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Sample records for calcium 44 target

  1. 44gSc from metal calcium targets for PET

    DEFF Research Database (Denmark)

    Severin, Gregory; Gagnon, K.; Engle, J. W.

    2012-01-01

    A low-cost and efficient method for producing pre-clinical scale quantities of 44gSc is presented. Production involves proton irradiation of natural unenriched calcium metal followed by rapid separation of radioscandium from the target using hydroxmate functionalized resin.© 2012 American Institu...

  2. Cyclotron Produced 44gSc from Natural Calcium

    Science.gov (United States)

    Severin, G.W.; Engle, J.W.; Valdovinos, H.F.; Barnhart, T.E.; Nickles, R.J.

    2012-01-01

    44gSc was produced by 16 MeV proton irradiation of unenriched calcium metal with radionuclidic purity greater than 95%. The thick target yield at saturation for 44gSc was 213 MBq/μA, dwarfing the yields of contaminants 43Sc,44mSc, 47Sc and 48Sc for practical bombardment times of 1–2 h. Scandium was isolated from the dissolved calcium target by filtration, and reconstituted in small volumes of dilute HCl. Reactions with the chelate 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) indicated a reactivity of 54±14 Gbq/μmol at end-of-bombardment. PMID:22728844

  3. Production of scandium-44m and scandium-44g with deuterons on calcium-44: cross section measurements and production yield calculations

    Science.gov (United States)

    Duchemin, C.; Guertin, A.; Haddad, F.; Michel, N.; Métivier, V.

    2015-09-01

    HIGHLIGHTS • Production of Sc-44m, Sc-44g and contaminants. • Experimental values determined using the stacked-foil technique. • Thick-Target production Yield (TTY) calculations. • Comparison with the TALYS code version 1.6. Among the large number of radionuclides of medical interest, Sc-44 is promising for PET imaging. Either the ground-state Sc-44g or the metastable-state Sc-44m can be used for such applications, depending on the molecule used as vector. This study compares the production rates of both Sc-44 states, when protons or deuterons are used as projectiles on an enriched Calcium-44 target. This work presents the first set of data for the deuteron route. The results are compared with the TALYS code. The Thick-Target production Yields of Sc-44m and Sc-44g are calculated and compared with those for the proton route for three different scenarios: the production of Sc-44g for conventional PET imaging, its production for the new 3 γ imaging technique developed at the SUBATECH laboratory and the production of a Sc-44m/Sc-44g in vivo generator for antibody labelling.

  4. Cyclotron production of high purity (44m,44)Sc with deuterons from (44)CaCO3 targets.

    Science.gov (United States)

    Alliot, C; Kerdjoudj, R; Michel, N; Haddad, F; Huclier-Markai, S

    2015-06-01

    Due to its longer half-life, (44)Sc (T1/2 = 3.97 h) as a positron emitter can be an interesting alternative to (68)Ga (T1/2 = 67.71 min). It has been already proposed as a PET radionuclide for scouting bone disease and is already available as a (44)Ti/(44)Sc generator. (44)Sc has an isomeric state, (44 m)Sc (T1/2 = 58.6 h), which can be co-produced with (44)Sc and that has been proved to be considered as an in-vivo PET generator (44 m)Sc/(44)Sc. This work presents the production route of (44 m)Sc/(44)Sc generator from (44)Ca(d,2n), its extraction/purification process and the evaluation of its performances. Irradiation was performed in a low activity target station using a deuteron beam of 16 MeV, which favors the number of (44 m)Sc atoms produced simultaneously to (44)Sc. Typical irradiation conditions were 60 min at 0.2 μA producing 44 MBq of (44)Sc with a (44)Sc/(44 m)Sc activity ratio of 50 at end of irradiation. Separations of the radionuclides were performed by means of cation exchange chromatography using a DGA® resin (Triskem). Then, the developed process was applied with bigger targets, and could be used for preclinical studies. The extraction/purification process leads to a radionucleidic purity higher than 99.99% ((43)Sc, (46)Sc, (48)Sc < DL). (44 m)Sc/(44)Sc labeling towards DOTA moiety was performed in order to get an evaluation of the specific activities that could be reached with regard to all metallic impurities from the resulting source. Reaction parameters of radiolabeling were optimized, reaching yields over 95%, and leading to a specific activity of about 10-20 MBq/nmol for DOTA. A recycling process for the enriched (44)Ca target was developed and optimized. The quality of the final batch with regard to radionucleidic purity, specific activity and metal impurities allowed a right away use for further radiopharmaceutical evaluation. This radionucleidic pair of (44 m)Sc/(44)Sc offers a quite interesting PET radionuclide for being further

  5. Proton bombarded reactions of Calcium target nuclei

    Directory of Open Access Journals (Sweden)

    Tel Eyyup

    2017-01-01

    Full Text Available In this study, proton bombarded nuclear reactions calculations of Calcium target nuclei have been investigated in the incident proton energy range of 1–50 MeV. The excitation functions for 40Ca target nuclei reactions have been calculated by using PCROSS nuclear reaction calculation code. Weisskopf-Ewing and the full exciton models were used for equilibrium and for pre-equilibrium calculations, respectively. The excitation functions for 40Ca target nuclei reactions (p,α, (p,n, (p,p have been calculated using the semi-empirical formula Tel et al. [5].

  6. Constraining calcium isotope fractionation (d44/40Ca) in modern and fossil scleractinian coral skeleton

    OpenAIRE

    Pretet Chloé; Samankassou Elias; Felis Thomas; Reynaud Stéphanie; Böhm Florian; Eisenhauer Anton; Ferrier-Pagès Christine; Gattuso Jean-Pierre; Camoin Gilbert

    2013-01-01

    The present study investigates the influence of environmental (temperature salinity) and biological (growth rate inter generic variations) parameters on calcium isotope fractionation (d44/40Ca) in scleractinian coral skeleton to better constrain this record. Previous studies focused on the d44/40Ca record in different marine organisms to reconstruct seawater composition or temperature but only few studies investigated corals. This study presents measurements performed on modern corals from n...

  7. Constraining calcium isotope fractionation (δ44/40Ca) in modern and fossil scleractinian coral skeleton

    OpenAIRE

    Pretet, Chloé; Samankassou, Elias; Felis, Thomas; Reynaud, Stéphanie; Böhm, Florian; Eisenhauer, Anton; Ferrier-Pagès, Christine; Gattuso, Jean-Pierre; Camoin, Gilbert

    2013-01-01

    The present study investigates the influence of environmental (temperature, salinity) and biological (growth rate, inter-generic variations) parameters on calcium isotope fractionation (δ44/40Ca) in scleractinian coral skeleton to better constrain this record. Previous studies focused on the δ44/40Ca record in different marine organisms to reconstruct seawater composition or temperature, but only few studies investigated corals. This study presents measurements performed on modern corals f...

  8. (44g)Sc production using a water target on a 13MeV cyclotron.

    Science.gov (United States)

    Hoehr, Cornelia; Oehlke, Elisabeth; Benard, Francois; Lee, Chris Jaeil; Hou, Xinchi; Badesso, Brian; Ferguson, Simon; Miao, Qing; Yang, Hua; Buckley, Ken; Hanemaayer, Victoire; Zeisler, Stefan; Ruth, Thomas; Celler, Anna; Schaffer, Paul

    2014-01-01

    Access to promising radiometals as isotopes for novel molecular imaging agents requires that they are routinely available and inexpensive to obtain. Proximity to a cyclotron center outfitted with solid target hardware, or to an isotope generator for the metal of interest is necessary, both of which can introduce significant hurdles in development of less common isotopes. Herein, we describe the production of ⁴⁴Sc (t1/2=3.97 h, Eavg,β⁺=1.47MeV, branching ratio=94.27%) in a solution target and an automated loading system which allows a quick turn-around between different radiometallic isotopes and therefore greatly improves their availability for tracer development. Experimental yields are compared to theoretical calculations. Solutions containing a high concentration (1.44-1.55g/mL) of natural-abundance calcium nitrate tetrahydrate (Ca(NO₃)2·4 H₂O) were irradiated on a 13MeV proton-beam cyclotron using a standard liquid target. (44g)Sc was produced via the ⁴⁴Ca(p,n)(44g)Sc reaction. (44g)Sc was produced for the first time in a solution target with yields sufficient for early radiochemical studies. Saturation yields of up to 4.6 ± 0.3 MBq/μA were achieved using 7.6 ± 0.3 μA proton beams for 60.0 ± 0.2 minutes (number of runs n=3). Experimental data and calculation results are in fair agreement. Scandium was isolated from the target mixture via solid-phase extraction with 88 ± 6% (n=5) efficiency and successfully used for radiolabelling experiments. The demonstration of the production of ⁴⁴Sc in a liquid target greatly improves its availability for tracer development. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Calcium oxalate crystal adherence to hyaluronan-, osteopontin-, and CD44-expressing injured/regenerating tubular epithelial cells in rat kidneys

    NARCIS (Netherlands)

    M. Asselman (Marino); A. Verhulst; M.E. de Broe; C.F. Verkoelen

    2003-01-01

    textabstractRetention of crystals in the kidney is an essential early step in renal stone formation. Studies with renal tubular cells in culture indicate that hyaluronan (HA) and osteopontin (OPN) and their mutual cell surface receptor CD44 play an important role in calcium oxalate

  10. The Importance of CD44 as a Stem Cell Biomarker and Therapeutic Target in Cancer

    Directory of Open Access Journals (Sweden)

    Ranjeeta Thapa

    2016-01-01

    Full Text Available CD44 is a cell surface HA-binding glycoprotein that is overexpressed to some extent by almost all tumors of epithelial origin and plays an important role in tumor initiation and metastasis. CD44 is a compelling marker for cancer stem cells of many solid malignancies. In addition, interaction of HA and CD44 promotes EGFR-mediated pathways, consequently leading to tumor cell growth, tumor cell migration, and chemotherapy resistance in solid cancers. Accumulating evidence indicates that major HA-CD44 signaling pathways involve a specific variant of CD44 isoforms; however, the particular variant almost certainly depends on the type of tumor cell and the stage of the cancer progression. Research to date suggests use of monoclonal antibodies against different CD44 variant isoforms and targeted inhibition of HA/CD44-mediated signaling combined with conventional radio/chemotherapy may be the most favorable therapeutic strategy for future treatments of advanced stage malignancies. Thus, this paper briefly focuses on the association of the major CD44 variant isoforms in cancer progression, the role of HA-CD44 interaction in oncogenic pathways, and strategies to target CD44-overexpressed tumor cells.

  11. MicroRNA miR-328 regulates zonation morphogenesis by targeting CD44 expression.

    Directory of Open Access Journals (Sweden)

    Chia-Hui Wang

    Full Text Available Morphogenesis is crucial to initiate physiological development and tumor invasion. Here we show that a microRNA controls zonation morphogenesis by targeting hyaluronan receptor CD44. We have developed a novel system to study microRNA functions by generating constructs expressing pre-miRNAs and mature miRNAs. Using this system, we have demonstrated that expression of miR-328 reduced cell adhesion, aggregation, and migration, and regulated formation of capillary structure. Protein analysis indicated that miR-328 repressed CD44 expression. Activities of luciferase constructs harboring the target site in CD44, but not the one containing mutation, were repressed by miR-328. Zonation morphogenesis appeared in cells transfected by miR-328: miR-328-transfected cells were present on the surface of zonating structures while the control cells stayed in the middle. MiR-328-mediated CD44 actions was validated by anti-CD44 antibody, hyaluronidase, CD44 siRNA, and CD44 expression constructs. In vivo experiments showed that CD44-silencing cells appeared as layers on the surfaces of nodules or zonating structures. Immuno-histochemistry also exhibited CD44-negative cells on the surface layers of normal rat livers and the internal zones of Portal veins. Our results demonstrate that miR-328 targets CD44, which is essential in regulating zonation morphogenesis: silencing of CD44 expression is essential in sealing the zonation structures to facilitate their extension and to inhibit complex expansion.

  12. The Role of CD44 in Disease Pathophysiology And Targeted Treatment

    Directory of Open Access Journals (Sweden)

    Andre R. Jordan

    2015-04-01

    Full Text Available The cell-surface glycoprotein CD44 is involved in a multitude of important physiological functions including cell proliferation, adhesion, migration, hematopoiesis, and lymphocyte activation. The diverse physiological activity of CD44 is manifested in the pathology of a number of diseases including cancer, arthritis, bacterial and viral infections, interstitial lung disease, vascular disease and wound healing. This diversity in biological activity is conferred by both a variety of distinct CD44 isoforms generated through complex alternative splicing, posttranslational modifications (e.g., N- and O-glycosylation, interactions with a number of different ligands and the abundance and spatial distribution of CD44 on the cell surface. The extracellular matrix glycosaminoglycan hyaluronan (HA is the principle ligand of CD44. This review focuses both CD44-hyaluronan dependent and independent CD44 signaling and the role of CD44-HA interaction in various pathophysiologies. The review also discusses recent advances in novel treatment strategies that exploit the CD44-HA interaction either for direct targeting or for drug delivery.

  13. Hyaluronic acid modified mesoporous carbon nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells

    Science.gov (United States)

    Wan, Long; Jiao, Jian; Cui, Yu; Guo, Jingwen; Han, Ning; Di, Donghua; Chang, Di; Wang, Pu; Jiang, Tongying; Wang, Siling

    2016-04-01

    In this paper, hyaluronic acid (HA) functionalized uniform mesoporous carbon spheres (UMCS) were synthesized for targeted enzyme responsive drug delivery using a facile electrostatic attraction strategy. This HA modification ensured stable drug encapsulation in mesoporous carbon nanoparticles in an extracellular environment while increasing colloidal stability, biocompatibility, cell-targeting ability, and controlled cargo release. The cellular uptake experiments of fluorescently labeled mesoporous carbon nanoparticles, with or without HA functionalization, demonstrated that HA-UMCS are able to specifically target cancer cells overexpressing CD44 receptors. Moreover, the cargo loaded doxorubicin (DOX) and verapamil (VER) exhibited a dual pH and hyaluronidase-1 responsive release in the tumor microenvironment. In addition, VER/DOX/HA-UMCS exhibited a superior therapeutic effect on an in vivo HCT-116 tumor in BALB/c nude mice. In summary, it is expected that HA-UMCS will offer a new method for targeted co-delivery of drugs to tumors overexpressing CD44 receptors.

  14. CD44: a validated target for improved delivery of cancer therapeutics.

    Science.gov (United States)

    Ghosh, Sukhen C; Neslihan Alpay, Sultan; Klostergaard, Jim

    2012-07-01

    Advances in cancer therapeutics, namely more effective and less toxic treatments, will occur with targeting strategies that enhance the tumor biodistribution and thwart normal tissue exposure of the drug. This review focuses on cancer drug targeting approaches that exploit the expression of the cell-surface proteoglycan family, CD44, on the tumor cell surface followed by some form of ligand binding and induced CD44 internalization and intracellular drug release: in effect using this as a 'Trojan Horse' to more selectively access tumor cells. This review defines the origins of evidence for a linkage between CD44 expression and malignancy, and invokes contemporary views of the importance of putative CD44(+) cancer stem cells in disease resistance. Although the primary emphasis is on the most advanced and developed paths, those that have either made it to the clinic or are well-poised to get there, a wide scope of additional approaches at various preclinical stages is also briefly reviewed. The future should see development of drug targeting approaches that exploit CD44 expression on CSCs/TICs, including applications to cytotoxic agents currently in the clinic.

  15. Low threshold T‐type calcium channels as targets for novel epilepsy treatments

    National Research Council Canada - National Science Library

    Powell, Kim L; Cain, Stuart M; Snutch, Terrance P; O'Brien, Terence J

    2014-01-01

    .... T ‐type calcium channels are expressed widely throughout the brain and peripheral tissues, and thus have been proposed as therapeutic targets for a variety of diseases such as epilepsy, insomnia, pain...

  16. Calcium

    Science.gov (United States)

    ... Turn to calcium-fortified (or "calcium-set") tofu, soy milk, tempeh, soy yogurt, and cooked soybeans (edamame). Calcium-fortified foods. Look for calcium-fortified orange juice, soy or rice milk, breads, and cereal. Beans. You can get decent ...

  17. Hyaluronan functionalizing QDs as turn-on fluorescent probe for targeted recognition CD44 receptor

    Science.gov (United States)

    Zhou, Shang; Huo, Danqun; Hou, Changjun; Yang, Mei; Fa, Huanbao

    2017-09-01

    The recognition of tumor markers in living cancer cells has attracted increasing interest. In the present study, the turn-on fluorescence probe was designed based on the fluorescence of thiolated chitosan-coated CdTe QDs (CdTe/TCS QDs) quenched by hyaluronan, which could provide the low background signal for sensitive cellular imaging. This system is expected to offer specific recognition of CD44 receptor over other substances owing to the specific affinity of hyaluronan and CD44 receptor ( 8-9 kcal/mol). The probe is stable in aqueous and has little toxicity to living cells; thus, it can be utilized for targeted cancer cell imaging. The living lung cancer cell imaging experiments further demonstrate its value in recognizing cell-surface CD44 receptor with turn-on mode. In addition, the probe can be used to recognize and differentiate the subtypes of lung cancer cells based on the difference of CD44 expression on the surface of lung cancer cells. And, the western blot test further confirmed that the expression level of the CD44 receptor in lung cancer cells is different. Therefore, this probe may be potentially applied in recognizing lung cancer cells with higher contrast and sensitivity and provide new tools for cancer prognosis and therapy. [Figure not available: see fulltext.

  18. Lipid-Based Nanovectors for Targeting of CD44-Overexpressing Tumor Cells

    Directory of Open Access Journals (Sweden)

    Silvia Arpicco

    2013-01-01

    Full Text Available Hyaluronic acid (HA is a naturally occurring glycosaminoglycan that exists in living systems, and it is a major component of the extracellular matrix. The hyaluronic acid receptor CD44 is found at low levels on the surface of epithelial, haematopoietic, and neuronal cells and is overexpressed in many cancer cells particularly in tumour initiating cells. HA has been therefore used as ligand attached to HA-lipid-based nanovectors for the active targeting of small or large active molecules for the treatment of cancer. This paper describes the different approaches employed for the preparation, characterization, and evaluation of these potent delivery systems.

  19. Targeting Calcium Signaling Induces Epigenetic Reactivation of Tumor Suppressor Genes in Cancer.

    Science.gov (United States)

    Raynal, Noël J-M; Lee, Justin T; Wang, Youjun; Beaudry, Annie; Madireddi, Priyanka; Garriga, Judith; Malouf, Gabriel G; Dumont, Sarah; Dettman, Elisha J; Gharibyan, Vazganush; Ahmed, Saira; Chung, Woonbok; Childers, Wayne E; Abou-Gharbia, Magid; Henry, Ryan A; Andrews, Andrew J; Jelinek, Jaroslav; Cui, Ying; Baylin, Stephen B; Gill, Donald L; Issa, Jean-Pierre J

    2016-03-15

    Targeting epigenetic pathways is a promising approach for cancer therapy. Here, we report on the unexpected finding that targeting calcium signaling can reverse epigenetic silencing of tumor suppressor genes (TSG). In a screen for drugs that reactivate silenced gene expression in colon cancer cells, we found three classical epigenetic targeted drugs (DNA methylation and histone deacetylase inhibitors) and 11 other drugs that induced methylated and silenced CpG island promoters driving a reporter gene (GFP) as well as endogenous TSGs in multiple cancer cell lines. These newly identified drugs, most prominently cardiac glycosides, did not change DNA methylation locally or histone modifications globally. Instead, all 11 drugs altered calcium signaling and triggered calcium-calmodulin kinase (CamK) activity, leading to MeCP2 nuclear exclusion. Blocking CamK activity abolished gene reactivation and cancer cell killing by these drugs, showing that triggering calcium fluxes is an essential component of their epigenetic mechanism of action. Our data identify calcium signaling as a new pathway that can be targeted to reactivate TSGs in cancer. ©2015 American Association for Cancer Research.

  20. Hyaluronic acid modified mesoporous silica nanoparticles for targeted drug delivery to CD44-overexpressing cancer cells

    Science.gov (United States)

    Yu, Meihua; Jambhrunkar, Siddharth; Thorn, Peter; Chen, Jiezhong; Gu, Wenyi; Yu, Chengzhong

    2012-12-01

    In this paper, a targeted drug delivery system has been developed based on hyaluronic acid (HA) modified mesoporous silica nanoparticles (MSNs). HA-MSNs possess a specific affinity to CD44 over-expressed on the surface of a specific cancer cell line, HCT-116 (human colon cancer cells). The cellular uptake performance of fluorescently labelled MSNs with and without HA modification has been evaluated by confocal microscopy and fluorescence-activated cell sorter (FACS) analysis. Compared to bare MSNs, HA-MSNs exhibit a higher cellular uptake via HA receptor mediated endocytosis. An anticancer drug, doxorubicin hydrochloride (Dox), has been loaded into MSNs and HA-MSNs as drug delivery vehicles. Dox loaded HA-MSNs show greater cytotoxicity to HCT-116 cells than free Dox and Dox-MSNs due to the enhanced cell internalization behavior of HA-MSNs. It is expected that HA-MSNs have a great potential in targeted delivery of anticancer drugs to CD44 over-expressing tumors.

  1. Calcium

    Science.gov (United States)

    ... and blood vessels contract and expand, to secrete hormones and enzymes and to send messages through the nervous system. It is important to get plenty of calcium in the foods you eat. Foods rich in calcium include Dairy products such as milk, cheese, and yogurt Leafy, green vegetables Fish with ...

  2. Subcellular targeting of nine calcium-dependent protein kinase isoforms from Arabidopsis

    Science.gov (United States)

    Dammann, Christian; Ichida, Audrey; Hong, Bimei; Romanowsky, Shawn M.; Hrabak, Estelle M.; Harmon, Alice C.; Pickard, Barbara G.; Harper, Jeffrey F.; Evans, M. L. (Principal Investigator)

    2003-01-01

    Calcium-dependent protein kinases (CDPKs) are specific to plants and some protists. Their activation by calcium makes them important switches for the transduction of intracellular calcium signals. Here, we identify the subcellular targeting potentials for nine CDPK isoforms from Arabidopsis, as determined by expression of green fluorescent protein (GFP) fusions in transgenic plants. Subcellular locations were determined by fluorescence microscopy in cells near the root tip. Isoforms AtCPK3-GFP and AtCPK4-GFP showed a nuclear and cytosolic distribution similar to that of free GFP. Membrane fractionation experiments confirmed that these isoforms were primarily soluble. A membrane association was observed for AtCPKs 1, 7, 8, 9, 16, 21, and 28, based on imaging and membrane fractionation experiments. This correlates with the presence of potential N-terminal acylation sites, consistent with acylation as an important factor in membrane association. All but one of the membrane-associated isoforms targeted exclusively to the plasma membrane. The exception was AtCPK1-GFP, which targeted to peroxisomes, as determined by covisualization with a peroxisome marker. Peroxisome targeting of AtCPK1-GFP was disrupted by a deletion of two potential N-terminal acylation sites. The observation of a peroxisome-located CDPK suggests a mechanism for calcium regulation of peroxisomal functions involved in oxidative stress and lipid metabolism.

  3. Biocompatible hyaluronic acid polymer-coated quantum dots for CD44+ cancer cell-targeted imaging

    Science.gov (United States)

    Wang, Hening; Sun, Hongfang; Wei, Hui; Xi, Peng; Nie, Shuming; Ren, Qiushi

    2014-10-01

    The cysteamine-modified hyaluronic acid (HA) polymer was employed to coat quantum dots (QDs) through a convenient one-step reverse micelle method, with the final QDs hydrodynamic size of around 22.6 nm. The HA coating renders the QDs with very good stability in PBS for more than 140 days and resistant to large pH range of 2-12. Besides, the HA-coated QDs also show excellent fluorescence stability in BSA-containing cell culture medium. In addition, the cell culture assay indicates no significant cytotoxicity for MD-MB-231 breast cancer cells, and its targeting ability to cancer receptor CD44 has been demonstrated on two breast cancer cell lines. The targeting mechanism was further proved by the HA competition experiment. This work has established a new approach to help solve the stability and toxicity problems of QDs, and moreover render the QDs cancer targeting property. The current results indicate that the HA polymer-coated QDs hold the potential application for both in vitro and in vivo cancer imaging researches.

  4. Low threshold T-type calcium channels as targets for novel epilepsy treatments.

    Science.gov (United States)

    Powell, Kim L; Cain, Stuart M; Snutch, Terrance P; O'Brien, Terence J

    2014-05-01

    Low voltage-activated T-type calcium channels were originally cloned in the 1990s and much research has since focused on identifying the physiological roles of these channels in health and disease states. T-type calcium channels are expressed widely throughout the brain and peripheral tissues, and thus have been proposed as therapeutic targets for a variety of diseases such as epilepsy, insomnia, pain, cancer and hypertension. This review discusses the literature concerning the role of T-type calcium channels in physiological and pathological processes related to epilepsy. T-type calcium channels have been implicated in pathology of both the genetic and acquired epilepsies and several anti-epileptic drugs (AEDs) in clinical use are known to suppress seizures via inhibition of T-type calcium channels. Despite the fact that more than 15 new AEDs have become clinically available over the past 20 years at least 30% of epilepsy patients still fail to achieve seizure control, and many patients experience unwanted side effects. Furthermore there are no treatments that prevent the development of epilepsy or mitigate the epileptic state once established. Therefore there is an urgent need for the development of new AEDs that are effective in patients with drug resistant epilepsy, are anti-epileptogenic and are better tolerated. We also review the mechanisms of action of the current AEDs with known effects on T-type calcium channels and discuss novel compounds that are being investigated as new treatments for epilepsy. © 2013 The British Pharmacological Society.

  5. Calcium

    Science.gov (United States)

    ... from dietary supplements are linked to a greater risk of kidney stones, especially among older adults. But calcium from foods does not appear to cause kidney stones. For most people, other factors (such as not drinking enough fluids) probably have ...

  6. Manufacturing of calcium, lithium and molybdenum targets for use in nuclear physics experiments

    Energy Technology Data Exchange (ETDEWEB)

    Kheswa, N.Y., E-mail: kheswa@tlabs.ac.z [iThemba Laboratory for Accelerator Based Science, P.O. Box 722, Somerset West 7129, Western Cape (South Africa); Papka, P.; Buthelezi, E.Z.; Lieder, R.M.; Neveling, R.; Newman, R.T. [iThemba Laboratory for Accelerator Based Science, P.O. Box 722, Somerset West 7129, Western Cape (South Africa)

    2010-02-11

    This paper describes methods used in the manufacturing of chemically reactive targets such as calcium ({sup nat}Ca), lithium-6 ({sup 6}Li) and molybdenum-97 ({sup 97}Mo) for nuclear physics experiments at the iThemba LABS cyclotron facility (Faure, South Africa). Due to the chemical properties of these materials a suitable and controlled environment was established in order to minimize oxygen contamination of targets. Calcium was prepared by means of vacuum evaporation while lithium was cold rolled to a desired thickness. In the case of molybdenum, the metallic powder was melted under vacuum using an e-gun followed by cold rolling of the metal bead to a desired thickness. In addition, latest developments toward the establishment of a dedicated nuclear physics target laboratory are discussed.

  7. Mapping calcium phosphate activated gene networks as a strategy for targeted osteoinduction of human progenitors.

    Science.gov (United States)

    Eyckmans, Jeroen; Roberts, Scott J; Bolander, Johanna; Schrooten, Jan; Chen, Christopher S; Luyten, Frank P

    2013-06-01

    Although calcium phosphate-containing biomaterials are promising scaffolds for bone regenerative strategies, the osteoinductive capacity of such materials is poorly understood. In this study, we investigated whether endogenous mechanisms of in vivo calcium phosphate-driven, ectopic bone formation could be identified and used to induce enhanced differentiation in vitro of the same progenitor population. To accomplish this, human periosteum derived cells (hPDCs) were seeded on hydroxyapatite/collagen scaffolds (calcium phosphate rich matrix or CPRM), or on decalcified scaffolds (calcium phosphate depleted matrix or CPDM), followed by subcutaneous implantation in nude mice to trigger ectopic bone formation. In this system, osteoblast differentiation occurred in CPRM scaffolds, but not in CPDM scaffolds. Gene expression was assessed by human full-genome microarray at 20 h after seeding, and 2, 8 and 18 days after implantation. In both matrices, implantation of the cell constructs triggered a similar gene expression cascade, however, gene expression dynamics progressed faster in CPRM scaffolds than in CPDM scaffolds. The difference in gene expression dynamics was associated with differential activation of hub genes and molecular signaling pathways related to calcium signaling (CREB), inflammation (TNFα, NFkB, and IL6) and bone development (TGFβ, β-catenin, BMP, EGF, and ERK signaling). Starting from this set of pathways, a growth factor cocktail was developed that robustly enhanced osteogenesis in vitro and in vivo. Taken together, our data demonstrate that through the identification and subsequent stimulation of genes, proteins and signaling pathways associated with calcium phosphate mediated osteoinduction, a focused approach to develop targeted differentiation protocols in adult progenitor cells can be achieved. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Target size of calcium pump protein from skeletal muscle sarcoplasmic reticulum.

    Science.gov (United States)

    Hymel, L; Maurer, A; Berenski, C; Jung, C Y; Fleischer, S

    1984-04-25

    The oligomeric size of calcium pump protein (CPP) in fast skeletal muscle sarcoplasmic reticulum membrane was determined using target theory analysis of radiation inactivation data. There was a parallel decrease of Ca2+-ATPase and calcium pumping activities with increasing radiation dose. The loss of staining intensity of the CPP band, observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, also correlated directly with the loss of activity. The target size molecular weight of the CPP in the normal sarcoplasmic reticulum membrane ranged between 210,000 and 250,000, which is consistent with a dimeric structure. Essentially the same size is obtained for the non-phosphorylated CPP or for the phosphoenzyme form generated from either ATP (E1 state) or inorganic phosphate (E2 state). Hence, the oligomeric state of the pump does not appear to change during the catalytic cycle. Similar results were obtained with reconstituted sarcoplasmic reticulum membrane vesicles with different lipid to protein ratios. We conclude that the CPP is a dimer in both native and reconstituted sarcoplasmic reticulum membranes. The target size of the calcium-binding protein (calsequestrin) was found to be 50,000 daltons, approximating a monomer.

  9. Designing calcium phosphate-based bifunctional nanocapsules with bone-targeting properties

    Energy Technology Data Exchange (ETDEWEB)

    Khung, Yit-Lung; Bastari, Kelsen; Cho, Xing Ling; Yee, Wu Aik; Loo, Say Chye Joachim, E-mail: joachimloo@ntu.edu.sg [Nanyang Technological University, School of Materials Science and Engineering (Singapore)

    2012-06-15

    Using sodium dodecyl sulphate micelles as template, hollow-cored calcium phosphate nanocapsules were produced. The surfaces of the nanocapsule were subsequently silanised by a polyethylene glycol (PEG)-based silane with an N-hydroxysuccinimide ester end groups which permits for further attachment with bisphosphonates (BP). Characterisations of these nanocapsules were investigated using Field Emission Scanning Electron Microscopy (FESEM), Transmission Electron Microscopy, Fourier Transform Infra-Red Spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy and Dynamic Light Scattering. To further validate the bone-targeting potential, dentine discs were incubated with these functionalised nanocapsules. FESEM analysis showed that these surface-modified nanocapsules would bind strongly to dentine surfaces compared to non-functionalised nanocapsules. We envisage that respective components would give this construct a bifunctional attribute, whereby (1) the shell of the calcium phosphate nanocapsule would serve as biocompatible coating aiding in gradual osteoconduction, while (2) surface BP moieties, acting as targeting ligands, would provide the bone-targeting potential of these calcium phosphate nanocapsules.

  10. Assessing potential targets of calcium action in light-modulated gravitropism

    Science.gov (United States)

    Roux, S. J.

    1995-01-01

    Light, through the mediation of the pigment phytochrome, modulates the gravitropic response of the shoots and roots of many plants. The transduction of both light and gravity stimuli appears to involve Ca(2+)-regulated steps, one or more of which may represent points of intersection between the two transduction chains. To be confident that Ca2+ plays a critical role in stimulus-response coupling for gravitropism, it will be important to identify specific targets of Ca2+ action whose function can be clearly linked to the regulation of growth. Calcium typically exerts its influence on cell metabolism through binding to and activating key regulatory proteins. The three best characterized of these proteins in plants are the calmodulins, calcium-dependent protein kinases, and annexins. In this review we summarize what is known about the structure and function of these proteins and speculate on how their activation by Ca2+ could influence the differential growth response of gravitropism.

  11. Characterization and subcellular targeting of GCaMP-type genetically-encoded calcium indicators.

    Directory of Open Access Journals (Sweden)

    Tianyi Mao

    2008-03-01

    Full Text Available Genetically-encoded calcium indicators (GECIs hold the promise of monitoring [Ca(2+] in selected populations of neurons and in specific cellular compartments. Relating GECI fluorescence to neuronal activity requires quantitative characterization. We have characterized a promising new genetically-encoded calcium indicator-GCaMP2-in mammalian pyramidal neurons. Fluorescence changes in response to single action potentials (17+/-10% DeltaF/F [mean+/-SD] could be detected in some, but not all, neurons. Trains of high-frequency action potentials yielded robust responses (302+/-50% for trains of 40 action potentials at 83 Hz. Responses were similar in acute brain slices from in utero electroporated mice, indicating that long-term expression did not interfere with GCaMP2 function. Membrane-targeted versions of GCaMP2 did not yield larger signals than their non-targeted counterparts. We further targeted GCaMP2 to dendritic spines to monitor Ca(2+ accumulations evoked by activation of synaptic NMDA receptors. We observed robust DeltaF/F responses (range: 37%-264% to single spine uncaging stimuli that were correlated with NMDA receptor currents measured through a somatic patch pipette. One major drawback of GCaMP2 was its low baseline fluorescence. Our results show that GCaMP2 is improved from the previous versions of GCaMP and may be suited to detect bursts of high-frequency action potentials and synaptic currents in vivo.

  12. Neospora caninum calcium-dependent protein kinase 1 is an effective drug target for neosporosis therapy.

    Science.gov (United States)

    Ojo, Kayode K; Reid, Molly C; Kallur Siddaramaiah, Latha; Müller, Joachim; Winzer, Pablo; Zhang, Zhongsheng; Keyloun, Katelyn R; Vidadala, Rama Subba Rao; Merritt, Ethan A; Hol, Wim G J; Maly, Dustin J; Fan, Erkang; Van Voorhis, Wesley C; Hemphill, Andrew

    2014-01-01

    Despite the enormous economic importance of Neospora caninum related veterinary diseases, the number of effective therapeutic agents is relatively small. Development of new therapeutic strategies to combat the economic impact of neosporosis remains an important scientific endeavor. This study demonstrates molecular, structural and phenotypic evidence that N. caninum calcium-dependent protein kinase 1 (NcCDPK1) is a promising molecular target for neosporosis drug development. Recombinant NcCDPK1 was expressed, purified and screened against a select group of bumped kinase inhibitors (BKIs) previously shown to have low IC50s against Toxoplasma gondii CDPK1 and T. gondii tachyzoites. NcCDPK1 was inhibited by low concentrations of BKIs. The three-dimensional structure of NcCDPK1 in complex with BKIs was studied crystallographically. The BKI-NcCDPK1 structures demonstrated the structural basis for potency and selectivity. Calcium-dependent conformational changes in solution as characterized by small-angle X-ray scattering are consistent with previous structures in low Calcium-state but different in the Calcium-bound active state than predicted by X-ray crystallography. BKIs effectively inhibited N. caninum tachyzoite proliferation in vitro. Electron microscopic analysis of N. caninum cells revealed ultra-structural changes in the presence of BKI compound 1294. BKI compound 1294 interfered with an early step in Neospora tachyzoite host cell invasion and egress. Prolonged incubation in the presence of 1294 interfered produced observable interference with viability and replication. Oral dosing of BKI compound 1294 at 50 mg/kg for 5 days in established murine neosporosis resulted in a 10-fold reduced cerebral parasite burden compared to untreated control. Further experiments are needed to determine the PK, optimal dosage, and duration for effective treatment in cattle and dogs, but these data demonstrate proof-of-concept for BKIs, and 1294 specifically, for therapy of bovine

  13. Neospora caninum calcium-dependent protein kinase 1 is an effective drug target for neosporosis therapy.

    Directory of Open Access Journals (Sweden)

    Kayode K Ojo

    Full Text Available Despite the enormous economic importance of Neospora caninum related veterinary diseases, the number of effective therapeutic agents is relatively small. Development of new therapeutic strategies to combat the economic impact of neosporosis remains an important scientific endeavor. This study demonstrates molecular, structural and phenotypic evidence that N. caninum calcium-dependent protein kinase 1 (NcCDPK1 is a promising molecular target for neosporosis drug development. Recombinant NcCDPK1 was expressed, purified and screened against a select group of bumped kinase inhibitors (BKIs previously shown to have low IC50s against Toxoplasma gondii CDPK1 and T. gondii tachyzoites. NcCDPK1 was inhibited by low concentrations of BKIs. The three-dimensional structure of NcCDPK1 in complex with BKIs was studied crystallographically. The BKI-NcCDPK1 structures demonstrated the structural basis for potency and selectivity. Calcium-dependent conformational changes in solution as characterized by small-angle X-ray scattering are consistent with previous structures in low Calcium-state but different in the Calcium-bound active state than predicted by X-ray crystallography. BKIs effectively inhibited N. caninum tachyzoite proliferation in vitro. Electron microscopic analysis of N. caninum cells revealed ultra-structural changes in the presence of BKI compound 1294. BKI compound 1294 interfered with an early step in Neospora tachyzoite host cell invasion and egress. Prolonged incubation in the presence of 1294 interfered produced observable interference with viability and replication. Oral dosing of BKI compound 1294 at 50 mg/kg for 5 days in established murine neosporosis resulted in a 10-fold reduced cerebral parasite burden compared to untreated control. Further experiments are needed to determine the PK, optimal dosage, and duration for effective treatment in cattle and dogs, but these data demonstrate proof-of-concept for BKIs, and 1294 specifically, for

  14. CD44 and CD74: The promising candidates for molecular targeted therapy in oral squamous cell carcinoma

    Science.gov (United States)

    Shakib, Pouyan Amini; Ensani, Fereshteh; Abdirad, Afshin; Valizadeh, Bahareh; Seyedmajidi, Maryam; Sum, Shima

    2015-01-01

    Background: Considering molecular target therapy concept in the treatment of oral squamous cell carcinoma (OSCC), many attempts have been performed to introduce an effective molecular marker during recent years. Several investigations have emphasized on the role of CD44 in various cancers and few studies have mentioned CD24 and CD74. The purpose of this study was to investigate the relationship between CD44, CD24 and CD74 expressions and several clinical or histopathological factors in OSCC patients. Materials and Methods: In our analytical cross-sectional study, forty primary OSCC specimens were immunohistochemically stained for CD44, CD24, and CD74 proteins. Then, the relationship between their expressions and age, sex, lymph node metastasis, and histopathologic grading was statistically analyzed using Mann-Whitney nonparametric and t-test. Furthermore, P < 0.05 was considered as significant. Results: CD44 and CD74 proteins were significantly over-expressed in OSCC patients with high grade (P = 0.001 and P = 0.001) as compared to those with low grade. Furthermore, CD74 immunoreactivity showed significantly higher expression in patients with lower age (P = 0.039). Considering lymph node metastasis, we observed significant overexpression of CD74 in patients with no lymph node involvement (P = 0.033). Conclusion: Our observations support the significant role of membranous CD44 protein in progression of OSCC and also introduce CD74 protein as a probable interfering factor in different aspects of OSCC. PMID:25878685

  15. CD44 and CD74: The promising candidates for molecular targeted therapy in oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Pouyan Amini Shakib

    2015-01-01

    Full Text Available Background: Considering molecular target therapy concept in the treatment of oral squamous cell carcinoma (OSCC, many attempts have been performed to introduce an effective molecular marker during recent years. Several investigations have emphasized on the role of CD44 in various cancers and few studies have mentioned CD24 and CD74. The purpose of this study was to investigate the relationship between CD44, CD24 and CD74 expressions and several clinical or histopathological factors in OSCC patients. Materials and Methods: In our analytical cross-sectional study, forty primary OSCC specimens were immunohistochemically stained for CD44, CD24, and CD74 proteins. Then, the relationship between their expressions and age, sex, lymph node metastasis, and histopathologic grading was statistically analyzed using Mann-Whitney nonparametric and t-test. Furthermore, P < 0.05 was considered as significant. Results: CD44 and CD74 proteins were significantly over-expressed in OSCC patients with high grade (P = 0.001 and P = 0.001 as compared to those with low grade. Furthermore, CD74 immunoreactivity showed significantly higher expression in patients with lower age (P = 0.039. Considering lymph node metastasis, we observed significant overexpression of CD74 in patients with no lymph node involvement (P = 0.033. Conclusion: Our observations support the significant role of membranous CD44 protein in progression of OSCC and also introduce CD74 protein as a probable interfering factor in different aspects of OSCC.

  16. An Induction Linac Driver For A 0.44 MJ Heavy-Ion Direct Drive Target

    Energy Technology Data Exchange (ETDEWEB)

    Seidl, P.A.; Lee, E.P.; Bangerter, R.O.; Faltens, A.

    2010-02-08

    The conceptual design of a heavy ion fusion driver system is described, including all major components. Particular issues emerging from this exercise are identified and discussed. The most important conclusion of our study is that due to stringent requirements on ion pulse phase space, we are unable to find a credible accelerator design that meets the requirements of the example target. Either the target design must be modified to accept larger ion ranges and larger focal spot sizes, or we must consider other target options.

  17. Why Basic Calcium Phosphate Crystals Should Be Targeted In the Treatment of Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Claire-Louise Murphy

    2014-07-01

    Full Text Available Osteoarthritis (OA is the most common form of arthritis and results in significant social, psychological, and economic costs. It is characterised by progressive cartilage loss, bone remodelling, osteophyte formation, and synovial inflammation with resultant joint pain and disability. Since OA affects the entire joint, it is not surprising that there has been difficulty developing an effective targeted treatment. Treatments available for structural disease modification are limited. Current options appear to mostly reduce symptoms. Basic calcium phosphate (BCP crystals represent a potential therapeutic target in OA; they have been found in 100% of knee and hip cartilages removed at joint replacement. Intra-articular BCP crystals are associated with large joint effusions and dissolution of intra-articular structures, synovial proliferation, and marked degeneration as assessed by diagnostic imaging. While BCP deposition has been considered by many to be simply a consequence of advanced OA, there is substantial evidence to support BCP crystal deposition as an active pathogenic mediator of OA. BCP crystals exhibit a multiplicity of biologic effects in vitro including the ability to stimulate mitogenesis and prostaglandin, cytokine, and matrix metalloproteinase (MMP synthesis in a number of cell types including macrophages, synovial fibroblasts, and chondrocytes. BCP crystals also contribute to inflammation in OA through direct interaction with the innate immune system. Intra-articular BCP crystals can elicit synovial inflammation and cartilage degradation in mice in vivo . Although intra-articular BCP crystals are difficult to detect at the bedside, advances in modern technology should allow improved identification and quantitation of BCP crystals. Our article focuses on why basic calcium crystals are important in the pathogenesis of OA. There is ample evidence that BCP crystals should be explored as a therapeutic target in OA.

  18. Calcium channels in the brain as targets for the calcium-channel modulators used in the treatment of neurological disorders

    NARCIS (Netherlands)

    Peters, Thies; WILFFERT, B; VANHOUTTE, PM; VANZWIETEN, PA

    1991-01-01

    Recent investigations of calcium channels in brain cells by voltage-clamp techniques have revealed that, in spite of electrophysiological similarities, the pharmacological properties of these channels differ considerably from channels in peripheral tissues, e.g., heart and smooth muscle. Therefore,

  19. Selectively Sensitizing Malignant Cells to Photothermal Therapy Using a CD44-Targeting Heat Shock Protein 72 Depletion Nanosystem.

    Science.gov (United States)

    Wang, Shouju; Tian, Ying; Tian, Wei; Sun, Jing; Zhao, Shuang; Liu, Ying; Wang, Chunyan; Tang, Yuxia; Ma, Xingqun; Teng, Zhaogang; Lu, Guangming

    2016-09-27

    Selectively enhance the therapeutic efficacy to malignancy is one of the most important issues for photothermal therapy (PTT). However, most solid tumors, such as triple negative breast cancer (TNBC), do not have identifiable surface markers to distinguish themselves from normal cells, thus it is challenging to selectively identify and eliminate those malignances by PTT. In this report, we hypothesized that, by targeting CD44 (one TNBC-overexpressed surface molecule) and depleting heat shock protein 72 (HSP72, one malignancy-specific-overexpressed thermotolerance-related chaperone) subsequently, the TNBC could be selectively sensitized to PTT and improve the accuracy of treatment. To this end, a rationally designed nanosystem gold nanostar (GNS)/siRNA against HSP72 (siHSP72)/hyaluronic acid (HA) was successfully constructed using a layer-by-layer method. Hydrodynamic diameter and zeta potential analysis demonstrated the formation of GNS/siHSP72/HA having a particle size of 73.2 ± 3.8 nm and a negative surface charge of -18.3 ± 1.6 mV. The CD44-targeting ability of GNS/siHSP72/HA was confirmed by the flow cytometer, confocal microscopic imaging, and competitive binding analysis. The HSP72 silencing efficacy of GNS/siHSP72/HA was ∼95% in complete culture medium. By targeting CD44 and depleting HSP72 sequentially, GNS/siHSP72/HA could selectively sensitize TNBC cells to hyperthermia and enhance the therapeutic efficacy to TNBC with minimal side effect both in vitro and in vivo. Other advantages of GNS/siHSP72/HA included easy synthesis, robust siRNA loading capacity, endosome/lysosome escaping ability, high photothermal conversion efficacy and superior hemo- and biocompatibility.

  20. Fe-bLf nanoformulation targets survivin to kill colon cancer stem cells and maintains absorption of iron, calcium and zinc.

    Science.gov (United States)

    Kanwar, Jagat R; Mahidhara, Ganesh; Roy, Kislay; Sasidharan, Sreenivasan; Krishnakumar, Subramanian; Prasad, Neerati; Sehgal, Rakesh; Kanwar, Rupinder K

    2015-01-01

    To validate the anticancer efficacy of alginate-enclosed, chitosan-conjugated, calcium phosphate, iron-saturated bovine lactoferrin (Fe-bLf) nanocarriers/nanocapsules (NCs) with improved sustained release and ability to induce apoptosis by downregulating survivin, as well as cancer stem cells. The stability, nanotoxicity of the modified nanoformulation was evaluated and their anticancer efficacy was re-examined. Their mechanism of internalization was studied and we identified the role of various miRNAs in absorption of these NCs/iron in various body parts of mice. We determined the effect of these NCs on survivin, stem cell markers, red blood cell count, iron, calcium and zinc concentration in mice, determined the antiangiogenic properties of these NCs and studied their effect on cancer stem-like cells. Spherical NCs (396.1 ± 27.2 nm) exceedingly reduced viability of Caco-2 cells (32 ± 2.83%). The NCs also showed effective internalization and reduction of cancer stem cell markers in triple-positive CD133, survivin and CD44 cancer stem-like cells. Mice treated with the NCs showed no nanotoxicity and did not develop any tumors in xenograft colon cancer models. We found that the serum iron, zinc and calcium absorption were increased. DMT1, LRP, transferrin and lactoferrin receptors were responsible for internalization of the NCs. Different miRNAs were responsible for iron regulation in different organs. Interestingly, NCs inhibited survivin and its different isoforms. Our results confirmed that NCs internalized and changed the expression of selected miRNAs that further enhanced their uptake. The NCs activated both extrinsic, as well as intrinsic apoptotic pathways to induce apoptosis by targeting survivin in cancer cells and cancer stem cells, without inducing any nonspecific nanotoxicity. Apart from inhibiting angiogenesis and stem cell markers, NCs also maintained iron and calcium levels.

  1. CD44 Receptor Targeting and Endosomal pH-Sensitive Dual Functional Hyaluronic Acid Micelles for Intracellular Paclitaxel Delivery.

    Science.gov (United States)

    Liu, Yanhua; Zhou, Chengming; Wang, Wenping; Yang, Jianhong; Wang, Hao; Hong, Wei; Huang, Yu

    2016-12-05

    A novel CD44 receptor targeting and endosome pH-sensitive dual functional hyaluronic acid-deoxycholic acid-histidine (HA-DOCA-His) micellar system was designed for intracellular paclitaxel (PTX) delivery. The HA-DOCA-His micelles exhibited desirable endosome pH (5.0-6.0)-induced aggregation and deformation behavior verified by size distribution, critical micellar concentration, and zeta potential changes. The HA-DOCA-His micelles presented excellent encapsulation efficiency and loading capacity of 90.0% and 18.9% for PTX, respectively. The PTX release from HA-DOCA-His micelles was pH-dependent, with more rapid PTX release at pH 6.0 and 5.0 than those at pH 7.4 and 6.5. The cellular uptake performance of HA-DOCA-His micelles was enhanced comparing with pH-insensitive HA-DOCA micelles by qualitative and quantitative measurements. HA-DOCA-His micelles could be taken up via CD44-receptor mediated endocytosis, transported into endosomes, and triggered drug release to cytoplasm. In vitro cytotoxicity study exhibited PTX-loaded HA-DOCA-His micelles were more active in tumor cell growth inhibition in MCF-7 cells at pH 5.8 than those at pH 6.8 and pH 7.4. A superior antitumor efficacy was demonstrated with HA-DOCA-His micelles in a MCF-7 breast tumor model. These indicated that the dual functional HA-DOCA-His micelles combined targeted intracellular delivery and endosomal release strategies could be developed as a promising nanocarrier for anticancer efficacy improvement of PTX.

  2. Production of a {sup 44} Ti target and its cross section of thermal neutron capture; Producao de um alvo de {sup 44} Ti e sua secao de choque para captura de neutrons termicos

    Energy Technology Data Exchange (ETDEWEB)

    Ejnisman, R

    1993-12-31

    A study of the production of a {sup 44} Ti target was carried out aiming the determination of its thermal neutron capture cross-section. With this purpose, the cross-section of the reaction {sup 45} Sc(p,2 n) {sup 44} Ti was determined in the energies 16-, 18-, 20-22- and 45 MeV. The cross-section of the reactions (p,n) {sup 45} Ti, (p,pn) {sup 44m} Sc, (p,pn) {sup 44g} Sc and (p,p2n){sup 43} Sc were also measured. The results in the low energy region are in good agreement with a previous work by McGee et al. On the other hand, the cross-section at 45 MeV is different from McGee`s result and indicates the existence of an abnormal behavior of the excitation function at higher energies. Furthermore, a radiochemical separation method was developed in order to eliminate Sc from the {sup 44} Ti target which was irradiated with neutrons. It was possible to determine an upper limit for the cross-section of the reaction {sup 44} Ti (n, {gamma}) of 4 x 10{sup 3} b. At last, it is presented a discussion of the results obtained and their possible astrophysical implications. (author) 94 refs.

  3. L-type calcium channel targeting and local signalling in cardiac myocytes.

    Science.gov (United States)

    Shaw, Robin M; Colecraft, Henry M

    2013-05-01

    In the heart, Ca(2+) influx via Ca(V)1.2 L-type calcium channels (LTCCs) is a multi-functional signal that triggers muscle contraction, controls action potential duration, and regulates gene expression. The use of LTCC Ca(2+) as a multi-dimensional signalling molecule in the heart is complicated by several aspects of cardiac physiology. Cytosolic Ca(2+) continuously cycles between ~100 nM and ~1 μM with each heartbeat due to Ca(2+) linked signalling from LTCCs to ryanodine receptors. This rapid cycling raises the question as to how cardiac myocytes distinguish the Ca(2+) fluxes originating through L-type channels that are dedicated to contraction from Ca(2+) fluxes originating from other L-type channels that are used for non-contraction-related signalling. In general, disparate Ca(2+) sources in cardiac myocytes such as current through differently localized LTCCs as well as from IP3 receptors can signal selectively to Ca(2+)-dependent effectors in local microdomains that can be impervious to the cytoplasmic Ca(2+) transients that drive contraction. A particular challenge for diversified signalling via cardiac LTCCs is that they are voltage-gated and, therefore, open and presumably flood their microdomains with Ca(2+) with each action potential. Thus spatial localization of Cav1.2 channels to different types of microdomains of the ventricular cardiomyocyte membrane as well as the existence of particular macromolecular complexes in each Cav1.2 microdomain are important to effect different types of Cav1.2 signalling. In this review we examine aspects of Cav1.2 structure, targeting and signalling in two specialized membrane microdomains--transverse tubules and caveolae.

  4. The calcium-dependent protein kinase 1 from Toxoplasma gondii as target for structure-based drug design.

    Science.gov (United States)

    Cardew, Emily M; Verlinde, Christophe L M J; Pohl, Ehmke

    2018-02-01

    The apicomplexan protozoan parasites include the causative agents of animal and human diseases ranging from malaria (Plasmodium spp.) to toxoplasmosis (Toxoplasma gondii). The complex life cycle of T. gondii is regulated by a unique family of calcium-dependent protein kinases (CDPKs) that have become the target of intensive efforts to develop new therapeutics. In this review, we will summarize structure-based strategies, recent successes and future directions in the pursuit of specific and selective inhibitors of T. gondii CDPK1.

  5. Mapping calcium phosphate activated gene networks as a strategy for targeted osteoinduction of human progenitors in vitro and in vivo

    Science.gov (United States)

    Eyckmans, J.; Roberts, S.J.; Bolander, J.; Schrooten, J.; Chen, C.S.; Luyten, F.P.

    2014-01-01

    Although calcium phosphate-containing biomaterials are promising scaffolds for bone regenerative strategies, the osteoinductive capacity of such materials is poorly understood. In this study, we investigated whether endogenous mechanisms of in vivo calcium phosphate-driven, ectopic bone formation could be identified and used to induce enhanced differentiation in vitro of the same progenitor population. To accomplish this, human periosteum derived cells (hPDCs) were seeded on hydroxyapatite/collagen scaffolds (calcium phosphate rich matrix or CPRM), or on decalcified scaffolds (calcium phosphate depleted matrix or CPDM), followed by subcutaneous implantation in nude mice to trigger ectopic bone formation. In this system, osteoblast differentiation occurred in CPRM scaffolds, but not in CPDM scaffolds. Gene expression was assessed by human full-genome microarray at 20 hours after seeding, and 2, 8 and 18 days after implantation. In both matrices, implantation of the cell constructs triggered a similar gene expression cascade, however, gene expression dynamics progressed faster in CPRM scaffolds than in CPDM scaffolds. The difference in gene expression dynamics was associated with differential activation of hub genes and molecular signaling pathways related to calcium signaling (CREB), inflammation (TNFα, NFkB, and IL6) and bone development (TGFβ, β-catenin, BMP, EGF, and ERK signaling). Starting from this set of pathways, a growth factor cocktail was developed that robustly enhanced osteogenesis in vitro and in vivo. Taken together, our data demonstrate that through the identification and subsequent stimulation of genes, proteins and signaling pathways associated with calcium phosphate mediated osteoinduction, a focused approach to develop targeted differentiation protocols in adult progenitor cells can be achieved. PMID:23537666

  6. Dual-targeting hybrid nanoparticles for the delivery of SN38 to Her2 and CD44 overexpressed human gastric cancer

    Science.gov (United States)

    Yang, Zhe; Luo, Huiyan; Cao, Zhong; Chen, Ya; Gao, Jinbiao; Li, Yingqin; Jiang, Qing; Xu, Ruihua; Liu, Jie

    2016-06-01

    Gastric cancer (GC), particularly of the type with high expression of both human epidermal growth factor receptor 2 (Her2) and cluster determinant 44 (CD44), is one of the most malignant human tumors which causes a high mortality rate due to rapid tumor growth and metastasis. To develop effective therapeutic treatments, a dual-targeting hybrid nanoparticle (NP) system was designed and constructed to deliver the SN38 agent specifically to human solid gastric tumors bearing excessive Her2 and CD44. The hybrid NPs consist of a particle core made of the biodegradable polymer PLGA and a lipoid shell prepared by conjugating the AHNP peptides and n-hexadecylamine (HDA) to the carboxyl groups of hyaluronic acid (HA). Upon encapsulation of the SN38 agent in the NPs, the AHNP peptides and HA on the NP surface allow preferential delivery of the drug to gastric cancer cells (e.g., HGC27 cells) by targeting Her2 and CD44. Cellular uptake and in vivo biodistribution experiments verified the active targeting and prolonged in vivo circulation properties of the dual-targeting hybrid NPs, leading to enhanced accumulation of the drug in tumors. Furthermore, the anti-proliferation mechanism studies revealed that the inhibition of the growth and invasive activity of HGC27 cells was not only attributed to the enhanced cellular uptake of dual-targeting NPs, but also benefited from the suppression of CD44 and Her2 expression by HA and AHNP moieties. Finally, intravenous administration of the SN38-loaded dual-targeting hybrid NPs induced significant growth inhibition of HGC27 tumor xenografted in nude mice compared with a clinical antitumor agent, Irinotecan (CPT-11), and the other NP formulations. These results demonstrate that the designed dual-targeting hybrid NPs are promising for targeted anti-cancer drug delivery to treat human gastric tumors over-expressing Her2 and CD44.Gastric cancer (GC), particularly of the type with high expression of both human epidermal growth factor receptor

  7. Exclusive breakup of 7Li incident on a proton target at 5.44 A MeV

    Science.gov (United States)

    Pakou, A.; Sgouros, O.; Soukeras, V.; Cappuzzello, F.; Keeley, N.; Acosta, L.; Agodi, C.; Aslanoglou, X.; Calabrese, S.; Carbone, D.; Cavallaro, M.; Foti, A.; Marquínez-Durán, G.; Martel, I.; Mazzocco, M.; Parascandolo, C.; Pierroutsakou, D.; Rusek, K.; Strano, E.; Zagatto, V. A. B.; Zerva, K.

    2017-04-01

    An exclusive measurement of the breakup of 7Li incident on a proton target was performed at 38.1 MeV (5.44 MeV/nucleon), probing the direct part of the excitation to the continuum. The two cluster constituents of 7Li, 4He, and 3H, were recorded in coincidence in the MAGNEX spectrometer and a silicon detector respectively. Both detection systems were set at forward angles and the measurement of both kinematical solutions allowed the determination of a breakup angular distribution over a wide angular range in the center-of-mass frame. Comprehensive simulations provided the detection efficiency of the system and via the appropriate kinematics the transformation of the cross sections from the laboratory to the center-of-mass reference frame. The experimental results are analyzed and discussed together with previous elastic scattering data using the Continuum Discretized Coupled Channels (CDCC) framework and are found to be in satisfactory agreement. It was found that while the breakup cross section was dominated by the nonresonant component, the most important influence on the elastic scattering was due to coupling to the 7 /2- resonance of 7Li.

  8. MiR-101 regulates apoptosis of trophoblast HTR-8/SVneo cells by targeting endoplasmic reticulum (ER) protein 44 during preeclampsia.

    Science.gov (United States)

    Zou, Y; Jiang, Z; Yu, X; Zhang, Y; Sun, M; Wang, W; Ge, Z; De, W; Sun, L

    2014-10-01

    To investigate a possible association between miR-101 and apoptosis of human trophoblast cells mediated by endoplasmic reticulum protein 44 (ERp44) in preeclampsia (PE), we explored the expression of miR-101 in PE placentas (n=30) compared with normotensive pregnant placentas (n=30) and the correlation between miR-101 and ERp44 was also analyzed. Furthermore, both the apoptotic rate of trophoblast cells and the ER stress-induced apoptotic proteins were assayed when the HTR-8/SVneo cells were treated with miR-101 mimics or inhibitors in vitro. We found a lower expression of miR-101 and an inverse correlation between miR-101 and ERp44 protein in PE placentas. Upregulation of miR-101 expression could inhibit trophoblast HTR-8/SVneo cell apoptosis and repress ER stress-induced apoptotic proteins by targeting ERp44 in vitro, whereas inhibition of miR-101 could induce HTR-8/SVneo cell apoptosis. Our findings indicated that overexpression of miR-101 could downregulate ERp44 and suppress apoptosis in trophoblast cells during PE. Therefore, loss of miR-101 expression could contribute to ER stress-induced trophoblast cell apoptosis by targeting ERp44.

  9. A FluoPol-ABPP PAD2 high-throughput screen identifies the first calcium site inhibitor targeting the PADs.

    Science.gov (United States)

    Lewallen, Daniel M; Bicker, Kevin L; Madoux, Franck; Chase, Peter; Anguish, Lynne; Coonrod, Scott; Hodder, Peter; Thompson, Paul R

    2014-04-18

    The protein arginine deiminases (PADs) catalyze the post-translational hydrolysis of peptidyl-arginine to form peptidyl-citrulline in a process termed deimination or citrullination. PADs likely play a role in the progression of a range of disease states because dysregulated PAD activity is observed in a host of inflammatory diseases and cancer. For example, recent studies have shown that PAD2 activates ERα target gene expression in breast cancer cells by citrullinating histone H3 at ER target promoters. To date, all known PAD inhibitors bind directly to the enzyme active site. PADs, however, also require calcium ions to drive a conformational change between the inactive apo-state and the fully active calcium bound holoenzyme, suggesting that it would be possible to identify inhibitors that bind the apoenzyme and prevent this conformational change. As such, we set out to develop a screen that can identify PAD2 inhibitors that bind to either the apo or calcium bound form of PAD2. Herein, we provide definitive proof of concept for this approach and report the first PAD inhibitor, ruthenium red (Ki of 17 μM), to preferentially bind the apoenzyme.

  10. Structural Insights into Membrane Targeting by the Flagellar Calcium-binding Protein (FCaBP) a Myristoylated and Palmitoylated Calcium Sensor in Trypanosoma cruzi

    Energy Technology Data Exchange (ETDEWEB)

    J Wingard; J Ladner; M Vanarotti; A Fisher; H Robinson; K Buchanan; D Engman; J Ames

    2011-12-31

    The flagellar calcium-binding protein (FCaBP) of the protozoan Trypanosoma cruzi is targeted to the flagellar membrane where it regulates flagellar function and assembly. As a first step toward understanding the Ca{sup 2+}-induced conformational changes important for membrane-targeting, we report here the x-ray crystal structure of FCaBP in the Ca{sup 2+}-free state determined at 2.2{angstrom} resolution. The first 17 residues from the N terminus appear unstructured and solvent-exposed. Residues implicated in membrane targeting (Lys-19, Lys-22, and Lys-25) are flanked by an exposed N-terminal helix (residues 26-37), forming a patch of positive charge on the protein surface that may interact electrostatically with flagellar membrane targets. The four EF-hands in FCaBP each adopt a 'closed conformation' similar to that seen in Ca{sup 2+}-free calmodulin. The overall fold of FCaBP is closest to that of grancalcin and other members of the penta EF-hand superfamily. Unlike the dimeric penta EF-hand proteins, FCaBP lacks a fifth EF-hand and is monomeric. The unstructured N-terminal region of FCaBP suggests that its covalently attached myristoyl group at the N terminus may be solvent-exposed, in contrast to the highly sequestered myristoyl group seen in recoverin and GCAP1. NMR analysis demonstrates that the myristoyl group attached to FCaBP is indeed solvent-exposed in both the Ca{sup 2+}-free and Ca{sup 2+}-bound states, and myristoylation has no effect on protein structure and folding stability. We propose that exposed acyl groups at the N terminus may anchor FCaBP to the flagellar membrane and that Ca{sup 2+}-induced conformational changes may control its binding to membrane-bound protein targets..

  11. Calcium channel TRPV6 as a potential therapeutic target in estrogen receptor-negative breast cancer.

    Science.gov (United States)

    Peters, Amelia A; Simpson, Peter T; Bassett, Johnathon J; Lee, Jane M; Da Silva, Leonard; Reid, Lynne E; Song, Sarah; Parat, Marie-Odile; Lakhani, Sunil R; Kenny, Paraic A; Roberts-Thomson, Sarah J; Monteith, Gregory R

    2012-10-01

    Calcium signaling is a critical regulator of cell proliferation. Elevated expression of calcium channels and pumps is a characteristic of some cancers, including breast cancer. We show that the plasma membrane calcium channel TRPV6, which is highly selective for Ca(2+), is overexpressed in some breast cancer cell lines. Silencing of TRPV6 expression in a breast cancer cell line with increased endogenous TRPV6 expression leads to a reduction in basal calcium influx and cellular proliferation associated with a reduction in DNA synthesis. TRPV6 gene amplification was identified as one mechanism of TRPV6 overexpression in a subset of breast cancer cell lines and breast tumor samples. Analysis of two independent microarray expression datasets from breast tumor samples showed that increased TRPV6 expression is a feature of estrogen receptor (ER)-negative breast tumors encompassing the basal-like molecular subtype, as well as HER2-positive tumors. Breast cancer patients with high TRPV6 levels had decreased survival compared with patients with low or intermediate TRPV6 expression. Our findings suggest that inhibitors of TRPV6 may offer a novel therapeutic strategy for the treatment of ER-negative breast cancers.

  12. Dose-escalation study for the targeting of CD44v+cancer stem cells by sulfasalazine in patients with advanced gastric cancer (EPOC1205).

    Science.gov (United States)

    Shitara, Kohei; Doi, Toshihiko; Nagano, Osamu; Imamura, Chiyo K; Ozeki, Takeshi; Ishii, Yuya; Tsuchihashi, Kenji; Takahashi, Shunji; Nakajima, Takako E; Hironaka, Shuichi; Fukutani, Miki; Hasegawa, Hiromi; Nomura, Shogo; Sato, Akihiro; Einaga, Yasuaki; Kuwata, Takeshi; Saya, Hideyuki; Ohtsu, Atsushi

    2017-03-01

    Cancer stem cells (CSCs) have enhanced mechanisms of protection from oxidative stress. A variant form of CD44 (CD44v), a major CSC marker, was shown to interact with xCT, a subunit of cystine-glutamate transporter, which maintains high levels of intracellular reduced glutathione (GSH) which defend the cell against oxidative stress. Sulfasalazine (SSZ) is an inhibitor of xCT and was shown to suppress the survival of CD44v-positive stem-like cancer cells both in vitro and in vivo. To find the dose of SSZ which can safely reduce the population of CD44v-positive cells in tumors, a dose-escalation study in patients with advanced gastric cancer was conducted. SSZ was given four times daily by oral administration with 2 weeks as one cycle. Tumor biopsies were obtained before and after 14 days of administration of SSZ to evaluate expression of CD44v and the intratumoral level of GSH. Eleven patients were enrolled and received a dosage from 8 to 12 g/day. Safety was confirmed up to a dosage of 12 g/day, which was considered the maximum tolerated dose. Among the eight patients with CD44v-positive cells in their pretreatment biopsy samples, the CD44v-positive cancer cell population appeared to be reduced in the posttreatment biopsy tissues of four patients. Intratumoral GSH levels were also decreased in two patients, suggesting biological effectiveness of SSZ at 8 g/day or greater. This is the first study of SSZ as an xCT inhibitor for targeting CSCs. Reduction of the levels of CD44v-positive cells and GSH was observed in some patients, consistent with the mode of action of SSZ in CSCs.

  13. MicroRNA-328 inhibits renal tubular cell epithelial-to-mesenchymal transition by targeting the CD44 in pressure-induced renal fibrosis.

    Science.gov (United States)

    Chen, Cheng-Hsien; Cheng, Chung-Yi; Chen, Yen-Cheng; Sue, Yuh-Mou; Liu, Chung-Te; Cheng, Tzu-Hurng; Hsu, Yung-Ho; Chen, Tso-Hsiao

    2014-01-01

    Epithelial-mesenchymal transition (EMT) occurs in stressed tubular epithelial cells, contributing to renal fibrosis. Initial mechanisms promoting EMT are unknown. Pressure force is an important mechanism contributing to the induction and progression of renal fibrogenesis in ureteric obstruction. In our study of cultured rat renal tubular cells (NRK-52E) under 60 mmHg of pressure, we found that the epithelial marker E-cadherin decreased and mesenchymal markers, e.g., α-smooth muscle actin, fibronectin and Snail, increased. Pressure also induced the expression of connective tissue growth factor and transforming growth factor-β. MicroRNA array assays showed that pressure reduced miR-328 at the initial stage of pressurization. We identified a potential target sequence of miR-328 in rat CD44 3'-untranslated regions. In contrast with the miR-328 expression, CD44 expression was up-regulated at the initial pressurization stage. We also found that miR-328 expression decreased and CD44 increased in ureteric obstruction kidneys in the animal study. CD44 siRNA transfection significantly increased E-cadherin expression and inhibited pressure-induced EMT. Both hyaluronan binding peptide pep-1 and osteopontin neutralizing antibody inhibited pressure-induced EMT. Our results suggest that miR-328-mediated CD44 transient upregulation is an important trigger of the pressure-induced EMT in renal fibrosis.

  14. MDR1 siRNA loaded hyaluronic acid-based CD44 targeted nanoparticle systems circumvent paclitaxel resistance in ovarian cancer

    Science.gov (United States)

    Yang, Xiaoqian; Lyer, Arun K.; Singh, Amit; Choy, Edwin; Hornicek, Francis J.; Amiji, Mansoor M.; Duan, Zhenfeng

    2015-02-01

    Development of multidrug resistance (MDR) is an almost universal phenomenon in patients with ovarian cancer, and this severely limits the ultimate success of chemotherapy in the clinic. Overexpression of the MDR1 gene and corresponding P-glycoprotein (Pgp) is one of the best known MDR mechanisms. MDR1 siRNA based strategies were proposed to circumvent MDR, however, systemic, safe, and effective targeted delivery is still a major challenge. Cluster of differentiation 44 (CD44) targeted hyaluronic acid (HA) based nanoparticle has been shown to successfully deliver chemotherapy agents or siRNAs into tumor cells. The goal of this study is to evaluate the ability of HA-PEI/HA-PEG to deliver MDR1 siRNA and the efficacy of the combination of HA-PEI/HA-PEG/MDR1 siRNA with paclitaxel to suppress growth of ovarian cancer. We observed that HA-PEI/HA-PEG nanoparticles can efficiently deliver MDR1 siRNA into MDR ovarian cancer cells, resulting in down-regulation of MDR1 and Pgp expression. Administration of HA-PEI/HA-PEG/MDR1 siRNA nanoparticles followed by paclitaxel treatment induced a significant inhibitory effect on the tumor growth, decreased Pgp expression and increased apoptosis in MDR ovarian cancer mice model. Our findings suggest that CD44 targeted HA-PEI/HA-PEG/MDR1 siRNA nanoparticles can serve as a therapeutic tool with great potentials to circumvent MDR in ovarian cancer.

  15. MicroRNA-27a regulates basal transcription by targeting the p44 subunit of general transcription factor IIH.

    Science.gov (United States)

    Portal, Maximiliano M

    2011-05-24

    General transcription factor IIH (TFIIH) is a complex RNA polymerase II basal transcription factor comprising 10 different polypeptides that display activities involved in transcription and DNA repair processes. Although biochemical studies have uncovered TFIIH importance, little is known about how the mRNAs that code for TFIIH subunits are regulated. Here it is shown that mRNAs encoding seven of the TFIIH subunits (p34, p44, p52, p62, XPB, CDK7, and p8) are regulated at the posttranscriptional level in a Dicer-dependent manner. Indeed, abolition of the miRNA pathway induces abnormal accumulation, stabilization, and translational activation of these seven mRNAs. Herein, miR-27a was identified as a key regulator of p44 mRNA. Moreover, miR-27a was shown to destabilize the p44 subunit of the TFIIH complex during the G2-M phase, thereby modulating the transcriptional shutdown observed during this transition. This work is unique in providing a demonstration of global transcriptional regulation through the action of a single miRNA.

  16. New Conotoxin SO-3 Targeting N-type Voltage-Sensitive Calcium Channels

    Directory of Open Access Journals (Sweden)

    Lei Wen

    2006-04-01

    Full Text Available Selective blockers of the N-type voltage-sensitive calcium (CaV channels are useful in the management of severe chronic pain. Here, the structure and function characteristics of a novel N-type CaV channel blocker, SO-3, are reviewed. SO-3 is a 25-amino acid conopeptide originally derived from the venom of Conus striatus, and contains the same 4-loop, 6-cysteine framework (C-C-CC-C-C as O-superfamily conotoxins. The synthetic SO-3 has high analgesic activity similar to ω-conotoxin MVIIA (MVIIA, a selective N-type CaV channel blocker approved in the USA and Europe for the alleviation of persistent pain states. In electrophysiological studies, SO-3 shows more selectivity towards the N-type CaV channels than MVIIA. The dissimilarity between SO-3 and MVIIA in the primary and tertiary structures is further discussed in an attempt to illustrate the difference in selectivity of SO-3 and MVIIA towards N-type CaV channels.

  17. Mitochondria and calcium flux as targets of neuroprotection caused by minocycline in cerebellar granule cells

    OpenAIRE

    Garcia-Martinez, Eva Maria; Sanz-Blasco, Sara; Karachitos, Andonis; Bandez, Miguel J.; Fernandez-Gomez, Francisco J; Perez-Alvarez, Sergio; Mera, Raquel Maria Melero Fernandez De; Jordan, Maria J.; Aguirre, Norberto; Galindo, Maria F.; Villalobos, Carlos; Navarro, Ana; Kmita, Hanna; Jordán, Joaquín

    2009-01-01

    Abstract Minocycline, an antibiotic of the tetracycline family, has attracted considerable interest for its theoretical therapeutic applications in neurodegenerative diseases. However, the mechanism of action underlying its effect remains elusive. Here we have studied the effect of minocycline under excitotoxic conditions. Fluorescence and bioluminescence imaging studies in rat cerebellar granular neuron cultures using fura-2/AM and mitochondria-targeted aequorin revealed that mino...

  18. Efficiency of calcium phosphate composite nanoparticles in targeting Ehrlich carcinoma cells transplanted in mice

    Directory of Open Access Journals (Sweden)

    Eman I. Abdel-Gawad

    2016-01-01

    Full Text Available The present study aimed to investigate the mode of action of nano-CaPs in vivo as a therapy for solid tumor in mice. To achieve this goal, Ehrlich Ascites Carcinoma (EAC was transplanted into 85 Swiss male albino mice. After nine days, the mice were divided into 9 groups. Groups 1 and 2 were allocated as the EAC control. Groups 3 and 4 were injected once intratumorally (IT by nano-calcium phosphate (nano-CaP. Groups 5 and 6 received once intraperitoneal injection (IP of nano-CaP. Groups 7, 8, and 9 received nano-CaP (IP weekly. Blood samples and thigh skeletal muscle were collected after three weeks from groups 1, 3, 5, and 7 and after four weeks from groups 2, 4, 6, and 8. On the other hand, group 9 received nano-CaP (IP for four weeks and lasted for three months to follow up the recurrence of tumor and to ensure the safety of muscle by histopathological analysis. Tumor growth was monitored twice a week throughout the experiment. DNA fragmentation of tumor cells was evaluated. In thigh tissue, noradrenaline, dopamine, serotonin (5HT, and gamma-aminobutyric acid (GABA were measured. In serum, 8-Hydroxy-deoxyguanosine (8-OHDG, adenosine triphosphate (ATP, and vascular endothelial growth factor (VEGF were analyzed. Histopathological and biochemical results showed a significant therapeutic effect of nano-CaP on implanted solid tumor and this effect was more pronounced in the animals treated IP for four weeks. This improvement was evident from the repair of fragmented DNA, the significant decrease of caspase-3, 8-OHDG, myosin, and VEGF, and the significant increase of neurotransmitters (NA, DA, 5HT, and GABA. Additionally, histopathological examination showed complete recovery of cancer cells in the thigh muscle after three months.

  19. Hyaluronic Acid Immobilized Polyacrylamide Nanoparticle Sensors for CD44 Receptor Targeting and pH Measurement in Cells

    DEFF Research Database (Denmark)

    Sun, Honghao; Benjaminsen, Rikke Vicki; Almdal, Kristoffer

    2012-01-01

    Our ability to design receptor-targeted nanocarriers aimed at drug release after endocytosis is limited by the current knowledge of intracellular nanoparticle (NP) trafficking. It is not clear if NP size, surface chemistry, and/or targeting of cell surface receptors changes the intracellular fate......H distribution profile in cells was measured for nanosensors with HA, cationic, and noncharged NP surface coatings giving a clear indication of the intracellular pH environment that the different NPs experience after internalization. The pH profile of cationic nanosensors in comparison to HA conjugated...

  20. Targeting voltage-gated calcium channels: developments in peptide and small-molecule inhibitors for the treatment of neuropathic pain

    Science.gov (United States)

    Vink, S; Alewood, PF

    2012-01-01

    Chronic pain affects approximately 20% of people worldwide and places a large economic and social burden on society. Despite the availability of a range of analgesics, this condition is inadequately treated, with complete alleviation of symptoms rarely occurring. In the past 30 years, the voltage-gated calcium channels (VGCCs) have been recognized as potential targets for analgesic development. Although the majority of the research has been focused on Cav2.2 in particular, other VGCC subtypes such as Cav3.2 have recently come to the forefront of analgesic research. Venom peptides from marine cone snails have been proven to be a valuable tool in neuroscience, playing a major role in the identification and characterization of VGCC subtypes and producing the first conotoxin-based drug on the market, the ω-conotoxin, ziconotide. This peptide potently and selectively inhibits Cav2.2, resulting in analgesia in chronic pain states. However, this drug is only available via intrathecal administration, and adverse effects and a narrow therapeutic window have limited its use in the clinic. Other Cav2.2 inhibitors are currently in development and offer the promise of an improved route of administration and safety profile. This review assesses the potential of targeting VGCCs for analgesic development, with a main focus on conotoxins that block Cav2.2 and the developments made to transform them into therapeutics. PMID:22725651

  1. Changes in Intracellular Calcium Concentration and pH of Target Cells During the Cytotoxic Process: A Quantitative Study at the Single Cell Level

    NARCIS (Netherlands)

    de Grooth, B.G.; Radosevic, Katarina; Greve, Jan; Radosevic, K.

    1995-01-01

    This study reports on the changes in intracellular calcium concentration ([Ca2+]in) and intracellular pH ([pH]in) that occur in K562 target cells during interaction with human Natural Killer (NK) cells. The data were obtained using a quantitative fluorescence microscope and fluorescent ratio probes

  2. A phase IIa study of HA-irinotecan, formulation of hyaluronic acid and irinotecan targeting CD44 in extensive-stage small cell lung cancer.

    Science.gov (United States)

    Alamgeer, Muhammad; Neil Watkins, D; Banakh, Ilia; Kumar, Beena; Gough, Daniel J; Markman, Ben; Ganju, Vinod

    2017-12-26

    Preclinical studies in small cell lung cancer (SCLC) have shown that hyaluronic acid (HA) can be effectively used to deliver chemotherapy and selectively decrease CD44 expressing (stem cell-like) tumour cells. The current study aimed to replicate these findings and obtain data on safety and activity of HA-irinotecan (HA-IR). Eligible patients with extensive stage SCLC were consented. A safety cohort (n = 5) was treated with HA-IR and Carboplatin (C). Subsequently, the patients were randomised 1:1 to receive experimental (HA-IR + C) or standard (IR + C) treatment, to a maximum of 6 cycles. The second line patients were added to the study and treated with open label HA-IR + C. Tumour response was measured after every 2 cycles. Baseline tumour specimens were stained for CD44s and CD44v6 expression. Circulating tumour cells (CTCs) were enumerated before each treatment cycle. Out of 39 patients screened, 34 were evaluable for the study. The median age was 66 (range 39-83). The overall response rates were 69% and 75% for experimental and standard arms respectively. Median progression free survival was 42 and 28 weeks, respectively (p = 0.892). The treatments were well tolerated. The incidence of grade III/IV diarrhea was more common in the standard arm, while anaemia was more common in the experimental arm. IHC analysis suggested that the patients with CD44s positive tumours may gain survival benefit from HA-IR. HA-IR is well tolerated and active in ES-SCLC. The effect of HA-IR on CD44s + cancer stem-like cells provide an early hint towards a potential novel target.

  3. Hyaluronic acid-shelled disulfide-crosslinked nano-polymersomes for ultrahigh-efficiency reactive encapsulation and CD44-targeted delivery of mertansine toxin.

    Science.gov (United States)

    Zhang, Yue; Wu, Kaiqi; Sun, Huanli; Zhang, Jian; Yuan, Jiandong; Zhong, Zhiyuan

    2017-12-22

    It was and remains a big challenge for cancer nanomedicines to achieve high and stable drug loading while fast drug release in the target cells. Here, we report on novel hyaluronic acid-shelled disulfide-crosslinked biodegradable polymersomes (HA-XPS) self-assembled from hyaluronic acid-b-poly(trimethylene carbonate-co-dithiolane trimethylene carbonate) diblock copolymer for ultrahigh-efficiency reactive encapsulation and CD44-targeted delivery of mertansine (DM1) toxin, a highly potent warhead for clinically used antibody-drug conjugates. Remarkably, HA-XPS showed quantitative encapsulation of DM1 even with a high drug loading content of 16.7 wt.%. DM1-loaded HA-XPS (HA-XPS-DM1) presented a small size of ~80 nm, low drug leakage under physiological condition and fast glutathione-triggered drug release. MTT assays revealed that HA-XPS was non-cytotoxic while HA-XPS-DM1 was highly potent to MDA-MB-231 cells with an IC50 comparable to free DM1. The in vitro and in vivo inhibition experiments indicated that HA-XPS could actively target to MDA-MB-231 cells. Notably, HA-XPS-DM1 while causing little adverse effects could effectively inhibit tumor growth and significantly prolong survival time in MDA-MB-231 human breast tumor-bearing mice. HA-XPS-DM1 provides a novel and unique treatment for CD44-positive cancers.

  4. Calcium-activated potassium channels - a therapeutic target for modulating nitric oxide in cardiovascular disease?

    DEFF Research Database (Denmark)

    Dalsgaard, Thomas; Kroigaard, Christel; Simonsen, Ulf

    2010-01-01

    IMPORTANCE OF THE FIELD: Cardiovascular risk factors are often associated with endothelial dysfunction, which is also prognostic for occurrence of cardiovascular events. Endothelial dysfunction is reflected by blunted vasodilatation and reduced nitric oxide (NO) bioavailability. Endothelium......-dependent vasodilatation is mediated by NO, prostacyclin, and an endothelium-derived hyperpolarising factor (EDHF), and involves small (SK) and intermediate (IK) conductance Ca(2+)-activated K(+) channels. Therefore, SK and IK channels may be drug targets for the treatment of endothelial dysfunction in cardiovascular...... disease. AREAS COVERED IN THIS REVIEW: SK and IK channels are involved in EDHF-type vasodilatation, but recent studies suggest that these channels are also involved in the regulation of NO bioavailability. Here we review how SK and IK channels may regulate NO bioavailability. WHAT THE READER WILL GAIN...

  5. Design and evaluation of dual CD44 receptor and folate receptor-targeting double-smart pH-response multifunctional nanocarrier

    Science.gov (United States)

    Chen, Daquan; Song, Xiaoyan; Wang, Kaili; Guo, Chunjing; Yu, Yueming; Fan, Huaying; Zhao, Feng

    2017-12-01

    In this article, in order to enhance the bioavailiability and tumor targeting of curcumin (Cur), the oligosaccharides of hyaluronan conjugates, folic acid-oligosaccharides of hyaluronan-acetal-menthone 1,2-glycerol ketal (FA-oHA-Ace-MGK) carried oHA as a ligand to CD44 receptor, double-pH-sensitive Ace-MGK as hydrophobic moieties, and FA as the target of folate receptor. The structure characteristics of this smart response multifunctional dual-targeting nano-sized carrier was measured by fourier-transform infrared (FT-IR) and nuclear magnetic resonance (1H-NMR). Cur, an anticancer drug, was successfully loaded in FA-oHA-Ace-MGK micelles by self-assembly. The measurement results of transmission electron microscopy (TEM) presented that the Cur-loaded micelles were spherical in shape with the average size of 166.3 ± 2.12 nm and zeta potential - 30.07 mV. Much more encapsulated Cur could be released at mildly acidic environments than at pH 7.4, from the Cur-FA-oHA-Ace-MGK micelles. Cytotoxicity assay indicated that non-Cur loaded micelles mostly had no cytotoxicity to MCF-7 cells and A549 cells, and Cur-loaded micelles had significantly lower survival rate than Cur suspension in the same concentration, which proved that the drug-loaded micelles can effectively inhibit tumor cell growth. The targeting of CD44 receptors and folate receptors was proved in vitro cellular uptake assay. These results showed the promising potential of FA-oHA-Ace-MGK as an effective nano-sized carrier for anti-tumor drug delivery.

  6. Receptor-Meditated Endocytosis by Hyaluronic Acid@Superparamagnetic Nanovetor for Targeting of CD44-Overexpressing Tumor Cells

    Directory of Open Access Journals (Sweden)

    Kwang Sik Yu

    2016-08-01

    Full Text Available The present report proposes a more rational hyaluronic acid (HA conjugation protocol that can be used to modify the surface of the superparamagnetic iron oxide nanoparticles (SPIONs by covalently binding the targeting molecules (HA with glutamic acid as a molecular linker on peripheral surface of SPIONs. The synthesis of HA-Glutamic Acid (GA@SPIONs was included oxidization of nanoparticle’s surface with H2O2 followed by activation of hydroxyl group and reacting glutamic acid as an intermediate molecule demonstrating transfection of lung cancer cells. Fourier transform infrared (FTIR and zeta-potential studies confirmed the chemical bonding between amino acid linker and polysaccharides. 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT cytotoxicity assay showed that HA-SPIONs-treated cells remained 82.9% ± 2.7% alive at high particle dosage (200 µg/mL iron concentration, whereas GA-SPIONs and bare SPIONs (B-SPIONs treated cells had only 59.3% ± 13.4% and 26.5% ± 3.1% survival rate at the same conditions, respectively. Confocal microscopy analysis showed increased cellular internalization of HA-SPIONs compared to non-interacting agarose coated SPIONs (AgA-SPIONs.

  7. Comparison of Calcium Dynamics and Specific Features for G Protein-Coupled Receptor-Targeting Drugs Using Live Cell Imaging and Automated Analysis.

    Science.gov (United States)

    Gupta, Rishikesh Kumar; Swain, Sarpras; Kankanamge, Dinesh; Priyanka, Pantula Devi; Singh, Ranjana; Mitra, Kishalay; Karunarathne, Ajith; Giri, Lopamudra

    2017-08-01

    G protein-coupled receptors (GPCRs) are targets for designing a large fraction of the drugs in the pharmaceutical industry. For GPCR-targeting drug screening using cell-based assays, measurement of cytosolic calcium has been widely used to obtain dose-response profiles. However, it remains challenging to obtain drug-specific features due to cell-to-cell heterogeneity in drug-cell responses obtained from live cell imaging. Here, we present a framework combining live cell imaging of a cell population and a feature extraction method for classification of responses of drugs targeting GPCRs CXCR4 and α2AR. We measured the calcium dynamics using confocal microscopy and compared the responses for SDF-1α and norepinephrine. The results clearly show that the clustering patterns of responses for the two GPCRs are significantly different. Additionally, we show that different drugs targeting the same GPCR induce different calcium response signatures. We also implemented principal component analysis and k means for feature extraction and used nondominated (ND) sorting for ranking a group of drugs at various doses. The presented approach can be used to model a cell population as a mixture of subpopulations. It also offers specific advantages, such as higher spatial resolution, classification of responses, and ranking of drugs, potentially providing a platform for high-content drug screening.

  8. Development and implementation of a high-throughput compound screening assay for targeting disrupted ER calcium homeostasis in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Kamran Honarnejad

    Full Text Available Disrupted intracellular calcium homeostasis is believed to occur early in the cascade of events leading to Alzheimer's disease (AD pathology. Particularly familial AD mutations linked to Presenilins result in exaggerated agonist-evoked calcium release from endoplasmic reticulum (ER. Here we report the development of a fully automated high-throughput calcium imaging assay utilizing a genetically-encoded FRET-based calcium indicator at single cell resolution for compound screening. The established high-throughput screening assay offers several advantages over conventional high-throughput calcium imaging technologies. We employed this assay for drug discovery in AD by screening compound libraries consisting of over 20,000 small molecules followed by structure-activity-relationship analysis. This led to the identification of Bepridil, a calcium channel antagonist drug in addition to four further lead structures capable of normalizing the potentiated FAD-PS1-induced calcium release from ER. Interestingly, it has recently been reported that Bepridil can reduce Aβ production by lowering BACE1 activity. Indeed, we also detected lowered Aβ, increased sAPPα and decreased sAPPβ fragment levels upon Bepridil treatment. The latter findings suggest that Bepridil may provide a multifactorial therapeutic modality for AD by simultaneously addressing multiple aspects of the disease.

  9. Using hyaluronic acid-functionalized pH stimuli-responsive mesoporous silica nanoparticles for targeted delivery to CD44-overexpressing cancer cells.

    Science.gov (United States)

    Wang, Zhihui; Tian, Yongfeng; Zhang, Hua; Qin, Yanmei; Li, Dong; Gan, Li; Wu, Fanhong

    In this study, novel hyaluronic acid-pH stimuli-responsive lipid membrane mesoporous silica nanoparticles (HA-PL-MSNs) were designed and assembled, with the chemotherapeutic agent doxorubicin (DOX) as the model drug. HA-PL-MSNs exhibited a well-defined mesostructure covered by lipid bilayer and particle size of ~150 nm. The drug loading capacity was up to ~18.2%. DOX release could be effectively retained by the lipid bilayer in pH 7.4 buffer and exhibited a pH-triggered burst release in the acidic condition. Confocal laser scanning microscopy and fluorescence-activated cell sorting showed that HA-PL-MSNs exhibited higher cellular uptake efficiency via CD44 receptor-mediated endocytosis compared with PL-MSNs in HeLa cells. In vitro cytotoxicity studies demonstrated that HA-PL-MSNs could effectively enhance the targeted delivery of DOX and restrain the growth of HeLa cells. This might provide a promising alternative for the development of a targeted anticancer drug delivery system.

  10. Novel CD44 receptor targeting multifunctional "nano-eggs" based on double pH-sensitive nanoparticles for co-delivery of curcumin and paclitaxel to cancer cells and cancer stem cells

    Science.gov (United States)

    Chen, Daquan; Wang, Guohua; Song, Weiguo; Zhang, Qiang

    2015-10-01

    Most anticancer drugs cannot kill cancer stem cells (CSCs) effectively, which lead to the failure of anticancer chemotherapy, such as relapse and metastasis. In this study, we prepared a multifunctional oligosaccharides of hyaluronan (oHA) conjugates, oHA-histidine-menthone 1,2-glycerol ketal (oHM). The oHM conjugates possess pH-sensitive menthone 1,2-glycerol ketal (MGK) as hydrophobic moieties and oHA as the target of CD44 receptor. Anticancer drugs, curcumin(Cur) and paclitaxel(PTX), were loaded into oHM micelles via self-assembly. Then, oHM micelles were mineralized through controlled deposition of inorganic calcium and phosphate ions on the nanoparticular shell via a sequential addition method to fabricate the "nano-eggs." The formed nano-eggs had a smaller size (120.6 ± 4.5 nm) than oHM micelles (158.6 ± 6.4 nm), indicating that mineralization made the appearance of compact nanoparticles. Interestingly, when the nano-eggs were put into the acidic conditions (pH 6.5), their outer shell(inorganic minerals) will be destroyed with the larger size, while the "nano-eggs" were stable under pH 7.4. For both nano-eggs and oHM micelles, the Cur and PTX were released in a sustained manner depending on the pH of the solution. However, the nano-eggs showed much lower released than the oHM micelles due to the dissolution of the inorganic minerals and pH-sensitive ketal at mildly acidic environments (pH 6.5). In vivo study, the nano-eggs could get to the tumor site more effectively than oHM micelles. CSCs were sorted by a side population assay from MDA-MB-231 breast cancer cell lines over-expressing CD44 receptors. Antitumor activity was also evaluated on MDA-MB-231 xenografts in nude mice. The antitumor efficacy indicated that nano-eggs with co-delivery of Cur and PTX produced the strongest antitumor efficacy, and nano-eggs showed strong activity against cancer stem cells. These double pH-sensitive nano-eggs may provide a promising strategy for drug delivery to both

  11. Novel CD44 receptor targeting multifunctional “nano-eggs” based on double pH-sensitive nanoparticles for co-delivery of curcumin and paclitaxel to cancer cells and cancer stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Daquan, E-mail: cdq1981@126.com [Peking University, School of Pharmaceutical Sciences, Health Science Center (China); Wang, Guohua [China Academy of Chinese Medical Sciences, Institute of Chinese Materia Madica (China); Song, Weiguo [Shouguang Fukang Pharmceutial Co., Ltd. (China); Zhang, Qiang, E-mail: zqdodo@bjmu.edu.cn [Peking University, School of Pharmaceutical Sciences, Health Science Center (China)

    2015-10-15

    Most anticancer drugs cannot kill cancer stem cells (CSCs) effectively, which lead to the failure of anticancer chemotherapy, such as relapse and metastasis. In this study, we prepared a multifunctional oligosaccharides of hyaluronan (oHA) conjugates, oHA-histidine-menthone 1,2-glycerol ketal (oHM). The oHM conjugates possess pH-sensitive menthone 1,2-glycerol ketal (MGK) as hydrophobic moieties and oHA as the target of CD44 receptor. Anticancer drugs, curcumin(Cur) and paclitaxel(PTX), were loaded into oHM micelles via self-assembly. Then, oHM micelles were mineralized through controlled deposition of inorganic calcium and phosphate ions on the nanoparticular shell via a sequential addition method to fabricate the “nano-eggs.” The formed nano-eggs had a smaller size (120.6 ± 4.5 nm) than oHM micelles (158.6 ± 6.4 nm), indicating that mineralization made the appearance of compact nanoparticles. Interestingly, when the nano-eggs were put into the acidic conditions (pH 6.5), their outer shell(inorganic minerals) will be destroyed with the larger size, while the “nano-eggs” were stable under pH 7.4. For both nano-eggs and oHM micelles, the Cur and PTX were released in a sustained manner depending on the pH of the solution. However, the nano-eggs showed much lower released than the oHM micelles due to the dissolution of the inorganic minerals and pH-sensitive ketal at mildly acidic environments (pH 6.5). In vivo study, the nano-eggs could get to the tumor site more effectively than oHM micelles. CSCs were sorted by a side population assay from MDA-MB-231 breast cancer cell lines over-expressing CD44 receptors. Antitumor activity was also evaluated on MDA-MB-231 xenografts in nude mice. The antitumor efficacy indicated that nano-eggs with co-delivery of Cur and PTX produced the strongest antitumor efficacy, and nano-eggs showed strong activity against cancer stem cells. These double pH-sensitive nano-eggs may provide a promising strategy for drug

  12. Congenital heart block maternal sera autoantibodies target an extracellular epitope on the α1G T-type calcium channel in human fetal hearts.

    Directory of Open Access Journals (Sweden)

    Linn S Strandberg

    Full Text Available BACKGROUND: Congenital heart block (CHB is a transplacentally acquired autoimmune disease associated with anti-Ro/SSA and anti-La/SSB maternal autoantibodies and is characterized primarily by atrioventricular (AV block of the fetal heart. This study aims to investigate whether the T-type calcium channel subunit α1G may be a fetal target of maternal sera autoantibodies in CHB. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate differential mRNA expression of the T-type calcium channel CACNA1G (α1G gene in the AV junction of human fetal hearts compared to the apex (18-22.6 weeks gestation. Using human fetal hearts (20-22 wks gestation, our immunoprecipitation (IP, Western blot analysis and immunofluorescence (IF staining results, taken together, demonstrate accessibility of the α1G epitope on the surfaces of cardiomyocytes as well as reactivity of maternal serum from CHB affected pregnancies to the α1G protein. By ELISA we demonstrated maternal sera reactivity to α1G was significantly higher in CHB maternal sera compared to controls, and reactivity was epitope mapped to a peptide designated as p305 (corresponding to aa305-319 of the extracellular loop linking transmembrane segments S5-S6 in α1G repeat I. Maternal sera from CHB affected pregnancies also reacted more weakly to the homologous region (7/15 amino acids conserved of the α1H channel. Electrophysiology experiments with single-cell patch-clamp also demonstrated effects of CHB maternal sera on T-type current in mouse sinoatrial node (SAN cells. CONCLUSIONS/SIGNIFICANCE: Taken together, these results indicate that CHB maternal sera antibodies readily target an extracellular epitope of α1G T-type calcium channels in human fetal cardiomyocytes. CHB maternal sera also show reactivity for α1H suggesting that autoantibodies can target multiple fetal targets.

  13. 20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol, a metabolite of ginseng, inhibits colon cancer growth by targeting TRPC channel-mediated calcium influx.

    Science.gov (United States)

    Hwang, Jeong Ah; Hwang, Mun Kyung; Jang, Yongwoo; Lee, Eun Jung; Kim, Jong-Eun; Oh, Mi Hyun; Shin, Dong Joo; Lim, Semi; Ji, Geun og; Oh, Uhtaek; Bode, Ann M; Dong, Zigang; Lee, Ki Won; Lee, Hyong Joo

    2013-06-01

    Abnormal regulation of Ca(2+) mediates tumorigenesis and Ca(2+) channels are reportedly deregulated in cancers, indicating that regulating Ca(2+) signaling in cancer cells is considered as a promising strategy to treat cancer. However, little is known regarding the mechanism by which Ca(2+) affects cancer cell death. Here, we show that 20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol (20-GPPD), a metabolite of ginseng saponin, causes apoptosis of colon cancer cells through the induction of cytoplasmic Ca(2+). 20-GPPD decreased cell viability, increased annexin V-positive early apoptosis and induced sub-G1 accumulation and nuclear condensation of CT-26 murine colon cancer cells. Although 20-GPPD-induced activation of AMP-activated protein kinase (AMPK) played a key role in the apoptotic death of CT-26 cells, LKB1, a well-known upstream kinase of AMPK, was not involved in this activation. To identify the upstream target of 20-GPPD for activating AMPK, we examined the effect of Ca(2+) on apoptosis of CT-26 cells. A calcium chelator recovered 20-GPPD-induced AMPK phosphorylation and CT-26 cell death. Confocal microscopy showed that 20-GPPD increased Ca(2+) entry into CT-26 cells, whereas a transient receptor potential canonical (TRPC) blocker suppressed Ca(2+) entry. When cells were treated with a TRPC blocker plus an endoplasmic reticulum (ER) calcium blocker, 20-GPPD-induced calcium influx was completely inhibited, suggesting that the ER calcium store, as well as TRPC, was involved. In vivo mouse CT-26 allografts showed that 20-GPPD significantly suppressed tumor growth, volume and weight in a dose-dependent manner. Collectively, 20-GPPD exerts potent anticarcinogenic effects on colon carcinogenesis by increasing Ca(2+) influx, mainly through TRPC channels, and by targeting AMPK. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Analysis of Post-Traumatic Brain Injury Gene Expression Signature Reveals Tubulins, Nfe2l2, Nfkb, Cd44, and S100a4 as Treatment Targets.

    Science.gov (United States)

    Lipponen, Anssi; Paananen, Jussi; Puhakka, Noora; Pitkänen, Asla

    2016-08-17

    We aimed to define the chronically altered gene expression signature of traumatic brain injury (TBI-sig) to discover novel treatments to reverse pathologic gene expression or reinforce the expression of recovery-related genes. Genome-wide RNA-sequencing was performed at 3 months post-TBI induced by lateral fluid-percussion injury in rats. We found 4964 regulated genes in the perilesional cortex and 1966 in the thalamus (FDR sig was used for a LINCS analysis which identified 11 compounds that showed a strong connectivity with the TBI-sig in neuronal cell lines. Of these, celecoxib and sirolimus were recently reported to have a disease-modifying effect in in vivo animal models of epilepsy. Other compounds revealed by the analysis were BRD-K91844626, BRD-A11009626, NO-ASA, BRD-K55260239, SDZ-NKT-343, STK-661558, BRD-K75971499, ionomycin, and desmethylclomipramine. Network analysis of overlapping genes revealed the effects on tubulins (Tubb2a, Tubb3, Tubb4b), Nfe2l2, S100a4, Cd44, and Nfkb2, all of which are linked to TBI-relevant outcomes, including epileptogenesis and tissue repair. Desmethylclomipramine modulated most of the gene targets considered favorable for TBI outcome. Our data demonstrate long-lasting transcriptomics changes after TBI. LINCS analysis predicted that these changes could be modulated by various compounds, some of which are already in clinical use but never tested in TBI.

  15. Calcium - urine

    Science.gov (United States)

    Urinary Ca+2; Kidney stones - calcium in urine; Renal calculi - calcium in your urine; Parathyroid - calcium in urine ... Urine calcium level can help your provider: Decide on the best treatment for the most common type of kidney ...

  16. Targeting CD44-STAT3 signaling by Gemini vitamin D analog leads to inhibition of invasion in basal-like breast cancer.

    Science.gov (United States)

    So, Jae Young; Smolarek, Amanda K; Salerno, David M; Maehr, Hubert; Uskokovic, Milan; Liu, Fang; Suh, Nanjoo

    2013-01-01

    CD44, a transmembrane glycoprotein, is a major receptor for extracellular proteins involved in invasion and metastasis of human cancers. We have previously demonstrated that the novel Gemini vitamin D analog BXL0124 [1α,25-dihydroxy-20R-21(3-hydroxy-3-deuteromethyl-4,4,4-trideuterobutyl)-23-yne-26,27-hexafluro-cholecalciferol] repressed CD44 expression in MCF10DCIS.com basal-like human breast cancer cells and inhibited MCF10DCIS xenograft tumor growth. In the present study, we investigated potential factors downstream of CD44 and the biological role of CD44 repression by BXL0124 in MCF10DCIS cells. The treatment with Gemini vitamin D BXL0124 decreased CD44 protein level, suppressed STAT3 signaling, and inhibited invasion and proliferation of MCF10DCIS cells. The interaction between CD44 and STAT3 was determined by co-immunoprecipitation. CD44 forms a complex with STAT3 and Janus kinase 2 (JAK2) to activate STAT3 signaling, which was inhibited by BXL0124 in MCF10DCIS cells. The role of CD44 in STAT3 signaling and invasion of MCF10DCIS cells was further determined by the knockdown of CD44 using small hairpin RNA in vitro and in vivo. MCF10DCIS cell invasion was markedly decreased by the knockdown of CD44 in vitro. The knockdown of CD44 also significantly decreased mRNA expression levels of invasion markers, matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA), in MCF10DCIS cells. In MCF10DCIS xenograft tumors, CD44 knockdown decreased tumor size and weight as well as invasion markers. The present study identifies STAT3 as an important signaling molecule interacting with CD44 and demonstrates the essential role of CD44-STAT3 signaling in breast cancer invasion. It also suggests that repression of CD44-STAT3 signaling is a key molecular mechanism in the inhibition of breast cancer invasion by the Gemini vitamin D analog BXL0124.

  17. Targeting CD44-STAT3 signaling by Gemini vitamin D analog leads to inhibition of invasion in basal-like breast cancer.

    Directory of Open Access Journals (Sweden)

    Jae Young So

    Full Text Available CD44, a transmembrane glycoprotein, is a major receptor for extracellular proteins involved in invasion and metastasis of human cancers. We have previously demonstrated that the novel Gemini vitamin D analog BXL0124 [1α,25-dihydroxy-20R-21(3-hydroxy-3-deuteromethyl-4,4,4-trideuterobutyl-23-yne-26,27-hexafluro-cholecalciferol] repressed CD44 expression in MCF10DCIS.com basal-like human breast cancer cells and inhibited MCF10DCIS xenograft tumor growth. In the present study, we investigated potential factors downstream of CD44 and the biological role of CD44 repression by BXL0124 in MCF10DCIS cells.The treatment with Gemini vitamin D BXL0124 decreased CD44 protein level, suppressed STAT3 signaling, and inhibited invasion and proliferation of MCF10DCIS cells. The interaction between CD44 and STAT3 was determined by co-immunoprecipitation. CD44 forms a complex with STAT3 and Janus kinase 2 (JAK2 to activate STAT3 signaling, which was inhibited by BXL0124 in MCF10DCIS cells. The role of CD44 in STAT3 signaling and invasion of MCF10DCIS cells was further determined by the knockdown of CD44 using small hairpin RNA in vitro and in vivo. MCF10DCIS cell invasion was markedly decreased by the knockdown of CD44 in vitro. The knockdown of CD44 also significantly decreased mRNA expression levels of invasion markers, matrix metalloproteinases (MMPs and urokinase plasminogen activator (uPA, in MCF10DCIS cells. In MCF10DCIS xenograft tumors, CD44 knockdown decreased tumor size and weight as well as invasion markers.The present study identifies STAT3 as an important signaling molecule interacting with CD44 and demonstrates the essential role of CD44-STAT3 signaling in breast cancer invasion. It also suggests that repression of CD44-STAT3 signaling is a key molecular mechanism in the inhibition of breast cancer invasion by the Gemini vitamin D analog BXL0124.

  18. pH-Sensitive Coiled-Coil Peptide-Cross-Linked Hyaluronic Acid Nanogels: Synthesis and Targeted Intracellular Protein Delivery to CD44 Positive Cancer Cells.

    Science.gov (United States)

    Ding, Lingling; Jiang, Yu; Zhang, Jian; Klok, Harm-Anton; Zhong, Zhiyuan

    2018-02-12

    The clinical translation of protein drugs that act intracellularly is limited by the absence of safe and efficient intracellular protein delivery vehicles. Here, pH-sensitive coiled-coil peptide-cross-linked hyaluronic acid nanogels (HA-cNGs) were designed and investigated for targeted intracellular protein delivery to CD44 overexpressing MCF-7 breast cancer cells. HA-cNGs were obtained with a small size of 176 nm from an equivalent mixture of hyaluronic acid conjugates with GY(EIAALEK) 3 GC (E3) and GY(KIAALKE) 3 GC (K3) peptides, respectively, at pH 7.4 by nanoprecipitation. Circular dichroism (CD) proved the formation of coiled-coil structures between E3 and K3 peptides at pH 7.4 while fast uncoiling at pH 5.0. HA-cNGs showed facile loading of cytochrome C (CC) and greatly accelerated CC release under mild acidic conditions (18.4%, 76.8%, and 91.4% protein release in 24 h at pH 7.4, 6.0, and 5.0, respectively). Confocal microscopy and flow cytometry displayed efficient internalization of CC-loaded HA-cNGs and effective endosomal escape of CC in MCF-7 cancer cells. Remarkably, HA-cNGs loaded with saporin, a ribosome inactivating protein, exhibited significantly enhanced apoptotic activity to MCF-7 cells with a low IC 50 of 12.2 nM. These coiled-coil peptide-cross-linked hyaluronic acid nanogels have appeared as a simple and multifunctional platform for efficient intracellular protein delivery.

  19. Effect of insecticidal fusion proteins containing spider toxins targeting sodium and calcium ion channels on pyrethroid-resistant strains of peach-potato aphid (Myzus persicae).

    Science.gov (United States)

    Yang, Sheng; Fitches, Elaine; Pyati, Prashant; Gatehouse, John A

    2015-07-01

    The recombinant fusion proteins Pl1a/GNA and Hv1a/GNA contain the spider venom peptides δ-amaurobitoxin-PI1a or ω-hexatoxin-Hv1a respectively, linked to snowdrop lectin (GNA). Pl1a targets receptor site 4 of insect voltage-gated sodium channels (NaCh), while Hv1a targets voltage-gated calcium channels. Insecticide-resistant strains of peach-potato aphid (Myzus persicae) contain mutations in NaCh. The pyrethroid-resistant kdr (794J) and super-kdr (UKO) strains contain mutations at residues L1014 and M918 in the channel α-subunit respectively, while the kdr + super-kdr strain (4824J), insensitive to pyrethroids, contains mutations at both L1014 and M918. Pl1a/GNA and Hv1a/GNA fusion proteins have estimated LC50 values of 0.35 and 0.19 mg mL(-1) when fed to wild-type M. persicae. For insecticide-resistant aphids, LC50 for the Pl1a/GNA fusion protein increased by 2-6-fold, correlating with pyrethroid resistance (wild type < kdr < super-kdr < kdr + super-kdr strains). In contrast, LC50 for the Hv1a/GNA fusion protein showed limited correlation with pyrethroid resistance. Mutations in the sodium channel in pyrethroid-resistant aphids also protect against a fusion protein containing a sodium-channel-specific toxin, in spite of differences in ligand-channel interactions, but do not confer resistance to a fusion protein targeting calcium channels. The use of fusion proteins with differing targets could play a role in managing pesticide resistance. © 2014 Society of Chemical Industry.

  20. Targeting Intracellular Calcium Signaling ([Ca2+]i to Overcome Acquired Multidrug Resistance of Cancer Cells: A Mini-Overview

    Directory of Open Access Journals (Sweden)

    Dietrich Büsselberg

    2017-05-01

    Full Text Available Cancer is a main public health problem all over the world. It affects millions of humans no matter their age, gender, education, or social status. Although chemotherapy is the main strategy for the treatment of cancer, a major problem limiting its success is the intrinsic or acquired drug resistance. Therefore, cancer drug resistance is a major impediment in medical oncology resulting in a failure of a successful cancer treatment. This mini-overview focuses on the interdependent relationship between intracellular calcium ([Ca2+]i signaling and multidrug resistance of cancer cells, acquired upon treatment of tumors with anticancer drugs. We propose that [Ca2+]i signaling modulates gene expression of multidrug resistant (MDR genes which in turn can be modulated by epigenetic factors which in turn leads to modified protein expression in drug resistant tumor cells. A precise knowledge of these mechanisms will help to develop new therapeutic strategies for drug resistant tumors and will improve current chemotherapy.

  1. Calcium Carbonate

    Science.gov (United States)

    Calcium carbonate is a dietary supplement used when the amount of calcium taken in the diet is not ... for healthy bones, muscles, nervous system, and heart. Calcium carbonate also is used as an antacid to relieve ...

  2. Calcium supplements

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007477.htm Calcium supplements To use the sharing features on this page, please enable JavaScript. WHO SHOULD TAKE CALCIUM SUPPLEMENTS? Calcium is an important mineral for the ...

  3. Rice calcium-dependent protein kinase OsCPK17 targets plasma membrane intrinsic protein and sucrose phosphate synthase and is required for a proper cold stress response

    KAUST Repository

    Almadanim, M. Cecília

    2017-01-19

    Calcium-dependent protein kinases (CDPKs) are involved in plant tolerance mechanisms to abiotic stresses. Although CDPKs are recognized as key messengers in signal transduction, the specific role of most members of this family remains unknown. Here we test the hypothesis that OsCPK17 plays a role in rice cold stress response by analyzing OsCPK17 knockout, silencing, and overexpressing rice lines under low temperature. Altered OsCPK17 gene expression compromises cold tolerance performance, without affecting the expression of key cold stress-inducible genes. A comparative phosphoproteomic approach led to the identification of six potential in vivo OsCPK17 targets, which are associated with sugar and nitrogen metabolism, and with osmotic regulation. To test direct interaction, in vitro kinase assays were performed, showing that the sucrose phosphate synthase OsSPS4, and the aquaporin OsPIP2;1/OsPIP2;6 are phosphorylated by OsCPK17 in a calcium-dependent manner. Altogether, our data indicates that OsCPK17 is required for a proper cold stress response in rice, likely affecting the activity of membrane channels and sugar metabolism.

  4. Targeting Tumor Cells with Anti-CD44 Antibody Triggers Macrophage-Mediated Immune Modulatory Effects in a Cancer Xenograft Model.

    Directory of Open Access Journals (Sweden)

    Daniela Maisel

    Full Text Available CD44, a transmembrane receptor reported to be involved in various cellular functions, is overexpressed in several cancer types and supposed to be involved in the initiation, progression and prognosis of these cancers. Since the sequence of events following the blockage of the CD44-HA interaction has not yet been studied in detail, we profiled xenograft tumors by RNA Sequencing to elucidate the mode of action of the anti-CD44 antibody RG7356. Analysis of tumor and host gene-expression profiles led us to the hypothesis that treatment with RG7356 antibody leads to an activation of the immune system. Using cytokine measurements we further show that this activation involves the secretion of chemo-attractants necessary for the recruitment of immune cells (i.e. macrophages to the tumor site. We finally provide evidence for antibody-dependent cellular phagocytosis (ADCP of the malignant cells by macrophages.

  5. Cosmic ray source abundance of calcium

    CERN Document Server

    Perron, C

    1978-01-01

    Re-examines the results of experiments in which ultra-high purity iron targets were irradiated by protons from the two CERN accelerators (600 MeV and 21 GeV); the spallation products were then chemically separated, and their isotopic composition determined by mass spectrometry. Ratios of cross-sections for calcium production by spallation of iron show that /sup 42/Ca, /sup 43/Ca and /sup 44/Ca have about the same abundance, about 10-15% that of iron, confirming earlier studies. (11 refs).

  6. Vinculin but not alpha-actinin is a target of PKC phosphorylation during junctional assembly induced by calcium

    DEFF Research Database (Denmark)

    Perez-Moreno, M; Avila, A; Islas, S

    1998-01-01

    proteins ZO1, ZO2 and ZO3, in a previous work we specifically explored these molecules but found no alteration in their phosphorylation pattern. To continue the search for the target of protein kinase C, in the present work we have studied the subcellular distribution and phosphorylation of vinculin...

  7. Bcl-2 regulation of the inositol 1,4,5-trisphosphate receptor and calcium signaling in normal and malignant lymphocytes: potential new target for cancer treatment.

    Science.gov (United States)

    Greenberg, Edward F; Lavik, Andrew R; Distelhorst, Clark W

    2014-10-01

    The anti-apoptotic protein Bcl-2 is a versatile regulator of cell survival. Its interactions with its own pro-apoptotic family members are widely recognized for their role in promoting the survival of cancer cells. These interactions are thus being targeted for cancer treatment. Less widely recognized is the interaction of Bcl-2 with the inositol 1,4,5-trisphosphate receptor (InsP3R), an InsP3-gated Ca(2+) channel located on the endoplasmic reticulum. The nature of this interaction, the mechanism by which it controls Ca(2+) release from the ER, its role in T-cell development and survival, and the possibility of targeting it as a novel cancer treatment strategy are summarized in this review. This article is part of a Special Issue entitled: Calcium signaling in health and disease. Guest Editors: Geert Bultynck, Jacques Haiech, Claus W. Heizmann, Joachim Krebs, and Marc Moreau. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. SU-E-J-44: A Novel Approach to Quantify Patient Setup and Target Motion for Real-Time Image-Guided Radiotherapy (IGRT)

    Energy Technology Data Exchange (ETDEWEB)

    Li, S; Charpentier, P; Sayler, E; Micaily, B; Miyamoto, C [Temple University Hospital, Phila., PA (United States); Geng, J [Xigen LLC, Gaithersburg, MD (United States)

    2015-06-15

    Purpose Isocenter shifts and rotations to correct patient setup errors and organ motion cannot remedy some shape changes of large targets. We are investigating new methods in quantification of target deformation for realtime IGRT of breast and chest wall cancer. Methods Ninety-five patients of breast or chest wall cancer were accrued in an IRB-approved clinical trial of IGRT using 3D surface images acquired at daily setup and beam-on time via an in-room camera. Shifts and rotations relating to the planned reference surface were determined using iterative-closest-point alignment. Local surface displacements and target deformation are measured via a ray-surface intersection and principal component analysis (PCA) of external surface, respectively. Isocenter shift, upper-abdominal displacement, and vectors of the surface projected onto the two principal components, PC1 and PC2, were evaluated for sensitivity and accuracy in detection of target deformation. Setup errors for some deformed targets were estimated by superlatively registering target volume, inner surface, or external surface in weekly CBCT or these outlines on weekly EPI. Results Setup difference according to the inner-surface, external surface, or target volume could be 1.5 cm. Video surface-guided setup agreed with EPI results to within < 0.5 cm while CBCT results were sometimes (∼20%) different from that of EPI (>0.5 cm) due to target deformation for some large breasts and some chest walls undergoing deep-breath-hold irradiation. Square root of PC1 and PC2 is very sensitive to external surface deformation and irregular breathing. Conclusion PCA of external surfaces is quick and simple way to detect target deformation in IGRT of breast and chest wall cancer. Setup corrections based on the target volume, inner surface, and external surface could be significant different. Thus, checking of target shape changes is essential for accurate image-guided patient setup and motion tracking of large deformable

  9. Antimicrobial peptaibols, novel suppressors of tumor cells, targeted calcium-mediated apoptosis and autophagy in human hepatocellular carcinoma cells

    Directory of Open Access Journals (Sweden)

    Chen Xiu-Lan

    2010-02-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC is one of the most common cancers in the world which is highly chemoresistant to currently available chemotherapeutic agents. Thus, novel therapeutic targets are needed to be sought for the successful treatment of HCC. Peptaibols, a family of peptides synthesized non-ribosomally by the Trichoderma species and other fungi, exhibit antibiotic activities against bacteria and fungi. Few studies recently showed that peptaibols exerted cytotoxicity toward human lung epithelial and breast carcinoma cells. However, the mechanism involved in peptaibol-induced cell death remains poorly understood. Results Here, we showed that Trichokonin VI (TK VI, a peptaibol from Trichoderma pseudokoningii SMF2, induced growth inhibition of HCC cells in a dose-dependent manner. It did not obviously impair the viability of normal liver cells at lower concentration. Moreover, the suppression of cell viability resulted from the programmed cell death (PCD with characteristics of apoptosis and autophagy. An influx of Ca2+ triggered the activation of μ-calpain and proceeded to the translocation of Bax to mitochondria and subsequent promotion of apoptosis. On the other hand, typically morphological characteristics consistent with autophagy were also observed by punctate distribution of MDC staining and the induction of LC3-II, including extensive autophagic vacuolization and enclosure of cell organelles by these autophagosomes. More significantly, specific depletion of Bak expression by small RNA interfering (siRNA could partly attenuate TK VI-induced autophagy. However, siRNA against Bax led to increased autophagy. Conclusion Taken together, these findings showed for the first time that peptaibols were novel regulators involved in both apoptosis and autophagy, suggesting that the class of peptaibols might serve as potential suppressors of tumor cells.

  10. Gene-Targeted Mice with the Human Troponin T R141W Mutation Develop Dilated Cardiomyopathy with Calcium Desensitization.

    Directory of Open Access Journals (Sweden)

    Mohun Ramratnam

    Full Text Available Most studies of the mechanisms leading to hereditary dilated cardiomyopathy (DCM have been performed in reconstituted in vitro systems. Genetically engineered murine models offer the opportunity to dissect these mechanisms in vivo. We generated a gene-targeted knock-in murine model of the autosomal dominant Arg141Trp (R141W mutation in Tnnt2, which was first described in a human family with DCM. Mice heterozygous for the mutation (Tnnt2R141W/+ recapitulated the human phenotype, developing left ventricular dilation and reduced contractility. There was a gene dosage effect, so that the phenotype in Tnnt2R141W/+mice was attenuated by transgenic overexpression of wildtype Tnnt2 mRNA transcript. Male mice exhibited poorer survival than females. Biomechanical studies on skinned fibers from Tnnt2R141W/+ hearts showed a significant decrease in pCa50 (-log[Ca2+] required for generation of 50% of maximal force relative to wildtype hearts, indicating Ca2+ desensitization. Optical mapping studies of Langendorff-perfused Tnnt2R141W/+ hearts showed marked increases in diastolic and peak systolic intracellular Ca2+ ([Ca2+]i, and prolonged systolic rise and diastolic fall of [Ca2+]i. Perfused Tnnt2R141W/+ hearts had slower intrinsic rates in sinus rhythm and reduced peak heart rates in response to isoproterenol. Tnnt2R141W/+ hearts exhibited a reduction in phosphorylated phospholamban relative to wildtype mice. However, crossing Tnnt2R141W/+ mice with phospholamban knockout (Pln-/- mice, which exhibit increased Ca2+ transients and contractility, had no effect on the DCM phenotype. We conclude that the Tnnt2 R141W mutation causes a Ca2+ desensitization and mice adapt by increasing Ca2+-transient amplitudes, which impairs Ca2+ handling dynamics, metabolism and responses to β-adrenergic activation.

  11. Elemental calcium intake associated with calcium acetate/calcium carbonate in the treatment of hyperphosphatemia.

    Science.gov (United States)

    Wilson, Rosamund J; Copley, J Brian

    2017-01-01

    Calcium-based and non-calcium-based phosphate binders have similar efficacy in the treatment of hyperphosphatemia; however, calcium-based binders may be associated with hypercalcemia, vascular calcification, and adynamic bone disease. A post hoc analysis was carried out of data from a 16-week, Phase IV study of patients with end-stage renal disease (ESRD) who switched to lanthanum carbonate monotherapy from baseline calcium acetate/calcium carbonate monotherapy. Of the intent-to-treat population (N=2520), 752 patients with recorded dose data for calcium acetate (n=551)/calcium carbonate (n=201) at baseline and lanthanum carbonate at week 16 were studied. Elemental calcium intake, serum phosphate, corrected serum calcium, and serum intact parathyroid hormone levels were analyzed. Of the 551 patients with calcium acetate dose data, 271 (49.2%) had an elemental calcium intake of at least 1.5 g/day at baseline, and 142 (25.8%) had an intake of at least 2.0 g/day. Mean (95% confidence interval [CI]) serum phosphate levels were 6.1 (5.89, 6.21) mg/dL at baseline and 6.2 (6.04, 6.38) mg/dL at 16 weeks; mean (95% CI) corrected serum calcium levels were 9.3 (9.16, 9.44) mg/dL and 9.2 (9.06, 9.34) mg/dL, respectively. Of the 201 patients with calcium carbonate dose data, 117 (58.2%) had an elemental calcium intake of at least 1.5 g/day, and 76 (37.8%) had an intake of at least 2.0 g/day. Mean (95% CI) serum phosphate levels were 5.8 (5.52, 6.06) mg/dL at baseline and 5.8 (5.53, 6.05) mg/dL at week 16; mean (95% CI) corrected serum calcium levels were 9.7 (9.15, 10.25) mg/dL and 9.2 (9.06, 9.34) mg/dL, respectively. Calcium acetate/calcium carbonate phosphate binders, taken to control serum phosphate levels, may result in high levels of elemental calcium intake. This may lead to complications related to calcium balance.

  12. Gualou Guizhi decoction reverses brain damage with cerebral ischemic stroke, multi-component directed multi-target to screen calcium-overload inhibitors using combination of molecular docking and protein-protein docking.

    Science.gov (United States)

    Hu, Juan; Pang, Wen-Sheng; Han, Jing; Zhang, Kuan; Zhang, Ji-Zhou; Chen, Li-Dian

    2018-12-01

    Stroke is a disease of the leading causes of mortality and disability across the world, but the benefits of drugs curative effects look less compelling, intracellular calcium overload is considered to be a key pathologic factor for ischemic stroke. Gualou Guizhi decoction (GLGZD), a classical Chinese medicine compound prescription, it has been used to human clinical therapy of sequela of cerebral ischemia stroke for 10 years. This work investigated the GLGZD improved prescription against intracellular calcium overload could decreased the concentration of [Ca2+]i in cortex and striatum neurone of MCAO rats. GLGZD contains Trichosanthin and various small molecular that they are the potential active ingredients directed against NR2A, NR2B, FKBP12 and Calnodulin target proteins/enzyme have been screened by computer simulation. "Multicomponent systems" is capable to create pharmacological superposition effects. The Chinese medicine compound prescriptions could be considered as promising sources of candidates for discovery new agents.

  13. Calcium Electroporation

    DEFF Research Database (Denmark)

    Frandsen, Stine Krog; Gibot, Laure; Madi, Moinecha

    2015-01-01

    BACKGROUND: Calcium electroporation describes the use of high voltage electric pulses to introduce supraphysiological calcium concentrations into cells. This promising method is currently in clinical trial as an anti-cancer treatment. One very important issue is the relation between tumor cell kill...... efficacy-and normal cell sensitivity. METHODS: Using a 3D spheroid cell culture model we have tested the effect of calcium electroporation and electrochemotherapy using bleomycin on three different human cancer cell lines: a colorectal adenocarcinoma (HT29), a bladder transitional cell carcinoma (SW780......), and a breast adenocarcinoma (MDA-MB231), as well as on primary normal human dermal fibroblasts (HDF-n). RESULTS: The results showed a clear reduction in spheroid size in all three cancer cell spheroids three days after treatment with respectively calcium electroporation (p

  14. Paclitaxel induces apoptosis in breast cancer cells through different calcium--regulating mechanisms depending on external calcium conditions.

    Science.gov (United States)

    Pan, Zhi; Avila, Andrew; Gollahon, Lauren

    2014-02-17

    Previously, we reported that endoplasmic reticulum calcium stores were a direct target for paclitaxel initiation of apoptosis. Furthermore, the actions of paclitaxel attenuated Bcl-2 resistance to apoptosis through endoplasmic reticulum-mediated calcium release. To better understand the calcium-regulated mechanisms of paclitaxel-induced apoptosis in breast cancer cells, we investigated the role of extracellular calcium, specifically; whether influx of extracellular calcium contributed to and/or was necessary for paclitaxel-induced apoptosis. Our results demonstrated that paclitaxel induced extracellular calcium influx. This mobilization of extracellular calcium contributed to subsequent cytosolic calcium elevation differently, depending on dosage. Under normal extracellular calcium conditions, high dose paclitaxel induced apoptosis-promoting calcium influx, which did not occur in calcium-free conditions. In the absence of extracellular calcium an "Enhanced Calcium Efflux" mechanism in which high dose paclitaxel stimulated calcium efflux immediately, leading to dramatic cytosolic calcium decrease, was observed. In the absence of extracellular calcium, high dose paclitaxel's stimulatory effects on capacitative calcium entry and apoptosis could not be completely restored. Thus, normal extracellular calcium concentrations are critical for high dose paclitaxel-induced apoptosis. In contrast, low dose paclitaxel mirrored controls, indicating that it occurs independent of extracellular calcium. Thus, extracellular calcium conditions only affect efficacy of high dose paclitaxel-induced apoptosis.

  15. A novel Gemini vitamin D analog represses the expression of a stem cell marker CD44 in breast cancer.

    Science.gov (United States)

    So, Jae Young; Lee, Hong Jin; Smolarek, Amanda K; Paul, Shiby; Wang, Chung-Xiou; Maehr, Hubert; Uskokovic, Milan; Zheng, Xi; Conney, Allan H; Cai, Li; Liu, Fang; Suh, Nanjoo

    2011-03-01

    CD44 is a multifunctional transmembrane protein involved in cell proliferation, angiogenesis, invasion, and metastasis. CD44 is identified as a cancer stem cell marker, and the CD44-positive breast cancer cells are enriched in residual breast cancer cell populations after conventional therapies, suggesting that CD44 may be an important target for cancer prevention and therapy. Therefore, we investigated for the inhibitory effect of a novel Gemini vitamin D analog, 1α,25-dihydroxy-20R-21(3-hydroxy-3-deuteromethyl-4,4,4-trideuterobutyl)-23-yne-26,27-hexafluoro-cholecalciferol (BXL0124), on mammary tumor growth and CD44 expression in MCF10DCIS.com human breast cancer in vitro and in vivo. MCF10DCIS.com cells were injected into mammary fat pads in immunodeficient mice, and BXL0124 was then administered intraperitoneally (0.1 μg/kg body weight) or orally (0.03 or 0.1 μg/kg body weight) 6 days a week for 5 weeks. At necropsy, mammary tumors and blood were collected for evaluating tumor growth, CD44 expression, and serum calcium level. BXL0124 suppressed mammary tumor growth and markedly decreased the expression of CD44 protein in MCF10DCIS xenograft tumors without causing hypercalcemic toxicity. BXL0124 also inhibited the expression of CD44 protein and mRNA as well as the transcriptional activity of the CD44 promoter in cultured MCF10DCIS.com cells. The repression of CD44 expression induced by BXL0124 was blocked by siRNA vitamin D receptor (VDR), indicating that the regulation of CD44 expression by BXL0124 is a VDR-dependent event. The novel Gemini vitamin D analog, BXL0124, represses CD44 expression in MCF10DCIS.com cells in vitro and in xenograft tumors, suggesting an inhibitory role of a Gemini vitamin D derivative on breast cancer stem cells.

  16. Get Enough Calcium

    Science.gov (United States)

    ... Calcium Print This Topic En español Get Enough Calcium Browse Sections The Basics Overview Foods and Vitamins ... women, don't get enough calcium. How much calcium do I need every day? Women: If you ...

  17. Calcium carbonate overdose

    Science.gov (United States)

    Tums overdose; Calcium overdose ... Calcium carbonate can be dangerous in large amounts. ... Some products that contain calcium carbonate are certain: ... and mineral supplements Other products may also contain calcium ...

  18. Calcium paradox and calcium entry blockers

    NARCIS (Netherlands)

    Ruigrok, T.J.C.; Slade, A.M.; Nayler, W.G.; Meijler, F.L.

    1984-01-01

    Reperfusion of isolated hearts with calcium-containing solution after a short period of calcium-free perfusion results in irreversible cell damage (calcium paradox). This phenomenon is characterized by an excessive influx of calcium into the cells, the rapid onset of myocardial contracture,

  19. Rice calcium-dependent protein kinase OsCPK17 targets plasma membrane intrinsic protein and sucrose-phosphate synthase and is required for a proper cold stress response.

    Science.gov (United States)

    Almadanim, M Cecília; Alexandre, Bruno M; Rosa, Margarida T G; Sapeta, Helena; Leitão, António E; Ramalho, José C; Lam, TuKiet T; Negrão, Sónia; Abreu, Isabel A; Oliveira, M Margarida

    2017-07-01

    Calcium-dependent protein kinases (CDPKs) are involved in plant tolerance mechanisms to abiotic stresses. Although CDPKs are recognized as key messengers in signal transduction, the specific role of most members of this family remains unknown. Here, we test the hypothesis that OsCPK17 plays a role in rice cold stress response by analysing OsCPK17 knockout, silencing and overexpressing rice lines under low temperature. Altered OsCPK17 gene expression compromises cold tolerance performance, without affecting the expression of key cold stress-inducible genes. A comparative phosphoproteomic approach led to the identification of six potential in vivo OsCPK17 targets, which are associated with sugar and nitrogen metabolism, and with osmotic regulation. To test direct interaction, in vitro kinase assays were performed, showing that the sucrose-phosphate synthase OsSPS4 and the aquaporin OsPIP2;1/OsPIP2;6 are phosphorylated by OsCPK17 in a calcium-dependent manner. Altogether, our data indicates that OsCPK17 is required for a proper cold stress response in rice, likely affecting the activity of membrane channels and sugar metabolism. © 2017 John Wiley & Sons Ltd.

  20. Separation of no-carrier-added {sup 203}Pb, a surrogate radioisotope, from proton irradiated {sup nat}Tl{sub 2}CO{sub 3} target using calcium alginate hydrogel beads

    Energy Technology Data Exchange (ETDEWEB)

    Sarkar, Kangkana; Sen, Kamalika [Univ. of Calcutta, Kolkata (India). Dept. of Chemistry; Lahiri, Susanta [Saha Institute of Nuclear Physics, Kolkata (India)

    2016-07-01

    {sup 203}Pb is a promising radioisotope in the field of medical science as an imaging surrogate of {sup 212}Pb. In the present investigation {sup 203}Pb was produced by proton irradiation of natural Tl{sub 2}CO{sub 3} target and was separated from the bulk Tl target using calcium alginate (CA) hydrogel beads with a high separation factor (3.8 x 10{sup 4} at 10{sup -3} M HNO{sub 3}). During the separation process {sup 203}Pb was encapsulated in CA beads and desorption of the radioisotope could only be achieved in 1M HNO{sub 3}. Possibility of Tl uptake was also checked in Fe doped CA (Fe-CA) beads after oxidation of Tl(I) to Tl(III) by sodium bismuthate. No significant uptake of Tl(III) was noticed in the Fe-CA beads. The matrix is therefore suitable for isolation of {sup 203}Pb from the target as well as its storage in the bead for therapeutic as well as diagnostic purpose.

  1. Temperature-Sensitive Cav1.2 Calcium Channels Support Intrinsic Firing of Pyramidal Neurons and Provide a Target for the Treatment of Febrile Seizures

    Science.gov (United States)

    Radzicki, Daniel; Yau, Hau-Jie; Pollema-Mays, Sarah L.; Mlsna, Lauren; Cho, Kangho; Koh, Sookyong

    2013-01-01

    Febrile seizures are associated with increased brain temperature and are often resistant to treatments with antiepileptic drugs, such as carbamazepine and phenytoin, which are sodium channel blockers. Although they are clearly correlated with the hyperthermic condition, the precise cellular mechanisms of febrile seizures remain unclear. We performed patch-clamp recordings from pyramidal cells in acute rat brain slices at temperatures up to 40°C and found that, at ≥37°C, L-type calcium channels are active at unexpectedly hyperpolarized potentials and drive intrinsic firing, which is also supported by a temperature-dependent, gadolinium-sensitive sodium conductance. Pharmacological data, RT-PCR, and the current persistence in Cav1.3 knock-out mice suggested a critical contribution of Cav1.2 subunits to the temperature-dependent intrinsic firing, which was blocked by nimodipine. Because intrinsic firing may play a critical role in febrile seizures, we tested the effect of nimodipine in an in vivo model of febrile seizures and found that this drug dramatically reduces both the incidence and duration of febrile seizures in rat pups, suggesting new possibilities of intervention for this important pathological condition. PMID:23761887

  2. Coronary Calcium Scan

    Science.gov (United States)

    ... Back To Health Topics / Coronary Calcium Scan Coronary Calcium Scan Also known as Calcium Scan Test A coronary calcium scan is a CT scan of your heart that detects and measures the amount of calcium in the walls of your coronary arteries. Overview ...

  3. Calcium source (image)

    Science.gov (United States)

    Getting enough calcium to keep bones from thinning throughout a person's life may be made more difficult if that person has ... as a tendency toward kidney stones, for avoiding calcium-rich food sources. Calcium deficiency also effects the ...

  4. Calcium and bones (image)

    Science.gov (United States)

    Calcium is one of the most important minerals for the growth, maintenance, and reproduction of the human ... body, are continually being re-formed and incorporate calcium into their structure. Calcium is essential for the ...

  5. Calcium hydroxide poisoning

    Science.gov (United States)

    Hydrate - calcium; Lime milk; Slaked lime ... Calcium hydroxide ... These products contain calcium hydroxide: Cement Limewater Many industrial solvents and cleaners (hundreds to thousands of construction products, flooring strippers, brick cleaners, cement ...

  6. Calcium Pyrophosphate Deposition (CPPD)

    Science.gov (United States)

    ... Patient / Caregiver Diseases & Conditions Calcium Pyrophosphate Deposition (CPPD) Calcium Pyrophosphate Deposition (CPPD) Fast Facts The risk of ... young people, too. Proper diagnosis depends on detecting calcium pyrophosphate crystals in the fluid of an affected ...

  7. Calcium blood test

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003477.htm Calcium blood test To use the sharing features on this page, please enable JavaScript. The calcium blood test measures the level of calcium in the blood. ...

  8. Enhanced expression of a calcium-dependent protein kinase from ...

    Indian Academy of Sciences (India)

    Among the downstream targets of calcium in plants, calcium-dependent protein kinases (CDPKs) form an interesting class of kinases which are activated by calcium binding. They have been implicated in a diverse array of responses to hormonal and environmental stimuli. In order to dissect the role of CDPKs in the moss ...

  9. Altered calcium signaling in cancer cells.

    Science.gov (United States)

    Stewart, Teneale A; Yapa, Kunsala T D S; Monteith, Gregory R

    2015-10-01

    It is the nature of the calcium signal, as determined by the coordinated activity of a suite of calcium channels, pumps, exchangers and binding proteins that ultimately guides a cell's fate. Deregulation of the calcium signal is often deleterious and has been linked to each of the 'cancer hallmarks'. Despite this, we do not yet have a full understanding of the remodeling of the calcium signal associated with cancer. Such an understanding could aid in guiding the development of therapies specifically targeting altered calcium signaling in cancer cells during tumorigenic progression. Findings from some of the studies that have assessed the remodeling of the calcium signal associated with tumorigenesis and/or processes important in invasion and metastasis are presented in this review. The potential of new methodologies is also discussed. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Diagnostic Phase of Calcium Scoring Scan Applied as the Center of Acquisition Window of Coronary Computed Tomography Angiography Improves Image Quality in Minimal Acquisition Window Scan (Target CTA Mode Using the Second Generation 320-Row CT

    Directory of Open Access Journals (Sweden)

    Eriko Maeda

    2016-01-01

    Full Text Available Objective. To compare the image quality of coronary computed tomography angiography (CCTA acquired under two conditions: 75% fixed as the acquisition window center (Group 75% and the diagnostic phase for calcium scoring scan as the center (CS; Group CS. Methods. 320-row cardiac CT with a minimal acquisition window (scanned using “Target CTA” mode was performed on 81 patients. In Group 75% (n = 40, CS was obtained and reconstructed at 75% and the center of the CCTA acquisition window was set at 75%. In Group CS (n = 41, CS was obtained at 75% and the diagnostic phase showing minimal artifacts was applied as the center of the CCTA acquisition window. Image quality was evaluated using a four-point scale (4-excellent and the mean scores were compared between groups. Results. The CCTA scan diagnostic phase occurred significantly earlier in CS (75.7 ± 3.2% vs. 73.6 ± 4.5% for Groups 75% and CS, resp., p = 0.013. The mean Group CS image quality score (3.58 ± 0.63 was also higher than that for Group 75% (3.19 ± 0.66, p < 0.0001. Conclusions. The image quality of CCTA in Target CTA mode was significantly better when the center of acquisition window is adjusted using CS.

  11. Intracellular calcium is a target of modulation of apoptosis in MCF-7 cells in the presence of IgA adsorbed to polyethylene glycol

    Directory of Open Access Journals (Sweden)

    Honorio-França AC

    2016-02-01

    Full Text Available Adenilda Cristina Honorio-França,1 Gabriel Triches Nunes,1 Danny Laura Gomes Fagundes,1 Patrícia Gelli Feres de Marchi,1 Rubian Trindade da Silva Fernandes,1 Juliana Luzia França,1,2 Aline do Carmo França-Botelho,2 Lucélia Campelo Albuquerque Moraes,1 Fernando de Pilla Varotti,3 Eduardo Luzía França1,3 1Institute of Biological and Health Science, Federal University of Mato Grosso, Barra do Garças, Mato Grosso, Brazil; 2Institute of Health Sciences, University Center of Planalto de Araxá, Araxá, Minas Gerais, Brazil; 3Campus Centro Oeste Dona Lindu – Federal University of São João Del Rei, Divinópolis, Minas Gerais, Brazil Purpose: Clinical and epidemiological studies have indicated that breastfeeding has a protective effect on breast cancer risk. Protein-based drugs, including antibodies, are being developed to attain better forms of cancer therapy. Secretory IgA (SIgA is the antibody class in human breast milk, and its activity can be linked to the protective effect of breastfeeding. The aim of this study was to investigate the effect of polyethylene glycol (PEG microspheres with adsorbed SIgA on MCF-7 human breast cancer cells.  Methods: The PEG microspheres were characterized by flow cytometry and fluorescence microscopy. The MCF-7 cells were obtained from American Type Culture Collection. MCF-7 cells were pre-incubated for 24 hours with or without SIgA (100 ng/mL, PEG microspheres or SIgA adsorbed in PEG microspheres (100 ng/mL. Viability, intracellular calcium release, and apoptosis in MCF-7 cells were determined by flow cytometry.  Results: Fluorescence microscopy and flow cytometry analyses revealed that SIgA was able to adsorb to the PEG microspheres. The MCF-7 cells that were incubated with PEG microspheres with adsorbed SIgA showed decreased viability. MCF-7 cells that were incubated with SIgA or PEG microspheres with adsorbed SIgA had increased intracellular Ca2+ levels. In the presence of SIgA, an increase in the

  12. Exploring the calcium isotope signature of

    NARCIS (Netherlands)

    Hippler, D.; Witbaard, R.; van Aken, H.M.; Buhl, D.; Immenhauser, A.

    2013-01-01

    The calcium-isotope composition (delta Ca-44/40) of the aragonitic bivalve Arctica islandica grown in laboratory and field cultures was investigated in terms of environmental and biological controls to explore its potential as a palaeoceanographic proxy. While we found no significant effect of

  13. Targeting of CaV3.2 T-type calcium channels in peripheral sensory neurons for the treatment of painful diabetic neuropathy.

    Science.gov (United States)

    Todorovic, Slobodan M; Jevtovic-Todorovic, Vesna

    2014-04-01

    Pain-sensing sensory neurons (nociceptors) of the dorsal root ganglion (DRG) can become sensitized (hyperexcitable) in response to pathological conditions such as diabetes, which in turn may lead to the development of painful peripheral diabetic neuropathy (PDN). Because of insufficient knowledge about the mechanisms for this hypersensitization, current treatment for painful PDN has been limited to somewhat nonspecific systemic drugs having significant side effects or potential for abuse. Recent studies have established that the CaV3.2 isoform of T-channels makes a previously unrecognized contribution to sensitization of pain responses by enhancing excitability of nociceptors in animal models of type 1 and type 2 PDN. Furthermore, it has been reported that the glycosylation inhibitor neuraminidase can inhibit the native and recombinant CaV3.2 T-currents in vitro and completely reverse mechanical and thermal hyperalgesia in diabetic animals with PDN in vivo. Understanding details of posttranslational regulation of nociceptive channel activity via glycosylation may facilitate development of novel therapies for treatment of painful PDN. Pharmacological targeting the specific pathogenic mechanism rather than the channel per se may cause fewer side effects and reduce the potential for drug abuse in patients with diabetes.

  14. Plant Calcium Content: Ready to Remodel

    Directory of Open Access Journals (Sweden)

    Mary Lou Guerinot

    2012-08-01

    Full Text Available By identifying the relationship between calcium location in the plant cell and nutrient bioavailability, the plant characteristics leading to maximal calcium absorption by humans can be identified. Knowledge of plant cellular and molecular targets controlling calcium location in plants is emerging. These insights should allow for better strategies for increasing the nutritional content of foods. In particular, the use of preparation-free elemental imaging technologies such as synchrotron X-ray fluorescence (SXRF microscopy in plant biology may allow researchers to understand the relationship between subcellular location and nutrient bioavailability. These approaches may lead to better strategies for altering the location of calcium within the plant to maximize its absorption from fruits and vegetables. These modified foods could be part of a diet for children and adults identified as at-risk for low calcium intake or absorption with the ultimate goal of decreasing the incidence and severity of inadequate bone mineralization.

  15. Plant Calcium Content: Ready to Remodel

    Science.gov (United States)

    Yang, Jian; Punshon, Tracy; Guerinot, Mary Lou; Hirschi, Kendal D.

    2012-01-01

    By identifying the relationship between calcium location in the plant cell and nutrient bioavailability, the plant characteristics leading to maximal calcium absorption by humans can be identified. Knowledge of plant cellular and molecular targets controlling calcium location in plants is emerging. These insights should allow for better strategies for increasing the nutritional content of foods. In particular, the use of preparation-free elemental imaging technologies such as synchrotron X-ray fluorescence (SXRF) microscopy in plant biology may allow researchers to understand the relationship between subcellular location and nutrient bioavailability. These approaches may lead to better strategies for altering the location of calcium within the plant to maximize its absorption from fruits and vegetables. These modified foods could be part of a diet for children and adults identified as at-risk for low calcium intake or absorption with the ultimate goal of decreasing the incidence and severity of inadequate bone mineralization. PMID:23016135

  16. Substitutions in Calcium Aluminates and Calcium Aluminoferrites.

    Science.gov (United States)

    ALUMINUM COMPOUNDS, *CEMENTS, * CALCIUM COMPOUNDS, * FERRITES , *SCIENTIFIC RESEARCH, INFRARED SPECTROSCOPY, X RAY DIFFRACTION, CHEMICAL COMPOSITION, SUBSTITUTES, CHEMICAL ANALYSIS, ALKALI METAL COMPOUNDS.

  17. Calcium channel blocker overdose

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/002580.htm Calcium-channel blocker overdose To use the sharing features on this page, please enable JavaScript. Calcium-channel blockers are a type of medicine used to ...

  18. Fenoprofen calcium overdose

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/002649.htm Fenoprofen calcium overdose To use the sharing features on this page, please enable JavaScript. Fenoprofen calcium is a type of medicine called a nonsteroidal ...

  19. Calcium and Mitosis

    Science.gov (United States)

    Hepler, P.

    1983-01-01

    Although the mechanism of calcium regulation is not understood, there is evidence that calcium plays a role in mitosis. Experiments conducted show that: (1) the spindle apparatus contains a highly developed membrane system that has many characteristics of sarcoplasmic reticulum of muscle; (2) this membrane system contains calcium; and (3) there are ionic fluxes occurring during mitosis which can be seen by a variety of fluorescence probes. Whether the process of mitosis can be modulated by experimentally modulating calcium is discussed.

  20. Calcium en cardioplegie

    NARCIS (Netherlands)

    Ruigrok, T.J.C.; Meijler, F.L.

    1985-01-01

    Coronary perfusion with a calcium-free solution, followed by reperfusion with a calcium containing solution, may result in acute myocardial cell death and in irreversible loss of the e1ectrical and mechanical activity of the heart. This phenomenon is known as the calcium paradox. A number of

  1. Calcium-induced calcium release supports recruitment of synaptic vesicles in auditory hair cells.

    Science.gov (United States)

    Castellano-Muñoz, Manuel; Schnee, Michael E; Ricci, Anthony J

    2016-01-01

    Hair cells from auditory and vestibular systems transmit continuous sound and balance information to the central nervous system through the release of synaptic vesicles at ribbon synapses. The high activity experienced by hair cells requires a unique mechanism to sustain recruitment and replenishment of synaptic vesicles for continuous release. Using pre- and postsynaptic electrophysiological recordings, we explored the potential contribution of calcium-induced calcium release (CICR) in modulating the recruitment of vesicles to auditory hair cell ribbon synapses. Pharmacological manipulation of CICR with agents targeting endoplasmic reticulum calcium stores reduced both spontaneous postsynaptic multiunit activity and the frequency of excitatory postsynaptic currents (EPSCs). Pharmacological treatments had no effect on hair cell resting potential or activation curves for calcium and potassium channels. However, these drugs exerted a reduction in vesicle release measured by dual-sine capacitance methods. In addition, calcium substitution by barium reduced release efficacy by delaying release onset and diminishing vesicle recruitment. Together these results demonstrate a role for calcium stores in hair cell ribbon synaptic transmission and suggest a novel contribution of CICR in hair cell vesicle recruitment. We hypothesize that calcium entry via calcium channels is tightly regulated to control timing of vesicle fusion at the synapse, whereas CICR is used to maintain a tonic calcium signal to modulate vesicle trafficking. Copyright © 2016 the American Physiological Society.

  2. Combination of using prodrug-modified cationic liposome nanocomplexes and a potentiating strategy via targeted co-delivery of gemcitabine and docetaxel for CD44-overexpressed triple negative breast cancer therapy.

    Science.gov (United States)

    Fan, Yang; Wang, Qingjie; Lin, Guimei; Shi, Yanbin; Gu, Zili; Ding, Tingting

    2017-10-15

    In this study, novel prodrug-modified cationic liposome nanocomplexes (Combo NCs) were reported for gemcitabine (GEM) and docetaxel (DTX) co-delivery. This nanoplatform exhibited multiple favorable characteristics, such as a 'green' fabrication with a one-step chemical reaction, appropriate size (∼200nm) and distribution (PDIinvolve in modulating GEM associated enzymes thus enhancing the efficacy of GEM. Consequently, this nanoplatform provided a novel solution for achieving targeted co-delivery and potentiating effect in cancer therapy. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  3. Separation of (44)Ti from proton irradiated scandium by using solid-phase extraction chromatography and design of (44)Ti/(44)Sc generator system.

    Science.gov (United States)

    Radchenko, V; Meyer, C A L; Engle, J W; Naranjo, C M; Unc, G A; Mastren, T; Brugh, M; Birnbaum, E R; John, K D; Nortier, F M; Fassbender, M E

    2016-12-16

    Scandium-44g (half-life 3.97h [1]) shows promise for positron emission tomography (PET) imaging of longer biological processes than that of the current gold standard, (18)F, due to its favorable decay parameters. One source of (44g)Sc is the long-lived parent nuclide (44)Ti (half-life 60.0 a). A (44)Ti/(44g)Sc generator would have the ability to provide radionuclidically pure (44g)Sc on a daily basis. The production of (44)Ti via the (45)Sc(p,2n) reaction requires high proton beam currents and long irradiation times. Recovery and purification of no-carrier added (nca) (44)Ti from scandium metal targets involves complex separation chemistry. In this study, separation systems based on solid phase extraction chromatography were investigated, including branched diglycolamide (BDGA) resin and hydroxamate based ZR resin. Results indicate that ZR resin in HCl media represents an effective (44)Ti/(44g)Sc separation system. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. The Function of the Mitochondrial Calcium Uniporter in Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Yajin Liao

    2017-02-01

    Full Text Available The mitochondrial calcium uniporter (MCU—a calcium uniporter on the inner membrane of mitochondria—controls the mitochondrial calcium uptake in normal and abnormal situations. Mitochondrial calcium is essential for the production of adenosine triphosphate (ATP; however, excessive calcium will induce mitochondrial dysfunction. Calcium homeostasis disruption and mitochondrial dysfunction is observed in many neurodegenerative disorders. However, the role and regulatory mechanism of the MCU in the development of these diseases are obscure. In this review, we summarize the role of the MCU in controlling oxidative stress-elevated mitochondrial calcium and its function in neurodegenerative disorders. Inhibition of the MCU signaling pathway might be a new target for the treatment of neurodegenerative disorders.

  5. Transgenic plants with increased calcium stores

    Science.gov (United States)

    Wyatt, Sarah (Inventor); Tsou, Pei-Lan (Inventor); Robertson, Dominique (Inventor); Boss, Wendy (Inventor)

    2004-01-01

    The present invention provides transgenic plants over-expressing a transgene encoding a calcium-binding protein or peptide (CaBP). Preferably, the CaBP is a calcium storage protein and over-expression thereof does not have undue adverse effects on calcium homeostasis or biochemical pathways that are regulated by calcium. In preferred embodiments, the CaBP is calreticulin (CRT) or calsequestrin. In more preferred embodiments, the CaBP is the C-domain of CRT, a fragment of the C-domain, or multimers of the foregoing. In other preferred embodiments, the CaBP is localized to the endoplasmic reticulum by operatively associating the transgene encoding the CaBP with an endoplasmic reticulum localization peptide. Alternatively, the CaBP is targeted to any other sub-cellular compartment that permits the calcium to be stored in a form that is biologically available to the plant. Also provided are methods of producing plants with desirable phenotypic traits by transformation of the plant with a transgene encoding a CaBP. Such phenotypic traits include increased calcium storage, enhanced resistance to calcium-limiting conditions, enhanced growth and viability, increased disease and stress resistance, enhanced flower and fruit production, reduced senescence, and a decreased need for fertilizer production. Further provided are plants with enhanced nutritional value as human food or animal feed.

  6. Paclitaxel Induces Apoptosis in Breast Cancer Cells through Different Calcium—Regulating Mechanisms Depending on External Calcium Conditions

    Directory of Open Access Journals (Sweden)

    Zhi Pan

    2014-02-01

    Full Text Available Previously, we reported that endoplasmic reticulum calcium stores were a direct target for paclitaxel initiation of apoptosis. Furthermore, the actions of paclitaxel attenuated Bcl-2 resistance to apoptosis through endoplasmic reticulum-mediated calcium release. To better understand the calcium-regulated mechanisms of paclitaxel-induced apoptosis in breast cancer cells, we investigated the role of extracellular calcium, specifically; whether influx of extracellular calcium contributed to and/or was necessary for paclitaxel-induced apoptosis. Our results demonstrated that paclitaxel induced extracellular calcium influx. This mobilization of extracellular calcium contributed to subsequent cytosolic calcium elevation differently, depending on dosage. Under normal extracellular calcium conditions, high dose paclitaxel induced apoptosis-promoting calcium influx, which did not occur in calcium-free conditions. In the absence of extracellular calcium an “Enhanced Calcium Efflux” mechanism in which high dose paclitaxel stimulated calcium efflux immediately, leading to dramatic cytosolic calcium decrease, was observed. In the absence of extracellular calcium, high dose paclitaxel’s stimulatory effects on capacitative calcium entry and apoptosis could not be completely restored. Thus, normal extracellular calcium concentrations are critical for high dose paclitaxel-induced apoptosis. In contrast, low dose paclitaxel mirrored controls, indicating that it occurs independent of extracellular calcium. Thus, extracellular calcium conditions only affect efficacy of high dose paclitaxel-induced apoptosis.

  7. Paclitaxel Induces Apoptosis in Breast Cancer Cells through Different Calcium—Regulating Mechanisms Depending on External Calcium Conditions

    Science.gov (United States)

    Pan, Zhi; Avila, Andrew; Gollahon, Lauren

    2014-01-01

    Previously, we reported that endoplasmic reticulum calcium stores were a direct target for paclitaxel initiation of apoptosis. Furthermore, the actions of paclitaxel attenuated Bcl-2 resistance to apoptosis through endoplasmic reticulum-mediated calcium release. To better understand the calcium-regulated mechanisms of paclitaxel-induced apoptosis in breast cancer cells, we investigated the role of extracellular calcium, specifically; whether influx of extracellular calcium contributed to and/or was necessary for paclitaxel-induced apoptosis. Our results demonstrated that paclitaxel induced extracellular calcium influx. This mobilization of extracellular calcium contributed to subsequent cytosolic calcium elevation differently, depending on dosage. Under normal extracellular calcium conditions, high dose paclitaxel induced apoptosis-promoting calcium influx, which did not occur in calcium-free conditions. In the absence of extracellular calcium an “Enhanced Calcium Efflux” mechanism in which high dose paclitaxel stimulated calcium efflux immediately, leading to dramatic cytosolic calcium decrease, was observed. In the absence of extracellular calcium, high dose paclitaxel’s stimulatory effects on capacitative calcium entry and apoptosis could not be completely restored. Thus, normal extracellular calcium concentrations are critical for high dose paclitaxel-induced apoptosis. In contrast, low dose paclitaxel mirrored controls, indicating that it occurs independent of extracellular calcium. Thus, extracellular calcium conditions only affect efficacy of high dose paclitaxel-induced apoptosis. PMID:24549172

  8. Nuclear Calcium Buffering Capacity Shapes Neuronal Architecture*

    Science.gov (United States)

    Mauceri, Daniela; Hagenston, Anna M.; Schramm, Kathrin; Weiss, Ursula; Bading, Hilmar

    2015-01-01

    Calcium-binding proteins (CaBPs) such as parvalbumin are part of the cellular calcium buffering system that determines intracellular calcium diffusion and influences the spatiotemporal dynamics of calcium signals. In neurons, CaBPs are primarily localized to the cytosol and function, for example, in nerve terminals in short-term synaptic plasticity. However, CaBPs are also expressed in the cell nucleus, suggesting that they modulate nuclear calcium signals, which are key regulators of neuronal gene expression. Here we show that the calcium buffering capacity of the cell nucleus in mouse hippocampal neurons regulates neuronal architecture by modulating the expression levels of VEGFD and the complement factor C1q-c, two nuclear calcium-regulated genes that control dendrite geometry and spine density, respectively. Increasing the levels of nuclear calcium buffers by means of expression of a nuclearly targeted form of parvalbumin fused to mCherry (PV.NLS-mC) led to a reduction in VEGFD expression and, as a result, to a decrease in total dendritic length and complexity. In contrast, mRNA levels of the synapse pruning factor C1q-c were increased in neurons expressing PV.NLS-mC, causing a reduction in the density and size of dendritic spines. Our results establish a close link between nuclear calcium buffering capacity and the transcription of genes that determine neuronal structure. They suggest that the development of cognitive deficits observed in neurological conditions associated with CaBP deregulation may reflect the loss of necessary structural features of dendrites and spines. PMID:26231212

  9. Calcium channel blocker poisoning

    Directory of Open Access Journals (Sweden)

    Miran Brvar

    2005-04-01

    Full Text Available Background: Calcium channel blockers act at L-type calcium channels in cardiac and vascular smooth muscles by preventing calcium influx into cells with resultant decrease in vascular tone and cardiac inotropy, chronotropy and dromotropy. Poisoning with calcium channel blockers results in reduced cardiac output, bradycardia, atrioventricular block, hypotension and shock. The findings of hypotension and bradycardia should suggest poisoning with calcium channel blockers.Conclusions: Treatment includes immediate gastric lavage and whole-bowel irrigation in case of ingestion of sustainedrelease products. All patients should receive an activated charcoal orally. Specific treatment includes calcium, glucagone and insulin, which proved especially useful in shocked patients. Supportive care including the use of catecholamines is not always effective. In the setting of failure of pharmacological therapy transvenous pacing, balloon pump and cardiopulmonary by-pass may be necessary.

  10. Regulation of calcium homeostasis in activated human neutrophils ...

    African Journals Online (AJOL)

    Objectives. The objectives of the current study were to: (i) present an integrated model for the restoration of calcium homeostasis in activated human neutrophils based on current knowledge and recent research; and (ii) identify potential targets for the modulation of calcium fluxes in activated neutrophils based on this model ...

  11. Clonorcis sinensis eggs are associated with calcium carbonate gallbladder stones.

    Science.gov (United States)

    Qiao, Tie; Ma, Rui-hong; Luo, Zhen-liang; Yang, Liu-qing; Luo, Xiao-bing; Zheng, Pei-ming

    2014-10-01

    Calcium carbonate gallbladder stones were easily neglected because they were previously reported as a rare stone type in adults. The aim of this study was to investigate the relationship between calcium carbonate stones and Clonorchis sinensis infection. A total of 598 gallbladder stones were studied. The stone types were identified by FTIR spectroscopy. The C. sinensis eggs and DNA were detected by microscopic examination and real-time fluorescent PCR respectively. And then, some egg-positive stones were randomly selected for further SEM examination. Corresponding clinical characteristics of patients with different types of stones were also statistically analyzed. The detection rate of C. sinensis eggs in calcium carbonate stone, pigment stone, mixed stone and cholesterol stone types, as well as other stone types was 60%, 44%, 36%, 6% and 30%, respectively, which was highest in calcium carbonate stone yet lowest in cholesterol stone. A total of 182 stones were egg-positive, 67 (37%) of which were calcium carbonate stones. The C. sinensis eggs were found adherent to calcium carbonate crystals by both light microscopy and scanning electron microscopy. Patients with calcium carbonate stones were mainly male between the ages of 30 and 60, the CO2 combining power of patients with calcium carbonate stones were higher than those with cholesterol stones. Calcium carbonate gallbladder stones are not rare, the formation of which may be associated with C. sinensis infection. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Koenimbin, a natural dietary compound of Murraya koenigii (L) Spreng: inhibition of MCF7 breast cancer cells and targeting of derived MCF7 breast cancer stem cells (CD44+/CD24−/low): an in vitro study

    Science.gov (United States)

    Ahmadipour, Fatemeh; Noordin, Mohamed Ibrahim; Mohan, Syam; Arya, Aditya; Paydar, Mohammadjavad; Looi, Chung Yeng; Keong, Yeap Swee; Siyamak, Ebrahimi Nigjeh; Fani, Somayeh; Firoozi, Maryam; Yong, Chung Lip; Sukari, Mohamed Aspollah; Kamalidehghan, Behnam

    2015-01-01

    Background Inhibition of breast cancer stem cells has been shown to be an effective therapeutic strategy for cancer prevention. The aims of this work were to evaluate the efficacy of koenimbin, isolated from Murraya koenigii (L) Spreng, in the inhibition of MCF7 breast cancer cells and to target MCF7 breast cancer stem cells through apoptosis in vitro. Methods Koenimbin-induced cell viability was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Nuclear condensation, cell permeability, mitochondrial membrane potential, and cytochrome c release were observed using high-content screening. Cell cycle arrest was examined using flow cytometry, while human apoptosis proteome profiler assays were used to investigate the mechanism of apoptosis. Protein expression levels of Bax, Bcl2, and heat shock protein 70 were confirmed using Western blotting. Caspase-7, caspase-8, and caspase-9 levels were measured, and nuclear factor kappa B (NF-κB) activity was assessed using a high-content screening assay. Aldefluor™ and mammosphere formation assays were used to evaluate the effect of koenimbin on MCF7 breast cancer stem cells in vitro. The Wnt/β-catenin signaling pathway was investigated using Western blotting. Results Koenimbin-induced apoptosis in MCF7 cells was mediated by cell death-transducing signals regulating the mitochondrial membrane potential by downregulating Bcl2 and upregulating Bax, due to cytochrome c release from the mitochondria to the cytosol. Koenimbin induced significant (P<0.05) sub-G0 phase arrest in breast cancer cells. Cytochrome c release triggered caspase-9 activation, which then activated caspase-7, leading to apoptotic changes. This form of apoptosis is closely associated with the intrinsic pathway and inhibition of NF-κB translocation from the cytoplasm to the nucleus. Koenimbin significantly (P<0.05) decreased the aldehyde dehydrogenase-positive cell population in MCF7 cancer stem cells and

  13. Koenimbin, a natural dietary compound of Murraya koenigii (L) Spreng: inhibition of MCF7 breast cancer cells and targeting of derived MCF7 breast cancer stem cells (CD44(+)/CD24(-/low)): an in vitro study.

    Science.gov (United States)

    Ahmadipour, Fatemeh; Noordin, Mohamed Ibrahim; Mohan, Syam; Arya, Aditya; Paydar, Mohammadjavad; Looi, Chung Yeng; Keong, Yeap Swee; Siyamak, Ebrahimi Nigjeh; Fani, Somayeh; Firoozi, Maryam; Yong, Chung Lip; Sukari, Mohamed Aspollah; Kamalidehghan, Behnam

    2015-01-01

    Inhibition of breast cancer stem cells has been shown to be an effective therapeutic strategy for cancer prevention. The aims of this work were to evaluate the efficacy of koenimbin, isolated from Murraya koenigii (L) Spreng, in the inhibition of MCF7 breast cancer cells and to target MCF7 breast cancer stem cells through apoptosis in vitro. Koenimbin-induced cell viability was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Nuclear condensation, cell permeability, mitochondrial membrane potential, and cytochrome c release were observed using high-content screening. Cell cycle arrest was examined using flow cytometry, while human apoptosis proteome profiler assays were used to investigate the mechanism of apoptosis. Protein expression levels of Bax, Bcl2, and heat shock protein 70 were confirmed using Western blotting. Caspase-7, caspase-8, and caspase-9 levels were measured, and nuclear factor kappa B (NF-κB) activity was assessed using a high-content screening assay. Aldefluor™ and mammosphere formation assays were used to evaluate the effect of koenimbin on MCF7 breast cancer stem cells in vitro. The Wnt/β-catenin signaling pathway was investigated using Western blotting. Koenimbin-induced apoptosis in MCF7 cells was mediated by cell death-transducing signals regulating the mitochondrial membrane potential by downregulating Bcl2 and upregulating Bax, due to cytochrome c release from the mitochondria to the cytosol. Koenimbin induced significant (P<0.05) sub-G0 phase arrest in breast cancer cells. Cytochrome c release triggered caspase-9 activation, which then activated caspase-7, leading to apoptotic changes. This form of apoptosis is closely associated with the intrinsic pathway and inhibition of NF-κB translocation from the cytoplasm to the nucleus. Koenimbin significantly (P<0.05) decreased the aldehyde dehydrogenase-positive cell population in MCF7 cancer stem cells and significantly (P<0.01) decreased the

  14. Calcium response to vitamin D supplementation

    Directory of Open Access Journals (Sweden)

    Francisco R. Spivacow

    2018-01-01

    Full Text Available Several studies show the importance of serum vitamin D sufficient levels to prevent multiple chronic diseases. However, vitamin D supplementation and its effects on urine calcium excretion remain controversial. The objective of this prospective and interventional study was to evaluate urine calcium excretion in women with normal calciuria or hypercalciuria, once serum vitamin D sufficiency was achieved. We studied 63 women with idiopathic hypercalciuria, (9 with renal lithiasis and 50 normocalciuric women. Both groups had serum vitamin D levels low (deficiency or insufficiency. Baseline urine calcium excretion was measured before being supplemented with vitamin D2 or D3 weekly or vitamin D3 100.000 IU monthly. Once serum vitamin D levels were corrected achieving at least 30 ng/ml, a second urine calcium excretion was obtained. Although in the whole sample we did not observe significant changes in urine calcium excretion according to the way of supplementation, some of those with weekly supplementation had significant higher urine calcium excretion, 19% (n = 12 of hypercalciuric women and 12% (n = 6 of the normocalciuric group. Monthly doses, also showed higher urine calcium excretion in 40% of hypercalciuric women (n = 4/10 and in 44% (n = 4/9 of the renal lithiasis hypercalciuric patients. In conclusion, different ways of vitamin D supplementation and adequate serum levels are safe in most patients, although it should be taken into account a subgroup, mainly with monthly loading doses, that could increase the calciuria significantly eventually rising renal lithiasis risk or bone mass loss, if genetically predisposed.

  15. Increased calcium absorption from synthetic stable amorphous calcium carbonate: double-blind randomized crossover clinical trial in postmenopausal women.

    Science.gov (United States)

    Vaisman, Nachum; Shaltiel, Galit; Daniely, Michal; Meiron, Oren E; Shechter, Assaf; Abrams, Steven A; Niv, Eva; Shapira, Yami; Sagi, Amir

    2014-10-01

    Calcium supplementation is a widely recognized strategy for achieving adequate calcium intake. We designed this blinded, randomized, crossover interventional trial to compare the bioavailability of a new stable synthetic amorphous calcium carbonate (ACC) with that of crystalline calcium carbonate (CCC) using the dual stable isotope technique. The study was conducted in the Unit of Clinical Nutrition, Tel Aviv Sourasky Medical Center, Israel. The study population included 15 early postmenopausal women aged 54.9 ± 2.8 (mean ± SD) years with no history of major medical illness or metabolic bone disorder, excess calcium intake, or vitamin D deficiency. Standardized breakfast was followed by randomly provided CCC or ACC capsules containing 192 mg elemental calcium labeled with 44Ca at intervals of at least 3 weeks. After swallowing the capsules, intravenous CaCl2 labeled with 42Ca on was administered on each occasion. Fractional calcium absorption (FCA) of ACC and CCC was calculated from the 24-hour urine collection following calcium administration. The results indicated that FCA of ACC was doubled (± 0.96 SD) on average compared to that of CCC (p calcium supplementation. © 2014 American Society for Bone and Mineral Research.

  16. Koenimbin, a natural dietary compound of Murraya koenigii (L Spreng: inhibition of MCF7 breast cancer cells and targeting of derived MCF7 breast cancer stem cells (CD44+/CD24-/low: an in vitro study

    Directory of Open Access Journals (Sweden)

    Ahmadipour F

    2015-02-01

    Full Text Available Fatemeh Ahmadipour,1 Mohamed Ibrahim Noordin,1 Syam Mohan,2 Aditya Arya,1 Mohammadjavad Paydar,3 Chung Yeng Looi,3 Yeap Swee Keong,4 Ebrahimi Nigjeh Siyamak,4 Somayeh Fani,1 Maryam Firoozi,5 Chung Lip Yong,1 Mohamed Aspollah Sukari,6 Behnam Kamalidehghan1 1Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2Medical Research Center, Jazan University, Jazan, Kingdom of Saudi Arabia; 3Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 4UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Malaysia; 5Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran; 6Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang, Malaysia Background: Inhibition of breast cancer stem cells has been shown to be an effective therapeutic strategy for cancer prevention. The aims of this work were to evaluate the efficacy of koenimbin, isolated from Murraya koenigii (L Spreng, in the inhibition of MCF7 breast cancer cells and to target MCF7 breast cancer stem cells through apoptosis in vitro. Methods: Koenimbin-induced cell viability was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay. Nuclear condensation, cell permeability, mitochondrial membrane potential, and cytochrome c release were observed using high-content screening. Cell cycle arrest was examined using flow cytometry, while human apoptosis proteome profiler assays were used to investigate the mechanism of apoptosis. Protein expression levels of Bax, Bcl2, and heat shock protein 70 were confirmed using Western blotting. Caspase-7, caspase-8, and caspase-9 levels were measured, and nuclear factor kappa B (NF-κB activity was assessed using a high-content screening assay. Aldefluor™ and mammosphere formation assays were used to evaluate the effect of koenimbin on MCF7

  17. The microRNA mir-71 inhibits calcium signaling by targeting the TIR-1/Sarm1 adaptor protein to control stochastic L/R neuronal asymmetry in C. elegans.

    Directory of Open Access Journals (Sweden)

    Yi-Wen Hsieh

    Full Text Available The Caenorhabditis elegans left and right AWC olfactory neurons communicate to establish stochastic asymmetric identities, AWC(ON and AWC(OFF, by inhibiting a calcium-mediated signaling pathway in the future AWC(ON cell. NSY-4/claudin-like protein and NSY-5/innexin gap junction protein are the two parallel signals that antagonize the calcium signaling pathway to induce the AWC(ON fate. However, it is not known how the calcium signaling pathway is downregulated by nsy-4 and nsy-5 in the AWC(ON cell. Here we identify a microRNA, mir-71, that represses the TIR-1/Sarm1 adaptor protein in the calcium signaling pathway to promote the AWC(ON identity. Similar to tir-1 loss-of-function mutants, overexpression of mir-71 generates two AWC(ON neurons. tir-1 expression is downregulated through its 3' UTR in AWC(ON, in which mir-71 is expressed at a higher level than in AWC(OFF. In addition, mir-71 is sufficient to inhibit tir-1 expression in AWC through the mir-71 complementary site in the tir-1 3' UTR. Our genetic studies suggest that mir-71 acts downstream of nsy-4 and nsy-5 to promote the AWC(ON identity in a cell autonomous manner. Furthermore, the stability of mature mir-71 is dependent on nsy-4 and nsy-5. Together, these results provide insight into the mechanism by which nsy-4 and nsy-5 inhibit calcium signaling to establish stochastic asymmetric AWC differentiation.

  18. 76 FR 71459 - Prohexadione Calcium; Pesticide Tolerances

    Science.gov (United States)

    2011-11-18

    ... requested that 40 CFR 180.547 be amended by establishing tolerances for residues of the plant growth... subgroups of consumers, including infants and children. Prohexadione calcium is not acutely toxic by the..., and kidneys were the target organ for toxicity in the dogs. Following repeated dermal exposures for 28...

  19. Acidosis and Urinary Calcium Excretion

    DEFF Research Database (Denmark)

    Alexander, R Todd; Cordat, Emmanuelle; Chambrey, Régine

    2016-01-01

    Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and inhibi...

  20. The relation of carotid calcium volume with carotid artery stenosis in symptomatic patients

    NARCIS (Netherlands)

    Marquering, H. A.; Majoie, C. B. L. M.; Smagge, L.; Kurvers, A. G.; Gratama van Andel, H. A.; van den Berg, R.; Nederkoorn, P. J.

    2011-01-01

    Recent research showed a strong correlation of calcium volume scores with degree of stenosis, suggesting that calcium volume could be used in the diagnosis of carotid artery stenosis. We investigated the accuracy of the use of calcium volume scores to diagnose carotid artery stenosis in our target

  1. Calcium and bones

    Science.gov (United States)

    ... eat in their diet. Vitamin D is the hormone that helps the gut absorb more calcium. Many older adults have common risks that make bone health worse. Calcium intake in the diet (milk, cheese, yogurt) is low. Vitamin D levels are ...

  2. Calcium D-saccharate

    DEFF Research Database (Denmark)

    Garcia, André Castilho; Hedegaard, Martina Vavrusova; Skibsted, Leif Horsfelt

    2016-01-01

    Molar conductivity of saturated aqueous solutions of calcium d-saccharate, used as a stabilizer of beverages fortified with calcium d-gluconate, increases strongly upon dilution, indicating complex formation between calcium and d-saccharate ions, for which, at 25 °C, Kassoc = 1032 ± 80, ΔHassoc......° = -34 ± 6 kJ mol-1, and ΔSassoc° = -55 ± 9 J mol-1 K-1, were determined electrochemically. Calcium d-saccharate is sparingly soluble, with a solubility product, Ksp, of (6.17 ± 0.32) × 10-7 at 25 °C, only moderately increasing with the temperature: ΔHsol° = 48 ± 2 kJ mol-1, and ΔSassoc° = 42 ± 7 J mol-1...... K-1. Equilibria in supersaturated solutions of calcium d-saccharate seem only to adjust slowly, as seen from calcium activity measurements in calcium d-saccharate solutions made supersaturated by cooling. Solutions formed by isothermal dissolution of calcium d-gluconate in aqueous potassium d...

  3. Extracellular Calcium and Magnesium

    African Journals Online (AJOL)

    ABSTRACT. The cause of preeclampsia remains unknown and calcium and magnesium supplement are being suggested as means of prevention. The objective of this study was to assess magnesium and calcium in the plasma and cerebrospinal fluid of Nigerian women with preedamp sia and eclampsia. Setting was ...

  4. Hyaluronan and calcium carbonate hybrid nanoparticles for colorectal cancer chemotherapy

    Science.gov (United States)

    Bai, Jinghui; Xu, Jian; Zhao, Jian; Zhang, Rui

    2017-09-01

    A hybrid drug delivery system (DDS) composed of hyaluronan and calcium carbonate (CC) was developed. By taking advantage of the tumor-targeting ability of hyaluronan and the drug-loading property of CC, the well-formed hyaluronan-CC nanoparticles were able to serve as a DDS targeting colorectal cancer with a decent drug loading content, which is beneficial in the chemotherapy of colorectal cancer. In this study, hyaluronan-CC nanoparticles smaller than 100 nm were successfully developed to load the wide-range anti-cancer drug adriamycin (Adr) to construct hyaluronan-CC/Adr nanoparticles. On the other hand, we also found that hyaluronan-CC/Adr nanoparticles can possibly increase the uptake ratio of Adr into HT29 colorectal cancer cells when compared with hyaluronan-free nanoparticles (CC/Adr) via the CD44 receptor-mediated endocytosis via competitive uptake and in vivo imaging assays. Note that both in vitro (CCK-8 assay on HT29 cells) and in vivo (anti-cancer assay on HT-29 tumor-bearing nude mice model) experiments revealed that hyaluronan-CC/Adr nanoparticles exhibited stronger anti-cancer activity than free Adr or CC/Adr nanoparticles with minimized toxic side effects and preferable cancer-suppression potential.

  5. Paclitaxel Induces Apoptosis in Breast Cancer Cells through Different Calcium—Regulating Mechanisms Depending on External Calcium Conditions

    OpenAIRE

    Zhi Pan; Andrew Avila; Lauren Gollahon

    2014-01-01

    Previously, we reported that endoplasmic reticulum calcium stores were a direct target for paclitaxel initiation of apoptosis. Furthermore, the actions of paclitaxel attenuated Bcl-2 resistance to apoptosis through endoplasmic reticulum-mediated calcium release. To better understand the calcium-regulated mechanisms of paclitaxel-induced apoptosis in breast cancer cells, we investigated the role of extracellular calcium, specifically; whether influx of extracellular calcium contributed to and...

  6. HYPERTHERMIA, INTRACELLULAR FREE CALCIUM AND CALCIUM IONOPHORES

    NARCIS (Netherlands)

    STEGE, GJJ; WIERENGA, PK; KAMPINGA, HH; KONINGS, AWT

    1993-01-01

    It is shown that heat-induced increase of intracellular calcium does not correlate with hyperthermic cell killing. Six different cell lines were investigated; in four (EAT, HeLa S3, L5178Y-R and L5178Y-S) heat treatments killing 90% of the cells did not affect the levels of intracellular free

  7. The Consequences of Modern Military Deployment on Calcium Status and Bone Health

    Science.gov (United States)

    2010-01-01

    studies found mean sweat calcium concentrations of 30 5 mg/L for runners and 44 12 mg/L for firefighters.13,18 Understanding the effect of sweat calcium...Soldiers reported they did not consume large quantities of milk in Baghdad because of its unpleasant taste. Increased skin pigmen- tation, obesity , and

  8. 44

    African Journals Online (AJOL)

    Primary production of agricultural products is performed by a large number of farms operating on a small scale. This write up sets out to describe the currently available systems, how they can be used as tools for quality assurance management and outlines a framework for. The Netherlands. their interaction and use.

  9. 44

    African Journals Online (AJOL)

    1996-07-06

    Jul 6, 1996 ... NEUROLOGICAL MANIFESTATIONS FOLLOWING PARTIAL EXCISION IN SPINAL MENINGIOMA: CASE. REPORT ... spine decompressive laminectomy was performed on 15* January 1996 at Nairobi West Hospital extending from T3 ... right leg was still held in flexion deformity at the knee. She was thus ...

  10. A randomized, double-blind, placebo-controlled trial of calcium acetate on serum phosphorus concentrations in patients with advanced non-dialysis-dependent chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Ho Chiang-Hong

    2011-02-01

    Full Text Available Abstract Background Hyperphosphatemia in patients with chronic kidney disease (CKD contributes to secondary hyperparathyroidism, soft tissue calcification, and increased mortality risk. This trial was conducted to examine the efficacy and safety of calcium acetate in controlling serum phosphorus in pre-dialysis patients with CKD. Methods In this randomized, double-blind, placebo-controlled trial, 110 nondialyzed patients from 34 sites with estimated GFR 2 and serum phosphorus > 4.5 mg/dL were randomized to calcium acetate or placebo for 12 weeks. The dose of study drugs was titrated to achieve target serum phosphorus of 2.7-4.5 mg/dL. Serum phosphorus, calcium, iPTH, bicarbonate and serum albumin were measured at baseline and every 2 weeks for the 12 week study period. The primary efficacy endpoint was serum phosphorus at 12 weeks. Secondary endpoints were to measure serum calcium and intact parathyroid hormone (iPTH levels. Results At 12 weeks, serum phosphorus concentration was significantly lower in the calcium acetate group compared to the placebo group (4.4 ± 1.2 mg/dL vs. 5.1 ± 1.4 mg/dL; p = 0.04. The albumin-adjusted serum calcium concentration was significantly higher (9.5 ± 0.8 vs. 8.8 ± 0.8; p p Conclusions In CKD patients not yet on dialysis, calcium acetate was effective in reducing serum phosphorus and iPTH over a 12 week period. Trial Registration www.clinicaltrials.gov NCT00211978.

  11. Imidazopyridazine inhibitors of Plasmodium falciparum calcium dependent protein kinase 1 also target cGMP-dependent protein kinase and heat shock protein 90 to kill the parasite at different stages of intracellular development.

    OpenAIRE

    Green, JL; Moon, RW; Whalley, D; Bowyer, PW; Wallace, C.; Rochani, A; Nageshan, RK; Howell, SA; Grainger, M.; Jones, HM; Ansell, KH; Chapman, TM; Taylor, DL; Osborne, SA; Baker, DA

    2015-01-01

    : Imidazopyridazine compounds are potent, ATP-competitive inhibitors of calcium-dependent protein kinase 1 (CDPK1) and of Plasmodium falciparum parasite growth in vitro. Here, we show that these compounds can be divided into two classes depending on the nature of the aromatic linker between the core and the R2 substituent group. Class 1 compounds have a pyrimidine linker and inhibit parasite growth at late schizogony, whereas class 2 compounds have a nonpyrimidine linker and inhibit growth in...

  12. Effects of Calcium Ion, Calpains, and Calcium Channel Blockers on Retinitis Pigmentosa

    Directory of Open Access Journals (Sweden)

    Mitsuru Nakazawa

    2011-01-01

    Full Text Available Recent advances in molecular genetic studies have revealed many of the causative genes of retinitis pigmentosa (RP. These achievements have provided clues to the mechanisms of photoreceptor degeneration in RP. Apoptosis is known to be a final common pathway in RP and, therefore, a possible therapeutic target for photoreceptor rescue. However, apoptosis is not a single molecular cascade, but consists of many different reactions such as caspase-dependent and caspase-independent pathways commonly leading to DNA fractionation and cell death. The intracellular concentration of calcium ions is also known to increase in apoptosis. These findings suggest that calpains, one of the calcium-dependent proteinases, play some roles in the process of photoreceptor apoptosis and that calcium channel antagonists may potentially inhibit photoreceptor apoptosis. Herein, the effects of calpains and calcium channel antagonists on photoreceptor degeneration are reviewed.

  13. Enhanced antitumor activity of cabazitaxel targeting CD44+ receptor ...

    African Journals Online (AJOL)

    coated, cabazitaxel- loaded solid lipid nanoparticles (HA-CZ-SLNs) for the treatment of breast cancer. Methods: HA-CZ-SLNs were prepared by a homogenization method. Nanoparticles were designed for prolonged circulation and slow ...

  14. Enhanced antitumor activity of cabazitaxel targeting CD44+ receptor ...

    African Journals Online (AJOL)

    coated, cabazitaxelloaded solid lipid nanoparticles (HA-CZ-SLNs) for the treatment of breast cancer. Methods: HA-CZ-SLNs were prepared by a homogenization method. Nanoparticles were designed for prolonged circulation and slow release ...

  15. Calcium sensing in exocytosis

    DEFF Research Database (Denmark)

    Gustavsson, Natalia; Wu, Bingbing; Han, Weiping

    2012-01-01

    Neurotransmitters, neuropeptides and hormones are released through regulated exocytosis of synaptic vesicles and large dense core vesicles. This complex and highly regulated process is orchestrated by SNAREs and their associated proteins. The triggering signal for regulated exocytosis is usually...... an increase in intracellular calcium levels. Besides the triggering role, calcium signaling modulates the precise amount and kinetics of vesicle release. Thus, it is a central question to understand the molecular machineries responsible for calcium sensing in exocytosis. Here we provide an overview of our...

  16. Bone repair in calcium-deficient rats: comparison of xylitol+calcium carbonate with calcium carbonate, calcium lactate and calcium citrate on the repletion of calcium.

    Science.gov (United States)

    Hämäläinen, M M

    1994-06-01

    The potential value of xylitol in calcium therapy was evaluated by comparing the effect of dietary xylitol (50 g/kg diet) + calcium carbonate with the effects of calcium carbonate, calcium lactate and calcium citrate on bone repair of young male rats after the rats consumed for 3 wk a calcium-deficient diet (0.2 g Ca/kg diet). After this calcium-depletion period, the rats were fed for 2 wk one of four diets, each containing 5 g Ca/kg diet as one of the four dietary calcium sources. The diet of the control animals was supplemented with CaCO3 (5 g Ca/kg diet) throughout the study. The Ca-deficient rats showed low bone mass, low serum calcium and high serum 1,25-dihydroxycholecalciferol, parathyroid hormone (1-34 fraction) and osteocalcin concentrations. They also excreted magnesium, phosphate and hydroxyproline in the urine in high concentrations, and had high bone alkaline phosphatase and tartrate-resistant acid phosphatase activities. Most of these changes were reversed by the administered of the calcium salts. The highest recoveries of femoral dry weight, calcium, magnesium and phosphate were observed in the groups receiving xylitol+CaCO3 and calcium lactate. Calcium lactate and calcium citrate caused low serum phosphate concentration compared with rats receiving CaCO3 and with the age-matched Ca-replete controls. Xylitol-treated rats excreted more calcium and magnesium in urine than did the other rats, probably due to increased absorption of these minerals from the gut. These results suggest that dietary xylitol improves the bioavailability of calcium salts.

  17. Calcium – how and why?

    Indian Academy of Sciences (India)

    Unknown

    Calcium is among the most commonly used ions, in a multitude of biological functions, so much so that it is impossible to imagine life without calcium. In this article I have attempted to address the question as to how calcium has achieved this status with a brief mention of the history of calcium research in biology. It appears ...

  18. Calcium and Your Child

    Science.gov (United States)

    ... Milk Allergy Figuring Out Food Labels What's a Vegetarian? Osteoporosis Minerals Your Bones Mineral Chart Vitamin D ... Need to Drink Milk? Lactose Intolerance Becoming a Vegetarian Soy Foods and Health Calcium Bones, Muscles, and ...

  19. Stoichiometry of Calcium Medicines

    Science.gov (United States)

    Pinto, Gabriel

    2005-01-01

    The topic of calcium supplement and its effects on human lives is presented in the way of questions to the students. It enables the students to realize the relevance of chemistry outside the classroom surrounding.

  20. Magnesium, calcium and cancer

    National Research Council Canada - National Science Library

    Anghileri, Leopoldo J

    2009-01-01

    Magnesium ion (Mg(2+)) and calcium ion (Ca(2+)) control a diverse and important range of cellular processes, such as gene transcription, cell proliferation, neoplastic transformation, immune response and therapeutic treatment...

  1. Optimisation and validation of a high throughput screening compatible assay to identify inhibitors of the plasma membrane calcium ATPase pump--a novel therapeutic target for contraception and malaria.

    Science.gov (United States)

    Mohamed, Tamer M A; Zakeri, Simon A; Baudoin, Florence; Wolf, Markus; Oceandy, Delvac; Cartwright, Elizabeth J; Gul, Sheraz; Neyses, Ludwig

    2013-01-01

    ATPases, which constitute a major category of ion transporters in the human body, have a variety of significant biological and pathological roles. However, the lack of high throughput assays for ATPases has significantly limited drug discovery in this area. We have recently found that the genetic deletion of the ATP dependent calcium pump PMCA4 (plasma membrane calcium/calmodulin dependent ATPase, isoform 4) results in infertility in male mice due to a selective defect in sperm motility. In addition, recent discoveries in humans have indicated that a single nucleotide polymorphism (SNP) in the PMCA4 gene determines the susceptibility towards malaria plasmodium infection. Therefore, there is an urgent need to develop specific PMCA4 inhibitors. In the current study, we aim to optimise and validate a high throughput screening compatible assay using recombinantly expressed PMCA4 and the HTRF® Transcreener® ADP (TR-FRET) assay to screen a drug library. PMCA4 membrane microsomes were prepared from HEK293 cells overexpressing PMCA4. Western blot quantification revealed nearly nine-fold increased expression of PMCA4 compared to LacZ (control virus)-infected cells. Maximal PMCA4 microsomal activity was achieved in the TR-FRET assay with 15ng/μl microsomal concentration, 30-minute pre-incubation with compounds at 37°C, and calcium buffering with 1mM EGTA providing 1μM free-calcium. Finally a dose-response curve for carboxyeosin (a non-specific PMCA inhibitor) under optimised conditions showed significant PMCA4 inhibition. Upon confirmation that the assay was suitable for high-throughput screening, we have screened the ChemBioNet small molecule library (~21,000 compounds) against the PMCA4 assay to identify those that are its apparent inhibitors. This screening yielded 1,494 primary hits. We have optimised the HTRF® Transcreener® ADP assay for high-throughput screening to identify PMCA4 inhibitors. The output of the screening campaign has provided preliminary chemical

  2. Voltage-Gated Calcium Channels in Nociception

    Science.gov (United States)

    Yasuda, Takahiro; Adams, David J.

    Voltage-gated calcium channels (VGCCs) are a large and functionally diverse group of membrane ion channels ubiquitously expressed throughout the central and peripheral nervous systems. VGCCs contribute to various physiological processes and transduce electrical activity into other cellular functions. This chapter provides an overview of biophysical properties of VGCCs, including regulation by auxiliary subunits, and their physiological role in neuronal functions. Subsequently, then we focus on N-type calcium (Cav2.2) channels, in particular their diversity and specific antagonists. We also discuss the role of N-type calcium channels in nociception and pain transmission through primary sensory dorsal root ganglion neurons (nociceptors). It has been shown that these channels are expressed predominantly in nerve terminals of the nociceptors and that they control neurotransmitter release. To date, important roles of N-type calcium channels in pain sensation have been elucidated genetically and pharmacologically, indicating that specific N-type calcium channel antagonists or modulators are particularly useful as therapeutic drugs targeting chronic and neuropathic pain.

  3. [Calcium suppletion for patients who use gastric acid inhibitors: calcium citrate or calcium carbonate?].

    NARCIS (Netherlands)

    Jonge, H.J. de; Gans, R.O.; Huls, G.A.

    2012-01-01

    Various calcium supplements are available for patients who have an indication for calcium suppletion. American guidelines and UpToDate recommend prescribing calcium citrate to patients who use antacids The rationale for this advice is that water-insoluble calcium carbonate needs acid for adequate

  4. Calcium in plant cells

    Directory of Open Access Journals (Sweden)

    V. V. Schwartau

    2014-04-01

    Full Text Available The paper gives the review on the role of calcium in many physiological processes of plant organisms, including growth and development, protection from pathogenic influences, response to changing environmental factors, and many other aspects of plant physiology. Initial intake of calcium ions is carried out by Ca2+-channels of plasma membrane and they are further transported by the xylem owing to auxins’ attractive ability. The level of intake and selectivity of calcium transport to ove-ground parts of the plant is controlled by a symplast. Ca2+enters to the cytoplasm of endoderm cells through calcium channels on the cortical side of Kaspary bands, and is redistributed inside the stele by the symplast, with the use of Ca2+-АТPases and Ca2+/Н+-antiports. Owing to regulated expression and activity of these calcium transporters, calclum can be selectively delivered to the xylem. Important role in supporting calcium homeostasis is given to the vacuole which is the largest depo of calcium. Regulated quantity of calcium movement through the tonoplast is provided by a number of potential-, ligand-gated active transporters and channels, like Ca2+-ATPase and Ca2+/H+ exchanger. They are actively involved in the inactivation of the calcium signal by pumping Ca2+ to the depo of cells. Calcium ATPases are high affinity pumps that efficiently transfer calcium ions against the concentration gradient in their presence in the solution in nanomolar concentrations. Calcium exchangers are low affinity, high capacity Ca2+ transporters that are effectively transporting calcium after raising its concentration in the cell cytosol through the use of protons gradients. Maintaining constant concentration and participation in the response to stimuli of different types also involves EPR, plastids, mitochondria, and cell wall. Calcium binding proteins contain several conserved sequences that provide sensitivity to changes in the concentration of Ca2+ and when you

  5. High speed two-photon imaging of calcium dynamics in dendritic spines: consequences for spine calcium kinetics and buffer capacity.

    Directory of Open Access Journals (Sweden)

    L Niels Cornelisse

    Full Text Available Rapid calcium concentration changes in postsynaptic structures are crucial for synaptic plasticity. Thus far, the determinants of postsynaptic calcium dynamics have been studied predominantly based on the decay kinetics of calcium transients. Calcium rise times in spines in response to single action potentials (AP are almost never measured due to technical limitations, but they could be crucial for synaptic plasticity. With high-speed, precisely-targeted, two-photon point imaging we measured both calcium rise and decay kinetics in spines and secondary dendrites in neocortical pyramidal neurons. We found that both rise and decay kinetics of changes in calcium-indicator fluorescence are about twice as fast in spines. During AP trains, spine calcium changes follow each AP, but not in dendrites. Apart from the higher surface-to-volume ratio (SVR, we observed that neocortical dendritic spines have a markedly smaller endogenous buffer capacity with respect to their parental dendrites. Calcium influx time course and calcium extrusion rate were both in the same range for spines and dendrites when fitted with a dynamic multi-compartment model that included calcium binding kinetics and diffusion. In a subsequent analysis we used this model to investigate which parameters are critical determinants in spine calcium dynamics. The model confirmed the experimental findings: a higher SVR is not sufficient by itself to explain the faster rise time kinetics in spines, but only when paired with a lower buffer capacity in spines. Simulations at zero calcium-dye conditions show that calmodulin is more efficiently activated in spines, which indicates that spine morphology and buffering conditions in neocortical spines favor synaptic plasticity.

  6. High speed two-photon imaging of calcium dynamics in dendritic spines: consequences for spine calcium kinetics and buffer capacity.

    Science.gov (United States)

    Cornelisse, L Niels; van Elburg, Ronald A J; Meredith, Rhiannon M; Yuste, Rafael; Mansvelder, Huibert D

    2007-10-24

    Rapid calcium concentration changes in postsynaptic structures are crucial for synaptic plasticity. Thus far, the determinants of postsynaptic calcium dynamics have been studied predominantly based on the decay kinetics of calcium transients. Calcium rise times in spines in response to single action potentials (AP) are almost never measured due to technical limitations, but they could be crucial for synaptic plasticity. With high-speed, precisely-targeted, two-photon point imaging we measured both calcium rise and decay kinetics in spines and secondary dendrites in neocortical pyramidal neurons. We found that both rise and decay kinetics of changes in calcium-indicator fluorescence are about twice as fast in spines. During AP trains, spine calcium changes follow each AP, but not in dendrites. Apart from the higher surface-to-volume ratio (SVR), we observed that neocortical dendritic spines have a markedly smaller endogenous buffer capacity with respect to their parental dendrites. Calcium influx time course and calcium extrusion rate were both in the same range for spines and dendrites when fitted with a dynamic multi-compartment model that included calcium binding kinetics and diffusion. In a subsequent analysis we used this model to investigate which parameters are critical determinants in spine calcium dynamics. The model confirmed the experimental findings: a higher SVR is not sufficient by itself to explain the faster rise time kinetics in spines, but only when paired with a lower buffer capacity in spines. Simulations at zero calcium-dye conditions show that calmodulin is more efficiently activated in spines, which indicates that spine morphology and buffering conditions in neocortical spines favor synaptic plasticity.

  7. [Microbial geochemical calcium cycle].

    Science.gov (United States)

    Zavarzin, G A

    2002-01-01

    The participation of microorganisms in the geochemical calcium cycle is the most important factor maintaining neutral conditions on the Earth. This cycle has profound influence on the fate of inorganic carbon, and, thereby, on the removal of CO2 from the atmosphere. The major part of calcium deposits was formed in the Precambrian, when prokaryotic biosphere predominated. After that, calcium recycling based on biogenic deposition by skeletal organisms became the main process. Among prokaryotes, only a few representatives, e.g., cyanobacteria, exhibit a special calcium function. The geochemical calcium cycle is made possible by the universal features of bacteria involved in biologically mediated reactions and is determined by the activities of microbial communities. In the prokaryotic system, the calcium cycle begins with the leaching of igneous rock predominantly through the action of the community of organotrophic organisms. The release of carbon dioxide to the soil air by organotrophic aerobes leads to leaching with carbonic acid and soda salinization. Under anoxic conditions, of major importance is the organic acid production by primary anaerobes (fermentative microorganisms). Calcium carbonate is precipitated by secondary anaerobes (sulfate reducers) and to a smaller degree by methanogens. The role of the cyanobacterial community in carbonate deposition is exposed by stromatolites, which are the most common organo-sedimentary Precambrian structures. Deposition of carbonates in cyanobacterial mats as a consequence of photoassimilation of CO2 does not appear to be a significant process. It is argued that carbonates were deposited at the boundary between the "soda continent", which emerged as a result of subaerial leaching with carbonic acid, and the ocean containing Ca2+. Such ecotones provided favorable conditions for the development of the benthic cyanobacterial community, which was a precursor of stromatolites.

  8. Expression of CD44 variants in human inflammatory synovitis

    Energy Technology Data Exchange (ETDEWEB)

    Hale, L.P. [Duke Univ. Medical Center, Durham, NC (United States); Haynes, B.F.; McCachren, S. [Duke Univ. Arthritis Center, Durham, NC (United States)

    1995-11-01

    The cell surface hyaluronate receptor CD44 has previously been shown to have immunomodulatory activity and to be upregulated in inflammatory synovitis. Since these findings were reported, the genomic structure of CD44 has been delineated, and multiple splice variants have been described. Therefore, we determined which CD44 variant exons are present during inflammatory synovitis by a combination of Northern blot analysis and reverse transcription followed by polymerase chain reaction amplification of synovial RNA. Immunohistochemical staining was used to define the sites of expression of individual v6 and v9 exons in synovial tissue. The standard (S) or hematopoietic isoform, CD44S, was the predominant form of CD44 expressed in synovium and was expressed by most cell types. Other isoforms, containing alternatively spliced exons in the proximal extracellular domain, were found by RT-PCR, but at lower levels than CD44S. The second most prevalent form was CD44E, which has an insertion of three exons (v8-v10) in the proximal extracellular domain. Immunohistochemical studies showed that reactivity with v9-specific antibodies was primarily in macrophages, particularly those in the synovial lining layer. CD44 exon v6, previously reported to be important in immune activation and in epithelial tumor metastasis, was also expressed in synovial lining cells and in occasional synovial interstitial cells. The presence of CD44 variants containing v9 in rheumatoid synovial macrophages may be important in the adhesion and activation of mononuclear phagocytes in the synovium and, thus, may be a target for novel antiinflammatory therapies in the future. The role of CD44 isoforms in cellular adhesion, immune activation, and joint erosion in inflammatory synovitis deserves further study. 7 figs., 2 tabs., 56 refs.

  9. Calcium orthophosphates in dentistry.

    Science.gov (United States)

    Dorozhkin, Sergey V

    2013-06-01

    Dental caries, also known as tooth decay or a cavity, remains a major public health problem in the most communities even though the prevalence of disease has decreased since the introduction of fluorides for dental care. Therefore, biomaterials to fill dental defects appear to be necessary to fulfill customers' needs regarding the properties and the processing of the products. Bioceramics and glass-ceramics are widely used for these purposes, as dental inlays, onlays, veneers, crowns or bridges. Calcium orthophosphates belong to bioceramics but they have some specific advantages over other types of bioceramics due to a chemical similarity to the inorganic part of both human and mammalian bones and teeth. Therefore, calcium orthophosphates (both alone and as components of various formulations) are used in dentistry as both dental fillers and implantable scaffolds. This review provides brief information on calcium orthophosphates and describes in details current state-of-the-art on their applications in dentistry and dentistry-related fields. Among the recognized dental specialties, calcium orthophosphates are most frequently used in periodontics; however, the majority of the publications on calcium orthophosphates in dentistry are devoted to unspecified "dental" fields.

  10. N = (4,4 Supersymmetry and T-Duality

    Directory of Open Access Journals (Sweden)

    Malin Göteman

    2012-10-01

    Full Text Available A sigma model with four-dimensional target space parametrized by chiral and twisted chiral N =(2,2 superfields can be extended to N =(4,4 supersymmetry off-shell, but this is not true for a model of semichiral fields, where the N = (4,4 supersymmetry can only be realized on-shell. The two models can be related to each other by T-duality. In this paper we perform a duality transformation from a chiral and twisted chiral model with off-shell N = (4,4 supersymmetry to a semichiral model. We find that additional non-linear terms must be added to the original transformations to obtain a semichiral model with N =(4,4 supersymmetry, and that the algebra closes on-shell as a direct consequence of the T-duality.

  11. Calcium Signalling: Fishing Out Molecules of Mitochondrial Calcium Transport

    OpenAIRE

    Hajnóczky, György; Csordás, György

    2010-01-01

    Cellular energy metabolism, survival and death are controlled by mitochondrial calcium signals originating in the cytoplasm. Now, RNAi studies link three proteins — MICU1, NCLX and LETM1 — to the previously unknown molecular mechanism of mitochondrial calcium transport.

  12. Gravimetric Determination of Calcium as Calcium Carbonate Hydrate.

    Science.gov (United States)

    Henrickson, Charles H.; Robinson, Paul R.

    1979-01-01

    The gravimetric determination of calcium as calcium carbonate is described. This experiment is suitable for undergraduate quantitative analysis laboratories. It is less expensive than determination of chloride as silver chloride. (BB)

  13. Tunable CD44-specific cellular retargeting with hyaluronic acid nanoshells

    DEFF Research Database (Denmark)

    Ebbesen, Morten F.; Olesen, Morten T. J.; Gjelstrup, Mikkel C.

    2014-01-01

    Purpose In this work we specifically investigate the molecular weight (Mw) dependent combinatorial properties of hyaluronic acid (HA) for exhibiting stealth and targeting properties using different Mw HA nanoshells to tune nanoparticle retargeting to CD44-expressing cancer cells. Methods HA...

  14. Calcium pathway machinery at fertilization in echinoderms.

    Science.gov (United States)

    Ramos, Isabela; Wessel, Gary M

    2013-01-01

    Calcium signaling in cells directs diverse physiological processes. The calcium waves triggered by fertilization is a highly conserved calcium signaling event essential for egg activation, and has been documented in every egg tested. This activity is one of the few highly conserved events of egg activation through the course of evolution. Echinoderm eggs, as well as many other cell types, have three main intracellular Ca(2+) mobilizing messengers - IP3, cADPR and NAADP. Both cADPR and NAADP were identified as Ca(2+) mobilizing messengers using the sea urchin egg homogenate, and this experimental system, along with the intact urchin and starfish oocyte/egg, continues to be a vital tool for investigating the mechanism of action of calcium signals. While many of the major regulatory steps of the IP3 pathway are well resolved, both cADPR and NAADP remain understudied in terms of our understanding of the fundamental process of egg activation at fertilization. Recently, NAADP has been shown to trigger Ca(2+) release from acidic vesicles, separately from the ER, and a new class of calcium channels, the two-pore channels (TPCs), was identified as the likely targets for this messenger. Moreover, it was found that both cADPR and NAADP can be synthesized by the same family of enzymes, the ADP-rybosyl cyclases (ARCs). In this context of increasing amount of information, the potential coupling and functional roles of different messengers, intracellular stores and channels in the formation of the fertilization calcium wave in echinoderms will be critically evaluated. Copyright © 2012. Published by Elsevier India Pvt Ltd.

  15. Discovery and Development of Calcium Channel Blockers

    Directory of Open Access Journals (Sweden)

    Théophile Godfraind

    2017-05-01

    Full Text Available In the mid 1960s, experimental work on molecules under screening as coronary dilators allowed the discovery of the mechanism of calcium entry blockade by drugs later named calcium channel blockers. This paper summarizes scientific research on these small molecules interacting directly with L-type voltage-operated calcium channels. It also reports on experimental approaches translated into understanding of their therapeutic actions. The importance of calcium in muscle contraction was discovered by Sidney Ringer who reported this fact in 1883. Interest in the intracellular role of calcium arose 60 years later out of Kamada (Japan and Heibrunn (USA experiments in the early 1940s. Studies on pharmacology of calcium function were initiated in the mid 1960s and their therapeutic applications globally occurred in the the 1980s. The first part of this report deals with basic pharmacology in the cardiovascular system particularly in isolated arteries. In the section entitled from calcium antagonists to calcium channel blockers, it is recalled that drugs of a series of diphenylpiperazines screened in vivo on coronary bed precontracted by angiotensin were initially named calcium antagonists on the basis of their effect in depolarized arteries contracted by calcium. Studies on arteries contracted by catecholamines showed that the vasorelaxation resulted from blockade of calcium entry. Radiochemical and electrophysiological studies performed with dihydropyridines allowed their cellular targets to be identified with L-type voltage-operated calcium channels. The modulated receptor theory helped the understanding of their variation in affinity dependent on arterial cell membrane potential and promoted the terminology calcium channel blocker (CCB of which the various chemical families are introduced in the paper. In the section entitled tissue selectivity of CCBs, it is shown that characteristics of the drug, properties of the tissue, and of the stimuli are

  16. Children's Bone Health and Calcium

    Science.gov (United States)

    ... Email Share Dialog × Print Children's Bone Health and Calcium: Condition Information What is bone health and how ... straight, walk, run, and lead an active life. Calcium is one of the key dietary building blocks ...

  17. Controls on Calcium Isotope Fractionation in Cultured Foraminifera

    Science.gov (United States)

    Kisakurek, B.; Boehm, F.; Eisenhauer, A.; Hathorne, E.; Garbe-Schoenberg, D.; Erez, J.

    2008-12-01

    Calcium isotopes have recently emerged as an important tool to study the biomineralization pathways and processes in foraminifera. We analyzed calcium isotopes in planktonic and benthic foraminifera grown under controlled laboratory conditions at different salinity, temperature and pH values. Our results indicate that calcium isotope fractionation in foraminifera is controlled by more than one environmental parameter, requiring a common mechanism to explain the observed trends. There is a significant negative correlation between calcium isotope fractionation and the distribution coefficient of strontium in planktonic foraminifera, which has the same slope (within error) as that in inorganic calcite (Tang et al, 2008). In analogy to these inorganic experiments, calcium isotopic fractionation and Sr/Ca ratios in planktonic foraminifera appear to be mainly controlled by the precipitation rate. However, the two regressions (inorganic vs. foraminiferal) have a small but constant offset from each other by about 0.2 permil in delta(44Ca/40Ca) for a given D(Sr). This offset is presumably due to a vital effect that can be modeled via Rayleigh distillation from an internal biomineralization reservoir (Elderfield et al., 1996). Our preliminary results suggest that such a reservoir behaves as a semi-open system, wherein only less than 25 percent of the calcium taken up from seawater is being utilized for calcification. Elderfield, H., Bertram, C.J., Erez, J. 1996. A biomineralization model for the incorporation of trace elements into foraminiferal calcium carbonate. Earth Planet. Sci. Lett., 142:409-423. Tang J., Dietzel M., Boehm F., Koehler S.J., Eisenhauer A. 2008. Sr2+/Ca2+ and 44Ca/40Ca fractionation during inorganic calcite formation: II. Ca isotopes. Geochim. Cosmochim. Acta, 72:3733-3745.

  18. Stable prenucleation calcium carbonate clusters

    OpenAIRE

    Gebauer, Denis; Völkel, Antje; Cölfen, Helmut

    2008-01-01

    Calcium carbonate forms scales, geological deposits, biominerals, and ocean sediments. Huge amounts of carbon dioxide are retained as carbonate ions, and calcium ions represent a major contribution to water hardness. Despite its relevance, little is known about the precipitation mechanism of calcium carbonate, and specified complex crystal structures challenge the classical view on nucleation considering the formation of metastable ion clusters. We demonstrate that dissolved calcium carbonate...

  19. Lipid raft association restricts CD44-ezrin interaction and promotion of breast cancer cell migration.

    LENUS (Irish Health Repository)

    Donatello, Simona

    2012-12-01

    Cancer cell migration is an early event in metastasis, the main cause of breast cancer-related deaths. Cholesterol-enriched membrane domains called lipid rafts influence the function of many molecules, including the raft-associated protein CD44. We describe a novel mechanism whereby rafts regulate interactions between CD44 and its binding partner ezrin in migrating breast cancer cells. Specifically, in nonmigrating cells, CD44 and ezrin localized to different membranous compartments: CD44 predominantly in rafts, and ezrin in nonraft compartments. After the induction of migration (either nonspecific or CD44-driven), CD44 affiliation with lipid rafts was decreased. This was accompanied by increased coprecipitation of CD44 and active (threonine-phosphorylated) ezrin-radixin-moesin (ERM) proteins in nonraft compartments and increased colocalization of CD44 with the nonraft protein, transferrin receptor. Pharmacological raft disruption using methyl-β-cyclodextrin also increased CD44-ezrin coprecipitation and colocalization, further suggesting that CD44 interacts with ezrin outside rafts during migration. Conversely, promoting CD44 retention inside lipid rafts by pharmacological inhibition of depalmitoylation virtually abolished CD44-ezrin interactions. However, transient single or double knockdown of flotillin-1 or caveolin-1 was not sufficient to increase cell migration over a short time course, suggesting complex crosstalk mechanisms. We propose a new model for CD44-dependent breast cancer cell migration, where CD44 must relocalize outside lipid rafts to drive cell migration. This could have implications for rafts as pharmacological targets to down-regulate cancer cell migration.

  20. Assay for calcium channels

    Energy Technology Data Exchange (ETDEWEB)

    Glossmann, H.; Ferry, D.R.

    1985-01-01

    This chapter focuses on biochemical assays for Ca/sup 2 +/-selective channels in electrically excitable membranes which are blocked in electrophysiological and pharmacological experiments by verapamil, 1,4-dihydropyridines, diltiazen (and various other drugs), as well as inorganic di- or trivalent cations. The strategy employed is to use radiolabeled 1,4-dihydropyridine derivatives which block calcium channels with ED/sub 50/ values in the nanomolar range. Although tritiated d-cis-diltiazem and verapamil can be used to label calcium channels, the 1,4-dihydropyridines offer numerous advantages. The various sections cover tissue specificity of channel labeling, the complex interactions of divalent cations with the (/sup 3/H)nimodipine-labeled calcium channels, and the allosteric regulation of (/sup 3/H)nimodipine binding by the optically pure enantiomers of phenylalkylamine and benzothiazepine calcium channel blockers. A comparison of the properties of different tritiated 1,4-dihydropyridine radioligands and the iodinated channel probe (/sup 125/I)iodipine is given.

  1. Solar Imagery - Chromosphere - Calcium

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset consists of full-disk images of the sun in Calcium (Ca) II K wavelength (393.4 nm). Ca II K imagery reveal magnetic structures of the sun from about 500...

  2. The Plasma Membrane Calcium Pump

    Science.gov (United States)

    Rasmussen, H.

    1983-01-01

    Three aspect of cellular calcium metabolism in animal cells was discussed including the importance of the plasma membrane in calcium homeostasis, experiments dealing with the actual mechanism of the calcium pump, and the function of the pump in relationship to the mitochondria and to the function of calmodulin in the intact cell.

  3. Calcium addition in straw gasification

    DEFF Research Database (Denmark)

    Risnes, H.; Fjellerup, Jan Søren; Henriksen, Ulrik Birk

    2003-01-01

    The present work focuses on the influence of calcium addition in gasification. The inorganic¿organic element interaction as well as the detailed inorganic¿inorganic elements interaction has been studied. The effect of calcium addition as calcium sugar/molasses solutions to straw significantly...

  4. Impregnating Coal With Calcium Carbonate

    Science.gov (United States)

    Sharma, Pramod K.; Voecks, Gerald E.; Gavalas, George R.

    1991-01-01

    Relatively inexpensive process proposed for impregnating coal with calcium carbonate to increase rates of gasification and combustion of coal and to reduce emission of sulfur by trapping sulfur in calcium sulfide. Process involves aqueous-phase reactions between carbon dioxide (contained within pore network of coal) and calcium acetate. Coal impregnated with CO2 by exposing it to CO2 at high pressure.

  5. Observations of 44i Bootis

    Science.gov (United States)

    Jurgenson, C.; Price, M. E.; Pereira, M.; Macinnes, D.; Snodgrass, H. B.

    1999-05-01

    Seven times of minimum were obtained for the W Ursae Majoris type system 44i Bootis; three primary and four secondary. These observations were taken using a 10-inch Newtonian reflector and 1P21 photomultiplier at Lewis & Clark College. Our times of minimum are used with previously observed minimum times for plotting an (o-c) curve to generate a function that describes how the system's ~ 6.5 hr. period is changing over time. After applying a parabolic least squares fit to the (o-c) curve we obtain a quadratic function F(E), where E is the eclipse number. Adding this to the 1991 ephemeris of Oprescu, we obtain a corrected non-linear ephemeris JD 2443604.5919 + 0.26781665 E + 5.9 x10(-11) E(2) . From this we find, in agreement with past observations, that the period of 44i Bootis is increasing over time, and determine the rate of increase. This work was supported by Partners in Science Grant HS0485, an M. J. Murdock Charitable Trust Award of Research Corporation.

  6. Concurrent imaging of synaptic vesicle recycling and calcium dynamics.

    Directory of Open Access Journals (Sweden)

    Haiyan eLi

    2011-11-01

    Full Text Available Synaptic transmission involves the calcium-dependent release of neurotransmitter from synaptic vesicles. Genetically encoded optical probes emitting different wavelengths of fluorescent light in response to neuronal activity offer a powerful approach to understand the spatial and temporal relationship of calcium dynamics to the release of neurotransmitter in defined neuronal populations. To simultaneously image synaptic vesicle recycling and changes in cytosolic calcium, we developed a red-shifted reporter of vesicle recycling based on a vesicular glutamate transporter, VGLUT1-mOrange2 (VGLUT1-mOr2, and a presynaptically-localized green calcium indicator, synaptophysin-GCaMP3 (SyGCaMP3 with a large dynamic range. The fluorescence of VGLUT1-mOr2 is quenched by the low pH of synaptic vesicles. Exocytosis upon electrical stimulation exposes the luminal mOr2 to the neutral extracellular pH and relieves fluorescence quenching. Re-acidification of the vesicle upon endocytosis again reduces fluorescence intensity. Changes in fluorescence intensity thus monitor synaptic vesicle exo- and endocytosis, as demonstrated previously for the green VGLUT1-pHluorin. To monitor changes in calcium, we fused the synaptic vesicle protein synaptophysin to the recently improved calcium indicator GCaMP3. SyGCaMP3 is targeted to presynaptic varicosities, and exhibits changes in fluorescence in response to electrical stimulation consistent with changes in calcium concentration. Using real-time imaging of both reporters expressed in the same synapses, we determine the time course of changes in VGLUT1 recycling in relation to changes in presynaptic calcium concentration. Inhibition of P/Q- and N-type calcium channels reduces calcium levels, as well as the rate of synaptic vesicle exocytosis and the fraction of vesicles released.

  7. Calcium signaling in taste cells.

    Science.gov (United States)

    Medler, Kathryn F

    2015-09-01

    The sense of taste is a common ability shared by all organisms and is used to detect nutrients as well as potentially harmful compounds. Thus taste is critical to survival. Despite its importance, surprisingly little is known about the mechanisms generating and regulating responses to taste stimuli. All taste responses depend on calcium signals to generate appropriate responses which are relayed to the brain. Some taste cells have conventional synapses and rely on calcium influx through voltage-gated calcium channels. Other taste cells lack these synapses and depend on calcium release to formulate an output signal through a hemichannel. Beyond establishing these characteristics, few studies have focused on understanding how these calcium signals are formed. We identified multiple calcium clearance mechanisms that regulate calcium levels in taste cells as well as a calcium influx that contributes to maintaining appropriate calcium homeostasis in these cells. Multiple factors regulate the evoked taste signals with varying roles in different cell populations. Clearly, calcium signaling is a dynamic process in taste cells and is more complex than has previously been appreciated. This article is part of a Special Issue entitled: 13th European Symposium on Calcium. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Interaction of H2S with Calcium Permeable Channels and Transporters

    Directory of Open Access Journals (Sweden)

    Weihua Zhang

    2015-01-01

    Full Text Available A growing amount of evidence has suggested that hydrogen sulfide (H2S, as a gasotransmitter, is involved in intensive physiological and pathological processes. More and more research groups have found that H2S mediates diverse cellular biological functions related to regulating intracellular calcium concentration. These groups have demonstrated the reciprocal interaction between H2S and calcium ion channels and transporters, such as L-type calcium channels (LTCC, T-type calcium channels (TTCC, sodium/calcium exchangers (NCX, transient receptor potential (TRP channels, β-adrenergic receptors, and N-methyl-D-aspartate receptors (NMDAR in different cells. However, the understanding of the molecular targets and mechanisms is incomplete. Recently, some research groups demonstrated that H2S modulates the activity of calcium ion channels through protein S-sulfhydration and polysulfide reactions. In this review, we elucidate that H2S controls intracellular calcium homeostasis and the underlying mechanisms.

  9. Expert review on coronary calcium

    Directory of Open Access Journals (Sweden)

    Matthew J Budoff

    2008-04-01

    Full Text Available Matthew J Budoff, Khawar M GulDivision of Cardiology, Saint John’s Cardiovascular Research Center, Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, California, USAAbstract: While there is no doubt that high risk patients (those with >20% ten year risk of future cardiovascular event need more aggressive preventive therapy, a majority of cardiovascular events occur in individuals at intermediate risk (10%–20% ten year risk. Accurate risk assessment may be helpful in decreasing cardiovascular events through more appropriate targeting of preventive measures. It has been suggested that traditional risk assessment may be refined with the selective use of coronary artery calcium (CAC or other methods of subclinical atherosclerosis measurement. Coronary calcification is a marker of atherosclerosis that can be quantified with the use of cardiac CT and it is proportional to the extent and severity of atherosclerotic disease. The published studies demonstrate a high sensitivity of CAC for the presence of coronary artery disease but a lower specificity for obstructive CAD depending on the magnitude of the CAC. Several large clinical trials found clear, incremental predictive value of CAC over the Framingham risk score when used in asymptomatic patients. Based on multiple observational studies, patients with increased plaque burdens (increased CAC are approximately ten times more likely to suffer a cardiac event over the next 3–5 years. Coronary calcium scores have outperformed conventional risk factors, highly sensitive C-reactive protein (CRP and carotid intima media thickness (IMT as a predictor of cardiovascular events. The relevant prognostic information obtained may be useful to initiate or intensify appropriate treatment strategies to slow the progression of atherosclerotic vascular disease. Current data suggests intermediate risk patients may benefit most from further risk stratification with cardiac CT, as CAC testing is

  10. DISTILLATION OF CALCIUM

    Science.gov (United States)

    Barton, J.

    1954-07-27

    This invention relates to an improvement in the process for the purification of caicium or magnesium containing an alkali metal as impurity, which comprises distiiling a batch of the mixture in two stages, the first stage distillation being carried out in the presence of an inert gas at an absolute pressure substantially greater than the vapor pressure of calcium or maguesium at the temperature of distillation, but less than the vaper pressure at that temperature of the alkali metal impurity so that only the alkali metal is vaporized and condensed on a condensing surface. A second stage distilso that substantially only the calcium or magnesium distills under its own vapor pressure only and condenses in solid form on a lower condensing surface.

  11. Calcium metabolism and cardiovascular function after spaceflight

    Science.gov (United States)

    Hatton, Daniel C.; Yue, Qi; Dierickx, Jacqueline; Roullet, Chantal; Otsuka, Keiichi; Watanabe, Mitsuaki; Coste, Sarah; Roullet, Jean Baptiste; Phanouvang, Thongchan; Orwoll, Eric; hide

    2002-01-01

    To determine the influence of dietary calcium on spaceflight-induced alterations in calcium metabolism and blood pressure (BP), 9-wk-old spontaneously hypertensive rats, fed either high- (2%) or low-calcium (0.02%) diets, were flown on an 18-day shuttle flight. On landing, flight animals had increased ionized calcium (P platelet free calcium (intracellular calcium concentration) were also reduced (P metabolism (P metabolism are relatively impervious to dietary calcium in the short term, 2) increased ionized calcium did not normalize low-calcium-induced elevations of BP, and 3) parathyroid hormone was paradoxically increased in the high-calcium-fed flight animals after landing.

  12. Diagnosis of alterations of serum calcium metabolism.

    Science.gov (United States)

    Lumachi, Franco; Cappelletti, Piero; Tozzoli, Renato; Basso, Stafano M M; Luisetto, Giovanni; Camozzi, Valentina

    2012-07-01

    Calcium is essential to homeostasis and functioning of multiple organ systems. Its circulating concentration is maintained within a very tight physiologic range: 2.25 and 2.50 mmol/L. Under physiological conditions, the ionized calcium concentration is regulated by the parathyroid hormone (PTH), and 1,25(OH)(2) vitamin D through interactions on target organs such as kidney, bone and intestine. In mild, moderate, and severe hypercalcemia, laboratory findings are essential in assessing and monitoring disease course and therapy. The main tools are specific standard biochemical tests able to assess calcium balance and renal function, and some specific biochemical tests, such as PTH, 25(OH) vitamin D, and genetic sequencing, used to clarify the cause of hypercalcemia and, subsequently, to determine appropriate therapy. Once hypercalcemia is confirmed by ionized calcium measurement, the intact PTH assay plays a crucial role to differentiate PTH-mediated from non-PTH-mediated hypercalcemia. Mild hypercalcemia is also present in up to 10-20% of patients treated with lithium for bipolar disorders, in 7-8% of those treated with thiazide diuretics, and in patients with prolonged immobilization, while very high (>3.5 mmol/L) serum calcium levels, together with low PTH, and a rapid increase of hypercalcemia, usually suggest a malignancy-associated hypercalcemic syndrome. The measurement of PTH-related protein, a tumor product that mimics certain action of PTH, is useful only in selected cases. The role of biochemical markers of bone turnover for predicting metastatic bone disease, and monitoring bone metabolic changes, and their usefulness as a predictive mean of the likelihood of bone loss or fractures risk is still unclear.

  13. Models of calcium signalling

    CERN Document Server

    Dupont, Geneviève; Kirk, Vivien; Sneyd, James

    2016-01-01

    This book discusses the ways in which mathematical, computational, and modelling methods can be used to help understand the dynamics of intracellular calcium. The concentration of free intracellular calcium is vital for controlling a wide range of cellular processes, and is thus of great physiological importance. However, because of the complex ways in which the calcium concentration varies, it is also of great mathematical interest.This book presents the general modelling theory as well as a large number of specific case examples, to show how mathematical modelling can interact with experimental approaches, in an interdisciplinary and multifaceted approach to the study of an important physiological control mechanism. Geneviève Dupont is FNRS Research Director at the Unit of Theoretical Chronobiology of the Université Libre de Bruxelles;Martin Falcke is head of the Mathematical Cell Physiology group at the Max Delbrück Center for Molecular Medicine, Berlin;Vivien Kirk is an Associate Professor in the Depar...

  14. 40 CFR 75.44 - Timeliness criteria.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Timeliness criteria. 75.44 Section 75.44 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTINUOUS EMISSION MONITORING Alternative Monitoring Systems § 75.44 Timeliness criteria. To demonstrate...

  15. 27 CFR 44.112 - Emergency premises.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Emergency premises. 44.112 Section 44.112 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... Warehouse Proprietors Changes in Location and Premises § 44.112 Emergency premises. In cases of emergency...

  16. 27 CFR 44.110 - [Reserved

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false 44.110 Section 44.110 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE... Proprietors Changes in Location and Premises § 44.110 ...

  17. 30 CFR 44.3 - Parties.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Parties. 44.3 Section 44.3 Mineral Resources... RULES OF PRACTICE FOR PETITIONS FOR MODIFICATION OF MANDATORY SAFETY STANDARDS General § 44.3 Parties. Parties to proceedings under this part shall include the Mine Safety and Health Administration, the...

  18. 8 CFR 1240.44 - Interpreter.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Interpreter. 1240.44 Section 1240.44 Aliens....44 Interpreter. Any person acting as interpreter in a hearing before an immigration judge under this part shall be sworn to interpret and translate accurately, unless the interpreter is an employee of the...

  19. 46 CFR 272.44 - Dates.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Dates. 272.44 Section 272.44 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS AFFECTING SUBSIDIZED VESSELS AND OPERATORS REQUIREMENTS... Examination, Audit, Review and Appeal Procedures § 272.44 Dates. The dates noted on the letters or...

  20. 40 CFR 61.44 - Stack sampling.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Stack sampling. 61.44 Section 61.44 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL... Firing § 61.44 Stack sampling. (a) Sources subject to § 61.42(b) shall be continuously sampled, during...

  1. 40 CFR 230.44 - Coral reefs.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Coral reefs. 230.44 Section 230.44... Aquatic Sites § 230.44 Coral reefs. (a) Coral reefs consist of the skeletal deposit, usually of calcareous... by increasing the level of suspended particulates. Coral organisms are extremely sensitive to even...

  2. 26 CFR 44.4412-1 - Registration.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Registration. 44.4412-1 Section 44.4412-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES TAXES ON WAGERING; EFFECTIVE JANUARY 1, 1955 Occupational Tax § 44.4412-1 Registration. (a) In...

  3. 34 CFR 300.44 - Universal design.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Universal design. 300.44 Section 300.44 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND... DISABILITIES General Definitions Used in This Part § 300.44 Universal design. Universal design has the meaning...

  4. 27 CFR 44.254 - Shipping containers.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Shipping containers. 44.254 Section 44.254 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... Requirements § 44.254 Shipping containers. Each shipping case, crate, or other container, in which cigars are...

  5. 27 CFR 44.184 - Mark.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Mark. 44.184 Section 44.184 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE... Tubes by Manufacturers and Export Warehouse Proprietors Packaging Requirements § 44.184 Mark. Every...

  6. 30 CFR 44.6 - Service.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Service. 44.6 Section 44.6 Mineral Resources... RULES OF PRACTICE FOR PETITIONS FOR MODIFICATION OF MANDATORY SAFETY STANDARDS General § 44.6 Service... modification may be served personally or by first class mail to the last known address of the party. Service...

  7. 48 CFR 44.307 - Reports.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Reports. 44.307 Section 44... SUBCONTRACTING POLICIES AND PROCEDURES Contractors' Purchasing Systems Reviews 44.307 Reports. The ACO shall distribute copies of CPSR reports; notifications granting, withholding, or withdrawing system approval; and...

  8. 12 CFR 4.4 - Washington office.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Washington office. 4.4 Section 4.4 Banks and... EXAMINERS Organization and Functions § 4.4 Washington office. The Washington office of the OCC is the main office and headquarters of the OCC. The Washington office directs OCC policy, oversees OCC operations...

  9. 29 CFR 44.3 - Election process.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Election process. 44.3 Section 44.3 Labor Office of the Secretary of Labor PROCESS FOR ELECTING STATE AGENCY EMPLOYMENT STATISTICS REPRESENTATIVES FOR CONSULTATIONS WITH DEPARTMENT OF LABOR § 44.3 Election process. (a) Process. The Commissioner of Labor Statistics of...

  10. 27 CFR 44.141 - Sign.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Sign. 44.141 Section 44... PAYMENT OF TAX, OR WITH DRAWBACK OF TAX Operations by Export Warehouse Proprietors § 44.141 Sign. Every... is located, or at the entrance of his warehouse, where it can be plainly seen, a sign, in plain and...

  11. 37 CFR 2.44 - Collective mark.

    Science.gov (United States)

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Collective mark. 2.44 Section 2.44 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE RULES OF PRACTICE IN TRADEMARK CASES The Written Application § 2.44 Collective mark. (a) In an...

  12. 7 CFR 1218.44 - Alternate members.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Alternate members. 1218.44 Section 1218.44... Council § 1218.44 Alternate members. An alternate member of the Council, during the absence of the member for whom the person is the alternate, shall act in the place and stead of such member and perform such...

  13. 12 CFR 561.44 - Security.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Security. 561.44 Section 561.44 Banks and... SAVINGS ASSOCIATIONS § 561.44 Security. The term security means any non-withdrawable account, note, stock... commonly known as a security, or any certificate of interest or participation in, temporary or interim...

  14. 45 CFR 96.44 - Community services.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Community services. 96.44 Section 96.44 Public... Indian Tribes and Tribal Organizations § 96.44 Community services. (a) This section applies to direct funding of Indian tribes and tribal organizations under the community services block grant. (b) The terms...

  15. 10 CFR § 1003.44 - Contents.

    Science.gov (United States)

    2017-01-01

    ... 10 Energy 4 2017-01-01 2017-01-01 false Contents. § 1003.44 Section § 1003.44 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) OFFICE OF HEARINGS AND APPEALS PROCEDURAL REGULATIONS Stays § 1003.44 Contents. (a) An Application for Stay shall contain a full and complete statement of all relevant facts...

  16. 7 CFR 930.44 - Quality control.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Quality control. 930.44 Section 930.44 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Control § 930.44 Quality control. (a) Quality standards. The Board may establish, with the approval of the...

  17. 18 CFR 420.44 - Cooling water.

    Science.gov (United States)

    2010-04-01

    ... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Cooling water. 420.44 Section 420.44 Conservation of Power and Water Resources DELAWARE RIVER BASIN COMMISSION ADMINISTRATIVE MANUAL BASIN REGULATIONS-WATER SUPPLY CHARGES Charges; Exemptions § 420.44 Cooling water. Water used...

  18. 21 CFR 20.44 - Expedited processing.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Expedited processing. 20.44 Section 20.44 Food and... Procedures and Fees § 20.44 Expedited processing. (a) The Food and Drug Administration will provide expedited processing of a request for records when the requester demonstrates a compelling need, or in other cases as...

  19. 48 CFR 44.302 - Requirements.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Requirements. 44.302 Section 44.302 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT SUBCONTRACTING POLICIES AND PROCEDURES Contractors' Purchasing Systems Reviews 44.302 Requirements. (a) The ACO...

  20. 7 CFR 2902.44 - Corrosion preventatives.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Corrosion preventatives. 2902.44 Section 2902.44... Items § 2902.44 Corrosion preventatives. (a) Definition. Products designed to prevent the deterioration (corrosion) of metals. (b) Minimum biobased content. The preferred procurement product must have a minimum...

  1. 26 CFR 44.0-1 - Introduction.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Introduction. 44.0-1 Section 44.0-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES TAXES ON WAGERING; EFFECTIVE JANUARY 1, 1955 Introduction § 44.0-1 Introduction. (a) In general. The...

  2. Glucocorticoids specifically enhance L-type calcium current amplitude and affect calcium channel subunit expression in the mouse hippocampus.

    Science.gov (United States)

    Chameau, Pascal; Qin, Yongjun; Spijker, Sabine; Smit, August Benjamin; Smit, Guus; Joëls, Marian

    2007-01-01

    Previous studies have shown that corticosterone enhances whole cell calcium currents in CA1 pyramidal neurons, through a pathway involving binding of glucocorticoid receptor homodimers to the DNA. We examined whether glucocorticoids show selectivity for L- over N-type of calcium currents. Moreover, we addressed the putative gene targets that eventually lead to the enhanced calcium currents. Electrophysiological recordings were performed in nucleated patches that allow excellent voltage control. Calcium currents in these patches almost exclusively involve N- and L-type channels. We found that L- but not N-type calcium currents were largely enhanced after treatment with a high dose of corticosterone sufficient to activate glucocorticoid receptors. Voltage dependency and kinetic properties of the currents were unaffected by the hormone. Nonstationary noise analysis suggests that the increased current is not caused by a larger unitary conductance, but rather to a doubling of the number of functional channels. Quantitative real-time PCR revealed that transcripts of the Ca(v)1 subunits encoding for the N- or L-type calcium channels are not upregulated in the mouse CA1 area; instead, a strong, direct, and consistent upregulation of the beta4 subunit was observed. This indicates that the corticosteroid-induced increase in number of L-type calcium channels is not caused by a simple transcriptional regulation of the pore-forming subunit of the channels.

  3. Limestone reaction in calcium aluminate cement–calcium sulfate systems

    OpenAIRE

    Bizzozero, Julien; Scrivener, Karen

    2015-01-01

    This paper reports a study of ternary blends composed of calcium aluminate cement, calcium sulfate hemihydrate and limestone. Compressive strength tests and hydration kinetics were studied as a function of limestone and calcium sulfate content. The phase evolution and the total porosity were followed and compared to thermodynamic simulation to understand the reactions involved and the effect of limestone on these binders. The reaction of limestone leads to the formation of hemicarboaluminate ...

  4. Mixed calcium-magnesium pre-nucleation clusters enrich calcium

    OpenAIRE

    Verch, Andreas; Antonietti, Markus; Cölfen, Helmut

    2012-01-01

    It is demonstrated that magnesium and carbonate ions can form pre-nucleation clusters in analogy to calcium carbonate. If a mixed calcium and magnesium solution is brought in contact with carbonate ions, mixed pre-nucleation clusters form. The equilibrium constants for their formation are reported revealing that over the entire range of possible cation mixing ratios, calcium gets enriched over magnesium in the pre-nucleation clusters. This can explain high magnesium contents in amorphous calc...

  5. Calcium-independent disruption of microtubule dynamics by nanosecond pulsed electric fields in U87 human glioblastoma cells

    Science.gov (United States)

    Carr, Lynn; Bardet, Sylvia M.; Burke, Ryan C.; Arnaud-Cormos, Delia; Leveque, Philippe; O’Connor, Rodney P.

    2017-01-01

    High powered, nanosecond duration, pulsed electric fields (nsPEF) cause cell death by a mechanism that is not fully understood and have been proposed as a targeted cancer therapy. Numerous chemotherapeutics work by disrupting microtubules. As microtubules are affected by electrical fields, this study looks at the possibility of disrupting them electrically with nsPEF. Human glioblastoma cells (U87-MG) treated with 100, 10 ns, 44 kV/cm pulses at a frequency of 10 Hz showed a breakdown of their interphase microtubule network that was accompanied by a reduction in the number of growing microtubules. This effect is temporally linked to loss of mitochondrial membrane potential and independent of cellular swelling and calcium influx, two factors that disrupt microtubule growth dynamics. Super-resolution microscopy revealed microtubule buckling and breaking as a result of nsPEF application, suggesting that nsPEF may act directly on microtubules. PMID:28117459

  6. Biological Reactions to Calcium Phosphate-coated Calcium Carbonate Particles

    National Research Council Canada - National Science Library

    Tetsunari NISHIKAWA; Kazuya MASUNO; Tomoharu OKAMURA; Kazuya TOMINAGA; Masahiro WATO; Mayu KOKUBU; Koichi IMAI; Shoji TAKEDA; Yoichro TAGUCHI; Masatoshi UEDA; Akio TANAKA

    2010-01-01

    [SYNOPSIS][Objectives]: In order to histopathologically investigate biological reactions to materials used for scaffolds, we examined the cytotoxicity to calcium particles in vitro and bioabsorption in vivo...

  7. ERP44 inhibits human lung cancer cell migration mainly via IP3R2.

    Science.gov (United States)

    Huang, Xue; Jin, Meng; Chen, Ying-Xiao; Wang, Jun; Zhai, Kui; Chang, Yan; Yuan, Qi; Yao, Kai-Tai; Ji, Guangju

    2016-06-01

    Cancer cell migration is involved in tumour metastasis. However, the relationship between calcium signalling and cancer migration is not well elucidated. In this study, we used the human lung adenocarcinoma A549 cell line to examine the role of endoplasmic reticulum protein 44 (ERP44), which has been reported to regulate calcium release inside of the endoplasmic reticulum (ER), in cell migration. We found that the inositol 1,4,5-trisphosphate receptors (IP3Rs/ITPRs) inhibitor 2-APB significantly inhibited A549 cell migration by inhibiting cell polarization and pseudopodium protrusion, which suggests that Ca2+ is necessary for A549 cell migration. Similarly, the overexpression of ERP44 reduced intracellular Ca2+ release via IP3Rs, altered cell morphology and significantly inhibited the migration of A549 cells. These phenomena were primarily dependent on IP3R2 because wound healing in A549 cells with IP3R2 rather than IP3R1 or IP3R3 siRNA was markedly inhibited. Moreover, the overexpression of ERP44 did not affect the migration of the human neuroblastoma cell line SH-SY5Y, which mainly expresses IP3R1. Based on the above observations, we conclude that ERP44 regulates A549 cell migration mainly via an IP3R2-dependent pathway.

  8. Osteoporosis, calcium and physical activity.

    OpenAIRE

    Martin, A. D.; Houston, C S

    1987-01-01

    Sales of calcium supplements have increased dramatically since 1983, as middle-aged women seek to prevent or treat bone loss due to osteoporosis. However, epidemiologic studies have failed to support the hypothesis that larger amounts of calcium are associated with increased bone density or a decreased incidence of fractures. The authors examine the evidence from controlled trials on the effects of calcium supplementation and physical activity on bone loss and find that weight-bearing activit...

  9. Relation between tipburn appearance of Chinese cabbage and calcium content and location

    Directory of Open Access Journals (Sweden)

    Jan Borkowski

    2013-12-01

    Full Text Available In 2000-2001 investigations were carried out on the dependence between the tipburn appearance on Chinese cabbage and the content of calcium and its distribution in leaves. It was found that the highest concentration of calcium (to 4,4% occurred in outside leaves and the lowest was found in leaves inside the head (to 1,0 %. The marginal part in every outside leaf contained more calcium than midrib of leaf. This dependence weakly appeared in leaves wrapping the head and was absent inside the head, where often the calcium concentration was higher in the midrib part of leaf than in the margin part. Distinct differences in the calcium content in leaves of four culti vars of F1, Chinese cabbage: ´Bilko', ´Parkin', 'Kasumi' and 'Yamiko' were not found. These cultivars differed clearly in the susceptibility to the tipburn incidence which appearance depended also on the temperature stress.

  10. A dynamic marine calcium cycle during the past 28 million years

    Science.gov (United States)

    Griffith, E.M.; Paytan, A.; Caldeira, K.; Bullen, T.D.; Thomas, E.

    2008-01-01

    Multiple lines of evidence have shown that the isotopic composition and concentration of calcium in seawater have changed over the past 28 million years. A high-resolution, continuous seawater calcium isotope ratio curve from marine (pelagic) barite reveals distinct features in the evolution of the seawater calcium isotopic ratio suggesting changes in seawater calcium concentrations. The most pronounced increase in the ??44/40Ca value of seawater (of 0.3 per mil) occurred over roughly 4 million years following a period of low values around 13 million years ago. The major change in marine calcium corresponds to a climatic transition and global change in the carbon cycle and suggests a reorganization of the global biogeochemical system.

  11. Calcium digestibility studies utilizing acid-insoluble ash measurements.

    Science.gov (United States)

    Cheng, T K; Coon, C N

    1990-12-01

    Laying hens were individually fed diets providing daily calcium intakes ranging from 2.0 to 4.5 g from two sources of limestone. Silica (washed sand) was added to the diets as filler for hens with less than 4.5 g of daily calcium intake. The calcium digestibility data were obtained both by the total collection (TC) method and b y using acid-insoluble ash (AIA) as an indicator. Source effect was not significant (P greater than .7) within each method tested, and data were pooled for analysis. The calcium digestibility values obtained by the TC method for hens with intake of 2.0, 2.5, 3.0, 3.5, 4.0, and 4.5 g daily were 59.16, 57.31, 54.29, 50.99, 44.63, and 41.76%, respectively. The AIA method consistently yielded higher digestibility values: 73.0, 65.36, 61.78, 54.19, 45.76, and 42.0%. The differences in calcium digestibility values between the two methods were linearly related to the levels of silica consumption (P less than .05).

  12. Cardiovascular Effects of Calcium Supplements

    Directory of Open Access Journals (Sweden)

    Ian R. Reid

    2013-07-01

    Full Text Available Calcium supplements reduce bone turnover and slow the rate of bone loss. However, few studies have demonstrated reduced fracture incidence with calcium supplements, and meta-analyses show only a 10% decrease in fractures, which is of borderline statistical and clinical significance. Trials in normal older women and in patients with renal impairment suggest that calcium supplements increase the risk of cardiovascular disease. To further assess their safety, we recently conducted a meta-analysis of trials of calcium supplements, and found a 27%–31% increase in risk of myocardial infarction, and a 12%–20% increase in risk of stroke. These findings are robust because they are based on pre-specified analyses of randomized, placebo-controlled trials and are consistent across the trials. Co-administration of vitamin D with calcium does not lessen these adverse effects. The increased cardiovascular risk with calcium supplements is consistent with epidemiological data relating higher circulating calcium concentrations to cardiovascular disease in normal populations. There are several possible pathophysiological mechanisms for these effects, including effects on vascular calcification, vascular cells, blood coagulation and calcium-sensing receptors. Thus, the non-skeletal risks of calcium supplements appear to outweigh any skeletal benefits, and are they appear to be unnecessary for the efficacy of other osteoporosis treatments.

  13. Laser Sintered Calcium Phosphate Bone

    National Research Council Canada - National Science Library

    Vail, Neil

    1999-01-01

    ...) technology selective laser sintering (SLS). BME has successfully implemented a pilot facility to fabricate calcium phosphate implants using anatomical data coupled with the selective laser sintering process...

  14. 21 CFR 73.1070 - Calcium carbonate.

    Science.gov (United States)

    2010-04-01

    ... precipitated calcium carbonate (CaCO3). (2) Color additive mixtures for drug use made with calcium carbonate... precipitated calcium carbonate in the United States Pharmacopeia XX (1980). (c) Uses and restrictions. Calcium... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Calcium carbonate. 73.1070 Section 73.1070 Food...

  15. 21 CFR 184.1191 - Calcium carbonate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium carbonate. 184.1191 Section 184.1191 Food... Specific Substances Affirmed as GRAS § 184.1191 Calcium carbonate. (a) Calcium carbonate (CaCO3, CAS Reg... soda process”; (2) By precipitation of calcium carbonate from calcium hydroxide in the “Carbonation...

  16. Calcium Signaling and Cardiac Arrhythmias.

    Science.gov (United States)

    Landstrom, Andrew P; Dobrev, Dobromir; Wehrens, Xander H T

    2017-06-09

    There has been a significant progress in our understanding of the molecular mechanisms by which calcium (Ca2+) ions mediate various types of cardiac arrhythmias. A growing list of inherited gene defects can cause potentially lethal cardiac arrhythmia syndromes, including catecholaminergic polymorphic ventricular tachycardia, congenital long QT syndrome, and hypertrophic cardiomyopathy. In addition, acquired deficits of multiple Ca2+-handling proteins can contribute to the pathogenesis of arrhythmias in patients with various types of heart disease. In this review article, we will first review the key role of Ca2+ in normal cardiac function-in particular, excitation-contraction coupling and normal electric rhythms. The functional involvement of Ca2+ in distinct arrhythmia mechanisms will be discussed, followed by various inherited arrhythmia syndromes caused by mutations in Ca2+-handling proteins. Finally, we will discuss how changes in the expression of regulation of Ca2+ channels and transporters can cause acquired arrhythmias, and how these mechanisms might be targeted for therapeutic purposes. © 2017 American Heart Association, Inc.

  17. Calcium signalling: fishing out molecules of mitochondrial calcium transport.

    Science.gov (United States)

    Hajnóczky, György; Csordás, György

    2010-10-26

    Cellular energy metabolism, survival and death are controlled by mitochondrial calcium signals originating in the cytoplasm. Now, RNAi studies link three proteins - MICU1, NCLX and LETM1 - to the previously unknown molecular mechanism of mitochondrial calcium transport. Copyright © 2010 Elsevier Ltd. All rights reserved.

  18. Calcium nutrition and extracellular calcium sensing: relevance for the pathogenesis of osteoporosis, cancer and cardiovascular diseases.

    Science.gov (United States)

    Peterlik, Meinrad; Kállay, Enikoe; Cross, Heide S

    2013-01-22

    Through a systematic search in Pubmed for literature, on links between calcium malnutrition and risk of chronic diseases, we found the highest degree of evidence for osteoporosis, colorectal and breast cancer, as well as for hypertension, as the only major cardiovascular risk factor. Low calcium intake apparently has some impact also on cardiovascular events and disease outcome. Calcium malnutrition can causally be related to low activity of the extracellular calcium-sensing receptor (CaSR). This member of the family of 7-TM G-protein coupled receptors allows extracellular Ca2+ to function as a "first messenger" for various intracellular signaling cascades. Evidence demonstrates that Ca2+/CaSR signaling in functional linkage with vitamin D receptor (VDR)-activated pathways (i) promotes osteoblast differentiation and formation of mineralized bone; (ii) targets downstream effectors of the canonical and non-canonical Wnt pathway to inhibit proliferation and induce differentiation of colorectal cancer cells; (iii) evokes Ca2+ influx into breast cancer cells, thereby activating pro-apoptotic intracellular signaling. Furthermore, Ca2+/CaSR signaling opens Ca2+-sensitive K+ conductance channels in vascular endothelial cells, and also participates in IP(3)-dependent regulation of cytoplasmic Ca2+, the key intermediate of cardiomyocyte functions. Consequently, impairment of Ca2+/CaSR signaling may contribute to inadequate bone formation, tumor progression, hypertension, vascular calcification and, probably, cardiovascular disease.

  19. Calcium electroporation in three cell lines; a comparison of bleomycin and calcium, calcium compounds, and pulsing conditions

    DEFF Research Database (Denmark)

    Frandsen, Stine Krog; Gissel, Hanne; Hojman, Pernille

    2013-01-01

    BACKGROUND: Electroporation with calcium (calcium electroporation) can induce ATP depletion-associated cellular death. In the clinical setting, the cytotoxic drug bleomycin is currently used with electroporation (electrochemotherapy) for palliative treatment of tumors. Calcium electroporation off...

  20. Hybrid Calcium Phosphate Coatings for Titanium Implants

    Science.gov (United States)

    Kharapudchenko, E.; Ignatov, V.; Ivanov, V.; Tverdokhlebov, S.

    2017-01-01

    Hybrid multilayer coatings were obtained on titanium substrates by the combination of two methods: the micro-arc oxidation in phosphoric acid solution with the addition of calcium compounds to high supersaturated state and RF magnetron sputtering of the target made of synthetic hydroxyapatite. 16 different groups of coatings were formed on titanium substrates and in vitro studies were conducted in accordance with ISO 23317 in the solution simulating body fluid. The studies using SEM, XRD of the coatings of the samples before and after exposure to SBF were performed. The features of morphology, chemical and phase composition of the studied coatings are shown.

  1. Natural calcium isotonic composition of urine as a marker of bone mineral balance

    Science.gov (United States)

    Skulan, J.; Bullen, T.; Anbar, A.D.; Puzas, J.E.; Shackelford, L.; LeBlanc, A.; Smith, S.M.

    2007-01-01

    Background: We investigated whether changes in the natural isotopic composition of calcium in human urine track changes in net bone mineral balance, as predicted by a model of calcium isotopic behavior in vertebrates. If so, isotopic analysis of natural urine or blood calcium could be used to monitor short-term changes in bone mineral balance that cannot be detected with other techniques. Methods: Calcium isotopic compositions are expressed as ??44Ca, or the difference in parts per thousand between the 44Ca/40Ca of a sample and the 44Ca/ 40Ca of a standard reference material. ??44Ca was measured in urine samples from 10 persons who participated in a study of the effectiveness of countermeasures to bone loss in spaceflight, in which 17 weeks of bed rest was used to induce bone loss. Study participants were assigned to 1 of 3 treatment groups: controls received no treatment, one treatment group received alendronate, and another group performed resistive exercise. Measurements were made on urine samples collected before, at 2 or 3 points during, and after bed rest. Results: Urine ??44Ca values during bed rest were lower in controls than in individuals treated with alendronate (P clinical and research tool. ?? 2007 American Association for Clinical Chemistry.

  2. Individual and family correlates of calcium-rich food intake among parents of early adolescent children.

    Science.gov (United States)

    Reicks, Marla; Ballejos, Miriam Edlefsen; Goodell, L Suzanne; Gunther, Carolyn; Richards, Rickelle; Wong, Siew Sun; Auld, Garry; Boushey, Carol J; Bruhn, Christine; Cluskey, Mary; Misner, Scottie; Olson, Beth; Zaghloul, Sahar

    2011-03-01

    Most adults do not meet calcium intake recommendations. Little is known about how individual and family factors, including parenting practices that influence early adolescents' intake of calcium-rich foods, affect calcium intake of parents. This information could inform the development of effective nutrition education programs. To identify individual and family factors associated with intake of calcium-rich foods among parents of early adolescents (aged 10 to 13 years). A cross-sectional survey was used with 14 scales to assess attitudes/preferences and parenting practices regarding calcium-rich foods and a calcium-specific food frequency questionnaire (2006-2007). A convenience sample of self-reporting non-Hispanic white, Hispanic, and Asian (n=661) parents was recruited in nine states. Parents were the primary meal planner/preparer and completed questionnaires in homes or community settings. Predictors of calcium intake from three food groupings-all food sources, dairy foods, and milk. Multivariate regression analyses identified demographic, attitude/preference, and behavioral factors associated with calcium intake. Most respondents were women (∼90%) and 38% had a college degree. Education was positively associated with calcium intake from all three food groupings, whereas having an Asian spouse compared to a non-Hispanic white spouse was negatively associated with calcium intake only from all food sources and from dairy foods. Expectations for and encouragement of healthy beverage intake for early adolescents were positively associated with calcium intake from dairy foods and milk, respectively. Parental concern regarding adequacy of intake was negatively associated, whereas perception of health benefits from calcium-rich foods was positively associated with calcium intake from all food sources and from dairy foods. Between 20% and 32% of the variance in calcium intake from all food groupings was explained in these models. Individual factors and positive

  3. Calcium-Sensitive MRI Contrast Agents Based on Superparamagnetic Iron Oxide Nanoparticles and Calmodulin

    National Research Council Canada - National Science Library

    Tatjana Atanasijevic; Maxim Shusteff; Peter Fam; Alan Jasanoff

    2006-01-01

    We describe a family of calcium indicators for magnetic resonance imaging (MRI), formed by combining a powerful iron oxide nanoparticle-based contrast mechanism with the versatile calciumsensing protein calmodulin and its targets...

  4. Hybrid calcium phosphate coatings for implants

    Science.gov (United States)

    Malchikhina, Alena I.; Shesterikov, Evgeny V.; Bolbasov, Evgeny N.; Ignatov, Viktor P.; Tverdokhlebov, Sergei I.

    2016-08-01

    Monophasic biomaterials cannot provide all the necessary functions of bones or other calcined tissues. It is necessary to create for cancer patients the multiphase materials with the structure and composition simulating the natural bone. Such materials are classified as hybrid, obtained by a combination of chemically different components. The paper presents the physical, chemical and biological studies of coatings produced by hybrid technologies (HT), which combine primer layer and calcium phosphate (CaP) coating. The first HT type combines the method of vacuum arc titanium primer layer deposition on a stainless steel substrate with the following micro-arc oxidation (MAO) in phosphoric acid solution with addition of calcium compounds to achieve high supersaturated state. MAO CaP coatings feature high porosity (2-8%, pore size 5-7 µm) and surface morphology with the thickness greater than 5 µm. The thickness of Ti primer layer is 5-40 µm. Amorphous MAO CaP coating micro-hardness was measured at maximum normal load Fmax = 300 mN. It was 3.1 ± 0.8 GPa, surface layer elasticity modulus E = 110 ± 20 GPa, roughness Ra = 0.9 ± 0.1 µm, Rz = 7.5 ± 0.2 µm, which is less than the titanium primer layer roughness. Hybrid MAO CaP coating is biocompatible, able to form calcium phosphates from supersaturated body fluid (SBF) solution and also stimulates osteoinduction processes. The second HT type includes the oxide layer formation by thermal oxidation and then CaP target radio frequency magnetron sputtering (RFMS). Oxide-RFMS CaP coating is a thin dense coating with good adhesion to the substrate material, which can be used for metal implants. The RFMS CaP coating has thickness 1.6 ± 0.1 µm and consists of main target elements calcium and phosphorus and Ca/P ratio 2.4. The second HT type can form calcium phosphates from SBF solution. In vivo study shows that hybrid RFMS CaP coating is biocompatible and produces fibrointegration processes.

  5. CCDC 1420580: Experimental Crystal Structure Determination : catena-[(mu-4,4'-sulfonyldibenzoato)-calcium acetylene

    KAUST Repository

    Plonka, Anna M.

    2016-01-01

    An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

  6. CCDC 1420581: Experimental Crystal Structure Determination : catena-[(mu-4,4'-sulfonyldibenzoato)-calcium ethylene

    KAUST Repository

    Plonka, Anna M.

    2016-01-01

    An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

  7. CCDC 1420582: Experimental Crystal Structure Determination : catena-[(mu-4,4'-sulfonyldibenzoato)-calcium ethane

    KAUST Repository

    Plonka, Anna M.

    2016-01-01

    An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

  8. Calcium, vitamin D, and your bones

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000490.htm Calcium, vitamin D, and your bones To use the sharing ... and maintain strong bones. How Much Calcium and Vitamin D do I Need? Amounts of calcium are ...

  9. Calcium Supplements: Do Men Need Them Too?

    Science.gov (United States)

    ... Lifestyle Nutrition and healthy eating Should men take calcium supplements? Answers from Katherine Zeratsky, R.D., L. ... Most healthy men don't need to take calcium supplements. Calcium is important for men for optimal ...

  10. Dietary calcium supplementation enhances efficacy but also toxicity of EGFR inhibitor therapy for colon cancer.

    Science.gov (United States)

    Rinella, Erica S; Bankaitis, Eric D; Threadgill, David W

    2012-02-01

    The inverse correlation between levels of dietary calcium and colorectal cancer (CRC) incidence has been extensively investigated. However, the impact of supplemental calcium on cancer therapy remains unknown. We used four models of CRC, Caco-2 and HCT116 human cancer cell lines and Apc (Min/+) and azoxymethane carcinogen-induced mouse models, to investigate the impact of a western-style diet low in calcium (0.05%) vs. a similar diet but supplemented with calcium (5%) on therapeutic targeting of the epidermal growth factor receptor (EGFR). We found that calcium supplementation combined with pharmacologic blockade of EGFR results in an additive effect on tumor growth inhibition in all models. Unexpectedly, the combined use of dietary calcium supplementation and EGFR inhibitors also resulted in elevated toxicity suggesting that careful consideration be given when combining dietary supplements with prescribed cancer therapies.

  11. Stable prenucleation calcium carbonate clusters.

    Science.gov (United States)

    Gebauer, Denis; Völkel, Antje; Cölfen, Helmut

    2008-12-19

    Calcium carbonate forms scales, geological deposits, biominerals, and ocean sediments. Huge amounts of carbon dioxide are retained as carbonate ions, and calcium ions represent a major contribution to water hardness. Despite its relevance, little is known about the precipitation mechanism of calcium carbonate, and specified complex crystal structures challenge the classical view on nucleation considering the formation of metastable ion clusters. We demonstrate that dissolved calcium carbonate in fact contains stable prenucleation ion clusters forming even in undersaturated solution. The cluster formation can be characterized by means of equilibrium thermodynamics, applying a multiple-binding model, which allows for structural preformation. Stable clusters are the relevant species in calcium carbonate nucleation. Such mechanisms may also be important for the crystallization of other minerals.

  12. A toxin from the spider Phoneutria nigriventer that blocks calcium channels coupled to exocytosis

    Science.gov (United States)

    Guatimosim, C; Romano-Silva, M A; Cruz, J S; Beirão, P S L; Kalapothakis, E; Moraes-Santos, T; Cordeiro, M N; Diniz, C R; Gomez, M V; Prado, M A M

    1997-01-01

    The aim of the present experiments was to investigate the pharmacological action of a toxin from the spider Phoneutria nigriventer, Tx3-3, on the function of calcium channels that control exocytosis of synaptic vesicles. Tx3-3, in confirmation of previous work, diminished the intracellular calcium increase induced by membrane depolarization with KCl (25 mM) in rat cerebrocortical synaptosomes. The toxin was very potent (IC50 0.9 nM) at inhibiting calcium channels that regulate calcium entry in synaptosomes. In addition, Tx3-3 blocked the exocytosis of synaptic vesicles, as measured with the fluorescent dye FM1-43. Using ω-toxins that interact selectively with distinct neuronal calcium channels, we investigated whether the target of Tx3-3 overlaps with known channels that mediate exocytosis. The results indicate that the main population of voltage-sensitive calcium channels altered by Tx3-3 can also be inhibited by ω-agatoxin IVA, an antagonist of P/Q calcium channels. ω-conotoxin GVIA, which inhibits N type calcium channels did not decrease significantly the entry of calcium or exocytosis of synaptic vesicles in depolarized synaptosomes. It is concluded that Tx3-3 potently inhibits ω-agatoxin IVA-sensitive calcium channels, which are involved in controlling exocytosis in rat brain cortical synaptosomes. PMID:9351520

  13. A CD44v+ subpopulation of breast cancer stem-like cells with enhanced lung metastasis capacity.

    Science.gov (United States)

    Hu, Jing; Li, Gang; Zhang, Peiyuan; Zhuang, Xueqian; Hu, Guohong

    2017-03-16

    Cancer stem-like cells (CSCs) are a subpopulation of cancer cells responsible for tumor growth, and recent evidence suggests that CSCs also contribute to cancer metastasis. However, the heterogeneity of CSCs in metastasis capacities is still unclear in breast cancer. Here we show that among the CD24-/CD44+ breast CSCs, a subset expressing the variant isoform of CD44 (CD44v) displays significantly higher capacity of lung metastasis than that expressing the standard CD44 isoform CD44s. Increasing or reducing the CD44v/CD44s ratio of breast cancer cells by regulating the expression of epithelial splicing regulatory protein 1 (ESRP1) leads to promotion or suppression of lung metastasis without influencing cancer cell stemness. Directly suppressing CD44v expression significantly alleviates the metastasis burden in lungs. Mechanically, CD44v, but not CD44s, responds to osteopontin (OPN) in the lung environment to enhance cancer cell invasiveness and promote lung metastasis. In clinical samples expression of ESRP1 and CD44v, rather than CD44s or total CD44, positively correlates with distant metastasis. Overall, our data identify a subset of metastatic breast CSCs characterized by CD44v expression, and suggest that CD44v and ESRP1 might be better prognosis markers and therapeutic targets for breast cancer metastasis.

  14. Phototheranostics of CD44-positive cell populations in triple negative breast cancer.

    Science.gov (United States)

    Jin, Jiefu; Krishnamachary, Balaji; Mironchik, Yelena; Kobayashi, Hisataka; Bhujwalla, Zaver M

    2016-06-15

    Triple-negative breast cancer (TNBC) is one of the most lethal subtypes of breast cancer that has limited treatment options. Its high rates of recurrence and metastasis have been associated, in part, with a subpopulation of breast cancer stem-like cells that are resistant to conventional therapies. A compendium of markers such as CD44(high)/CD24(low), and increased expression of the ABCG2 transporter and increased aldehyde dehydrogenase (ALDH1), have been associated with these cells. We developed a CD44-targeted monoclonal antibody photosensitizer conjugate for combined fluorescent detection and photoimmunotherapy (PIT) of CD44 expressing cells in TNBC. The CD44-targeted conjugate demonstrated acute cell killing of breast cancer cells with high CD44 expression. This cell death process was dependent upon CD44-specific cell membrane binding combined with near-infrared irradiation. The conjugate selectively accumulated in CD44-positive tumors and caused dramatic tumor shrinkage and efficient elimination of CD44-positive cell populations following irradiation. This novel phototheranostic strategy provides a promising opportunity for the destruction of CD44-positive populations that include cancer stem-like cells, in locally advanced primary and metastatic TNBC.

  15. 27 CFR 6.44 - Free warehousing.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Free warehousing. 6.44 Section 6.44 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... warehousing. The furnishing of free warehousing by delaying delivery of distilled spirits, wine, or malt...

  16. 21 CFR 211.44 - Lighting.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Lighting. 211.44 Section 211.44 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL... Lighting. Adequate lighting shall be provided in all areas. ...

  17. 27 CFR 44.144 - Opening.

    Science.gov (United States)

    2010-04-01

    ... PAYMENT OF TAX, OR WITH DRAWBACK OF TAX Operations by Export Warehouse Proprietors Inventories § 44.144 Opening. An opening inventory shall be made by the export warehouse proprietor at the time of commencing... permit issued under § 44.93. A similar inventory shall be made by the export warehouse proprietor when he...

  18. 27 CFR 44.83 - Corporate documents.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Corporate documents. 44.83... Proprietors § 44.83 Corporate documents. Every corporation, before commencing business as an export warehouse... the same; the authority of persons to sign other documents, required by this part, for the corporation...

  19. 16 CFR 4.4 - Service.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Service. 4.4 Section 4.4 Commercial... Service. (a) By the Commission. (1) Service of complaints, initial decisions, final orders and other..., registered or certified, and mailed; service under this provision is complete upon delivery of the document...

  20. 28 CFR 540.44 - Regular visitors.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Regular visitors. 540.44 Section 540.44... and if there exists no reason to exclude them. (c) Friends and associates. The visiting privilege ordinarily will be extended to friends and associates having an established relationship with the inmate...

  1. 40 CFR 30.44 - Procurement procedures.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Procurement procedures. 30.44 Section 30.44 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE... procured. In competitive procurements, such a description shall not contain features which unduly restrict...

  2. 27 CFR 44.227 - Customs procedure.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Customs procedure. 44.227..., WITHOUT PAYMENT OF TAX, OR WITH DRAWBACK OF TAX Drawback of Tax § 44.227 Customs procedure. The customs... having inspected the articles and supervised the lading thereof on the export carrier, the customs...

  3. 27 CFR 44.249 - Lottery features.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Lottery features. 44.249... Requirements § 44.249 Lottery features. No certificate, coupon, or other device purporting to be or to represent a ticket, chance, share, or an interest in, or dependent on, the event of a lottery shall be...

  4. Calcium metabolism & hypercalcemia in adults.

    Science.gov (United States)

    Lumachi, F; Motta, R; Cecchin, D; Ave, S; Camozzi, V; Basso, S M M; Luisetto, G

    2011-01-01

    Calcium is essential for many metabolic process, including nerve function, muscle contraction, and blood clotting. The metabolic pathways that contribute to maintain serum calcium levels are bone remodeling processes, intestinal absorption and secretion, and renal handling, but hypercalcemia occurs when at least 2 of these 3 metabolic pathways are altered. Calcium metabolism mainly depends on the activity of parathyroid hormone (PTH). Its secretion is strictly controlled by the ionized serum calcium levels through a negative feed-back, which is achieved by the activation of calcium-sensing receptors (CaSRs) mainly expressed on the surface of the parathyroid cells. The PTH receptor in bone and kidney is now referred as PTHR1. The balance of PTH, calcitonin, and vitamin D has long been considered the main regulator of calcium metabolism, but the function of other actors, such as fibroblast growth factor-23 (FGF-23), Klotho, and TPRV5 should be considered. Primary hyperparathyroidism and malignancy are the most common causes of hypercalcemia, accounting for more than 90% of cases. Uncontrolled hypercalcemia may cause renal impairment, both temporary (alteration of renal tubular function) and progressive (relapsing nephrolithiasis), leading to a progressive loss of renal function, as well as severe bone diseases, and heart damages. Advances in the understanding of all actors of calcium homeostasis will be crucial, having several practical consequences in the treatment and prevention of hypercalcemia. This would allow to move from a support therapy, sometimes ineffective, to a specific and addressed therapy, especially in patients with chronic hypercalcemic conditions unsuitable for surgery.

  5. Absorption of calcium from milk and tempeh consumed by postmenopausal Malay women using the dual stable isotope technique.

    Science.gov (United States)

    Haron, Hasnah; Shahar, Suzana; O'Brien, Kimberly O; Ismail, Amin; Kamaruddin, Norazmi; Rahman, Suriah Abdul

    2010-03-01

    Assessment of calcium bioavailability from non-dairy foods containing moderate amounts of calcium is especially important in populations that have habitually low dairy consumption. Absorption of calcium from milk and tempeh (a traditional fermented soy product) was compared in a sample of Malay subjects. A randomized, crossover design was utilized to assess calcium absorption in 20 postmenopausal women from either a glass of milk (114 g) or from a meal of tempeh (206 g); each containing 130 mg calcium. At each study of Phase 1 (mid-July) and Phase 2 (mid-August), intravenous (42)Ca and oral (44)Ca were administered and calcium absorption was measured in 24-h urine collections post-dosing; with a 1-month washout period between phases. Absorption of calcium from tempeh did not differ significantly from milk (36.9 +/- 10.6% vs. 34.3 +/- 8.6%, respectively). Due to differences in the calcium content of tempeh, four servings of this product would be needed to get the same amount of absorbed calcium as that obtained from a 4-ounce glass of milk. Tempeh may provide readily available calcium for this population of women at risk for low bone mass.

  6. Calcium and Calcium Supplements: Achieving the Right Balance

    Science.gov (United States)

    ... Duyff RL. American Dietetic Association Complete Food and Nutrition Guide. 4th ed. Hoboken, N.J.: John Wiley & Sons; 2012:140. Rosen HN. Calcium and vitamin D supplementation in osteoporosis. http://www.uptodate.com/home/index. ...

  7. Calcium carbonate and calcium sulfate in Martian meteorite EETA79001

    Science.gov (United States)

    Gooding, J. L.; Wentworth, S. J.

    1987-01-01

    Chips of glassy Lithology C of EETA79001 were studied by scanning electron microscopy and energy dispersive X-ray spectroscopy to determine the mineralogy and petrogenesis of the glass that was shown by others to contain trapped Mars-like gases. Calcium carbonite was identified as massive to acicular crystals for which Ca, C, and O were the major elements. Calcium sulfate was identified as prismatic-acicular crystals with Ca and S as the major elements.

  8. A calcium isotope test of end-Permian ocean acidification using biogenic apatite

    Science.gov (United States)

    Hinojosa, J.; Brown, S. T.; DePaolo, D. J.; Paytan, A.; Shen, S.; Chen, J.; Payne, J.

    2011-12-01

    Submarine erosional truncation of uppermost Permian carbonate strata has been interpreted to reflect ocean acidification coincident with the end-Permian mass extinction. Although this scenario is consistent with carbon isotope and paleontological data, several alternative scenarios, such as ocean overturn or collapse of the biological pump, can also account for the carbon isotope and paleontological evidence. Calcium isotopes provide a geochemical proxy to test between acidification and alternative scenarios. Specifically, a negative shift in the calcium isotope composition (δ44/40Ca) of seawater is predicted under the acidification scenario but not the alternatives. The δ44/40Ca of carbonate rocks from south China exhibits a negative excursion of approximately 0.3%, but this shift could result from either a change in the δ44/40Ca of seawater or a change in carbonate mineralogy because calcite and aragonite exhibit substantially different fractionation factors relative to seawater. To test whether the negative shift in δ44/40Ca reflects seawater δ44/40Ca or carbonate mineralogy, we measured the δ44/40Ca of conodont microfossils (calcium hydroxyapatite) from the global stratotype section for the Permian-Triassic boundary at Meishan, China. The conodont δ44/40Ca record shows a negative excursion similar in stratigraphic position and magnitude to that previously observed in carbonate rocks. Parallel negative excursions in the δ44/40Ca of carbonate rocks and conodont microfossils cannot be accounted for by a change in carbonate mineralogy but are consistent with a negative shift in the δ44/40Ca of seawater. These data add further support for the ocean acidification scenario, pointing toward strong similarities between the greatest catastrophe in the history of animal life and anticipated global change during the 21st century.

  9. Isolation of All CD44 Transcripts in Human Epidermis and Regulation of Their Expression by Various Agents.

    Science.gov (United States)

    Teye, Kwesi; Numata, Sanae; Ishii, Norito; Krol, Rafal P; Tsuchisaka, Atsunari; Hamada, Takahiro; Koga, Hiroshi; Karashima, Tadashi; Ohata, Chika; Tsuruta, Daisuke; Saya, Hideyuki; Haftek, Marek; Hashimoto, Takashi

    2016-01-01

    CD44, a cell surface proteoglycan, is involved in many biological events. CD44 transcripts undergo complex alternative splicing, resulting in many functionally distinct isoforms. To date, however, the nature of these isoforms in human epidermis has not been adequately determined. In this study, we isolated all CD44 transcripts from normal human epidermis, and studied how their expressions are regulated. By RT-PCR, we found that a number of different CD44 transcripts were expressed in human epidermis, and we obtained all these transcripts from DNA bands in agarose and acrylamide gels by cloning. Detailed sequence analysis revealed 18 CD44 transcripts, 3 of which were novel. Next, we examined effects of 10 different agents on the expression of CD44 transcripts in cultured human keratinocytes, and found that several agents, particularly epidermal growth factor, hydrogen peroxide, phorbol 12-myristate 13-acetate, retinoic acid, calcium and fetal calf serum differently regulated their expressions in various patterns. Furthermore, normal and malignant keratinocytes were found to produce different CD44 transcripts upon serum stimulation and subsequent starvation, suggesting that specific CD44 isoforms are involved in tumorigenesis via different CD44-mediated biological pathways.

  10. 21 CFR 184.1187 - Calcium alginate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium alginate. 184.1187 Section 184.1187 Food... Specific Substances Affirmed as GRAS § 184.1187 Calcium alginate. (a) Calcium alginate (CAS Reg. No. 9005.... Calcium alginate is prepared by the neutralization of purified alginic acid with appropriate pH control...

  11. Extracellular and Intracellular Regulation of Calcium Homeostasis

    Directory of Open Access Journals (Sweden)

    Felix Bronner

    2001-01-01

    Full Text Available An organism with an internal skeleton must accumulate calcium while maintaining body fluids at a well-regulated, constant calcium concentration. Neither calcium absorption nor excretion plays a significant regulatory role. Instead, isoionic calcium uptake and release by bone surfaces causes plasma calcium to be well regulated. Very rapid shape changes of osteoblasts and osteoclasts, in response to hormonal signals, modulate the available bone surfaces so that plasma calcium can increase when more low-affinity bone calcium binding sites are made available and can decrease when more high-affinity binding sites are exposed. The intracellular free calcium concentration of body cells is also regulated, but because cells are bathed by fluids with vastly higher calcium concentration, their major regulatory mechanism is severe entry restriction. All cells have a calcium-sensing receptor that modulates cell function via its response to extracellular calcium. In duodenal cells, the apical calcium entry structure functions as both transporter and a vitamin D–responsive channel. The channel upregulates calcium entry, with intracellular transport mediated by the mobile, vitamin D–dependent buffer, calbindin D9K, which binds and transports more than 90% of the transcellular calcium flux. Fixed intracellular calcium binding sites can, like the body's skeleton, take up and release calcium that has entered the cell, but the principal regulatory tool of the cell is restricted entry.

  12. Calcium phosphates for biomedical applications

    Energy Technology Data Exchange (ETDEWEB)

    Canillas, M.; Pena, P.; Aza, A.H. de; Rodriguez, M.A.

    2017-07-01

    The history of calcium phosphates in the medicine field starts in 1769 when the first evidence of its existence in the bone tissue is discovered. Since then, the interest for calcium phosphates has increased among the scientific community. Their study has been developed in parallel with new advances in materials sciences, medicine or tissue engineering areas. Bone tissue engineering is the field where calcium phosphates have had a great importance. While the first bioceramics are selected according to bioinert, biocompatibility and mechanical properties with the aim to replace bone tissue damaged, calcium phosphates open the way to the bone tissue regeneration challenge. Nowadays, they are present in the majority of commercial products directed to repair or regenerate damaged bone tissue. Finally, in the last few decades, they have been suggested and studied as drug delivering devices and as vehicles of DNA and RNA for the future generation therapies. (Author)

  13. Polysulfide calcium as multyfunctional product

    Directory of Open Access Journals (Sweden)

    G. Abramova

    2012-12-01

    Full Text Available A modified method of producing of polysulfide calcium, the influence of various factors on the degree of polysulfide of product, as well as possible directions for its use as a multifunctional compound were considered.

  14. [Calcium metabolism after the menopause].

    Science.gov (United States)

    Kanovitch, D; Klotz, H P

    1976-02-16

    The authors recall the antagonism between estradiol and parathormone. Estradiol tends to lower serum calcium and fix calcium in the bones as shown by one of us 25 years ago. The mechanism of this action of estrogen on calcium metabolism has been determined by numerous authors but some points are still not clear, e.g. the interferences between estrogen and calcitonin. Classically, parathormone is known to increase bony reabsorption and raise serum calcium. After the menopause the gradual reduction in estradiol secretion leads to post-menopausal osteoporosis. It is better to administer estrogens prophylactically to women after the menopause provided a cervical smear and mammography have been carried out to eliminate latent carcinoma of the breast or uterine cervix.

  15. Calcium-sensing beyond neurotransmitters

    DEFF Research Database (Denmark)

    Gustavsson, Natalia; Han, Weiping

    2009-01-01

    Neurotransmitters, neuropeptides and hormones are released through the regulated exocytosis of SVs (synaptic vesicles) and LDCVs (large dense-core vesicles), a process that is controlled by calcium. Synaptotagmins are a family of type 1 membrane proteins that share a common domain structure. Most....... Also, we discuss potential roles of synaptotagmins in non-traditional endocrine systems....... synaptotagmins are located in brain and endocrine cells, and some of these synaptotagmins bind to phospholipids and calcium at levels that trigger regulated exocytosis of SVs and LDCVs. This led to the proposed synaptotagmin-calcium-sensor paradigm, that is, members of the synaptotagmin family function...... as calcium sensors for the regulated exocytosis of neurotransmitters, neuropeptides and hormones. Here, we provide an overview of the synaptotagmin family, and review the recent mouse genetic studies aimed at understanding the functions of synaptotagmins in neurotransmission and endocrine-hormone secretion...

  16. Induction of epithelial-mesenchymal transition (EMT) in breast cancer cells is calcium signal dependent.

    Science.gov (United States)

    Davis, F M; Azimi, I; Faville, R A; Peters, A A; Jalink, K; Putney, J W; Goodhill, G J; Thompson, E W; Roberts-Thomson, S J; Monteith, G R

    2014-05-01

    Signals from the tumor microenvironment trigger cancer cells to adopt an invasive phenotype through epithelial-mesenchymal transition (EMT). Relatively little is known regarding key signal transduction pathways that serve as cytosolic bridges between cell surface receptors and nuclear transcription factors to induce EMT. A better understanding of these early EMT events may identify potential targets for the control of metastasis. One rapid intracellular signaling pathway that has not yet been explored during EMT induction is calcium. Here we show that stimuli used to induce EMT produce a transient increase in cytosolic calcium levels in human breast cancer cells. Attenuation of the calcium signal by intracellular calcium chelation significantly reduced epidermal growth factor (EGF)- and hypoxia-induced EMT. Intracellular calcium chelation also inhibited EGF-induced activation of signal transducer and activator of transcription 3 (STAT3), while preserving other signal transduction pathways such as Akt and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. To identify calcium-permeable channels that may regulate EMT induction in breast cancer cells, we performed a targeted siRNA-based screen. We found that transient receptor potential-melastatin-like 7 (TRPM7) channel expression regulated EGF-induced STAT3 phosphorylation and expression of the EMT marker vimentin. Although intracellular calcium chelation almost completely blocked the induction of many EMT markers, including vimentin, Twist and N-cadherin, the effect of TRPM7 silencing was specific for vimentin protein expression and STAT3 phosphorylation. These results indicate that TRPM7 is a partial regulator of EMT in breast cancer cells, and that other calcium-permeable ion channels are also involved in calcium-dependent EMT induction. In summary, this work establishes an important role for the intracellular calcium signal in the induction of EMT in human breast cancer cells. Manipulation of

  17. 21 CFR 172.330 - Calcium pantothenate, calcium chloride double salt.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium pantothenate, calcium chloride double salt. 172.330 Section 172.330 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN..., calcium chloride double salt. The food additive calcium chloride double salt of calcium pantothenate may...

  18. Urine risk factors in children with calcium kidney stones and their siblings.

    Science.gov (United States)

    Bergsland, Kristin J; Coe, Fredric L; White, Mark D; Erhard, Michael J; DeFoor, William R; Mahan, John D; Schwaderer, Andrew L; Asplin, John R

    2012-06-01

    Calcium nephrolithiasis in children is increasing in prevalence and tends to be recurrent. Although children have a lower incidence of nephrolithiasis than adults, its etiology in children is less well understood; hence, treatments targeted for adults may not be optimal in children. To better understand metabolic abnormalities in stone-forming children, we compared chemical measurements and the crystallization properties of 24-h urine collections from 129 stone formers matched to 105 non-stone-forming siblings and 183 normal, healthy children with no family history of stones, all aged 6 to 17 years. The principal risk factor for calcium stone formation was hypercalciuria. Stone formers have strikingly higher calcium excretion along with high supersaturation for calcium oxalate and calcium phosphate, and a reduced distance between the upper limit of metastability and supersaturation for calcium phosphate, indicating increased risk of calcium phosphate crystallization. Other differences in urine chemistry that exist between adult stone formers and normal individuals such as hyperoxaluria, hypocitraturia, abnormal urine pH, and low urine volume were not found in these children. Hence, hypercalciuria and a reduction in the gap between calcium phosphate upper limit of metastability and supersaturation are crucial determinants of stone risk. This highlights the importance of managing hypercalciuria in children with calcium stones.

  19. Calcium affects on vascular endpoints

    Directory of Open Access Journals (Sweden)

    Patel Vaishali B

    2012-03-01

    Full Text Available Abstract Calcium is one of the most abundant minerals in the body and its metabolism is one of the basic biologic processes in humans. Although historically linked primarily to bone structural development and maintenance, calcium is now recognized as a key component of many physiologic pathways necessary for optimum health including cardiovascular, neurological, endocrine, renal, and gastrointestinal systems. A recent meta-analysis published in August 2011 showed a potential increase in cardiovascular events related to calcium supplementation. The possible mechanism of action of this correlation has not been well elucidated. This topic has generated intense interest due to the widespread use of calcium supplements, particularly among the middle aged and elderly who are at the most risk from cardiac events. Prior studies did not control for potential confounding factors such as the use of statins, aspirin or other medications. These controversial results warrant additional well-designed studies to investigate the relationship between calcium supplementation and cardiovascular outcomes. The purpose of this review is to highlight the current literature in regards to calcium supplementation and cardiovascular health; and to identify areas of future research.

  20. 27 CFR 44.145 - Special.

    Science.gov (United States)

    2010-04-01

    ... PAYMENT OF TAX, OR WITH DRAWBACK OF TAX Operations by Export Warehouse Proprietors Inventories § 44.145 Special. A special inventory shall be made by the export warehouse proprietor whenever required by any...

  1. 27 CFR 44.146 - Closing.

    Science.gov (United States)

    2010-04-01

    ... PAYMENT OF TAX, OR WITH DRAWBACK OF TAX Operations by Export Warehouse Proprietors Inventories § 44.146 Closing. A closing inventory shall be made by the export warehouse proprietor when he transfers ownership...

  2. 48 CFR 44.202-1 - Responsibilities.

    Science.gov (United States)

    2010-10-01

    ... SUBCONTRACTING POLICIES AND PROCEDURES Consent to Subcontracts 44.202-1 Responsibilities. (a) The cognizant... notification and supporting data to ensure that the proposed subcontract is appropriate for the risks involved...

  3. Downregulation of CD44 reduces doxorubicin resistance of CD44+CD24- breast cancer cells

    Directory of Open Access Journals (Sweden)

    Phuc PV

    2011-06-01

    Full Text Available Pham Van Phuc, Phan Lu Chinh Nhan, Truong Hai Nhung, Nguyen Thanh Tam, Nguyen Minh Hoang, Vuong Gia Tue, Duong Thanh Thuy, Phan Kim NgocLaboratory of Stem Cell Research and Application, University of Science, Vietnam National University, Ho Chi Minh, VietnamBackground: Cells within breast cancer stem cell populations have been confirmed to have a CD44+CD24- phenotype. Strong expression of CD44 plays a critical role in numerous types of human cancers. CD44 is involved in cell differentiation, adhesion, and metastasis of cancer cells.Methods: In this study, we reduced CD44 expression in CD44+CD24- breast cancer stem cells and investigated their sensitivity to an antitumor drug. The CD44+CD24- breast cancer stem cells were isolated from breast tumors; CD44 expression was downregulated with siRNAs followed by treatment with different concentrations of the antitumor drug.Results: The proliferation of CD44 downregulated CD44+CD24- breast cancer stem cells was decreased after drug treatment. We noticed treated cells were more sensitive to doxorubicin, even at low doses, compared with the control groups.Conclusions: It would appear that expression of CD44 is integral among the CD44+CD24- cell population. Reducing the expression level of CD44, combined with doxorubicin treatment, yields promising results for eradicating breast cancer stem cells in vitro. This study opens a new direction in treating breast cancer through gene therapy in conjunction with chemotherapy.Keywords: antitumor drugs, breast cancer stem cells, CD44, CD44+CD24- cells, doxorubicin

  4. Lung cancer tumorigenicity and drug resistance are maintained through ALDH(hi)CD44(hi) tumor initiating cells.

    Science.gov (United States)

    Liu, Jing; Xiao, Zhijie; Wong, Sunny Kit-Man; Tin, Vicky Pui-Chi; Ho, Ka-Yan; Wang, Junwen; Sham, Mai-Har; Wong, Maria Pik

    2013-10-01

    Limited improvement in long term survival of lung cancer patients has been achieved by conventional chemotherapy or targeted therapy. To explore the potentials of tumor initiating cells (TIC)-directed therapy, it is essential to identify the cell targets and understand their maintenance mechanisms. We have analyzed the performance of ALDH/CD44 co-expression as TIC markers and treatment targets of lung cancer using well-validated in vitro and in vivo analyses in multiple established and patient-derived lung cancer cells. The ALDH(hi)CD44(hi) subset showed the highest enhancement of stem cell phenotypic properties compared to ALDH(hi)CD44(lo), ALDH(lo)CD44(hi), ALDH(lo)CD44(lo) cells and unsorted controls. They showed higher invasion capacities, pluripotency genes and epithelial-mesenchymal transition transcription factors expression, lower intercellular adhesion protein expression and higher G2/M phase cell cycle fraction. In immunosuppressed mice, the ALDH(hi)CD44(hi)xenografts showed the highest tumor induction frequency, serial transplantability, shortest latency, largest volume and highest growth rates. Inhibition of sonic Hedgehog and Notch developmental pathways reduced ALDH+CD44+ compartment. Chemotherapy and targeted therapy resulted in higher AALDH(hi)CD44(hi) subset viability and ALDH(lo)CD44(lo) subset apoptosis fraction. ALDH inhibition and CD44 knockdown led to reduced stemness gene expression and sensitization to drug treatment. In accordance, clinical lung cancers containing a higher abundance of ALDH and CD44-coexpressing cells was associated with lower recurrence-free survival. Together, results suggested theALDH(hi)CD44(hi)compartment was the cellular mediator of tumorigenicity and drug resistance. Further investigation of the regulatory mechanisms underlying ALDH(hi)CD44(hi)TIC maintenance would be beneficial for the development of long term lung cancer control.

  5. Prospective studies of total and ionized serum calcium in relation to incident and fatal ovarian cancer.

    Science.gov (United States)

    Schwartz, Gary G; Skinner, Halcyon G

    2013-04-01

    Biological markers that could aid in the detection of ovarian cancer are urgently needed. Many ovarian cancers express parathyroid hormone-related protein, which acts to raise calcium levels in serum. Thus, we hypothesized that high serum calcium levels might predict ovarian cancer. We examined the associations between total and ionized serum calcium and ovarian cancer mortality in the Third National Health and Nutrition Survey (NHANES III) using Cox proportional hazard models. We then examined the associations of serum calcium with incident ovarian cancer in a second prospective cohort, the NHANES Epidemiological Follow-up Study (NHEFS). There were eleven deaths from ovarian cancer over 95,556 person-years of follow-up in NHANES III. After multivariable adjustment, the risk for fatal ovarian cancer was 52% higher for each 0.1 mmol/L increase in total serum calcium (RH=1.52, 95% CI 1.06-2.19) and 144% higher for each 0.1 mmol/L increase in ionized serum calcium (RH=2.44, 95% CI=1.45-4.09). Associations persisted after adjusting for nulliparity and the use of oral contraceptives. Eight incident ovarian cancers occurred over 31,089 person-years of follow-up in the NHEFS. After adjusting for covariates, there was a 63% higher risk for ovarian cancer with each 0.1 mmol/L increase in total serum calcium (95% CI 1.14-2.34). Similar results were observed for albumin-adjusted serum calcium. Higher serum calcium may be a biomarker of ovarian cancer. This is the first report of prospective positive associations between indices of calcium in serum and ovarian cancer. Our findings require confirmation in other cohorts. Copyright © 2013. Published by Elsevier Inc.

  6. Calcium-activated chloride channels in the apical region of mouse vomeronasal sensory neurons.

    Science.gov (United States)

    Dibattista, Michele; Amjad, Asma; Maurya, Devendra Kumar; Sagheddu, Claudia; Montani, Giorgia; Tirindelli, Roberto; Menini, Anna

    2012-07-01

    The rodent vomeronasal organ plays a crucial role in several social behaviors. Detection of pheromones or other emitted signaling molecules occurs in the dendritic microvilli of vomeronasal sensory neurons, where the binding of molecules to vomeronasal receptors leads to the influx of sodium and calcium ions mainly through the transient receptor potential canonical 2 (TRPC2) channel. To investigate the physiological role played by the increase in intracellular calcium concentration in the apical region of these neurons, we produced localized, rapid, and reproducible increases in calcium concentration with flash photolysis of caged calcium and measured calcium-activated currents with the whole cell voltage-clamp technique. On average, a large inward calcium-activated current of -261 pA was measured at -50 mV, rising with a time constant of 13 ms. Ion substitution experiments showed that this current is anion selective. Moreover, the chloride channel blockers niflumic acid and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid partially inhibited the calcium-activated current. These results directly demonstrate that a large chloride current can be activated by calcium in the apical region of mouse vomeronasal sensory neurons. Furthermore, we showed by immunohistochemistry that the calcium-activated chloride channels TMEM16A/anoctamin1 and TMEM16B/anoctamin2 are present in the apical layer of the vomeronasal epithelium, where they largely colocalize with the TRPC2 transduction channel. Immunocytochemistry on isolated vomeronasal sensory neurons showed that TMEM16A and TMEM16B coexpress in the neuronal microvilli. Therefore, we conclude that microvilli of mouse vomeronasal sensory neurons have a high density of calcium-activated chloride channels that may play an important role in vomeronasal transduction.

  7. Target Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — [Part of the ATLAS user facility.] The Physics Division operates a target development laboratory that produces targets and foils of various thickness and substrates,...

  8. Mutant p53 promotes cell spreading and migration via ARHGAP44.

    Science.gov (United States)

    Xu, Jinjin; Jiao, Jian; Xu, Wei; Ji, Lei; Jiang, Dongjie; Xie, Shaofang; Kubra, Syeda; Li, Xiaotao; Fu, Junjiang; Xiao, Jianru; Zhang, Bianhong

    2017-09-01

    The tumor suppressor p53 protein is either lost or mutated in about half of all human cancers. Loss of p53 function is well known to influence cell spreading, migration and invasion. While expression of mutant p53 is not equivalent to p53 loss, mutant p53 can acquire new functions to drive cell spreading and migration via different mechanisms. In our study, we found that mutant p53 significantly increased cell spreading and migration when comparing with p53-null cells. RNA-Seq analysis suggested that Rho GTPase activating protein 44 (ARHGAP44) is a new target of mutant p53, which suppressed ARHGAP44 transcription. ARHGAP44 has GAP activity and catalyze GTP hydrolysis on Cdc42. Higher level of GTP-Cdc42 was correlated with increase expression of mutant p53 and reduced ARHGAP44. Importantly, wt-ARHGAP44 but not mutant ARHGAP44 (R291A) suppressed mutant p53 mediated cell spreading and migration. Bioinformatics analysis indicated lower expression of ARHGAP44 in lung carcinoma compared with normal tissues, which was verified by RT-qPCR using specimens from patients. More interestingly, ARHGAP44 mRNA level was lower in tumors with mutant p53 than those with normal p53. Collectively, our results disclose a new mechanism by which mutant p53 stimulates cell spreading and migration.

  9. Asante Calcium Green and Asante Calcium Red--novel calcium indicators for two-photon fluorescence lifetime imaging.

    Directory of Open Access Journals (Sweden)

    Karolina Jahn

    Full Text Available For a comprehensive understanding of cellular processes and potential dysfunctions therein, an analysis of the ubiquitous intracellular second messenger calcium is of particular interest. This study examined the suitability of the novel Ca2+-sensitive fluorescent dyes Asante Calcium Red (ACR and Asante Calcium Green (ACG for two-photon (2P-excited time-resolved fluorescence measurements. Both dyes displayed sufficient 2P fluorescence excitation in a range of 720-900 nm. In vitro, ACR and ACG exhibited a biexponential fluorescence decay behavior and the two decay time components in the ns-range could be attributed to the Ca(2+-free and Ca(2+-bound dye species. The amplitude-weighted average fluorescence decay time changed in a Ca(2+-dependent way, unraveling in vitro dissociation constants K(D of 114 nM and 15 nM for ACR and ACG, respectively. In the presence of bovine serum albumin, the absorption and steady-state fluorescence behavior of ACR was altered and its biexponential fluorescence decay showed about 5-times longer decay time components indicating dye-protein interactions. Since no ester derivative of ACG was commercially available, only ACR was evaluated for 2P-excited fluorescence lifetime imaging microscopy (2P-FLIM in living cells of American cockroach salivary glands. In living cells, ACR also exhibited a biexponential fluorescence decay with clearly resolvable short (0.56 ns and long (2.44 ns decay time components attributable to the Ca(2+-free and Ca(2+-bound ACR species. From the amplitude-weighted average fluorescence decay times, an in situ K(D of 180 nM was determined. Thus, quantitative [Ca(2+]i recordings were realized, unraveling a reversible dopamine-induced [Ca(2+]i elevation from 21 nM to 590 nM in salivary duct cells. It was concluded that ACR is a promising new Ca(2+ indicator dye for 2P-FLIM recordings applicable in diverse biological systems.

  10. Calcium: the molecular basis of calcium action in biology and medicine

    National Research Council Canada - National Science Library

    Pochet, Roland; Donato, Rosario

    2000-01-01

    ... of Calcium Calcium Signalling in Excitable Cells Ca2+ Release in Muscle Cells by N. Macrez and J. Mironneau Calcium Signalling in Neurons Exemplified by Rat Sympathetic Ganglion Cells by S.J. M...

  11. Differentiation of breast cancer stem cells by knockdown of CD44: promising differentiation therapy

    Directory of Open Access Journals (Sweden)

    Pham Phuc V

    2011-12-01

    Full Text Available Abstract Background Breast cancer stem cells (BCSCs are the source of breast tumors. Compared with other cancer cells, cancer stem cells show high resistance to both chemotherapy and radiotherapy. Targeting of BCSCs is thus a potentially promising and effective strategy for breast cancer treatment. Differentiation therapy represents one type of cancer stem-cell-targeting therapy, aimed at attacking the stemness of cancer stem cells, thus reducing their chemo- and radioresistance. In a previous study, we showed that down-regulation of CD44 sensitized BCSCs to the anti-tumor agent doxorubicin. This study aimed to determine if CD44 knockdown caused BCSCs to differentiate into breast cancer non-stem cells (non-BCSCs. Methods We isolated a breast cancer cell population (CD44+CD24- cells from primary cultures of malignant breast tumors. These cells were sorted into four sub-populations based on their expression of CD44 and CD24 surface markers. CD44 knockdown in the BCSC population was achieved using small hairpin RNA lentivirus particles. The differentiated status of CD44 knock-down BCSCs was evaluated on the basis of changes in CD44+CD24- phenotype, tumorigenesis in NOD/SCID mice, and gene expression in relation to renewal status, metastasis, and cell cycle in comparison with BCSCs and non-BCSCs. Results Knockdown of CD44 caused BCSCs to differentiate into non-BCSCs with lower tumorigenic potential, and altered the cell cycle and expression profiles of some stem cell-related genes, making them more similar to those seen in non-BCSCs. Conclusions Knockdown of CD44 is an effective strategy for attacking the stemness of BCSCs, resulting in a loss of stemness and an increase in susceptibility to chemotherapy or radiation. The results of this study highlight a potential new strategy for breast cancer treatment through the targeting of BCSCs.

  12. Radiolabeling of DOTATOC with the long-lived positron emitter {sup 44}Sc

    Energy Technology Data Exchange (ETDEWEB)

    Pruszynski, Marek; Majkowska-Pilip, Agnieszka [Centre of Radiochemistry and Nuclear Chemistry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warszawa (Poland); Loktionova, Natalia S.; Eppard, Elisabeth [Institute of Nuclear Chemistry, Johannes Gutenberg-University of Mainz, Fritz-Strassmann-Weg 2, D-55128 Mainz (Germany); Roesch, Frank, E-mail: frank.roesch@uni-mainz.de [Institute of Nuclear Chemistry, Johannes Gutenberg-University of Mainz, Fritz-Strassmann-Weg 2, D-55128 Mainz (Germany)

    2012-06-15

    The positron-emitting radionuclide {sup 44}Sc with a half-life of 3.97 h and a {beta}{sup +} branching of 94.3% is of potential interest for clinical PET. As so far it is available from a {sup 44}Ti/{sup 44}Sc generator in Mainz, where long-lived {sup 44}Ti decays to no-carrier-added (nca) {sup 44}Sc. The {sup 44}Sc is a trivalent metal cation and should be suitable for complexation with many well established bifunctional chelators conjugated to peptides or other molecular targeting vectors. Thus, the aim of this work was to investigate the potential of {sup 44}Sc for labeling of DOTA-conjugated peptides. DOTA-D-Phe{sup 1}-Tyr{sup 3}-octreotide (DOTATOC) was used as a model molecule to study and optimize labeling procedure. Reaction parameters such as buffer conditions, concentration of peptide, pH range, reaction temperature and time were optimized. Addition of 21 nmol of DOTATOC to {sup 44}Sc in ammonium acetate buffer pH 4.0 provided labeling yields >98% within 25 min of heating in an oil-bath at 95 Degree-Sign C. This time can be reduced to 3 min only by applying microwave supported heating. {sup 44}Sc-DOTATOC was found to be stable in 0.9% NaCl, PBS pH 7.4, fetal calf and human serums, and also in the presence of competing metal cations (Fe{sup 3+}, Ca{sup 2+}, Cu{sup 2+}, Mg{sup 2+}), as well as other ligand competitors, like EDTA and DTPA, even after almost 25 h incubation at 37 Degree-Sign C. Present study shows that nca {sup 44}Sc forms stable complexes with the macrocyclic ligand DOTA and that {sup 44}Sc-DOTATOC and analog targeting vectors may be synthesized for further preclinical and clinical investigations. - Highlights: Black-Right-Pointing-Pointer Labeling of somatostatin analouges with positron emitter {sup 44}Sc was tested. Black-Right-Pointing-Pointer DOTATOC was labeled with {sup 44}Sc isotope. Black-Right-Pointing-Pointer Optimal conditions for {sup 44}Sc-DOTATOC synthesis were found. Black-Right-Pointing-Pointer Stability of {sup 44}Sc

  13. Alpha clustering in Ti isotopes: 40,44,48Ca + α resonant scattering

    Directory of Open Access Journals (Sweden)

    Bailey Sam

    2016-01-01

    Full Text Available Measurements were made of the 4He(40,44,48Ca,α resonant scattering reactions at 180° and up to Ec.m. ~ 11.5MeV, using the Thick Target Inverse Kinematics technique. These measurements are discussed, with a focus on assessing their usefulness for investigating α-clustering in medium mass 44,48,52Ti nuclei.

  14. Presynaptic calcium signalling in cerebellar mossy fibres

    DEFF Research Database (Denmark)

    Thomsen, Louiza Bohn; Jörntell, Henrik; Midtgaard, Jens

    2010-01-01

    Whole-cell recordings were obtained from mossy fibre terminals in adult turtles in order to characterize the basic membrane properties. Calcium imaging of presynaptic calcium signals was carried out in order to analyse calcium dynamics and presynaptic GABA B inhibition. A tetrodotoxin (TTX....... Calcium imaging using Calcium-Green dextran revealed a stimulus-evoked all-or-none TTX-sensitive calcium signal in simple and complex rosettes. All compartments of a complex rosette were activated during electrical activation of the mossy fibre, while individual simple and complex rosettes along an axon...... appeared to be isolated from one another in terms of calcium signalling. CGP55845 application showed that GABA B receptors mediated presynaptic inhibition of the calcium signal over the entire firing frequency range of mossy fibres. A paired-pulse depression of the calcium signal lasting more than 1 s...

  15. Salivary calcium concentration as a screening tool for postmenopausal osteoporosis.

    Science.gov (United States)

    Rabiei, Maryam; Masooleh, Irandokht Shenavar; Leyli, Ehsan Kazemnejad; Nikoukar, Laia Rahbar

    2013-04-01

    Measurements of salivary calcium level may be a useful screening tool for osteoporosis in postmenopausal women. The purpose of this study was to clarify whether this measure is valid compared with dual-energy X-ray (Bone Mineral Density) screening tools in osteoporosis. A case-control study was carried out in 40 postmenopausal women with osteoporosis (T-score ≤ -2.5) and 40 women without osteoporosis (T-score > -1 bone mineral density). Salivary samples were collected and calcium concentrations were measured and expressed as mg/dL. Receiver operating characteristic curve analyses was used to determine the optimal cut-off thresholds for salivary calcium in healthy postmenopausal women. The cut-off point for salivary calcium was 6.1 mg/dL. The sensitivity and specificity, respectively, for identifying women with osteoporosis, were 67.5 (95%CI 52.33-82.67) and 60% (95%CI 44.62-75.38). The area under curve (AUC) was 0.678 (95%CI 0.56-0.79), the positive predictive value (PPV) was 62.79 (95%CI 47.74-77.84) and negative predictive value (NPV) was 64.86% (95%CI 49.27-80.46). The positive likelihood ratio was 1.688 and the negative likelihood ratio was 0.542. Salivary calcium concentration discriminates between women with and without osteoporosis and constitutes a useful tool for screening for osteoporosis. © 2012 The Authors International Journal of Rheumatic Diseases © 2012 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  16. SPE-44 implements sperm cell fate.

    Directory of Open Access Journals (Sweden)

    Madhura Kulkarni

    Full Text Available The sperm/oocyte decision in the hermaphrodite germline of Caenorhabditis elegans provides a powerful model for the characterization of stem cell fate specification and differentiation. The germline sex determination program that governs gamete fate has been well studied, but direct mediators of cell-type-specific transcription are largely unknown. We report the identification of spe-44 as a critical regulator of sperm gene expression. Deletion of spe-44 causes sperm-specific defects in cytokinesis, cell cycle progression, and organelle assembly resulting in sterility. Expression of spe-44 correlates precisely with spermatogenesis and is regulated by the germline sex determination pathway. spe-44 is required for the appropriate expression of several hundred sperm-enriched genes. The SPE-44 protein is restricted to the sperm-producing germline, where it localizes to the autosomes (which contain sperm genes but is excluded from the transcriptionally silent X chromosome (which does not. The orthologous gene in other Caenorhabditis species is similarly expressed in a sex-biased manner, and the protein likewise exhibits autosome-specific localization in developing sperm, strongly suggestive of an evolutionarily conserved role in sperm gene expression. Our analysis represents the first identification of a transcriptional regulator whose primary function is the control of gamete-type-specific transcription in this system.

  17. H I in group interactions: HCG 44

    Science.gov (United States)

    Hess, Kelley M.; Cluver, M. E.; Yahya, Sahba; Leisman, Lukas; Serra, Paolo; Lucero, Danielle M.; Passmoor, Sean S.; Carignan, Claude

    2017-01-01

    Extending deep observations of the neutral atomic hydrogen (H I) to the environment around galaxy groups can reveal a complex history of group interactions which is invisible to studies that focus on the stellar component. Hickson Compact Group 44 (HCG 44) is a nearby example, and we have combined H I data from the Karoo Array Telescope, Westerbork Synthesis Radio Telescope, and Arecibo Legacy Fast ALFA survey, in order to achieve high column density sensitivity (N _{H {I}}HCG 44 contains 1.1 × 109 M⊙ of gas and extends 450 kpc from the compact group: twice as much mass and 33 per cent further than previously detected. However, the additional gas is still unable to account for the known H I deficiency of HCG 44. The tail likely formed through a strong tidal interaction and H I clouds in the tail have survived for 1 Gyr or more after being stripped. This has important implications for understanding the survival of neutral clouds in the intragroup and circumgroup medium, and we discuss their survival in the context of simulations of cold gas in hot haloes. HCG 44 is one of a growing number of galaxy groups found to have more extended H I in the intragroup and circumgroup medium than previously measured. Our results provide constraints for simulations on the properties of galaxy group haloes, and reveal a glimpse of what will be seen by future powerful H I telescopes and surveys.

  18. Mechanism of the induction of endoplasmic reticulum stress by the anti-cancer agent, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT): Activation of PERK/eIF2α, IRE1α, ATF6 and calmodulin kinase.

    Science.gov (United States)

    Merlot, Angelica M; Shafie, Nurul H; Yu, Yu; Richardson, Vera; Jansson, Patric J; Sahni, Sumit; Lane, Darius J R; Kovacevic, Zaklina; Kalinowski, Danuta S; Richardson, Des R

    2016-06-01

    The endoplasmic reticulum (ER) plays a major role in the synthesis, maturation and folding of proteins and is a critical calcium (Ca(2+)) reservoir. Cellular stresses lead to an overwhelming accumulation of misfolded proteins in the ER, leading to ER stress and the activation of the unfolded protein response (UPR). In the stressful tumor microenvironment, the UPR maintains ER homeostasis and enables tumor survival. Thus, a novel strategy for cancer therapeutics is to overcome chronically activated ER stress by triggering pro-apoptotic pathways of the UPR. Considering this, the mechanisms by which the novel anti-cancer agent, Dp44mT, can target the ER stress response pathways were investigated in multiple cell-types. Our results demonstrate that the cytotoxic chelator, Dp44mT, which forms redox-active metal complexes, significantly: (1) increased ER stress-associated pro-apoptotic signaling molecules (i.e., p-eIF2α, ATF4, CHOP); (2) increased IRE1α phosphorylation (p-IRE1α) and XBP1 mRNA splicing; (3) reduced expression of ER stress-associated cell survival signaling molecules (e.g., XBP1s and p58(IPK)); (4) increased cleavage of the transcription factor, ATF6, which enhances expression of its downstream targets (i.e., CHOP and BiP); and (5) increased phosphorylation of CaMKII that induces apoptosis. In contrast to Dp44mT, the iron chelator, DFO, which forms redox-inactive iron complexes, did not affect BiP, p-IRE1α, XBP1 or p58(IPK) levels. This study highlights the ability of a novel cancer therapeutic (i.e., Dp44mT) to target the pro-apoptotic functions of the UPR via cellular metal sequestration and redox stress. Assessment of ER stress-mediated apoptosis is fundamental to the understanding of the pharmacology of chelation for cancer treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Sensitization and cross-reactivity patterns of contact allergy to diisocyanates and corresponding amines: investigation of diphenylmethane-4,4'-diisocyanate, diphenylmethane-4,4'-diamine, dicyclohexylmethane-4,4'-diisocyanate, and dicylohexylmethane-4,4'-diamine.

    Science.gov (United States)

    Hamada, Haneen; Bruze, Magnus; Zimerson, Erik; Isaksson, Marléne; Engfeldt, Malin

    2017-10-01

    Isocyanates are used in polyurethane production. Dermal exposure to isocyanates can induce contact allergy. The most common isocyanate is diphenylmethane diisocyanate used for industrial purposes. The isomer diphenylmethane-4,4'-diisocyanate (4,4'-MDI) is used in patch testing. Diphenylmethane-4,4'-diamine (4,4'-MDA) is its corresponding amine. Concurrent reactions to 4,4'-MDI and 4,4'-MDA have been reported, as have concurrent reactions to 4,4'-MDI and dicyclohexylmethane-4,4'-diisocyanate (4,4'-DMDI). To investigate the sensitization capacities and the cross-reactivity of 4,4'-MDI, 4,4'-MDA, 4,4'-DMDI, and dicyclohexylmethane-4,4'-diamine (4,4'-DMDA). The guinea-pig maximization test (GPMT) was used. The GPMT showed sensitizing capacities for all investigated substances: 4,4'-MDI, 4,4'-MDA, 4,4'-DMDI, and 4,4'-DMDA (all p < 0.001). 4,4'-MDI-sensitized animals showed cross-reactivity to 4,4'-MDA (p < 0.001) and 4,4'-DMDI (all p < 0.05). 4,4'-MDA-sensitized animals showed cross-reactivity to 4,4'-DMDA (p = 0.008). All of the investigated substances were shown to be strong sensitizers. Animals sensitized to 4,4'-MDI showed cross-reactivity to 4,4'-MDA and 4,4'-DMDI, supporting previous findings in the literature. The aromatic amine 4,4'-MDA showed cross-reactivity to the aliphatic amine 4,4'-DMDA. © 2017 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.

  20. Fractional Absorption of Active Absorbable Algal Calcium (AAACa and Calcium Carbonate Measured by a Dual Stable-Isotope Method

    Directory of Open Access Journals (Sweden)

    Steven A. Abrams

    2010-07-01

    Full Text Available With the use of stable isotopes, this study aimed to compare the bioavailability of active absorbable algal calcium (AAACa, obtained from oyster shell powder heated to a high temperature, with an additional heated seaweed component (Heated Algal Ingredient, HAI, with that of calcium carbonate. In 10 postmenopausal women volunteers aged 59 to 77 years (mean ± S.D., 67 ± 5.3, the fractional calcium absorption of AAACa and CaCO3 was measured by a dual stable isotope method. 44Ca-enriched CaCO3 and AAACa were administered in all subjects one month apart. After a fixed-menu breakfast and pre-test urine collection (Urine 0, 42Ca-enriched CaCl2 was intravenously injected, followed by oral administration of 44Ca-enriched CaCO3 without carrier 15 minutes later, and complete urine collection for the next 24 hours (Urine 24. The fractional calcium absorption was calculated as the ratio of Augmentation of 44Ca from Urine 0 to Urine 24/ augmentation of 42Ca from Urine 0 to Urine 24. Differences and changes of 44Ca and 42Ca were corrected by comparing each with 43Ca. Fractional absorption of AAACa (mean ± S.D., 23.1 ± 6.4, was distinctly and significantly higher than that of CaCO3 (14.7 ± 6.4; p = 0.0060 by paired t-test. The mean fractional absorption was approximately 1.57-times higher for AAACa than for CaCO3. The serum 25(OH vitamin D level was low (mean ± S.D., 14.2 ± 4.95 ng/ml, as is common in this age group in Japan. Among the parameters of the bone and mineral metabolism measured, none displayed a significant correlation with the fractional absorption of CaCO3 and AAACa. Higher fractional absorption of AAACa compared with CaCO3 supports previous reports on the more beneficial effect of AAACa than CaCO3 for osteoporosis.

  1. The genetic background affects the vascular response in T-type calcium channels 3.2 deficient mice

    DEFF Research Database (Denmark)

    Svenningsen, Per; Hansen, Pernille B L

    2016-01-01

    Voltage-gated calcium channels (Cav ) are important regulators of vascular tone and are attractive targets for pharmacological treatment of hypertension. The clinical used calcium blockers are often not selective for one channel but affect several types of calcium channels (Hansen 2015). L......-type channels are the dominant Ca(2+) entry pathway in vascular smooth muscle cells, however, T-type calcium channels are also expressed in the cardiovascular system where they play a functional role in the regulation of both contraction and vasodilation in (Chen et al. 2003; Hansen et al. 2001). This article...... is protected by copyright. All rights reserved....

  2. Calcium metabolism and cardiovascular function after spaceflight

    Science.gov (United States)

    Hatton, Daniel C.; Yue, Qi; Dierickx, Jacqueline; Roullet, Chantal; Otsuka, Keiichi; Watanabe, Mitsuaki; Coste, Sarah; Roullet, Jean Baptiste; Phanouvang, Thongchan; Orwoll, Eric; hide

    2002-01-01

    To determine the influence of dietary calcium on spaceflight-induced alterations in calcium metabolism and blood pressure (BP), 9-wk-old spontaneously hypertensive rats, fed either high- (2%) or low-calcium (0.02%) diets, were flown on an 18-day shuttle flight. On landing, flight animals had increased ionized calcium (P parathyroid hormone levels (P animals (P = 0.057). However, mean arterial pressure was elevated (P animals fed low- compared with high-calcium diets (P parathyroid hormone was paradoxically increased in the high-calcium-fed flight animals after landing.

  3. The calcium concentration of public drinking waters and bottled mineral waters in Spain and its contribution to satisfying nutritional needs.

    Science.gov (United States)

    Vitoria, Isidro; Maraver, Francisco; Ferreira-Pêgo, Cíntia; Armijo, Francisco; Moreno Aznar, Luis; Salas-Salvadó, Jordi

    2014-07-01

    A sufficient intake of calcium enables correct bone mineralization. The bioavailability of calcium in water is similar to that in milk. To determine the concentration of calcium in public drinking water and bottled mineral water. We used ion chromatography to analyse the calcium concentrations of public drinking waters in a representative sample of 108 Spanish municipalities (21,290,707 people) and of 109 natural mineral waters sold in Spain, 97 of which were produced in Spain and 12 of which were imported. The average calcium concentration of public drinking waters was 38.96 ± 32.44 mg/L (range: 0.40- 159.68 mg/L). In 27 municipalities, the water contained 50-100 mg/L of calcium and in six municipalities it contained over 100 mg/L. The average calcium concentration of the 97 Spanish natural mineral water brands was 39.6 mg/L (range: 0.6-610.1 mg/L). Of these, 34 contained 50-100 mg/L of calcium and six contained over 100 mg/L. Of the 12 imported brands, 10 contained over 50 mg/L. Assuming water consumption is as recommended, water containing 50-100 mg/L of calcium provides 5.4-12.8% of the recommended intake of calcium for children aged one to thirteen, up to 13.6% for adolescents, 5.8-17.6% for adults, and up to 20.8% for lactating mothers. Water with 100-150 mg/L of calcium provides 10-31% of the recommended dietary allowance, depending on the age of the individual. Public drinking water and natural mineral water consumption in a third of Spanish cities can be considered an important complementary source of calcium. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  4. [Regulatory mechanism of calcium metabolism.

    Science.gov (United States)

    Ozono, Keiichi

    It is often difficult for terrestrial animals to take enough calcium. To maintain serum or extracellular calcium levels is very important for muscle and nerve function. Two major regulators to increase the serum calcium levels are parathyroid hormone(PTH)and vitamin D. PTH binds to the G protein coupling receptor, PTH1R, and increases intracellular cAMP levels. Impirement in the PTH signalling causes many diseases such as pseudohypoparathyroidism and acrodysostosis with hormone resistance. Vitamin D is activated to 1,25-dihydroxyvitamin D[1,25(OH)2D]by two steps of hydroxylation which occurs in the Liver and Kidney. Then, 1,25(OH)2D binds to vitamin D receptor(VDR), which works as a ligand-dependent transcription factor. Hypocalcemia and hypercalcemia are caused by various disorders including abnormal regulation of PTH and vitamin D production and their signal transduction.

  5. Calcium signaling and cell proliferation.

    Science.gov (United States)

    Pinto, Mauro Cunha Xavier; Kihara, Alexandre Hiroaki; Goulart, Vânia A M; Tonelli, Fernanda M P; Gomes, Katia N; Ulrich, Henning; Resende, Rodrigo R

    2015-11-01

    Cell proliferation is orchestrated through diverse proteins related to calcium (Ca(2+)) signaling inside the cell. Cellular Ca(2+) influx that occurs first by various mechanisms at the plasma membrane, is then followed by absorption of Ca(2+) ions by mitochondria and endoplasmic reticulum, and, finally, there is a connection of calcium stores to the nucleus. Experimental evidence indicates that the fluctuation of Ca(2+) from the endoplasmic reticulum provides a pivotal and physiological role for cell proliferation. Ca(2+) depletion in the endoplasmatic reticulum triggers Ca(2+) influx across the plasma membrane in an phenomenon called store-operated calcium entries (SOCEs). SOCE is activated through a complex interplay between a Ca(2+) sensor, denominated STIM, localized in the endoplasmic reticulum and a Ca(2+) channel at the cell membrane, denominated Orai. The interplay between STIM and Orai proteins with cell membrane receptors and their role in cell proliferation is discussed in this review. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Polymorphism of felodipine co-crystals with 4,4'-bipyridine

    DEFF Research Database (Denmark)

    Surov, Artem Olegovich; Solanko, Katarzyna A.; Bond, Andrew

    2014-01-01

    The calcium-channel blocking agent felodipine (Fel) forms co-crystals with 4,4′-bipyridine (BP) with 1:1 and 2:1 molar ratios. The [Fel + BP] (1:1) co-crystal exists in two polymorphic forms. Differential scanning calorimetry and solution calorimetry show that form I of the [Fel + BP] (1:1) co-cr...... that the packing energy gain originates from only weak van der Waals interactions. Analysis of Hirshfeld surfaces of the felodipine molecule shows a similar distribution of intermolecular contacts in the co-crystals and pure felodipine....

  7. Calcium regulation of muscle contraction.

    Science.gov (United States)

    Szent-Györgyi, A G

    1975-07-01

    Calcium triggers contraction by reaction with regulatory proteins that in the absence of calcium prevent interaction of actin and myosin. Two different regulatory systems are found in different muscles. In actin-linked regulation troponin and tropomyosin regulate actin by blocking sites on actin required for complex formation with myosin; in myosin-linked regulation sites on myosin are blocked in the absence of calcium. The major features of actin control are as follows: there is a requirement for tropomyosin and for a troponin complex having three different subunits with different functions; the actin displays a cooperative behavior; and a movement of tropomyosin occurs controlled by the calcium binding on troponin. Myosin regulation is controlled by a regulatory subunit that can be dissociated in scallop myosin reversibly by removing divalent cations with EDTA. Myosin control can function with pure actin in the absence of tropomyosin. Calcium binding and regulation of molluscan myosins depend on the presence of regulatory light chains. It is proposed that the light chains function by sterically blocking myosin sites in the absence of calcium, and that the "off" state of myosin requires cooperation between the two myosin heads. Both myosin control and actin control are widely distributed in different organisms. Many invertebrates have muscles with both types of regulation. Actin control is absent in the muscles of molluscs and in several minor phyla that lack troponin. Myosin control is not found in striated vertebrate muscles and in the fast muscles of crustacean decapods, although regulatory light chains are present. While in vivo myosin control may not be excluded from vertebrate striated muscles, myosin control may be absent as a result of mutations of the myosin heavy chain.

  8. Nuclear Calcium Signaling Induces Expression of the Synaptic Organizers Lrrtm1 and Lrrtm2*

    Science.gov (United States)

    Hayer, Stefanie N.; Bading, Hilmar

    2015-01-01

    Calcium transients in the cell nucleus evoked by synaptic activity in hippocampal neurons function as a signaling end point in synapse-to-nucleus communication. As an important regulator of neuronal gene expression, nuclear calcium is involved in the conversion of synaptic stimuli into functional and structural changes of neurons. Here we identify two synaptic organizers, Lrrtm1 and Lrrtm2, as targets of nuclear calcium signaling. Expression of both Lrrtm1 and Lrrtm2 increased in a synaptic NMDA receptor- and nuclear calcium-dependent manner in hippocampal neurons within 2–4 h after the induction of action potential bursting. Induction of Lrrtm1 and Lrrtm2 occurred independently of the need for new protein synthesis and required calcium/calmodulin-dependent protein kinases and the nuclear calcium signaling target CREB-binding protein. Analysis of reporter gene constructs revealed a functional cAMP response element in the proximal promoter of Lrrtm2, indicating that at least Lrrtm2 is regulated by the classical nuclear Ca2+/calmodulin-dependent protein kinase IV-CREB/CREB-binding protein pathway. These results suggest that one mechanism by which nuclear calcium signaling controls neuronal network function is by regulating the expression of Lrrtm1 and Lrrtm2. PMID:25527504

  9. Nuclear calcium signaling induces expression of the synaptic organizers Lrrtm1 and Lrrtm2.

    Science.gov (United States)

    Hayer, Stefanie N; Bading, Hilmar

    2015-02-27

    Calcium transients in the cell nucleus evoked by synaptic activity in hippocampal neurons function as a signaling end point in synapse-to-nucleus communication. As an important regulator of neuronal gene expression, nuclear calcium is involved in the conversion of synaptic stimuli into functional and structural changes of neurons. Here we identify two synaptic organizers, Lrrtm1 and Lrrtm2, as targets of nuclear calcium signaling. Expression of both Lrrtm1 and Lrrtm2 increased in a synaptic NMDA receptor- and nuclear calcium-dependent manner in hippocampal neurons within 2-4 h after the induction of action potential bursting. Induction of Lrrtm1 and Lrrtm2 occurred independently of the need for new protein synthesis and required calcium/calmodulin-dependent protein kinases and the nuclear calcium signaling target CREB-binding protein. Analysis of reporter gene constructs revealed a functional cAMP response element in the proximal promoter of Lrrtm2, indicating that at least Lrrtm2 is regulated by the classical nuclear Ca(2+)/calmodulin-dependent protein kinase IV-CREB/CREB-binding protein pathway. These results suggest that one mechanism by which nuclear calcium signaling controls neuronal network function is by regulating the expression of Lrrtm1 and Lrrtm2. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Constraints on ocean biogeochemistry during the end-Guadalupian biotic crisis from stable calcium isotopes

    Science.gov (United States)

    Jost, A. B.; Mundil, R.; He, B.; Brown, S. T.; DePaolo, D. J.; Payne, J.

    2011-12-01

    The end-Guadalupian biotic crisis (ca. 260 Mya) has been linked to flood basalt volcanism from the Emeishan LIP (South China) and its environmental effects; however, the exact environmental consequences of volcanism and the causes of diversity loss, as well as a temporal link, remain poorly constrained. Anomalously high carbonate carbon isotope (δ13C) values are ubiquitous in Capitanian-age carbonates (referred to as the "Kamura Event"), and are followed by a negative excursion in δ13C during the latest Capitanian. Carbon isotopes alone are insufficient to distinguish among numerous scenarios for changes in ocean biogeochemistry, such as ocean acidification, ocean stagnation and overturn, and collapse of the biological pump. Because the carbon and calcium cycles are intimately linked via the weathering and burial of CaCO3 sediment, changes in the calcium cycle and calcium isotope record can be used to place further constraints on carbon cycle behavior and Earth system change. In this study, we present the first record of stable calcium isotopes (δ44/40Ca) for Guadalupian- and Lopingian-age carbonates from Penglaitan, south China, the global stratotype section and point (GSSP) for the Guadalupian-Lopingian boundary. We further corroborate the δ44/40Ca record of carbonates with a δ44/40Ca record from conodont calcium hydroxapatite. We use a coupled model of the calcium and carbon cycles to investigate the behavior of the respective isotope systems during hypothesized causes of the end-Guadalupian crisis. Results indicate that if ocean acidification occurred during this interval, the magnitude of change in ocean pH and carbonate saturation state was much smaller than that associated with the subsequent end-Permian mass extinction. Ongoing efforts aim at expanding and refining these records, and at establishing a temporal framework that allows the correlation of purported causes and effects of the biotic crisis (this research is supported by NSF grants 0923669 and

  11. Can total cardiac calcium predict the coronary calcium score?

    Science.gov (United States)

    Pressman, Gregg S; Crudu, Vitalie; Parameswaran-Chandrika, Anoop; Romero-Corral, Abel; Purushottam, Bhaskar; Figueredo, Vincent M

    2011-01-21

    Mitral annular calcification (MAC) shares the same risk factors as atherosclerosis and is associated with coronary artery disease as well as cardiovascular events. However, sensitivity and positive predictive value are low. We hypothesized that a global echocardiographic calcium score would better predict coronary atherosclerotic burden, as assessed by coronary artery calcium score (CAC), than MAC alone. An echocardiographic score was devised to measure global cardiac calcification in a semi-quantitative manner; this included calcification in the aortic valve and root, the mitral valve and annulus, and the sub-mitral apparatus. This score, and a simplified version, were compared with a similar calcification score by CT scan, as well as the CAC. There was a good correlation between the two global calcification scores; the echocardiographic score also correlated with CAC. Using CAC >400 as a measure of severe coronary atherosclerosis, an echocardiographic score ≥5 had a positive predictive value of 60%. Importantly, the simplified score performed equally well (≥3 had a positive predictive value of 62%). Global cardiac calcification, assessed by CT scan or echocardiography, correlates with the extent of coronary calcium. A semi-quantitative calcium score can be easily applied during routine echocardiographic interpretation and can alert the reader to the possibility of severe coronary atherosclerosis. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

  12. Calcium ferrite formation from the thermolysis of calcium tris (maleato)

    Indian Academy of Sciences (India)

    stoichiometric quantities of aqueous solutions of calcium maleate, iron(III) maleate and maleic acid. The reaction mixture was concentrated on a water bath until a brown coloured product formed after the addition of excess of acetone. The complex was vacuum dried and its identity was established by chemical analysis.

  13. Calcium ferrite formation from the thermolysis of calcium tris ...

    Indian Academy of Sciences (India)

    Various physico-chemical techniques i.e. TG, DTG, DTA, Mössbauer, XRD, IR etc have been used to study the decomposition behaviour from ambient to 900°C and ferrite formation. Three consecutive decomposition steps leading to the formation of -Fe2O3 and calcium carbonate have been observed at various stages of ...

  14. CD44 antibodies and immune thrombocytopenia in the amelioration of murine inflammatory arthritis.

    Directory of Open Access Journals (Sweden)

    Patrick J Mott

    Full Text Available Antibodies to CD44 have been used to successfully ameliorate murine models of autoimmune disease. The most often studied disease model has been murine inflammatory arthritis, where a clear mechanism for the efficacy of CD44 antibodies has not been established. We have recently shown in a murine passive-model of the autoimmune disease immune thrombocytopenia (ITP that some CD44 antibodies themselves can induce thrombocytopenia in mice, and the CD44 antibody causing the most severe thrombocytopenia (IM7, also is known to be highly effective in ameliorating murine models of arthritis. Recent work in the K/BxN serum-induced model of arthritis demonstrated that antibody-induced thrombocytopenia reduced arthritis, causing us to question whether CD44 antibodies might primarily ameliorate arthritis through their thrombocytopenic effect. We evaluated IM7, IRAWB14.4, 5035-41.1D, KM201, KM114, and KM81, and found that while all could induce thrombocytopenia, the degree of protection against serum-induced arthritis was not closely related to the length or severity of the thrombocytopenia. CD44 antibody treatment was also able to reverse established inflammation, while thrombocytopenia induced by an anti-platelet antibody targeting the GPIIbIIIa platelet antigen, could not mediate this effect. While CD44 antibody-induced thrombocytopenia may contribute to some of its therapeutic effect against the initiation of arthritis, for established disease there are likely other mechanisms contributing to its efficacy. Humans are not known to express CD44 on platelets, and are therefore unlikely to develop thrombocytopenia after CD44 antibody treatment. An understanding of the relationship between arthritis, thrombocytopenia, and CD44 antibody treatment remains critical for continued development of CD44 antibody therapeutics.

  15. CD44-engineered mesoporous silica nanoparticles for overcoming multidrug resistance in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xin; Liu, Ying; Wang, Shouju; Shi, Donghong [Department of Radiology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002 (China); Zhou, Xianguang [National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing 210016 (China); Wang, Chunyan; Wu, Jiang; Zeng, Zhiyong; Li, Yanjun; Sun, Jing [Department of Radiology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002 (China); Wang, Jiandong [Department of Pathology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002 (China); Zhang, Longjiang [Department of Radiology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002 (China); Teng, Zhaogang, E-mail: tzg@fudan.edu.cn [Department of Radiology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002 (China); State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China); Lu, Guangming, E-mail: cjr.luguangming@vip.163.com [Department of Radiology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002 (China); State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China)

    2015-03-30

    Graphical abstract: - Highlights: • CD44-engineered mesoporous silica nanoparticles are synthesized. • The mechanism of CD44-engineered mesoporous silica nanoparticles is revealed. • This new delivery system increased the drug accumulation in vitro and in vivo. • This new delivery system offers an effective approach to treat multidrug resistance. - Abstract: Multidrug resistance is a major impediment for the successful chemotherapy in breast cancer. CD44 is over-expressed in multidrug resistant human breast cancer cells. CD44 monoclonal antibody exhibits anticancer potential by inhibiting proliferation and regulating P-glycoprotein-mediated drug efflux activity in multidrug resistant cells. Thereby, CD44 monoclonal antibody in combination with chemotherapeutic drug might be result in enhancing chemosensitivity and overcoming multidrug resistance. The purpose of this study is to investigate the effects of the CD44 monoclonal antibody functionalized mesoporous silica nanoparticles containing doxorubicin on human breast resistant cancer MCF-7 cells. The data showed that CD44-modified mesoporous silica nanoparticles increased cytotoxicity and enhanced the downregulation of P-glycoprotein in comparison to CD44 antibody. Moreover, CD44-engineered mesoporous silica nanoparticles provided active target, which promoted more cellular uptake of DOX in the resistant cells and more retention of DOX in tumor tissues than unengineered counterpart. Animal studies of the resistant breast cancer xenografts demonstrated that CD44-engineered drug delivery system remarkably induced apoptosis and inhibited the tumor growth. Our results indicated that the CD44-engineered mesoporous silica nanoparticle-based drug delivery system offers an effective approach to overcome multidrug resistance in human breast cancer.

  16. Estimation of presynaptic calcium currents and endogenous calcium buffers at the frog neuromuscular junction with two different calcium fluorescent dyes

    Directory of Open Access Journals (Sweden)

    Dmitry eSamigullin

    2015-01-01

    Full Text Available At the frog neuromuscular junction, under physiological conditions, the direct measurement of calcium currents and of the concentration of intracellular calcium buffers—which determine the kinetics of calcium concentration and neurotransmitter release from the nerve terminal—has hitherto been technically impossible. With the aim of quantifying both Ca2+ currents and the intracellular calcium buffers, we measured fluorescence signals from nerve terminals loaded with the low-affinity calcium dye Magnesium Green or the high-affinity dye Oregon Green BAPTA-1, simultaneously with microelectrode recordings of nerve-action potentials and end-plate currents. The action-potential-induced fluorescence signals in the nerve terminals developed much more slowly than the postsynaptic response. To clarify the reasons for this observation and to define a spatiotemporal profile of intracellular calcium and of the concentration of mobile and fixed calcium buffers, mathematical modeling was employed. The best approximations of the experimental calcium transients for both calcium dyes were obtained when the calcium current had an amplitude of 1.6 ± 0.08 рА and a half-decay time of 1.2 ± 0.06 ms, and when the concentrations of mobile and fixed calcium buffers were 250 ± 13 µM and 8 ± 0.4 mM, respectively. High concentrations of endogenous buffers define the time course of calcium transients after an action potential in the axoplasm, and may modify synaptic plasticity.

  17. Calcium fertilization increases the concentration of calcium in sapwood and calcium oxalate in foliage of red spruce

    Science.gov (United States)

    Kevin T. Smith; Walter C. Shortle; Jon H. Connolly; Rakesh Minocha; Jody Jellison

    2009-01-01

    Calcium cycling plays a key role in the health and productivity of red spruce forests in the northeastern US. A portion of the flowpath of calcium within forests includes translocation as Ca2+ in sapwood and accumulation as crystals of calcium oxalate in foliage. Concentrations of Ca in these tree tissues have been used as markers of...

  18. 44 CFR 206.438 - Project management.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Project management. 206.438 Section 206.438 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... Project management. (a) General. The State serving as grantee has primary responsibility for project...

  19. 44 CFR 206.373 - Eligibility criteria.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Eligibility criteria. 206.373... Eligibility criteria. (a) Local government. (1) The local government must be located within the area eligible... government from incurring the indebtedness resulting from a Federal loan. (2) Criteria considered by FEMA in...

  20. 44 CFR 206.363 - Eligibility criteria.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Eligibility criteria. 206.363... Eligibility criteria. (a) Local government. (1) The local government must be located within the area... incurring the indebtedness resulting from a Federal loan. (2) Criteria considered by FEMA in determining the...

  1. 44 CFR 208.43 - Rehabilitation.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Rehabilitation. 208.43... Agreements § 208.43 Rehabilitation. DHS will reimburse costs incurred to return System equipment and... Activation. (3) Personnel costs associated with equipment cache rehabilitation. DHS will reimburse costs...

  2. 2 CFR 215.44 - Procurement procedures.

    Science.gov (United States)

    2010-01-01

    ....44 Grants and Agreements OFFICE OF MANAGEMENT AND BUDGET CIRCULARS AND GUIDANCE Reserved UNIFORM... characteristics or minimum acceptable standards. (iv) The specific features of “brand name or equal” descriptions... expected to exceed the small purchase threshold, specifies a “brand name” product. (4) The proposed award...

  3. 44 CFR 5.89 - Waiver.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Waiver. 5.89 Section 5.89 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY... appropriate in order that a response in strict compliance with the terms of a subpoena duces tecum or the...

  4. Water SA - Vol 44, No 1 (2018)

    African Journals Online (AJOL)

    Evaluation of the effectiveness of the National Benchmarking Initiative (NBI) in improving the productivity of water services authorities in South Africa · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Warren Brettenny, Gary Sharp, 37-44 ...

  5. 44 CFR 65.2 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Definitions. 65.2 Section 65.2 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND..., a certification by a registered professional engineer or other party does not constitute a warranty...

  6. 44 CFR 12.4 - Interpretations.

    Science.gov (United States)

    2010-10-01

    ... SECURITY GENERAL ADVISORY COMMITTEES § 12.4 Interpretations. Except as specifically authorized in writing by the Administrator, including internal instructions, no interpretation of the meaning of the... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Interpretations. 12.4 Section...

  7. 44 CFR 5.25 - Available materials.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Available materials. 5.25... Agency Information, Rules, Orders, Policies, and Similar Material § 5.25 Available materials. FEMA materials which are available under this subpart are as follows: (a) Final opinions and orders made in the...

  8. 44 CFR 206.17 - Effective date.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Effective date. 206.17 Section 206.17 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY DISASTER ASSISTANCE FEDERAL DISASTER ASSISTANCE General § 206.17 Effective date. These...

  9. 44 CFR 80.21 - Closeout requirements.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Closeout requirements. 80.21 Section 80.21 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... was mitigated and that the deed restrictions recorded are consistent with the FEMA model deed...

  10. 44 CFR 206.431 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... Definitions. Activity means any mitigation measure, project, or action proposed to reduce risk of future... application means the request to FEMA for HMGP funding, as outlined in § 206.436, by a State or tribal... subgrantee as a condition of receiving a project subgrant under the HMGP as outlined in 44 CFR 201.6...

  11. 27 CFR 44.104 - Fiduciary successor.

    Science.gov (United States)

    2010-04-01

    ... warehouse proprietor, as a continuing operation, such fiduciary shall, before commencing operations, make... Warehouse Proprietors Changes in Ownership and Control § 44.104 Fiduciary successor. If an administrator... the business, qualification as an export warehouse proprietor will not be required if he promptly...

  12. 27 CFR 44.143 - General.

    Science.gov (United States)

    2010-04-01

    ... PAYMENT OF TAX, OR WITH DRAWBACK OF TAX Operations by Export Warehouse Proprietors Inventories § 44.143 General. (a) Every export warehouse proprietor shall at the times specified in this subpart make a true... export warehouse proprietor for 3 years following the close of the calendar year in which the inventory...

  13. 27 CFR 44.147 - General.

    Science.gov (United States)

    2010-04-01

    ... PAYMENT OF TAX, OR WITH DRAWBACK OF TAX Operations by Export Warehouse Proprietors Reports § 44.147 General. Every export warehouse proprietor shall make a report on Form 5220.4 of all tobacco products... any operations or transactions occurred during the period covered by the report. A copy of each report...

  14. 44 CFR 329.2 - Policies.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Policies. 329.2 Section 329.2 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY PREPAREDNESS USE OF PRIORITIES AND ALLOCATION AUTHORITY FOR FEDERAL SUPPLY CLASSIFICATION (FSC) COMMON USE...

  15. 44 CFR 206.225 - Emergency work.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Emergency work. 206.225 Section 206.225 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... Emergency work. (a) General. (1) Emergency protective measures to save lives, to protect public health and...

  16. 44 CFR 350.3 - Background.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Background. 350.3 Section 350.3 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND... § 350.3 Background. (a) On December 7, 1979, the President directed the Administrator of FEMA to take...

  17. 44 CFR 334.3 - Background.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Background. 334.3 Section 334.3 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY PREPAREDNESS GRADUATED MOBILIZATION RESPONSE § 334.3 Background. (a) The GMR system is designed to...

  18. 44 CFR 295.42 - Arbitration.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Arbitration. 295.42 Section... SECURITY CERRO GRANDE FIRE ASSISTANCE CERRO GRANDE FIRE ASSISTANCE Dispute Resolution § 295.42 Arbitration. (a) Initiating arbitration. A Claimant who is dissatisfied with the outcome of the Administrative...

  19. 44 CFR 206.221 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... buildings, structures, equipment, or systems used to provide emergency services, such as fire protection... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Definitions. 206.221 Section 206.221 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF...

  20. 44 CFR 151.02 - Scope.

    Science.gov (United States)

    2010-10-01

    ..., Definitions § 151.02 Scope. Fire services, in any State, may file claims for reimbursement under section 11... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Scope. 151.02 Section 151.02 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY...

  1. 44 CFR 204.42 - Eligible costs.

    Science.gov (United States)

    2010-10-01

    ... are providing services directly associated with eligible fire-related activities may be eligible. (2... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Eligible costs. 204.42 Section 204.42 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF...

  2. 44 CFR 13.25 - Program income.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Program income. 13.25 Section... LOCAL GOVERNMENTS Post-Award Requirements Financial Administration § 13.25 Program income. (a) General. Grantees are encouraged to earn income to defray program costs. Program income includes income from fees...

  3. RJHS Vol 4(4).cdr

    African Journals Online (AJOL)

    ABEOLUGBENGAS

    . J Pak. Med Assoc 2010; 60(7): 543-47. 43. Diagnosis of zinc deficiency step by step, BMJ publishing group limited 2011, available at th htp;/eso.cdn.bmj.com, accessed on 14. September 2016. 44. Solomon NW. Assesment of copper and zinc.

  4. 44 CFR 206.227 - Snow assistance.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Snow assistance. 206.227 Section 206.227 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... Snow assistance. Emergency or major disaster declarations based on snow or blizzard conditions will be...

  5. 44 CFR 6.2 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Definitions. 6.2 Section 6.2 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY... those concerning education, financial transactions, medical history, and criminal or employment history...

  6. 44 CFR 206.204 - Project performance.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Project performance. 206.204... § 206.204 Project performance. (a) General. This section describes the policies and procedures applicable during the performance of eligible work. (b) Advances of funds. Advances of funds will be made in...

  7. 27 CFR 30.44 - Weighing containers.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Weighing containers. 30.44... Weighing containers. (a) Weighing containers of more than 10 wine gallons. The weight of containers having.... (b) Weighing containers of 10 wine gallons or less. The weight for containers of a capacity of 10...

  8. 27 CFR 44.187 - Shipping containers.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Shipping containers. 44... Shipping containers. Each shipping case, crate, or other container in which tobacco products, or cigarette... same containers in which they were received from the factory. (72 Stat. 1418, as amended; 26 U.S.C...

  9. 44 CFR 206.402 - Compliance.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Compliance. 206.402 Section... HOMELAND SECURITY DISASTER ASSISTANCE FEDERAL DISASTER ASSISTANCE Minimum Standards § 206.402 Compliance. A... compliance with this subpart following the completion of any repair or construction activities. ...

  10. 44 CFR 13.31 - Real property.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Real property. 13.31 Section 13.31 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND... any actual and reasonable selling and fixing-up expenses. If the grant is still active, the net...

  11. 44 CFR 401.3 - Reports.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Reports. 401.3 Section 401.3... RESTRICTIONS (T-1) § 401.3 Reports. Persons subject to this order shall submit such reports to the Assistant... Reports Act. ...

  12. 44 CFR 321.8 - Reports.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Reports. 321.8 Section 321.8... ADMINISTRATION) § 321.8 Reports. The Department of Defense, Department of Energy, and Maritime Administration shall furnish the Administrator of the Federal Emergency Management Agency with reports on items and...

  13. 44 CFR 327.5 - Reports.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Reports. 327.5 Section 327.5 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY... Reports. Such reports of operations under this order as may be required by the Federal Emergency...

  14. 44 CFR 150.3 - Nomination process.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Nomination process. 150.3 Section 150.3 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... Nomination process. (a) The Nominating Officials nominating Firefighters and Civil Defense Officers shall...

  15. 44 CFR 150.7 - Selection process.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Selection process. 150.7 Section 150.7 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... Selection process. (a) President's Award. Nominations for the President's Award shall be reviewed, and...

  16. 44 CFR 79.5 - Application process.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Application process. 79.5 Section 79.5 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... § 79.5 Application process. (a) Applicant or grantee. (1) States will be notified of the amount...

  17. 44 CFR 352.29 - Appeal process.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Appeal process. 352.29 Section 352.29 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... Participation § 352.29 Appeal process. (a) Any interested party may appeal a determination made by the Deputy...

  18. 44 CFR 1.2 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Definitions. 1.2 Section 1.2... GENERAL RULEMAKING; POLICY AND PROCEDURES General § 1.2 Definitions. (a) Rule or regulation means the... effect on the economy of $100 million or more; (2) A major increase in costs or prices for consumers...

  19. 44 CFR 6.85 - Reproduction fees.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Reproduction fees. 6.85... HOMELAND SECURITY GENERAL IMPLEMENTATION OF THE PRIVACY ACT OF 1974 Fees § 6.85 Reproduction fees. (a... over 81/2 x 14 inches or whose physical characteristics do not permit reproduction by routine...

  20. 44 CFR 208.25 - Obsolete equipment.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Obsolete equipment. 208.25... Cooperative Agreements § 208.25 Obsolete equipment. (a) The Assistant Administrator will periodically identify obsolete items on the Equipment Cache List and provide such information to Sponsoring Agencies. (b) Neither...

  1. 44 CFR 13.32 - Equipment.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Equipment. 13.32 Section 13... LOCAL GOVERNMENTS Post-Award Requirements Changes, Property, and Subawards § 13.32 Equipment. (a) Title. Subject to the obligations and conditions set forth in this section, title to equipment acquired under a...

  2. 44 CFR 354.3 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... exercise means the joint licensee/State and local government exercise, evaluated by FEMA, conducted around a commercial nuclear power plant site once every two years in conformance with 44 CFR part 350. EPZ... or Licensee means the utility or organization that has applied for or has received from the NRC: (1...

  3. 44 CFR 19.310 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Recruitment. 19.310 Section... RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 19.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 19.300 through 19...

  4. 44 CFR 19.510 - Recruitment.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Recruitment. 19.510 Section... Programs or Activities Prohibited § 19.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a...

  5. 44 CFR 19.235 - Statutory amendments.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Statutory amendments. 19.235 Section 19.235 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... of factors related to the individual's personal appearance, poise, and talent. The pageant, however...

  6. 44 CFR 5.41 - FEMA publications.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false FEMA publications. 5.41 Section 5.41 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... obtain FEMA publications without charge from the FEMA Headquarters, Regional Offices, the FEMA Library at...

  7. 44 CFR 12.7 - Charter.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Charter. 12.7 Section 12.7 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY... also be furnished at the time of filing to the Library of Congress, Exchange and Gift Division, Federal...

  8. 44 CFR 9.2 - Policy.

    Science.gov (United States)

    2010-10-01

    ... Agency to provide leadership in floodplain management and the protection of wetlands. Further, the Agency... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Policy. 9.2 Section 9.2 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY...

  9. 44 CFR 206.347 - Requirements.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Requirements. 206.347 Section... Requirements. (a) Location determination. For each disaster assistance action which is proposed on the Atlantic... requirements of these regulations needs to be met, and the action may be processed under other applicable...

  10. 44 CFR 5.3 - Definitions.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Definitions. 5.3 Section 5.3 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF HOMELAND SECURITY... transaction of public business and preserved, or appropriate for preservation, as evidence of the organization...

  11. 44 CFR 15.8 - Gambling.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Gambling. 15.8 Section 15.8... CENTER § 15.8 Gambling. We prohibit participating in games for money or other personal property, including the operation of gambling devices, the conduct of a lottery or pool, or the sale or purchase of...

  12. 27 CFR 44.182 - Lottery features.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Lottery features. 44.182... Lottery features. No certificate, coupon, or other device purporting to be or to represent a ticket, chance, share, or an interest in, or dependent on, the event of a lottery shall be contained in, attached...

  13. 44 CFR 19.540 - Advertising.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Advertising. 19.540 Section 19.540 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... Programs or Activities Prohibited § 19.540 Advertising. A recipient shall not in any advertising related to...

  14. 44 CFR 208.41 - Administrative allowance.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Administrative allowance. 208... Cooperative Agreements § 208.41 Administrative allowance. (a) The administrative allowance is intended to... administrative allowance will be equal to the following: (1) If total allowable costs are less than $100,000, 3...

  15. 44 CFR 9.18 - Responsibilities.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Responsibilities. 9.18... HOMELAND SECURITY GENERAL FLOODPLAIN MANAGEMENT AND PROTECTION OF WETLANDS § 9.18 Responsibilities. (a) Regional Administrators' responsibilities. Regional Administrators shall, for all actions falling within...

  16. 44 CFR 201.3 - Responsibilities.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Responsibilities. 201.3... HOMELAND SECURITY DISASTER ASSISTANCE MITIGATION PLANNING § 201.3 Responsibilities. (a) General. This section identifies the key responsibilities of FEMA, States, and local/tribal governments in carrying out...

  17. 44 CFR 79.3 - Responsibilities.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Responsibilities. 79.3... § 79.3 Responsibilities. (a) Federal Emergency Management Agency (FEMA). Administer and provide... responsibilities of the “State” as the term is used in this part, as applicant or grantee, described in paragraphs...

  18. 44 CFR 206.362 - Responsibilities.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Responsibilities. 206.362 Section 206.362 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... Responsibilities. (a) The local government shall submit the financial information required by FEMA in the...

  19. 44 CFR 10.5 - Responsibilities.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Responsibilities. 10.5... Responsibilities. (a) The Regional Administrators shall, for each action not categorically excluded from this... impact statements and assign lead agency responsibility when more than one FEMA office or administration...

  20. 44 CFR 323.3 - Responsibilities.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Responsibilities. 323.3...) § 323.3 Responsibilities. (a) As stated in The National Plan for Emergency Preparedness, the direction of resources mobilization is a Federal responsibility. However, in the period immediately following...

  1. 44 CFR 78.3 - Responsibilities.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Responsibilities. 78.3 Section 78.3 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... ASSISTANCE § 78.3 Responsibilities. (a) Federal. The Administrator will allocate available funds to each FEMA...

  2. 44 CFR 206.372 - Responsibilities.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Responsibilities. 206.372 Section 206.372 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... Responsibilities. (a) The local government shall submit the financial information required by FEMA in the...

  3. 44 CFR 16.140 - Employment.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Employment. 16.140 Section 16... CONDUCTED BY THE FEDERAL EMERGENCY MANAGEMENT AGENCY § 16.140 Employment. No qualified individual with handicaps shall, on the basis of handicap, be subject to discrimination in employment under any program or...

  4. 44 CFR 19.500 - Employment.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Employment. 19.500 Section 19... FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 19.500 Employment. (a) General. (1) No person shall, on the basis of sex, be excluded...

  5. 44 CFR 13.41 - Financial reporting.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Financial reporting. 13.41... Financial reporting. (a) General. (1) Except as provided in paragraphs (a) (2) and (5) of this section... supplementary or other forms as may from time to time be authorized by OMB, for: (i) Submitting financial...

  6. Calcium release from experimental dental materials.

    Science.gov (United States)

    Okulus, Zuzanna; Buchwald, Tomasz; Voelkel, Adam

    2016-11-01

    The calcium release from calcium phosphate-containing experimental dental restorative materials was examined. The possible correlation of ion release with initial calcium content, solubility and degree of curing (degree of conversion) of examined materials was also investigated. Calcium release was measured with the use of an ion-selective electrode in an aqueous solution. Solubility was established by the weighing method. Raman spectroscopy was applied for the determination of the degree of conversion, while initial calcium content was examined with the use of energy-dispersive spectroscopy. For examined materials, the amount of calcium released was found to be positively correlated with solubility and initial calcium content. It was also found that the degree of conversion does not affect the ability of these experimental composites to release calcium ions. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Familial hypocalciuric hypercalcemia and calcium sensing receptor

    DEFF Research Database (Denmark)

    Mrgan, Monija; Nielsen, Sanne; Brixen, Kim

    2014-01-01

    Familial hypocalciuric hypercalcemia (FHH) is a lifelong, benign autosomal dominant disease characterized by hypercalcemia, normal to increased parathyroid hormone level, and a relatively low renal calcium excretion. Inactivation of the calcium-sensing receptor in heterozygous patients results in...

  8. Vitamin D, Calcium, and Bone Health

    Science.gov (United States)

    ... Bone Health Featured Resource Find an Endocrinologist Search Vitamin D, Calcium, and Bone Health March 2012 Download ... also helps keep your bones strong. Why are vitamin D and calcium important to bone health? Vitamin ...

  9. Vitamin D treatment in calcium-deficiency rickets: a randomised controlled trial.

    Science.gov (United States)

    Thacher, Tom D; Fischer, Philip R; Pettifor, John M

    2014-09-01

    To determine whether children with calcium-deficiency rickets have a better response to treatment with vitamin D and calcium than with calcium alone. Randomised controlled trial. Jos University Teaching Hospital, Jos, Nigeria. Nigerian children with active rickets treated with calcium carbonate as limestone (approximately 938 mg elemental calcium twice daily) were, in addition, randomised to receive either oral vitamin D2 50,000 IU (Ca+D, n=44) or placebo (Ca, n=28) monthly for 24 weeks. Achievement of a 10-point radiographic severity score ≤1.5 and serum alkaline phosphatase ≤350 U/L. The median (range) age of enrolled children was 46 (15-102) months, and baseline characteristics were similar in the two groups. Mean (±SD) 25-hydroxyvitamin D (25(OH)D) was 30.2±13.2 nmol/L at baseline, and 29 (43%) had values children (94% of original cohort) who completed 24 weeks of treatment, 29 (67%) in the Ca+D group and 11 (44%) in the Ca group achieved the primary outcome (p=0.06). Baseline 25(OH)D did not alter treatment group effects (p=0.99 for interaction). At the end of 24 weeks, 25(OH)D values were 55.4±17.0 nmol/L and 37.9±20.0 nmol/L in the Ca+D and Ca groups, respectively, (pchildren with calcium-deficiency rickets, there is a trend for vitamin D to improve the response to treatment with calcium carbonate as limestone, independent of baseline 25(OH)D concentrations. ClinicalTrials.gov NCT00949832. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  10. Intestinal absorption of calcium from foodstuffs as compared to a pharmaceutical preparation.

    Science.gov (United States)

    Werner, E; Hansen, Ch; Roth, P; Kaltwasser, J P

    1999-01-01

    Only few data are available on intestinal calcium absorption from foodstuffs and composite meals in humans. The aim of the study was to compare intraindividually the calcium absorption from milk and from a breakfast with that from a pharmaceutical calcium preparation of equal calcium content. In 8 healthy volunteers between 44 and 58 years of age, the intestinal calcium absorption was measured in randomized order applying the double isotope technique from: (1) 500ml of fresh milk (equivalent to 620mg Ca), (2) a test meal composed of 250 g curd, 150g yoghurt, 3 slices pineapple, 2 breakfast rolls, 2 cups of coffee, 10g of coffee cream, 20g butter, 50g jam and 20g honey (equivalent to 580mg Ca), and (3) a lactogluconate effervescent tablet (equivalent to 500mgCa). All test doses were given on an empty stomach and labelled with 20mg 44Ca. Simultaneously, 5mg 42Ca in a sterile isotonic solution were injected intravenously. The mean values of the absorbed fractions are 24.0% +/- 5.4% (mean +/-SD), 17.9% +/- 7.1%, and 28.7% +/- 9.1% for the milk, for the meal and for the tablet respectively. The data show that less calcium is absorbed from foodstuffs as compared to a preparation of optimal bioavailability. But in this study only the difference between absorption from the milk and from the meal was statistically significant. Therefore, it is possible to obtain a sufficient calcium supply of the human body also by properly selected foodstuffs.

  11. 21 CFR 184.1229 - Calcium stearate.

    Science.gov (United States)

    2010-04-01

    ... Specific Substances Affirmed as GRAS § 184.1229 Calcium stearate. (a) Calcium stearate (Ca(C17H35COO)2, CAS Reg. No. 1529-23-0) is the calcium salt of stearic acid derived from edible sources. It is prepared as... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium stearate. 184.1229 Section 184.1229 Food...

  12. Bioactive and Hemocompatible Calcium Sulphoaluminate Cement

    OpenAIRE

    Acuña-Gutiérrez, Iván Omar; Escobedo-Bocardo, José Concepción; Almanza-Robles, José Manuel; Cortés-Hernández, Dora Alicia; Saldívar-Ramírez, Mirna María Guadalupe; Reséndiz-Hernández, Perla Janet; Zugasti-Cruz, Alejandro

    2015-01-01

    Calcium sulphoaluminate cement (CSAC) is an attractive candidate for biomedical applications due to its appropriate mechanical properties and high calcium content. In vitro bioactivity and hemocompatibility of calcium sulphoaluminate cement were assessed. The cement was prepared from a mixture of calcium sulphoaluminate (CSA) clinker, gypsum and water. Cement samples were immersed in a simulated body fluid (SBF) at 37 °C for different periods of time (7, 14 and 21 days). The analyses of these...

  13. Calcium Balance in Chronic Kidney Disease

    OpenAIRE

    Hill Gallant, Kathleen M.; Spiegel, David M.

    2017-01-01

    Purpose of Review The kidneys play a critical role in the balance between the internal milieu and external environment. Kidney failure is known to disrupt a number of homeostatic mechanisms that control serum calcium and normal bone metabolism. However, our understanding of calcium balance throughout the stages of chronic kidney disease is limited and the concept of balance itself, especially with a cation as complex as calcium, is often misunderstood. Both negative and positive calcium balan...

  14. Calcium Balance in Chronic Kidney Disease.

    Science.gov (United States)

    Hill Gallant, Kathleen M; Spiegel, David M

    2017-06-01

    The kidneys play a critical role in the balance between the internal milieu and external environment. Kidney failure is known to disrupt a number of homeostatic mechanisms that control serum calcium and normal bone metabolism. However, our understanding of calcium balance throughout the stages of chronic kidney disease is limited and the concept of balance itself, especially with a cation as complex as calcium, is often misunderstood. Both negative and positive calcium balance have important implications in patients with chronic kidney disease, where negative balance may increase risk of osteoporosis and fracture and positive balance may increase risk of vascular calcification and cardiovascular events. Here, we examine the state of current knowledge about calcium balance in adults throughout the stages of chronic kidney disease and discuss recommendations for clinical strategies to maintain balance as well as future research needs in this area. Recent calcium balance studies in adult patients with chronic kidney disease show that neutral calcium balance is achieved with calcium intake near the recommended daily allowance. Increases in calcium through diet or supplements cause high positive calcium balance, which may put patients at risk for vascular calcification. However, heterogeneity in calcium balance exists among these patients. Given the available calcium balance data in this population, it appears clinically prudent to aim for recommended calcium intakes around 1000 mg/day to achieve neutral calcium balance and avoid adverse effects of either negative or positive calcium balance. Assessment of patients' dietary calcium intake could further equip clinicians to make individualized recommendations for meeting recommended intakes.

  15. Electrochemical Induced Calcium Phosphate Precipitation

    NARCIS (Netherlands)

    Lei, Yang; Song, Bingnan; Weijden, van der Renata D.; Saakes, M.; Buisman, Cees J.N.

    2017-01-01

    Phosphorus (P) is an essential nutrient for living organisms and cannot be replaced or substituted. In this paper, we present a simple yet efficient membrane free electrochemical system for P removal and recovery as calcium phosphate (CaP). This method relies on in situ formation of hydroxide

  16. 21 CFR 582.7187 - Calcium alginate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium alginate. 582.7187 Section 582.7187 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Calcium alginate. (a) Product. Calcium alginate. (b) Conditions of use. This substance is generally...

  17. Abnormalities of serum calcium and magnesium

    Science.gov (United States)

    Neonatal hypocalcemia is defined as a total serum calcium concentration of <7 mg/dL or an ionized calcium concentration of <4 mg/dL (1mmol/L). In very low birth weight (VLBW) infants, ionized calcium values of 0.8 to 1 mmol/L are common and not usually associated with clinical symptoms. In larger in...

  18. Modularized study of human calcium signalling pathway

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    When there is an extracellular change, cells get the message either by introduction of calcium ions into ... as it precipitates phosphate, the established energy currency of cells. Prolonged high intracellular calcium ... trigger proteins upon binding with free calcium ion(s) change their confirmation to modulate enzymes and ion ...

  19. 21 CFR 582.1191 - Calcium carbonate.

    Science.gov (United States)

    2010-04-01

    ... Additives § 582.1191 Calcium carbonate. (a) Product. Calcium carbonate. (b) Conditions of use. This... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium carbonate. 582.1191 Section 582.1191 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL...

  20. 21 CFR 582.5191 - Calcium carbonate.

    Science.gov (United States)

    2010-04-01

    ... Supplements 1 § 582.5191 Calcium carbonate. (a) Product. Calcium carbonate. (b) Conditions of use. This... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium carbonate. 582.5191 Section 582.5191 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL...

  1. Mechanism of store-operated calcium entry

    Indian Academy of Sciences (India)

    Activation of receptors coupled to the phospholipase C/IP3 signalling pathway results in a rapid release of calcium from its intracellular stores, eventually leading to depletion of these stores. Calcium store depletion triggers an influx of extracellular calcium across the plasma membrane, a mechanism known as the ...

  2. Mitochondrial Calcium Sparkles Light Up Astrocytes.

    Science.gov (United States)

    MacVicar, Brian A; Ko, Rebecca W Y

    2017-02-27

    Discrete calcium signals in the fine processes of astrocytes are a recent discovery and a new mystery. In a recent issue of Neuron, Agarwal et al. (2017) report that calcium efflux from mitochondria during brief openings of the mitochondrial permeability transition pore (mPTP) contribute to calcium microdomains. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  3. 21 CFR 182.1217 - Calcium phosphate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium phosphate. 182.1217 Section 182.1217 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... Substances § 182.1217 Calcium phosphate. (a) Product. Calcium phosphate (mono-, di-, and tribasic). (b...

  4. 21 CFR 582.1217 - Calcium phosphate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium phosphate. 582.1217 Section 582.1217 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1217 Calcium phosphate. (a) Product. Calcium phosphate (mono-, di-, and tribasic). (b...

  5. ORIGINAL ARTICLES Calcium supplementation to prevent pre ...

    African Journals Online (AJOL)

    ORIGINAL ARTICLES. Calcium supplementation to prevent pre-eclampsia - a systematic review. G J Hofmeyr, A Roodt, A N Atallah, L Duley. Background. Calcium supplementation during pregnancy may prevent high blood pressure and preterm labour. Objective. To assess the effects of calcium supplementation.

  6. The Incredible, Embryological Egg: Calcium and Strontium Isotopes Recapitulate Ontogeny

    Science.gov (United States)

    Gordon, G. W.; Skulan, J. L.

    2011-12-01

    Embryological development reflects evolutionary history. Understanding the processes of fetal growth is important for curing human birth defects and predicting damage to ecosystems from environmental insults. Tracing enzymatic and hormonal gradients during development, and correlating them to genetic cues dominate modern embryology. Previous work done tracing the mass transfer of elements has generally been limited to isotope spikes in vitro. Natural mass-dependent Ca and Sr isotopic ratios and radiogenic Sr isotopes have the potential to reveal both source and biochemical mechanism information about processes in vivo, but have not previously been extensively explored. The process when a hen lays a fertilized egg that becomes a chick includes formation and dissolution of calcium phosphate (bone) and calcium carbonate (shell). Skulan and DePaolo (1999) showed that chickens have 2% δ44/42Ca between a hen's bones and an egg white; this span represents more than 80% of the entire range of natural Ca isotope variation and illustrates there is significant variation to investigate. A striking feature of archosaurian development that also occurs in many mammals, including humans, is mass transfer of calcium from mother to embryo. The yolk of the domestic hen matures over 7-9 days, but the albumen, shell membranes and shell form in less than 20 hours. Domestic laying hens are at the physiological limit of egg production and selective breeding is no longer an effective method of increasing egg production. 60-75% of the shell's ~1.5 g of calcium comes from dietary sources, while 25-40% comes from the hen's medullary bone. Medullary bone is spicules formed in the marrow of long bones, and is a store of dietary calcium rapidly available for eggshell secretion. During in ovo development, the embryo's skeleton is formed from calcium in the yolk and by bulk dissolution of the eggshell's inner aspect via carbonic anhydrase in a process that has an effect on bone density similar to

  7. Calcium Orthophosphate-Based Bioceramics

    Directory of Open Access Journals (Sweden)

    Sergey V. Dorozhkin

    2013-09-01

    Full Text Available Various types of grafts have been traditionally used to restore damaged bones. In the late 1960s, a strong interest was raised in studying ceramics as potential bone grafts due to their biomechanical properties. A bit later, such synthetic biomaterials were called bioceramics. In principle, bioceramics can be prepared from diverse materials but this review is limited to calcium orthophosphate-based formulations only, which possess the specific advantages due to the chemical similarity to mammalian bones and teeth. During the past 40 years, there have been a number of important achievements in this field. Namely, after the initial development of bioceramics that was just tolerated in the physiological environment, an emphasis was shifted towards the formulations able to form direct chemical bonds with the adjacent bones. Afterwards, by the structural and compositional controls, it became possible to choose whether the calcium orthophosphate-based implants remain biologically stable once incorporated into the skeletal structure or whether they were resorbed over time. At the turn of the millennium, a new concept of regenerative bioceramics was developed and such formulations became an integrated part of the tissue engineering approach. Now calcium orthophosphate scaffolds are designed to induce bone formation and vascularization. These scaffolds are often porous and harbor different biomolecules and/or cells. Therefore, current biomedical applications of calcium orthophosphate bioceramics include bone augmentations, artificial bone grafts, maxillofacial reconstruction, spinal fusion, periodontal disease repairs and bone fillers after tumor surgery. Perspective future applications comprise drug delivery and tissue engineering purposes because calcium orthophosphates appear to be promising carriers of growth factors, bioactive peptides and various types of cells.

  8. Calcium antagonists: a ready prescription for treating infectious diseases?

    Science.gov (United States)

    Clark, Kevin B; Eisenstein, Edward M; Krahl, Scott E

    2013-01-01

    Emergence of new and medically resistant pathogenic microbes continues to escalate toward worldwide public health, wild habitat, and commercial crop and livestock catastrophes. Attempts at solving this problem with sophisticated modern biotechnologies, such as smart vaccines and microbicidal and microbistatic drugs that precisely target parasitic bacteria, fungi, and protozoa, remain promising without major clinical and industrial successes. However, discovery of a more immediate, broad spectrum prophylaxis beyond conventional epidemiological approaches might take no longer than the time required to fill a prescription at your neighborhood pharmacy. Findings from a growing body of research suggest calcium antagonists, long approved and marketed for various human cardiovascular and neurological indications, may produce safe, efficacious antimicrobial effects. As a general category of drugs, calcium antagonists include compounds that disrupt passage of Ca(2+) molecules across cell membranes and walls, sequestration and mobilization of free intracellular Ca(2+), and downstream binding proteins and sensors of Ca(2+)-dependent regulatory pathways important for proper cell function. Administration of calcium antagonists alone at current therapeutically relevant doses and schedules, or with synergistic compounds and additional antimicrobial medications, figures to enhance host immunoprotection by directly altering pathogen infection sequences, life cycles, homeostasis, antibiotic tolerances, and numerous other infective, survival, and reproductive processes. Short of being miracle drugs, calcium antagonists are welcome old drugs with new tricks capable of controlling some of the most virulent and pervasive global infectious diseases of plants, animals, and humans, including Chagas' disease, malaria, and tuberculosis.

  9. Calcium sensing receptor signalling in physiology and cancer.

    Science.gov (United States)

    Brennan, Sarah C; Thiem, Ursula; Roth, Susanne; Aggarwal, Abhishek; Fetahu, Irfete Sh; Tennakoon, Samawansha; Gomes, Ana Rita; Brandi, Maria Luisa; Bruggeman, Frank; Mentaverri, Romuald; Riccardi, Daniela; Kallay, Enikö

    2013-07-01

    The calcium sensing receptor (CaSR) is a class C G-protein-coupled receptor that is crucial for the feedback regulation of extracellular free ionised calcium homeostasis. While extracellular calcium (Ca(2+)o) is considered the primary physiological ligand, the CaSR is activated physiologically by a plethora of molecules including polyamines and l-amino acids. Activation of the CaSR by different ligands has the ability to stabilise unique conformations of the receptor, which may lead to preferential coupling of different G proteins; a phenomenon termed 'ligand-biased signalling'. While mutations of the CaSR are currently not linked with any malignancies, altered CaSR expression and function are associated with cancer progression. Interestingly, the CaSR appears to act both as a tumour suppressor and an oncogene, depending on the pathophysiology involved. Reduced expression of the CaSR occurs in both parathyroid and colon cancers, leading to loss of the growth suppressing effect of high Ca(2+)o. On the other hand, activation of the CaSR might facilitate metastasis to bone in breast and prostate cancer. A deeper understanding of the mechanisms driving CaSR signalling in different tissues, aided by a systems biology approach, will be instrumental in developing novel drugs that target the CaSR or its ligands in cancer. This article is part of a Special Issue entitled: 12th European Symposium on Calcium. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Calcium Treatment for FeSi-killed Fe-13 Pct Cr Stainless Steel with Various Top Slag Compositions

    Science.gov (United States)

    Wang, Qi; Wang, Lijun; Zhai, Jun; Li, Jianmin; Chou, Kuochih

    2017-12-01

    Calcium treatment of Fe-13 pct Cr stainless steel, with inclusion modification as its main purpose, was evaluated on a laboratory scale. The stability diagram of Ca-Al was obtained using the FactSage software and could be divided into three parts based on the [Al] content: the ultra-low-Al region, the low-Al region, and the medium-high-Al region. Each of these regions required different amounts of calcium for inclusion modification. The ferrosilicon deoxidation product could be modified into low melting temperature inclusions by a CaO-SiO2 top slag in the ultra-low-Al region ([Al] content less than 40 ppm). Calcium treatment was necessary to modify the ferrosilicon deoxidation product into low melting temperature inclusions in the low-Al region ([Al] content from 40 to 100 ppm) for the CaO-SiO2-Al2O3 top slag. Calcium addition has a "liquid window" where adding calcium can accelerate inclusion modification. Adding calcium for 15 and 30 minutes resulted in complete modification times of 45 and 60 minutes, respectively, which indicates that early calcium treatment can produce plastic inclusions sooner. The relationship between the steel and inclusion content was determined by fitting the experimental data in the low-Al region. An appropriate range of T.Ca/T.O (total calcium content/total oxygen content) for inclusion modification is 0.99 to 1.44.

  11. Up-regulation of CD44 in the development of metastasis, recurrence and drug resistance of ovarian cancer.

    Science.gov (United States)

    Gao, Yan; Foster, Rosemary; Yang, Xiaoqian; Feng, Yong; Shen, Jacson K; Mankin, Henry J; Hornicek, Francis J; Amiji, Mansoor M; Duan, Zhenfeng

    2015-04-20

    The clinical significance of Cluster of Differentiation 44 (CD44) remains controversial in human ovarian cancer. The aim of this study is to evaluate the clinical significance of CD44 expression by using a unique tissue microarray, and then to determine the biological functions of CD44 in ovarian cancer. In this study, a unique ovarian cancer tissue microarray (TMA) was constructed with paired primary, metastatic, and recurrent tumor tissues from 26 individual patients. CD44 expression in TMA was assessed by immunohistochemistry. Both the metastatic and recurrent ovarian cancer tissues expressed higher level of CD44 than the patient-matched primary tumor. A significant association has been shown between CD44 expression and both the disease free survival and overall survival. A strong increase of CD44 was found in the tumor recurrence of mouse model. Finally, when CD44 was knocked down, proliferation, migration/invasion activity, and spheroid formation were significantly suppressed, while drug sensitivity was enhanced. Thus, up-regulation of CD44 represents a crucial event in the development of metastasis, recurrence, and drug resistance to current treatments in ovarian cancer. Developing strategies to target CD44 may prevent metastasis, recurrence, and drug resistance in ovarian cancer.

  12. Morphological Investigation of Calcium Carbonate during Ammonification-Carbonization Process of Low Concentration Calcium Solution

    OpenAIRE

    Huaigang Cheng; Xiaoxi Zhang; Huiping Song

    2014-01-01

    Ultrafine calcium carbonate is a widely used cheap additive. The research is conducted in low degree supersaturation solution in order to study the polymorphic phases’ change and its factors of the calcium carbonate precipitate in the ammonification-carbonization process of the solution with calcium. Fine particles of calcium carbonate are made in the solution containing 0.015 mol/L of Ca2+. Over 98% of the calcium carbonate precipitate without ammonification resembles the morphology of calci...

  13. Mammary-Specific Ablation of the Calcium-Sensing Receptor During Lactation Alters Maternal Calcium Metabolism, Milk Calcium Transport, and Neonatal Calcium Accrual

    Science.gov (United States)

    Mamillapalli, Ramanaiah; VanHouten, Joshua; Dann, Pamela; Bikle, Daniel; Chang, Wenhan; Brown, Edward

    2013-01-01

    To meet the demands for milk calcium, the lactating mother adjusts systemic calcium and bone metabolism by increasing dietary calcium intake, increasing bone resorption, and reducing renal calcium excretion. As part of this adaptation, the lactating mammary gland secretes PTHrP into the maternal circulation to increase bone turnover and mobilize skeletal calcium stores. Previous data have suggested that, during lactation, the breast relies on the calcium-sensing receptor (CaSR) to coordinate PTHrP secretion and milk calcium transport with calcium availability. To test this idea genetically, we bred BLG-Cre mice with CaSR-floxed mice to ablate the CaSR specifically from mammary epithelial cells only at the onset of lactation (CaSR-cKO mice). Loss of the CaSR in the lactating mammary gland did not disrupt alveolar differentiation or milk production. However, it did increase the secretion of PTHrP into milk and decreased the transport of calcium from the circulation into milk. CaSR-cKO mice did not show accelerated bone resorption, but they did have a decrease in bone formation. Loss of the mammary gland CaSR resulted in hypercalcemia, decreased PTH secretion, and increased renal calcium excretion in lactating mothers. Finally, loss of the mammary gland CaSR resulted in decreased calcium accrual by suckling neonates, likely due to the combination of increased milk PTHrP and decreased milk calcium. These results demonstrate that the mammary gland CaSR coordinates maternal bone and calcium metabolism, calcium transport into milk, and neonatal calcium accrual during lactation. PMID:23782944

  14. Apatite Formation from Amorphous Calcium Phosphate and Mixed Amorphous Calcium Phosphate/Amorphous Calcium Carbonate.

    Science.gov (United States)

    Ibsen, Casper J S; Chernyshov, Dmitry; Birkedal, Henrik

    2016-08-22

    Crystallization from amorphous phases is an emerging pathway for making advanced materials. Biology has made use of amorphous precursor phases for eons and used them to produce structures with remarkable properties. Herein, we show how the design of the amorphous phase greatly influences the nanocrystals formed therefrom. We investigate the transformation of mixed amorphous calcium phosphate/amorphous calcium carbonate phases into bone-like nanocrystalline apatite using in situ synchrotron X-ray diffraction and IR spectroscopy. The speciation of phosphate was controlled by pH to favor HPO4 (2-) . In a carbonate free system, the reaction produces anisotropic apatite crystallites with large aspect ratios. The first formed crystallites are highly calcium deficient and hydrogen phosphate rich, consistent with thin octacalcium phosphate (OCP)-like needles. During growth, the crystallites become increasingly stoichiometric, which indicates that the crystallites grow through addition of near-stoichiometric apatite to the OCP-like initial crystals through a process that involves either crystallite fusion/aggregation or Ostwald ripening. The mixed amorphous phases were found to be more stable against phase transformations, hence, the crystallization was inhibited. The resulting crystallites were smaller and less anisotropic. This is rationalized by the idea that a local phosphate-depletion zone formed around the growing crystal until it was surrounded by amorphous calcium carbonate, which stopped the crystallization. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to lactose and increase in calcium absorption leading to an increase in calcium retention (ID 668) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    claims in relation to lactose and increase in calcium absorption leading to an increase in calcium retention. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims and references that EFSA has received from Member...... States or directly from stakeholders. The food constituent that is the subject of the health claim is lactose. The Panel considers that lactose is sufficiently characterised. The claimed effect is “calcium absorption”. The target population is assumed to be the general population. The Panel notes...... between the consumption of lactose and an increase in calcium absorption leading to an increase in calcium retention....

  16. Ovarian lesions in 44 rabbits (Oryctolagus cuniculus)

    Science.gov (United States)

    BERTRAM, Christof Albert; KLOPFLEISCH, Robert; MÜLLER, Kerstin

    2017-01-01

    The clinical and pathological records of 44 domestic, female rabbits with an age ranging from 6–124 months (median age: 63.5 month) were assessed retrospectively for ovarian lesions. Included were all rabbits that underwent an ovariohysterectomy with a subsequent pathological examination of the genital tract between March 1997 and June 2016. Pathological examination revealed ovarian lesions in 12 of the 44 rabbits including follicular cysts (n=7), cystic rete ovarii (n=3), widespread ovarian necrosis with dystrophic calcification (n=2), ovarian adenoma (n=1). Clinical examination including radiographs only suggested ovarian disorders in two cases of ovarian necrosis with dystrophic calcification and in two cases of cystic rete ovarii. Clinical significance was only conclusive in a case of cystic rete ovarii. PMID:29057758

  17. The Physiology, Pathology, and Pharmacology of Voltage-Gated Calcium Channels and Their Future Therapeutic Potential

    Science.gov (United States)

    Zamponi, Gerald W.; Striessnig, Joerg; Koschak, Alexandra

    2015-01-01

    Voltage-gated calcium channels are required for many key functions in the body. In this review, the different subtypes of voltage-gated calcium channels are described and their physiologic roles and pharmacology are outlined. We describe the current uses of drugs interacting with the different calcium channel subtypes and subunits, as well as specific areas in which there is strong potential for future drug development. Current therapeutic agents include drugs targeting L-type CaV1.2 calcium channels, particularly 1,4-dihydropyridines, which are widely used in the treatment of hypertension. T-type (CaV3) channels are a target of ethosuximide, widely used in absence epilepsy. The auxiliary subunit α2δ-1 is the therapeutic target of the gabapentinoid drugs, which are of value in certain epilepsies and chronic neuropathic pain. The limited use of intrathecal ziconotide, a peptide blocker of N-type (CaV2.2) calcium channels, as a treatment of intractable pain, gives an indication that these channels represent excellent drug targets for various pain conditions. We describe how selectivity for different subtypes of calcium channels (e.g., CaV1.2 and CaV1.3 L-type channels) may be achieved in the future by exploiting differences between channel isoforms in terms of sequence and biophysical properties, variation in splicing in different target tissues, and differences in the properties of the target tissues themselves in terms of membrane potential or firing frequency. Thus, use-dependent blockers of the different isoforms could selectively block calcium channels in particular pathologies, such as nociceptive neurons in pain states or in epileptic brain circuits. Of important future potential are selective CaV1.3 blockers for neuropsychiatric diseases, neuroprotection in Parkinson’s disease, and resistant hypertension. In addition, selective or nonselective T-type channel blockers are considered potential therapeutic targets in epilepsy, pain, obesity, sleep, and

  18. Calcium homeostasis is altered in skeletal muscle of spontaneously hypertensive rats: cytofluorimetric and gene expression analysis.

    Science.gov (United States)

    Liantonio, Antonella; Camerino, Giulia M; Scaramuzzi, Antonia; Cannone, Maria; Pierno, Sabata; De Bellis, Michela; Conte, Elena; Fraysse, Bodvael; Tricarico, Domenico; Conte Camerino, Diana

    2014-10-01

    Hypertension is often associated with skeletal muscle pathological conditions related to function and metabolism. The mechanisms underlying the development of these pathological conditions remain undefined. Because calcium homeostasis is a biomarker of muscle function, we assessed whether it is altered in hypertensive muscles. We measured resting intracellular calcium and store-operated calcium entry (SOCE) in fast- and slow-twitch muscle fibers from normotensive Wistar-Kyoto rats and spontaneously hypertensive rats (SHRs) by cytofluorimetric technique and determined the expression of SOCE gene machinery by real-time PCR. Hypertension caused a phenotype-dependent dysregulation of calcium homeostasis; the resting intracellular calcium of extensor digitorum longus and soleus muscles of SHRs were differently altered with respect to the related muscle of normotensive animals. In addition, soleus muscles of SHR showed reduced activity of the sarcoplasmic reticulum and decreased sarcolemmal calcium permeability at rest and after SOCE activation. Accordingly, we found an alteration of the expression levels of some SOCE components, such as stromal interaction molecule 1, calcium release-activated calcium modulator 1, and transient receptor potential canonical 1. The hypertension-induced alterations of calcium homeostasis in the soleus muscle of SHRs occurred with changes of some functional outcomes as excitability and resting chloride conductance. We provide suitable targets for therapeutic interventions aimed at counterbalancing muscle performance decline in hypertension, and propose the reported calcium-dependent parameters as indexes to predict how the antihypertensive drugs could influence muscle function. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  19. Computational study of a calcium release-activated calcium channel

    Science.gov (United States)

    Talukdar, Keka; Shantappa, Anil

    2016-05-01

    The naturally occurring proteins that form hole in membrane are commonly known as ion channels. They play multiple roles in many important biological processes. Deletion or alteration of these channels often leads to serious problems in the physiological processes as it controls the flow of ions through it. The proper maintenance of the flow of ions, in turn, is required for normal health. Here we have investigated the behavior of a calcium release-activated calcium ion channel with pdb entry 4HKR in Drosophila Melanogaster. The equilibrium energy as well as molecular dynamics simulation is performed first. The protein is subjected to molecular dynamics simulation to find their energy minimized value. Simulation of the protein in the environment of water and ions has given us important results too. The solvation energy is also found using Charmm potential.

  20. LERF Basin 44 Process Test Plan

    Energy Technology Data Exchange (ETDEWEB)

    LUECK, K.J.

    1999-08-31

    This document presents a plan to process a portion of the Liquid Effluent Retention Facility (LERF) Basin 44 wastewater through the 200 Area Effluent Treatment Facility (ETF). The objective of this process test is to determine the most effective/efficient method to treat the wastewater currently stored in LERF Basin 44. The process test will determine the operational parameters necessary to comply with facility effluent discharge permit limits (Ecology 1995) and the Environmental Restoration Disposal Facility (ERDF) acceptance criteria (BHI-00139), while achieving ALARA goals and maintaining the integrity of facility equipment. A major focus of the test plan centers on control of contamination due to leaks and/or facility maintenance. As a pre-startup item, all known leaks will be fixed before the start of the test. During the course of the test, a variety of contamination control measures will be evaluated for implementation during the treatment of the remaining Basin 44 inventory. Of special interest will be techniques and tools used to prevent contamination spread during sampling and when opening contaminated facility equipment/piping. At the conclusion of the test, a post ALARA review will be performed to identify lessons learned from the test run which can be applied to the treatment of the remaining Basin 44 inventory. The volume of wastewater to be treated during this test run is 500,000 gallons. This volume limit is necessary to maintain the ETF radiological inventory limits per the approved authorization basis. The duration of the process test is approximately 30 days.

  1. The Calcium Wave of Vegetable Cells

    Directory of Open Access Journals (Sweden)

    TD. Geydan

    2007-08-01

    Full Text Available Calcium is an essential nutrient for plants; it is involved in developmental processes and in responses to biotic and abiotic factors. Several signals that modify the calcium concentration in the cytoplasm, endoplasmic reticulum, nucleus and/or plastids have been observed. These changes in the calcium concentration in the cell interior are rapidly returned to basal levels, in the meantime, innumerable and complex signaling cascades. This note exposes the mechanisms of calcium transport through the cell membranes of the entrance of calcium in the plant cells.

  2. Calcium intake in the United States from dietary and supplemental sources across adult age groups: new estimates from the National Health and Nutrition Examination Survey 2003-2006.

    Science.gov (United States)

    Mangano, Kelsey M; Walsh, Stephen J; Insogna, Karl L; Kenny, Anne M; Kerstetter, Jane E

    2011-05-01

    Adequate lifelong calcium intake is essential in optimizing bone health. Recent National Health and Nutrition Examination Survey data were used to quantify variation in calcium intake across adult age groups and to relate age-associated changes in calcium intake with energy intake. Additional goals were to assess differences in dietary calcium intake between supplemental calcium users and nonusers and to evaluate associations between age and calcium density in the diet. This cross-sectional analysis determined calcium and energy intake for National Health and Nutrition Examination Survey respondents during 2003-2006. Diet was assessed with 24-hour recall and supplement use via questionnaire. Trends in median intakes for dietary calcium, total calcium, and energy across age categories were assessed using survey analysis methods. Nutrient density was represented using calcium to energy intake ratios. The analyses included data from 9,475 adults. When compared to the 19- to 30-year age group, median dietary calcium intake was lower in the ≥81-year age group by 23% in men (Pcalcium supplement use increased (Pcalcium intake was greater than in nonusers (P=0.02). Calcium density in the diet significantly increased relative to age in men and women (Pcalcium to energy ratios were insufficient to meet target ratios inferred by adequate intake standards after age 50 years. Although supplemental calcium use and calcium density were highest in older age groups, they were not sufficient in meeting recommended levels. New approaches to increasing the frequency and level of calcium supplement use to enhance calcium density in diets may be necessary to reduce osteoporosis risk among older Americans. Copyright © 2011 American Dietetic Association. Published by Elsevier Inc. All rights reserved.

  3. FOXP3 suppresses breast cancer metastasis through downregulation of CD44.

    Science.gov (United States)

    Zhang, Cun; Xu, Yujin; Hao, Qiang; Wang, Shuning; Li, Hong; Li, Jialin; Gao, Yuan; Li, Meng; Li, Weina; Xue, Xiaochang; Wu, Shouzhen; Zhang, Yingqi; Zhang, Wei

    2015-09-15

    Forkhead box protein 3 (FOXP3) plays an important role in breast cancer as an X-linked tumor suppressor gene. However, the biological functions and significance of FOXP3 in breast cancer metastasis remain unclear. Here, we find that, clinically, nuclear FOXP3 expression is inversely correlated with breast cancer metastasis. Moreover, we demonstrate that FOXP3 significantly inhibits adhesion, invasion and metastasis of breast cancer cells in vivo and in vitro. In addition, the adhesion molecule CD44 is found to be suppressed by FOXP3 through transcriptome sequence analysis (RNA-seq). A luciferase reporter assay, chromatin immunoprecipitation and electrophoretic mobility shift assay identify CD44 as a direct target of FOXP3. The expression of CD44 is downregulated by FOXP3 in breast cancer cells. Importantly, anti-CD44 antibody reverses the FOXP3 siRNA-induced effects on the breast cancer cells in vitro and FOXP3 expression level in the nucleus of breast cancer cells is inversely correlated with CD44 expression level in clinic breast cancer tissues. Taken together, the results from the present study suggest that FOXP3 is a suppressor of breast cancer metastasis. FOXP3 directly binds to the promoter of CD44 and inhibits its protein expression, thereby suppressing adhesion and invasion of human breast cancer cells. This finding highlights the therapeutic potential of FOXP3-CD44 signaling to inhibit breast cancer metastasis. © 2015 UICC.

  4. Effects of CD44 Ligation on Signaling and Metabolic Pathways in Acute Myeloid Leukemia

    KAUST Repository

    Madhoun, Nour Y.

    2017-04-01

    Acute myeloid leukemia (AML) is characterized by a blockage in the differentiation of myeloid cells at different stages. CD44-ligation using anti-CD44 monoclonal antibodies (mAbs) has been shown to reverse the blockage of differentiation and to inhibit the proliferation of blasts in most AML-subtypes. However, the molecular mechanisms underlying this property have not been fully elucidated. Here, we sought to I) analyze the effects of anti-CD44 mAbs on downstream signaling pathways, including the ERK1/2 (extracellular signal-regulated kinase 1 and 2) and mTOR (mammalian target of rapamycin) pathways and II) use state-of-the-art Nuclear Magnetic Resonance (NMR) technology to determine the global metabolic changes during differentiation induction of AML cells using anti-CD44 mAbs and other two previously reported differentiation agents. In the first objective (Chapter 4), our studies provide evidence that CD44-ligation with specific mAbs in AML cells induced an increase in ERK1/2 phosphorylation. The use of the MEK inhibitor (U0126) significantly inhibited the CD44-induced differentiation of HL60 cells, suggesting that ERK1/2 is critical for the CD44-triggered differentiation in AML. In addition, this was accompanied by a marked decrease in the phosphorylation of the mTORC1 and mTORC2 complexes, which are strongly correlated with the inhibition of the PI3K/Akt pathway. In the second objective (Chapter 5), 1H NMR experiments demonstrated that considerable changes in the metabolic profiles of HL60 cells were induced in response to each differentiation agent. These most notable metabolites that significantly changed upon CD44 ligation were involved in the tricarboxylic acid (TCA) cycle and glycolysis such as, succinate, fumarate and lactate. Therefore, we sought to analyze the mechanisms underlying their alterations. Our results revealed that anti-CD44 mAbs treatment induced upregulation in fumarate hydratase (FH) expression and its activity which was accompanied by a

  5. Calcium Intake in the Moroccan Elderly

    Directory of Open Access Journals (Sweden)

    Sebbar El-houcine

    2017-08-01

    Full Text Available Introduction: Calcium intakes of elderly people are often below the recommendations which are 1200 mg/day. The advancing age may be accompanied by a loss of capacity to absorb additional calcium in case of deficiency. The aim of our work is to evaluate the calcium intake in the Moroccan elderly. Methods: The version translated into Arabic dialect Fardellone questionnaire is tested on a sample of 159 subjects aged over 60 years. Results: The study population includes 87 women (55%, 72 men (45%. The mean calcium intake was respectively 3078 mg by week (that means 440 mg/day. The assessment of calcium intake showed a deficiency and the average consumption of calcium per day is significantly lower than the recommended daily amount for this population. The comparison of both gender found a deficit higher among women than among men. Conclusion: Evaluation of the calcium intake is an essential tool for better management of metabolic bone diseases.

  6. Calcium Impact on Milk Gels Formation

    DEFF Research Database (Denmark)

    Koutina, Glykeria

    Calcium is one of the several elements that can be found in milk distributed between the micellar and the serum milk phase. Calcium is important from a nutritional point of view, but its contribution to the functional and structural properties of dairy products has only recently been...... acknowledgement. The presence of calcium in a dynamic equilibrium between the serum and the micellar milk phase make the distribution susceptible to certain physicochemical conditions and to technological treatments of milk resulting in fluctuations in pH and temperature and also sensitive to addition of calcium...... salts. The perturbation of calcium equilibria by these factors will affect the final properties of acid, calcium and rennet milk gels. By decreasing the pH from 6.0 to 5.2 (acid gels), the calcium equilibrium was significantly affected by temperature (4, 20, 30, 40 oC), and different combinations...

  7. Calcium channel-dependent molecular maturation of photoreceptor synapses.

    Directory of Open Access Journals (Sweden)

    Nawal Zabouri

    Full Text Available Several studies have shown the importance of calcium channels in the development and/or maturation of synapses. The Ca(V1.4(α(1F knockout mouse is a unique model to study the role of calcium channels in photoreceptor synapse formation. It features abnormal ribbon synapses and aberrant cone morphology. We investigated the expression and targeting of several key elements of ribbon synapses and analyzed the cone morphology in the Ca(V1.4(α(1F knockout retina. Our data demonstrate that most abnormalities occur after eye opening. Indeed, scaffolding proteins such as Bassoon and RIM2 are properly targeted at first, but their expression and localization are not maintained in adulthood. This indicates that either calcium or the Ca(V1.4 channel, or both are necessary for the maintenance of their normal expression and distribution in photoreceptors. Other proteins, such as Veli3 and PSD-95, also display abnormal expression in rods prior to eye opening. Conversely, vesicle related proteins appear normal. Our data demonstrate that the Ca(V1.4 channel is important for maintaining scaffolding proteins in the ribbon synapse but less vital for proteins related to vesicular release. This study also confirms that in adult retinae, cones show developmental features such as sprouting and synaptogenesis. Overall we present evidence that in the absence of the Ca(V1.4 channel, photoreceptor synapses remain immature and are unable to stabilize.

  8. Exopolysaccharides regulate calcium flow in cariogenic biofilms.

    Science.gov (United States)

    Astasov-Frauenhoffer, Monika; Varenganayil, Muth M; Decho, Alan W; Waltimo, Tuomas; Braissant, Olivier

    2017-01-01

    Caries-associated biofilms induce loss of calcium from tooth surfaces in the presence of dietary carbohydrates. Exopolysaccharides (EPS) provide a matrix scaffold and an abundance of primary binding sites within biofilms. The role of EPS in binding calcium in cariogenic biofilms is only partially understood. Thus, the aim of the present study is to investigate the relationship between the calcium dissolution rates and calcium tolerance of caries-associated bacteria and yeast as well as to examine the properties of EPS to quantify its binding affinity for dissolved calcium. Calcium dissolution was measured by dissolution zones on Pikovskaya's agar. Calcium tolerance was assessed by isothermal microcalorimetry (IMC) by adding CaCl2 to the bacterial cultures. Acid-base titration and Fourier transform infrared (FTIR) spectroscopy were used to identify possible functional groups responsible for calcium binding, which was assessed by isothermal titration calorimetry (ITC). Lactobacillus spp. and mutans streptococci demonstrated calcium dissolution in the presence of different carbohydrates. All strains that demonstrated high dissolution rates also revealed higher rates of calcium tolerance by IMC. In addition, acidic functional groups were predominantly identified as possible binding sites for calcium ions by acid-base titration and FTIR. Finally, ITC revealed EPS to have a higher binding affinity for calcium compared, for example, to lactic acid. In conclusion, this study illustrates the role of EPS in terms of the calcium tolerance of cariogenic microbiota by determining the ability of EPS to control free calcium concentrations within the biofilms as a self-regulating mode of action in the pathogenesis of dental caries.

  9. Exopolysaccharides regulate calcium flow in cariogenic biofilms.

    Directory of Open Access Journals (Sweden)

    Monika Astasov-Frauenhoffer

    Full Text Available Caries-associated biofilms induce loss of calcium from tooth surfaces in the presence of dietary carbohydrates. Exopolysaccharides (EPS provide a matrix scaffold and an abundance of primary binding sites within biofilms. The role of EPS in binding calcium in cariogenic biofilms is only partially understood. Thus, the aim of the present study is to investigate the relationship between the calcium dissolution rates and calcium tolerance of caries-associated bacteria and yeast as well as to examine the properties of EPS to quantify its binding affinity for dissolved calcium. Calcium dissolution was measured by dissolution zones on Pikovskaya's agar. Calcium tolerance was assessed by isothermal microcalorimetry (IMC by adding CaCl2 to the bacterial cultures. Acid-base titration and Fourier transform infrared (FTIR spectroscopy were used to identify possible functional groups responsible for calcium binding, which was assessed by isothermal titration calorimetry (ITC. Lactobacillus spp. and mutans streptococci demonstrated calcium dissolution in the presence of different carbohydrates. All strains that demonstrated high dissolution rates also revealed higher rates of calcium tolerance by IMC. In addition, acidic functional groups were predominantly identified as possible binding sites for calcium ions by acid-base titration and FTIR. Finally, ITC revealed EPS to have a higher binding affinity for calcium compared, for example, to lactic acid. In conclusion, this study illustrates the role of EPS in terms of the calcium tolerance of cariogenic microbiota by determining the ability of EPS to control free calcium concentrations within the biofilms as a self-regulating mode of action in the pathogenesis of dental caries.

  10. Functional Differences between Human NKp44(-) and NKp44(+) RORC(+) Innate Lymphoid Cells.

    Science.gov (United States)

    Hoorweg, Kerim; Peters, Charlotte P; Cornelissen, Ferry; Aparicio-Domingo, Patricia; Papazian, Natalie; Kazemier, Geert; Mjösberg, Jenny M; Spits, Hergen; Cupedo, Tom

    2012-01-01

    Human RORC(+) lymphoid tissue inducer cells are part of a rapidly expanding family of innate lymphoid cells (ILC) that participate in innate and adaptive immune responses as well as in lymphoid tissue (re) modeling. The assessment of a potential role for innate lymphocyte-derived cytokines in human homeostasis and disease is hampered by a poor characterization of RORC(+) innate cell subsets and a lack of knowledge on the distribution of these cells in adults. Here we show that functionally distinct subsets of human RORC(+) innate lymphoid cells are enriched for secretion of IL-17a or IL-22. Both subsets have an activated phenotype and can be distinguished based on the presence or absence of the natural cytotoxicity receptor NKp44. NKp44(+) IL-22 producing cells are present in tonsils while NKp44(-) IL-17a producing cells are present in fetal developing lymph nodes. Development of human intestinal NKp44(+) ILC is a programmed event that is independent of bacterial colonization and these cells colonize the fetal intestine during the first trimester. In the adult intestine, NKp44(+) ILC are the main ILC subset producing IL-22. NKp44(-) ILC remain present throughout adulthood in peripheral non-inflamed lymph nodes as resting, non-cytokine producing cells. However, upon stimulation lymph node ILC can swiftly initiate cytokine transcription suggesting that secondary human lymphoid organs may function as a reservoir for innate lymphoid cells capable of participating in inflammatory responses.

  11. Calcium precipitate induced aerobic granulation.

    Science.gov (United States)

    Wan, Chunli; Lee, Duu-Jong; Yang, Xue; Wang, Yayi; Wang, Xingzu; Liu, Xiang

    2015-01-01

    Aerobic granulation is a novel biotechnology for wastewater treatment. This study refined existing aerobic granulation mechanisms as a sequencing process including formation of calcium precipitate under alkaline pH to form inorganic cores, followed by bacterial attachment and growth on these cores to form the exopolysaccharide matrix. Mature granules comprised an inner core and a matrix layer and a rim layer with enriched microbial strains. The inorganic core was a mix of different crystals of calcium and phosphates. Functional strains including Sphingomonas sp., Paracoccus sp. Sinorhizobium americanum strain and Flavobacterium sp. attached onto the cores. These functional strains promote c-di-GMP production and the expression by Psl and Alg genes for exopolysaccharide production to enhance formation of mature granules. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Calcium Co-regulates Oxidative Metabolism and ATP Synthase-dependent Respiration in Pancreatic Beta Cells

    Science.gov (United States)

    De Marchi, Umberto; Thevenet, Jonathan; Hermant, Aurelie; Dioum, Elhadji; Wiederkehr, Andreas

    2014-01-01

    Mitochondrial energy metabolism is essential for glucose-induced calcium signaling and, therefore, insulin granule exocytosis in pancreatic beta cells. Calcium signals are sensed by mitochondria acting in concert with mitochondrial substrates for the full activation of the organelle. Here we have studied glucose-induced calcium signaling and energy metabolism in INS-1E insulinoma cells and human islet beta cells. In insulin secreting cells a surprisingly large fraction of total respiration under resting conditions is ATP synthase-independent. We observe that ATP synthase-dependent respiration is markedly increased after glucose stimulation. Glucose also causes a very rapid elevation of oxidative metabolism as was followed by NAD(P)H autofluorescence. However, neither the rate of the glucose-induced increase nor the new steady-state NAD(P)H levels are significantly affected by calcium. Our findings challenge the current view, which has focused mainly on calcium-sensitive dehydrogenases as the target for the activation of mitochondrial energy metabolism. We propose a model of tight calcium-dependent regulation of oxidative metabolism and ATP synthase-dependent respiration in beta cell mitochondria. Coordinated activation of matrix dehydrogenases and respiratory chain activity by calcium allows the respiratory rate to change severalfold with only small or no alterations of the NAD(P)H/NAD(P)+ ratio. PMID:24554722

  13. Protein arginine deiminase 2 binds calcium in an ordered fashion: implications for inhibitor design.

    Science.gov (United States)

    Slade, Daniel J; Fang, Pengfei; Dreyton, Christina J; Zhang, Ying; Fuhrmann, Jakob; Rempel, Don; Bax, Benjamin D; Coonrod, Scott A; Lewis, Huw D; Guo, Min; Gross, Michael L; Thompson, Paul R

    2015-04-17

    Protein arginine deiminases (PADs) are calcium-dependent histone-modifying enzymes whose activity is dysregulated in inflammatory diseases and cancer. PAD2 functions as an Estrogen Receptor (ER) coactivator in breast cancer cells via the citrullination of histone tail arginine residues at ER binding sites. Although an attractive therapeutic target, the mechanisms that regulate PAD2 activity are largely unknown, especially the detailed role of how calcium facilitates enzyme activation. To gain insights into these regulatory processes, we determined the first structures of PAD2 (27 in total), and through calcium-titrations by X-ray crystallography, determined the order of binding and affinity for the six calcium ions that bind and activate this enzyme. These structures also identified several PAD2 regulatory elements, including a calcium switch that controls proper positioning of the catalytic cysteine residue, and a novel active site shielding mechanism. Additional biochemical and mass-spectrometry-based hydrogen/deuterium exchange studies support these structural findings. The identification of multiple intermediate calcium-bound structures along the PAD2 activation pathway provides critical insights that will aid the development of allosteric inhibitors targeting the PADs.

  14. Testosterone increases urinary calcium excretion and inhibits expression of renal calcium transport proteins

    DEFF Research Database (Denmark)

    Hsu, Yu-Juei; Dimke, Henrik Anthony; Schoeber, Joost P H

    2010-01-01

    Although gender differences in the renal handling of calcium have been reported, the overall contribution of androgens to these differences remains uncertain. We determined here whether testosterone affects active renal calcium reabsorption by regulating calcium transport proteins. Male mice had...... higher urinary calcium excretion than female mice and their renal calcium transporters were expressed at a lower level. We also found that orchidectomized mice excreted less calcium in their urine than sham-operated control mice and that the hypocalciuria was normalized after testosterone replacement...... calcium transport. Thus, our study shows that gender differences in renal calcium handling are, in part, mediated by the inhibitory actions of androgens on TRPV5-mediated active renal calcium transport....

  15. A Closer look at calcium absorption and the benefits and risks of dietary versus supplemental calcium.

    Science.gov (United States)

    Booth, Anna; Camacho, Pauline

    2013-11-01

    To perform a thorough search of the literature on calcium research and specifically address the topic of calcium absorption. PubMed and Ovid were the main engines used for primary literature searches; textbooks, review articles, and book chapters are examples of the other sources used for supplemental information. Regarding calcium absorption, it seems apparent that the absorption efficiency of all calcium salts, regardless of solubility, is fairly equivalent and not significantly less than the absorption efficiency of dietary calcium. However, dietary calcium has been shown to have greater impact in bone building than supplemental calcium. This is likely due to improved absorption with meals and the tendency of people to intake smaller amounts more frequently, which is more ideal for the body's method of absorption. In addition, the cardiovascular risks of excessive calcium intake appear to be more closely related to calcium supplements than dietary calcium; this relationship continues to be controversial in the literature. We conclude that further studies are needed for direct comparison of supplemental and dietary calcium to fully establish if one is superior to the other with regard to improving bone density. We also propose further studies on the cardiovascular risk of long-term increased calcium intake and on physician estimates of patients' daily calcium intake to better pinpoint those patients who require calcium supplementation.

  16. CCN3 and calcium signaling

    Directory of Open Access Journals (Sweden)

    Li Chang Long

    2003-08-01

    Full Text Available Abstract The CCN family of genes consists presently of six members in human (CCN1-6 also known as Cyr61 (Cystein rich 61, CTGF (Connective Tissue Growth Factor, NOV (Nephroblastoma Overexpressed gene, WISP-1, 2 and 3 (Wnt-1 Induced Secreted Proteins. Results obtained over the past decade have indicated that CCN proteins are matricellular proteins, which are involved in the regulation of various cellular functions, such as proliferation, differentiation, survival, adhesion and migration. The CCN proteins have recently emerged as regulatory factors involved in both internal and external cell signaling. CCN3 was reported to physically interact with fibulin-1C, integrins, Notch and S100A4. Considering that, the conformation and biological activity of these proteins are dependent upon calcium binding, we hypothesized that CCN3 might be involved in signaling pathways mediated by calcium ions. In this article, we review the data showing that CCN3 regulates the levels of intracellular calcium and discuss potential models that may account for the biological effects of CCN3.

  17. Kinetics of calcium sulfoaluminate formation from tricalcium aluminate, calcium sulfate and calcium oxide

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xuerun, E-mail: xuerunli@163.com; Zhang, Yu; Shen, Xiaodong, E-mail: xdshen@njut.edu.cn; Wang, Qianqian; Pan, Zhigang

    2014-01-15

    The formation kinetics of tricalcium aluminate (C{sub 3}A) and calcium sulfate yielding calcium sulfoaluminate (C{sub 4}A{sub 3}$) and the decomposition kinetics of calcium sulfoaluminate were investigated by sintering a mixture of synthetic C{sub 3}A and gypsum. The quantitative analysis of the phase composition was performed by X-ray powder diffraction analysis using the Rietveld method. The results showed that the formation reaction 3Ca{sub 3}Al{sub 2}O{sub 6} + CaSO{sub 4} → Ca{sub 4}Al{sub 6}O{sub 12}(SO{sub 4}) + 6CaO was the primary reaction < 1350 °C with and activation energy of 231 ± 42 kJ/mol; while the decomposition reaction 2Ca{sub 4}Al{sub 6}O{sub 12}(SO{sub 4}) + 10CaO → 6Ca{sub 3}Al{sub 2}O{sub 6} + 2SO{sub 2} ↑ + O{sub 2} ↑ primarily occurred beyond 1350 °C with an activation energy of 792 ± 64 kJ/mol. The optimal formation region for C{sub 4}A{sub 3}$ was from 1150 °C to 1350 °C and from 6 h to 1 h, which could provide useful information on the formation of C{sub 4}A{sub 3}$ containing clinkers. The Jander diffusion model was feasible for the formation and decomposition of calcium sulfoaluminate. Ca{sup 2+} and SO{sub 4}{sup 2−} were the diffusive species in both the formation and decomposition reactions. -- Highlights: •Formation and decomposition of calcium sulphoaluminate were studied. •Decomposition of calcium sulphoaluminate combined CaO and yielded C{sub 3}A. •Activation energy for formation was 231 ± 42 kJ/mol. •Activation energy for decomposition was 792 ± 64 kJ/mol. •Both the formation and decomposition were controlled by diffusion.

  18. Presenilin-mediated modulation of capacitative calcium entry.

    Science.gov (United States)

    Yoo, A S; Cheng, I; Chung, S; Grenfell, T Z; Lee, H; Pack-Chung, E; Handler, M; Shen, J; Xia, W; Tesco, G; Saunders, A J; Ding, K; Frosch, M P; Tanzi, R E; Kim, T W

    2000-09-01

    We studied a novel function of the presenilins (PS1 and PS2) in governing capacitative calcium entry (CCE), a refilling mechanism for depleted intracellular calcium stores. Abrogation of functional PS1, by either knocking out PS1 or expressing inactive PS1, markedly potentiated CCE, suggesting a role for PS1 in the modulation of CCE. In contrast, familial Alzheimer's disease (FAD)-linked mutant PS1 or PS2 significantly attenuated CCE and store depletion-activated currents. While inhibition of CCE selectively increased the amyloidogenic amyloid beta peptide (Abeta42), increased accumulation of the peptide had no effect on CCE. Thus, reduced CCE is most likely an early cellular event leading to increased Abeta42 generation associated with FAD mutant presenilins. Our data indicate that the CCE pathway is a novel therapeutic target for Alzheimer's disease.

  19. Increased Calcium Supplementation Postpartum Is Associated with Breastfeeding among Chinese Mothers: Finding from Two Prospective Cohort Studies.

    Science.gov (United States)

    Zhao, Jian; Zhao, Yun; Binns, Colin W; Lee, Andy H

    2016-10-09

    The calcium supplementation status during the postpartum period among Chinese lactating women is still unclear. The objective of this study is to utilize data from two population-based prospective cohort studies to examine the calcium supplementation status and to identify whether breastfeeding is associated with increased calcium supplementation among Chinese mothers after child birth. Information from 1540 mothers on breastfeeding and calcium supplementation measured at discharge, 1, 3, and 6 months postpartum were extracted to evaluate the association between breastfeeding and calcium supplementation postpartum. A generalized linear mixed model was applied to each study initially to account for the inherent correlation among repeated measurements, adjusting for socio-demographic, obstetric factors and calcium supplementation during pregnancy. In addition, breastfeeding status measured at different follow-up time points was treated as a time dependent variable in the longitudinal analysis. Furthermore, the effect sizes of the two cohort studies were pooled using fixed effect model. Based on the two cohort studies, the pooled likelihood of taking calcium supplementation postpartum among breastfeeding mothers was 4.02 times (95% confidence interval (2.30, 7.03)) higher than that of their non-breastfeeding counterparts. Dietary supplementation intervention programs targeting different subgroups should be promoted in Chinese women, given currently a wide shortage of dietary calcium intake and calcium supplementation postpartum.

  20. 4,4'-Dichlorodiphenyltrichloroethane (DDT) and 4,4'-dichlorodiphenyldichloroethylene (DDE) inhibit myogenesis in C2C12 myoblasts.

    Science.gov (United States)

    Kim, Jonggun; Park, Min Young; Kim, Yoo; Yoon, Kyong Sup; Clark, John Marshall; Park, Yeonhwa; Whang, Kwang-Youn

    2017-12-01

    Most countries have banned the use of 4,4'-dichlorodiphenyltrichloroethane (DDT). However, owing to its extremely high lipophilic characteristics, DDT and its metabolite 4,4'-dichlorodiphenyldichloroethylene (DDE) are ubiquitous in the environment and in many types of food. The positive correlation between exposure to insecticides, including DDT and DDE, and weight gain, resulting in impaired energy metabolism in offspring following perinatal DDT and DDE exposure, was previously reported. Therefore the influence of DDT and DDE on myogenesis using C2C12 myoblasts was investigated in this study. DDT and DDE decreased myotube formation dose- and time-dependently. Among myogenic regulatory factors, DDT and DDE mainly decreased MyoD1 and Myf5 expression. DDT and DDE treatment also altered Myostatin expression, phosphorylation of protein kinase B, p70 ribosomal protein S6 kinase, forkhead box O protein 3 and mammalian target of rapamycin, resulting in attenuation of myotube formation. These results may have significant implications for understanding the effects of developmental exposure of DDT and DDE on myogenesis and development of obesity and type 2 diabetes later in life. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  1. Cross-talk between ROS and calcium in regulation of nuclear activities.

    Science.gov (United States)

    Mazars, Christian; Thuleau, Patrice; Lamotte, Olivier; Bourque, Stéphane

    2010-07-01

    Calcium and Reactive Oxygen Species (ROS) are acknowledged as crucial second messengers involved in the response to various biotic and abiotic stresses. However, it is still not clear how these two compounds can play a role in different signaling pathways leading the plant to a variety of processes such as root development or defense against pathogens. Recently, it has been shown that the concept of calcium and ROS signatures, initially discovered in the cytoplasm, can also be extended to the nucleus of plant cells. In addition, it has been clearly proved that both ROS and calcium signals are intimately interconnected. How this cross-talk can finally modulate the translocation and/or the activity of nuclear proteins leading to the control of specific genes expression is the main focus of this review. We will especially focus on how calcium and ROS interact at the molecular level to modify their targets.

  2. Chemical Composition Measurements of LAWA44 Glass Samples

    Energy Technology Data Exchange (ETDEWEB)

    Fox, K. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Edwards, T. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Riley, W. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2016-11-15

    DOE is building the Hanford Tank Waste Treatment and Immobilization Plant (WTP) at the Hanford Site in Washington to remediate 55 million gallons of radioactive waste that is temporarily stored in 177 underground tanks. Both low-activity and high-level wastes will then be vitrified into borosilicate glass using Joule-heated ceramic melters. Efforts are being made to increase the loading of Hanford tank wastes in the glass. One area of work is enhancing waste glass composition/property models and broadening the compositional regions over which those models are applicable. In this report, the Savannah River National Laboratory provides chemical analysis results for several samples of a simulated low-activity waste glass, LAWA44, provided by the Pacific Northwest National Laboratory as part of an ongoing development task. The measured chemical composition data are reported and compared with the targeted values for each component for each glass. A detailed review showed no indications of errors in the preparation or measurement of the study glasses. All of the measured sums of oxides for the study glasses fell within the interval of 97.9 to 102.6 wt %, indicating acceptable recovery of the glass components. Comparisons of the targeted and measured chemical compositions showed that the measured values for the glasses met the targeted concentrations within 10% for those components present at more than 5 wt %. It was noted that the measured B2O3 concentrations are somewhat above the targeted values for the study glasses. No obvious trends were observed with regard to the multiple melting steps used to prepare the study glasses, indicating that any potential effects of volatility were below measurable thresholds.

  3. Vitamin D is positively associated with sperm motility and increases intracellular calcium in human spermatozoa

    DEFF Research Database (Denmark)

    Blomberg Jensen, Martin; Bjerrum, Poul J; Jessen, Torben E

    2011-01-01

    motility and acrosome reaction. All men delivered samples for routine semen analysis and blood for measurements of follicle stimulating hormone, Inhibin B, 25-hydroxy-VD, albumin, alkaline phosphatase, calcium and parathyroid hormone (PTH). RESULTS In the association study, 44% were VD insufficient (75 n...... concentration, sperm motility and induced the acrosome reaction in mature spermatozoa, and VD serum levels were positively associated with sperm motility, suggesting a role for VD in human sperm function....

  4. The Role of Calcium in Osteoporosis

    Science.gov (United States)

    Arnaud, C. D.; Sanchez, S. D.

    1991-01-01

    Calcium requirements may vary throughout the lifespan. During the growth years and up to age 25 to 30, it is important to maximize dietary intake of calcium to maintain positive calcium balance and achieve peak bone mass, thereby possibly decreasing the risk of fracture when bone is subsequently lost. Calcium intake need not be greater than 800 mg/day during the relatively short period of time between the end of bone building and the onset of bone loss (30 to 40 years). Starting at age 40 to 50, both men and women lose bone slowly, but women lose bone more rapidly around the menopause and for about 10 years after. Intestinal calcium absorption and the ability to adapt to low calcium diets are impaired in many postmenopausal women and elderly persons owing to a suspected functional or absolute decrease in the ability of the kidney to produce 1,25(OH)2D2. The bones then become more and more a source of calcium to maintain critical extracellular fluid calcium levels. Excessive dietary intake of protein and fiber may induce significant negative calcium balance and thus increase dietary calcium requirements. Generally, the strongest risk factors for osteoporosis are uncontrollable (e.g., sex, age, and race) or less controllable (e.g., disease and medications). However, several factors such as diet, physical activity, cigarette smoking, and alcohol use are lifestyle related and can be modified to help reduce the risk of osteoporosis.

  5. Assessment of calcium intake by adolescents

    Directory of Open Access Journals (Sweden)

    Cristiane Franco de Oliveira

    2014-06-01

    Full Text Available OBJECTIVE: To evaluate the daily calcium intake of adolescents in schools from Chapecó, Santa Catarina, Southern Brazil, to check if calcium intake is in accordance with the Dietary Reference Intakes (DRI, and to investigate variables associated with daily calcium intake.METHODS: Cross-sectional study approved by the Institutional Review Board and developed in 2010. Students of the 8th grade completed questionnaires with personal data and questions about the calcium-rich foods intake frequency. In order to compare students with adequate (1300mg or inadequate intake of calcium/day (<1300mg, parametric and nonparametric tests were used.RESULTS: A total of 214 students with a mean age of 14.3±1.0 years were enrolled. The median daily calcium intake was 540mg (interquartile range - IQ: 312-829mg and only 25 students (11.7% had calcium intake within the recommendations of the DRI for age. Soft drink consumption ≥3 times/week was associated with a lower intake of calcium.CONCLUSIONS: Few students ingested adequate levels of calcium for the age group. It is necessary to develop a program to encourage a greater intake of calcium-rich foods in adolescence.

  6. The Risks and Benefits of Calcium Supplementation

    Directory of Open Access Journals (Sweden)

    Chan Soo Shin

    2015-03-01

    Full Text Available The association between calcium supplementation and adverse cardiovascular events has recently become a topic of debate due to the publication of two epidemiological studies and one meta-analysis of randomized controlled clinical trials. The reports indicate that there is a significant increase in adverse cardiovascular events following supplementation with calcium; however, a number of experts have raised several issues with these reports such as inconsistencies in attempts to reproduce the findings in other populations and questions concerning the validity of the data due to low compliance, biases in case ascertainment, and/or a lack of adjustment. Additionally, the Auckland Calcium Study, the Women's Health Initiative, and many other studies included in the meta-analysis obtained data from calcium-replete subjects and it is not clear whether the same risk profile would be observed in populations with low calcium intakes. Dietary calcium intake varies widely throughout the world and it is especially low in East Asia, although the risk of cardiovascular events is less prominent in this region. Therefore, clarification is necessary regarding the occurrence of adverse cardiovascular events following calcium supplementation and whether this relationship can be generalized to populations with low calcium intakes. Additionally, the skeletal benefits from calcium supplementation are greater in subjects with low calcium intakes and, therefore, the risk-benefit ratio of calcium supplementation is likely to differ based on the dietary calcium intake and risks of osteoporosis and cardiovascular diseases of various populations. Further studies investigating the risk-benefit profiles of calcium supplementation in various populations are required to develop population-specific guidelines for individuals of different genders, ages, ethnicities, and risk profiles around the world.

  7. Effects on anionic salts in a pre-partum dairy ration on calcium metabolism

    Directory of Open Access Journals (Sweden)

    C.J. Van Dijk

    2001-07-01

    Full Text Available The effects of anionic salts in the transition diet on serum and urine calcium at calving and on peripartal health, subsequent milk production and fertility performance were studied in a well-managed, high-producing Friesland dairy herd. Over a period of a year, approximately 21 days before the expected date of calving, 28 pre-partum heifers and 44 multiparous dry cows were randomly allocated within parity to 1 of 2 transition diets, designated control and experimental anionic diets. The anionic diet contained the same quantities of the basic transition ration fed to the control group as well as a standard anionic salt mixture containing 118 g NH4Cl, 36 g (NH42SO4 and 68 g MgSO4 (total 222 g per animal per day. This reduced the DCAD to -11.68 mEq/100 g dietary dry matter compared to +13.57 for the control diet. Blood and urine were randomly sampled from 7 to 8 animals within each category within 3 hours post-partum. Serum calcium (total and ionised and creatinine, urine calcium and creatinine and the fractional clearance of calcium were assessed. Relevant clinical, milk production, and fertility data were collected. The total serum calcium (2.07 versus 1.60 mmol/ , serum ionised calcium (1.12 vs 1.02 mmol/ , urine calcium (0.92 vs 0.10 mmol/ and the fractional clearance of calcium (1.88 vs 0.09 % were significantly higher (P <0.01 at calving for multiparous cows fed the anionic diet compared to those fed the control diet. In the primiparous cows there were no significant differences in serumcalcium levels. However, the urine calcium (1.07 vs 0.43 mmol/ and the fractional clearance of calcium was higher (1.75 vs 0.45 % in cows fed the anionic diet (P <0.05 and 0.01 respectively. These results illustrated that there were benefits, although no differences were demonstrated with respect to health, milk production or fertility. The supplementation of diets with anionic salts in the last 2-3 weeks before calving has the potential to significantly

  8. Calcium signals can freely cross the nuclear envelope in hippocampal neurons: somatic calcium increases generate nuclear calcium transients

    OpenAIRE

    Eder, Anja; Bading, Hilmar

    2007-01-01

    Abstract Background In hippocampal neurons, nuclear calcium signaling is important for learning- and neuronal survival-associated gene expression. However, it is unknown whether calcium signals generated by neuronal activity at the cell membrane and propagated to the soma can unrestrictedly cross the nuclear envelope to invade the nucleus. The nuclear envelope, which allows ion transit via the nuclear pore complex, may represent a barrier for calcium and has been suggested to insulate the nuc...

  9. Antiproton Target

    CERN Multimedia

    1980-01-01

    Antiproton target used for the AA (antiproton accumulator). The first type of antiproton production target used from 1980 to 1982 comprised a rod of copper 3mm diameter and 120mm long embedded in a graphite cylinder that was itself pressed into a finned aluminium container. This assembly was air-cooled and it was used in conjunction with the Van der Meer magnetic horn. In 1983 Fermilab provided us with lithium lenses to replace the horn with a view to increasing the antiproton yield by about 30%. These lenses needed a much shorter target made of heavy metal - iridium was chosen for this purpose. The 50 mm iridium rod was housed in an extension to the original finned target container so that it could be brought very close to the entrance to the lithium lens. Picture 1 shows this target assembly and Picture 2 shows it mounted together with the lithium lens. These target containers had a short lifetime due to a combination of beam heating and radiation damage. This led to the design of the water-cooled target in...

  10. Catalytic pyrolysis using UZM-44 aluminosilicate zeolite

    Science.gov (United States)

    Nicholas, Christopher P; Boldingh, Edwin P

    2013-12-17

    A new family of aluminosilicate zeolites designated UZM-44 has been synthesized. These zeolites are represented by the empirical formula Na.sub.nM.sub.m.sup.k+T.sub.tAl.sub.1-xE.sub.xSi.sub.yO.sub.z where "n" is the mole ratio of Na to (Al+E), M represents a metal or metals from zinc, Group 1, Group 2, Group 3 and or the lanthanide series of the periodic table, "m" is the mole ratio of M to (Al+E), "k" is the average charge of the metal or metals M, T is the organic structure directing agent or agents, and E is a framework element such as gallium. The process involves contacting a carbonaceous biomass feedstock with UZM-44 at pyrolysis conditions to produce pyrolysis gases comprising hydrocarbons. The catalyst catalyzes a deoxygenation reaction converting oxygenated hydrocarbons into hydrocarbons and removing the oxygen as carbon oxides and water. A portion of the pyrolysis gases is condensed to produce low oxygen biomass-derived pyrolysis oil.

  11. Bis(4,4'-bipyridinium) dodeca-tungsto-silicate 4,4'-bipyridine hexa-hydrate.

    Science.gov (United States)

    Ma, Feng-Xia; Zhao, Quan

    2008-09-06

    The title compound, (C(10)H(10)N(2))(2)[SiW(12)O(40)]·C(10)H(8)N(2)·6H(2)O or (4,4'-bipyH(2))(2)[SiW(12)O(40)].(4,4'-bipy)·6H(2)O (4,4'-bipy is 4,4'-bipyridine), was prepared under hydro-thermal conditions. The asymmetric unit contains a discrete Keggin-type [SiW(12)O(40)](4-) anion (located on a twofold axis), one 4,4'-bipy (located on a twofold axis), two (4,4'-bipyH(2))(2+) cations and six uncoordinated water mol-ecules. The polyoxoanion is constructed from a central SiO(4) tetra-hedron which shares its O atoms with four trinuclear W(3)O(13) groups, each of which is made up of three edge-sharing WO(6) octa-hedra. The water mol-ecules and [SiW(12)O(40)](4-) anions are linked through hydrogen bonds.

  12. 4,4'-Dimethylaminorex ("4,4'-DMAR"; "Serotoni") misuse: A Web-based study.

    Science.gov (United States)

    Loi, Barbara; Zloh, Mire; De Luca, Maria Antonietta; Pintori, Nicholas; Corkery, John; Schifano, Fabrizio

    2017-05-01

    4,4'-DMAR (4,4'-dimethylaminorex; "Serotoni") is a potent stimulant drug that has recently been associated with a number of fatalities in Europe. Over the last few years, online communities have emerged as important resources for disseminating levels of technical knowledge on novel psychoactive substances. Analysing the information provided by the fora communities on 4,4'-DMAR use, additionally critical reviewing the available evidence-based literature on this topic. Different website drug fora were identified. A critical review of the existing evidence-based literature was undertaken. Individuation and analysis of qualitative data from the identified website fora were performed. The combined search results identified six website fora from which a range of qualitative data on recurring themes was collected. These themes included routes of administration and doses; desired effects; adverse effects; comparison with other drugs; association with other drugs; medications self-administered to reverse 4,4'-DMAR action; overall impression; and provision of harm-reduction advice. Although being characterized by a number of methodological limitations, the social networks' Web monitoring approach (netnography) may be helpful to better understand some of the clinical and psychopharmacological issues pertaining to a range of novel psychoactive substances, including 4,4'-DMAR, for which only extremely little, if any, scientific knowledge is available. Copyright © 2017 John Wiley & Sons, Ltd.

  13. Calcium gluconate supplementation is effective to balance calcium homeostasis in patients with gastrectomy.

    Science.gov (United States)

    Krause, M; Keller, J; Beil, B; van Driel, I; Zustin, J; Barvencik, F; Schinke, T; Amling, M

    2015-03-01

    We demonstrate histological evidence for hyperparathyroidism in patients with gastrectomy. This is, at least in part, explained by impaired calcium absorption, resulting in mineralization defects and secondary hyperparathyroidism. Additionally, we demonstrate improved bone mineralization in patients with gastrectomy after gluconate therapy and showed the effectiveness of calcium gluconate over carbonate to balance impaired calcium hemostasis in mice. Gastrectomy and hypochlorhydria due to long-term proton pump inhibitor therapy are associated with increased fracture risk because of intestinal calcium malabsorption. Hence, our objectives were to histologically investigate bone metabolism in patients with gastrectomy and to analyze the impact of calcium gluconate supplementation on skeletal integrity in the setting of impaired gastric acidification. Undecalcified bone biopsies of 26 gastrectomized individuals were histologically analyzed. In the clinical setting, we retrospectively identified 5 gastrectomized patients with sufficient vitamin D level, who were additionally supplemented with calcium gluconate and had a real bone mineral density (aBMD) follow-up assessments. A mouse model of achlorhydria (ATP4b-/-) was used to compare the effect of calcium gluconate and calcium carbonate supplementation on bone metabolism. Biopsies from gastrectomized individuals showed significantly increased osteoid, osteoclast, and osteoblast indices and fibroosteoclasia (p < 0.05) as well as impaired calcium distribution in mineralized bone matrix compared to healthy controls. Five gastrectomized patients with sufficient vitamin D level demonstrated a significant increase in aBMD after a treatment with calcium gluconate alone for at least 6 months (p < 0.05). Calcium gluconate was superior to calcium carbonate in maintaining calcium metabolism in a mouse model of achlorhydria. Gastrectomy is associated with severe osteomalacia, marrow fibrosis, and impaired calcium distribution

  14. Influence of calcium sources on microbially induced calcium carbonate precipitation by Bacillus sp. CR2.

    Science.gov (United States)

    Achal, Varenyam; Pan, Xiangliang

    2014-05-01

    Stimulation of microbially induced calcium carbonate precipitation (MICCP) is likely to be influenced by calcium sources. In order to study such influences, we performed MICCP using Bacillus sp. CR2 in nutrient broth containing urea, supplemented with different calcium sources (calcium chloride, calcium oxide, calcium acetate and calcium nitrate). The experiment lasted 7 days, during which bacterial growth, urease activity, calcite production and pH were measured. Our results showed that calcium chloride is the better calcium source for MICCP process, since it provides higher urease activity and more calcite production. The influences of calcium sources on MICCP were further studied using Fourier transform-infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and X-ray diffraction (XRD) analyses. These analyses confirmed that the precipitate formed was CaCO3 and composed of predominantly calcite crystals with a little amount of aragonite and vaterite crystals. The maximum yield of calcite precipitation was achievable with calcium chloride followed by calcium nitrate as a calcium source. The results of present study may be applicable to media preparation during efficient MICCP process.

  15. Calcium signals can freely cross the nuclear envelope in hippocampal neurons: somatic calcium increases generate nuclear calcium transients

    Directory of Open Access Journals (Sweden)

    Bading Hilmar

    2007-07-01

    Full Text Available Abstract Background In hippocampal neurons, nuclear calcium signaling is important for learning- and neuronal survival-associated gene expression. However, it is unknown whether calcium signals generated by neuronal activity at the cell membrane and propagated to the soma can unrestrictedly cross the nuclear envelope to invade the nucleus. The nuclear envelope, which allows ion transit via the nuclear pore complex, may represent a barrier for calcium and has been suggested to insulate the nucleus from activity-induced cytoplasmic calcium transients in some cell types. Results Using laser-assisted uncaging of caged calcium compounds in defined sub-cellular domains, we show here that the nuclear compartment border does not represent a barrier for calcium signals in hippocampal neurons. Although passive diffusion of molecules between the cytosol and the nucleoplasm may be modulated through changes in conformational state of the nuclear pore complex, we found no evidence for a gating mechanism for calcium movement across the nuclear border. Conclusion Thus, the nuclear envelope does not spatially restrict calcium transients to the somatic cytosol but allows calcium signals to freely enter the cell nucleus to trigger genomic events.

  16. Calcium signals can freely cross the nuclear envelope in hippocampal neurons: somatic calcium increases generate nuclear calcium transients

    Science.gov (United States)

    Eder, Anja; Bading, Hilmar

    2007-01-01

    Background In hippocampal neurons, nuclear calcium signaling is important for learning- and neuronal survival-associated gene expression. However, it is unknown whether calcium signals generated by neuronal activity at the cell membrane and propagated to the soma can unrestrictedly cross the nuclear envelope to invade the nucleus. The nuclear envelope, which allows ion transit via the nuclear pore complex, may represent a barrier for calcium and has been suggested to insulate the nucleus from activity-induced cytoplasmic calcium transients in some cell types. Results Using laser-assisted uncaging of caged calcium compounds in defined sub-cellular domains, we show here that the nuclear compartment border does not represent a barrier for calcium signals in hippocampal neurons. Although passive diffusion of molecules between the cytosol and the nucleoplasm may be modulated through changes in conformational state of the nuclear pore complex, we found no evidence for a gating mechanism for calcium movement across the nuclear border. Conclusion Thus, the nuclear envelope does not spatially restrict calcium transients to the somatic cytosol but allows calcium signals to freely enter the cell nucleus to trigger genomic events. PMID:17663775

  17. Impact of calcium sulphate and calcium carbide on nitrogen use efficiency of wheat in normal and saline sodic soils

    Directory of Open Access Journals (Sweden)

    I.A. Mahmood

    2009-05-01

    Full Text Available pot experiment was conducted to study the effect of calcium as CaSO4 or CaC2 (20 mg Ca kg-1 of soil from each source on N use efficiency of wheat (Triticum aestivum L. var. Inqlab-91 under normal (ECe=0.7 dS m-1, SAR=4.37 and pH=8.1 and saline-sodic soils (ECe=8.7 dS m-1, SAR=21.43 and pH=9.2 in glass house at National Agricultural Research Centre, Islamabad during Kharif season 2007-08. The crop was grown to maturity and data on tillering, plant height, panicle length, grains spike-1, straw and grain yields were recorded at the time of crop harvest. A considerable reduction in plant height (38% and grain yield (44% was observed when grown in saline-sodic soil (ECe=8.7 dS m-1 as compared to normal soil (ECe=0.7 dS m-1 while N application significantly improved plant growth and yield in both conditions. Among the treatments, N application even at lower rate supplemented with calcium as CaSO4, CaC2 or their mixture (1:1 showed better performance than that of straight N application in both soils. A 41 to 53% increase in plant growth and 36 to 44% in grain yield over control (without N were observed through N fertilization at 25 and 50 mg kg-1 of soil supplemented with calcium as CaC2 in salinesodic soil. Similarly, calcium as CaSO4 application also caused a considerable improvement in plant growth (34 to 52% and grain yield (25 to 43%. However, the effect of mixture application of CaSO4 and CaC2 (1:1 on plant growth and yield was comparatively more pronounced for both the soils. Interestingly, lower dose ofN (25 mg kg-1 with calcium as CaC2 alone or in combination with CaSO4 (1:1 supplementation showed statistically equal performance to that of higher dose (N=50 mg kg-1 alone. Tissue Na+ significantly decreased while K+ and Ca2+ concentrations were elevated due to N application along with calcium nutrition. Maximum N uptake and apparent N recovery were revealed from treatments where N was applied @ 50 mg kg-1 soil supplemented with calcium as CaC2

  18. Induced calcium carbonate precipitation using Bacillus species.

    Science.gov (United States)

    Seifan, Mostafa; Samani, Ali Khajeh; Berenjian, Aydin

    2016-12-01

    Microbially induced calcium carbonate precipitation is an emerging process for the production of self-healing concrete. This study was aimed to investigate the effects and optimum conditions on calcium carbonate biosynthesis. Bacillus licheniformis, Bacillus sphaericus, yeast extract, urea, calcium chloride and aeration were found to be the most significant factors affecting the biomineralization of calcium carbonate. It was noticed that the morphology of microbial calcium carbonate was mainly affected by the genera of bacteria (cell surface properties), the viscosity of the media and the type of electron acceptors (Ca2+). The maximum calcium carbonate concentration of 33.78 g/L was achieved at the optimum conditions This value is the highest concentration reported in the literature.

  19. Calcium excretion in feces of ungulates.

    Science.gov (United States)

    Schryver, H F; Foose, T J; Williams, J; Hintz, H F

    1983-01-01

    1. Fecal excretion of calcium was examined in 122 individual ungulates representing 7 species of Equidae, 3 species of Tapiridae, 3 species of Rhinocerotidae, 2 species of Elephantidae, 2 species of Hippopotamidae, 12 species of Bovidae, 2 species of Cervidae, 3 species of Camellidae and 1 species of Giraffidae. 2. Animals were fed timothy hay, a low calcium diet or alfalfa hay, a high calcium diet. 3. In a few cases oat straw or prairie hay was used instead of timothy hay. 4. Samples of feces were obtained from individuals daily for 4 days following a 20 day dietary equilibration period. 5. Feces of equids, tapirs, rhinoceros and elephants had a lower calcium concentration and a lower Ca/P ratio than feces of ruminants when the animals were fed diets of equivalent calcium content. 6. The findings suggest that the non-ruminant ungulate equids, tapirs, rhinoceros and elephants absorb a larger proportion of dietary calcium than ruminants do.

  20. Binding of calcium and carbonate to polyacrylates.

    Science.gov (United States)

    Tribello, Gareth A; Liew, CheeChin; Parrinello, Michele

    2009-05-21

    Polyacrylate molecules can be used to slow the growth of calcium carbonate. However, little is known about the mechanism by which the molecules impede the growth rate. A recent computational study (Bulo et al. Macromolecules 2007, 40, 3437) used metadynamics to investigate the binding of calcium to polyacrylate chains and has thrown some light on the coiling and precipitation of these polymers. We extend these simulations to examine the binding of calcium and carbonate to polyacrylate chains. We show that calcium complexed with both carbonate and polyacrylate is a very stable species. The free energies of calcium-carbonate-polyacrylate complexes, with different polymer configurations, are calculated, and differences in the free energy of the binding of carbonate are shown to be due to differences in the amount of steric hindrance about the calcium, which prevents the approach of the carbonate ion.

  1. WAYS TO CORRECT CALCIUM DEFFICIT AMONG CHILDREN

    Directory of Open Access Journals (Sweden)

    N.I. Taibulatov

    2007-01-01

    Full Text Available The article is dedicated to the urgent issue of the pediatrics — calcium deficit among children. The authors provide modern data on the scheme of the normal calcium exchange in the human body. They also review the main diseases related to the disorders of the pho sphorocalcic metabolism, requiring prompt prevention and treatment by calcium based medications. The researchers stress the diseases of the musculoskeletal system, as insufficient calcium, phosphorus and vitamins supply of the child's body chiefly effects the state of the skeletal and muscular tissue. They give recommendations how to use the vitamin and mineral complex to correct calcium deficit.Key words: calcium deficit, diseases of the musculoskeletal system, vitamin and mineral complex, children.

  2. CD44v10, osteopontin and lymphoma growth retardation by a CD44v10-specific antibody.

    Science.gov (United States)

    Megaptche, Amelie Pajip; Erb, Ulrike; Büchler, Markus Wolfgang; Zöller, Margot

    2014-09-01

    Blockade of CD44 is considered a therapeutic option for the elimination of leukemia-initiating cells. However, the application of anti-panCD44 can be burdened by severe side effects. We determined whether these side effects could be avoided by replacing anti-panCD44 with CD44 variant isoform (CD44v)-specific antibodies in CD44v-positive hematological malignancies using the EL4 thymoma and CD44v10-transfected EL4 (EL4-v10) as models. Subcutaneous growth of EL4 and EL4-v10 was equally well inhibited by the anti-panCD44 and anti-CD44v10 antibodies, respectively. Ex vivo analysis indicated that natural killer cytotoxicity and antibody-dependent cellular cytotoxicity were the main effector mechanisms. Under local inflammation, the efficacy of anti-CD44v10 prolonged the survival time twofold compared with untreated, EL4-v10 tumor-bearing mice, and this was due to inflammation-induced expression of osteopontin (OPN). A high level of OPN in EL4-v10 tumors supported leukocyte recruitment and tumor-infiltrating T-cell activation. Taken together, in hematological malignancies expressing CD44v, anti-panCD44 can be replaced by CD44v-specific antibodies without a loss in efficacy. Furthermore, CD44v10-specific antibodies appear particularly advantageous in cutaneous leukemia therapy, as CD44v10 binding of OPN drives leukocyte recruitment and activation.

  3. Calcium dobesilate: pharmacology and future approaches.

    Science.gov (United States)

    Tejerina, T; Ruiz, E

    1998-09-01

    1. Calcium dobesilate (2,5-dihydroxybenzene sulfonate) is a drug commonly used in the treatment of diabetic retinopathy and chronic venous insufficiency. 2. The pharmacology of calcium dobesilate reveals its ability to decrease capillary permeability, as well as platelet aggregation and blood viscosity. 3. Furthermore, recent data show that calcium dobesilate increases endothelium-dependent relaxation owing to an increase in nitric oxide synthesis.

  4. Presynaptic calcium dynamics of learning neurons

    OpenAIRE

    Meyer-Hermann, Michael; Erler, Frido; Soff, Gerhard

    2002-01-01

    We present a new model for the dynamics of the presynaptic intracellular calcium concentration in neurons evoked by various stimulation protocols. The aim of the model is twofold: We want to discuss the calcium transients during and after specific stimulation protocols as they are used to induce long-term-depression and long-term-potentiation. In addition we would like to provide a general tool which allows the comparison of different calcium experiments. This may help to draw conclusions on ...

  5. Protein-Mediated Precipitation of Calcium Carbonate

    OpenAIRE

    Izabela Polowczyk; Anna Bastrzyk; Marta Fiedot

    2016-01-01

    Calcium carbonate is an important component in exoskeletons of many organisms. The synthesis of calcium carbonate was performed by mixing dimethyl carbonate and an aqueous solution of calcium chloride dihydrate. The precipitation product was characterized by means of scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) measurements. In addition, the turbidity of the reaction solution was acquire...

  6. Side population cells from HXO-Rb44 retinoblastoma cell line have cancer-initiating property.

    Science.gov (United States)

    She, Jun-Jun; Zhang, Peng-Ge; Che, Xiang-Ming; Wang, Xuan; Wang, Zi-Ming

    2011-01-01

    To ascertain whether side population (SP) cells in HXO-Rb44 retinoblastoma cell line have cancer stem cell-like property in vitro and in vivo. We analyzed and sorted SP from HXO-Rb44 retinoblastoma cell line by Hoechst 33342 staining on flow cytometry. SP and NSP cells were determined their ability of proliferation and self-renewal by SP reanalysis, soft agar assay and tumor sphere assay in vitro. Clone formation was detected by seeding HXO-Rb44 and HXO-Rb44 -RFP cells into soft agar. The expression of ABCG2, MDRI, Bmi-1 and Oct-4 was determined by RT-PCR between SP and non-SP (NSP) cells. Moreover, they were injected into nude mice to determine their tumorigency in vivo. SP from HXO-Rb44 retinoblastoma cell line could grow clonally in soft agar assays and form tumor spheres from single cells in conditioned media. The expressions of ABCG2, MDRI, Bmi-1 and Oct-4 were significantly higher in SP than NSP cells. As few as SP cells resulted in tumor formation in 6 of 12 injected sites, however, the injection of NSP cells failed to form new tumor. SP cells isolated by Hoechst 33342 from the HXO-Rb44 retinoblastoma cell line had property of high tumorigency in vivo and in vitro. Therefore, SP might be a target while developing retinoblastoma therapies.

  7. Mechanical Properties of a Calcium Dietary Supplement, Calcium Fumarate Trihydrate.

    Science.gov (United States)

    Sun, Shijing; Henke, Sebastian; Wharmby, Michael T; Yeung, Hamish H-M; Li, Wei; Cheetham, Anthony K

    2015-12-07

    The mechanical properties of calcium fumarate trihydrate, a 1D coordination polymer considered for use as a calcium source for food and beverage enrichment, have been determined via nanoindentation and high-pressure X-ray diffraction with single crystals. The nanoindentation studies reveal that the elastic modulus (16.7-33.4 GPa, depending on crystallographic orientation), hardness (1.05-1.36 GPa), yield stress (0.70-0.90 GPa), and creep behavior (0.8-5.8 nm/s) can be rationalized in view of the anisotropic crystal structure; factors include the directionality of the inorganic Ca-O-Ca chain and hydrogen bonding, as well as the orientation of the fumarate ligands. High-pressure single-crystal X-ray diffraction studies show a bulk modulus of ∼ 20 GPa, which is indicative of elastic recovery intermediate between small molecule drug crystals and inorganic pharmaceutical ingredients. The combined use of nanoindentation and high-pressure X-ray diffraction techniques provides a complementary experimental approach for probing the critical mechanical properties related to tableting of these dietary supplements.

  8. Calcium dependence of inactivation of calcium release from the sarcoplasmic reticulum in skeletal muscle fibers.

    Science.gov (United States)

    Simon, B J; Klein, M G; Schneider, M F

    1991-03-01

    The steady-state calcium dependence of inactivation of calcium release from the sarcoplasmic reticulum was studied in voltage-clamped, cut segments of frog skeletal muscle fibers containing two calcium indicators, fura-2 and anti-pyrylazo III (AP III). Fura-2 fluorescence was used to monitor resting calcium and relatively small calcium transients during small depolarizations. AP III absorbance signals were used to monitor larger calcium transients during larger depolarizations. The rate of release (Rrel) of calcium from the sarcoplasmic reticulum was calculated from the calcium transients. The equilibrium calcium dependence of inactivation of calcium release was determined using 200-ms prepulses of various amplitudes to elevate [Ca2+] to various steady levels. Each prepulse was followed by a constant test pulse. The suppression of peak Rrel during the test pulse provided a measure of the extent of inactivation of release at the end of the prepulse. The [Ca2+] dependence of inactivation indicated that binding of more than one calcium ion was required to inactivate each release channel. Half-maximal inactivation was produced at a [Ca2+] of approximately 0.3 microM. Variation of the prepulse duration and amplitude showed that the suppression of peak release was consistent with calcium-dependent inactivation of calcium release but not with calcium depletion. The same calcium dependence of inactivation was obtained using different amplitude test pulses to determine the degree of inactivation. Prepulses that produced near maximal inactivation of release during the following test pulse produced no suppression of intramembrane charge movement during the test pulse, indicating that inactivation occurred at a step beyond the voltage sensor for calcium release. Three alternative set of properties that were assumed for the rapidly equilibrating calcium-binding sites intrinsic to the fibers gave somewhat different Rrel records, but gave very similar calcium dependence of

  9. /sup 3/H)Nitrendipine binding to calcium channels in bovine and rat pituitary

    Energy Technology Data Exchange (ETDEWEB)

    Titeler, M.; De Souza, E.B.; Kuhar, M.J.

    1985-06-01

    (/sup 3/H)Nitrendipine was used to label sites in homogenates of bovine anterior and neurointermediate lobes of the pituitary gland. The amount of specific binding in the anterior lobe was 1.82 +/- 0.30 pmol/g wet weight of tissue and the KD was 1.44 +/- 0.02 X 10(-10) M. Preliminary experiments indicated a similar amount of binding in bovine neurointermediate lobe. In competition studies nimodipine and nisoldipine (two potent voltage-sensitive calcium channel blockers) displayed IC50 values of 1.6 and 6.8 X 10(-10) M, respectively. Verapamil and the verapamil-like calcium channel blockers D-600 and tiapamil competed in a complex manner for the (/sup 3/H)nitrendipine specific binding to bovine anterior pituitary homogenates. Autoradiographical studies demonstrated specific (/sup 3/H)nitrendipine binding sites distributed approximately equally in the anterior and posterior lobes, but not in the intermediate lobe of the rat pituitary. In general the properties of (/sup 3/H)nitrendipine binding in the pituitary tissue resemble strongly the properties of (/sup 3/H)nitrendipine binding in the brain which is believed to be to voltage-sensitive calcium channels. These results provide support for the hypothesis that calcium channels are involved in pituitary hormone secretion and that drugs that interact with calcium channels may modulate the secretory process directly at the level of the pituitary.

  10. Protein-Mediated Precipitation of Calcium Carbonate.

    Science.gov (United States)

    Polowczyk, Izabela; Bastrzyk, Anna; Fiedot, Marta

    2016-11-22

    Calcium carbonate is an important component in exoskeletons of many organisms. The synthesis of calcium carbonate was performed by mixing dimethyl carbonate and an aqueous solution of calcium chloride dihydrate. The precipitation product was characterized by means of scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) measurements. In addition, the turbidity of the reaction solution was acquired to monitor the kinetics of the calcium carbonate structure's growth in the investigated system. In this study, samples of CaCO₃ particles obtained with individual proteins, such as ovalbumin, lysozyme, and a mixture of the proteins, were characterized and compared with a control sample, i.e., synthesized without proteins. The obtained data indicated that the addition of ovalbumin to the reaction changed the morphology of crystals from rhombohedral to 'stack-like' structures. Lysozyme, however, did not affect the morphology of calcium carbonate, yet the presence of the protein mixture led to the creation of more complex composites in which the calcium carbonate crystals were constructed in protein matrices formed by the ovalbumin-lysozyme interaction. It was also observed that in the protein mixture, ovalbumin has a major influence on the CaCO₃ formation through a strong interaction with calcium ions, which leads to the coalescence and creation of a steric barrier reducing particle growth. The authors proposed a mechanism of calcium carbonate grain growth in the presence of both proteins, taking into account the interaction of calcium ions with the protein.

  11. Diuretics and disorders of calcium homeostasis.

    Science.gov (United States)

    Grieff, Marvin; Bushinsky, David A

    2011-11-01

    Diuretics commonly are administered in disorders of sodium balance. Loop diuretics inhibit the Na-K-2Cl transporter and also increase calcium excretion. They are often used in the treatment of hypercalcemia. Thiazide diuretics block the thiazide-sensitive NaCl transporter in the distal convoluted tubule, and can decrease calcium excretion. They are often used in the treatment of nephrolithiasis. Carbonic anhydrase inhibitors decrease bicarbonate absorption and the resultant metabolic acidosis can increase calcium excretion. Their use can promote nephrocalcinosis and nephrolithiasis. This review will address the use of diuretics on disorders of calcium homeostasis. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. [ZINK IS ACTIVATOR OF ENTERAL CALCIUM METABOLISM].

    Science.gov (United States)

    Polyakova, E P; Ksenofontov, D A; Revyakin, A O; Ivanov, A A

    2015-01-01

    Experiments on goats and rabbits showed that zinc supplement to the diet leads to calcium concentration rise in muscle, bone and blood of animals. However, this rise was not adequate to increase in.zinc consumption. The bulk of alimentary zinc stayed in soluble fraction, dense endogen fraction and infusoria fraction of digesta and stimulated calcium release from food particles, it's accumulation in digesta fractions and calcium utilization on the whole. Authors estimate animal digesta as homeostatic, spatial organized, endogenic formation in which zinc and calcium are functionally dependent through enteral mucosa.

  13. The Electronic Structure of Calcium

    DEFF Research Database (Denmark)

    Jan, J.-P.; Skriver, Hans Lomholt

    1981-01-01

    .149 Ryd, respectively, relative to the s band, give the best possible agreement. Under increasing pressure the s and p electrons are found to transfer into the d band, and Ca undergoes metal-semimetal-metal electronic transitions. Calculations of the bandstructure and the electronic pressure, including......The electronic structure of calcium under pressure is re-examined by means of self-consistent energy band calculations based on the local density approximation and using the linear muffin-tin orbitals (LMTO) method with corrections to the atomic sphere approximation included. At zero pressure...

  14. Distinct Calcium Sources Support Multiple Modes of Synaptic Release from Cranial Sensory Afferents.

    Science.gov (United States)

    Fawley, Jessica A; Hofmann, Mackenzie E; Andresen, Michael C

    2016-08-24

    sources: CaVs and TRPV1. We demonstrate that calcium segregation distinguishes three vesicle release mechanisms. Most surprisingly, asynchronous release is associated with CaV and not TRPV1 calcium entry. This reveals that asynchronous release is an additional and separate phenotypic marker of unmyelinated afferents rather than operated by TRPV1. The functional independence of the two calcium sources expands the regulatory repertoire of transmission and imbues these inputs with additional modulation targets for synaptic release not present at conventional CaV synapses. Peptides and lipid mediators may target one or both of these calcium sources at afferent terminals within the solitary tract nucleus to independently modify release from distinct, functionally segregated vesicle pools. Copyright © 2016 the authors 0270-6474/16/368957-10$15.00/0.

  15. Magnetoelectric coupling in 4,4'-stilbenedinitrene

    Science.gov (United States)

    Günaydın-Şen, Ö.; Chen, P.; Fosso-Tande, J.; Allen, T. L.; Cherian, J.; Tokumoto, T.; Lahti, P. M.; McGill, S.; Harrison, R. J.; Musfeldt, J. L.

    2013-05-01

    We investigated the optical properties of 4,4'-stilbenedinitrene at low temperature and in high magnetic fields and compared the results with complementary first principles calculations. Both physical tuning parameters allow us to manipulate the singlet-triplet equilibrium, and by doing so, control the optical contrast (which is on the order of -2.5 × 102 cm-1 at 555 nm and 35 T). Moreover, analysis of the magneto-optical response using a combined population and Beer's law framework reveals the singlet-triplet spin gap and identifies particular features in the absorption difference spectrum as deriving from singlet or triplet state excitations. These findings deepen our understanding of coupling in open shell molecules and show how chemical structure modification can modulate charge-spin interactions in organic biradicals.

  16. 44-BWR WASTE PACKAGE LOADING CURVE EVALUATION

    Energy Technology Data Exchange (ETDEWEB)

    J.M. Scaglione

    2004-08-25

    The objective of this calculation is to evaluate the required minimum burnup as a function of initial boiling water reactor (BWR) assembly enrichment that would permit loading of spent nuclear fuel into the 44 BWR waste package configuration as provided in Attachment IV. This calculation is an application of the methodology presented in ''Disposal Criticality Analysis Methodology Topical Report'' (YMP 2003). The scope of this calculation covers a range of enrichments from 0 through 5.0 weight percent (wt%) U-235, and a burnup range of 0 through 40 GWd/MTU. This activity supports the validation of the use of burnup credit for commercial spent nuclear fuel applications. The intended use of these results will be in establishing BWR waste package configuration loading specifications. Limitations of this evaluation are as follows: (1) The results are based on burnup credit for actinides and selected fission products as proposed in YMP (2003, Table 3-1) and referred to as the ''Principal Isotopes''. Any change to the isotope listing will have a direct impact on the results of this report. (2) The results of 100 percent of the current BWR projected waste stream being able to be disposed of in the 44-BWR waste package with Ni-Gd Alloy absorber plates is contingent upon the referenced waste stream being sufficiently similar to the waste stream received for disposal. (3) The results are based on 1.5 wt% Gd in the Ni-Gd Alloy material and having no tuff inside the waste package. If the Gd loading is reduced or a process to introduce tuff inside the waste package is defined, then this report would need to be reevaluated based on the alternative materials.

  17. Cardioprotection mechanism of mangiferin on doxorubicin-induced rats: Focus on intracellular calcium regulation.

    Science.gov (United States)

    Agustini, Femmi Dwinda; Arozal, Wawaimuli; Louisa, Melva; Siswanto, Soni; Soetikno, Vivian; Nafrialdi, Nafrialdi; Suyatna, Franciscus

    2016-07-01

    The molecular mechanism of doxorubicin (DOX) cardiotoxicity involves overproduction of free radicals that leads to intracellular calcium dysregulation and apoptosis. Mangiferin (MGR), a naturally occurring glucosylxanthone, has antioxidant and cardioprotective properties. However, its cardioprotection mechanism has yet to be revealed. This study determines whether the cardioprotective effect of MGR is caused by its effect on intracellular calcium regulation. Male Sprague-Dawley rats were induced by DOX intraperitoneally with a total dose of 15 mg/kg bw. MGR was given orally at the doses of 30 and 60 mg/kg bw/d for seven consecutive weeks. The parameters examined were mRNA expression levels of proinflammatory cytokine gene (TNF-α), calcium regulatory gene (SERCA2a) and proapoptotic genes (caspase-9 and caspase-12), as well as cytosolic and mitochondrial calcium levels. Treatment with MGR at 60 mg/kg bw/d significantly decreased the mRNA expression levels of TNF-α by 44.55% and caspase-9 by 52.79%, as well as the cytosolic calcium level by 24.15% (p  0.05). Meanwhile, MGR 30 mg/kg bw/d gave insignificant results in all parameters. MGR protected against DOX-induced cardiac inflammation and apoptosis via down-regulation of proapoptotic and proinflammatory gene expressions, upregulation of SERCA2a gene expression, and normalization of cytosolic calcium level. Thus, the cardioprotective effect of MGR is at least in part due to the regulation of intracellular calcium homeostasis.

  18. Experiments on the formation of titanium-44 in supernovae; Experimente zur Entstehung von Titan-44 in Supernovae

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Konrad

    2012-11-01

    In this thesis the astrophysically interesting resonance triplet of the {sup 40}Ca({alpha},{gamma}){sup 44}Ti reaction at 4.5 MeV has been studied. For this purpose energies of proton and {alpha} beams provided by 3 MV Tandetron at Helmholtz-Zentrum Dresden-Rossendorf have been calibrated. Excitation functions of energy regions near the resonances and in-beam spectra of four different targets have been measured. The {sup 40}Ca(p,{gamma}){sup 41}Sc reaction has been used to scan the structure of the activated targets. Afterwards their activity has been measured in the underground laboratory Felsenkeller Dresden. Hence the sum of resonance strengths at laboratory {alpha} energies of 4497 and 4510 keV of (12.8{+-}2.3) eV has been determined as well as the sum of the total triplet strength, including 4523 keV, of (12.0{+-}2.0) eV. In the case of the first resonance, the uncertainty was decreased from 19% to 18 %. Furthermore the results of this work establish a basis for reaching much lower uncertainties in the future.

  19. Short communication: Urinary oxalate and calcium excretion by dogs and cats diagnosed with calcium oxalate urolithiasis

    NARCIS (Netherlands)

    Dijcker, J.C.; Kummeling, A.; Hagen-Plantinga, E.A.; Hendriks, W.H.

    2012-01-01

    Introduction Urine concentrations of oxalate and calcium play an important role in calcium oxalate (CaOx) urolith formation in dogs and cats, with high excretions of both substances increasing the chance of CaOx urolithiasis. In 17 CaOx-forming dogs, urine calcium:creatinine ratio (Ca:Cr) was found

  20. Impaired body calcium metabolism with low bone density and compensatory colonic calcium absorption in cecectomized rats

    NARCIS (Netherlands)

    Jongwattanapisan, P.; Suntornsaratoon, P.; Wongdee, K.; Dorkkam, N.; Krishnamra, N.; Charoenphandhu, N.

    2012-01-01

    An earlier study reported that cecal calcium absorption contributes less than 10% of total calcium absorbed by the intestine, although the cecum has the highest calcium transport rate compared with other intestinal segments. Thus, the physiological significance of the cecum pertaining to body

  1. Pharmacological modulation of mitochondrial calcium homeostasis.

    Science.gov (United States)

    Arduino, Daniela M; Perocchi, Fabiana

    2018-01-10

    Mitochondria are pivotal organelles in calcium (Ca2+ ) handling and signalling, constituting intracellular checkpoints for numerous processes that are vital for cell life. Alterations in mitochondrial Ca2+ homeostasis have been linked to a variety of pathological conditions and are critical in the etiology of several human diseases. Efforts have been taken to harness mitochondrial Ca2+ transport mechanisms for therapeutic intervention but pharmacological compounds that direct and selectively modulate mitochondrial Ca2+ homeostasis are currently lacking. New avenues have however emerged with the breakthrough discoveries on the genetic identification of the main players involved in mitochondrial Ca2+ influx and efflux pathways and with recent hints towards a deep understanding of the function of these molecular systems. Here, we review the current advances in the understanding of the mechanisms and regulation of mitochondrial Ca2+ homeostasis and its contribution to physiology and human disease. We also introduce and comment on the recent progresses towards a systems-level pharmacological targeting of mitochondrial Ca2+ homeostasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. Plasma membrane calcium pump and sodium-calcium exchanger in maintenance and control of calcium concentrations in platelets.

    Science.gov (United States)

    Juska, Alfonsas

    2010-01-29

    The purpose of this research was to elucidate the activity of the mechanisms responsible for control of cytosolic calcium concentration in platelets by modeling the time-course of the concentration changing in response to discharge of the intracellular stores or store-operated calcium entry (SOCE). The parameters estimated as a result of model fitting to experimental data are related to physiological or pathological state of the cells. It has been shown that: (a) the time-course is determined by the passive calcium fluxes and activities of the corresponding mechanisms; (b) the decline in the concentration (after its rise) develops due to activity of plasma membrane calcium ATPase (PMCA) both in the case of discharge of the stores of platelets contained in calcium-free medium and in the case of SOCE; (c) impulsive extrusion of calcium in response to its sudden influx, presumably, is the main function of PMCA; (d) the function of sodium-calcium exchanger (NCX) is to extrude calcium excess by permanent counteracting its influx. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  3. Calcium dobesilate in the treatment of diabetic retinopathy.

    Science.gov (United States)

    Garay, Ricardo P; Hannaert, Patrick; Chiavaroli, Carlo

    2005-01-01

    The incidence of diabetic retinopathy is still increasing in developed countries. Tight glycemic control and laser therapy reduce vision loss and blindness, but do not reverse existing ocular damage and only slow the progression of the disease. New pharmacologic agents that are currently under development and are specifically directed against clearly defined biochemical targets (i.e. aldose reductase inhibitors and protein kinase C-beta inhibitors) have failed to demonstrate significant efficacy in the treatment of diabetic retinopathy in clinical trials. In contrast, calcium dobesilate (2,5-dihydroxybenzenesulfonate), which was discovered more than 40 years ago and is registered for the treatment of diabetic retinopathy in more than 20 countries remains, to our knowledge, the only angioprotective agent that reduces the progression of this disease. An overall review of published studies involving calcium dobesilate (CLS 2210) depicts a rather 'non-specific' compound acting moderately, but significantly, on the various and complex disorders that contribute to diabetic retinopathy. Recent studies have shown that calcium dobesilate is a potent antioxidant, particularly against the highly damaging hydroxyl radical. In addition, it improves diabetic endothelial dysfunction, reduces apoptosis, and slows vascular cell proliferation.

  4. Pseudogout and Calcium Pyrophosphate Disease

    Directory of Open Access Journals (Sweden)

    Andrew Williamson

    2017-01-01

    Full Text Available History of present illness: A 53-year-old male presented with worsening right knee pain and swelling over the past 48 hours. He denied recent trauma to the knee, history of IV drug use, and recent illness. He had no history of diabetes, immunodeficiency, chronic steroids, rheumatologic disease, or knee replacement. He described the pain as sharp, non-radiating, and worse with movement. He was unable to walk due to pain. Significant findings: Radiographs of the knee showed multiple radio-dense lines paralleling the articular surface (see red arrows consistent with calcium pyrophosphate crystal deposition within the joint often seen in calcium pyrophosphate disease (CPPD also known as pseudogout. Discussion: Patients commonly present to the emergency department with non-traumatic joint pain. Arthrocentesis is an important diagnostic tool to evaluate for septic arthritis, gout, or pseudogout. Arthrocentesis can demonstrate crystals or abnormal cell count, gram stain, and culture.[1] In the evaluation of joint pain, plain films are usually obtained to evaluate for fracture, dislocation, effusion, or secondary signs of infection. In this case the classic x-ray supported the diagnosis of CPPD.2 The patient was found to have positively birefringent rhomboid shaped crystals consistent with pseudogout on arthrocentesis. Gram stain and culture were both negative. The patient was discharged with NSAIDs and had significant improvement in symptoms upon follow up with primary care physician in 3 days.

  5. Spatiotemporal intracellular calcium dynamics during cardiac alternans

    Science.gov (United States)

    Restrepo, Juan G.; Karma, Alain

    2009-09-01

    Cellular calcium transient alternans are beat-to-beat alternations in the peak cytosolic calcium concentration exhibited by cardiac cells during rapid electrical stimulation or under pathological conditions. Calcium transient alternans promote action potential duration alternans, which have been linked to the onset of life-threatening ventricular arrhythmias. Here we use a recently developed physiologically detailed mathematical model of ventricular myocytes to investigate both stochastic and deterministic aspects of intracellular calcium dynamics during alternans. The model combines a spatially distributed description of intracellular calcium cycling, where a large number of calcium release units are spatially distributed throughout the cell, with a full set of ionic membrane currents. The results demonstrate that ion channel stochasticity at the level of single calcium release units can influence the whole-cell alternans dynamics by causing phase reversals over many beats during fixed frequency pacing close to the alternans bifurcation. They also demonstrate the existence of a wide range of dynamical states. Depending on the sign and magnitude of calcium-voltage coupling, calcium alternans can be spatially synchronized or desynchronized, in or out of phase with action potential duration alternans, and the node separating out-of-phase regions of calcium alternans can be expelled from or trapped inside the cell. This range of states is found to be larger than previously anticipated by including a robust global attractor where calcium alternans can be spatially synchronized but out of phase with action potential duration alternans. The results are explained by a combined theoretical analysis of alternans stability and node motion using general iterative maps of the beat-to-beat dynamics and amplitude equations.

  6. [Food sources and average intake of calcium in a representative sample of Spanish schoolchildren].

    Science.gov (United States)

    Ortega, R M; López-Sobaler, A M; Jiménez Ortega, A I; Navia Lombán, B; Ruiz-Roso Calvo de Mora, B; Rodríguez-Rodríguez, E; López Plaza, B

    2012-01-01

    There is controversy about the adequacy of calcium intake to that recommended in Spanish schoolchildren. Some studies indicate that the intake is inadequate in a variable percentage of children, while others insist on the danger of an excessive intake in a huge percentage of this population. To assess calcium intake and food sources of this nutrient in a representative sample of Spanish children and to judge the adequacy of its contribution to the coverage of recommended intakes. 903 schoolchildren (7 to 11 years) from 10 Spanish provinces (Tarragona, Caceres, Burgos, Guadalajara, Valencia, Salamanca, Cordoba, Vizcaya, Lugo and Madrid) were studied. They constituted a representative sample of the Spanish schoolchildren population. The energy and nutrient intake was determined using a "Food record questionnaire" for 3 days, including a Sunday. Calcium intake was compared with the recommended intakes (RI) for the mineral. Weight and height were recorded and body mass index (BMI) calculated. In the studied group (55.3% girls and 44.7% of children), 30.7% had an excess body weight (23.3% overweight and 7.4% obesity). Calcium intake was 859.9 ± 249.2 mg / day (79.5% of the recommendations). 76.7% of children had intakes below 100% of those recommended and 40.1% below of 67% of RI. The ratios calcium/phosphorus (0.74 ± 0.21) and calcium/protein (10.1 ± 2.8) and the index of nutritional quality for calcium (0.78 ± 0.29) were lower than recommended in 91.6%, 99.8% and 81.1% of children, respectively. Dietary calcium came from dairy products (64.7%), dietetic products and infant formulae (7.6%), cereals (7.3%), vegetables (3.5%), fruits (3.4%), pre-cooked meals (3.3%), meats (2.8%), fishes (2.8%) and pulses (2.2%), with no differences by gender. Calcium intake was lower than recommended in 76.7% of the children and 40.1% had insufficient intake (calcium source was dairy products (64.7%), increase consumption of this food group is recommended, especially in the 37.1% of

  7. Recruited renin-containing renal microvascular cells demonstrate the calcium paradox regulatory phenotype

    Directory of Open Access Journals (Sweden)

    MacGriff S

    2014-01-01

    Full Text Available Spencer MacGriff,1 Richard E Woo,1 M Cecilia Ortiz-Capisano,1 Douglas K Atchison,1,2 William H Beierwaltes1,2 1Department of Internal Medicine, Hypertension and Vascular Research Division, Henry Ford Hospital, 2Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA Abstract: Renin is the critical regulatory enzyme for production of angiotensin (Ang-II, a potent vasoconstrictor involved in regulating blood pressure and in the pathogenesis of hypertension. Chronic sodium deprivation enhances renin secretion from the kidney, due to recruitment of additional cells from the afferent renal microvasculature to become renin-producing rather than just increasing release from existing juxtaglomerular (JG cells. JG cells secrete renin inversely proportional to extra- and intracellular calcium, a unique phenomenon characteristic of the JG regulatory phenotype known as the “calcium paradox.” It is not known if renin secreted from recruited renin-containing cells is regulated similarly to native JG cells, and therefore acquires this JG cell phenotype. We hypothesized that non-JG cells in renal microvessels recruited to produce renin in response to chronic dietary sodium restriction would demonstrate the calcium paradox, characteristic of the JG cell phenotype. Histology showed recruitment of upstream arteriolar renin in response to sodium restriction compared to normal-diet rats. Renin fluorescence intensity increased 53% in cortices of sodium-restricted rats (P<0.001. We measured renin release from rat afferent microvessels, isolated using iron oxide nanopowder and incubated in either normal or low-calcium media. Basal renin release from normal sodium-diet rat microvessels in normal calcium media was 298.1±44.6 ng AngI/mL/hour/mg protein, and in low-calcium media increased 39% to 415.9±71.4 ng AngI/mL/hour/mg protein (P<0.025. Renin released from sodium-restricted rat microvessels increased 50% compared to samples from

  8. Calcium bioavailability from bovine milk and dairy products in premenopausal women using intrinsic and extrinsic labeling techniques.

    Science.gov (United States)

    Nickel, K P; Martin, B R; Smith, D L; Smith, J B; Miller, G D; Weaver, C M

    1996-05-01

    Stable isotopes were used to compare calcium fractional absorption from intrinsically and extrinsically labeled bovine milk as well as intrinsically labeled dairy product and cheese analogue. Healthy Caucasian women were fed a controlled diet for 4 d during the follicular phase of their menstrual cycle. With breakfast on the third day, participants ingested milk containing 44Ca (intrinsic) and 42CaCl2 (extrinsic) or dairy products containing 44Ca. Total feces were collected for 2 d prior to and 10 d after isotope ingestion. Polyethylene glycol was administered to monitor completeness of fecal collections. Total calcium was determined by atomic absorption spectrophotometry, and isotopic abundance was determined by high resolution fast atom bombardment mass spectrometry. Fractional absorption was determined as the difference between the administered isotopic dose and the quantity of 44Ca or 42Ca excreted in feces. The fractional absorption of calcium from milk was not affected by the method of labeling, lactose content, fermentation or the chemical form of calcium in dairy products or cheese analogue.

  9. Effect of Three Calmodulin Antagonists on Subpopulations of CD44 ...

    African Journals Online (AJOL)

    MB-468 breast cancer cell lines. ... cells, CD44 and CD24, markers of breast cancer .... marker expression. They demonstrated that the cancer cells with the immunophenotype,. CD44+CD24-, were able to initiate tumor whereas other phenotype.

  10. When Neurons Encounter Nanoobjects: Spotlight on Calcium Signalling

    Directory of Open Access Journals (Sweden)

    Davide Lovisolo

    2014-09-01

    Full Text Available Nanosized objects are increasingly present in everyday life and in specialized technological applications. In recent years, as a consequence of concern about their potential adverse effects, intense research effort has led to a better understanding of the physicochemical properties that underlie their biocompatibility or potential toxicity, setting the basis for a rational approach to their use in the different fields of application. Among the functional parameters that can be perturbed by interaction between nanoparticles (NPs and living structures, calcium homeostasis is one of the key players and has been actively investigated. One of the most relevant biological targets is represented by the nervous system (NS, since it has been shown that these objects can access the NS through several pathways; moreover, engineered nanoparticles are increasingly developed to be used for imaging and drug delivery in the NS. In neurons, calcium homeostasis is tightly regulated through a complex set of mechanisms controlling both calcium increases and recovery to the basal levels, and even minor perturbations can have severe consequences on neuronal viability and function, such as excitability and synaptic transmission. In this review, we will focus on the available knowledge about the effects of NPs on the mechanisms controlling calcium signalling and homeostasis in neurons. We have taken into account the data related to environmental NPs, and, in more detail, studies employing engineered NPs, since their more strictly controlled chemical and physical properties allow a better understanding of the relevant parameters that determine the biological responses they elicit. The literature on this specific subject is all quite recent, and we have based the review on the data present in papers dealing strictly with nanoparticles and calcium signals in neuronal cells; while they presently amount to about 20 papers, and no related review is available, the field is

  11. Targeted Learning

    CERN Document Server

    van der Laan, Mark J

    2011-01-01

    The statistics profession is at a unique point in history. The need for valid statistical tools is greater than ever; data sets are massive, often measuring hundreds of thousands of measurements for a single subject. The field is ready to move towards clear objective benchmarks under which tools can be evaluated. Targeted learning allows (1) the full generalization and utilization of cross-validation as an estimator selection tool so that the subjective choices made by humans are now made by the machine, and (2) targeting the fitting of the probability distribution of the data toward the targe

  12. Inositol 1, 4, 5-trisphosphate-dependent nuclear calcium signals regulate angiogenesis and cell motility in triple negative breast cancer.

    Directory of Open Access Journals (Sweden)

    Erika Guimarães

    Full Text Available Increases in nuclear calcium concentration generate specific biological outcomes that differ from those resulting from increased cytoplasmic calcium. Nuclear calcium effects on tumor cell proliferation are widely appreciated; nevertheless, its involvement in other steps of tumor progression is not well understood. Therefore, we evaluated whether nuclear calcium is essential in other additional stages of tumor progression, including key steps associated with the formation of the primary tumor or with the metastatic cascade. We found that nuclear calcium buffering impaired 4T1 triple negative breast cancer growth not just by decreasing tumor cell proliferation, but also by enhancing tumor necrosis. Moreover, nuclear calcium regulates tumor angiogenesis through a mechanism that involves the upregulation of the anti-angiogenic C-X-C motif chemokine 10 (CXCL10-IP10. In addition, nuclear calcium buffering regulates breast tumor cell motility, culminating in less cell invasion, likely due to enhanced vinculin expression, a focal adhesion structural protein. Together, our results show that nuclear calcium is essential for triple breast cancer angiogenesis and cell migration and can be considered as a promising strategic target for triple negative breast cancer therapy.

  13. Optogenetic monitoring identifies phosphatidylthreonine-regulated calcium homeostasis in Toxoplasma gondii

    Directory of Open Access Journals (Sweden)

    Arunakar Kuchipudi

    2016-05-01

    Full Text Available Toxoplasma gondii is an obligate intracellular parasite, which inflicts acute as well as chronic infections in a wide range of warm-blooded vertebrates. Our recent work has demonstrated the natural occurrence and autonomous synthesis of an exclusive lipid phosphatidylthreonine in T. gondii. Targeted gene disruption of phosphatidylthreonine synthase impairs the parasite virulence due to unforeseen attenuation of the consecutive events of motility, egress and invasion. However, the underlying basis of such an intriguing phenotype in the parasite mutant remains unknown. Using an optogenetic sensor (gene-encoded calcium indicator, GCaMP6s, we show that loss of phosphatidylthreonine depletes calcium stores in intracellular tachyzoites, which leads to dysregulation of calcium release into the cytosol during the egress phase of the mutant. Consistently, the parasite motility and egress phenotypes in the mutant can be entirely restored by ionophore-induced mobilization of calcium. Collectively, our results suggest a novel regulatory function of phosphatidylthreonine in calcium signaling of a prevalent parasitic protist. Moreover, our application of an optogenetic sensor to monitor subcellular calcium in a model intracellular pathogen exemplifies its wider utility to other entwined systems.

  14. Calcium homeostasis and signaling in fungi and their relevance for pathogenicity of yeasts and filamentous fungi

    Directory of Open Access Journals (Sweden)

    Renata Tisi

    2016-09-01

    Full Text Available Though fungi show peculiarities in the purposes and specific traits of calcium signaling pathways, the general scheme and the most important players are well conserved if compared to higher eukaryotes. This provides a powerful opportunity either to investigate shared features using yeast as a model or to exploit fungal specificities as potential targets for antifungal therapies. The sequenced genomes from yeast Saccharomyces cerevisiae, Schizosaccharomyces pombe and the filamentous fungus Neurospora crassa were already published more than ten years ago. More recently the genome sequences of filamentous fungi of Aspergillus genus, some of which threatening pathogens, and dimorphic fungi Ustilago maydis were published, giving the chance to identify several proteins involved in calcium signaling based on their homology to yeast or mammalian counterparts. Nonetheless, unidentified calcium transporters are still present in these organisms which await to be molecularly characterized. Despite the relative simplicity in yeast calcium machinery and the availability of sophisticated molecular tools, in the last years, a number of new actors have been identified, albeit not yet fully characterized. This review will try to describe the state of the art in calcium channels and calcium signaling knowledge in yeast, with particular attention to the relevance of this knowledge with respect to pathological fungi.

  15. Calcium Blood Test: MedlinePlus Lab Test Information

    Science.gov (United States)

    ... this page: https://medlineplus.gov/labtests/calciumbloodtest.html Calcium Blood Test To use the sharing features on this page, please enable JavaScript. What is a Calcium Blood Test? A calcium blood test measures the ...

  16. Calcium channel regulator Mid1 links TORC2-mediated changes in mitochondrial respiration to autophagy

    OpenAIRE

    Vlahakis, Ariadne; Lopez Muniozguren, Nerea; Powers, Ted

    2016-01-01

    Autophagy is a catabolic process that recycles cytoplasmic contents and is crucial for cell survival during stress. The target of rapamycin (TOR) kinase regulates autophagy as part of two distinct protein complexes, TORC1 and TORC2. TORC1 negatively regulates autophagy according to nitrogen availability. In contrast, TORC2 functions as a positive regulator of autophagy during amino acid starvation, via its target kinase Ypk1, by repressing the activity of the calcium-dependent phosphatase cal...

  17. D1 receptors physically interact with N-type calcium channels to regulate channel distribution and dendritic calcium entry.

    Science.gov (United States)

    Kisilevsky, Alexandra E; Mulligan, Sean J; Altier, Christophe; Iftinca, Mircea C; Varela, Diego; Tai, Chao; Chen, Lina; Hameed, Shahid; Hamid, Jawed; Macvicar, Brian A; Zamponi, Gerald W

    2008-05-22

    Dopamine signaling through D1 receptors in the prefrontal cortex (PFC) plays a critical role in the maintenance of higher cognitive functions, such as working memory. At the cellular level, these functions are predicated to involve alterations in neuronal calcium levels. The dendrites of PFC neurons express D1 receptors and N-type calcium channels, yet little information exists regarding their coupling. Here, we show that D1 receptors potently inhibit N-type channels in dendrites of rat PFC neurons. Using coimmunoprecipitation, we demonstrate the existence of a D1 receptor-N-type channel signaling complex in this region, and we provide evidence for a direct receptor-channel interaction. Finally, we demonstrate the importance of this complex to receptor-channel colocalization in heterologous systems and in PFC neurons. Our data indicate that the N-type calcium channel is an important physiological target of D1 receptors and reveal a mechanism for D1 receptor-mediated regulation of cognitive function in the PFC.

  18. 27 CFR 44.111 - Change in export warehouse premises.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Change in export warehouse premises. 44.111 Section 44.111 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... Qualification of Export Warehouse Proprietors Changes in Location and Premises § 44.111 Change in export...

  19. 27 CFR 44.109 - Change in address.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Change in address. 44.109 Section 44.109 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT... Warehouse Proprietors Changes in Location and Premises § 44.109 Change in address. Whenever any change...

  20. 19 CFR 147.44 - Entry for another fair.

    Science.gov (United States)

    2010-04-01

    ... TREASURY (CONTINUED) TRADE FAIRS Disposition of Articles Entered for Fairs § 147.44 Entry for another fair. Articles entered for a fair which are to be entered for another fair under the provisions of this part... 19 Customs Duties 2 2010-04-01 2010-04-01 false Entry for another fair. 147.44 Section 147.44...