WorldWideScience

Sample records for calcium release events

  1. Automated Detection of Elementary Calcium Release Events Using the À Trous Wavelet Transform

    OpenAIRE

    Wegner, F. v.; Both, M.; Fink, R H A

    2005-01-01

    We developed an algorithm for the automated detection and analysis of elementary Ca2+ release events (ECRE) based on the two-dimensional nondecimated wavelet transform. The transform is computed with the “à trous” algorithm using the cubic B-spline as the basis function and yields a multiresolution analysis of the image. This transform allows for highly efficient noise reduction while preserving signal amplitudes. ECRE detection is performed at the wavelet levels, thus using the whole spectra...

  2. 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.

  3. Calcium release-activated calcium current in rat mast cells.

    Science.gov (United States)

    Hoth, M; Penner, R

    1993-06-01

    1. Whole-cell patch clamp recordings of membrane currents and fura-2 measurements of free intracellular calcium concentration ([Ca2+]i) were used to study the biophysical properties of a calcium current activated by depletion of intracellular calcium stores in rat peritoneal mast cells. 2. Calcium influx through an inward calcium release-activated calcium current (ICRAC) was induced by three independent mechanisms that result in store depletion: intracellular infusion of inositol 1,4,5-trisphosphate (InsP3) or extracellular application of ionomycin (active depletion), and intracellular infusion of calcium chelators (ethylene glycol bis-N,N,N',N'-tetraacetic acid (EGTA) or 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)) to prevent reuptake of leaked-out calcium into the stores (passive depletion). 3. The activation of ICRAC induced by active store depletion has a short delay (4-14 s) following intracellular infusion of InsP3 or extracellular application of ionomycin. It has a monoexponential time course with a time constant of 20-30 s and, depending on the complementary Ca2+ buffer, a mean normalized amplitude (at 0 mV) of 0.6 pA pF-1 (with EGTA) and 1.1 pA pF-1 (with BAPTA). 4. After full activation of ICRAC by InsP3 in the presence of EGTA (10 mM), hyperpolarizing pulses to -100 mV induced an instantaneous inward current that decayed by 64% within 50 ms. This inactivation is probably mediated by [Ca2+]i, since the decrease of inward current in the presence of the fast Ca2+ buffer BAPTA (10 mM) was only 30%. 5. The amplitude of ICRAC was dependent on the extracellular Ca2+ concentration with an apparent dissociation constant (KD) of 3.3 mM. Inward currents were nonsaturating up to -200 mV. 6. The selectivity of ICRAC for Ca2+ was assessed by using fura-2 as the dominant intracellular buffer (at a concentration of 2 mM) and relating the absolute changes in the calcium-sensitive fluorescence (390 nm excitation) with the calcium current integral

  4. Teaching Calcium-Induced Calcium Release in Cardiomyocytes Using a Classic Paper by Fabiato

    Science.gov (United States)

    Liang, Willmann

    2008-01-01

    This teaching paper utilizes the materials presented by Dr. Fabiato in his review article entitled "Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum." In the review, supporting evidence of calcium-induced calcium release (CICR) is presented. Data concerning potential objections to the CICR theory are discussed as well. In…

  5. A calcium-induced calcium release mechanism mediated by calsequestrin.

    Science.gov (United States)

    Lee, Young-Seon; Keener, James P

    2008-08-21

    Calcium (Ca(2+))-induced Ca(2+) release (CICR) is widely accepted as the principal mechanism linking electrical excitation and mechanical contraction in cardiac cells. The CICR mechanism has been understood mainly based on binding of cytosolic Ca(2+) with ryanodine receptors (RyRs) and inducing Ca(2+) release from the sarcoplasmic reticulum (SR). However, recent experiments suggest that SR lumenal Ca(2+) may also participate in regulating RyR gating through calsequestrin (CSQ), the SR lumenal Ca(2+) buffer. We investigate how SR Ca(2+) release via RyR is regulated by Ca(2+) and calsequestrin (CSQ). First, a mathematical model of RyR kinetics is derived based on experimental evidence. We assume that the RyR has three binding sites, two cytosolic sites for Ca(2+) activation and inactivation, and one SR lumenal site for CSQ binding. The open probability (P(o)) of the RyR is found by simulation under controlled cytosolic and SR lumenal Ca(2+). Both peak and steady-state P(o) effectively increase as SR lumenal Ca(2+) increases. Second, we incorporate the RyR model into a CICR model that has both a diadic space and the junctional SR (jSR). At low jSR Ca(2+) loads, CSQs are more likely to bind with the RyR and act to inhibit jSR Ca(2+) release, while at high SR loads CSQs are more likely to detach from the RyR, thereby increasing jSR Ca(2+) release. Furthermore, this CICR model produces a nonlinear relationship between fractional jSR Ca(2+) release and jSR load. These findings agree with experimental observations in lipid bilayers and cardiac myocytes. PMID:18538346

  6. Construction of calcium release sites in cardiac myocytes

    Directory of Open Access Journals (Sweden)

    Alexandra eZahradnikova

    2012-08-01

    Full Text Available Local character of calcium release in cardiac myocytes, as defined by confocal recordings of calcium sparks, implies independent activation of individual calcium release sites based on ryanodine receptor (RyR channel recruitment. We constructed virtual calcium release sites (vCRSs composed of a variable number of RyR channels distributed in clusters in accordance with the experimentally observed cluster size distribution. The vCRSs consisted either of a single virtual calcium release unit, in which all clusters shared a common dyadic space, or of multiple virtual calcium release units containing one cluster each and having separate dyadic spaces. We explored the stochastic behavior of vCRSs to understand the activation and recruitment of RyRs during calcium sparks. RyRs were represented by the published allosteric gating model that included regulation by cytosolic Ca2+ and Mg2+. The interaction of Mg2+ with the RyR Ca2+-binding sites and the refractory period of vCRSs were optimized to accord with the experimentally observed calcium dependence of calcium spark frequency. The Mg2+-binding parameters of RyRs that provided the best description of spark frequency depended on the number of RyRs assembled in the virtual calcium release sites. Adequate inhibitory effect of Mg2+ on the calcium dependence of RyR open probability was achieved if the virtual calcium release sites contained at least three clusters. For the distribution of the number of open RyRs in evoked calcium sparks to correspond to the experimentally observed distribution of spark calcium release fluxes, at least 3 clusters had to share a common virtual calcium release unit, in which ~ 3 RyRs open to form an average spark. These results reconcile the small cluster size and stochastic placement of RyRs in the release sites with the estimates of the amount of RyR protein, volume density of calcium release sites, and the size of calcium release sites in rat cardiac myocytes.

  7. Releasing effects in flame photometry: Determination of calcium

    Science.gov (United States)

    Dinnin, J.I.

    1960-01-01

    Strontium, lanthanum, neodymium, samarium, and yttrium completely release the flame emission of calcium from the depressive effects of sulfate, phosphate, and aluminate. Magnesium, beryllium, barium, and scandium release most of the calcium emission. These cations, when present in high concentration, preferentially form compounds with the depressing anions when the solution is evaporated rapidly in the flame. The mechanism of the interference and releasing effects is explained on the basis of the chemical equilibria in the evaporating droplets of solution and is shown to depend upon the nature of the compounds present in the aqueous phase of the solution. The need for background correction techniques is stressed. The releasing effect is used in the determination of calcium in silicate rocks without the need for separations.

  8. Intracellular calcium release modulates polycystin-2 trafficking

    Directory of Open Access Journals (Sweden)

    Miyakawa Ayako

    2013-02-01

    Full Text Available Abstract Background Polycystin-2 (PC2, encoded by the gene that is mutated in autosomal dominant polycystic kidney disease (ADPKD, functions as a calcium (Ca2+ permeable ion channel. Considerable controversy remains regarding the subcellular localization and signaling function of PC2 in kidney cells. Methods We investigated the subcellular PC2 localization by immunocytochemistry and confocal microscopy in primary cultures of human and rat proximal tubule cells after stimulating cytosolic Ca2+ signaling. Plasma membrane (PM Ca2+ permeability was evaluated by Fura-2 manganese quenching using time-lapse fluorescence microscopy. Results We demonstrated that PC2 exhibits a dynamic subcellular localization pattern. In unstimulated human or rat proximal tubule cells, PC2 exhibited a cytosolic/reticular distribution. Treatments with agents that in various ways affect the Ca2+ signaling machinery, those being ATP, bradykinin, ionomycin, CPA or thapsigargin, resulted in increased PC2 immunostaining in the PM. Exposing cells to the steroid hormone ouabain, known to trigger Ca2+ oscillations in kidney cells, caused increased PC2 in the PM and increased PM Ca2+ permeability. Intracellular Ca2+ buffering with BAPTA, inositol 1,4,5-trisphosphate receptor (InsP3R inhibition with 2-aminoethoxydiphenyl borate (2-APB or Ca2+/Calmodulin-dependent kinase inhibition with KN-93 completely abolished ouabain-stimulated PC2 translocation to the PM. Conclusions These novel findings demonstrate intracellular Ca2+-dependent PC2 trafficking in human and rat kidney cells, which may provide new insight into cyst formations in ADPKD.

  9. Diffusive spatio-temporal noise in a first-passage time model for intracellular calcium release

    KAUST Repository

    Flegg, Mark B.

    2013-01-01

    The intracellular release of calcium from the endoplasmic reticulum is controlled by ion channels. The resulting calcium signals exhibit a rich spatio-temporal signature, which originates at least partly from microscopic fluctuations. While stochasticity in the gating transition of ion channels has been incorporated into many models, the distribution of calcium is usually described by deterministic reaction-diffusion equations. Here we test the validity of the latter modeling approach by using two different models to calculate the frequency of localized calcium signals (calcium puffs) from clustered IP3 receptor channels. The complexity of the full calcium system is here limited to the basic opening mechanism of the ion channels and, in the mathematical reduction simplifies to the calculation of a first passage time. Two models are then studied: (i) a hybrid model, where channel gating is treated stochastically, while calcium concentration is deterministic and (ii) a fully stochastic model with noisy channel gating and Brownian calcium ion motion. The second model utilises the recently developed two-regime method [M. B. Flegg, S. J. Chapman, and R. Erban, "The two-regime method for optimizing stochastic reaction-diffusion simulations," J. R. Soc., Interface 9, 859-868 (2012)] in order to simulate a large domain with precision required only near the Ca2+ absorbing channels. The expected time for a first channel opening that results in a calcium puff event is calculated. It is found that for a large diffusion constant, predictions of the interpuff time are significantly overestimated using the model (i) with a deterministic non-spatial calcium variable. It is thus demonstrated that the presence of diffusive noise in local concentrations of intracellular Ca2+ ions can substantially influence the occurrence of calcium signals. The presented approach and results may also be relevant for other cell-physiological first-passage time problems with small ligand concentration

  10. Expanding the neuron's calcium signaling repertoire: intracellular calcium release via voltage-induced PLC and IP3R activation.

    Directory of Open Access Journals (Sweden)

    Stefanie Ryglewski

    2007-04-01

    Full Text Available Neuronal calcium acts as a charge carrier during information processing and as a ubiquitous intracellular messenger. Calcium signals are fundamental to numerous aspects of neuronal development and plasticity. Specific and independent regulation of these vital cellular processes is achieved by a rich bouquet of different calcium signaling mechanisms within the neuron, which either can operate independently or may act in concert. This study demonstrates the existence of a novel calcium signaling mechanism by simultaneous patch clamping and calcium imaging from acutely isolated central neurons. These neurons possess a membrane voltage sensor that, independent of calcium influx, causes G-protein activation, which subsequently leads to calcium release from intracellular stores via phospholipase C and inositol 1,4,5-trisphosphate receptor activation. This allows neurons to monitor activity by intracellular calcium release without relying on calcium as the input signal and opens up new insights into intracellular signaling, developmental regulation, and information processing in neuronal compartments lacking calcium channels.

  11. Modulation of elementary calcium release mediates a transition from puffs to waves in an IP3R cluster model.

    Directory of Open Access Journals (Sweden)

    Martin Rückl

    2015-01-01

    Full Text Available The oscillating concentration of intracellular calcium is one of the most important examples for collective dynamics in cell biology. Localized releases of calcium through clusters of inositol 1,4,5-trisphosphate receptor channels constitute elementary signals called calcium puffs. Coupling by diffusing calcium leads to global releases and waves, but the exact mechanism of inter-cluster coupling and triggering of waves is unknown. To elucidate the relation of puffs and waves, we here model a cluster of IP3R channels using a gating scheme with variable non-equilibrium IP3 binding. Hybrid stochastic and deterministic simulations show that puffs are not stereotyped events of constant duration but are sensitive to stimulation strength and residual calcium. For increasing IP3 concentration, the release events become modulated at a timescale of minutes, with repetitive wave-like releases interspersed with several puffs. This modulation is consistent with experimental observations we present, including refractoriness and increase of puff frequency during the inter-wave interval. Our results suggest that waves are established by a random but time-modulated appearance of sustained release events, which have a high potential to trigger and synchronize activity throughout the cell.

  12. Evaluation of calcium ion, hydroxyl ion release and pH levels in various calcium hydroxide based intracanal medicaments: An in vitro study

    OpenAIRE

    Punit Fulzele; Sudhindra Baliga; Nilima Thosar; Debaprya Pradhan

    2011-01-01

    Aims: Evaluation of calcium ion and hydroxyl ion release and pH levels in various calcium hydroxide based intracanal medicaments. Objective: The purpose of this study was to evaluate calcium and hydroxyl ion release and pH levels of calcium hydroxide based products, namely, RC Cal, Metapex, calcium hydroxide with distilled water, along with the new gutta-percha points with calcium hydroxide. Materials and Methods: The materials were inserted in polyethylene tubes and immersed in deionized wat...

  13. Tailored sequential drug release from bilayered calcium sulfate composites

    International Nuclear Information System (INIS)

    The current standard for treating infected bony defects, such as those caused by periodontal disease, requires multiple time-consuming steps and often multiple procedures to fight the infection and recover lost tissue. Releasing an antibiotic followed by an osteogenic agent from a synthetic bone graft substitute could allow for a streamlined treatment, reducing the need for multiple surgeries and thereby shortening recovery time. Tailorable bilayered calcium sulfate (CS) bone graft substitutes were developed with the ability to sequentially release multiple therapeutic agents. Bilayered composite samples having a shell and core geometry were fabricated with varying amounts (1 or 10 wt.%) of metronidazole-loaded poly(lactic-co-glycolic acid) (PLGA) particles embedded in the shell and simvastatin directly loaded into either the shell, core, or both. Microcomputed tomography showed the overall layered geometry as well as the uniform distribution of PLGA within the shells. Dissolution studies demonstrated that the amount of PLGA particles (i.e., 1 vs. 10 wt.%) had a small but significant effect on the erosion rate (3% vs. 3.4%/d). Mechanical testing determined that introducing a layered geometry had a significant effect on the compressive strength, with an average reduction of 35%, but properties were comparable to those of mandibular trabecular bone. Sustained release of simvastatin directly loaded into CS demonstrated that changing the shell to core volume ratio dictates the duration of drug release from each layer. When loaded together in the shell or in separate layers, sequential release of metronidazole and simvastatin was achieved. By introducing a tunable, layered geometry capable of releasing multiple drugs, CS-based bone graft substitutes could be tailored in order to help streamline the multiple steps needed to regenerate tissue in infected defects. - Highlights: • Bilayered CS composites were fabricated as potential bone graft substitutes. • The shell

  14. Tailored sequential drug release from bilayered calcium sulfate composites

    Energy Technology Data Exchange (ETDEWEB)

    Orellana, Bryan R.; Puleo, David A., E-mail: puleo@uky.edu

    2014-10-01

    The current standard for treating infected bony defects, such as those caused by periodontal disease, requires multiple time-consuming steps and often multiple procedures to fight the infection and recover lost tissue. Releasing an antibiotic followed by an osteogenic agent from a synthetic bone graft substitute could allow for a streamlined treatment, reducing the need for multiple surgeries and thereby shortening recovery time. Tailorable bilayered calcium sulfate (CS) bone graft substitutes were developed with the ability to sequentially release multiple therapeutic agents. Bilayered composite samples having a shell and core geometry were fabricated with varying amounts (1 or 10 wt.%) of metronidazole-loaded poly(lactic-co-glycolic acid) (PLGA) particles embedded in the shell and simvastatin directly loaded into either the shell, core, or both. Microcomputed tomography showed the overall layered geometry as well as the uniform distribution of PLGA within the shells. Dissolution studies demonstrated that the amount of PLGA particles (i.e., 1 vs. 10 wt.%) had a small but significant effect on the erosion rate (3% vs. 3.4%/d). Mechanical testing determined that introducing a layered geometry had a significant effect on the compressive strength, with an average reduction of 35%, but properties were comparable to those of mandibular trabecular bone. Sustained release of simvastatin directly loaded into CS demonstrated that changing the shell to core volume ratio dictates the duration of drug release from each layer. When loaded together in the shell or in separate layers, sequential release of metronidazole and simvastatin was achieved. By introducing a tunable, layered geometry capable of releasing multiple drugs, CS-based bone graft substitutes could be tailored in order to help streamline the multiple steps needed to regenerate tissue in infected defects. - Highlights: • Bilayered CS composites were fabricated as potential bone graft substitutes. • The shell

  15. Fabrications of zinc-releasing biocement combining zinc calcium phosphate to calcium phosphate cement.

    Science.gov (United States)

    Horiuchi, Shinya; Hiasa, Masahiro; Yasue, Akihiro; Sekine, Kazumitsu; Hamada, Kenichi; Asaoka, Kenzo; Tanaka, Eiji

    2014-01-01

    Recently, zinc-releasing bioceramics have been the focus of much attention owing to their bone-forming ability. Thus, some types of zinc-containing calcium phosphate (e.g., zinc-doped tricalcium phosphate and zinc-substituted hydroxyapatite) are examined and their osteoblastic cell responses determined. In this investigation, we studied the effects of zinc calcium phosphate (ZCP) derived from zinc phosphate incorporated into calcium phosphate cement (CPC) in terms of its setting reaction and MC3T3-E1 osteoblast-like cell responses. Compositional analysis by powder X-ray diffraction analysis revealed that HAP crystals were precipitated in the CPC containing 10 or 30wt% ZCP after successfully hardening. However, the crystal growth observed by scanning electron microscopy was delayed in the presence of additional ZCP. These findings indicate that the additional zinc inhibits crystal growth and the conversion of CPC to the HAP crystals. The proliferation of the cells and alkaline phosphatase (ALP) activity were enhanced when 10wt% ZCP was added to CPC. Taken together, ZCP added CPC at an appropriate fraction has a potent promotional effect on bone substitute biomaterials. PMID:24090874

  16. Outward potassium current oscillations in macrophage polykaryons: extracellular calcium entry and calcium-induced calcium release

    Directory of Open Access Journals (Sweden)

    Saraiva R.M.

    1997-01-01

    Full Text Available Outward current oscillations associated with transient membrane hyperpolarizations were induced in murine macrophage polykaryons by membrane depolarization in the absence of external Na+. Oscillations corresponded to a cyclic activation of Ca2+-dependent K+ currents (IKCa probably correlated with variations in intracellular Ca2+ concentration. Addition of external Na+ (8 mM immediately abolished the outward current oscillations, suggesting that the absence of the cation is necessary not only for their induction but also for their maintenance. Oscillations were completely blocked by nisoldipine. Ruthenium red and ryanodine reduced the number of outward current cycles in each episode, whereas quercetin prolonged the hyperpolarization 2- to 15-fold. Neither low molecular weight heparin nor the absence of a Na+ gradient across the membrane had any influence on oscillations. The evidence suggests that Ca2+ entry through a pathway sensitive to Ca2+ channel blockers is elicited by membrane depolarization in Na+-free medium and is essential to initiate oscillations, which are also dependent on the cyclic release of Ca2+ from intracellular Ca2+-sensitive stores; Ca2+ ATPase acts by reducing intracellular Ca2+, thus allowing slow deactivation of IKCa. Evidence is presented that neither a Na+/Ca2+ antiporter nor Ca2+ release from IP3-sensitive Ca2+ stores participate directly in the mechanism of oscillation

  17. Release of Crude Oil from Silica and Calcium Carbonate Surfaces

    DEFF Research Database (Denmark)

    Liu, Xiaoyan; Yan, Wei; Stenby, Erling Halfdan;

    2016-01-01

    on the bare surfaces, surfaces with an adsorbed oil layer, and surfaces after being exposed to aqueous salt solutions. This showed that the silica surface became more hydrophobic after oil adsorption, while the wettability of the calcium carbonate surface was not significantly changed by adsorption of an oil...... oil was investigated by exposing the surfaces with an adsorbed oil layer to a series of NaCl and CaCl2 solutions of decreasing salt concentrations. Here, it was found that the oil release from silica was achieved only by injections of low-salinity solutions, and it is suggested that this observation...... or reduction in ion bridging in the presence of high-salinity NaCl, while the low-salinity effect again was attributed to an expansion of the electrical double layer....

  18. Spontaneous Neurotransmitter Release Depends on Intracellular Rather than ER Calcium Stores in Cultured Xenopus NMJ

    Institute of Scientific and Technical Information of China (English)

    GE Song; LI Ruxin; QI Lei; HE Xiangping; XIE Zuoping

    2006-01-01

    Calcium ions are important in many vital neuron processes, including spontaneous neurotransmitter release. Extracellular calcium has long been known to be related to spontaneous neurotransmitter release, but the detailed mechanism for the effect of intracellular Ca2+ on synaptic release has not yet been understood. In this research, 1,2-bis-(o-aminophenoxy)-ethane-N, N, N', N'-tetraacetic acid tetraacetoxy-methyl ester (BAPTA-AM) was used to combine with cytosolic free Ca2+ in a calcium free medium of cultured Xenopus neuromuscular junctions (NMJ). The spontaneous synaptic current (SSC) frequency was obviously reduced. Then, drugs were applied to interrupt and activate the Ca2+ release channels in the endoplasmic reticulum (ER) membrane, but the SSC frequency was not affected. The results show that spontaneous neurotransmitter release depends on intracellular rather than ER calcium in cultured Xenopus NMJ without extracellular calcium.

  19. Microtubule-Dependent Mitochondria Alignment Regulates Calcium Release in Response to Nanomechanical Stimulus in Heart Myocytes

    Directory of Open Access Journals (Sweden)

    Michele Miragoli

    2016-01-01

    Full Text Available Arrhythmogenesis during heart failure is a major clinical problem. Regional electrical gradients produce arrhythmias, and cellular ionic transmembrane gradients are its originators. We investigated whether the nanoscale mechanosensitive properties of cardiomyocytes from failing hearts have a bearing upon the initiation of abnormal electrical activity. Hydrojets through a nanopipette indent specific locations on the sarcolemma and initiate intracellular calcium release in both healthy and heart failure cardiomyocytes, as well as in human failing cardiomyocytes. In healthy cells, calcium is locally confined, whereas in failing cardiomyocytes, calcium propagates. Heart failure progressively stiffens the membrane and displaces sub-sarcolemmal mitochondria. Colchicine in healthy cells mimics the failing condition by stiffening the cells, disrupting microtubules, shifting mitochondria, and causing calcium release. Uncoupling the mitochondrial proton gradient abolished calcium initiation in both failing and colchicine-treated cells. We propose the disruption of microtubule-dependent mitochondrial mechanosensor microdomains as a mechanism for abnormal calcium release in failing heart.

  20. Evaluation of pH, calcium ion release and antimicrobial activity of a new calcium aluminate cement

    Directory of Open Access Journals (Sweden)

    Fernanda de Carvalho Panzeri Pires-de-Souza

    2013-07-01

    Full Text Available This study evaluated the pH, calcium ion release and antimicrobial activity of EndoBinder (EB, containing different radiopacifiers: bismuth oxide (Bi2O3, zinc oxide (ZnO or zirconium oxide (ZrO2, in comparison to MTA. For pH and calcium ion release tests, 5 specimens per group (n = 5 were immersed into 10 mL of distilled and deionized water at 37°C. After 2, 4, 12, 24, 48 h; 7, 14 and 28 days, the pH was measured and calcium ion release quantified in an atomic absorption spectrophotometer. For antimicrobial activity, the cements were tested against S. aureus, E. coli, E. faecalis and C. albicans, in triplicate. MTA presented higher values for pH and calcium ion release than the other groups, however, with no statistically significant difference after 28 days (p > 0.05; and the largest inhibition halos for all strains, with no significant difference (E. coli and E. faecalis for pure EB and EB + Bi2O3 (p > 0.05. EB presented similar performance to that of MTA as regards pH and calcium ion release; however, when ZnO and ZrO2 were used, EB did not present antimicrobial activity against some strains.

  1. Inhibition of parathyroid hormone release by maitotoxin, a calcium channel activator

    International Nuclear Information System (INIS)

    Maitotoxin, a toxin derived from a marine dinoflagellate, is a potent activator of voltage-sensitive calcium channels. To further test the hypothesis that inhibition of PTH secretion by calcium is mediated via a calcium channel we studied the effect of maitotoxin on dispersed bovine parathyroid cells. Maitotoxin inhibited PTH release in a dose-dependent fashion, and inhibition was maximal at 1 ng/ml. Chelation of extracellular calcium by EGTA blocked the inhibition of PTH by maitotoxin. Maitotoxin enhanced the effects of the dihydropyridine calcium channel agonist (+)202-791 and increased the rate of radiocalcium uptake in parathyroid cells. Pertussis toxin, which ADP-ribosylates and inactivates a guanine nucleotide regulatory protein that interacts with calcium channels in the parathyroid cell, did not affect the inhibition of PTH secretion by maitotoxin. Maitotoxin, by its action on calcium channels allows entry of extracellular calcium and inhibits PTH release. Our results suggest that calcium channels are involved in the release of PTH. Inhibition of PTH release by maitotoxin is not sensitive to pertussis toxin, suggesting that maitotoxin may act distal to the site interacting with a guanine nucleotide regulatory protein, or maitotoxin could interact with other ions or second messengers to inhibit PTH release

  2. Kinetics of release of methylene blue immobilized in calcium alginate microparticles

    OpenAIRE

    Inal Bakhytkyzy; R. Ussenkyzy; D. Rahimbaeva

    2013-01-01

    The swelling kinetics of microparticles obtained with different concentrations of calcium chloride was studied to learn the ability of sodium alginate to gelation. To increase the effect of prolongation it is necessary to obtain microparticles with sustained release of drugs. For this purpose the drying kinetics of alginate microparticles was investigated. Also the kinetics of release of methylene blue immobilized in calcium alginate microparticles was studied. It was found that the release o...

  3. Preparation of TiO2 nanotubes/mesoporous calcium silicate composites with controllable drug release.

    Science.gov (United States)

    Xie, Chunling; Li, Ping; Liu, Yan; Luo, Fei; Xiao, Xiufeng

    2016-10-01

    Nanotube structures such as TiO2 nanotube (TNT) arrays produced by self-ordering electrochemical anodization have been extensively explored for drug delivery applications. In this study, we presented a new implantable drug delivery system that combined mesoporous calcium silicate coating with nanotube structures to achieve a controllable drug release of water soluble and antiphlogistic drug loxoprofen sodium. The results showed that the TiO2 nanotubes/mesoporous calcium silicate composites were successfully fabricated by a simple template method and the deposition of mesoporous calcium silicate increased with the soaking time. Moreover, the rate of deposition of biological mesoporous calcium silicate on amorphous TNTs was better than that on anatase TNTs. Further, zinc-incorporated mesoporous calcium silicate coating, produced by adding a certain concentration of zinc nitrate into the soaking system, displayed improved chemical stability. A significant improvement in the drug release characteristics with reduced burst release and sustained release was demonstrated. PMID:27287140

  4. Reduced levels of intracellular calcium releasing in spermatozoa from asthenozoospermic patients

    Directory of Open Access Journals (Sweden)

    García Juan F

    2009-02-01

    Full Text Available Abstract Background Asthenozoospermia is one of the most common findings present in infertile males characterized by reduced or absent sperm motility, but its aetiology remains unknown in most cases. In addition, calcium is one of the most important ions regulating sperm motility. In this study we have investigated the progesterone-evoked intracellular calcium signal in ejaculated spermatozoa from men with normospermia or asthenozoospermia. Methods Human ejaculates were obtained from healthy volunteers and asthenospermic men by masturbation after 4–5 days of abstinence. For determination of cytosolic free calcium concentration, spermatozoa were loaded with the fluorescent ratiometric calcium indicator Fura-2. Results Treatment of spermatozoa from normospermic men with 20 micromolar progesterone plus 1 micromolar thapsigargin in a calcium free medium induced a typical transient increase in cytosolic free calcium concentration due to calcium release from internal stores. Similar results were obtained when spermatozoa were stimulated with progesterone alone. Subsequent addition of calcium to the external medium evoked a sustained elevation in cytosolic free calcium concentration indicative of capacitative calcium entry. However, when progesterone plus thapsigargin were administered to spermatozoa from patients with asthenozoospermia, calcium signal and subsequent calcium entry was much smaller compared to normospermic patients. As expected, pretreatment of normospermic spermatozoa with both the anti-progesterone receptor c262 antibody and with progesterone receptor antagonist RU-38486 decreased the calcium release induced by progesterone. Treatment of spermatozoa with cytochalasin D or jasplakinolide decreased the calcium entry evoked by depletion of internal calcium stores in normospermic patients, whereas these treatments proved to be ineffective at modifying the calcium entry in patients with asthenozoospermia. Conclusion Our results suggest

  5. Calcium Occupancy of N-terminal Sites within Calmodulin Induces Inhibition of the Ryanodine Receptor Calcium Release Channel

    Energy Technology Data Exchange (ETDEWEB)

    Boschek, Curt B; Jones, Terry E; Squier, Thomas C; Bigelow, Diana J

    2007-08-01

    Calmodulin (CaM) regulates calcium release from intracellular stores in skeletal muscle through its association with the ryanodine receptor (RyR1) calcium release channel, where CaM association enhances channel opening at resting calcium levels and its closing at micromolar calcium levels associated with muscle contraction. A high-affinity CaM-binding sequence (RyRp) has been identified in RyR1, which corresponds to a 30-residue sequence (i.e., K3614 – N3643) located within the central portion of the primary sequence. However, it is currently unclear whether the identified CaM-binding sequence a) senses calcium over the physiological range of calcium-concentrations associated with RyR1 regulation or b) plays a structural role unrelated to the calcium-dependent modulation of RyR1 function. Therefore, we have measured the calcium-dependent activation of the individual domains of CaM in association with RyRp and their relationship to the CaM-dependent regulation of RyR1. These measurements utilize an engineered CaM, permitting the site-specific incorporation of N-(1-pyrene) maleimide at either T34C (PyN-CaM) or T110C (PyC-CaM) in the N- and C-domains, respectively. Consistent with prior measurements, we observe a high-affinity association between both apo- and calcium-activated CaM and RyRp. Upon association with RyRp, fluorescence changes in PyN-CaM or PyC-CaM permit the measurement of the calcium-activation of these individual domains. Fluorescence changes upon calcium-activation of PyC-CaM in association with RyRp are indicative of high-affinity calcium-dependent activation of the C-terminal domain of CaM bound to RyRp at resting calcium levels and the activation of the N-terminal domain at levels of calcium associated cellular activation. In comparison, occupancy of calcium-binding sites in the N-domain of CaM mirrors the calcium-dependence of RyR1 inhibition observed at activating calcium levels, where [Ca]1/2 = 4.3 0.4 μM, suggesting a direct regulation of Ry

  6. Maturation of calcium-dependent GABA, glycine, and glutamate release in the glycinergic MNTB-LSO pathway.

    Directory of Open Access Journals (Sweden)

    Javier Alamilla

    Full Text Available The medial nucleus of the trapezoid body (MNTB is a key nucleus in high-fidelity temporal processing that underlies sound localization in the auditory brainstem. While the glycinergic principal cells of the MNTB project to all primary nuclei of the superior olive, during development the projection from MNTB to the lateral superior olive (LSO is of interest because this immature inhibitory projection is known to undergo tonotopic refinement during an early postnatal period, and because during this period individual MNTB terminals in the LSO transiently release glycine GABA and glutamate. Developmental changes in calcium-dependent release are understood to be required to allow various auditory nuclei to follow high frequency activity; however, little is known about maturation of calcium-dependent release in the MNTB-LSO pathway, which has been presumed to have less stringent requirements for high-fidelity temporal following. In acute brainstem slices of rats age postnatal day 1 to 15 we recorded whole-cell responses in LSO principal neurons to electrical stimulation in the MNTB in order to measure sensitivity to external calcium, the contribution of different voltage-gated calcium channel subtypes to vesicular release, and the maturation of these measures for both GABA/glycine and glutamate transmission. Our results establish that release of glutamate at MNTB-LSO synapses is calcium-dependent. Whereas no significant developmental changes were evident for glutamate release, GABA/glycine release underwent substantial changes over the first two postnatal weeks: soon after birth L-type, N-type, and P/Q-type voltage-gated calcium channels (VGCCs together mediated release, but after hearing onset P/Q-type VGCCs predominated. Blockade of P/Q-type VGCCs reduced the estimated quantal number for GABA/gly and glutamate transmission at P5-8 and the frequency of evoked miniature glycinergic events at P12-15, without apparent effects on spontaneous release of

  7. Evaluation of calcium ion release and change in pH on combining calcium hydroxide with different vehicles

    Directory of Open Access Journals (Sweden)

    Charu Grover

    2014-01-01

    Full Text Available Introduction: Intracanal medicaments have traditionally been used in endodontics to disinfect root canals between appointments. Calcium hydroxide is widely used as an intracanal medicament for disinfection and to promote periapical healing. It is stable for long periods, harmless to the body, and bactericidal in a limited area. The efficacy of calcium hydroxide as a disinfectant is dependent on the availability of the hydroxyl ions in the solution that depends on the vehicle in which the calcium hydroxide is carried. In general, three types of vehicles are used: Aqueous, viscous or oily. Some in vitro studies have shown that the type of vehicle has a direct relationship with the concentration and the velocity of ionic liberation as well as with the antibacterial action when the paste is carried into a contaminated area. Aim of the Study: To evaluate the calcium ion release and measure the change in pH of the environment that occurred when calcium hydroxide was combined with different vehicles (distilled water, propylene glycol, calcium hydroxide containing gutta-percha points and chitosan over different time periods. Materials and Methods: Forty single rooted mandibular first premolar teeth were decoronated for this study. Working length was established and the root canals were enlarged and irrigation accomplished with 2 ml of NaOCl solution after every file. The teeth were then randomly divided into four groups. The canals were then packed with different preparations of calcium hydroxide using the following vehicles-distilled water, propylene glycol, gutta-percha points and chitosan. Calcium ion release in different groups was analyzed using an ultraviolet spectrophotometer at 220 nm. The change in pH of was determined using a pH meter. Results were statistically evaluated using one-way ANOVA test. Result: For calcium ion release, Group 2 showed cumulative drug release of 81.97% at the end of 15 days, whereas Group 1, 3 and 4 showed a release

  8. Do Ca2+-adsorbing ceramics reduce the release of calcium ions from gypsum-based biomaterials?

    Science.gov (United States)

    Belcarz, Anna; Zalewska, Justyna; Pałka, Krzysztof; Hajnos, Mieczysław; Ginalska, Grazyna

    2015-02-01

    Bone implantable materials based on calcium sulfate dihydrate dissolve quickly in tissue liquids and release calcium ions at very high levels. This phenomenon induces temporary toxicity for osteoblasts, may cause local inflammation and delay the healing process. Reduction in the calcium ion release rate by gypsum could be therefore beneficial for the healing of gypsum-filled bone defects. The aim of this study concerned the potential use of calcium phosphate ceramics of various porosities for the reduction of high Ca(2+) ion release from gypsum-based materials. Highly porous ceramics failed to reduce the level of Ca(2+) ions released to the medium in a continuous flow system. However, it succeeded to shorten the period of high calcium level. It was not the phase composition but the high porosity of ceramics that was found crucial for both the shortening of the Ca(2+) release-related toxicity period and intensification of apatite deposition on the composite. Nonporous ceramics was completely ineffective for this purpose and did not show any ability to absorb calcium ions at a significant level. Moreover, according to our observations, complex studies imitating in vivo systems, rather than standard tests, are essential for the proper evaluation of implantable biomaterials. PMID:25492196

  9. The impact of calcium current reversal on neurotransmitter release in the electrically stimulated retina

    Science.gov (United States)

    Werginz, Paul; Rattay, Frank

    2016-08-01

    Objective. In spite of intense theoretical and experimental investigations on electrical nerve stimulation, the influence of reversed ion currents on network activity during extracellular stimulation has not been investigated so far. Approach. Here, the impact of calcium current reversal on neurotransmitter release during subretinal stimulation was analyzed with a computational multi-compartment model of a retinal bipolar cell (BC) that was coupled with a four-pool model for the exocytosis from its ribbon synapses. Emphasis was laid on calcium channel dynamics and how these channels influence synaptic release. Main results. Stronger stimulation with anodic pulses caused transmembrane voltages above the Nernst potential of calcium in the terminals and, by this means, forced calcium ions to flow in the reversed direction from inside to the outside of the cell. Consequently, intracellular calcium concentration decreased resulting in a reduced vesicle release or preventing release at all. This mechanism is expected to lead to a pronounced ring-shaped pattern of exocytosis within a group of neighbored BCs when the stronger stimulated cells close to the electrode fail in releasing vesicles. Significance. Stronger subretinal stimulation causes failure of synaptic exocytosis due to reversal of calcium flow into the extracellular space in cells close to the electrode.

  10. Somatic ATP release from guinea pig sympathetic neurons does not require calcium-induced calcium release from internal stores

    OpenAIRE

    Merriam, Laura A.; Locknar, Sarah A.; Girard, Beatrice M.; Parsons, Rodney L.

    2010-01-01

    Prior studies indicated that a Ca2+-dependent release of ATP can be initiated from the soma of sympathetic neurons dissociated from guinea pig stellate ganglia. Previous studies also indicated that Ca2+-induced Ca2+ release (CICR) can modulate membrane excitability in these same neurons. As Ca2+ release from internal stores is thought to support somatodendritic transmitter release in other neurons, the present study investigated whether CICR is essential for somatic ATP release from dissociat...

  11. Maitotoxin: Effects on calcium channels, phosphoinositide breakdown, and arachidonate release in pheochromocytoma PC12 cells

    International Nuclear Information System (INIS)

    Maitotoxin (MTX) increases formation of [3H]inositol phosphates from phosphoinositides and release of [3H]arachidonic acid from phospholipids in pheochromocytoma PC12 cells. Formation of [3H]inositol phosphates is detected within 1 min of incubation even with concentrations as low as 0.3 ng/ml (90 pm) MTX, whereas release of [3H]arachidonic acid is not detected until 20 min even with concentrations as high as 1 ng/ml (300 pm) MTX. Stimulation of arachidonic acid release can be detected at 0.03 ng/ml (9 pm) MTX, whereas 0.1 ng/ml (30 pm) MTX is the threshold for detection of phosphoinositide breakdown. Organic and inorganic calcium channel blockers, except Cd2+ and a high concentration of Mn2+, have no effect on MTX-elicited phosphoinositide breakdown, whereas inorganic blockers (e.g., Co2+, Mn2+, Cd2+), but not organic blockers (nifedipine, verapamil, diltiazem), inhibit MTX-stimulated arachidonic acid release. All calcium channel blockers, however, inhibited MTX-elicited influx of 45Ca2+ and the MTX-elicited increase in internal Ca2+ measured with fura-2 was markedly reduced by nifedipine. MTX-elicited phosphoinositide breakdown and arachidonic acid release are abolished or reduced, respectively, in the absence of extracellular calcium plus chelating agent. The calcium ionophore A23187 has little or no effect alone but, in combination with MTX, A23187 inhibits MTX-elicited phosphoinositide breakdown and enhances arachidonic acid release, the latter even in the absence of extracellular calcium. The results suggest that different sites and/or mechanisms are involved in stimulation of calcium influx, breakdown of phosphoinositides, and release of arachidonic acid by MTX

  12. Renin release from permeabilized juxtaglomerular cells is stimulated by chloride but not by low calcium

    DEFF Research Database (Denmark)

    Jensen, B L; Skøtt, O

    1994-01-01

    M]. These maneuvers had no effect on renin release, while 1.5 mM calcium caused a stimulation, which was not inhibited by 50 mM sucrose. Isosmotic increases in the chloride concentration to 25, 60, and 132 mM resulted in prompt stimulations of renin release. Similarly, iodide and nitrate stimulated renin release. We...... of chloride channels followed by a drop in the intracellular chloride concentration. The stimulation caused by the high calcium concentration may be a toxic effect or may be due to stimulation of the fusion between granules and cell membrane in a way analogous to other secretory cells.......The intracellular concentrations of calcium and chloride have been suggested to be involved in the control of renin secretion from juxtaglomerular (JG) cells. We have tested these propositions on permeabilized JG cells. Rat glomeruli with attached JG cells were isolated by the magnetic iron...

  13. Dynamic Data-Driven Event Reconstruction for Atmospheric Releases

    Energy Technology Data Exchange (ETDEWEB)

    Kosovic, B; Belles, R; Chow, F K; Monache, L D; Dyer, K; Glascoe, L; Hanley, W; Johannesson, G; Larsen, S; Loosmore, G; Lundquist, J K; Mirin, A; Neuman, S; Nitao, J; Serban, R; Sugiyama, G; Aines, R

    2007-02-22

    Accidental or terrorist releases of hazardous materials into the atmosphere can impact large populations and cause significant loss of life or property damage. Plume predictions have been shown to be extremely valuable in guiding an effective and timely response. The two greatest sources of uncertainty in the prediction of the consequences of hazardous atmospheric releases result from poorly characterized source terms and lack of knowledge about the state of the atmosphere as reflected in the available meteorological data. In this report, we discuss the development of a new event reconstruction methodology that provides probabilistic source term estimates from field measurement data for both accidental and clandestine releases. Accurate plume dispersion prediction requires the following questions to be answered: What was released? When was it released? How much material was released? Where was it released? We have developed a dynamic data-driven event reconstruction capability which couples data and predictive models through Bayesian inference to obtain a solution to this inverse problem. The solution consists of a probability distribution of unknown source term parameters. For consequence assessment, we then use this probability distribution to construct a ''''composite'' forward plume prediction which accounts for the uncertainties in the source term. Since in most cases of practical significance it is impossible to find a closed form solution, Bayesian inference is accomplished by utilizing stochastic sampling methods. This approach takes into consideration both measurement and forward model errors and thus incorporates all the sources of uncertainty in the solution to the inverse problem. Stochastic sampling methods have the additional advantage of being suitable for problems characterized by a non-Gaussian distribution of source term parameters and for cases in which the underlying dynamical system is non-linear. We initially

  14. Asenapine modulates nitric oxide release and calcium movements in cardiomyoblasts

    Directory of Open Access Journals (Sweden)

    Elena Grossini

    2016-01-01

    Full Text Available Objective: To examine the effects of asenapine on nitric oxide (NO release and Ca2+ transients in H9C2 cell line, which were either subjected to peroxidation or not. Materials and Methods: H9C2 were treated with asenapine alone or in presence of intracellular kinase blockers, serotoninergic and dopaminergic antagonists, and voltage Ca2+ channels inhibitors. Experiments were also performed in H9C2 treated with hydrogen peroxide. NO release and intracellular Ca2+ were measured through specific probes. Results: In H9C2, asenapine differently modulated NO release and Ca2+ movements depending on peroxidative condition. The Ca2+ pool mobilized by asenapine mainly originated from the extracellular space and was slightly affected by thapsigargin. Moreover, the effects of asenapine were reduced or prevented by kinases blockers, dopaminergic and serotoninergic receptors inhibitors, and voltage Ca2+ channels blockers.Conclusions: On the basis of our findings, we can conclude that asenapine by interacting with its specific receptors, exerts dual effects on NO release and Ca2+ homeostasis in H9C2; this would be of particular clinical relevance when considering their role in cardiac function modulation.

  15. Specific association of growth-associated protein 43 with calcium release units in skeletal muscles of lower vertebrates

    Directory of Open Access Journals (Sweden)

    G.A. Caprara

    2014-10-01

    Full Text Available Growth-associated protein 43 (GAP43, is a strictly conserved protein among vertebrates implicated in neuronal development and neurite branching. Since GAP43 structure contains a calmodulin-binding domain, this protein is able to bind calmodulin and gather it nearby membrane network, thus regulating cytosolic calcium and consequently calcium-dependent intracellular events. Even if for many years GAP43 has been considered a neuronal-specific protein, evidence from different laboratories described its presence in myoblasts, myotubes and adult skeletal muscle fibers. Data from our laboratory showed that GAP43 is localized between calcium release units (CRUs and mitochondria in mammalian skeletal muscle suggesting that, also in skeletal muscle, this protein can be a key player in calcium/calmodulin homeostasis. However, the previous studies could not clearly distinguish between a mitochondrion- or a triad-related positioning of GAP43. To solve this question, the expression and localization of GAP43 was studied in skeletal muscle of Xenopus and Zebrafish known to have triads located at the level of the Z-lines and mitochondria not closely associated with them. Western blotting and immunostaining experiments revealed the expression of GAP43 also in skeletal muscle of lower vertebrates (like amphibians and fishes, and that the protein is localized closely to the triad junction. Once more, these results and GAP43 structural features, support an involvement of the protein in the dynamic intracellular Ca2+ homeostasis, a common conserved role among the different species.

  16. Regulation of dendritic calcium release in striatal spiny projection neurons

    OpenAIRE

    Plotkin, Joshua L.; Shen, Weixing; Rafalovich, Igor; Sebel, Luke E.; Day, Michelle; Chan, C. Savio; Surmeier, D. James

    2013-01-01

    The induction of corticostriatal long-term depression (LTD) in striatal spiny projection neurons (SPNs) requires coactivation of group I metabotropic glutamate receptors (mGluRs) and L-type Ca2+ channels. This combination leads to the postsynaptic production of endocannabinoids that act presynaptically to reduce glutamate release. Although the necessity of coactivation is agreed upon, why it is necessary in physiologically meaningful settings is not. The studies described here attempt to answ...

  17. Sarcoplasmic Reticulum Calcium Release Channels in Ventricles of Older Adult Hamsters

    Science.gov (United States)

    Nicholl, Peter A.; Howlett, Susan E.

    2006-01-01

    Whether the density of sarcoplasmic reticulum (SR) calcium release channels/ryanodine receptors in the heart declines with age is not clear. We investigated age-related changes in the density of [3H]-ryanodine receptors in crude ventricular homogenates, which contained all ligand binding sites in heart and in isolated junctional SR membranes.…

  18. The role of calcium in endotoxin-induced release of calcitonin gene-related peptide (CGRP) from rat spinal cord

    Institute of Scientific and Technical Information of China (English)

    唐跃明; 韩启德; 王宪

    1997-01-01

    In the present study, the role of calcium in endotoxin-induced CGRP release was studied. 2 .5-50 μg/mL endotoxin and 1 -10 mmol/L caffeine caused concentration-dependent increase of CGRP release from rat spinal cord in vitro. However, no additive effect could he found when caffeine and endotoxin were concomitantly incubated. By using capsaicin, Ca2+-free medium, Omega-Conotoxin, nifedipine, W-7, ryanodine, MgCl2, Tris-ATP, rutheni-um red, the results indicate that the release of CGRP evoked by endotoxin from the sensory fibers of rat spinal cord is dependent on extracellular calcium. After entering into the cell through the N-type calcium channel, calcium binds to calmodulin, and triggers calcium release from intracellular calcium store by activating the caffeine-sensitive but ryan-odine-insensitive mechanism.

  19. A slow release calcium delivery system for the study of reparative dentine formation.

    Science.gov (United States)

    Hunter, A R; Kirk, E E; Robinson, D H; Kardos, T B

    1998-06-01

    Several liquid, semi-solid and solid delivery systems were formulated and tested to devise a method of reproducibly administering accurate micro-doses of calcium into a 700 microns diameter cavity in a rat maxillary incisor tooth, in the absence of hydroxyl ions. Development of this delivery system was necessary to facilitate studies of the mechanisms of pulpal repair and odontoblast differentiation. The principal requirements for the delivery system were that it should be easily administered into a small pulp exposure in the rat incisor and that a greater than 1000-fold range in calcium ion concentrations could be incorporated and delivered for a period of 2-3 days, preferably in an acidic environment to minimize the effect of non-specific nucleation under alkaline conditions. Poly- (ethylene) glycol microspheres were found to be an ideal vehicle. Under the in vitro dissolution conditions used, complete release of all calcium salts occurred within 12-15 hours, except for the very water-insoluble calcium stearate. It was anticipated that the release of calcium ions would be significantly more prolonged in vivo because of the physical constraints of the prepared cavity as well as the restricted access to fluid flow. PMID:9863419

  20. Calcium influx and release mechanism(s) in histamine-induced myometrial contraction in buffaloes.

    Science.gov (United States)

    Sharma, Abhishek; Choudhury, Soumen; Nakade, Udayraj P; Yadav, Rajkumar Singh; Garg, Satish Kumar

    2014-05-01

    The present study was undertaken to characterize the presence of histamine H1R using molecular biology tools and unravel the influx and release mechanism(s) involved in calcium signalling cascades in histamine-induced myometrial contraction in buffaloes. The presence of H1R mRNA transcript and immunoreactive membrane protein in buffalo myometrium was confirmed by RT-PCR and Western blot analysis. Further, histamine produced concentration-dependent (1nM-10μM) contraction in buffalo myometrium with a potency of 7.13±0.11. When myometrial strips were pre-incubated either with Ca(2+) free solution or with nifedipine, a L-type Ca(2+) channel blocker, dose response curve (DRC) of histamine was significantly (PCPA (blocker of sarco-endoplasmic reticulum Ca(2+)-ATPase). Interestingly, following concurrent exposure to U-73122 (a PL-C inhibitor) and nifedipine, the DRC of histamine was significantly (P<0.05) shifted towards left with increase in maximal contraction (126.30±3.36%). Our findings in buffalo uterus thus suggest that influx of extracellular calcium plays a major role in histamine-induced myometrial contraction, while release of intracellular calcium through calcium-release channels of sarcoplasmic reticulum has a minor role. A possible involvement of non-selective cation channels in histamine-induced myometrial contraction cannot be ruled out, and therefore requires further investigations. PMID:24631173

  1. ATP releasing connexin 30 hemichannels mediate flow-induced calcium signaling in the collecting duct

    DEFF Research Database (Denmark)

    Svenningsen, Per; Burford, James L; Peti-Peterdi, János

    2013-01-01

    ATP in the renal tubular fluid is an important regulator of salt and water reabsorption via purinergic calcium signaling that involves the P2Y2 receptor, ENaC, and AQP2. Recently, we have shown that connexin (Cx) 30 hemichannels are localized to the non-junctional apical membrane of cells...... by suramin. Taken together, these data confirm that mechanosensitive Cx30 hemichannels mediate tubular ATP release and purinergic calcium signaling in the CD which mechanism plays an important role in the regulation of CD salt and water reabsorption....

  2. Preparation of calcium chloride-loaded solid lipid particles and heat-triggered calcium ion release

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Huangying; Kim, Jin-Chul [Kangwon National University, Chunchon (Korea, Republic of)

    2015-08-15

    CaCl{sub 2}-loaded solid lipid particles (SLPs) were prepared by a melt/emulsification/solidification method. CaCl{sub 2} microparticles (1-5 μm) could be obtained in a mortar with aid of the dispersant (Tween 80/Span80 (35/65, w/w)) when the ratio of CaCl{sub 2} to dispersant was 2 : 0.1 (w/w). SLP was prepared by dispersing 0.42 g of micronized CaCl{sub 2} particles in 2 g of molten PBSA, emulsifying the mixture at 85 .deg. C in 40 ml of Tween 20 solution (0.5% w/v), and quenching the emulsion in an ice bath. The diameter of CaCl{sub 2}-loaded SLP was 10-150 μm. The unenveloped CaCl{sub 2} could be removed by dialysis and the specific loading of CaCl{sub 2} in SLP was 0.036mg/mg. An EDS spectrum of CaCl{sub 2}-loaded SLP, which was dialyzed, showed that the unenveloped CaCl{sub 2} was completely removed. Any excipients (dispersant, Tween 20, CaCl{sub 2}) had little effect on the melting point of SLPs. No appreciable amount of Ca2+ was released in 20-50 .deg. C for 22 h. But the release degree at 60 .deg. C was significant (about 2.3%) during the same period. The matrix of the lipid particle was in a liquid state at 60 .deg. C, so CaCl{sub 2} particles could move freely and contact the surrounding water, leading to the release. At 70 .deg. C, the release degree at a given time was a few times higher than that obtained at 60 .deg. C.

  3. Phagosome-lysosome fusion is a calcium-independent event in macrophages

    OpenAIRE

    1996-01-01

    Phagosome-lysosome membrane fusion is a highly regulated event that is essential for intracellular killing of microorganisms. Functionally, it represents a form of polarized regulated secretion, which is classically dependent on increases in intracellular ionized calcium ([Ca2+]i). Indeed, increases in [Ca2+]i are essential for phagosome- granule (lysosome) fusion in neutrophils and for lysosomal fusion events that mediate host cell invasion by Trypanosoma cruzi trypomastigotes. Since several...

  4. Dissolution of the inorganic phase of bone leading to release of calcium regulates osteoclast survival

    DEFF Research Database (Denmark)

    Nielsen, Rasmus H; Karsdal, Morten A; Sørensen, Mette G;

    2007-01-01

    Osteoclasts are the sole cells possessing the ability to resorb calcified bone matrix. This occurs via secretion of hydrochloric acid mediated by the V-ATPase and the chloride channel ClC-7. Loss of acidification leads to osteopetrosis characterized by ablation of bone resorption and increased...... osteoclast numbers, indicating increased life span of the osteoclasts. To investigate the role of the inorganic phase of bone with respect to osteoclast life span, we used the V-ATPase inhibitor bafilomycin and the calcium uptake antagonist ryanodine on human osteoclasts cultured on calcified and decalcified...... bone slices. Bafilomycin inhibited bone resorption and increased osteoclast survival on calcified but not decalcified bones. Ryanodine attenuated calcium uptake and thereby augmented osteoclast survival on calcified bones. In summary, we found that acidification leading to calcium release from bone...

  5. Role for voltage gated calcium channels in calcitonin gene-related peptide release in the rat trigeminovascular system

    DEFF Research Database (Denmark)

    Amrutkar, D V; Ploug, K B; Olesen, J;

    2011-01-01

    Clinical and genetic studies have suggested a role for voltage gated calcium channels (VGCCs) in the pathogenesis of migraine. Release of calcitonin gene-related peptide (CGRP) from trigeminal neurons has also been implicated in migraine. The VGCCs are located presynaptically on neurons and are...... potassium releases CGRP, and the release is regulated by Ca2+ ions and voltage-gated calcium channels....... potassium induced CGRP release. In the absence of calcium ions (Ca2+) and in the presence of a cocktail of blockers, the stimulated CGRP release from dura mater was reduced almost to the same level as basal CGRP release. In the TG ω-conotoxin GVIA inhibited the potassium induced CGRP release significantly...

  6. Role for voltage gated calcium channels in calcitonin gene-related peptide release in the rat trigeminovascular system

    DEFF Research Database (Denmark)

    Amrutkar, D V; Ploug, K B; Olesen, J;

    2011-01-01

    Clinical and genetic studies have suggested a role for voltage gated calcium channels (VGCCs) in the pathogenesis of migraine. Release of calcitonin gene-related peptide (CGRP) from trigeminal neurons has also been implicated in migraine. The VGCCs are located presynaptically on neurons and are...... potassium releases CGRP, and the release is regulated by Ca2+ ions and voltage-gated calcium channels....... potassium induced CGRP release. In the absence of calcium ions (Ca2+) and in the presence of a cocktail of blockers, the stimulated CGRP release from dura mater was reduced almost to the same level as basal CGRP release. In the TG ¿-conotoxin GVIA inhibited the potassium induced CGRP release significantly...

  7. Releasing phosphorus from calcium for struvite fertilizer production from anaerobically digested dairy effluent.

    Science.gov (United States)

    Zhang, Tianxi; Bowers, Keith E; Harrison, Joseph H; Chen, Shulin

    2010-01-01

    Being a non-renewable resource and a source of potential water pollution, phosphorus could be recovered from animal manure in the form of struvite (MgNH4PO4.6H2O) to be used as a slow-release fertilizer. It was found recently that the majority of phosphorus in anaerobically digested dairy effluent is tied up in a fine suspended calcium-phosphate solid, thus becoming unavailable for struvite formation. Acidification and use of a chelating agent were investigated for converting the calcium-associated phosphorus in the digested effluent to dissolved phosphate ions, so that struvite can be produced. The results demonstrated that the phosphorus in the effluent was released into the solution by lowering the pH. In addition, the phosphorus concentration in the solution increased significantly with increased ethylenediaminetetraacetic acid (EDTA) concentration, as EDTA has a high stability constant with calcium. Most of the phosphorus (91%) was released into the solution after adding EDTA. Further, the freed phosphorus ion precipitated out as struvite provided that sufficient magnesium ions (Mg2+) were present in the solution. Furthermore, the phase structure of the solid precipitate obtained from the EDTA treatment matched well with standard struvite, based on the data from X-ray diffraction analysis. These results provide methods for altering the forms of phosphorus for the design and application of phosphorus-removal technologies for dairy wastewater management. PMID:20112536

  8. Effects of coronal leakage on concentration of hydrogen ions and calcium release of several calcium hydroxide pastes over different periods of time

    Directory of Open Access Journals (Sweden)

    Mariana Pires Crespo

    2013-10-01

    Full Text Available PURPOSE: To evaluate the effects of coronal leakage on concentration of hydrogen ions (pH and calcium release of several calcium hydroxide pastes, over different periods of time. MATERIAL AND METHODS:  Fifty extracted human mandibular central incisors (n=10 were instrumented up to the F2 instrument and assigned to the following intracanal dressing: G1- Calen, G2- Calen with 0.4% chlorhexidine (CHX, G3- Calcium hydroxide with camphorated paramonochlorophenol (CPMC and glycerin, G4- Calen, but temporary filling material maintained during all test (positive control and G5- Root canal without intracanal dressing (negative control. All groups were immersed in distilled water for 7 days. In sequence, the temporary filling materials were removed, except in controls groups. All specimens were individually mounted on a specific device and only its root again immersed in distilled water. Concentration of hydrogen ions and calcium release by calcium hydroxide pastes in distilled water were evaluated in 24h, 7, 14 and 28 days. The results were submitted to ANOVA test (p = 0.05. After 28 days, root canals from experimental groups were examined in SEM. RESULTS: G1, G2, G3 and G4 presented similar pH values and calcium release and did not differ from each other (p>0.05, up to 7 days. After this time G1, G2 and G3 presented values lower values than G4 (p<0.05. In SEM analysis, calcium hydroxide residues were observed in all experimental groups. CONCLUSIONS: After 7 days, coronal leakage decreased the concentration of hydrogen ions and calcium ion release provided by all calcium hydroxide pastes.

  9. A highly calcium-selective cation current activated by intracellular calcium release in MDCK cells.

    Science.gov (United States)

    Delles, C; Haller, T; Dietl, P

    1995-08-01

    1. The whole-cell patch clamp technique and fluorescence microscopy with the Ca2+ indicators fura-2 and fluo-3 were used to measure the whole-cell current and the free intracellular Ca2+ concentration ([Ca2+]i) in Madin-Darby canine kidney (MDCK) cells. 2. In a Ca(2+)-free bath solution, thapsigargin (TG) caused a transient increase of [Ca2+]i. Subsequent addition of Ca2+ caused a long lasting elevation of [Ca2+]i. 3. In a Ca(2+)-free bath solution, extracellular application of TG, ATP or ionomycin, or intracellular application of inositol 1,4,5-trisphosphate (IP3), caused a small but significant inward current (Iin) and a transient outward Ca(2+)-dependent K+ current (IK(Ca)), consistent with intracellular Ca2+ release. Subsequent addition of Ca2+ induced a prominent Iin with a current density of -4.2 +/- 0.7 pA pF-1. This Iin was unaffected by inositol 1,3,4,5-tetrakisphosphate (IP4). 4. Na+ replacement by mannitol, N-methyl-D-glucamine+ (NMG+), aminomethylidin-trimethanol+ (Tris+) or choline+ reduced Iin by 54, 65, 52 and 56%, respectively. This indicates an apparent Ca2+ selectivity over Na+ of 26:1. Iin was, however, unaffected by replacing Cl- with gluconate- or by the K+ channel blocker charybdotoxin (CTX). 5. Iin was completely blocked by La3+ (IC50 = 0.77 microM). Consistently, La3+ completely reversed the TG-induced elevation of [Ca2+]i. SK&F 96365 (1-[3-(4-methoxyphenyl)-propoxyl]-1-(4-methoxy-phenyl)-ethyl-1H-im idazole) HCl did not inhibit the TG-induced Iin. It did, however, exhibit a biphasic effect on [Ca2+]i, consisting of an initial Ca2+ decay and a subsequent Ca2+ elevation. La3+ completely reversed the SK&F 96365-induced elevation of [Ca2+]i. 6. In the absence of Na+, Iin was dependent on the bath Ca2+ concentration (EC50 = 1.02 mM). Ca2+ replacement by Ba2+ or Mn2+ resulted in a reduction of Iin by 95 and 94%, respectively. 7. From these experiments we conclude that Ca2+ release from intracellular Ca2+ stores, induced by different independent

  10. Mechanism of histamine release from rat mast cells induced by the ionophore A23187: effects of calcium and temperature

    DEFF Research Database (Denmark)

    Johansen, Torben

    1978-01-01

    1 The mechanism of histamine release from a pure population of rat mast cells induced by the lipid soluble antibiotic, A23187, has been studied and compared with data for anaphylactic histamine release reported in the literature. 2 Histamine release induced by A23187 in the presence of calcium 10...

  11. Histamine release induced from rat mast cells by the ionophore A23187 in the absence of extracellular calcium

    DEFF Research Database (Denmark)

    Johansen, Torben

    1980-01-01

    Isolated rat mast cells were used to study whether ionophore A23187 could induce histamine release by mobilizing cellular calcium. The histamine release was a slow process which was completed after about 20 min incubation with A23187. The A23187-induced histamine release was inhibited after...

  12. Radioligand assay of cardiac calcium release channel and its application in SHR

    International Nuclear Information System (INIS)

    Purpose: To establish the best condition in assaying the calcium release channel (ryanodine receptor) in cardiac sarcoplasmic reticulum (CSR), and analyse the CSR ryanodine receptor in spantanous hypertensive rat (SHR). Methods: 3H-ryanodine was used as a radioligand to analyse the binding in Sprague Dawley rat cardiac homogenate in following conditions: varied protein concentrations, different free calcium concentrations, different incubation time. The effect of sarcoplasmic reticulum purifying process and ryanodine competitive binding were also studied. Using these best conditions, SHR and control group (WKY) CSR ryanodine receptor were studied. Results: 1) There was a positive linear correlation between 3H-ryanodine binding and the homogenate protein concentration. 2) When the free calcium concentration was 30 μmol/L∼1 mmol/L, the 3H-ryanodine binding reached the maximum. While the free calcium concentration was lower than 1 μmol/L, there was no 3H-ryanodine binding. 3) The 3H-ryanodine binding kept increasing during incubation, from 0 to 60 min, and equilibrium reached by 90 min. 4) The ryanodine specifically inhibited 3H-ryanodine binding in cardiac homogenate. 5) During the sarcoplasmic reticulum purifying process, the 3H-ryanodine binding in a unit amount of cardiac homogenate decreased with the centrifugal force and times applied in centrifugation. 6) SHR and WKY CSR ryanodine receptor saturation curve and Scatchard analysis showed this method produced a very high level of specific binding, up to 45 nmol/L ryanodine, which inferred a single class of binding sites. The Bmax value of CSR ryanodine receptor in SHR left ventricle was significantly higher than that in WKY (P3H-ryanodine can be used as a radioligand to analyse the calcium release channel in cardiac homogenate, and ryanodine receptor may play an important role in hypertensive left ventricular remodeling process

  13. Release of C2 Radicals after the Deep Impact Event

    Science.gov (United States)

    Schulz, R.; Stüwe, J. A.; Erd, C.; Martin, D.; Smit, H.

    We present the results of investigating the coma of comet 9P/Tempel 1 in C2 and continuum, before and after the Deep Impact event of 4 July 2005. A jet-like coma feature was produced by the impact, and its temporal evolution in morphology and brightness has been compared for the dust and gas coma. It shows that the feature remains visible in the dust coma for several days, whereas in the C2 coma it is visible only on the image taken 15.8 hours after the impact and has vanished when the coma was observed again in the following night. The observational evidence strongly supports that the C2 in the feature observed on 4 July 2005 was produced from fresh dust particles released by the outburst and forming an extended source for the production of the C2 radical. This indicates that the disintegration of C2-bearing dust species can directly be observed during the non-steady state conditions present immediately after outbursts and/or nucleus splitting.

  14. Solution combustion synthesis of calcium phosphate particles for controlled release of bovine serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Junfeng, E-mail: daidai02304@163.com [School of Chemistry and Materials Engineering, Changshu Institute of Technology, Changshu (China); Jiangsu Laboratory of Advanced Functional Materials, Changshu Institute of Technology, Changshu (China); Zhao, Junjie; Qian, Yu; Zhang, Xiali; Zhou, Feifei; Zhang, Hong [School of Chemistry and Materials Engineering, Changshu Institute of Technology, Changshu (China); Lu, Hongbin [National Laboratory of Solid State Microstructures, College of Engineering and Applied Sciences, Nanjing University, Nanjing (China); Chen, JianHua; Wang, XuHong [School of Chemistry and Materials Engineering, Changshu Institute of Technology, Changshu (China); Jiangsu Laboratory of Advanced Functional Materials, Changshu Institute of Technology, Changshu (China); Yu, Wencong [School of Chemistry and Materials Engineering, Changshu Institute of Technology, Changshu (China)

    2015-05-01

    Four different phase compositions of calcium phosphate (CaP) particles were prepared via a solution combustion method. X-ray diffraction (XRD) and Rietveld analysis results revealed that the variations in the nominal Ca/P (molar) ratios were found to provide a favorable control in the different proportions of CaP materials. Bovine serum albumin (BSA) was used as a model protein to study the loading and release behavior. The release profile indicated that the BSA release rates depended on the phase compositions of the CaP particles, and showed an order of TCP-BSA > BCP-1-BSA > BCP-2-BSA > HA-BSA. The results suggested that the BSA protein release rate can be controlled by varying the phase compositions of CaP carriers. Moreover, the release process involved two stages: firstly surface diffusion via ion exchange and secondly intraparticle diffusion. - Highlights: • Solution combustion method was an efficient way to produced CaP powders. • Ca/P (molar) ratios provided a favorable control in the different proportions of phase composition. • BSA release rate varied depending on the phase composition of the CaP particles. • Two kinetic models were chosen to simulate the release kinetics of the drugs from CaP carriers.

  15. Calcium binding-mediated sustained release of minocycline from hydrophilic multilayer coatings targeting infection and inflammation.

    Directory of Open Access Journals (Sweden)

    Zhiling Zhang

    Full Text Available Infection and inflammation are common complications that seriously affect the functionality and longevity of implanted medical implants. Systemic administration of antibiotics and anti-inflammatory drugs often cannot achieve sufficient local concentration to be effective, and elicits serious side effects. Local delivery of therapeutics from drug-eluting coatings presents a promising solution. However, hydrophobic and thick coatings are commonly used to ensure sufficient drug loading and sustained release, which may limit tissue integration and tissue device communications. A calcium-mediated drug delivery mechanism was developed and characterized in this study. This novel mechanism allows controlled, sustained release of minocycline, an effective antibiotic and anti-inflammatory drug, from nanoscale thin hydrophilic polyelectrolyte multilayers for over 35 days at physiologically relevant concentrations. pH-responsive minocycline release was observed as the chelation between minocycline and Ca(2+ is less stable at acidic pH, enabling 'smart' drug delivery in response to infection and/or inflammation-induced tissue acidosis. The release kinetics of minocycline can be controlled by varying initial loading, Ca(2+ concentration, and Ca(2+ incorporation into different layers, enabling facile development of implant coatings with versatile release kinetics. This drug delivery platform can potentially be used for releasing any drug that has high Ca(2+ binding affinity, enabling its use in a variety of biomedical applications.

  16. Synthesis of porous poly(acrylamide hydrogels using calcium carbonate and its application for slow release of potassium nitrate

    Directory of Open Access Journals (Sweden)

    2009-05-01

    Full Text Available Porous poly(acrylamide was synthesized using calcium carbonate microparticles and subsequent acid treatment to remove the calcium carbonate. Methylenebisacrylamide and ammonium persulfate/sodium metabisulfite were used as crosslinking agent and redox initiator, respectively. The porous structure of resulted hydrogels was confirmed using SEM micrographs. The effect of methylenebisacrylamide concentration and calcium carbonate amount on the swelling of the hydrogels was investigated. The results showed that the effect of methylenebisacrylamide and calcium carbonate variables on the swelling is reverse. The hydrogels were subsequently utilized for the loading of potassium nitrate. Potassium nitrate as active agent was loaded into hydrogels and subsequently the release of this active agent was investigated. In these series of investigation, the effect of content of loading, methylenebisacrylamide and calcium carbonate amount on the release of potassium nitrate from hydrogels was investigated.

  17. Calmodulin modulates the delay period between release of calcium from internal stores and activation of calcium influx via endogenous TRP1 channels.

    Science.gov (United States)

    Vaca, Luis; Sampieri, Alicia

    2002-11-01

    In the present study we have explored the role of calmodulin (CaM) and inositol 1,4,5-trisphosphate receptor (IP(3)R) in the communication process activated after the release of calcium from the endoplasmic reticulum (ER) and the activation of calcium influx via endogenous TRP1 channels from Chinese hamster ovary cells. Experiments using combined rapid confocal calcium and electrophysiology measurements uncovered a consistent delay of around 900 ms between the first detectable calcium released from the ER and the activation of the calcium current. This delay was evident with two different methods used to release calcium from the ER: either the blockade of the microsomal calcium ATPase with thapsigargin or activation of bradykinin receptors linked to the IP(3) cascade. Direct application of IP(3) or a peptide from the NH(2)-terminal region of the IP(3)R activated store operated calcium, reducing the delay period. Introduction of CaM into the cell via the patch pipette increased the delay period from 900 +/- 100 ms to 10 +/- 2.1 s (n = 18). Furthermore, the use of selective CaM antagonists W7 and trifluoperazine maleate resulted in a substantial reduction of the delay period to 200 +/- 100 ms with 5 microm trifluoperazine maleate (n = 16) and 150 +/- 50 ms with 500 nm W7 (n = 22). CaM reduced also the current density activated by thapsigargin or brandykinin to about 60% from control. The CaM antagonists did not affect significantly the current density. The results presented here are consistent with an antagonistic effect of IP(3)R and CaM for the activation of store operated calcium after depletion of the ER. The functional competition between the activating effect of IP(3)R and the inhibiting effect of CaM may modulate the delay period between the release of calcium from the ER and the activation of calcium influx observed in different cells, as well as the amount of current activated after depletion of the ER.

  18. Dopamine receptors on adrenal chromaffin cells modulate calcium uptake and catecholamine release

    Energy Technology Data Exchange (ETDEWEB)

    Bigornia, L.; Suozzo, M.; Ryan, K.A.; Napp, D.; Schneider, A.S.

    1988-10-01

    The presence of dopamine-containing cells in sympathetic ganglia, i.e., small, intensely fluorescent cells, has been known for some time. However, the role of dopamine as a peripheral neurotransmitter and its mechanism of action are not well understood. Previous studies have demonstrated the presence of D2 dopamine receptors on the surface of bovine adrenal chromaffin cells using radioligand binding methods and dopamine receptor inhibition of catecholamine release from perfused adrenal glands. In the present study, we provide evidence confirming a role of dopamine receptors as inhibitory modulators of adrenal catecholamine release from bovine chromaffin cell cultures and further show that the mechanism of modulation involves inhibition of stimulated calcium uptake. Apomorphine gave a dose-dependent inhibition (IC50 = 1 microM) of 45Ca2+ uptake stimulated by either nicotine (10 microM) or membrane depolarization with an elevated K+ level (60 mM). This inhibition was reversed by a series of specific (including stereospecific) dopamine receptor antagonists: haloperidol, spiperone, sulpiride, and (+)-butaclamol, but not (-)-butaclamol. In addition, the calcium channel agonist Bay K 8644 was used to stimulate uptake of 45Ca2+ into chromaffin cells, and this uptake was also inhibited by the dopamine receptor agonist apomorphine. The combined results suggest that dopamine receptors on adrenal chromaffin cells alter Ca2+ channel conductance, which, in turn, modulates catecholamine release.

  19. Stimulatory effects of maitotoxin on insulin release in insulinoma HIT cells: Role of calcium uptake and phosphoinositide breakdown

    International Nuclear Information System (INIS)

    In hamster insulinoma (HIT) cells, maitotoxin (MTX) induces a time-dependent and concentration-dependent release of insulin that requires the presence of extracellular calcium. The response is nearly completely blocked by cinnarizine and cadmium, but is not inhibited by the L-type calcium channel blocker nifedipine or by manganese. MTX induces 45Ca+ uptake in these cells in a dose-dependent mode, and the uptake is blocked with cinnarizine, nifedipine and cadmium, and is partially inhibited by manganese. MTX induces phosphoinositide breakdown in HIT cells, and the response is partially blocked by cadmium, but is not affected by nifedipine, cinnarizine or manganese. High concentrations of potassium ions also induce insulin release and calcium uptake in HIT cells. Both effects of potassium are blocked partially by nifedipine, cadmium and cinnarizine. High concentrations of potassium do not induce phosphoinositide breakdown in HIT cells. The results suggest that MTX-elicited release of insulin is attained by two mechanisms: (1) a nifedipine-sensitive action, which results from MTX-induced activation of L-type calcium channels, which can be mimicked with high potassium concentrations; and (2) a nifedipine-insensitive action, which may be initiated by the activation of phosphoinositide breakdown by MTX. Such an activation of phospholipase C would result in the formation of 1,4,5-inositol trisphosphate, a release of intracellular calcium and then release of insulin to the extracellular space. Cinnarizine is proposed to block both MTX-elicited mechanisms, the first by blockade of calcium channels and the second by blocking 1,4,5-inositol trisphosphate-induced release of internal calcium. Either mechanism alone appears capable of eliciting release of insulin

  20. Effects of Arecoline on Calcium Channel Currents and Caffeine-induced Calcium Release in Isolated Single Ventricular Myocyte of Guinea Pig

    Institute of Scientific and Technical Information of China (English)

    林先明; 李真; 胡本容; 夏国瑾; 姚伟星; 向继洲

    2002-01-01

    Summary: The effects of Arecoline (Are) on calcium mobilization were investigated. In isolatedsingle ventricular myocyte of guinea pig, patch clamp whole cell recording techniques were used torecord the current of L-type calcium channel and cytosolic Ca2+ level ([Ca2+]i) labeled with fluo-rescence probe Fluo-3/AM was measured under a laser scanning confocal microscope. Results re-vealed that Are (3-100 μmol/L) could inhibit L-type calcium current in a concentration-depen-dent manner and the value of IC50 was 33. 73μmol/L (n= 5). In the absence of extracellular calci-um, the resting levels of [Ca2+]i was not affected by Are (n=6, P>0. 05), but pretreatmentwith Are (30 μmol/L) could significantly inhibit the [Ca2+]i elevation induced by caffeine (10mmol/L, n = 6, P < 0. 01). It was concluded that Are could inhibit not only calcium influxthrough L-type calcium channel but also calcium release from sarcoplasmic reticulum.

  1. Polychlorinated biphenyl quinone induces endoplasmic reticulum stress, unfolded protein response, and calcium release.

    Science.gov (United States)

    Xu, Demei; Su, Chuanyang; Song, Xiufang; Shi, Qiong; Fu, Juanli; Hu, Lihua; Xia, Xiaomin; Song, Erqun; Song, Yang

    2015-06-15

    Organisms are able to respond to environmental insult to maintain cellular homeostasis, which include the activation of a wide range of cellular adaptive responses with tightly controlled mechanisms. The endoplasmic reticulum (ER) is an organelle responsible for protein folding and calcium storage. ER stress leads to the accumulation of unfolded proteins in the ER lumen. To be against or respond to this effect, cells have a comprehensive signaling system, called unfolded protein response (UPR), to restore homeostasis and normal ER function or activate the cell death program. Therefore, it is critical to understand how environmental insult regulates the ingredients of ER stress and UPR signalings. Previously, we have demonstrated that polychlorinated biphenyl (PCB) quinone caused oxidative stress, cytotoxicity, genotoxicity, and apoptosis in HepG2 cells. Here, we investigated the role of a PCB quinone, PCB29-pQ on ER stress, UPR, and calcium release. PCB29-pQ markedly increased the hallmark genes of ER stress, namely, glucose-regulated protein 78 (GRP78), GRP94, and C/EBP homologous protein (CHOP) on both protein and mRNA levels in HepG2 cells. We also confirmed PCB29-pQ induced ER morphological defects by using transmission electron microscopy. Moreover, PCB29-pQ induced intracellular calcium accumulation and calpain activity, which were significantly inhibited by the pretreatment of BAPTA-AM (Ca(2+) chelator). These results were correlated with the outcome that PCB29-pQ induces ER stress-related apoptosis through caspase family gene 12, while salubrinal and Z-ATAD-FMK (a specific inhibitor of caspase 12) partially ameliorated this effect, respectively. N-Acetyl-l-cysteine (NAC) scavenged ROS formation and consequently alleviated PCB29-pQ-induced expression of ER stress-related genes. In conclusion, our result demonstrated for the first time that PCB quinone leads to ROS-dependent induction of ER stress, and UPR and calcium release in HepG2 cells, and the

  2. Incorporation of a controlled-release glass into a calcium phosphate cement.

    Science.gov (United States)

    Khairoun, I; Boltong, M G; Gil, F J; Driessens, F C; Planell, J A; Seijas, M M; Martínez, S

    1999-04-01

    A so-called controlled-release glass was synthesized occurring in the system CaO-Na2O-P2O5. A certain sieve fraction of this glass was incorporated in a calcium phosphate cement, of which the powder contained alpha-tricalcium phosphate (alpha-TCP), dicalcium phosphate (DCP) and precipitated hydroxyapatite (HA). The glass appeared to retard the cement setting slightly and it reduced considerably the compressive strength after aging in aqueous solutions which were continuously refreshed. Scanning electron microscope (SEM) pictures and X-ray diffraction (XRD) patterns of the samples after 5 weeks of aging showed that the glass was not dissolved but that large brushite crystals were formed. Thereby, aging in CaCl2 solutions resulted in more brushite formation than aging in NaCl solutions. The brushite crystals did not reinforce the cement. Neither was the aged glass-containing cement weaker than it was before the brushite formation right after complete setting. In conclusion, the incorporation of controlled-release glasses into a calcium phosphate cement and subsequent aging in aqueous solutions did not result in the formation of macropores in the cement structure, but that of brushite crystals. This incorporation reduced the compressive strength of the cement considerably.

  3. Hydrogen ion and calcium releasing of mTA fillapex® and mTA-based formulations

    Directory of Open Access Journals (Sweden)

    Milton Carlos Kuga

    2011-07-01

    Full Text Available Introduction: MTA is composed of various metal oxides, calcium oxide and bismuth. It has good biological properties and is indicated in cases of endodontic complications. Several commercial formulations are available and further studies are necessary to evaluate these materials. Objective: To evaluate pH and calcium releasing of MTA Fillapex® compared with gray and white MTA. Material and methods: Gray and white MTA (Angelus and MTA Fillapex® (Angelus were manipulated and placed into polyethylene tubes and immersed in distilled water. The pH of these solutions was measured at 24 hours, 7 days and 14 days. Simultaneously, at these same aforementioned periods, these materials’ calcium releasing was quantified, through atomic absorption spectrophotometry. The results were submitted to ANOVA, with level of significance at 5%. Results: Concerning to pH, the materials present similar behaviors among each other at 24 hours (p > 0.05. At 7 and 14 days, MTA Fillapex® provided significantly lower pH values than the other materials (p < 0.05. Regarding to calcium releasing, at 24 hours and 7 days, MTA Fillapex® provided lower releasing than the other materials (p < 0.05. After 14 days, differences were found between MTA Fillapex® and gray MTA (p < 0.05. Conclusion: All materials showed alkaline pH and calcium releasing, with significantly lower values for MTA Fillapex® sealer.

  4. Effects of inorganic mercury (Hg{sup 2+}) on calcium channel currents and catecholamine release from bovine chromaffin cells

    Energy Technology Data Exchange (ETDEWEB)

    Weinsberg, F. [Medical Inst. of Environmental Hygiene, Heinrich Heine University, Duesseldorf (Germany); Bickmeyer, U. [Medical Inst. of Environmental Hygiene, Heinrich Heine University, Duesseldorf (Germany); Wiegand, H. [Medical Inst. of Environmental Hygiene, Heinrich Heine University, Duesseldorf (Germany)

    1995-01-01

    The effects of Hg{sup 2+} on calcium channel currents and the potassium-evoked catecholamine release of bovine chromaffin cells in culture were examined. The effects of Cd{sup 2+} were studied for comparison. Calcium channel currents were recorded in the whole-cell configuration of the patch-clamp technique. In a concentration of 100 {mu}M, Hg{sup 2+} blocked the currents completely; 100 {mu}M Cd{sup 2+} had the same effect. Potassium-evoked catecholamine release from chromaffin cells was measured at different timepoints with HPLC under control conditions and in the presence of different Hg{sup 2+} concentrations. Low Hg{sup 2+} concentrations (0.1 and 1 {mu}M) did not affect the amount of the catecholamines epinephrine (E) and norepinephrine (NE) which was released. Under identical conditions 1 {mu}M Cd{sup 2+} also had no effect on release. With 10 {mu}M Hg{sup 2+} there was a time-dependent increase in the potassium-evoked catecholamine release (by 27% after 8 min). The E/NE ratio was not altered. In contrast to this, the release was slightly reduced with 10 {mu}M Cd{sup 2+}. In the presence of 100 {mu}M Hg{sup 2+}, there was a reduction of the release during an early phase, followed by an increase. The calcium channel block by 100 {mu}M Cd{sup 2+} also reduced the release significantly. Catecholamine release of bovine chromaffin cells is driven into two opposite directions by Hg{sup 2+}. On the one hand, a calcium channel block reduces the release, while on the other hand effects occur which can increase the release. Both tendencies occur simultaneously, but have different concentration- and time-dependencies. The catecholamine output at a given timepoint reflects the `sum` of these different effects. (orig.)

  5. Estradiol coupling to human monocyte nitric oxide release is dependent on intracellular calcium transients: evidence for an estrogen surface receptor.

    Science.gov (United States)

    Stefano, G B; Prevot, V; Beauvillain, J C; Fimiani, C; Welters, I; Cadet, P; Breton, C; Pestel, J; Salzet, M; Bilfinger, T V

    1999-10-01

    We tested the hypothesis that estrogen acutely stimulates constitutive NO synthase (cNOS) activity in human peripheral monocytes by acting on an estrogen surface receptor. NO release was measured in real time with an amperometric probe. 17beta-estradiol exposure to monocytes stimulated NO release within seconds in a concentration-dependent manner, whereas 17alpha-estradiol had no effect. 17beta-estradiol conjugated to BSA (E2-BSA) also stimulated NO release, suggesting mediation by a membrane surface receptor. Tamoxifen, an estrogen receptor inhibitor, antagonized the action of both 17beta-estradiol and E2-BSA, whereas ICI 182,780, a selective inhibitor of the nuclear estrogen receptor, had no effect. We further showed, using a dual emission microfluorometry in a calcium-free medium, that the 17beta-estradiol-stimulated release of monocyte NO was dependent on the initial stimulation of intracellular calcium transients in a tamoxifen-sensitive process. Leeching out the intracellular calcium stores abolished the effect of 17beta-estradiol on NO release. RT-PCR analysis of RNA obtained from the cells revealed a strong estrogen receptor-alpha amplification signal and a weak beta signal. Taken together, a physiological dose of estrogen acutely stimulates NO release from human monocytes via the activation of an estrogen surface receptor that is coupled to increases in intracellular calcium. PMID:10490972

  6. Ions Release and pH of Calcium Hydroxide-, Chlorhexidine- and Bioactive Glass-Based Endodontic Medicaments.

    Science.gov (United States)

    Carvalho, Ceci Nunes; Freire, Laila Gonzales; Carvalho, Alexandre Pinheiro Lima de; Duarte, Marco Antonio Húngaro; Bauer, José; Gavini, Giulio

    2016-01-01

    This study evaluated pH and release of calcium, sodium and phosphate ions from different medications in human dentin. Fifty premolars were prepared and randomly divided into groups: (CHX) - 2% chlorhexidine gel; (CHX + CH) - CHX + calcium hydroxide PA; (CH) - CH + propylene glycol 600; (NPBG) - experimental niobium phosphate bioactive glass + distilled water; (BG) - bioactive glass (Bio-Gran) + distilled water. The specimens were immersed in deionized water and the pH variations were measured. The quantification of ions in the solutions was made by inductively coupled plasma - atomic emission spectroscopy (ICP/AES) at 10 min, 24 h, 7, 14, 21 and 30 days. The results were analyzed by ANOVA and Tukey`s test, with a significance level of 5%. CH had the highest level of calcium ions release at 30 days, while CHX and BG released more sodium ions. BG, NPBG and CHX released a higher amount of phosphate ions. The pH of CH was significantly higher compared with the other groups. CH favored the greatest increase of pH and calcium ions release. The bioactive glasses released more sodium and phosphate ions and presented an alkaline pH immediately and after 30 days. PMID:27224568

  7. pH and calcium ion release evaluation of pure and calcium hydroxide-containing Epiphany for use in retrograde filling

    Directory of Open Access Journals (Sweden)

    Mário Tanomaru-Filho

    2011-02-01

    Full Text Available OBJECTIVE: Hydroxyl (OH- and calcium (Ca++ ion release was evaluated in six materials: G1 Sealer 26, G2 White mineral trioxide aggregate (MTA, G3 Epiphany, G4 Epiphany + 10% calcium hydroxide (CH, G5 Epiphany + 20% CH, and G6 zinc oxide and eugenol. MATERIAL AND METHODS: Specimens were placed in polyethylene tubes and immersed in distilled water. After 3, 6, 12, 24, and 48 h, 7, 14, and 28 days, the water was assessed for pH with a pH meter and for Ca++ release by atomic absorption spectrophotometry. RESULTS: G1, G2, G4, and G5 had the highest pH until 14 days (p<0.05. G1 presented the highest Ca++ release until 6 h, and G4 and G5, from 12 h through 14 days. Ca++ release was greater for G1 and G2 at 28 days. G6 released the least Ca++. CONCLUSIONS: MTA, Sealer 26, Epiphany, and Epiphany + CH release OH- and Ca++ ions. Epiphany + CH may be an alternative as retrofilling material.

  8. Coronary artery calcium and exercise electrocardiogram as predictors of coronary events in asymptomatic adults.

    Science.gov (United States)

    Grossman, Chagai; Ehrlich, Shay; Shemesh, Joseph; Koren-Morag, Nira; Grossman, Ehud

    2015-03-15

    Early identification of patients at risk for coronary heart disease is crucial to formulate effective preventive strategies. The elevated risk of coronary artery calcium (CAC) for coronary heart disease is well established. Our aim was to estimate the relative risk of abnormal exercise electrocardiography (Ex ECG) in the presence of CAC. During the year 2001, 566 asymptomatic subjects performed a treadmill exercise test and consented to perform an unenhanced computed tomography to assess CAC. Patients were followed until December 2012. The relative risk for coronary events (acute myocardial infarction, hospitalization for unstable angina or coronary catheterization that resulted in angioplasty or coronary artery bypass surgery), of abnormal Ex ECG and presence of CAC were analyzed. An abnormal Ex ECG was found in 71 subjects (12.5%), and CAC was found in 286 subjects (50.5%). During a mean follow-up of 6.5 ± 3.3 years, 35 subjects experienced a first coronary event. In those without CAC, the rate of coronary events was low (4 of 280; 1.4%) regardless of the Ex ECG results. Subjects with both CAC and abnormal Ex ECG had the highest rate of coronary events (13 of 39; 33%). The adjusted hazard ratio for coronary events, in subjects with CAC, was 5.16 (95% confidence interval 2.52 to 10.60) in those with abnormal Ex ECG compared with those with normal Ex ECG. In conclusion, in subjects with CAC, further risk stratification can be achieved by an Ex ECG, whereas in those without CAC, an Ex ECG has less additional value in predicting coronary events. PMID:25616536

  9. Comparison of the calcium release channel of cardiac and skeletal muscle sarcoplasmic reticulum by target inactivation analysis

    International Nuclear Information System (INIS)

    The calcium release channel of sarcoplasmic reticulum which triggers muscle contraction in excitation-contraction coupling has recently been isolated. The channel has been found to be morphologically identical with the feet structures of the junctional face membrane of terminal cisternae and consists of an oligomer of a unique high molecular weight polypeptide. In this study, the authors compare the target size of the calcium release channel from heart and skeletal muscle using target inactivation analysis. The target molecular weights of the calcium release channel estimated by measuring ryanodine binding after irradiation are similar for heart (139,000) and skeletal muscle (143,000) and are smaller than the monomeric unit (estimated to be about 360,000). The target size, estimated by measuring polypeptide remaining after irradiation, was essentially the same for heart and skeletal muscle, 1,061,000 and 1,070,000, respectively, indicating an oligomeric association of protomers. Thus, the calcium release channel of both cardiac and skeletal muscle reacts uniquely with regard to target inactivation analysis in that (1) the size by ryanodine binding is smaller than the monomeric unit and (2) a single hit leads to destruction of more than one polypeptide, by measuring polypeptide remaining. The target inactivation analysis studies indicate that heart and skeletal muscle receptors are structurally very similar

  10. Fluoride varnishes with calcium glycerophosphate: fluoride release and effect on in vitro enamel demineralization

    Directory of Open Access Journals (Sweden)

    Thiago Saads CARVALHO

    2015-01-01

    Full Text Available The aims of this study were (1 to assess the amount of fluoride (F released from varnishes containing calcium glycerophosphate (CaGP and (2 to assess the effect of the experimental varnishes on in vitro demineralization. Six test groups using 5 varnishes: base varnish (no active ingredients; Duraphat® (2.26% NaF; Duofluorid® (5.63% NaF/CaF2; experimental varnish 1 (1% CaGP/5.63% NaF/CaF2; experimental varnish 2 (5% CaGP/5.63% NaF/CaF2; and no varnish were set up. In stage 1, 60 acrylic blocks were randomly distributed into 6 groups (n = 10. Then 300 µg of each varnish was applied to each block. The blocks were immersed in deionized water, which was changed after 1, 8, 12, 24, 48 and 72 hours. Fluoride concentration in the water was analyzed using a fluoride electrode. In stage 2, 60 bovine enamel samples were distributed into 6 groups (n = 10, and treated with 300 µg of the respective varnish. After 6 h the varnish was removed and the samples were subjected to a 7-day in vitro pH cycle (6 h demineralization/18 h remineralization per day. The demineralization was measured using surface hardness. The results showed that both experimental varnishes released more fluoride than Duofluorid® and Duraphat® (p < 0.05, but Duraphat® showed the best preventive effect by decreasing enamel hardness loss (p < 0.05. Therefore, we conclude that even though (1 the experimental varnishes containing CaGP released greater amounts of F, (2 they did not increase in the preventive effect against enamel demineralization.

  11. Membrane Properties Involved in Calcium-Stimulated Microparticle Release from the Plasma Membranes of S49 Lymphoma Cells

    Directory of Open Access Journals (Sweden)

    Lauryl E. Campbell

    2014-01-01

    Full Text Available This study answered the question of whether biophysical mechanisms for microparticle shedding discovered in platelets and erythrocytes also apply to nucleated cells: cytoskeletal disruption, potassium efflux, transbilayer phospholipid migration, and membrane disordering. The calcium ionophore, ionomycin, disrupted the actin cytoskeleton of S49 lymphoma cells and produced rapid release of microparticles. This release was significantly inhibited by interventions that impaired calcium-activated potassium current. Microparticle release was also greatly reduced in a lymphocyte cell line deficient in the expression of scramblase, the enzyme responsible for calcium-stimulated dismantling of the normal phospholipid transbilayer asymmetry. Rescue of the scrambling function at high ionophore concentration also resulted in enhanced particle shedding. The effect of membrane physical properties was addressed by varying the experimental temperature (32–42°C. A significant positive trend in the rate of microparticle release as a function of temperature was observed. Fluorescence experiments with trimethylammonium diphenylhexatriene and Patman revealed significant decrease in the level of apparent membrane order along that temperature range. These results demonstrated that biophysical mechanisms involved in microparticle release from platelets and erythrocytes apply also to lymphocytes.

  12. Differential release of eicosanoids by bradykinin, arachidonic acid and calcium ionophore A23187 in guinea-pig isolated perfused lung.

    OpenAIRE

    Bakhle, Y. S.; Moncada, S.; de Nucci, G.; Salmon, J A

    1985-01-01

    The effects of infusions of bradykinin (0.2 microM), calcium ionophore A23187 (0.5 microM) and arachidonic acid (13 microM) on the release of eicosanoids from the guinea-pig isolated perfused lung were investigated using radioimmunoassay for thromboxane B2 (TXB2), 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha), PGE2, leukotriene B4 (LTB4) and LTC4 and bioassay using the superfusion cascade. Bradykinin released more 6-oxo-PGF1 alpha than TXB2, whereas arachidonic acid and ionophore released m...

  13. Self-Setting Calcium Phosphate Cements with Tunable Antibiotic Release Rates for Advanced Antimicrobial Applications.

    Science.gov (United States)

    Ghosh, Shreya; Wu, Victoria; Pernal, Sebastian; Uskoković, Vuk

    2016-03-01

    Osteomyelitis, an infectious disease predominantly tied to poor sanitary conditions in underdeveloped regions of the world, is in need of inexpensive, easily in situ synthesizable and administrable materials for its treatment. The results of this study stem from the attempt to create one such affordable and minimally invasive therapeutic platform in the form of a self-setting, injectable cement with a tunable drug release profile, composed of only nanoparticulate hydroxyapatite, the synthetic version of the bone mineral. Cements comprised two separately synthesized hydroxyapatite powders, one of which, HAP2, was precipitated abruptly, retaining the amorphous nature longer, and the other one of which, HAP1, was precipitated at a slower rate, more rapidly transitioning to the crystalline structure. Cements were made with four different weight ratios of the two hydroxyapatite components: 100/0, 85/15, 50/50, and 0/100 with respect to HAP1 and HAP2. Both the setting and the release rates measured on two different antibiotics, vancomycin and ciprofloxacin, were controlled using the weight ratio of the two hydroxyapatite components. Various inorganic powder properties were formerly used to control drug release, but here we demonstrate for the first time that the kinetics of the mechanism of formation of a solid compound can be controlled to produce tunable drug release profiles. Specifically, it was found that the longer the precursor calcium phosphate component of the cement retains the amorphous nature of the primary precipitate, the more active it was in terms of speeding up the diffusional release of the adsorbed drug. The setting rate was, in contrast, inversely proportional to the release rate and to the content of this active hydroxyapatite component, HAP2. The empirical release profiles were fitted to a set of equations that could be used to tune the release rate to the therapeutic occasion. All of the cements loaded with vancomycin or ciprofloxacin inhibited the

  14. Soil Manganese and Iron Released due to Calcium Salts:Bioavailability to Pepper (Capsicum frutescens L.)

    Institute of Scientific and Technical Information of China (English)

    SI You-Bin; ZHOU Jing; ZHOU Dong-Mei; CHEN Huai-Man

    2004-01-01

    Releases of manganese and iron ions from an albic soil (Albic-Udic Luvisol), a yellow-red soil (Hap-Udic Ferrisol) and a yellow-brown soil (Arp-Udic Luvisol) induced by calcium salt addition and their bioavailability to pepper (Capsicum frutescens L.) were studied in a pot experiment. Addition of Ca(NO3)2 decreased soil pH and increased both exchangeable and DTPA (diethylenetriamine pentaacetic acid)-extractable Mn and Fe in soils. Meanwhile, total Mn accumulation in the shoots of Capsicum frutescens L. on the salt-treated soils increased significantly (P < 0.01) compared with the control, suggesting that salt addition to soil induced Mn toxicity in Capsicum frutescens L. Although exchangeable and DTPA-extractable Fe increased also in the salt-treated soils, Fe uptake by the shoots of Capsicum frutescens L. decreased. The effect of added salts in soils on dry matter weight of pepper varied with the soil characteristics, showing different buffer capacities of the soils for salt toxicity in an order of yellow-brown soil > albic soil > yellow-red soil. Fe/Mn ratio in shoots of Capsicum frutescens L. decreased with increasing salt addition for all the soils, which was ascribed to the antagonistic effect of Mn on Fe accumulation. The ratio of Fe/Mn in the tissue was a better indicator of the appearance of Mn toxicity symptoms than Mn concentration alone.

  15. Contractile function is unaltered in diaphragm from mice lacking calcium release channel isoform 3

    Science.gov (United States)

    Clancy, J. S.; Takeshima, H.; Hamilton, S. L.; Reid, M. B.

    1999-01-01

    Skeletal muscle expresses at least two isoforms of the calcium release channel in the sarcoplasmic reticulum (RyR1 and RyR3). Whereas the function of RyR1 is well defined, the physiological significance of RyR3 is unclear. Some authors have suggested that RyR3 participates in excitation-contraction coupling and that RyR3 may specifically confer resistance to fatigue. To test this hypothesis, we measured contractile function of diaphragm strips from adult RyR3-deficient mice (exon 2-targeted mutation) and their heterozygous and wild-type littermates. In unfatigued diaphragm, there were no differences in isometric contractile properties (twitch characteristics, force-frequency relationships, maximal force) among the three groups. Our fatigue protocol (30 Hz, 0.25 duty cycle, 37 degrees C) depressed force to 25% of the initial force; however, lack of RyR3 did not accelerate the decline in force production. The force-frequency relationship was shifted to higher frequencies and was depressed in fatigued diaphragm; lack of RyR3 did not exaggerate these changes. We therefore provide evidence that RyR3 deficiency does not alter contractile function of adult muscle before, during, or after fatigue.

  16. Interleukin-2 stimulates osteoclastic activity: Increased acid production and radioactive calcium release

    International Nuclear Information System (INIS)

    Recombinant human interleukin-2 (IL-2) was studied to determine effects on acid production by individual osteoclasts in situ on mouse calvarial bones. This analysis was performed using a microspectrofluorimetric technique to quantify acid production in individual cells. Radioactive calcium release was determined using calvarial bones in a standard tissue culture system. This allowed us to correlate changes in acid production with a measure of bone resorption. IL-2 stimulated acid production and bone resorbing activity. Both effects were inhibited by calcitonin. No stimulation of bone resorption occurred when IL-2-containing test media was incubated with a specific anti-IL-2 antibody and ultrafiltered. Our data demonstrated a correlation between acid production and bone resorbing activity in mouse calvaria exposed to parathyroid hormone (PTH). The data obtained from cultured mouse calvaria exposed to IL-2 demonstrated similar stimulatory effects to those seen during PTH exposure. These data suggest that calvaria exposed to IL-2 in vitro have increased osteoclastic acid production corresponding with increased bone resorption. (author)

  17. Intracellular calcium stores drive slow non-ribbon vesicle release from rod photoreceptors

    OpenAIRE

    Minghui eChen; David eKrizaj; Thoreson, Wallace B

    2014-01-01

    Rods are capable of greater slow release than cones contributing to overall slower release kinetics. Slow release in rods involves Ca2+-induced Ca2+ release (CICR). By impairing release from ribbons, we found that unlike cones where release occurs entirely at ribbon-style active zones, slow release from rods occurs mostly at ectopic, non-ribbon sites. To investigate the role of CICR in ribbon and non-ribbon release from rods, we used total internal reflection fluorescence microscopy (TIRFM) a...

  18. Comparing Titanium Release from Ceramic Tiles using a waste material characterization test - Influence of Calcium and Organic Matter concentrations

    DEFF Research Database (Denmark)

    Heggelund, Laura Roverskov; Hansen, Steffen Foss; Astrup, Thomas Fruergaard;

    2015-01-01

    be deposited in landfills for construction and demolition waste or other types of landfills, depending on the local waste management system. Hence, the potential release of nano-Ti under landfill conditions is relevant to investigate. In this study we used a standard waste material characterization method...... waste material to the landfill leachate, it is expected that the calcium and organic matter content in the liquid will affect the stability of the nanoparticles. The concentration of calcium in the landfill percolate is expected to decrease the stability of the particles due to compression...... of the electric double layer surrounding the particle, causing increased particle agglomeration and settling. Natural organic matter might have both a stabilizing and destabilizing effect on the released nano-Ti particles depending on the concentration, since this will specifically influence the ability...

  19. Ryanodine modification of cardiac muscle responses to potassium-free solutions. Evidence for inhibition of sarcoplasmic reticulum calcium release

    OpenAIRE

    1983-01-01

    To test whether ryanodine blocks the release of calcium from the sarcoplasmic reticulum in cardiac muscle, we examined its effects on the aftercontractions and transient depolarizations or transient inward currents developed by guinea pig papillary muscles and voltage-clamped calf cardiac Purkinje fibers in potassium-free solutions. Ryanodine (0.1-1.0 microM) abolished or prevented aftercontractions and transient depolarizations by the papillary muscles without affecting any of the other sequ...

  20. Dopamine release in organotypic cultures of foetal mouse mesencephalon: effects of depolarizing agents, pargyline, nomifensine, tetrodotoxin and calcium

    DEFF Research Database (Denmark)

    Larsen, Trine R; Rossen, Sine; Gramsbergen, Jan B

    2008-01-01

    endogenous DA release (assessed by high-performance liquid chromatography) in organotypic cultures of foetal mouse (E12) midbrain following single or multiple challenges (1-h incubations) with high K(+) or veratridine in the presence or absence of pargyline, nomifensine, calcium and/or tetrodotoxin (TTX......Organotypic mesencephalic cultures provide an attractive in vitro alternative to study development of the nigrostriatal system and pathophysiological mechanisms related to Parkinson's disease. However, dopamine (DA) release mechanisms have been poorly characterized in such cultures. We report here...

  1. Immunoglobulin Fc gamma receptor promotes immunoglobulin uptake, immunoglobulin-mediated calcium increase, and neurotransmitter release in motor neurons

    Science.gov (United States)

    Mohamed, Habib A.; Mosier, Dennis R.; Zou, Ling L.; Siklos, Laszlo; Alexianu, Maria E.; Engelhardt, Jozsef I.; Beers, David R.; Le, Wei-dong; Appel, Stanley H.

    2002-01-01

    Receptors for the Fc portion of immunoglobulin G (IgG; FcgammaRs) facilitate IgG uptake by effector cells as well as cellular responses initiated by IgG binding. In earlier studies, we demonstrated that amyotrophic lateral sclerosis (ALS) patient IgG can be taken up by motor neuron terminals and transported retrogradely to the cell body and can alter the function of neuromuscular synapses, such as increasing intracellular calcium and spontaneous transmitter release from motor axon terminals after passive transfer. In the present study, we examined whether FcgammaR-mediated processes can contribute to these effects of ALS patient immunoglobulins. F(ab')(2) fragments (which lack the Fc portion) of ALS patient IgG were not taken up by motor axon terminals and were not retrogradely transported. Furthermore, in a genetically modified mouse lacking the gamma subunit of the FcR, the uptake of whole ALS IgG and its ability to enhance intracellular calcium and acetylcholine release were markedly attenuated. These data suggest that FcgammaRs appear to participate in IgG uptake into motor neurons as well as IgG-mediated increases in intracellular calcium and acetylcholine release from motor axon terminals. Copyright 2002 Wiley-Liss, Inc.

  2. Spatiotemporal Organization of Energy Release Events in the Quiet Solar Corona

    Science.gov (United States)

    Uritsky, Vadim M.; Davila, Joseph M.

    2014-01-01

    Using data from the STEREO and SOHO spacecraft, we show that temporal organization of energy release events in the quiet solar corona is close to random, in contrast to the clustered behavior of flaring times in solar active regions. The locations of the quiet-Sun events follow the meso- and supergranulation pattern of the underling photosphere. Together with earlier reports of the scale-free event size statistics, our findings suggest that quiet solar regions responsible for bulk coronal heating operate in a driven self-organized critical state, possibly involving long-range Alfvenic interactions.

  3. Comparative evaluation of the calcium release from mineral trioxide aggregate and its mixture with glass ionomer cement in different proportions and time intervals – An in vitro study

    Directory of Open Access Journals (Sweden)

    Surbhi Sawhney

    2015-10-01

    Conclusions: Adding GIC to improve the setting time and handling properties of the MTA powder can be detrimental to the calcium-releasing ability of the resultant mixture, depending on the proportion of GIC added. Adding MTA and GIC at a proportion of 2:1 by volume did not impact calcium release from the mixture. These findings should be verified through further clinical studies.

  4. Nicotine enhancement of dopamine release by a calcium-dependent increase in the size of the readily releasable pool of synaptic vesicles.

    Science.gov (United States)

    Turner, Timothy J

    2004-12-15

    A major factor underlying compulsive tobacco use is nicotine-induced modulation of dopamine release in the mesolimbic reward pathway (Wise and Rompre, 1989). An established biochemical mechanism for nicotine-enhanced dopamine release is by activating presynaptic nicotinic acetylcholine receptors (nAChRs) (Wonnacott, 1997). Prolonged application of 10(-7) to 10(-5) m nicotine to striatal synaptosomes promoted a sustained efflux of [3H]dopamine. This nicotine effect was mediated by non-alpha7 nAChRs, because it was blocked by 5 mum mecamylamine but was resistant to 100 nm alpha-bungarotoxin (alphaBgTx). Dopamine release was diminished by omitting Na+ or by applying peptide calcium channel blockers, indicating that nAChRs trigger release by depolarizing the nerve terminals. However, because alpha7 receptors rapidly desensitize in the continuous presence of agonists, a repetitive stimulation protocol was used to evaluate the possible significance of desensitization. This protocol produced a transient increase in [3H]dopamine released by depolarization and a significant increase in the response to hypertonic solutions that measure the size of the readily releasable pool (RRP) of synaptic vesicles. The nicotine-induced increase in the size of the readily releasable pool was blocked by alphaBgTx and by the calmodulin antagonist calmidazolium, suggesting that Ca2+ entry through alpha7 nAChRs specifically enhances synaptic vesicle mobilization at dopamine terminals. Thus, nicotine enhances dopamine release by two complementary actions mediated by discrete nAChR subtypes and suggest that the alpha7 nAChR-mediated pathway is tightly and specifically coupled to refilling of the RRP of vesicles in dopamine terminals.

  5. Neuronal calcium sensor-1 deletion in the mouse decreases motivation and dopamine release in the nucleus accumbens.

    Science.gov (United States)

    Ng, Enoch; Varaschin, Rafael K; Su, Ping; Browne, Caleb J; Hermainski, Joanna; Le Foll, Bernard; Pongs, Olaf; Liu, Fang; Trudeau, Louis-Eric; Roder, John C; Wong, Albert H C

    2016-03-15

    Calcium sensors detect intracellular calcium changes and interact with downstream targets to regulate many functions. Neuronal Calcium Sensor-1 (NCS-1) or Frequenin is widely expressed in the nervous system, and involved in neurotransmission, synaptic plasticity and learning. NCS-1 interacts with and regulates dopamine D2 receptor (D2R) internalization and is implicated in disorders like schizophrenia and substance abuse. However, the role of NCS-1 in behaviors dependent on dopamine signaling in the striatum, where D2R is most highly expressed, is unknown. We show that Ncs-1 deletion in the mouse decreases willingness to work for food. Moreover, Ncs-1 knockout mice have significantly lower activity-dependent dopamine release in the nucleus accumbens core in acute slice recordings. In contrast, food preference, responding for conditioned reinforcement, ability to represent changes in reward value, and locomotor response to amphetamine are not impaired. These studies identify novel roles for NCS-1 in regulating activity-dependent striatal dopamine release and aspects of motivated behavior.

  6. Inhibition of anaphylactic histamine release from heterologously sensitized mast cells: differential effects of drugs which interfere with calcium influx.

    Directory of Open Access Journals (Sweden)

    Kurose,Masao

    1981-11-01

    Full Text Available Drug effects were studied on anaphylactic histamine release from rat mast cells sensitized in vitro with mouse IgE antibody. When histamine release was elicited by adding Ca-++ at various times after antigen-stimulation of sensitized cells in Ca++-free medium, the drugs to be tested were added shortly before each Ca++ addition. Quercetin was effective only when added before or immediately after antigen. Theophylline and disodium cromoglycate (DSCG were active irrespective of the time interval between antigen and Ca++ addition. Verapamil was more effective when added before or simultaneously with antigen than when added later. When tested in the two-stage experiments, quercetin showed inhibition only in Stage 1 and verapamil was inhibitive primarily in Stage 1, while theophylline and DSCG wee only inhibitive in Stage 2. It seems that quercetin selectively and verapamil primarily act to block calcium-gate opening resulting from antigen-antibody interaction on the mast cell membrane, while theophylline and DSCG selectively inhibit the passage of calcium through open calcium channels.

  7. Caffeine Modulates Vesicle Release and Recovery at Cerebellar Parallel Fibre Terminals, Independently of Calcium and Cyclic AMP Signalling.

    Directory of Open Access Journals (Sweden)

    Katharine L Dobson

    Full Text Available Cerebellar parallel fibres release glutamate at both the synaptic active zone and at extrasynaptic sites-a process known as ectopic release. These sites exhibit different short-term and long-term plasticity, the basis of which is incompletely understood but depends on the efficiency of vesicle release and recycling. To investigate whether release of calcium from internal stores contributes to these differences in plasticity, we tested the effects of the ryanodine receptor agonist caffeine on both synaptic and ectopic transmission.Whole cell patch clamp recordings from Purkinje neurons and Bergmann glia were carried out in transverse cerebellar slices from juvenile (P16-20 Wistar rats.Caffeine caused complex changes in transmission at both synaptic and ectopic sites. The amplitude of postsynaptic currents in Purkinje neurons and extrasynaptic currents in Bergmann glia were increased 2-fold and 4-fold respectively, but paired pulse ratio was substantially reduced, reversing the short-term facilitation observed under control conditions. Caffeine treatment also caused synaptic sites to depress during 1 Hz stimulation, consistent with inhibition of the usual mechanisms for replenishing vesicles at the active zone. Unexpectedly, pharmacological intervention at known targets for caffeine--intracellular calcium release, and cAMP signalling--had no impact on these effects.We conclude that caffeine increases release probability and inhibits vesicle recovery at parallel fibre synapses, independently of known pharmacological targets. This complex effect would lead to potentiation of transmission at fibres firing at low frequencies, but depression of transmission at high frequency connections.

  8. Ca(2+ release events in cardiac myocytes up close: insights from fast confocal imaging.

    Directory of Open Access Journals (Sweden)

    Vyacheslav M Shkryl

    Full Text Available The spatio-temporal properties of Ca(2+ transients during excitation-contraction coupling and elementary Ca(2+ release events (Ca(2+ sparks were studied in atrial and ventricular myocytes with ultra-fast confocal microscopy using a Zeiss LSM 5 LIVE system that allows sampling rates of up to 60 kHz. Ca(2+ sparks which originated from subsarcolemmal junctional sarcoplasmic reticulum (j-SR release sites in atrial myocytes were anisotropic and elongated in the longitudinal direction of the cell. Ca(2+ sparks in atrial cells originating from non-junctional SR and in ventricular myocytes were symmetrical. Ca(2+ spark recording in line scan mode at 40,000 lines/s uncovered step-like increases of [Ca(2+]i. 2-D imaging of Ca(2+ transients revealed an asynchronous activation of release sites and allowed the sequential recording of Ca(2+ entry through surface membrane Ca(2+ channels and subsequent activation of Ca(2+-induced Ca(2+ release. With a latency of 2.5 ms after application of an electrical stimulus, Ca(2+ entry could be detected that was followed by SR Ca(2+ release after an additional 3 ms delay. Maximum Ca(2+ release was observed 4 ms after the beginning of release. The timing of Ca(2+ entry and release was confirmed by simultaneous [Ca(2+]i and membrane current measurements using the whole cell voltage-clamp technique. In atrial cells activation of discrete individual release sites of the j-SR led to spatially restricted Ca(2+ release events that fused into a peripheral ring of elevated [Ca(2+]i that subsequently propagated in a wave-like fashion towards the center of the cell. In ventricular myocytes asynchronous Ca(2+ release signals from discrete sites with no preferential subcellular location preceded the whole-cell Ca(2+ transient. In summary, ultra-fast confocal imaging allows investigation of Ca(2+ signals with a time resolution similar to patch clamp technique, however in a less invasive fashion.

  9. LKB1 Regulates Mitochondria-Dependent Presynaptic Calcium Clearance and Neurotransmitter Release Properties at Excitatory Synapses along Cortical Axons.

    Directory of Open Access Journals (Sweden)

    Seok-Kyu Kwon

    2016-07-01

    Full Text Available Individual synapses vary significantly in their neurotransmitter release properties, which underlie complex information processing in neural circuits. Presynaptic Ca2+ homeostasis plays a critical role in specifying neurotransmitter release properties, but the mechanisms regulating synapse-specific Ca2+ homeostasis in the mammalian brain are still poorly understood. Using electrophysiology and genetically encoded Ca2+ sensors targeted to the mitochondrial matrix or to presynaptic boutons of cortical pyramidal neurons, we demonstrate that the presence or absence of mitochondria at presynaptic boutons dictates neurotransmitter release properties through Mitochondrial Calcium Uniporter (MCU-dependent Ca2+ clearance. We demonstrate that the serine/threonine kinase LKB1 regulates MCU expression, mitochondria-dependent Ca2+ clearance, and thereby, presynaptic release properties. Re-establishment of MCU-dependent mitochondrial Ca2+ uptake at glutamatergic synapses rescues the altered neurotransmitter release properties characterizing LKB1-null cortical axons. Our results provide novel insights into the cellular and molecular mechanisms whereby mitochondria control neurotransmitter release properties in a bouton-specific way through presynaptic Ca2+ clearance.

  10. LKB1 Regulates Mitochondria-Dependent Presynaptic Calcium Clearance and Neurotransmitter Release Properties at Excitatory Synapses along Cortical Axons

    Science.gov (United States)

    Kwon, Seok-Kyu; Sando, Richard; Maximov, Anton; Polleux, Franck

    2016-01-01

    Individual synapses vary significantly in their neurotransmitter release properties, which underlie complex information processing in neural circuits. Presynaptic Ca2+ homeostasis plays a critical role in specifying neurotransmitter release properties, but the mechanisms regulating synapse-specific Ca2+ homeostasis in the mammalian brain are still poorly understood. Using electrophysiology and genetically encoded Ca2+ sensors targeted to the mitochondrial matrix or to presynaptic boutons of cortical pyramidal neurons, we demonstrate that the presence or absence of mitochondria at presynaptic boutons dictates neurotransmitter release properties through Mitochondrial Calcium Uniporter (MCU)-dependent Ca2+ clearance. We demonstrate that the serine/threonine kinase LKB1 regulates MCU expression, mitochondria-dependent Ca2+ clearance, and thereby, presynaptic release properties. Re-establishment of MCU-dependent mitochondrial Ca2+ uptake at glutamatergic synapses rescues the altered neurotransmitter release properties characterizing LKB1-null cortical axons. Our results provide novel insights into the cellular and molecular mechanisms whereby mitochondria control neurotransmitter release properties in a bouton-specific way through presynaptic Ca2+ clearance. PMID:27429220

  11. Preparation and characterization of nano-sized calcium carbonate as controlled release pesticide carrier for validamycin against Rhizoctonia solani

    International Nuclear Information System (INIS)

    Nano-sized calcium carbonate (nano-CC) was studied in terms of acting as a carrier for a pesticide. Nano-CC was prepared by reaction of calcium chloride and sodium carbonate by the reversed-phase microemulsion method and then loaded with the pesticide validamycin. The resulting material was characterized by X-ray diffraction analysis and scanning electron microscopy. The loading efficiency, sustained-release performance, germicidal efficacy, and stability also were investigated. The size of the loaded nano-CC can be adjusted to between 50 to 200 nm by varying the water/surfactant molar ratio from 30/1 to 10/1, and the loading efficiency can be increased to about 20% by increasing the size of the nano-CC. The material displayed better germicidal efficacy against Rhizoctonia solani compared to conventional technical validamycin after about 7 days, and the time of the release of validamycin was extended to 2 weeks. Given the loading efficiency, stability, sustained-release performance and good environmental compatibility of the material, the method for its preparation may be extended to other hydrophilic pesticide. (author)

  12. Discrepancy in calcium release from the sarcoplasmic reticulum and intracellular acidic stores for the protection of the heart against ischemia/reperfusion injury.

    Science.gov (United States)

    Khalaf, Aseel; Babiker, Fawzi

    2016-09-01

    We and others have demonstrated a protective effect of pacing postconditioning (PPC) against ischemia/reperfusion (I/R) injury. However, the mechanisms underlying this protection are not completely clear. In the present study, we evaluated the effects of calcium release from the sarcoplasmic reticulum (SR) and the novel intracellular acidic stores (AS). Isolated rat hearts (n = 6 per group) were subjected to coronary occlusion followed by reperfusion using a modified Langendorff system. Cardiac hemodynamics and contractility were assessed using a data acquisition program, and cardiac injury was evaluated by creatine kinase (CK) and lactate dehydrogenase (LDH) levels. Hearts were subjected to 30 min of regional ischemia, produced by ligation of the left anterior descending (LAD) coronary artery, followed by 30 min of reperfusion. The hearts were also subjected to PPC (3 cycles of 30 s of left ventricle (LV) pacing alternated with 30 s of right atrium (RA) pacing) and/or were treated during reperfusion with agonists or antagonists of release of calcium from SR or AS. PPC significantly (P < 0.05) normalized LV, contractility, and coronary vascular dynamics and significantly (P < 0.001) decreased heart enzyme levels compared to the control treatments. The blockade of SR calcium release resulted in a significant (P < 0.01) recovery in LV function and contractility and a significant reduction in CK and LDH levels (P < 0.01) when applied alone or in combination with PPC. Interestingly, the release of calcium from AS alone or in combination with PPC significantly improved LV function and contractility (P < 0.05) and significantly decreased the CK and LDH levels (P < 0.01) compared to the control treatments. An additive effect was produced when agonism of calcium release from AS or blockade of calcium release from the SR was combined with PPC. Calcium release from AS and blockade of calcium release from the SR protect the heart against I

  13. Initial concepts on energetics and mass releases during nonnuclear explosive events in fuel cycle facilities

    International Nuclear Information System (INIS)

    Non-nuclear explosions are one of the initiating events (accidents) considered in the US Nuclear Regulatory Commission study of formal methods for estimating the airborne release of radionuclides from fuel cycle facilities. Methods currently available to estimate the energetics and mass airborne release from the four types of non-nuclear explosive events (fast and slow physical explosions and fast and slow chemical explosions) are reviewed. The likelihood that fast physical explosions will occur in fuel cycle facilities appears to be remote and this type of explosion is not considered. Methods to estimate the consequences of slow physical and fast chemical explosions are available. Methods to estimate the consequences of slow chemical explosions are less well defined

  14. Response of Hanford's double wall tank to a gas release event

    International Nuclear Information System (INIS)

    The paper considers a hypothetical explosion of hydrogen-air mixtures at a gas release event in an underground Hanford double wall tank. It determines mechanical loadings to walls of prime (steel) and secondary (concrete) tank. With the aim of determining criteria, destruction of tank walls and results of explosive experiments with steel and reinforced-concrete vessels and with the double-wall vessels are discussed

  15. Methodology for fission product release calculations during an ACR-1000 end-fitting failure event

    International Nuclear Information System (INIS)

    The ACR-1000® reactor enhances and retains the proven features of the CANDU® design such as the concept of the horizontal fuel channel core. At each end of a fuel channel, there is an end-fitting incorporating a feeder connection through which pressurized coolant enters and leaves the fuel channel, where 12 fuel bundles are inserted. The safety analysis cases include postulated end-fitting failure events to assess the fission product releases from all fuel bundles which would be ejected out of the channel and oxidized in the air-steam environment under decay power. This paper presents the methodology used in assessing the fuel behaviour and the fission product releases during a postulated end-fitting failure in an ACR-1000 reactor. After the end-fitting failure, the 12 fuel bundles are ejected out of the channel and drop onto the fuelling machine vault floor. The fuel bundles are likely heavily damaged by impact and would break into small clusters of elements or fragments. To calculate the fission product releases from an individual fragment, the transient fuel temperature is numerically solved by differential heat equations; the air oxidation model is chosen for the event accordingly; and the fission product inventory and releases are estimated by computer codes ORIGEN-S, CATHENA, ELESTRES and SOURCE-IST. Finally, the total fission product releases from all fragments into containment are calculated. This methodology has been developed for ACR-1000 safety analysis, which is also applicable to CANDU. With the new methodology, the transient releases from up to 150 fission products can be estimated as detail as in fragment. In this paper, a sample calculation is also provided to show the application of the methodology in ACR-1000 safety analysis for end-fitting failure. (author)

  16. Dual pathways of calcium entry in spike and plateau phases of luteinizing hormone release from chicken pituitary cells: sequential activation of receptor-operated and voltage-sensitive calcium channels by gonadotropin-releasing hormone

    Energy Technology Data Exchange (ETDEWEB)

    Davidson, J.S.; Wakefield, I.K.; King, J.A.; Mulligan, G.P.; Millar, R.P.

    1988-04-01

    It has previously been shown that, in pituitary gonadotrope cells, the initial rise in cytosolic Ca2+ induced by GnRH is due to a Ca2+ mobilization from intracellular stores. This raises the possibility that the initial transient spike phase of LH release might be fully or partially independent of extracellular Ca2+. We have therefore characterized the extracellular Ca2+ requirements, and the sensitivity to Ca2+ channel blockers, of the spike and plateau phases of secretion separately. In the absence of extracellular Ca2+ the spike and plateau phases were inhibited by 65 +/- 4% and 106 +/- 3%, respectively. Both phases exhibited a similar dependence on concentration of extracellular Ca2+. However, voltage-sensitive Ca2+ channel blockers D600 and nifedipine had a negligible effect on the spike phase, while inhibiting the plateau phase by approximately 50%. In contrast, ruthenium red, Gd3+ ions, and Co2+ ions inhibited both spike and plateau phases to a similar extent as removal of extracellular Ca2+. A fraction (35 +/- 4%) of spike phase release was resistant to removal of extracellular Ca2+. This fraction was abolished after calcium depletion of the cells by preincubation with EGTA in the presence of calcium ionophore A23187, indicating that it depends on intracellular Ca2+ stores. Neither absence of extracellular Ca2+, nor the presence of ruthenium red or Gd3+ prevented mobilization of 45Ca2+ from intracellular stores by GnRH. We conclude that mobilization of intracellular stored Ca2+ is insufficient by itself to account for full spike phase LH release.

  17. Complex actions of ionomycin in cultured cerebellar astrocytes affecting both calcium-induced calcium release and store-operated calcium entry

    DEFF Research Database (Denmark)

    Müller, Margit S; Obel, Linea Lykke Frimodt; Waagepetersen, Helle S;

    2013-01-01

    The polyether antibiotic ionomycin is a common research tool employed to raise cytosolic Ca(2+) in almost any cell type. Although initially thought to directly cause physicochemical translocation of extracellular Ca(2+) into the cytosol, a number of studies have demonstrated that the mechanism of......(2+), consisting of an initial peak and a subsequent sustained plateau. The response was dependent on concentration and exposure time. While the plateau phase was abolished in the absence of extracellular Ca(2+), the peak phase persisted. The peak amplitude could be lowered significantly...... by application of dantrolene, demonstrating involvement of Ca(2+)-induced Ca(2+)-release (CICR). The plateau phase was markedly reduced when store-operated Ca(2+)-entry (SOCE) was blocked with 2-aminoethoxydiphenyl borate. Our results show that ionomycin directly affects internal Ca(2+) stores in astrocytes...

  18. Membrane sialic acid influences basophil histamine release by interfering with calcium dependence

    DEFF Research Database (Denmark)

    Jensen, C; Norn, S; Skov, P S;

    1987-01-01

    The influence of the cell membrane content of sialic acid on basophil histamine release was examined in vitro in allergic patients and normal controls. Enzymatical removal of sialic acid enhanced histamine release induced by allergen and anti-IgE, whereas an increase in membrane sialic acid content...

  19. Mouse neuroblastoma cell-based model and the effect of epileptic events on calcium oscillations and neural spikes

    Science.gov (United States)

    Kim, Suhwan; Jung, Unsang; Baek, Juyoung; Lee, Sangwon; Jung, Woonggyu; Kim, Jeehyun; Kang, Shinwon

    2013-01-01

    Recently, mouse neuroblastoma cells have been considered as an attractive model for the study of human neurological and prion diseases, and they have been intensively used as a model system in different areas. For example, the differentiation of neuro2a (N2A) cells, receptor-mediated ion current, and glutamate-induced physiological responses have been actively investigated with these cells. These mouse neuroblastoma N2A cells are of interest because they grow faster than other cells of neural origin and have a number of other advantages. The calcium oscillations and neural spikes of mouse neuroblastoma N2A cells in epileptic conditions are evaluated. Based on our observations of neural spikes in these cells with our proposed imaging modality, we reported that they can be an important model in epileptic activity studies. We concluded that mouse neuroblastoma N2A cells produce epileptic spikes in vitro in the same way as those produced by neurons or astrocytes. This evidence suggests that increased levels of neurotransmitter release due to the enhancement of free calcium from 4-aminopyridine causes the mouse neuroblastoma N2A cells to produce epileptic spikes and calcium oscillations.

  20. Mouse neuroblastoma cell based model and the effect of epileptic events on calcium oscillations and neural spikes

    Science.gov (United States)

    Kim, Suhwan; Baek, Juyeong; Jung, Unsang; Lee, Sangwon; Jung, Woonggyu; Kim, Jeehyun; Kang, Shinwon

    2013-05-01

    Recently, Mouse neuroblastoma cells are considered as an attractive model for the study of human neurological and prion diseases, and intensively used as a model system in different areas. Among those areas, differentiation of neuro2a (N2A) cells, receptor mediated ion current, and glutamate induced physiological response are actively investigated. The reason for the interest to mouse neuroblastoma N2A cells is that they have a fast growing rate than other cells in neural origin with a few another advantages. This study evaluated the calcium oscillations and neural spikes recording of mouse neuroblastoma N2A cells in an epileptic condition. Based on our observation of neural spikes in mouse N2A cell with our proposed imaging modality, we report that mouse neuroblastoma N2A cells can be an important model related to epileptic activity studies. It is concluded that the mouse neuroblastoma N2A cells produce the epileptic spikes in vitro in the same way as produced by the neurons or the astrocytes. This evidence advocates the increased and strong level of neurotransmitters release by enhancement in free calcium using the 4-aminopyridine which causes the mouse neuroblastoma N2A cells to produce the epileptic spikes and calcium oscillation.

  1. Effects of extracellular calcium concentration on the glutamate release by bioactive glass (BG60S) preincubated osteoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Valerio, P; Leite, M Fatima [Department of Physiology and Biophysics, Federal University of Minas Gerais (Brazil); Pereira, M M [Department of Metallurgical Engineering, Federal University of Minas Gerais (Brazil); Goes, A M, E-mail: patricia.valerio@terra.com.b, E-mail: leitemd@dedalus.lcc.ufmg.b, E-mail: mpereira@demet.ufmg.b, E-mail: goes@icb.ufmg.b [Department of Biochemistry and Immunology, Federal University of Minas Gerais (Brazil)

    2009-08-15

    Glutamate released by osteoblasts sharing similarities with its role in neuronal transmission is a very new scientific concept which actually changed the understanding of bone physiology. Since glutamate release is a calcium (Ca{sup 2+})-dependent process and considering that we have previously demonstrated that the dissolution of bioactive glass with 60% of silicon (BG60S) can alter osteoblast Ca{sup 2+}-signaling machinery, we investigated whether BG60S induces glutamate secretion in osteoblasts and whether it requires an increase in intracellular Ca{sup 2+}. Here we showed that the extracellular Ca{sup 2+} increase due to BG60S dissolution leads to an intracellular Ca{sup 2+} increase in the osteoblast, through the activation of an inositol 1,4,5-triphosphate receptor (InsP{sub 3}R) and a ryanodine receptor (RyR). Additionally, we also demonstrated that glutamate released by osteoblasts can be profoundly altered by BG60S. The modulation of osteoblast glutamate released by the extracellular Ca{sup 2+} concentration opens a new window in the field of tissue engineering, since many biomaterials used for bone repair are able to increase the extracellular Ca{sup 2+} concentration due to their dissolution products.

  2. Caspase-1 activation and mature interleukin-1β release are uncoupled events in monocytes

    Institute of Scientific and Technical Information of China (English)

    Amy; J; Galliher-Beckley; Li-Qiong; Lan; Shelly; Aono; Lei; Wang; Jishu; Shi

    2013-01-01

    AIM:To investigate whether caspase-1 activation/intracellular processing of pro-interleukin-1β(pro-IL-1β) and extracellular release of mature IL-1β from activated monocytes are separable events.METHODS:All experiments were performed on fresh or overnight cultured human peripheral blood monocytes(PBMCs) that were isolated from healthy donors.PBMCs were activated by lipopolysaccharide(LPS) stimulation before being treated with Adenosine triphosphate(ATP,1 mmol/L),human α-defensin-5(HD-5,50 μg/mL),and/or nigericin(Nig,30 μmol/L).For each experiment,the culture supernatants were collected separately from the cells.Cell lysates and supernatants were both subject to immunoprecipitation with anti-IL1β antibodies followed by western blot analysis with anti-caspase-1 and anti-IL-1β antibodies.RESULTS:We found that pro-IL-1β was processed to mature IL-1β in LPS-activated fresh and overnight cultured human monocytes in response to ATP stimulation.In the presence of HD-5,this release of IL-1β,but not the processing of pro-IL-1β to IL-1β,was completely inhibited.Similarly,in the presence of HD-5,the release of IL-1β,but not the processing of IL-1β,was significantly inhibited from LPS-activated monocytes stimulated with Nig.Finally,we treated LPS-activated monocytes with ATP and Nig and collected the supernatants.We found that both ATP and Nig stimulation could activate and release cleaved caspase-1 from the monocytes.Interestingly,and contrary to IL-1β processing and release,caspase-1 cleavage and release was not blocked by HD-5.All images are representative of three independent experiments.CONCLUSION:These data suggest that caspase-1 activation/processing of pro-IL-1β by caspase-1 and the release of mature IL-1β from human monocytes are distinct and separable events.

  3. Action potential-evoked calcium release is impaired in single skeletal muscle fibers from heart failure patients.

    Directory of Open Access Journals (Sweden)

    Marino DiFranco

    Full Text Available BACKGROUND: Exercise intolerance in chronic heart failure (HF has been attributed to abnormalities of the skeletal muscles. Muscle function depends on intact excitation-contraction coupling (ECC, but ECC studies in HF models have been inconclusive, due to deficiencies in the animal models and tools used to measure calcium (Ca2+ release, mandating investigations in skeletal muscle from HF patients. The purpose of this study was to test the hypothesis that Ca2+ release is significantly impaired in the skeletal muscle of HF patients in whom exercise capacity is severely diminished compared to age-matched healthy volunteers. METHODS AND FINDINGS: Using state-of-the-art electrophysiological and optical techniques in single muscle fibers from biopsies of the locomotive vastus lateralis muscle, we measured the action potential (AP-evoked Ca2+ release in 4 HF patients and 4 age-matched healthy controls. The mean peak Ca2+ release flux in fibers obtained from HF patients (10±1.2 µM/ms was markedly (2.6-fold and significantly (p<0.05 smaller than in fibers from healthy volunteers (28±3.3 µM/ms. This impairment in AP-evoked Ca2+ release was ubiquitous and was not explained by differences in the excitability mechanisms since single APs were indistinguishable between HF patients and healthy volunteers. CONCLUSIONS: These findings prove the feasibility of performing electrophysiological experiments in single fibers from human skeletal muscle, and offer a new approach for investigations of myopathies due to HF and other diseases. Importantly, we have demonstrated that one step in the ECC process, AP-evoked Ca2+ release, is impaired in single muscle fibers in HF patients.

  4. Ethanol's effects on neurotransmitter release and intracellular free calcium in PC12 cells

    International Nuclear Information System (INIS)

    The effect of ethanol on muscarine-stimulated release of [3H]NE was studied using the rat pheochromocytoma cell line, PC12. At concentrations of 25 mM and above, ethanol produced a dose dependent inhibition of muscarine-stimulated release of [3H]NE. The inhibition of muscarine-stimulated transmitter release occurred in the absence of any effect of ethanol on [3H]NE uptake, metabolism or on muscarinic binding to the cells. However, ethanol produced an inhibition of muscarine-stimulated elevation of intracellular free Ca2+ which corresponded with the inhibition of transmitter release. At concentrations greater than 100 mM, ethanol produced both a stimulation of the release of [3H]NE as well as an increase in intracellular free Ca2+. The increase in basal transmitter release and intracellular free Ca2+ occurred independent of the inhibition by ethanol of muscarine-stimulated elevation of intracellular free Ca2+ or transmitter section. These results demonstrate the relationship of the effects of ethanol on cellular free Ca2+ and neurotransmitter release

  5. Models for recurrent gas release event behavior in hazardous waste tanks

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, D.N. [Pacific Northwest Lab., Richland, WA (United States); Arnold, B.C. [California Univ., Riverside, CA (United States). Dept. of Statistics

    1994-08-01

    Certain radioactive waste storage tanks at the United States Department of Energy Hanford facilities continuously generate gases as a result of radiolysis and chemical reactions. The congealed sludge in these tanks traps the gases and causes the level of the waste within the tanks to rise. The waste level continues to rise until the sludge becomes buoyant and ``rolls over``, changing places with heavier fluid on top. During a rollover, the trapped gases are released, resulting, in a sudden drop in the waste level. This is known as a gas release event (GRE). After a GRE, the wastes leading to another GRE. We present nonlinear time waste re-congeals and gas again accumulates leading to another GRE. We present nonlinear time series models that produce simulated sample paths that closely resemble the temporal history of waste levels in these tanks. The models also imitate the random GRE, behavior observed in the temporal waste level history of a storage tank. We are interested in using the structure of these models to understand the probabilistic behavior of the random variable ``time between consecutive GRE`s``. Understanding the stochastic nature of this random variable is important because the hydrogen and nitrous oxide gases released from a GRE, are flammable and the ammonia that is released is a health risk. From a safety perspective, activity around such waste tanks should be halted when a GRE is imminent. With credible GRE models, we can establish time windows in which waste tank research and maintenance activities can be safely performed.

  6. Release of intracellular Calcium increase production of mitochondrial reactive oxygen species in renal distal epithelial cells

    DEFF Research Database (Denmark)

    Bjerregaard, Henning F.

    was inhibited by buffering of intracellular calcium with BAPTA, by the antioxidant N-acetylcysteine and by uncoupling of mitochondrial oxidative phosphorylation from respiration with CCCP. These results indicate that Cd generate a prompt initiation of ROS production from mitochondria due to an increase...... peroxide (H2O2) has traditionally been regarded as toxic by-products of aerobic metabolism. However, recent findings indicate that H2O2 act as a signalling molecule. The aim of the present study was to monitor, in real time, the rates of ROS generation in order to directly determine their production...

  7. In vitro study of vancomycin release and osteoblast-like cell growth on structured calcium phosphate-collagen

    Energy Technology Data Exchange (ETDEWEB)

    Pon-On, Weeraphat, E-mail: wponun@yahoo.com [Department of Physics, Faculty of Science, Kasetsart University, Bangkok 10900 (Thailand); Charoenphandhu, Narattaphol; Teerapornpuntakit, Jarinthorn; Thongbunchoo, Jirawan; Krishnamra, Nateetip [Center of Calcium and Bone Research, Faculty of Science, Mahidol University, Bangkok 10400 (Thailand); Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400 (Thailand); Tang, I-Ming [ThEP Center, Commission of Higher Education. 328 Si Ayuthaya Rd., Bangkok 10400 (Thailand); Department of Physics, Faculty of Science, Mahidol University, Bangkok 10400 (Thailand)

    2013-04-01

    A drug delivery vehicle consisting of spherical calcium phosphate-collagen particles covered by flower-like (SFCaPCol) blossoms composed of nanorod building blocks and their cellular response is studied. The spherical structure was achieved by a combination of sonication and freeze-drying. The SFCaPCol blossoms have a high surface area of approximately 280 m{sup 2}g{sup −1}. The blossom-like formation having a high surface area allows a drug loading efficiency of 77.82%. The release profile for one drug, vancomycin (VCM), shows long term sustained release in simulated body fluid (SBF), in a phosphate buffer saline (PBS, pH 7.4) solution and in culture media over 2 weeks with a cumulative release ∼ 53%, 75% and 50%, respectively, over the first 7 days. The biocompatibility of the VCM-loaded SFCaPCol scaffold was determined by in vitro cell adhesion and proliferation tests of rat osteoblast-like UMR-106 cells. MTT tests indicated that UMR-106 cells were viable after exposure to the VCM loaded SFCaPCol, meaning that the scaffold (the flower-like blossoms) did not impair the cell's viability. The density of cells on the substrate was seen to increase with increasing cultured time. - Graphical abstract: A spherical calcium phosphate-collagen with flower-like blossoms consisting of nanorod building blocks (SFCaPCol) particles was achieved by a combination of sonication and freeze-drying. In vitro drug release profile and the biocompatibility of the VCM-loaded SFCaPCol composite cell adhesion and proliferation in rat osteoblast-like UMR-106 cells were determined for biomaterial applications. Highlights: ► SFCaPCol and VCM-loaded SFCaPCol composite were synthesized by a combination of ultra sonication and freeze-drying. ► VCM drug-loaded SFCaPCol composite was used as substrate for the growth of rat osteoblast-like UMR-106 cells. ► Controlled release of VCM from the composite is critically medium dependent. ► The VCM-loaded SFCaPCol composite is also

  8. Dissolving behavior and calcium release from fibrous wollastonite in acetic acid solution

    International Nuclear Information System (INIS)

    The degradability of fibrous wollastonite (CaSiO3) in an aqueous solution of acetic acid and leaching of Ca2+ ions were investigated in the temperature range from 22 to 50 oC. The Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-OES) was used for the assessment of calcium and other selected cations in the leaching medium. The amount of calcium in the solvent can be significantly enhanced through leaching at higher temperature. Fibrous silica particles are the main by-product of the leaching process. The properties of by-product were examined by thermal analysis (simultaneous TG-DTA-EGA), infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The formation of silica layer on the surface of fibrous wollastonite particles is an important factor in the leaching process. Particles were covered by the silica layer and wollastonite core size was continually decreasing during leaching. The shape of resulting silica particles shows no significant changes during this process. Specific surface of the formed fibrous silica particles strongly depends on the leaching temperature.

  9. Pectin/anhydrous dibasic calcium phosphate matrix tablets for in vitro controlled release of water-soluble drug.

    Science.gov (United States)

    Mamani, Pseidy Luz; Ruiz-Caro, Roberto; Veiga, María Dolores

    2015-10-15

    Different pectin/anhydrous dibasic calcium phosphate (ADCP) matrix tablets have been developed in order to obtain controlled release of a water-soluble drug (theophylline). Swelling, buoyancy and dissolution studies have been carried out in different aqueous media (demineralized water, progressive pH medium, simulated gastric fluid, simulated intestinal fluid and simulated colonic fluid), to characterize the matrix tablets. When the pectin/ADCP ratio was ≥0.26 (P1, P2, P3 and P4 tablets) a continuous swelling and low theophylline dissolution rate from the matrices were observed. So, pectin gel forming feature predominated over the ADCP properties, yielding pH-independent drug release behavior from these matrices. On the contrary, pectin/ADCP ratios ≤0.11 (P5 and P6 tablets) allowed to achieve drug dissolution pH dependent. Consequently, the suitable selection of the pectin/ADCP ratio will allow to tailor matrix tablets for controlled release of water-soluble drugs in a specific manner in the gastrointestinal tract. PMID:26276258

  10. Ca(2+)-activation kinetics modulate successive puff/spark amplitude, duration and inter-event-interval correlations in a Langevin model of stochastic Ca(2+) release.

    Science.gov (United States)

    Wang, Xiao; Hao, Yan; Weinberg, Seth H; Smith, Gregory D

    2015-06-01

    Through theoretical analysis of the statistics of stochastic calcium (Ca(2+)) release (i.e., the amplitude, duration and inter-event interval of simulated Ca(2+) puffs and sparks), we show that a Langevin description of the collective gating of Ca(2+) channels may be a good approximation to the corresponding Markov chain model when the number of Ca(2+) channels per Ca(2+) release unit (CaRU) is in the physiological range. The Langevin description of stochastic Ca(2+) release facilitates our investigation of correlations between successive puff/spark amplitudes, durations and inter-spark intervals, and how such puff/spark statistics depend on the number of channels per release site and the kinetics of Ca(2+)-mediated inactivation of open channels. When Ca(2+) inactivation/de-inactivation rates are intermediate-i.e., the termination of Ca(2+) puff/sparks is caused by an increase in the number of inactivated channels-the correlation between successive puff/spark amplitudes is negative, while the correlations between puff/spark amplitudes and the duration of the preceding or subsequent inter-spark interval are positive. These correlations are significantly reduced or change signs when inactivation/de-inactivation rates are extreme (slow or fast) and puff/sparks terminate via stochastic attrition. PMID:25843352

  11. Nitrogen, phosphorus, potassium, calcium and magnesium release from two compressed fertilizers: column experiments

    OpenAIRE

    M. J. Fernández-Sanjurjo; E. Alvarez-Rodríguez; Núñez-Delgado, A.; M. L. Fernández-Marcos; A. Romar-Gasalla

    2014-01-01

    We used soil columns to study nutrients release from two compressed NPK fertilizers. The columns were filled with soil material from the surface horizon of a granitic soil. Tablets of two slow-release NPK fertilizers (11-18-11 or 8-8-16) were placed into the soil, and then water was percolated through the columns in a saturated regime. Percolates were analyzed for N, P, K, Ca and Mg. These nutrients were also determined in soil and fertilizer tablets at the ...

  12. Nitrogen, phosphorus, potassium, calcium and magnesium release from two compressed fertilizers: column experiments

    OpenAIRE

    M. J. Fernández-Sanjurjo; E. Alvarez-Rodríguez; A. Núñez-Delgado; M. L. Fernández-Marcos; Romar-Gasalla, A.

    2014-01-01

    The objective of this work was to study nutrients release from two compressed nitrogen–potassium–phosphorous (NPK) fertilizers. In the Lourizán Forest Center, tablet-type controlled-release fertilizers (CRF) were prepared by compressing various mixtures of fertilizers without covers or binders. We used soil columns (50 cm long and 7.3 cm inner diameter) that were filled with soil from the surface layer (0–20 cm) of an A horizon corresponding to a Cambic Umbrisol. Tablets of ...

  13. The BRCA1 Tumor Suppressor Binds to Inositol 1,4,5-Trisphosphate Receptors to Stimulate Apoptotic Calcium Release*

    Science.gov (United States)

    Hedgepeth, Serena C.; Garcia, M. Iveth; Wagner, Larry E.; Rodriguez, Ana M.; Chintapalli, Sree V.; Snyder, Russell R.; Hankins, Gary D. V.; Henderson, Beric R.; Brodie, Kirsty M.; Yule, David I.; van Rossum, Damian B.; Boehning, Darren

    2015-01-01

    The inositol 1,4,5-trisphosphate receptor (IP3R) is a ubiquitously expressed endoplasmic reticulum (ER)-resident calcium channel. Calcium release mediated by IP3Rs influences many signaling pathways, including those regulating apoptosis. IP3R activity is regulated by protein-protein interactions, including binding to proto-oncogenes and tumor suppressors to regulate cell death. Here we show that the IP3R binds to the tumor suppressor BRCA1. BRCA1 binding directly sensitizes the IP3R to its ligand, IP3. BRCA1 is recruited to the ER during apoptosis in an IP3R-dependent manner, and, in addition, a pool of BRCA1 protein is constitutively associated with the ER under non-apoptotic conditions. This is likely mediated by a novel lipid binding activity of the first BRCA1 C terminus domain of BRCA1. These findings provide a mechanistic explanation by which BRCA1 can act as a proapoptotic protein. PMID:25645916

  14. Real time imaging of live cell ATP leaking or release events by chemiluminescence microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yun

    2008-12-18

    The purpose of this research was to expand the chemiluminescence microscopy applications in live bacterial/mammalian cell imaging and to improve the detection sensitivity for ATP leaking or release events. We first demonstrated that chemiluminescence (CL) imaging can be used to interrogate single bacterial cells. While using a luminometer allows detecting ATP from cell lysate extracted from at least 10 bacterial cells, all previous cell CL detection never reached this sensitivity of single bacteria level. We approached this goal with a different strategy from before: instead of breaking bacterial cell membrane and trying to capture the transiently diluted ATP with the firefly luciferase CL assay, we introduced the firefly luciferase enzyme into bacteria using the modern genetic techniques and placed the CL reaction substrate D-luciferin outside the cells. By damaging the cell membrane with various antibacterial drugs including antibiotics such as Penicillins and bacteriophages, the D-luciferin molecules diffused inside the cell and initiated the reaction that produces CL light. As firefly luciferases are large protein molecules which are retained within the cells before the total rupture and intracellular ATP concentration is high at the millmolar level, the CL reaction of firefly luciferase, ATP and D-luciferin can be kept for a relatively long time within the cells acting as a reaction container to generate enough photons for detection by the extremely sensitive intensified charge coupled device (ICCD) camera. The result was inspiring as various single bacterium lysis and leakage events were monitored with 10-s temporal resolution movies. We also found a new way of enhancing diffusion D-luciferin into cells by dehydrating the bacteria. Then we started with this novel single bacterial CL imaging technique, and applied it for quantifying gene expression levels from individual bacterial cells. Previous published result in single cell gene expression quantification

  15. Real time imaging of live cell ATP leaking or release events by chemiluminescence microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yun [Iowa State Univ., Ames, IA (United States)

    2008-12-18

    The purpose of this research was to expand the chemiluminescence microscopy applications in live bacterial/mammalian cell imaging and to improve the detection sensitivity for ATP leaking or release events. We first demonstrated that chemiluminescence (CL) imaging can be used to interrogate single bacterial cells. While using a luminometer allows detecting ATP from cell lysate extracted from at least 10 bacterial cells, all previous cell CL detection never reached this sensitivity of single bacteria level. We approached this goal with a different strategy from before: instead of breaking bacterial cell membrane and trying to capture the transiently diluted ATP with the firefly luciferase CL assay, we introduced the firefly luciferase enzyme into bacteria using the modern genetic techniques and placed the CL reaction substrate D-luciferin outside the cells. By damaging the cell membrane with various antibacterial drugs including antibiotics such as Penicillins and bacteriophages, the D-luciferin molecules diffused inside the cell and initiated the reaction that produces CL light. As firefly luciferases are large protein molecules which are retained within the cells before the total rupture and intracellular ATP concentration is high at the millmolar level, the CL reaction of firefly luciferase, ATP and D-luciferin can be kept for a relatively long time within the cells acting as a reaction container to generate enough photons for detection by the extremely sensitive intensified charge coupled device (ICCD) camera. The result was inspiring as various single bacterium lysis and leakage events were monitored with 10-s temporal resolution movies. We also found a new way of enhancing diffusion D-luciferin into cells by dehydrating the bacteria. Then we started with this novel single bacterial CL imaging technique, and applied it for quantifying gene expression levels from individual bacterial cells. Previous published result in single cell gene expression quantification

  16. Solar Energetic Particle Event of 2005 January 20: Release Times and Possible Sources

    Institute of Scientific and Technical Information of China (English)

    Gui-Ming Le; Yu-Hua Tang; Yan-Ben Han

    2006-01-01

    Based on cosmic ray data obtained by neutron monitors at the Earth's surface, and data on near-relativistic electrons measured by the WIND satellite, as well as on solar X-ray and radio burst data, the solar energetic particle (SEP) event of 2005 January 20 is studied. The results show that this event is a mixed event where the flare is dominant in the acceleration of the SEPs, the interplanetary shock accelerates mainly solar protons with energies below 130 MeV, while the relativistic protons are only accelerated by the solar flare. The interplanetary shock had an obvious acceleration effect on relativistic electrons with energies greater than 2 MeV. It was found that the solar release time for the relativistic protons was about 06:41 UT, while that for the near-relativistic electrons was about 06:39 UT. The latter turned out to be about 2 min later than the onset time of the interplanetary type Ⅲ burst.

  17. Results of critical velocity experiments with barium, strontium, and calcium releases from CRRES satellite

    Science.gov (United States)

    Wescott, E. M.; Stenbaek-Nielsen, H. C.; Hampton, D. L.; Delamere, P. A.

    1994-01-01

    As part of the NASA Combined Release and Radiation Effects Satellite (CRRES) chemical release program in September 1990, two Ba and also one each Sr and Ca canisters of a boron-titanium thermite mixture, which vaporizes the element on ignition, were released near perigee after dusk in the South Pacific to study the critical velocity effect proposed by Alfven. The critical velocities of these three elements are 2.7, 3.5, and 5.4 km/s respectively, all well below the orbital velocity of 9.4 km/s. On September 10, 1990, a Sr and Ba pair (G-13, or critical ionization velocity (CIV) I) was released near Rarotonga at approximately 515 km altitude in a background electron density of 3.4 x 10(exp 6)/cu cm. On September 14, 1990, G-14 or CIV II released a Ca and Ba pair west of New Caledonia near 595 km at an electron density of 1.5 x 10(exp 6)/cu cm. Ions of all three elements were observed with low-light level imagers from two aircraft after they had transited up the magnetic field lines into the sunlight. Emissions from the spherically expanding neutral gas shells below the solar terminator, observed with cameras filtered for the Ba(+) ion line at 4554 A and also in unfiltered imagers for approximately 15 s after release, are probably due to excitation by hot electrons created in the CIV process. The ions created clearly lost much of their energy, which we now show can be explained by elastic collisions: Ba(+) + O. Inventories of the observed ions indicate yields of 0.15% and 1.84% for Ba in the first and second experiments, 0.02% for Sr and 0.27% for Ca. Ionization from all the releases continued along the satellite trajectory much longer (greater than 45 s) than expected for a CIV process. The ion production along the satellite track versus time typically shows a rapid rise to a peak in a few seconds followed by an exponential decrease to a level essentially constant rate. The characteristic distances for CIV I and II are 47 and 62 km, respectively. We interpret the

  18. Calcium isotopes in caves as a proxy for aridity: Modern calibration and application to the 8.2 kyr event

    Science.gov (United States)

    Owen, R. A.; Day, C. C.; Hu, C.-Y.; Liu, Y.-H.; Pointing, M. D.; Blättler, C. L.; Henderson, G. M.

    2016-06-01

    We present the first study of Ca isotope cycling in a natural cave system, with measurements of bedrock, dripwater and recently formed carbonate, coupled to a first stalagmite time-series spanning the 8.2 kyr event. Dripwaters at Heshang Cave (Central China; 30°27‧N, 110°25‧E) are isotopically heavy relative to the dolomite bedrock, the result of prior calcite precipitation (PCP) occurring earlier in the drip flow path. A simple Rayleigh fractionation model quantifies the extent of PCP in the modern environment at 36% Ca removal. The observed in situ calcium isotope fractionation factor between dripwater and carbonate is Δ 44 / 42 Ca = - 0.63 ± 0.03 ‰ and does not vary during the annual cycle. Measurements of speleothem carbonate spanning the 8.2 kyr event show the response of Ca isotopes to changing climate. δ44/42Ca increases by 0.35‰ at the onset of the event, coeval with changes in δ18O and Mg/Ca, and remains high for 80 yr. This change is explained by decreased rainfall leading to increased PCP; an interpretation supported by established PCP proxies (Mg/Ca, Sr/Ca and Ba/Ca). Ca isotopes indicate that PCP increased to 60% Ca removal during the event, which, from application of a simple box model, suggests mean annual rainfall decreased by approximately a third in Central China during the 8.2 kyr event. The response of Ca isotopes across this event demonstrates their potential for the assessment of past conditions, including past dripwater flow rates and rainfall.

  19. Role of mitochondrial calcium in metabolism-secretion coupling in nutrient-stimulated insulin release

    OpenAIRE

    Kennedy, Eleanor; Wollheim, Claes

    1998-01-01

    Glucose-stimulated insulin release from pancreatic beta cells involves a complex series of signalling pathways. In many forms of diabetes, lesions in this process cause or aggravate the diabetic phenotype. A common motif in these cascades is the elevation of intracellular Ca2+ both in the cytosolic compartment ([Ca2+]c) and within the mitochondria ([Ca2+]m). These parameters can be effectively monitored using the photoprotein aequorin which can be targeted to subcellular compartments by trans...

  20. Block by ruthenium red of the ryanodine-activated calcium release channel of skeletal muscle

    OpenAIRE

    1993-01-01

    The effects of ruthenium red and the related compounds tetraamine palladium (4APd) and tetraamine platinum (4APt) were studied on the ryanodine activated Ca2+ release channel reconstituted in planar bilayers with the immunoaffinity purified ryanodine receptor. Ruthenium red, applied at submicromolar concentrations to the myoplasmic side (cis), induced an all-or-none flickery block of the ryanodine activated channel. The blocking effect was strongly voltage dependent, as large positive potenti...

  1. Nitrogen, phosphorus, potassium, calcium and magnesium release from two compressed fertilizers: column experiments

    Directory of Open Access Journals (Sweden)

    M. J. Fernández-Sanjurjo

    2014-07-01

    Full Text Available We used soil columns to study nutrients release from two compressed NPK fertilizers. The columns were filled with soil material from the surface horizon of a granitic soil. Tablets of two slow-release NPK fertilizers (11-18-11 or 8-8-16 were placed into the soil, and then water was percolated through the columns in a saturated regime. Percolates were analyzed for N, P, K, Ca and Mg. These nutrients were also determined in soil and fertilizer tablets at the end of the trials. Nutrient concentrations were high in the first percolates, reaching a steady state when 1426 mm water have percolated, which is equivalent to approximately 1.5 years of rainfall in the geographic area. In the whole trial, both tablets lost more than 80% of their initial N, P and K contents. However, K, Ca and Mg were the most leached, whereas N and P were lost in leachates to a lesser extent. Nutrient release was slower from the tablet with composition 8-8-16 than from the 11-18-11 fertilizer. In view of that, the 8-8-16 tablet can be considered more adequate for crops with a nutrient demand sustained over time. At the end of the trial, the effects of these fertilizers on soil chemical parameters were still evident.

  2. Use of clopidogrel and calcium channel blockers and risk of major adverse cardiovascular events

    DEFF Research Database (Denmark)

    Schmidt, Morten; Johansen, Martin B; Robertson, Douglas J;

    2012-01-01

    Eur J Clin Invest 2011 ABSTRACT: Background  The CYP3A4 inhibition by calcium channel blockers (CCBs) may attenuate the effectiveness of clopidogrel. Using time-varying drug exposure ascertainment, we examined whether CCB use modified the association between clopidogrel use and major adverse......-month follow-up, we tracked the use of clopidogrel and CCBs and the rate of MACE (composite of myocardial infarction, ischaemic stroke, stent thrombosis, target lesion revascularization, or cardiac death). We used Cox regression to compute hazard ratios, controlling for potential confounders. Results......  Overall, the 12-month risk for MACE was 14·5%. The rate was 130 per 1000 person years for concomitant clopidogrel and CCB use, 106 for clopidogrel without CCB use, 213 for CCB without clopidogrel use, and 248 for no use of either drug. The adjusted hazard ratio for MACE comparing clopidogrel use...

  3. Are There Two Distinct Solar Energetic Particle Releases in the 2012 May 17 Ground Level Enhancement Event?

    Science.gov (United States)

    Ding, Liu-Guan; Jiang, Yong; Li, Gang

    2016-02-01

    We examine ion release times in the solar vicinity for the 2012 May 17 Ground Level Enhancement event using the velocity dispersion analysis method. In situ energetic proton data from Solar and Heliospheric Observatory (SOHO)/Energetic and Relativistic Nuclei and Electron and Geostationary Operational Environmental Satellite are used. We find two distinct releases of Solar Energetic Particles (SEPs) near the Sun, separated by ∼40 minutes. From soft X-ray observations, we find that the first release coincides with the solar flare eruption: the release starts from the flare onset and ends near the peak of the soft X-ray; type-III radio bursts also occur when the release starts. A type II radio burst may also start at the begining of the release. However, the associated Coronal Mass Ejection (CME) only has a height of 0.08Rs from extrapolation of SOHO/LASCO data. At the start of the second release, the CME propagates to more than 8.4Rs in height, and there are signatures of an enhanced type II radio burst. The time-integrated spectra for the two releases differ. The spectrum for the second release shows the common double-power-law feature of gradual SEP events. The spectrum for the first release does not resemble power laws because there is considerable modulation at lower energies. Based on our analysis, we suggest that SEPs of the first release were dominated by particles accelerated at the flare, and those of the second release were dominated by particles accelerated at the associated CME-driven shock. Our study may be important to understand certain extreme SEP events.

  4. Nitrogen, phosphorus, potassium, calcium and magnesium release from two compressed fertilizers: column experiments

    Science.gov (United States)

    Fernández-Sanjurjo, M. J.; Alvarez-Rodríguez, E.; Núñez-Delgado, A.; Fernández-Marcos, M. L.; Romar-Gasalla, A.

    2014-12-01

    The objective of this work was to study nutrients release from two compressed nitrogen-potassium-phosphorous (NPK) fertilizers. In the Lourizán Forest Center, tablet-type controlled-release fertilizers (CRF) were prepared by compressing various mixtures of fertilizers without covers or binders. We used soil columns (50 cm long and 7.3 cm inner diameter) that were filled with soil from the surface layer (0-20 cm) of an A horizon corresponding to a Cambic Umbrisol. Tablets of two slow-release NPK fertilizers (11-18-11 or 8-8-16) were placed into the soil (within the first 3 cm), and then water was percolated through the columns in a saturated regime for 80 days. Percolates were analyzed for N, P, K+, Ca2+ and Mg2+. These elements were also determined in soil and fertilizer tablets at the end of the trials. Nutrient concentrations were high in the first leachates and reached a steady state when 1426 mm of water had been percolated, which is equivalent to approximately 1.5 years of rainfall in this geographic area. In the whole trial, both tablets lost more than 80% of their initial N, P and K contents. However, K+, Ca2+ and Mg2+ were the most leached, whereas N and P were lost in leachates to a lesser extent. Nutrient release was slower from the tablet with a composition of 8-8-16 than from the 11-18-11 fertilizer. In view of that, the 8-8-16 tablet can be considered more adequate for crops with a nutrient demand sustained over time. At the end of the trial, the effects of these fertilizers on soil chemical parameters were still evident, with a significant increase of pH, available Ca2+, Mg2+, K+, P and effective cation exchange capacity (eCEC) in the fertilized columns, as well as a significant decrease in exchangeable Al3+, reaching values < 0.08 cmol (+) kg-1.

  5. Acute hazardous substance releases resulting in adverse health consequences in children: Hazardous Substances Emergency Events Surveillance system, 1996-2003.

    Science.gov (United States)

    Wattigney, Wendy A; Kaye, Wendy E; Orr, Maureen F

    2007-11-01

    Because of their small size and ongoing organ development, children may be more susceptible than adults to the harmful effects of toxic chemicals. The objective of the study reported here was to identify frequent locations, released substances, and factors contributing to short-term chemical exposures associated with adverse health consequences experienced by children. The study examined the Hazardous Substances Emergency Events Surveillance (HSEES) system data from 1996-2003. Eligible events involved the acute release of a hazardous substance associated with at least one child being injured. The study found that injured children were predominantly at school, home, or a recreational center when events took place. School-related events were associated with the accidental release of acids and the release of pepper spray by pranksters. Carbon monoxide poisonings occurring in the home, retail stores, entertainment facilities, and hotels were responsible for about 10 percent of events involving child victims. Chlorine was one of the top chemicals harmful to children, particularly at public swimming pools. Although human error contributed to the majority of releases involving child victims, equipment failure was responsible for most chlorine and ammonia releases. The authors conclude that chemical releases resulting in injury to children occur mostly in schools, homes, and recreational areas. Surveillance of acute hazardous chemical releases helped identify contributing causes and can guide the development of prevention outreach activities. Chemical accidents cannot be entirely prevented, but efforts can be taken to provide safer environments in which children can live, learn, and play. Wide dissemination of safety recommendations and education programs is required to protect children from needless environmental dangers. PMID:18044249

  6. Carbon-Based Solid-State Calcium Ion-Selective Microelectrode and Scanning Electrochemical Microscopy: A Quantitative Study of pH-Dependent Release of Calcium Ions from Bioactive Glass.

    Science.gov (United States)

    Ummadi, Jyothir Ganesh; Downs, Corey J; Joshi, Vrushali S; Ferracane, Jack L; Koley, Dipankar

    2016-03-15

    Solid-state ion-selective electrodes are used as scanning electrochemical microscope (SECM) probes because of their inherent fast response time and ease of miniaturization. In this study, we report the development of a solid-state, low-poly(vinyl chloride), carbon-based calcium ion-selective microelectrode (Ca(2+)-ISME), 25 μm in diameter, capable of performing an amperometric approach curve and serving as a potentiometric sensor. The Ca(2+)-ISME has a broad linear response range of 5 μM to 200 mM with a near Nernstian slope of 28 mV/log[a(Ca(2+))]. The calculated detection limit for Ca(2+)-ISME is 1 μM. The selectivity coefficients of this Ca(2+)-ISME are log K(Ca(2+),A) = -5.88, -5.54, and -6.31 for Mg(2+), Na(+), and K(+), respectively. We used this new type of Ca(2+)-ISME as an SECM probe to quantitatively map the chemical microenvironment produced by a model substrate, bioactive glass (BAG). In acidic conditions (pH 4.5), BAG was found to increase the calcium ion concentration from 0.7 mM ([Ca(2+)] in artificial saliva) to 1.4 mM at 20 μm above the surface. In addition, a solid-state dual SECM pH probe was used to correlate the release of calcium ions with the change in local pH. Three-dimensional pH and calcium ion distribution mapping were also obtained by using these solid-state probes. The quantitative mapping of pH and Ca(2+) above the BAG elucidates the effectiveness of BAG in neutralizing and releasing calcium ions in acidic conditions. PMID:26861499

  7. Absence of triadin, a protein of the calcium release complex, is responsible for cardiac arrhythmia with sudden death in human

    Science.gov (United States)

    Roux-Buisson, Nathalie; Cacheux, Marine; Fourest-Lieuvin, Anne; Fauconnier, Jeremy; Brocard, Julie; Denjoy, Isabelle; Durand, Philippe; Guicheney, Pascale; Kyndt, Florence; Leenhardt, Antoine; Le Marec, Hervé; Lucet, Vincent; Mabo, Philippe; Probst, Vincent; Monnier, Nicole; Ray, Pierre F.; Santoni, Elodie; Trémeaux, Pauline; Lacampagne, Alain; Fauré, Julien; Lunardi, Joël; Marty, Isabelle

    2012-01-01

    Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease so far related to mutations in the cardiac ryanodine receptor (RYR2) or the cardiac calsequestrin (CASQ2) genes. Because mutations in RYR2 or in CASQ2 are not retrieved in all CPVT cases, we searched for mutations in the physiological protein partners of RyR2 and CSQ2 in a large cohort of CPVT patients with no detected mutation in these two genes. Based on a candidate gene approach, we focused our investigations on triadin and junctin, two proteins that link RyR2 and CSQ2. Mutations in the triadin (TRDN) and in the junctin (ASPH) genes were searched in a cohort of 97 CPVT patients. We identified three mutations in triadin which cosegregated with the disease on a recessive mode of transmission in two families, but no mutation was found in junctin. Two TRDN mutations, a 4 bp deletion and a nonsense mutation, resulted in premature stop codons; the third mutation, a p.T59R missense mutation, was further studied. Expression of the p.T59R mutant in COS-7 cells resulted in intracellular retention and degradation of the mutant protein. This was confirmed after in vivo expression of the mutant triadin in triadin knock-out mice by viral transduction. In this work, we identified TRDN as a new gene responsible for an autosomal recessive form of CPVT. The mutations identified in the two families lead to the absence of the protein, thereby demonstrating the importance of triadin for the normal function of the cardiac calcium release complex in humans. PMID:22422768

  8. Acetylene Resembling Effect of Ethylene on Seed Germination: Evaluating the Effect of Acetylene Released from Calcium Carbide

    Directory of Open Access Journals (Sweden)

    Kambiz MASHAYEKHI

    2015-09-01

    Full Text Available Some vegetable seeds need a very long time to germinate. In these kinds of seeds the second phase of germination is very long. As acetylene’s chemical structure is almost similar to the gaseous hormone ethylene, its’ physiological effect on seed germination should be very similar as well. Therefore, an experiment was established in order to enhance seed germination, by treating seeds with acetylene released from interaction of calcium carbide (CaC2 with water (H2O. A simple system was designed for efficient and proper use of gaseous acetylene resulted from the two substrates interaction, which conducted the produced gas obtained inside the interaction chamber into a sealed container wherein seeds were floating in water. This experiment aimed to evaluate the effect of one concentration of acetylene with different exposure periods (between 1 to 8 hours on parsley, celery and Swees chard seeds’ germination (chosen as late germinating vegetables. The effect of acetylene on seed germination speed and percent was investigated. There were significant differences in both percent and speed of germination within the various treatments. By floating for 3, 5 and 3 hours for parsley, celery and Swiss chard respectively, the highest germination rates were observed. The highest germination speed was achieved by 5, 5 and 3 hours floating respectively for parsley, celery and Swiss chard. Based on the results obtained, the current experiment suggests that acetylene has positive effect on enhancing seed germination of named vegetables, and played the role of ethylene, its effects resembling in regard to seed germination process.

  9. Aseismic moment release and triggered creep following the June 23 2001 Peru event.

    Science.gov (United States)

    Melbourne, T. I.; Webb, F. H.; Simons, M. O.

    2001-12-01

    The June 23rd 2001 South Peru mainshock (Mw 8.4) produced near-field coseismic offsets in excess of 52 cm at the IGS global tracking station located at Arequipa, Peru, despite over 200 km separation between this station and available first motion hypocenters. Also visible in the continuous time series are the near-field displacements from the Mw 6.6 and Mw 7.5 aftershocks on June 26 and July 07. 2 hour GPS solutions from Arequipa are computed by estimating carrier phase biases, zenith troposphere delays and station clocks using 24 hour data arcs and applying stochastic resets to the station coordinates only. Using this method, the geometric strength of the 24-hour data arc for estimating biases and atmospheric delays is retained and higher rate station position estimates are obtained without the introduction of significant systematic higher frequency errors. After correcting for the co-seismic offsets due to aftershocks, the Arequipa time series shows a pronounced post-seismic signal decaying from over 1 cm per week of southwesterly horizontal motion immediately following the mainshock to less than 3 mm/week southwesterly at the present time (09/01). Updated time series will be discussed at the December meeting. The vertical component of motion, which showed co-seismic subsidence of 4 cm during the mainshock, reversed its sense of post-seismic motion and to date has nearly rebounded to its pre-June 23rd level. Co-seismic subsidence followed by post-seismic uplift without significant change in the horizontal offset azimuth requires faulting down-dip of the mainshock asperity, rather than simply after-slip along it, as predicted by rate- and state-dependent constitutive relations. The post-seismic deformation is therefore consistent with fault creep in the meta-stable region of the plate interface triggered by shear loading from the mainshock asperity located directly up-dip in the seismogenic region. This event therefore joins a growing list of subduction zone

  10. Capsaicin mimics mechanical load-induced intracellular signaling events: involvement of TRPV1-mediated calcium signaling in induction of skeletal muscle hypertrophy.

    Science.gov (United States)

    Ito, Naoki; Ruegg, Urs T; Kudo, Akira; Miyagoe-Suzuki, Yuko; Takeda, Shin'ichi

    2013-01-01

    Mechanical load-induced intracellular signaling events are important for subsequent skeletal muscle hypertrophy. We previously showed that load-induced activation of the cation channel TRPV1 caused an increase in intracellular calcium concentrations ([Ca ( 2+) ]i) and that this activated mammalian target of rapamycin (mTOR) and promoted muscle hypertrophy. However, the link between mechanical load-induced intracellular signaling events, and the TRPV1-mediated increases in [Ca ( 2+) ]i are not fully understood. Here we show that administration of the TRPV1 agonist, capsaicin, induces phosphorylation of mTOR, p70S6K, S6, Erk1/2 and p38 MAPK, but not Akt, AMPK or GSK3β. Furthermore, the TRPV1-induced phosphorylation patterns resembled those induced by mechanical load. Our results continue to highlight the importance of TRPV1-mediated calcium signaling in load-induced intracellular signaling pathways.

  11. In vitro gentamicin release from commercially available calcium-phosphate bone substitutes influence of carrier type on duration of the release profile

    Directory of Open Access Journals (Sweden)

    Bronckers Antonius LJJ

    2006-02-01

    Full Text Available Abstract Background Polymethyl-methacrylate (PMMA beads releasing antibiotics are used extensively to treat osteomyelitis, but require surgical removal afterwards because they do not degrade. Methods As an alternative option, this report compares the in vitro gentamicin release profile from clinically used, biodegradable carrier-materials: six injectable cements and six granule-types. Cement cylinders and coated granules containing 3% gentamicin were submerged in dH2O and placed in a 48-sample parallel drug-release system. At regular intervals (30, 90, 180 min. and then every 24 h, for 21 days, the release fluid was exchanged and the gentamicin concentration was measured. The activity of released gentamicin was tested on Staphylococcus aureus. Results All combinations showed initial burst-release of active gentamicin, two cements had continuous-release (17 days. The relative release of all cements (36–85% and granules (30–62% was higher than previously reported for injectable PMMA-cements (up to 17% and comparable to other biodegradable carriers. From the cements residual gentamicin could be extracted, whereas the granules released all gentamicin that had adhered to the surface. Conclusion The high release achieved shows great promise for clinical application of these biodegradable drug-carriers. Using the appropriate combination, the required release profile (burst or sustained may be achieved.

  12. Large isoforms of UNC-89 (obscurin are required for muscle cell architecture and optimal calcium release in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Patrick M Spooner

    Full Text Available Calcium, a ubiquitous intracellular signaling molecule, controls a diverse array of cellular processes. Consequently, cells have developed strategies to modulate the shape of calcium signals in space and time. The force generating machinery in muscle is regulated by the influx and efflux of calcium ions into the muscle cytoplasm. In order for efficient and effective muscle contraction to occur, calcium needs to be rapidly, accurately and reliably regulated. The mechanisms underlying this highly regulated process are not fully understood. Here, we show that the Caenorhabditis elegans homolog of the giant muscle protein obscurin, UNC-89, is required for normal muscle cell architecture. The large immunoglobulin domain-rich isoforms of UNC-89 are critical for sarcomere and sarcoplasmic reticulum organization. Furthermore, we have found evidence that this structural organization is crucial for excitation-contraction coupling in the body wall muscle, through the coordination of calcium signaling. Thus, our data implicates UNC-89 in maintaining muscle cell architecture and that this precise organization is essential for optimal calcium mobilization and efficient and effective muscle contraction.

  13. Calcium homeostasis in a local/global whole cell model of permeabilized ventricular myocytes with a Langevin description of stochastic calcium release.

    Science.gov (United States)

    Wang, Xiao; Weinberg, Seth H; Hao, Yan; Sobie, Eric A; Smith, Gregory D

    2015-03-01

    Population density approaches to modeling local control of Ca(2+)-induced Ca(2+) release in cardiac myocytes can be used to construct minimal whole cell models that accurately represent heterogeneous local Ca(2+) signals. Unfortunately, the computational complexity of such "local/global" whole cell models scales with the number of Ca(2+) release unit (CaRU) states, which is a rapidly increasing function of the number of ryanodine receptors (RyRs) per CaRU. Here we present an alternative approach based on a Langevin description of the collective gating of RyRs coupled by local Ca(2+) concentration ([Ca(2+)]). The computational efficiency of this approach no longer depends on the number of RyRs per CaRU. When the RyR model is minimal, Langevin equations may be replaced by a single Fokker-Planck equation, yielding an extremely compact and efficient local/global whole cell model that reproduces and helps interpret recent experiments that investigate Ca(2+) homeostasis in permeabilized ventricular myocytes. Our calculations show that elevated myoplasmic [Ca(2+)] promotes elevated network sarcoplasmic reticulum (SR) [Ca(2+)] via SR Ca(2+)-ATPase-mediated Ca(2+) uptake. However, elevated myoplasmic [Ca(2+)] may also activate RyRs and promote stochastic SR Ca(2+) release, which can in turn decrease SR [Ca(2+)]. Increasing myoplasmic [Ca(2+)] results in an exponential increase in spark-mediated release and a linear increase in nonspark-mediated release, consistent with recent experiments. The model exhibits two steady-state release fluxes for the same network SR [Ca(2+)] depending on whether myoplasmic [Ca(2+)] is low or high. In the later case, spontaneous release decreases SR [Ca(2+)] in a manner that maintains robust Ca(2+) sparks. PMID:25485896

  14. Compatibility Studies of Atorvastatin Calcium with Selected Excipients By Means of Thermal and FT-IR Spectroscopic Methods for the Development of Immediate Release Tablet

    Directory of Open Access Journals (Sweden)

    Bipul Nath

    2016-05-01

    Full Text Available The objectives of present investigation is to evaluate the compatibility of Atorvastatin calcium with immediate release excipients and to optimize the tablet which release is best comparable with innovator product by varying different super disintegrants. Various excipients used were sodium starch glycollate, cross carmellose sodium, cross-povidone, lactose, micro crystalline cellulose, mannitol, sodium lauryl sulfate, magnesium stearate, and stearic acid. Thermal characterization of the drug was done by DSC and FT-IR. From the DSC studies, the excipients such as microcrystalline cellulose (Avicel 101, magnesium stearate, mannitol, sodium lauryl sulfate were found to have physical interactions with Atorvastatin. Immediate release tablet was prepared by direct compression method and its release profile was compared with the marketed IR tablet. The prepared tablet have conform the pharmacopoeial limit for hardness, thickness, friability, weight variation and content uniformity. Formulation F11 containing two super disintegrants have shown the disintegration time less than 25 sec and better dissolution than all other formulations releasing more than 80% of the drug after 20 minutes. Kinetic data reveals that the drug release follows best order by Higuchi model, followed by korsemeyer peppas, zero order and first order mechanisms. The results of accelerated stability studies as per ICH guidelines indicated that the tablet was stable as there were no any significant physical changes after the study.

  15. Effect of particle size of calcium phosphate based bioceramic drug delivery carrier on the release kinetics of ciprofloxacin hydrochloride: an in vitro study

    Science.gov (United States)

    Sasikumar, Swamiappan

    2013-09-01

    Hydroxyapatite (HAP) is the constituent of calcium phosphate based bone cement and it is extensively used as a bone substitute and drug delivery vehicle in various biomedical applications. In the present study we investigated the release kinetics of ciprofloxacin loaded HAP and analyzed its ability to function as a targeted and sustained release drug carrier. Synthesis of HAP was carried out by combustion method using tartaric acid as a fuel and nitric acid as an oxidizer. Powder XRD and FTIR techniques were employed to characterize the phase purity of the drug carrier and to verify the chemical interaction between the drug and carrier. The synthesized powders were sieve separated to make two different drug carriers with different particle sizes and the surface topography of the pellets of the drug carrier was imaged by AFM. Surface area and porosity of the drug carrier was carried out using surface area analyzer. The in-vitro drug release kinetics was performed in simulated body fluid, at 37.3°C. The amount of ciprofloxacin released is measured using UV-visible spectroscopy following the characteristic λ max of 278 nm. The release saturates around 450 h which indicates that it can be used as a targeted and sustained release carrier for bone infections.

  16. Natural and industrial analogues for release of CO2 from storagereservoirs: Identification of features, events, and processes and lessonslearned

    Energy Technology Data Exchange (ETDEWEB)

    Lewicki, Jennifer L.; Birkholzer, Jens; Tsang, Chin-Fu

    2006-03-03

    The injection and storage of anthropogenic CO{sub 2} in deep geologic formations is a potentially feasible strategy to reduce CO{sub 2} emissions and atmospheric concentrations. While the purpose of geologic carbon storage is to trap CO{sub 2} underground, CO{sub 2} could migrate away from the storage site into the shallow subsurface and atmosphere if permeable pathways such as well bores or faults are present. Large-magnitude releases of CO{sub 2} have occurred naturally from geologic reservoirs in numerous volcanic, geothermal, and sedimentary basin settings. Carbon dioxide and natural gas have also been released from geologic CO{sub 2} reservoirs and natural gas storage facilities, respectively, due to influences such as well defects and injection/withdrawal processes. These systems serve as natural and industrial analogues for the potential release of CO{sub 2} from geologic storage reservoirs and provide important information about the key features, events, and processes (FEPs) that are associated with releases, as well as the health, safety, and environmental consequences of releases and mitigation efforts that can be applied. We describe a range of natural releases of CO{sub 2} and industrial releases of CO{sub 2} and natural gas in the context of these characteristics. Based on this analysis, several key conclusions can be drawn, and lessons can be learned for geologic carbon storage. First, CO{sub 2} can both accumulate beneath, and be released from, primary and secondary reservoirs with capping units located at a wide range of depths. Both primary and secondary reservoir entrapments for CO{sub 2} should therefore be well characterized at storage sites. Second, many natural releases of CO{sub 2} have been correlated with a specific event that triggered the release, such as magmatic fluid intrusion or seismic activity. The potential for processes that could cause geomechanical damage to sealing cap rocks and trigger the release of CO{sub 2} from a storage

  17. Single-Cell Phenotypic Characterization of Human Pituitary GHomas and Non-Functioning Adenomas Based on Hormone Content and Calcium Responses to Hypothalamic Releasing Hormones

    Science.gov (United States)

    Senovilla, Laura; Núñez, Lucía; de Campos, José María; de Luis, Daniel A.; Romero, Enrique; García-Sancho, Javier; Villalobos, Carlos

    2015-01-01

    Human pituitary tumors are generally benign adenomas causing considerable morbidity due to excess hormone secretion, hypopituitarism, and other tumor mass effects. Pituitary tumors are highly heterogeneous and difficult to type, often containing mixed cell phenotypes. We have used calcium imaging followed by multiple immunocytochemistry to type growth hormone secreting (GHomas) and non-functioning pituitary adenomas (NFPAs). Individual cells were typed for stored hormones and calcium responses to classic hypothalamic releasing hormones (HRHs). We found that GHomas contained growth hormone cells either lacking responses to HRHs or responding to all four HRHs. However, most GHoma cells were polyhormonal cells responsive to both thyrotropin-releasing hormone (TRH) and GH-releasing hormone. NFPAs were also highly heterogeneous. Some of them contained ACTH cells lacking responses to HRHs or polyhormonal gonadotropes responsive to LHRH and TRH. However, most NFPAs were made of cells storing no hormone and responded only to TRH. These results may provide new insights on the ontogeny of GHomas and NFPAs. PMID:26106585

  18. The current status of ARAC (Atmospheric Release Advisory Capability) and its application to the Chernobyl event

    Energy Technology Data Exchange (ETDEWEB)

    Gudiksen, P.H.; Sullivan, T.J.; Harvey, T.F.

    1986-10-01

    The Atmospheric Release Advisory Capability (ARAC) project, developed by the Lawrence Livermore National Laboratory (LLNL), provides real-time dose assessments and estimates of the extent of surface contamination that may result from an atmospheric release of radioactivity. It utilizes advanced computer-based data communication and processing systems to acquire the meteorological and source term information needed by the three-dimensional atmospheric dispersion models to derive the consequence assessments. The ARAC responded to the recent Chernobyl reactor accident in the Soviet Union by estimating the source term and the radiation dose distribution due to exposure to the radioactive cloud over Europe and the Northern Hemisphere. This analysis revealed that approximately 50% of the estimated core inventories of I-131 and Cs-137 were released. The estimated committed effective dose equivalent due to inhalation of radioactivty during cloud passage is of the order of 10 mrem within parts of Scandinavia and eastern Europe, while most of the populations within central Europe were exposed to levels ranging from 1 to 10 mrem. The amount of Cs-137 released by the Chernobyl accident far exceeds that released by previous reactor accidents, but is only about 6% of the Cs-137 produced by the atmospheric weapon testing programs. 9 refs., 4 figs., 2 tabs.

  19. Coupling order release methods with autonomous control methods – an assessment of potentials by literature review and discrete event simulation

    Directory of Open Access Journals (Sweden)

    Sebastian Grundstein

    2015-01-01

    Full Text Available Production planning and control faces increasing uncertainty, dynamics and complexity. Autonomous control methods proved themselves as a promising approach for coping with these challenges. However, there is a lack of knowledge regarding the interaction between autonomous control and precedent functions of production planning and control. In particular, up to now previous research has paid no attention to the influence of order release methods on the efficiency of autonomous control methods. Thereby, many researchers over the last decades provided evidence that the order release function has great influence on the logistic objective achievement in conventional production systems. Therefore, this paper examines the influence of order release methods on the efficiency of autonomous control methods by both theoretic evaluation and discrete event simulation. The simulation results indicate an overall high influence. Moreover, the logistic performance differs considerably depending on the implemented order release methods and the combinations of order release methods with autonomous control methods. The findings highlight demand for further research in this field.

  20. Hydrogeochemical signatures of catchment evolution - the role of calcium and sulphate release in the constructed Hühnerwasser ("Chicken Creek") catchment

    Science.gov (United States)

    Pohle, Ina; Hu, Yuzhu; Schaaf, Wolfgang; Gerwin, Werner; Hinz, Christoph

    2016-04-01

    The constructed Hühnerwasser ("Chicken Creek") catchment is an ecohydrological system in an initial state of development. The catchment with an area of 6 ha was built up from quaternary sediments in the post-mining landscape of Lusatia in Eastern Germany and serves as a critical zone observatory for detecting ecosystem transition. The soil substrate is characterized as sands to loamy sands with low carbonate contents but significant amounts of gypsum in the sediments of the catchment. The catchment undergoes a strong transition from an abiotic system in the initial years to a system with growing influence of biota. Concerning the hydrology, a regime shift from surface runoff to groundwater flow dominated processes is significant. It is of interest, whether the catchment transition is also reflected by hydrogeochemical indicators. We assume gypsum dissolution as dominant process at the catchment scale. In order to investigate the hydrogeochemical evolution of the catchment we analysed electric conductivity, calcium and sulphate concentrations and pH-values of biweekly composite samples from 2007-2013 of the atmospheric deposition, of runoff and soil water. The two observation points in the flowing water represent surface runoff and groundwater discharge respectively. Soil water has been analysed at four soil pits in three depths. The monitoring data were provided by the Research Platform Chicken Creek (https://www.tu-cottbus.de/projekte/en/oekosysteme/startseite.html). From the macroscopic data analysis we found an exponential decay of the electric conductivity, calcium and sulphate concentrations in the flowing waters and some of the soil pits. In the flowing water, the decrease slope of the electric conductivity and the calcium and sulphate concentrations is almost identical. The calcium / sulphate molar ratio as an indicator of gypsum dissolution is almost equal to one up to 2010, afterwards more calcium than sulphate is released. The pH-values in the flowing

  1. Gradual and sustained carbon dioxide release during Aptian Oceanic Anoxic Event 1a

    Science.gov (United States)

    Naafs, B. D. A.; Castro, J. M.; de Gea, G. A.; Quijano, M. L.; Schmidt, D. N.; Pancost, R. D.

    2016-02-01

    During the Aptian Oceanic Anoxic Event 1a, about 120 million years ago, black shales were deposited in all the main ocean basins. The event was also associated with elevated sea surface temperatures and a calcification crisis in calcareous nannoplankton. These environmental changes have been attributed to variations in atmospheric CO2 concentrations, but the evolution of the carbon cycle during this event is poorly constrained. Here we present records of atmospheric CO2 concentrations across Oceanic Anoxic Event 1a derived from bulk and compound-specific δ13C from marine rock outcrops in southern Spain and Tunisia. We find that CO2 concentrations doubled in two steps during the oceanic anoxic event and remained above background values for approximately 1.5-2 million years before declining. The rise of CO2 concentrations occurred over several tens to hundreds of thousand years, and thus was unlikely to have resulted in any prolonged surface ocean acidification, suggesting that CO2 emissions were not the primary cause of the nannoplankton calcification crisis. We find that the period of elevated CO2 concentrations coincides with a shift in the oceanic osmium-isotope inventory associated with emplacement of the Ontong Java Plateau flood basalts, and conclude that sustained volcanic outgassing was the primary source of carbon dioxide during Oceanic Anoxic Event 1a.

  2. HEPARIN-INSENSITIVE CALCIUM-RELEASE FROM INTRACELLULAR STORES TRIGGERED BY THE RECOMBINANT HUMAN PARATHYROID-HORMONE RECEPTOR

    NARCIS (Netherlands)

    SEUWEN, K; BODDEKE, HGWM

    1995-01-01

    1 In the present study we have characterized the parathyroid hormone (PTH)-induced calcium signalling in 293 cells stably transfected with the human PTH receptor cDNA. In these cells, human PTH-I(1-38) strongly stimulates adenosine 3':5'-cyclic monophosphate (cyclic AMP) formation (EC(50) = 0.39 nM)

  3. Developmental profile of localized spontaneous Ca(2+) release events in the dendrites of rat hippocampal pyramidal neurons.

    Science.gov (United States)

    Miyazaki, Kenichi; Manita, Satoshi; Ross, William N

    2012-12-01

    Recent experiments demonstrate that localized spontaneous Ca(2+) release events can be detected in the dendrites of pyramidal cells in the hippocampus and other neurons (J. Neurosci. 29 (2009) 7833-7845). These events have some properties that resemble ryanodine receptor mediated "sparks" in myocytes, and some that resemble IP(3) receptor mediated "puffs" in oocytes. They can be detected in the dendrites of rats of all tested ages between P3 and P80 (with sparser sampling in older rats), suggesting that they serve a general signaling function and are not just important in development. However, in younger rats the amplitudes of the events are larger than the amplitudes in older animals and almost as large as the amplitudes of Ca(2+) signals from backpropagating action potentials (bAPs). The rise time of the event signal is fast at all ages and is comparable to the rise time of the bAP fluorescence signal at the same dendritic location. The decay time is slower in younger animals, primarily because of weaker Ca(2+) extrusion mechanisms at that age. Diffusion away from a brief localized source is the major determinant of decay at all ages. A simple computational model closely simulates these events with extrusion rate the only age dependent variable. PMID:22951184

  4. Effects of two fast-setting calcium-silicate cements on cell viability and angiogenic factor release in human pulp-derived cells.

    Science.gov (United States)

    Chung, Chooryung J; Kim, Euiseong; Song, Minju; Park, Jeong-Won; Shin, Su-Jung

    2016-05-01

    Mineral trioxide aggregate (MTA) is considered a pulp-capping agent of choice, but has the drawback of a long setting time. This study aimed to assess two different types of calcium-silicate cements as pulp-capping agents, by investigating their in vitro cytotoxicity and angiogenic effects in human pulp cells. ProRoot MTA, Endocem Zr, and Retro MTA were prepared as set or freshly mixed pellets. Human pulp-derived cells were grown in direct contact with these three cements, Dycal, or no cement, for 7 days. Initial cell attachment, viability, calcium release, and the levels of vascular endothelial growth factor (VEGF), angiogenin, and basic fibroblast growth factor (FGF-2) were evaluated statistically using a linear mixed model (P calcium concentration compared with the control group (P  0.05). We demonstrate that Retro MTA, which has a short setting time, has similar biocompatibility and angiogenic effects on human pulp cells, and can therefore potentially be as effective in pulp capping as ProRoot MTA. Endocem Zr showed intermittent cytotoxicity and elicited lower levels of VEGF and angiogenin expression. PMID:25596932

  5. 17β-estradiol rapidly activates calcium release from intracellular stores via the GPR30 pathway and MAPK phosphorylation in osteocyte-like MLO-Y4 cells

    KAUST Repository

    Ren, Jian

    2012-03-06

    Estrogen regulates critical cellular functions, and its deficiency initiates bone turnover and the development of bone mass loss in menopausal females. Recent studies have demonstrated that 17β-estradiol (E 2) induces rapid non-genomic responses that activate downstream signaling molecules, thus providing a new perspective to understand the relationship between estrogen and bone metabolism. In this study, we investigated rapid estrogen responses, including calcium release and MAPK phosphorylation, in osteocyte-like MLO-Y4 cells. E 2 elevated [Ca 2+] i and increased Ca 2+ oscillation frequency in a dose-dependent manner. Immunolabeling confirmed the expression of three estrogen receptors (ERα, ERβ, and G protein-coupled receptor 30 [GPR30]) in MLO-Y4 cells and localized GPR30 predominantly to the plasma membrane. E 2 mobilized calcium from intracellular stores, and the use of selective agonist(s) for each ER showed that this was mediated mainly through the GPR30 pathway. MAPK phosphorylation increased in a biphasic manner, with peaks occurring after 7 and 60 min. GPR30 and classical ERs showed different temporal effects on MAPK phosphorylation and contributed to MAPK phosphorylation sequentially. ICI182,780 inhibited E 2 activation of MAPK at 7 min, while the GPR30 agonist G-1 and antagonist G-15 failed to affect MAPK phosphorylation levels. G-1-mediated MAPK phosphorylation at 60 min was prevented by prior depletion of calcium stores. Our data suggest that E 2 induces the non-genomic responses Ca 2+ release and MAPK phosphorylation to regulate osteocyte function and indicate that multiple receptors mediate rapid E 2 responses. © 2012 Springer Science+Business Media, LLC.

  6. 17β-estradiol rapidly activates calcium release from intracellular stores via the GPR30 pathway and MAPK phosphorylation in osteocyte-like MLO-Y4 cells.

    Science.gov (United States)

    Ren, Jian; Wu, Jun Hua

    2012-05-01

    Estrogen regulates critical cellular functions, and its deficiency initiates bone turnover and the development of bone mass loss in menopausal females. Recent studies have demonstrated that 17β-estradiol (E(2)) induces rapid non-genomic responses that activate downstream signaling molecules, thus providing a new perspective to understand the relationship between estrogen and bone metabolism. In this study, we investigated rapid estrogen responses, including calcium release and MAPK phosphorylation, in osteocyte-like MLO-Y4 cells. E(2) elevated [Ca(2+)]( i ) and increased Ca(2+) oscillation frequency in a dose-dependent manner. Immunolabeling confirmed the expression of three estrogen receptors (ERα, ERβ, and G protein-coupled receptor 30 [GPR30]) in MLO-Y4 cells and localized GPR30 predominantly to the plasma membrane. E(2) mobilized calcium from intracellular stores, and the use of selective agonist(s) for each ER showed that this was mediated mainly through the GPR30 pathway. MAPK phosphorylation increased in a biphasic manner, with peaks occurring after 7 and 60 min. GPR30 and classical ERs showed different temporal effects on MAPK phosphorylation and contributed to MAPK phosphorylation sequentially. ICI182,780 inhibited E(2) activation of MAPK at 7 min, while the GPR30 agonist G-1 and antagonist G-15 failed to affect MAPK phosphorylation levels. G-1-mediated MAPK phosphorylation at 60 min was prevented by prior depletion of calcium stores. Our data suggest that E(2) induces the non-genomic responses Ca(2+) release and MAPK phosphorylation to regulate osteocyte function and indicate that multiple receptors mediate rapid E(2) responses. PMID:22392527

  7. Streptococcus pneumoniae Infection of Host Epithelial Cells via Polymeric Immunoglobulin Receptor Transiently Induces Calcium Release from Intracellular Stores*

    OpenAIRE

    Asmat, T. M.; Agarwal, V; Rath, S.; Hildebrandt, J.-P.; Hammerschmidt, S.

    2011-01-01

    The pneumococcal surface protein C (PspC) is a major adhesin of Streptococcus pneumoniae (pneumococci) that interacts in a human-specific manner with the ectodomain of the human polymeric immunoglobulin receptor (pIgR) produced by respiratory epithelial cells. This interaction promotes bacterial colonization and bacterial internalization by initiating host signal transduction cascades. Here, we examined alterations of intracellular calcium ([Ca2+]i) levels in epithelial cells during host cell...

  8. Risk of cardiovascular thrombotic events after surgical castration versus gonadotropin-releasing hormone agonists in Chinese men with prostate cancer

    Directory of Open Access Journals (Sweden)

    Jeremy YC Teoh

    2015-06-01

    Full Text Available We investigated the cardiovascular thrombotic risk after surgical castration (SC versus gonadotropin-releasing hormone agonists (GnRHa in Chinese men with prostate cancer. All Chinese prostate cancer patients who were treated with SC or GnRHa from year 2000 to 2009 were reviewed and compared. The primary outcome was any new-onset of cardiovascular thrombotic events after SC or GnRHa, which was defined as any event of acute myocardial infarction or ischemic stroke. The risk of new-onset cardiovascular thrombotic event was compared between the SC group and the GnRHa group using Kaplan-Meier method. Multivariate Cox regression analysis was performed to adjust for other potential confounding factors. A total of 684 Chinese patients was included in our study, including 387 patients in the SC group and 297 patients in the GnRHa group. The mean age in the SC group (75.3 ± 7.5 years was significantly higher than the GnRHa group (71.8 ± 8.3 years (P < 0.001. There was increased risk of new cardiovascular thrombotic events in the SC group when compared to the GnRHa group upon Kaplan-Meier analysis (P = 0.014. Upon multivariate Cox regression analysis, age (hazard ratio [HR] 1.072, 95% confidence interval [CI] 1.04-1.11, P< 0.001, hyperlipidemia (HR 2.455, 95% CI 1.53-3.93, P< 0.001, and SC (HR 1.648, 95% CI 1.05-2.59, P= 0.031 were significant risk factors of cardiovascular thrombotic events. In conclusion, SC was associated with increased risk of cardiovascular thrombotic events when compared to GnRHa. This is an important aspect to consider while deciding on the method of androgen deprivation therapy, especially in elderly men with known history of hyperlipidemia.

  9. Involvement of phospholipase C and intracellular calcium signaling in the gonadotropin-releasing hormone regulation of prolactin release from lactotrophs of tilapia (Oreochromis mossambicus)

    DEFF Research Database (Denmark)

    Tipsmark, Christian Kølbæk; Weber, G M; Strom, C N;

    2005-01-01

    Gonadotropin-releasing hormone (GnRH) is a potent stimulator of prolactin (PRL) secretion in various vertebrates including the tilapia, Oreochromis mossambicus. The mechanism by which GnRH regulates lactotroph cell function is poorly understood. Using the advantageous characteristics of the teleo...

  10. Review article: loss of the calcium-sensing receptor in colonic epithelium is a key event in the pathogenesis of colon cancer.

    LENUS (Irish Health Repository)

    Rogers, Ailín C

    2012-03-01

    The calcium-sensing receptor (CaSR) is expressed abundantly in normal colonic epithelium and lost in colon cancer, but its exact role on a molecular level and within the carcinogenesis pathway is yet to be described. Epidemiologic studies show that inadequate dietary calcium predisposes to colon cancer; this may be due to the ability of calcium to bind and upregulate the CaSR. Loss of CaSR expression does not seem to be an early event in carcinogenesis; indeed it is associated with late stage, poorly differentiated, chemo-resistant tumors. Induction of CaSR expression in neoplastic colonocytes arrests tumor progression and deems tumors more sensitive to chemotherapy; hence CaSR may be an important target in colon cancer treatment. The CaSR has a complex role in colon cancer; however, more investigation is required on a molecular level to clarify its exact function in carcinogenesis. This review describes the mechanisms by which the CaSR is currently implicated in colon cancer and identifies areas where further study is needed.

  11. Electrospinning of calcium phosphate-poly (d,l-lactic acid) nanofibers for sustained release of water-soluble drug and fast mineralization

    Science.gov (United States)

    Fu, Qi-Wei; Zi, Yun-Peng; Xu, Wei; Zhou, Rong; Cai, Zhu-Yun; Zheng, Wei-Jie; Chen, Feng; Qian, Qi-Rong

    2016-01-01

    Calcium phosphate-based biomaterials have been well studied in biomedical fields due to their outstanding chemical and biological properties which are similar to the inorganic constituents in bone tissue. In this study, amorphous calcium phosphate (ACP) nanoparticles were prepared by a precipitation method, and used for preparation of ACP-poly(d,l-lactic acid) (ACP-PLA) nanofibers and water-soluble drug-containing ACP-PLA nanofibers by electrospinning. Promoting the encapsulation efficiency of water-soluble drugs in electrospun hydrophobic polymer nanofibers is a common problem due to the incompatibility between the water-soluble drug molecules and hydrophobic polymers solution. Herein, we used a native biomolecule of lecithin as a biocompatible surfactant to overcome this problem, and successfully prepared water-soluble drug-containing ACP-PLA nanofibers. The lecithin and ACP nanoparticles played important roles in stabilizing water-soluble drug in the electrospinning composite solution. The electrospun drug-containing ACP-PLA nanofibers exhibited fast mineralization in simulated body fluid. The ACP nanoparticles played the key role of seeds in the process of mineralization. Furthermore, the drug-containing ACP-PLA nanofibers exhibited sustained drug release which simultaneously occurred with the in situ mineralization in simulated body fluid. The osteoblast-like (MG63) cells with spreading filopodia were well observed on the as-prepared nanofibrous mats after culturing for 24 hours, indicating a high cytocompatibility. Due to the high biocompatibility, sustained drug release, and fast mineralization, the as-prepared composite nanofibers may have potential applications in water-soluble drug loading and release for tissue engineering. PMID:27785016

  12. Reconstruction of the Magnetkoepfl rockfall event - Detecting rock fall release zones using terrestrial laser scanning, Hohe Tauern, Austria

    Science.gov (United States)

    Hartmeyer, I.; Keuschnig, M.; Delleske, R.; Schrott, L.

    2012-04-01

    Instability of rock faces in high mountain areas is an important risk factor for man and infrastructure, particularly within the context of climate change. Numerous rock fall events in the European Alps suggest an increasing occurrence of mass movements due to rising temperatures in recent years. Within the MOREXPERT project ('Monitoring Expert System for Hazardous Rock Walls') a new long-term monitoring site for mass movement and permafrost interaction has been initiated in the Austrian Alps. The study area is located at the Kitzsteinhorn (Hohe Tauern), a particularly interesting site for the investigation of glacier retreat and potential permafrost degradation and their respective consequences for the stability of alpine rock faces. To detect and quantify changes occurring at the terrain surface an extensive terrestrial laser scanning (TLS) monitoring campaign was started in 2011. TLS creates three-dimensional high-resolution images of the scanned area allowing precise quantification of changes in geometry and volume in steep rock faces over distances of up to several hundreds of meters. Within the TLS monitoring campaign at the Kitzsteinhorn a large number of differently dimensioned rock faces is examined (varying size, slope inclination etc.). Scanned areas include the Kitzsteinhorn northwest and south face, the Magnetkoepfl east face as well as a couple of small rock faces in the vicinity of the summit station. During the night from August 27th to August 28th 2011 a rock fall event was documented by employees of the cable car company. The release zone could not immediately be detected. The east face of the Magnetkoepfl covers approximately 70 meters in height and about 200 meters in width. It is made up of calcareous mica-schist and displays an abundance of well-developed joint sets with large joint apertures. Meteorological data from a weather station located at the same altitude (2.950m) and just 500m away from the release zone show that the rock fall event

  13. Rapid kinetic analysis of the calcium-release channels of skeletal muscle sarcoplasmic reticulum: The effect of inhibitors

    International Nuclear Information System (INIS)

    During excitation of skeletal muscle fibers, Ca ions stored in the cisternal compartments of the sarcoplasmic reticulum (SR) are released to the cytosol within milliseconds. In this study, the kinetics of the fast release of Ca were analyzed by means of a newly developed rapid filtration apparatus. Isolated SR vesicles of cisternal origin were preloaded with 1 mM 45CaCl2, Ca efflux was studied after dilution into media of various composition. The effect of extravesicular Ca on the gating of the Ca-release channels and its susceptibility to the influence of drugs were thoroughly investigated. In the presence of 1 mM MgCl2 and 3 mM ATP, highest rates of Ca release were observed at a free Ca concentration between 1 and 50 μM. In the lower micromolar Ca range, compounds such as neomycin and FLA 365 inhibited the release monophasically and with an IC50 of 0.37 and 3.4 μM, respectively. At Ca concentrations between 10 and 50 μM, the inhibitors could not block Ca release effectively. Close analysis of the dose-response curves revealed a biphasic pattern, indicative of the presence of two substrates of the Ca-release channel, displaying high- and low-affinity binding sites for the inhibitors. The results indicate the existence of various open substrates of the Ca channels that can be distinguished pharmacologically. Effective blockade of rapid Ca release requires inhibition of all substrates coexisting under a given condition

  14. Inhibition of anaphylactic histamine release from heterologously sensitized mast cells: differential effects of drugs which interfere with calcium influx.

    OpenAIRE

    Kurose, Masao

    1981-01-01

    Drug effects were studied on anaphylactic histamine release from rat mast cells sensitized in vitro with mouse IgE antibody. When histamine release was elicited by adding Ca-++ at various times after antigen-stimulation of sensitized cells in Ca++-free medium, the drugs to be tested were added shortly before each Ca++ addition. Quercetin was effective only when added before or immediately after antigen. Theophylline and disodium cromoglycate (DSCG) were active irrespective of the time interva...

  15. A toxic extract of the marine phytoflagellate Prymnesium parvum induces calcium-dependent release of glutamate from rat brain synaptosomes.

    Science.gov (United States)

    Mariussen, Espen; Nelson, George Nicholas; Fonnum, Frode

    2005-01-01

    Blooms of the marine phytoflagellate Prymnesium parvum produced mass mortality of fish in Norway and many other parts of the world. The effects of a purified algae extract of P. parvum on transmitter release from rat brain synaptosomes were studied to characterize its toxic action. Synaptosomes are detached nerve terminals and represent a simple system that has retained the machinery for uptake, synthesis, storage, and release of neurotransmitters. A crude methanol extract of P. parvum was purified by reverse-phase column for fast protein liquid chromatography (FPLC). The purified extract stimulated Ca2+-dependent spontaneous release of glutamate in a concentration-dependent manner. The release was increased by addition of extracellular Ca2+. The release of glutamate was suppressed by the Ca2+-channel blockers flunarizine (10 microM), diltiazem (10 microM), and verapamil (10 microM). The stimulation of release of glutamate from rat brain synaptosomes induced by the toxin may be due to an ionophorelike property of the algae extract such as previously reported for the potent algal toxin maitotoxin. At high concentrations the toxin primarily acts as a powerful lytic agent. PMID:15739805

  16. The First Ground Level Enhancement Event of Solar Cycle 24: Direct Observation of Shock Formation and Particle Release Heights

    Science.gov (United States)

    Gopalswamy, N.; Xie, H.; Akiyama, S.; Yashiro, S.; Usoskin, I. G.; Davila, J. M.

    2013-01-01

    We report on the 2012 May 17 ground level enhancement (GLE) event, which is the first of its kind in solar cycle 24. This is the first GLE event to be fully observed close to the surface by the Solar Terrestrial Relations Observatory (STEREO) mission.We determine the coronal mass ejection (CME) height at the start of the associated metric type II radio burst (i.e., shock formation height) as 1.38 Rs (from the Sun center). The CME height at the time of GLE particle release was directly measured from a STEREO image as 2.32 Rs, which agrees well with the estimation from CME kinematics. These heights are consistent with those obtained for cycle-23 GLEs using back-extrapolation. By contrasting the 2012 May 17 GLE with six other non-GLE eruptions from well-connected regions with similar or larger flare sizes and CME speeds, we find that the latitudinal distance from the ecliptic is rather large for the non-GLE events due to a combination of non-radial CME motion and unfavorable solar B0 angle, making the connectivity to Earth poorer. We also find that the coronal environment may play a role in deciding the shock strength.

  17. A controlled release of antibiotics from calcium phosphate-coated poly(lactic-co-glycolic acid) particles and their in vitro efficacy against Staphylococcus aureus biofilm.

    Science.gov (United States)

    Bastari, Kelsen; Arshath, Mohamed; Ng, Zhi Hui Melissa; Chia, Jia Hua; Yow, Zhi Xian Daniel; Sana, Barindra; Tan, Meng Fong Cherine; Lim, Sierin; Loo, Say Chye Joachim

    2014-03-01

    Ceramic-polymer hybrid particles, intended for osteomyelitis treatment, were fabricated by preparing poly(lactic-co-glycolic acid) particles through an emulsion solvent evaporation technique, followed by calcium phosphate (CaP) coating via a surface adsorption-nucleation method. The presence of CaP coating on the surface of the particles was confirmed by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy. Subsequently, two antibiotics for treating bone infection, nafcillin (hydrophilic) and levofloxacin (amphiphilic), were loaded into these hybrid particles and their in vitro drug release studies were investigated. The CaP coating was shown to reduce burst release, while providing sustained release of the antibiotics for up to 4 weeks. In vitro bacterial study against Staphylococcus aureus demonstrated the capability of these antibiotic-loaded hybrid particles to inhibit biofilm formation as well as deteriorate established biofilm, making this hybrid system a potential candidate for further investigation for osteomyelitis treatment.

  18. Events

    Directory of Open Access Journals (Sweden)

    Igor V. Karyakin

    2016-02-01

    Full Text Available The 9th ARRCN Symposium 2015 was held during 21st–25th October 2015 at the Novotel Hotel, Chumphon, Thailand, one of the most favored travel destinations in Asia. The 10th ARRCN Symposium 2017 will be held during October 2017 in the Davao, Philippines. International Symposium on the Montagu's Harrier (Circus pygargus «The Montagu's Harrier in Europe. Status. Threats. Protection», organized by the environmental organization «Landesbund für Vogelschutz in Bayern e.V.» (LBV was held on November 20-22, 2015 in Germany. The location of this event was the city of Wurzburg in Bavaria.

  19. Ultrastructure of cardiac muscle in reptiles and birds: optimizing and/or reducing the probability of transmission between calcium release units.

    Science.gov (United States)

    Perni, Stefano; Iyer, V Ramesh; Franzini-Armstrong, Clara

    2012-06-01

    It is known that cardiac myocytes contain three categories of calcium release units (CRUs) all bearing arrays of RyR2: peripheral couplings, constituted of an association of the junctional SR (jSR) with the plasmalemma; dyads, associations between jSR and T tubules; internal extended junctional jSR (EjSR)/corbular jSR that is not associated with plasmalemma/T tubules. The bird hearts, even if fast beating (e.g., in finch and hummingbird) have no T tubules, despite fiber sizes comparable to those of mammalian ventricle, but are rich in EjSR/corbular SR. The heart of small lizard also lacks T tubule, but it has only peripheral couplings and compensates for lack of internal CRUs by the small diameter of its cells. We have extended previous information on chicken heart to finch and lizard by establishing a spatial relationship between RyR2 clusters in jSR of peripheral couplings and clusters of intra-membrane particles identifiable as voltage sensitive calcium channels (CaV1.2) in the adjacent plasmalemma. This provides the structural basis for initiation of the heart beat in all three species. Further we evaluated the distances separating peripheral couplings from each other and between EjSR/corbular SR sites within the bird muscles in all three hearts. The distances suggest that peripheral coupling sites are most likely to act independently of each other and that a calcium wave-front propagation from one internal CRU site to the other across the level of the Z line, may be marginally successful in the chicken, but certainly very effective in the finch. PMID:22576825

  20. Release of dopamine from human neocortex nerve terminals evoked by different stimuli involving extra- and intraterminal calcium

    OpenAIRE

    Bonanno, Giambattista; Sala, Roberta; Cancedda, Laura; Cavazzani, Paolo; Cossu, Massimo; Raiteri, Maurizio

    2000-01-01

    The release of [3H]-dopamine ([3H]-DA) from human neocortex nerve terminals was studied in synaptosomes prepared from brain specimens removed in neurosurgery and exposed during superfusion to different releasing stimuli.Treatment with 15 mM KCl, 100 μM 4-aminopyridine, 1 μM ionomycin or 30 mM caffeine elicited almost identical overflows of tritium. Removal of external Ca2+ ions abolished the overflow evoked by K+ or ionomycin and largely prevented that caused by 4-aminopyridine; the overflow ...

  1. C-terminal clipping of chemokine CCL1/I-309 enhances CCR8-mediated intracellular calcium release and anti-apoptotic activity.

    Science.gov (United States)

    Denis, Catherine; Deiteren, Kathleen; Mortier, Anneleen; Tounsi, Amel; Fransen, Erik; Proost, Paul; Renauld, Jean-Christophe; Lambeir, Anne-Marie

    2012-01-01

    Carboxypeptidase M (CPM) targets the basic amino acids arginine and lysine present at the C-terminus of peptides or proteins. CPM is thought to be involved in inflammatory processes. This is corroborated by CPM-mediated trimming and modulation of inflammatory factors, and expression of the protease in inflammatory environments. Since the function of CPM in and beyond inflammation remains mainly undefined, the identification of natural substrates can aid in discovering the (patho)physiological role of CPM. CCL1/I-309, with its three C-terminal basic amino acids, forms a potential natural substrate for CPM. CCL1 plays a role not only in inflammation but also in apoptosis, angiogenesis and tumor biology. Enzymatic processing differently impacts the biological activity of chemokines thereby contributing to the complex regulation of the chemokine system. The aim of the present study was to investigate whether (i) CCL1/I-309 is prone to trimming by CPM, and (ii) the biological activity of CCL1 is altered after C-terminal proteolytic processing. CCL1 was identified as a novel substrate for CPM in vitro using mass spectrometry. C-terminal clipping of CCL1 augmented intracellular calcium release mediated by CCR8 but reduced the binding of CCL1 to CCR8. In line with the higher intracellular calcium release, a pronounced increase of the anti-apoptotic activity of CCL1 was observed in the BW5147 cellular model. CCR8 signaling, CCR8 binding and anti-apoptotic activity were unaffected when CPM was exposed to the carboxypeptidase inhibitor DL-2-mercaptomethyl-3-guanidino-ethylthiopropanoic acid. The results of this study suggest that CPM is a likely candidate for the regulation of biological processes relying on the CCL1-CCR8 system. PMID:22479563

  2. Combinations of physiologic estrogens with xenoestrogens alter calcium and kinase responses, prolactin release, and membrane estrogen receptor trafficking in rat pituitary cells

    Directory of Open Access Journals (Sweden)

    Watson Cheryl S

    2010-10-01

    Full Text Available Abstract Background Xenoestrogens such as alkylphenols and the structurally related plastic byproduct bisphenol A have recently been shown to act potently via nongenomic signaling pathways and the membrane version of estrogen receptor-α. Though the responses to these compounds are typically measured individually, they usually contaminate organisms that already have endogenous estrogens present. Therefore, we used quantitative medium-throughput screening assays to measure the effects of physiologic estrogens in combination with these xenoestrogens. Methods We studied the effects of low concentrations of endogenous estrogens (estradiol, estriol, and estrone at 10 pM (representing pre-development levels, and 1 nM (representing higher cycle-dependent and pregnancy levels in combinations with the same levels of xenoestrogens in GH3/B6/F10 pituitary cells. These levels of xenoestrogens represent extremely low contamination levels. We monitored calcium entry into cells using Fura-2 fluorescence imaging of single cells. Prolactin release was measured by radio-immunoassay. Extracellular-regulated kinase (1 and 2 phospho-activations and the levels of three estrogen receptors in the cell membrane (ERα, ERβ, and GPER were measured using a quantitative plate immunoassay of fixed cells either permeabilized or nonpermeabilized (respectively. Results All xenoestrogens caused responses at these concentrations, and had disruptive effects on the actions of physiologic estrogens. Xenoestrogens reduced the % of cells that responded to estradiol via calcium channel opening. They also inhibited the activation (phosphorylation of extracellular-regulated kinases at some concentrations. They either inhibited or enhanced rapid prolactin release, depending upon concentration. These latter two dose-responses were nonmonotonic, a characteristic of nongenomic estrogenic responses. Conclusions Responses mediated by endogenous estrogens representing different life stages are

  3. Short-term microbial release during rain events from on-site sewers and cattle in a surface water source.

    Science.gov (United States)

    Aström, Johan; Pettersson, Thomas J R; Reischer, Georg H; Hermansson, Malte

    2013-09-01

    The protection of drinking water from pathogens such as Cryptosporidium and Giardia requires an understanding of the short-term microbial release from faecal contamination sources in the catchment. Flow-weighted samples were collected during two rainfall events in a stream draining an area with on-site sewers and during two rainfall events in surface runoff from a bovine cattle pasture. Samples were analysed for human (BacH) and ruminant (BacR) Bacteroidales genetic markers through quantitative polymerase chain reaction (qPCR) and for sorbitol-fermenting bifidobacteria through culturing as a complement to traditional faecal indicator bacteria, somatic coliphages and the parasitic protozoa Cryptosporidium spp. and Giardia spp. analysed by standard methods. Significant positive correlations were observed between BacH, Escherichia coli, intestinal enterococci, sulphite-reducing Clostridia, turbidity, conductivity and UV254 in the stream contaminated by on-site sewers. For the cattle pasture, no correlation was found between any of the genetic markers and the other parameters. Although parasitic protozoa were not detected, the analysis for genetic markers provided baseline data on the short-term faecal contamination due to these potential sources of parasites. Background levels of BacH and BacR makers in soil emphasise the need to including soil reference samples in qPCR-based analyses for Bacteroidales genetic markers. PMID:23981872

  4. 5-Hydroxytryptamino-induced calcium sparks in cultured rat stomach fundus smooth muscle cells

    Institute of Scientific and Technical Information of China (English)

    张小玲; 阎宏涛; 闫炀

    2003-01-01

    With a new fluorescence probe of Ca2+, STDIn-AM, 5-hydroxytryptamino (5-HT)-induced spontaneous calcium release events (calcium sparks) in cultured rat stomach fundus smooth muscle cells (SFSMC) are investigated by laser scanning confocal microscope. The mechanisms of initiation of Ca2+ sparks, propagating Ca2+ waves and their relation to E-C coupling are discussed. After the extracellular [Ca2+] is increased to 10 mmol/L, addition of 5-HT causes hot spots throughout the cytoplasm, which is brighter near the plasmalemma. The amplitude of the event is at least two times greater than the standard deviation of fluorescence intensity fluctuations measured in the neighboring region and the duration of the Ca2+ signal is over 100 ms. The results suggest that 5-HT acts by the way of 5-HT2 receptors on SFSMC, then through 5-HT2 receptors couples IP3/Ca2+ and DG/PKC double signal transduction pathways to cause Ca2+ release from intracellular Ca2+ stores and followed Ca2+ influx possibly through calcium release-activated calcium influx. The acceptor of activated 5-HT2 can also cause membrane depolarization, which then stimulates the L-type Ca2+ channels leading to Ca2+ influx. Thenthe local Ca2+ entry mentioned above activates ryanodine-sensitive Ca2+ releasechannels (RyR) on sarcoplasmic reticulum (SR) to cause local Ca2+ release events (Ca2+ sparks) through calcium-induced calcium release (CICR).

  5. Slow-release of methanogenic inhibitors derived from encapsulated calcium carbide using paraffin wax and/or rosin: matrix optimization and diffusion characteristics.

    Science.gov (United States)

    Tiantao, Zhao; Youcai, Zhao; Lijie, Zhang; Haoquan, Chen; Feng, Shi; Haiyan, Zhou

    2011-11-01

    Acetylene has been found to significantly inhibit biological activity of methanogens and thus might be applicable for reducing the generation and emission of methane from municipal solid waste landfills. However, acetylene is gaseous and so it is considered physically infeasible to directly apply this gas to waste in landfill conditions. In the present study, a novel acetylene release mechanism was tested, using a matrix of acetylene entrapped in high hydrophobic paraffin wax and/or rosin and calcium carbide capsules with a ratio of 1.0 g g(-1) matrix and a diameter of 10 mm to facilitate the gradual release of acetylene. A diffusion mechanism model (Q = &b.gamma; × t (0.5)) for the matrix was derived based on the T. Higuchi equation, and the effective diffusion coefficients (D(e)) were acquired by linear fitting. Additionally, it was found that D(e) remained constant when the rosin content was up to more than 20% g g(-1) matrix.

  6. Regulation of physicochemical properties, osteogenesis activity, and fibroblast growth factor-2 release ability of β-tricalcium phosphate for bone cement by calcium silicate

    Energy Technology Data Exchange (ETDEWEB)

    Su, Ching-Chuan [Antai Medical Care Cooperation Antai Tian-Sheng Memorial Hospital, Pingtung, Taiwan (China); Kao, Chia-Tze; Hung, Chi-Jr [School of Dentistry, Chung Shan Medical University, Taichung, Taiwan (China); Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Chen, Yi-Jyun [School of Dentistry, Chung Shan Medical University, Taichung, Taiwan (China); Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Dental Department, Taichung Hospital, Ministry of Health and Welfare, Taichung City, Taiwan (China); Huang, Tsui-Hsien, E-mail: thh@csmu.edu.tw [School of Dentistry, Chung Shan Medical University, Taichung, Taiwan (China); Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Shie, Ming-You, E-mail: eviltacasi@gmail.com [Institute of Oral Science, Chung Shan Medical University, Taichung, Taiwan (China)

    2014-04-01

    β-Tricalcium phosphate (β-TCP) is an osteoconductive material. For this research we have combined it with a low degradation calcium silicate (CS) to enhance its bioactive and osteostimulative properties. To check its effectiveness, a series of β-TCP/CS composites with different ratios were prepared to make new bioactive and biodegradable biocomposites for bone repair. Formation of bone-like apatite, the diametral tensile strength, and weight loss of composites were considered before and after immersion in simulated body fluid (SBF). In addition, we also examined the effects of fibroblast growth factor-2 (FGF-2) released from β-TCP/CS composites and in vitro human dental pulp cell (hDPC) and studied its behavior. The results showed that the apatite deposition ability of the β-TCP/CS composites was enhanced as the CS content was increased. For composites with more than 50% CS contents, the samples were completely covered by a dense bone-like apatite layer. At the end of the immersion point, weight losses of 19%, 24%, 33%, 42%, and 51% were observed for the composites containing 0%, 30%, 50%, 70% and 100% β-TCP cements, respectively. In vitro cell experiments show that the CS-rich composites promote human dental pulp cell (hDPC) proliferation and differentiation. However, when the CS quantity in the composite is less than 70%, the amount of cells and osteogenesis protein of hDPCs was stimulated by FGF-2 released from β-TCP/CS composites. The combination of FGF-2 in degradation of β-TCP and osteogenesis of CS gives a strong reason to believe that these calcium-based composite cements may prove to be promising bone repair materials. - Highlights: • CS improved physicochemical properties and osteogenic activity of β-TCP. • The higher the CS in the cement, the shorter the setting time and the higher the DTS. • The cell behavior was stimulated by FGF-2 released from composite containing 50% CS. • β-TCP/CS composite with FGF-2 has optimal properties for

  7. Regulation of physicochemical properties, osteogenesis activity, and fibroblast growth factor-2 release ability of β-tricalcium phosphate for bone cement by calcium silicate

    International Nuclear Information System (INIS)

    β-Tricalcium phosphate (β-TCP) is an osteoconductive material. For this research we have combined it with a low degradation calcium silicate (CS) to enhance its bioactive and osteostimulative properties. To check its effectiveness, a series of β-TCP/CS composites with different ratios were prepared to make new bioactive and biodegradable biocomposites for bone repair. Formation of bone-like apatite, the diametral tensile strength, and weight loss of composites were considered before and after immersion in simulated body fluid (SBF). In addition, we also examined the effects of fibroblast growth factor-2 (FGF-2) released from β-TCP/CS composites and in vitro human dental pulp cell (hDPC) and studied its behavior. The results showed that the apatite deposition ability of the β-TCP/CS composites was enhanced as the CS content was increased. For composites with more than 50% CS contents, the samples were completely covered by a dense bone-like apatite layer. At the end of the immersion point, weight losses of 19%, 24%, 33%, 42%, and 51% were observed for the composites containing 0%, 30%, 50%, 70% and 100% β-TCP cements, respectively. In vitro cell experiments show that the CS-rich composites promote human dental pulp cell (hDPC) proliferation and differentiation. However, when the CS quantity in the composite is less than 70%, the amount of cells and osteogenesis protein of hDPCs was stimulated by FGF-2 released from β-TCP/CS composites. The combination of FGF-2 in degradation of β-TCP and osteogenesis of CS gives a strong reason to believe that these calcium-based composite cements may prove to be promising bone repair materials. - Highlights: • CS improved physicochemical properties and osteogenic activity of β-TCP. • The higher the CS in the cement, the shorter the setting time and the higher the DTS. • The cell behavior was stimulated by FGF-2 released from composite containing 50% CS. • β-TCP/CS composite with FGF-2 has optimal properties for

  8. Association between adherence to calcium-channel blocker and statin medications and likelihood of cardiovascular events among US managed care enrollees

    Directory of Open Access Journals (Sweden)

    Yeaw Jason

    2010-06-01

    Full Text Available Abstract Background Prior studies have found that patients taking single-pill amlodipine/atorvastatin (SPAA have greater likelihood of adherence at 6 months than those taking 2-pill calcium-channel blocker and statin combinations (CCB/statin. This study examines whether this adherence benefit results in fewer cardiovascular (CV events. Methods A retrospective cohort study was conducted using administrative claims data from the IMS LifeLink: US Health Plan Claims database, identifying adults already taking CCB or statin (but not both who had an index event of either initiating treatment with SPAA or adding CCB to statin (or vice versa between April 1, 2004 to August 31, 2005. Inclusion criteria included age 18+ years, continuously enrolled for minimum of 6 months prior and 18 months following treatment initiation, >1 diagnosis of hypertension, and no prescription claims for SPAA or added CCB or statin for 6 months prior. Exclusion criteria included >1 claim with missing or invalid days supplied, age 65+ years and not enrolled in Medicare Advantage, or history of prior CV events, cancer diagnosis, or chronic renal failure. The primary outcome measure was the rate of CV events (myocardial infarction, heart failure, angina, other ischemic heart disease, stroke, peripheral vascular disease, or revascularization procedure from 6 to 18 months following index date, analyzed at three levels: 1 all adherent vs. non-adherent patients, 2 SPAA vs. dual-pill patients (regardless of adherence level, and 3 adherent SPAA, adherent dual-pill, and non-adherent SPAA patients vs. non-adherent dual-pill patients. Results Of 1,537 SPAA patients, 56.5% were adherent at 6 months, compared with 21.4% of the 17,910 CCB/statin patients (p Conclusions Patients receiving SPAA rather than a 2-pill CCB/statin regimen are more likely to be adherent. In turn, adherence to CCB and statin medications is associated with lower risk of CV events in primary prevention patients.

  9. Development and Optimization of Gastro-Retentive Controlled-Release Tablet of Calcium-Disodium Edentate and its In Vivo Gamma Scintigraphic Evaluation.

    Science.gov (United States)

    Kumar, Neeraj; Soni, Sandeep; Singh, Thakuri; Kumar, Amit; Ahmad, Farhan Jalees; Bhatnagar, Aseem; Mittal, Gaurav

    2015-12-01

    Medical management of heavy metal toxicity, including radioactive ones, is a cause for concern because of their increased use in energy production, healthcare, and mining. Though chelating agents like EDTA and DTPA in parenteral form are available, no suitable oral formulation is there that can trap ingested heavy metal toxicants in the stomach itself, preventing their systemic absorption. The objective of the present study was to develop and optimize gastro-retentive controlled-release tablets of calcium-disodium edentate (Ca-Na2EDTA). Gastro-retentive tablet of Ca-Na2EDTA was prepared by direct compression method. Thirteen tablet formulations were designed using HPMC-K4M, sodium chloride, and carbopol-934 along with effervescing agents sodium bicarbonate and citric acid. Tablet swelling ability, in vitro buoyancy, and drug dissolution studies were conducted in 0.1 N HCl at 37 ± 0.5°C. Ca-Na2EDTA was radiolabeled with technetium-99m for scintigraphy-based in vivo evaluation. Formula F8 (Ca-Na2EDTA 200 mg, carbopol 100 mg, avicel 55 mg, citric acid 30 mg, NaHCO3 70 mg, NaCl 100 mg, and HPMC 95 mg) was found to be optimum in terms of excellent floating properties and sustained drug release. F8 fitted best for Korsmeyer-Peppas equation with an R (2) value of 0.993. Gamma scintigraphy in humans showed mean gastric retention period of 6 h. Stability studies carried out in accordance with ICH guidelines and analyzed at time intervals of 0, 1, 2, 4, and 6 months have indicated insignificant difference in tablet hardness, drug content, total floating duration, or matrix integrity of the optimized formulation. Gastro-retentive, controlled-release tablet of Ca-Na2EDTA was successfully developed using effervescent technique as a potential oral antidote for neutralizing ingested heavy metal toxicity.

  10. Lumbar interbody fusion with porous biphasic calcium phosphate enhanced by recombinant bone morphogenetic protein-2/silk fibroin sustained-released microsphere: an experimental study on sheep model.

    Science.gov (United States)

    Chen, Liang; Liu, Hai-Long; Gu, Yong; Feng, Yu; Yang, Hui-Lin

    2015-03-01

    Biphasic calcium phosphate (BCP) has been investigated extensively as a bone substitute nowadays. However, the bone formation capacity of BCP is limited owing to lack of osteoinduction. Silk fibroin (SF) has a structure similar to type I collagen, and could be developed to a microsphere for the sustained-release of rhBMP-2. In our previous report, bioactivity of BCP could be enhanced by rhBMP-2/SF microsphere (containing 0.5 µg rhBMP-2) in vitro. However, the bone regeneration performance of the composite in vivo was not investigated. Thus, the purpose of this study was to evaluate the efficacy of BCP/rhBMP-2/SF in a sheep lumbar fusion model. A BCP and rhBMP-2/SF microsphere was developed, and then was integrated into a BCP/rhBMP-2/SF composite. BCP, BCP/rhBMP-2 and BCP/rhBMP-2/SF were implanted randomly into the disc spaces of 30 sheep at the levels of L1/2, L3/4 and L5/6. After sacrificed, the fusion segments were evaluated by manual palpation, CT scan, biomechanical testing and histology at 3 and 6 months, respectively. The composite demonstrated a burst-release of rhBMP-2 (39.1 ± 2.8 %) on the initial 4 days and a sustained-release (accumulative 81.3 ± 4.9 %) for more than 28 days. The fusion rates, semi-quantitative CT scores, fusion stiffness in bending in all directions and histologic scores of BCP/rhBMP-2/SF were significantly greater than BCP and BCP/rhBMP-2 at each time point, respectively (P sheep using BCP constructs.

  11. Growth differentiation factor-15 promotes glutamate release in medial prefrontal cortex of mice through upregulation of T-type calcium channels

    Science.gov (United States)

    Liu, Dong-Dong; Lu, Jun-Mei; Zhao, Qian-Ru; Hu, Changlong; Mei, Yan-Ai

    2016-01-01

    Growth differentiation factor-15 (GDF-15) has been implicated in ischemic brain injury and synapse development, but its involvement in modulating neuronal excitability and synaptic transmission remain poorly understood. In this study, we investigated the effects of GDF-15 on non-evoked miniature excitatory post-synaptic currents (mEPSCs) and neurotransmitter release in the medial prefrontal cortex (mPFC) in mice. Incubation of mPFC slices with GDF-15 for 60 min significantly increased the frequency of mEPSCs without effect on their amplitude. GDF-15 also significantly elevated presynaptic glutamate release, as shown by HPLC. These effects were blocked by dual TGF-β type I receptor (TβRI) and TGF-β type II receptor (TβRII) antagonists, but not by a TβRI antagonist alone. Meanwhile, GDF-15 enhanced pERK level, and inhibition of MAPK/ERK activity attenuated the GDF-15-induced increases in mEPSC and glutamate release. Blocking T-type calcium channels reduced the GDF-15 induced up-regulation of synaptic transmission. Membrane-protein extraction and use of an intracellular protein-transport inhibitor showed that GDF-15 promoted CaV3.1 and CaV3.3 α-subunit expression by trafficking to the membrane. These results confirm previous findings in cerebellar granule neurons, in which GDF-15 induces its neurobiological effects via TβRII and activation of the ERK pathway, providing novel insights into the mechanism of GDF-15 function in cortical neurons. PMID:27353765

  12. Local inflammatory events induced by Bothrops atrox snake venom and the release of distinct classes of inflammatory mediators.

    Science.gov (United States)

    Moreira, Vanessa; Dos-Santos, Maria Cristina; Nascimento, Neide Galvão; Borges da Silva, Henrique; Fernandes, Cristina Maria; D'Império Lima, Maria Regina; Teixeira, Catarina

    2012-07-01

    Bothrops atrox is responsible for most accidents involving snakes in the Brazilian Amazon and its venom induces serious systemic and local effects. The local effects are not neutralized effectively by commercial antivenoms, resulting in serious sequelae in individuals bitten by this species. This study investigates the local inflammatory events induced in mice by B. atrox venom (BaV), such as vascular permeability, leukocyte influx and the release of important inflammatory mediators such as cytokines, eicosanoids and the chemokine CCL-2, at the injection site. The effect of BaV on cyclooxygenase (COX-1 and COX-2) expression was also investigated. The results showed that intraperitoneal (i.p.) injection of BaV promoted a rapid and significant increase in vascular permeability, which reached a peak 1 h after venom administration. Furthermore, BaV caused leukocyte infiltration into the peritoneal cavity between 1 and 8 h after i.p. injection, with mononuclear leukocytes (MNs) predominating in the first 4 h, and polymorphonuclear leukocytes (PMNs) in the last 4 h. Increased protein expression of COX-2, but not of COX-1, was detected in leukocytes recruited in the first and fourth hours after injection of BaV. The venom caused the release of eicosanoids PGD₂, PGE₂, TXA₂ and LTB₄, cytokines TNF-α, IL-6, IL-10 and IL-12p70, but not IFN-γ, and chemokine CCL-2 at different times. The results show that BaV is able to induce an early increase in vascular permeability and a leukocyte influx to the injection site consisting mainly of MNs initially and PMNs during the later stages. These phenomena are associated with the production of cytokines, the chemokine CCL-2 and eicosanoids derived from COX-1 and COX-2. PMID:22465491

  13. Critical role of intracellular RyR1 calcium release channels in skeletal muscle function and disease

    Directory of Open Access Journals (Sweden)

    Erick Omar Hernández-Ochoa

    2016-01-01

    Full Text Available The skeletal muscle Ca2+ release channel, also known as ryanodine receptor type 1 (RyR1, is the largest ion channel protein known and is crucial for effective skeletal muscle contractile activation. RyR1 function is controlled by Cav1.1, a voltage gated Ca2+ channel that works mainly as a voltage sensor for RyR1 activity during skeletal muscle contraction and is also fine-tuned by Ca2+, several intracellular compounds (e.g., ATP, and modulatory proteins (e.g., calmodulin. Dominant and recessive mutations in RyR1, as well as acquired channel alterations, are the underlying cause of various skeletal muscle diseases. The aim of this mini review is to summarize several current aspects of RyR1 function, structure, regulation, and to describe the most common diseases caused by hereditary or acquired RyR1 malfunction.

  14. Reactive calcium-phosphate-containing poly(ester-co-ether) methacrylate bone adhesives: setting, degradation and drug release considerations.

    Science.gov (United States)

    Zhao, Xin; Olsen, Irwin; Pratten, Jonathan; Knowles, Jonathan C; Young, Anne M

    2011-09-01

    This study has investigated novel bone adhesives consisting of fluid photo-polymerizable poly(lactide-co-propylene glycol-co-lactide)dimethacrylate (PGLA-DMA) mixed with systematically varying fillers of β-tricalcium phosphate (β-TCP) and monocalcium phosphate monohydrate (MCPM), for the delivery of an antibacterial drug chlorhexidine (CHX). All formulations were found to polymerize fully within 200 s after exposure to blue light. In addition, water sorption by the polymerized materials catalyzed varying filler conversion to dicalcium phosphate (DCP) (i.e. brushite and monetite). With greater DCP levels, faster degradation was observed. Moreover, increase in total filler content enhanced CHX release, associated with higher antibacterial activity. These findings thus suggest that such rapid-setting and degradable adhesives with controllable drug delivery property could have potential clinical value as bone adhesives with antibacterial activity.

  15. Lesion-specific coronary artery calcium quantification for predicting cardiac event with multiple instance support vector machines.

    Science.gov (United States)

    Liu, Qingshan; Qian, Zhen; Marvasty, Idean; Rinehart, Sarah; Voros, Szilard; Metaxas, Dimitris N

    2010-01-01

    Conventional whole-heart CAC quantification has been demonstrated to be insufficient in predicting coronary events, especially in accurately predicting near-term coronary events in high-risk adults. In this paper, we propose a lesion-specific CAC quantification framework to improve CAC's near-term predictive value in intermediate to high-risk populations with a novel multiple instance support vector machines (MISVM) approach. Our method works on data sets acquired with clinical imaging protocols on conventional CT scanners without modifying the CT hardware or updating the imaging protocol. The calcific lesions are quantified by geometric information, density, and some clinical measurements. A MISVM model is built to predict cardiac events, and moreover, to give a better insight of the characterization of vulnerable or culprit lesions in CAC. Experimental results on 31 patients showed significant improvement of the predictive value with the ROC analysis, the net reclassification improvement evaluation, and the leave-one-out validation against the conventional methods. PMID:20879266

  16. In vitro bone formation by human marrow cell culture on the surface of zinc-releasing calcium phosphate ceramics

    Energy Technology Data Exchange (ETDEWEB)

    Ikeuchi, M.; Noshi, T.; Horiuchi, K.; Yamamoto, K.; Sugimura, M. [Nara Medical Univ., Kashihara (Japan). Dept. of Oral and Maxillofacial Surgery; Dohi, Y. [Nara Medical Univ., Kashihara (Japan). Dept. of Public Health; Ohgushi, H. [Nara Medical Univ., Kashihara (Japan). Dept. of Orthopedics; Ito, A. [National Inst. for Advanced Interdisciplinary Research, MITI, Ibaraki (Japan)

    2001-07-01

    We examined the effect of zinc on the osteogenic differentiation of cultured human marrow cells on the surface of zinc-releasing TCP/HAP (Zn-TCP/HAP) ceramics in the shape of a disk. Three ml of human bone marrow harvested from the ilium was cultured in a medium containing 15% fetal bovine serum to reach confluent. After trypsinization, the cells were seeded at 20 x 10{sup 3} cells/16 mm {phi} on Falcon tissue wells with the ceramic disks (TCP/HAP containing 0, 0.32, 0.42, 0.63, 0.88 and 1.26 wt% Zn). After 2 weeks of subculture in the presence of {beta}-glycerophosphate, vitamin C phosphate, and dexamethasone (Dex), the cells were stained for alkaline phosphatase (ALP). The ALP stain was strengthened as zinc content of the disk increased. The data demonstrated that Zn-TCP/HAP influenced cell differentiation in human marrow cell culture and resulted in high osteoblastic activity. Furthermore, ALP activities of the cell layer significantly increased depending on zinc content of the disk in the presence of Dex. These results indicate that the surface of Zn-TCP/HAP stimulates osteogenic differentiation in human cultured marrow cells as well as in rat ones. Thus, Zn-TCP/HAP ceramics are expected to be useful materials for bone reconstructive surgery. (orig.)

  17. Calsequestrin (CASQ1) rescues function and structure of calcium release units in skeletal muscles of CASQ1-null mice.

    Science.gov (United States)

    Tomasi, Mirta; Canato, Marta; Paolini, Cecilia; Dainese, Marco; Reggiani, Carlo; Volpe, Pompeo; Protasi, Feliciano; Nori, Alessandra

    2012-02-01

    Amplitude of Ca(2+) transients, ultrastructure of Ca(2+) release units, and molecular composition of sarcoplasmic reticulum (SR) are altered in fast-twitch skeletal muscles of calsequestrin-1 (CASQ1)-null mice. To determine whether such changes are directly caused by CASQ1 ablation or are instead the result of adaptive mechanisms, here we assessed ability of CASQ1 in rescuing the null phenotype. In vivo reintroduction of CASQ1 was carried out by cDNA electro transfer in flexor digitorum brevis muscle of the mouse. Exogenous CASQ1 was found to be correctly targeted to the junctional SR (jSR), as judged by immunofluorescence and confocal microscopy; terminal cisternae (TC) lumen was filled with electron dense material and its width was significantly increased, as judged by electron microscopy; peak amplitude of Ca(2+) transients was significantly increased compared with null muscle fibers transfected only with green fluorescent protein (control); and finally, transfected fibers were able to sustain cytosolic Ca(2+) concentration during prolonged tetanic stimulation. Only the expression of TC proteins, such as calsequestrin 2, sarcalumenin, and triadin, was not rescued as judged by Western blot. Thus our results support the view that CASQ1 plays a key role in both Ca(2+) homeostasis and TC structure. PMID:22049211

  18. Zeolite-based hemostat QuikClot releases calcium into blood and promotes blood coagulation in vitro

    Institute of Scientific and Technical Information of China (English)

    Jing LI; Wei CAO; Xiao-xing LV; Li JIANG; Yue-jun LI; Wang-zhou LI; Shao-zong CHEN

    2013-01-01

    Aim:To examine the changes in electrolyte concentrations after addition of zeolite-based hemostat QuikClot in blood and the effects of zeolite on blood coagulation in vitro.Methods:Fresh blood was taken from healthy adult volunteers and sheep,and the electrolyte concentrations in blood were measured using a blood electrolyte analyzer.Zeolite Saline Solution (ZSS) was prepared by addition of 2 g zeolite to 0.9% NaCl solution (4,8,or 16 mL).The electrolytes in ZSS were measured using inductively coupled plasma atomic emission spectroscopy.The prothrombin time (PT) and activated partial thromboplastin time (APTT) of blood were measured using the test tube method.The activated clotting time (ACT) and clotting rate (CR) of blood were measured with Sonoclot Coagulation and Platelet Function Analyzer.Results:Addition of zeolite (50 and 100 mg) in 2 mL human blood significantly increased Ca2+ concentration,while Na+ and K+ concentrations were significantly decreased.Addition of zeolite (50 and 100 mg) in 0.9% NaCl solution (2 mL) caused similar changes in Ca2+ and Na+ concentrations.Si4+ (0.2434 g/L) and Al3+ (0.2575 g/L) were detected in ZSS (2 g/8 mL).Addition of ZSS in sheep blood shortened APTT in a concentration dependent manner,without changing PT.ZSS or aqueous solution of CaCl2 that contained Ca2+ concentration identical to that of ZSS significantly shortened ACT in human blood without significantly changing CR,and the effect of ZSS on ACT was not significantly different from that of CaCl2.Conclusion:Zeolite releases Ca2+ into blood,thus accelerating the intrinsic pathway of blood coagulation and shortening the clot formation time.

  19. Extent of use of immediate-release formulations of calcium channel blockers as antihypertensive monotherapy by primary care physicians: multicentric study from Bahrain.

    Directory of Open Access Journals (Sweden)

    Sequeira R

    2002-07-01

    Full Text Available BACKGROUND: The issue of cardiovascular safety of calcium channel blockers (CCBs has been widely debated in view of reflex increase in sympathetic activity induced by immediate release (IR / short acting formulations. It is generally agreed that such CCBs should not be used alone in the management of hypertension. AIMS: We have determined the extent to which primary care physicians prescribe CCBs as monotherapy, especially the immediate release formulations, in the management of uncomplicated hypertension and diabetic hypertension - with an emphasis upon the age of the patients. SETTING, DESIGN AND METHODS: A retrospective prescription-based study was carried out in seven out of 18 Health Centres in Bahrain. The study involved a registered population of 229,300 representing 46% of registered individuals, and 35 physicians representing 43% of all primary care physicians. The data was collected between November 1998 and January 1999 using chronic dispensing cards. RESULTS: In all categories CCBs were the third commonly prescribed antihypertensive as monotherapy, with a prescription rate of 11.1% in uncomplicated hypertension, 18% in diabetic hypertension and 20.1% in elderly patients above 65 years of age. Nifedipine formulations were the most extensively prescribed CCBs. Almost half of the CCB-treated patients were on IR-nifedipine, whereas IR-diltiazem and IR-verapamil, and amlodipine were infrequently prescribed. CONCLUSION: Prescription of IR-formulations of CCBs as monotherapy by primary care physicians does not conform with recommended guidelines. In view of concerns about the safety of such practice, measures to change the prescribing pattern are required.

  20. Application of the specular and diffuse reflection analysis for in vitro diagnostics of dental erosion: correlation with enamel softening, roughness, and calcium release

    Science.gov (United States)

    Rakhmatullina, Ekaterina; Bossen, Anke; Höschele, Christoph; Wang, Xiaojie; Beyeler, Barbara; Meier, Christoph; Lussi, Adrian

    2011-10-01

    We present assembly and application of an optical reflectometer for the analysis of dental erosion. The erosive procedure involved acid-induced softening and initial substance loss phases, which are considered to be difficult for visual diagnosis in a clinic. Change of the specular reflection signal showed the highest sensitivity for the detection of the early softening phase of erosion among tested methods. The exponential decrease of the specular reflection intensity with erosive duration was compared to the increase of enamel roughness. Surface roughness was measured by optical analysis, and the observed tendency was correlated with scanning electron microscopy images of eroded enamel. A high correlation between specular reflection intensity and measurement of enamel softening (r2 >= -0.86) as well as calcium release (r2 >= -0.86) was found during erosion progression. Measurement of diffuse reflection revealed higher tooth-to-tooth deviation in contrast to the analysis of specular reflection intensity and lower correlation with other applied methods (r2 = 0.42-0.48). The proposed optical method allows simple and fast surface analysis and could be used for further optimization and construction of the first noncontact and cost-effective diagnostic tool for early erosion assessment in vivo.

  1. Combination of calcium sulfate and simvastatin-controlled release microspheres enhances bone repair in critical-sized rat calvarial bone defects.

    Science.gov (United States)

    Fu, Yin-Chih; Wang, Yan-Hsiung; Chen, Chung-Hwan; Wang, Chih-Kuang; Wang, Gwo-Jaw; Ho, Mei-Ling

    2015-01-01

    Most allogenic bone graft substitutes have only osteoconductive properties. Developing new strategies to improve the osteoinductive activity of bone graft substitutes is both critical and practical for clinical application. Previously, we developed novel simvastatin-encapsulating poly(lactic-co-glycolic acid) microspheres (SIM/PLGA) that slowly release simvastatin and enhance fracture healing. In this study, we combined SIM/PLGA with a rapidly absorbable calcium sulfate (CS) bone substitute and studied the effect on bone healing in critical-sized calvarial bone defects in a rat model. The cytotoxicity and cytocompatibility of this combination was tested in vitro using lactate dehydrogenase leakage and a cell attachment assay, respectively. Combination treatment with SIM/PLGA and the CS bone substitute had no cytotoxic effect on bone marrow stem cells. Compared with the control, cell adhesion was substantially enhanced following combination treatment with SIM/PLGA and the CS bone substitute. In vivo, implantation of the combination bone substitute promoted healing of critical-sized calvarial bone defects in rats; furthermore, production of bone morphogenetic protein-2 and neovascularization were enhanced in the area of the defect. In summary, the combination of SIM/PLGA and a CS bone substitute has osteoconductive and osteoinductive properties, indicating that it could be used for regeneration of bone in the clinical setting. PMID:26664114

  2. Combination of calcium sulfate and simvastatin-controlled release microspheres enhances bone repair in critical-sized rat calvarial bone defects

    Directory of Open Access Journals (Sweden)

    Fu YC

    2015-12-01

    Full Text Available Yin-Chih Fu,1–4 Yan-Hsiung Wang,1,5 Chung-Hwan Chen,1,3,4 Chih-Kuang Wang,1,6 Gwo-Jaw Wang,1,3,4 Mei-Ling Ho1,3,7,8 1Orthopaedic Research Center, 2Graduate Institute of Medicine, 3Department of Orthopaedics, 4Department of Orthopaedics, College of Medicine, 5School of Dentistry, College of Dental Medicine, 6Department of Medicinal and Applied Chemistry, 7Department of Physiology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 8Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, TaiwanAbstract: Most allogenic bone graft substitutes have only osteoconductive properties. Developing new strategies to improve the osteoinductive activity of bone graft substitutes is both critical and practical for clinical application. Previously, we developed novel simvastatin-encapsulating poly(lactic-co-glycolic acid microspheres (SIM/PLGA that slowly release simvastatin and enhance fracture healing. In this study, we combined SIM/PLGA with a rapidly absorbable calcium sulfate (CS bone substitute and studied the effect on bone healing in critical-sized calvarial bone defects in a rat model. The cytotoxicity and cytocompatibility of this combination was tested in vitro using lactate dehydrogenase leakage and a cell attachment assay, respectively. Combination treatment with SIM/PLGA and the CS bone substitute had no cytotoxic effect on bone marrow stem cells. Compared with the control, cell adhesion was substantially enhanced following combination treatment with SIM/PLGA and the CS bone substitute. In vivo, implantation of the combination bone substitute promoted healing of critical-sized calvarial bone defects in rats; furthermore, production of bone morphogenetic protein-2 and neovascularization were enhanced in the area of the defect. In summary, the combination of SIM/PLGA and a CS bone substitute has osteoconductive and osteoinductive properties, indicating that it could be used for regeneration

  3. Prediction of Peak Hydrogen Concentrations for Deep Sludge Retrieval in Tanks AN-101 and AN-106 from Historical Data of Spontaneous Gas Release Events

    Energy Technology Data Exchange (ETDEWEB)

    Wells, Beric E.; Cooley, Scott K.; Meacham, Joseph E.

    2013-10-21

    Radioactive and chemical wastes from nuclear fuel processing are stored in large underground storage tanks at the Hanford Site. The Tank Operations Contractor is continuing a program of moving solid wastes from single-shell tanks (SSTs) to double-shell tanks (DSTs) and preparing for waste feed delivery (WFD). A new mechanism for a large spontaneous gas release event (GRE) in deep sludge sediments has been postulated. The creation of this potential new GRE hazard, deep sludge gas release events (DSGREs), is the retrieval of sludge waste into a single DST that results in a sediment depth greater than operating experience has demonstrated is safe. The Tank Operations Contractor program of moving solid wastes from SSTs to DSTs and preparing for WFD is being negatively impacted by this sediment depth limit.

  4. Calcium - urine

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003603.htm Calcium - urine To use the sharing features on this ... enable JavaScript. This test measures the amount of calcium in urine. All cells need calcium in order ...

  5. 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 ...

  6. Source Regions and Multiple Water Release Events in Valley Networks of the Libya Montes Region on Mars

    Science.gov (United States)

    Jaumann, R.; Reiss, D.; Sander, T.; Gwinner, K.; Hauber, E.; Hoffmann, H.; Roatsch, T.; Erkeling, G.; Friedrich, S.; Neukum, G.

    2007-07-01

    The morphology and topography of the source regions provide information about the origin of water on the surface. Furthermore, the analysis of internal valley structures in combination with crater counts allows reconstructing water release with time.

  7. Nicotinic acetylcholine receptor-mediated calcium signaling in the nervous system

    Institute of Scientific and Technical Information of China (English)

    Jian-xin SHEN; Jerrel L YAKEL

    2009-01-01

    Based on the composition of the five subunits forming functional neuronal nicotinic acetylcholine receptors (nAChRs), they are grouped into either heteromeric (comprising both α and β subunits) or homomeric (comprising only α subunits) recep-tors. The nAChRs are known to be differentially permeable to calcium ions, with the α7 nAChR subtype having one of the highest permeabilities to calcium. Calcium influx through nAChRs, particularly through the α-bungarotoxin-sensitive α7-containing nAChRs, is a very efficient way to raise cytoplasmic calcium levels. The activation of nAChRs can mediate three types of cytoplasmic calcium signals: (1) direct calcium influx through the nAChRs, (2) indirect calcium influx through voltage-dependent calcium channels (VDCCs) which are activated by the nAChR-mediated depolarization, and (3) calcium-induced calcium release (CICR) (triggered by the first two sources) from the endoplasmic reticulum (ER) through the ryanodine receptors and inositol (1,4,5)-triphosphate receptors (IP3Rs). Downstream signaling events mediated by nAChR-mediated calcium responses can be grouped into instantaneous effects (such as neurotransmitter release, which can occur in milliseconds after nAChR activation), short-term effects (such as the recovery of nAChR desensitization through cellular signaling cascades), and long-term effects (such as neuroprotection via gene expression). In addition, nAChR activity can be regulated by cytoplasmic calcium levels, suggesting a complex reciprocal relationship. Further advances in imaging techniques, animal models, and more potent and subtype-selective ligands for neuronal nAChRs would help in understand-ing the neuronal nAChR-mediated calcium signaling, and lead to the development of improved therapeutic treatments.

  8. Nitric oxide-dependent activation of CaMKII increases diastolic sarcoplasmic reticulum calcium release in cardiac myocytes in response to adrenergic stimulation.

    Directory of Open Access Journals (Sweden)

    Jerry Curran

    Full Text Available Spontaneous calcium waves in cardiac myocytes are caused by diastolic sarcoplasmic reticulum release (SR Ca(2+ leak through ryanodine receptors. Beta-adrenergic (β-AR tone is known to increase this leak through the activation of Ca-calmodulin-dependent protein kinase (CaMKII and the subsequent phosphorylation of the ryanodine receptor. When β-AR drive is chronic, as observed in heart failure, this CaMKII-dependent effect is exaggerated and becomes potentially arrhythmogenic. Recent evidence has indicated that CaMKII activation can be regulated by cellular oxidizing agents, such as reactive oxygen species. Here, we investigate how the cellular second messenger, nitric oxide, mediates CaMKII activity downstream of the adrenergic signaling cascade and promotes the generation of arrhythmogenic spontaneous Ca(2+ waves in intact cardiomyocytes. Both SCaWs and SR Ca(2+ leak were measured in intact rabbit and mouse ventricular myocytes loaded with the Ca-dependent fluorescent dye, fluo-4. CaMKII activity in vitro and immunoblotting for phosphorylated residues on CaMKII, nitric oxide synthase, and Akt were measured to confirm activity of these enzymes as part of the adrenergic cascade. We demonstrate that stimulation of the β-AR pathway by isoproterenol increased the CaMKII-dependent SR Ca(2+ leak. This increased leak was prevented by inhibition of nitric oxide synthase 1 but not nitric oxide synthase 3. In ventricular myocytes isolated from wild-type mice, isoproterenol stimulation also increased the CaMKII-dependent leak. Critically, in myocytes isolated from nitric oxide synthase 1 knock-out mice this effect is ablated. We show that isoproterenol stimulation leads to an increase in nitric oxide production, and nitric oxide alone is sufficient to activate CaMKII and increase SR Ca(2+ leak. Mechanistically, our data links Akt to nitric oxide synthase 1 activation downstream of β-AR stimulation. Collectively, this evidence supports the hypothesis

  9. Biomimetic coating of organic polymers with a protein-functionalized layer of calcium phosphate: the surface properties of the carrier influence neither the coating characteristics nor the incorporation mechanism or release kinetics of the protein.

    Science.gov (United States)

    Wu, Gang; Liu, Yuelian; Iizuka, Tateyuki; Hunziker, Ernst B

    2010-12-01

    Polymers that are used in clinical practice as bone-defect-filling materials possess many essential qualities, such as moldability, mechanical strength and biodegradability, but they are neither osteoconductive nor osteoinductive. Osteoconductivity can be conferred by coating the material with a layer of calcium phosphate, which can be rendered osteoinductive by functionalizing it with an osteogenic agent. We wished to ascertain whether the morphological and physicochemical characteristics of unfunctionalized and bovine-serum-albumin (BSA)-functionalized calcium-phosphate coatings were influenced by the surface properties of polymeric carriers. The release kinetics of the protein were also investigated. Two sponge-like materials (Helistat® and Polyactive®) and two fibrous ones (Ethisorb™ and poly[lactic-co-glycolic acid]) were tested. The coating characteristics were evaluated using state-of-the-art methodologies. The release kinetics of BSA were monitored spectrophotometrically. The characteristics of the amorphous and the crystalline phases of the coatings were not influenced by either the surface chemistry or the surface geometry of the underlying polymer. The mechanism whereby BSA was incorporated into the crystalline layer and the rate of release of the truly incorporated depot were likewise unaffected by the nature of the polymeric carrier. Our biomimetic coating technique could be applied to either spongy or fibrous bone-defect-filling organic polymers, with a view to rendering them osteoconductive and osteoinductive.

  10. Glutamate (mGluR-5 gene expression in brain regions of streptozotocin induced diabetic rats as a function of age: role in regulation of calcium release from the pancreatic islets in vitro

    Directory of Open Access Journals (Sweden)

    Paulose CS

    2009-11-01

    Full Text Available Abstract Metabotrophic glutamate receptors (mGluRs modulate cellular activities involved in the processes of differentiation and degeneration. In this study, we have analysed the expression pattern of group-I metabotropic glutamate receptor (mGlu-5 in cerebral cortex, corpus striatum, brainstem and hippocampus of streptozotocin induced and insulin treated diabetic rats (D+I as a function of age. Also, the functional role of glutamate receptors in intra cellular calcium release from the pancreatic islets was studied in vitro. The gene expression studies showed that mGlu-5 mRNA in the cerebral cortex increased siginficantly in 7 weeks old diabetic rats whereas decreased expression was observed in brainstem, corpus striatum and hippocampus when compared to control. 90 weeks old diabetic rats showed decreased expression in cerebral cortex, corpus striatum and hippocampus whereas in brainstem the expression increased significantly compared to their respective controls. In 7 weeks old D+I group, mGlu-5 mRNA expression was significantly decreased in cerebral cortex and corpus striatum whereas the expression increased significantly in brainstem and hippocampus. 90 weeks old D+I group showed an increased expression in cerebral cortex, while it was decreased significantly in corpus striatum, brainstem and hippocampus compared to their respective controls. In vitro studies showed that glutamate at lower concentration (10-7 M stimulated calcium release from the pancreatic islets. Our results suggest that mGlu-5 receptors have differential expression in brain regions of diabetes and D+I groups as a function of age. This will have clinical significance in management of degeneration in brain function and memory enhancement through glutamate receptors. Also, the regulatory role of glutamate receptors in calcium release has immense therapeutic application in insulin secretion and function.

  11. Localization of large conductance calcium-activated potassium channels and their effect on calcitonin gene-related peptide release in the rat trigemino-neuronal pathway

    DEFF Research Database (Denmark)

    Wulf-Johansson, H.; Amrutkar, D.V.; Hay-Schmidt, Anders;

    2010-01-01

    Large conductance calcium-activated potassium (BK(Ca)) channels are membrane proteins contributing to electrical propagation through neurons. Calcitonin gene-related peptide (CGRP) is a neuropeptide found in the trigeminovascular system (TGVS). Both BK(Ca) channels and CGRP are involved in migraine...

  12. Calcium in plant cells

    Directory of Open Access Journals (Sweden)

    V. V. Schwartau

    2014-04-01

    connect ion conformationally rearranged, thus passing the signal through the chain of intermediaries. The most important function of calcium is its participation in many cell signaling pathways. Channels, pumps, gene expression, synthesis of alkaloids, protective molecules, NO etc. respond to changes in [Ca2+]cyt, while transductors are represented by a number of proteins. The universality of calcium is evident in the study in connection with other signaling systems, such as NO, which is involved in the immune response and is able to control the feedback activity of protein activators channels, producing nitric oxide. Simulation of calcium responses can determine the impact of key level and their regulation, and also depends on the type of stimulus and the effector protein that specifically causes certain changes. Using spatiotemporal modeling, scientists showed that the key components for the formation of Ca2+ bursts are the internal and external surfaces of the nucleus membrane. The research was aimed at understanding of the mechanisms of influence of Ca2+-binding components on Ca2+ oscillations. The simulation suggests the existence of a calcium depot EPR with conjugated lumen of the nucleus which releases its contents to nucleoplasm. With these assumptions, the mathematical model was created and confirmed experimentally. It describes the oscillation of nuclear calcium in root hairs of Medicago truncatula at symbiotic relationship of plants and fungi (rhizobia. Calcium oscillations are present in symbiotic relationships of the cortical layer of plant root cells. Before penetration of bacteria into the cells, slow oscillations of Ca2+ are observed, but with their penetration into the cells the oscillation frequency increases. These processes take place by changing buffer characteristics of the cytoplasm caused by signals from microbes, such as Nod-factor available after penetration of bacteria through the cell wall. Thus, the basic known molecular mechanisms for

  13. Mast cells facilitate local VEGF release as an early event in the pathogenesis of postoperative peritoneal adhesions.

    LENUS (Irish Health Repository)

    Cahill, Ronan A

    2012-02-03

    BACKGROUND: Peritoneal injury sustained at laparotomy may evoke local inflammatory responses that result in adhesion formation. Peritoneal mast cells are likely to initiate this process, whereas vascular permeability\\/endothelial growth factor (VEGF) may facilitate the degree to which subsequent adhesion formation occurs. METHODS: Mast cell deficient mice (WBB6F1-\\/-), along with their mast cell sufficient counterparts (WBB6F1+\\/+), underwent a standardized adhesion-inducing operation (AIS) with subsequent sacrifice and adhesion assessment 14 days later in a blinded fashion. Additional CD-1 and WBB6F1+\\/+, and WBB6F1-\\/- mice were killed 2, 6, 12, and 24 hours after operation for measurement of VEGF by ELISA in systemic serum and peritoneal lavage fluid. Two further groups of CD-1 mice underwent AIS and received either a single perioperative dose of anti-VEGF monoclonal antibody (10 mug\\/mouse) or a similar volume of IgG isotypic antibody and adhesion formation 2 weeks later was evaluated. RESULTS: WBB6F1-\\/- mice had less adhesions then did their WBB6F1+\\/+ counterparts (median [interquartile range] adhesion score 3[3-3] vs 1.5[1-2] respectively; P < .003). Local VEGF release peaked 6 hours after AIS in both WBB6F1+\\/+ and CD-1 mice whereas levels remained at baseline in WBB6F1-\\/- mice. CD-1 mice treated with a single dose of anti-VEGF therapy during operation had less adhesions than controls (2[1.25-2] vs 3[2.25-3], P = .0002). CONCLUSIONS: Mast cells and VEGF are central to the formation of postoperative intra-abdominal adhesions with mast cells being responsible, either directly or indirectly, for VEGF release into the peritoneal cavity after operation. In tandem with the recent clinical success of anti-VEGF monoclonal antibodies in oncologic practice, our observations suggest an intriguing avenue for research and development of anti-adhesion strategy.

  14. 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.

  15. Release of transforming growth factor beta 1 and platelet derived growth factor type AB from canine platelet gels obtained by the tube method and activated with calcium salts

    Directory of Open Access Journals (Sweden)

    RF Silva

    2013-01-01

    Full Text Available The objectives of this study were: 1 to measure the concentrations of transforming growth factor beta 1 (TGF-β1 and platelet-derived growth factor type AB (PDGF-AB in plasma and platelet gel (PG activated with calcium salts (gluconate or chloride in dogs, and 2 to determine correlations between cell results and growth factors (GF concentrations. Blood samples were collected from fourteen Brazilian Fila dogs. EDTA was used to obtain whole blood and plasma while ACD-A solution was used to prepare platelet concentrates (PC. Calcium salts were added to PC to induce their gelification. Platelet and leukocyte count was performed before PC activation. The concentration of growth factors in PG supernatants and plasma was determined by ELISA. Statistically significant differences (P < 0.01 between platelet and leukocyte count were observed when comparing whole blood and PC. No statistically significant differences were found between the concentrations of TGF-β1 and PDGF-AB in PC and plasma according to the calcium salt used for the activation of PC. The TGF-β1 concentration was highly correlated with the number of platelets concentrated in the PC. This methodology was useful for producing PG with therapeutic potential for canine regenerative medicine.

  16. Decalcification of calcium polycarbophil in rats.

    Science.gov (United States)

    Yamada, T; Saito, T; Takahara, E; Nagata, O; Tamai, I; Tsuji, A

    1997-03-01

    The in vivo decalcification of calcium polycarbophil was examined. The decalcification ratio of [45Ca]calcium polycarbophil in the stomach after oral dosing to rats was more than 70% at each designated time and quite closely followed in the in vitro decalcification curve, indicating that the greater part of the calcium ion is released from calcium polycarbophil under normal gastric acidic conditions. The residual radioactivity in rat gastrointestine was nearly equal to that after oral administration of either [45Ca]calcium chloride + polycarbophil. The serum level of radioactivity was nearly equal to that after oral dosing of [45Ca]calcium lactate. These results indicate that the greater part of orally administered calcium polycarbophil released calcium ions to produce polycarbophil in vivo.

  17. Down the Rabbit Hole: toward appropriate discussion of methane release from gas hydrate systems during the Paleocene-Eocene thermal maximum and other past hyperthermal events

    Directory of Open Access Journals (Sweden)

    G. R. Dickens

    2011-08-01

    Full Text Available Enormous amounts of 13C-depleted carbon rapidly entered the exogenic carbon cycle during the onset of the Paleocene-Eocene thermal maximum (PETM, as attested to by a prominent negative carbon isotope (δ13C excursion and deep-sea carbonate dissolution. A widely cited explanation for this carbon input has been thermal dissociation of gas hydrate on continental slopes, followed by release of CH4 from the seafloor and its subsequent oxidation to CO2 in the ocean or atmosphere. Increasingly, papers have argued against this mechanism, but without fully considering existing ideas and available data. Moreover, other explanations have been presented as plausible alternatives, even though they conflict with geological observations, they raise major conceptual problems, or both. Methane release from gas hydrates remains a congruous explanation for the δ13C excursion across the PETM, although it requires an unconventional framework for global carbon and sulfur cycling, and it lacks proof. These issues are addressed here in the hope that they will prompt appropriate discussions regarding the extraordinary carbon injection at the start of the PETM and during other events in Earth's history.

  18. A large thermogenic-methane release event in the SW Barents Sea, during the Last Glacial Maximum. Indications from numerical modelling and seismic reflection data

    Science.gov (United States)

    Anka, Z.; Rodrigues, E.; di Primio, R.; Ostanin, I.; Stoddart, D.; Horsfield, B.

    2011-12-01

    The Barents Sea, located in the Norwegian Artic area, has undergone a series of tectonic, paleoceanographic and paleo-climatic events during the Cenozoic, which most likely have caused the redistribution and leakage of hydrocarbons accumulations (Ohm et al., 2008). (Dimakis et al., 1998). Present-day under-filled accumulations are known to have leaked in the past providing a source of hydrocarbons, mostly thermogenic methane. However, the timing, extent and driving factors for this event are largely unconstrained. We built a 3D basin model of the Hammerfest Basin in the SW Barents Sea, in order to quantify the masses of liquid and gaseous hydrocarbons generated, accumulated and eventually leaked from the reservoirs during the evolution of the basin. Particular emphasis was placed on analysing the fate of leaked volumes within the dynamics of Plio-Quaternary glacial cycles and formation or destabilization of gas hydrate deposits. The model was calibrated with maturity and temperature well data and reconstructs, with large degree of accuracy, the composition and volume of the hydrocarbons, particularly the gaseous phase present in the main reservoirs. Our results predict the development of overpressures in the reservoirs due to the ice loading of the basin during the glacial periods. Pressure fluctuations derived from cyclic loading-unloading during the glacial-interglacial periods reached up to 5 MPa. The under-filled nature of the present-day accumulations would result from leakage events during the episodes of glacial retreat, in the transition from glacial to interglacial periods. Considerations of the gas hydrate stability conditions in the basin during the time span between 1.00Ma and ≈11,500 years indicate that the leaking thermogenic methane was probably trapped as gas hydrate deposits during the glacial events and then released at once upon hydrate destabilisation during the Last Glacial Maximun (LGM). These results are supported by the presence of km

  19. Dihydropyridine-sensitive calcium channel activity related to prolactin, growth hormone, and luteinizing hormone release from anterior pituitary cells in culture: interactions with somatostatin, dopamine, and estrogens

    International Nuclear Information System (INIS)

    In the present work, we determined the activity of voltage-dependent dihydropyridine (DHP)-sensitive Ca2+ channels related to PRL, GH, and LH secretion in primary cultures of pituitary cells from male or female rats. We investigated their modulation by 17 beta-estradiol (E2) and their involvement in dopamine (DA) and somatostatin (SRIF) inhibition of PRL and GH release. BAY-K-8644 (BAYK), a DHP agonist which increases the opening time of already activated channels, stimulated PRL and GH secretion in a dose-dependent manner. The effect was more pronounced on PRL than on GH release. BAYK-evoked hormone secretion was further amplified by simultaneous application of K+ (30 or 56 mM) to the cell cultures; in parallel, BAYK-induced 45Ca uptake by the cells was potentiated in the presence of depolarizing stimuli. In contrast, BAYK was unable to stimulate LH secretion from male pituitary cells, but it potentiated LHRH- as well as K+-induced LH release; it had only a weak effect on LH secretion from female cell cultures. Basal and BAYK-induced pituitary hormone release were blocked by the Ca2+ channel antagonist nitrendipine. Under no condition did BAYK affect the hydrolysis of phosphoinositides or cAMP formation. Pretreatment of female pituitary cell cultures with E2 (10(-9) M) for 72 h enhanced LH and PRL responses to BAYK, but was ineffective on GH secretion. DA (10(-7) M) inhibited basal and BAYK-induced PRL release from male or female pituitary cells treated or not treated with E2 (10(-9) M). SRIF (10(-9) and 10(-8) M) reversed BAYK-evoked GH release to the same extent in cell cultures derived from male or female animals. It was ineffective on BAYK-induced PRL secretion in the absence of E2, but antagonized it after E2 pretreatment. The effect was dependent upon the time of steroid treatment and was specific, since 17 alpha-estradiol was inactive

  20. [Calcium carbide of different crystal formation synthesized by calcium carbide residue].

    Science.gov (United States)

    Lu, Zhong-yuan; Kang, Ming; Jiang, Cai-rong; Tu, Ming-jing

    2006-04-01

    To recycle calcium carbide residue effectively, calcium carbide of different crystal form, including global aragonite, calcite and acicular calcium carbide was synthesized. Both the influence of pretreatment in the purity of calcium carbide, and the influence of temperatures of carbonization reaction, release velocity of carbon dioxide in the apparition of calcium carbide of different crystal form were studied with DTA-TG and SEM. The result shows that calcium carbide residue can take place chemistry reaction with ammonia chlorinate straight. Under the condition that pH was above 7, the purity of calcium carbide was above 97%, and the whiteness was above 98. Once provided the different temperatures of carbonization reaction and the proper release velocity of carbon dioxide, global aragonite, calcite and acicular calcium carbide were obtained.

  1. Calcium phosphate bone cement containing ABK and PLLA. Sustained release of ABK, the BMD of the femur in rats, and histological examination

    Energy Technology Data Exchange (ETDEWEB)

    Kusaka, T.; Tanaka, A.; Sasaki, S.; Takano, I.; Tahara, Y.; Ishii, Y. [Kyorin Univ., Tokyo (Japan). Dept. of Orhtopaedic Surgery

    2001-07-01

    Bone cement was prepared by mixing CPC95 (Mitsubishi Material Co., Ltd.), ABK, and PLLA at a ratio of 14 : 1 : 2. In vitro, Antibiotic sustained release tests were performed by the total amount exchange method. In animal experiments, the bone cement was infused into the right femur of 18-month-old female SD rats. After 1, 2, 4, or 6 months, the BMD was determined by DXA in the bilateral femoral bones. In addition, hard tissue specimens were prepared, and the state of bone formation was observed. The release of the antibiotic was 1.73 {mu}g/ml until 18 days after administration, maintaining a concentration over the MIC80 for MRSA. In the animal experiments, the BMD significantly increased after 2 - 4 months. In the hard tissue specimens, direct binding on the bone-cement interface and bone formation in the cement were observed after 1 month. (orig.)

  2. Naringin administration inhibits platelet aggregation and release by reducing blood cholesterol levels and the cytosolic free calcium concentration in hyperlipidemic rabbits

    OpenAIRE

    Xiao, Yang; LI, LAI-LAI; Guo, Jing-Jing; XU, WEN-PING; Wang, Yan-Yan; Wang, Yi

    2014-01-01

    This study investigated the effects of naringin on platelet aggregation and release in hyperlipidemic rabbits, and the underlying mechanisms. The safety of naringin was also investigated. The rabbits were orally administered 60, 30 or 15 mg/kg of naringin once a day for 14 days after being fed a high fat/cholesterol diet for four weeks. Following the two weeks of drug administration, the degree of platelet aggregation induced by arachidonic acid, adenosine diphosphate and collagen was signifi...

  3. Heliocentric Distance of Coronal Mass Ejections at the Time of Energetic Particle Release: Revisiting the Ground Level Enhancement Events of Solar Cycle 23

    Science.gov (United States)

    Gopalswamy, Natchimuthuk

    2011-01-01

    Using the kinematics of coronal mass ejections (CMEs), onset time of soft X-ray flares, and the finite size of the pre-eruption CME structure, we derive the heliocentric distane at which the energetic particles during the ground level enhancement (GLE) events of Solar Cycle 23. We find that the GLE particles are released when the CMEs reach an average heliocentric distance of approx.3.25 solar radii (Rs). From this we infer that the shocks accelerating the particles are located at similar heights. Type II radio burst observations indicate that the CMEs are at much lower distances (average approx.1.4 Rs) when the CME-driven shock first forms. The shock seems to travel approx.1.8 Rs over a period of approox.30 min on the average before releasing the GLE particles. In deriving these results, we made three assumptions that have observational support: (i) the CME lift off occurs from an initial distance of about 1.25 Rs; (ii) the flare onset and CME onset are one and the same because these are two different manifestations of the same eruption; and (iii) the CME has positive acceleration from the onset to the first appearance in the coronagraphic field of view (2.5 to 6 Rs). Observations of coronal cavities in eclipse pictures and in coronagraphic images justify the assumption (i). The close relationship between the flare reconnection magnetic flux and the azimuthal flux of interplanetary magnetic clouds justify assumption (ii) consistent with the standard model (CSHKP) of solar eruption. Coronagraphic observations made close to the solar surface indicate a large positive acceleration of CMEs to a heliocentric distance of approx.3 Rs before they start slowing down due to the drag force. The inferred acceleration (approx.1.5 km/s/s) is consistent with reported values in the literature.

  4. The potential for buoyant displacement gas release events in Tank 241-SY-102 after waste transfer from Tank 241-SY-101

    International Nuclear Information System (INIS)

    Tank 241-SY-101 (SY-101) is a double-shell, radioactive waste storage tank with waste that, before the recent transfer and water back-dilution operations, was capable of retaining gas and producing buoyant displacement (BD) gas release events (GREs). Some BD GREs caused gas concentrations in the tank headspace to exceed the lower flammability limit (LFL). A BD GRE occurs when a portion of the nonconvective layer retains enough gas to become buoyant, rises to the waste surface, breaks up, and releases some of its stored gas. The installation of a mixer pump in 1993 successfully mitigated gas retention in the settled solids layer in SY-101 and has since prevented BD GREs. However, operation of the mixer pump over the years caused gas retention in the floating crust layer and a corresponding accelerated waste level growth. The accelerating crust growth trend observed in 1997--98 led to initiation of sequences of waste removal and water back-dilutions in December 1999. Waste is removed from the mixed slurry layer in Tank SY-101 and transferred into Tank 241-Sy-102 (SY-102). Water is then added back to dissolve soluble solids that retain gas. The initial transfer of 89,500 gallons of SY-101 waste, diluted in-line at 0.94:1 by volume with water, to SY-102 was conducted in December 1999. The second transfer of 230,000 gallons of original SY-101 waste, diluted approximately 0.9:1, was completed in January 2000, and the third transfer of 205,500 gallons of original SY-101 waste diluted at 0.9:1 was completed in March 2000

  5. JTT-305, an orally active calcium-sensing receptor antagonist, stimulates transient parathyroid hormone release and bone formation in ovariectomized rats.

    Science.gov (United States)

    Kimura, Shuichi; Nakagawa, Takashi; Matsuo, Yushi; Ishida, Yuji; Okamoto, Yoshihisa; Hayashi, Mikio

    2011-10-01

    Intermittent administration of parathyroid hormone (PTH) has a potent anabolic effect on bone in humans and animals. Calcium-sensing receptor (CaSR) antagonists stimulate endogenous PTH secretion through CaSR on the surface of parathyroid cells and thereby may be anabolic agents for osteoporosis. JTT-305 is a potent oral short-acting CaSR antagonist and transiently stimulates endogenous PTH secretion. The objective of the present study was to investigate the effects of JTT-305 on PTH secretion and bone in ovariectomized rats. Female rats, immediately after ovariectomy (OVX), were orally administered vehicle or JTT-305 (0.3, 1, or 3 mg/kg) for 12 weeks. The serum PTH concentrations were transiently elevated with increasing doses of JTT-305. In the proximal tibia, JTT-305 prevented OVX-induced decreases in both the cancellous and total bone mineral density (BMD) except for the 0.3mg/kg dose. At the 3mg/kg dose, JTT-305 increased the mineralizing surface and bone formation rate in histomorphometry. The efficacy of JTT-305 at the 3mg/kg dose on the BMD corresponded to that of exogenous rat PTH1-84 injection at doses between 3 and 10 μg/kg. In conclusion, JTT-305 stimulated endogenous transient PTH secretion and bone formation, and consequently prevented bone loss in OVX rats. These results suggest that JTT-305 is orally active and has the potential to be an anabolic agent for the treatment of osteoporosis.

  6. Mechanism of store-operated calcium entry

    Indian Academy of Sciences (India)

    Devkanya Dutta

    2000-12-01

    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 store-operated calcium entry or capacitative calcium entry. Capacitative calcium current plays a key role in replenishing calcium stores and activating various physiological processes. Despite considerable efforts, very little is known about the molecular nature of the capacitative channel and the signalling pathway that activates it. This review summarizes our current knowledge about store operated calcium entry and suggests possible hypotheses for its mode of activation.

  7. Clinic Research of Calcium Sulphate Mixed with Vancomycin Delayed Released Antibiotics in the Human Body%载万古霉素硫酸钙在人体内缓释药物的临床研究#

    Institute of Scientific and Technical Information of China (English)

    张展; 张春; 张晓文; 郭峭峰; 沈立锋

    2015-01-01

    目的:探讨载万古霉素人工骨在人体内局部缓释抗生素的规律。方法:将医用硫酸钙人工骨与万古霉素混合植入创伤性骨髓炎患者体内,测量病灶内局部的抗生素浓度、每日释药量、释药百分率,同时记录上述指标何时达到高峰,以及持续维持有效浓度时间。测量患者血液中万古霉素的浓度,以及肝功能检查,进行安全性评估。并对病灶植骨处术后X检查,观察将硫酸钙人工骨显影吸收消失过程。结果:载万古霉素人工骨在人体内局部缓释出的万古霉素浓度大大超过最低抑菌浓度;而血药浓度低,肝肾功能正常;硫酸钙人工骨影在各组织中吸收时间各不相同。结论:载万古霉素硫酸钙人工骨病灶局部可以释放高浓度万古霉素,而全身浓度低,安全性高,又有骨引导作用。其在人体内的药物缓释规律,完全符合治疗骨髓炎的要求。%Objective: To discuss the law of calcium sulphate mixed with vancomycin delayed released antibiotics in the human body. Methods:We implant calcium sulphate mixed with vancomycin in the osteomyelitic human body , then measure antibiotic concentration in focus,the amount of antibiotics in focus,the percentage of antibiotics released in focus, and when these index achieve peak, how long effective antibiotic concentration can persist. The concentration of vancomycin in patient’s blood and liver function, renal function are measured to evaluate the security of osteoset mixed with vancomycin. Osteoset implanted in focus is examined with X-ray, to observe how osteoset absorbs in focus.Results:Vancomycin concentration in focus exceeds MIC, blood concentration is low; liver and renal function of patients are normal. The absorption time of calcium sulphate is different in different organization. Conclusion:Osteoset mixed with vancomycin could release high concentration of vancomycin in focus, and low concentration of

  8. Quantification of coronary artery calcium in nongated CT to predict cardiovascular events in male lung cancer screening participants : Results of the NELSON study

    NARCIS (Netherlands)

    Takx, Richard A. P.; Isgum, Ivana; Willemink, Martin J.; van der Graaf, Yolanda; de Koning, Harry J.; Vliegenthart, Rozemarijn; Oudkerk, Matthijs; Leiner, Tim; de Jong, Pim A.

    2015-01-01

    Objective: To evaluate the incremental prognostic value of the number and maximum volume of coronary artery calcifications over modified Agatston score strata, age, pack-years, and smoking status for predicting cardiovascular events. Methods: A total of 3559 male current and former smokers received

  9. The effect of dimethylsulfoxide on the calcium paradox.

    OpenAIRE

    Ruigrok, T. J.; Moes, D.; Slade, A.M.; Nayler, W. G.

    1981-01-01

    Reperfusion of isolated rat hearts with calcium-containing solution after a short period of calcium-free perfusion results in irreversible cell damage (calcium paradox). Experiments were undertaken to study the effect of dimethylsulfoxide (DMSO) on the occurrence of the calcium paradox in rat heart muscle. DMSO (1.4 mol/l) was added to the calcium-free or the reperfusion medium. Cell damage was quantitated in terms of creatine kinase (CK) release, cardiac electrogram (CEG) changes, and ultras...

  10. Cardiac calcium release channel (ryanodine receptor) in control and cardiomyopathic human hearts: mRNA and protein contents are differentially regulated.

    Science.gov (United States)

    Sainte Beuve, C; Allen, P D; Dambrin, G; Rannou, F; Marty, I; Trouvé, P; Bors, V; Pavie, A; Gandgjbakch, I; Charlemagne, D

    1997-04-01

    Abnormal intracellular calcium handling in cardiomyopathic human hearts has been associated with an impaired function of the sarcoplasmic reticulum, but previous reports on the gene expression of the ryanodine receptors (Ry2) are contradictory. We measured the mRNA levels, the protein levels and the number of high affinity [3H]ryanodine binding sites in the left ventricle of non-failing (n = 9) and failing human hearts [idiopathic dilated (IDCM n = 16), ischemic (ICM n = 7) or mixed (MCM n = 8) cardiomyopathies]. Ry2 mRNA levels were significantly reduced in IDCM (-30%) and unchanged in MCM and ICM and Ry2 protein levels were similar. In contrast, we observed a two-fold increase in the number of high affinity Ry2 (B(max) = 0.43 +/- 0.11 v 0.22 +/- 0.13 pmol/mg protein, respectively; P<0.01) and an unchanged K(d). Furthermore, levels of myosin heavy chain mRNA and protein per g of tissue were similar in failing and non-failing hearts, suggesting that the observed differences in Ry2 are not caused by the increase in fibrosis in failing heart. Therefore, the dissociation between the two-fold increase in the number of high affinity ryanodine receptors observed in all failing hearts and the slightly decreased mRNA level or unchanged protein level suggests that the ryanodine binding properties are affected in failing myocardium and that such modifications rather than a change in gene expression alter the channel activity and could contribute to abnormalities in intracellular Ca2+ handling. PMID:9160875

  11. Combinatorial chemopreventive effect of butyric acid, nicotinamide and calcium glucarate against the 7,12-dimethylbenz(a)anthracene induced mouse skin tumorigenesis attained by enhancing the induction of intrinsic apoptotic events.

    Science.gov (United States)

    Tiwari, Prakash; Sahay, Satya; Pandey, Manuraj; Qadri, Syed S Y H; Gupta, Krishna P

    2015-01-25

    We explored the basis of the combinatorial chemopreventive effect of butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG) on mouse skin exposed to 7,12-dimethylbenz(a)anthracene (DMBA). We studied the effects of topical application of DMBA in the presence or absence of BA, NA and CAG on the regulators of apoptosis. DMBA treatment suppressed Bax, Bax/Bcl-2 ratio, release of cyt c, Apaf1, caspase-9, -3 mediated apoptosis. Downregulation of p21 and upregulation of Bcl-2, mut p53 were also observed in only DMBA treated mice. Simultaneous application of BA, NA and CAG induced a mitochondria-mediated apoptosis, characterized by a rise in the Bax, Bax/Bcl-2 ratio, release of cyt c, upregulation of Apaf1 with down-stream activation of caspase-9, -3. Furthermore treatment with BA, NA and CAG demonstrated an upregulation of p21 and downregulation of Bcl-2, mut p53. But this effect was enhanced in the presence of all the three compounds together in combination. Chemoprevention by a combination of BA, NA and CAG by inducing the apoptosis, the natural cell death, suggest the importance of the potential combinational strategies capable of preventing skin tumor development.

  12. Combinatorial chemopreventive effect of butyric acid, nicotinamide and calcium glucarate against the 7,12-dimethylbenz(a)anthracene induced mouse skin tumorigenesis attained by enhancing the induction of intrinsic apoptotic events.

    Science.gov (United States)

    Tiwari, Prakash; Sahay, Satya; Pandey, Manuraj; Qadri, Syed S Y H; Gupta, Krishna P

    2015-01-25

    We explored the basis of the combinatorial chemopreventive effect of butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG) on mouse skin exposed to 7,12-dimethylbenz(a)anthracene (DMBA). We studied the effects of topical application of DMBA in the presence or absence of BA, NA and CAG on the regulators of apoptosis. DMBA treatment suppressed Bax, Bax/Bcl-2 ratio, release of cyt c, Apaf1, caspase-9, -3 mediated apoptosis. Downregulation of p21 and upregulation of Bcl-2, mut p53 were also observed in only DMBA treated mice. Simultaneous application of BA, NA and CAG induced a mitochondria-mediated apoptosis, characterized by a rise in the Bax, Bax/Bcl-2 ratio, release of cyt c, upregulation of Apaf1 with down-stream activation of caspase-9, -3. Furthermore treatment with BA, NA and CAG demonstrated an upregulation of p21 and downregulation of Bcl-2, mut p53. But this effect was enhanced in the presence of all the three compounds together in combination. Chemoprevention by a combination of BA, NA and CAG by inducing the apoptosis, the natural cell death, suggest the importance of the potential combinational strategies capable of preventing skin tumor development. PMID:25478867

  13. Synaptotagmin-7 is an asynchronous calcium sensor for synaptic transmission in neurons expressing SNAP-23.

    Directory of Open Access Journals (Sweden)

    Jens P Weber

    Full Text Available Synchronization of neurotransmitter release with the presynaptic action potential is essential for maintaining fidelity of information transfer in the central nervous system. However, synchronous release is frequently accompanied by an asynchronous release component that builds up during repetitive stimulation, and can even play a dominant role in some synapses. Here, we show that substitution of SNAP-23 for SNAP-25 in mouse autaptic glutamatergic hippocampal neurons results in asynchronous release and a higher frequency of spontaneous release events (mEPSCs. Use of neurons from double-knock-out (SNAP-25, synaptotagmin-7 mice in combination with viral transduction showed that SNAP-23-driven release is triggered by endogenous synaptotagmin-7. In the absence of synaptotagmin-7 release became even more asynchronous, and the spontaneous release rate increased even more, indicating that synaptotagmin-7 acts to synchronize release and suppress spontaneous release. However, compared to synaptotagmin-1, synaptotagmin-7 is a both leaky and asynchronous calcium sensor. In the presence of SNAP-25, consequences of the elimination of synaptotagmin-7 were small or absent, indicating that the protein pairs SNAP-25/synaptotagmin-1 and SNAP-23/synaptotagmin-7 might act as mutually exclusive calcium sensors. Expression of fusion proteins between pHluorin (pH-sensitive GFP and synaptotagmin-1 or -7 showed that vesicles that fuse using the SNAP-23/synaptotagmin-7 combination contained synaptotagmin-1, while synaptotagmin-7 barely displayed activity-dependent trafficking between vesicle and plasma membrane, implying that it acts as a plasma membrane calcium sensor. Overall, these findings support the idea of alternative syt∶SNARE combinations driving release with different kinetics and fidelity.

  14. Calcium Carbonate

    Science.gov (United States)

    ... before being swallowed; do not swallow them whole. Drink a full glass of water after taking either the regular or chewable tablets or capsules. Some liquid forms of calcium carbonate must be shaken well before use.Do not ...

  15. Calcium Calculator

    Science.gov (United States)

    ... Latvia - Lebanon - Libya - Lithuania - Luxembourg - Macedonia, Republic of - Malaysia - Malta - Mexico - Moldova - Morocco - Netherlands - New Zealand - Nigeria - ... and Statistics Popular content Calcium content of common foods What is Osteoporosis? The Board Introduction to Bone ...

  16. 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

  17. Cardiac sarcoplasmic reticulum calcium leak: basis and roles in cardiac dysfunction.

    Science.gov (United States)

    Bers, Donald M

    2014-01-01

    Synchronized SR calcium (Ca) release is critical to normal cardiac myocyte excitation-contraction coupling, and ideally this release shuts off completely between heartbeats. However, other SR Ca release events are referred to collectively as SR Ca leak (which includes Ca sparks and waves as well as smaller events not detectable as Ca sparks). Much, but not all, of the SR Ca leak occurs via ryanodine receptors and can be exacerbated in pathological states such as heart failure. The extent of SR Ca leak is important because it can (a) reduce SR Ca available for release, causing systolic dysfunction; (b) elevate diastolic [Ca]i, contributing to diastolic dysfunction; (c) cause triggered arrhythmias; and (d) be energetically costly because of extra ATP used to repump Ca. This review addresses quantitative aspects and manifestations of SR Ca leak and its measurement, and how leak is modulated by Ca, associated proteins, and posttranslational modifications in health and disease. PMID:24245942

  18. L-glutamine alteration of gene expression, not of polyphosphate and calcium metabolism, is a key event in arresting fungal sporulation.

    Science.gov (United States)

    LéJohn, H B

    1983-05-01

    Vegetatively growing cells of the coenocytic freshwater mould Achlya developed asexual sporangia and sporulated within 6 h of postransfer to a nutrient-free (starvation) medium. Sporangial development was arrested by the addition of L-glutamine to starving cells. During starvation (minus glutamine), three polyphosphate substances accumulated intracellularly, ATP was rapidly depleted, and a protein of molecular weight 42 000 (presumed to be actin) was actively synthesized, whereas synthesis of the most abundant detergent-soluble protein of molecular weight 83 000 (p83) ceased. In the presence of glutamine, starving cells used up the polyphosphates faster than they were formed. ATP depletion was delayed, cell calcium (Ca) exited rapidly, and synthesis of actin diminished while p83 synthesis continued unabated. Several pyrimidine analogues, including 5-diazouracil (which inhibited pyridimide nucleotide biosynthesis), and inorganic phosphate prevented Ca exit from glutamine-supplemented starving cells. The pyrimidine analogues delayed but did not inhibit sporangial development; however, they did not overcome glutamine suppression of sporangial development. Vegetatively growing and starving cells displayed significantly different protein synthesis patterns (monitored by polyacrylamide gel electrophoresis) but, when glutamine was added, it changed the protein synthesis pattern of starving cells to a form typical of vegetatively growing cells. Glutamine withdrawal reversed the effect and the cells differentiated. Pyrimidine analogues and inorganic phosphate did not alter the protein synthesis patterns of starving cells in the presence and absence of glutamine. The conclusion is that glutamine inhibition of sporangial development may be linked to its ability to subvert starving cell metabolism by making it vegetative like.

  19. Butyrate increases intracellular calcium levels and enhances growth hormone release from rat anterior pituitary cells via the G-protein-coupled receptors GPR41 and 43.

    Directory of Open Access Journals (Sweden)

    Maria Consolata Miletta

    Full Text Available Butyrate is a short-chain fatty acid (SCFA closely related to the ketone body ß-hydroxybutyrate (BHB, which is considered to be the major energy substrate during prolonged exercise or starvation. During fasting, serum growth hormone (GH rises concomitantly with the accumulation of BHB and butyrate. Interactions between GH, ketone bodies and SCFA during the metabolic adaptation to fasting have been poorly investigated to date. In this study, we examined the effect of butyrate, an endogenous agonist for the two G-protein-coupled receptors (GPCR, GPR41 and 43, on non-stimulated and GH-releasing hormone (GHRH-stimulated hGH secretion. Furthermore, we investigated the potential role of GPR41 and 43 on the generation of butyrate-induced intracellular Ca2+ signal and its ultimate impact on hGH secretion. To study this, wt-hGH was transfected into a rat pituitary tumour cell line stably expressing the human GHRH receptor. Treatment with butyrate promoted hGH synthesis and improved basal and GHRH-induced hGH-secretion. By acting through GPR41 and 43, butyrate enhanced intracellular free cytosolic Ca2+. Gene-specific silencing of these receptors led to a partial inhibition of the butyrate-induced intracellular Ca2+ rise resulting in a decrease of hGH secretion. This study suggests that butyrate is a metabolic intermediary, which contributes to the secretion and, therefore, to the metabolic actions of GH during fasting.

  20. [An experimental study on a slow-release complex with rifampicin-polylactic-co-glycolic acid-calcium 
phosphate cement].

    Science.gov (United States)

    Wu, Jianhuang; Ding, Zhou; Lei, Qing; Li, Miao; Liang, Yan; Lu, Tao

    2016-09-28

    目的:制备利福平(rifampicin,RFP)-聚乳酸-羟基乙酸(polylactic-co-glycolic acid,PLGA)-磷酸钙骨水泥(calcium phosphate cement,CPC)缓释复合体(RFP-PLGA-CPC复合体),并研究其理化性质及体外释药性能。方法:采用乳化-溶剂挥发法制备RFP-PLGA缓释微球。实验分为CPC组、包埋了RFP的CPC组(RFP-CPC组)、载有RFP的PLGA缓释微球与自固化CPC复合体组(RFP-PLGA-CPC复合体组)。测定3组材料的凝固时间﹑孔隙率。通过体外药物释放实验观察释药前后的抗压强度、断面形态的变化以及体外释药情况。结果:CPC组的凝固时间最短,RFP-PLGA-CPC复合体组的凝固时间最长。CPC组的孔隙率同RFP-CPC组比较,差异有统计学意义(P<0.05);CPC组和RFP-CPC组的孔隙率与RFP-PLGA-CPC复合体组比较,差异均有统计学意义(均P<0.01)。RFP-PLGA-CPC复合体组的抗压强度与CPC组比较,差异有统计学意义(P<0.01);而RFP-CPC组和CPC组之间的抗压强度随着时间的变化逐渐表现出显著性差异(3 d: P<0.05;30和60 d:P<0.01)。CPC组在降解过程中的抗压强度的变化不大。PLGA微球的大小均一,粒径基本在100~150 μm之间,微球的形态呈现出球体或是类球体,微球的表面圆润光滑,无杂质附着; CPC组的断面空隙在浸泡3 d直至60 d都没有明显变化;而RFP-CPC组的微结构变化亦不大,其断面均是小的微粒形成的;RFP-PLGA-CPC复合体组断面的孔隙明显增多,一直到60 d时PLGA微球逐渐消失,剩下空洞。RFP-PLGA-CPC复合体组无明显短时间内药物大量释放现象,60 d累计释药率达到近95%,将该复合体释药行为进行线性拟合,发现药物以恒速进行局部释放,符合零级动力学方程F=0.168×t。结论:RFP-PLGA-CPC复合体孔隙率显著高于CPC,能够持续缓慢释放有效抗结核药物,并能较长时间维持一定的力学强度。.

  1. THERMAL DEGRADATION AND FLAME RETARDANCY OF CALCIUM ALGINATE FIBERS

    Institute of Scientific and Technical Information of China (English)

    Qing-shan Kong; Bing-bing Wang; Quan Ji; Yan-zhi Xia; Zhao-xia Guo; Jian Yu

    2009-01-01

    Calcium alginate fibers were prepared by wet spinning of sodium alginate into a coagulating bath containing calcium chloride. The thermal degradation and flame retardancy of calcium alginate fibers were investigated with thermal gravimetry (TG), X-ray diffraction (XRD), limiting oxygen index (LOI) and cone calorimeter (CONE). The results show that calcium alginate fibers are inherently flame retardant with a LOI value of 34, and the heat release rate (HRR), total heat release (THR), CO and CO_2 concentrations during combustion are much lower compared with those of viscose fibers. Calcium carbonate and calcium oxide were formed during thermal degradation of calcium alginate fibers at different temperatures. The shape of calcium alginate fibers is well kept after LOI test. The rigid combustion residue char acts as an effective barrier to the outward diffusion of flame and heat. The combustion process and flame retardant mechanism of calcium alginate fibers are also discussed.

  2. The phosphorylation status of extracellular-regulated kinase 1/2 in astrocytes and neurons from rat hippocampus determines the thrombin-induced calcium release and ROS generation.

    Science.gov (United States)

    Zündorf, Gregor; Reiser, Georg

    2011-12-01

    Challenge of protease-activated receptors induces cytosolic Ca(2+) concentration ([Ca(2+) ](c)) increase, mitogen-activated protein kinase activation and reactive oxygen species (ROS) formation with a bandwidth of responses in individual cells. We detected in this study in situ the thrombin-induced [Ca(2+) ](c) rise and ROS formation in dissociated hippocampal astrocytes and neurons in a mixed culture. In identified cells, single cell responses were correlated with extracellular-regulated kinase (ERK)1/2 phosphorylation level. On average, in astrocytes, thrombin induced a transient [Ca(2+) ](c) rise with concentration-dependent increase in amplitude and extrusion rate and high ERK1/2 phosphorylation level. Correlation analysis of [Ca(2+) ](c) response characteristics of single astrocytes reveals that astrocytes with nuclear phosphoERK1/2 localization have a smaller Ca(2+) amplitude and extrusion rate compared with cells with a cytosolic phosphoERK1/2 localization. In naive neurons, without thrombin challenge, variable ERK1/2 phosphorylation patterns are observed. ROS were detected by hydroethidine. Only in neurons with increased ERK1/2 phosphorylation level, we see sustained intracellular rise in fluorescence of the dye lasting over several minutes. ROS formation was abolished by pre-incubation with the NADPH oxidase inhibitor apocynin. Additionally, thrombin induced an immediate, transient hydroethidine fluorescence increase. This was interpreted as NADPH oxidase-mediated O(2) (•-) -release into the extracellular milieu, because it was decreased by pre-incubation with apocynin, and could be eluted by superfusion. In conclusion, the phosphorylation status of ERK1/2 determines the thrombin-dependent [Ca(2+) ](c) increase and ROS formation and, thus, influences the capacity of thrombin to regulate neuroprotection or neurodegeneration. PMID:21988180

  3. Osteoblasts detect pericellular calcium concentration increase via neomycin-sensitive voltage gated calcium channels.

    Science.gov (United States)

    Sun, Xuanhao; Kishore, Vipuil; Fites, Kateri; Akkus, Ozan

    2012-11-01

    The mechanisms underlying the detection of critically loaded or micro-damaged regions of bone by bone cells are still a matter of debate. Our previous studies showed that calcium efflux originates from pre-failure regions of bone matrix and MC3T3-E1 osteoblasts respond to such efflux by an increase in the intracellular calcium concentration. The mechanisms by which the intracellular calcium concentration increases in response to an increase in the pericellular calcium concentration are unknown. Elevation of the intracellular calcium may occur via release from the internal calcium stores of the cell and/or via the membrane bound channels. The current study applied a wide range of pharmaceutical inhibitors to identify the calcium entry pathways involved in the process: internal calcium release from endoplasmic reticulum (ER, inhibited by thapsigargin and TMB-8), calcium receptor (CaSR, inhibited by calhex), stretch-activated calcium channel (SACC, inhibited by gadolinium), voltage-gated calcium channels (VGCC, inhibited by nifedipine, verapamil, neomycin, and ω-conotoxin), and calcium-induced-calcium-release channel (CICRC, inhibited by ryanodine and dantrolene). These inhibitors were screened for their effectiveness to block intracellular calcium increase by using a concentration gradient induced calcium efflux model which mimics calcium diffusion from the basal aspect of cells. The inhibitor(s) which reduced the intracellular calcium response was further tested on osteoblasts seeded on mechanically loaded notched cortical bone wafers undergoing damage. The results showed that only neomycin reduced the intracellular calcium response in osteoblasts, by 27%, upon extracellular calcium stimulus induced by concentration gradient. The inhibitory effect of neomycin was more pronounced (75% reduction in maximum fluorescence) for osteoblasts seeded on notched cortical bone wafers loaded mechanically to damaging load levels. These results imply that the increase in

  4. Amifostine-conjugated pH-sensitive calcium phosphate-covered magnetic-amphiphilic gelatin nanoparticles for controlled intracellular dual drug release for dual-targeting in HER-2-overexpressing breast cancer.

    Science.gov (United States)

    Li, Wei-Ming; Chiang, Chih-Sheng; Huang, Wei-Chen; Su, Chia-Wei; Chiang, Min-Yu; Chen, Jian-Yi; Chen, San-Yuan

    2015-12-28

    We developed a surfactant-free method utilizing amifostine to stably link a targeting ligand (Herceptin) to amphiphilic gelatin (AG)-iron oxide@calcium phosphate (CaP) nanoparticles with hydrophobic curcumin (CUR) and hydrophilic doxorubicin (DOX) encapsulated in the AG core and CaP shell (AGIO@CaP-CD), respectively. This multi-functional nanoparticle system has a pH-sensitive CaP shell and degradable amphiphilic gelatin (AG) core, which enables controllable sequential release of the two drugs. The dual-targeting system of AGIO@CaP-CD (HER-AGIO@CaP-CD) with a bioligand and magnetic targeting resulted in significantly elevated cellular uptake in HER2-overexpressing SKBr3 cells and more efficacious therapy than delivery of targeting ligand alone due to the synergistic cell multi-drug resistance/apoptosis-inducing effect of the CUR and DOX combination. This nanoparticle combined with Herceptin and iron oxide nanoparticles not only provided a dual-targeting functionality, but also encapsulated CUR and DOX as a dual-drug delivery system for the combination therapy. This study further demonstrated that the therapeutic efficacy of this dual-targeting co-delivery system can be improved by modifying the application duration of magnetic targeting, which makes this combination therapy system a powerful new tool for in vitro/in vivo cancer therapy, especially for HER2-positive cancers. PMID:26478017

  5. Opening of small and intermediate calcium-activated potassium channels induces relaxation mainly mediated by nitric-oxide release in large arteries and endothelium-derived hyperpolarizing factor in small arteries from rat

    DEFF Research Database (Denmark)

    Stankevicius, Edgaras; Dalsgaard, Thomas; Kroigaard, Christel;

    2011-01-01

    current, and NO release that were blocked by apamin and TRAM-34 or charybdotoxin. These findings suggest that opening of SK(Ca) and IK(Ca) channels leads to endothelium-dependent relaxation that is mediated mainly by NO in large mesenteric arteries and by EDHF-type relaxation in small mesenteric arteries......This study was designed to investigate whether calcium-activated potassium channels of small (SK(Ca) or K(Ca)2) and intermediate (IK(Ca) or K(Ca)3.1) conductance activated by 6,7-dichloro-1H-indole-2,3-dione 3-oxime (NS309) are involved in both nitric oxide (NO) and endothelium......-derived hyperpolarizing factor (EDHF)-type relaxation in large and small rat mesenteric arteries. Segments of rat superior and small mesenteric arteries were mounted in myographs for functional studies. NO was recorded using NO microsensors. SK(Ca) and IK(Ca) channel currents and mRNA expression were investigated in...

  6. Calcium and bones

    Science.gov (United States)

    Bone strength and calcium ... calcium (as well as phosphorus) to make healthy bones. Bones are the main storage site of calcium in ... your body does not absorb enough calcium, your bones can get weak or will not grow properly. ...

  7. 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 ...

  8. Get Enough Calcium

    Science.gov (United States)

    ... Calcium Print This Topic En español Get Enough Calcium Browse Sections The Basics Overview Foods and Vitamins ... 2 of 4 sections Take Action! Take Action: Calcium Sources Protect your bones – get plenty of calcium ...

  9. Estimation of the environmental or radiological impact in the event of accidental release of radionuclides in a DCLL fusion reactor; Estimacion del impacto radiologico ambiental en caso de liberacion accidental de radionucleidos en un reactor de fusion DCLL

    Energy Technology Data Exchange (ETDEWEB)

    Palermo, I.; Gomez Ros, J. M.; Sanz, J.; Mota, F.

    2013-07-01

    Tritium production and activation in the LiPb products can pose a radiological risk in the event of accidental release in a fusion reactor. Within the research programme Consolider TECNO{sub F}US (CSD2008-079) fusion technology has developed a design for a reactor with regenerative wrap with dual refrigeration (DCLL). The purpose of this communication is to present estimates of the radiological impact derived from an accidental release of radionuclides from the circuit of LiPb provinients. (Author)

  10. Caffeine-induced myocardial injury in calcium-free perfused rat hearts.

    OpenAIRE

    Vander Heide, R. S.; Ganote, C. E.

    1985-01-01

    Hearts depleted of extracellular calcium become susceptible to injury caused by repletion of extracellular calcium (calcium paradox). It has been suggested that calcium-free perfusion causes weakening of intercalated disks and that the physical stress of contracture may cause sarcolemmal membrane rupture and creatine kinase (CK) release. To further investigate this hypothesis, the effects of caffeine on contracture, cellular morphology, and CK release were studied in control and calcium-free ...

  11. Localization and pharmacological characterization of voltage dependent calcium channels in cultured neocortical neurons

    DEFF Research Database (Denmark)

    Timmermann, D B; Lund, Trine Meldgaard; Belhage, B;

    2001-01-01

    The physiological significance and subcellular distribution of voltage dependent calcium channels was defined using calcium channel blockers to inhibit potassium induced rises in cytosolic calcium concentration in cultured mouse neocortical neurons. The cytosolic calcium concentration was measured...... using the fluorescent calcium chelator fura-2. The types of calcium channels present at the synaptic terminal were determined by the inhibitory action of calcium channel blockers on potassium-induced [3H]GABA release in the same cell preparation. L-, N-, P-, Q- and R-/T-type voltage dependent calcium...... most important voltage dependent calcium channel in all parts of the neuron. After treatment with thapsigargin the increase in cytosolic calcium was halved, indicating that calcium release from thapsigargin sensitive intracellular calcium stores is an important component of the potassium induced rise...

  12. Stochastic models of intracellular calcium signals

    International Nuclear Information System (INIS)

    Cellular signaling operates in a noisy environment shaped by low molecular concentrations and cellular heterogeneity. For calcium release through intracellular channels–one of the most important cellular signaling mechanisms–feedback by liberated calcium endows fluctuations with critical functions in signal generation and formation. In this review it is first described, under which general conditions the environment makes stochasticity relevant, and which conditions allow approximating or deterministic equations. This analysis provides a framework, in which one can deduce an efficient hybrid description combining stochastic and deterministic evolution laws. Within the hybrid approach, Markov chains model gating of channels, while the concentrations of calcium and calcium binding molecules (buffers) are described by reaction–diffusion equations. The article further focuses on the spatial representation of subcellular calcium domains related to intracellular calcium channels. It presents analysis for single channels and clusters of channels and reviews the effects of buffers on the calcium release. For clustered channels, we discuss the application and validity of coarse-graining as well as approaches based on continuous gating variables (Fokker–Planck and chemical Langevin equations). Comparison with recent experiments substantiates the stochastic and spatial approach, identifies minimal requirements for a realistic modeling, and facilitates an understanding of collective channel behavior. At the end of the review, implications of stochastic and local modeling for the generation and properties of cell-wide release and the integration of calcium dynamics into cellular signaling models are discussed

  13. Stochastic models of intracellular calcium signals

    Energy Technology Data Exchange (ETDEWEB)

    Rüdiger, Sten, E-mail: sten.ruediger@physik.hu-berlin.de

    2014-01-10

    Cellular signaling operates in a noisy environment shaped by low molecular concentrations and cellular heterogeneity. For calcium release through intracellular channels–one of the most important cellular signaling mechanisms–feedback by liberated calcium endows fluctuations with critical functions in signal generation and formation. In this review it is first described, under which general conditions the environment makes stochasticity relevant, and which conditions allow approximating or deterministic equations. This analysis provides a framework, in which one can deduce an efficient hybrid description combining stochastic and deterministic evolution laws. Within the hybrid approach, Markov chains model gating of channels, while the concentrations of calcium and calcium binding molecules (buffers) are described by reaction–diffusion equations. The article further focuses on the spatial representation of subcellular calcium domains related to intracellular calcium channels. It presents analysis for single channels and clusters of channels and reviews the effects of buffers on the calcium release. For clustered channels, we discuss the application and validity of coarse-graining as well as approaches based on continuous gating variables (Fokker–Planck and chemical Langevin equations). Comparison with recent experiments substantiates the stochastic and spatial approach, identifies minimal requirements for a realistic modeling, and facilitates an understanding of collective channel behavior. At the end of the review, implications of stochastic and local modeling for the generation and properties of cell-wide release and the integration of calcium dynamics into cellular signaling models are discussed.

  14. Calcium pump kinetics determined in single erythrocyte ghosts by microphotolysis and confocal imaging.

    OpenAIRE

    Kubitscheck, U; Pratsch, L; Passow, H; Peters, R.

    1995-01-01

    The activity of the plasma membrane calcium pump was measured in single cells. Human red blood cell ghosts were loaded with a fluorescent calcium indicator and either caged calcium and ATP (protocol A) or caged ATP and calcium (protocol B). In a suitably modified laser scanning microscope either calcium or ATP were released by a short UV light pulse. The time-dependent fluorescence intensity of the calcium indicator was then followed in single ghosts by repetitive confocal imaging. The fluore...

  15. 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, exhausti

  16. Concurrent Imaging of Synaptic Vesicle Recycling and Calcium Dynamics

    OpenAIRE

    Li, Haiyan; Foss, Sarah M.; Dobryy, Yuriy L.; Park, C. Kevin; Hires, Samuel Andrew; Shaner, Nathan C.; Tsien, Roger Y.; Osborne, Leslie C.; Voglmaier, Susan M.

    2011-01-01

    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-sh...

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

    OpenAIRE

    Haiyan eLi; Foss, Sarah M.; Yuriy eDobryy; C. Kevin ePark; Samuel Andrew Hires; Shaner, Nathan C.; Tsien, Roger Y.; Osborne, Leslie C.; Voglmaier, Susan M.

    2011-01-01

    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-...

  18. Abortive and propagating intracellular calcium waves: analysis from a hybrid model.

    Directory of Open Access Journals (Sweden)

    Nara Guisoni

    Full Text Available The functional properties of inositol(1,4,5-triphosphate (IP3 receptors allow a variety of intracellular Ca(2+ phenomena. In this way, global phenomena, such as propagating and abortive Ca(2+ waves, as well as local events such as puffs, have been observed. Several experimental studies suggest that many features of global phenomena (e.g., frequency, amplitude, speed wave depend on the interplay of biophysical processes such as diffusion, buffering, efflux and influx rates, which in turn depend on parameters such as buffer concentration, Ca(2+ pump density, cytosolic IP3 level, and intercluster distance. Besides, it is known that cells are able to modify some of these parameters in order to regulate the Ca(2+ signaling. By using a hybrid model, we analyzed different features of the hierarchy of calcium events as a function of two relevant parameters for the calcium signaling, the intercluster distance and the pump strength or intensity. In the space spanned by these two parameters, we found two modes of calcium dynamics, one dominated by abortive calcium waves and the other by propagating waves. Smaller distances between the release sites promote propagating calcium waves, while the increase of the efflux rate makes the transition from propagating to abortive waves occur at lower values of intercluster distance. We determined the frontier between these two modes, in the parameter space defined by the intercluster distance and the pump strength. Furthermore, we found that the velocity of simulated calcium waves accomplishes Luther's law, and that an effective rate constant for autocatalytic calcium production decays linearly with both the intercluster distance and the pump strength.

  19. Simulating Real-World Exposures during Emergency Events: Studying Effects of Indoor and Outdoor Releases in the Urban Dispersion Project in Upper Manhattan, NY

    Science.gov (United States)

    A prospective personal exposure study, involving indoor and outdoor releases, was conducted in upper Midtown Manhattan in New York City as part of the Urban Dispersion Program (UDP) focusing on atmospheric dispersion of chemicals in complex urban settings. The UDP experiments inv...

  20. 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 ...

  1. 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 ...

  2. 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 ...

  3. Coronary Calcium Scan

    Science.gov (United States)

    ... the NHLBI on Twitter. What Is a Coronary Calcium Scan? A coronary calcium scan is a test ... you have calcifications in your coronary arteries. Coronary Calcium Scan Figure A shows the position of the ...

  4. 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 ...

  5. 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.

  6. THERMAL DEGRADATION AND FLAME RETARDANCY OF CALCIUM ALGINATE FIBERS

    Institute of Scientific and Technical Information of China (English)

    于建; 夏延致

    2009-01-01

    Calcium alginate fibers were prepared by wet spinning of sodium alginate into a coagulating bath containing calcium chloride.The thermal degradation and flame retardancy of calcium alginate fibers were investigated with thermal gravimetry(TG),X-ray diffraction(XRD),limiting oxygen index(LOI) and cone calorimeter(CONE).The results show that calcium alginate fibers are inherently flame retardant with a LOI value of 34,and the heat release rate(HRR),total heat release(THR),CO and CO_2 concentrations during ...

  7. Free calcium concentration in brain nerve endings of spontaneously hypertensive rats

    Energy Technology Data Exchange (ETDEWEB)

    Orlov, S.N.; Pokudin, N.I.; Kravstov, G.M.; Postnov, Yu.V.; Okun' , I.M.; Shukanova, N.A.; Rakovich, A.A.; Aksentsev, S.L.; Konev, S.V.

    1987-10-01

    The frequency of neurotransmitter release from the synaptic vesicles of nerve endings by exocytosis depends primarily on the free calcium concentration in the cytoplasm which is controlled by calcium transporting and calcium binding systems. In this paper, in an attempt to determine the state of these systems in primary hypertension and the effects of neurotransmitter release on the increased resistance in the peripheral circulatory system, the authors study the exchange, uptake, and concentration of calcium 45 cations by synaptosomes.

  8. Calcium induced regulation of skeletal troponin--computational insights from molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Georgi Z Genchev

    Full Text Available The interaction between calcium and the regulatory site(s of striated muscle regulatory protein troponin switches on and off muscle contraction. In skeletal troponin binding of calcium to sites I and II of the TnC subunit results in a set of structural changes in the troponin complex, displaces tropomyosin along the actin filament and allows myosin-actin interaction to produce mechanical force. In this study, we used molecular dynamics simulations to characterize the calcium dependent dynamics of the fast skeletal troponin molecule and its TnC subunit in the calcium saturated and depleted states. We focused on the N-lobe and on describing the atomic level events that take place subsequent to removal of the calcium ion from the regulatory sites I and II. A main structural event - a closure of the A/B helix hydrophobic pocket results from the integrated effect of the following conformational changes: the breakage of H-bond interactions between the backbone nitrogen atoms of the residues at positions 2, 9 and sidechain oxygen atoms of the residue at position 12 (N(2-OE(12/N(9-OE(12 in sites I and II; expansion of sites I and II and increased site II N-terminal end-segment flexibility; strengthening of the β-sheet scaffold; and the subsequent re-packing of the N-lobe hydrophobic residues. Additionally, the calcium release allows the N-lobe to rotate relative to the rest of the Tn molecule. Based on the findings presented herein we propose a novel model of skeletal thin filament regulation.

  9. Calcium quarks.

    Science.gov (United States)

    Niggli, Ernst; Egger, Marcel

    2002-05-01

    Elementary subcellular Ca2+ signals arising from the opening of single ion channels may offer the possibility to examine the stochastic behavior and the microscopic chemical reaction rates of these channel proteins in their natural environment. Such an analysis can yield detailed information about the molecular function that cannot be derived from recordings obtained from an ensemble of channels. In this review, we summarize experimental evidence suggesting that Ca2+ sparks, elementary Ca2+ signaling events of cardiac and skeletal muscle excitation contraction coupling, may be comprised of a number of smaller Ca2+ signaling events, the Ca2+ quarks.

  10. Altered calcium signaling following traumatic brain injury

    Directory of Open Access Journals (Sweden)

    John Thomas Weber

    2012-04-01

    Full Text Available Cell death and dysfunction after traumatic brain injury (TBI is caused by a primary phase, related to direct mechanical disruption of the brain, and a secondary phase which consists of delayed events initiated at the time of the physical insult. Arguably, the calcium ion contributes greatly to the delayed cell damage and death after TBI. A large, sustained influx of calcium into cells can initiate cell death signaling cascades, through activation of several degradative enzymes, such as proteases and endonucleases. However, a sustained level of intracellular free calcium is not necessarily lethal, but the specific route of calcium entry may couple calcium directly to cell death pathways. Other sources of calcium, such as intracellular calcium stores, can also contribute to cell damage. In addition, calcium-mediated signal transduction pathways in neurons may be perturbed following injury. These latter types of alterations may contribute to abnormal physiology in neurons that do not necessarily die after a traumatic episode. This review provides an overview of experimental evidence that has led to our current understanding of the role of calcium signaling in death and dysfunction following TBI.

  11. Amylase release from rat parotid glands. II

    International Nuclear Information System (INIS)

    The kinetics of 45Ca2+ uptake, efflux, and calcium potentiation of amylase release by slices of rat parotid glands were examined. Pretreatment of the tissue with 11.25 mM 45Ca2+ medium increased the total tissue 45calcium content. Lanthanum (1 mM) decreased tissue uptake, blocked the slow components of exchange and appeared to inhibit transcellular calcium movement. Neither dibutyryl cyclic AMP nor caffeine caused consistently significant effects on 45Ca2+ kinetics, or total 45calcium content. Carbamylcholine increased the initial rate of 45Ca2+ uptake, but had no effect on total uptake. Elevation of the extracellular Ca2+ concentration of 11.25 mM during stimulation of amylase release resulted in an initial decrease in the rate of amylase release followed by a potentiation of release which developed slowly, requiring 40-50 min to reach the maximal response. The inability to detect release-related changes in either calcium influx or mobilization, and the lengthy times and high Ca2+ concentrations required to achieve calcium potentiation suggests that calcium does not couple amylase release. (Auth.)

  12. Effect of nicotine on exocytotic pancreatic secretory response: role of calcium signaling

    Directory of Open Access Journals (Sweden)

    Chowdhury Parimal

    2013-01-01

    Full Text Available Abstract Background Nicotine is a risk factor for pancreatitis resulting in loss of pancreatic enzyme secretion. The aim of this study was to evaluate the mechanisms of nicotine-induced secretory response measured in primary pancreatic acinar cells isolated from Male Sprague Dawley rats. The study examines the role of calcium signaling in the mechanism of the enhanced secretory response observed with nicotine exposure. Methods Isolated and purified pancreatic acinar cells were subjected to a nicotine exposure at a dose of 100 μM for 6 minutes and then stimulated with cholecystokinin (CCK for 30 min. The cell’s secretory response was measured by the percent of amylase released from the cells in the incubation medium Calcium receptor antagonists, inositol trisphosphate (IP3 receptor blockers, mitogen activated protein kinase inhibitors and specific nicotinic receptor antagonists were used to confirm the involvement of calcium in this process. Results Nicotine exposure induced enhanced secretory response in primary cells. These responses remained unaffected by mitogen activated protein kinases (MAPK’s inhibitors. The effects, however, have been completely abolished by nicotinic receptor antagonist, calcium channel receptor antagonists and inositol trisphosphate (IP3 receptor blockers. Conclusions The data suggest that calcium activated events regulating the exocytotic secretion are affected by nicotine as shown by enhanced functional response which is inhibited by specific antagonists… The results implicate the role of nicotine in the mobilization of both intra- and extracellular calcium in the regulation of stimulus-secretory response of enzyme secretion in this cell system. We conclude that nicotine plays an important role in promoting enhanced calcium levels inside the acinar cell.

  13. Calcium and Vitamin D

    Science.gov (United States)

    ... Home › Patients › Treatment › Calcium/Vitamin D Calcium/Vitamin D Getting enough calcium and vitamin D is essential ... counter medications and calcium supplements. What is Vitamin D and What Does it Do? Vitamin D plays ...

  14. Slow-release fertilizer

    Science.gov (United States)

    Ming, Douglas W.; Golden, D. C.

    1992-10-01

    A synthetic apatite containing agronutrients and a method for making the apatite are disclosed. The apatite comprises crystalline calcium phosphate having agronutrients dispersed in the crystalline structure. The agronutrients can comprise potassium, magnesium, sulfur, iron, manganese, molybdenum, chlorine, boron, copper and zinc in amounts suited for plant growth. The apatite can optionally comprise a carbonate and/or silicon solubility control agent. The agronutrients are released slowly as the apatite dissolves.

  15. Deoxynivalenol (Vomitoxin)-Induced Cholecystokinin and Glucagon-Like Peptide-1 Release in the STC-1 Enteroendocrine Cell Model Is Mediated by Calcium-Sensing Receptor and Transient Receptor Potential Ankyrin-1 Channel.

    Science.gov (United States)

    Zhou, Hui-Ren; Pestka, James J

    2015-06-01

    Food refusal is a hallmark of exposure of experimental animals to the trichothecene mycotoxin deoxynivalenol (DON), a common foodborne contaminant. Although studies in the mouse suggest that DON suppresses food intake by aberrantly inducing the release of satiety hormones from enteroendocrine cells (EECs) found in the gut epithelium, the underlying mechanisms for this effect are not understood. To address this gap, we employed the murine neuroendocrine tumor STC-1 cell line, a widely used EEC model, to test the hypothesis that DON-induced hormone exocytosis is mediated by G protein-coupled receptor (GPCR)-mediated Ca(2+) signaling. The results indicate for the first time that DON elicits Ca(2)-dependent secretion of cholecystokinin (CCK) and glucagon-like peptide-1(7-36) amide (GLP-1), hormones that regulate food intake and energy homeostasis and that are products of 2 critical EEC populations--I cells of the small intestine and L cells of the large intestine, respectively. Furthermore, these effects were mediated by the GPCR Ca(2+)-sensing receptor (CaSR) and involved the following serial events: (1)PLC-mediated activation of the IP3 receptor and mobilization of intracellular Ca(2+) stores, (2) activation of transient receptor potential melastatin-5 ion channel and resultant L-type voltage-sensitive Ca(2+) channel-facilitated extracellular Ca(2+) entry, (3) amplification of extracellular Ca(2+) entry by transient receptor potential ankyrin-1 channel activation, and finally (4) Ca(2+)-driven CCK and GLP-1 excytosis. These in vitro findings provide a foundation for future investigation of mechanisms by which DON and other trichothecenes modulate EEC function in ex vivo and in vivo models. PMID:25787141

  16. Study on the in vitro release behavior of bovine serum albumin from calcium phosphate coating on pure titanium surface%纯钛表面仿生钙磷涂层中牛血清白蛋白的释放行为研究

    Institute of Scientific and Technical Information of China (English)

    朱晓晶; 王焱; 张辉; 滕伟; 宁成云; 郑华德

    2014-01-01

    Objective To study the incorporation rate and release behavior of bovine serum albumin(BSA) incorporated into the calcium phosphate coating by biomimetic deposition,as well as the physical and chemical properties of the hybrid coating,and to provide experimental basis for the fabrication of growth factor/biomimetic calcium phosphate coating and exploration for the loading/release behavior of growth factors.Methods Pure titanium specimens were immersed into saturated calcium phosphate solutions(SCP) containing no BSA(controlled group) and 3 different concentrations of BSA(experimental groups):1,10 and 100 mg/L.Biomimetic calcium phosphate coating was formed on titanium surface and BSA was incorporated into the coating through co-deposition.The topography of the specimen was observed using scanning electron microscopy(SEM).Chemical structure and phase composition of coatings were detected by Fourier infrared spectroscopy(FTIR) analysis and X-ray diffraction(XRD) respectively.BSA incorporation rate and release profile were determined by bicinchoninic acid protein assay kit.Results The biomimetic calcium phosphate coating was mainly composed of hydroxyapatite and octacalcium phosphate.BSA was successfully incorporated into the calcium phosphate coatings in all the 3 experimental groups.With the increase of BSA concentration,plate-like units of the coatings were turned into small grid structure.BSA incorporation rates of the three experimental groups were(72.4 ± 2.4)%,(62.3 ± 0.9)% and (42.2 ± 1.7)% respectively.The in vitro release test showed that all three BSA release profiles could be divided into two significant different stages:early burst release stage and later sustained release stage.The amount of BSA release of the 3 experimental groups in 24 h and 30 d were (1.57±0.09),(8.82±0.93),(140.24±3.12) μg,and (2.39±0.29),(14.39±0.70),(151.06±2.00) μg respectively.Conclusions Biomimetic calcium phosphate coating can be used as an effective carrier for

  17. Localization and pharmacological characterization of voltage dependent calcium channels in cultured neocortical neurons

    DEFF Research Database (Denmark)

    Timmermann, D B; Lund, T M; Belhage, B;

    2001-01-01

    in cytosolic calcium concentration. The results of this investigation demonstrate that pharmacologically distinct types of voltage dependent calcium channels are differentially localized in cell bodies, neurites and nerve terminals of mouse cortical neurons but that the Q-type calcium channel appears......The physiological significance and subcellular distribution of voltage dependent calcium channels was defined using calcium channel blockers to inhibit potassium induced rises in cytosolic calcium concentration in cultured mouse neocortical neurons. The cytosolic calcium concentration was measured...... using the fluorescent calcium chelator fura-2. The types of calcium channels present at the synaptic terminal were determined by the inhibitory action of calcium channel blockers on potassium-induced [3H]GABA release in the same cell preparation. L-, N-, P-, Q- and R-/T-type voltage dependent calcium...

  18. A geostatistical approach to recover the release history of groundwater pollution events; L'approccio geostatistico per la ricostruzione della storia di rilascio di inquinanti in falda

    Energy Technology Data Exchange (ETDEWEB)

    Butera, I.; Tanda, M. G. [Milan Politecnico, Milan (Italy). Dipt. di Ingegneria Idraulica, Ambientale e del Rilevamento

    2001-08-01

    In this work, on the basis of the spatial concentration data available at a given time, the temporal release history of a pollutant is recovered by a geostatistical methodology. The problem in hand belongs to the inverse problems category: in literature different approaches are proposed for their solution. The methodology adopted in this study has been developed by Snodgras and Kitanidis (1997) for one dimensional flow and transport case. In this work the methodology is developed to the case of two dimensional transport (one dimensional transport assumption implies not negligible approximations, even if transversal dispersivity is small compared to the longitudinal one). The study, applied to a literature case, considers the quality of the results and the performance of the algorithm used to implement the procedure with regard of: plume sampling scheme (location and number of the measurement points); the impact of concentration measurement errors; the impact of errors in the aquifer parameters estimate (velocity, longitudinal and transversal dispersion coefficients); erroneous identification of the hydraulic gradient direction. The results of the numerical analysis show that the method provides a likely description of the release history jointed to the estimate error variance. [Italian] Nel presente lavoro si propone un'applicazione di un metodo sviluppato nell'ambito della geostatistica, per la ricostruzione della storia temporale dei rilasci di un agente presente in falda, sulla base dei dati di concentrazione d'inquinante rilevati in diversi punti dell'acquifero. Il problema in esame rientra nella categoria dei problemi inversi, per la cui soluzione in letteratura sono prooposti metodi di impostazione diversa. La metodologia adottata in questo studio e' stata sviluppata ed applicata da Snodgrass e Kitanidis (1997) per condizioni di flusso e trasporto monodimensionali; nella presente memoria, essa e' estesa a non trascurabili, anche

  19. Altered Calcium Handling in Reperfusion Injury.

    Science.gov (United States)

    Bompotis, Georgios C; Deftereos, Spyridon; Angelidis, Christos; Choidis, Efthymios; Panagopoulou, Vasiliki; Kaoukis, Andreas; Vassilikos, Vassilios P; Cleman, Michael W; Giannopoulos, Georgios

    2016-01-01

    Coronary Heart Disease (CHD) is the major mortality cause in the Western Hemisphere. Reinstituting blood flow in the acutely occluded coronary vessel became the standard intervention to prevent Myocardial Infarct (MI) progression. Ever since their conception, thrombolysis, Percutaneous Coronary Intervention (PCI) and Coronary Artery Bypass Grafting (CABG) have been at the forefront of CHD treatment, limiting MI size. However, it quickly became apparent that after a period of ischemia, reperfusion itself sets off a cascade of events leading to cell injury. It seems that cellular changes in the ischemic period, prime the cell for a loss of homeostasis once blood flow returns. Loss of calcium (Ca(2+)) regulation has been found to be a main culprit in both ischemia and reperfusion. Indeed, sarcoplasmic Ca(2+) overload during reperfusion is related to hypercontracture, proteolysis and mitochondrial failure--the so-called Reperfusion Injury (RI). Ca(2+) channels of the sarcolemma (SL) (L-Type Ca((2+)) Channels, Sodium / Calcium Exchanger) initiate Ca(2+) flux and those of the Sarcoplasmic Reticulum (SR) (Ca(2+) ATPase, Ca(2+) release channel) sustain the rise in intracellular Ca(2+) concentration. Ensuing interplay between Ca(2+), SR, mitochondria, myofilaments and proteolytic cascades i.e. calpain activation, results in cell injury. Novel insight about this interplay and details about the extent by which each of these players contributes to the RI, may allow scientists to devise and design proper interventions that ultimately reduce RI in clinical practice. The present article reviews the literature about key subcellular players participating in the sustained rise of cardiac myocyte cytosolic Ca(2+) during ischemia and reperfusion.

  20. Activation of a cGMP-sensitive calcium-dependent chloride channel may cause transition from calcium waves to whole cell oscillations in smooth muscle cells

    DEFF Research Database (Denmark)

    Jacobsen, Jens Christian Brings; Aalkjær, Christian; Nilsson, Holger;

    2007-01-01

    waves sweeping through the cytoplasm when the sarcoplasmic reticulum (SR) is stimulated to release calcium. A rise in cGMP leads to the experimentally observed transition from waves to whole cell calcium oscillations. At the same time, membrane potential starts to oscillate and the frequency...... approximately doubles. In this transition, the simulated results point to a key role for a recently discovered cGMP-sensitive calcium-dependent chloride channel. This channel depolarizes the membrane in response to calcium released from the SR. In turn, depolarization causes a uniform opening of L-type calcium...

  1. Intracellular calcium and cyclic nucleotide levels modulate neurite guidance by microtopographical substrate features.

    Science.gov (United States)

    Li, Shufeng; Tuft, Bradley; Xu, Linjing; Polacco, Marc; Clarke, Joseph C; Guymon, C Allan; Hansen, Marlan R

    2016-08-01

    Micro- and nanoscale surface features have emerged as potential tools to direct neurite growth into close proximity with next generation neural prosthesis electrodes. However, the signaling events underlying the ability of growth cones to respond to topographical features remain largely unknown. Accordingly, this study probes the influence of [Ca(2+) ]i and cyclic nucleotide levels on the ability of neurites from spiral ganglion neurons (SGNs) to precisely track topographical micropatterns. Photopolymerization and photomasking were used to generate micropatterned methacrylate polymer substrates. Dissociated SGN cultures were plated on the micropatterned surfaces. Calcium influx and release from internal stores were manipulated by elevating extracellular K(+) , maintenance in calcium-free media, or bath application of various calcium channel blockers. Cyclic nucleotide activity was increased by application of cpt-cAMP or 8-Br-cGMP. Elevation of [Ca(2+) ]i by treatment of cultures with elevated potassium reduced neurite alignment to physical microfeatures. Maintenance of cultures in Ca(2+) -free medium or treatment with the non-selective voltage-gated calcium channel blocker cadmium or L-type Ca(2+) channel blocker nifedipine did not signficantly alter SGN neurite alignment. By contrast, ryanodine or xestospongin C, which block release of internal calcium stores via ryanodine-sensitive channels or inositol-1,4,5-trisphosphate receptors respectively, each significantly decreased neurite alignment. Cpt-cAMP significantly reduced neurite alignment while 8-Br-cGMP significantly enhanced neurite alignment. Manipulation of [Ca(2+) ]i or cAMP levels significantly disrupts neurite guidance while elevation of cGMP levels increases neurite alignment. The results suggest intracellular signaling pathways similar to those recruited by chemotactic cues are involved in neurite guidance by topographical features. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2037

  2. Liberação de benzoato de cálcio de filmes de alginato de sódio reticulados com íons cálcio Release of calcium benzoate from films of sodium alginate crosslinked with calcium ions

    Directory of Open Access Journals (Sweden)

    Franciele R. B. Turbiani

    2011-01-01

    Full Text Available Biofilmes confeccionados à base de alginato de sódio foram reticulados com íons Ca++ provenientes de duas fontes, cloreto e benzoato de cálcio, e continham glicerol como plastificante. Inicialmente, devido ao alto poder gelificante do Ca++, um filme de baixo grau de reticulação foi confeccionado por casting (1º estágio. Esse filme sofreu uma reticulação complementar por imersão em uma solução contendo de 3 a 7% de CaCl2.2H2O, além de glicerol (2º estágio. A liberação de benzoato de cálcio foi avaliada em diferentes concentrações de agente ativo no filme e dois níveis de reticulação do alginato. O mecanismo envolvido no processo de difusão foi investigado usando o modelo da Lei de Potência. Os resultados indicaram que a difusão de benzoato de cálcio em filmes de alginato apresenta características de comportamentos Fickiano e não-Fickiano. Os coeficientes de difusão efetivos obtidos usando a solução em série derivada da 2ª Lei de Fick são próximos aos valores obtidos pela solução em tempos curtos, com valores de difusividade efetiva do benzoato variando de 3 a 5.10-7 cm²/s. Os valores de difusividade diminuíram com o aumento da intensidade de reticulação e aumentaram com a concentração de benzoato no filme.Alginate-based biofilms were reticulated with Ca++ supplied by two sources, calcium chloride and benzoate, and using glycerol as plasticizer. The strong gelling power of the Ca++ ions hindered smooth casting procedures, so that films with low degree of reticulation were initially manufactured (1st stage. These films were further crosslinked with an excess of Ca++ by immersion in a solution of 3 to 7% of CaCl2.2H2O (2nd stage. The release of sorbate was evaluated considering different active agent concentrations in the film and two levels of alginate crosslinking. The mechanism involved in the diffusional process was investigated using the Power Law Model. The results indicated that potassium sorbate

  3. Astrocyte calcium signaling: the third wave.

    Science.gov (United States)

    Bazargani, Narges; Attwell, David

    2016-02-01

    The discovery that transient elevations of calcium concentration occur in astrocytes, and release 'gliotransmitters' which act on neurons and vascular smooth muscle, led to the idea that astrocytes are powerful regulators of neuronal spiking, synaptic plasticity and brain blood flow. These findings were challenged by a second wave of reports that astrocyte calcium transients did not mediate functions attributed to gliotransmitters and were too slow to generate blood flow increases. Remarkably, the tide has now turned again: the most important calcium transients occur in fine astrocyte processes not resolved in earlier studies, and new mechanisms have been discovered by which astrocyte [Ca(2+)]i is raised and exerts its effects. Here we review how this third wave of discoveries has changed our understanding of astrocyte calcium signaling and its consequences for neuronal function.

  4. Discrete stochastic modeling of calcium channel dynamics

    CERN Document Server

    Baer, M E; Levine, H; Tsimring, L S; Baer, Markus; Falcke, Martin; Levine, Herbert; Tsimring, Lev S.

    1999-01-01

    We propose a simple discrete stochastic model for calcium dynamics in living cells. Specifically, the calcium concentration distribution is assumed to give rise to a set of probabilities for the opening/closing of channels which release calcium thereby changing those probabilities. We study this model in one dimension, analytically in the mean-field limit of large number of channels per site N, and numerically for small N. As the number of channels per site is increased, the transition from a non-propagating region of activity to a propagating one changes in nature from one described by directed percolation to that of deterministic depinning in a spatially discrete system. Also, for a small number of channels a propagating calcium wave can leave behind a novel fluctuation-driven state, in a parameter range where the limiting deterministic model exhibits only single pulse propagation.

  5. Arachidonic acid and calcium metabolism in rnelittin stimulated neutrophils

    OpenAIRE

    Nielsen, Ole H.; Bouchelouche, Pierre N.; Dag Berild

    1992-01-01

    Melittin, the predominant fraction of bee venom proteins, was studied in an experimental model of human neutrophil granulocytes to reveal its influence on eicosanoid release, metabolism and receptor function in relation to intracellular calcium metabolism. Melittin (2 μmol/l) was as potent as the calcium ionophore A23187 (10 μmol/l) for activation of 5-lipoxygenase, releasing arachidonate only from phosphatidyl-choline and phosphatidyl-ethanolamine of cellular membranes, as judged from the de...

  6. Calcium channel blocker overdose

    Science.gov (United States)

    ... this 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 ...

  7. 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 ...

  8. 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.

  9. 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.

  10. A comparative study of calcium absorption following a single serving administration of calcium carbonate powder versus calcium citrate tablets in healthy premenopausal women

    Directory of Open Access Journals (Sweden)

    Haiyuan Wang

    2014-04-01

    Full Text Available Background: Calcium is an essential mineral often taken as a daily, long-term nutritional supplement. Data suggests that once-daily dosing is important with regard to long-term compliance of both drugs and nutritional supplements. Objective: This study was undertaken to compare the bioavailability of a single serving of two calcium supplements in healthy, premenopausal women. Design: A two-period, crossover bioavailability study of a single serving of calcium citrate tablets (two tablets=500 mg calcium versus a single serving of calcium carbonate powder (one packet of powder=1,000 mg calcium was performed in healthy women aged between 25 and 45. All subjects were on a calcium-restricted diet 7 days prior to testing and fasted for 12 h before being evaluated at 0, 1, 2, and 4 h after oral administration of the test agents. Blood measurements for total and ionized calcium and parathyroid hormone were performed and adverse events were monitored. Results: Twenty-three women were evaluable with a mean age of 33.2±8.71. Results showed that administration of a single serving of a calcium carbonate powder resulted in greater absorption in total and ionized calcium versus a single serving of calcium citrate tablets at 4 h (4.25±0.21 vs. 4.16±0.16, p=0.001. There were minimal side effects and no reported serious adverse events. Conclusions: This study shows that a single serving of a calcium carbonate powder is more bioavailable than a single serving of calcium citrate tablets. This may be beneficial for long-term compliance.

  11. ATP- and gap junction-dependent intercellular calcium signaling in osteoblastic cells

    DEFF Research Database (Denmark)

    Jorgensen, N R; Geist, S T; Civitelli, R;

    1997-01-01

    Many cells coordinate their activities by transmitting rises in intracellular calcium from cell to cell. In nonexcitable cells, there are currently two models for intercellular calcium wave propagation, both of which involve release of inositol trisphosphate (IP3)- sensitive intracellular calcium...

  12. 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 cardiop

  13. Calcium-Mediated Abiotic Stress Signaling in Roots.

    Science.gov (United States)

    Wilkins, Katie A; Matthus, Elsa; Swarbreck, Stéphanie M; Davies, Julia M

    2016-01-01

    Roots are subjected to a range of abiotic stresses as they forage for water and nutrients. Cytosolic free calcium is a common second messenger in the signaling of abiotic stress. In addition, roots take up calcium both as a nutrient and to stimulate exocytosis in growth. For calcium to fulfill its multiple roles must require strict spatio-temporal regulation of its uptake and efflux across the plasma membrane, its buffering in the cytosol and its sequestration or release from internal stores. This prompts the question of how specificity of signaling output can be achieved against the background of calcium's other uses. Threats to agriculture such as salinity, water availability and hypoxia are signaled through calcium. Nutrient deficiency is also emerging as a stress that is signaled through cytosolic free calcium, with progress in potassium, nitrate and boron deficiency signaling now being made. Heavy metals have the capacity to trigger or modulate root calcium signaling depending on their dose and their capacity to catalyze production of hydroxyl radicals. Mechanical stress and cold stress can both trigger an increase in root cytosolic free calcium, with the possibility of membrane deformation playing a part in initiating the calcium signal. This review addresses progress in identifying the calcium transporting proteins (particularly channels such as annexins and cyclic nucleotide-gated channels) that effect stress-induced calcium increases in roots and explores links to reactive oxygen species, lipid signaling, and the unfolded protein response. PMID:27621742

  14. Calcium electrotransfer for termination of transgene expression in muscle

    DEFF Research Database (Denmark)

    Hojman, Pernille; Spanggaard, Iben; Olsen, Caroline Holkman;

    2011-01-01

    Gene electrotransfer is expanding in clinical use, thus we have searched for an emergency procedure to stop transgene expression in case of serious adverse events. Calcium is cytotoxic at high intracellular levels, so we tested effects of calcium electrotransfer on transgene expression in muscle....

  15. Calcium and calcium isotope changes during carbon cycle perturbations at the end-Permian

    Science.gov (United States)

    Komar, Nemanja; Zeebe, Richard

    2016-04-01

    Negative carbon and calcium isotope excursions, as well as climate shifts, took place during the most severe mass extinction event in Earth's history, the end-Permian (˜252 Ma). Investigating the connection between carbon and calcium cycles during transient carbon cycle perturbation events, such as the end-Permian, may help resolve the intricacies between the coupled calcium-carbon cycles, as well as provide a tool for constraining the causes of mass extinction. Here, we identify the deficiencies of a simplified calcium model employed in several previous studies and we demonstrate the importance of a fully coupled carbon-cycle model when investigating the dynamics of carbon and calcium cycling. Simulations with a modified version of the LOSCAR model, which includes a fully coupled carbon-calcium cycle, indicate that increased weathering rates and ocean acidification (potentially caused by Siberian Trap volcanism) are not capable of producing trends observed in the record, as previously claimed. Our model results suggest that combined effects of carbon input via Siberian Trap volcanism (12,000 Pg C), the cessation of biological carbon export, and variable calcium isotope fractionation (due to a change in the seawater carbonate ion concentration) represents a more plausible scenario. This scenario successfully reconciles δ13C and δ44Ca trends observed in the sediment record, as well as the proposed warming of >6oC.

  16. The secretory pathway calcium ATPase PMR-1/SPCA1 has essential roles in cell migration during Caenorhabditis elegans embryonic development.

    Directory of Open Access Journals (Sweden)

    Vida Praitis

    2013-05-01

    Full Text Available Maintaining levels of calcium in the cytosol is important for many cellular events, including cell migration, where localized regions of high calcium are required to regulate cytoskeletal dynamics, contractility, and adhesion. Studies show inositol-trisphosphate receptors (IP3R and ryanodine receptors (RyR, which release calcium into the cytosol, are important regulators of cell migration. Similarly, proteins that return calcium to secretory stores are likely to be important for cell migration. The secretory protein calcium ATPase (SPCA is a Golgi-localized protein that transports calcium from the cytosol into secretory stores. SPCA has established roles in protein processing, metal homeostasis, and inositol-trisphosphate signaling. Defects in the human SPCA1/ATP2C1 gene cause Hailey-Hailey disease (MIM# 169600, a genodermatosis characterized by cutaneous blisters and fissures as well as keratinocyte cell adhesion defects. We have determined that PMR-1, the Caenorhabditis elegans ortholog of SPCA1, plays an essential role in embryogenesis. Pmr-1 strains isolated from genetic screens show terminal phenotypes, such as ventral and anterior enclosure failures, body morphogenesis defects, and an unattached pharynx, which are caused by earlier defects during gastrulation. In Pmr-1 embryos, migration rates are significantly reduced for cells moving along the embryo surface, such as ventral neuroblasts, C-derived, and anterior-most blastomeres. Gene interaction experiments show changing the activity of itr-1/IP3R and unc-68/RyR modulates levels of embryonic lethality in Pmr-1 strains, indicating pmr-1 acts with these calcium channels to regulate cell migration. This analysis reveals novel genes involved in C. elegans cell migration, as well as a new role in cell migration for the highly conserved SPCA gene family.

  17. 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...

  18. Calcium signaling and epilepsy.

    Science.gov (United States)

    Steinlein, Ortrud K

    2014-08-01

    Calcium signaling is involved in a multitude of physiological and pathophysiological mechanisms. Over the last decade, it has been increasingly recognized as an important factor in epileptogenesis, and it is becoming obvious that the excess synchronization of neurons that is characteristic for seizures can be linked to various calcium signaling pathways. These include immediate effects on membrane excitability by calcium influx through ion channels as well as delayed mechanisms that act through G-protein coupled pathways. Calcium signaling is able to cause hyperexcitability either by direct modulation of neuronal activity or indirectly through calcium-dependent gliotransmission. Furthermore, feedback mechanisms between mitochondrial calcium signaling and reactive oxygen species are able to cause neuronal cell death and seizures. Unravelling the complexity of calcium signaling in epileptogenesis is a daunting task, but it includes the promise to uncover formerly unknown targets for the development of new antiepileptic drugs.

  19. Calcium and cell death signaling in neurodegeneration and aging.

    Science.gov (United States)

    Smaili, Soraya; Hirata, Hanako; Ureshino, Rodrigo; Monteforte, Priscila T; Morales, Ana P; Muler, Mari L; Terashima, Juliana; Oseki, Karen; Rosenstock, Tatiana R; Lopes, Guiomar S; Bincoletto, Claudia

    2009-09-01

    Transient increase in cytosolic (Cac2+) and mitochondrial Ca2+ (Ca m2+) are essential elements in the control of many physiological processes. However, sustained increases in Ca c2+ and Ca m2+ may contribute to oxidative stress and cell death. Several events are related to the increase in Ca m2+, including regulation and activation of a number of Ca2+ dependent enzymes, such as phospholipases, proteases and nucleases. Mitochondria and endoplasmic reticulum (ER) play pivotal roles in the maintenance of intracellular Ca2+ homeostasis and regulation of cell death. Several lines of evidence have shown that, in the presence of some apoptotic stimuli, the activation of mitochondrial processes may lead to the release of cytochrome c followed by the activation of caspases, nuclear fragmentation and apoptotic cell death. The aim of this review was to show how changes in calcium signaling can be related to the apoptotic cell death induction. Calcium homeostasis was also shown to be an important mechanism involved in neurodegenerative and aging processes.

  20. Calcium Domains around Single and Clustered IP3 Receptors and Their Modulation by Buffers

    OpenAIRE

    Rüdiger, S; Nagaiah, Ch.; Warnecke, G; J. W. Shuai

    2010-01-01

    We study Ca2+ release through single and clustered IP3 receptor channels on the ER membrane under presence of buffer proteins. Our computational scheme couples reaction-diffusion equations and a Markovian channel model and allows our investigating the effects of buffer proteins on local calcium concentrations and channel gating. We find transient and stationary elevations of calcium concentrations around active channels and show how they determine release amplitude. Transient calcium domains ...

  1. Smoking, calcium, calcium antagonists, and aging.

    Science.gov (United States)

    Nicita-Mauro, V

    1990-01-01

    Aging is characterized, besides other changes, by a progressive increase in calcium content in the arterial wall, which is enhanced by diabetes mellitus, osteoporosis, arterial hypertension, and tabagism. As to tabagism, experiments in animals have shown that nicotine can increase calcium content of the arterial wall, and clinical studies have demonstrated that cigarette smoking induces peripheral vasoconstriction, with consequent increase in blood pressure levels. In order to study the role of calcium ions in the pathogenesis of the vasoconstrictive lesions caused by "acute" smoking, the author has studied the peripheral vascular effects of the calcium-channel antagonist nifedipine, a dihydropyridine derivative, and calcitonin, a hypocalcemizing hormone which possess vasoactive actions on 12 elderly regular smokers (mean age 65.8 years). The results demonstrated that both nifedipine (10 mg sublingually 20 min before smoking) and salmon calcitonin (100 MRC U/daily intramuscularly for three days) are able to prevent peripheral vasoconstriction evaluated by Doppler velocimetry, as well as the increase of blood pressure induced by smoking. On the basis of our results, the author proposes that cigarette smoking-induced vasoconstriction is a calcium-mediated process, which can be hindered by drugs with calcium antagonist action. PMID:2226675

  2. Calcium absorption and achlorhydria

    International Nuclear Information System (INIS)

    Defective absorption of calcium has been thought to exist in patients with achlorhydria. The author compared absorption of calcium in its carbonate form with that in a pH-adjusted citrate form in a group of 11 fasting patients with achlorhydria and in 9 fasting normal subjects. Fractional calcium absorption was measured by a modified double-isotope procedure with 0.25 g of calcium used as the carrier. Mean calcium absorption (+/- S.D.) in the patients with achlorhydria was 0.452 +/- 0.125 for citrate and 0.042 +/- 0.021 for carbonate (P less than 0.0001). Fractional calcium absorption in the normal subjects was 0.243 +/- 0.049 for citrate and 0.225 +/- 0.108 for carbonate (not significant). Absorption of calcium from carbonate in patients with achlorhydria was significantly lower than in the normal subjects and was lower than absorption from citrate in either group; absorption from citrate in those with achlorhydria was significantly higher than in the normal subjects, as well as higher than absorption from carbonate in either group. Administration of calcium carbonate as part of a normal breakfast resulted in completely normal absorption in the achlorhydric subjects. These results indicate that calcium absorption from carbonate is impaired in achlorhydria under fasting conditions. Since achlorhydria is common in older persons, calcium carbonate may not be the ideal dietary supplement

  3. Discussion on the mechanism of the calcium absorption in the human body

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The present article discusses a new mechanism of calcium absorption in the human body. The mechanism is revealed as follows. First, after food is digested in the stomach, calcium ions (Ca2+) are released. The small intestine secretes amino acid or short peptide chain with small molecniar weight automatically, which are called chelating agent; when the calcium ions from the stomach get to the small intestine, the reaction of the chelating agent with the calcium ions occurs, producing the neutral amino acid calcium chelate. Then, this kind of calcium chelate with small molecular weight is absorbed as a whole into the tissues of the small intestine. After being absorbed, in the cell the calcium chelate can break down its chelating bond automatically and decompose into the amino acid and calcium ion again. Finally, the calcium ion goes into blood through portal vein and is transferred to the organs and also deposits on the bone. The reason for the body's calcium insufficiency, which has no linear relation with the calcium intake amount, is the lack of the amino acid secreted by the small intestine. The main barrier that influences the calcium absorption is anion pollution. The calcium absorptivity of the body has nothing to do with the solubility of the calcium source out of the body.A new kind of calcium supplement agent--glycine calcium chelate--is synthesized, whose molecular weight is 206.06(containing a molecular water). If the glycine calcium chelate is used to make calcium supplement agent, about 20 mg calcium element (converted from the glycine calcium chelate,the same below, no longer indicated) per day for one person,50 mg at most, is enough to maintain the positive balance of calcium metabolism.``

  4. Dysbalance of astrocyte calcium under hyperammonemic conditions.

    Directory of Open Access Journals (Sweden)

    Nicole Haack

    Full Text Available Increased brain ammonium (NH4(+/NH3 plays a central role in the manifestation of hepatic encephalopathy (HE, a complex syndrome associated with neurological and psychiatric alterations, which is primarily a disorder of astrocytes. Here, we analysed the influence of NH4(+/NH3 on the calcium concentration of astrocytes in situ and studied the underlying mechanisms of NH4(+/NH3-evoked calcium changes, employing fluorescence imaging with Fura-2 in acute tissue slices derived from different regions of the mouse brain. In the hippocampal stratum radiatum, perfusion with 5 mM NH4(+/NH3 for 30 minutes caused a transient calcium increase in about 40% of astrocytes lasting about 10 minutes. Furthermore, the vast majority of astrocytes (∼ 90% experienced a persistent calcium increase by ∼ 50 nM. This persistent increase was already evoked at concentrations of 1-2 mM NH4(+/NH3, developed within 10-20 minutes and was maintained as long as the NH4(+/NH3 was present. Qualitatively similar changes were observed in astrocytes of different neocortical regions as well as in cerebellar Bergmann glia. Inhibition of glutamine synthetase resulted in significantly larger calcium increases in response to NH4(+/NH3, indicating that glutamine accumulation was not a primary cause. Calcium increases were not mimicked by changes in intracellular pH. Pharmacological inhibition of voltage-gated sodium channels, sodium-potassium-chloride-cotransporters (NKCC, the reverse mode of sodium/calcium exchange (NCX, AMPA- or mGluR5-receptors did not dampen NH4(+/NH3-induced calcium increases. They were, however, significantly reduced by inhibition of NMDA receptors and depletion of intracellular calcium stores. Taken together, our measurements show that sustained exposure to NH4(+/NH3 causes a sustained increase in intracellular calcium in astrocytes in situ, which is partly dependent on NMDA receptor activation and on release of calcium from intracellular stores. Our study

  5. Modeling Calcium Wave Based on Anomalous Subdiffusion of Calcium Sparks in Cardiac Myocytes

    Science.gov (United States)

    Chen, Xi; Kang, Jianhong; Fu, Ceji; Tan, Wenchang

    2013-01-01

    sparks and waves play important roles in calcium release and calcium propagation during the excitation-contraction (EC) coupling process in cardiac myocytes. Although the classical Fick’s law is widely used to model sparks and waves in cardiac myocytes, it fails to reasonably explain the full-width at half maximum(FWHM) paradox. However, the anomalous subdiffusion model successfully reproduces sparks of experimental results. In this paper, in the light of anomalous subdiffusion of sparks, we develop a mathematical model of calcium wave in cardiac myocytes by using stochastic release of release units (CRUs). Our model successfully reproduces calcium waves with physiological parameters. The results reveal how concentration waves propagate from an initial firing of one CRU at a corner or in the middle of considered region, answer how large in magnitude of an anomalous spark can induce a wave. With physiological currents (2pA) through CRUs, it is shown that an initial firing of four adjacent CRUs can form a wave. Furthermore, the phenomenon of calcium waves collision is also investigated. PMID:23483894

  6. Calcium intake is not associated with increased coronary artery calcification: The Framingham Study

    Science.gov (United States)

    Adequate calcium intake is known to protect the skeleton. However, studies that have reported adverse effects of calcium supplementation on vascular events have raised widespread concern. We assessed the association between calcium intake (from diet and supplements) and coronary artery calcification...

  7. Human osteoblastic cells propagate intercellular calcium signals by two different mechanisms

    DEFF Research Database (Denmark)

    Jørgensen, Niklas Rye; Henriksen, Z; Brot, C;

    2000-01-01

    Effective bone remodeling requires the coordination of bone matrix deposition by osteoblastic cells, which may occur via soluble mediators or via direct intercellular communication. We have previously identified two mechanisms by which rat osteoblastic cell lines coordinate calcium signaling among...... intercellular calcium signaling, and if so, by which mechanisms. Upon mechanical stimulation, human osteoblasts propagated fast intercellular calcium waves, which required activation of P2 receptors and release of intracellular calcium stores but did not require calcium influx or gap junctional communication....... After the fast intercellular calcium waves were blocked, we observed slower calcium waves that were dependent on gap junctional communication and influx of extracellular calcium. These results show that human osteoblastic cells can propagate calcium signals from cell to cell by two markedly different...

  8. Dysferlin Binds SNAREs (Soluble N-Ethylmaleimide-sensitive Factor (NSF) Attachment Protein Receptors) and Stimulates Membrane Fusion in a Calcium-sensitive Manner.

    Science.gov (United States)

    Codding, Sara J; Marty, Naomi; Abdullah, Nazish; Johnson, Colin P

    2016-07-01

    Resealing of tears in the sarcolemma of myofibers is a necessary step in the repair of muscle tissue. Recent work suggests a critical role for dysferlin in the membrane repair process and that mutations in dysferlin are responsible for limb girdle muscular dystrophy 2B and Miyoshi myopathy. Beyond membrane repair, dysferlin has been linked to SNARE-mediated exocytotic events including cytokine release and acid sphingomyelinase secretion. However, it is unclear whether dysferlin regulates SNARE-mediated membrane fusion. In this study we demonstrate a direct interaction between dysferlin and the SNARE proteins syntaxin 4 and SNAP-23. In addition, analysis of FRET and in vitro reconstituted lipid mixing assays indicate that dysferlin accelerates syntaxin 4/SNAP-23 heterodimer formation and SNARE-mediated lipid mixing in a calcium-sensitive manner. These results support a function for dysferlin as a calcium-sensing SNARE effector for membrane fusion events. PMID:27226605

  9. In vitro macrophage cytotoxicity of five calcium silicates.

    OpenAIRE

    Skaug, V; Davies, R.; Gylseth, B

    1984-01-01

    Five calcium silicate minerals (two naturally occurring and three synthetic compounds) with defined morphology and chemical composition were compared for their cytotoxic and lysosomal enzyme releasing effects on unstimulated mouse peritoneal macrophages in vitro. One synthetic material, a fibrous tobermorite, was cytotoxic towards the cells, and two naturally occurring wollastonites induced selective release of beta-glucuronidase from the cells.

  10. Extracellular calcium sensing and extracellular calcium signaling

    Science.gov (United States)

    Brown, E. M.; MacLeod, R. J.; O'Malley, B. W. (Principal Investigator)

    2001-01-01

    , localized changes in Ca(o)(2+) within the ECF can originate from several mechanisms, including fluxes of calcium ions into or out of cellular or extracellular stores or across epithelium that absorb or secrete Ca(2+). In any event, the CaR and other receptors/sensors for Ca(o)(2+) and probably for other extracellular ions represent versatile regulators of numerous cellular functions and may serve as important therapeutic targets.

  11. Information flow through calcium binding proteins

    Science.gov (United States)

    Bak, Ji Hyun; Bialek, William

    2013-03-01

    Calcium signaling is a ubiquitous mode of biological communication, which regulates a great variety of vital processes in living systems. Such a signal typically begins with an elementary event, in which calcium ions bind to a protein, inducing a change in the protein's structure. Information can only be lost, from what was conveyed through this initial event, as the signal is further transduced through the downstream networks. In the present work we analyze and optimize the information flow in the calcium binding process. We explicitly calculate the mutual information between the calcium concentration and the states of the protein, using a simple model for allosteric regulation in a dimeric protein. The optimal solution depends on the dynamic range of the input as well as on the timescale of signal integration. According to our result, the optimizing strategy involves allowing the calcium-binding protein to be ``activated'' by a partial occupation of its sites, and tuning independently the strengths of cooperative interactions in the binding and unbinding processes.

  12. The role of voltage-gated calcium channels in neurotransmitter phenotype specification: Coexpression and functional analysis in Xenopus laevis

    OpenAIRE

    Lewis, Brittany B.; Miller, Lauren E.; Herbst, Wendy A; Saha, Margaret S.

    2014-01-01

    Calcium activity has been implicated in many neurodevelopmental events, including the specification of neurotransmitter phenotypes. Higher levels of calcium activity lead to an increased number of inhibitory neural phenotypes, whereas lower levels of calcium activity lead to excitatory neural phenotypes. Voltage-gated calcium channels (VGCCs) allow for rapid calcium entry and are expressed during early neural stages, making them likely regulators of activity-dependent neurotransmitter phenoty...

  13. Measurements of intracellular calcium

    International Nuclear Information System (INIS)

    Intracellular calcium concentration ([Ca2+]i) has been measured in cultured cells by using Fura-2 load cells and a computer-controlled Perkin Elmer LS-5B spectrofluorometer. Increased [Ca2+]i in cells exposed to extracellular bilirubin was observed both with and without extracellular calcium. However, the increase was considerable larger with extracellular calcium. The enhancement of [Ca2+]i became smaller with decreasing bilirubin/BSA (bovine serum albumine) ratio. 5 refs., 5 figs

  14. Localized intracellular calcium signaling in muscle: calcium sparks and calcium quarks.

    Science.gov (United States)

    Niggli, E

    1999-01-01

    Subcellularly localized Ca2+ signals in cardiac and skeletal muscle have recently been identified as elementary Ca2+ signaling events. The signals, termed Ca2+ sparks and Ca2+ quarks, represent openings of Ca2+ release channels located in the membrane of the sarcoplasmic reticulum (SR). In cardiac muscle, the revolutionary discovery of Ca2+ sparks has allowed the development of a fundamentally different concept for the amplification of Ca2+ signals by Ca(2+)-induced Ca2+ release. In such a system, a graded amplification of the triggering Ca2+ signal entering the myocyte via L-type Ca2+ channels is accomplished by a recruitment process whereby individual SR Ca2+ release units are locally controlled by L-type Ca2+ channels. In skeletal muscle, the initial SR Ca2+ release is governed by voltage-sensors but subsequently activates additional Ca2+ sparks by Ca(2+)-induced Ca2+ release from the SR. Results from studies on elementary Ca2+ release events will improve our knowledge of muscle Ca2+ signaling at all levels of complexity, from the molecule to normal cellular function, and from the regulation of cardiac and skeletal muscle force to the pathophysiology of excitation-contraction coupling.

  15. Amelioration of apoptotic events in the skeletal muscle of intra-nigrally rotenone-infused Parkinsonian rats by Morinda citrifolia--up-regulation of Bcl-2 and blockage of cytochrome c release.

    Science.gov (United States)

    Narasimhan, Kishore Kumar S; Paul, Liya; Sathyamoorthy, Yogesh Kanna; Srinivasan, Ashokkumar; Chakrapani, Lakshmi Narasimhan; Singh, Abhilasha; Ravi, Divya Bhavani; Krishnan, Thulasi Raman; Velusamy, Prema; Kaliappan, Kathiravan; Radhakrishnan, Rameshkumar; Periandavan, Kalaiselvi

    2016-02-01

    Parkinson's disease is a progressive neurodegenerative movement disorder with the cardinal symptoms of bradykinesia, resting tremor, rigidity, and postural instability, which lead to abnormal movements and lack of activity, which in turn cause muscular damage. Even though studies have been carried out to elucidate the causative factors that lead to muscular damage in Parkinson's disease, apoptotic events that occur in the skeletal muscle and a therapeutical approach to culminate the muscular damage have not been extensively studied. Thus, this study evaluates the impact of rotenone-induced SNPc lesions on skeletal muscle apoptosis and the efficacy of an ethyl acetate extract of Morinda citrifolia in safeguarding the myocytes. Biochemical assays along with apoptotic markers studied by immunoblot and reverse transcription-polymerase chain reaction in the current study revealed that the supplementation of Morinda citrifolia significantly reverted alterations in both biochemical and histological parameters in rotenone-infused PD rats. Treatment with Morinda citrifolia also reduced the expression of pro-apoptotic proteins Bax, caspase-3 and caspase-9 and blocked the release of cytochrome c from mitochondria induced by rotenone. In addition, it augmented the expression of Bcl2 both transcriptionally and translationally. Thus, this preliminary study paves a way to show that the antioxidant and anti-apoptotic activities of Morinda citrifolia can be exploited to alleviate skeletal muscle damage induced by Parkinsonism.

  16. Cellular Mechanisms of Calcium-Mediated Triggered Activity

    Science.gov (United States)

    Song, Zhen

    proteins. How those various factors interact synergistically to promote DADs is not well understood. Furthermore, at an even more basic level, it remains unclear to what degree spontaneous Ca2+ release and the appearance of DADs are deterministic, meaning reproducible under identical conditions, or inherently stochastic like nucleation in the physical context of phase transitions. In this thesis, we use and further develop a biologically detailed computational model to investigate basic aspects of TA in isolated heart cells (cardiac myocytes). Isolated cells can be obtained by enzymatic dissociation of heart tissue and studied experimentally using standard electrophysiological recording methods and confocal imaging of Ca2+ dynamics. Hence they provide a well controlled setting to investigate the generation of DADs under well controlled conditions. Our computational model captures essential aspects of the hierarchical architecture of ventricular myocytes, which consists of a large number of approximately 20,000 to 50,000 regularly spaced submicron regions containing clusters of 50-100 Ryanodine receptor (RyR) Ca2+ release channels. Each of those regions acts as a discrete "calcium release unit'' (CRU). Therefore our model allows us to address for the first time quantitatively the fundamental question of whether Ca2+ release, which is highly stochastic at the level of a single calcium release unit, is stochastic or deterministic at the whole cell level where the Ca 2+ signal is the summation of releases from a large number of units. Addressing this question is the focus of the first part of this thesis. Our results demonstrate that both the initiation and termination of TA are highly stochastic at the whole cell level due to the spatiotemporal organization of discrete release events into multiple Ca2+ waves. Our results allow us to characterize the probability distributions that govern the number of DADs preceding a triggered action potential and the number of triggered

  17. 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.

  18. Concurrent Imaging of Synaptic Vesicle Recycling and Calcium Dynamics

    Science.gov (United States)

    Li, Haiyan; Foss, Sarah M.; Dobryy, Yuriy L.; Park, C. Kevin; Hires, Samuel Andrew; Shaner, Nathan C.; Tsien, Roger Y.; Osborne, Leslie C.; Voglmaier, Susan M.

    2011-01-01

    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. Reacidification 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. PMID:22065946

  19. 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

  20. Homer regulates calcium signalling in growth cone turning

    Directory of Open Access Journals (Sweden)

    Thompson Michael JW

    2009-08-01

    component of the calcium signalling repertoire within motile growth cones, regulating guidance-cue-induced calcium release and maintaining basal cytosolic calcium.

  1. Glial calcium signaling in physiology and pathophysioilogy

    Institute of Scientific and Technical Information of China (English)

    Alexei VERKHRASKY

    2006-01-01

    Neuronal-glial circuits underlie integrative processes in the nervous system.Function of glial syncytium is,to a very large extent,regulated by the intracellular calcium signaling system.Glial calcium signals are triggered by activation of multiple receptors,expressed in glial membrane,which regulate both Ca2+ entry and Ca2+ release from the endoplasmic reticulum.The endoplasmic reticulum also endows glial cells with intracellular excitable media,which is able to produce and maintain long-ranging signaling in a form of propagating Ca2+ waves.In pathological conditions,calcium signals regulate glial response to injury,which might have both protective and detrimental effects on the nervous tissue.

  2. Comparison of growth-induced resorption and denervation-induced resorption on the release of [3H]tetracycline, 45calcium, and [3H]collagen from whole bones of growing rats

    International Nuclear Information System (INIS)

    The major effect of immobilization during growth is a smaller bone mass induced by either an increased bone resorption or a decreased bone formation. Using a method of analyzing radioisotopic loss of [3H]tetracycline and [3H]collagen from bone prelabeled in vivo, we compared the amount of bone resorption due to immobilization with bone resorption induced by growth. One hind limb was denervated in growing male rats, 6 weeks of age, that had been chronically prelabeled with [3H]tetracycline, 45calcium, and [3H]proline. The total radioactivity of the whole femur and tibia/fibula from the denervated limb was compared with that from bones of the control limb at 0, 1, 2, 4, and 8 weeks after denervation. The effect of growth on bone formation was measured by net increases in bone length, volume, and mass of matrix and mineral. Experimental bones had a significantly smaller volume and mass. Bone resorption was much greater during growth modeling than during denervation. The additional bone resorption induced by denervation was a small fraction (one-fourth) of the resorption induced by growth. Denervation during growth resulted in less bone being formed due to a smaller gain in matrix and mineral mass as a result of a reduction in bone formation

  3. Hybrid Markov-mass action law for cell activation by rare binding events

    CERN Document Server

    Holcman, C Guerrier D

    2016-01-01

    The binding of molecules, ions or proteins to specific target sites is a generic step for cell activation. However, this step relies on rare events where stochastic particles located in a large bulk are searching for small and often hidden targets and thus remains difficult to study. We present here a hybrid discrete-continuum model where the large ensemble of particles is described by mass-action laws. The rare discrete binding events are modeled by a Markov chain for the encounter of a finite number of small targets by few Brownian particles, for which the arrival time is Poissonian. This model is applied for predicting the time distribution of vesicular release at neuronal synapses that remains elusive. This release is triggered by the binding of few calcium ions that can originate either from the synaptic bulk or from the transient entry through calcium channels. We report that the distribution of release time is bimodal although triggered by a single fast action potential: while the first peak follows a ...

  4. Expression of the calcium receptor CaR in the parathyroid of secondary hyperparathyroidism patients

    Institute of Scientific and Technical Information of China (English)

    王宁宁; 王笑云; 彭韬; 吴宏飞; 胡建明; 赵卫红; 俞香宝

    2004-01-01

    @@ The effects of calcium on parathyroid hormone (PTH) has further discovered in recent years. It has been known that calcium ion concentration in the extracellular fluid is a major determinant of PTH secretion. The relationship between serum intact PTH (iPTH) and calcium ion levels is described by a sigmoidal curve. The calcium concentration that produces half-maximal change in PTH release (the midpoint between maximal and minimal change in PTH release) represents the sensitivity of parathyroid cells to serum calcium. In secondary hyperparathyroidism (SHPT) patients, higher calcium concentrations are needed to suppress PTH secretion, as demonstrated by the PTH-calcium sigmoidal curve. The loss of physiological control over the secretory function and growth of parathyroid tissue in hyperparathyroid disease is still incompletely understood.

  5. Event management

    OpenAIRE

    Urban, Zdeněk

    2013-01-01

    The thesis deals with event management and is formally divided into three sections. The first section provides the theoretical basis for the practical part. It primarily defines the terms event, event management and event marketing. The theoretical part proceeds from the general introduction to more detailed examination of the issue, which includes the classification of event marketing within the marketing and communication mix of the company, the typology of events and explanation of various...

  6. Event management

    OpenAIRE

    Jandová, Dita

    2011-01-01

    The thesis deal with event management. For better insight into this field event management is described on case of management of conference. The thesis has three main parts. In the theoretical part there are definitions of terms like event management, conference and other related terms. Further chapters are concerned with the position of event management in the communication mix, typologies of events and mostly with the crucial aspects of event management. In the second part of the thesis the...

  7. Event management

    OpenAIRE

    Šubrtová, Veronika

    2013-01-01

    This bachelor thesis on the topic event management develops this concept, focuses mainly on the creation of the event and its application in practice. Management, event and event management are described in the theoretical section. The importace of event management in the marketing communications mix is shown subsequently and especially the creation of the event is more detailed described. This is then reflected in the practical part of the thesis, in which the awards gala is planed and orga...

  8. Event management

    OpenAIRE

    Grebíková, Kristýna

    2014-01-01

    The thesis in theoretical part focuses on the concepts of event management and their interaction. The theoretical part focuses on the creation of event planning and marketing strategies, typology of events, and provides a situational analysis, objectives events, defines the target group, plan the resources, establish a budget and will focus on event controlling. The practical part carries theory into practice and deals with the organization of the event in the company TON in Chile. Based on a...

  9. The mechanism of hetero-synaptic interaction based on spatiotemporal intracellular calcium dynamics.

    Directory of Open Access Journals (Sweden)

    Daiki Futagi

    2014-03-01

    Full Text Available In recent physiological experiments focusing on synaptic plasticity, it is shown that synaptic modifications induced at one synapse are accompanied by hetero-synaptic changes at neighbor sites (Bi, 2002. These evidences imply that the hetero-synaptic interaction plays an important role in reconfiguration of synaptic connections to form and maintain functional neural circuits (Takahashi et al., 2012. Although the mechanism of the interaction is still unclear, some physiological studies suggest that the hetero-synaptic interaction could be caused by propagation of intracellular calcium signals (Nishiyama et al., 2000. Concretely, a spike-triggered calcium increase initiates calcium ion propagation along a dendrite through activation of molecular processes at neighboring sites. Here we hypothesized that the mechanism of the hetero-synaptic interaction was based on the intracellular calcium signaling, which is regulated by interactions between NMDA receptors (NMDARs, voltage-dependent calcium channels (VDCCs and Ryanodine receptors (RyRs on endoplasmic reticulum (ER. To assess realizability of the hypothesized interaction mechanism, we simulated intracellular calcium dynamics at a cellular level, using the computational model that integrated the model of intracellular calcium dynamics (Keizer and Levine, 1996 and the multi-compartment neuron model (Poirazi et al., 2003. Using the proposed computational model, we induced calcium influxes at a local site in postsynaptic dendrite by controlling the spike timings of pre- and postsynaptic neurons. As a result, synchronized calcium influxes through NMDARs and VDCCs caused calcium release from ER. According to the phase plane analysis, RyR-mediated calcium release occurred when the calcium concentration in cytoplasm sufficiently increased under the condition of a high calcium concentration in ER. An NMDAR-mediated calcium influx was slow and persistent, consequently responsible for maintaining a high

  10. Impairment of ciprofloxacin absorption by calcium polycarbophil.

    Science.gov (United States)

    Kato, Ryuji; Ueno, Kazuyuki; Imano, Hideki; Kawai, Masayuki; Kuwahara, Shiro; Tsuchishita, Yoshimasa; Yonezawa, Emi; Tanaka, Kazuhiko

    2002-07-01

    The effect of calcium polycarbophil on the absorption of ciprofloxacin, a broad-spectrum antibacterial agent, was evaluated in an in vitro and in vivo study. In the in vitro study, the release of ciprofloxacin from the cellulose membrane in the presence or absence of metal cations was measured using the dissolution test procedure. In the in vivo study, male ST Wistar rats and male volunteers were employed. First, 20 mg/kg of ciprofloxacin alone (Rat Study 1) or 20 mg/kg of ciprofloxacin in combination with 64 mg/kg of calcium chloride (Rat Study 2) was administered orally to 3 rats. Second, a volunteer study was employed and a randomized crossover design with twophases was used. In onephase, volunteers received 400 mg of ciprofloxacin alone (Study 1); in the other phase, they received 400 mg of ciprofloxacin and 1200 mg of fine calcium polycarbophil granules concomitantly (Study 2). The plasma and serum concentrations of ciprofloxacin were measured by high-performance liquid chromatography. The release of ciprofloxacin from the cellulose membrane in the presence of aluminum, calcium, or iron ions was slower than that in the absence of these metal ions. The AUC0-4 and Cmax in Rat Study 2 were lower than those respective values in Rat Study 1. AUC0-4 was approximately 60% lower in Rat Study 2 than Rat Study 1. In the volunteer study, the AUC0-12 and Cmax in Study 2 were lower than those respective values in Study 1. In particular, AUC0-12 was approximately 50% lowerin Study 2 than in Study 1. These findings suggest that when ciprofloxacin and calcium polycarbophil were coadministered concomitantly, a decrease of ciprofloxacin absorption was observed, and this action was caused by the formation of chelate complexes. Therefore, it seems clear that we should avoid the concomitant administration of ciprofloxacin and calcium polycarbophil.

  11. Markov chain models of coupled calcium channels: Kronecker representations and iterative solution methods

    International Nuclear Information System (INIS)

    Mathematical models of calcium release sites derived from Markov chain models of intracellular calcium channels exhibit collective gating reminiscent of the experimentally observed phenomenon of stochastic calcium excitability (i.e., calcium puffs and sparks). Calcium release site models are stochastic automata networks that involve many functional transitions, that is, the transition probabilities of each channel depend on the local calcium concentration and thus the state of the other channels. We present a Kronecker-structured representation for calcium release site models and perform benchmark stationary distribution calculations using both exact and approximate iterative numerical solution techniques that leverage this structure. When it is possible to obtain an exact solution, response measures such as the number of channels in a particular state converge more quickly using the iterative numerical methods than occupation measures calculated via Monte Carlo simulation. In particular, multi-level methods provide excellent convergence with modest additional memory requirements for the Kronecker representation of calcium release site models. When an exact solution is not feasible, iterative approximate methods based on the power method may be used, with performance similar to Monte Carlo estimates. This suggests approximate methods with multi-level iterative engines as a promising avenue of future research for large-scale calcium release site models

  12. 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...

  13. A mathematical model of T lymphocyte calcium dynamics derived from single transmembrane protein properties

    Directory of Open Access Journals (Sweden)

    Christine Dorothee Schmeitz

    2013-09-01

    Full Text Available Fate decision processes of T lymphocytes are crucial for health and disease. Whether a T lymphocyte is activated, divides, gets anergic or initiates apoptosis depends on extracellular triggers and intracellular signalling. Free cytosolic calcium dynamics plays an important role in this context. The relative contributions of store-derived calcium entry and calcium entry from extracellular space to T lymphocyte activation are still a matter of debate. Here we develop a quantitative mathematical model of T lymphocyte calcium dynamics in order to establish a tool which allows to disentangle cause-effect relationships between ion fluxes and observed calcium time courses. The model is based on single transmembrane protein characteristics which have been determined in independent experiments. This reduces the number of unknown parameters in the model to a minimum and ensures the predictive power of the model. Simulation results are subsequently used for an analysis of whole cell calcium dynamics measured under various experimental conditions. The model accounts for a variety of these conditions, which supports the suitability of the modelling approach. The simulation results suggest a model in which calcium dynamics dominantly relies on the opening of channels in calcium stores while calcium entry through calcium-release activated channels (CRAC is more associated with the maintenance of the T lymphocyte calcium levels and prevents the cell from calcium depletion. Our findings indicate that CRAC guarantees a long-term stable calcium level which is required for cell survival and sustained calcium enhancement.

  14. Mechanisms, pools, and sites of spontaneous vesicle release at synapses of rod and cone photoreceptors.

    Science.gov (United States)

    Cork, Karlene M; Van Hook, Matthew J; Thoreson, Wallace B

    2016-08-01

    Photoreceptors have depolarized resting potentials that stimulate calcium-dependent release continuously from a large vesicle pool but neurons can also release vesicles without stimulation. We characterized the Ca(2+) dependence, vesicle pools, and release sites involved in spontaneous release at photoreceptor ribbon synapses. In whole-cell recordings from light-adapted horizontal cells (HCs) of tiger salamander retina, we detected miniature excitatory post-synaptic currents (mEPSCs) when no stimulation was applied to promote exocytosis. Blocking Ca(2+) influx by lowering extracellular Ca(2+) , by application of Cd(2+) and other agents reduced the frequency of mEPSCs but did not eliminate them, indicating that mEPSCs can occur independently of Ca(2+) . We also measured release presynaptically from rods and cones by examining quantal glutamate transporter anion currents. Presynaptic quantal event frequency was reduced by Cd(2+) or by increased intracellular Ca(2+) buffering in rods, but not in cones, that were voltage clamped at -70 mV. By inhibiting the vesicle cycle with bafilomycin, we found the frequency of mEPSCs declined more rapidly than the amplitude of evoked excitatory post-synaptic currents (EPSCs) suggesting a possible separation between vesicle pools in evoked and spontaneous exocytosis. We mapped sites of Ca(2+) -independent release using total internal reflectance fluorescence (TIRF) microscopy to visualize fusion of individual vesicles loaded with dextran-conjugated pHrodo. Spontaneous release in rods occurred more frequently at non-ribbon sites than evoked release events. The function of Ca(2+) -independent spontaneous release at continuously active photoreceptor synapses remains unclear, but the low frequency of spontaneous quanta limits their impact on noise.

  15. Mechanisms, pools, and sites of spontaneous vesicle release at synapses of rod and cone photoreceptors.

    Science.gov (United States)

    Cork, Karlene M; Van Hook, Matthew J; Thoreson, Wallace B

    2016-08-01

    Photoreceptors have depolarized resting potentials that stimulate calcium-dependent release continuously from a large vesicle pool but neurons can also release vesicles without stimulation. We characterized the Ca(2+) dependence, vesicle pools, and release sites involved in spontaneous release at photoreceptor ribbon synapses. In whole-cell recordings from light-adapted horizontal cells (HCs) of tiger salamander retina, we detected miniature excitatory post-synaptic currents (mEPSCs) when no stimulation was applied to promote exocytosis. Blocking Ca(2+) influx by lowering extracellular Ca(2+) , by application of Cd(2+) and other agents reduced the frequency of mEPSCs but did not eliminate them, indicating that mEPSCs can occur independently of Ca(2+) . We also measured release presynaptically from rods and cones by examining quantal glutamate transporter anion currents. Presynaptic quantal event frequency was reduced by Cd(2+) or by increased intracellular Ca(2+) buffering in rods, but not in cones, that were voltage clamped at -70 mV. By inhibiting the vesicle cycle with bafilomycin, we found the frequency of mEPSCs declined more rapidly than the amplitude of evoked excitatory post-synaptic currents (EPSCs) suggesting a possible separation between vesicle pools in evoked and spontaneous exocytosis. We mapped sites of Ca(2+) -independent release using total internal reflectance fluorescence (TIRF) microscopy to visualize fusion of individual vesicles loaded with dextran-conjugated pHrodo. Spontaneous release in rods occurred more frequently at non-ribbon sites than evoked release events. The function of Ca(2+) -independent spontaneous release at continuously active photoreceptor synapses remains unclear, but the low frequency of spontaneous quanta limits their impact on noise. PMID:27255664

  16. Activation of a cGMP-sensitive calcium-dependent chloride channel may cause transition from calcium waves to whole-cell oscillations in smooth muscle cells

    DEFF Research Database (Denmark)

    Jacobsen, Jens Christian; Aalkjær, Christian; Nilsson, Holger;

    2007-01-01

    waves sweeping through the cytoplasm when the SR is stimulated to release calcium. A rise in cyclic guanosine monophosphate (cGMP) leads to the experimentally observed transition from waves to whole-cell calcium oscillations. At the same time membrane potential starts to oscillate and the frequency...... approximately doubles. In this transition, the simulated results point to a key role for a recently discovered cGMP-sensitive calcium-dependent chloride channel. This channel depolarizes the membrane in response to calcium released from the SR. In turn, depolarization causes uniform opening of L-type calcium...... onset of oscillations in membrane potential within the individual cell may underlie sudden intercellular synchronization and the appearance of vasomotion. Key words: Vasomotion, Chloride channel, cGMP, Mathematical model, Calcium waves....

  17. 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 calciu

  18. Calcium phosphate ceramics in drug delivery

    Science.gov (United States)

    Bose, Susmita; Tarafder, Solaiman; Edgington, Joe; Bandyopadhyay, Amit

    2011-04-01

    Calcium phosphate (CaP) particulates, cements and scaffolds have attracted significant interest as drug delivery vehicles. CaP systems, including both hydroxyapaptite and tricalcium phosphates, possess variable stoichiometry, functionality and dissolution properties which make them suitable for cellular delivery. Their chemical similarity to bone and thus biocompatibility, as well as variable surface charge density contribute to their controlled release properties. Among specific research areas, nanoparticle size, morphology, surface area due to porosity, and chemistry controlled release kinetics are the most active. This article discusses CaP systems in their particulate, cements, and scaffold forms for drug, protein, and growth factor delivery toward orthopedic and dental applications.

  19. A review paper on biomimetic calcium phosphate coatings

    OpenAIRE

    Lin, X.; De Groot,, P.A.J.; Wang, D.; Hu, Q; Wismeijer, D.; Liu, Y

    2015-01-01

    Biomimetic calcium phosphate coatings have been developed for bone regeneration and repair because of their biocompatibility, osteoconductivity, and easy preparation. They can be rendered osteoinductive by incorporating an osteogenic agent, such as bone morphogenetic protein 2 (BMP-2), into the crystalline lattice work in physiological situations. The biomimetic calcium phosphate coating enables a controlled, slow and local release of BMP-2 when it undergoes cell mediated coating degradation ...

  20. FORMULATION AND EVALUATION OF SOLID DISPERSION OF ATORVASTATIN CALCIUM

    OpenAIRE

    Monika Sharma; Rajeev Garg; G D Gupta

    2013-01-01

    The present study was designed to improve the solubility and hence enhance the dissolution of hydrophobic drug Atorvastatin calcium (ATC) in order to increase its bioavailability. Solid dispersion of atorvastatin calcium using carrier PEG 4000 was formulated in different ratios by conventional fusion and microwave induced fusion method. In particular, the Microwave technology has been considered in order to prepare an enhanced release dosage form for poorly water soluble drug ATC. Their physi...

  1. Event marketing

    OpenAIRE

    Pham, Quynh Trang

    2008-01-01

    This study aims to analyze event-marketing activities of the small firm and propose new events. At first the theoretical part describes marketing and communication mix and then especially planning and development of event marketing campaign. Research data were collected by the method of survey to propose the new events. Randomly selected customers were asked to fill the questionnaire. Its results were integrated into the proposal of the new events. The interview was realized with the owner of...

  2. Event management

    OpenAIRE

    Pavléková, Markéta

    2013-01-01

    The main theme of the work is event management, which deals with the social events of various types. Event as a mean of communication is a common part of business strategy today and the organization became a separate industry. Procedures how to implement successful event are the essential part of the work. Organizationally demanding activity of event managers, which includes planning, organizing, staffing, leadership and control is supported by marketing activities, which are described in the...

  3. Event management

    OpenAIRE

    Michňa, Michal

    2011-01-01

    The theoretical part of this thesis deals with event management in general. The stress of its theoretical part is put on relation between event management and the other communication channels usually used by marketing experts in a firm. There is also described a confrontation of event management with processes which are basically used in project management. The theoretical part is mainly concerned with event management and organisation of events. There is a deep description of its prepara...

  4. Event management

    OpenAIRE

    Vomáčková, Kateřina

    2013-01-01

    This thesis deals with event management from theory to practice. First part of the thesis consists of literature review of this topic – from definition of basic terms, through event management’s classification in marketing of a company, to description of different stages of event management process. The second part of the thesis is based on practice – an agency that organized for the third year an event focusing on children and sport, is presented here. Last year of this event including...

  5. Optogenetic measurement of presynaptic calcium transients using conditional genetically encoded calcium indicator expression in dopaminergic neurons.

    Directory of Open Access Journals (Sweden)

    Carmelo Sgobio

    Full Text Available Calcium triggers dopamine release from presynaptic terminals of midbrain dopaminergic (mDA neurons in the striatum. However, calcium transients within mDA axons and axon terminals are difficult to study and little is known about how they are regulated. Here we use a newly-developed method to measure presynaptic calcium transients (PreCaTs in axons and terminals of mDA neurons with a genetically encoded calcium indicator (GECI GCaMP3 expressed in transgenic mice. Using a photomultiplier tube-based system, we measured electrical stimulation-induced PreCaTs of mDA neurons in dorsolateral striatum slices from these mice. Single-pulse stimulation produced a transient increase in fluorescence that was completely blocked by a combination of N- and P/Q-type calcium channel blockers. DA and cholinergic, but not serotoninergic, signaling pathways modulated the PreCaTs in mDA fibers. These findings reveal heretofore unexplored dynamic modulation of presynaptic calcium in nigrostriatal terminals.

  6. In vivo calcium imaging of evoked calcium waves in the embryonic cortex

    Directory of Open Access Journals (Sweden)

    Mikhail eYuryev

    2016-01-01

    Full Text Available The dynamics of intracellular calcium fluxes are instrumental in the proliferation, differentiation and migration of neuronal cells. Knowledge thus far of the relationship between these calcium changes and physiological processes in the developing brain has derived principally from ex vivo and in vitro experiments. Here, we present a new method to image intracellular calcium flux in the cerebral cortex of live rodent embryos, whilst attached to the dam through the umbilical cord. Using this approach we demonstrate induction of calcium waves by laser stimulation. These waves are sensitive to ATP-receptor blockade and are significantly increased by pharmacological facilitation of intracellular-calcium release. This approach is the closest to physiological conditions yet achieved for imaging of calcium in the embryonic brain and as such opens new avenues for the study of prenatal brain development. Furthermore, the developed method could open the possibilities of preclinical translational studies in embryos particularly important for developmentally related diseases such as schizophrenia and autism.

  7. Modulation of cytosolic-free calcium transients by changes in intracellular calcium-buffering capacity: correlation with exocytosis and O2-production in human neutrophils

    OpenAIRE

    1984-01-01

    The intracellularly trapped fluorescent calcium indicator, quin 2, was used not only to monitor changes in cytosolic-free calcium, [Ca2+]i, but also to assess the role of [Ca2+]i in neutrophil function. To increase cytosolic calcium buffering, human neutrophils were loaded with various quin 2 concentrations, and [Ca2+]i transients, granule content release as well as superoxide [O2-] production were measured in response to the chemotactic peptide formyl-methionyl-leucyl- phenylalanine (fMLP) a...

  8. 实电解质钙可诱发人肥大细胞组胺和类胰蛋白酶分泌%CALCIUM IONOPHORE INDUCED HISTAMINE AND TRYPTASE RELEASE FROM HUMAN MAST CELLS

    Institute of Scientific and Technical Information of China (English)

    何韶衡; 何永松; 谢华

    2005-01-01

    目的: 利用人大肠组织的肥大细胞和肥大细胞激活的体外研究系统,评价实电解质钙(calcium ionophore A23187, CI)诱导肥大细胞释放类胰蛋白酶和组胺的能力和机制.方法: 经酶悬浮的人大肠肥大细胞与CI共同培养后收集上清液,并用酶联免疫吸附试验(ELISA)的方法检测类胰蛋白酶分泌量,用以玻璃纤维为基础的荧光比色法检测组胺释放量.结果: 经过15 min的培养,CI可引起浓度相关性的组胺和类胰蛋白酶释放.其中组胺的最大分泌量比基础分泌量超出了5.3倍以上,而类胰蛋白酶的最大分泌量则比基础分泌量超出了2.8倍以上.CI在浓度高于1.0 μmol/L时引起的组胺释放量明显多于类胰蛋白酶释放量.时间关系曲线显示,CI的作用从加样后10 s开始,6 min后达高峰并至少持续15 min.百日咳毒素和代谢抑制剂均能抑制CI引起的组胺和类胰蛋白酶释放.结论: 人大肠肥大细胞在受到CI刺激时具有释放类胰蛋白酶和组胺的能力,这个过程与肥大细胞膜G蛋白偶联受体的激活有关,并消耗能量.

  9. Should we prescribe calcium supplements for osteoporosis prevention?

    Science.gov (United States)

    Reid, Ian R

    2014-02-01

    Advocacy for the use of calcium supplements arose at a time when there were no other effective interventions for the prevention of osteoporosis. Their promotion was based on the belief that increasing calcium intake would increase bone formation. Our current understandings of the biology of bone suggest that this does not occur, though calcium does act as a weak antiresorptive. Thus, it slows postmenopausal bone loss but, despite this, recent meta-analyses suggest no significant prevention of fractures. In sum, there is little substantive evidence of benefit to bone health from the use of calcium supplements. Against this needs to be balanced the likelihood that calcium supplement use increases cardiovascular events, kidney stones, gastrointestinal symptoms, and admissions to hospital with acute gastrointestinal problems. Thus, the balance of risk and benefit seems to be consistently negative. As a result, current recommendations are to obtain calcium from the diet in preference to supplements. Dietary calcium intake has not been associated with the adverse effects associated with supplements, probably because calcium is provided in smaller boluses, which are absorbed more slowly since they come together with quantities of protein and fat, resulting in a slower gastric transit time. These findings suggest that calcium supplements have little role to play in the modern therapeutics of osteoporosis, which is based around the targeting of safe and effective anti-resorptive drugs to individuals demonstrated to be at increased risk of future fractures. PMID:24707464

  10. Disturbed calcium signaling in spinocerebellar ataxias and Alzheimer's disease.

    Science.gov (United States)

    Egorova, Polina; Popugaeva, Elena; Bezprozvanny, Ilya

    2015-04-01

    Neurodegenerative disorders, such as spinocerebellar ataxias (SCAs) and Alzheimer's disease (AD) represent a huge scientific and medical question, but the molecular mechanisms of these diseases are still not clear. There is increasing evidence that neuronal calcium signaling is abnormal in many neurodegenerative disorders. Abnormal neuronal calcium release from the endoplasmic reticulum may result in disturbances of cell homeostasis, synaptic dysfunction, and eventual cell death. Neuronal loss is observed in most cases of neurodegenerative diseases. Recent experimental evidence supporting the role of neuronal calcium signaling in the pathogenesis of SCAs and AD is discussed in this review.

  11. Role of intracellular calcium in contraction of internal anal sphincter

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    @@ INTRODUCTION Internal anal sphincter (IAS) is a continuation of the smooth circular muscle layer thickened at the rectum, innervated by vegetative nerve. IAS is a special smooth muscle, which is different from colonic smooth muscle in physiology and pharmaology[1]. It was found that contraction of gastric smooth muscle depends on the influx of extracellular calcium and release of intracellular calcium[2]. In present study, we observed and compared the effects of extra- and intracellular calcium on the contraction of IAS and colonic smooth muscle.

  12. The calcium sensor synaptotagmin 7 is required for synaptic facilitation.

    Science.gov (United States)

    Jackman, Skyler L; Turecek, Josef; Belinsky, Justine E; Regehr, Wade G

    2016-01-01

    It has been known for more than 70 years that synaptic strength is dynamically regulated in a use-dependent manner. At synapses with a low initial release probability, closely spaced presynaptic action potentials can result in facilitation, a short-term form of enhancement in which each subsequent action potential evokes greater neurotransmitter release. Facilitation can enhance neurotransmitter release considerably and can profoundly influence information transfer across synapses, but the underlying mechanism remains a mystery. One proposed mechanism is that a specialized calcium sensor for facilitation transiently increases the probability of release, and this sensor is distinct from the fast sensors that mediate rapid neurotransmitter release. Yet such a sensor has never been identified, and its very existence has been disputed. Here we show that synaptotagmin 7 (Syt7) is a calcium sensor that is required for facilitation at several central synapses. In Syt7-knockout mice, facilitation is eliminated even though the initial probability of release and the presynaptic residual calcium signals are unaltered. Expression of wild-type Syt7 in presynaptic neurons restored facilitation, whereas expression of a mutated Syt7 with a calcium-insensitive C2A domain did not. By revealing the role of Syt7 in synaptic facilitation, these results resolve a longstanding debate about a widespread form of short-term plasticity, and will enable future studies that may lead to a deeper understanding of the functional importance of facilitation.

  13. Calcium's Role in Mechanotransduction during Muscle Development

    Directory of Open Access Journals (Sweden)

    Tatiana Benavides Damm

    2014-01-01

    Full Text Available Mechanotransduction is a process where cells sense their surroundings and convert the physical forces in their environment into an appropriate response. Calcium plays a crucial role in the translation of such forces to biochemical signals that control various biological processes fundamental in muscle development. The mechanical stimulation of muscle cells may for example result from stretch, electric and magnetic stimulation, shear stress, and altered gravity exposure. The response, mainly involving changes in intracellular calcium concentration then leads to a cascade of events by the activation of downstream signaling pathways. The key calcium-dependent pathways described here include the nuclear factor of activated T cells (NFAT and mitogen-activated protein kinase (MAPK activation. The subsequent effects in cellular homeostasis consist of cytoskeletal remodeling, cell cycle progression, growth, differentiation, and apoptosis, all necessary for healthy muscle development, repair, and regeneration. A deregulation from the normal process due to disuse, trauma, or disease can result in a clinical condition such as muscle atrophy, which entails a significant loss of muscle mass. In order to develop therapies against such diseased states, we need to better understand the relevance of calcium signaling and the downstream responses to mechanical forces in skeletal muscle. The purpose of this review is to discuss in detail how diverse mechanical stimuli cause changes in calcium homeostasis by affecting membrane channels and the intracellular stores, which in turn regulate multiple pathways that impart these effects and control the fate of muscle tissue.

  14. Effects of calcium hydroxide addition on the physical and chemical properties of a calcium silicate-based sealer

    Directory of Open Access Journals (Sweden)

    Milton Carlos KUGA

    2014-06-01

    Full Text Available Recently, various calcium silicate-based sealers have been introduced for use in root canal filling. The MTA Fillapex is one of these sealers, but some of its physicochemical properties are not in accordance with the ISO requirements. Objective: The aim of this study was to evaluate the flowability, pH level and calcium release of pure MTA Fillapex (MTAF or containing 5% (MTAF5 or 10% (MTAF10 calcium hydroxide (CH, in weight, in comparison with AH Plus sealer. Material and Methods: The flowability test was performed according to the ISO 6876:2001 requirements. For the pH level and calcium ion release analyses, the sealers were placed individually (n=10 in plastic tubes and immersed in deionized water. After 24 hours, 7 and 14 days, the water in which each specimen had been immersed was evaluated to determine the pH level changes and calcium released. Flowability, pH level and calcium release data were analyzed statistically by the ANOVA test (α=5%. Results: In relation to flowability: MTAF>AH Plus>MTAF5>MTAF10. In relation to the pH level, for 24 h: MTAF5=MTAF10=MTAF>AH Plus; for 7 and 14 days: MTAF5=MTAF10>MTAF>AH Plus. For the calcium release, for all periods: MTAF>MTAF5=MTAF10>AH Plus. Conclusions: The addition of 5% CH to the MTA Fillapex (in weight is an alternative to reduce the high flowability presented by the sealer, without interfering in its alkalization potential.

  15. Effects of calcium hydroxide addition on the physical and chemical properties of a calcium silicate-based sealer

    OpenAIRE

    KUGA, Milton Carlos; DUARTE Marco Antonio Hungaro; SANT'ANNA-JÚNIOR, Arnaldo; KEINE, Kátia Cristina; FARIA, Gisele; Andrea Abi Rached DANTAS; GUIOTTI, Flávia Angélica

    2014-01-01

    Recently, various calcium silicate-based sealers have been introduced for use in root canal filling. The MTA Fillapex is one of these sealers, but some of its physicochemical properties are not in accordance with the ISO requirements. Objective: The aim of this study was to evaluate the flowability, pH level and calcium release of pure MTA Fillapex (MTAF) or containing 5% (MTAF5) or 10% (MTAF10) calcium hydroxide (CH), in weight, in comparison with AH Plus sealer. Material and Methods: The...

  16. Event management

    OpenAIRE

    Palkosková, Barbora

    2011-01-01

    The diploma thesis deals with a term of event management and its connection to the event marketing. First part of the work focuses on terms that are superior to event management and those are marketing and marketing mix of 4P´s. Communication mix is than separated into smaller parts, defining the position of event marketing and management among them. Accent is put on the current possibilities of typology and separation of event and its practical use. Issue of events is connected to the...

  17. Calcium Signaling and Meiotic Exit at Fertilization in Xenopus Egg

    Directory of Open Access Journals (Sweden)

    Alexander A. Tokmakov

    2014-10-01

    Full Text Available Calcium is a universal messenger that mediates egg activation at fertilization in all sexually reproducing species studied. However, signaling pathways leading to calcium generation and the mechanisms of calcium-induced exit from meiotic arrest vary substantially among species. Here, we review the pathways of calcium signaling and the mechanisms of meiotic exit at fertilization in the eggs of the established developmental model, African clawed frog, Xenopus laevis. We also discuss calcium involvement in the early fertilization-induced events in Xenopus egg, such as membrane depolarization, the increase in intracellular pH, cortical granule exocytosis, cortical contraction, contraction wave, cortical rotation, reformation of the nuclear envelope, sperm chromatin decondensation and sister chromatid segregation.

  18. Event management

    OpenAIRE

    Štefl, Petr

    2011-01-01

    This bachelor thesis on the topic of event management deals with planning, organizing, managing, monitoring and implementation of special social events, termed event. It explains what they mean by this term we can imagine and as you can in terms of typology to distinguish events. Literature review consists of the acquired theoretical knowledge in management, project management and marketing. It describes the principles and procedure in place, we should keep the successful organization of ...

  19. Event management

    OpenAIRE

    Strýhalová, Veronika

    2013-01-01

    The Diploma thesis is focused on the Event management company, which organizes a big family minded sport day and describes its activity plan. The thesis consists three main parts, the first – the teoretic part specifices proffesional terms about an event management. This part also describes different event forms which are focused on the right selection and final strategy, the following control of financial situation and event overall what is in general a part of marketing mixture. The second ...

  20. Event management

    OpenAIRE

    Stružková, Tereza

    2014-01-01

    The main objective of this thesis is based on theoretical knowledge and analysis of the actual implementation event action in congress centre of 4*hotel. Asesment of importance, correctnesand effectivess of the vatious procedures of organizin events and create new complete schematic principle of organizin events Implementation actions will be considered from two sides – from side of the company organizer and from the side of event managment coordinator. All the outputs of these two aspect ...

  1. Calcium binding by dietary fibre

    International Nuclear Information System (INIS)

    Dietary fibre from plants low in phytate bound calcium in proportion to its uronic-acid content. This binding by the non-cellulosic fraction of fibre reduces the availability of calcium for small-intestinal absorption, but the colonic microbial digestion of uronic acids liberates the calcium. Thus the ability to maintain calcium balance on high-fibre diets may depend on the adaptive capacity on the colon for calcium. (author)

  2. 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 inhibition of calcium transport processes within the renal tubule. The mechanisms whereby acid alters the integrity and stability of bone have been examined extensively in the published literature. Here, after briefly reviewing this literature, we consider the effects of acid on calcium transport...

  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 ab

  4. Analysis of Intracellular Calcium Signaling in Human Embryonic Stem Cells.

    Science.gov (United States)

    Péntek, Adrienn; Pászty, Katalin; Apáti, Ágota

    2016-01-01

    Measurement of changes in intracellular calcium concentration is one of the most common and useful tools for studying signal transduction pathways or cellular responses in basic research and drug screening purposes as well. Increasing number of such applications using human pluripotent stem cells and their derivatives requires development of calcium signal measurements for this special cell type. Here we describe a modified protocol for analysis of calcium signaling events in human embryonic stem cells, which can be used for other pluripotent cell types (such as iPSC) or their differentiated offspring as well.

  5. Circulating calcium concentrations, vascular disease and mortality: a systematic review.

    Science.gov (United States)

    Reid, I R; Gamble, G D; Bolland, M J

    2016-06-01

    Associations between serum calcium and vascular disease have been reported, but the consistency of these findings is unknown. We conducted a systematic review to determine whether circulating calcium concentrations are associated with risks of cardiovascular disease and death in normocalcaemic populations. We conducted PubMed searches up to 18 December 2014 and scrutinized reference lists of papers. Eligible studies related serum calcium to mortality or cardiovascular events in humans. A follow-up of at least one year was required for longitudinal studies. Studies in populations selected on the basis of renal disease or abnormal serum calcium were excluded. Two investigators performed independent data extraction. The results were tabulated and, where possible, meta-analysed. Five of 11 studies reported a statistically significant positive association between serum calcium and mortality. Meta-analysis of eight of these studies showed a hazard ratio of death of 1.13 (1.09, 1.18) per standard deviation of serum calcium. Eight of 13 studies reported a statistically significant positive association between serum calcium and cardiovascular disease. Meta-analysis of eight studies showed a hazard ratio of cardiovascular disease of 1.08 (1.04, 1.13) per standard deviation of serum calcium. For two studies reporting odds ratios, the pooled odds ratio per standard deviation was 1.22 (1.11, 1.32). When hazard ratios adjusted for cardiovascular risk factors were meta-analysed, the pooled hazard ratio was 1.04 (1.01, 1.08). Other studies demonstrated associations between serum calcium and stroke and between serum calcium and direct measurements of arterial disease and calcification. These observational data indicate that serum calcium is associated with vascular disease and death, but they cannot determine causality. PMID:26749423

  6. A nitrite poisoning event associated with intentional chemical releases%一起蓄意投放亚硝酸盐引发中毒事件的现场流行病学调查

    Institute of Scientific and Technical Information of China (English)

    李刚; 李斌; 林琳; 张茂棠; 刘渠; 黄薇; 谢显清; 陈林; 张顺祥

    2013-01-01

    Objective To compare the field epidemiological investigation and the criminal investigation on a nitrite poisoning event caused by deliberate contamination.Methods Cases were searched according to the definition of the disease.Information on the histories of onset and diet of all the cases and normal population on site,were investigated face to face.Information as ingredients,processing and sales of foods was also gathered.Samples were collected and nitrite detection were performed.Relevant materials were searched,cases were interviewed and data related to criminal results were collected.Results Poisoned persons were staff of a big company in Longgang district of Shenzhen.The overall attack rate was 56.25% (63/112),with suspected and confirmed rates as 41.96% and 14.28%,respectively.The fatality rate was 3.17% (2/63).Clinical manifestation and effect of treatment were in accordance with the characteristics of an episode related to acute nitrite food poisoning in terms of factors as the time of onset,involving different age,sex and jobs of the patients.A total of 191 samples,including vomits from patients and seven batches of food and environment samples,were collected,with a positive detected rate of nitrite as 18.84%.Information gathered from the field environment,food distribution and processing supported the assumption that this was an incident of nitrite poisoning event with intention.Results from the criminal investigation showed that the suspect stemmed from the market management rivalry,bought nitrite,dissolved and spread on food stalls F9 and F10.Conclusion This event of intentional nitrite release resulting in food contamination which further leading to food poisoning,was completely proved by the joint efforts of the teams and expertise from the field epidemiology survey and the criminal investigation.%目的 通过对一起蓄意投放亚硝酸盐引起食物中毒的现场流行病学调查和刑事侦查比较,加强流

  7. Slow-Release Fertilizers For Plants

    Science.gov (United States)

    Ming, Douglas W.; Golden, D. C.

    1995-01-01

    Synthetic mineral provides growing plants with nutrients, including micronutrients. Dissolves slowly in moist soil or in hydroponic solution, releasing constituents. Mineral synthetic apatite into which nutrients calcium, phosphorous, iron, manganese, copper, zinc, molybdenum, chlorine, boron, and sulfur incorporated in form of various salts. Each pellet has homogeneous inorganic composition. Composition readily adjusted to meet precise needs of plant.

  8. Calcium-dependent and calcium-sensitizing pathways in the mature and immature ductus arteriosus.

    Science.gov (United States)

    Clyman, Ronald I; Waleh, Nahid; Kajino, Hiroki; Roman, Christine; Mauray, Francoise

    2007-10-01

    Studies performed in sheep and baboons have shown that after birth, the normoxic muscle media of ductus arteriosus (DA) becomes profoundly hypoxic as it constricts and undergoes anatomic remodeling. We used isolated fetal lamb DA (pretreated with inhibitors of prostaglandin and nitric oxide production) to determine why the immature DA fails to remain tightly constricted during the hypoxic phase of remodeling. Under normoxic conditions, mature DA constricts to 70% of its maximal active tension (MAT). Half of its normoxic tension is due to Ca(2+) entry through calcium L-channels and store-operated calcium (SOC) channels. The other half is independent of extracellular Ca(2+) and is unaffected by inhibitors of sarcoplasmic reticulum (SR) Ca(2+) release (ryanodine) or reuptake [cyclopiazonic acid (CPA)]. The mature DA relaxes slightly during hypoxia (to 60% MAT) due to decreases in calcium L-channel-mediated Ca(2+) entry. Inhibitors of Rho kinase and tyrosine kinase inhibit both Ca(2+)-dependent and Ca(2+)-independent DA tension. Although Rho kinase activity may increase during gestation, immature DA develop lower tensions than mature DA, primarily because of differences in the way they process Ca(2+). Calcium L-channel expression increases with advancing gestation. Under normoxic conditions, differences in calcium L-channel-mediated Ca(2+) entry account for differences in tension between immature (60% MAT) and mature (70% MAT) DA. Under hypoxic conditions, differences in both calcium L-channel-dependent and calcium L-channel-independent Ca(2+) entry, account for differences in tension between immature (33% MAT) and mature (60% MAT) DA. Stimulation of Ca(2+) entry through reverse-mode Na(+)/Ca(2+) exchange or CPA-induced SOC channel activity constrict the DA and eliminate differences between immature and mature DA during both hypoxia and normoxia.

  9. Role of calcium in growth inhibition induced by a novel cell surface sialoglycopeptide

    Science.gov (United States)

    Betz, N. A.; Westhoff, B. A.; Johnson, T. C.; Spooner, B. S. (Principal Investigator)

    1995-01-01

    Our laboratory has purified an 18 kDa cell surface sialoglycopeptide growth inhibitor (CeReS-18) from intact bovine cerebral cortex cells. Evidence presented here demonstrates that sensitivity to CeReS-18-induced growth inhibition in BALB-c 3T3 cells is influenced by calcium, such that a decrease in the calcium concentration in the growth medium results in an increase in sensitivity to CeReS-18. Calcium did not alter CeReS-18 binding to its cell surface receptor and CeReS-18 does not bind calcium directly. Addition of calcium, but not magnesium, to CeReS-18-inhibited 3T3 cells results in reentry into the cell cycle. A greater than 3-hour exposure to increased calcium is required for escape from CeReS-18-induced growth inhibition. The calcium ionophore ionomycin could partially mimic the effect of increasing extracellular calcium, but thapsigargin was ineffective in inducing escape from growth inhibition. Increasing extracellular calcium 10-fold resulted in an approximately 7-fold increase in total cell-associated 45Ca+2, while free intracellular calcium only increased approximately 30%. However, addition of CeReS-18 did not affect total cell-associated calcium or the increase in total cell-associated calcium observed with an increase in extracellular calcium. Serum addition induced mobilization of intracellular calcium and influx across the plasma membrane in 3T3 cells, and pretreatment of 3T3 cells with CeReS-18 appeared to inhibit these calcium mobilization events. These results suggest that a calcium-sensitive step exists in the recovery from CeReS-18-induced growth inhibition. CeReS-18 may inhibit cell proliferation through a novel mechanism involving altering the intracellular calcium mobilization/regulation necessary for cell cycle progression.

  10. Semi-Discrete Systems and Intracellular Calcium Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Pearson, J.; Dawson, S.P.; Mitkov, I.

    1998-10-24

    Intracellular calcium is sequestered in closed membranes such as the sarcoplasmic or endoplasmic reticula and released at discretely distributed protein/receptor channels. The release kinetics can result in the propagation of waves of elevated calcium concentration. The main physical processes are reactions at the release sites and diffusion between the sites. The theory of chemical wave propagation in reaction-diffusion systems is in large part devoted to the study of systems in which there are no extrinsic inhomogeneities. The discrete distribution of the release sites plays a key role in determining the nature of the propagating wave. The authors analyze some simple reaction-diffusion models in order to elucidate the role of discreteness for chemical wave propagation.

  11. Significant event of patient radiation protection in radiotherapy (criterion 2.1): declaration and rating on the ASN-SFRO scale - ASN guide nr 16 - Release of the 01/01/2010

    International Nuclear Information System (INIS)

    This document brings together all the tools for the management of a significant event in radiation protection concerning a patient in radiotherapy. It contains the declaration form, a model for the reporting of significant events, and the ASN-SFRO scale which allows the event to be rated. After a presentation of the regulatory context and references, of the scope of application, this guide addresses the declaration of a significant event: general principles, definition of the 2.1 criterion, examples, delays and modalities of declaration, addressees of a declaration. It addresses the reporting of a significant event: general principles, sending delays and modalities. It addresses the rating on the ASN-SFRO scale: general principles, scale, and rating process. The last part deals with public information

  12. Transmitter release from cochlear hair cells is phase locked to cyclic stimuli of different intensities and frequencies.

    Science.gov (United States)

    Goutman, Juan D

    2012-11-21

    The auditory system processes time and intensity through separate brainstem pathways to derive spatial location as well as other salient features of sound. The independent coding of time and intensity begins in the cochlea, where afferent neurons can fire action potentials at constant phase throughout a wide range of stimulus intensities. We have investigated time and intensity coding by simultaneous presynaptic and postsynaptic recording at the hair cell-afferent synapse from rats. Trains of depolarizing steps to the hair cell were used to elicit postsynaptic currents that occurred at constant phase for a range of membrane potentials over which release probability varied significantly. To probe the underlying mechanisms, release was examined using single steps to various command voltages. As expected for vesicular release, first synaptic events occurred earlier as presynaptic calcium influx grew larger. However, synaptic depression produced smaller responses with longer first latencies. Thus, during repetitive hair cell stimulation, as the hair cell is more strongly depolarized, increased calcium channel gating hurries transmitter release, but the resulting vesicular depletion produces a compensatory slowing. Quantitative simulation of ribbon function shows that these two factors varied reciprocally with hair cell depolarization (stimulus intensity) to produce constant synaptic phase. Finally, we propose that the observed rapid vesicle replenishment would help maintain the vesicle pool, which in turn would equilibrate with the stimulus intensity (and therefore the number of open Ca(2+) channels), so that for trains of different levels the average phase will be conserved. PMID:23175853

  13. Arachidonic acid and calcium metabolism in rnelittin stimulated neutrophils

    Directory of Open Access Journals (Sweden)

    Ole H. Nielsen

    1992-01-01

    Full Text Available Melittin, the predominant fraction of bee venom proteins, was studied in an experimental model of human neutrophil granulocytes to reveal its influence on eicosanoid release, metabolism and receptor function in relation to intracellular calcium metabolism. Melittin (2 μmol/l was as potent as the calcium ionophore A23187 (10 μmol/l for activation of 5-lipoxygenase, releasing arachidonate only from phosphatidyl-choline and phosphatidyl-ethanolamine of cellular membranes, as judged from the decreases in radioactivity by 15.4% and 30.5%, respectively. The mechanism responsible for the release of arachidonate from cellular membranes is closely coupled to cellular calcium metabolism, and melittin was found to promote calcium entry through receptor gated calcium channels, probably due to an activation of phospholipase A2. Furthermore, a down-regulation of leukotriene B4 receptors was seen. The maximal number of binding sites per cell was reduced from a median of 1520 to 950 with melittin (1 μmol/l. The study has revealed some factors important for the inflammatory mechanisms mediated by melittin.

  14. Event Modeling

    DEFF Research Database (Denmark)

    Bækgaard, Lars

    2001-01-01

    The purpose of this chapter is to discuss conceptual event modeling within a context of information modeling. Traditionally, information modeling has been concerned with the modeling of a universe of discourse in terms of information structures. However, most interesting universes of discourse...... are dynamic and we present a modeling approach that can be used to model such dynamics. We characterize events as both information objects and change agents (Bækgaard 1997). When viewed as information objects events are phenomena that can be observed and described. For example, borrow events in a library can...

  15. Event Modeling

    DEFF Research Database (Denmark)

    Bækgaard, Lars

    2001-01-01

    The purpose of this chapter is to discuss conceptual event modeling within a context of information modeling. Traditionally, information modeling has been concerned with the modeling of a universe of discourse in terms of information structures. However, most interesting universes of discourse...... are dynamic and we present a modeling approach that can be used to model such dynamics.We characterize events as both information objects and change agents (Bækgaard 1997). When viewed as information objects events are phenomena that can be observed and described. For example, borrow events in a library can...

  16. Ovarian, hormonal, and reproductive events associated with synchronization of ovulation and timed appointment breeding of Bos indicus-influenced cattle using intravaginal progesterone, gonadotropin-releasing hormone, and prostaglandin F2alpha.

    Science.gov (United States)

    Saldarriaga, J P; Cooper, D A; Cartmill, J A; Zuluaga, J F; Stanko, R L; Williams, G L

    2007-01-01

    The objectives of this study were to 1) compare cumulative pregnancy rates in a traditional management (TM) scheme with those using a synchronization of ovulation protocol (CO-Synch + CIDR) for timed AI (TAI) in Bos indicus-influenced cattle; 2) evaluate ovarian and hormonal events associated with CO-Synch + CIDR and CO-Synch without CIDR; and 3) determine estrual and ovulatory distributions in cattle synchronized with Select-Synch + CIDR. The CO-Synch + CIDR regimen included insertion of a controlled internal drug-releasing device (CIDR) and an injection of GnRH (GnRH-1) on d 0, removal of the CIDR and injection of PGF2alpha (PGF) on d 7, and injection of GnRH (GnRH-2) and TAI 48 h later. For Exp. 1, predominantly Brahman x Hereford (F1) and Brangus females (n = 335) were stratified by BCS, parity, and day postpartum (parous females) before random assignment to CO-Synch + CIDR or TM. To maximize the number of observations related to TAI conception rate (n = 266), an additional 96 females in which TM controls were not available for comparison also received CO-Synch + CIDR. Conception rates to TAI averaged 39 +/- 3% and were not affected by location, year, parity, AI sire, or AI technician. Cumulative pregnancy rates were greater (P < 0.05) at 30 and 60 d of the breeding season in CO-Synch + CIDR (74.1 and 95.9%) compared with TM (61.8 and 89.7%). In Exp. 2, postpartum Brahman x Hereford (F1) cows (n = 100) were stratified as in Exp. 1 and divided into 4 replicates of 25. Within each replicate, approximately one-half (12 to 13) received CO-Synch + CIDR, and the other half received CO-Synch only (no CIDR). No differences were observed between treatments, and the data were pooled. Percentages of cows ovulating to GnRH-1, developing a synchronized follicular wave, exhibiting luteal regression to PGF, and ovulating to GnRH-2 were 40 +/- 5, 60 +/- 5, 93 +/- 2, and 72 +/- 4%, respectively. In Exp. 3, primiparous Brahman x Hereford, (F1) heifers (n = 32) and pluriparous

  17. Ovarian, hormonal, and reproductive events associated with synchronization of ovulation and timed appointment breeding of Bos indicus-influenced cattle using intravaginal progesterone, gonadotropin-releasing hormone, and prostaglandin F2alpha.

    Science.gov (United States)

    Saldarriaga, J P; Cooper, D A; Cartmill, J A; Zuluaga, J F; Stanko, R L; Williams, G L

    2007-01-01

    The objectives of this study were to 1) compare cumulative pregnancy rates in a traditional management (TM) scheme with those using a synchronization of ovulation protocol (CO-Synch + CIDR) for timed AI (TAI) in Bos indicus-influenced cattle; 2) evaluate ovarian and hormonal events associated with CO-Synch + CIDR and CO-Synch without CIDR; and 3) determine estrual and ovulatory distributions in cattle synchronized with Select-Synch + CIDR. The CO-Synch + CIDR regimen included insertion of a controlled internal drug-releasing device (CIDR) and an injection of GnRH (GnRH-1) on d 0, removal of the CIDR and injection of PGF2alpha (PGF) on d 7, and injection of GnRH (GnRH-2) and TAI 48 h later. For Exp. 1, predominantly Brahman x Hereford (F1) and Brangus females (n = 335) were stratified by BCS, parity, and day postpartum (parous females) before random assignment to CO-Synch + CIDR or TM. To maximize the number of observations related to TAI conception rate (n = 266), an additional 96 females in which TM controls were not available for comparison also received CO-Synch + CIDR. Conception rates to TAI averaged 39 +/- 3% and were not affected by location, year, parity, AI sire, or AI technician. Cumulative pregnancy rates were greater (P breeding season in CO-Synch + CIDR (74.1 and 95.9%) compared with TM (61.8 and 89.7%). In Exp. 2, postpartum Brahman x Hereford (F1) cows (n = 100) were stratified as in Exp. 1 and divided into 4 replicates of 25. Within each replicate, approximately one-half (12 to 13) received CO-Synch + CIDR, and the other half received CO-Synch only (no CIDR). No differences were observed between treatments, and the data were pooled. Percentages of cows ovulating to GnRH-1, developing a synchronized follicular wave, exhibiting luteal regression to PGF, and ovulating to GnRH-2 were 40 +/- 5, 60 +/- 5, 93 +/- 2, and 72 +/- 4%, respectively. In Exp. 3, primiparous Brahman x Hereford, (F1) heifers (n = 32) and pluriparous cows (n = 18) received the

  18. Binding of [125I]iodipine to parathyroid cell membranes: Evidence of a dihydropyridine-sensitive calcium channel

    International Nuclear Information System (INIS)

    The parathyroid cell is unusual, in that an increase in extracellular calcium concentrations inhibits PTH release. Calcium channels are glycoproteins that span cell membranes and allow entry of extracellular calcium into cells. We have demonstrated that the calcium channel agonist (+)202-791, which opens calcium channels, inhibits PTH release and that the antagonist (-)202-791, which closes calcium channels, stimulates PTH release. To identify the calcium channels responsible for these effects, we used a radioligand that specifically binds to calcium channels. Bovine parathyroid cell membranes were prepared and incubated under reduced lighting with [125I] iodipine (SA, 2000 Ci/mmol), which recognizes 1,4-dihydropyridine-sensitive calcium channels. Bound ligand was separated from free ligand by rapid filtration through Whatman GF/B filters. Nonspecific binding was measured by the inclusion of nifedipine at 10 microM. Specific binding represented approximately 40% of the total binding. The optimal temperature for [125I] iodipine binding was 4 C, and binding reached equilibrium by 30 min. The equilibrium dissociation constant (Kd) was approximately 550 pM, and the maximum number of binding sites was 780 fmol/mg protein. Both the calcium channel agonist (+)202-791 and antagonist (-)202-791 competitively inhibited [125I] iodipine binding, with 50% inhibition concentrations of 20 and 300 nM, respectively. These data indicate the presence of dihydropyridine-sensitive calcium channels on parathyroid cell membranes

  19. CALCIUM-INDUCED SUPRAMOLECULAR STRUCTURES IN THE CALCIUM CASEINATE SYSTEM

    Science.gov (United States)

    The molecular details deciphering the spontaneous calcium-induced protein aggregation process in the calcium caseinate system remain obscure. Understanding this complex process could lead to potential new applications of this important food ingredient. In this work, we studied calcium-induced supra...

  20. Calcium signaling during reproduction and biotrophic fungal interactions in plants.

    Science.gov (United States)

    Chen, Junyi; Gutjahr, Caroline; Bleckmann, Andrea; Dresselhaus, Thomas

    2015-04-01

    Many recent studies have indicated that cellular communications during plant reproduction, fungal invasion, and defense involve identical or similar molecular players and mechanisms. Indeed, pollen tube invasion and sperm release shares many common features with infection of plant tissue by fungi and oomycetes, as a tip-growing intruder needs to communicate with the receptive cells to gain access into a cell and tissue. Depending on the compatibility between cells, interactions may result in defense, invasion, growth support, or cell death. Plant cells stimulated by both pollen tubes and fungal hyphae secrete, for example, small cysteine-rich proteins and receptor-like kinases are activated leading to intracellular signaling events such as the production of reactive oxygen species (ROS) and the generation of calcium (Ca(2+)) transients. The ubiquitous and versatile second messenger Ca(2+) thereafter plays a central and crucial role in modulating numerous downstream signaling processes. In stimulated cells, it elicits both fast and slow cellular responses depending on the shape, frequency, amplitude, and duration of the Ca(2+) transients. The various Ca(2+) signatures are transduced into cellular information via a battery of Ca(2+)-binding proteins. In this review, we focus on Ca(2+) signaling and discuss its occurrence during plant reproduction and interactions of plant cells with biotrophic filamentous microbes. The participation of Ca(2+) in ROS signaling pathways is also discussed.

  1. The Role of Calcium Scoring in Coronary CTA

    Directory of Open Access Journals (Sweden)

    N Shirvandehi

    2009-01-01

    Full Text Available "nCoronary artery disease is the single largest cause of mortality, and is implicated in one of every five deaths. Conventional risk factors fail to identify one third of deaths caused by CAD. The currently available screening tools for coronary artery disease include Framingham risk assessment, clinical examination, and stress testing. "nIt is of interest that most coronary events occur in the territory of coronary arteries that do not demonstrate prior high grade stenosis. "nComplications of atherosclerotic plaque such as rupture or erosion with subsequent thrombus formation are important events leading to acute coronary syndrome. "nMany different factors including plaque composition, hemodynamic, endothelial function, and blood thrombogenicity may influence which plaques lead to hemodynamically significant events. "nNonetheless, there is a strong relation between the extent of coronary plaque burden and the risk of coronary event. "nSince atherosclerosis is the only disease process associated with calcification of coronary arteries, the degree of coronary calcification as demonstrated by CT is predictive of the overall burden of atherosclerotic plaque. "nThe role of coronary calcium scoring in assessing the risk for future coronary events has been a subject of considerable controversy. It is most important to understand that an elevated burden of coronary calcium may not indicate the presence of significant coronary stenosis, but is associated with a higher risk of a coronary event. "nCalcium scoring is based on the identification of high density material within the coronary circulation on a noncontrast CTscan. Both the EBCT and MDCT have been used for the evaluation of coronary calcium. "nThe current literature suggests that MDCT is comparable to EBCT for coronary calcium screening. "nCalcium scoring is a simple test that should take no more than 5 minutes. A prospective ECG gated scan with 3 mm slice thickness is obtained from the level of

  2. A sensor for calcium uptake

    OpenAIRE

    Collins, Sean; Meyer, Tobias

    2010-01-01

    Mitochondria — the cell’s power plants — increase their energy production in response to calcium signals in the cytoplasm. A regulator of the elusive mitochondrial calcium channel has now been identified.

  3. Children's Bone Health and Calcium

    Science.gov (United States)

    ... Trials Resources and Publications Children's Bone Health and Calcium: Condition Information Skip sharing on social media links ... straight, walk, run, and lead an active life. Calcium is one of the key dietary building blocks ...

  4. Point mutation in the mouse P2X7 receptor affects intercellular calcium waves in astrocytes

    Directory of Open Access Journals (Sweden)

    Sylvia O Suadicani

    2009-04-01

    Full Text Available Purinergic P2 receptors and gap junctions are two groups of proteins involved in the transmission of ICWs (intercellular calcium waves) between astrocytes. The extent to which ICWs spread among these glial cells depends on the amount of ATP released, which can occur through membrane channels, as well as other pathways. Our previous studies have shown that the pore-forming P2X7R (P2X7 receptor) contributes to the amplification of ICW spread by providing sites of ATP release through Panx1 (Pannexin1) channels. To gain insight into the signal transduction events mediating this response we compared the properties of the P2X7R–Panx1 complex in astrocytes from a mouse strain (C57Bl/6) containing a naturally occurring point mutation (P451L) in the C-terminus of the P2X7R to that of non-mutated receptors (Balb/C mice). Electrophysiological, biochemical, pharmacological and fluorescence imaging techniques revealed that the P451L mutation located in the SH3 domain (a Src tyrosine kinase-binding site) of the C-terminus of the P2X7R attenuates Panx1 currents, ATP release and the distance of ICW spread between astrocytes. Similar results were obtained when using the Src tyrosine inhibitor (PP2) and a membrane-permeant peptide spanning the P451L mutation of the P2X7R of the C57Bl6 astrocytes. These results support the participation of a tyrosine kinase of the Src family in the initial steps mediating the opening of Panx1 channels following P2X7R stimulation and in the transmission of calcium signals among astrocytes.

  5. Formate oxidation driven calcium carbonate precipitation by Methylocystis parvus OBBP

    NARCIS (Netherlands)

    Ganendra, G; De Muynck, W; Ho, A.; Arvaniti, EC; Hosseinkhani, B; Ramos, JA; Rahier, H; Boon, N.

    2014-01-01

    Microbially Induced Carbonate Precipitation (MICP) applied in the construction industry poses several disadvantages such as ammonia release to the air and nitric acid production. An alternative MICP from calcium formate by Methylocystis parvus OBBP is presented in this study to overcome these disadv

  6. TMEM16A is associated with voltage-gated calcium channels in mouse retina and its function is disrupted upon mutation of the auxiliary α2δ4 subunit

    Science.gov (United States)

    Caputo, Antonella; Piano, Ilaria; Demontis, Gian Carlo; Bacchi, Niccolò; Casarosa, Simona; Santina, Luca Della; Gargini, Claudia

    2015-01-01

    Photoreceptors rely upon highly specialized synapses to efficiently transmit signals to multiple postsynaptic targets. Calcium influx in the presynaptic terminal is mediated by voltage-gated calcium channels (VGCC). This event triggers neurotransmitter release, but also gates calcium-activated chloride channels (TMEM), which in turn regulate VGCC activity. In order to investigate the relationship between VGCC and TMEM channels, we analyzed the retina of wild type (WT) and Cacna2d4 mutant mice, in which the VGCC auxiliary α2δ4 subunit carries a nonsense mutation, disrupting the normal channel function. Synaptic terminals of mutant photoreceptors are disarranged and synaptic proteins as well as TMEM16A channels lose their characteristic localization. In parallel, calcium-activated chloride currents are impaired in rods, despite unaltered TMEM16A protein levels. Co-immunoprecipitation revealed the interaction between VGCC and TMEM16A channels in the retina. Heterologous expression of these channels in tsA-201 cells showed that TMEM16A associates with the CaV1.4 subunit, and the association persists upon expression of the mutant α2δ4 subunit. Collectively, our experiments show association between TMEM16A and the α1 subunit of VGCC. Close proximity of these channels allows optimal function of the photoreceptor synaptic terminal under physiological conditions, but also makes TMEM16A channels susceptible to changes occurring to calcium channels. PMID:26557056

  7. Understanding release kinetics of biopolymer drug delivery microcapsules for biomedical applications

    Energy Technology Data Exchange (ETDEWEB)

    Desai, Salil, E-mail: sdesai@ncat.ed [Department of Industrial and Systems Engineering, North Carolina A and T State University, NC 27411 (United States); Center for Advanced Materials and Smart Structures, North Carolina A and T State University, Greensboro, NC 27411 (United States); Wake Forest University Institute for Regenerative Medicine, Winston-Salem, NC 27157 (United States); Perkins, Jessica [Department of Industrial and Systems Engineering, North Carolina A and T State University, NC 27411 (United States); Center for Advanced Materials and Smart Structures, North Carolina A and T State University, Greensboro, NC 27411 (United States); Harrison, Benjamin S. [Wake Forest University Institute for Regenerative Medicine, Winston-Salem, NC 27157 (United States); Sankar, Jag [Center for Advanced Materials and Smart Structures, North Carolina A and T State University, Greensboro, NC 27411 (United States)

    2010-04-15

    Drug delivery and dosage concentrations are considered as major focal points in conventional as well as battlefield emergency medicine. The concept of localizing drug delivery via microcapsules is an evolving field to confine the adverse side effects of high concentration drug doses. This paper focuses on understanding release kinetics through biopolymer microcapsules for time-dependent drug release. Calcium alginate microcapsules were manufactured using a direct-write inkjet technique. Rhodamine 6G was used as the release agent to observe the release kinetics from calcium alginate beads in distilled water. A design of experiments was constructed to compare the effect of the microcapsule diameter and different concentrations of calcium chloride (M) and sodium alginate (%, w/v) solutions on the release kinetics profiles of the microcapsules. This research gives insight to identify favorable sizes of microcapsules and concentrations of sodium alginate and calcium chloride solutions for controlled release behavior of drug delivery microcapsules.

  8. Calcium ion channel and epilepsy

    Institute of Scientific and Technical Information of China (English)

    Yudan Lü; Weihong Lin; Dihui Ma

    2006-01-01

    OBJECTIVE: To review the relationship between calcium ion channel and epilepsy for well investigating the pathogenesis of epilepsy and probing into the new therapeutic pathway of epilepsy.DATA SOURCES: A computer-based online research Calcium ion channel and epilepsy related articles published between January 1994 and December 2006 in the CKNI and Wanfang database with the key words of "calcium influxion, epilepsy, calcium-channel blocker". The language was limited to Chinese. At the same time,related articles published between January 1993 and December 2006 in Pubmed were searched for on online with the key words of "calcium influxion, epilepsy" in English.STUDY SELECTION: The materials were selected firstly. Inclusive criteria: ① Studies related to calcium ion channel and the pat1hogenesis of epilepsy. ② Studies on the application of calcium ion channel blocker in the treatment of epilepsy. Exclusive criteria: repetitive or irrelated studies.DATA EXTRACTION: According to the criteria, 123 articles were retrieved and 93 were excluded due to repetitive or irrelated studies. Altogether 30 articles met the inclusive criteria, 11 of them were about the structure and characters of calcium ion channel, 10 about calcium ion channel and the pathogenesis of epilepsy and 9 about calcium blocker and the treatment of epilepsy.DATA SYNTHESIS: Calcium ion channels mainly consist of voltage dependent calcium channel and receptor operated calcium channel. Depolarization caused by voltage gating channel-induced influxion is the pathological basis of epileptic attack, and it is found in many studies that many anti-epileptic drugs have potential and direct effect to rivalizing voltage-dependent calcium ion channel.CONCLUSION: Calcium influxion plays an important role in the seizure of epilepsy. Some calcium antagonists seen commonly are being tried in the clinical therapy of epilepsy that is being explored, not applied in clinical practice. If there are enough evidences to

  9. A Novel Synthesis Method of Porous Calcium Silicate Hydrate Based on the Calcium Oxide/Polyethylene Glycol Composites

    Directory of Open Access Journals (Sweden)

    Wei Guan

    2013-01-01

    Full Text Available This paper proposed a novel method to prepare porous calcium silicate hydrate (CSH based on the calcium oxide/polyethylene glycol (CaO/PEG2000 composites as the calcium materials. The porosity formation mechanism was revealed via X-ray diffraction (XRD, field-emission scanning electron microscopy (FESEM, Brunauer-Emmett-Teller (BET, and Fourier transformed infrared spectroscopy (FT-IR. The reactivity of silica materials (SiO2 enhanced by increasing pH value. Ca2+ could not sustain release from CaO/PEG2000 and reacted with caused by silica to form CSH until the hydrothermal temperature reached to 170°C, avoiding the hardly dissolved intermediates formation efficiently. The as-prepared CSH, due to the large specific surface areas, exhibited excellent release capability of Ca2+ and OH−. This porous CSH has potential application in reducing the negative environmental effects of continual natural phosphate resource depletion.

  10. 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...

  11. Calcium aluminate in alumina

    Science.gov (United States)

    Altay, Arzu

    The properties of ceramic materials are determined not only by the composition and structure of the phases present, but also by the distribution of impurities, intergranular films and second phases. The phase distribution and microstructure both depend on the fabrication techniques, the raw materials used, the phase-equilibrium relations, grain growth and sintering processes. In this dissertation research, various approaches have been employed to understand fundamental phenomena such as grain growth, impurity segregation, second-phase formation and crystallization. The materials system chosen was alumina intentionally doped with calcium. Atomic-scale structural analyses of grain boundaries in alumina were carried on the processed samples. It was found that above certain calcium concentrations, CA6 precipitated as a second phase at all sintering temperatures. The results also showed that abnormal grain growth can occur after precipitation and it is not only related to the calcium level, but it is also temperature dependent. In order to understand the formation mechanism of CA6 precipitates in calcium doped alumina samples, several studies have been carried out using either bulk materials or thin films The crystallization of CA2 and CA6 powders has been studied. Chemical processing techniques were used to synthesize the powders. It was observed that CA2 powders crystallized directly, however CA6 powders crystallized through gamma-Al 2O3 solid solution. The results of energy-loss near-edge spectrometry confirmed that gamma-Al2O3 can dissolve calcium. Calcium aluminate/alumina reaction couples have also been investigated. All reaction couples were heat treated following deposition. It was found that gamma-Al2O3 was formed at the interface as a result of the interfacial reaction between the film and the substrate. gamma-Al 2O3 at the interface was stable at much higher temperatures compared to the bulk gamma-Al2O3 formed prior to the CA6 crystallization. In order to

  12. First Indico Virtual Event

    CERN Document Server

    CERN. Geneva

    2014-01-01

    The first Indico virtual event will take place on February 4th 15:00 and will focus on two main topics The release of Indico v1.2 The migration of the OO Indico backend database (ZODB) to a more standard DBMS It will be fully virtual using the CERN Vidyo service and will foster discussions between developers and administrators of Indico servers worldwide. Connections to the virtual room will be open, but attendees are encouraged to register to the event, in order to be informed of any changes in the organisation if any. If you would like to add a topic of discussion or propose yourself a contribution, please let us know at indico-team@cern.ch. Connection to Vidyo Vidyo connection details are available here CERN Vidyo service documentation can be found here First-time users are encouraged to try the service before connecting to the real event

  13. Calmodulin activation by calcium transients in the postsynaptic density of dendritic spines.

    Directory of Open Access Journals (Sweden)

    Daniel X Keller

    Full Text Available The entry of calcium into dendritic spines can trigger a sequence of biochemical reactions that begins with the activation of calmodulin (CaM and ends with long-term changes to synaptic strengths. The degree of activation of CaM can depend on highly local elevations in the concentration of calcium and the duration of transient increases in calcium concentration. Accurate measurement of these local changes in calcium is difficult because the spaces are so small and the numbers of molecules are so low. We have therefore developed a Monte Carlo model of intracellular calcium dynamics within the spine that included calcium binding proteins, calcium transporters and ion channels activated by voltage and glutamate binding. The model reproduced optical recordings using calcium indicator dyes and showed that without the dye the free intracellular calcium concentration transient was much higher than predicted from the fluorescent signal. Excitatory postsynaptic potentials induced large, long-lasting calcium gradients across the postsynaptic density, which activated CaM. When glutamate was released at the synapse 10 ms before an action potential occurred, simulating activity patterns that strengthen hippocampal synapses, the calcium gradient and activation of CaM in the postsynaptic density were much greater than when the order was reversed, a condition that decreases synaptic strengths, suggesting a possible mechanism underlying the induction of long-term changes in synaptic strength. The spatial and temporal mechanisms for selectivity in CaM activation demonstrated here could be used in other signaling pathways.

  14. Effect of high calcium concentration influents on enhanced biological phosphorus removal process

    International Nuclear Information System (INIS)

    In this work, the effect of calcium concentration in wastewater on the polyphosphate accumulating organisms (PAO) is investigated as well as its influence in PAO metabolism, specifically in the YPO4 (ratio between phosphorus release and acetic acid uptake). For this study a sequencing batch reactor (SBR) anaerobic-aerobic was used, in which the PAO enriched biomass was exposed to different calcium concentrations in the influent wastewater. The results indicate that until a given calcium level in the influent wastewater (35 mg Ca/l) the metabolism is not affect, but higher calcium concentrations lead to significant YPO4 decline. (Author) 18 refs.

  15. Model of Calcium Oscillations Due to Negative Feedback in Olfactory Cilia

    DEFF Research Database (Denmark)

    Reidl, Juergen; Borowski, Peter; Sensse, Anke;

    2006-01-01

    We present a mathematical model for Ca oscillations in the cilia of olfactory sensory neurons. The underlying mechanism is based on direct negative regulation of cyclic nucleotide-gated channels by calcium/calmodulin and does not require any autocatalysis such as calcium-induced calcium release....... The model is in quantitative agreement with available experimental data, both with respect to oscillations and to fast adaptation. We give predictions for the ranges of parameters in which oscillations should be observable. Relevance of the model to calcium oscillations in other systems is discussed....

  16. Structural phase transitions and adduct release in calcium borohydride

    Energy Technology Data Exchange (ETDEWEB)

    Paolone, A.; Palumbo, O.; Rispoli, P.; Miriametro, A.; Cantelli, R.; Luedtke, A.; Rönnebro, E.; Chandra, D.

    2011-09-01

    Ca(BH4)2 compounds were investigated above room temperature by anelastic spectroscopy (AS) and concomitant measurements of thermogravimetry and mass spectrometry (TGA/MS). Both AS and TGA/MS indicate that even after a thermal treatment at 125 °C for 20 h, a non-negligible residual of THF adduct is still present in the sample, which can be removed on a subsequent thermal treatment at temperatures lower than 250 °C. Above 250 °C dehydrogenation takes place. Moreover, AS sensitively detects the occurrence of the α → α’ structural phase transition around 180 °C, and the α’ → β transformation, which is completed around 330 °C. Finally, we also show that both transitions are irreversible and are not accompanied by a latent heat.

  17. Effect of lactose on intestinal absorption of calcium

    International Nuclear Information System (INIS)

    Calcium absorption was immediately increased when lactose was administered in large amounts in the intestine of standard rats fed on a vitamin D diet. The same effect could be reproduced with lactulose, a glucid un-hydrolyzed by lactase and unabsorbed. The occurrence of a saturation process for high doses of calcium agrees with a biochemical process through a carrier; this process was not inhibited by actinomycin D, which does not agree with a 'de novo' synthesis of a calcium binding protein; yet activation of the preexisting protein cannot be excluded. The intestinal effect of lactose resulted in an inhibition of bone catabolism in the adult normocalcemic rat indicating a possible interference of thyrocalcitonin. Finally in the young rat, hypocalcemic by lack of vitamin D, on account of the lactose effect, calcium can be considered as a 'third messenger' in the chain of intracellular events between the interaction of the parathyroid hormone with the bone receptor and the expression of its activity. (author)

  18. Calcium electrotransfer for termination of transgene expression in muscle

    DEFF Research Database (Denmark)

    Hojman, Pernille; Spanggaard, Iben; Olsen, Caroline Holkman;

    2011-01-01

    Gene electrotransfer is expanding in clinical use, thus we have searched for an emergency procedure to stop transgene expression in case of serious adverse events. Calcium is cytotoxic at high intracellular levels, so we tested effects of calcium electrotransfer on transgene expression in muscle....... A clinical grade calcium solution (20 µl, 168 mM) was injected into transfected mouse or rat tibialis cranialis muscle. Ca(2+) uptake was quantified using calcium 45 ((45)Ca), and voltage and time between injection and pulsation were varied. Extinction of transgene expression was investigated by using both...... voltage pulses of 1000 V/cm. Using these parameters, in vivo imaging showed that transgene expression significantly decreased 4 hr after Ca(2+) electrotransfer and was eliminated within 24 hr. Similarly, serum erythropoietin was reduced by 46% at 4 hr and to control levels at 2 days. Histological analyses...

  19. Imaging Calcium in Drosophila at Egg Activation.

    Science.gov (United States)

    Derrick, Christopher J; York-Andersen, Anna H; Weil, Timothy T

    2016-01-01

    Egg activation is a universal process that includes a series of events to allow the fertilized egg to complete meiosis and initiate embryonic development. One aspect of egg activation, conserved across all organisms examined, is a change in the intracellular concentration of calcium (Ca(2+)) often termed a 'Ca(2+) wave'. While the speed and number of oscillations of the Ca(2+) wave varies between species, the change in intracellular Ca(2+) is key in bringing about essential events for embryonic development. These changes include resumption of the cell cycle, mRNA regulation, cortical granule exocytosis, and rearrangement of the cytoskeleton. In the mature Drosophila egg, activation occurs in the female oviduct prior to fertilization, initiating a series of Ca(2+)-dependent events. Here we present a protocol for imaging the Ca(2+) wave in Drosophila. This approach provides a manipulable model system to interrogate the mechanism of the Ca(2+) wave and the downstream changes associated with it. PMID:27584955

  20. Automatic coronary calcium scoring in low-dose chest computed tomography

    NARCIS (Netherlands)

    Isgum, I.; Prokop, M.; Niemeijer, M.; Viergever, M.; Ginneken, B. van

    2012-01-01

    The calcium burden as estimated from non-ECGsynchronized CT exams acquired in screening of heavy smokers has been shown to be a strong predictor of cardiovascular events. We present a method for automatic coronary calcium scoring with low-dose, non-contrast-enhanced, non-ECG-synchronized chest CT. F

  1. Event management

    OpenAIRE

    Plechatý, Josef

    2012-01-01

    This theses focused on Event management is divided into two parts. First part includes theoretical knowledge while the second part is strictly practical. The first part is focused on marketing, its importance and basic terms. The chapter about marketing is followed by marketing mix, which is shortly characterized and divided into advertisement, sales promotion, public relations and other elements of the communication mix. The last part is a detailed study of Event marketing which includes th...

  2. Histamine release from cord blood basophils

    DEFF Research Database (Denmark)

    Nielsen, Bent Windelborg; Damsgaard, Tine Engberg; Herlin, Troels;

    1990-01-01

    The histamine release (HR) after challenge with anti-IgE, concanavalin A, N-formyl-met-leu-phe and the calcium ionophore A23187 from 97 cord blood samples was determined by a microfiber-based assay. Maximum HR with anti-IgE showed great inter-individual variation (median: 20.5; range: 1-104 ng...... stimulated by the calcium ionophore A 23187 was found to be highly dependent on the storage time of the EDTA-anticoagulated blood samples, which should be carefully controlled....

  3. Visualization of Golgia apparatus as an intracellular calcium store by laser scanning confocal microscope

    Institute of Scientific and Technical Information of China (English)

    CUIJIE; YANLI; 等

    1995-01-01

    Using laser scanning confocal microscopy,we have found that the in cells loaded with fluo-3/AM,highest intracellular Ca2+ in the perinuclear region is associated with the Golgi apparatus.The spatiotemporal subcellular distribution of Ca2+ in living human fibroblasts exposing to calcium-free medium in response to agonists has been investigated.PDGF,which releases Ca2+ from intracellular stores by inositol(1,4,5)-trisphosphate pathway ,produced a biphasic transient rise in intracellular calcium.The initial rise was resulted from a direct release of calcium from the golgi apparatus.Calcium could be also released from and reaccumulated into the Golgi apparatus by the stimulation of thapsigargin,an inhibitor of the Ca2+ transport ATPase of intracellular calcium store,Permeablizing the plasma membrane by 10μM digitonin resulted in the calcium release from the Golgi apparatus and depletion of the internal calcium store.These results suggest that the Golgi apparatus plays a role in Ca2+ regulation in signal transduction.

  4. Multilevel complexity of calcium signaling:Modeling angiogenesis

    Institute of Scientific and Technical Information of China (English)

    Luca; Munaron; Marco; Scianna

    2012-01-01

    Intracellular calcium signaling is a universal,evolutionary conserved and versatile regulator of cell biochemistry.The complexity of calcium signaling and related cell machinery can be investigated by the use of experimental strategies,as well as by computational approaches.Vascular endothelium is a fascinating model to study the specific properties and roles of calcium signals at multiple biological levels.During the past 20 years,live cell imaging,patch clamp and other techniques have allowed us to detect and interfere with calcium signaling in endothelial cells(ECs),providing a huge amount of information on the regulation of vascularization(angiogenesis) in normal and tumoral tissues.These data range from the spatiotemporal dynamics of calcium within different cell microcompartments to those in entire multicellular and organized EC networks.Beside experimental strategies,in silico endothelial models,specifically designed for simulating calcium signaling,are contributing to our knowledge of vascular physiol-ogy and pathology.They help to investigate and predict the quantitative features of proangiogenic events moving through subcellular,cellular and supracellular levels.This review focuses on some recent developments of computational approaches for proangiogenic endothelial calcium signaling.In particular,we discuss the creation of hybrid simulation environments,which combine and integrate discrete Cellular Potts Models.They are able to capture the phenomenological mechanisms of cell morphological reorganization,migration,and intercellular adhesion,with single-cell spatiotemporal models,based on reaction-diffusion equations that describe the agonist-induced intracellular calcium events.

  5. Mobility of calcium channels in the presynaptic membrane.

    Science.gov (United States)

    Schneider, Romy; Hosy, Eric; Kohl, Johannes; Klueva, Julia; Choquet, Daniel; Thomas, Ulrich; Voigt, Andreas; Heine, Martin

    2015-05-01

    Unravelling principles underlying neurotransmitter release are key to understand neural signaling. Here, we describe how surface mobility of voltage-dependent calcium channels (VDCCs) modulates release probabilities (P(r)) of synaptic vesicles (SVs). Coupling distances of 100 nm have been reported for SVs and VDCCs in different synapses. Tracking individual VDCCs revealed that within hippocampal synapses, ∼60% of VDCCs are mobile while confined to presynaptic membrane compartments. Intracellular Ca(2+) chelation decreased VDCC mobility. Increasing VDCC surface populations by co-expression of the α2δ1 subunit did not alter channel mobility but led to enlarged active zones (AZs) rather than higher channel densities. VDCCs thus scale presynaptic scaffolds to maintain local mobility. We propose that dynamic coupling based on mobile VDCCs supports calcium domain cooperativity and tunes neurotransmitter release by equalizing Pr for docked SVs within AZs. PMID:25892305

  6. Fruit Calcium: Transport and Physiology

    Directory of Open Access Journals (Sweden)

    Bradleigh eHocking

    2016-04-01

    Full Text Available Calcium has well-documented roles in plant signaling, water relations and cell wall interactions. Significant research into how calcium impacts these individual processes in various tissues has been carried out; however, the influence of calcium on fruit ripening has not been thoroughly explored. Here, we review the current state of knowledge on how calcium may impact fruit development, physical traits and disease susceptibility through facilitating developmental and stress response signaling, stabilizing membranes, influencing water relations and modifying cell wall properties through cross-linking of de-esterified pectins. We explore the involvement of calcium in hormone signaling integral to ripening and the physiological mechanisms behind common disorders that have been associated with fruit calcium deficiency (e.g. blossom end rot in tomatoes or bitter pit in apples. This review works towards an improved understanding of how the many roles of calcium interact to influence fruit ripening, and proposes future research directions to fill knowledge gaps. Specifically, we focus mostly on grapes and present a model that integrates existing knowledge around these various functions of calcium in fruit, which provides a basis for understanding the physiological impacts of sub-optimal calcium nutrition in grapes. Calcium accumulation and distribution in fruit is shown to be highly dependent on water delivery and cell wall interactions in the apoplasm. Localized calcium deficiencies observed in particular species or varieties can result from differences in xylem morphology, fruit water relations and pectin composition, and can cause leaky membranes, irregular cell wall softening, impaired hormonal signaling and aberrant fruit development. We propose that the role of apoplasmic calcium-pectin crosslinking, particularly in the xylem, is an understudied area that may have a key influence on fruit water relations. Furthermore, we believe that improved

  7. Ca2+ sparks evoked by depolarization of rat ventricular myocytes involve multiple release sites

    Institute of Scientific and Technical Information of China (English)

    ZANGWei-Jin; YUXiao-Jiang; ZANGYi-Min

    2003-01-01

    AIM:To investigate the fundamental nature of calcium release events (Ca2+‘sparks’) evoked in rat ventricular myocytes during excitation-contraction (E-C) coupling. METHODS: High-resolution line-scan confocal imaging with the fluorescent calcium indicator and patch-clamp techniques were used to study the spontaneous Ca2+ sparks and sparks evoked by depolarization. RESULTS: 1)Line scans oriented along the length of the cell showed that both spontaneous sparks and sparks evoked by depolarization to -35mV appeared to arise at single sites spacing about 1.80μm apart (ie, the sarcomere length), and measurements of their longitudinal spread (full-width at halfmaximal amplitude:FWHM) followed single Gaussian distributions with means of 2.6μm. 2)Different to this,transverse line scans often revealed spontaneous and evoked sparks that appeared to arise near-synchronously from paired sites. Measurements of transverse FWHM of both spontaneous and evoked sparks showed bimodal distributions, which were fit well by the sums of two Gaussian curves with means of 1.8 and 2.9μm for spontaneous sparks and ith means of 1.9 and 3.1 μm for evoked sparks. Relative areas under the two Gaussian curves were 1.73:1 and 1.85:1, respectively, for spontaneous and evoked sparks. CONCLUSIONS: Ca2+ sparks evoked by depolarization are not ′unitary′ events, but often involve multiple sites of origin along Z-lines, as previously shown for spontaneous sparks. Thus, Ca2+ released during sparks directly triggered by influx through L-type Ca2+ channels may, in turn, trigger neighboring sites. The restricted involvement of only a few transverse release sites preserves the essential feature of the ‘local control’ theory of E-C coupling.

  8. 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.

  9. Effect of resorbable calcium aluminate ceramics on regulation of calcium and phosphorus in rats.

    Science.gov (United States)

    Carvalho, B A; Bajpai, P K; Graves, G A

    1976-06-01

    Ions released from resorbable ceramics could be toxic to the animal. Experiments were designed to study the effect of implanting three different weights of porous resorbable calcium aluminate ceramics (0.172, 0.332, and 0.504 g) in rats for a total duration of 300 days. Gross and microscopic examination of heart, liver, kidneys, trachea with thyroid, and muscle adjacent to the implant did not show any pathological changes. Calcium and inorganic phosphate content of bone, serum and urine were not affected by the implants. Urine hydroxyproline excretion did not change in the animals implanted with ceramics. Animals implanted with 0.332 g of ceramics had a significantly higher serum alkaline phosphatase activity than the control animals. Resorption of calcium and depositon of inorganic phosphates in the implanted ceramics suggested that ions were being exchanged with the body fluids. Implantation of 0.172 to 0.332 g porous resorbable calcium aluminate ceramic was not toxic to the animal.

  10. COMMERCIAL SNF ACCIDENT RELEASE FRACTIONS

    Energy Technology Data Exchange (ETDEWEB)

    S.O. Bader

    1999-10-18

    The purpose of this design analysis is to specify and document the total and respirable fractions for radioactive materials that are released from an accident event at the Monitored Geologic Repository (MGR) involving commercial spent nuclear fuel (CSNF) in a dry environment. The total and respirable release fractions will be used to support the preclosure licensing basis for the MGR. The total release fraction is defined as the fraction of total CSNF assembly inventory, typically expressed as an activity inventory (e.g., curies), of a given radionuclide that is released to the environment from a waste form. The radionuclides are released from the inside of breached fuel rods (or pins) and from the detachment of radioactive material (crud) from the outside surfaces of fuel rods and other components of fuel assemblies. The total release fraction accounts for several mechanisms that tend to retain, retard, or diminish the amount of radionuclides that are available for transport to dose receptors or otherwise can be shown to reduce exposure of receptors to radiological releases. The total release fraction includes a fraction of airborne material that is respirable and could result in inhalation doses. This subset of the total release fraction is referred to as the respirable release fraction. Potential accidents may involve waste forms that are characterized as either bare (unconfined) fuel assemblies or confined fuel assemblies. The confined CSNF assemblies at the MGR are contained in shipping casks, canisters, or disposal containers (waste packages). In contrast to the bare fuel assemblies, the container that confines the fuel assemblies has the potential of providing an additional barrier for diminishing the total release fraction should the fuel rod cladding breach during an accident. However, this analysis will not take credit for this additional bamer and will establish only the total release fractions for bare unconfined CSNF assemblies, which may however be

  11. Methane release

    International Nuclear Information System (INIS)

    The Swiss Gas Industry has carried out a systematic, technical estimate of methane release from the complete supply chain from production to consumption for the years 1992/1993. The result of this survey provided a conservative value, amounting to 0.9% of the Swiss domestic output. A continuation of the study taking into account new findings with regard to emission factors and the effect of the climate is now available, which provides a value of 0.8% for the target year of 1996. These results show that the renovation of the network has brought about lower losses in the local gas supplies, particularly for the grey cast iron pipelines. (author)

  12. Differential Dendritic Integration of Synaptic Potentials and Calcium in Cerebellar Interneurons.

    Science.gov (United States)

    Tran-Van-Minh, Alexandra; Abrahamsson, Therése; Cathala, Laurence; DiGregorio, David A

    2016-08-17

    Dendritic voltage integration determines the transformation of synaptic inputs into output firing, while synaptic calcium integration drives plasticity mechanisms thought to underlie memory storage. Dendritic calcium integration has been shown to follow the same synaptic input-output relationship as dendritic voltage, but whether similar operations apply to neurons exhibiting sublinear voltage integration is unknown. We examined the properties and cellular mechanisms of these dendritic operations in cerebellar molecular layer interneurons using dendritic voltage and calcium imaging, in combination with synaptic stimulation or glutamate uncaging. We show that, while synaptic potentials summate sublinearly, concomitant dendritic calcium signals summate either linearly or supralinearly depending on the number of synapses activated. The supralinear dendritic calcium triggers a branch-specific, short-term suppression of neurotransmitter release that alters the pattern of synaptic activation. Thus, differential voltage and calcium integration permits dynamic regulation of neuronal input-output transformations without altering intrinsic nonlinear integration mechanisms.

  13. Differential Dendritic Integration of Synaptic Potentials and Calcium in Cerebellar Interneurons.

    Science.gov (United States)

    Tran-Van-Minh, Alexandra; Abrahamsson, Therése; Cathala, Laurence; DiGregorio, David A

    2016-08-17

    Dendritic voltage integration determines the transformation of synaptic inputs into output firing, while synaptic calcium integration drives plasticity mechanisms thought to underlie memory storage. Dendritic calcium integration has been shown to follow the same synaptic input-output relationship as dendritic voltage, but whether similar operations apply to neurons exhibiting sublinear voltage integration is unknown. We examined the properties and cellular mechanisms of these dendritic operations in cerebellar molecular layer interneurons using dendritic voltage and calcium imaging, in combination with synaptic stimulation or glutamate uncaging. We show that, while synaptic potentials summate sublinearly, concomitant dendritic calcium signals summate either linearly or supralinearly depending on the number of synapses activated. The supralinear dendritic calcium triggers a branch-specific, short-term suppression of neurotransmitter release that alters the pattern of synaptic activation. Thus, differential voltage and calcium integration permits dynamic regulation of neuronal input-output transformations without altering intrinsic nonlinear integration mechanisms. PMID:27537486

  14. 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...

  15. Mechanical characterization of calcium pectinate hydrogel for controlled drug delivery

    Directory of Open Access Journals (Sweden)

    Chung Jin Thau

    2003-01-01

    Full Text Available Calcium pectinate beads, a paniculate hydrogel system, is an attractive drug carrier for oral delivery. In this study, a poorly water-soluble model drug indomethacin was incorporated into calcium pectinate beads made of different pectin concentrations, which were produced by an extrusion method. The effect of pectin concentration on bead size, circularity, swelling behavior, and mechanical properties, as well as in vitro drug release profile was investigated. The mechanical properties of calcium pectinate beads were determined by a micromanipulation technique. The drug release profile was measured using a standard British Pharmacopoeia method. It was found that the beads made of higher pectin concentration in general had a less permeable matrix structure and greater mechanical rigidity, although they swelled more after hydration. However, such an effect was not significant when the pectin concentration was increased to above 8%. Micromanipulation measurements showed that there was significant relaxation of the force being imposed on single hydrated beads when they were held, but this phenomenon did not occur on dry beads, which means that the force relaxation was dominated by liquid loss from the beads. The rate of the force relaxation was determined, and has been related to the release rate of the model drug entrapped in the calcium pectinate beads.

  16. Calcium carbonate microspheres as carriers for the anticancer drug camptothecin

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Neng [Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8LT (United Kingdom); State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Department of Bio-pharmaceutical Engineering, School of Chemical Engineering, Sichuan University, Chengdu ,610065 (China); Yin, Huabing, E-mail: huabing.yin@glasgow.ac.uk [Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8LT (United Kingdom); Ji, Bozhi; Klauke, Norbert; Glidle, Andrew [Division of Biomedical Engineering, School of Engineering, University of Glasgow, Glasgow, G12 8LT (United Kingdom); Zhang, Yongkui; Song, Hang [Department of Bio-pharmaceutical Engineering, School of Chemical Engineering, Sichuan University, Chengdu ,610065 (China); Cai, Lulu; Ma, Liang; Wang, Guangcheng [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Chen, Lijuan, E-mail: lijuan17@hotmail.com [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Wang, Wenwen [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China)

    2012-12-01

    Biogenic calcium carbonate has come to the attention of many researchers as a promising drug delivery system due to its safety, pH sensitivity and the large volume of information already in existence on its medical use. In this study, we employed bovine serum albumin (BSA) as an additive to synthesize a series of porous calcium carbonate microspheres (CCMS). These spheres, identified as vaterite, are stable both in aqueous solutions and organic solvents. Camptothecin, an effective anticancer agent, was loaded into the CCMS by simple diffusion and adsorption. The camptothecin loaded CCMS showed sustained cell growth inhibitory activity and a pH dependent release of camptothecin. With a few hours, the release is negligible under physiological conditions (pH = 7.4) but almost complete at pH 4 to 6 (i.e. pHs found in lysosomes and solid tumor tissue respectively). These findings suggest that porous, biogenic calcium carbonate microspheres could be promising carriers for the safe and efficient delivery of anticancer drugs of low aqueous solubility. - Highlights: Black-Right-Pointing-Pointer BSA-doped calcium carbonate microspheres with porous structure were prepared. Black-Right-Pointing-Pointer Camptothecin was encapsulated in the spherical microparticles with encapsulation efficiency up to 11%. Black-Right-Pointing-Pointer The release of encapsulated camptothecin is pH dependent Black-Right-Pointing-Pointer In vitro studies showed an effective anticancer activity of the camptothecin- microspheres.

  17. Calcium carbonate microspheres as carriers for the anticancer drug camptothecin

    International Nuclear Information System (INIS)

    Biogenic calcium carbonate has come to the attention of many researchers as a promising drug delivery system due to its safety, pH sensitivity and the large volume of information already in existence on its medical use. In this study, we employed bovine serum albumin (BSA) as an additive to synthesize a series of porous calcium carbonate microspheres (CCMS). These spheres, identified as vaterite, are stable both in aqueous solutions and organic solvents. Camptothecin, an effective anticancer agent, was loaded into the CCMS by simple diffusion and adsorption. The camptothecin loaded CCMS showed sustained cell growth inhibitory activity and a pH dependent release of camptothecin. With a few hours, the release is negligible under physiological conditions (pH = 7.4) but almost complete at pH 4 to 6 (i.e. pHs found in lysosomes and solid tumor tissue respectively). These findings suggest that porous, biogenic calcium carbonate microspheres could be promising carriers for the safe and efficient delivery of anticancer drugs of low aqueous solubility. - Highlights: ► BSA-doped calcium carbonate microspheres with porous structure were prepared. ► Camptothecin was encapsulated in the spherical microparticles with encapsulation efficiency up to 11%. ► The release of encapsulated camptothecin is pH dependent ► In vitro studies showed an effective anticancer activity of the camptothecin- microspheres.

  18. Coatless alginate pellets as sustained-release drug carrier for inflammatory bowel disease treatment.

    Science.gov (United States)

    Md Ramli, Siti Hajar; Wong, Tin Wui; Naharudin, Idanawati; Bose, Anirbandeep

    2016-11-01

    Conventional alginate pellets underwent rapid drug dissolution and failed to exert colon targeting unless subjected to complex coating. This study designed coatless delayed-release oral colon-specific alginate pellets for ulcerative colitis treatment. Alginate pellets, formulated with water-insoluble ethylcellulose and various calcium salts, were prepared using solvent-free melt pelletization technique which prevented reaction between processing materials during agglomeration and allowed reaction to initiate only in dissolution. Combination of acid-soluble calcium carbonate and highly water-soluble calcium acetate did not impart colon-specific characteristics to pellets due to pore formation in fragmented matrices. Combination of moderately water-soluble calcium phosphate and calcium acetate delayed drug release due to rapid alginate crosslinking by soluble calcium from acetate salt followed by sustaining alginate crosslinking by calcium phosphate. The use of 1:3 ethylcellulose-to-alginate enhanced the sustained drug release attribute. The ethylcellulose was able to maintain the pellet integrity without calcium acetate. Using hydrophobic prednisolone as therapeutic, hydrophilic alginate pellets formulated with hydrophobic ethylcellulose and moderately polar calcium phosphate exhibited colon-specific in vitro drug release and in vivo anti-inflammatory action. Coatless oral colon-specific alginate pellets can be designed through optimal formulation with melt pelletization as the processing technology. PMID:27516284

  19. Calcium signaling properties of a thyrotroph cell line, mouse TαT1 cells.

    Science.gov (United States)

    Tomić, Melanija; Bargi-Souza, Paula; Leiva-Salcedo, Elias; Nunes, Maria Tereza; Stojilkovic, Stanko S

    2015-12-01

    TαT1 cells are mouse thyrotroph cell line frequently used for studies on thyroid-stimulating hormone beta subunit gene expression and other cellular functions. Here we have characterized calcium-signaling pathways in TαT1 cells, an issue not previously addressed in these cells and incompletely described in native thyrotrophs. TαT1 cells are excitable and fire action potentials spontaneously and in response to application of thyrotropin-releasing hormone (TRH), the native hypothalamic agonist for thyrotrophs. Spontaneous electrical activity is coupled to small amplitude fluctuations in intracellular calcium, whereas TRH stimulates both calcium mobilization from intracellular pools and calcium influx. Non-receptor-mediated depletion of intracellular pool also leads to a prominent facilitation of calcium influx. Both receptor and non-receptor stimulated calcium influx is substantially attenuated but not completely abolished by inhibition of voltage-gated calcium channels, suggesting that depletion of intracellular calcium pool in these cells provides a signal for both voltage-independent and -dependent calcium influx, the latter by facilitating the pacemaking activity. These cells also express purinergic P2Y1 receptors and their activation by extracellular ATP mimics TRH action on calcium mobilization and influx. The thyroid hormone triiodothyronine prolongs duration of TRH-induced calcium spikes during 30-min exposure. These data indicate that TαT1 cells are capable of responding to natively feed-forward TRH signaling and intrapituitary ATP signaling with acute calcium mobilization and sustained calcium influx. Amplification of TRH-induced calcium signaling by triiodothyronine further suggests the existence of a pathway for positive feedback effects of thyroid hormones probably in a non-genomic manner.

  20. [Study on the Influence of Mineralizer on the Preparation of Calcium Aluminates Based on Infrared Spectroscopy].

    Science.gov (United States)

    Fan, Wei; Wang, Liang; Zheng, Huai-li; Chen, Wei; Tang, Xiao-min; Shang, Juan-fang; Qian, Li

    2015-05-01

    In this study, effect of mineralizer on the structure and spectraproperties of calcium aluminates formation was extensively studied. Medium or low-grade bauxite and calcium carbonate were used as raw material and mineralizer CaF2 as additive. Calcium aluminates can be obtained after mixing fully, calcination and grinding. The prepared calcium aluminates can be directly used for the production of polyaluminiumchloride (PAC), polymeric aluminum sulfate, sodium aluminate and some other water treatment agents. The calcium aluminates preparation technology was optimized by investigating the mass ratio of raw materials (bauxiteand calcium carbonate) and mineralizer CaF2 dosage. The structure and spectra properties of bauxite and calcium aluminates were characterized by Fourier transform infrared(FTIR) spectroscopy analysis and the mineralization mechanism of the mineralizer was studied. FTIR spectra indicated that the addition of mineralizer promoted the decomposition and transformation of the diaspore, gibbsite and kaolinite, the decomposition of calcium carbonate, and more adequately reaction between bauxite and calcium carbonate. In addition, not only Ca in calcium carbonate and Si in bauxite were more readily reacted, but also Si-O, Si-O-Al and Al-Si bonds in the bauxite were more fractured which contributed to the release of Al in bauxite, and therefore, the dissolution rate of Al2O3 could be improved. The dissolution rate of Al2O3 can be promoted effectively when the mineralizer CaF2 was added in a mass ratio amount of 3%. And the mineralizer CaF2 cannot be fully functioned, when its dosage was in a mass percent of 1. 5%. Low-grade bauxite was easier to sinter for the preparation of calcium aluminates comparing with the highgrade one. The optimum material ratio for the preparation of calcium aluminates calcium at 1 250 °C was the mass ratio between bauxite and calcium carbonate of 1 : 0. 6 and mineralizer CaF2 mass ratio percent of 3%. PMID:26415430

  1. Event management

    OpenAIRE

    Myslivcová, Hana Bc.

    2007-01-01

    V práci je popsán teoretický postup při pořádání eventů, který vychází ze zásad projektového řízení. Tyto postupy jsou také aplikovány v praktické realizaci eventu. Následuje výzkum aktuálních trendů v event managementu a výzkum cílových skupin s pomocí dat MML/TGI.

  2. Calcium and ER stress mediate hepatic apoptosis after burn injury

    Science.gov (United States)

    Gauglitz, Gerd G.; Song, Juquan; Kulp, Gabriela A.; Finnerty, Celeste C.; Cox, Robert A.; Barral, José M.; Herndon, David N.; Boehning, Darren

    2009-01-01

    Abstract A hallmark of the disease state following severe burn injury is decreased liver function, which results in gross metabolic derangements that compromise patient survival. The underlying mechanisms leading to hepatocyte dysfunction after burn are essentially unknown. The aim of the present study was to determine the underlying mechanisms leading to hepatocyte dysfunction and apoptosis after burn. Rats were randomized to either control (no burn) or burn (60% total body surface area burn) and sacrificed at various time‐points. Liver was either perfused to isolate primary rat hepatocytes, which were used for in vitro calcium imaging, or liver was harvested and processed for immunohistology, transmission electron microscopy, mitochondrial isolation, mass spectroscopy or Western blotting to determine the hepatic response to burn injury in vivo. We found that thermal injury leads to severely depleted endoplasmic reticulum (ER) calcium stores and consequent elevated cytosolic calcium concentrations in primary hepatocytes in vitro. Burn‐induced ER calcium depletion caused depressed hepatocyte responsiveness to signalling molecules that regulate hepatic homeostasis, such as vasopressin and the purinergic agonist ATP. In vivo, thermal injury resulted in activation of the ER stress response and major alterations in mitochondrial structure and function – effects which may be mediated by increased calcium release by inositol 1,4,5‐trisphosphate receptors. Our results reveal that thermal injury leads to dramatic hepatic disturbances in calcium homeostasis and resultant ER stress leading to mitochondrial abnormalities contributing to hepatic dysfunction and apoptosis after burn injury. PMID:20141609

  3. Lipid body accumulation alters calcium signaling dynamics in immune cells.

    Science.gov (United States)

    Greineisen, William E; Speck, Mark; Shimoda, Lori M N; Sung, Carl; Phan, Nolwenn; Maaetoft-Udsen, Kristina; Stokes, Alexander J; Turner, Helen

    2014-09-01

    There is well-established variability in the numbers of lipid bodies (LB) in macrophages, eosinophils, and neutrophils. Similarly to the steatosis observed in adipocytes and hepatocytes during hyperinsulinemia and nutrient overload, immune cell LB hyper-accumulate in response to bacterial and parasitic infection and inflammatory presentations. Recently we described that hyperinsulinemia, both in vitro and in vivo, drives steatosis and phenotypic changes in primary and transformed mast cells and basophils. LB reach high numbers in these steatotic cytosols, and here we propose that they could dramatically impact the transcytoplasmic signaling pathways. We compared calcium release and influx responses at the population and single cell level in normal and steatotic model mast cells. At the population level, all aspects of FcɛRI-dependent calcium mobilization, as well as activation of calcium-dependent downstream signaling targets such as NFATC1 phosphorylation are suppressed. At the single cell level, we demonstrate that LB are both sources and sinks of calcium following FcɛRI cross-linking. Unbiased analysis of the impact of the presence of LB on the rate of trans-cytoplasmic calcium signals suggest that LB enrichment accelerates calcium propagation, which may reflect a Bernoulli effect. LB abundance thus impacts this fundamental signaling pathway and its downstream targets.

  4. Cellular calcium mobilization

    International Nuclear Information System (INIS)

    In vascular and other smooth muscles, occurrence of intracellular Ca stores which can be mobilized to support contraction may be a general phenomenon. The Ca stores are characterized by the requirement for release by high concentrations of agonists acting on plasma membrane receptors, by the failure of the released Ca2+ to recycle to the store, by the occurrence of rapid refilling of the store from the extracellular space, and by disappearance of the store when the plasma membrane is made leaky by saponin. In contrast to agonist-released Ca stores, those released by caffeine to support contraction in Ca2+-free solutions are more slowly lost and refilled, are not always emptied when the agonist-related store is emptied, and do not disappear after saponin treatment. Stores released by agonists have been suggested to be in the endoplasmic reticulum near the plasma membrane or at the inner aspect of the plasma membrane related to high affinity, pH-dependent Ca-binding sites. Caffeine-released stores are assumed to be in endoplasmic reticulum. Continued exposure of some tissues to Ca2+-free solutions unmasks what is considered to be a recycling Ca store releasable by agonists. Release of Ca2+ and its reaccumulation in this store appear to be slower than at the nonrecycling store. The contractions which persist for many hours in Ca2+-free solution are inhibited temporarily by Ca2+ restoration. Existence of a recycling store of releasable Ca2+ requires occurrence of mechanisms to abolish Ca2+ extrusion or leak-out of the cell and to ensure recycling to the same store

  5. Topography's event

    DEFF Research Database (Denmark)

    Munck Petersen, Rikke

    The aim of the paper is first to discuss how horizon and scale can be understood, secondly how they differ and what they might have in common? If topography can be seen as a way of working with these relations experiences, creations and latencies? Thirdly if diagrams and diagrammatology can bring...... space formation - to stimulate and elaborate the event of conception and topological thinking....

  6. Investigating calcium polyphosphate addition to a conventional calcium phosphate cement for bone-interfacing applications

    Science.gov (United States)

    Krausher, Jennifer Lynn

    Calcium phosphate cements (CPCs) are of great interest in bone regeneration applications because of their biocompatibility and osteoconductivity, and as delivery vehicles for therapeutics; however, delivery applications have been limited by adverse interactions between therapeutics and the cement setting reaction. Amorphous calcium polyphosphate (CPP) yields a biodegradable material with a demonstrated drug delivery capacity following appropriate processing. The incorporation of drug-loaded CPP into a CPC is under consideration as a method of minimizing adverse interactions and extending drug release. This thesis represents the first investigation into the effects of CPP addition on the properties, setting and antibiotic release profile of a conventional apatitic calcium phosphate cement. As-made, gelled and vancomycin-loaded CPP particulate were added to the powder component of a conventional dicalcium phosphate/tetracalcium phosphate CPC. The setting behaviour, set properties and microstructure of the resulting CPP-CPCs were evaluated with setting time testing (Gilmore needle method), pH testing, mechanical testing, SEM imaging, XRD and FTIR analysis. In vitro degradation and elution behaviour were evaluated by monitoring calcium release (atomic absorbance spectroscopy), mechanical strength and vancomycin release (UV-visual spectrophotometry). CPP addition was found to increase the setting time, reduce the mechanical strength and inhibit the conversion of the CPC starting powders to the set apatitic phase. The most likely mechanism for the observed effect of CPP addition was the adsorption of polyphosphate chains on the particle surfaces, which would inhibit the dissolution of the starting powders and the conversion of apatite precursor phases to apatite, leading to reduced mechanical properties. The detrimental effects of CPP were reduced by limiting the CPP fraction to less than a few weight per cent and increasing the size of the CPP particulate. CPP

  7. Effect of sepsis on calcium uptake and content in skeletal muscle and regulation in vitro by calcium of total and myofibrillar protein breakdown in control and septic muscle: Results from a preliminary study

    International Nuclear Information System (INIS)

    Because high calcium concentration in vitro stimulates muscle proteolysis, calcium has been implicated in the pathogenesis of increased muscle breakdown in different catabolic conditions. Protein breakdown in skeletal muscle is increased during sepsis, but the effect of sepsis on muscle calcium uptake and content is not known. In this study the influence of sepsis, induced in rats by cecal ligation and puncture, on muscle calcium uptake and content was studied. Sixteen hours after cecal ligation and puncture or sham operation, calcium content of the extensor digitorum longus (EDL) and soleus (SOL) muscles was determined with an atomic absorption spectrometer. Calcium uptake was measured in intact SOL muscles incubated in the presence of calcium 45 (45Ca) for between 1 and 120 minutes. Total and myofibrillar protein breakdown was determined in SOL muscles, incubated in the presence of different calcium concentrations (0; 2.5; 5.0 mmol/L), and measured as release into the incubation medium of tyrosine and 3-methylhistidine (3-MH), respectively. Calcium content was increased by 51% (p less than 0.001) during sepsis in SOL and by 10% (p less than 0.05) in EDL muscle. There was no difference in 45Ca uptake between control and septic muscles during the early phase (1 to 5 minutes) of incubation. During more extended incubation (30 to 120 minutes), muscles from septic rats took up significantly more 45Ca than control muscles (p less than 0.05). Tyrosine release by incubated SOL muscles from control and septic rats was increased when calcium was added to the incubation medium, and at a calcium concentration of 2.5 mmol/L, the increase in tyrosine release was greater in septic than in control muscle. Addition of calcium to the incubation medium did not affect 3-MH release in control or septic muscle

  8. Effect of sepsis on calcium uptake and content in skeletal muscle and regulation in vitro by calcium of total and myofibrillar protein breakdown in control and septic muscle: Results from a preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Benson, D.W.; Hasselgren, P.O.; Hiyama, D.T.; James, J.H.; Li, S.; Rigel, D.F.; Fischer, J.E.

    1989-07-01

    Because high calcium concentration in vitro stimulates muscle proteolysis, calcium has been implicated in the pathogenesis of increased muscle breakdown in different catabolic conditions. Protein breakdown in skeletal muscle is increased during sepsis, but the effect of sepsis on muscle calcium uptake and content is not known. In this study the influence of sepsis, induced in rats by cecal ligation and puncture, on muscle calcium uptake and content was studied. Sixteen hours after cecal ligation and puncture or sham operation, calcium content of the extensor digitorum longus (EDL) and soleus (SOL) muscles was determined with an atomic absorption spectrometer. Calcium uptake was measured in intact SOL muscles incubated in the presence of calcium 45 (45Ca) for between 1 and 120 minutes. Total and myofibrillar protein breakdown was determined in SOL muscles, incubated in the presence of different calcium concentrations (0; 2.5; 5.0 mmol/L), and measured as release into the incubation medium of tyrosine and 3-methylhistidine (3-MH), respectively. Calcium content was increased by 51% (p less than 0.001) during sepsis in SOL and by 10% (p less than 0.05) in EDL muscle. There was no difference in 45Ca uptake between control and septic muscles during the early phase (1 to 5 minutes) of incubation. During more extended incubation (30 to 120 minutes), muscles from septic rats took up significantly more 45Ca than control muscles (p less than 0.05). Tyrosine release by incubated SOL muscles from control and septic rats was increased when calcium was added to the incubation medium, and at a calcium concentration of 2.5 mmol/L, the increase in tyrosine release was greater in septic than in control muscle. Addition of calcium to the incubation medium did not affect 3-MH release in control or septic muscle.

  9. Calcium signaling in neocortical development.

    Science.gov (United States)

    Uhlén, Per; Fritz, Nicolas; Smedler, Erik; Malmersjö, Seth; Kanatani, Shigeaki

    2015-04-01

    The calcium ion (Ca(2+) ) is an essential second messenger that plays a pivotal role in neurogenesis. In the ventricular zone (VZ) of the neocortex, neural stem cells linger to produce progenitor cells and subsequently neurons and glial cells, which together build up the entire adult brain. The radial glial cells, with their characteristic radial fibers that stretch from the inner ventricular wall to the outer cortex, are known to be the neural stem cells of the neocortex. Migrating neurons use these radial fibers to climb from the proliferative VZ in the inner part of the brain to the outer layers of the cortex, where differentiation processes continue. To establish the complex structures that constitute the adult cerebral cortex, proliferation, migration, and differentiation must be tightly controlled by various signaling events, including cytosolic Ca(2+) signaling. During development, cells regularly exhibit spontaneous Ca(2+) activity that stimulates downstream effectors, which can elicit these fundamental cell processes. Spontaneous Ca(2+) activity during early neocortical development depends heavily on gap junctions and voltage dependent Ca(2+) channels, whereas later in development neurotransmitters and synapses exert an influence. Here, we provide an overview of the literature on Ca(2+) signaling and its impact on cell proliferation, migration, and differentiation in the neocortex. We point out important historical studies and review recent progress in determining the role of Ca(2+) signaling in neocortical development.

  10. Functional separation of deep cytoplasmic calcium from subplasmalemmal space calcium in cultured human uterine smooth muscle cells.

    Science.gov (United States)

    Young, Roger C; Zhang, PeiSheng

    2004-07-01

    For smooth muscle, two important functions of free intracellular calcium (Ca(2+)(i)) are modulation of plasma membrane excitability properties and modulation of the contractile apparatus. As proposed by van Breemen, Ca(2+)(i) can be divided into the subplasmalemmal space (Ca(2+)(sps)) and the deep cytosol (Ca(2+)(d)) by the superficial calcium buffer barrier. Using these distinctions, Ca(2+)(sps) activates the large conductance calcium-activated potassium channel (BK), and Ca(2+)(d) binds calcium-dependent fluorescent probes in the cytoplasm. We present here combined fluorescence-patch clamp experiments designed to simultaneously assess Ca(2+)(d) and Ca(2+)(sps) in cultured human uterine smooth muscle cells. Open probabilities (P(o)) of the BK channel were measured using the cell-attached patch clamp technique. P(o) was used to approximate changes of [Ca(2+)(sps)]. Relative concentrations of Ca(2+)(d) were approximated by observing fluorescence of Calcium green-1 (F). Under control conditions, we found similar time courses for rises of P(o) and F following 10nM oxytocin (OT) addition. In parallel experiments, but with lanthanum (La(3+)) added to the bath to block transmembrane calcium flux, P(o) was only slightly affected, but F increases were delayed and blunted. These data paradoxically indicate that following OT stimulation, the primary source of calcium for Ca(2+)(sps) is internal stores, and calcium entry from the extracellular space is required to raise Ca(2+)(d). When cells were exposed to cyclopiazonic acid (CPA) to release SR calcium stores, P(o) increased slowly, then persisted at large values. The persistence of P(o) rises suggests that removal of calcium from the subplasmalemmal space is primarily via reuptake into the SR. In the presence of La(3+), OT-induced rises of F were slightly prolonged, suggesting that transmembrane calcium flux contributes to decreasing Ca(2+)(d), but is not the primary mechanism. In summary, these data demonstrate that Ca(2

  11. Adsorption of Potassium and Calcium Ions by Variable Charge Soils

    Institute of Scientific and Technical Information of China (English)

    LIHONG-YAN; JIGUO-LIANG

    1992-01-01

    Interactions of potassium and calcium ions with four typical variable charge soils in South China were examined by measuring pK-0.5pCa value with a potassium ion-selective electrode and a calcium ion-selective electrode,and pK value with a potassium ion-selective electrode.The results showed that adsorption of potassium and calcium ions increased with soil suspension pH,and the tendency of the pK-0.5pCa value changing with pH differed with respect to pH range and potassium to calcium ratio.Adsorption of equal amount of calcium and potassium ions led to release of an identical number of protons,suggesting similar adsorption characteristics of these two ions when adsorbed by variable charge soils.Compared with red soil,latosol and lateritic red soil had higher adsorption selectivities for calcium ion.The red soil had a greater affinity for potassium ion than that for calcium ion at low concentration,which seems to result from its possession of 2:1 type minerals,such as vermiculite and mica with a high affinity for potassium ion.The results indicated that adsorption of potassium and calcium ions by the variable charge soils was chiefly caused by the electrostatic attraction between the cations and the soil surfaces.Moreover,it was found that sulfate could affect the adsorption by changing soil surface properties and by forming ion-pair.

  12. Mefloquine-Induced Disruption of Calcium Homeostasis in Mammalian Cells Is Similar to That Induced by Ionomycin▿

    OpenAIRE

    Caridha, D.; Yourick, D.; Cabezas, M.; De Wolf, L.; Hudson, T. H.; Dow, G. S.

    2007-01-01

    In previous studies, we have shown that mefloquine disrupts calcium homeostasis in neurons by depletion of endoplasmic reticulum (ER) stores, followed by an influx of external calcium across the plasma membrane. In this study, we explore two hypotheses concerning the mechanism(s) of action of mefloquine. First, we investigated the possibility that mefloquine activates non-N-methyl-d-aspartic acid receptors and the inositol phosphate 3 (IP3) signaling cascade leading to ER calcium release. Sec...

  13. Effects of rifampin-chitosan-calcium alginate sustained release microspheres in spinal tuberculosis models in rabbits%利福平-壳聚糖-海藻酸钙缓释微球在兔脊柱结核模型中的作用

    Institute of Scientific and Technical Information of China (English)

    尚博; 方继锋; 侯耀鹏; 李庆富; 王先泉

    2015-01-01

    目的 观察利福平-壳聚糖(CS)-海藻酸钙(CA)纳米缓释微球在体内外释药效果及对兔脊柱结核模型的治疗作用.方法 合成利福平-CS-CA纳米缓释微球,对该微球进行形态学观察和测定其分布.取新西兰大白兔60只,随机分为A、B、C3组,通过兔腰椎椎体钻孔植入结核标准菌株H37Rv,建立兔脊柱结核模型.A组为对照组,不予用药.B组每只兔灌喂利福平每天12 mg/kg;C组每只兔灌喂利福平12 mg/(kg·d),于第十腰椎旁给予缓释利福平微球(含利福平75 mg/kg),观察3组兔模型在体内的释药性质及抗结核的作用效果.结果 (1)利福平缓释微球表面光滑,球体均匀度好,无粘连现象.(2)利福平微球的载药量为(34.58±1.47)%,包封率为(56.23±1.55)%.(3)A组兔模型腰5、6椎体均有明显破坏,椎间隙变窄,1只出现明显后凸畸形.5只兔腰大肌肿胀,腰大肌内可见低密度暗区.B组兔模型中6只兔腰5椎体和腰6椎体有较明显破坏,2只兔腰大肌肿胀.C组中7只兔腰6椎体上部有轻度骨质破坏,腰5、6椎间隙无明显改变,另3只兔观察至术后12周仍无明显影像学改变.(4)体内实验结果显示,将利福平微球按含利福平75 mg/kg的剂量植入C组兔模型椎旁后,椎旁肌和椎体内利福平浓度可维持在结核菌最低抑菌浓度(MCI)以上,持续到术后49 d.结论 通过椎体钻孔植入结核菌的方法可以建立兔脊柱结核模型,利福平-CS-CA纳米缓释微球的控释化疗可增加椎旁局部药物浓度,有效抑制结核杆菌生长.%Objective To investigate the drug release effect of rifampin (RFP)-chitosan (CS)-calcium alginate (CA) sustained release microspheres (Ms) in vivo and in vitro in the treatment of spinal tuberculosis model in rabbits.Methods RFP-CS-CA nano microspheres were synthesized,and their morphology was observer,and distribution was determined.Sixty New Zealand rabbits were randomly divided into three groups.the rabbit lumbar

  14. Calcium titration of Chlamydomonas reinhardtii centrin and its structural changes

    Science.gov (United States)

    Ocaña, Wanda; Pastrana-Ríos, Belinda

    2014-07-01

    Chlamydomonas reinhardtii centrin is a highly conserved calcium binding protein belonging to the EF-hand superfamily. Centrin, like other calcium binding proteins, changes conformation upon calcium binding. In addition, the calcium binding sites are comprised mainly of aspartates and glutamates which would serve as probes for a calcium binding event. 2D IR correlation spectroscopy has proven to be a valuable technique to determine the differences in the molecular behavior of the EF-hand domains within centrin. Moreover, the differences in affinity for calcium displayed by these domains were correlated to differences in the molecular behavior of these EF-hand domains when compared with each other and the full-length protein. We were able to confirm the nature of the two independent domains within centrin. Furthermore, we established the mechanism of aggregation was self-association due to adsorption of centrin to the ZnSe ATR crystal and estimated the extent of aggregation of the full-length protein.

  15. Calcium – how and why?

    Indian Academy of Sciences (India)

    J K Jaiswal

    2001-09-01

    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 that during the origin and early evolution of life the Ca2+ ion was given a unique opportunity to be used in several biological processes because of its unusual physical and chemical properties.

  16. Calcium Phosphate Biomaterials: An Update

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Current calcium phosphate (CaP) biomaterials for bone repair, substitution, augmentation and regeneration include hydroxyapatite ( HA ) from synthetic or biologic origin, beta-tricalcium phosphate ( β-TCP ) , biphasic calcium phosphate (BCP), and are available as granules, porous blocks, components of composites (CaP/polymer) cements, and as coatings on orthopedic and dental implants. Experimental calcium phosphate biomaterials include CO3- and F-substituted apatites, Mg-and Zn-substituted β-TCP, calcium phosphate glasses. This paper is a brief review of the different types of CaP biomaterials and their properties such as bioactivity, osteoconductivity, osteoinductivity.

  17. 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.

  18. Cytosolic organelles shape calcium signals and exo-endocytotic responses of chromaffin cells.

    Science.gov (United States)

    García, Antonio G; Padín, Fernando; Fernández-Morales, José C; Maroto, Marcos; García-Sancho, Javier

    2012-01-01

    The concept of stimulus-secretion coupling was born from experiments performed in chromaffin cells 50 years ago. Stimulation of these cells with acetylcholine enhances calcium (Ca(2+)) entry and this generates a transient elevation of the cytosolic Ca(2+) concentration ([Ca(2+)](c)) that triggers the exocytotic release of catecholamines. The control of the [Ca(2+)](c) signal is complex and depends on various classes of plasmalemmal calcium channels, cytosolic calcium buffers, the uptake and release of Ca(2+) from cytoplasmic organelles, such as the endoplasmic reticulum, mitochondria, chromaffin vesicles and the nucleus, and Ca(2+) extrusion mechanisms, such as the plasma membrane Ca(2+)-stimulated ATPase, and the Na(+)/Ca(2+) exchanger. Computation of the rates of Ca(2+) fluxes between the different cell compartments support the proposal that the chromaffin cell has developed functional calcium tetrads formed by calcium channels, cytosolic calcium buffers, the endoplasmic reticulum, and mitochondria nearby the exocytotic plasmalemmal sites. These tetrads shape the Ca(2+) transients occurring during cell activation to regulate early and late steps of exocytosis, and the ensuing endocytotic responses. The different patterns of catecholamine secretion in response to stress may thus depend on such local [Ca(2+)](c) transients occurring at different cell compartments, and generated by redistribution and release of Ca(2+) by cytoplasmic organelles. In this manner, the calcium tetrads serve to couple the variable energy demands due to exo-endocytotic activities with energy production and protein synthesis. PMID:22209033

  19. Calcium measurement methods

    Directory of Open Access Journals (Sweden)

    CarloAlberto Redi

    2010-09-01

    Full Text Available Rightly stressed by prof. Wolfgang Walz in the Preface to the series Neuromethods series, the “careful application of methods is probably the most important step in the process of scientific inquiry”. Thus, I strongly suggest to all those interested in calcium signaling and especially to the new-comers in the hot topic of neuroscience (which has so much space even in science-society debate for its implications in legal issues and in the judge-decision process to take profit from this so well edited book. I am saying this since prof. Verkhratsky and prof. Petersen......

  20. 21 CFR 573.240 - Calcium periodate.

    Science.gov (United States)

    2010-04-01

    ... with calcium hydroxide or calcium oxide to form a substance consisting of not less than 60 percent by... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium periodate. 573.240 Section 573.240 Food... Additive Listing § 573.240 Calcium periodate. The food additive calcium periodate may be safely used...

  1. 21 CFR 573.260 - Calcium silicate.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium silicate. 573.260 Section 573.260 Food and... Listing § 573.260 Calcium silicate. Calcium silicate, including synthetic calcium silicate, may be safely used as an anticaking agent in animal feed, provided that the amount of calcium silicate does...

  2. The number and spatial distribution of IP3 receptors underlying calcium puffs in Xenopus oocytes.

    Science.gov (United States)

    Shuai, Jianwei; Rose, Heather J; Parker, Ian

    2006-12-01

    Calcium puffs are local Ca(2+) release events that arise from a cluster of inositol 1,4,5-trisphosphate receptor channels (IP(3)Rs) and serve as a basic "building block" from which global Ca(2+) waves are generated. Important questions remain as to the number of IP(3)Rs that open during a puff, their spatial distribution within a cluster, and how much Ca(2+) current flows through each channel. The recent discovery of "trigger" events-small Ca(2+) signals that immediately precede puffs and are interpreted to arise through opening of single IP(3)R channels-now provides a useful yardstick by which to calibrate the Ca(2+) flux underlying puffs. Here, we describe a deterministic numerical model to simulate puffs and trigger events. Based on confocal linescan imaging in Xenopus oocytes, we simulated Ca(2+) release in two sequential stages; representing the trigger by the opening of a single IP(3)R in the center of a cluster for 12 ms, followed by the concerted opening of some number of IP(3)Rs for 19 ms, representing the rising phase of the puff. The diffusion of Ca(2+) and Ca(2+)-bound indicator dye were modeled in a three-dimensional cytosolic volume in the presence of immobile and mobile Ca(2+) buffers, and were used to predict the observed fluorescence signal after blurring by the microscope point-spread function. Optimal correspondence with experimental measurements of puff spatial width and puff/trigger amplitude ratio was obtained assuming that puffs arise from the synchronous opening of 25-35 IP(3)Rs, each carrying a Ca(2+) current of approximately 0.4 pA, with the channels distributed through a cluster 300-800 nm in diameter. PMID:16980372

  3. Hydration of Portland cement with additions of calcium sulfoaluminates

    Energy Technology Data Exchange (ETDEWEB)

    Le Saout, Gwenn, E-mail: gwenn.le-saout@mines-ales.fr [Empa, Swiss Federal Laboratories for Materials Science and Technology, Concrete and Construction Chemistry Laboratory, Ueberlandstrasse 129, CH-8600 Duebendorf (Switzerland); Lothenbach, Barbara [Empa, Swiss Federal Laboratories for Materials Science and Technology, Concrete and Construction Chemistry Laboratory, Ueberlandstrasse 129, CH-8600 Duebendorf (Switzerland); Hori, Akihiro [DENKA Chemicals GmbH, Wehrhahn-Center, Cantadorstr. 3, D-40211 Duesseldorf (Germany); Higuchi, Takayuki [Denki Kagaku Kogyo Kabushiki Kaisha (DENKA), Omi, Itoigawa, Niigata, 949-0393 (Japan); Winnefeld, Frank [Empa, Swiss Federal Laboratories for Materials Science and Technology, Concrete and Construction Chemistry Laboratory, Ueberlandstrasse 129, CH-8600 Duebendorf (Switzerland)

    2013-01-15

    The effect of mineral additions based on calcium aluminates on the hydration mechanism of ordinary Portland cement (OPC) was investigated using isothermal calorimetry, thermal analysis, X-ray diffraction, scanning electron microscopy, solid state nuclear magnetic resonance and pore solution analysis. Results show that the addition of a calcium sulfoaluminate cement (CSA) to the OPC does not affect the hydration mechanism of alite but controls the aluminate dissolution. In the second blend investigated, a rapid setting cement, the amorphous calcium aluminate reacts very fast to ettringite. The release of aluminum ions strongly retards the hydration of alite but the C-S-H has a similar composition as in OPC with no additional Al to Si substitution. As in CSA-OPC, the aluminate hydration is controlled by the availability of sulfates. The coupling of thermodynamic modeling with the kinetic equations predicts the amount of hydrates and pore solution compositions as a function of time and validates the model in these systems.

  4. Hydration of Portland cement with additions of calcium sulfoaluminates

    International Nuclear Information System (INIS)

    The effect of mineral additions based on calcium aluminates on the hydration mechanism of ordinary Portland cement (OPC) was investigated using isothermal calorimetry, thermal analysis, X-ray diffraction, scanning electron microscopy, solid state nuclear magnetic resonance and pore solution analysis. Results show that the addition of a calcium sulfoaluminate cement (CSA) to the OPC does not affect the hydration mechanism of alite but controls the aluminate dissolution. In the second blend investigated, a rapid setting cement, the amorphous calcium aluminate reacts very fast to ettringite. The release of aluminum ions strongly retards the hydration of alite but the C–S–H has a similar composition as in OPC with no additional Al to Si substitution. As in CSA–OPC, the aluminate hydration is controlled by the availability of sulfates. The coupling of thermodynamic modeling with the kinetic equations predicts the amount of hydrates and pore solution compositions as a function of time and validates the model in these systems.

  5. Biodegradable magnetic calcium phosphate nanoformulation for cancer therapy.

    Science.gov (United States)

    Tang, Zhaomin; Zhou, Yangbo; Sun, Huili; Li, Dan; Zhou, Shaobing

    2014-05-01

    We fabricated a magnetic calcium phosphate nanoformulation by the biomineralization of calcium phosphate on the surface of magnetic nanoparticles with abundant amino groups, and thus the inorganic layer of calcium phosphate can improve the biocompatibility and simultaneously the magnetic iron oxide can maintain the magnetic targeting function. Two types of anticancer drug models, doxorubicin hydrochloride and DNA, were entrapped in these nanocarriers, respectively. This delivery system displayed high pH sensitivity in drug-controlled release profile as the dissolution of CaP under acid pH condition. Magnetofection was performed to investigate the intracellular uptake and the anti-proliferative effect of tumor cells in the presence of an external magnet. The transfection of the DNA-loaded magnetic system in A549 and HepG2 tumor cells demonstrated that the magnetic nanoformulation could enhance the transfection efficiency to 30% with an applied external magnetic field. PMID:24462792

  6. Impairment of mycophenolate mofetil absorption by calcium polycarbophil.

    Science.gov (United States)

    Kato, Ryuji; Ooi, Kazuya; Ikura-Mori, Megumi; Tsuchishita, Yoshimasa; Hashimoto, Hiroshi; Yoshimura, Hironori; Uenishi, Kohji; Kawai, Masayuki; Tanaka, Kazuhiko; Ueno, Kazuyuki

    2002-11-01

    The effect of calcium polycarbophil on the absorption of mycophenolate mofetil, an immunosuppressive agent, was evaluated in healthy subjects. In vitro studies were performed to further evaluate the mechanism of the potential interaction. In the in vitro study, the release of mycophenolate mofetil from a cellulose membrane in the presence or absence of metal cations was measured using the dissolution test procedure. In the in vivo study, a randomized crossover design with two phases was used. In one phase, 6 male healthy volunteers received 1000 mg of mycophenolate mofetil alone (treatment 1); in the other phase, they received 1000 mg of mycophenolate mofetil and 2400 mg of calcium polycarbophil fine granules concomitantly (treatment 2). They received 30 mg of lansoprazole for 5 days and, on the 6th day, received mycophenolate mofetil and 2400 mg of calcium polycarbophil fine granules concomitantly (treatment 3). The serum concentration of mycophenolic acid was measured by high-performance liquid chromatography. In the in vitro study, the release from a cellulose membrane in the presence of calcium or iron ions was slower than that in the absence of these metal ions. In the in vivo study, the AUC0-12 and C(max) in treatment 2 were less than those in treatment 1. About 50% and 25% decreases in AUC0-12 in treatment 2 and treatment 3 were observed compared with those in treatment 1, respectively. These findings suggest that when mycophenolate mofetil and calcium polycarbophil were coadministered concomitantly, a decrease in mycophenolate mofetil absorption was observed. Therefore, it appears clear that the concomitant administration of mycophenolate mofetil and calcium polycarbophil should be avoided.

  7. On the origin of rhythmic calcium transients in the ICC-MP of the mouse small intestine.

    Science.gov (United States)

    Lowie, Bobbi-Jo; Wang, Xuan-Yu; White, Elizabeth J; Huizinga, Jan D

    2011-11-01

    Interstitial cells of Cajal associated with the myenteric plexus (ICC-MP) are pacemaker cells of the small intestine, producing the characteristic omnipresent electrical slow waves, which orchestrate peristaltic motor activity and are associated with rhythmic intracellular calcium oscillations. Our objective was to elucidate the origins of the calcium transients. We hypothesized that calcium oscillations in the ICC-MP are primarily regulated by the sarcoplasmic reticulum (SR) calcium release system. With the use of calcium imaging, study of the effect of T-type calcium channel blocker mibefradil revealed that T-type channels did not play a major role in generating the calcium transients. 2-Aminoethoxydiphenyl borate, an inositol 1,4,5 trisphosphate receptor (IP(3)R) inhibitor, and U73122, a phospholipase C inhibitor, both drastically decreased the frequency of calcium oscillations, suggesting a major role of IP(3) and IP(3)-induced calcium release from the SR. Immunohistochemistry proved the expression of IP(3)R type I (IP(3)R-I), but not type II (IP(3)R-II) and type III (IP(3)R-III) in ICC-MP, indicating the involvement of the IP(3)R-I subtype in calcium release from the SR. Cyclopiazonic acid, a SR/endoplasmic reticulum calcium ATPase pump inhibitor, strongly reduced or abolished calcium oscillations. The Na-Ca exchanger (NCX) in reverse mode is likely involved in refilling the SR because the NCX inhibitor KB-R7943 markedly reduced the frequency of calcium oscillations. Immunohistochemistry revealed 100% colocalization of NCX and c-Kit in ICC-MP. Testing a mitochondrial NCX inhibitor, we were unable to show an essential role for mitochondria in regulating calcium oscillations in the ICC-MP. In summary, ongoing IP(3) synthesis and IP(3)-induced calcium release from the SR, via the IP(3)R-I, are the major drivers of the calcium transients associated with ICC pacemaker activity. This suggests that a biochemical clock intrinsic to ICC determines the pacemaker

  8. Calcium and cell death signaling in neurodegeneration and aging

    Directory of Open Access Journals (Sweden)

    Soraya Smaili

    2009-09-01

    Full Text Available Transient increase in cytosolic (Cac2+ and mitochondrial Ca2+ (Ca m2+ are essential elements in the control of many physiological processes. However, sustained increases in Ca c2+ and Ca m2+ may contribute to oxidative stress and cell death. Several events are related to the increase in Ca m2+, including regulation and activation of a number of Ca2+ dependent enzymes, such as phospholipases, proteases and nucleases. Mitochondria and endoplasmic reticulum (ER play pivotal roles in the maintenance of intracellular Ca2+ homeostasis and regulation of cell death. Several lines of evidence have shown that, in the presence of some apoptotic stimuli, the activation of mitochondrial processes maylead to the release of cytochrome c followed by the activation of caspases, nuclear fragmentation and apoptotic cell death. The aim of this review was to show how changes in calcium signaling can be related to the apoptotic cell death induction. Calcium homeostasis was also shown to be an important mechanism involved in neurodegenerative and aging processes.Aumentos transientes no cálcio citosólico (Ca c2+ e mitocondrial (Ca m2+ são elementos essenciais no controle de muitos processos fisiológicos. No entanto, aumentos sustentados do Ca c2+ e do Ca m2+ podem contribuir para o estresse oxidativo ea morte celular. Muitos eventos estão relacionados ao aumentono Ca c2+, incluindo a regulação e ativação de várias enzimas dependentes de Ca2+ como as fosfolipases, proteases e nucleases. A mitocôndria e o retículo endoplasmático têm um papel central na manutenção da homeostase intracellular de Ca c2+ e na regulação da morte celular. Várias evidências mostraram que, na presença de certos estímulos apoptóticos, a ativação dos processos mitocondriais pode promover a liberação de citocromo c, seguida da ativação de caspases, fragmentação nuclear e morte celular por apoptose. O objetivo desta revisão é mostrar como aumentos na sinalização de

  9. 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 ...

  10. Vitamin D, Calcium, and Bone Health

    Science.gov (United States)

    ... Balance › Vitamin D, Calcium, and Bone Health Vitamin D, Calcium, and Bone Health March 2012 Download PDFs ... helps keep your bones strong. Why are vitamin D and calcium important to bone health? Vitamin D ...

  11. Doc2b synchronizes secretion from chromaffin cells by stimulating fast and inhibiting sustained release

    DEFF Research Database (Denmark)

    da Silva Pinheiro, Paulo César; de Wit, Heidi; Walter, Alexander M;

    2013-01-01

    is still high. We conclude that Doc2b acts to inhibit vesicle priming during prolonged calcium elevations, thus protecting unprimed vesicles from fusing prematurely, and redirecting them to refill the readily releasable pool after relaxation of the calcium signal. In sum, Doc2b favors fast, synchronized...

  12. Event Index - a LHCb Event Search System

    CERN Document Server

    Ustyuzhanin, Andrey; Kazeev, Nikita; Redkin, Artem

    2015-01-01

    LHC experiments generate up to $10^{12}$ events per year. This paper describes Event Index - an event search system. Event Index's primary function is quickly selecting subsets of events from a combination of conditions, such as the estimated decay channel or stripping lines output. Event Index is essentially Apache Lucene optimized for read-only indexes distributed over independent shards on independent nodes.

  13. CALCIUM ENHANCES ANTIINFLAMMATORY ACTIVITY OF ASPIRIN

    OpenAIRE

    Choksi Krishna; Shenoy Ashoka M; A. R. Shabharaya; Lala Minaxi

    2011-01-01

    The objective of present study is to evaluate the effects of calcium carbonate and calcium gluconate on acute and subacute inflammation and to study their possible interactions with Aspirin. Calcium carbonate (10 mg/kg) and calcium gluconate (5 mg/kg) were administered individually and also co-administered along with sub therapeutic dose Aspirin (50mg/kg) to study their interaction. The inflammation was induced by carrageenan or a foreign body. Both calcium carbonate and calcium gluconate cou...

  14. 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...... affected the ash chemistry and the ash sintering tendency but much less the char reactivity. Thermo balance test are made and high-temperature X-ray diffraction measurements are performed, the experimental results indicate that with calcium addition major inorganic¿inorganic reactions take place very late...... in the char conversion process. Comprehensive global equilibrium calculations predicted important characteristics of the inorganic ash residue. Equilibrium calculations predict the formation of liquid salt if sufficient amounts of Ca are added and according to experiments as well as calculations calcium binds...

  15. A Novel Hydrolytic Product from Flesh of Mactra veneriformis and Its Bioactivities in Calcium Supplement

    Institute of Scientific and Technical Information of China (English)

    WANG Lingchong; CHEN Shiyong; LIU Rui; WU Hao

    2012-01-01

    To prepare calcium-binding peptides,the flesh residue of Mactra Veneriformis was subjected to enzymatic hydrolysis.By comparing the capability of combining calcium of the hydrolyzates,pepsin was confirmed to be the most suitable enzyme for hydrolyzing the flesh residue to release calcium-binding peptides among the seven tested proteases.The pepsin hydrolyzate(PHM)was divided into three fractions according to the molecule weight of its composition,which ranged from 0.5 to 15 kDa.The low-molecule-weight fraction named PHM-3 had the highest capability in combining calcium.The peptides existing in the PHM-3fraction consisted of higher contents of Glu,Ala and Leu,and could produce one type of calcium-peptide complex by powerfully chelating calcium ions.PHM-3 products could effectively increase calcium absorption and retention while they decreased the calcium excretion in animal tests.Additionally,symptoms caused by low calcium bioavailability in ovariectomized rats,such as bone mineral density reduction and mechanical strength loss could be significantly ameliorated by the hydrolytic products addition in diet.

  16. A novel hydrolytic product from flesh of Mactra veneriformis and its bioactivities in calcium supplement

    Science.gov (United States)

    Wang, Lingchong; Chen, Shiyong; Liu, Rui; Wu, Hao

    2012-09-01

    To prepare calcium-binding peptides, the flesh residue of Mactra Veneriformis was subjected to enzymatic hydrolysis. By comparing the capability of combining calcium of the hydrolyzates, pepsin was confirmed to be the most suitable enzyme for hydrolyzing the flesh residue to release calcium-binding peptides among the seven tested proteases. The pepsin hydrolyzate (PHM) was divided into three fractions according to the molecule weight of its composition, which ranged from 0.5 to 15 kDa. The low-molecule-weight fraction named PHM-3 had the highest capability in combining calcium. The peptides existing in the PHM-3 fraction consisted of higher contents of Glu, Ala and Leu, and could produce one type of calcium-peptide complex by powerfully chelating calcium ions. PHM-3 products could effectively increase calcium absorption and retention while they decreased the calcium excretion in animal tests. Additionally, symptoms caused by low calcium bioavailability in ovariectomized rats, such as bone mineral density reduction and mechanical strength loss could be significantly ameliorated by the hydrolytic products addition in diet.

  17. Growth control in colon epithelial cells: gadolinium enhances calcium-mediated growth regulation.

    Science.gov (United States)

    Attili, Durga; Jenkins, Brian; Aslam, Muhammad Nadeem; Dame, Michael K; Varani, James

    2012-12-01

    Gadolinium, a member of the lanthanoid family of transition metals, interacts with calcium-binding sites on proteins and other biological molecules. The overall goal of the present investigation was to determine if gadolinium could enhance calcium-induced epithelial cell growth inhibition in the colon. Gadolinium at concentrations as low as 1-5 μM combined with calcium inhibits proliferation of human colonic epithelial cells more effectively than calcium alone. Gadolinium had no detectable effect on calcium-induced differentiation in the same cells based on change in cell morphology, induction of E-cadherin synthesis, and translocation of E-cadherin from the cytosol to the cell surface. When the colon epithelial cells were treated with gadolinium and then exposed to increased calcium concentrations, movement of extracellular calcium into the cell was suppressed. In contrast, gadolinium treatment had no effect on ionomycin-induced release of stored intracellular calcium into the cytoplasm. Whether these in vitro observations can be translated into an approach for reducing abnormal proliferation in the colonic mucosa (including polyp formation) is not known. These results do, however, provide an explanation for our recent findings that a multi-mineral supplement containing all of the naturally occurring lanthanoid metals including gadolinium are more effective than calcium alone in preventing colon polyp formation in mice on a high-fat diet.

  18. Biomimetic synthesis of calcium-strontium apatite hollow nanospheres

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    In this work,calcium-strontium apatite (Sr-HA) hollow nanospheres were synthesized by a facile biomimetic method.The structure and property of Sr-HA were characterized by FESEM,TEM,HRTEM,XRD and FT-IR spectroscopy.The influences of different ratios of calcium and strontium on the morphologies of the Sr-HA products were investigated.The experimental results revealed that the hollow spherical Sr-HA,with a size of 30-120 nm in diameter,could be synthesized when the molar ratio of Ca/Sr was 1:1.The possible formation mechanism of the hollow Sr-HA was proposed.The drug release experiments indicated that the hollow spherical Sr-HA had the property of sustained release.

  19. Chronic stress and calcium oxalate stone disease: is it a potential recurrence risk factor?

    Science.gov (United States)

    Arzoz-Fabregas, Montserrat; Ibarz-Servio, Luis; Edo-Izquierdo, Sílvia; Doladé-Botías, María; Fernandez-Castro, Jordi; Roca-Antonio, Josep

    2013-04-01

    Chronic emotional stress is associated with increased cortisol release and metabolism disorders. However, few studies have evaluated the influence of chronic stress on calcium oxalate (CaOx) stone disease and its recurrence. A total of 128 patients were enrolled in this case-control study over a period of 20 months. All patients were CaOx stone formers with a recent stone episode (stone formers (FS) and 33 recurrent stone formers (RS). Dimensions of chronic stress were evaluated with self-reported validated questionnaires measuring stressful life events, perceived stress, anxiety, depression, burnout and satisfaction with life. An ad hoc self-reporting questionnaire was designed to evaluate stress-related specifically to stone episodes. Blood and urine samples were collected to determine cortisol levels and urinary composition. In addition, epidemiological data, socioeconomic information, diet and incidences of metabolic syndrome (MS) were reported. Overall, no significant differences were observed in the scores of cases and controls on any of the questionnaires dealing with stress. The number (p incidences of MS (p = 0.07) than FS. Although no differences were observed in cases and controls among any dimension of chronic stress, the number and intensity of stressful life events were higher in RS than in FS. These differences correlate with variations in blood and urinary levels and with metabolic disorders, indicating an association between chronic stress and risk of recurrent CaOx stone formation.

  20. Calcium and actin in the saga of awakening oocytes

    Energy Technology Data Exchange (ETDEWEB)

    Santella, Luigia, E-mail: santella@szn.it; Limatola, Nunzia; Chun, Jong T.

    2015-04-24

    The interaction of the spermatozoon with the egg at fertilization remains one of the most fascinating mysteries of life. Much of our scientific knowledge on fertilization comes from studies on sea urchin and starfish, which provide plenty of gametes. Large and transparent, these eggs have served as excellent model systems for studying egg activation and embryo development in seawater, a plain natural medium. Starfish oocytes allow the study of the cortical, cytoplasmic and nuclear changes during the meiotic maturation process, which can also be triggered in vitro by hormonal stimulation. These morphological and biochemical changes ensure successful fertilization of the eggs at the first metaphase. On the other hand, sea urchin eggs are fertilized after the completion of meiosis, and are particularly suitable for the study of sperm–egg interaction, early events of egg activation, and embryonic development, as a large number of mature eggs can be fertilized synchronously. Starfish and sea urchin eggs undergo abrupt changes in the cytoskeleton and ion fluxes in response to the fertilizing spermatozoon. The plasma membrane and cortex of an egg thus represent “excitable media” that quickly respond to the stimulus with the Ca{sup 2+} swings and structural changes. In this article, we review some of the key findings on the rapid dynamic rearrangements of the actin cytoskeleton in the oocyte/egg cortex upon hormonal or sperm stimulation and their roles in the modulation of the Ca{sup 2+} signals and in the control of monospermic fertilization. - Highlights: • Besides microtubules, microfilaments may anchor the nucleus to oocyte surface. • The cortical Ca{sup 2+} flash and wave at fertilization mirror electrical membrane change. • Artificial egg activation lacks microvilli extension in the perivitelline space. • Calcium is necessary but not sufficient for cortical granules exocytosis. • Actin cytoskeleton modulates Ca{sup 2+} release at oocyte maturation

  1. [Comparative in vitro evaluation of modern glass ionomer cements for adhesion strength and fluoride release].

    Science.gov (United States)

    Zhitkov, M Yu; Rusanov, F S; Poyurovskaya, I Ya

    2016-01-01

    The study proved similar adhesion strength and fluoride release level in aqueous extracts of glass ionomer cements Cemion (VladMiVa, Russia), Glassin Rest (Omega-Dent, Russia), Cemfil 10 (StomaDent, Russia) and Fuji VIII (GC Corporation, Japan). Despite of close concentrations of fluoride in glasses, the rate of fluoride release in water from calcium and calcium-barium glasses is much higher than that of strontium glasses. PMID:27239999

  2. Evolution of the Calcium Paradigm: The Relation between Vitamin D, Serum Calcium and Calcium Absorption

    Directory of Open Access Journals (Sweden)

    Borje E. Christopher Nordin

    2010-09-01

    Full Text Available Osteoporosis is the index disease for calcium deficiency, just as rickets/osteomalacia is the index disease for vitamin D deficiency, but there is considerable overlap between them. The common explanation for this overlap is that hypovitaminosis D causes malabsorption of calcium which then causes secondary hyperparathyroidism and is effectively the same thing as calcium deficiency. This paradigm is incorrect. Hypovitaminosis D causes secondary hyperparathyroidism at serum calcidiol levels lower than 60 nmol/L long before it causes malabsorption of calcium because serum calcitriol (which controls calcium absorption is maintained until serum calcidiol falls below 20 nmol/L. This secondary hyperparathyroidism, probably due to loss of a “calcaemic” action of vitamin D on bone first described in 1957, destroys bone and explains why vitamin D insufficiency is a risk factor for osteoporosis. Vitamin D thus plays a central role in the maintenance of the serum (ionised calcium, which is more important to the organism than the preservation of the skeleton. Bone is sacrificed when absorbed dietary calcium does not match excretion through the skin, kidneys and bowel which is why calcium deficiency causes osteoporosis in experimental animals and, by implication, in humans.

  3. Calcium-sensing receptor activation depresses synaptic transmission

    OpenAIRE

    Phillips, Cecilia G.; Harnett, Mark T.; Chen, Wenyan; Smith, Stephen M.

    2008-01-01

    At excitatory synapses, decreases in cleft [Ca] arising from activity-dependent transmembrane Ca flux reduce the probability of subsequent transmitter release. Intense neural activity, induced by physiological and pathological stimuli, disturb the external microenvironment reducing extracellular [Ca] ([Ca]o) and thus may impair neurotransmission. Increases in [Ca]o activate the extracellular calcium sensing receptor (CaSR) which in turn inhibits non-selective cation channels (NSCC) at the maj...

  4. Sensitivity to calcium intake in calcium stone forming patients.

    Science.gov (United States)

    Heilberg, I P; Martini, L A; Draibe, S A; Ajzen, H; Ramos, O L; Schor, N

    1996-01-01

    The absorptive or renal origin of hypercalciuria can be discriminated using an acute oral calcium load test (ACLT). Of 86 patients with calcium oxalate kidney stones, 28 (23%) were found to be hypercalciuric (HCa) and 58 (67%) normocalciuric (NCa) on their customary free diet, containing 542 +/- 29 mg/day (mean +/- SE) of calcium. Since the apparently normal 24-hour calcium excretion of many calcium stone formers (CSF) may be due to a combination of high calcium absorption with moderately low calcium intake, all patients were investigated by ACLT. Of 28 HCa patients, 13 (46%) were classified as absorptive (AH) and 15 (54%) as renal hypercalciuria (RH). Of the 58 NCa patients, 38 (65%) presented features of intestinal hyperabsorption and were therefore designated as AH-like, and 20 (35%) as RH-like. To further elucidate the role of dietary calcium in these CSF, a chronic calcium load test (CCLT), consisting of 1 g/day of oral Ca for 7 days, was designed. A positive response to the CCLT was considered to occur when urinary calcium (uCa) was > or = 4 mg/ kg/24 h on the 7th day. Among NCa patients, 29% of AH-like subjects responded to the CCLT and 71% did not; 50% of RH-like subjects also responded and 50% did not. In HCa patients, 85% of AH and 67% of RH subjects maintained uCa > or = 4 mg/kg/24 h after the CCLT and 15% of AH and 23% of RH subjects did not. However, a significant additional increase in mean uCa was not observed among HCa patients. All patients were submitted to a second evaluation of fasting calciuria (Ca/Cr). A modification of this parameter was noticed in 89% of RH-like and 78% of RH patients. In conclusion, these data suggest the presence of subpopulations of patients sensitive or not to calcium intake, regardless of whether the acute response to a calcium overload test suggested AH or RH. The CCLT disclosed dietary hypercalciuria in 21/58 (36%) of previously NCa patients. In these NCa patients, the ACLT may be replaced by the CCLT. The distinction

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

    Energy Technology Data Exchange (ETDEWEB)

    Bizzozero, Julien, E-mail: julien.bizzozero@gmail.com; Scrivener, Karen L.

    2015-10-15

    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 and monocarboaluminate. Increasing the ratio between sulfate and aluminate decreases the extent of limestone reaction.

  6. Simulating events

    Energy Technology Data Exchange (ETDEWEB)

    Ferretti, C.; Bruzzone, L. [Techint Italimpianti, Milan (Italy)

    2000-06-01

    The Petacalco Marine terminal on the Pacific coast in the harbour of Lazaro Carclenas (Michoacan) in Mexico, provides coal to the thermoelectric power plant at Pdte Plutarco Elias Calles in the port area. The plant is being converted from oil to burn coal to generate 2100 MW of power. The article describes the layout of the terminal and equipment employed in the unloading, coal stacking, coal handling areas and the receiving area at the power plant. The contractor Techint Italimpianti has developed a software system, MHATIS, for marine terminal management which is nearly complete. The discrete event simulator with its graphic interface provides a real-type decision support system for simulating changes to the terminal operations and evaluating impacts. The article describes how MHATIS is used. 7 figs.

  7. Modeling of progesterone-induced intracellular calcium signaling in human spermatozoa.

    Science.gov (United States)

    Li, Long-Fei; Xiang, Cheng; Zhu, Ya-Bing; Qin, Kai-Rong

    2014-06-21

    Calcium ion is a secondary messenger of mammalian spermatozoa. The dynamic change of its concentration plays a vital role in the process of sperm motility, capacitation, acrosome and fertilization. Progesterone released by the cumulus cells, as a potent stimulator of fertilization, can activate the calcium channels on the plasma membrane, which in turn triggers the dynamic change of intracellular calcium concentration. In this paper, a mathematical model of calcium dynamic response in mammalian spermatozoa induced by progesterone is proposed and numerical simulation of the dynamic model is conducted. The results show that the dynamic response of calcium concentration predicted by the model is in accordance with experimental evidence. The proposed dynamic model can be used to explain the phenomena observed in the experiments and predict new phenomena to be revealed by experimental investigations, which will provide the basis to quantitatively investigate the fluid mechanics and biochemistry for the sperm motility induced by progesterone.

  8. 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

    BACKGROUND The vitamin D receptor (VDR) is expressed in human spermatozoa, and VDR-knockout mice and vitamin D (VD) deficiency in rodents results in impaired fertility, low sperm counts and a low number of motile spermatozoa. We investigated the role of activated VD (1,25(OH)(2)D(3)) in human...... spermatozoa and whether VD serum levels are associated with semen quality. METHODS Cross-sectional association study of semen quality and VD serum level in 300 men from the general population, and in vitro studies on spermatozoa from 40 men to investigate the effects of VD on intracellular calcium, sperm......M). 1,25(OH)(2)D(3) increased intracellular calcium concentration in human spermatozoa through VDR-mediated calcium release from an intracellular calcium storage, increased sperm motility and induced the acrosome reaction in vitro. CONCLUSIONS 1,25(OH)(2)D(3) increased intracellular calcium...

  9. Filamin and phospholipase C-ε are required for calcium signaling in the Caenorhabditis elegans spermatheca.

    Directory of Open Access Journals (Sweden)

    Ismar Kovacevic

    2013-05-01

    Full Text Available The Caenorhabditis elegans spermatheca is a myoepithelial tube that stores sperm and undergoes cycles of stretching and constriction as oocytes enter, are fertilized, and exit into the uterus. FLN-1/filamin, a stretch-sensitive structural and signaling scaffold, and PLC-1/phospholipase C-ε, an enzyme that generates the second messenger IP3, are required for embryos to exit normally after fertilization. Using GCaMP, a genetically encoded calcium indicator, we show that entry of an oocyte into the spermatheca initiates a distinctive series of IP3-dependent calcium oscillations that propagate across the tissue via gap junctions and lead to constriction of the spermatheca. PLC-1 is required for the calcium release mechanism triggered by oocyte entry, and FLN-1 is required for timely initiation of the calcium oscillations. INX-12, a gap junction subunit, coordinates propagation of the calcium transients across the spermatheca. Gain-of-function mutations in ITR-1/IP3R, an IP3-dependent calcium channel, and loss-of-function mutations in LFE-2, a negative regulator of IP3 signaling, increase calcium release and suppress the exit defect in filamin-deficient animals. We further demonstrate that a regulatory cassette consisting of MEL-11/myosin phosphatase and NMY-1/non-muscle myosin is required for coordinated contraction of the spermatheca. In summary, this study answers long-standing questions concerning calcium signaling dynamics in the C. elegans spermatheca and suggests FLN-1 is needed in response to oocyte entry to trigger calcium release and coordinated contraction of the spermathecal tissue.

  10. Simulating Heinrich event 1 with interactive icebergs

    NARCIS (Netherlands)

    Jongma, J.I.; Renssen, H.; Roche, D.M.V.A.P.

    2012-01-01

    During the last glacial, major abrupt climate events known as Heinrich events left distinct fingerprints of ice rafted detritus, and are thus associated with iceberg armadas; the release of many icebergs into the North Atlantic Ocean. We simulated the impact of a large armada of icebergs on glacial

  11. Calcium binding protein-mediated regulation of voltage-gated calcium channels linked to human diseases

    Institute of Scientific and Technical Information of China (English)

    Nasrin NFJATBAKHSH; Zhong-ping FENG

    2011-01-01

    Calcium ion entry through voltage-gated calcium channels is essential for cellular signalling in a wide variety of cells and multiple physiological processes. Perturbations of voltage-gated calcium channel function can lead to pathophysiological consequences. Calcium binding proteins serve as calcium sensors and regulate the calcium channel properties via feedback mechanisms. This review highlights the current evidences of calcium binding protein-mediated channel regulation in human diseases.

  12. Induction of tryptase and histmine release from human colon mast cells by IgE dependent or independent mechanisms

    Institute of Scientific and Technical Information of China (English)

    Shao-Heng He; Hua Xie; Yong-Song He

    2004-01-01

    AIM: To investigate the tryptase and histamine release ability of human colon mast cells upon IgE dependent or independent activation and the potential mechanisms.METHODS: Enzymatically dispersed cells from human colons were challenged with anti-IgE or calcium ionophore A23187, and the cell supernatants after challenge were collected. Both concentration dependent and time course studies with anti-IgE or calcium ionophore A23187 were performed. Tryptase release was determined with a sandwich ELISA procedure and histamine release was measured usina a glass fibre-based fluorometric assay.RESULTS: Both anti-IgE and calcium ionophore were able to induce dose dependent release of histamine from colon mast cells with up to approximately 60% and 25% net histamine release being achieved with 1 μg/mL calcium ionophore and 10 μg/mL anti-IgE, respectively. Dose dependent release of tryptase was also observed with up to approximately 19 ng/mL and 21 ng/mL release of tryptase being achieved with 10 μg/mL anti-IgE and 1 μg/mL calcium ionophore, respectively. Time course study revealed that both tryptase and histamine release from colon mast cells stimulated by anti-IgE initiated within 10 sec and reached their maximum release at 6 min following challenge. Pretreatment of cells with metabolic inhibitors abolished the actions of anti-IgE as well as calcium ionophore. Tryptase and histamine release, particularly that induced by calcium ionophore was inhibited by pretreatment of cells with pertussis toxin.CONCLUSION: Both anti-IgE and calcium ionophore are able to induce significant release of tryptase and histamine from colon mast cells, indicating that this cell type is likely to contribute to the pathogenesis of colitis and other mast cell associated intestinal diseases.

  13. Riola release report

    International Nuclear Information System (INIS)

    Eleven hours after execution of the Riola Event (at 0826 PDT on 25 September 1980) in hole U2eq of the Nevada Test Site (NTS), a release of radioactivity began. When the seepage stopped at about noon the following day, up to some 3200 Ci of activity had been dispersed by light variable winds. On 26 September, examination of the geophone records showed six hours of low-level, but fairly continuous, activity before the release. Electrical measurements indicated that most cables were still intact to a depth below the stemming platform. A survey of the ground zero area showed that the seepage came through cracks between the surface conductor and the pad, through cracks in the pad, and through a crack adjacent to the pad around the mousehole (a small hole adjacent to the emplacement hole). To preclude undue radiation exposure or injury from a surprise subsidence, safety measures were instituted. Tritium seepage was suffucient to postpone site activities until a box and pipeline were emplaced to contain and remove the gas. Radiation release modeling and calculations were generally consistent with observations. Plug-hole interaction calculations showed that the alluvium near the bottom of the plug may have been overstressed and that improvements in the design of the plug-medium interface can be made. Experimental studies verified that the surface appearance of the plug core was caused by erosion, but, assuming a normal strength for the plug material, that erosion alone could not account for the disappearance of such a large portion of the stemming platform. Samples from downhole plug experiments show that the plug may have been considerably weaker than had been indicted by quality assurance (QA) samples. 19 references, 32 figures, 10 tables

  14. Events diary

    Science.gov (United States)

    2000-01-01

    as Imperial College, the Royal Albert Hall, the Royal College of Art, the Natural History and Science Museums and the Royal Geographical Society. Under the heading `Shaping the future together' BA2000 will explore science, engineering and technology in their wider cultural context. Further information about this event on 6 - 12 September may be obtained from Sandra Koura, BA2000 Festival Manager, British Association for the Advancement of Science, 23 Savile Row, London W1X 2NB (tel: 0171 973 3075, e-mail: sandra.koura@britassoc.org.uk ). Details of the creating SPARKS events may be obtained from creating.sparks@britassoc.org.uk or from the website www.britassoc.org.uk . Other events 3 - 7 July, Porto Alegre, Brazil VII Interamerican conference on physics education: The preparation of physicists and physics teachers in contemporary society. Info: IACPE7@if.ufrgs.br or cabbat1.cnea.gov.ar/iacpe/iacpei.htm 27 August - 1 September, Barcelona, Spain GIREP conference: Physics teacher education beyond 2000. Info: www.blues.uab.es/phyteb/index.html

  15. Air leaks and vasopressin release.

    OpenAIRE

    McIntosh, N.; Prakash, P.; Smith, A.

    1990-01-01

    Eleven very low birthweight babies being ventilated for respiratory problems during the first week of life developed air leaks on 22 occasions. On 16 out of 19 occasions the infants showed increases in urinary excretion of vasopressin after these events and on 10 occasions out of 13 there was a rise in the plasma arginine vasopressin concentration. The peripheral signs of the syndrome of inappropriate antidiuretic hormone release were seen on only one occasion in response to the sometimes hig...

  16. Calcium signals in olfactory neurons.

    Science.gov (United States)

    Tareilus, E; Noé, J; Breer, H

    1995-11-01

    Laser scanning confocal microscopy in combination with the fluorescent calcium indicators Fluo-3 and Fura-Red was employed to estimate the intracellular concentration of free calcium ions in individual olfactory receptor neurons and to monitor temporal and spatial changes in the Ca(2+)-level upon stimulation. The chemosensory cells responded to odorants with a significant increase in the calcium concentration, preferentially in the dendritic knob. Applying various stimulation paradigma, it was found that in a population of isolated cells, subsets of receptor neurons display distinct patterns of responsiveness. PMID:7488645

  17. Calcium signals in olfactory neurons.

    Science.gov (United States)

    Tareilus, E; Noé, J; Breer, H

    1995-11-01

    Laser scanning confocal microscopy in combination with the fluorescent calcium indicators Fluo-3 and Fura-Red was employed to estimate the intracellular concentration of free calcium ions in individual olfactory receptor neurons and to monitor temporal and spatial changes in the Ca(2+)-level upon stimulation. The chemosensory cells responded to odorants with a significant increase in the calcium concentration, preferentially in the dendritic knob. Applying various stimulation paradigma, it was found that in a population of isolated cells, subsets of receptor neurons display distinct patterns of responsiveness.

  18. Experimental models of renal calcium stones in rodents.

    Science.gov (United States)

    Bilbault, Héloïse; Haymann, Jean-Philippe

    2016-03-01

    In human nephrolithiasis, most stones are containing calcium and are located within urinary cavities; they may contain monohydrate calcium oxalate, dihydrate calcium oxalate and/or calcium phosphates in various proportion. Nephrolithiasis may also be associated with nephrocalcinosis, i.e., crystal depositions in tubular lumen and/or interstitium, an entity which suggests specific pathological processes. Several rodents models have been developed in order to study the pathophysiology of intrarenal crystal formation. We review here calcium rodent models classified upon the presence of nephrolithiasis and/or nephrocalcinosis. As rodents are not prone to nephrolithiasis, models require the induction of a long standing hypercalciuria or hyperoxaluria (thus explaining the very few studies reported), conversely to nephrocalcinosis which may occur within hours or days. Whereas a nephrotoxicity leading to tubular injury and regeneration appears as a critical event for crystal retention in nephrocalcinosis models, surprisingly very little is known about the physiopathology of crystal attachment to urothelium in nephrolithiasis. Creating new models of nephrolithiasis especially in different genetic mice strains appears an important challenge in order to unravel the early mechanisms of urinary stone formation in papilla and fornices. PMID:26981444

  19. Analyzing Strategies for Press Release of Government's Important Events --A Case Study of Guangzhou Asian Games%重大事件政府新闻发布传播策略分析——以广州亚运会为例

    Institute of Scientific and Technical Information of China (English)

    侯迎忠; 李玮

    2011-01-01

    政府在重大事件中的新闻发布活动是树立政府形象的良好机会。2010年广州亚运会作为亚洲体坛盛会,是一次展示国家形象和广州城市形象的绝佳时机,其新闻发布策略与传播效果尤其值得关注。文章在系统阐述重大事件新闻发布传播策略的基础上,针对广州亚运会裳间广东省及广州市政府新闻发布运行机制与传播策略进行分析,总结出包括制度规范、主题制定、模拟演练,现场应对、舆情监测等传播策略,并对其效果进行分析。%It is a good opportunity for the government to establish its image in the news release activities. The 2010 Guangzhou Asian Games as a sports event in Asia, is a showcase of the national image and the image of Guangzhou city. Its press re/ease strategT and dissemination effects are worth particu/ar concern. Based on a systematic illustration of the communication strategies for major events, this paper studies the press release mechanisms of Guangzhou Asian Games held in Guangzhou City, and analyzes the strategies for news dissemination adopted by the govern- ments of Guangdong province and Guangzhou city and their effects. It has been found that strategies used include setting up a rigid system, defining themes and related policies, carrying on simulation exercises and on-spot respon ses and monitoring public; opinions

  20. Blockade of chloride channels by DIDS stimulates renin release and inhibits contraction of afferent arterioles

    DEFF Research Database (Denmark)

    Jensen, B L; Skøtt, O

    1996-01-01

    or without ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] and DIDS were not additive. In the absence of chloride, basal renin release was suppressed and the stimulatory effect of DIDS was abolished. The DIDS-induced enhancement of renin release was not dependent on bicarbonate...... arterioles with the chloride channel blocker 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). Renin secretion was equally enhanced by omission of extracellular calcium and by addition of 0.5 mM DIDS. The inhibitory effect of calcium was blocked by DIDS. The stimulatory effects of low calcium [with...

  1. Role of connectivity and fluctuations in the nucleation of calcium waves in cardiac cells

    Science.gov (United States)

    Hernandez-Hernandez, Gonzalo; Alvarez-Lacalle, Enric; Shiferaw, Yohannes

    2015-11-01

    Spontaneous calcium release (SCR) occurs when ion channel fluctuations lead to the nucleation of calcium waves in cardiac cells. This phenomenon is important since it has been implicated as a cause of various cardiac arrhythmias. However, to date, it is not understood what determines the timing and location of spontaneous calcium waves within cells. Here, we analyze a simplified model of SCR in which calcium release is modeled as a stochastic processes on a two-dimensional network of randomly distributed sites. Using this model we identify the essential parameters describing the system and compute the phase diagram. In particular, we identify a critical line which separates pinned and propagating fronts, and show that above this line wave nucleation is governed by fluctuations and the spatial connectivity of calcium release units. Using a mean-field analysis we show that the sites of wave nucleation are predicted by localized eigenvectors of a matrix representing the network connectivity of release sites. This result provides insight on the interplay between connectivity and fluctuations in the genesis of SCR in cardiac myocytes.

  2. Variability of calcium absorption

    International Nuclear Information System (INIS)

    Variability in calcium absorption was estimated in three groups of normal subjects in whom Ca absorption was measured by standard isotopic-tracer methods at interstudy intervals ranging from 1 to 4 mo. Fifty absorption tests were performed in 22 subjects. Each was done in the morning after an overnight fast with an identical standard breakfast containing a Ca load of approximately 250 mg. Individual fractional absorption values were normalized to permit pooling of the data. The coefficient of variation (CVs) for absorption for the three groups ranged from 10.57 to 12.79% with the size of the CV increasing with interstudy duration. One other published study presenting replicate absorption values was analyzed in a similar fashion and was found to have a CV of absorption of 9.78%. From these data we estimate that when the standard double-isotope method is used to measure Ca absorption there is approximately 10% variability around any given absorption value within an individual human subject and that roughly two-thirds of this represents real biological variability in absorption

  3. News/Press Releases

    Data.gov (United States)

    Office of Personnel Management — A press release, news release, media release, press statement is written communication directed at members of the news media for the purpose of announcing programs...

  4. Skeletal muscle sarcolemma in malignant hyperthermia: evidence for a defect in calcium regulation.

    Science.gov (United States)

    Mickelson, J R; Ross, J A; Hyslop, R J; Gallant, E M; Louis, C F

    1987-03-12

    Sarcolemmal properties implicated in the skeletal muscle disorder, malignant hyperthermia (MH), were examined using sarcolemma-membrane vesicles isolated from normal and MH-susceptible (MHS) porcine skeletal muscle. MHS and normal sarcolemma did not differ in the distribution of the major proteins, cholesterol or phospholipid content, vesicle size and sidedness, (Na+ + K+)-ATPase activity, ouabain binding, or adenylate cyclase activity (total and isoproterenol sensitivity). The regulation of the initial rates of MHS and normal sarcolemmal ATP-dependent calcium transport (calcium uptake after 1 min) by Ca2+ (K1/2 = 0.64-0.81 microM), calmodulin, and cAMP-dependent protein kinase were similar. However, when sarcolemmal calcium content was measured at either 2 or 20 min after the initiation of active calcium transport, a significant difference between MHS and normal sarcolemmal calcium uptake became apparent, with MHS sarcolemma accumulating approximately 25% less calcium than normal sarcolemma. Calcium transport by MHS and normal sarcolemma, at 2 or 20 min, had a similar calmodulin dependence (C1/2 = 150 nM), and was stimulated to a similar extent by cAMP-dependent protein kinase or calmodulin. Halothane inhibited MHS and normal sarcolemmal active calcium uptake in a similar fashion (half-maximal inhibition at 10 mM halothane), while dantrolene (30 microM) and nitrendipine (1 microM) had little effect on either MHS or normal sarcolemmal calcium transport. After 20 min of ATP-supported calcium uptake, 2 mM EGTA plus 10 microM sodium orthovanadate were added to initiate sarcolemmal calcium efflux. Following an initial rapid phase of calcium release, an extended slow phase of calcium efflux (k = 0.012 min-1) was similar for both MHS and normal sarcolemma vesicles. We conclude that although a number of sarcolemmal properties, including passive calcium permeability, are normal in MH, a small but significant defect in MHS sarcolemmal ATP-dependent calcium transport may

  5. Arg-Phe-amide-related peptides influence gonadotropin-releasing hormone neurons

    Institute of Scientific and Technical Information of China (English)

    Haluk Kelestimur; Emine Kacar; Aysegul Uzun; Mete Ozcan; Selim Kutlu

    2013-01-01

    The hypothalamic Arg-Phe-amide-related peptides, gonadotropin-inhibitory hormone and orthologous mammalian peptides of Arg-Phe-amide, may be important regulators of the hypothalamus-pituitary-gonadal reproductive axis. These peptides may modulate the effects of kisspeptins because they are presently recognized as the most potent activators of the hypothalamus-pituitary-gonadal axis. However, their effects on gonadotropin-releasing hormone neurons have not been investigated. In the current study, the GT1–7 cell line-expressing gonadotropin-releasing hormone was used as a model to explore the effects of Arg-Phe- amide-related peptides on kisspeptin activation. Intracellular calcium concentration was quantified using the calcium-sensitive dye, fura-2 acetoxymethyl ester. Gonadotropin-releasing hormone released into the medium was detected via enzyme-linked immunosorbent assay. Results showed that 100 nmol/L kisspeptin-10 significantly increased gonadotropin-releasing hormone levels (at 120 minutes of exposure) and intracellular calcium concentrations. Co-treatment of kisspeptin with 1 μmol/L gonadotropin-inhibitory hormone or 1 μmol/L Arg-Phe-amide-related peptide-1 significantly attenuated levels of kisspeptin-induced gonadotropin-releasing hormone but did not affect kisspeptin-induced elevations of intracellular calcium concentration. Overall, the results suggest that gonadotropin-inhibitory hormone and Arg-Phe-amide-related peptide-1 may have inhibitory effects on kisspeptin-activated gonadotropin-releasing hormone neurons independent of the calcium signaling pathway.

  6. A minimalist model of calcium-voltage coupling in GnRH cells

    Energy Technology Data Exchange (ETDEWEB)

    Rennie, Martin; Chan, Rossanna; Duan Wen; Sneyd, James [Department of Mathematics, University of Auckland, Auckland 1142 (New Zealand); Schneider, David, E-mail: schneide@tandar.cnea.gov.ar [Departamento de Fisica, Comision Nacional de Energia Atomica. Av. del Libertador 8250, 1429 Buenos Aires (Argentina)

    2011-03-01

    We present a minimalist model to describe the interplay between burst firing and calcium dynamics in Gonadotropin-releasing hormone (GnRH) cells. This model attempts to give a qualitative representation of Duan's model [3], and it comprises two FithzHugh-Nagumo (FHN) coupled systems describing the dynamics of the membrane potential and calcium concentration in the GnRH cells. Within the framework of our minimalist model, we find that the calcium subsystem drives burst firing by making the voltage subsystem to undergo a Hopf bifurcation. Specifically, fast relaxation oscillations occur in a specific region of the c-z plane (c being the calcium concentration, and z a calcium-dependent gating variable). Slow calcium oscillations, instead, are carried by the voltage subsystem by successive shifts of the calcium steady state, and have the net effect of an external perturbation. The full comprehension of the phase-plane of the voltage subsystem and the 3-dimensional phase-space of the calcium subsystem ultimately allows us to study the behaviours of the entire model under the change of certain parameters. Those special parameters do not necessarily follow realistic assumptions, but merely intend to mimic some pharmacological tests which have been performed experimentally and also simulated by Duan's model under the corresponding physiological considerations.

  7. Muscarinic receptor-mediated calcium changes in a rat model of facial nerve nucleus injury

    Institute of Scientific and Technical Information of China (English)

    Dawei Sun; Huamin Liu; Fugao Zhu; Yanqing Wang; Junfeng Wen; Rui Zhou; Yanjun Wang; Banghua Liu

    2010-01-01

    The muscarinic receptor modulates intracellular free calcium ion levels in the facial nerve nucleus via different channels.In the present study,muscarinic receptor-mediated free calcium ions levels were detected by confocal laser microscopy in the facial nerve nucleus following facial nerve injury in rats.There was no significant difference in muscarinic receptor expression at the affected facial nerve nucleus compared with expression prior to injury,but muscarinic receptor-mediated free calcium ion levels increased in the affected side following facial nerve injury(P < 0.01).At day 30after facial nerve injury,50 μmol/L muscarinic-mediated free calcium ion levels were significantly inhibited at the affected facial nerve nucleus in calcium-free artificial cerebrospinal fluid,and the change range was 82% of artificial cerebrospinal fluid(P < 0.05).These results suggest that increased free calcium ion concentrations are achieved by intracellular calcium ion release,and that the transmembrane flow of calcium ions is also involved in this process.

  8. Mitochondrial response and calcium ion change in apoptotic insect cells induced by SfaMNPV

    Institute of Scientific and Technical Information of China (English)

    XIU Meihong; PENG Jianxin; HONG Huazhu

    2005-01-01

    Mitochondrial responses and changes of calcium ions in apoptotic insect SL-1 cells induced by Syngrapha falcifera multiple nuclear polyhedrosis virus (SfaMNPV) are reported in this paper. By using Rhodamine 123 as a fluorescent labeling probe, flow cytometry analysis and confocal laser scanning microscope observation we observed that the mitochondrial transmembrane potential (△Ψm) began to decrease in SL-1 cells at 4 h post infection and △Ψm reduced continuously with the extension of virus infection. Western blotting indicated that the Bcl-2 level in the mitochondria gradually declined and was down- regulated. Cells undergoing apoptosis were found to have an elevation of cytochrome c in the cytosol and a corresponding decrease in the mitochondria, which indicated that cytochrome c was released from mitochondria into cytosol. These results suggest that mitochondrion-mediated apoptotic signal transduction pathway exists in apoptotic insect cell induced by SfaMNPV. Cytosolic free calcium ([Ca2+]i) concentration rapidly increased after SfaMNPV infection and the elevated calcium was tested to come partly from extracelllular calcium ion influx. Flow cytometry analysis indicated that the apoptosis in SL-1 cells was not influenced by established cytosolic calcium clamped conditions and the EGTA inhibiting calcium influx. Therefore, neither the elevation of cytosolic calcium ion nor extracellular calcium entry was the inducing factor of apoptosis, which hinted that the depletion of ER Ca2+ store contributed to SL-1 cell apoptosis induced by SfaMNPV.

  9. Wnt-induced calcium signaling mediates axon growth and guidance in the developing corpus callosum.

    Science.gov (United States)

    Hutchins, B Ian; Li, Li; Kalil, Katherine

    2012-01-10

    Wnt5a gradients guide callosal axons by repulsion through Ryk receptors in vivo. We recently found that Wnt5a repels cortical axons and promotes axon outgrowth through calcium signaling in vitro. Here, using cortical slices, we show that Wnt5a signals through Ryk to guide and promote outgrowth of callosal axons after they cross the midline. Calcium transient frequencies in callosal growth cones positively correlate with axon outgrowth rates in vitro. In cortical slices, calcium release through inositol 1,4,5-trisphosphate (IP(3)) receptors and calcium entry through transient receptor potential channels modulate axon growth and guidance. Knocking down Ryk inhibits calcium signaling in cortical axons, reduces rates of axon outgrowth subsequent to midline crossing, and causes axon guidance defects. Calcium- and calmodulin-dependent protein kinase II (CaMKII) is required downstream of Wnt-induced calcium signaling for postcrossing callosal axon growth and guidance. Taken together, these results suggest that growth and guidance of postcrossing callosal axons by Wnt-Ryk-calcium signaling involves axon repulsion through CaMKII.

  10. Abnormal Calcium "Sparks" in Cardiomyocytes of Post-myocardial Infarction Heart

    Institute of Scientific and Technical Information of China (English)

    Kai HUANG; Dan HUANG; Shengquan FU; Chongzhe YANG; Yuhua LIAO

    2008-01-01

    In ischemic hypertrophic myocardium, contractile dysfunction can be attributed to the decreased calcium induced calcium release (CICR) in cytoplasm. This study aimed to investigate the electrophysiological properties and the expression of L calcium channel subunits in post-MI myocardium. The ischemic heart remodeling model was established in SD rats. The expressions of calcium channel subunits were determined by realtime RT-PCR. Whole cell patch clamp was used to record the electrophysiological properties of L calcium channel. The results showed that the L calcium channel agonist Bayk 8644 induced the significantly decreased CICR in the rat cardiomyocyte 6weeks after myocardial infarction (MI). In the post-MI cardiomyocytes, the amplitude of ICaL decreased dramatically and the inactivation curve of the current shifted to more negative potential. At mRNA level, the expression of the calcium channel alphalc, beta2c subunits decreased dramatically in the ventricle of post-MI rats. The expression of alpha2/delta subunit, however, remained constant.It is concluded that the abnormal expression of the L calcium channel subunits in post-MI cardiomyocytes contributes to the ICaL decrease at early stage of the ischemic remodeling in cardiomyocytes,which leads to the decreased CICR in the cell and contractile dysfunction of myocardium.

  11. Calcium regulates the commitment of murine erythroleukemia cells to terminal erythroid differentiation

    OpenAIRE

    1981-01-01

    An alteration in the rate of calcium transport appears to be the rate- limiting event for the commitment of murine erythroleukemia (MEL) cells to initiate a program of terminal erythroid differentiation. The dimethyl sulfoxide (DMSO)-induced commitment of MEL cells to erythroid differentiation can be inhibited by treatment of cells with the calcium- chelating agent EGTA. Upon removal of EGTA, cells initiate commitment without the 12-h lag normally observed after treatment with DMSO alone. Tre...

  12. Dihydropyridines as inhibitors of capacitative calcium entry in leukemic HL-60 cells

    Science.gov (United States)

    Harper, Jacquie L.; Camerini-Otero, Carol S.; Li, An-Hu; Kim, Soon-Ai; Jacobson, Kenneth A.; Daly, John W.

    2016-01-01

    A series of 1,4-dihydropyridines (DHPs) were investigated as inhibitors of capacitative calcium influx through store-operated calcium (SOC) channels. Such channels activate after ATP-elicited release of inositol trisphosphate (IP3)-sensitive calcium stores in leukemia HL-60 cells. The most potent DHPs were those containing a 4-phenyl group with an electron-withdrawing substituent, such as m- or p-nitro- or m-trifluoromethyl (IC50 values: 3–6 μM). Benzyl esters, corresponding to the usual ethyl/methyl esters of the DHPs developed as L-type calcium channel blockers, retained potency at SOC channels, as did N-substituted DHPs. N-Methylation reduced by orders of magnitude the potency at L-type channels resulting in DHPs nearly equipotent at SOC and L-type channels. DHPs with N-ethyl, N-allyl, and N-propargyl groups also had similar potencies at SOC and L-type channels. Replacement of the usual 6-methyl group of DHPs with larger groups, such as cyclobutyl or phenyl, eliminated activity at the SOC channels; such DHPs instead elicited formation of inositol phosphates and release of IP3-sensitive calcium stores. Other DHPs also caused a release of calcium stores, but usually at significantly higher concentrations than those required for the inhibition of capacitative calcium influx. Certain DHPs appeared to cause an incomplete blockade of SOC channel-dependent elevations of calcium, suggesting the presence of more than one class of such channels in HL-60 cells. N-Methylnitrendipine (IC50 2.6 μM, MRS 1844) and N-propargylnifrendipine (IC50 1.7 μM, MRS 1845) represent possible lead compounds for the development of selective SOC channel inhibitors. PMID:12527326

  13. [Roles of intracellular calcium and monomeric G-proteins in regulating exocytosis of human neutrophils].

    Science.gov (United States)

    Zhu, Ying; Wang, Jun-Han; Wu, Jian-Min; Xu, Tao; Zhang, Chun-Guang

    2003-12-25

    Neutrophils play a major role in host defense against microbial infection. There are some clues indicate that neutrophils may also play a role in the pathophysiology of the airway obstruction in chronic asthma. We studied the roles of intracellular calcium and GTP gamma S in the regulation of neutrophils exocytosis using pipette perfusion and membrane capacitance measurement technique in whole cell patch clamp configuration. The results showed that the membrane capacitance increase induced by calcium revealed a biphasic process. The first phase occurred when the calcium level was between 0.2-14 micromol/L with a plateau amplitude of 1.23 pF and a calcium EC50 of 1.1 micromol/L. This phase might correspond to the release of the tertiary granules. The second phase occurred when the calcium concentration was between 20-70 micromol/L with a plateau increment of 6.36 pF, the calcium EC50 being about 33 micromol/L. This phase might represent the release of the primary and secondary granules. Intracellular calcium also simultaneously increased the exocytotic rate and the eventual extent in neutrophils. On the other hand, GTP gamma S can increase the exocytotic rate in a dose-dependent manner but had no effect on the eventual extent of membrane capacitance increment (>6 pF) if the cell was stimulated for a long period (>20 min). GTP gamma S (ranging from 20 to 100 micromol/L) induced the neutrophils to release all four types of the granules at very low intracellular calcium level. PMID:14695488

  14. Clinical Evaluation of Aspirin and Sustained-release Dipyridamole in the Prevention and Treatment of Ischaemic Cerebrovascular Events After Acute Ischemic Stroke%阿司匹林联合缓释型双嘧达莫防治急性缺血性卒中后脑血管缺血事件的临床评价

    Institute of Scientific and Technical Information of China (English)

    冯慧玲; 杨冠涛

    2012-01-01

    目的 评价阿司匹林联合缓释型双嘧达莫防治急性缺血性卒中后脑血管缺血事件的临床作用.方法 选择2009年2月-2012年1月清苑县人民医院收治的63例急性缺血性卒中患者作为研究对象,根据抗血小板治疗药物使用情况分为A组33例和B组30例,A组采用阿司匹林联合缓释型双嘧达莫治疗,B组仅采用阿司匹林治疗,比较两组对脑血管缺血事件的防治作用.结果 A、B两组治疗后的神经功能缺损评分均明显改善,以A组改善更为明显(P<0.05);随访6个月,A组脑血管缺血事件发生率为3.0%,B组为23.3%,组间差异有统计学意义(P<0.05);两组均无严重不良反应发生.结论 阿司匹林联合缓释型双嘧达莫防治急性缺血性卒中后脑血管缺血事件的临床作用显著,能明显改善患者的神经功能,减少脑血管缺血事件的发生,并且安全性好,是临床首选的药物治疗方案之一.%Objective To evaluate the clinical effect of aspirin and sustained - release dipyridamole in the prevention and treatment of ischaemic cerebrovascular events after acute ischemic stroke. Methods From February 2009 to January 2012, 63 patients with acute ischemic stroke in the People's Hospital of Qingyuan County were selected as the research objects. According to the usage of antiplatelet therapy, they were divided into group A (n= 33) and group B (n= 30). The patients in group A were treated with aspirin plus sustained — release dipyridamole, while the patients in group B were only treated with aspirin. The prevention and treatment effects in the two groups were compared. Results After the treatment, the neurological deficit scores of groups A and B were both significantly improved, but the score in group A was improved more significantly (P< 0.05). Six- month follow — up outcome showed that the incidence rates of ischaemic cerebrovascular event in groups A and B were 3.0% and 23.3% respectively, and the difference

  15. Mitochondrial calcium uptake.

    Science.gov (United States)

    Williams, George S B; Boyman, Liron; Chikando, Aristide C; Khairallah, Ramzi J; Lederer, W J

    2013-06-25

    Calcium (Ca(2+)) uptake into the mitochondrial matrix is critically important to cellular function. As a regulator of matrix Ca(2+) levels, this flux influences energy production and can initiate cell death. If large, this flux could potentially alter intracellular Ca(2+) ([Ca(2+)]i) signals. Despite years of study, fundamental disagreements on the extent and speed of mitochondrial Ca(2+) uptake still exist. Here, we review and quantitatively analyze mitochondrial Ca(2+) uptake fluxes from different tissues and interpret the results with respect to the recently proposed mitochondrial Ca(2+) uniporter (MCU) candidate. This quantitative analysis yields four clear results: (i) under physiological conditions, Ca(2+) influx into the mitochondria via the MCU is small relative to other cytosolic Ca(2+) extrusion pathways; (ii) single MCU conductance is ∼6-7 pS (105 mM [Ca(2+)]), and MCU flux appears to be modulated by [Ca(2+)]i, suggesting Ca(2+) regulation of MCU open probability (P(O)); (iii) in the heart, two features are clear: the number of MCU channels per mitochondrion can be calculated, and MCU probability is low under normal conditions; and (iv) in skeletal muscle and liver cells, uptake per mitochondrion varies in magnitude but total uptake per cell still appears to be modest. Based on our analysis of available quantitative data, we conclude that although Ca(2+) critically regulates mitochondrial function, the mitochondria do not act as a significant dynamic buffer of cytosolic Ca(2+) under physiological conditions. Nevertheless, with prolonged (superphysiological) elevations of [Ca(2+)]i, mitochondrial Ca(2+) uptake can increase 10- to 1,000-fold and begin to shape [Ca(2+)]i dynamics.

  16. FORMULATION AND EVALUATION OF SOLID DISPERSION OF ATORVASTATIN CALCIUM

    Directory of Open Access Journals (Sweden)

    Monika Sharma

    2013-08-01

    Full Text Available The present study was designed to improve the solubility and hence enhance the dissolution of hydrophobic drug Atorvastatin calcium (ATC in order to increase its bioavailability. Solid dispersion of atorvastatin calcium using carrier PEG 4000 was formulated in different ratios by conventional fusion and microwave induced fusion method. In particular, the Microwave technology has been considered in order to prepare an enhanced release dosage form for poorly water soluble drug ATC. Their physicochemical characteristics and dissolution properties were compared to the corresponding dispersions and pure drug. Three different formulations were prepared using Conventional fusion method and Microwave induced fusion method in different ratios i.e., 1:1, 1:2, 1:3 and 1:1, 1:2, 1:3 respectively, were further characterized by FTIR, DSC and SEM analysis. The results of FTIR revealed that no chemical interaction between the drug and the polymer exist. DSC studies showed that the drug was in amorphous state completely entrapped by the polymer. SEM studies showed the surface morphology of the solid dispersion. All the formulations showed a marked increase in drug release with the increase in the concentration of PEG 4000 when tested for their in vitro studies. Formulation T5 showed the best release with a cumulative release of 86.15 % in 30 minutes, when compared to the pure drug and marketed formulation. The microwave assisted method was found to be better than conventional fusion method for preparation of solid dispersion.

  17. Lithium prevents early cytosolic calcium increase and secondary injurious calcium overload in glycolytically inhibited endothelial cells

    International Nuclear Information System (INIS)

    Highlights: •We investigate free calcium as a central signalling element in endothelial cells. •Inhibition of glycolysis with 2-deoxy-D-glucose reduces cellular ATP. •This manoeuvre leads to a biphasic increase and overload of free calcium. •Pre-treatment with lithium for 24 h abolishes both phases of the calcium increase. •This provides a new strategy to protect endothelial calcium homeostasis and barrier function. -- Abstract: Cytosolic free calcium concentration ([Ca2+]i) is a central signalling element for the maintenance of endothelial barrier function. Under physiological conditions, it is controlled within narrow limits. Metabolic inhibition during ischemia/reperfusion, however, induces [Ca2+]i overload, which results in barrier failure. In a model of cultured porcine aortic endothelial monolayers (EC), we addressed the question of whether [Ca2+]i overload can be prevented by lithium treatment. [Ca2+]i and ATP were analysed using Fura-2 and HPLC, respectively. The combined inhibition of glycolytic and mitochondrial ATP synthesis by 2-desoxy-D-glucose (5 mM; 2-DG) plus sodium cyanide (5 mM; NaCN) caused a significant decrease in cellular ATP content (14 ± 1 nmol/mg protein vs. 18 ± 1 nmol/mg protein in the control, n = 6 culture dishes, P 2+]i (278 ± 24 nM vs. 71 ± 2 nM in the control, n = 60 cells, P 2+]i response of EC was biphasic with a peak after 1 min (183 ± 6 nM vs. 71 ± 1 nM, n = 60 cells, P 2+]i. A 24-h pre-treatment with 10 mM of lithium chloride before the inhibition of ATP synthesis abolished both phases of the 2-DG-induced [Ca2+]i increase. This effect was not observed when lithium chloride was added simultaneously with 2-DG. We conclude that lithium chloride abolishes the injurious [Ca2+]i overload in EC and that this most likely occurs by preventing inositol 3-phosphate-sensitive Ca2+-release from the endoplasmic reticulum. Though further research is needed, these findings provide a novel option for therapeutic strategies to

  18. Buffer regulation of calcium puff sequences

    International Nuclear Information System (INIS)

    Puffs are localized Ca2+ signals that arise in oocytes in response to inositol 1,4,5-trisphosphate (IP3). They are the result of the liberation of Ca2+ from the endoplasmic reticulum through the coordinated opening of IP3 receptor/channels clustered at a functional release site. The presence of buffers that trap Ca2+ provides a mechanism that enriches the spatio–temporal dynamics of cytosolic calcium. The expression of different types of buffers along the cell's life provides a tool with which Ca2+ signals and their responses can be modulated. In this paper we extend the stochastic model of a cluster of IP3R-Ca2+ channels introduced previously to elucidate the effect of buffers on sequences of puffs at the same release site. We obtain analytically the probability laws of the interpuff time and of the number of channels that participate of the puffs. Furthermore, we show that under typical experimental conditions the effect of buffers can be accounted for in terms of a simple inhibiting function. Hence, by exploring different inhibiting functions we are able to study the effect of a variety of buffers on the puff size and interpuff time distributions. We find the somewhat counter-intuitive result that the addition of a fast Ca2+ buffer can increase the average number of channels that participate of a puff. (paper)

  19. Buffer regulation of calcium puff sequences.

    Science.gov (United States)

    Fraiman, Daniel; Dawson, Silvina Ponce

    2014-02-01

    Puffs are localized Ca(2 +) signals that arise in oocytes in response to inositol 1,4,5-trisphosphate (IP3). They are the result of the liberation of Ca(2 +) from the endoplasmic reticulum through the coordinated opening of IP3 receptor/channels clustered at a functional release site. The presence of buffers that trap Ca(2 +) provides a mechanism that enriches the spatio-temporal dynamics of cytosolic calcium. The expression of different types of buffers along the cell's life provides a tool with which Ca(2 +) signals and their responses can be modulated. In this paper we extend the stochastic model of a cluster of IP3R-Ca(2 +) channels introduced previously to elucidate the effect of buffers on sequences of puffs at the same release site. We obtain analytically the probability laws of the interpuff time and of the number of channels that participate of the puffs. Furthermore, we show that under typical experimental conditions the effect of buffers can be accounted for in terms of a simple inhibiting function. Hence, by exploring different inhibiting functions we are able to study the effect of a variety of buffers on the puff size and interpuff time distributions. We find the somewhat counter-intuitive result that the addition of a fast Ca(2 +) buffer can increase the average number of channels that participate of a puff.

  20. Escore de cálcio coronariano prediz estenose e eventos na insuficiência renal crônica pré-transplante Score de calcio coronario predice estenosis y eventos en la insuficiencia renal crónica pre trasplante Coronary calcium score as predictor of stenosis and events in pretransplant renal chronic failure

    Directory of Open Access Journals (Sweden)

    Miguel Abraão Rosário

    2010-02-01

    este grupo. La evaluación del score de calcio coronario (SCC por tomografía computarizada ha estado comprobando valor pronóstico en la población sin enfermedad renal. OBJETIVO: Evaluar la exactitud del SCC para detectar EAC obstructiva y prever eventos cardiovasculares en candidatos a trasplante renal comparada a la angiografía coronaria invasiva (ACI cuantitativa. MÉTODOS: Se evaluaron a 97 pacientes con IRC y edad > 35 años. Se consideró como EAC obstructiva la presencia de estenosis > 50% o > 70% por la ACI. Datos descriptivos, concordancia, pruebas diagnósticas, Kaplan-Meier y análisis multivariado se utilizaron. RESULTADOS: El score de Agatston promedio fue de 580,6 ± 1.102,2; los valores mínimos y máximos fueron 0 y 7.994, y mediana de 176. Solamente 14 pacientes tenían score de calcio de cero. No hubo diferencias entre las etnias y la mayor presencia de calcio regional se asoció a la mayor probabilidad de estenosis coronaria en el mismo segmento. El score de calcio de Agatston presentó buena exactitud para el diagnóstico de estenosis, > 50% y > 70% con área bajo la curva ROC de 0,75 y 0,70, respectivamente. En el umbral de 400, el score de calcio identificó el subgrupo con mayor tasa de eventos cardiovasculares en tiempo promedio de seguimiento de 29,1 ± 11,0 meses. CONCLUSIÓN: El SCC en la evaluación de EAC presentó una buena performance diagnóstica y pronostica para eventos cardiovasculares en pacientes con insuficiencia renal crónica (IRC.BACKGROUND: Coronary artery disease (CAD is the major cause of death among chronic renal failure (CRF patients. Traditional, non-invasive exams to detect CAD and to predict events have shown insufficient results in this group. CT Scan evaluation of Coronary Calcium Score (CCS has proven to be of prognostic value for the population reporting no renal condition. OBJECTIVE: To investigate CCS accuracy in detecting obstructive CAD and in predicting cardiovascular events in candidates to renal transplant

  1. Genetic evidence in the mouse solidifies the calcium hypothesis of myofiber death in muscular dystrophy.

    Science.gov (United States)

    Burr, A R; Molkentin, J D

    2015-09-01

    Muscular dystrophy (MD) refers to a clinically and genetically heterogeneous group of degenerative muscle disorders characterized by progressive muscle wasting and often premature death. Although the primary defect underlying most forms of MD typically results from a loss of sarcolemmal integrity, the secondary molecular mechanisms leading to muscle degeneration and myofiber necrosis is debated. One hypothesis suggests that elevated or dysregulated cytosolic calcium is the common transducing event, resulting in myofiber necrosis in MD. Previous measurements of resting calcium levels in myofibers from dystrophic animal models or humans produced equivocal results. However, recent studies in genetically altered mouse models have largely solidified the calcium hypothesis of MD, such that models with artificially elevated calcium in skeletal muscle manifest fulminant dystrophic-like disease, whereas models with enhanced calcium clearance or inhibited calcium influx are resistant to myofiber death and MD. Here, we will review the field and the recent cadre of data from genetically altered mouse models, which we propose have collectively mostly proven the hypothesis that calcium is the primary effector of myofiber necrosis in MD. This new consensus on calcium should guide future selection of drugs to be evaluated in clinical trials as well as gene therapy-based approaches. PMID:26088163

  2. Electric pulses: a flexible tool to manipulate cytosolic calcium concentrations and generate spontaneous-like calcium oscillations in mesenchymal stem cells

    Science.gov (United States)

    de Menorval, Marie-Amelie; Andre, Franck M.; Silve, Aude; Dalmay, Claire; Français, Olivier; Le Pioufle, Bruno; Mir, Lluis M.

    2016-01-01

    Human adipose mesenchymal stem cells (haMSCs) are multipotent adult stem cells of great interest in regenerative medicine or oncology. They present spontaneous calcium oscillations related to cell cycle progression or differentiation but the correlation between these events is still unclear. Indeed, it is difficult to mimic haMSCs spontaneous calcium oscillations with chemical means. Pulsed electric fields (PEFs) can permeabilise plasma and/or organelles membranes depending on the applied pulses and therefore generate cytosolic calcium peaks by recruiting calcium from the external medium or from internal stores. We show that it is possible to mimic haMSCs spontaneous calcium oscillations (same amplitude, duration and shape) using 100 μs PEFs or 10 ns PEFs. We propose a model that explains the experimental situations reported. PEFs can therefore be a flexible tool to manipulate cytosolic calcium concentrations. This tool, that can be switched on and off instantaneously, contrary to chemicals agents, can be very useful to investigate the role of calcium oscillations in cell physiology and/or to manipulate cell fate. PMID:27561994

  3. Event Index - an LHCb Event Search System

    CERN Document Server

    Ustyuzhanin, Andrey

    2015-01-01

    During LHC Run 1, the LHCb experiment recorded around 1011 collision events. This paper describes Event Index | an event search system. Its primary function is to quickly select subsets of events from a combination of conditions, such as the estimated decay channel or number of hits in a subdetector. Event Index is essentially Apache Lucene [1] optimized for read-only indexes distributed over independent shards on independent nodes.

  4. Event Index - an LHCb Event Search System

    OpenAIRE

    Ustyuzhanin, Andrey; Artemov, Alexey; Kazeev, Nikita; Redkin, Artem

    2015-01-01

    During LHC Run 1, the LHCb experiment recorded around $10^{11}$ collision events. This paper describes Event Index - an event search system. Its primary function is to quickly select subsets of events from a combination of conditions, such as the estimated decay channel or number of hits in a subdetector. Event Index is essentially Apache Lucene optimized for read-only indexes distributed over independent shards on independent nodes.

  5. Extracting Event Dynamics from Event-by-Event Analysis

    OpenAIRE

    Fu, Jinghua; Liu, Lianshou

    2003-01-01

    The problem of eliminating the statistical fluctuations and extracting the event dynamics from event-by-event analysis is discussed. New moments $G_p$ (for continuous distribution), and $G_{q,p}$ (for anomalous distribution) are proposed, which are experimentally measurable and can eliminate the Poissonian type statistical fluctuations to recover the dynamical moments $C_p$ and $C_{q,p}$. In this way, the dynamical distribution of the event-averaged transverse momentum $\\bar{\\pt}$ can be extr...

  6. Gastrointestinal events with clopidogrel

    DEFF Research Database (Denmark)

    Grove, Erik Lerkevang; Würtz, Morten; Schwarz, Peter;

    2013-01-01

    Clopidogrel prevents cardiovascular events, but has been linked with adverse gastrointestinal (GI) complications, particularly bleeding events.......Clopidogrel prevents cardiovascular events, but has been linked with adverse gastrointestinal (GI) complications, particularly bleeding events....

  7. Aging and calcium as an environmental factor.

    Science.gov (United States)

    Fujita, T

    1985-12-01

    Calcium deficiency is a constant menace to land-abiding animals, including mammals. Humans enjoying exceptional longevity on earth are especially susceptible to calcium deficiency in old age. Low calcium and vitamin D intake, short solar exposure, decreased intestinal absorption, and falling renal function with insufficient 1,25(OH)2 vitamin D biosynthesis all contribute to calcium deficiency, secondary hyperparathyroidism, bone loss and possibly calcium shift from the bone to soft tissue, and from the extracellular to the intracellular compartment, blunting the sharp concentration gap between these compartments. The consequences of calcium deficiency might thus include not only osteoporosis, but also arteriosclerosis and hypertension due to the increase of calcium in the vascular wall, amyotrophic lateral sclerosis and senile dementia due to calcium deposition in the central nervous system, and a decrease in cellular function, because of blunting of the difference in extracellular-intracellular calcium, leading to diabetes mellitus, immune deficiency and others (Fig. 6). PMID:2943880

  8. Optimizing calcium selective fluorimetric nanospheres.

    Science.gov (United States)

    Kisiel, Anna; Kłucińska, Katarzyna; Gniadek, Marianna; Maksymiuk, Krzysztof; Michalska, Agata

    2015-11-01

    Recently it was shown that optical nanosensors based on alternating polymers e.g. poly(maleic anhydride-alt-1-octadecene) were characterized by a linear dependence of emission intensity on logarithm of concentration over a few of orders of magnitude range. In this work we focus on the material used to prepare calcium selective nanosensors. It is shown that alternating polymer nanosensors offer competitive performance in the absence of calcium ionophore, due to interaction of the nanospheres building blocks with analyte ions. The emission increase corresponds to increase of calcium ions contents in the sample within the range from 10(-4) to 10(-1) M. Further improvement in sensitivity (from 10(-6) to 10(-1) M) and selectivity can be achieved by incorporating calcium ionophore in the nanospheres. The optimal results were obtained for core-shell nanospheres, where the core was prepared from poly(styrene-co-maleic anhydride) and the outer layer from poly(maleic anhydride-alt-1-octadecene). Thus obtained chemosensors were showing linear dependence of emission on logarithm of calcium ions concentration within the range from 10(-7) to 10(-1) M. PMID:26452839

  9. Early pre- and postsynaptic calcium signaling abnormalities mask underlying synaptic depression in presymptomatic Alzheimer’s disease mice

    Science.gov (United States)

    Chakroborty, Shreaya; Kim, Joyce; Schneider, Corinne; Jacobson, Christopher; Molgó, Jordi; Stutzmann, Grace E.

    2012-01-01

    Alzheimer’s disease (AD)-linked presenilin mutations result in pronounced endoplasmic reticulum (ER) calcium disruptions that occur prior to detectable histopathology and cognitive deficits. More subtly, these early AD-linked calcium alterations also reset neurophysiological homeostasis, such that calcium-dependent pre- and postsynaptic signaling appear functionally normal yet are actually operating under aberrant calcium signaling systems. In these 3xTg-AD mouse brains, upregulated RyR activity is associated with a shift towards synaptic depression, likely through a reduction in presynaptic vesicle stores and increased postsynaptic outward currents through SK2 channels. The deviant RyR-calcium involvement in the 3xTg-AD mice also compensates for an intrinsic predisposition for hippocampal LTD and reduced LTP. In this study we detail the impact of disrupted ryanodine receptor (RyR)-mediated calcium stores on synaptic transmission properties, long term depression (LTD) and calcium-activated membrane channels of hippocampal CA1 pyramidal neurons in presymptomatic 3xTg-AD mice. Using electrophysiological recordings in young 3xTg-AD and NonTg hippocampal slices, we show that increased RyR-evoked calcium release in 3xTg-AD mice ‘normalizes’ an altered synaptic transmission system operating under a shifted homeostatic state that is not present in NonTg mice. In the process, we uncover compensatory signaling mechanisms recruited early in the disease process which counterbalance the disrupted RyR-calcium dynamics, namely increases in presynaptic spontaneous vesicle release, altered probability of vesicle release, and upregulated postsynaptic SK channel activity. As AD is increasingly recognized as a ‘synaptic disease’, calcium-mediated signaling alterations may serve as a proximal trigger for the synaptic degradation driving the cognitive loss in AD. PMID:22699914

  10. Chemical release module facility

    Science.gov (United States)

    Reasoner, D. L.

    1980-01-01

    The chemical release module provides the capability to conduct: (1) thermite based metal vapor releases; (2) pressurized gas releases; (3) dispersed liquid releases; (4) shaped charge releases from ejected submodules; and (5) diagnostic measurements with pi supplied instruments. It also provides a basic R-F and electrical system for: (1) receiving and executing commands; (2) telemetering housekeeping data; (3) tracking; (4) monitoring housekeeping and control units; and (5) ultrasafe disarming and control monitoring.

  11. Morphology of Gas Release in Physical Simulants

    Energy Technology Data Exchange (ETDEWEB)

    Daniel, Richard C.; Burns, Carolyn A.; Crawford, Amanda D.; Hylden, Laura R.; Bryan, Samuel A.; MacFarlan, Paul J.; Gauglitz, Phillip A.

    2014-07-03

    This report documents testing activities conducted as part of the Deep Sludge Gas Release Event Project (DSGREP). The testing described in this report focused on evaluating the potential retention and release mechanisms of hydrogen bubbles in underground radioactive waste storage tanks at Hanford. The goal of the testing was to evaluate the rate, extent, and morphology of gas release events in simulant materials. Previous, undocumented scoping tests have evidenced dramatically different gas release behavior from simulants with similar physical properties. Specifically, previous gas release tests have evaluated the extent of release of 30 Pa kaolin and 30 Pa bentonite clay slurries. While both materials are clays and both have equivalent material shear strength using a shear vane, it was found that upon stirring, gas was released immediately and completely from bentonite clay slurry while little if any gas was released from the kaolin slurry. The motivation for the current work is to replicate these tests in a controlled quality test environment and to evaluate the release behavior for another simulant used in DSGREP testing. Three simulant materials were evaluated: 1) a 30 Pa kaolin clay slurry, 2) a 30 Pa bentonite clay slurry, and 3) Rayleigh-Taylor (RT) Simulant (a simulant designed to support DSGREP RT instability testing. Entrained gas was generated in these simulant materials using two methods: 1) application of vacuum over about a 1-minute period to nucleate dissolved gas within the simulant and 2) addition of hydrogen peroxide to generate gas by peroxide decomposition in the simulants over about a 16-hour period. Bubble release was effected by vibrating the test material using an external vibrating table. When testing with hydrogen peroxide, gas release was also accomplished by stirring of the simulant.

  12. Visualizing Presynaptic Calcium Dynamics and Vesicle Fusion with a Single Genetically Encoded Reporter at Individual Synapses.

    Science.gov (United States)

    Jackson, Rachel E; Burrone, Juan

    2016-01-01

    Synaptic transmission depends on the influx of calcium into the presynaptic compartment, which drives neurotransmitter release. Genetically encoded reporters are widely used tools to understand these processes, particularly pHluorin-based reporters that report vesicle exocytosis and endocytosis through pH dependent changes in fluorescence, and genetically encoded calcium indicators (GECIs) that exhibit changes in fluorescence upon binding to calcium. The recent expansion of the color palette of available indicators has made it possible to image multiple probes simultaneously within a cell. We have constructed a single molecule reporter capable of concurrent imaging of both presynaptic calcium influx and exocytosis, by fusion of sypHy, the vesicle associated protein synaptophysin containing a GFP-based pHluorin sensor, with the red-shifted GECI R-GECO1. Due to the fixed stoichiometry of the two probes, the ratio of the two responses can also be measured, providing an all optical correlate of the calcium dependence of release. Here, we have characterized stimulus-evoked sypHy-RGECO responses of hippocampal synapses in vitro, exploring the effects of different stimulus strengths and frequencies as well as variations in external calcium concentrations. By combining live sypHy-RGECO imaging with post hoc fixation and immunofluorescence, we have also investigated correlations between structural and functional properties of synapses. PMID:27507942

  13. Creating Special Events

    Science.gov (United States)

    deLisle, Lee

    2009-01-01

    "Creating Special Events" is organized as a systematic approach to festivals and events for students who seek a career in event management. This book looks at the evolution and history of festivals and events and proceeds to the nuts and bolts of event management. The book presents event management as the means of planning, organizing, directing,…

  14. Solar Eruptive Events

    Science.gov (United States)

    Holman, Gordon D.

    2012-01-01

    It s long been known that the Sun plays host to the most energetic explosions in the solar system. But key insights into the forms that energy takes have only recently become available. Solar flares have been phenomena of both academic and practical interest since their discovery in 1859. From the academic point of view, they are the nearest events for studying the explosive release of energy in astrophysical magnetized plasmas. From the practical point of view, they disrupt communication channels on Earth, from telegraph communications in 1859 to radio and television signals today. Flares also wreak havoc on the electrical power grid, satellite operations, and GPS signals, and energetic charged particles and radiation are dangerous to passengers on high-altitude polar flights and to astronauts. Flares are not the only explosive phenomena on the Sun. More difficult to observe but equally energetic are the large coronal mass ejections (CMEs), the ejection of up to ten billion tons of magnetized plasma into the solar wind at speeds that can exceed 1000 km/s. CMEs are primarily observed from the side, with coronagraphs that block out the bright disk of the Sun and lower solar atmosphere so that light scattered from the ejected mass can be seen. Major geomagnetic storms are now known to arise from the interaction of CMEs with Earth's magnetosphere. Solar flares are observed without CMEs, and CMEs are observed without flares. The two phenomena often occur together, however, and almost always do in the case of large flares and fast CMEs. The term solar eruptive event refers to the combination of a flare and a CME. Solar eruptive events generate a lot of heat: They can heat plasma to temperatures as high at 50 million Kelvin, producing radiation across the electromagnetic spectrum. But that s not all. A fascinating aspect of solar eruptive events is the acceleration of electrons and ions to suprathermal often relativistic energies. The accelerated particles are primarily

  15. Augmentation of cholinergic-mediated amylase release by forskolin in mouse parotid gland

    International Nuclear Information System (INIS)

    Cholinergic-mediated amylase release in mouse parotid acini was augmented by forskolin; the potency but not the maximal response to carbachol was altered. Amylase released by carbachol plus forskolin was dependent on extracellular calcium and was mimicked by the calcium ionophore, A23187 plus forskolin. Forskolin was also shown to enhance carbachol-stimulated 45Ca2+ uptake into isolated acini. Hydroxylamine, nitroprusside, and 8-bromo-c-GMP each in combination with forskolin mimicked the effects of carbachol plus forskolin on amylase release. In the presence of carbachol (10-8M) forskolin did not augment c-AMP levels. However, in the presence of carbachol (5 x 10-7 M) or hydroxylamine (50 μM) forskolin did significantly augment c-AMP accumulation. These results suggest that calcium and c-GMP may mediate the augmentation of cholinergic-mediated amylase release by effects on c-AMP metabolism. 21 references, 1 figure, 3 tables

  16. The effect of variable calcium and very low calcium diets on human calcium metabolism. Ph.D. Thesis. Final Report

    Science.gov (United States)

    Chu, J.

    1971-01-01

    The effects of a very low calcium diet, with variable high and low protein intake, on the dynamics of calcium metabolism and the mechanism of calciuretics, are examined. The experiment, using male subjects, was designed to study the role of intestinal calcium absorption on urinary calcium excretion, and the rate of production of endogeneously secreted calcium in the gastrointestinal tract. The study showed an average of 70% fractional absorption rate during very low calcium intake, and that a decrease in renal tubular reabsorption of calcium is responsible for calciuretic effects of high protein intake. The study also indicates that there is a tendency to develop osteoporosis after long periods of low calcium intake, especially with a concurrent high protein intake.

  17. Calcium-phosphate-osteopontin particles for caries control

    DEFF Research Database (Denmark)

    Schlafer, Sebastian; Birkedal, Henrik; Olsen, Jakob;

    2016-01-01

    Caries is caused by acid production in biofilms on dental surfaces. Preventing caries therefore involves control of microorganisms and/or the acid produced. Here, calcium-phosphate-osteopontin particles are presented as a new approach to caries control. The particles are made by co......-precipitation and designed to bind to bacteria in biofilms, impede biofilm build-up without killing the microflora, and release phosphate ions to buffer bacterial acid production if the pH decreases below 6. Analysis of biofilm formation and pH in a five-species biofilm model for dental caries showed that treatment......H always remained above 5.5. Hence, calcium-phosphate-osteopontin particles show potential for applications in caries control....

  18. Calcium-phosphate-osteopontin particles for caries control

    DEFF Research Database (Denmark)

    Schlafer, Sebastian

    Oftentimes caries lesions develop in protected sites that are difficult to access by self-performed mechanical tooth cleaning. At present, there is a growing interest in chemical adjuncts to mechanical procedures of oral hygiene that aim at biofilm control rather than biofilm eradication. Calcium......-phosphate-osteopontin particles are a new promising therapeutic approach to caries control. They are designed to bind to dental biofilms and interfere with biofilm build-up, lowering the bacterial burden on the tooth surface without affecting bacterial viability in the oral cavity. Moreover, they dissolve when pH in the biofilm...... drops to 6 or below and release buffering phosphate ions that stabilize biofilm pH above the critical level for enamel dissolution. With that twofold approach, calcium-phosphate-osteopontin particles may make a relevant contribution to clinical caries control....

  19. Ca2+ signals induced from calcium stores in pancreatic islet β cells

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    In single rat pancreatic β cells,using fura-2 microfluorometry to measure [Ca2+]i response upon different stimuli,the ways of calcium regulation have been studied.When the extracellular calcium concentration was 2.5 mmol/L,either 60 mmol/L KCl,20 mmol/L D-glucose or 0.1 mmol/L tolbutamide induced increase in [Ca2+]i.Such increase in [Ca2+]i was absent when the same stimuli were applied under zero extracellular calcium.These results indicate that the increase of [Ca2+]i is induced by the activation of voltage-dependent calcium channels in β cells.The manifold forms of [Ca2+]i change induced by glucose imply that the effects of glucose are complex.5 mmol/L caffeine or 5 mmol/L MCh increase the [Ca2+]i ,which is independent of the external calcium,suggesting that [Ca2+]i can be regulated by Ca2+ release from not only the IP3-sensitive but also the ryanodine sensitive calcium stores in β cells.The latency of Ca responses for IP3 pathway (5 s) is faster than that for ryanodine pathway (30 s).It is concluded that there are multiple calcium stores in rat pancreatic β cells.

  20. Physiological responses of osteoblasts to cyclic stretching and the change of intracellular calcium concentration

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The development of bone tissues is regulated by mechanical stimulation. Cyclic stretching was applied to the osteoblasts that were delivered from rat calvarie. The results showed that stretching at 500 με increased the cell proliferation while loading at 1000 με and 1500 με inhabited cell growth. Loading alsoincreased the adhesive force between cells and substrate as well as spreading areas of osteobalsts. Furthermore, the fluorescence probe Fluo-3/AM was used to investigate the effect of stretching stimulation on the intracellular calcium concentration of osteoblasts. The intracellular calcium concentration of osteoblasts that were stretched at 500 με for 5 min was 92.9% higher than the control. After being treated with the panax ontoginseng saponins, the stretched osteoblasts still expressed 28.6% higher intracellular calcium concentration than that of the control, which proved that both the influx of extracellular calcium and the release of intracellular calcium store were involved in the increase of intracellular calcium concentration when osteoblasts responded to the cyclic stretching. And the influx of extracellular calcium through transmembrance channel played a main role.