values of 0.71 (F-Pyr vs Pyr), 0.67 (F-Pyr vs D-Pyr), and 0.71 (F-Pyr vs T-Pyr). In conclusion, the present study shows that the newly introduced ELISA for determination of the free pyridinolines is less sensitive than pyridinium crosslinks measured by high performance liquid chromatography (HPLC) in hydrolyzed urine for the changes in calcium metabolism that occur at menopause and during hormone replacement therapy. Whether this limitation will be balanced out by avoiding the inconvenience of the complicated, expensive, and time-consuming HPLC procedure is still being debated.

Diet-related changes in mechanical properties of rat vertebrae.

High fat and sucrose (HFS) diets may induce glucose intolerance, alter calcium metabolism, and lead to deficits in bone mineralization, development, and mechanical properties. To determine the mechanical and structural consequences of a HFS diet on rapidly growing vertebrae, female Sprague-Dawley rats (8 wk) were assigned randomly (2:1) either to a control group (n = 20) fed a low-fat complex-carbohydrate diet or an experimental group (n = 10) fed a HFS diet for 10-12 wk. The sixth lumbar vertebral body (L6) was isolated from the pedicles, morphological measures were taken, and compression was tested at a fast strain rate, while immersed in a warmed (37 degrees C) isotonic physiological buffer solution. No significant difference in body mass existed between HFS and control groups; nevertheless, HFS L6 cross-sectional areas, lengths, and volumes were significantly smaller than controls. The HFS L6 also had significantly lower mechanical properties, including initial maximum load, energy at initial maximum load, and strain energy density at initial maximum load. Diets high in sucrose and fat content have been associated with changes in calcium metabolism, and the results of the current study suggest that in immature vertebrae, a HFS diet may adversely affect vertebral body mechanical integrity and strength.

Lead in bone: implications for toxicology during pregnancy and lactation.

Advances in understanding the distribution and retention of lead in mineralized tissues are important for two reasons: first, bone lead may be a more accurate dosimeter of integrated absorption associated with chronic exposures, and second, bone lead may be a source of internal exposure to the host organism. Little attention has been paid to this second aspect, the remobilization of lead from bone. Mobilization of lead from bone is likely to occur during periods of altered mineral metabolism; since calciotropic factors determine the uptake and storage of lead in this compartment, changes in calcium-related regulatory factors are likely to affect lead compartmentation. Calcium metabolism changes drastically in humans during pregnancy and lactation; although relatively little is known of lead kinetics during these critical periods, it is likely that bone lead is mobilized and transferred to the more bioavailable compartment of the maternal circulation, with potential toxic effects on the fetus and the mother.

Lead in Bone: Implications for Toxicology during Pregnancy and Lactation

Advances in understanding the distribution and retention of lead in mineralized tissues are important for two reasons: first, bone lead may be a more accurate dosimeter of integrated absorption associated with chronic exposures, and second, bone lead may be a source of internal exposure to the host organism. Little attention has been paid to this second aspect, the remobilization of lead from bone. Mobilization of lead from bone is likely to occur during periods of altered mineral metabolism; since calciotropic factors determine the uptake and storage of lead in this compartment, changes in calcium-related regulatory factors are likely to affect lead compartmentation. Calcium metabolism changes drastically in humans during pregnancy and lactation; although relatively little is known of lead kinetics during these critical periods, it is likely that bone lead is mobilized and transferred to the more bioavailable compartment of the maternal circulation, with potential toxic effects on the fetus and the mother.

The tumor necrosis factor receptor and human neutrophil function. Deactivation and cross-deactivation of tumor necrosis factor-induced neutrophil responses by receptor down-regulation.

Despite numerous reports, the role of tumor necrosis factor (TNF) in polymorphonuclear leukocyte (PMN) function remains controversial. We found TNF to be a potent, pertussis toxin-independent stimulator of PMN adhesion (ED50 2.6 pM). TNF-stimulated PMN under adherent conditions released up to 65% of their transcobalamine content (ED50 3.9 pM) and increased their burst activity 10-fold (ED50 3.2 pM) as measured by the hexose monophosphate shunt, whereas PMN held in suspension hardly degranulated at all and only little burst activity was demonstrable. However, preincubation of PMN with TNF in suspension led to a decrease in cellular adhesiveness, degranulation, and burst activity in response to a secondary stimulus of TNF under adherent conditions, although cells remained fully responsive toward phorbol myristate acetate. A concomitant dose-dependent decline of TNF receptor numbers that correlated well with the inhibition of PMN function (r = 0.91) suggests receptor down-regulation as the mechanism of functional PMN deactivation. Remarkably, preincubation with other PMN stimuli such as N-formyl-methionyl-leucyl-phenylalanine, platelet-activating factor, leukotriene B4, complement component fragment 5a (C5a)/C5a (desarginated), and endotoxin also led to a reduction of TNF-specific PMN responses (cross-deactivation) from 35% (LTB4) to 90% (endotoxin), corresponding with the down-regulation of TNF receptors. Deactivation and receptor down-regulation are independent of pertussis toxin-sensitive G proteins and protein kinase C but seemed to depend on changes in calcium metabolism. Granulocyte hyporesponsiveness towards TNF in sepsis (with elevated blood levels of endotoxin and TNF) might be a mechanism of self-protection or, to the contrary, might impair a possibly central mode of host defense.

Proliferation‐associated changes of Ca2+ transport in myeloid leukemic cell lines

Proliferation-associated changes in calcium metabolism were investigated employing the promyelocytic HL-60 and monoblastic U-937 cell lines. The cells were stimulated to proliferate employing mitogenic factors as follows. 1) Transferrin or insulin: HL-60 cells were adjusted for growth in serum-free medium, and 24 h prior to the experiment, the cells were deprived of transferrin or insulin. The re-addition of either one of them stimulated cell proliferation as was evident by increased [3H]-tymidine incorporation activity. Cell proliferation was associated with an enhanced Ca2+ influx rate, measured by 45Ca2+ uptake activity. 2) Granulocyte-monocyte colony-stimulating factor (GM-CSF): addition of GM-CSF to proliferating or quiescent HL-60 cells resulted in increased cell proliferation, which was also accompanied by increased rate of Ca2+ influx. 3) Serum: HL-60 and U-937 were grown for 24 h in serum-depleted medium. Re-addition of serum to the cells was not associated with immediate or delayed change in calcium influx rate but rather with an immediate increase in the cytosolic free calcium concentration, measured employing the fluorescent probe, fura-2AM. This increase was independent of extracellular calcium, unaffected by verapamil, diltiazem, and lanthanum, and associated with enhanced 45Ca2+ efflux. Thus, in all three cases evoked cell proliferation was accompanied by quantitative changes in Ca2+ metabolism. While the transferrin-, insulin-, and GM-CSF-stimulated cell proliferation was accompanied by delayed increases in 45Ca2+ influx, the serum-stimulated cell proliferation was accompanied by an immediate elevation of free cytosolic Ca2+.

Effect of trifluphenazine on Ca-ATPase activity of fibroblasts and Ehrlich's ascites cells

Calcium ions are intracellular mediators of many functionally important processes. Explanation of the specific changes in calcium metabolism in transformed cells and the study of the properties of the proteins and enzymes involved in malignant change of cells are topics for investigation in modern membrane biology of tumor cells. Transport of calcium ions through the plasma membrane is the basic mechanism regulating and maintaining a low concentration of calcium ions in the cell, and is responsible for the normal course of metabolic processes [i, 3]. An important role in the regulation of work in the calciumATPase system for calcium transport through the plasma membrane is played by calmodulin [2]. It was discovered previously that active transport of calcium, coupled with increased Ca-ATPase activity, is observed in tumor cells [4].

Blood pressure and hypothalamic norepinephrine and dopamine in calcium-deficient rats.

The influence of dietary calcium (Ca) on systolic blood pressure (BP) and hypothalamic norepinephrine (NE), dopamine (DA) and DA metabolites dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) concentrations was investigated in male Sprague-Dawley rats raised on diets containing 0.005, 0.17, 1.4, and 2.8% Ca for eight weeks starting at four weeks of age. Blood pressure was significantly higher in the 0.005% Ca and lower in the 2.8% Ca group respectively, compared with the control (1.4% Ca) group. Hypothalamic NE and DA were lower only in the 0.005% Ca group. DOPAC concentration was higher in both Ca-deficient and -excess groups. No change in HVA was observed in any group. Plasma Ca was reduced and parathyroid hormone (PTH) was increased in Ca-deficient groups, but plasma Ca and PTH were increased and decreased, respectively, (nondetectable) in the Ca-excess group. These results suggest that changes in BP due to altered dietary Ca metabolism may be due in part to altered adrenergic system, as well as to dietary-induced changes in calcium metabolism.

The contribution of nutrition to the pathogenesis of osteoporosis

Osteoporosis primarily affects women and is a bone disease of great social, medical and economic importance. The pathogenesis is thought to be of multifactorial origin. The current work discusses nutritional aspects relative to osteoporosis. In this aspect, calcium supply seems to have the largest preventional importance. In contrast, food statistics and individual food records show that calcium intake of females is below the DGE's recommendation of 800 mg/daily. Furthermore, in view of skeletal integrity, calcium intake should be increased up to 1,500 mg/daily after menopause, because of endocrinological changes in calcium metabolism. Therefore, calcium intake on the whole is usually found to not be sufficient. The importance of further nutritional aspects for manifestation of osteoporosis are discussed. In some cases, influences on skeletal integrity are quite evident, whereas the literature has only infrequently drawn conclusions about the pathogenesis of osteoporosis.