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Dysregulated calcium homeostasis is common in chronic kidney disease and causally associated with disorders of bone mineralization. However, radiological measures and biomarkers do not allow accurate evaluation of bone calcium balance. Non-radioactive calcium isotopes, 42Ca and 44Ca, are present in our diet and sequestered into body compartments following principles of kinetic isotope fractionation. Isotopically light 42Ca is preferentially incorporated into bone, while heavier 44Ca is excreted. The ratio (44/42Caserum) increases when bone formation exceeds resorption and vice versa, reflecting bone calcium balance. We measured these calcium isotopes by inductively coupled plasma mass-spectrometry in blood, urine and feces of 42 children with chronic kidney disease and 92 receiving dialysis therapy. We compared the isotope ratios with bone biomarkers and determined total bone mineral content by dual-energy x-ray absorptiometry and peripheral quantitative CT expressed as age-adjusted z-scores. The 44/42Caserum ratio positively correlated with serum calcium, 25-hydroxyvitamin D and alkaline phosphatases and inversely with serum parathyroid hormone and other bone resorption markers. The 44/42Caserum ratio positively correlated with age-adjusted z-scores of tibial trabecular bone mineral density and total bone mineral content measured by peripheral quantitative CT, and hip bone mineral density measured by dual-energy X-ray absorptiometry. Significant and independent predictors of total bone mineral content, measured by, were the 44/42Caserum ratio and parathyroid hormone. The 44/42Caserum ratio, repeated after four weeks, highly correlated with baseline values. When adjusted for calcium-containing medications and kidney impairment, the 44/42Caserum ratio in patients receiving dialysis was 157% lower than that of age-matched children and 29% lower than levels in elderly women with osteoporosis, implying significantly lower bone mineral content. Thus, calcium isotope ratios may provide a novel, sensitive and non-invasive method of assessing bone calcium balance in chronic kidney disease.

The effect of the dialysate calcium concentration (D[Ca]) on mineral and bone metabolism in patients on peritoneal dialysis (PD) is overlooked. D[Ca] of 1.75 mmol/L is still prescribed to many patients on PD around the world. Previous studies on the effects of reducing D[Ca] have been carried out before the incorporation of calcimimetics in clinical practice. We hypothesized that a reduction in D[Ca] is safe and without the risk of a rise in serum parathyroid hormone (PTH).In this non-randomized clinical trial, the D[Ca] was reduced from 1.75 mmol/L to 1.25 mmol/L for one year in prevalent patients on PD. Demographic, clinical, and CKD-MBD-related biomarkers were evaluated at baseline, 3, 6, and 12 months of follow-up.20 patients completed 1-year follow-up (56 ± 16 years, 50 % male, 25 % diabetic, 55 % with baseline parathyroid hormone - PTH300 pg/mL). Over time, there was no significant change in calcium, phosphate, total alkaline phosphatase, 25(OH)-vitamin D or PTH, although adjustments in calcitriol and sevelamer prescription were required. After 1 year, absolute and percentual change in PTH levels were 36 (-58, 139) pg/mL, and 20 % (-28, 45) respectively. The proportion of patients with PTH 300 pg/mL did not change during the follow-up (p = 0.173).Knowing the risk of a positive calcium balance in patients on PD, reducing the D[Ca] concentration is a safe and valuable option, although medication adjustments are needed to detain PTH rising.

Calcium supplements for prevention and treatment of mineral and bone disorders in chronic kidney disease (CKD) have been alternately praised and damned. Clinical evidence in favor of either attitude has been lacking. The calcium balance study by Spiegel and Brady in patients with late stage 3 and stage 4 CKD suggests that CKD subjects ingesting 2000mg of elemental calcium per day are in marked positive balance. Methodological limitations such as unproven steady state warrant caution and confirmatory studies.

Calcium is an important nutrient but also contributes to the texture, taste and functionality of most dairy products. The balance between micellar and free calcium in curd and serum phase during direct acidification of bovine milk was studied by changing organic acid type, pH and acidification temperature. Concentration of free calcium increased with decreasing pH and increasing temperature. Citric acid was more efficient than lactic acid at lowering free calcium concentration, while temperature effect was larger for acidification with lactic acid. These findings are rationalized by the stronger binding of calcium to citrate compared to lactate with an almost athermal binding for citrate and an endothermal binding for lactate. Curd yield decreased by decreasing pH as solubilization of colloidal calcium phosphate causes loss of minerals into the serum phase decreasing the concentration of both calcium and phosphate left in the curd, while acidification temperature had little effect on curd yield. These results are important to improve yield and tailor the properties and functionality of dairy products, such as for example Mozzarella cheese.

Calcium balance in chronic kidney disease is poorly understood as calcium deficiency is a stimulus for secondary hyperparathyroidism and consequent bone loss while calcium excess promotes extraosseous calcifications. To help resolve this, we evaluated calcium balance in normal individuals and in patients with chronic kidney disease (CKD) on daily diets containing 800 and 2000 mg elemental calcium. Both normal individuals and patients with late stage 3 and stage 4 CKD were in slightly negative to neutral calcium balance on the 800-mg calcium diet. Normal individuals were in modest positive calcium balance on the 2000-mg diet, while patients with CKD on the same diet were in marked positive calcium balance at least over the 9 days of study; and significantly greater than the normal individuals. Increased calcium intake significantly decreased 1,25-dihydroxy-vitamin D and intact parathyroid hormone levels but did not alter the serum calcium concentration. Thus, our findings have important implications for both preventing calcium deficiency and loading in individuals with late stage 3 and stage 4 CKD.

Few calcium balance data are available from young children on which to base dietary recommendations.The objective of the study was to evaluate the relation between calcium intake and balance in healthy children aged 1-4 y consuming typical American diets.Subjects were assigned to a diet with nutrient intakes similar to those of their usual diet. Calcium absorption was assessed by using a dual-tracer stable-isotope technique. Endogenous fecal excretion was measured in a subset of children, and net calcium balance was calculated.Mean calcium intake was 551 mg/d (range: 124-983 mg/d), and mean (+/-SEM) calcium retention was 161 +/- 17 mg/d. Both linear and nonlinear modeling of balance data showed that a calcium intake of approximately 470 mg/d led to calcium retention of 140 mg/d, which is the amount that meets expected bone growth needs in children of this age. No evidence was found that calcium intakes of 800 to 900 mg/d reached the threshold intake beyond which no additional increase in calcium retention would occur.Bone growth needs in 1-4-y-old children following American diets are met by a daily calcium intake of approximately 470 mg/d, which suggests that the current Adequate Intake of 500 mg/d is close to the actual Estimated Average Requirement. The benefits and risks of higher calcium intakes consistent with threshold values should be evaluated in a controlled trial before those intakes could be used as a basis for dietary recommendations.

Vitamin K2 (menatetrenone) has been used for the treatment of osteoporosis in Japan. We investigated the effects of ovariectomy (OVX) and vitamin K2 on the calcium (Ca) balance in 20-week-old female Fischer rats. Vitamin K2 (31 mg/kg per day) was given to animals as a dietary supplement. At weeks 4 and 8 after OVX, a Ca balance study was performed for 5 days. The intestinal Ca transport was determined using the everted gut-sac technique at week 9. The Ca balance was poorer in the OVX-control group than in the sham-control group at weeks 4 and 8 after OVX. The Ca balance improved significantly in the vitamin K2 groups as compared with the sham- and OVX-control groups. The intestinal Ca transport decreased due to OVX and was higher in the vitamin K2 administration groups than in the sham- and OVX-control groups, but not to a significant extent. The bone mineral density in the femoral metaphysis as well as the cortical area and cortical thickness in the femoral diaphysis in the OVX-control group were lower than in the sham-control group. The administration of vitamin K2 significantly inhibited an OVX-induced decrease in cortical area and cortical thickness in the femur. These findings suggest that the poor Ca balance observed in ovariectomized rats may be improved by vitamin K2; vitamin K2 may be involved in preventing bone loss in vivo.

Calcium signaling has been implicated in plant graviperception. In order to investigate the role of intracellular calcium in the process, I used lithium ions (LiCl), which suppress inositol 1,4,5-trisphosphate (IP 3 ) cycling and signaling by inhibiting inositol-1-phosphatase. After 4 h of gravistimulation, no curvature was observed in 81% of the roots of 5-day Pisum sativum seedlings pretreated with 5 mM LiCl. Structural features of statocyte ultrastructure in these roots were the following: loss of a cellular polarity, appearance of amyloplast clusters, condensed mitochondria, local dilations in a perinuclear space, increases in a relative volume of vacuoles. The intensity of a cytochemical reaction (pyroantimonate staining which detected Ca 2+ ions) was moderate: the Ca 2+ pyroantimonate deposits were observed in all organelles. There were few granules of this precipitate in a hyaloplasm of the statocytes. Mitochondria and vacuoles were found to contain more granules of the precipitate compared with the controls. Additionally, Ca 2+ -ATPase activity in the statocytes of pea roots pretreated with LiCl was approximately the same as in control roots. Data obtained by using inhibitor of inositol signaling suggest that the observed effects of LiCl on root gravicurvature and ultrastructure of root statocytes were due to effects on Ca 2+ homeostasis, particularly on IP 3 -mediated release of intracellular Ca 2+ which can be inhibited by inositol depletion. The work demonstrates the key role played by second messengers (Ca 2+ and IP 3 ) in a gravity perception and response.

BENNION and Warren (1933) and Warren and Schnepel (1940) reported that shell thickness is reduced markedly if hens are subjected to high environmental temperatures. Their experiments further suggested that the depressing effect of high temperature is accentuated by high humidity. The mechanism or mechanisms which cause poor shell quality at high air temperatures are still not definitely established. Conrad (1939) found that blood calcium levels were reduced at high environmental temperatures. From this evidence Warren and Schnepel (1940) concluded that: “The decrease in shell thickness when the birds are subjected to high temperatures is probably due to a reduction in calcium content of the blood.” Warren and Schnepel (1940) also reported that hens kept at 95°F. consumed about 26% less feed than hens kept at 60°F. It is possible that this reduction of feed intake is at least partially responsible for the poor shell quality at high air temperatures. Finally, …

Dietary calcium and serum 1,25-(OH) 2 -vitamin D concentrations as determinants of calcium balance in healthy men. We previously reported that experimental elevations of serum 1,25-(OH) 2 -vitamin D [1,25-(OH) 2 -D] concentrations produced by the chronic oral administration of calcitriol, 0.75 µg every 6 hr, to healthy human males eating diets providing only 4 mmoles Ca/day stimulate net bone resorption as evidenced by more negative Ca balances and higher rates of urinary hydroxyproline excretion. To determine whether increased dietary Ca intake modifies this response we have compared serum 1,25-(OH) 2 -D and iPTH concentrations, Ca and PO 4 balances, and urinary hydroxyproline excretion in three healthy human males adapted to diets providing 22.3 ± 1.3 mmoles Ca/day and three healthy human males adapted to diets providing 9.3 ± 0.7 mmoles Ca/day before and during the continuous oral administration of calcitriol 0,5 µg every 6hr. For all six subjects, serum 1,25-(OH) 2 -D levels averaged 89 ± 25 pM during control and 143 ± 26 pM during calcitriol. Net intestinal Ca absorption and urinary Ca excretion rose during calcitriol but Ca balances did not change, averaging +2.2 ± 2.2 mmoles/day during control and +4.3 ± 2,2 mmoles/day during calcitriol for the subjects fed 22 mmoles Ca/day and - 1.6 ± 1.5 mmoles Ca/day during control and - 1.7 ± 2.0 mmoles Ca/day during calcitriol for the subjects fed 9 mmoles Ca/day. Urinary hydroxyproline excretion also did not change. Thus, when serum 1,25-(OH) 2 -D levels are elevated, the availability of dietary Ca appears to prevent more negative Ca balances and increased urinary hydroxyproline excretion suggesting that net bone resorption is not stimulated. Le calcium alimentaire et les concentrations seriques de 1,25-(OH) 2 -vitamine D determinants de la balance calcique chez des hommes sains. Nous avons prealablement rapporte que des elevations experimentales des concentrations seriques de 1,25-(OH) 2 -D par administration chronique orale de calcitriol, 0,75 µg toutes les 6 heures a des hommes sains ingerant des regimes n'apportant que 4 mmoles Ca/jour stimulent la resorption osseuse nette, ce qui est mis en evidence par des balances Ca plus negatives et par des debits d'excretion urinaire d'hydroxyproline plus eleves. Afin de determiner si une augmentation de l'apport en Ca alimentaire modifie cette reponse, nous avons compare les concentrations seriques de 1,25-(OH) 2 -D et d'iPTH, les balances Ca et PO 4 et l'excretion urinaire d'hydroxyproline chez trois hommes sains adaptes a des regimes apportant 22,3 ± 1,3 mmoles Ca/jour et chez trois hommes sains adaptes a des regimes apportant 9,3 ± 0,7 mmoles Ca/jour avant et pendant l'administration orale continue de calcitriol, 0,5 µg toutes les 6 heures. Pour les six sujets, les niveaux seriques de 1,25-(OH) 2 -D etaient en moyenne de 89 ± 25 pM pendant le controle et de 143 ± 26 pM pendant le calcitriol. L'absorption intestinale nette de Ca et l'excretion urinaire de Ca se sont elevees pendant le calcitriol, mais les balances Ca n'ont pas change, etant en moyenne de +2,2 ± 2,2 mmoles/jour pendant le controle et de 4,3 ± 2,2 mmoles/jour pendant le calcitriol chez les sujets ingerant 22 mmoles Ca/jour et de - 1,6 ± 1,5 mmoles Ca/jour pendant le controle et de 1,7 ± 2,0 mmoles Ca/jour pendant le calcitriol chez les sujets ingerant 9 mmoles Ca/jour. L'hydroxyproline urinaire aussi ne s'est pas modifiee. Ainsi, lorsque les niveaux seriques de 1,25-(OH) 2 -D sont eleves, la disponibilite du calcium alimentaire parait prevenir des balances Ca plus negatives et une excretion urinaire d'hydroxyproline elevee, suggerant que la resorption osseuse nette n'est pas stimulee.

Young adult male and laying female quail, fed with a diet containing 2.64% Ca and 0.70% P, were used to study nutritive utilization, corporal calcium retention and endogenous excretion, calcemia, laying and properties of the egg (including the shell structure), mineralization of the femur bone, as well as the influence of diethylstilbestrol upon these parameters. The coefficient of nutritive utilization (C.N.U.) in the female was high and logically superior to that of the male, while the corporal retention was quite similar for both sexes. Most of the Ca absorbed (81.8%) and not excreted in urine, went to the egg and only 18.2% remained in the body. The diethylstilbestrol caused a big reduction of the C.N.U. in the female, but not in the male, parallel to an inhibition of laying, and an increase of corporal retention of used calcium. In both sexes the calcemia surprisingly increased, and the calcium level of the femur bone was higher, and even though the cortical osseous zone was slightly wider, the effect of treatment was noticeable, particularly in the medular tissue, which incremented in the female and appeared in the male. When quail were fed a calcium-restricted diet, the endogenous excretion of this mineral was small in the case of the female and significantly smaller in the male. This situation suppressed egg laying and resulted in a clearly decreased bone mineralization. The ingestion of diethylstilbestrol before feeding a diet poor in calcium provoked an increase of the endogenous excretion of calcium in both female and male quail.

Myocardial function is tuned by dynamic changes in length and load via mechano-calcium feedback. This regulation may be significantly affected by heart rhythm. We evaluated the mechano-induced modulation of contractility and Ca-transient (CaT) in the rat myocardium subjected to twitch-by-twitch shortening–re-lengthening (↓–↑) trains of different lengths (N = 1 … 720 cycles) at low (1 Hz) and near-physiological (3.5 Hz) pacing rates. Force/CaT characteristics were evaluated in the first post-train isometric twitch (immediate effect) and during slow changes (delayed maximal elevation/decrease) and compared with those of the pre-train twitch. The immediate inotropic effect was positive for N = 30 … 720 and negative for N = 1 … 20, while the delayed effect was always positive. The immediate and delayed inotropic effects were significantly higher at 3.5-Hz vs 1-Hz (P < 0.05). The prominent inotropism was accompanied by much smaller changes in the CaT diastolic level/amplitude. The shortening–re-lengthening train induced oscillations of the slow change in force at 3.5-Hz (always) and at 1-Hz (∼50% of muscles), which were dependent of the train length and independent of the pacing rate. We suggest that twitch-by-twitch shortening–re-lengthening of cardiac muscle decreases Ca2+ buffering by troponin C and elevates Ca2+ loading of the sarcoplasmic reticulum (SR); the latter cumulatively depends on the train length. A high pacing rate intensifies the cumulative transient shift in the SR Ca2+ loading, augmenting the post-train inotropic response and prolonging its recovery to the pre-train level. The pacing-dependent mechano-induced inotropic effects remain to be elucidated in the myocardium with impaired Ca handling. © 2020 Elsevier Ltd The study was supported by RFBR grant # 18-04-00572 and by RF Government Act #211 of March 16, 2013 (agreement 02.A03.21.0006 ), and was carried out within the framework of the IIF UrB RAS theme No АААА-А18-118020590031-8 .

To achieve adequate dietary calcium intake, several choices are available that accommodate a variety of lifestyles and tastes. Liberal consumption of dairy products in the diet is the approach of most Americans. Some plants provide absorbable calcium, but the quantity of vegetables required to reach sufficient calcium intake make an exclusively plant-based diet impractical for most individuals unless fortified foods or supplements are included. Also, dietary constituents that decrease calcium retention, such as salt, protein, and caffeine, can be high in the vegetarian diet. Although it is possible to obtain calcium balance from a plant-based diet in a Western lifestyle, it may be more convenient to achieve calcium balance by increasing calcium consumption than by limiting other dietary factors.

An experiment was conducted to evaluate the potential dietary interaction between 1,4-diaminobutane (putrescine) and calcium on eggshell quality and overall laying performance. One hundred ninety-two 30-wk-old White Leghorn hens were fed a corn-and soybean-meal-based diet supplemented with 0.00, 0.05, 0.10, or 0.15% putrescine and 2.5, 3.0, 3.5, or 4.0% calcium in a factorial design (12 birds per diet) for 4 wk. The percentage of egg production increased linearly (P < 0.05) with increasing levels of dietary calcium. Significant interactions (P < 0.05) were observed between dietary putrescine and calcium for eggshell thickness, eggshell deformation, percentage of eggshell, calcium intake, total calcium retention, total eggshell calcium, and percentage of eggshell calcium. Interactions were due to quadratic effects of putrescine or calcium on these parameters. Eggshell thickness and percent eggshell increased when hens were fed 3.5% calcium in combination with 0.1% putrescine; however, calcium intake and calcium retention were significantly lower (P < 0.05). Eggshell quality improved with increasing dietary levels of calcium due to increased calcium retention and calcium balance. Increasing levels of dietary putrescine did not have a negative effect on eggshell quality; however, calcium intake was lower at higher-supplemented levels of putrescine. It was observed that dietary calcium in excess of requirements resulted in increased egg production and eggshell quality. Eggshell quality improved when hens were fed 3.5% calcium diet in combination with 0.10% putrescine. It was concluded that small supplements of dietary putrescine may improve eggshell quality, depending on dietary calcium concentration.

Experiments were conducted to evaluate the potential for dietary 1,4-diaminobutane (putrescine) to influence eggshell quality and overall laying performance in hens. Forty-eight, 60-wk-old White Leghorn hens laying thin-shelled eggs were fed a corn and soybean meal-based diet supplemented with 0.00 (control), 0.05, 0.10, or 0.15% putrescine for 4 wk. Twelve hens that laid thick-shelled eggs were also fed the control diet. The feeding of supplemental putrescine decreased feed consumption; however, egg weight decreased only at higher levels of supplementation. Increasing dietary levels of putrescine responded quadratically in eggshell deformation, eggshell weight, and eggshell weight as a percentage of egg weight (P < 0.05). There were no significant differences in shell deformation, shell thickness, or shell weight when comparing hens laying thick-shelled eggs and those laying thin-shelled eggs that were fed 0.05% supplemental putrescine. Calcium intake, calcium retention, and calcium balance decreased linearly (P < 0.05) with increasing levels of dietary putrescine. Pancreatic putrescine concentrations were significantly higher (P < 0.05) in hens laying thick-shelled eggs compared with hens laying thin-shelled eggs. It appeared that pancreatic cells synthesized more polyamines in hens laying thick-shelled eggs. This increase in polyamines might have caused improved eggshell quality by increasing calcium transport. It was concluded that 0.05% supplemental putrescine improved eggshell quality; however, higher levels proved to be toxic.

Background: Variation in absorption efficiency explains more of the variability in calcium balance than does actual calcium intake. Several investigators have suggested that the relatively high phosphorus and protein intakes of the diets of industrialized nations reduce calcium absorption and thereby aggravate the problem of calcium deficiency. Objective: My objective was to test whether variation in phosphorus and protein intakes is associated with variation in calcium absorption. Design: One hundred ninety-one Roman Catholic nuns aged 48.7 ± 7.0 y were studied 3 times each over a >20-y period with a full metabolic balance regimen; controlled, chemically analyzed diets; and double-tracer measurement of calcium absorption. Results: Although the expected associations with absorption were found for age, calcium intake, and estrogen status, no association was observed for intakes of either phosphorus or protein. Conclusion: Phosphorus and protein intakes do not contribute to the wide variability in calcium absorption efficiency.

In the last 20 years, the biomedical problems facing man in space have been brought into sharper focus. Space motion sickness is presently the most serious problem. Its etiology remains obscure, but the 'sensory conflict' theory appears most plausible. No valid predictive tests of susceptibility exist and presently medication for prevention or mitigation of symptoms must be relied on. Adaptation/biofeedback techniques may prove useful. Cardiovascular 'deconditioning' may be effectively attenuated by use of anti-g suits or plasma expanding techniques. Recent bedrest simulation studies would seem to indicate that concerns about chronically elevated central venous pressure during space flight are unfounded. The loss of red cell mass in space flight appears to be self-limited, independent of mission duration, and not of clinical concern, based on recent Soviet experiences. And finally, clodronate, a new diphosphonate effective in preventing hypercalciuria and negative calcium balance in normal human bedrested subjects, may prove effective in preventing or lessening skeletal mineral loss in space.

FOURTEEN to sixteen days before the onset of egg production, (Hurwitz, 1964), the pullet undergoes profound changes in its mineral metabolism. This stage coincides with the development of the primary and secondary sex organs and is characterized by increased plasma calcium, increase in calcium retention and formation of medullary bone (Simkiss, 1961). Such an intense mineral metabolism is preceded by a period of about two months of low intensity mineral metabolism during which the calcium and phosphorus requirements are extremely low (Berg et al., 1964). During the pre-laying period the calcium and phosphate retention reach 800 and 400–500 mg./day, respectively (Taylor and Moore, 1958). It thus must follow that the mineral requirements during the pre-laying period are increased. It has been shown that during the early production period, the young hen is in a negative calcium balance (Morgan and Mitchell, 1938) which cannot be alleviated by high dietary calcium…

IT HAS been known for a long time that estrogens play an important role in calcium metabolism in the bird. Due to the enormous amount of calcium excreted during the period of egg shell formation it is likely that the hen requires a special mechanism to control calcium balance at that time. Riddle and Reinhart (1926) showed that the blood calcium rises in the pigeon prior to egg shell formation and is maintained until shell formation is completed. Similarly a hypercalcemia has been shown in the laying hen (Parhon, 1926; Hughes, Titus and Smits, 1927). Treatment with estrogens causes a marked rise in the blood calcium of the pigeon (Riddle and Dotti, 1936; Pfeiffer and Gardner, 1938), the chicken (Altman and Hutt, 1938; Zondek and Marx, 1939; Landauer et al., 1939) the duck (Landauer et al., 1941) and the sparrow (Pfeiffer et al., 1940). Similar results are obtained in the . . .

THE retention of radiocalcium or radiostrontium in bones of humans (Spencer et al., 1961), rats (Cohn et al., 1961) and non-laying pullets (Hurwitz, 1965a), following a single intravenous dose, is reduced by the feeding of high-calcium diets. However, in the laying hen, the severe calcium depletion from bone during calcium restriction (Taylor and Moore, 1954; Hurwitz and Griminger, 1961) would suggest the possibility of reducing the body burden of bone-seeking radiosotopes by calcium restriction. It was the purpose of the present study to investigate the effects of variation in dietary calcium level and sources, and the timing of this variation, on the retention of calcium-45 and strontium-85 in various bone segments, and the deposition of these nuclides in the egg shell. METHODS AND RESULTS General procedure: The method for preparation of samples for analysis was given in detail in the preceding paper (Hurwitz and Bar, 1966). For calcium-45 determinations, calcium …