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The dynamic balance of Ca2+ in oocytes promotes the recovery of the meiotic arrest phase, consequently promoting oocyte maturation. Hence, the analysis of the maintenance and role of calcium homeostasis in oocytes has important guiding significance for obtaining high-quality eggs and maintaining the development of preimplantation embryos. Inositol 1,4,5-trisphosphate receptors (IP 3 Rs) are calcium channel proteins that regulate the dynamic balance between the endoplasmic reticulum (ER) and mitochondrial Ca2+. Nevertheless, the expression and role of IP 3 R in normal pig oocytes have not been reported, and other studies have focused on the role of IP 3 R in damaged cells. The purpose of this study was to investigate the potential role of IP 3 R in regulating calcium homeostasis in oocyte maturation and early embryonic development. Our results showed that IP 3 R1 is stably expressed at different stages of porcine oocyte meiosis, IP 3 R1 gradually converges to the cortex, and cortical clusters are formed in MII stages. The loss of IP 3 R1 activity contributeds to the failure of porcine oocyte maturation and cumulus cell expansion, as well as the obstruction of polar body excretion. Further analysis showed that IP 3 R1 plays an important role in affecting calcium balance by regulating the IP 3 R1-GRP75-VDAC1 channel between mitochondria and the endoplasmic reticulum (ER) during porcine oocyte maturation. Inhibiting IP 3 R1 expression-induced ER dysfunction, contributeding to ER calcium concentration ([Ca2+] ER) release outwards into mitochondria and causing mitochondrial free calcium concentration ([Ca2+] m) overload and mitochondrial oxidative stress, which was confirmed by the increase in the level of reactive oxygen species (ROS) and apoptosis. Thereby, IP 3 R1 plays an important role in affecting calcium balance by regulating the IP 3 R1-GRP75 -VDAC1 channel between mitochondria and the ER during porcine oocyte maturation, inhibiting IP 3 R1 expression-induced calcium overload and mitochondrial oxidative stress, and increasing ROS levels and apoptosis. • IP 3 R1 plays an important role in affecting calcium balance by regulating the IP 3 R1-GRP75 -VDAC1 channel between mitochondria and the ER during porcine oocyte maturation. • Inhibiting IP 3 R1 expression-induced ER dysfunction, contributeding to ER calcium concentration ([Ca2+]ER) release outwards into mitochondria and causing mitochondrial free calcium concentration ([Ca2+]m) overload. • Inhibiting IP 3 R1 expression-induced mitochondrial oxidative stress, and increasing ROS levels and apoptosis. [ABSTRACT FROM AUTHOR]

Introduction: The composition of the dialysate is a crucial feature in the dialysis treatment. Two of its most debated elements are the optimal calcium concentration and the use of acetate as a buffer. Moreover, among the different alternatives to achieve acetate-free dialysis, the use of citrate is postulated as the most suitable option. The objective of this study is to identify the potential beneficial effects of citrate when compared to acetate dialysate (AD) both in short-term effects (especially regarding intradialytic calcium balance and cardiac damage biomarkers) and in medium-term ones with CKD-mineral and bone disorder (CKD-MBD) and inflammatory biomarkers measured after twelve sessions performed with each dialysate. Methods: This is a unicentric, cross-over, prospective study. Each patient underwent 24 dialysis sessions, 12 with each dialysate buffer. Blood samples were taken in 2 different sessions with each acidifier. They include CKD-MBD and inflammatory biomarkers. The calcium concentration of both dialysates was 1.5 mmol/L, while all other dialysis parameters and patients' treatment remained unchanged during the study period. Results: When comparing AD and citrate dialysate (CD), there were no differences in pre-dialysis ionized calcium (iCa) (1.11 vs. 1.08 mmol/L) in both groups. However, there was a significant increase in iCa with the use of AD in immediate and 30-min post-dialysis blood samples. In contrast, iCa levels remained stable with the use of citrate. Inflammatory biomarkers were also reduced after the use of CD. Conclusions: The use of citrate provides interesting advantages when compared to acetate. It maintains iCa levels stable during dialysis sessions with a neutral or negative effect on calcium balance, and it improves the chronic inflammatory condition that comes with long-time hemodialysis treatment. These beneficial effects may lead to an improvement in clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: The potential effects of dietary oxalate (Ox) intake on cardio-renal function have remained unestablished. We evaluated the effect of usual Ox intake and its interaction with dietary calcium (Ca) on incident hypertension (HTN) and chronic kidney disease (CKD). Methods: Adult men and women, free of HTN and CKD at baseline (2006–2008), were recruited. Dietary intakes were assessed using a validated food frequency questionnaire, and the outcomes were documented up to 2014–2017. Multivariate Cox proportional hazard regression models were used to estimate the development of HTN and CKD in relation to Ox intakes. Repeated-measures generalized estimating equation (GEE) linear regression models were used to assess possible effect of Ox-intake on the estimated glomerular filtration rate (eGFR) and blood pressure levels over eight years. Results: Dietary Ox intakes were positively associated with incident CKD (HR = 2.59, 95% CI = 1.46–4.64) and HTN (HR = 1.79, 95% CI = 1.05–3.04). Compared to high-Ca consumers, subjects who had lower Ca intakes (< 990 vs. 1580 mg/d) had a higher incidence of CKD and HTN (HR = 2.43, 95% CI = 1.06–5.55, and HR = 1.72, 95% CI = 0.76–3.78). Participants with higher intakes of Ox (> 220 vs. < 150 mg/d) had lower eGFR values (75.3, 95% CI = 75.0–76.5 vs. 77.3, 95% CI = 76.6–78.1 mL/min/1.73m2, Ptime×group = 0.004) and higher SBP levels (112, 95% CI = 111–113 vs. 109, 95% CI = 108–110 mmHg, Ptime×group = 0.007) overtime. Conclusion: Higher dietary Ox intake may increase the risk of HTN and CKD. The relation between dietary Ox and risk of HTN and CKD seems to be varied by Ca intake, and subjects with lower Ca intakes may be more burdened by excessive amounts of dietary Ox. [ABSTRACT FROM AUTHOR]

Serum calcium isotopes (δ44/42Ca) have been suggested as a non-invasive and sensitive Ca balance marker. Quantitative δ44/42Ca changes associated with Ca flux across body compartment barriers relative to the dietary Ca and the correlation of δ44/42CaSerum with bone histology are unknown. We analyzed Ca and δ44/42Ca by mass-spectrometry in rats after two weeks of standard-Ca-diet (0.5%) and after four subsequent weeks of standard- and of low-Ca-diet (0.25%). In animals on a low-Ca-diet net Ca gain was 61 ± 3% and femur Ca content 68 ± 41% of standard-Ca-diet, bone mineralized area per section area was 68 ± 15% compared to standard-Ca-diet. δ44/42Ca was similar in the diets, and decreased in feces and urine and increased in serum in animals on low-Ca-diet. δ44/42CaBone was higher in animals on low-Ca-diet, lower in the diaphysis than the metaphysis and epiphysis, and unaffected by gender. Independent of diet, δ44/42CaBone was similar in the femora and ribs. At the time of sacrifice, δ44/42CaSerum inversely correlated with intestinal Ca uptake and histological bone mineralization markers, but not with Ca content and bone mineral density by µCT. In conclusion, δ44/42CaBone was bone site specific, but mechanical stress and gender independent. Low-Ca-diet induced marked changes in feces, serum and urine δ44/42Ca in growing rats. δ44/42CaSerum inversely correlated with markers of bone mineralization. [ABSTRACT FROM AUTHOR]

Introduction: To assess the safety, efficacy, and calcium flux of an accelerated algorithm for regional citrate anticoagulation in membrane-based plasma exchange. Methods: This was an observational study in patients receiving citrate anticoagulated, membrane-based plasma exchange at the Canberra Hospital between July 2017 and May 2020. Data were collected prospectively using an electronic medical record and compared to data from our previous published algorithm. Results: There were 134 plasma exchange sessions performed during the observational period. Circuit clotting occurred in 4 sessions, and 1 session was affected by symptomatic hypocalcaemia. A systemic ionized calcium <0.96 mmol/L was seen in 19.4% of sessions, which was a similar frequency to that seen in our previous algorithm. A systemic ionized Ca <0.81 mmol/L occurred in 4 sessions (all asymptomatic). This hypocalcaemia occurred towards the end of the sessions, after switching from albumin to fresh frozen plasma replacement fluid. Median treatment time was 135 min, compared to 219 min in our previously published algorithm. Mean net Ca gain/session was 7.7 ± 2.3 mmol. Conclusion: An accelerated algorithm for regional citrate anticoagulation achieves substantial time saving while maintaining efficacy and safety. The 4 episodes of systemic ionized calcium <0.81 mmol/L may have been due to recirculation of infused citrate but, probably more likely, are due to the additional citrate load imposed by use of fresh frozen plasma in these sessions. Future algorithms need to better account for the citrate load present in fresh frozen plasma. [ABSTRACT FROM AUTHOR]

Previous research documented that furosemide negatively impacted calcium balance for 3 days but did not determine when calcium balance returned to baseline. This study hypothesized that furosemide's impact on calcium would return to control values before 7 days post‐administration. Ten mature geldings were assigned to either control (CON, n = 5) or treatment (FUR, n = 5) for the first of two 8‐day total collections in crossover design. Treatment horses received one administration of furosemide (1 mg/kg, IV). A 10% sample of pooled faeces and urine from each day was kept. Calcium concentrations in hay, faeces and urine were determined by an atomic absorption spectrophotometer. Data were analysed using mixed‐model‐repeated measures ANOVA to determine influence of day and treatment. For urine output, FUR urinated twice as much during the 24 hr after administration than CON (p <.001). Horses in FUR excreted more urinary calcium 24‐hr post‐administration as compared to CON (9.3 ± 1.0 and 4.2 ± 1.0 g, respectively; p <.001). Calcium balance in FUR was more negative on day 1 than day 3 (p <.05). Faecal calcium concentrations remained the same from day 1 to day 7 in CON (6.3 ± 1.3 and 5.5 ± 1.3 g/kg, respectively; p >.10) but were lower in FUR on day 7 as compared to day 1 (4.8 ± 1.3 and 7.3 ± 1.3 g/kg, respectively; p <.001), indicating a potential mechanism to restore calcium balance. These findings corroborate previous studies on furosemide and calcium balance and provide evidence for a possible mechanism to recover net calcium losses after furosemide administration. Since calcium balance returns to baseline in 3 days and previous results have examined frequent, long‐term use, furosemide may not negatively impact bone mineral content even if used over long periods. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is a neurodegenerative, dominantly inherited genetic disease caused by expansion of the polyglutamine tract in the huntingtin gene. At the cellular level, HD is characterized by the accumulation of mutant huntingtin protein in brain cells, resulting in the development of the HD phenotype, which includes mental disorders, decreased cognitive abilities, and progressive motor impairments in the form of chorea. Despite numerous studies, no unambigous connection between the accumulation of mutant protein and selective death of striatal neurons has yet been established. Recent studies have shown impairments in the calcium homeostasis in striatal neurons in HD. These cells are extremely sensitive to changes in the cytoplasmic concentration of calcium and its excessive increase leads to their death. One of the possible ways to normalize the balance of calcium in striatal neurons is through the sigma 1 receptor (S1R), which act as a calcium sensor that also exhibits modulating chaperone activity upon the cell stress observed during the development of many neurodegenerative diseases. The fact that S1R is a ligand-operated protein makes it a new promising molecular target for the development of drug therapy of HD based on the agonists of this receptor. [ABSTRACT FROM AUTHOR]

There is controversy about the choice of dialysate calcium concentration (DCa), with strong arguments both in favor of and against the use of a low or high DCa, as they can both be potentially harmful. Evidence suggests that calcium mass balance is positive with a DCa 3.5 mEq/L, negative or neutral with the use of DCa 2.5 mEq/L, whereas both positive and negative balances have been observed with the use of DCa 3.0 mEq/L. Overall, the use of DCa >2.5 mEq/L is usually associated with an increase in serum calcium level and a decrease in serum PTH level and use of lower vitamin D analogue dose, with the opposite effects usually observed with the use of lower DCa. Most of the available evidence is from small-sized and crossover studies; hence, evidence should be regarded with caution and applied in a patient-specific manner. As there are a lot of significant unanswered questions regarding calcium balance and the optimal DCa in hemodialysis patients, further high-quality research is needed to clarify many still unclear aspects of calcium homeostasis and balance in these patients. In conclusion, with the existing evidence the choice of DCa needs to be individualized and contextualized in the setting of each patient's calcium balance needs and homeostatic response, taking also into account oral calcium intake (dietary and medicinal), any other relevant therapy administered, such as vitamin D analogues, the type of renal mineral bone disorder, and associated cardiovascular comorbidity. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To assess the efficacy, safety and calcium balance of a membrane based regional citrate anticoagulation plasma exchange protocol. Methods: This was an observational, prospective, single centre study of membrane separation plasma exchange using regional citrate anticoagulation. It was performed using a fixed dose pre‐filter citrate infusion that was based on the plasma flow rate. Patients received a post filter calcium infusion that was modified during treatment based on systemic ionized calcium monitoring. Post filter ionized calcium was not assessed. Safety and efficacy were assessed by extraction of clinical events and laboratory data contemporaneously recorded in electronic health records. Results: Thirty‐six sessions in five patients were performed. No patients developed symptomatic hypocalcaemia, and no patient had a recorded ionized calcium below 0.81 mmol/L. Filter clotting occurred in two sessions. The mean net calcium gained was 9.6 ± 1.8 mmol per session. Conclusion: Regional citrate anticoagulated membrane separation plasma exchange can be performed safely and effectively without the need for post filter ionized calcium monitoring. The algorithm employed resulted in a net calcium gain. [ABSTRACT FROM AUTHOR]

The debate on the most adequate dialysate calcium concentration for intermittent haemodialysis therapy is ongoing. There is probably no one optimal concentration. In general, one would like to maintain a neutral calcium balance in adult haemodialysis patients. However, a slightly negative balance may be preferable to avoid soft-tissue calcium accumulation in face of net calcium loss from the bone with ageing. The problem with measurements of calcium balance is that they are generally imprecise, as are estimations of total body calcium and its distribution in various compartments, unless done with labour-intensive methods and great care. The choice of the dialysate calcium will depend on several factors, including parathyroid and vitamin D status, type and severity of concomitant bone disease, presence or absence of arterial calcification, dietary habits, drug treatment and dialysis modality. Ideally the dialysate calcium would be adapted to each patient's needs. This is not feasible, however, in most dialysis settings and neither is it cost-effective. From a practical point of view, a relatively high dialysate calcium concentration in the range of of 1.50–1.75 mmol/L (3.0–3.5 mEq/L) should probably be preferred in haemodialysis patients with high serum PTH levels who are not prescribed calcium-based phosphate binders or high doses of active vitamin D sterols, and in those who are receiving a calcimimetic. In those who are treated with high doses of calcium-based binders and/or active vitamin D derivatives or who have a very low serum PTH level, the optimal dialysate calcium concentration is probably lower, in the range of 1.25–1.50 mmol/L (2.50–3.0 mEq/L). In the present pro/con debate about the optimal dialysate calcium concentration used for the haemodialysis session, we have accepted to defend the viewpoint that a low calcium concentration may do more harm than benefit in many patients. This viewpoint is opposite to that taken by Gotch [1]. He argues that since calcitriol and other active vitamin D derivatives have become available virtually all haemodialysis patients are in positive calcium balance. We would like to take issue with this statement and warn against the indiscriminate use of a low calcium dialysate in all patients receiving haemodialysis therapy. [ABSTRACT FROM PUBLISHER]

With the aim of determining the effect of the Na gene (naked neck) on the calcium balance in laying hens under dry tropical conditions, thirty Creole hens were used: 10 NaNa hens (homozygotic naked neck), 10 Nana (heterozygotic naked neck), and 10 nana (homozygotic normal plumage). The feed contained 16 % crude protein, 11.95 MJ of metabolizable energy per kilogram of feed, 3.5 % calcium, and 0.45 % available phosphorus. The data were collected during the weeks 34, 44, and 54 of age. The feed intake, the calcium intake, the daily and night excreted calcium, the calcium in shell, and serum calcium were measured in three times relative to oviposition: with the egg in uterus, 7 h postoviposition and the day of no laying. There was no genotype effect or of the interactions genotype per age and genotype per time of oviposition on the serum Ca levels. However, there was effect of the age of the hen, oviposition time (P < 0.01) and their interaction on the concentration of serum Ca. The means and standard errors for the levels of serum Ca were 22.67 ± 1.22, 23.01 ± 1.25, and 25.58 ± 1.42 mg/dL, for the genotypes nana, Nana, and NaNa, respectively. The serum calcium levels were significantly higher (P < 0.05) 7 h after the oviposition (27.65 ± 1.29 mg/dL), compared to the levels of serum Ca in hens with eggs in uterus (21.12 ± 1.29 mg/dL) or when there was not egg formation (22.25 ± 1.29 mg/dL). The age of the hens had positive effect (P < 0.05) on the serum Ca levels. The genotype had no effect on feed intake, calcium ingested, shell weight and calcium in shell, but there was effect on calcium retention. The Ca retention, was higher in the NaNa and Nana hens than in those of normal plumage. The apparent calcium balance was positive in the three genotypes and the dietary calcium retention was higher in naked neck hens. [ABSTRACT FROM AUTHOR]

Juvenile gilthead sea bream were exposed to diluted seawater (2.5‰ salinity; DSW) for 3 h or, in a second experiment, acclimated to DSW and fed a control or calcium-deficient diet for 30 days. Branchial Ca2+ influx, drinking rate and plasma calcium levels were assessed. Sea bream plasma parathyroid hormone related protein (sPTHrP) was measured, and mRNAs of pthrp, its main receptor, pthlr, and the calcium-sensing receptor (casr) were quantified in osmoregulatory tissues and the pituitary gland. When calcium is limited in water or diet, sea bream maintain calcium balance; however, both plasma Ca2+ and plasma sPTHrP concentrations were lower when calcium was restricted in both water and diet. Positive correlations between plasma sPTHrP and plasma Ca2+ (R²=0.30, N=39, P<0.05), and plasma sPTHrP and body mass of the fish (R²=0.37, N=148, P<0.001) were found. Immunoreactive sPTHrP was demonstrated in pituitary gland pars intermedia cells that border the pars nervosa and co-localises with somatolactin. In the pituitary gland, pthrp, pthlr and casr mRNAs were downregulated after both short- and long-term exposure to DSW. A correlation between pituitary gland pthrp mRNA expression and plasma Ca2+ (R²=0.71, N=7, P<0.01) was observed. In gill tissue, pthrp and pthlr mRNAs were significantly upregulated after 30 days exposure to DSW, whereas no effect was found for casr mRNA expression. We conclude that in water of low salinity, declining pituitary gland pthrp mRNA expression accompanied by constant plasma sPTHrP levels points to a reduced sPTHrP turnover and that sPTHrP, through paracrine interaction, is involved in the regulation of branchial calcium handling, independently of endocrine pituitary gland sPTHrP. [ABSTRACT FROM AUTHOR]

Fructus Ligustri Lucidi (FLL) is an edible herb with anti-osteoporotic activity, yet whether and how the aqueous extract of this herb affect calcium metabolism in preservation of bone quality remain unclear. To investigate the effects of FLL aqueous extract on calcium balance and short-chain fatty acids (SCFAs) production in ovariectomized (OVX) rats. OVX rats were daily and orally administrated with FLL aqueous extract (3.5 g/kg) for 14 weeks. The levels of N-terminal propeptide of type I collagen (PINP) and C-terminal telopeptide of type I collagen (CTx-I) in rat serum were evaluated by ELISA assays. The concentration of calcium in serum, urine, and feces were determined by biochemical assays. Bone quality was determined by Micro-CT, a three-point bending assay, and Fourier Transform Infrared (FTIR) Spectrometry. The expressions of Calbindin D28K and Calcium-sensing receptor (CaSR) in kidney as well as the Vitamin D receptor (VDR), the transient receptor potential vanilloid receptor 6 (TRPV6), Calbindin D9k in the duodenum were measured by immunohistochemistry, western blotting, or real-time PCR. The short-chain fatty acids (SCFAs) levels in the feces of the cecum were tested by gas chromatograghy. The administration of FLL to OVX rats resulted in a significant improvement in bone mineral density and biomechanical strength as well as in maintaining bone microstructures and material quality. Meanwhile, the decreased levels of PINP and increased levels of CTx-I in OVX rats were restored by FLL treatment. Additionally, FLL treatment increased calcium absorption, upregulated VDR, TRPV6, Calbindin D9k expressions in the duodenum, Calbindin D28K in kidney, and down-regulated CaSR expression in the kidney, as well as enhanced SCFAs levels in the feces of OVX rats. FLL aqueous extract may preserve bone quality through regulation of the calcium balance and intestinal SCFAs production in OVX rats. This offers translational value of FLL into osteoporosis clinical trial. [Display omitted] [ABSTRACT FROM AUTHOR]

We studied the role of calcium-regulating structures of slow- ( m. soleus, SOL) and fast-twitch ( m. extensor digitorum longus, EDL) skeletal muscles of rats during adaptation to exhausting physical activity and the possibility of modulating this adaptation with decaffeinated green tea extract. It was established that EDL adaptation is mainly aimed at Са elimination from the sarcoplasm by Са-ATPase and its retention in the reticulum by calsequestrin. Administration of green tea extract increased endurance due to involvement of slow-twitch muscles whose adaptation is associated with enhanced expression of all the studied genes responsible for the regulation of Ca balance. [ABSTRACT FROM AUTHOR]

Calcium balance is an overall assessment of the net calcium taken in minus the net calcium taken out. It can only be assessed when patients are in steady state and requires complicated isotope methods that can simultaneously assess intestinal absorption and endogenous secretion, urinary and stool excretion, bone calcium uptake and removal, and dialysate calcium removal. By virtue of the need for steady state, formal balance studies cannot be accurately carried out in patients on dialysis. However, many of the components of calcium balance have been assessed. Importantly, because 99% of calcium is in bone, studies must accurately assess both the rapidly exchangeable calcium from the bone surface and the net bone calcium balance that results from the difference in bone formation minus resorption. While it is tempting to adjust the dialysate calcium concentration to correct the net positive calcium balance that is likely present in patients who receive calcium-based phosphate binders, the reality is that the highly variable, yet important, role of bone cannot be easily assessed at the bedside. Thus, it is best to prevent the calcium overload in the first place by avoiding high-dose calcium-based phosphate binders and optimizing bone remodeling. [ABSTRACT FROM AUTHOR]

1. The influences of dietary phosphorus (P) and food concentration on the calcium (Ca) balance in Daphnia magna were examined in this study at two different ambient Ca concentrations (0.5 and 10 mg Ca L−1). Daphnia were grown by feeding the young adults differentially under contrasting dietary P conditions [molar C : P ratio = c. 900 and c. 90 as low P (LP) and high P (HP), respectively], ambient Ca concentrations [0.5 mg and 10 mg Ca L−1 as low Ca (LCa) or high Ca (HCa), respectively] and food levels [0.15 or 1.5 mg C L−1 as low food (LF) or high food (HF), respectively] for 5 days. 2. The specific Ca contents of daphniids (1.9–6.5% of dry weight−1) increased with increasing Ca concentration, food level and dietary P content, although the food level did not affect the Ca content in the HPHCa treatment. A radioactive tracer method showed that the food level did not affect the influx of Ca from the water under LP conditions, but the Ca influx under HP conditions doubled with a HF level. A LP condition also led to a decrease in Ca influx with a HF level. 3. During the 3 days of efflux, generally only a small proportion of Ca (2.6–3.3%) was retained by the daphniids, but this retention increased (14–23%) under low ambient Ca concentrations and under P-limitation. Excretion was the most important pathway for Ca loss (accounting for 50–60% of body Ca), followed by moulting (20–47%), but the relative contribution of these two pathways (excretion and moulting) did not vary among all the different treatments. The absolute loss of Ca through excretion and moulting, on the contrary, differed with different ambient Ca concentrations and dietary P conditions. A HF level led to an increase in the loss rates in most cases. 4. Our study strongly suggested that there is an interaction between an essential metal (Ca) and macronutrients (C and P) in freshwater crustaceans with HCa and P contents. The results imply that variation in environmental nutrient conditions may change the Ca budget in crustaceans and may affect the dynamics of Ca in the epilimnion of freshwaters. [ABSTRACT FROM AUTHOR]

Objective: We examined the effect of vitamin D supplementation on bone growth in young rats fed a normal or low calcium diet. Methods: Fifty female Sprague-Dawley rats, 6 weeks of age, were randomized by stratified weight method into five groups with 10 rats in each group: baseline control, 0.5% (normal) or 0.1% (low) calcium diet, and 0.5 or 0.1% calcium diet + vitamin D (25 μg/100 g, food intake). Duration of the experiment was 10 weeks. Results: Vitamin D supplementation stimulated intestinal calcium absorption and increased urinary calcium excretion in rats fed a low or normal calcium diet. Vitamin D supplementation prevented the reduction in periosteal bone gain but enhanced enlargement of the marrow cavity and reduced the maturation-related cancellous bone gain in rats fed a low calcium diet, and increased the maturation-related cancellous and cortical bone gains in rats fed a normal calcium diet. Conclusion: This study shows the differential effects of vitamin D supplementation on born growth in young rats fed a normal or low calcium diet. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Our previous studies found that different extracts or fractions of Fructus ligustri lucidi (FLL) played different roles in altering the regulation of bone and mineral metabolism in different animal models. The present study was designed to compare the actions of FLL ethanol (EE) and water extracts (WE) on bone and mineral metabolism in a 6-month-old mature ovariectomized (OVX) rat model. Our results showed that FLL extracts did not significantly improve systematic Ca balance in mature OVX rats. However, EE, but not WE treatment, significantly increased serum 1,25(OH)2D3 levels in mature OVX rats. An in vitro study using human proximal tubule (HKC-8) cells showed that EE, but not WE, significantly enhanced renal 25-dihydroxyvitamin D3-1-hydroxylase (1-OHase) mRNA expressions and simultaneously repressed renal 25-dihydroxyvitamin D3-24-hydroxylase (24-OHase) mRNA expressions. Further investigation indicated that EE could significantly induce the protein expression of 1-OHase, but did not alter 24-OHase expression in HKC-8 cells. Our results demonstrated that EE increased circulating 1,25(OH)2D3 levels in OVX rats, possibly via upregulation of renal 1-OHase expressions in renal proximal tubule cells. Our study indicates that FLL is a natural oral agent that could directly regulate renal vitamin D metabolism in vivo and in vitro. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Calcium balance during hemodialysis (HD) is important in determining short-term cardiovascular function, this influences the hemodynamic tolerability of dialysis. In the longer term, calcium flux during HD is an important determinant of overall calcium balance in a patient and may also influence the development and progression of vascular calcification, with its attendant consequences. This article aims to review the assessment and mechanisms of calcium flux during HD, choice of dialysate calcium concentration, influence of HD modality, and potential consequences of therapy choices (cardiovascular and skeletal) resulting from an inappropriate intradialytic calcium balance. [ABSTRACT FROM AUTHOR]

Calcium regulation in sturgeon is of special interest because they are a representative of the ancient fishes possessing mainly cartilaginous skeletons and a supposedly low calcium demand. The present study aimed to characterize the effect of a chronic absence of dietary calcium and the effect of parathyroid hormone-related protein (PTHrPA) (1-34) (7) on calcium balance in juvenile sturgeon (Acipenser naccarii). At rest, sturgeon juveniles are in net positive calcium balance, since whole body calcium uptake is significantly higher than efflux and calcium accumulates in the body. To study the importance of dietary calcium, the sturgeon were kept on a calcium-free diet for 8 wk. This manipulation impaired growth as measured by failure to gain weight or increase in length and indicates that dietary calcium is important for growth in sturgeon. An increased whole body calcium uptake partially compensated dietary calcium deficiency and was associated with increased gill chloride cell number in lamellae and filaments in parallel with increased gill Na+K+-ATPase activity. In addition, a single injection of piscine PTHrP(1-34) significantly increased whole body calcium uptake and decreased whole body calcium efflux. Administration of PTHrP significantly increased circulating plasma calcium 4-24 h postinjection. The increase in net calcium transport and increased plasma levels of calcium is consistent with the actions of a hypercalcemic factor. It would appear that the sturgeon rely on calcium for growth and tightly regulate calcium transport. The action in calcium balance is consistent with PTHrP acting as a hypercalcemic factor in sturgeon. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to examine the effects of vitamin K2 administration on calcium balance and bone mass in young rats fed a normal or low calcium diet. Methods: Forty female Sprague-Dawley rats, 6 weeks of age, were randomized by stratified weight method into four groups with 10 rats in each group: 0.5% (normal) calcium diet, 0.1% (low) calcium diet, 0.5% calcium diet + vitamin K2 (menatetrenone, 30 mg/100 g chow diet), and 0.1% calcium diet + vitamin K2. After 10 weeks of feeding, serum calcium and calciotropic hormone levels were measured, and intestinal calcium absorption and renal calcium reabsorption were evaluated. Bone histomorphometric analyses were performed on cortical bone of the tibial shaft and cancellous bone of the proximal tibia. Results: Feeding a low calcium diet induced hypocalcemia, increased serum parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1,25(OH)2D] levels with decreased serum 25-hydrovyvitamin D [25(OH)D] level, stimulated intestinal calcium absorption and renal calcium reabsorption, and reduced cortical bone mass as a result of decreased periosteal bone gain and enlarged marrow cavity, but did not significantly influence cancellous bone mass. Vitamin K2 administration in rats fed a low calcium diet stimulated renal calcium reabsorption, retarded the abnormal elevation of serum PTH level, increased cancellous bone mass, and retarded cortical bone loss, while vitamin K2 administration in rats fed a normal calcium diet stimulated intestinal calcium absorption by increasing serum 1,25(OH)2D level, and increased cortical bone mass. Conclusion: This study clearly shows the differential response of calcium balance and bone mass to vitamin K2 administration in rats fed a normal or low calcium diet. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

High-protein (HP) diets exert a hypercalciuric effect at constant levels of calcium intake, even though the effect may depend on the nature of the dietary protein. Lower urinary pH is also consistently observed for subjects consuming HP diets. The combination of these two effects was suspected to be associated with a dietary environment favorable for demineralization of the skeleton. However, increased calcium excretion due to HP diet does not seem to be linked to impaired calcium balance. In contrast, some data indicate that HP intakes induce an increase of intestinal calcium absorption. Moreover, no clinical data support the hypothesis of a detrimental effect of HP diet on bone health, except in a context of inadequate calcium supply. In addition, HP intake promotes bone growth and retards bone loss and low-protein diet is associated with higher risk of hip fractures. The increase of acid and calcium excretion due to HP diet is also accused of constituting a favorable environment for kidney stones and renal diseases. However, in healthy subjects, no damaging effect of HP diets on kidney has been found in either observational or interventional studies and it seems that HP diets might be deleterious only in patients with preexisting metabolic renal dysfunction. Thus, HP diet does not seem to lead to calcium bone loss, and the role of protein seems to be complex and probably dependent on other dietary factors and the presence of other nutrients in the diet. [ABSTRACT FROM AUTHOR]

Assesses the calcium balance and its major components by a six-day balance technique in young rats. Significance of calcium balance on skeletal growth; Intestinal calcium secretion; Effects of age on the body weight gain among sham operated and oophorectomized groups; Body weight as a determinant of calcium balance and true calcium absorption.

Backgrounds. Calcium (Ca) and bone metabolism in continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) patients show a remarkable difference depending on dialysis modalities. The levels of serum Ca and phosphate (P) in HD patients fluctuate contributing to the intermittent and rapid removal of plasma solute unlike in CAPD. Characteristics of plasma solute transport in automated peritoneal dialysis (APD) patients are resembled with that in HD. The purpose of the present study was to examine the difference of transperitoneal Ca removal between APD and CAPD anuric patients. Subjects and Methods. Twenty-three APD anuric patients were enrolled in this study. Biochemical parameters responsible for transperitoneal Ca removal in 24-hour and 4-hour peritoneal effluents were analyzed on CAPD and APD. Results. Transperitoneal Ca removal on APD was smaller compared with that on CAPD. The Ca removal was related to the ultrafiltration during short-time dwell. Decrease of the Ca removal during NPD induced by short-time dialysate dwell caused negative or small Ca removal in APD patients. The levels of intact PTH were increased at the end of PET. Conclusion. It appears that short-time dwell and frequent dialysate exchanging might suppress the transperitoneal Ca removal in anuric APD patients. [ABSTRACT FROM AUTHOR]

Objective: Opposite to lanthanum carbonate (LC), sevelamer hydrochloride (SH) may increase intestinal calcium absorption. The study compared the effects of LC and SH on serum and urine phosphate and calcium, and on hormones regulating mineral-bone metabolism.Patients and Methods: A prospective randomized crossover study included 34 patients with eGFR <60 mL/min. A single oral dose of LC (1,000 mg) or SH (2,400 mg) was administered in random order 15 minutes after a standardized meal fortified with 5 g calcium carbonate. Serum calcium, phosphate, and parathormone were measured before and 3, 6, 12, and 24 hours after each medication. Bone alkaline phosphatase (BAP), sclerostin, calcitriol, and FGF-23 were measured at baseline and after 12 and 24 hours. A 24-hour calcium and phosphate excretion was measured after each drug.Results: Serum calcium increased 3 and 6 hours after SH then returned to baseline. After LC calcium was unchanged for up to 3 hours then transiently increased and eventually returned to baseline. The area under curve (AUC) of serum calcium for 12 hours after SH was larger than after LC (p=0.04). Serum phosphate decreased after each drug with a nadir 3 hours post-SH and 6 hours post-LC. AUC of serum phosphate was similar after both medications. PTH decreased transiently after both drugs. BAP did not change. FGF-23 was constant for the first 12 hours but later decreased after each drug.Conclusion: A 2,400 mg SH and 1,000 mg LC are similarly effective in lowering serum phosphate in CKD, but LC induce in less intestinal calcium absorption after a meal. The trial was registered on February 23, 2018 in the clinicaltrial.gov database - NCT03451019. [ABSTRACT FROM AUTHOR]

Chronic renal failure (CRF) is a progressive, irreversible deterioration of kidney function that leads to complete loss of kidney function and the need for dialysis treatment. Bone disease is a chronic complication in the CRF and poses a significant problem in hemodialysis patients. The aim of our study was to assess the influence of peritoneal dialysis treatment on biochemical parameters of mineral and bone metabolism in hemodialysis patients, and identify the most important parameters for the monitoring of this disorder. The research involved 172 patients, mean age 58.69±12:54, divided into groups in respect to the length of dialysis treatment (group I - 5 years, group II - 5-10 years and group III - over 10 years). Serum phosphorus in all the patients was increased, but the values increased with duration of dialysis (I: 1.77±0.58, II: 1.97±0.66, III: 1.92±0.82), with no statistical differences (p>0.05). Calcemia values were significantly increased (I vs. II. and I vs. III, p<0.0001), as well as the values of Ca x P (I vs. II., p<0.001, II vs. III., p<0.01), primarily on the account of the increased calcium value. The values of alkaline phosphatase (I: 105.12±65.60; II: 125.27±96.79, III: 172.43±163.99) were significantly higher in group III compared to other groups (p <0.05). Also, the values of PTH (I: 234.21±18.74; II: 273.09±247.98; III: 489.46±468.49) were significantly higher in group III compared to other groups (p<0.001). In the group of patients with duration of dialysis up to 5 years, the values of phosphorus were increased, the values of calcemia were decreased, with mild elevation of AF and PTH values, which best corresponds to the bone disease with rapid turnover. In the P group, there is a significant increase in calcemia in respect to phosphorus, alkaline phosphatase, and PTH. The most reliable marker for clinical monitoring of bone disease in dialysis patients is PTH, which correlates well with the values of alkaline phosphatase and calcium. The values of calcium and phosphorus are highly variable and not the most reliable markers for bone disease monitoring. Acta Medica Medianae 2011;50(1):32-37. [ABSTRACT FROM AUTHOR]

Auditory transduction occurs by opening of Ca2+-permeable mechanotransducer (MT) channels in hair cell stereociliary bundles. Ca2+clearance from bundles was followed in rat outer hair cells (OHCs) using fast imaging of fluorescent indicators. Bundle deflection caused a rapid rise in Ca2+that decayed after the stimulus, with a time constant of about 50 ms. The time constant was increased by blocking Ca2+uptake into the subcuticular plate mitochondria or by inhibiting the hair bundle plasma membrane Ca2+ATPase (PMCA) pump. Such manipulations raised intracellular Ca2+and desensitized the MT channels. Measurement of the electrogenic PMCA pump current, which saturated at 18 pA with increasing Ca2+loads, indicated a maximum Ca2+extrusion rate of 3.7 fmol·s–1. The amplitude of the Ca2+transient decreased in proportion to the Ca2+concentration bathing the bundle and in artificial endolymph (160 mM K+, 20 µM Ca2+), Ca2+carried 0.2% of the MT current. Nevertheless, MT currents in endolymph displayed fast adaptation with a submillisecond time constant. In endolymph, roughly 40% of the MT current was activated at rest when using 1 mM intracellular BAPTA compared with 12% with 1 mM EGTA, which enabled estimation of the in vivo Ca2+load as 3 pA at rest. The results were reproduced by a model of hair bundle Ca2+diffusion, showing that the measured PMCA pump density could handle Ca2+loads incurred from resting and maximal MT currents in endolymph. The model also indicated the endogenous mobile buffer was equivalent to 1 mM BAPTA. [ABSTRACT FROM AUTHOR]

Abstract: We explored the possibility of using natural calcium (Ca) isotope variations in the urine (δ44/40Caurine) as a proxy for the Ca balance in the human body. We chose two test persons extremely different in their health status, gender and age (4-year-old healthy boy and a 60-year-old woman known to suffer from osteoporosis). During a 5 day interval the Ca isotope composition of the individual diet (δ44/40Cadiet) was monitored for both test persons to be in general agreement to the Ca isotope composition of the normal western European diet (∼−1.02±0.1‰). However, measurements showed that (1) δ44/40Caurine of both test persons are ∼1.37 and ∼2.49‰, respectively, heavier than δ44/40Cadiet and that (2) the δ44/40Caurine-boy is ∼1.1‰ heavier when compared to the value of the woman. The individual offset between diet and test persons is interpreted to reflect individual Ca reabsorption rates in the kidneys being the result of Rayleigh type Ca isotope fractionation related to the partitioning of Ca between the glomerular filtrate and filtered residue. The relative difference between δ44/40Caurine-boy and δ44/40Caurine-woman of ∼1.1‰ may reflect individual differences in the balance of bone mineralization and demineralization processes related to age, gender and health status. By arbitrarily defining an equilibrium value for Δ44/40Cadiet-urine of −1.93‰ being the arithmetic mean of δ44/40Caurine for both test persons the measured δ44/40Caurine values may be applied to model the individual bone mineralization and demineralization processes in a qualitative way. Note, second order influences of intestinal Ca absorption during sequestration of Ca between intestine and blood have to be subject of further studies. [Copyright &y& Elsevier]

AbstractCalcium mass balance (CaMB) is determined by the difference between Ca absorbed between dialyses (CaAbs) and the Ca removed during dialysis (JdCa2+). A mathematical model to quantify (1) CaAbsas a function of Ca intake (CaINT) and the doses of vitamin D analogues, and (2) JdCa2+as a function of Ca2+dialysance, the mean plasma Ca2+(MCpiCa2+) minus dialysate Ca2+(CdiCa2+), ultrafiltration rate (Qf) and treatment time is developed in this paper. The model revealed a basic design flaw in clinical studies of Ca-based as opposed to non-Ca-based binders in that CdiCa2+must be reduced with the Ca-based binders in order to avoid a positive CaMBrelative to the non-Ca-based binders. The model was also used to analyze CaMBin 320 Renal Research Institute hemodialysis patients and showed that all patients irrespective of type of binder were in positive CaMBbetween dialyses (mean ± SD 160 ± 67 mg/day) with current doses of vitamin D analogues prescribed. Calculation of the optimal CdiCa2+for the 320 Renal Research Institute patients revealed that in virtually all instances, the CdiCa2+required for neutral CaMB, where Ca removal during dialysis was equal to Ca accumulation between dialyses, was less than 2.50 mEq/l and averaged about 2.00 mEq/l. This sharply contradicts the recent KDIGO (Kidney Disease: Improving Global Outcomes) Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease – Mineral and Bone Disorder, that suggests a CdiCa2+of 2.5–3.0 mEq/l. Review of the KDIGO work group discussions shows that this discrepancy stems from the unwarranted work group assumption that intradialytic CaMBis zero. We strongly believe that this guideline for dialysate Ca2+is inappropriate and should be modified to more realistically reflect the needs of dialysis patients.Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Chinese dietary reference intakes (DRIs) for calcium were developed mainly from studies conducted amongst Caucasians, yet a recent review showed that reference calcium intakes for Asians are likely to be different from those of Caucasians (Lee and Jiang, 2008). In order to develop calcium DRIs for Chinese adolescents, it is necessary to explore the characteristics and potential influencing factors of calcium metabolic balance in Chinese adolescents. A total of 80 students (15.1±0.8 years) were recruited stratified by gender from a 1-year calcium supplementation study. Subjects were randomly designed to four groups and supplemented with calcium carbonate tablets providing elemental calcium at 63, 354, 660, and 966 mg/day, respectively. Subjects consumed food from a 3-day cycle menu prepared by staff for 10 days. Elemental calcium in samples of foods, feces, and urine was determined in duplicates by inductively coupled plasma atomic emission spectrometry. The total calcium intake ranged from 352 to 1323 mg/day. The calcium apparent absorption efficiency and retention in boys were significantly higher than that in girls (68.7% vs. 46.4%, 480 mg/day vs. 204 mg/day, P <0.05). Calcium retention increased with calcium intakes, but did not reach a plateau. Calcium absorption efficiency in boys increased with calcium intake up to 665 mg/day, and decreased after that. In girls, calcium absorption efficiency decreased with calcium intake. Calcium absorption efficiency increased within 1 year after first spermatorrhea in boys, but decreased with pubertal development in girls. Sex, calcium intake, age, and pubertal development were the most important determinants of calcium absorption (R 2 =0.508, P <0.01) and retention (R 2 =0.745, P <0.05). This study indicates that sex, calcium intake, age, and pubertal development are important factors for calcium retention and absorption during growth, which should be considered for the development of calcium DRIs for Chinese adolescents. [Copyright &y& Elsevier]

Abstract: Objective: To determine whether during hypokinesia (diminished movement) periodic physical exercise affects calcium (Ca2+) balance and Ca2+ loss. Methods: Studies were conducted on 30 physically healthy male volunteers during the preexperimental period of 30 days and the experimental period of 364 days. They were equally divided into three groups: active control subjects (ACS), hypokinetic subjects (HKS), and periodic training subjects (PTS). The ACS group ran an average distance of 9.3±1.2 km/d; the HKS group walked an average distance of 1.3±0.2 km/d; and PTS group walked and ran average distances of 1.3±0.2 km/d and 9.2±1.2 km/d for 5 and 2 days per week, respectively. Results: Serum Ca2+ level, fecal and urine Ca2+ loss, and Ca2+ imbalance increased (P <0.05) in the PTS and HKS groups compared with their preexperimental levels and the values in their respective ACS group. The serum Ca2+ concentration, urine and fecal Ca2+ loss, and Ca2+ imbalance increased more (P <0.05) in the PTS group than in the HKS group. Conclusion: During hypokinesia, Ca2+ imbalance is more evident with than without physical exercise and Ca2+ loss is exacerbated more with higher than lower Ca2+ imbalance. [Copyright &y& Elsevier]

Investigates the impaired osteoblast function in osteoporosis. Comparison of calcium balance and dynamic histomorphometry; Regulation of the life span of mature osteoblasts; Condition of the matrix formation and mineralization.

Calcium homeostasis in crustaceans is influenced by their natural molting cycle that periodically requires replacement of the calcified exoskeleton in order for growth to occur. Whole body Ca balance transitions from intermolt (zero net flux) to premolt (net efflux) and postmolt (net influx at the rate of 2 mmol kg−1 h−1). As such, molting provides a convenient model to study up- and down-regulation of epithelial Ca transporting proteins (such as Ca pumps and exchangers), the genes that encode them, and the steroid hormone (ecdysone) that putatively regulates the genes. Species residing in either freshwater or in terrestrial environments are more limited in their Ca availability than are marine species. Further the advance towards terrestriality is accompanied by decreased reliance upon branchial Ca uptake and increased reliance upon digestive uptake. This review will correlate Ca handling strategies with environment in semi-terrestrial and terrestrial crabs through examining environmental sources of Ca uptake. Ca homeostasis will also be discussed at the whole animal level, cellular, subcellular and molecular levels of regulation. [Copyright &y& Elsevier]

Sulfate accumulation may reduce calcium (Ca) activity in solution. The objective of this study was to relate solution and foliar nutrients for greenhouse tomato (Lycopersicon esculentum Mill. cv ‘Trust’) receiving nutrient solutions enriched with 0.1, 5.2, 10.4, or 20.8 mM of sulfate. Solution components were expressed as crude or free concentrations, which were row-centered log ratioed (RCLR). As an expression for nutrient balance, RCLR adjusts any nutrient value to the geometric mean of all nutrient levels. Solution and foliar datasets were related to each other using canonical correlations. RCLR produced greatest redundancy between the two datasets (R2=0.640–0.654), and raw data, the smallest (R2=0.498–0.513). Canonical analysis of RCLR-transformed free concentrations indicated a dominant sulfate effect and significant secondary effects due to adjustment of the anion–cation balance in solution. Free sulfate concentration as RCLR explained 66% of the variation in foliar sulfur (S) and 71% of the variation in foliar Ca. The RCLR transformation should be further examined in relation with Ca imbalance and interactions in fruit crops. [ABSTRACT FROM AUTHOR]

The use of citrate, through reversible binding of calcium, has become the preferred choice for anticoagulation in continuous renal replacement therapy in the critically ill patient. Though generally considered as very efficacious in acute kidney injury, this type of anticoagulation can cause acid–base disorders as well as citrate accumulation and overload, phenomena which have been well described. The purpose of this narrative review is to provide an overview of some other, non-anticoagulation effects of citrate chelation during its use as anticoagulant. We highlight the effects seen on the calcium balance and hormonal status, phosphate and magnesium balance, as well as oxidative stress resulting from these unapparent effects. As most of these data on these non-anticoagulation effects have been obtained in small observational studies, new and larger studies documenting both short- and long-term effects should be undertaken. Subsequent future guidelines for citrate-based continuous renal replacement therapy should take not only the metabolic but also these unapparent effects into account. [ABSTRACT FROM AUTHOR]

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 2000 mg of elemental calcium per day are in marked positive balance. Methodological limitations such as unproven steady state warrant caution and confirmatory studies. [ABSTRACT FROM AUTHOR]

The article addresses the debate whether the calculation on calcium balance in dialysis reduces the dialysate calcium concentrations. It presents the equation for determining the total calcium absorbed between dialyses. A kinetic model of calcium absorption as a function of calcium intake and calcitriol concentration is presented. It determines the level of dialysate inlet calcium concentration that is required to realize a neutral calcium mass balance.

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. • Micellar and free calcium in curd are affected by pH, temperature, and type acid. • Calcium was dissociated during the first 10 min after acidification. • For citric acid, pH had a strong effect on free calcium but not temperature. • For lactic acid, effects of both pH and temperature on free calcium were observed. • Curd yield decreased by decreasing pH but temperature had little effect. [ABSTRACT FROM AUTHOR]

Background: Diagnosis of subclinical hypocalcemia in cattle is based on concentration of total Ca ([TCa]) in serum or plasma below the reference range, with [TCa] serving as proxy for the concentration of ionized Ca ([iCa]). Hypothesis/Objectives: To investigate the relation between [iCa] and [TCa] in periparturient cows over time, and its association with various metabolites. Animals: Thirty periparturient dairy cows. Methods: Prospective observational study. Blood from periparturient cows was obtained between 4 days before and 7 days after calving. Samples underwent blood gas analysis and blood biochemical analysis. The ratio of [iCa] : [TCa] was computed. Repeated measures linear regression analyses, spearman correlation‐, Deming regression‐ and receiver operating characteristic (ROC) analyses were conducted. Results: Correlations between [iCa] and [TCa] ranged from r = 0.55 to r = 0.84. The diagnostic value of [TCa] to identify cows with [iCa] below the arbitrary cut‐off of 1.1 mmol/L was weak in particular during the first 24 hours of lactation, but continuously improved toward the end of the study with areas under the ROC curve increasing from 0.64 at d 0 to 0.93 at d +4 after calving. Strongest association with [iCa] : [TCa] were found for albumin (r2 = 0.58, P <.0001), pCO2 (r2 = 0.45, P =.0003), the standard [HCO3] (r2 = 0.22, P =.01), lactate (r2 = 0.16, P =.04) and [NEFA] (r2 = 0.15, P =.05). Conclusion and Clinical Importance: The [TCa] is of limited value to identify cows with subnormal [iCa] in the first hours and days of lactation, a finding apparently attributable to the increased variation of a number of metabolic variables that affect the ratio of [iCa] : [TCa]. [ABSTRACT FROM AUTHOR]

Regional citrate anticoagulation use in intermittent hemodialysis is limited by the increased risk of metabolic complications due to faster solute exchanges than with continuous renal replacement therapies. Several simplifications have been proposed. The objective of this study was to validate a mathematical model of hemodialysis anticoagulated with citrate that was then used to evaluate different prescription scenarios on anticoagulant effectiveness (free calcium concentration in dialysis filter) and calcium balance. A study was conducted in hemodialyzed patients with a citrate infusion into the arterial line and a 1.25 mmol/L calcium dialysate. Calcium and citrate concentrations were measured upstream and downstream of the citrate infusion site and in the venous line. The values measured in the venous lines were compared with those predicted by the model using Bland and Altman diagrams. The model was then used with 22 patients to make simulations. The model can predict the concentration of free calcium, bound to citrate or albumin, accurately. Irrespective of the prescription scenario a decrease in free calcium below 0.4 mmol/L was obtained only in a fraction of the dialysis filter. A zero or slightly negative calcium balance was observed, and should be taken into account in case of prolonged use. [ABSTRACT FROM AUTHOR]

The hair bundle of cochlear hair cells comprises specialized microvilli, the stereocilia, which fulfil the role of mechanotransduction. Genetic defects and environmental noise challenge the maintenance of hair bundle structure, critically contributing to age‐related hearing loss. Stereocilia fusion is a major component of the hair bundle pathology in mature hair cells, but its role in hearing loss and its molecular basis are poorly understood. Here, we utilized super‐resolution expansion microscopy to examine the molecular anatomy of outer hair cell stereocilia fusion in mouse models of age‐related hearing loss, heightened endoplasmic reticulum stress and prolonged noise exposure. Prominent stereocilia fusion in our model of heightened endoplasmic reticulum stress, Manf (Mesencephalic astrocyte‐derived neurotrophic factor)‐inactivated mice in a background with Cadherin 23 missense mutation, impaired mechanotransduction and calcium balance in stereocilia. This was indicated by reduced FM1‐43 dye uptake through the mechanotransduction channels, reduced neuroplastin/PMCA2 expression and increased expression of the calcium buffer oncomodulin inside stereocilia. Sparse BAIAP2L2 and myosin 7a expression was retained in the fused stereocilia but mislocalized away from their functional sites at the tips. These hair bundle abnormalities preceded cell soma degeneration, suggesting a sequela from stereociliary molecular perturbations to cell death signalling. In the age‐related hearing loss and noise‐exposure models, stereocilia fusion was more restricted within the bundles, yet both models exhibited oncomodulin upregulation at the fusion sites, implying perturbed calcium homeostasis. We conclude that stereocilia fusion is linked with the failure to maintain cellular proteostasis and with disturbances in stereociliary calcium balance. Key points: Stereocilia fusion is a hair cell pathology causing hearing loss.Inactivation of Manf, a component of the endoplasmic reticulum proteostasis machinery, has a cell‐intrinsic mode of action in triggering outer hair cell stereocilia fusion and the death of these cells.The genetic background with Cadherin 23 missense mutation contributes to the high susceptibility of outer hair cells to stereocilia fusion, evidenced in Manf‐inactivated mice and in the mouse models of early‐onset hearing loss and noise exposure.Endoplasmic reticulum stress feeds to outer hair cell stereocilia bundle pathology and impairs the molecular anatomy of calcium regulation.The maintenance of the outer hair cell stereocilia bundle cohesion is challenged by intrinsic and extrinsic stressors, and understanding the underlying mechanisms will probably benefit the development of interventions to promote hearing health. [ABSTRACT FROM AUTHOR]

Calcium balance is an overall assessment of the net calcium taken in minus the net calcium taken out. It can only be assessed when patients are in steady state and requires complicated isotope methods that can simultaneously assess intestinal absorption and endogenous secretion, urinary and stool excretion, bone calcium uptake and removal, and dialysate calcium removal. By virtue of the need for steady state, formal balance studies cannot be accurately carried out in patients on dialysis. However, many of the components of calcium balance have been assessed. Importantly, because 99% of calcium is in bone, studies must accurately assess both the rapidly exchangeable calcium from the bone surface and the net bone calcium balance that results from the difference in bone formation minus resorption. While it is tempting to adjust the dialysate calcium concentration to correct the net positive calcium balance that is likely present in patients who receive calcium-based phosphate binders, the reality is that the highly variable, yet important, role of bone cannot be easily assessed at the bedside. Thus, it is best to prevent the calcium overload in the first place by avoiding high-dose calcium-based phosphate binders and optimizing bone remodeling. [ABSTRACT FROM AUTHOR]

The mitochondrial calcium uniporter (MCU) is a transmembrane protein facilitating the entry of calcium ions into mitochondria from the cell cytosol. Maintaining calcium balance is crucial for enhancing cellular energy supply and regulating cell death. The interplay of calcium balance through MCU and the sodium-calcium exchanger is known, but its regulation in the breast cancer tumor microenvironment remains elusive. Further investigations are warranted to explore MCU's potential in BRCA clinical pathology, tumor immune microenvironment, and precision oncology. Our study, employing a multi-omics approach, identifies MCU as an independent diagnostic biomarker for breast cancer (BRCA), correlated with advanced clinical status and poor overall survival. Utilizing public datasets from GEO and TCGA, we discern differentially expressed genes in BRCA and examine their associations with immune gene expression, overall survival, tumor stage, gene mutation status, and infiltrating immune cells. Spatial transcriptomics is employed to investigate MCU gene expression in various regions of BRCA, while spatial transcriptomics and single-cell RNA-sequencing methods explore the correlation between MCUs and immune cells. Our findings are validated through the analysis of 59 BRCA patient samples, utilizing immunohistochemistry and bioinformatics to examine the relationship between MCU expression, clinicopathological features, and prognosis. The study uncovers the expression of key gene regulators in BRCA associated with genetic variations, deletions, and the tumor microenvironment. Mutations in these regulators positively correlate with different immune cells in six immune datasets, playing a pivotal role in immune cell infiltration in BRCA. Notably, high MCU performance is linked to CD8 + T cells infiltration in BRCA. Furthermore, pharmacogenomic analysis of BRCA cell lines indicates that MCU inactivation is associated with increased sensitivity to specific small molecule drugs. Our findings suggest that MCU alterations may be linked to BRCA progression, unveiling new diagnostic and prognostic implications for MCU in BRCA. The study underscores MCU's role in the tumor immune microenvironment and cell cycle progression, positioning it as a potential tool for BRCA precision medicine and drug screening. [ABSTRACT FROM AUTHOR]

To provide new estimates of the average Ca requirement for men and women, we determined the dietary Ca intake required to maintain neutral Ca balance. Ca balance data (Ca intake - [fecal Ca + urinary Ca]) were collected from 154 subjects (females: n=73, weight=-77.1±18.5 kg, age=47.0±18.5 y [range: 20-75 y]; males: n=81, weight=-76.6±12.6 kg, age=28.2±7.7 y [range: 19-64 y]) who participated in 19 different tightly-controlled feeding studies conducted in a metabolic unit. Balance data from the last 6-14 d of each dietary period (rain. length 28 d) of each study (1-9 observations per subject) were analyzed. Data were excluded if individual intakes of Mg, Cu, Fe, P, or Zn fell below the Estimated Average Requirements or exceeded the 99th %tile of 1994 CSFII usual intakes (for Fe, above the UL). Daily intakes of Ca ranged between 415 and 1740 mg. The relation between intake and output was examined by fitting random coefficient models using SAS Proc Mixed. Coefficients were included to test for gender differences. The models predicted neutral Ca balance (defined as Ca output (Y) equal to Ca intake (C)) of 741 mg/d [507 - 1035, 95% prediction interval (PI); Y = 148.29 + 0.80C], 9.4 mg/kg/d [6.4 - 12.9, 95% PI; Y = 1.44 + 0.85C], or 0.28 mg/kcal/d [0.19 - 0.38, 95% PI; Y = 0.051 + 0.816]. Neither age nor sex affected the estimates when expressed as mg/d or mg/kg/d. The findings suggest a lower Ca requirement for men and women than estimated previously. [ABSTRACT FROM AUTHOR]

Mineral and bone disorders (MBD) are common in patients with chronic kidney disease (CKD), contributing to significant morbidity and mortality. For several decades, the first-line approach to controlling hyperparathyroidism in CKD was by exogenous calcium loading. Since the turn of the millennium, however, a growing awareness of vascular calcification risk has led to a paradigm shift in management and a move away from calcium-based phosphate binders. As a consequence, contemporary CKD patients may be at risk of a negative calcium balance, which, in turn, may compromise bone health, contributing to renal bone disease and increased fracture risk. A calcium intake below a certain threshold may be as problematic as a high intake, worsening the MBD syndrome of CKD, but is not addressed in current clinical practice guidelines. The CKD-MBD and European Renal Nutrition working groups of the European Renal Association (ERA), together with the CKD-MBD and Dialysis working groups of the European Society for Pediatric Nephrology (ESPN), developed key evidence points and clinical practice points on calcium management in children and adults with CKD across stages of disease. These were reviewed by a Delphi panel consisting of ERA and ESPN working groups members. The main clinical practice points include a suggested total calcium intake from diet and medications of 800–1000 mg/day and not exceeding 1500 mg/day to maintain a neutral calcium balance in adults with CKD. In children with CKD, total calcium intake should be kept within the age-appropriate normal range. These statements provide information and may assist in decision-making, but in the absence of high-level evidence must be carefully considered and adapted to individual patient needs. [ABSTRACT FROM AUTHOR]