Browsing by Subject "Calcium"

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  • Cano, Antonio; Chedraui, Peter; Goulis, Dimitrios G.; Lopes, Patrice; Mishra, Gita; Mueck, Alfred; Senturk, Levent M.; Simoncini, Tommaso; Stevenson, John C.; Stute, Petra; Tuomikoski, Pauliina; Rees, Margaret; Lambrinoudaki, Irene (2018)
    Introduction: Postmenopausal osteoporosis is a highly prevalent disease. Prevention through lifestyle measures includes an adequate calcium intake. Despite the guidance provided by scientific societies and governmental bodies worldwide, many issues remain unresolved. Aims: To provide evidence regarding the impact of calcium intake on the prevention of postmenopausal osteoporosis and critically appraise current guidelines. Materials and methods: Literature review and consensus of expert opinion. Results and conclusion: The recommended daily intake of calcium varies between 700 and 1200 mg of elemental calcium, depending on the endorsing source. Although calcium can be derived either from the diet or supplements, the former source is preferred. Intake below the recommended amount may increase fragility fracture risk; however, there is no consistent evidence that calcium supplementation at, or above, recommended levels reduces risk. The addition of vitamin D may minimally reduce fractures, mainly among institutionalised people. Excessive intake of calcium, defined as higher than 2000 mg/day, can be potentially harmful. Some studies demonstrated harm even at lower dosages. An increased risk for cardiovascular events, urolithiasis and even fractures has been found in association with excessive calcium intake, but this issue remains unresolved. In conclusion, an adequate intake of calcium is recommended for general bone health. Excessive calcium intake seems of no benefit, and could possibly be harmful.
  • Itkonen, Suvi T.; Rita, Hannu J.; Saarnio, Elisa M.; Kemi, Virpi E.; Karp, Heini J.; Kärkkäinen, Merja; Pekkinen, Minna H.; Laitinen, E. Kalevi; Risteli, Juha; Koivula, Marja-Kaisa; Sievanen, Harri; Lamberg-Allardt, Christel J. E. (2017)
    High dietary phosphorus (P) intake has acute negative effects on calcium (Ca) and bone metabolism, but long-term clinical data are contradictory. We hypothesized that high P intake is associated with impaired bone health as suggested by earlier short-term studies on bone metabolism. In this cross-sectional study, we investigated associations between dietary P intake, bone traits in the radius and tibia, and bone turnover in a population-based sample of 37- to 47-year-old Caucasian premenopausal women (n = 333) and men (n = 179) living in Southern Finland (60 degrees N). We used various regression models in an "elaboration approach" to elucidate the role of P intake in bone traits and turnover. The addition of relevant covariates to the models mainly removed the significance of P intake as a determinant of bone traits. In the final regression model (P intake, weight, height, age, Ca intake, serum 25-hydroxyvitamin D, physical activity, smoking, contraceptive use in women), P intake was slightly positively associated only with bone mineral content and cross-sectional cortical bone area in the tibia of men. Among women, inclusion of Ca removed all existing significance in the crude models for any bone trait. In women P intake was negatively associated with the bone formation marker serum intact pro-collagen type I amino-terminal propeptide, whereas no association was present between P intake and bone turnover in men. In conclusion, these findings disagree with the hypothesis; P intake was not deleteriously associated with bone traits; however, P intake may negatively contribute to bone formation among women. (C) 2016 Elsevier Inc. All rights reserved.
  • Ruiz, Sandra R.; Eeva, Tapio; Kanerva, Mirella; Blomberg, Anna; Lilley, Thomas M. (2019)
    Metal elements, ubiquitous in the environment, can cause negative effects in long-lived organisms even after low but prolonged exposure. Insectivorous bats living near metal emission sources can be vulnerable to such contaminants. Although it is known that bats can bioaccumulate metals, little information exists on the effects of metal elements on their physiological status. For example, oxidative status markers are known to vary after detoxification processes and immune reactions. Here, for two consecutive summers, we sampled individuals from a natural population of the insectivorous bat, Myotis daubentonii, inhabiting a site close to a metal emission source. We quantified metals and metalloids (As, Ca, Cd, Co, Cu, Mn, Ni, Pb, Se, Zn) from individual fecal pellets. We measured enzymatic antioxidants (GP, CAT, SOD), total glutathione (tGSH) and ratio between reduced and oxidized glutathione (GSH:GSSG) from their red blood cells together with biometrics, hematocrit and parasite prevalence. In general, metal concentrations in feces of M. daubentonii reflected the exposure to ambient contamination. This was especially evident in the higher concentrations of Cd, Co, Cu and Ni close to a smelter compared to a site with less contaminant exposure. Annual differences were also observed for most elements quantified. Sex-specific differences were observed for calcium and zinc excretion. SOD and CAT enzymatic activities were associated with metal levels (principal components of six metal elements), suggesting early signs of chronic stress in bats. The study also shows promise for the use of non-invasive sampling to assess the metal exposure on an individual basis and metal contamination in the environment.
  • Pulli, Ilari; Lassila, Taru; Pan, Guoping; Yan, Daoguang; Olkkonen, Vesa M.; Törnquist, Kid (2018)
    Oxysterol-binding protein related-protein 5 and 8 (ORP5/8) localize to the membrane contact sites (MCS) of the endoplasmic reticulum (ER) and the mitochondria, as well as to the ER-plasma membrane (PM) MCS. The MCS are emerging as important regulators of cell signaling events, including calcium (Ca2+) signaling. ORP5/8 have been shown to interact with phosphatidylinositol-4,5-bisphosphate (PIP2) in the PM, and to modulate mitochondrial respiration and morphology. PIP2 is the direct precursor of inositol trisphosphate (IP3), a key second messenger responsible for Ca2+-release from the intracellular Ca2+ stores. Further, mitochondrial respiration is linked to Ca2+ transfer from the ER to the mitochondria. Hence, we asked whether ORP5/8 would affect Ca2+ signaling in these cell compartments, and employed genetically engineered aequorin Ca2+ probes to investigate the effect of ORP5/8 in the regulation of mitochondrial and caveolar Ca2+. Our results show that ORP5/8 overexpression leads to increased mitochondrial matrix Ca2+ as well as to increased Ca2+ concentration at the caveolar subdomains of the PM during histamine stimulation, while having no effect on the cytoplasmic Ca2+. Also, we found that ORP5/8 overexpression increases cell proliferation. Our results show that ORP5/8 regulate Ca2+ signaling at specific MCS foci. These local ORP5/8-mediated Ca2+ signaling events are likely to play roles in processes such as mitochondrial respiration and cell proliferation.
  • Rinne, Maiju K.; Leino, Teppo O.; Turku, Ainoleena; Turunen, Pauli M.; Steynen, Yana; Xhaard, Henri; Wallen, Erik A. A.; Kukkonen, Jyrki P. (2018)
    One promising series of small-molecule orexin receptor agonists has been described, but the molecular pharmacological properties, i.e. ability and potency to activate the different orexin receptor-regulated signal pathways have not been reported for any of these ligands. We have thus here assessed these properties for the most potent ligand of the series, 4'-methoxy-N,N-dimethyl-3'4N-(3-{[2-(3-methylbenzamido)ethyl]amino}phenyl sulfamoy1]-(1,1'-biphenyl)-3-carboxamide (Nag 26). Chinese hamster ovary-K1 cells expressing human orexin receptor subtypes OX1 and OX2 were used. Ca2+ elevation and cell viability and death were assessed by fluorescent methods, the extracellular signal-regulated kinase pathway by a luminescent Elk-1 reporter assay, and phospholipase C and adenylyl cyclase activities by radioactive methods. The data suggest that for the G(q)-dependent responses, Ca2+, phospholipase C and Elk-1, Nag 26 is a full agonist for both receptors, though of much lower potency. However, saturation was not always reached for OX1, partially due to Nag 26s low solubility and partially because the response decreased at high concentrations. The latter occurs in the same range as some reduction of cell viability, which is independent of orexin receptors. Based on the EC50, Nag 26 was OX2 selective by 20-200 fold in different assays, with some indication of biased agonism (as compared to orexin-A). Nag 26 is a potent orexin receptor agonist with a largely similar pharmacological profile as orexin-A. However, its weaker potency (low-mid micromolar) and low water solubility as well as the non-specific effect in the mid-micromolar range may limit its usefulness under physiological conditions.
  • Nordström, Tommy; Andersson, Leif C.; Åkerman, Karl E. O. (2019)
    A stroke causes a hypoxic brain microenvironment that alters neural cell metabolism resulting in cell membrane hyperpolarization and intracellular acidosis. We studied how intracellular pH (pH(i)) is regulated in differentiated mouse neural progenitor cells during hyperpolarizing conditions, induced by prompt reduction of the extra cellular K+ concentration. We found that the radial glia-like population in differentiating embryonic neural progenitor cells, but not neuronal cells, was rapidly acidified under these conditions. However, when extra cellular calcium was removed, an instant depolarization and recovery of the pH(i), back to normal levels, took place. The rapid recovery phase seen in the absence of calcium, was dependent on extracellular bicarbonate and could be inhibited by 50859, a potent Na/HCO3 cotransporter inhibitor. Immunostaining and PCR data, showed that NBCe1 (SLC4A4) and NBCn1 (SLC4A7) were expressed in the cell population and that the pH(i) recovery in the radial glial-like cells after calcium removal was mediated mainly by the electrogenic sodium bicarbonate transporter NBCe1 (SLC4A4). Our results indicate that extracellular calcium might hamper pH(i) regulation and Na/HCO3 cotransporter activity in a brain injury microenvironment. Our findings show that the NBC-type transporters are the main pH(i) regulating systems prevailing in glia-like progenitor cells and that these calcium sensitive transporters are important for neuronal progenitor cell proliferation, survival and neural stem cell differentiation.
  • Zeng, Zhen; Li, Cheng; Ertbjerg, Per (2017)
    The purpose of this study was to increase the knowledge on the relationship between proteolysis of myofibrillar proteins and the water-holding of meat. Myofibrils isolated from porcine longissimus thoracic et lumborum muscle were used as a model system. Myofibrils were incubated with either calpain-2, the proteasome or a lysosomal extract at 25 degrees C for 2 h. All three proteolytic systems improved the relative water-holding and generally there was a larger effect with increasing amount of enzymes in the incubation. The improved water-holding occurred in parallel to degradation of myofibrillar proteins. Desmin was degraded by calpain-2 as well as by lysosomal enzymes and a-actinin was released by the proteasome. We here propose a model in which degradation of proteins in and around the Z-disk allows overall swelling of the filament lattice and more specifically in the I band area. In conclusion, proteolytic degradation of myofibrillar proteins by calpain-2, the proteasome or lysosomal enzymes improves the water-holding of myofibrils.
  • Pulli, Ilari; Lof, C.; Blom, T.; Asghar, M. Y.; Lassila, T.; Back, N.; Lin, K-L; Nystrom, J. H.; Kemppainen, K.; Toivola, D. M.; Dufour, E.; Sanz, A.; Cooper, H. M.; Parys, J. B.; Tornquist, K. (2019)
    Sphingosine kinase 1 (SKI) converts sphingosine to the bioactive lipid sphingosine 1-phosphate (SIP). SW binds to G-protein-coupled receptors (S1PR(1-5)) to regulate cellular events, including Ca2+ signaling. The SK1/S1P axis and Ca2+ signaling both play important roles in health and disease. In this respect, Ca2+ microdomains at the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are of importance in oncogenesis. Mitofusin 2 (MFN2) modulates ER-mitochondria contacts, and dysregulation of MFN2 is associated with malignancies. We show that overexpression of SKI augments agonist-induced Ca2+ release from the ER resulting in increased mitochondria] matrix Ca2+. Also, overexpression of SK1 induces MFN2 fragmentation, likely through increased calpain activity. Further, expressing putative calpain-cleaved MFN2 N- and C-terminal fragments increases mitochondrial matrix Ca2+ during agonist stimulation, mimicking the SK1 overexpression in cells. Moreover, SK1 overexpression enhances cellular respiration and cell migration. Thus, SK1 regulates MFN2 fragmentation resulting in increased mitochondrial Ca2+ and downstream cellular effects.
  • McAlister, Louise; Pugh, Pearl; Greenbaum, Laurence; Haffner, Dieter; Rees, Lesley; Anderson, Caroline; Desloovere, An; Nelms, Christina; Oosterveld, Michiel; Paglialonga, Fabio; Polderman, Nonnie; Qizalbash, Leila; Renken-Terhaerdt, Jose; Tuokkola, Jetta; Warady, Bradley; Walle, Johan Vande; Shaw, Vanessa; Shroff, Rukshana (2020)
    In children with chronic kidney disease (CKD), optimal control of bone and mineral homeostasis is essential, not only for the prevention of debilitating skeletal complications and achieving adequate growth but also for preventing vascular calcification and cardiovascular disease. Complications of mineral bone disease (MBD) are common and contribute to the high morbidity and mortality seen in children with CKD. Although several studies describe the prevalence of abnormal calcium, phosphate, parathyroid hormone, and vitamin D levels as well as associated clinical and radiological complications and their medical management, little is known about the dietary requirements and management of calcium (Ca) and phosphate (P) in children with CKD. The Pediatric Renal Nutrition Taskforce (PRNT) is an international team of pediatric renal dietitians and pediatric nephrologists, who develop clinical practice recommendations (CPRs) for the nutritional management of various aspects of renal disease management in children. We present CPRs for the dietary intake of Ca and P in children with CKD stages 2-5 and on dialysis (CKD2-5D), describing the common Ca- and P-containing foods, the assessment of dietary Ca and P intake, requirements for Ca and P in healthy children and necessary modifications for children with CKD2-5D, and dietary management of hypo- and hypercalcemia and hyperphosphatemia. The statements have been graded, and statements with a low grade or those that are opinion-based must be carefully considered and adapted to individual patient needs based on the clinical judgment of the treating physician and dietitian. These CPRs will be regularly audited and updated by the PRNT.
  • Makitaipale, J.; Sankari, S.; Sievänen, H.; Laitinen-Vapaavuori, O. (2020)
    Background Vitamin D deficiency and related metabolic bone diseases in pet rabbits have been intermittently debated. In human research, the parathyroid hormone concentration in relation to the 25-hydroxyvitamin D concentration is used to determine vitamin D deficiency. Thus, this study aimed to identify the breakpoint in the 25-hydroxyvitamin D concentration indicating a significant change in the parathyroid hormone concentration in 139 pet rabbits. An enzyme immunoassay kit was used for 25-hydroxyvitamin D analysis and the intact parathyroid hormone (PTH 1-84) immunoradiometric assay kit for parathyroid hormone analysis. The mid-tibial cortical bone density was measured using peripheral quantitative computed tomography. A segmented linear regression analysis was performed, with the 25-hydroxyvitamin D concentration as the independent variable, and parathyroid hormone, ionised calcium, total calcium, inorganic phosphorus concentrations and the mid-tibial cortical density as the dependent variables. Results The breakpoint for the parathyroid hormone concentration occurred at a 25(OH)D concentration of 17 ng/mL, whereas the cortical bone density breakpoint occurred at a 25-hydroxyvitamin D concentration of 19 ng/mL. No breakpoints were found for ionised calcium, total calcium or phosphorus. Conclusions These results suggest that a serum 25-hydroxyvitamin D concentration of 17 ng/mL serves as the threshold for vitamin D deficiency in rabbits. Nearly one-third of the rabbits had a serum 25-hydroxyvitamin D concentration below this threshold. Concerns persist regarding the high prevalence of vitamin D deficiency in pet rabbits and the possible health consequences caused by a chronic vitamin D deficiency, including the risk for metabolic bone diseases.
  • Mäkitaipale, J.; Sankari, S.; Sievänen, H.; Laitinen-Vapaavuori, O. (BioMed Central, 2020)
    Abstract Background Vitamin D deficiency and related metabolic bone diseases in pet rabbits have been intermittently debated. In human research, the parathyroid hormone concentration in relation to the 25-hydroxyvitamin D concentration is used to determine vitamin D deficiency. Thus, this study aimed to identify the breakpoint in the 25-hydroxyvitamin D concentration indicating a significant change in the parathyroid hormone concentration in 139 pet rabbits. An enzyme immunoassay kit was used for 25-hydroxyvitamin D analysis and the intact parathyroid hormone (PTH 1–84) immunoradiometric assay kit for parathyroid hormone analysis. The mid-tibial cortical bone density was measured using peripheral quantitative computed tomography. A segmented linear regression analysis was performed, with the 25-hydroxyvitamin D concentration as the independent variable, and parathyroid hormone, ionised calcium, total calcium, inorganic phosphorus concentrations and the mid-tibial cortical density as the dependent variables. Results The breakpoint for the parathyroid hormone concentration occurred at a 25(OH)D concentration of 17 ng/mL, whereas the cortical bone density breakpoint occurred at a 25-hydroxyvitamin D concentration of 19 ng/mL. No breakpoints were found for ionised calcium, total calcium or phosphorus. Conclusions These results suggest that a serum 25-hydroxyvitamin D concentration of 17 ng/mL serves as the threshold for vitamin D deficiency in rabbits. Nearly one-third of the rabbits had a serum 25-hydroxyvitamin D concentration below this threshold. Concerns persist regarding the high prevalence of vitamin D deficiency in pet rabbits and the possible health consequences caused by a chronic vitamin D deficiency, including the risk for metabolic bone diseases.
  • Maack, Christoph; Eschenhagen, Thomas; Hamdani, Nazha; Heinzel, Frank R.; Lyon, Alexander R.; Manstein, Dietmar J.; Metzger, Joseph; Papp, Zoltan; Tocchetti, Carlo G.; Yilmaz, M. Birhan; Anker, Stefan D.; Balligand, Jean-Luc; Bauersachs, Johann; Brutsaert, Dirk; Carrier, Lucie; Chlopicki, Stefan; Cleland, John G.; de Boer, Rudolf A.; Dietl, Alexander; Fischmeister, Rodolphe; Harjola, Veli-Pekka; Heymans, Stephane; Hilfiker-Kleiner, Denise; Holzmeister, Johannes; de Keulenaer, Gilles; Limongelli, Giuseppe; Linke, Wolfgang A.; Lund, Lars H.; Masip, Josep; Metra, Marco; Mueller, Christian; Pieske, Burkert; Ponikowski, Piotr; Ristic, Arsen; Ruschitzka, Frank; Seferovic, Petar M.; Skouri, Hadi; Zimmermann, Wolfram H.; Mebazaa, Alexandre (2019)
    Acute heart failure (HF) and in particular, cardiogenic shock are associated with high morbidity and mortality. A therapeutic dilemma is that the use of positive inotropic agents, such as catecholamines or phosphodiesterase-inhibitors, is associated with increased mortality. Newer drugs, such as levosimendan or omecamtiv mecarbil, target sarcomeres to improve systolic function putatively without elevating intracellular Ca2+. Although meta-analyses of smaller trials suggested that levosimendan is associated with a better outcome than dobutamine, larger comparative trials failed to confirm this observation. For omecamtiv mecarbil, Phase II clinical trials suggest a favourable haemodynamic profile in patients with acute and chronic HF, and a Phase III morbidity/mortality trial in patients with chronic HF has recently begun. Here, we review the pathophysiological basis of systolic dysfunction in patients with HF and the mechanisms through which different inotropic agents improve cardiac function. Since adenosine triphosphate and reactive oxygen species production in mitochondria are intimately linked to the processes of excitation-contraction coupling, we also discuss the impact of inotropic agents on mitochondrial bioenergetics and redox regulation. Therefore, this position paper should help identify novel targets for treatments that could not only safely improve systolic and diastolic function acutely, but potentially also myocardial structure and function over a longer-term.